Lectures on Bacteriology and Pathology, 
delivered at the Medical Department 
of George Washington University, 
1897 - 1898. 
By 
Walter Reed* 
Washington. 
1925. Contents• 
Bacteriology* 
1. History. —— n.d. 
2. Remarks on classification.- n.d. 
3* Diphtheria. — 1897. 
Pathology* 
1* Inflammation — 1898. 
2* Inflammation continued. 1898. 
3* Hissing. 
4. Missing. 
5* Catarrhal inflammation. 1898• 
6* Oedema and dropsy. — 1898. 
7. Thrombosis. 1898. 
8. Embolism. 1898. 
9. Degeneration. 1898. 
10* Disorders of the hepatic circulation. 1898. 
11* Fatty infiltration and fatty degeneration of the liver. 1898. 
12* Cirrhosis of the liver. 1898. 
13. 1.Acute supourative inflammation of the liver. 
2. Acute suppurative hepatitis. 
3. Abscess of the liver. 
14. Liver:acute degenerative changes,Small-pox, 
Yellow-fever. Scarlet fever. Diphtheria. 
Thyphoid fever. Acute yellow atrophy.-- 1898* 
15. Lung: chronic passive congestion. 1898. 
16. oedema. 1898. 
17. Missing. 
18. Pneumonia. — 1898. 
19. Acute croupous pneumonia. — 1898. 
20. Broncho-pneumonia. Lobular pneumonia. 
Catarrhal pneumonia. —---■— 1898. 
21. Missing. 
22. Emphysema, Interstitial. Vesicular. Vicarious 
or compensatory chronic substantive emphysema. 1898. * 
23. Missing. 
24. Tuberculosis. — —— -4898. 
25. Tuberculosis, continued. — — — — 1898. 
26. Tuberculosis, continued. 1898. 
27. Kidney. 1898. 
28. Missing. 
29. 1. Acute Pyrenchamatous degeneration. 
Granular degeneration. Cloudy swelling. 1898. 
2. Acute Bright’s disease. Acute inflammation 
of the kidney. Acute diffuse nephritis. 
30. Acute suppurative nephritis. 
Acute purulent nephritis. 1898. 
31. 1.Acute glomerular nephritis. Chronic diffuse 
Chronic diffuse nephritis. 1898. 
32. Missing. 
33. Small contracted kidney.l. Chronic interstitial 
nephritis.2.Chronic arterio-sclerotic kidney.1898. 
34. Spleen. -4898. period of scientific research upon the sub- 
ject of infective diseases we are brought in contact with the be- 
A A 
"H. 
lief that thereat cause of these diseases is a entity endow- 
u A 7; 
ed with vital properties, a contagium animaltffefctum. As to the more 
* 
intimate nature of this supposed entity, or as to the exact mode 
\ ... 
of its propagation, there were very many queer notions and sugges- 
tions. So long ago as 1658, there was published in'Rome a volume 
having the fo 11 owing title: " Scrutinium physico-medicum contagio- 
sae luis, quae pest is dicitur;*1 a physico-medical scrutiny of the 
contagious disease called the pest. The author was Athanasius 
Kircher, physician, philosopher and writer. Amongst other things 
says: 11 These little worms, which propogate the pest, 
are so small and subtile that they elude the natural sense, and can 
be brought to view only by the best microscope; atoms you might call 
rrt 
them* /.hey appear in such multitude that they cannot be counted; 
these are born of putrefaction, are forced out through the pores 
and air passages of the body with the sudorific exudations, and as 
they are agitated by the slightest movement of the air, just as the 
atoms in a ray of the sun in a darkened room, they are diffused 
here and there, and light on articles, and adhere to them most ten- 
(f 
aciously, and enter into all their innermost pores. I have become 
convinced the human being, not only dead but also living, is 
filled with innumerable invisible little worms; therefore, not only 2 
the patient infected with pestiferous putrefaction, but also his 
dead body throws out through the said pores the little worms into 
the surrounding air and also into neighboring bodies; and as such 
living exudations are adhesive and subtile they penetrate into the 
innermost parts of the linen and clothing; therefore, when a patient 
is visited by a well person not used to the inclosed air; it happens 
that such poisonous exudations escape from the patient’s body, as 
well as from his bed and linen;are convoyed by the motion of the 
air, and blown on the hands of the visitor and on his clothes, and. 
as they penetrate surreptitiously through the pores, enter the in- 
nermost parts of the body, whereupon the visitor is attacked by the 
symptoms which all so afflicted have, and if his nature be not very 
strong and good, and throwl the poison off again, death must neces- 
sarily follow. Cats, dogs, pigeons, chickens, end all other do- 
mestic animals that live in the infected house take the contagion 
as soon as they touch an infected article; and though they do not 
have the disease on account of their nature, they carry the same 
into the neighboring houses, and sow the disease carry 
tkera in the city, etc. r 
A 
Now, although Kirch or mistook the blood corpuscles and 
pus cells for little worms, we must, nevertheless, concede that he 
puts forth in clear language the idea that putrefactive changes in 
dead matter, and even disease in the living body might be due to 3 
the action.of minute living organisms, and that he propounded the 
definite view that the transmission of the infective diseases de- 
pended on the growth of independent minute organisms. 
icy tftur . - 
' ' It appears to be well established that Van Leeuwenhoek, 
a native of Holland, and by trade a linen draper, but who added to 
his other accomplishments that of a grinder of lenses, was the first 
to observe very minute, active, motile bodies, which he naturally 
regarded as small animals, and hence designated them animalcules. 
/nu.. ~ S L 1 
he found in rain water, in the intestinal contents of frogs 
and birds, in various infusions, and in the scrapings from his own 
He did not attempt further to name these organisms, but 
was satisfied with the plain objective description of them. From 
a paper with drawings submitted to the Eoyal Society in 1685, we 
are able to state that he saw round forms, forms having the shape 
of a short rod, and spiral forms. 
In 1673 Leeuwenhoek commenced, communieating his discov- 
eries with the microscope to the Loyal Society; beyond the occasion' 
al statement that his observations were made with simple microscopes 
he explained nothing by which his contemporaries could furnish them- 
selves with instruments like those he employed; and this silence 
added to the mysterious awe with which he and his work were regard- 
ed. He was extremely shy of exhibiting his microscopes to any one, 
and some of his contemporaries taxed him with greater love of praise 
Hayall, John, Jr., Journal of the Society of Arts, London, Sept. 
10, 1886, p. 1015. 4 
than of truth, because of his eagerness in claiming discoveries. 
Even as late as 1709 the real construction of Leeuwen- 
hoek’s microscopes was not certainly known. Now that we know ex- 
actly the kind of instrument Leeuwenhoek employed, there can be no 
difficulty in the admission that his reputation as a discoverer 
in microscopy was really based on his patience and dexterity in the 
preparation of his objocts, and on the skill he brought to bear on 
the interpretation of his observations. As to his microscopes, 
their construction was of the rudest kind mechanically, whilst op- 
tically, they consist of simple bi-convex lenses, with worked sur- 
faces mounted between two thin metal plates, with minute apertures 
through which the objects were viewed directly. At his death he 
bequeathed to the Royal Society a cabinet containing 26 of his mi- 
croscopes, which were reported upon by-Martin Folkes, Vice Presi- 
dent of the Society, in the Philosophical Transactions, Vol. XXII, 
pp. 446-463. 
Van Leeuwenhoek’s discovery of bacteria, or rather of 
these minute animalculae, led to the revival of the doctrine of 
(i L> rs - / o */■ 
" contagium vivum," and Nicholas Andry replaced Kircher’s worms by 
A 
these newly described animalculae or germs, and pushing the theory 
i' -an*. 
to its legitimate and logical conclusion, he evolved^^rgerm theory 
of putrefaction and fermentation; he feel-toyed that the blood and 
pustules of smallpox contained these minute living organisms, and 
that other diseases very rife about this period were the result of 5 
activity of these organsims. 
V-arro-and-Lano-isi- ascribecl—LIi«dangerous-charact-e^-oiL^ 
to the actl-on of iiiv 1 siL 1~g osiiaaloulae, ond-tlio 
theory was acasyso freely and forcibly propagated that, even where 
y " a 
no microorganism could bo found, their presence was inferred, with 
the inevitable result, as Loeffler points out, that these invisible 
worms became the legitimate butts to shafts of ridicule, and the 
system being thus laughingly held up to satire, the germ theory of 
disease nigh discredited. 
Linnaeus with his marvellous powers of observation bo- 
C_ 
lieved that it was possible to rescue from this M chaos 
living beings, which were as yet insufficiently separated, and in 
which he thought might lie not only the actual contagium of certain 
eruptive diseases and acute fevers, but also the exciting causes of 
fermentation and putrefaction. The physician who most recognized 
the importance of these observations of Linnaeus was Plenciz, a 
Viennese doctor. He promulgated a causal connection between these 
minute animalcules discovered by Leeuwenhoek and the etiology of 
infective diseases. He believed that each of these diseases had 
its own special causative agent; that there was one germ for scar- 
let fever, and another for smallpox, otc. He believed that it was 
possible for this organism to become disseminated through the air,  6 
and for it to multiply in the body, and he explained the incubation 
period of febrile disease as dependent on the growth of a germ 
within the body during the period after its introduction, when its 
presence had not yet been made manifest. He recognized the absur- 
dity of ascribing all diseases to their agency, but he put forth, 
with much emphasis the idea that each specific disease had a spe- 
cific organism as its cause• 
Now, although Plenciz propounded in its essentials the 
modern germ theory of disease, it was impossible, with the crude 
instruments and means then at hand, to make the necessary observa- 
tions to confirm his theory, and we are not surprised to find that 
many prominent writers of the day reje cted his explanation of the 
causes of disease and of fermentation. From this time until near- 
ly the middle of this century, the struggle was to be continued, 
and the theory of a contagium vivum was to pass through a stage of 
desperate attack and defence. Indeed, the origin of these minute 
anirnalculae was now beginning to occupy the minds of the most in- 
fluential and intellectual in our profession. Whether these tiny 
forms of life were the result of spontaneous generation—whether 
they owed their existence to preexisting forms,-was the burning 
question which was occupying the minds of those within and without 
. ' [ (r^rxJ\ 
the profession who were scientifically bent. Some' observers sup- 
posed (although they could bring forward no groat amount of evidence 
to substantiate their theory), that these little organisms were the 7 
offspring of other organisms which were present in aM large num- 
bers in the air, from which they could be deposited on the material 
of v/hich the various infusions, etc., were made. Dr. Needham explains the whole phenomenon of the generation of 
living beings by the presence of a certain vegetative force which 
he supposes to exist in all nature, and which is always ready to 
form,under given circumstances the tissues of organized bodies. 
He wrote a comprehensive treatise in order to establish this opin- 
ion, making use of microscopic observations of different substances 
taken from the vegetable and animal kingdom. In the beginning he 
made infusions of vegetable and animal substances in ordinary water 
and, at the end of a certain time, upon examination with the micros- 
cope, found that these bodies had taken on a new fon? and a new ar- 
rangement of particles. They appeared as so many groups or little 
masses, which one observes, little by little, to swell, move, and 
transfer themselves from place to place. Finally they become de- 
veloped into real animalcules, which ran freely in the liquid. 
Needham having placed infusions of various vegetable and ani- 
mal substances in glass vessels, and having corked them, exposed 
them for a short time to the action of heat. He found in all 
cases that after a few days there were signs of life present in his 
infusions, microscopic organisms having motion were to be seen in 
large numbers. He argued that inasmuch as the heat had been suf- 
ficient to destroy the eggs if any were present, that the minute 
organisms which appeared had been produced by his so-called vege- 
tative force, which pervaded the minutest atom of the contained material. Upon these observations he founded the theory of spon- 
taneous generation, which he advocated with great vigor. He be- 
lieved that vegetable matter in infusion could give rise to animal 
life, and that this animal life could again be converted into a 
vegetable form of life. These observations of Needham were made 
during thejearly part of the eighteenth century, and exercised a 
great influence upon the opinions of men within and without the 
medical profession. 
Charles Bonnet, of Geneva, reviewed Needham’s experiments, and 
n . «... fHt tZt^T 
made the following criticisms?- h^wdvorr is Mr-— lie odnam sur-e that • 
-fi±£ Bottles had been sealed as carefully as if he nad sealed tiiem 
/( 1 A 
1 (f 
hen® tically, A Did there not remain certain invisible openings 
which could have been the entrance point for animalcules of such 
little size as those under consideration? Is-Mr-* Needham quite 
Ni~f 
euro that or their’sp&fi, which can sustain 
t hurt— 
a heat equal to thd@E of plashes without perishing, or without 
LG. 
losing their prolific qualities 'ft* Is he quite sure that while the 
observer was preparing a drop of liquid for the microscope, and 
while he was adjusting his instrument, the animalculao which ex- 
isted in the air, or simply their seed, may not have been precip- 
77 
itated into this drop ? Is he, finally, quite sure that there did 
not exist animals, whose multiplication may be so rapid that they 
Sonnet ( C.) Considerations sur los.corps or,--anises, etc., Amster- 
dam, 1768, Vol. II, Chap. VI, p. 181 only require a few minutes in order to appear perfectly formed ? 
When one explains the presence of certain animalcules in a liquid, 
by having recourse to productive or vegetative forces, is one not 
apt to put the words in place of the things ? What idea has he 
of these forces ? How does he conceive that they organize matter? 
Transform inanimate particles into living beings, the vegetable 
into the animal ? Hoes he bring about this marvelous operation 
all at once, or by degrees ? If it is all at once, then let him 
describe its course of progress. All nature is opposed to the 
idea of spontaneous generation. Behold the varieties of fecunda- 
tion and of generation. Animals so unlike to each other by the 
manner in which they are fecundated and in which they are generated 
resemble each other in this, that they owe their origin to an animal 
of this same species. We should bo very careful in going against 
general laws; the exception should be rigorously demonstrated be- 
fore being admitted, especially when they controvert a lav/ the most 
universal and most constant, and the most invariable of all those 
of which we know anything/ therefore, 
whether he ha^suff iedrigorously demonstrated that the ani- 
malcules contained in infusions have not an origin similar to those 
of other animals. 
cm 7) 
Spallanzan Needham's experiments, and found that al- 
though he carefully boiled his infusions, and filled his vessels with the boiling infusion, and when they had become cool carefully 
stoppered thorn, just as Needham had stated, there always occurred 
a growth of minute animalcules within the vessels. Spallanzani 
did not believe, however, that sprang from any vege- 
tative force. He made many experiments on this subject, and 
finally contrived the following to see if possible 
whether it would not .finally, settle the matter. Having put to 
himself the question whether these minute bodies were not possibly 
on the walls of his vessels, or were not deposited by the atmos- 
phere during the process of cooling, in order to obviate every pos- 
sible source of contamination he subjected the vessels to the ac- 
tion of a flame; he then placed within a certain quantity of infus- 
ion, and proceeded to hermetically- seal the vessels. Next he 
placed them in boiling water for from an hour to an hour and a half. 
Infusions tins treated remained absolutely devoid of any develop- 
ment of microscopic organisms until such time as he broke the seal, 
when, within a few days; he found the presence of living organisms. 
Spallanzani then concluded that living organisms were necessary in 
order to bring about putrefaction; and that these living organisms 
owed their origin to pre-existing living organisms. 
Dr. Needham criticised severely Spallanzani1s last experiments 
and stated that the reason no growth had taken place in the flasks 
hermetically sealed was because the heat of the flame had been so 
great as to destroy the qualities of the contained air; that no organism could live without a certain amount of unaltered air, and 
that hence Spallanzani*s experiments amounted to nothing against 
his theory. 
Thus the matter stood at the end of the eighteenth century, 
and no further decisive experiments in this line were made until 
1836, when Schultze began again an investigation of the matter. 
He perforated the stopper of the flask containing his infusions 
and introduced two bent glass tubes. One of these tubes led to a 
vessel containing sulphuric acid the other to one containing solu- 
» , 
tion of caustic potash. Having carefully boiled the contents of 
the flask, and while the s^rearning steam was still escaping from the 
tubes, he collected them with the chemicals before mentioned; then 
A 
from time to time, by sucking upon a tube connected with the potash 
vessel he drew air through the sulphuric acid into the infusion. 
His idea was that sulphuric acid would kill all organisms contained 
in the air. As the result of these experiments the growth remain- 
ed sterile, although a large amount of air was aspirated into the 
vessel containing the infusion. 
The advocates of spontaneous generation were still not satis- 
fied, and maintained that the atmospheric air had been so altered 
in its passage through the sulphuric acid as to be no further fit 
for sustaining organic life. 
Schwann later, instead of using sulphuric acid, used heat as 13 
a moans of destroying any particles that might be present in the 
air and be drawn into the flask. 
In 1854 Schroeder and, v« Busch made a great advance in 
this line of experimental work; they proved that simple filtration 
through a layer of cotton wool was sufficient to deprive the air of 
its organisms. Pasteur and Chevreul soon afterwards demonstrated 
-t 
that it was quite sufficient to draw out and bend downwards the 
neck of the bottle in which the germ free infusion was contained, 
in order to insure the perfect freedom from germs of the fluid con- 
tained within the flask. They argued that germs, like*all* other 
solid particles, obey the law of gravitation, when noijpblown about 
by currents of air, and must settle down upon an upper surface; so 
that when the tube was bent downwards the organisms could not fall 
into its mouth. Tyndall proved that the appearance of a ray of 
light in a closed chamber was due to the presence of a multitude 
of minute particles floating in the air. When the particles had 
all settled to the bottom of the chamber, the ray of light disap- 
peared. Now, organic infusion placed in such a chamber from which 
the ray of light had disappeared, did not undergo decomposition, 
although they were left open. Schwann had already shown that 
blood drawn with proper precautions and put into a flask in which 
the air was kept germ free, might be preserved for a considerable 
length of time without the development of putrefaction; and later 
(1857) Van Dor Broeck demonstrated that the juice of grapes, urine 14 
and blood could bo kopt froe of decomposition, if the vessels into 
which they wore received were first thoroughly sterilised by heat, 
and afterwards not allowed to come in contact with the outside air. 
humorous observers in England, Germany and France, not only con- 
firmed these observations, but also extended them, showing that milk 
egg-albumen, various vegetable substances and portions of the or- 
gans of freshly killed animals, could be kept from decomposition by 
carefully excluding the external air with its organisms. 
\ 
Thus the supports of the foundation of spontaneous genera- 
tion were being cut away one by one^—Me v orlihoIcry inch -s-f 
Ylrrn TirvK1y TJioy cti-H: had milk and loft 
l£u-thom as their strongholds-* ''£n~h^nod°r f 1 s +■ at ~i T4 rc nd 
mirik with subjecting.-it-t-o ..s^-tGmpQratu'^e-of 4-00. 
f-er a eonsiderttbdre-^ie; and Pact our—cuccoeded- in- st or ill sing it 
o-f-lhQ °—g-t 
Ablate as J872C Bastian, a supporter of the( doctrine of 
sncnt i on, to bring&orvrard an experiment 
was beliovnd to present \ very strongyargument in faior of 
that theory. Having carefullylfiltered and sterilized an infusion 
of white turnip, l|e placed a snail fragment of cheese within pie 
infusion. This was thon boiled for ten minutes\ and whilst still 
boiling was hermetically sealed. m, the end of three days, as 
countless Irying organisms were to be\ seen, Bastian considered piat 
these were produced from\>ion-living albuminoid materials. 15 
repeatingrthese experiments, whs able to show that the Resting spores 
contained within thek centre of )the piece of cheese had kot been sub- 
jected t/o sufficient neat to destroy them/ Longer boiling, in his 
hands, prevented aly appearance of life* With the discov3ry of those 
more resistant spores the doctrine of spontaneous generation receiv- 
ed its final blow. ) It was easy now to explain the irregularities 
in the success or want of success of the foregoing experiments; nor 
could it be longer (doubted that bacteria were the cause ol\ putrefac- 
tion and fermentation, and that /these bacteria were the offspring of 
pre-exista ng forms, j In other words, Harveyjs law, "omne 'vivum ex 
ovo," or its modification, Mornr/e vivum ex mro," was shown to apply 
not only to the more highly organized members of the animal and veg- 
etable kingdoms, also to trie most microscopic unicellular crea- 
tures*. But we must not forget that the opponents of biogenesis had 
good cause for their opinions. They had applied a degree of heat 
to various animal and vegetable infusions such as was fully believ- 
ed to bring about the certain destruction of all forms of life. It 
would quickly destroy the ova of the higher animals, and why not, 
with greater the ova of these microscopic beings, which, 
in all probability were less tenacious of life. 
It is true that Muller, of Copenhagen, had, long before 
this date, described as occurring, especially in certain of the rod 
shaped forms, little shining points, arranged at regular intervals; 16 
points which wo must now conclude were veritable spores; but we ov/o 
to Frederick Cohn the positive knowledge that certain of the rod- 
shaped bacteria possess the power of passing into a resting or 
spore stage in the course of their life history. There were sev- 
eral facts which led to a belief in the self of bacter- 
ia. First, neither the defenders nor opponents of spontaneous 
generation had any knowledge or concept!021 of the extraordinary 
powers of resistance possessed by these spore forms. Secondly, 
the difficulty with which heat penetrates equably into the interior 
of bodies was little appreciated. Certainly where the heat had not 
penetrated sufficiently, spores could, under certain circumstances, 
find a place of refuge whore they could escape destruction. Third- 
ly, we had no idea of the wide distribution, the well-nigh omni- 
presence of these little organisms. There is indeed scarcely any- 
thing that is free from these minute, invisible beings. The great 
masses which surround us, the air, the earth, the water, are as 
much stocked with them, as are the objects of daily use. The 
greater part of our food, our clothing, our dwellings, our intos- 
final canal, and the surface of our skin, all swarm with micro-or- 
ganisms. Indeed, the only field which appears impregnable to them 
are the fluids and tissues of the healthy body. Small wonder that 
the battle was a prolonged and stubborn one, and that every weak 
point in the armor of the opposing forces was found out and advan- 
tage taken of it. 17 
Via oil) diov/over, trfre momentous question was—finally settled 
to the credit of both sides, attention b$u^neti 
A 
to the probable position of these minute organisms as exciters of 
disease. 
vifr-TO»t- i on*--¥^hiT&^!rhB&e''4^^ 
c4, %Zlri 
% " f I Remarks upon classification. 
Although, as we have seen, Leeuwenhoek was the first to de- 
scribe the organisms which we now designate as bacteria, he was 
satisfied, as we have stated with a simple objective description 
of them. He made no attempt whatever, to classify than. He evi- 
dently believed that they belonged to the animal kingdom. Subse- 
quent to his time there was being gradually accumulated a large 
mass of facts bearing upon these interesting and wonderfully minute 
living organisms. numerous isolated observations were being 
constantly made by the various workers, none of whom, however, 
were sufficiently master of their subject to enable them to make a 
\ 
any systematic attempt at classification, and the scientific re- 
sults obtained Y/ere hence comparatively insignificant, standing in 
no proportion to the amount of work expended and the number of ob- 
servations made, Linnaeus published tho first edition of his 
Systeana naturae, etc., at Leyden, in 1735, With this epoch making 
work the modern classification of living beings in class^orders, 
I . A V 
families, genera and species began. He established no class for 
microscopic organisms, although aY/are of their existence. 
In 1769 Ledcrmuller proposed for all such microscopic 
■ - ' ' 
organisms the name of infusoria, and he and others described a 
number of forms which were discernible with the microscopes of that 
day. 
The first intelligent attempt at a classification of bac- teria was made in 1773 by Muller, of Copenhagen, Ho appeared to 
have a thorough appreciation of the work which he was undertaking, 
and, with a well defined plan set himself to arrange systematically 
the various organisms that had been described by previous observers. 
Under the head of infusoria he divided them into two classes; those 
that could be seen with the naked eye, and those that were invisi- 
ble except with the aid of a microscope. The latter class he 
again divided into those forming thin surface membranes, and those 
forming thick membranes. Under the latter he included the genus 
Monad, all spheroidal in form, of which he described ten species; 
and the genus Vibrio, including all elongated forms, whether straight 
or spiral, with thirty-one species. It was interesting that he 
distinguished species not only by their form but also by the media 
in which they lived or could be cultivated. Relying principally 
on the form of the organism, he described round and slightly oval 
forms, short and long rods, corkscrew shaped and snake-like organ- 
isms, undulating but not spiral in their movements, and also long 
threads or bacilli. He also referred to certain minute shining 
points which he saw in the rod-like forms. We have every reason 
to believe that these were spores, which, ninety years later, were 
scarcely understood, and whose signification was first pointed out, 
as we have already stated by :uas4criek Cohn. It must not be omit- 
A 
ted, that Muller included in each genus forms which were unquestion- 
ably animals. St. Vincent, in 1824, separated the monads from the vib- 
rio Ss, as sociating the former with a number of undoubted animals. 
Ehrenburg, in 1828,studying the infusoria with microscopes 
of modern make, was the first to establish a group consisting sole- 
ly of bacteria. However, like others of his day, he recorded 
forms included as animals. His family of Vibrionae included four 
genera, all filamentous bacteria, which he distinguished by their 
forms, viz.: 1. Bacterium, filaments linear and inflexible, three 
species. 2. Vibrio, filaments linear and snake-like, flexible, 
nine species. 3. Spirillum, filaments spiral, inflexible, three 
species. 4. Spiroclnaete, filaments spiral, flexible, one species 
The Vibrionae were described by Eh enburg as filiform animals, dis- 
tinctly or apparently polygastric, naked, without external organs, 
with a body united in chains or in filiform series as a result of 
inc omp1et e division. 
Dujardin ( 1841 ) added very little to the classification 
given by Muller and Ehrenburg, but he brought out several most im- 
portant facts. In certain large vibrions he was able to make out 
distinct bifurcations, the two new limbs becoming segmented trans- 
versely; he was also able to recognize an outer membrane or resist- 
ant covering on these organisms, and within this a gelatinous or 
protoplasmic material, and this led him him to doubt whether, after 
all, he was dealing with an animal form, and several forms descri- 
bed he relegated to the plant kingdom as algae. He also made im- portant observations on the chemistry of bacteria. He describes & <5 
especially suitable for the development of bacteria fluids contain- 
ing such substances as phosphate of soda, hyponitrous acid, oxalate 
of ammonia and carbonate of soda, and ho points out that the nitrog- 
enous principles of the oxalate of ammonia are gradually used up 
in the presence of organic substances. He united the two genera 
Spirillum and Spirochaete of Ehrenberg, and added to the descrip- 
tion of the generic characters as follows: !• Bacterium, fila- 
ments rigid, with a vacillating movement. 2. Vibrio, filaments 
flexible, with an undulatory movement. 3. Spirillum, filaments 
spiral, movement rotatory. It will be seen that this classifica- 
tion leaves no place for the motionless bacilli, such as anthrax 
and others, and does not include spherical bacteria, now called 
micrococci. 
In 1852 Perty announced that some of these minute organ- 
isms belong to animal and some to the vegetable kingdom, whilst 
certain others appeared to him to stand on the borderland between 
8jl 
the two. He considered that the bacteria ms*an active animal, but 
v A 
that they also pass through a stage during which they must be look- 
ed upon as vegetable in character. 
Robin in 1853 pointed out the affinity of bacterium and 
vibrio (of Ehrenberg ) to leptothrix, which belongs to the algae, 
and this v/as followed by the demonstration by Davaine, in 1859, of 
the vegetable nature of the bacteria and their affinity with the 
algae as then defined. In 1854 Cohn even more strongly insisted on the vegetable na- 
ture of these microorganisms. He summed up his researches as fol- 
lows: First, all vibriones appear to belong to the vegetable 
kingdom, and exhibit a very close relationship to the larger algae.., 
and, second, in respect to their want of chlorophyl and in their 
occurrence in putrefying infusions the vibriones belong to the 
group of water fungi. 
In 185r/ M&geli, placing the bacteria among the lower 
fungi, which give rise to the decomposition of organic substances 
divides these into three groups: 1. the Macorini, or mould fungi. 
2, the Saccharomycetes, or budding fungi. 3. the Schizomycetes, or 
fission fungi, which produce putrefactive processes. Nageli col- 
lected all the forms then known which had certain characteristic 
$ - sit 
physiological features in common, into a he termed 
Schizomycetes, or fission fungi, a group which is now fully recog- 
nized by morphologists and physicians. He included all those low- 
er forms of plant life in which chlorophyl was absent, and which 
containwKcarbon, oxygen, hydrogen and nitrogen in definite propor- 
tions, which elements they were not able to assimilate and utilize 
in building up their substance from inorganic materials, "'hhikc the 
other fungi and animals they can utilize as food only such material 
as is presented to them in the form of living or dead organic mat- 
ter held in solution or combined with a considerable quantity of 
water. They usually set free any uncombined oxygen, and this char- actoristic feature, along with their want of chlorophyl Nageli 
looked upon as a special feature by which they might be distin- 
guished from ordinary fungi. Amongst his fission fungi he placed 
the forms bacterium, vibrio, spirillum and sarcinae. 
The classification of Davaine ( 1868 ) provides for the 
motionless filamentous bacteria, but does not include the micro- 
cocci. He makes four genera, as follows: /. Bacterium: rigid fila- 
ments, straight or bent, but not in a spiral, moving spontaneously. 
.Vibrio; flexible filaments, straight or bent, but not in a spiral, 
moving spontaneously. filaments straight or bent, 
but not in a spiral, motionless. Spirillum, filaments spiral. 
Following Davainefs classification, the French bacteriologists 
frequently speak 01 the motionless anthrax bacillus as _la pact6vi- 
coe. The vegetable character of the bacteria and other fungi, 
with what were then regarded as the lower algae having been recog- 
nized, the first important classification of them as plants was 
made by the German botanist Cohn, in 1872. He regarded them as a 
family of algae, with a fungal mode of life, but distributed them 
according to their form into four tribes: 1. Sphaerobacteria. or 
globules, with one genus, Micrococcus. 2. Microbacteria, or short 
rods, with one genus. Bacterium. 3. Dosmobactoria, or long rods, 
including two genera.Bacillus, straight forms, andtVibrio, undula- 
ting forms, or spirals, with two goner a; /-Spirillum 
(rigid spirals), andtfpirochaete(flexible spirals.) Colin re- garded this classification as provisional merely; nor did he believe 
at that time that genera and species were to be permanently estab- 
o 
lished by characters based on form alone; but adopted such charac- 
ters provisionally, and in accordance with the usage of his time. 
The observations of that day upon various fungi showed that some of 
them had the power, under varying conditions to assume forms diffor- 
f ( 
ing by degrees hitherto regarded as specific, or even generic. The 
following will show she view on this subject held by observers 
at that time: . 
M Within the last ten years I have examined thousands 
A 
of divided yeast forms, and I should bo unable to maintain, I 
except that there is a need oven of a division into two 
specific forms;" and again: " If my view is correct, the same 
species, in the course of generations take different morphological 
and physiological forms, which in the course of "ears bring about 
sometimes the sourness of milk, or the fermentation of wine, or 
the putrefaction of albuminous substances, sometimes producing ty- 
phus fever, cholera or intermittent fever." 
These erroneous observations which led to the ideas as 
to the extent to which such changes in form were possible were in- 
fluenced to a great extent by the impress then being made on the 
minds of biologists by the doctrine of the origin of species by 
descent of modification. As a result of this belief in polymor- 
phism, Billroth, in 1874, propounded the doctrine that true or 
constant genera and species id not exist amongst bacteria, holding that all known forms, with the exception of spirillum and spiro- 
chaete were possible modifications of a single polymorphic genus 
and species, for which he proposed the name of Goccobactoria sop- 
tica. These he declared to be capable of assuming any form from 
a coccus to a filament, and to be capable of any mode of bacterial 
activity from that of a harmless ferment to that of a virulent 
cause of any of the specific diseases, its transmutation depending 
upon varying circumstances yet to be discovered. 
Now although there are certain bacteria which are more or less 
«fchse^morphic, that is they may exhibit more than one growth form, 
in the course of their normal development-there are others that 
are strictly monomorphic, exhibiting, as far as our observations 
extend, only a single growth form. The discussion of these ques- 
tions, and the various researches which they calJc d forth, caused 
Cohn to make a revision of his classification of bacteria. Recog- 
nizing more clearly the relations existing between thorn and the 
fission-algae, and the differences between them and the true fungi, 
he published, in 1875, a classification in which he established as 
a primary division of the vegetable kingdom the group Schizophyta, 
including therein the fission-algae and the bacteria. 
Ke divided the Schizophytes into two tribes: 
1. Olaeogenes.—Cells free, or united into glairy fam- 
ilies by an intercellular substance Genera.— a. Micrococcus. 
b. Bacterium. 
c. Merispomedia. 
d. Sarcina. 
e. Ascococcus. 
together with various unicellular algae containing chlorophyl. 
2. Ilaematogenos. —Cells disposed in filaments. 
G-ener a. a. Bac i 1 lu s. 
b. Leptothrix. 
c. Vibrio. 
d. Spirillum. 
e. Spirochaete. 
f. Streptococcus. 
g. Cladothrix. 
h. Streptothrix. 
associated with genera of green filamentous algae. 
” The following decade was fruitful in research concerning the 
morphology, physiology and classification of bacteria. The dis- 
tinctness of the group Schizomycetes, and its relation to the Schy- 
zophyces, as forming with it a division of the vegetable kingdom, 
the Schyzophyta, were rendered more and more apparent, although 
unanimity of opinion upon either of these opinions has not been 
reached up to the present time." (Tuttle.) 
Zopf, who loans strongly to pleomorphism, published, in 1885, 
the following classification, dividing the bacteria into four groups: 
1. Coccacoae. —up to the present time only known in the form of 
cocci. 
Genera. Streptococcus 
Mer i smopecl ia 
Sarcina 
Micrococcus 
Ascococcus. 
2„ Bacteriaceae.—Have for the most part spherical, rod-like, and 
filamentous forms; the first (cocci) may be wanting; the last are 
not different at the two extremities; filaments straight or spiral. 
G-enera. Bact erium. 
Spirillum. 
Vibrio 
Leuconostoc 
Bacillus 
Clostridium. 
o. Leptotricheae.--Spherical, rod-shaped, and filamentous forms; 
tie last show a difference between the two extremities; filaments 
straight or spiral; spore formation not known. 
Genera. Grenothrix. 
Beggiatoa 
Phragmidi othri x 
Leptothrix 
4. Cladotricheae.—Spherical, rod-shaped, filamentous, and spiral 
forms; the filamentous form presents pseudo-branches; spore for- 
mation not known. 
Genera. Oladothrix. 
The period which has followed the classifications above given 
has been more fruitful in efforts to extend our knowledge of the pathogenic relations of bacteria rather them of their botanical 
affinities. The tendency on thepart of pathologists has been in 
the direction of studying the activities of bacteria in living tis- 
sues, and in ascertaining the results brought about by their pres- 
ence, while less attention has been paid to their morphological re- 
lations. 
Bearing in mind, however, that a scientific classification 
of bacteria, when reached, must be founded on botanical principles, 
physicians have been willing to leave this to the botanists, and 
have boon more inclined to discard generic distinctions which havo 
for them but slight importance. As the result, the latest clas- 
sification, that of the distinguished Prof. Baumgarten (1890), is 
the one that recommends itself to physicians.and bacteriologists. 
It is the one adopted by Sternberg, with slight modifications. 
Group I. Species relatively monomorphous. 
1 Coccus 
2 Bacillus 
3 Spirillum 
a. Diploccoccus 
b. streptococcus. 
c. Merismopedia. 
cl. Sarcina 
o. Mi or o c o ccu s (St aphy 1 o c o ccu s) 
Genera 
The bacilli are included in a single genus, embracing all of 
those species which only form rod-shaped cells, .and filaments com- 
posed of rod-like segments, or straight filaments not distinctly 
segmented, which may be rigid or flexible• The spirilla are included in a single genus, embracing all 
those species in which the filaments are spiral in form, and the 
segments more or less spiral or comma shaped; filaments either 
rigid or flexible. 
Group II. .1. Spiralina. 
2• Lcpt ot ri cheae. 
5. Cladotricheae. 
These arc water bacteria and do not concern us here. 
The pleomorphous species described by Hauser, under the gen- 
eric name of Proteus, is included under the second group by Baum- 
garten; but has very properly, we think, been placed under the first 
group by Sternberg, and put amongst the bacilli. 
There is often difficulty in deciding to which genus a partic- 
ular microorganism should be assigned, whether to the cocci or 
bacilli. If we are confident that our culture is pure, we must be 
guided by the appearance of the separate organisms. If wo find 
bacilli, however short, we must assign the organisms to the bacil- 
li; that is, if the length exceeds the transverse diameter. 
There is no longer good reason for continuing the genus Bac- 
terium as distinguished from bacillus; since in the same culture 
we may have short rods and long filaments. So, too, with regard 
to tho genus Yibrio, the fact that the filaments are flexible, and 
movements sinuous, is not a sufficient generic character; for in a pure culture there nay be short rods which arc rigid, and long fil- 
aments which are flexible and have a sinuous movement (Sternberg.) 
Hence all elongated forms are spoken of as bacilli, and all spiral 
forms, with cork-screw like motion, as spirilla. The round forms, 
however grouped, are cocci or micrococci.  no. 
Hr. R»<M. HOT-89-97, 
nm-THSaiA.—At our last mooting I told you that the study of 
th® dlphthoriabaolXlus of apodal importance* Inasmuch as it 
plnys ouch a prominent part in clinical diagnosis of throat trouble* 
a cuts dice of the threat, ami 3 shall thus count it vary worthy 
of our close study* I also i oasd stao of the charset era cf this 
bacillus——tH-»fe It appeared generally as a slightly curved rod, 
that however, one of the characteristics of tv.a organism waa its 
variety of &!&*$ arid aliap&s, cesurring as short rods and w» long 
rods, as straight rods* bent rods, curved rods, rods often * tdge 
shaped and pear shaped, frequently swollen. at both extremities, sene 
tiniee m/ollcn in the middle and smaller at the Ice, and 
tht* t it did not grow out into aha ins of bacilli—wo find single rods 
not two rods end to end* ~-hat of ton appears 4r vo ro<3r is’ simply 
one rod, the prc$oplum of which lc broken in the oento* into sever- 
al pari talcs* a he d iph thirls bn oc I Hoc then does r.d ;;rcw in chats 
the rods though often lying together in pairs, throe, half n desen. 
As they grow they fall together side by side, like 00 many pickets 
tn a fence* Often evirved pairs lying together like th* bovis of 
spoons. Another Interesting oha.r. stnrlaila Is its Irregularity in 
staining. t, irregularity in r Ixo, t on irrepuXarli? in ntain- 
ing, go much sc that w© have points of protoplasm deeply stained, 
and those are joined by fainter stained parts of the rod* $ho rod 
frequently In broken into a number of pro top la eric manfcot, so much 
so that -a fir«t sight w believe Uc streptococci nre present, but 
a little experience enables us to exclude the strep 1reoccur, ami not 
mistake iU chairs for the diphtheria bacillus.* The diphtheria bud 
lus is of importance because you can diagnose this bacillus under 
the raiaresoopa* 1'hcrc are certain which w© carrot diag- 
nose under the nlcroocopc, but the diphtheria bad lifts? "rein its 
peculiar staining car* bo dlagnoa^d• I probably told you that when 
this organism effects lodgment In the threats of human beings {those 
between the ago® of H und 15 ymr® being more sue.coptlbl© to this 
infection) it gives rice to v.n Inf? anoint ion of the throat which la 
Sea®rally d&Mgmtcd rvtribraiicu© or peeudone:-.brunaus• Thin I* an 
Inflasrmtion attended by the formation of a fnlm ner.bn no in the 
throat, or an vre say In inflanmtlon attended by the presence cf an 
exudate* It la really tt fibrlnoui. axudnic which appet rs In the 
throat. It consists largely d dilt« blood cells th.i t arc migrating 
to the port, of fibrin, and of epithelial colls, nurface eplthelItin 
which hi5 undergone a*orool£; indeed, not only th® louoc ?yta« that 
nlgtutcd to that point, but %} o epithelial cells become tn-erotic, 
they die, and the false membrane is* made up of theao leucocytes awl 
epithelial cells mixad with fibrin, an oxudnia that nffacte the 
superficial part of the mcnbmno* *hc dIphthnrin bacilli ore found 
not in gran test numbers on th© our face, but Just a little bo low thin 
surface. They do not pa not rate xn deeply Into the mucous membrane, 
they lie tolerably superficial* 00 it its ©any to roach thorn with a 
or swab carried into d-s throat* This bad 11 ins la one of the 
instances of un organism affecting led.;, nan* at a given point; In 
h**nan bo Inga, generally in the throat, and the**® giving rice not 
only to this local change in the throat, which ue designate diph- 
theritic Inf Ismmt Ion, but also producing groat const 1 tut I ©mil rip*'. ’m**x« n. 
and I have occasion to toll you that thin particular 
bacillus hringn about time &f*at constitutional d teenier* by mans 
of toxic prodiicto atexlnt a tox&lhursin, uo it Id often spoken of, 
which In fofMd during its growth* and is taken up by the lyegtf&tlcd 
and blood vessels, You knew forsnwrly physic Isms wm «rml :n Ad In 
two schools; thee» who said that diphtheria was first a local af- 
fection and afterwards a constitutional affection, and the others 
who said that diphtheria w«« always first a constitutional affectIon 
attended by this local molestation* The fIght was kept up until 
wwSam haste rider! cal raothods settled the dispute, Kovf we know 
that diphtheria in the beginning la purely a local process, but 
those bacilli in their local growth produce a toxin which being ab- 
sorbed brings about the greatest pothclogioul changes In the organs 
of the body* 
Mow having considered the local mvxhito and hawing sat;tied that 
let w> turn to pathological ehangea vliioh the diphtheria baa 111m 
prod note in h.ua&n beings. One of the moot mxrkoC pathological 
change* Is produced Ir the lymphatic glands, the lymphatic* structure 
throughout the body, and this I0 rot confined to the nearest lysapha- 
tics in * he throat, but Involves all of the lymphatic ylandi? of the 
body, even the lymphatic structure of the raucous nonibraa# of th© 
mu 1 tntceti m n • 
hocallsacd necrosis arc protlucoO in the lymphatic gland©, charuo- 
tar Used by fragmentation of the nuclei of the cells, oo that micros* 
copd&Hfly one find® little am*© In section stained brightly with 
eo»in» and upon exrnnl nation with the higher poorer* the ram ins of 
the nuclei era found there in large mtihor© broken vp into little 
pr*rtlol*i» fr*gn*ntfttion of the miolai be It le spoken of. Not 
only nr© the lymphatic involved« but ve find in tho liver 
fatty fjexoneration of the hepatic colls, She 00236 fatty dO£fm$ra~ 
tlon of the <rU8 in found in the kidney, following which is the 
gnuaudnr degeneration of the kidney epithelium, or cloudy milling 
of the epithelium m It is eall®4, Slowly evening of the ©.-jsfeo 
lug optthal 1 \m of the kidney, this afterwards, If the patient lives 
long enought undergoing fatty degeneration, ihmi there ur« ala© 
found distinct tseoroftl* in he heart, b# lug* fatty do go no rat ion of 
the ?mieele fiber© of the heart, and another of the pathological 
ehrnigee la an affection of the norvec, frequently the nerve floors 
Replying th# hemrt-—wfKlergoing a distinct pathological change 
it is not necessary to enter into here, but those nerve 
Iciaionft lie at \.h& bottom of the paralyoig vhlah occurs in U i phi her 
la. I have ©aid that tho diphtheria he oillug acta locally in 
a few onoers where careful examination© have been mdt both of human 
being ami animals, the diphtheria baoDlua Kuo hmn rteevared from 
th© internal or an© In assail numbers. Shis is not the rule at all; 
It Is thg exception. 'SFHEoH' an experimenter showed about four yea# 
ago that when you take large piece© of tic liver or >g aplecn you 
occasionally ret a few colonic® of the diphtheria buetlluii. 
diphtheria bacillus la pa thegenic not only to man* but 
various anipmlsj the guinea-pig* om of cur laboratory animals* is 
specially nusceptihle ia I ho pathogenic action of the diphtheria 
bdellium. On# centimeter of & culture in bouillon 
ni thermos tat temperature f,eae rally kills a pig «etching 400 or 500 
grajarms, In about SO hours. The rabbit l« lb sc susceptible* though 
It to «nthojt«nie for the rabbit. Chickens* pigeons* mtd bird*- aro 
all susceptible to the action of the diphtheria bacillus. The i %c* 
the sheepy the calf, the wonkeys* indeed the mouse and the rut are mph. — p. ». 
about the only two antasls which. sees not to bo aueeoptiblo to the 
action of this bnoI list* You give n mouse an enormous quantity In 
order to kill hfn, but a» a rule five times the cose to kill a 
guinsnpig or n rabbit does riot affect th© mouse or the rut. The 
diphtheria bacillus if. pathogenic for tie horse* which I have not m 
rvOfltlonod. £o* the loinlono which babe boon found It* human beings 
vhich nay r.re duo to action of the diphtheria bacillus* can all 
ho produced with pure ettf tures In animals* even to the format Ion of 
the false tie rib rr no. The kitten end V-& rabbit ar« the best animals 
to perform on to prod no© tHe trim mmfomnQ of t> $ tmetea. 
Mr. f ohn Wish of fohns Hopkins showed that if you a bra id the mu- 
cous numbrans or the trachea a little bit in the oonrm of 4U hours 
the an 1ml shows all i ret lent lone and cl led t of constrictIon of the 
larynx. Autopsy showed tipicul di-phi her I it lo membranes Just as you 
cso in hursim ha 1 ngs. kll of the changes which have been produced 
in tins Intirml <>r-y\nn-—-nerves, liver, spleen* kidm. t fatty <;arbit- 
ration, cloudy swelling* nnd paralysis—»hav© been produced in 
unimls. Mot only that, but 1 . has bmn found that he toxinlllo 
the bouillon culture in which th<> bacillus has boon grown can bo 
filtered through n Pustour filter, and the ck«mr filtrate contain- 
lug toxin can be injected Intb unlmle* and will produce all the 
aynpto’35 except the false membrane. If you wish to produce tl a 
false .'.-’sonbran* you- mmt Introduce the living or doc«J bacillus into 
animals, these ntkimlft ordinarily arc not susceptible to diththor* 
la they have to be Inoculated with It, octio dnngl must be done 
to mucous membrnn© cf the animl in order to produce dlththoria* 
or wo rrast inject a culture beneath the akin, and there lo no par- 
ticular reason to think that diphtheria has been sokhsusi looted by 
human beings to animals, net oven the ent* The diphtheria in fouls 
Is dnn to an entirely different bacillus, Mow, 1 think I told you 
the other nlyht that the diphtheria bacillus did not always produce 
some local change In the throat, that while in the gr© it majority of 
or.sos one finds a tjpnioal ps ouc«onmuhrurm or fibrinour exudate in the 
throat, while in other oases ti e patients will not hstvs lt9 and yet 
the patient hnn diphtheria. In other words* xho diphtheria baolllUS 
tmj produce Vm greatest inflarwttlrm in the throat, or practically 
nono at all, depending u|>oti the ituaosptibllity of the particular 
Individual, lactsrIologioal i im.eUaatlonr, have been of x no a finable 
value In bringing out thin point—-cases which formerly were never 
supposed to bo diphtheria, have clearly boon shown to ho by the 
finding of the bee Ulna in the throat, I think 1 mentioned that 
In oo3*3S vhloh clinically produced the appearance. of diphtheria* 
nO;i of these are really diphtheria, and 20;- are pseudo diphthe- 
ria. 
divided Innaw&iations of the throat into diphtheritic and 
psoudodlphth©rltlo, 1 think I told you that the tern diphtheritic 
not limited alone to e influrvnation ascribed to the Klebs- 
boefflr-r bacillus, but often the tens diphthtritio la applied to 
false diphtheria** If you wish to fee absolutely oorrewt, you will 
consider diphtheria ns that oaueed only fey the K1afes-hoefflar bacil- 
lus, and peeudodlplitfterle ao being produce! by all othere. It would 
be bettor If -> dropped the tom ’diphtheria* ami adopted hlphthori- 
tls according to t* c bacillus which cuur.es it. Diphtheritic I think 
I told yen mn applied to all of these various nffactions of the t 
throat, -tad ua.-ul purely in on anatomical carise. If you have an in- 
flart-intlon of the throat attended by an exudate It is called acute !)iph* r—4 
diphthoritla—It m? bo c ’.unsd by tho Btroptocoeauf* pjo&Qmmt 
Klobs-hoofflus or soa* othor bnolllua. Thus diphtheria lc always 
dtie to ths Ki«dB-lioafflor bciolllas* tho bneill 119 diphtheria®. 
All inflammations of the throat of whatever .prado should ho 
ecnatiered true diphtheria, until, on rtlwoftodpio tv*Ion It. is 
proveu that tho baoll#u? present- le the $tphths*iaibHolllua or not. 
How own bo e.a about it to diagnose a co«o of acute if rout trouble? 
I mentioned tha fn$t that tin diphtheria baoilltui grew# very well 
on all sroc of our madia* on a&ar-agar on w latin nt u temperature 
of 20 to 22; slowly on gala tin* rapidly on «#ar at thermostat t&m~ 
peraturo, grove rapidly in bcuillo?? at the mm tat torsp ora turn. In 
sons oasoft uniformly cloud I nr: the bouillon, In others tn little 
granules distributed over t a surf too and rid s, and In others in 
little pellicles, and on gXyoarlne ayar (7d- glycerine) this was 
the medium on which they were formerly grown until hoerfler the 
Corrmn physician who first isolated the diphtheria bacillus and 
proved It to be the cause of diphtheria, introduced hi a mod i ms 
known as? hosffXar #8 21ood~aorumf and that ha» bean found to be the 
very boot medium on which to grow the diphtheria bacillus. 
I win mention briefly how tv» so nun ts prepared. TM« t s$ oerj* 
pos&l of Z par to of t? e blood ttcrua of the cow, *and om part glucose 
bouillon, bouillon containing of glucose. Ordinary bouillon you 
fcnew contains l/> peptone ana half of n paresat of aalt. It docs 
not contain any glucose, thi« mixed with th* blood aonvi contains 
1 part nf grape asigar—-10 gran# to tba XI.tar* ?hln nsnsn Is ob- 
tained by bleeding the animal into & sterilised vessel. A half 
grown calf can blood 3 or 3 liters* A vary cl eon vests*! • rh S ch will 
hold about 2 lotors Is carried to the slaughterhouse, and. si the 
an 1ml *3 throat la out the froah blood la caught. After it has 
dotted* a sterilised rod is Introduced and th* clot stirred fran 
the side of tie veenel, whtsh wnniMoo t> o clot to contract, and 
then the vessel is put Into the loo box for about 4H ’ oura, during 
d i eh. time the dot contracts uilte firmly. a laics to V e button* 
and the scrum renalna an a straw colored liquid. If ou are fortu- 
nate, cone time «i yon my get one-half of the quantity cf blood ewrue% 
but usually ono-thlrd in all we can net. Out of 3 11 'arc of blood 
if you yet one you «i£W arc doing well. *lavl??g obtained your acruci 
you siphon it off* if it is stained trtth blood it makes no differon 
cc {thou.-h it is siot clear). filter imd to 3 parts of Mr. add cm 
pari of the gmja sufinr bouillon, formrly thcao tubes were then 
sterilised at a tariff a two net exceeding C5° In n blood norvm ap- 
paratus The r* imilory net hod La. used in this? country. 
Slant your tubaa and place then cither in the hot air or etean slorl 
User. ?he tubes are placed on t'otr oldos so that yen really have 
a slant* Just ar an agar riant would be* and the IhcrnoMn| Si; Hottd 
to DO or £5$, until the eerun !© solid tried. n *<m tb*» tube a are 
thoroughly eelId ifled* tube then out, r- place then by others ami go 
on with the heatIng until nil of the tubes are solidified ar slants. 
Thia given you a vary qranuo brown inti of yellowish redim with an 
extremely slick looking surface, nmr, of the watery part of the 
ssnw exuding and collect Ion at the hot ton of the tub*. 7* on Fieri- 
lis© t1 ©si two days preferably at a temperature of $fr; 30 minutes 
the first day* and the rgwt day you ear. pjutjs t*on in the fitarili* 
sor ant- sterliizo at 100 o for 30 rrbuuten mors. tt has been found 
that on thlr nediua the baoilltfl cf diphtheria grow© reratrhably lux* 
rlamily. It formerly said that it outgrew all other organisms* r> i ph* 
As a rule, for Id hours the diphtheria bacillus hn* outgrown all 
Others, though DOROtimoe you trill find that other organisms have 
grown equally rapidly* Xh£ colonies of diphtheria appear act opaque 
brow I ah colon loo, $otmwh&% like the mud turn; they nr a rathsr fftria* 
You will huva to see yourealfos in order to got a proper apprecia- 
tion of how they look* It Is not no cos nay# In prattle*! diagnosis 
that yon should pick out tho individual colonies* If you can aae 
them on *• ho slant it la bast to pick tvom out* out generally there 
are &o miy colonies that you will have $o go In with your loop, 
touch hare tnd there and stain for the or.anla-4* in pr.-jotioal 
work, the sterilised rrrnb la used. A little piece. of start lined 
cotton or a little place of absorbent cotton is trapped U ;htly 
around a ptooe of Iron wire -5 or h inches In length, or around a 
small a is ad glasa rad filed at ho end to roughen it* Xhoae are pin 
pieced In glass tubes with cotton plugs and utori' Is mi in the hot 
air atorll la or* *he health do-par treant uondr out in a little box n 
eternised swnfc ami tlno a blood ourt&t nl&nt, Tho raoo mmlatlori 
Id Vrt'i the physic Inn shall pi:, co the patient in u goou light und 
with thid&t- rltisod «wsb touch sono arts of the nombrine, or &imply 
wipe ov if f} o Interior of the throat, muovc V a swab and very 
lightly draw this over the surface without breaking the surface* 
If you have a Bd and a 3d tub* go into ono and tboij lnt*> Ue other, 
and into The third, lor - enlnc the organism* For pract i cal work 
one tube only ie used. ?his tr placed on the thereto# tat at 37", 
ami he next morning is ro-ady for ex&fflinntIon—after l;i to la 
hours. boomer* a thy line Blue is aacu ae the riuln preferably* 
On® aan uco the Iran stain or the other analino dies, but the hoof- 
florfa ‘■ lue in tre cno which stains the organisia more c):nr; oteristi* 
cal 1 y. * 
T-O'-v Swntlonon, H ir in berating to knw that the diphtheria 
h>%ci Hub row* inn lit the t* rcat {another point tearing on the ding-* 
nostio oor?$ 16 oration? after the p&tl«nl has gotten owr it. It Is 
important to kner? that In snuny cares, although £ Hi oxudalft is gene, 
culturon rhow th® dlphthnrla taiolllu* st-ill In U o throat. In 
other words, that patient U> still a course of ctaniser« It ba« b®sn 
found that after the oxvdAte <H$nipe&rs In about one-hair or u.« .,3*111 
aafto®, the bacillus can bo foumi in the sours® of a wmK, ths 
poronntagi? cf oas®® has varied in the bond a or various observers. 
The diphtheria he,cHim has been found at iho omi of the 4, 
up to the M day after tr$ exudat® had one* I have aeon Wo oases 
wharo ••■o cO covered if# fencUlus dvr inf: t ho ;Hh week, and U.# patient 
had hml nc exults in t t throat for about & week® in ®a®h care. 
In one of thrso cuss® It va® pr-'ictlosilly a pure culture cf ihe d iphis 
thori® ft-icHlu®. during the 0%h week J)r* Carroll injeciad it into 
a guinea pig r,r$ It promptly killed the U la eta tod that 
usually it has become &ttopuatod after thin tla®, but jqh a*«y often 
find a virulent diphtheria bacillus In ;hv< throat of th# patient 
after weak®, and you cannot let the patient so*-is In contact with 
others until Ihs bacteriological diagnosis shirks that ih« diphtheria 
bacillus is no longer present. In the absence of bacteriologies! 
diathesis the only safe rule Tor t * physician to follow It, to oot- 
tlder ©very cane of acuta iiifltraratior. of the throat ns & ease of 
diphtheria. It la th« m>lT sr*T5 rule to folios. I think I av.ld 
th7. oiTTf^nipht that 11 mu a n'fl'Tija i n ®p I *i on lea 3m<« or i g i s*a t #4 f rem a 
of raiid Inflammation of throat which no phyoioism wuX4 ham 
hnve aiagnoMcd ns diphtheria. Thin patient having a creator Plph. a—6. 
resistance Hid H-ynpionii with uo fjenbrnne at all, and the >. 
next arse nay to one of very ftro&t severity, if you nan mk« use 
of the bacteriological d lag-nos la, of ooari-# you mk# use of it, and 
decide the c*so find relieve yemr own anxiety, but la ot> or cn»os 
non# it as diphtheria of If a throat and isolate V c 
m%I there 1# no rollw* Vhs Kioto* dl 
Xto tos toon found to mint®in its vitality for ion*jj periods—in 
tto' first place -no have fjo reasonsto toltevo t?at the diphtheria 
broilIns Hmc in the external xorld,—-that t liven rn a saproyhyS 
It is tto dlcoaso of all diseases that Is cornunicat d by persem! 
contact, and it is Interesting to know ho* v -ry rodistunt l-In gntfel 
asttopg. rasrtlonXar bacillus is under certain oirocsss toots* • In I - 
dry mnribrane it ht\B boon found alive after I? or 9 w.-ake, It has 
‘boon cultivated from a toy -which a child bavin*: diphtheria played 
with 5 months before, tbs child having gotten Its saliva on tho toy. 
It ton to*n found alive on blood or rum tubes nt the end of I a 5 day si, 
am? I to1 laws In rows old cult Tiros of gelatin h j*m r old. It is 
•hilled by toa'tlfig in minute® at 5i; ' 0, You ee® it does not require 
to boil the cloth Inc to kill tie diphtheria tocl11ns, to far as 
that in oomntrnsdi it is not necessary to boil tr e olot’.ing to 1111 
any pathogenic bacteria nnlmm there are spores• If roe your boil- 
• “ re eontsm.tuat-u' -. It! • r diphtheria 
bacillus yon hill it at ortoe——that ends it. 1 tcld you the other 
right Thftt It tod born found on %r.>: bad clothing, pi Hows, etc. It 
haa boon found on the shoes of tiurscs rhe were attending diphtheria 
patients, and on t* c hair bcch of tie ear whuro they v©r# |J> the 
habit of fitting the pencilf they were using, and from tie amt of 
the ward, all of •"’hioh nmn&9 gentlemen, that yen must Isolate your 
sn»6» of diphtheria nw' that you must dis.infect every particle of 
the slothing, nil of tto cloths that the child expoetorstee on and 
her’ slothing and all ary to to disinfected by putting Into i 
carbolic solution* or a XjaOOO bichloride, and articles hang I a?? upon 
the vail r.f the occupied room, should also be boiled. If the patlot 
has bean properly cared for, ha a been property isolated, tbs chances 
or spread of cliphttoris In very flight, nom Interestting otoorva- 
tiers hnvft been **ade upon the throats of other mentors of the family 
ottor children of i>e- family 'Where diphtheria has occurred. 
Parks found In to* York rsty that Thorn there ea» noiIsolation and 
no si Tty rvf the disease, 401 developed jttphtherla, ana that where 
only alight isolation vats used only 10;l had it, to, *d*>on you have 
one patient In a family The has diphtheria, you should taka cultures 
from the months of nil of the family, IT# virulent bacillus hit# 
boon found in the throats of pore cor. not suffering* from diphtheria. 
If tray have com# its contact srlf• ijhe disenre, then It is found in 
largs rmrbfro; I have mentioned 50;.' in children in one Instance of 
330 c ?ros of healthy throats examined in which the f.at Xante stated 
that they tort not knowingly eons in contact with diphtheria, a vifS» 
lent diphtheria bacillus ms I elated* li .a. % I 
bacillus m& isc-lated which grew nltogattor like the dIph- 
Plft bacillus, but which to« not pot ho ..cnic to gttincapli#* to uo 
havo the vimjlnnt diphtheria in hsnithy indivldunis, though if any 
of the pars or a wra ru«dO|>tthl#, such votild have tod it. 
sronp, is r*a nxutf&to in tl rfcat* is 
dno to *!»• T'ldbs-bos'ffler b*soilln«. Bnotertologioal culturo© hrtvo 
shown that in 00$ of tfco oft ft on tt iftr. boon shown that they wars 
Xftrynsoal dlphthopi*—-r.rohnhly 9C&4 of a dw« to iht K1 
tho othor 10 to tho fttroptoooceus pyogottes; and etain rtanbr^Mo# IHph, p 7 
Inflamatloa of th# nos#, knwm ns rombi*ts»$u8 rhinitis, Is oausad 
by the Klfcb~booffl«r haeillw. rfhc fern of mral diphtheria whore 
the £«ras olimb tip buck cf the pal«to (volm ffllwt ) lr> vary fata) 
the ot!nr to called KCttbrniiou# rhinitis ( "Ibrinouc rhlnltioK You 
can look Into v # no&o nml «oe a lltt.1# grayish *:?ud« and when you 
trip* It a’my pork ops 0 little blooding will follow, and yau can 
Instate trMB thie a culture cf the &ftito'*Lo3ffl$r bacillus* 
thr no pat Ionic show no constitutional *yniptan89 mJ r,$mrnhly t hooo 
onus or* do not give rice to diphtheria, ctlil thoro lfs danger, cause 
for appro ho no ion# 00 one relict bo on hie the bacillus isola- 
ted fron the none in about ono-half of th? msas 1- s been attenuated 
hac not killed to 0&in&Api£, but has given rise to a little swell- 
ing, %hllo in the other half of tm oases the bacillus uae virulent 
and killed es readily a# the diphtheria bacillus# 
Tho a«v?>rlty of tM id no indict ion of tha vtrulorujy of 
tho oiiltur® mass the throat. You may fl«d tho nost virnlont stimu- 
lus in tho TnJldor throat Inflursnatlons. *n.it lr. a mntt#r of 
lbM i ty on t 4 part £n of tha InO ivtouul. 
You' will hr nr something* and I mint mutton it, about the paett- 
d ©diphtheria bacillus. A te»eillue which \n%& denaribed sort© roar® 
aro by von ?offr-nn. He found It in the throats of a healthy tmlivi- 
duals, so did toe f fie r, and • M«? bacillus bit© been found • Ince by a 
number of abaft nr# rs, cultures being taken from n variety of throat 
roubles, generally e&aaedingl/ ..- light* A bacillu® hac boon obtain* 
ec? from tha threat grows nlmoot exactly like rClfcbe-boe frier1 s 
bast Hue nnC stal nu alfsaat exactly like it al&o, so that with the 
only the diagnosis could not bo mode* Yne diphtheria, 
bacillus stains n*ore r&gtfl&rly; the psoudodiphtherla bacillus grows 
no re luxuriantly on agar thrm the genuine diphtheria baelllue. 
The genuine total Hus in glucoee bouillon produces a deoidodly aold 
reaction nt first, Elicit afterwards bo omen alkaline* thw pseudo- 
diphtheria bacillus tioia not produce nay no id must, ion when growing 
In he bouillon practically. ilthcur.ii wo clan* as paeud<xi iphthe r 1 a 
bra 111 tot ho so organ 1 eras tfhSofc by oortn In cultural ehnrretoris »ic3 
differ from the •■ • Icbs-ho©f flor bacillus (hrmvler growth on agar, 
nctd production on gl ucooe-boul lion) —a I though wo sake then# differ- 
entials-—Co not pay tho olightoet attention to the pseudo-d I phther£ 
bad linn. Xf you find the pseudodi pht) •« rift bacillus having the 
sane appenrsmoo rc the genuine, tak* it for the genuine, and let 
«rne genUimsii into re c ted in bacteriology mn whether or not it will 
kill'; Just omit the p©oud<H#iphthor la bacillus, lust for# 
get the pseudodIphtherla bacillus* practically do not pay any atten- 
tion to It. Howard' every organism that you find In the throat of a 
blck Individual an dl " 1 to olllus* fbe paondoi I irli b&eil* 
lu© had nothing to do with pr.eudodIphtheria—-an unfortunate tern 
that *re should have. Pseudod iphtherla is caused, as n rule by the 
streptococcus pyogonos, In an few oaaes by the fttephyloeoecue asmai 
etnrouo, aiid In ©till fewer case© to the- ftifAecoeaus laneeclatufu 
i*o physician, no natter how skilfpl hln clinical diagnosis, can tell 
which one of there bao cau©ing U c trouble, if you find a 
kleb©-VK» filer bacillus in tis throat of a henXthy individual* we 
could not at that he hud diphtl-oria, but ho is dangerous to Kins elf 
and to those who cone in contact with bin. 
wuoxtn ttUSATrSMs Yci; imv that by of *lm 
sroolflo toxin of the diphtheria. bn ell Ins (filtered n*a? from tho 
tootling* whor* tho inoculation of the filtrate in minute quant lit# 
into animals at stater. inlorvaldt It has boon shown that the animal Mfh* 
bo Imuiilued a&iinst this toxin, saps dully If tho 
toxin at tho beginning wan mod Ifind & little bit by the addition of 
sorte oh&slocl, ftran9* Liquid vns uhsiI to neutraltss# it, so to 
spsuk, and this was injected at in i?&U doses, *a»d ~r«dimlly 
increased until thn animal burs dosas mny titans than ho 
have bctirn lit the beginning* 5'Jow-, the siost Interesting re cult 
that ha® been attained for yanre, 5 d ;;ht ray In aluert ICO y«:.trs, 
bKC been the finding that the blood mrm of this hi&llj 1 ssunised 
anln&X covtlfj be uasd to teiunlas oth*r an Inals agaiuct a toxin of 
diphtheria. If I hava a rabbit which I have in*ionised in the course 
of 5 or 4 Honthft a,£Un«t the ton In of diphtheria# oo that tl nt ani%-. 
wtX f s bearing doses 1*0 to 100 times greater than what would have 
killed him in the beginning* if I draw off his blood a?xd lot the 
««n« strata and inject u smtl portion of t..rt into a guincapig, 
I find that that gninsftpig In not killed by 10 ti&oa V- . &iount of" 
the diphtheria bacillus* and that lftp«mlslag &$oot -*c o.XX an *&ntl* 
♦ "-ot only have found t?a*.t if yon inject tfc* at the 
«&**» tlm that you inject Vho dip’ therla culture that your nnlmX 
f’o*« not tUo, but -’4 have found ‘Ant ...ftcr tV» anIml botuuse rich 
ycu could uso it to effect n cure. Prof, droo at the International 
Congress in 13IH showed that t’ « homo could bo itrrsrtisotf higher 
than any ©ther an 1ml up to that time and vac particularly adapted 
■f£-’ ihi;. x>ur«ose. The 1 ".v-Mate effect of this ruitltonlr* is rW.lly 
& ufr-ct. To frequently find physiol *;ns saying that anti- 
toxin h oumtlvs but not sped fie, but whoa wo ©&*& to arl that* 
what they moan by that mttai they i - y 'U d©#» not euro thoir cue os 
of diphtheria, that hn« noth!f f* to do with the spsslflo char rater—* 
of aonrse, if .you do no t |ivs antitoxin until the renal epithelium 
If cloudy, and fatty degeneration of t e heart musolas h&s tc&en 
the Ufi of the colls fire lost *nd you do not expect It to 
patient* A»UteKta I not vitalise any deed i.-c 
but if you use it surly enough, 1U effect Is absolutely spot 
T'/c.. uo-tpt -The ha* done co nneh to la Indues the antitoxin rt diph- 
theria, vsluted irtxl it you use It by tV: *ft$oad day that It. would 
euro 9f>h of tbs mass, an-.’ that has been found to tu~ the result, 
oortainly It *euld be wh hotter to m® it ths first day. All 
that vs can do Is to ass It Jurt as soon as we find tint 'm huvs 
throat i* I do net naan In nl»rl * Inf vitheut 
an exudate hut In cnees you diagnoss as diphtheria, j; so ado or nc-t 
If thn is nna thn antitoxin turn* h-ko /our 
culture and study it. I think any om who ha® sm the result of 
ex per |(3S >i tat Ion cn air' will sss Hu effect irs the future tn 
tsunwa boin&& suffering- with diphtheria, Hit m oonvlnood :hut its 
sffssts ar* nothing but cpseifl% Ws find In ths Xabefiitory if wo 
luosuluts too with a swll doso, 10O <Us— 
they a 1 die; now if take another 100 and give' Vrw the do^f 
cr tor that, shooss 10 ti-ur -iofe, but give ihr:*> n &m%Xl «!aue of an- 
titexin* and how r-any Ilya?—100, you have an ox^erl.tont like 
i ' re aomthl •/ epos If |© about that kind of thoatmontf 
fic t to use antitoxin. 1 think your Professor of ?-•-asU^o 
of ’Ticino (hr. V. t, Johnston) will Ivo -J;o ca-ne advice. ?bo 
b».d urticaria {fain cf t e Joints) is producaa by th% 
or tho horsoi not by tb# antitoxin, and cusec havo been rcy®rtsdf 
There thsm was a fetal frun tb# antitoxin, but of thsai 
havs found to be duo to ntV*r l^i^|on»t a.nd 1 go not ■ now that 
any oaaa has found to bo am to tdlosyfisrusf so the part of inph. r—■-o. 
tho I nynolf r- i »t that. nntotf»Kir; c»v r 
kill, although lift it) o\u*ntIve. 
mr thorta f •' t?ts middle Own, r-.*D •:!* !.n t/ib*;;, sauaiag 
mIridic aar d l.wijso. 
Reported by 
»v. B. Grubbs* Dr. Sidney Martin, Professor of pathology in University 
College, London, reports the following results of the antitoxine 
treatment at the University College Hospital ( Lancet, October 17, 
1896.) The antitoxine treatment was begun at the commencement 
of 1895, and has been continued methodically down to the present 
time. The following table shows the total mortality of all cases 
of diphtheria admitted from 1891 to 1896, ( 1895 and 1896 being the 
antitoxine years:) 
Years. 
Cases. 
Deaths 
Percentage. 
1891 
62 
27 
41.9 
1892 
60 
20 
33.3 
1893 
105 
39 
37.0 
1894 
64 
25 
39.0 
1895 
75 
21 
28.0 
1896 
68f 
*About Sep. 22. 
14 
20.5 
In other words, from 1891 to 1894 there were 291 cases 
admitted with 111 deaths, a percentage of 38.1. 
In 1895 and 1896 there were 143 cases with 35 deaths, 
a percentage of 25.1. 
The mortality in all cases of diphtheria from 1891 to 
1894, according to the day of illness when admitted was: 
1st to 4th day of illness, 156 cases, 58 deaths, 37.1 % 
5th day and later of illness, 102 cases, 44 deaths, 43. 2 
For 1895 and 1896: 
1st to 4th day of illness, 97 cases, 15 deaths, 15.4 % 
5th day and later of illness, 42 cases, 18 deaths, 42.8 % 
Under five years of age, from 1891 to 1894: 
1st to 4th day of illness, 90 cases, 49 deaths, 54.4% 
5th day and later of illness, 54 cases, 28 deaths, 51.8 % 
While in 1895 and 1896, they were: 
1st to 4th day of illness, 55 cases, 11 deaths, 20.0 % 
5th day and later of illness, 33 cases, 16 deaths, 48.4% 
The contrast between the mortality of 20.0 % and one of 
54.4 % is very marked. 
For all cases in 1896 of those admitted during the first 
four days of illness, 13.7'have died. Of those admitted on the 
fifth day or later, 35.7 % have died. 
Or. Hermann M. Biggs, of New York, reports ( The Medical 
ews, December 12, 19, 1896 ) 1172 cases treated amongst the poor 
in New York City, with 118 deaths, a mortality of 10.0 %. 
574 were reported to be suffering from severe or septic 
diphtheria at the time of the first injection. 268, or about 21.0% 
were reported as in good condition, or as apparently affected with a 
mild form of the disease when first seen.. In 355, or more than 
28.0 % of the whole number, the larynx, with or without the pharynx 
tonsils and nares was involved. In 242 cases, in addition to the 
pharynx and tonsils, the nares were involved. 3 
108 deaths occurred among the 355 laryngeal cases, giving 
a mortality of 30.4./^ 
72 of the laryngeal cases were intubated, and of these 
29 died, or 40.2 % 
in 283 of the laryngeal cases there was no operative in- 
terference, and in these the mortality was 27.9.% 
Of the fatal laryngeal cases 38 were moribund at the time 
of the first injection, or died within twenty-four hours afterward. 
If these be excluded, there remain 317 cases, with 70 deaths, or a 
mortality of 22.0 
In a large majority of the cases treated, that is 793, 
only one injection of antitoxins was administered; in 352, two in- 
jections were made, and, in 108, three or more* In the severe 
cases the initial dose was large, varying from 1500 to 3500 units. 
Experience was that the best results were obtained from 
large initial ooses, and the tendency has been to constantly in- 
crease the size of this dose. 
As a rule tne patients were seen the second time at the 
end of twenty-four hours, and, where it was considered necessary, 
a second injection was then administered. 
The serum employed has been generally twice as potent as 
Behring's No. 3. 
During the past three months the serum contained from 
400 to 500 units in each cubic centimetre. 4 
Better results have been obtained from the high grade 
preparation, and with larger doses. 
In the earlier months when large quantities of serum were 
administered rashes were of frequent occurrence; the percentage of 
cases in which they appeared cannot be obtained. Since the use of 
the higher grade preparation of antitoxine, in which smaller doses 
of serum are employed, there has been a considerable diminution in 
the frequency with which these rashes have occurred.. 
Joint symptoms were of very unusual occurrence; in five 
# t 
instances abscesses followed the administration of the serum, and 
in none of these could the abscesses be properly charged to the 
serum itself. 
Aside from the symptoms referred to, and an occasional but 
temporary pyrexia, no disagreeable effects in any way attributable 
to the antitoxine were observed. 
Immunizing injections, varying from 50 to 500 units in 
amount were administered to 1207 persons. In five children who 
had been immunized laryngeal diphtheria developed within twenty- 
four hours of the time of the injection, and in seven others laryn- 
geal diphtheria appeared. A1J of these cases promptly recovered. 
In nine cases diphtheria developed within thirty days of the time 
of immunization. 
N° data of value are at hand regarding the occurrence of 
cases of diphtheria among those immunized, after thirty days; but 5 
in one instance it is known that a child developed diphtheria on 
the 55th day after immunization, and, although it had received a 
curative injection, it nevertheless died of the disease. 
Experience shows that the protective influence cannot be 
depended to last longer than about four weeks, although, in many 
cases the period is apparently longer. 
In the earlier work, when larger quantities of serum were 
used for immunizing, especially in young and feeble infants, rest- 
lessness v/ith more or less pyrexia occurred in many cases during 
the first tv/enty-four hours, and not infrequently a rash appeared 
later. Since the employment of very small doses of the serum it 
has been unusual to see any disturbance. In one group of forty 
cases recently immunized with small doses, in only one case was 
there a local rash near the site of the injection. Mother series 
of one hundred and thirty cases immunized in an infant asylum, in 
which relatively large doses were administered to children varying 
in age from one day up, in seven cases only was there a mild body 
rash. 6 
In this hospital the serum was not used. At the hospital Enfants- 
Malades in 1890T91~92-93, the average mortality was 33.94 ( in pure 
throat diphtheria.) During the months of the treatment by serum 
in 1894 the average mortality was 12% for those same cases. During 
the same time at the hospital Trousseau the mortality was 32/o (pure 
anginas.) The cases operated on by tracheotomy gave in former 
years a mortality of under the serum treatment, 49^. 
During the same time at the hospital Trousseau, Q6% 
M. Tezenas, at Lyons, has treated 146 cases with 3 deaths. 
Now it is necessary to subtract 128 cases from the 448, as those 
did not prove to be time diphtheria. There remain 320 cases of 
pure diphtheria, 20 of whom died within a few hours of their admis- 
sion to hospital, and did not receive tho serum. There remain 300 
cases of v/hom 78 died, a mortality of 26%. In tho same hospital 
the mortality of pure diphtheria heretofore has been 50 per cent. 
The scrum was furnished by horses immunized by between 50 end 100000* 
All the children upon their entrance received 20 c.c. of the serum, 
one injection; 24 hours later from 10 to 20 c.c. of the serum. 
Pulse and temperature are the guides. If the temperature remains 
elevated, repeated the injection once more. The average weight 
of the children was 14 kilograms; so that at first injection they 
received a little more than l/lOOO of their weight in serum; maxi- 
mum quantity of serum used in any case, 125 c.c. Of pure anginas 
120 causes, 9 deaths, mortality 7.5; quantity of serum usod in those cases varied from 20 to 25 c.c.. The result of the injection was 
that the false membrane disappeared promptly, becoming detached as 
a rule in 36 to 48 hours— at the latest on the third day; membrane 
in only seven cases persisted longer; one time, 10 days* The 
bacilli disappears with the false membrane. Cultures have ceased 
to give colonies, save in a few cases, after the third to the fifth 
day. Fever disappears promptly. In the less severe anginas the 
fall even takes place the day after the injection. The pulse 
falls less rapidly. Respiration does not seem to be affected; 
of those 120 cases 54 showed albumen in the urine. As a rule 66 
per cent show albumen in the urine. 
Contrasting these statistics with those of MM. Martin and 
Chaillou we can establish with exactness the mortality of pure diph- 
theria anginas. Of 96 children observed by them in 1891-92 there 
ii-0 . 
were 38 deaths, a mortality of 41%. Amongst the 9 infants with 
pure anginas, 7 wore in the hospital less than 24 hours, and should 
not be reckoned in estimating the success of the treatment. So 
that of 113 pure anginas there were two deaths, mortality 1.7% 
One of these infants showed at the autopsy tuberculosis, peritoni- 
tis and ameloid degeneration of the kidneys and liver; and the other 
child had a Pott’s abscess. When we come to consider diphtheria 
associated with other bacteria the mortality is quite different; 
with the staphylococcus pyogenes the mortality in five cases—all 
recovered; duration of disease was longer than in the pure anginas; amount of serum required, from 30 to 50 c.c.. Associated with the 
streptococcus, 35 cases with 12 deaths, mortality 34.2; these are 
grave cases. A number of cases of laryngeal croup were saved 
from an operation by the prompt use of the scrum. There were 121 
cases operated upon; 56 deaths; mortality 46%. Former statistics 
in the same hospital gave a mortality of 68%. In pure diphtheria 
. b 
croups there were 49 cases; 15 deaths; mortality 30.9%. Of the 
croups associated with staphyloccoccus, 8 cases and 4 deaths, 50%. 
Associated with streptococcus, 52 cases, 33 deaths, mortality 63%. 
The last are the grave cases. Roux expresses the belief that by 
the prompt use of the scrum, even in diptheritic croup, the opera- 
tion of tracheotomy will be entirely displaced by the tubage. Roux, Contribution a lr6tude de la dans la diphtdr- 
ic, in Lg Bulletin Medical, Sept. 5', 1894, p.799. 
Since 1891, Roux has pursued his studies in relation to diph- 
theria by antitoxine serum both upon animals and upon children. 
Proportion of toxine. It is necessary to plant virulent diphther- 
ia bacilli in bouillon, and to keep the cultures at 37° C., for 
several months. Roux and Yersin recommend a more rapid procedure 
which consists in placing the bouillon with 2% peptone in vessels 
with a flat bottom, and forcing a current of moist air, by means of 
a bellows and v/ash bottle through the culture. At the end of 
three weeks use of this method the culture is sufficiently rich in 
toxine to be employed. The cultures are then filtered through 
a Chamberland filter and kept in small flasks well-stoppered, and 
in the dark. As a rule the toxine thus prepared in doses of l/lO 
c.c. kills in 48 hours guinea-pigs weighing 400 grams. It can be 
kept for a long time provided the above directions are observed. 
Immunizat i on of anirria.Is. Carl Frankel first immunized guinea 
pigs against diphtheria by injecting them with a toxine somewhat 
modified by heating to 70° C. Behring recommended the mixture of 
the toxine with the trichloride of iodine. He prefers to inject 
the animal at frequent intervals with little doses. Brieger and 
Wassermann have obtained the same result by injecting a culture 
of diphtheria bacilli grown in thymus bouillon having heated it to 706 for a quarter of an hour. It was always difficult, 
however, to highly immunize small animals, such as rabbits and guin- 
ea pigs. Roux prefers to use the iodinized toxine as the diphtheria 
toxine; that the addition of iodine is much less dangerous than 
pure toxine. One should add to the toxine 1/3 of its volume of 
Gram's liquor just before employment, and then inject the mixture 
under the skin. A rabbit of average size will bear 1/2 c. c. of 
this liquid. At the end of a few days the injection is renewed, 
and continued several weeks; then the dose of the toxine is increas- 
ed and later the pure toxine can be used. The animals should bo 
weighed frequently and the injection interrupted if they begin to 
/ 
lose weight. In these experiments to go slow is to gain time. 
Immunized dogs have been used by Bardach and Aronson, furnish- 
ed with very active serum; sheep and goats are also very sensitive 
§ 
to the action of the poison. Roux believes that of all animals 
the horse is the easiest to immunize. If one agrees with Behring 
that the animal furnishes a serum more antitoxic according to its 
greater sensibility to toxine, the choice of the horse may not ap- 
pear to be a bad one. Nevertheless, in 1892, Roux and Nocard 
undertook to immunize horses against diphtheria since the experience 
of Roux and Vail lard in tetanus had shown that the serum of the 
horse, even in large doses was harmless when injected beneath the 
skin of other animals, and did not lead to any local reaction; be- 
sides nothing is easier than to draw from the jugular vein of the horse as often as one wishes, large quantities of blood. I have 
a horse whose jugular vein has been wounded more than twenty times 
with a trocar of large caliber, and yot the vessel remains perfect- 
'! 
ly soft and permeable. The immunizing power of this serum is in 
the neighborhood of in other words this serum has a pre- 
ventive power such that a guinea pig injected twelve hours before 
sS"0 * (Tlr& 
with l/l00096^0f its weight in serum is immunized against the inocu- 
lation of a half c.c. of a recent and very virulent culture of 
diphtheria. He begins with small doses ( 2 to 5 c.c. ), and states 
that in a month and twenty days one of his horses had received 
more than 800 c.c. of the toxine without presenting any other symp- 
toms than a temporary local oedema at the site of injection. He 
says a mixture of l/lO a c.c. of this sorum and one c.c. of the 
diphtheria toxine does not provoke any oedema injected under the 
skin of guinea pigs. 
Anti-diphoheritic scrum. II the serum of an immunised animal 
is added go the uoxine tho latter becomes inoffensive; this takes 
place not only in the body but in tho tost tube. This property of 
the anti-diphtheritic serum was discovered by Behring, and is the 
basis of his treatment of diphtheria. The nature of antitoxine 
is unknown to us. Animals which receive the antitoxine become 
refractory totho disease in a very short time. The immunity is 
suddenly acquired, but it does not last long; in a few weeks it disappears according to the antitoxic value and quantity of the se- 
rum administered* 
What is the action which antitoxine exercises upon the toxine? 
V/hen these two substances are mixed do they mutually neutralize each 
other, or do they continue to exist side by side ? If they do 
not neutralize each other why do not the effects of the poison man- 
ifest themselves ? We have stated that a mixture of one part of 
the serum to nine parts of the toxine is injected under the skin 
of a guinea pig it is so inoffensive that there is not even oedema; 
it appears that all of the toxine has been destroyed; but we do 
not come to this conclusion, because the same mixture which does 
not produce any swelling in guinea pigs produced a marked oedema 
in a rabbit. We would say that the anti-diphtheritic serum is not 
antitoxic in the proper sense of the word. Added to the toxine it 
leaves the latter intact. Injected inside of animals it acts upon 
their cells, and renders them for a time insensible to the poison 
of the diphtheria. The proof of this is in the fact that if a 
quantity of serum amply sufficient to protect young guinea pigs 
against a fatal dose of the virus does not prevent the death of 
guinea pigs of the same w eight whose resistance has been weakened 
by prior inoculation of organisms or the products of bacteria, if 
the antitoxine destroys the toxine the same quantity of the serum 
will show its effects with all guinea pigs of the same weight, 
which is not the fact. Action of serum in diphtheria of mucous Roux 
first studied this by inoculating guinea pigs in tho vagina after 
Loffler1s method. Female guinea pigs always resist the toxine if 
the serum is injected in a sufficient dose before the local inocu- 
lation. Although a false membrane forms there is less redness, 
less oedema, less fever, the general condition of the animal re- 
mains better than in control animals. On the second day the local 
lesions diminish and the false membranes begin to loosen themselves; 
the control animals die in from three to six days. He states that 
his serum and preventive injection of an amount equal to l/lOOOO 
of the animal’s weight is quite sufficient. If he waits until 12 
hours after the inoculation it requires a much larger amount of 
scrum, as much as l/lOOO to cure the animal. He has also repeated 
these experiments by inoculating guinea pigs and rabbits into the 
trachea. He has also inoculated these animals into the trachea 
with a mixture of streptococcus and the diphtheria organisms, and 
finds that tho cases are much more difficult to cure; as a rule 
the animals die of a mixed infection. 
Results obtained with children* From the first of February 
until the 24th of July 448 children were treated s,t the hospital 
des Enfants-Malades; 109 died; percentage 24*5. During the years 
1890, *91, f92, *93, 3971 infants were admitted, of whom 2029 died 
. 4 - ■ - 
per cent 51.71. Daring the same months of 1894, there onto rod 
the hospital Trousseau, 520 infants, of whom 316 died, equal to 60% PATHOLOGY NO. 1. 
Jan. o, 1898. 
ffe begin the subject of Pathology to night, .gentlemen, with the con- 
sideration of inf lamination. 
This is a process of fundamental importance, lying as it dees at the 
very oasis of our pathological knowledge. It is therefore, quite impor~ 
tant that as students of pathology, you should have a correct conception 
of what constitutes inflammation, Bntil modern methods began to be used, 
the ideas of the profession and of students of pathology concerning in- 
flammation were exceedingly vague ana confused. After Oonnheim, the great 
German patftoiogist, showed us now to study inflammation, pointed out at 
the 
least the tissue or tissues in wmen we couia study inflammation to best 
advantage under the microscope, and observe the various phenomena which 
there take place, the ideas concerning inflammation began to crystalize 
somewhat for the first time. 
It is very difficult to define inflammation, and a number of authors 
decline to give any definition. 1 have been in the habit of giving the 
class two definitions- one by an American, the other by a German.patholo- 
gist. They seem to oe about as good definitions as we have of the pro- 
cess. The first is one given by Oouncillman of Harvard, fie defines in- 
flammation as: “The sum of the phenomena which take place in the tissue 
as the result of an injury." Do not understand me to say some of the 
phenomena, but “the sum of the phenomena." Ziegler defines inflammation 
as: “An essential local tissue degeneration, combined with pathological 
exudation from the bloodvessels, brought about by some injury." The lat- 
ter defini ion contains many large words, and may not be clear to you, but as'we go on, you will see that it is not a difficult definition for 
you to understand.' You see that both of these definitions imply that 
some damage has been done to the tissue prior to the occurrence of inflam- 
mation. That'is true; inflammation follows injury to the tissue, ana this 
injury may be brought about by various causes. In the first place, we may 
divid-e the causes into five classes: 
1. Thermic, (either beat or oold) 
2. Mechanical. 
5. Electrical. ( You can readily see that electrical injuries 
ao not enter largely in to the Question.) 
4. Chemical. 
5. Bacterial. 
And we believe that bacteria aot, as a rule, chemically. -All these causes may 
serve to do some damage to the tissues in some part of the body, and to be 
followed by all of the phenomena which take place in inf 1 animation, end which 
I may say tend toward the resair of the tissue against some injury that has 
been done. I said that Gohnheim taught us bow to study inflammation: He 
made use of the mesentery of the frog in order to be able to study micro- 
scopically the changes whion take place in the bloodvessels during inflam- 
mation. You appreciate that this structure*is extremely delicate- you nave 
a layer of endothelial cells, and beneath this delicate connective tissue 
fibers, arteries, veins, capillaries, lymphatics and a few nerves, row Gobn- 
heirn was particularly interested in studying the vascular changes which take 
place in inflammation, so he made use of the frog's mesentery for this pur- 
pose, and iouni that it was^most useful tissue in whicn to siuay the changes 
that occur. For a moment, consider the circulation of blood through the 
normal vessels of the frog's mesentery: You notice that the blood flows through certain vessels intermittently, with a pulsating current- these are 
the 
the blood flowing so rapidly through them that you are not able to 
8 3? 0 
distinguish the individual blood cells. Then thereAvesseis of the same size 
carrying the current in an opposite direction, usually a continuous fiow- 
these are the veins. Then some small vessels showing a slow irregular cur- 
rent, sometimes interrupted for a moment, and then going on again- these 
are the capillaries- the vessels connecting the arterial system with the ve- 
nous system. Now in the veins of the frog's mesentery, where the blood is 
flowing continuously, it is difficult to observe the blood cells both red 
A, 
and white; you select a medium sized vein- a vessel which appears to carry 
the blood toward .the intestine (of course it. is flowing in the inverse di- 
rection) and you will observe that there is a central core of red ceils, an 
axial stream of red blood cells, and between this and the wall of the vessel 
a olear zone in which the blood plasma flows along known as the 
“plasmatic zone*, and here and there in this zone you also notice white cells 
floating along, a few of them only, Let us suppose that the cut to the left 
represents a section of a frog's mesentery- of course 1 represent it, gentle- 
men, very diagramatioally- only to give you some slight conception of its ap- 
pearance. We will take this to be a vein in which the blood is flowing con- 
tinuously. You observe under the microscope the red blood cells in the cen- 
ter, and a olear zone between the stream of red blood cells and the vessel 
wall; here and there in this plasmatic zone you observe a white cell tumbling 
along, a granular body, now stopping, now being carried on by the blood cur- 
rent. In the capillaries also, you observe red cells proceeding singly- 
there is not room enough for them to flow two abreast; occasionally along passes a white ceil- a white granular body. Mow a little while after the 
membrane has been exposed. I have said nothing to you of the way in which 
the membrane should be prepared- it is not essential- how the frog is ren- 
dered motionless, the incision made and the mesentery drawn out. At any 
rate it is placed over a block of glass elevated on a slide (called a frog 
board) and kept continually wet with normal salt solution, so that as little 
injury as possible should be done to the mesentery. 8 hen you have done this 
carefully, you can observe ail that I am telling you here. After 15 minutes 
or less time, after exposure of the mesentery, you will observe a very strik- 
ing chenomenon; that is, the vessels become dilated. Vou observe a marked 
dilatation of the vessels. In other words, this yein that was normal in size 
when we began to look at it under the microscope, is of quite a different 
size now, and at the same time that the dilatation of the vessel has taken 
place, the rapidity of the current has also increased, so that you may 
put down as tie first phenomenon,dilstation of the blood vessels with in- 
creased rapidity of current. , , . . t . 
Whereas you could distinguish before the indi- 
vidual blood ceils, now they rush along with such rapidity, even in the ca- 
pillaries that you cannot distinguish them; at the same time you recognize 
that there is a red stream and a plasmatic stream, and you will catch sight 
occasionally, of white cells.in that stream; more of them than you saw be- 
fore, and you will notice in the capillaries also more white blood ceils 
than you saw before. The next phenomenon is equally interesting; the di- 
latation continues, but the current becomes slower. The second phenomenon: 
The dilatation of the vessels continues, but the current becomes slower. There is a distinct retardation in the flow of the blood current, and now 
you observe distinctly, what I have attempted to represent above,that in the 
plasmatic zone, in the clear zone, there are more white blood cells than you 
saw in tie normal vessel. They roil along as they did in the normal vessel, 
adhering here and there and being carried on further, delaying a moment and 
being washed on by the blood current. The 3rd phenomenon, which occurs later 
is a still further accumulation of the white cells in tile plasmatic zone. 
In other words, the white ceils pass over to the outer margin of the plasmatic 
zone in large numbers, until they completely line the interior of the vessel 
wall. You see that the interior of the vessel as you bring it into focus is 
// 
lined with white blood ceils. This is known as the marginal disposition of 
H 
the white blood cells. If 1 represented a cross section of such a vessel, 
I would put the red cells in the interior of the vessel (small cells in dia- 
gram), and then I would line its wall with the white cells (large ones). 
There (cross-section) you see we have an axial zone of red ceils and the white 
■cells completely lining the inner surface of the wail of the bloodvessel, 
therefore, when you turn down on the in changing the plane of your 
•s 
focus, you come first upon the vessel wall, then a layer of leucocytes, and 
as you go down deeper you have the axial stream and the leucocytes on either 
side/, then £oing through the stream you catch the leucocytes below. 
This lining of the interior of the vessel with white blood cells is, as I 
have said, known as“tne marginal disposition of leucocytes”. Kow another 
phenomenon occurs which is generally seen in vigorous frogs in the course of 
an hour and a half or two hours after the vessel has been exposed, sometimes 
earlier, sometimes later; the dilatation of the vessel continuing, the cur- rent being still slow, we notice a white cell attached to the vessel wall. 
Observing closely, you will be able to see that the cell has a projection on 
the outer side of the vessel just at the point at which the cell lies, and 
still observing this you will be surprised to see that the bud increases in 
size (grows larger) at the same time the part in the interior of the vessel 
grows smaller, and after a while you have simply a bud inside with the larger 
mass on the exterior, and then the next event is c-resence of the cell entire- 
A /- 
ly outside of tr.e vessel. In other words, the blood cell which we have been 
observing, has passed through the vessel wall. This is known as the“emigra- 
And this will be found at various points 
along the vessel- white blood cells emigrating. This goes on until on the 
outside of the vessel we have them present in large numbers. connective 
tissue spaces outside of the vessel become quite crowded with these cells 
which have passed out. These are the vascular phenomena which are observed 
in the exposed frog’s mesentery. It is not necessary to do anything more 
than to withdraw it from the abdominal cavity and expose it to the contact 
of the atmosphere. In this case that is sufficient injury. If the mesen- 
tery is left exposed long enough it will . become .intensely inflamed and will 
necrosis, if it~Sarefully returned to the frog’s ab- 
domen, even after tee emigration of leucocytes has taken place and the wound 
closed, the whole process subsides and the health of the animal is not ma- 
terially disordered. You can see under the microscope these various phenom- 
ena, but there is another important thing which takes place that you cannot 
see under the microscope, though we can observe its effects in various ways: 
at the same time that the leucocytes are emigrating there is a fluid passing from the vessels to the tissues outside of the vessel. An exudation of 
lymph, and of a lymph whiob differs from the normal lymph. You have al- 
ready been taught that in the ordinary nutrition of the tissues lymph is 
passing from the bloodvessels to the tissues, intended for their nourish- 
ment. This takes place in ail the tissues of the body, and this lymph con- 
tains a few white blood cells and a certain amount of albumin. This partic- 
ular lymph is a lymph- which is much richer in albumen than normal lymph, and 
we call this fluid lymph which has escaped from the vessels into the tissues 
an “exudation, ”and now you see what Ziegler means by a “pathological exuda- 
tion”. This is not a normal physiological transudation,, but an exudation that 
is pathological, in that it is different from the normal lymph, being richer 
in albumin. This continues and often distends the tissues to a considerable 
extent. In the case of the frog's mesentery it reaches the surface, and you 
Qaa, ti> 
can see the lymphocytes being washed away in currents of lymph. Now so much 
4' 
for the phenomena which take place in a transparent membrane like the frog's 
mesentery. Let as for a moment look at the process of. inf 1 animation in a 
nontransparent tissue. Take the ear of the rabbit or the kitten. If you 
apply to the surface of the kitten’s ear, or a rabbit’s ear a mixture of 
one part of croton oil to 5 or 6 parts of olive oil, rubbing it into the 
skin of the ear, you will produce a marked inflammation of the ear. In the 
course of a few hours, if you look at the ear by transmitted light you will 
notice that it is much redder than the fellow ear. In other words, there is 
an increased flow of blood to the part. The stage of hyperaemia has already 
set in. More blood is going to the rabbit’s ear and more blood is going away. 
You oan easily observe the increased size of the bloodvessels, and this is followed by a decided swelling of the ear. The redness may be greater in 
certain parts. There may have taken place hemorrhage at various points 
within the tissue and you may find that along with the swelling the .super- 
ficial epidermis is elevated into little blisters. The swelling would have 
told us that something haa escaped from the vessels into the tissues, caus- 
ing the thickening of the animals ear. If we break one of these little 
blebs or blisters we find that it contains a straw colored fluid, perhaps a 
little bit turbid- lymph richer in albumin. ?*e do not see it pass out of 
the bloodvessels but we find.it .present; it must have escaped from the vessels 
This reminds me that there is one point I did not mention in connection with 
the vascular phenomena that should be placed amongst those which you observe 
in the frog’s mesentery. After the inflammation reaches a certain stage, one 
observes not only the pas sag's of the white cells red ceils also es- 
cape from the vessels. That is generally present, more or less, in the ma- 
jority of inflammations. In some inflammations the exudate is really so rich 
in blood ceils that we speak of it .as hemorrhagic. The red blood cells are 
often observed to pass through the wall of the vessel just at the point where 
n iA 
the white blood ceils escape, and this is known as diapedesis of the red 
blood ceils. The engorgement may become so intense in the capillaries that 
A Lg 
the vessels break. The escape of, red blood cells by rupture of the vessel is 
often spoken of as rhexis.” Another point that escaped me at the time we 
were speaking.of emigration:of the ,white, ceils. These emigrate principally 
the 
from,small veins, also from trie capillaries: they do not emigrate from the 
arteries— the diapedesis of the red ceils takes place largely from the 
veins and also from the capillaries. 9 
After observing tne rabbits ear as I said before you may find points 
where decided hemorrhage has taken place irrtep tie tissues. In this non- 
transparent tissue we found the same phenomenon that bad taken place in the 
transparent tissue. Let us, for a moment, take a nonvascular tissue for the 
study of inflammation- the cornea. If the center of a cat's cornea or a 
rabbit's cornea, or a frog's cornea is touched with a stick of lunar caustic 
a certain amount of chemical.injury is caused at the.point, just as the ap- 
plication of croton oil to the rabbits ear produced a chemical injury. Now, 
within a few hours, the bloodvessels around the margin of the cornea,- the 
scleral bloodvessels- are observed to.be markedly dilated, apparently in- 
creasing in number,, and the circumference of of the cornea begins to show a 
slight clouding. At the end. of 24 or 36 hours, the whole cornea has a de- 
cidedly ,hazy, cloudy appearance and this cloud slowly advances to the cen- 
tral point of injury; later the'periphery of the cornea clears up and the in- I 
jured spot is surrounded by quite a dense whitish looking ring. Now, if the 
cornea is removed and split up into its lamellae and examined microscopically, 
it is found that the cloud which appeared-is really due to the presence of 
white blood cells, which have evidently escaped from the vessels of the 
sclera and invaded the lymph spaces of the cornea, and advanced toward the 
central point of injury. In this case you have dilatation of the vessels 
and evidently an escape of blood cells. They must have escaped from the sole-1 
ral vessels, as the cornea has no vessels. 
Now, gentlemen, let os consider-for:a moment- for we can only take in a 
pert of the subject of * inf 1 animation this - evening- tee' various clinical symp- 
toms which'inflammation-presents,; the so-called “cardinal* symptoms of in- flanimation, observed since the days of Oelsus in the first century of the 
Christian era, and which have been the common property of physicians ever 
since that time. ~They*are 1. redness- rubor; 2. heat- oalor; 5. swelling- 
tumor; 4. pain- dolor; 5. disturbance of function- functio laesa. These are 
the symptoms which you see clinically when you examine an inflammatory dis- 
turbance of the surface of the body: A boil,which is a ioc sliced inflammation 
00 
of the skin, ordinarily caused by the stapbyloccus aureus will present the 
creased 
cardinal symptoms of infianimation. In the first place you appreciate the m-A 
redness. If a surface' thermometer is applied to the furuncle, the column 
ascends; there is increased neat as compared with tne normal skin. The swell- 
ing is auite evident, especially so in the later stages; the pain is invari- 
ably there, and-even the disturbance of function, because; wherever a boil is 
located you appreciate that it interferes with the action of the part. Kow 
let us inquire into these several symptoms. The redness- hyperaemia- implies 
an increased supply of blood to the part, ft’cat is the cause of this hyper- 
aemia? After Bernard bad demonstrated that section of the cervical sympathet- 
ic nerve would cause a very intense redness or hyperaemia of the animal's ear 
on the corresponding side, it was thought that the hyperaemia in inflammation 
was due to paralysis of the vdso-aotor nerves supplying the part. However 
the paralysis of tne vdso-motor nerves does not account for the hyperaemia of 
inflammation. The hyperaemia attending the section of the sympathetic nerve 
comes on at once, whereas the hyperaemia of inflammation is gradual. Hyper- 
aemia due to section of the sympathetic is not followed by migration of leu- 
cocytes and escape of a pathological exudation from the bloodvessels, so that 
paralysis of the vdsc-motcr nerves does not account for the hyperaemia in inflammation. The two theories which are of most importance, are those of 
Gohnheim and Virchow. Cohnbeim believed that in inflammation the essential 
feature was an alteration in the wall of the bloodvessel, due to the injuri- 
ous influence of the agent producing the inflammation, and that this altera- 
tion, which could not be seen microscopically permitted the vessel to dilate 
rapidly and caused more blood to be brought to the part. Be considered that 
the injury to the vessel wall was the most important matter in inflamma- 
tion, and he attempted to prove this by ligating a vessel, thus depriving a 
certain district of its blood supply, and after an interval, allowing the 
blood to flow into the vessel again, fie found that the phenomena of inflam- 
mation took place in the parts supplied by this bloodvessel (emigration of 
leucocytes, dilstation.etc.) and he believed that hiscligstore had deprived 
the vessel wail of its blood supply and hence had, in some way, brought about 
the alteration in its delicate wall, the alteration be had so much in mind 
when he wrote of inflammation. Now the criticism that might be made to this 
view of Gohnheim is that in depriving the vessel wall of its blood supply, he 
was also depriving the tissue ceils adjacent to the vessel, and hence be was 
not only doing damage to tee vessel walls but to the tissue outside. We do 
not believe that the injury could be so limited as only to affect the vessel 
wall and not the tissue cells. That I think, is quite a justifiable .criticism. 
Then as Gounciiman says, it has been observed that the bloodvessels become di- 
lated sc far away from the center of inflammation as to render it impossible 
for us to believe that the vessel wall was injured. If the tip of a rabbit’s 
ear is inflamed the main artery dilates far away from the injury. Again 
Gounciiman calls attention to the fact that if you pass a thread- a mechanical 12 
agent- through the center of a oat's cornea you produce dilatation of blood 
vessels around the sclera followed by emigration of ieboocytes-bloodvessels 
so far from the point of injury that we cannot believe that they were injured. 
On this account, these views of Cohnheim as to the increased hyperaemia cannot 
be accepted. The second view, seems to be nearer the truth. 
Virchow long ago expressed the opinion that the hyperaemia was due to an alter- 
ation in the attraction of the tissues for the blood. That in inflammation 
there was an increased attraction on the part of the tissues for the blood, 
and responding to this nature supplied more blood to the tissue, fie know that 
where increased functional activity is called for on the part of the tissues 
or a secreting organ, nature responds at once by increasing the flow of blood 
to tie part, it has been observed that if a part of an organ is destroyed- 
undergoes atrophy- the vessel supplying that organ becomes distinctly smaller 
as the need of ,blood is lessened. Where the main vessel of a limb is ligat- 
ed and the same amount of blood is required, the smaller and collateral vesseisl 
increase in size- Hence Virchow believes that an increased demand is made by 
the tissues for' blood, and that the hyperaemia is brought about by this in- 
creased necessity for repair on the part of the tissue and for getting rid of 
the consequences of the injury. 
At the next lecture we will take up the other cardinal; symptoms of inflam- 
mation. I & H'L AM M AT 10 \ oontinu ed. 
Dr. Reed. 
It may be well, gentlemen, for me to recall to your minds, in a 
brief review, some of the remarks that I made to you on Friday evening, on 
the subject of inflammation. You recall that the vascular phenomena consist- 
ed of a dilatation of the blood-vessels with increased rapidity of flow of 
the blood current; this representing the stage of active byperaeaia; that the 
dilation continuing the blood current became slower; that during this stage 
the leucocytes or the white blood ceils, which, prior to this, were seen in 
comparatively few numbers in the plasmatic zone (the clear space between the 
axial current of the red blood cells and the wall of the vessels) became, in 
this stage, increased in numbers, and lined the interior of the vessel. Fol- 
lowing this they were seen to pass through the vessel wall in considerable 
numbers, and I said that we had every reason to believe that a fluid exudate 
passed from the blood vessels at the same time. I also mentioned that the 
emigration was chiefly from the small veins, also from the capillaries, and 
that often the red blood cells were seen to leave the vessels; this phenom- 
enon being known as diapedesis of the red bicod ceils. I told you that the 
phenomena of inflammation were essentially the same when observed in a trans- 
parent membrane, like the frog's mesentery, or in a non-transparent part, 
like the rabbit's ear, or in a non-vascular part, such as the cornea. I also 
cailsd your attention to the cardinal symptoms of inflammation; redness, neat, 
pain, swelling, and disturbance of function, and told you that these cardi- 
Inal symptoms could be observed very readily in an inflammation of the skin, 
sucg as an ordinary, boil. As to the hypsraemia of the part, I mentioned sev- 
eral of the theories on that subject; the first being that the hyperaemia was due to the paralysis of the vase•motor nerves supplying the parts, especially 
after Bernard had shown that section of the cervical sympathetic in the rab- 
bit would cause marked ail station of the blood vessels of the ear on the 
same sias. I also called your .attention to the fact that this nyperaemia 
after section of. the sympathetic came on rapidly, whereas the hyperaemia of 
inflammation takes place slowly; that the nyperaemia from the vase-motor par- 
alysis was not followed oy emigration of leucocytes ana exudation. I mention- 
ed Ochnheim’s theory to account for the nyperaemia; due to an alteration in 
the wails of the bloodvessels caused by the agent producing the inflammation. 
I cited nis experiment of ligating the vessels for a time and afterwards al- 
lowing the blood current to be restored, ana that this was followed by emigra- 
tion of leucocytes ana exudation of lymph. Cofanheim believed- that this was 
entirely due tc,,t,b.e change taking place in the wall, as the result of the de- 
privation of its normal blood supply. I referred to the fact that , not only 
in a case of this kind were the cells of the vessel affected, but the cells 
of the tissues adjacent to the vessel-wail would also be affected, and that 
hence we could not accept, entirely, Oohnheim’s theory. Then too, the di- 
latation of the vessels and the nyperaemia may take place at a considerable 
distance from the actual focus of inflammation. I think I stated that di- 
latation of the main vessel of the rabbit’s ear took place when the tip of 
the ear only was inflamed, and the fact that destruction of tissue at the 
center of tne cornea woula be followed,very promptly,by dilatation of the 
vessels of the sclera- too far away to have their wails injured in any way 
by the inflammatory irritation. Then 1 said that Virchow’s theory, that in 
inflammation there was an altered attraction existing between the tissues and the blood, was probably nearer the truth. The fayperaemia was called 
forth by the needs of the tissue for repair, ana to set aside the effects of 
the inflammatory irritant. 
The temperature of the inflamed part is increased; this is due to the 
greater quantity of arterial blood flowing to the part in a given time, the 
current being too rapid to allow of the dissipation of its heat. If the in- 
jected ear of the rabbit whose sympathetic nerve has been cut is folded over 
the thermometer, the mercury ascends higher than if the normal ear is folded 
over tne thermometer, showing that the increased supply of arterial blood 
passing through in a given time, even where there is no inflammation, will 
cause an elevation of temnerature. John Hunter long ago showed that the tem- 
perature of the interior of a hydrocele sac in which inflammation had been 
set up was decidedly greater than the temperature of the sac immediately 
after the fluid baa oeen taken from it, and he further showed that the local 
temperature in an inflamed pleural cavity, or ‘the temperature in an inflam- 
mation of the deep muscles of the back, might be even less than that of the 
general blood temperature. In other words, Hunter showed that the tempera- 
ture of the inflamed part is not greater than the general blood temperature. 
You know that with a local inflammation we may have a rise of bony tempera- 
ture, known as“inf lamina tor y fever7'. This is due to influences affecting the 
heat center. It does net mean that the general temperature has been In- 
creased oy the blood flowing through the inflamea part. Careful experiments 
have shown that tne inflamed rabbits ear is hotter than the normal ear of the 
that 
rabbit, butAthe temperature of the inflamed ear is not greater than the tern- perature taken in the animals rectum; on the contrary, it is less- an in- 
flamed part may have even a less temperature than the normal part, provided 
the ciroulation has almost come to a stand still in the part. The pain in 
.is and 
inf1 to the pressure of the exudate upon the nerves of the part, 
will vary very muoh, according to the abundance of the nerve supply. A parr 
poorly supplied with nerves will be less painful than one which is richly 
supplied. A part in which the tissue.Pan. be. easily distended by the exudate 
will be less .painful; so that the anatomical structure of the part has a good- 
deal to do with the amount of pain. Inflammation of the periosteum (a fi- 
brous structure) is extremely painful, owing to its lack of distensibility. 
Inflammation about the fibrous structures of joints is also extremely painful. 
Sometimes the pain seems to be due to the character of the inflammatory agent 
acting upon the nerve fibers. The inflamed part is swollen- the swelling is 
due in slight part to the dilation of the blood vessels, to some extent to 
the increased emigration of the white blood ceils, but chiefly to the fluid 
exudation. Not only is the amount of exudation (lymph) which escapes from the 
blood vessels in inflammation greater than that under normal conditions, but 
more lymph is carried away from the inflamed part by the lymphatics. Gohnheim 
showed that if a dog's foot was placed in water sufficiently hot to produce 
inflammation, and a canula was inserted in the main lymphatic coming from the 
very . 
foot, the quantity of lymph was mhch increased, as compared with that which 
escaped from tne main lymphatic of the non-inflamed foot. This lymph, I have 
already told you, is much richer in albumen. The salts are not increased. 
This lymph is more ooagulable than normal lymph? due to the presence of white blood cells in increased numbers. Cohnheim thought that the increased exu- 
dation of lymph was simply due to an alteration of the vessel wall. He did 
not think that it was doe to increased pressure, because he observed that the 
lymph 'which escaped from blood vessels in chronic passive congestion of a part 
was not so rich in albumen as the inflammatory lymph. He thought that the 
walls of the blood vessels were in some way changed. The filter was changed, 
in character, and hence the filtrate was changed. This view leaves out of 
sight entirely the endothelial cells lining the blood vessels. Heidenhain has 
shown that, under the normal condition of nutrition of a part, the lymph which 
escapes from the vessels in one organ is different from that whioh passes from 
the vessels in another. The lymph which escapes from the lymphatics of the 
kidney is different from that of the and certainly here we must 
ascribe some influence to the endothelial cells which line the bloodvessels; 
it is believed now tiat the difference in the exudation is due to the altered 
secretory function of the endothelial cells of the bloodvessels. The swollen 
part contains often considerable fibrin. You have seen fibrin already in 
your section of the rabbits ear. The lymph which exudes from the bloodvessels 
is rich in fibrinogen, and the whits blood cells, many of which are undergo- 
ing disintegration in the inflamed part, furnish the other necessary ingre- 
dient, the fibrin ferment. There is also a certain amount of lime salts con- 
tained in the lymph, so that we have here ail of the elements necessary for 
the production of fibrin. This may be present in certain inflammations in 
very large amount. Occasionally an inflamed part is very hard and brawny, 
due to the amount of fibrin contained therein. The swelling of the inflamed 
part will depend very much upon the anatomical structure of the part. In the ease of an organ, saoh as the parotid gland, or the kidney, .the 
swelling will affeot the whole organ. Here the inflammatory exudate will 
escape into the interstitial connective tissue of the organ. In the case 
of an inflamed long, the inflammatory exudate will escape into the air cells, 
such as we see in croupous pneumonia. In the case of an inflamed pleura 
the exudate will accumulate within the pleural sac; and in the pericardial sac 
in inflammation of the pericardium. In inflammation of cartilage, which has 
no spaces between the ceils for the escape of the lymph, the exudation takes 
place within the joint. In inflammation of the skin, the exudation takes place 
in the subcutaneous connective tissue, ana if considerable, frequently raises 
the external layer of epidermis in the form of a bleb or blister. So I say 
the character of the swelling will depend very much upon the anatomical struc- 
ture of the part affected.I have stated that the white blood cells escape 
from the vessels- in what way do they pass through the walls of the vessels ? 
Oohnheim taught at first that they made their escape.by means of their ameboid 
movements. He afterwards abandoned this theory, observing that where the blood 
current came to a stand still, where there was stasis in the vessel- that em- 
He 
igration oeased-.afterwards concluded that they escaped by increased pressure, 
just as we believe the red blood cells are forced through the walls by in- 
creased pressure. However it must not be forgotten that if the.blood current 
ceases to flow through the vessel the leucocytes must very soon feel the want 
of a proper blood supply, and this may account for the arrest of their ame- 
boid movements am emigration, it has been found that solutions applied to 
the frog's mesentery which arrest the ameboid movement of the leucocyte, will also arrest their emigration from the vessels- a solution of quinine 
for instance. It has been shown that if the frog is completely chloroformed 
this will put an end to movement and emigration of the leucocytes. There 
seems to be no doubt that the white blood cells pass trough tbs vessel walls 
by their own active movements. Their escape is not a passive matter, but im- 
plies action on- their part. The red blood ceils, however, must escape from 
increased pressure. There seems to.be no other satisfactory explanation for 
t. . ' .... , . , what point ? 
their passage. 'A'ft ere ao tne leucocytes pass out oi the blood* vessels r A t A 
Arnold has shown pretty conclusively that they pass.,between the endothelial 
ceils, through tne delicate cement substance which holds the cells together. 
In the dilatation of the vessels, this cement substance becomes thin and 
wider, and furnishes a place where the leucocytes may pass through. It is 
not believed that they pass through the endothelial cells, but between them. 
As to the cause of the emigration from the vessels; in the first place, it 
has been found that necrotic tissue, dead tissue of all kinds, has an attrac- 
tion for the white blood ceils, tie can hardly imagine an inflammatory trouble 
so slight as not to bring about the destruction of a few cells, and wherever 
there are dead cells, there will be a focus for the attraction of leucocytes. 
Then again it has .been shown that various bacteria exert a very positive at- 
traction for white,blood ceils. One experimenter placed a culture.of the 
staphylococcus aureus inmall glass tubes, and with all precautions inserted 
these into the abdominal cavity of the Guinea pig (and rabbit) and found that 
in a short time these tubes became packed with leucocytes. In other words, 
cu 
the pus bacteria are among those which possessApositive attraction for the leucocytes. We speak of this as “chemotaxis”. Those substances whioh at- 
tract leucocytes we speak of as possessing positive cbemotaxis, and those 
whioh seem to repel the leucocytes (and there are such substances) as possess- 
ing negative ohemotaxis. Kow the majority of bacteria possess a positive 
cbemotaxis for the leucocytes, and 1 have already told you that necrotic tis- 
sue has also this effect. In inf 1 animation we have the two substances which 
particularly attract leucocytes from the blood vessels, necrotic tissue and 
bacteria. The variety of leucocyte which emigrates is the polynuclear or 
polymorphonuclear.leucocyte. - This leucocyte constitutes about 75% of the 
white blood ceils in normal blood, so that it is by far the most important 
leucocyte found in the blood. , This is the one which emigrates from the olood 
vessels. Gohnheim taught that ail of the cells found in the inflamed tissue 
consisted of polymorphonuclear leucocytes- that these constituted ail of the 
ceils in the inflamed part. Virchow believed that all of the ceils in the in- 
flamed part were derived from proliferation of the tissue ceils. He had 
blood 
called attention to the similarity between the pus cell and a but 
he did not consider the cells in the inflammatory exudate as being really 
white blood ceils. Of course Ccnnheim’s discovery of the emigration of leu- 
cocytes (‘/faller , of England, a number oi years before cohnheis made his ob- 
servation, had seen the leucocyte migrate from the bloodvessels, but his ob- 
servation attracted no attention).attracted the attention oi patnologists and 
explained the origin of many of the cells found in the inflamed tissue. 
CobnheiiB afterwards ascertained that the cells proper ot .the cornea in in- 
flammation underwent division, and acknowledged that, although at first, ail 
of the ceils in the inflamed part consisted of leucocytes, other cells also 9 
appeared later, .and he was willing to admit that these were derived from the 
tissue ceils of the part; that these underwent division as we now know. So 
that during the first 56 or 48 hours the cells found in tne inflamed tissue 
3 
are escaped leucocytes. Later we find other cells, cells withAround nucleus 
and comparatively little protoplasm, and elongated cells, fibro-blasts, which 
are derived from the cells of the tissue through proliferation (division) of 
these cells. Councilman very properly observes that the presence of the em- 
igrated white blood cells and of tne fluid exudate fulfil a good ourpose. 
ihe leucocytes, as you know, not only can take up bacteria, especially dead 
bacteria, but they also serve to remove the dead ceils (necrotic tissue) of 
the part. It is believe! that they serve to a certain extent as food for the 
young eoitbeiioid cells. Certainly the lymph serves the purpose of diluting 
the chemical substances produced by bacteria or by necrotic tissue, and so 
lessens the injurious influences of such substances upon the tissues. PATHOLOGY So. 5. 
January 14, 1898. 
I shall speak to you this evening, gentlemen, concerning certain varieties 
of inflammation, especially those based upon the character of exudation. Be- 
fore I do this, let me say a word as to the meaning of "catarrhal inflammation" 
which you commonly meet with in your text books. This was a term introduced 
by Virchow to express an increased functional activity of mucous membrane, and 
is applied to mild inflammations affecting mucous surfaces. In the so-called 
catarrhal inflammations of mucous surfaces there is a certain amount of serous 
exudate which can easily make its way to the surface from the tissue beneath, 
since the mucous membrane has no such resistent layer of epithelium as that of 
the skin. Not only is there a certain amount of serous exulate making its way 
to the surface and flowing away, but the secretion of the glands is much in- 
creased, and added to this ere also leucocytes in small quantity. The ordi- 
nary mill inflammation of the mucous membrane of the nose, such as an acute 
coryza is usually nothing more than sn inflammation of this character; we 
also apply the term to certain miia inflammations of the mucous membrane of 
toe small intestine, especially where we do not understand very well the 
■J 
causation of these. Inflammations are very properly divided into certain 
classes according to toe character of the exudate: serous or ©edematous, 
fibrinous, hemorrhagic and purulent. These inflammations attended by a se- 
ll 
rous exudation are known as “serous inflammations" or “oedematous inflamma- 
tions", to tne next class Delong the “fibrinous inflammations", to the next 
“hemorrhagic inflammations", and to the last “purulent inflammations;" In 
other words, inflammations attended in the one case with a serous exudation, 
in the other with a fibrinous exudation, in the third a hemorrhagic exudation, I 2 
and in the last by a purulent exudation. Certain inilammationf, owing to the 
mild action of, or the prompt removal of the cause, amount to nothing more 
than.serous inflammations. Here we have tie connective tissue meshes filled 
with a fluid containing very little fibrin and comparatively few leucocytes. 
Inflammation of the skin, caused by exposure to the sun is a very good example 
of this form of serous inflammations. The exudate may reach the surface if 
it is in sufficient quantity and the oau&e continues, and elevate the epitheli- 
um iu the form of blebs or blisters. If an individual with “sunburn” re- 
mains in doors, or covers the surface very promptly, this fluid may be absorb- 
ed and disappear, even without a rupture of the vesicle or bleb. These are 
the mild inflammations. We may find in the periphery of a boil for instance, 
meshes of the tissue filled with a serous, exudate, so that by pressing the 
finger one may be sole to make a pit in tpe part. Instead of calling this an 
oedematous or serous infianimation, it is more proper to speak of it as an 
“inflammatory oedema”. Certain other inflammations owing to the cause being 
continued, or owing to the particular specific cause, are attended with a 
fibrinous exudate. In all inflammations there is s certain amount of fibrin. 
In certain infiaffiliations, especially inflammations due to certain bacteria, 
the amount of fibrinous exudate is considerable. Her instance the diplococcus 
lanosolatus produces generally a fibrinous exudate, inflammation of the'lung 
produced -by this organism is attended by the outpouring•of .an exudation'ex- 
ceedingly rich in fibrin. This * microorganism may also cause, as I have al- 
ready told you, such a fibrinous exudate on the mucous surfaces of the.throat. 
Here there is a certain amount of necrosis of the surface epithelium, and the 
exudation coming-in contact with the necrotic cells, fibrin is found in large amounts and deposited upon the surface of tie tissue, "ibis inflammation is 
known, as I have heretofore told you, as“diphtheritio inflammation.” We have 
an inflammation produced by the diphtheria bacillus (Klebe- Lceffier) which is 
a typical fibrinous or diphtheritic inflammation, formerly, a difference was 
made between an inflammation attended by croupous exudate and a diphtheritic 
exudate. That is, if the exudate could be removed, from the mucous membrane 
without causing any hemorrhage, could be polled from the surface, it was des- 
ignated croupous inflammation. If it oould not be so removed, but its removal 
was attended by more or less hemorrhage from the surface, it was designated 
as diphtheritic - inflammation. Now it so happens that this depends upon the 
anatomical character of the mucous membrane, and there is really no difference 
in the character of the exudate in these two forms, the croupous and diphthe- 
ritic. If a fibrinous inflammation affects the larynx or the trachae, a mu- 
cous membrane which has a distinct limiting basement membrane, then the exudate 
can be removed, but we remove the epithelium with it. The idea that the epi- 
thelium was left behind undisturbed is known no longer to be true. In both 
cases the epithelium of the surface is removed. In the one case, where we 
have the basement membrane, 'it is readily lifted-off, but in the other case 
f 
where there is no basement membrane, as on the tonsil or the palate the fi- 
brinous exudate is intermingled with the membrane - below and cannot be easily 
removed. There should no longer be any distinction made between croupous and 
diphtheritic inflammation. Inf1amstions attended by a fibrinous exudation 
also affect'serous surfaces, Se have more or less of a fibrinous exudate in 
ail forms of acute pleurisy, pericarditis, and in many of the forms of perito- 
nitis. If the exudate contains a considerable Quantity of red blood cells, then it is spoken of as ,g £orffi q£ inflaMation is 
found especially in certain animals inoculated with the bacteria of the hem- 
orrhagic soeptoo semia group, and occurs in individuals with certain consti- 
tutional conditions, such as scurvy and purpura haemorrhagica- some constitu- 
tional condition, the nature of which is not known, but probably involves 
some change of structure of the minute bloodvessels (their walls) by which 
there is a great dianedesis of the red blood cells, ibat form of inflammation, 
known as purulent inflammation, is the one of most importance. We may by pro- 
longing tHe duration of the cause produce either a serous or fibrinous, or 
hemorrhagic exudate, such as the application of varying degrees of heat to the 
rabbits ear, or varying degrees in the concentration of the croton oil solu- 
tion. We can produce either serous, fibrinous or hemorrhagic inflammation, 
but we cannot produce a purulent inflammation in this way. mis is the form 
of -inflammation that is more especially <xt tended by tbs presence of bacteria. 
This is the inflammation in which there takes place within the tissue an 
udate rich in leucocytes. It may simply infiltrate the meshes of the tissue, 
as in a serous inflammation, or it may be distinctly limited, coniined to 
hollowed space in toe tissue, and then constitute an abscess. The exudate in 
serous inflammation does not seem to produce any particular harm in the tissue, 
except by pressure if it becomes excessive, i/ot so with the purulent exudate. 
This has s decidedly harmful effect upon the tissue,causing the destruction of 
the cells of the part, and dissolving the intercellular substance also, and it 
becomes very often necessary to relieve the part by operative procedure where 
the purulent exudate is excessive. The spread of the abscess is only arrested 
by the proliferation of the tissues about it. If an abscess is to be arrestee, then the cells of the tissue in whioh it lies must undergo proliferation, 
and form a distinct limiting boundary to the abscess, ‘ibis limiting membrane 
is often spoken of as “.pyogenic membrane". It consists of young connective 
tissue cells with newly formed bloodvessels; has rather a smooth, velvety ap- 
pearance when it is exposed. Regarding some of the influences which modify 
inflammation as‘a whole; in the first place, if the part affected by inflam- 
mation is deprived of its proper blood supply, if it is anaemic, any inflam- 
mation produced in such a part will run a severe course. In order that any 
part of the body should perform'its normal functions, there must be a normal 
supply of bicoa brought to toe part under normal pressure, and a normal sup- 
ply carried away from the part, do that if toe vessel is constricted, and 
the part is rendered anaemic its vitality is lowered, and any inflammation of 
such a tissue runs a severe course. It has also been found that the too free 
supply of blood to the part exercises an unfavorable influence. Experiment 
has been made by inflaming the ear of a rabbit on the side on which the sym- 
pathetic nerve has been cut, and this compared with inflammation induces in 
the normal ear. It has been found that the inflammatory disturbance runs a 
severer course in the hyperaemic ear. Then again, it has been found that in* 
f 1 animations run a severer course in those parts of the body which are in a 
state of passive congestion, in which the outflow of blood from the psrt has 
been interferred with. In cases of certain of the infectious diseases, in 
which the patients lay upon the oack, typhoid fever for instance, in which 
the base or lower portion of tee lung becomes very much congested, any in- 
flammatory irritant reaching this part of the lung is apt to set up a severe 
infl summation. Inflammation affecting tne lower extremely in patients with chronic passive congestion from valvular disease of the heart attended with 
oedema of the lower extremities generally results in the formation of an 
ulaer, and runs an unfavorable course. Then again inflammations arising in 
patients subject to general anaemia, or patients suffering with diabetes mil- 
litus are very apt to terminate unfavorably. A simole furuncle which in a nor- 
mal individual is Quite limited, may readily spread and form an extensive car- 
buncle- even be attended with fatal results in a diabetic individual. These 
are some of the most important influences modifying the course 01 inflammations 
Mow if a part has become inflamed and an exudate has taken place in that part, 
if the exudate is removed by means of the lymphatics and bloodvessels of the 
part we speak of that as healing by “resolution”. If the vessels of the part 
cannot bring about the absorption of the products of inflammation, then it is 
necessary that there should be a certain■amount of organization taking place 
in the exudate, and we speak of that as healing by ’organization”. In any in- 
flammation if the cause is removed promptly, the inflammation quickly subsides. 
The dilated vessels recover their normal caliber (size); the leucocytes cease 
to migrate and the stasis in the bloodvessels rapidly passes away. There is 
no trouble in the removal of the fluid portion of the exudate- this is readily 
taken up by the lymphatics and veins of the part. Those inflammations attend- 
ed with exudates rich in cells are those which undergo resolution with more 
difficulty. If the leucocytes are few in number they can also be readily 
taken up by the lymphatics. They can enter the lymphatics and so be removed. 
The fibrin contained in tne exudate may undergo a granular degeneration and 
also be removed by the lymphatics. If the cells, however are very numerous, 
such as we find in purulent inflammations, resolution , as a rule, does not take place. is I have said before, it becomes necessary often in such forms 
of inflammation to aid nature in the removal by means of an incision. The 
same occurs in certain inflammations of the pleura attended by an enormous 
exudate in the pleural cavity. The removal of this exudate is more than the 
lymphatics can bring about and so it becomes necessary to remove the cause by 
onerative procedures. If the vessels of the part cannot remove the exuaate 
then it undergoes, as a rule, organization. A frequent form of this, is the 
organization of the fibrinous exudate on the serous surface of the pleura. 
?or instance we may find a considerable fibrinous exudate which the Lymphatics 
of the part do not remove, under these circumstances the young connective tis- 
sue ceils begin to enter into the exudate, young bloodvessels are produced 
from the old bloodvessels, loops of bloodvessels enter the exudate and in this 
way organization is affected and the exudate removed by the new bloodvessels. 
The same exudate is found on the opposite pleural membrane and when these two 
corns together organization -takes place; they become promptly united (adherent) 
and the cavity becomes obliterated. If the cells proper of the missus are de- 
stroyed in considerable amount, it becomes necessary to fill their pieces with 
new tissue. Here we nave also healing by organization. Take a case of de- 
struction of a minute portion of the cornea- if it is exceedingly small, the 
cells of tne cornea may undergo multiplication and repair the injury. If it 
is consider^1!ere or in any other tissue then the ceils which have been de- 
stoyed must be taken by new tissue and this tissue is particularly rich in 
young connective tissue cells and in young bloodvessels and is known as gran- 
ulation tissue. Later these bloodvessels disappear and when it occurs on the 
surface of tne body we designate it as “scar tissue77.. OEDEMA MD DROPSY 
The question of lymph-formation is so closely connected with that 
of oedema and dropsy that I propose to preface what I have to say of 
the latter with a brief consideration of the factors concerned in 
the former. 
Lymph-formation. There is constantly passing through the capillary 
walls into the tissues a certain amount of serous fluid, known asj.ymph. 
At the present time, two views are held as to the mode of lymph-forma- 
tion. According to the first view lymph is normally separated from the 
blood by a process akin to filtration, assisted by osmotic interchange } 
&f the due to chemical differences between the lymph and the 
blood-plasma; this we may des-igaat-s the physical bneory of lymph-form- 
ation. The opposite view, which is gaining in prominence and importance 
holds that normally the lymph is actively secreted by the endothelial 
cells lining ## the vessel-wall. This may be called the vital theory 
of lymph-formation. 
The physical theory of lymph-formation was elaborated by Ludwig and 
his pupils. They taught that the difference in pressure existing within 
the capillaries and in the lymph spaces that surround the capillaries 
is the essential condition upon which depends lymph-formation; thav as 
the result of this difference in pressure, a portion of the blood-plasma 
filters through the capillary walls and constitutes the lympn. The 
latter, therefore, was held to be a filtrate. Its quantity, £o a fil- 
trate, was looked upon as dependent necessarily upon the difference 
between intra and extra-oapillary pressure; and when, therefore, the 
capillary pressure was raised there was a corresponding increase in the outflow of lymph. !his factor, they considered, was to be seen 
in the larger amount of lymph-formation, which takes place when the 
venous pressure in a part is increased, further, tbs oedema seen in 
heart disease was regarded as a complete demonstration that increased 
transudation of lymph accompanies increased venous and capillary pres- 
ure. 
Notwithstanding that certain difficulties were found in this theory 
of Ludwig's,: such as the absence of increased flow of lymph from the 
fore leg of a dog 'whose bracheal plexus had been divided pleading to 
increased arterial dilatation, the latter further aided by stimulation 
of the cervical spinal cord; nor any increase of lymph flow from the 
hind leg after division of the sciatic nerve, in which, also, removal 
of peripheral resistance must have increased tne capillary pressure,^) 
this theory of lymph-formation continued to be almost universally held 
until figerstedt and Santesson, in 1885 and fieidenhain in 1891, brought 
forward experimental evidence which they regarded as incompatible with 
Ludwig's mechanical explanation. Heidenhain's experiments were of two 
kinds- In one series he altered the pressure relations in the blood ves- 
4 • ll I' 
s.els, and in the other he injected so-called lymphagogues into the blood- 
strearn*Without entering into the particulars of his experiments,it may 
be stated that although Beidenhain considered as certain that under 
some conditions increased pressure in the blood vessels leads oo in- 
creased lymph flow (as for instance when an increase of watery lymph 
from the throaoic duct follows legation of the portal vein), he aioO 
showed that the careful injection of substances, such as peptone, leech extract, musses extract, including crystalloids like glucose, chloride 
A 
of sodium, etc., without producing any rise in the blood-pressure, 
CL. 
would lead to the outpouring in the one case, of larger quantity of 
f\ 
concentrated lymph, and in the other, of an increased flow of watery 
lymph. This au# ke explained , in the first class of substances by 
their specific action on the endothelial cells, causing them to secrete 
an increased amount of fluid more concentrated than the blood plasma. 
In the second class of substances, he believes that the crystalloids 
having been excreted by the epithelial cells into the lymph spaces lead 
by osmosis to a flow of water from the tissue cells, and hence to an 
increase of watery Bamberger investigating the lymph that flowed 
from the cervical lymphatic of a horse, he horse’s head 
that when the ainmal was made to walk, 
A 
though at the same time the carotid pressure sank, the amount of lymph 
obtained was 3 to 5 times as great as when the animal was at rest. 
from these and ether results, he concluded that lymph-formation cannot 
be due to filtration, but is a secretory process, and that under normal 
conditions the metabolic products of the tissues are the stimulus which 
excites the endothelial cells of the capillaries to activity. The in- 
♦ 
vestigations of Lazarus-Barlow lead him to the conclusion that osmoses 
has no part in lymph formation, but that the lymph is formed by a secre- 
tory process, This observer showed that after injection of a crystal- 
loid into the blood, the increased flow of lymph did not correspond 
with the increased blood-pressure but continued for sometime after 
— /TV w ■P' v-i Pw>- . 
the blood had even fallen below normal, Se, therefore, see tnat this escape of fluid from the vessels, in the process of nutrition, is not 
it*-L' £w 
one of simple filtration, but there other factors which enter into the 
A A 
problem, and that at all events the capillaries walls must not be con- 
*mJ! 
sidered as lifeless membranes having no part in the process. 
The secreted fluid, mingled with the waste products cf the tissues, 
is absorbed by the lymphatics and returned to the veins by the ductus 
thoracicifcs. If the quantity of fluid transuded is more than can be 
carried away by the lymphatics and blood vessels, it accumulates in the 
meshes of the tissues and cavities of the body. This condition is des- 
ignated dropsy. 
Tie*tern* oedema is applied to the accumulation of serous fluid in the 
tissues, particularly in the meshes of connective tissue. Subcutaneous 
oedema, extending over the greater part of the body, receives the tame 
A 
anasarca. Dropsies of the serous cavities are designated by prefixing 
hydro to the cavity affected: thus hydro-thorax, hydro-pericardium, hydro- 
peritoneum, or ascites, and hydro-cephalus. An accumulation of serous 
fluid in the tunica vaginalis testis is called hydrocele. (Accumulation 
of serous fluid in glands and canals, the outlets of which are obstructed, 
for example in the fallopian tube, (hydrops tubae) and in the gall blad- 
der, are to be distinguished from the real dropsical effusions, although 
the appearance of the fluids may be similar.) 
Although the terms transudation and exudation may be used synonymously, 
CL 
it is better to Ripply the former to dropsical effusions and the latter 
A 
to inflammatory products. The dropsical transudate collects first in 
the mesRhes of the tissue as free fluid, and may afterwards soak into the the tissue fibre and cells, causing spelling of these and the forma- 
tion of vacuoles due to the presence of drops of fluid within the 
cells. 1'his is most often seen in glandular epithelium, but may 
also be found in muscle fibres. 
Tissues which are oedematous appear swollen, the amount of swelling, 
however, being dependent largely upon the structure of the tissue, The 
skin and especially the subcutaneous connective tissue is able to take 
into its meshes large Quantities of fluid, and hence an extremity may 
become enormously swollen. It will then be pale, present a doughy 
feeling and will pit on pressure. An incision sets free an abundance 
of clear liquid and the tissues are seen to be thoroughly saturated with 
fluid. The internal organs are less capable of retaining fluids, although 
the lungs can contain considerable in its numerous air-sacs. Open section 
of an oedematous kidney, its surface will appear moist and glistening, 
although little fluid will escape. 
Character and composition. Dropsical effusions are generally clear, 
colorless or slightly yellow, and of an alkaline reaction. Ihey may be- 
st ained by an admixture of blood or biliary coloring matter. 
The composition of fluids, speaking generally, is the same 
as that of blood-plasma, excepting that it is more dilute. Instead of 
containing 91 per cent of water, as does blood-serum, dropsical fluids 
contain 98 per cent, or more. The amount of salts in both is about the 
same, but they differ as to the relative amountof protein which they con- 
tain. In this respect dropsical fluids resemble lymph, but they contain 
a greater amount of proteid than ordinary lymph; and even in those oases where the fluid contains the least amount of proteid, there is usually 
enough present to convert the fluid into a solid mass on boiling. The 
composition of dropsical fluids varies in the different forms of oedema. 
■Thus the fluid which exudes in parts that are the subject of venous 
congestion is of a lower specific gravity and contains less proteid than 
fluid which is poured out during an inflammatory process. In the former 
case the specific gravity will be, perhaps, 1008, and in the latter 1018. 
Moreover, in the same general disease and under similar conditions the 
per cent of albumen varies with the location of the transudation. They 
say be arranged in the following order, according to their richness in 
albumen. 1. Tunica vaginalis testis; 2._pleura; 3_perioardiun; 4,perito- 
neum; 5_sub-arachncid spaces; @-suboutaneous tissue. Dropsical effusions 
contain but few cells and very little or no fibrin. Microscopically but 
few leucocytes and red blood cells are to be seen, but occasionally the 
latter are present in considerable number. 
Varieties of oedema. According to their etiology we distinguish three 
(3( varieties of oedema. 1. Inflammatory; 2 mechanical; 3 cachectic or 
hydhtfemio. 
/A 
Inflammatory odema is that which occurs in the neighborhood of a focus 
of inflammation. It is often designated collateral oedema. The sudden 
oedema of glottis, or uVula, which sometimes accompanies inflammation 
of the fauces is a typical example of inflammatory oedema. Here the 
effusion is richer in albumen than in the dropsy of passive congestion 
or venous obstruction (mechanical dropsy). I have already emphasized 
the importance of the capillary endothelium in the secretion of inflam- 7 
matory lymph, and we have reason to believe that in inflammatory oedema. 
the same factor is concerned. Mechanical dropsy is due to some obstruc- 
of 
tion to the current blood in the veins. If the current is impeded be- 
yond certain limits, then the fluid part of the blood seeks a lateral out- 
let and escapes from the vessels. Mechanical dropsies may be general or 
local. The dropsy is general, when, in consequence of disease of the 
heart or lungs, the return flow of blood from the venae cavae is im- 
peded. Valvular disease of the heart is the most frequent of the gen- 
eral causes of mechanical dropsy. General dropsy is characterized by 
oedema of the subcutaneous tissues and transudation into the serous 
cavities. Good examples of local dropsies, due to mechanical causes, 
are the collection of fluid in the peritoneal cavity resulting from 
obstruction in the portal vein, as by cirrhosis of the liver (atrophic) 
or by thrombosis of the same vessel, and the oedema of an extremity from 
compression upon or thrombosis of its veins. 
Pathology of Dropsy. 
1 Mechanical Dropsy. The explanation usually given for the oedema 
consequent upon venous obstruction is, that it is due to increased fil- 
tration of serum from the blood, caused by the rise of intravenous and 
intracapillary pressure resulting from the obstruction. It seems, how- 
ever, that other factors may be concerned, as to the nature of which 
there is a considerable difference of opinion. The two hypotheses as 
to this form of oedema may be designated as the mechanical and vital 
or * Conheim attributed this form of oedema to increased 
raapiIl an y_ pressure combined with permeability of the capillary wall due to malnutrition. 
According to Hamburger and Lazarus- Barlow the chief factor in the 
oedema of venous obstruction is the increased secretion of lymph by 
the capillaries incited thereto by starvation of the tissues and by 
accumulation of waste metabolic products. 
Recording to Welch the important factors are : 
1. Increased intravenous and intr&oaplilary pressure with consequent 
increased transudation of serum (not alone sufficient since tying of the 
femoral vein generally causes no oedema.)- 2. Increased permeability 
of the capillary walls, which may be due to stretching by the larger 
quantity of blood, and starvation of the oanillary endothelium from 
lack of fresh supply of nutriment and oxygen. 3. Diminished absorp- 
tion of lymph from lack of muscular movement, from imbibition of the 
capillary walls with fluid, and especially as the resultAretarded capil- 
lary and venous flow. 4. Sometimes a watery condition of the blood 
rendering it easier of filtration. He should not leave out of consid- 
eration, as one of the important factors, the probable increased se- 
cretory action of the endothelial cells due to accumulation of waste 
products in both blood and tissues. 
2. Hydraemio or oaoheotio oedema has generally been atributed to 
an impoverished and abnormally watery condition of the blood. 
It was formerly believed that diminution of the solids of the blood 
as well as retention of water in the blood could be the immediate 
cause of increased transudation from the bloodvessels. It was sup- posed that the vessel walls behaved like animal membranes and allowed 
fluid poor in albumen to esoape more readily than a fluid rioh in al- 
bumen. In this conception, the vessel walls are considered as life- 
less animal membranes, having no part in the passage of fluids from 
the vessels, fie have repeatedly stated that such a view is entirely 
erroneous, and that the vessel wall must be considered as a living 
organ, having an important function to perform in the secretion of 
lymph. The experiments of Oonheim and Litcheim have shown that when 
the vascular wails are healthy, the injection of large Quantities of 
salt solutions into the bloodvessels of animals causes no increased 
transudation in the situation in which dropsy occurs in man. We are, 
therefore, compelled to assume thet hydraemic or cachectic dropsy is 
due to some change in the capillary walls. Whether this alteration 
consists in increased permeability of the capillary walls or increased 
secretory activity of the capillary endothelium brought about by toxic 
products in the blood, or waste products held in the tissues, can- 
not be definitely stated. The most important cause of hydraemic 
dropsy is Bright's disease, though this form of dropsy may attend 
other cachectic conditions, such as tuberculosis, cancer, chronic ma- 
laria and chronic dysentery. .This form of dropsy is prone to appear 
in dependent parts of the body, and where the connective tissue is 
particularly lax in texture, as in eyelids and about the genitals. 1 
THROMBOSIS. 
jf is usually defined as a blood ooagulum formed in 
the heart or vessels during life- it may be more broadly defined 
as a solid mass or plug formed in the living heart or vessels. 
This latter definition gives due prominence to the participation 
of platelets and leucocytes in the formation of the thrombus. 
Structure. The elements which enter into the formation of fresh 
thrombi are blood-platelets, fibrin, leucocytes and red corpuscles. 
According to the varying number, proportion and arrangement of these, 
is due the diversity in appearance and structure of thrombi. The 
red and the white are the main anatomical groups of thrombi. Many 
of the mixed thrombi may be regarded as a variety of the white throm- 
bus. Red thrombi are formed from stagnating blood and consists of 
fibrin, red and white corpuscles in the same proportion as occur in 
the circulating blood. Most thrombi are formed from the blood in 
motion and are white,or mixed white and red. The white color is due 
to the presence of platelets, fibrin and leucocytes, singly or in 
combination. The admixture of red corpuscles is not an essential 
character of the thrombus. Microscopically, fresh white thrombi con- 
sists of a granular material, usually in island or strands of various 
shapes and size, fibrin, leucocytes and a larger or smaller number of 
entangled red corpuscles. The granular material is derived chiefly 
from altered blood platelets. 
As to the exact manner of the formation of the thrombus, it was 
generally believed that the coagulation of the fibrin was the primary and essential step. 
Zahn taught that the first step, after injury of the vessel 
wall, was the accumulation of leucocytes at the damaged point, 
followed by the formation of fibrin. More exact and later studies 
would seem to show that the white thrombus starts with an accumulation, 
not of leucocytes, but of blood platelets. 
iberth and Schimmelbusoh have snown that in the mesenteric vessels 
of the dog, the first step consists in the collection of blood plate- 
lets at the seat of injury. These platelets, in consequence of their 
viscous metamorphosis, at once become adherent to each other and to the 
wall of the vessel and thus form plugs. Later (lomin. to half hour) 
leucocytes accumulate in large numbers followed by the formation of 
fibrin and the entanglement of red corpuscles. The platelets are be- 
lieved to be derived from disintegrating red corpuscles. The leuco- 
cytes accumulate, partly by reason of the sticky, projecting masses 
of platelets and partly attracted by ohemidtafi-tio influences. The 
fibrin is formed from disintegrating platelets and leucocytes. 
Growth, me t amor phi)stf and organization. 
A thrombus formed from blood in motion is at first mural or parietal! 
later, by increase it may fill the calibre of the vessel and become an 
occluding or obstructing thrombus. A primitive or autochthonous throm- 
bus may be the starting point of a fiflniiaufid or propogated thrombus, 
extending in the course of the thrombosed vessels and perhaps into com- 
municating Vessels. A continued thrombus is sometimes spoken of as 
a secondary thrombus. Thrombi are with rare exceptions (cardiac ball-thrombi) adherent to the wall of the heart or vessel. Their 
free surface is generally rough. The thrombus grows in length 
chiefly in the direction of the current of blood, but may grow in 
the opposite direction. The growing end of the thrombus is usually 
not adherent to the wall of the vessels and is in the shape of a 
flattened,blunt cone, A venous thrombus extends in the direction 
of the circulating blood,not only as far as the next branch, but 
frequently beyond it, in the form of a mural thrombus. At first 
the thrombus is soft and moist, but by contraction and extension of 
fluid it becomes more compact, drier, firmer and more granular in 
texture. 
The liquefactive softenings that may occur in old thrombi are espe- 
cially important. These may be simple or bland, septic or purulent, 
and putrid softenings. The simple softenings occur in bland thrombi, 
being especially common in globular cardiac thrombi. The interior of 
d 
these consists of a whitish or redish fluid derived from disintegra- 
* 
tion and liquefaction of the solid part of the thrombus and consists 
of necrotic, fatty leucocytes, albuminous and fatty granules, blood 
pigment and altered blood corpuscles. This softening, probably due 
to the action of some ferment, occurs in ordinary bland thrombi and 
is not generally supposed to be due to the presence of micro-organisms. 
Bacteria have been respectively found of late years in these thrombi, 
and possibly are more concerned in this softening than is generally 
supposed. 
Septic or purulent softening is a true suppuration due to the presence of bacteria, and is most frequently met with in infective 
thrombophlebitis. The suppuration is the result of the accumula- 
tion of leucocytes, which are attracted from the blood of the throm- 
bosed vessels and from the vasa vasorum and surrounding capillaries. 
Most frequently streptococci are present in the thrombus and in the 
walls of the vessel. 
Putrid softening is the result of the access of putrefactive bac- 
teria. Here the thrombus is dirty brown or green in color and of foul 
odoflf. 
White thrombi in veins, less frequently in arteries, may undergo 
calcification, forming phlebolith/s or arteriolittufs. They are gen 
orally spherical and lie loosely in the lumen of the vessel. Most 
frequently found in veins around the prostate and bladder in men, in 
the plexus pampiniformis of women, and in the spleen. 
The organization of the thrombus is one of the most interesting and 
important changes that take place, consisting of the substitution for 7u7 
thrombus of vascularized connective tissue. The thrombus behaves as a 
foreign body and takes no part in the change. It is gradually disin- 
tegrated and absorbed largely through the activities of phagocytes. 
The new tissue springs from the vessel wall, the tissue forming cells 
being derived from the endothelium and other fixed cells in the wall. 
Kew vessels spring from the vasa vasorum. The new tissue, rich in 
cells at first, afterwards becomes fibrous and contracted. 
Lacunar spaces between the thrombus and the vessel wall may become 
lined with endothelium and serve as channels for the circulating blood. Hew vessels in the thrombus may establish connection with the lumen 
of the thrombosed vessel, above or below the thrombus, or on both 
sides. The rapidity of the onset and the course of the organizing 
process, will depend upon the location of the thrombus, the condi- 
tion of the wail of the vessel, the state of the patient and the 
presence or absence of infection. In favorable cases the process 
may be well under way within a week. The diseased wall of the vessel 
. 
may be incapable of furnishing new tissue, as in aneurysmal sacs. The 
uyogenio bacteria prevents or delays the process of organ- 
A 
ization. This process is a proliferative angeiitis, and is the pro- 
cess which leads to the closure of a vessel after ligation. The form- 
ation of a thrombus is no assistance in securing obliteration of a 
ligated vessel. 
Etiology. (a) flowing and other irregularities of the circulation. 
Diminished velocity of the blood current is not by itself a sufficient 
cause of thrombosis. A stationary column of blood between ligatures 
antiseptically applied may remain fluid for weeks. Slow circulation in 
combination with lesions of the cardiac, or vessel wall, or with the 
presence of micro-organisms or other changes of the blood, is an effi- 
cient cause of thrombi. Whirling or eddying motion of the current 
such as occurs when blood enters into normally or pathologically dilated 
channels from narrower ones, or over obstructions, may be of more im- 
portance. Thrombi ascribed to slowing of the current, often combined 
with eddying motion of the blood, are designated stagnation thrombi. 
These are divided into two groups (a) those due to local circulatory disturbances, as from ligation, or partial compression of the vessel, 
or from circumscribed dilations, as aneurisms, and (b) marantic throm- 
bi resulting from weakened hearts action, with consequent feebleness 
of the general circulation. Virchow, who gave this name to thrombi 
complicating or following anaemic and cachectic states and general 
infective diseases (typhoid fever and general constitutional diseases) 
considered that a condition of marasmus, or great prostration was the 
underlying factor. While mechanical of the circulation 
in an important accessory factor, other factors, especially lesions of 
the walls of the heart or vessels, enter decisively into the causation. 
(b) Contact of the blood with abnormal surfaces.- Lesions of 
the oardiao and vasoalar walls. 
She influence of the endothelial lining of the blood is very impor- 
tant in maintaining the fluid state of the blood. This influence is 
partly physical and partly chemical. The smooth, non—adhesive character 
*tuC 
of the inner surface of the is the physical property which 
comes primarily into consideration. While foreign bodies such as threads 
or bristles with rough surfaces introduced into the vessels cause tnrom— 
bosis, perfectly smooth bodies, as glass balls, may be introduced with- 
out producing coagulation. 
Blood oolleoted in vessels lined with oil or vaseline, remains fluid 
for a long time. Mere oontaot, therefore, with a foreign surface does 
not suffice to induce clotting; the result depends upon the character 
of this surface. Changes which impair or destroy the smooth, non-ad- 
hesive surface of the normal inner lining of the vessels play an important part in the etiology of thrombosis, ihere is evidence 
that chemical influences may incite thrombosis, That necrotic en- 
dothelial cells may liberate fibrin-ferment is in accordance with 
both physiological and pathological observations relating to the or- 
igin of this ferment from dead or disintergrating protoplasm in gen- 
eral. 
Contrasting the effects of mere traumation with those of trauma- 
tism combined with infection of the intima, lends strong support to 
a belief in the participation of chemical substances in the causation 
of certain thrombi due. to internal lesions. This has been shown in 
the experimental studies of valvular lesions of the heart. Aseptic 
laceration of the cardiac valvesgenerally leads to but slight pro- 
duction of thrombi upon the injured surfaces. The same lesions com- 
bined with the lodgement and growth of pyogenic bacteria are generally 
attended by the formation of considerable thrombo^ifi-vegetations. 
Of the structural changes of the vascular and cardiac walls which 
cause thrombosis, the most important are those due to inflammation, 
atheroma, calcification, necrosis, tumors, compression and injury. 
Phlebitis must be considered as an important and common cause of 
thrombosis. Displaced from its position, for a while by Virchow's 
investigations, as the primary cause, and assigned a secondary place, 
it has of recent years through bacteriological investigations, especial- 
ly of so-called marantic thrombi of infective diseases come to occupy 
its former position of importance. The studies of Cornil and his pupils, 
Widal and Vaquez, have had a great influence in maintaining the doctrine of the mycotic origin of marantic thrombi and particularly that of 
primahy phlebitis as the cause of these thromboses. 
thrombosis occurs as a complication of various infective diseases: 
typhoid fever, influenza, pneumonia, acute rheumatism, erysipelas, 
scarlet fever, tuberculosis, syphilis &c. Likewise in chlorosis, gout 
leukaemia, senile debility, and chronic wasting diseases and cachectic 
diseasis, particularly cancer, thrombosis is a recognized complication, 
Virchow attributed their causation to enfeebled circulation. Impaired 
circulation cannot serve as a common etiological factor for tnis whole 
class of thromboses. While many appear during great debility, others 
occur when the hearts action is notably weak, 'Thrombosis may ensue early 
A 
in influenza. Many of these so called marantic thrombi are unquestionably 
of infective origin. The observations of Vaauez on phlebitis of the ex- 
tremities, and Widal's have demonstrated that bacteria are often pres- 
ent in these thrombi and in the adjacent vascular wall. Puerperal throm- 
bi and the marantic thrombi of pulmonary tuberculosis have furnished the 
largest number of positive results, but bacteria have been found in 
thrombi complioatitittor following typhoid fever, influenza, pneumonia, 
cancer and other infective and cachectic conditions. In only a few in- 
stances has the specific been present: more frequently 
secondary invaders, especially streptococci and other pyogenetic bac- 
teria have been found; so that the thrombosis is considered to be often- 
er the result of some secondary infection than of the primary one. 
Bacteria have also been found in cachectic thrombosis, and here again 
most frequently pyogenic bacteria. Flexner has shown the frequency of secondary infections in chronic diseases. The bacteria may enter the 
vessel wall from the circulating blood, or from without, through the 
vasa vasorum or the lymphatics. In many oases bacteriological exami- 
nation of the thrombi of infective and cachectic diseases have given 
negative results. In some of these, bacteria originally present, may 
have died out, or we may assume with the French writers that bacterial 
toxins or toxic products from other sources have caused the damage to 
the endothelial lining of the vessels. 
(o) Chemical changes in the blood. 
There seems to be no definite and constant relation between the amount 
of fibrin obtainable from the blood and the occurrence of thrombosis. 
Peripheral thrombosis is less common in pneumonia and acute articular 
rheumatism, both having high fibrin-content, than in typhoid fever and 
cachectic states having low fibrin-content. The belief that the liber- 
ation of fibrin ferment in the blood-stream is an important cause 01 
thrombosis, is based on the results of experiments which show that the 
injection of various substances into the circulation, such as laky 
blood, fresh defibrinatad blood, emulsions or extracts from lymphoid 
cells &o., may cause intravascular clotting. Just how the conditions 
set up in these experiments are analogous to those occurring in human 
beings, cannot be said; but they are probably exceptional. We lack 
satisfactory observations, in cases of thrombosis in human beings, 
of increase of fibrin-ferment in tie blood. Gonsiderable Quantities 
of fibrin-ferment, more than are likely to be liberated under probable 
circumstances in man, can be injected into the circulation without causing coagulation. Still it would be unreasonable to suppose that 
chemical changes in the blood are without influence upon the occur- 
ence of thrombosis in man. In infective and toxic conditions such 
changes are doubtless the,underlying factors. The circulatory dis- 
turbances and the alterations in the vascular wall, to which we at- 
tribute the production of thrombi are the result of the damage done 
to the heart and vessels by bacterial and other toxins. There is rea- 
son to believe that alterations in the formed elements of the blood, 
caused directly or indirectly by toxic substances, are of great signif- 
icance in the etiology of thrombosis. Since the platelets are probably 
cell derivatives, damage done to leucocytes and red cells may favor 
their production, and that in consequence of abnormal composition of 
the plasma, the platelets may more readily undergo viscous metamorpho- 
sis and form plugs. 
(d)Increase of blood platelets. Whether the occurrence of thrombosis 
can be brought into relationship with the increase of platelets in the 
blood cannot be stated. Muir's observations point to marked increase 
of these in chlorosis in which thrombosis is common. Several observers 
have found the number reduced in pernicious anaemia, which is rarely, 
if ever complicated with thrombosis. In febrile infections there is 
often a correspondence between leuoooytosis and the number of platelets. 
Thus in influenza, pneumonia, erysipelas, meningitis and septic infec- 
tions, the number of platelets is often increased; in severe oases 
sometimes diminished: whereas in enteric fever and malaria, the number 
is diminished. Hayem's observation of a rapid increase of platelets as a sequel of many aoute diseases is of interest in vies? of the 
greater frequency of thrombosis as a sequel than in the course of 
many aoute diseases. This was noted by Hayem after pneumonia and 
typhoid fever. Platelets are said to be often increased toward the 
end of pregnancy and after delivery. In cachectic conditions, in 
tuberculosis, and in states of bad nutrition, increase is the rule. 
They are said by Muir to be increased in spleno-myelogenous leukae- 
mia. Opon the whole there is much in support of the view that increase 
of platelets is an index of lowered resistance of the red corpuscles. 
While the foregoing statements need confirmation, attention cannot 
fail to be arrested by the parallelism, in many instances, between dis- 
position to thrombosis and increase in the number of platelets.: Al- 
though in others no such relationship is seen. The mere increase of 
platelets is insufficient to explain the occurrence of thrombosis, ie 
are brought back to changes in the vascular wall and disturbance of the 
circulation as the determinants of the localization of thrombi, whic.lf' 
we must recognize changes in the chemistry and morphology of the blood 
as important predisposing causes. 
Localization. Thrombosis may occur in any part of the circulating 
system. We distinguish arterial, venous, capillary and cardiac thrombi. 
(a) Arterial thrombi. {the majority of these are caused by some 
local injury or disease of the arterial wall, or by the lodgment of an 
embolus. Especially important are the thromboses of 
the brain, heart and extremities. Relation of arterial thrombosis to gangrene of extremities. 
Senile gangrene is caused either by embolism, which may lead to 
thrombosis, or by arterio-sohlerosis, usually associated with throm- 
bosis. Primary arterial thrombosis may occasion gangrene in various 
chronic and infective diseases. Many of these thrombosis are infec- 
tive in origin. We cannot say that all are caused by micro-organisms. 
Ihe action of infective agents in the causation of focal and diffuse 
diseases of the arteries is now admitted. It is reasonable to believe 
that arterial thrombosis complicating or following typhoid fever, acute 
rheumatism, pnuemonia, small-pox, &c. are often to be referred to an 
infected arteritis, I'he most frequent site of arterial thrombosis is 
in the extremities, and far more frequently in the lower than the upper 
extremity. Unlike venous, arterial thrombosis occurs as often on the 
right side as on the left. Other situations, more or less common, are 
the cerebral pulmonary, coronary of heart, mesentirio arteries and the 
aorta and its primary branches. 
(b) Venous thrombi. These may result from local causes, such as 
traumatic, compression, phlebitis, phlebo- sohlerosis, inflammation of 
surrounding parts, and connection of venous terminals with septic or 
gangrenous foci. Vascular thrombosis, due to general causes, are in 
the great majority of cases, situated in th:e veins. The greater ef- 
fectiveness of these general causes in the veins must be sought for 
the 
in special characters of the venous circulation. The slower mean 
speed of the blood; the low blood pressure; the flow from smaller into larger channels; the absence of pulsation; the presence of valves; 
fixation of the venous walls to the fasciae and bone; the existence 
of wide dilatations; the agency of muscular contraction; the composi- 
tion of venous blood, such as the higher per cent of Co all must 
come into consideration since they render the venous system more fa- 
vorable to retardation of the blood-current, and to damage of the 
vascular wall from impoverished and insufficient blood supply, or to 
prolonged contact of micro-organisms and toxic substances. That me- 
chanical conditions determine the localization of the majority of 
thrombi of infective, anaemic and chachectic diseases is shown by the 
preference of such thrombi for places where these conditions are in the 
highest degree operative. The tendency of venous thrombi to start from 
valvular pockets must be mentioned in this connection. Thrombi due to 
general causes, unlike those starting from septic foci, do not begin 
in the rootlits, but start usually in the main venous trunks of a mem- 
ber. Beginning in a medium sized vein, the thrombi may grow in a large 
vein, as from the femoral into the iliac and vena cava. The greater 
frequency of venous thrombosis in the left leg than in the right is to 
be attributed to the more difficult return flow from the former, due to 
greater length and obliquity of the left common iliac vein and its pas- 
sage beneath the right iliac artery. Mechanical disturbance of the cir- 
culation are not by themselves, alone, efficient causes for thrombosis. 
They simply make certain parts of the vascular system seats of election 
for thrombi. It is possible to exaggerate their function. The presence 
of micro-organisms may induce lesions of the vascular wall in any part of the circulatory system. 
(c) Capillary thrombi. Unless necrosis or gangrene of the tissue,, 
ensue, in which case, as in infarctions the capillaries are always 
plugged, the blood remaining fluid in the capillaries, even with ex- 
tensive venous and arterial thrombosis, fibrinous and hyaline throm- 
boses of capillaries occur in connection with the acute infective di- 
seases. 
(d) Cardiac thrombi. Post-mortem fibrinous clots must not be 
mistaken for true cardiac thrombi. The fresh vegetations of endocar- 
ditis, although generally not included in the consideration of cardiac 
thrombi still are genuine thrombi. Putting aside these vegetations, 
the conditions leading to cardiac thrombosis are different from those 
concerned in peripheral venous thrombosis. Cardiac thrombi are especial- 
ly connected with the diseases of the heart, lungs, arteries and kidneys 
in all of which, except pulmonary tuberculosis, venous thrombosis is un- 
common. Cardiac thrombosis is less apt to occur in typhoid fever, in- 
fleuenza and pneumonia, in which venous thrombosis is so important a 
complication. In cachectic states, especially phthisis and cancer, 
thrombi are often found in the heart, particularly when there is well 
marked fatty degeneration. The greater field for cardiac thrombi is 
afforded by diseases of the valves and walls of the heart, and especi- 
ally by dilation of one or more of its cavities, with cardiac insuffi- 
ciency; conditions in which peripheral venous thrombosis is not oosmon, 
/r 
unless in association with diseases known to dispose,\f the latter. 
I'ke Seats for oardiao thrombi are the auricular appendioies and the and the apices of the ventricles between the columnae comae. These 
recesses and pockets, in cardiac insufficiency offer the best condi- 
tions for slovfing of the blood-current. There is no actual stasis 
as is shown by the gray or reddish gray color of the thrombi. 
Globular thrombi are by far the commonest form of cardiac thrombi. 
They vary in size from a pea to a hazel-nut and may attain the size 
of a hen's egg. They are usually multiple; thin surface smooth or 
marked by lines or ribs, and their interior usually converted into an 
opaque gray or brownish red, grumous fluid, the whole resembling a cyst 
with puriform contents. The liquefaction is of the bland variety. 
These cysts, which have often very thin walls, rarely burst. Although 
no localized mural disease is to be seen with the naked eye beneath 
these thrombi, microscopically there is found degeneration of the epi- 
thelium. It is most exceptional for any organization to be found in 
these thrombi. 
The Mural thrombi found on areas of circumscribed disease of the heart 
wall, as on infarctions, fibroid patches, gummata, and in partial aneur- 
ism, are somewhat different. They may be identical in appearance with 
the globular cysts; but are often flat, or polypoid, stratified and 
more intimately incorporated with the heart wall. 
Apart from endocardial vegetations not much is known of infective 
thrombi in the heart 
Ball thrombi, loose in the left auricle, are rare forms of cardiac 
thrombi. Effects and symptoms. 1'he lesions and the symptoms produced by 
thrombi are due to the obstruction of the blood current caused by 
the thrombus and to the effects of the toxic and irritative sub- 
stances which may be present in the thrombus. ‘These vary with the 
functional importance of the part supplied by the vessel; with the rapid- 
ity, extent and completeness of the obstruction; with the location of 
the plug in heart, artery, or vein: with the size of the vessel; with the 
time consumed in establishing a collateral circulation, and with the 
nature of the thrombus. 
Arterial thrombosis.If colateral circulation can be readily estab- 
lished, an artery may be obstructed without any mechanical effects. 
In the cases of certain terminal arteries, as the brain, spleen and 
kidney, even with a slowly forming thrombus, a collateral circulation 
cannot be established. When an artery of the lower extremity is throm- 
bosed, unless collateral circulation is established the termination is 
in gangrene. 
Venous thrombosis. The direct effects of venous thrombosis are refer- 
able to the mechanical obstruction to the circulation and to the prop- 
erties of the thrombus. The free venous anastomoses in many parts of 
the body prevent any disturbance of the circulation of venous occlu- 
sion by benign thrombi. This is seen especially in the pelvic veins. 
A vein (renal for example) may be slowly plogged without harm. When its 
rapid occlusion would lead to serious results. Local dropsy, the con- 
■■ 
sequence of passive hyperaemia constitutes the characteristic symptoms of uncompensated and venous obstruction by a thrombus, just as local 
necrosis does that of uncompensated arterial thrombosis. $hen venous 
obstruction is extreme, diapedesis of the red cells may occur. Such 
hemorrhages are rare in peripheral venous thrombosis, but are common 
with thrombosis of the portal,mesenteric, cerebral, and retinal veins. 
In addition to these mechanical effects, so-called benign thrombi, 
often set up an acute inflammation of the venous wall and surrounding 
e» 
parts; or the inflammation may antedate the thrombosis. 
The explanation usually given for the oedema consequent upon venous 
obstruction, is that it is due to increased filtration of serum from 
the blood, in consequence of the rise of intravenous and intracapillary 
pressure resulting from the obstruction. It seems, however, that other 
factors may be concerned, as to the nature of which there is considerable 
difference of opinion. The two hypotheses as to the oedema of passive 
congestion are the mechanical and vital or secretory. Gonheim attrib- 
uted this form of oedema to increased venous and capillary pressure 
combined with increased permeability of the capillary wall due to mal- 
nutrition. According to Lazarus Barlow the principal factor in the 
oedema of passive congestion is the increased secretion of lymph by 
e(3 Dy starvation of the tissues and by aooumula- 
lion_of_waste metabolic products . According to $elch the important 
factors are (1) Increased intravenous and intra-capillary pressure, with 
consequent increased transudation of serum (not alone sufficient, since 
tying of the femoral vein generally causes no oedema.) (2) Increased permeability of the capillary walls, which may be due 
to stretching from larger content of blood, starvation of capillary en- 
dothelium from lack of fresh supply of nutriment and oxygen, and in- 
jury from abnormal composition of blood in anaemic, infective cachec- 
tic and constitutional diseases, or from inflammatory irritants, 
(3)- Diminished absorption of lymph from lack of muscular movement, of 
imbibition of the capillary walls with fluid, and especially of retard- 
ed capillary and venous flow. (4) Arterial dilatation from irritative 
or inflammatory influences emanating from adjacent thrombosed veins, 
probably also from the asphyxiated tissues, and acting either ciirecoly 
upon the arterial wall or directly upon vaso-motor nerves, or reflexly. 
(5) Sometimes a watery condition of the blood rendering it easier of 
filtration. EMBOLISM. 
Definition, ftelch defines embolism as the impaction in some part 
of the vascular system of any undissolved material brought there by 
the blood current. The transported material is an embolus. 
Varieties of emboli. Unless some special epithet be used, an 
embolus is generally understood to be a detached thrombus, or part 
of it, including under this designation endocarditic vegetations. 
Other sorts of emboli are fragments of diseased heart-valves, calcific 
masses, bits of tissue, tumor cells, par. each am a to us cells, animal or 
parasites, fat, air, pigment granules and foreign bodies. 
An important classification is into bland aseptic emboli, and 
toxic or septic emboli, 
Sources of emboli, Emboli in the lungs come from the systemic veins, 
the right heart, or the pulmonary artery; those in branches of the por- 
tal veins come from tke radicles or trunk of this vein; those in sys- 
temic arteries from the pulmonary veins, the left heart, or some artery 
between the heart and the location of the embolus. She continuation of 
an occluding venous thrombus in the form of a partly obstructing throm- 
bus beyond the entrance of an important branch, and the occurrance of 
softening in the interior of older thrombi, are conditions favorable to 
the detachment of fragments. Globular thrombi in the right heart, par- 
ticularly in the auricular appendix, are a fruitful source of the em- 
boli which cause pulmonary infarction in heart disease. Vegetations of 
the aortic and mitral valves, especially of the latter, furnish the 
great majority of the emboli in the aortic system. Sits of Deposit. Emboli are carried along by the blood-stream 
until they are caught on some obstruction, or become lodged in a 
channel too narrow tc permit their further passage. Very often 
an embolus is caught at a bifurcation, which it rides with a part 
extending into each branch (riding embolus). The course followed by 
an embolus is determined by purely mechanical factors, of which the 
most important are the size and weight of the plug, the direction, 
volume and energy of the carrying blood-stream: the size of branches 
and the angles at which they are given off; and the position of the 
body and its members. Henoe we find emboli in the lower lobes of the 
lungs oftener than in the upper; and in the right lung oftener than 
in the left, the right pulmonary artery being larger than the left. 
Emboli from the left heart are carried more frequently into the ab- 
dominal aorta and its branches than into the carotid and subclavian 
arteries. The left common carotid, which is in a more direct line 
with the aortic stream than the right, receives more emboli. 
Aberrant or paradoxical embolism, ‘this designation refers to the 
transportation of emboli derived from veins into the systemic arteries 
without passing through the pulmonary circulation. Oonheim was the 
first to note the passage of venous emboli through an open foramen 
ovale into the aortic system. 
Anatomical characters. In cases of recent embolism, the ping can 
generally be recognized as an embolus without much difficulty. Such a 
plug lies loosely or is but slightly adherent to the vessel wall. It 
often presents a broken or fractured surface, which sometimes may be the 
fit to corresponding surface of the thrombus from which it was 
broken off. After tue embolus has become adherent and surround- 
ed by a secondary thrombus, the diagnosis becomes more difficult. 
An adherent plug which rides an arterial bifurcation is much more 
likely to be an embolus than a primary thrombus. In reaching a 
conclusion, weight must be given to the condition of the arterial 
wall: whether there be any cause for thrombosis. The detection of 
the source of an embolus will be of importance. An embolus is the 
starting point of a secondary thrombus which usually, although not 
always, completes the closure of the vessel, if this had not already 
been done by the embolus itself, and extends on either side to the 
next vessel given off. The same metamorphoses and process of organ- 
ization with consecutive changes in the vascular wall, occur with em- 
boli and encapsulation thrombi, as already described for primary thrombi. 
Mfeots. Bland emboli produce--chiefly mechanical effects refer- 
able to obstruction to the circulation. Septic or toxic cause also, 
othar changes which may be described as infective or chemical. If an 
artery be closed by a bland embolus, the fate of the part supplied de- 
pends altogether upon whether it is fed within a certain time after 
the obstruction with anough arterial blood to preserve its integrity 
and function. If the vessel is not comnletely plugged by the embolus, 
there may be no appreciable interference with circulation, but the 
closure of the lumen is usually soon effected by a secondary thrombus. 
The occlusion by a bland embolus of an artery with abundant anastomoses 
such as the arteries supplying bone, the voluntary muscles, the skin, the thyroid, the uterus, usually causes no circulatory disturbance 
of any importance. Sudden death say result from embolism of the 
trunk or main division of the pulmonary artery, of one of the cor- 
onary arteries of the heart, or of arteries. If an ade- 
ouate collateral circulation be not established, tha part dies, This 
occurs regularly as the result of embolism of the splenic and venal 
arteries, of the basal arteries of the brain, of the central artery 
of the retina and of the superior mesenteric artery. It is the usu- 
al result of one of the coronary arteries of the heart, if the pa- 
tient live long enough: and it is the inconstant result of embolism 
of the medium- smaller branches of the pulmonary arteries, 
of cerebral arteries, other than the basal, and of the main arteries 
of the extremities. Ffhen tha dead part is so surrounded with living 
tissue that it can be permiated with lymph, as is usually the case in 
the viscera, the mode of death is that described by Weigert, and named 
by Gonheim “ooagulative necrosis”. Here the dead protoplasm and to 
some extent intercellular substances, undergo chemical changes, be- 
lieved to be in part ooagulative. If there be enough coaguable ma- 
terial present, the necrotic part becomes hard, dry, opaque and some- 
what swollen. An area of ooagulative necrosis resulting from cutting 
off the blood supply is an infarct, (inf arc to stuff). Its shape 
corresponds to that of the arterial tree supplying it and is, therefore, 
as a rule, conical or wedge shape, the base being towards the periphery 
of the organ . The wedge shape is most marked in smaller infarcts. 
The colol£ is opaqse, white or yellowish, unless hemorrhage is added to the necrosis. thus have anaemic, pale or white infarcts, and red 
or hemorrhagic infarcts; but in the latter, no less than in the former, 
the essential thing is the coagulative: necrosis, the hemorrhage being 
merely something added to the necrosis. In the kidney, the infarct is 
nearly always pale in the lungs and intestine, as constantly hemorr- 
hagic; in the spleen or heart it may be either white or red. 
Hemorrhagic infarction. The explanation of the accumulation and 
extravasation of blood in hemorrhagic infarcts has been the subject 
of much speculation and experimental study. Gonheim attributed the 
hyperaemia in the infaroted area to the regurgitant flow from the venis 
and that the red cells escape by diapedesis, due to some molecular 
change in the vascular walls deprived of their normal supply of nutri- 
ment. and Little have shown that the congestion and hyperaemia 
are not the result of regurgitation from the venis. In situations where 
closure of an artery is followed by hemorrhagic infarction, tying the 
veins also, so as to shut off reflux from the veins, only serves to in- 
crease the hyperaemia and hemorrhage, and may render an infarct hemorr- 
hagic which would otherwise be anaemic. If, on the other hand, all vas- 
cular communication of a part be cut off, except that with the veins, 
the part undergoes necrosis, without hemorrhagic infarction. It is then 
quite certain that the blood which accumulates in the capillaries and 
small veins and is extravasted in hemorrhagic infarction, comes in 
through the capillary, and if they exist, the arterial anastomoses, 
and is not regurgitated through the veins. The red corpuscles escape 
by diapedesis and not by rhexis. The diapedesis does not appear to be due to molecular changes in the vascular walls, but to the slowing 
and stagnation of the blood and to the blood pressure- without a 
certain height of pressure there is no diapedesis; and with a given 
retardation and stasis of the blood-current, the higher the intra- 
capillary and intravenous pressure the greater the diapedesis. In 
general a high venous pressure favors hemorrhage in an infarction 
and a low arterial pressure opposes it. The studies of recent years 
upon the formation of lymph have shown that the blood-vessels in dif- 
ferent regions differ markedly as to their permeability, those of the 
intestine being probably the most permeable. This difference in per., t 
meability may be an important factor in determining diapedesis. How- 
ever, the greatest influence seems to be exercised by the resistance 
offered by the tissues to the escape of red corpuscles from the vessels, 
as pointed out by Weigart. Where this tissue resistance is low, as in 
the lung and in the mucosa and submuoosa of the bowel, hemorrhagic in- 
farction especially occurs. The resistance offered by the firm con- 
sistence of the kidney, is increased by the swelling and hardness result- 
ing from coagulative necrosis of the epithelial and other cells, and 
hence kidney infarcts are nearly always anaemic, although often hemorr- 
hagic at their margins. 
Metamorphoses of infarcts. A bland infarct is a foreign body, most 
of the oonstitutents of which ar capable of absorption and replacement 
by connective tissue. The red corpuscles lose their coloring matter, 
some of which is transformed into amorphous or crystalline haematoidin. 
Polynuclear leucocytes wander in from the margins; many undergo nuclear fragmentation.. This nuclear detritus mingles with that de- 
rived from the dead cells of the part. Granulative tissue develops 
from the living tissue around the infarct. In the course of time, the 
debris which becomes very fatty, is disintegrated and removed: new, 
vessels and new connective tissue grow in, and finally a scar marks 
the site of the infarct. 
Infective emboli. On account of their frequency and serious oonse- 
.are of 
auenoies, infective emboli containing pathogenic bacteria^especial sig- 
nificance. Such emboli constitute an important means of distribution 
of infective agents from primary foci of infection to distant parts of 
the body where the sain organisms multiply and by their chemical products 
A 
continue to show their specific activities. These emboli are often de- 
rived from infective venous thrombi, connected with some primary area 
of infection. The portal of infection may be through the skin, the 
alimentary canal, the respiratory, the genito-urinary passages, the 
middle ear, or the eye, with corresponding infective thrombophlebitis 
in these several situations. Or there may be, as in many oases of in- 
fective endocarditis, no demonstrable portal of infection. Coarse em- 
boli are by no means essential for causation of infective metastases, 
nor is it necessary that there should be any thrombosis to afford op- 
portunity for the distribution of micro-organisms from a primary focus. 
Bacteria may gain entrance to the circulation singly or in clumps; and 
such bacteria, without being enclosed in plugs of even capillary size, 
may become attached to the walls of capillaries and small vessels and 
o- 
produce local metastasis. In this way infective material coming from the systemic veins may pass through the pulmonary canil-laries without 
damage to the lungs, and become localized in various organs of the 
body. In explaining the various localizations of the infective pro- 
cesses in the organs of the body, we must not rely wholly on the 
mechanical distribution by the circulation, but must consider the vital 
resistance of the tissues, which varies in different parts of the body. 
Infective emboli are capable of producing all of the mechanical ef- 
fects of bland emboli, to which are added the specific effects of the 
micro-organisms or their products. These latter effects are essentially 
chemical in nature, the most important of which consist of hemorrhages, 
usually of small size, and of an entirely different causation from those 
of hemorrhagic infarction: necroses; inflammation, often suppurative in 
character; and in case of putrefactive bacteria, gangrenous putrefaction. 
The most important function of infective embolism is in the causation of 
pyaemia. D1G1/81RATI0H. 
(1) Cloudy swelling . Granular degeneration, or parenchymatous 
degeneration. This was a term"applied by Virchow to cells which 
had become enlarged in size, as he thought, by increased nutri- 
tion, or to cells that had become hypertrophied and showed a ten- 
dency to degeneration. The process is to be regarded as one of 
degeneration in the cell protoplasm. This change consists in the 
appearance in the cells of abundant albuminous granules. Especially 
subject to this alteration are the muscular fibres, such as those 
of the heart, and the parenchymatous cells of glandular organs, such 
as the liver and kidney. The affected car os appear swollen and of n 
grayish color, giving an opacity as if the tissue had been subjected 
to contact with boiling water. It is best seen in tne cortex 01 the 
kidney in patients that have died of one of the acute infections. 
The minor details of the structure are obsSwed-. On microscopical 
A. 
examination the cell is filled with numerous fine granules which 
hide the nucleus., Upon the addition of acetic acid these granules 
disappear and the nucleus may then be seen. They are insoluble in 
caustic potash, or ether. 
In cloudy swelling of the heart muscle, the muscle fibres contain 
these albuminous granules which obscure the normal striation of the 
fibres. Cloudy swelling sometimes passes into fatty degeneration of 
the cell. The process is to be regarded as a disorganization of the 
cell protoplasm, following the absorption of liquid into its substance 
and leading to a partial separation of its solid and liquid constituents 'i:he nucleus may undergo the same change. 
Recovery from a moderate degree of this degeneration is quite 
possible, in which case the cell is restored to its normal condi- 
tion; but after there is a complete destruction of the cell, which 
then breaks up into fine granular fragments. 
Cloudy swelling occurs especially in connection with the acute in- 
fectious diseases, such as scarlet fever, typhoid fever, small-pox, 
pneumonia, diphtheria, erysipelas, septecaemia, &c. It occurs also 
in poisoning with arsenic, phosphorous, and the mineral acids. 
It has been developed within six hours after extensive burns. Cloudy 
swelling is sometimes combined with a dropsical degeneration (hydropic 
degeneration), due to a swelling of the cells from the absorption of 
liauid. from the absorption of the fluid the contents of the cell ap- 
pear clear, and the nucleus and protoplasm are pushed to one side, 
sometimes vacuoles appear in the cell, Buch changes in the cells are 
found in oedematous tissue, in inflammatory foci and in tumors. DISORDERS OF THE HEPATIC CIRCULATION. 
Congestion of the liver say be either active or passive. Active con- 
gestion is caused by an increased flow of blood to the liver through the 
hepatic artery or the portal vein. Passive congestion is the result of 
some obstruction to the outflow of blood from the hepatic veins. 
Active congestion of the liver occurs during digestion and is a physio- 
logical condition. It also occurs in the early stages of inflammatory affec- 
tions of the liver and in diseases that determine an increased flow of blood 
to the intestine and is then pathological. Active congestion quie&Ly passes 
away with the removal of the cause. 
CHRONIC PASSIVii CONGESTION. 
This is a well defined condition, the causation of which is understood, 
it is due to any interference with the outflow of blood from the liver. 
Anything which obstructs the current of blood through the hepatic veins, 
through tne inferior vena cava above the entrance of the hepatic vein$,thro* 
the lung or through the heart causes passive congestion the liver. The 
obstruction is usually seated either in the heart or in the iangs. 
The various forms of uncompensated valvular lesions of the heart, particu- 
larly mitral ana tricuspid lesions, insuffienoy of the power of the 
hearts action due to myocarditis ana obstructions in the pulmonary circu- 
lation, such as those resulting from emphysema,Iibroida*Iiidapation of the lung are toe most frequent causes of chronic passive congestion. Tumors of 
the mediastinum and aneurism may bring about this condition. 
In consequence of the damming back of blood upon the hepatic veins, the 
central veinsof the lobules first, and then the lobular capillaries imnie- 
dlately surrounding these veins become iiMed with blood. In advanced stages 
A 
of the disease all of the capillaries are affected. As a result of the dis- 
tension of the capillaries the hepatic cells become compressed and undergo 
7tc 
atrophy, especially those at the centre of ihe peripheral ceils may 
show fatty degeneration. Yellow or brown pigment granules are often found in 
the liver cells. In later stages of the disease the central ceils entirely 
disappear and all of the cells of the lobule may disappear. This advanced 
condition is designated red cyanotic atrophy. Cyanotic atrophy is often 
associated with more or less increase of interlobular connective tissue. 
In the early stages of me disease the liver is enlarged; in later stages 
the organ may be reduced in size and its surface may be uneven and granular. 
Upon section of the liver dark red points are observed surrounded by light- 
er areas, the red portion representing the central veins and the lighter part 
the periphery of the lobule, constituting the so-called nutmeg liver. nm ISPILTRAl'IOH AKD PA'I'iY DEGERIRAilOS OP MB LIVER. 
These are not conditions which one can diagnose clinically, but as Students 
of Pathology you should be acquainted with some of the conditions which lead 
to fatty infiltration, as well as to fatty degeneration of the cellular oon- 
stitutents of organs. Under normal conditions fat is found in various local- 
ities in the body, chiefly in the subcutaneous connective tissue, or beneath 
certain serous membranes, as beneath the visceral pericardium, between the 
layers of the mesentery, in the omentum, in bone marrow and In the liver. 
Physiologists tell us that tne fat found in the body is derived from three 
sources: 
1. Prom the ingestion of foods containing fat. 
2. Prom the carbohydrates. 
3. Prom albuminous foods. 
So that fat may be introduced either as fat already, or as carbohydrates or as 
albumin. Formerly it was not thought that an albuminous diet led to the pro- 
duction of fat, but now physiologists consider this an important source of 
f at. 
The protoplasm of the cells of the body (liver cells for example) can 
take such complex bodies as albumin and carbohydrates from the blood and con- 
vert them into a simpler body f at,{previdea the protoplasm of the cells is 
of food . 
in a healthy condition.) If the assimil not in excess of the ability 
of the body to make use of it, then fat will be found in moderate amount in 
such locations as have already been mentioned. u* however there is an over consumption of fat, or substances that can be 
converted into iao, and at the same time, if the metabolic activity of the 
cell is lessened so that it cannot further decompose the fa_t elaborated from 
i/us albumen brought to it, then there will be an acoumuiation of fat greater 
than should occur in the ceils of the organ. If these two conditions act to- 
gether the effect will be the greater. 
under these oiroumst8Do.es we may have fat deposited in large quantities in 
the, subcutaneous connective tissue; in excessive quantities about the heart, 
under the visceral pericardium, between it and the myocardium; it may even be 
deposited between the fibers of smooth musole(heart muscle for instance) and 
between the fibers of voluntary muscle, these being situations where, normally, 
we do not find fat. 
This condition is ordinarily described as obesity or lipomatosis, and may 
be so excessive ss to constitute a pathological condition. Over consumption 
of food, lack of exercise and indulgence in alcoholic drinks lead to the ac- 
cumulation of fat within the oelis of the fiver, where it is normally found- 
in small amount. 
Under these oiroinstances the liver cells are found to be the seat of con- 
siderable deposition of fat, and we speak of this condition as fatty infil- 
tration of the liver. 
fatty Degeneration.- As contrasted with fatty infiltration, which may net 
be pathological, there is the condition of fatty.degeneration of cells. Here 
the fat is produced, not from ordinary albumin that is taken in the process 
of nutrition, but at the expense of the protoplasm of the cell itself. The 
albumin in the protoplasm of the cell itself is used up and becomes changed 3 
into minute drops of fat. In fatty degeneration of a oell not only does its 
protoplasm beoome converted into fat, which is deposited generally in the 
form of small drops of varying size, but even the nucleus may be destroyed and 
disappear, provided the condition is one of complete fatty degeneration of the 
ceil. 
Fatty degeneration points very plainly to a lowered vitality of the cell, 
as well as to a changed composition of the blood itself. It is generally con- 
ceded that a diminution of the supply of oxygen to the cells plays an impor- 
tant part in the production of fatty degeneration. 
Now, there are various conditions which cause a diminution of the oxygen 
carrying capacity of the blood. In general anaemia in which disease the haem- 
oglobin of the blood is reduced, unci cor.seqentiy its oxygen- carrying capacity, 
we find_|atty degeneration of the ceils of various organs, muscles which have 
been forna long time paralyzed, undergo various degrees of fatty degeneration- 
a fact which points clearly to diminished oxidation. 
„ . . . sin . . 
Id chronic pulmonary tuberculosis, where tnere isAextensive aestruction 01 
the lung sabstanoe and henoe diminution in the oxygen-carrying capacity of the 
blood, we have a condition productive of fatty degeneration. Sudden hemor- 
rhage, sudden extensive hemorrhage may cause a marked fatty degeneration of 
ceils. Ziegler refers to sudden blindness, which sometimes occurs soon after 
an excessive hemorrhage, as being due to a fatty degeneration of the cells of 
the retina and of the optic nerve. 
Then again certain poisons lead to fatty degeneration of cells. Phosphor- 
us is one of the most important. If a dog is fed from ten to fifteen days 
with large quantities of phosphorus in his food, at the end of that time ex- 4 
treme fatty degeneration of the liver will have taken plaoe. Iodoform, arsen- 
ic, the mineral acids and many of the toxic substances produced oy bacteria 
and fever bring about fatty degeneration. If to a fresh section of the liv- 
er acetic acid is added, it brings out the fat very plainly; if ether is added 
the fat drops are dissolved. If the section is hardened in chromic or osmic 
acid then the fat drops are stained very darkly. 
It is not always easy to determine between fatty infiltration and fatty de- 
I ‘ 
generation. In the first place, if you find fat droplets in smooth muscle, 
or in heart muscle, or in striated muscle, you would know that this was fatty 
degeneration, because fat has no business here. Ordinarily in fatty infiltra- 
1 arge 
tion tne. a roc is quite 1 arse, a sin?ieAaroc: and but a small uart of the cells 
are affected. One must be governed by tne size of the fat drops, which are 
generally larger in fatty infiltration. In fatty degeneration the fat is de- 
posited, as a rule, in small drops, sometimes in excessively minute droplets, 
but at least in small drops of irregular size, and these are distributed uni- 
formly over the cell. One may still find the nucleus or this may have dis- 
appeared. If you find a great number of small drops in the cell and the nu- 
cleus has disappeared you are justified in pronouncing this to be fatty de- 
generation. 
The number and size of the fat drops in a oell, the seat of fatty degen- 
eration, vary, but in general the drops are very much smaller than we find 
them, where they have oeen deposited in the course of normal nutrition (fat- 
ty infiltration). AMYLOID DEGENERATION. 
0-v ?TcZ/& l/^4si^c/4_ 
There is deposited under certain conditions, a peculiar substance, which 
A " 
is called amyloid. It is quite insoluble and remains permanently, not being 
afterwards absorbed. It leads to permanent loss of functions of the organ. 
Virchow, its discoverer, found that it gave a peculiar reaction with iodine 
and sulphuric acid. When stained with iodine and afterwards treated with acid, 
it may give a blue color. On account of this reaction it was formerly sup- 
posed to be of a starchy nature, but it has since been shown not to be starch 
or cellulose, but a nitrogeneous substance, from its supposed relation to 
starch it was called Amyloid. The terms waxy and lardaceous are applied to 
this degeneration. 
Tfie organs ohiefly affected are the spleen, liver, kidneys, intestine, stom- 
ach, adrenals, pancreas and lymphatic glands, the frequency of attack being in 
the order named. It may be also found in dated muscles, ovaries and 
uterus. 
It is deposited in the wail of the bloodvessels, especially in the middle 
coat of small arteries. It does not affeot the endothelium, ft is not de- 
posited in the muscle sells, but between them. It is also deposited in the 
connective tissue frame work of organs- between the connective tissue fibers. 
Though spoken of as a degeneration, it is not produced by a metamorphosis of 
the tissue, but is an infiltration which is deposited between the cells of the 
tissue. The situation of the amyloid in the walls of the bloodvessels would 
seem to indicate that it was formed in the blood and afterward deposited in 
the walls of the vessels. The amyloid itself is not, however, preformed in the blood but the material of which it is formed is derived 
from the blood. It is believed that it is derived from some albuminous materi- 
al of the blood, but as the result of the lowered metabolic power of the tis- 
sue, the substance thus derived cannot be converted, as under normal condi- 
tions, into nutritive matter, but lies in the tissues and undergoes change 
into the peculiar material called amyloid. This is the veiw held by Ziegler. 
This view receives support from tie fact that it is found in chronic diseases 
attended by lowered metabolic power of the ceils, lowered vitality, such as 
pulmonary tuberculosis, syphilis, chronic disease of bone (Potts’ disease of 
of the spine) and chronic suppurative processes. CIRRHOSIS CP THE LIVER. 
The term cirrhosis, signifyling a tawny or orange color, was applied by 
Laennec to the disease under ponsideration on account of the yellowish col- 
or of the nodules which the liver usually presents in this affection. These 
nodules were supposed by Laenneo to oe new growths replacing the original 
parenchyma, but are now knowp to be parts of the pre- existing 1iver-substanceJ 
As the essential change, however, was found to consist in the development of 
fibrous tissue, the term cirrhosis cams to be applied, not only to the liver, 
but also to the fibrous induration of other organs, especially of the lungs 
and kidney, although this applioation is etymologically incorrect. This di- 
sease is sometimes designated chronic indurative inflammation of the liver 
and chronic interstitial hepatitis. In using the term inflammation in this 
connection, it does not mean that the process is attended by the emigration 
of leucocytes and exudation of lymph. It should not, properly speaking, be 
designated an inflammation, since the essential change consists of an in- 
crease of the normal connective tissue of the organ. 
7"/z<l 
Gross appearances. ci^troni? iiver is usually small, but it may be of 
normal size or even enlarged. The surface is generally nodular, although it 
may be smooth. The nodules vary in size from a pins bead to a pea, and may 
be larger. In some oases the surface is finely granular; in others, coarse- 
ly nodular, the size of the nodules varying much in the same liver. The 
nodules are usually of a yellowish, or greenish color and consist of one or 
more hepatic lobules in which the liver ceils are fatty or bile-stained. 
The nodules are separated from each other by grayish-white bands of newly 2 
formed connective tissue. This nodulated appearance has given rise to the 
i 
term hob-nailed, as applied to some examples of cirrhosis liver. The con- 
A 
sistence of the liver is firm; sometimes very hard. The organ is resistent 
to the knife and the cut surface is dry and pale. 
Microscopic Examination. The most important change is an increase of 
the connective tissue, which, under the name of Glisson's capsule, accom- 
panies the medium sized and small branches of the portal vein. This increase 
of the interlobular tissue is not uniform, but is in the form of bands which 
surround, usually, a number of lobules. The new growth of connective tissue 
often invades the lobules and also appears around the central vein, so that 
the lobule may be split up into several parts by the fibrous growth. In the 
early stages of the disease the new tissue is rich in round cells, but later 
it becomes more fibrous. It invades the walls of xhe interlobular veins, sc 
that they lose their elasticity and many of them become obliterated. The 
bile ducts and branches of the hepatic artery suffer less from the compres- 
sion of the fibrous tissue than the thin walled portal vessels. Destruction 
of these latter vessels bring about some of the most important symptoms of 
cirrhosis, Atrophy of the liver lobules and destruction of liver cells is 
brought about by the growth of this new connective tissue. The atrophy of 
the liver cells has usually been attributed to the compression of the newly 
formed connective tissue, but an equally important factor is the interfer- 
ence with the nutrition of the ceils consequent upon obliteration of the 
interlobular veins. Toe hepatic ceils, wni'Ch remain, very oi ten contain fat 
drops. According to the views of Seigert, the primary change in cirrhosis 
is degeneration and necrosis of the liver cells, and this is followed 3 
by increased growth of connective tissue. With cur present knowledge of 
primary degeneration of epithelium in other organs, as the kidney, and the 
secondary growth of connective tissue consequent upon this destruction, it 
is impossible to deny the importance of these views of Weigert. In many 
cases of cirrhosis there are seen in the newly formed connective tissue, 
many narrow, often branching channels, consisting of a single, or double 
row of cubical epithelial cells and which resemble the interlobular bile 
ducts. There has been much discussion as to their origin, since they are 
too many to be simply nre-existing bile ducts. One theory is that they are 
rows of liver cells which have been altered in shape by the growth and pres- 
sure of the fibrous tissue. According to another, they are the intra-lobular 
capillaries which have acquired an epithelial lining. The third and most 
probable explanation is that they are really newly formed bile dr-cts-of f shoots 
five tissue 
iron the old bile-ducts ahiob penetrate the newly formed hyperplastic ©©i&ec-J 
There are two varieties cf cirrhosis- atrophic and hypertrophic. In both 
of these forms there is e marked increase in the connective tissue of the 
organ, but there is a marked difference in the relative situation of the con- 
nective tissue in these varieties and in the size of the organ. 
In the atrophic form, the connective tissue increase is chiefly about the 
portal spaces and in the interlobular region,and the liver is much reduced 
in size; in the hypertrophic variety there is a more diffused growth of fi- 
brous tissue. Kot only is it found between the lobules, but it, also, free- 
ly penetrates into the lobules, between the rows of liver cells and between 
individual cells. In this variety, although there may be some destruction 
of liver cells, the increase of iutra- lobular connective tissue more than counterbalances the loss, and we find the liver considerably enlarged. It 
is in this for® that we especially find the most marked proliferation of 
the bile ducts. Dropsy is frequent in atrophic cirrhosis, and jaundice 
rare; whereas in hypertrophic cirrhosis, jaundice is generally present and 
dropsy does not occur. 
Etiology. ‘T'he causes of interstitial hepatitis ere still not fully un- 
derstood, but there can be no doubt that noxious irritating agents, that 
either ere introduced from without, such as alcoholic liquors, or are formed 
within the intestine, or in the tissues of the body, and then brought to the 
liver by way of the blood, may produce cirrhosis. The use of alcohol ac- 
counts for a large number of both varieties. Syphilis is another important 
cause. Cirrhosis may follow prolonged malarial poisoning. This cause ap- 
pears to be rare. Scarlet fever is sometimes followed by an acute intersti- 
hjlftaJ-i f<s 
tial nephritic. It is highly probable that what we call cirrhosis of the 
A 
liver may, in some oases, be the terminal stage of an infective or toxaeaiio 
affection, which began acutely. PATHOLOGY No. 15 
Feb.?, 1898. 
Sub jest: 
1. Aoute suppurative infi ammation of toe liver, 
i?. Aoute suppurative hepatitis. 
3. Abscess of the liver. 
Causes pyogenic bacteria: Through systemic circulation; 
Through portal circulation. 
Amoeba Gcli (Lcsoh). 
Bacillus Coli Communis (through billiary channels). 
We have spoken to you, gentlemen, already concerning interstitial inflam- 
or 
rnation of the as it is generally designated. This so-called 
interstitial inflammation of the liver is not a true inflammation in the sense 
of being attended with emigration of leucocytes and exudation of lymph. It 
consists really in hyperplasia of the connective tissue of the organ. Now, 
to night I propose to say to you a few words concerning acute suppurative in- 
flamination of the liver, also designated as acute suppurative hepatitis, an 
inflammation which is characterized by the presence of foci of pus somewhere 
in the liver substance, constituting therefore an abscess of the liver. Ab- 
scesses of the liver may be single or multiple, they may be large or small, 
generally sneaking the single abscesses pf the liver are large and the multi- 
ple abscesses of the liver are small. They may be exceedingly small, miliary 
in size and very numerous, scattered throughout the liver parenchyma, such as 
we find, foe instance in pyemia. Abscesses of the liver are met with more 
frequently in tropical than in temperate climates. It was at one time thought 
that the so-called tropical abscesses of the liver, found in English soldiers 
serving in India, were due to a combination of homesickness and alcohol. 2 
More careful investigations have shown, however, that this theory is not 
correct. 1 need hardly tell you that suppuration of the liver is, as suppur- 
ation elsewhere in the body, due to the presence of micro-organisms, whether 
of vegetable or animal origin. 
Concerning the etiology of abscess: Let as consider first some of the more 
infrequent causes of abscess of the liver. A violent blow over tne surface of 
the liver leading to CL trauma of the organ (a rupturing of the liver sub- 
stance) may be followed oy the formation of an abscess. If, under these cir- 
cumstances, pyogenic bacteria chance to enter tne circulation and reach this 
point, they find a place of “resser resistance” as we say, ana they proceed 
to multiply, causing a focalized sue Duration of tee liver. A stab wound pass- 
ing through the abdominal wall entering the liver may be the cause of an infec- 
tion of the organ end sc give rise to abscess of tne liver. A not uncommon 
cause of abscess of tne liver is obstruction of the common bile duct by gall 
stones. Under these circumstances numerous small abscesses may be found in 
the liver substance, having their starting point in the interlobular bile ducts 
in 
and the majority of these cases the bacillus coli communis has been isolated, 
and is believed to be an important causative factor in this variety of abscess 
of the liver. This is sometimes designated “acute suppurative col angitis,* 
The colon bacillus is believed to enter toe biliary channels from tne intestine 
A few oases have been reported where a luabriooid worm has entered the common 
bile duct and has worked its way into the biliary channels until its course 
was arrested and there gave rise to an abscess. Then again a echinococcus 
•cyst of the liver may undergo suppuration, or may be diagnosed and opened by 
the Surgeon’s knife (and the technioue not being very careful) in this wav bacteria may be introduced into the cyst and cause suppuration of the liver. 
These are the more infrequent causes, hew as to the more common causes of 
abscess of the liver: Any wound on the surface of the bodv becoming infested 
with pyogenic bacteria may be the starting point for the entrance of bacteria 
into the circulation- suppurative wounds of the scalp, of the lower extremities, 
and of other parts of the body surface have furnished the portal of entrance 
for pyogenic organisms to the circulation. It is interesting to know that 
under these circumstances bacteria must first pass through the lung before 
reaching the liver by way of the hepatic artery, and that very rarely any sup- 
purative disturbance is created in the lungs. It is quite the exception for 
any abscess of the lung to be thus occasioned. The bacteria, however, when 
they reach the liver lodge in the liver capillaries and give rise to hepatic 
suppuration. This is believed to be due to the fact that the circulation of 
the liver is so slow, and there is such a slight amount of propulsive force, 
what the physiologists call vis s tergo, that any substance, such as bacteria 
reaching the portal circulation have the best opportunity of lodging in the 
is 
lobular capillaries. ThisAinfection of the liver through the systemic circu- 
lation, *by pyogenic .bacteria. More frequently the source of infection i.s the 
portal circulation. Some inflammatory disturbance of the intestine, small 
intestine, or large- the rectum; suppuration of the spleen or within the pel- 
vis may be the starting point for the infective material, such as dysentery, 
thrombosis of the hemorrhoidal veins, round ulcer of the stomach, and occa- 
sionally infection in unborn children occurs from the umbilical vein. When 
we come to sneak of infection of the lung I will have something to say to 
you concerning thrombosis and embolism. I will only remark here, that an in.iurv to the vessel- wall or inflammation adjacent to the vessel may involve 
itc wall and give rise to a clot of blood within the vessel (a localized co- 
agulation of the blood within the vessel). This is designated “thrombosis of 
a vessel” ana it may ooour in either the arterial or the venous system, most 
often in the venous system. Now these thrombi may be either bland thrombi 
(innocent thrombi as they are called) or they may be septic thrombi. In other 
words may contain bacteria). Any part of thrombus broken off and carried to 
another part of the circulation (swept away from its original site) dnd lodged 
in the vessels somewhere else in the body, is designated as an “embolus". It 
is generally carried until it can go no further, enters a vessel and becomes 
impacted. Now very frequently, in dysentery, for instance, and during in- 
flammatory disturbance of the hemorrhoidal veins, and in suppurations in the 
pelvis, we have a coagulation of the blood and thrombosis somewhere in the 
rootlets of the portal system as a result of this inflammatory disturbance; 
these thrombi are generally infective (septic) thrombi. They are due to the 
presence of bacteria, and being dislodged from their original site are carried 
by the portal circulation to the liver. Now it is not necessary that the em- 
bolus cr these particles swept away should really be large enough to 
plug the liver capillaries, in other words, it is not necessary that they 
should be. true emboli in that sense. They may be exceedingly small, but I 
have already told you that owing to the slowness of the liver circulation, 
minute particles are easily deposited in the liver. These bacteria adhere 
somewhere to the capillary wail and begin to develop if it is very favorable. 
Very soon they plug one or more liver capillaries and now we have just the 
same changes taking place which would be found in any other portion of the body (recall the experimental abscess in the rabbit's kidney). The cells im- 
mediately around the occluded capillaries become clouded, necrotic and dis- 
integrated, and upon out section you see localized grayish or grayish- yellow 
areas involving one or several hepatic lobules. This necrotic material under- 
goes liquefaction, leucocytes emigrate around and enter the necrotic area and 
we have an abscess in the liver, an acute suppurative inflammation of the 
liver. Abscesses of this kind may be very numerous, and they may be largely 
confined to the interlobular portal veins, constituting acute suppurative 
pylephlebitis, as it is called. Under these circumstances, upon examining the 
abscess with a probe, it may be found that each one of them connects with some 
small branch of the portal- vein. Inflammation of the walls of a vein is des- 
ignated “phlebitis”, of the portal veins pylephlebitis. Under these circum- 
stances thrombi may lodge in the portal veins and gave rise to an inflammation 
this would be an acute pylephlebitis of the liver. The contents of the abscess 
may consist largely of pus cells, it does consist largely of pus cells 
mixed with necrotic liver ceils and larger masses of necrotic tissue. In old 
mavf 
abscesses, however, weA f ind that the pus cells have become (almost) completely 
disintegrated, and we nave the abscess material consisting .of the aebris of 
fat and albuminous granules-mingled with necrotic shreds of liver tissue. The 
wall of the abscess is ragged and infiltrated with leucocytes. Of course ad- 
ded to the other contents of the abscess, there must be mentioned pyogenic 
bacteria. Now another important cause of abscess- by the way X have been 
speaking to you of what are known as secondary or metastatic abscesses of 
the liver, because their real origin was in someother region and are trans- 
ferred from some other point in the body to the liver. Writers also used to 
speak of “primary” or “tropical abscesses”. They were considered as primary 6 
as contrasted with the metastatic abscesses. Now we know that these are 
really also secondary abscesses, abscesses which are due not to the combi- 
nation of homesickness and alcohol, but to an animal parasite, the amoeba 
coli of Bosch. Losoh in investigating a case of dysentery which was under his 
observation in 1875 described an amoeba which be found in considerable num- 
bers in the patient's discharges: (his patient unfortunately died, or possibly 
for science, fortunately). Be found in the intestinal wail large numbers of 
this parasite, especially in the submucosa, and he raised the Question whether 
(bis patient, by tie way, came from India) the so-called tropical dysentery 
was not due to this amoeba. This was in 1875. ien years passed and Kartulis 
(I take it he was a Greek) confirmed the observation of Losch. He found in the 
discharges of dysenteric, patients in kgypt toe same amoeba, and what is of 
some interest to us he found certain of these cases complicated with abscess 
of the liver, and found the same amoeba within the contents (the pus) of these 
hepatic abscesses. Be, moreover, experimented by injecting the discharges of 
his dysenteric patient into the rectum of e cat and found that after inject- 
ing a certain amount of the discharge into the cat's bowel and ligating the 
rectum for a while, that he could produce quite an inflammation of the colon, 
an inflammation which sometimes was accompanied by superficial ulceration of 
the mucous membrane- not a typical dysentery as we see it in human beings, 
but something approaching it. This was in 1885. The next important investi- 
gation was made in this country at the Johns Hopkins Hospital in Baltimore, 
by Councilman, now of Harvard, and Loeffler, who was the risident physician 
of the hospital. They investigated 14 cases of the so-called “tropical dysen- 
tery" which originated, by the way, within the vicinity of the city of Baltimore, and were enabled to confirm the observations of Losch and 
Kartulis. They published an extensive monograph on this subject accompan- 
ied by illustrations, and went into the staining peculiarities of the amoeba 
ooii, etc. What is of peculiar interest is, that in seven of these cases of 
dysentery there were present abscesses of the liver; in six single large ab- 
scesses, and in one numerous miliary abscesses. Councilman came to the con- 
clusion that inasmuch as in six of his oases the abscess was in the right 
lobe of the liver on the under surface where it comes in contact with the 
colon, the junction of the transverse and ascending colon, that the amoeba 
coil worked their way through the wall of the intestine, entering the liver 
in that way. Be never found them in the lymphatic glands, nor did he find 
any suppuration of the lymphatic glands, sc he excluded the lymphatic system 
and also the portal system as being portals of entry, inasmuch as he found 
the pus sc conveniently located to the surface of the colon. In his last 
case, however (the one which bad mi Liarv abscesses of the liver) it was no 
longer a Question that the infection took place through the portal system. 
He stated very plainly his belief on that point. Be did not change his be- 
lief as to the organism having entered in the other cases directly through 
the bowel wail and into the liver. That is a point, however, concerning 
which we cannot be absolutely sure. Just a few words as to the parasite, the 
amoeba ccli: in the first place, in several of Councilman's cases the amoeba 
coli was found in the abscesses, the pus being sterile as far as bacteria 
were concerned..Of course an amoebic abscess may be secondarily affected 
with bacteria. Losch described this parasite as being from 6-8 (6 to 8) times 
the size of a red blood cell. Councilman and other Observers confirm Losoh in 
this respect. It is sometimes larger even than that, and it is one of the few 8 
amoeba which seems to have a limiting membrane, whioh in the fresh specimen 
from the stools has the appearance of rather e refractive limiting membrane, 
and is designated by Zoologists as the “eotosarc”. It also has certain con- 
tents which are. known as tbe“endosaro.* Lying within this granular material 
we find a nucleus. It is not seen in fresh specimens according to Councilman's 
statement. The nucleus does not stain with hematoxylon or mythyline blue, but 
with eosin. In addition to the nucleus the amoeba contains numerous vacuoles, 
rather refractive, clear looking vacuoles, and according to Councilman, the 
are, 
granular appearance of the amoeba is due to the fact that thereAso many minute 
vacuoles lying in the homogeneous protoplasm that it really gives it a granu- 
lar appearance, so that he figures a very large number of vaouoies within 
the amoeba. In the discharges of dysenteric patients or in an abscess in the 
liver of these patients these bodies are found to present active amoeboid 
movements, just ss a whits blood ceil, shows. They put out large blunt pseudo11 
pods, clear at first, into which the granular material or endosarc Quickly 
flows and they msv oe found at times to include within- them foreign oodles, 
red blood cells- and fragments of cells within the endosarc of this active am- 
oeba. Just a word of caution, if you are examining tne discharges oi'dysen- 
t-eriopatient with tne idea of seeing whether your patient has amoebic dysen- 
tery or not, be certain that vou get amoeboid movements, and that the body is 
a large body. 0 or 8 times the size of a red ceil, and do not mistake it for 
large fatty leucocytes which vou can find in these oases. There are various 
large granular cells which one sees in foeoai discharges which must not be 
confounded with tne amoeba coii. $ben these bodies reach the liver (and 
Councilman has been able to investigate an abscess at an early stage) they 
become lodged and cause a localized necrosis of the tissue, very much as bac- teria do. Ihey are found in the wail of the absoess (and not only in its 
contents) and this necrosis advances ail around the wall of the abscess en- 
larging it. If the absoess is to be arrested of course this is done by the 
f ormation of:connective tissue in'the wail of the absoess, and where the am- 
/ 
oeba coii absoess in the liver is of considerable size, just as in an absoess 
of the liver caused by bacteria, one finds Quite a rich granulation tissue 
within its wall. I think the section tonight will show you a well marked con- 
nective tissue wall constituting a part id the wail of an amoebic abscess. In 
a large majority of the cases of amoebic dysentery these investigations of 
Losob, Kartuiis and Councilman have been confirmed' by a number of observers. 
Now a few words as to the termination of absoess in the liver: If the patient 
in 
survives (lives long .enough) the abscess slowly advances andAthe direction, 
of course, of least resistance, towards the surface of the liver. If the case 
is not diagnosed and attended to by operative measures, the abscess having 
reached the surface of the liver may break into the peritoneal cavity causing 
a rapidly fatal peritonitis. If, when tue absoess acroaohes the surface of 
the liver, sufficient inflammatory change takes place, then we have an exuda_ 
tion of lymph on the liver, and this may cause adhesion between the liver and 
a loop of intestine, or between the liver and the diaphragm, or the abdominal 
wall, and so an adhesive inflammation may oe set up and the abscess rupture 
into the intestine or into the pleural cavity, or through the abdominal wall. 
In the majority of cases the rupture takes' place either through the abdominal 
wall or the thoracic wail. Breaking into the pleura, it may cause an exten- 
sive suppurative pieuritis, or if the two layers of the pleura adhere togeth- 
er the abscess may break into tne lung. Several oases of amoebic absoess are on record where the abscess has perforated the diaphragm and the layers of 
the pleura and broken into the lung and the contents coughed up in large 
quantities by the patient through the bronchial tubes. One of Loeffiers cases 
at the Johns Hopkins Hospital was diagnosed first by finding amoeba in the 
sputum, active as they are in the intestinal discharges. The pus from an am- 
oebic abscess is of a reddish brown color ana may contain considerable blood. 
If the abscess ruptures into the intestinal canal that is a fortunate occurs 
anoe. If it ruptures through the abdominal wall it is another fortunate oo- 
curranoe. If it breaks into the pleural cayity, that is not so fortunate. 
Bowewer several cases which have ruptured into the lung have recovered per- 
manently. Borne of the rare places are rupture into the parioardial sac, 
quickly killing the patient. Into the pelvis of the right kidney, the pus 
passing off through the urinary channels- not an unfortunate result. Into 
the vena cava giving rise to a fatal purulent infection. In a few cases the 
contents of the abscess become absorbed to a considerable extent, and the pus 
undergoes a cheesy degeneration, or lime salts say be deposited and we may find 
dcJ* 
simpiv a led mass in Us liver as the‘remains of an old abscess of the 
liver. I think mis will about close the subject, gentlemen, and 1 will ask 
you to examine with particular attention the section of amoebic abscess. We 
cannot always find sections of abscess that are perfectly suited for class 
work. If you get bold of an old abscess, what you see is largely; tie abscess 
wall. Amoebic abscess material is not easy to get bold of, and I might say 
that sometimes upon microscopic section you fail to find the amoeba in the 
been . a .. , 
walls of the abscess when they haveAfound in the pus and contents ot the ab- 
scess. The section which we have to night, however, will show you tne amoeba , 
c oli. PATHOLOGY So. 14. 
f'eby. 11, 1898. 
(No loature on. Feb* 9, 1898,) 
Asute degenerative changes- faaMfox, Yellow Fever, Soarlet Fever. 
Dim. 
Diphtheria- Typhoid fever. 
Aoute Yellow Atrophv . 
Pigmentary Deposits 
In liver C eils 
aapilaries 
r A 
Deposition of various oelis- pigmented and 
non pigmented- within bepatio oapiilaries 
Leukaemia 
Malaria. 
I wish to speak to you tonight, gentlemen, sonseraing sertain patbologisal 
sbanges that tale pl-aoe in the liver in many of the asute infections diseases, 
formerly these changes were spoken of anler the head of “parenchymatous inflam- 
mation” of the liver. Be no longer regard these lesions as°ln inflammatory 
snaraster, Bat rather as purely degenerative changes. the most important of 
•r 
these ssote infeotions I nave indicated aoove- small, pox. yellow fever, diph- 
theria, typhoid fever, soarlel fever. If one has the opportunity to examine 
the liver from a fatal- saae of smallpox, the attention will be arrested, not 
only by the appearsnoe of cells in various stages of fatty degeneration, but 
also by the appearanoe of bodies which stain, brightly with eosin- refraotive, 
round or oval; bodies ossupying the position of the hepatis sells. Councilman 
jailed attention to these jhanges in the liver of.small- pox, and we know that < 
the eosin staining jells simply represent dead liver jells (those shioh have 
undergone necrosis), for what reason, we will, have something to say later. 
You nave already seen a seotion of the liver of yellow fever, that was given 
to you in order to show you the ajute fatty degeneration of the liver sells. 
I am sertain that you must resall- the picture, and probably your attention was 
also sailed to the number of cells that Stained with eosin; the number of cells Path. No. 14. 
whicih appear'd to contain no fat drops, bat were rather refractive hyaline 
looking bodies, $hen tness were first seen they were taken To he the parasite 
ot yellow lever. The pathologist who first noted then- Councilman- was under 
the impression,that he had at last found the parasite of yellow fever, ana 
it belonged to the protozoa. Impressed with this fact that a large number of 
these brightly staining sells seemeo. to contain other sell bodies, which we 
now know as polynuclear leucocytes that have entered into the dead sells he 
began to examine the liver in other aoute infections, especially smallpox, 
and to his astonishment found the parasite tnere. Of course, that upset the 
parasitic theory, and showed that these were simply bodies which had undergone 
coagulation necrosis (rapidly degenerated) They are especially prominent in 
yellow fever, and may sometimes include a large number of cells in a lobule 
generally though tne necrotic cells are scattered here and there, only two or 
three, in various parts of the lobule. Ko other disease shows such a marked 
fatty degeneration of the-liver ceils as yellow fever. If the patient has 
died at aoout the ena of a week, then the gross appearance of the liver indi- 
cates extreme fatty degeneration of the sells by its light color, and it has 
a greasy feeling upon cut section. You may not know that Sanarelii, the Ital- 
ian bacteriologist who beleives that he has isolated at last tne bacillus of 
yellow fever, which be designated as Bacillus loteroides, claims that a pure 
culture of this bacillus when injected into a dog’s veins, or subcutaneously 
into the monkey, or into tne ear veins of a goat will bring about the death 
of the animal with the most marked acute fatty degeneration of the ceils of 
the liver. Now without confirming or denying that Sanarelii has isolated the 
specific causative agent of yellow fever, I will say that Dr. Carroll and my- 3 
experimented with this bacillus during the past summer and fall, have found 
in the liver of dogs auite a marked, fatty degeneration of the cells. You have 
already bad a specimen of the liver of a dog, that died from the intravenous 
injection of Sanareili’s bacillus. Moreover, we find that Sanerelii does not 
mention numerous necrotic cells in the liver, in animals which have died from 
the bacillus icteroides. It is impossible yet to deny or affirm Sanareiii’s 
claim, fie can only say that he has probably isolated the specific agent of 
this disease. 
Row in the next disease- diphtheria- we net only find at times extreme fat- 
ty degeneration of the liver oeiis, but the most marked localized necrosis of 
liver cells. Masses of cells which nave lost their nuclei and which stain uni- 
formly with eosin. They are sometimes quits a marked feature in fatal diphthe- 
ria. What is of interest is that the bacillus of diphtheria remains, as a ruie; 
purely local (in the throat) and yet the absorption of the toxins produced by 
this bacillus, which I referred to in the course on bacteriology, into the 
blood, brings about the most remarkable necrosis of tbe liver cells. Further, 
h&en 
it that these necroses can oe produced by the inoculation intra- 
venously of the toxins free of all the beoillus (particularly well in the kit- 
ten ). 
In scarlet fever: Now-a-days we do not see much fatal soariet fever, but 
in fatal oases the liver is the seat of the most marked neorosis, sometimes 
involving an entire lobule. 
This brings me to aoute degenerative changes found in the liver of typhoid 
fever. You hare already had a section of the liver of typhoid. Many years 
ago a German pathologist- Vagner ?- called attention to certain minute collec- 4 
tions of cells within the parenchyma of the liver in patients who had died 
from typhoid fever, and designated them as so many collections of lymphoid 
cells. That type of ceil which is designated as the lymphoid ceil resembles 
in all respects the cells of the lymphatic glands. Small cells whose nuclei 
stain intensely with hematoxylon and have a very little protoplasm, correspond- 
ing to the small lymphocyte of the blood, only a little bit smaller, Wagner(?) 
believed that the nodules were composed of these cells which had wandered out 
from the portal vessels, and from that time, early in the sixties, until almost 
the present time, pathologists and clinicians in their descriptions of typhoid 
fever referred to these collections of cells as lymphoid nodules in the liver 
of typhoid. A few years ago a French writer, Siredey, celled attention espec- 
ially to these changes in the liver of typhoid, and also to the fact that these 
areas often stained diffusely with eosin, and gave somewhat the impression of 
caseation, still he said that these areas which he considered quite character- 
istic, almost diagnostic for typhoid fever, differed from the areas of casea- 
tion which we see in the lung in tuberculosis. Be failed to find any giant 
cells in them, and he sometimes found that he could distinguish the individual 
liver ceils still in these areas, and ns raised the point whether these partic- 
ular areas wete not cue to some specific action of the typhoid bacillus. Anr 
other French observer experimented by inoculating rabbits with a pure culture 
of the typhoid bacillus with the idea of producing areas. Be found them 
in the liver of human beings as described; he stated, however, that he never 
found clumps of typhoid bacilli in the areas. His experiments were not fol- 
lowed by any successful results. In 1891, at Pro f. flelsb's reqsest, I took 
up this subject, and inoculated rabbits with pure cultures of the typhoid 
bacillus, into the mesenteric vein. Prof. $elsb, or rather Prof Councilman v?as convinced that the designation “lymphoid nodules” was not the proper one 
for these areas, and upon staining sections with eosin and methylin blue, I 
found that the areas were brought^with sore prominence. It is bard to see 
them when stained with hematoxylon. ft ben you have once detected them with the 
low power and turned down with the high power, it is very easy to see that you 
have an area of degeneration- stained with methylin blue and eosin, which brings 
them out with particular prominence. $s find them in very nearly every field 
of the microscope where you miss them with the ordinary stain. You find them 
in the various situations in the lobule. They may be around a central vein, or 
in the midst of a lobule. They may involve only a few cells. In one of my 
oases of human typhoid, the necrosis of single liver cells was quite a marked 
feature. As a rule they are larger; they say be elongated, two may be joined, 
giving you curved areas, etc. An interesting point about these experiments 
was this; in 50% of the rabbits inoculated (injected) with pure cultures of 
the typhoid bacillus (into the mesenteric veins) lesions were produced in their 
livers which were identical with those found in the human liver in typhoid 
fever. Stained in the same way end contained the same character of cells. 
The result of this investigation demonstrated clearly that the so-called nod- 
ules of tee liver were not lymphoid nodules at ail- they are not collections 
of lymphoid ceils- they are really collections of necrosed liver cells. These 
areas do contain various nuclei, and in tne early stages they are the nuclei 
, . , , , especially) 
of polymorphonuclear leucocytes, sometimes in the rabbits liver, Awe ima a 
vast number of leucocytes which have wandered into the area. According to 
Bandy the number of leucocytes that have wandered into the area ere suffi- 
cientiy large to constitute really a miliary abscess. That I have never seen 6 
Id human liver, but I have seen lesions which approached it in the rabbit's 
liver. It is interesting to know that we find them as early as 40 hours (the 
second day) in the rabbit's liver. They have been found in the human liver 
as early as the fifth day, and in one of the oases as late as the 9th week. 
These areas are especially those of necrosis into which polynuclear leucocytes 
have collected in greater or less number, and about whose periphery later we 
find round connective tissue cells, fibrolasts entering, because those areas 
appear afterwards to have their places supplied by the development of new con- 
nective tissue. 3c that the lesions which are found in the liver of typhoid 
fever, and which are simply touched upon by the textbooks are of a great deal 
::.f importance. I would not say that they were absolutely characteristic of the 
condition, and yet from the section I think I could diagnose whether the pa- 
tient died from typhoid fever or not. 
Now we come to another disease of the liver which is characterized by the 
most astonishing degenerative changes, namely: Acute yellow atrophy of the 
liver, This is a rare disease and one which, with few exceptions, is fatal. 
Osier states that he has seen one patient that was convalescent from acute 
yellow atrophy. You have already had a section of this, and I dare say that 
you bad trouble in even recognizing the liver structure in certain fields. 
Here the cells undergo the most marked acute fatty degeneration, and an es- 
pecially acute cloudy albuminous degeneration, rapidly break down ana are 
readily absorbed, their places being taken by the dilated capillaries, The 
disease takes its name from the rapid reduction in the size of the liver which 
occurs- the rapid atrophy which may take place within s week, or two weeks, the 
liver being reduced to one half or even less than one half in weight, and from 7 
the faot that it is of an intensely yellow color, due to the bile pigments. 
This disease is also designated as you know "icterus gravus* or "black 
dice”. To the eye the liver is not only very much reduced in size, it is ex- 
ceedingly ilaoid and pliable, the capsule is very much wrinkled, and upon cut 
section it is either of an intense yellow ochre color, or a Bottled color, 
yellow mottled or red, the red areas representing the points where the liver 
cells have completely degenerated and been absorbed and whose places are taken 
up by the enlarged capillaries of the lobule, if the patient lives long enough 
there is considerable connective tissue increase in such a liver, and Ziegler 
mentions a case reported by some investigator where a- number of rows of cu- 
boid al cells,one or two rows of liver cells, such as you have seen in 
phic cirrhosis, were very prevalent. In other words, as we believe, represent- 
ing an effort at repair, at regeneration of the liver, the formation of numer- 
ous new bile ducts. Ae to the etiology of this disease, we know, I may say, 
scarcely nothing. The majority of cases occur in women, and many 0f them 
during pregnancy. Acute yellow atrophy of the liver sometimes occurs in con- 
nection with septicaemia. It is not known whether it is a specific infection 
or not. If so. the organism has not been isolated. Probably it is due to 
bacterial toxins, or to some powerful chemical poison possibly absorbed from 
the alimentary canal. Fortunately it is a rare disease, and one for which 
medicine can do absolutely nothing. You may or may not meet with it. 
how a few words as to the pigmentary deposits which may take place either 
within the ceils of the liver or within the capillaries. You are aware that 
one of the most important functions of the liver is the secretion of bile, a 
fluid which is secreted at the rate of about 60G or 800 cubic centimeters daily and which is poured into the upper part of the intestinal canal during di- 
gestion there to aid in the digestion of fats especially, and has, we suppose 
a certain amount of antiseptic effect in the alimentary canal: not that it will 
kill bacteria at all, for bacteria really seems to be very fend of bile. Now 
it is necessary that this secretion of the liver cells should be daily carried 
atvay from the liver. We know that it is stored up in the gall bladder until 
needed for the process of digestion. If any obstruction occurs, especially in 
the common duct, or the duct which is formed by the Junction of the 
the gall bladder and the main hepatic duct, known as the ductus communis oho- 
liaious, if any obstruction occurs here or any obstruction in the main hepatic 
duct above its Junction with the or even in the main branches of 
the hepatic duct, then the bile from the whole or a part of the liver cannot 
reach its proper destination. Unaer these circumstances the bile capillaries 
interlobular anc intraioouiar, become rapidly distended, the amount excreted 
daily being very large. Tne bile under these circumstances, is very promptly 
taken up by the lymphatics of the liver and carried by way of the thoracic duct 
tc the general blood circulation. Be knew that it is taken uv by the lymphat- 
ics because it can be detected chemically, not only tbe biliary pigments but 
the bile acids in the lymph of the thoracic duct in cases of obstruction tc 
the hepatic duct. Under these circumstances, also, according tc several in- 
vestigators, the bile passes from rupture of the bile capillaries directly 
into tbe blood capillaries of the liver, and so reaches the blood by a more 
direct channel. As a result of this we have what is known as, and it is really 
only a symptom, icterus or jaundice. The bile pigment reaching the blood in 
excess, is excreted by the kidney, its pigment appearing within tbe secreting 8 
epithelium of the kidney, and especially in the excretion of the kidney,- the 
urine, under these circumstances also various tissues and mucous membranes of 
the body, the conjunctiva especially,the skin, the subcutaneous connective tis- 
sue, the various tissues throughout the body are stained a yellow color, and 
what is of interest to us here, the biliary pigment may accumulate in consid- 
erable quantity in the liver cells themselves, how let me mention a few causes 
of this obstruction to the flow of bile. The most common cause is the result 
of an inflammation of the upper portion of the small intestine, that part known 
as the duodenum. This inflammation creeping up the common duct affects its 
perhaps 
mucous membrane, anaApassing up into the ramifications of the hepatic duct; the 
swelling of the mucous membrane and the increase flow of muolts. all helping to 
diminish the caliber of the billiary canals. This is the most common cause of 
Jaundice, and one which can be treated by the physician with most success. 
Then another frequent cause is gall stones (not within the gall bladder but 
within the hepatic ducts, or main duct especially) an obstruction which is 
often removed at the present time by surgical interference. Then again various 
cicatrices the result of .ulceration of the mucous membrane of the duct may 
serve to narrow its caliber. Ini argefl retro-peritoneal lymphatic glands may 
press upon it; tumors of the 1iver(carcinomata of the liver) often press upon 
the common duct or the main hepatic duct. Carcinoma of the pancreas occasion- 
ally presses upon the duct and obstructs it. Now you understand that ail of 
the causes which I have given you refer especially to the liver, and some in- 
terference with the outflow of tke bile, and this form of Jaundice is spoken 
of as “hepatogenous” Jaundice,, in contradistinction to that fora which is be- 
lieved not to originate in the liver, and which is designated as “bsematogen- 
00s” jaundice, having the blood as its originating point. According to exner- aments which have been made cd the baeiatogenous form of jaundice, it would ap- 
pear doubtful whether there is such a form. You know the bile pigments, the 
bilirubin, is derives from haemoglobin, and of course this haemoglobin comes 
from the red blood ceils, i'here is a daily disintegration of a certain amount 
of red blood ceils which run their life course, and as the result of this dis- 
f 
integration we have bilirubin produced in the liver. Experimentally it has 
been shown that geese, for instance, can have the liver removed without any 
immediately fatal result. It has also been ascertained that by inhalation of 
the vapor of arsenious acid an enormous desrtuction of the red blood cells 
takes place, accompanied by a large increase in the amount of bilirubin secrete* 
by the liver cells. If, during the experiment while the bird has been made to : 
inhale the vapor of arsenous acid and the red blood cell destruction is going 
on accompanied by a largely increased flow of bilirubin in the’urine of the 
goose, the liver is extricated, notwithstanding the enormous destruction of 
red blood ceils still going on, the production of bilirubin decreases. In 
other words, it seems to be here purely hepatogenous. The reason why the 
baematogenous origin Is insisted upon is that during certain of the acute in- 
fections 1 typhoid fever, yellow fever), there is a certain amount of jaundice 
at times, and we know that tbere-is a certain amount of destruction of red 
Dlood cells. It is more than likely, though, that the bilirubin having been 
found in an increased amount in the liver is absorbed, certain circulatory 
changes taking place in the liver. 1 think kieglsr is correct in saying that 
as the result of animal experimentation, a purely baematogenous jaundice does 
not exist, he can only speak of a haematogenous jaundice when we have this 
rapid disintegration of the blood combined with some obstructive lesion of 
the biliary ducts. So much* for .the etiology of jaundice. 11 
It is Id this disease that the liver ceils contain a certain amount of 
pigmentary deposit. Cf course it consists of bilrubin depositee within the 
cells. There is another form of pigmentary degeneration cf the cells of the 
liver which has no relation whatever to the flow of bile or the obstruction 
of the bile ducts,- poisoning from chlorate of potash, arsenous acid, fatal 
mushroom poisoning, and in such diseases especially as pernicious anaemia and 
certain pernicious salaries. Under these circumstances there is a considerable 
destruction of the red clood ceils, consequently the amount of haemoglobin 
dissolved in the blood plasmas, as the result of the destruction of the red 
blood cells, caused a deep ruby red color of the plasma. Under these circum- 
stances haemoglobin will be excreted by the Kidneys in considerable amount, 
coloring the urine a ruby red or dark smoky red odor, known as haemoglobin- 
uria. It has been found as the result of observation and experiment that when 
haemoglobin undergoes disivfegroMon two derivatives of this body are formed, 
known as “bematoidin” (same as bilirubin chemically) and “heosiderind Serna- 
told in contains no iron, hemosiderin is the iron containing element cf haemo- 
globin. Hematoidin appears as ruby red or sometimes reddish brown granules or 
crystals.* hemosiderin never takes a crystalline form, but appears as yellow or 
yellowish brown granules. Now in pernicious anaemia, or poisoning from potas- 
sium chlorate, if the destruction cf red blood cells is so great that the haem- 
oglobin is not execre led simply by the kidneys and particles of the red blood 
cells are brought to the liver, tnese there undergo a further degeneration. 
Hemosiderin is found not only within the endothelial cells of the capillaries 
of the liver, but is taken up by the liver cells as well, and appears as yel- 12 
low or yellowish browe granular material in the cells, taking place, as a rule, 
first at the periphery ana afterwards in the interlobular region. Now if you 
were investigating a section of the liver and you dia not know whether had a 
A 
bile pigment or this derivative pigment from the blood (hemosiderin) you would 
use a chemical test. You would first wash your section with a solution of the 
ferrocyanide of potassium, and then with a weak hydroohloridic acid. If it is 
hemosiderin you get an intense blue color from the formation of Prussian blue. 
If it is bilirubin you note no such change. Ammonium sulphide also turns this 
into black iron sulphide. So much for the pigmentary deposits that may take 
place in the liver. 
Now this pigment may be deposited also within the endothelial cells, and it 
may be deposited in certain cells, star»shaped connective tissue cells that 
lie just without the capillaries and between them and the liver cells, and 
known as Kaplers stellate ceils. Not only may we have the pigment deposit- 
ed in this region, but within the liver capillaries- in leukaemia and mala- 
ria-various pigmented masses lying within the capillaries, and various ceils, 
pigmented and non-plamented lying within the capillaries. You have had a sec- 
tion of leukaiia. This disease is really an affection of the spleen and bone 
marrow combined, so that it is designated now-a-days “splenomyelogenous ,leuka- 
iia". Just remember that it refers to the spleen and. bone marrow. “Lienomyei- 
cgencus” is another designation cf it. This is tee form which is most fre- 
quently met with. Lymphatic ieukamia is a very acute blood disease. In this 
disease we have a most remarkable increase of the white blood ceils. Instead 
of bieng 6000 to 8000 in cubic millimeter, we have sometimes as many as ?00,00( 
or more. Instead cf being in the proportion of 1 to 500 or 1 to 1000 of the red blood cells, they may be to 100 or 1 to 50, or 1 to 7, and a large pro- 
portion of these white blood oells consist of certain cell which is derived 
from the bone narrow, and which never appears in normal blood, but appears in 
various pathological conditions, and especially in spleonomylogenous leukemia, 
a cell which you will hear something about next year, a large ceil with a round 
oval nueoleus, and the only cell of its kind that you ere going to find with a 
fine granulation, larger, as a rule, than any other of the blood cells, and 
this granulation gives you a light violet stain. This is known as the “myelo- 
cyte* because it is derived from the marrow. These cells, together with the 
other white blood oells collect- in enormous numbers in the capillaries of the 
liver in leukemia, at places distending the capillaries, forming quite large 
masses. I think your section showed this condition remarkably well. Those 
large round deeply stained nuclei which you saw were the nuclei of these my- 
elocytes. The cells which collect in the liver in leukemia are the white 
blood oelis-there is no pigment. In another disease-malaria- we have masses 
cf pigment, an exceedingly black pigment. The material from pernicious malaria 
was exhausted and I regret teat you could not be furnished with a specimen. 
It is almost impossible to get a case of malaria; physicians now give such 
large doses of quinine in sued cases that they do:not allow the patient to die, 
unless it is some patient who comes from South America, so saturated with the 
parasite that he dies in spite of treatment. These masses cf pigment are found 
in the liver, and you also find swollen epithelial ceils containing pigment 
and then we find numerous pigmented leucocytes lying within the capillaries, 
and also large numbers of the malarial parasite containing this pigment. This 
pigment is a derivative-of haemogcblin, but sc transmitted by the parasite in 
its growth that so far its chemical composition has not been determined. PATHOLOGY. No. 15. 
Feb. 18, 18S8. 
LONG: GBPONIO PASSIVE: CONGESTION . 
take- up tonight, gentlemen, the diseases of the lung. These are of 
greater importance than diseases of the liver, indeed there is no organ of 
the body which requires more careful study on account of the frequency of di- 
sease processes met therein. First we will cone-idoe- some general considers- 
tious as to the lung. I do not propose to enter at ail into the histology of 
this organ; with that you should already be familiar. In its development the 
lung resembles, in some respects, the epithelial glands. The air secs, or, 
rather the alveoli in an uninffated, or foetal lung very closely the 
racemose glands; the bronchial tubes, also, can represent very well the excre- 
tory ducts of these glands; but in general structure and in function the lungs 
differ very widely from the epithelial glands. There is no secretion here to 
be taken into consideration. 1 am now referring to the parenchyma of the 
organ proper and not. .to the bronchial tubes, for of course there is a certain 
amount of secretion from these, but none from the parenchyma of the lungs, 
then, again, there is no well developed epithelial structure in the inflated 
lung. In place of ordinary glandular epithelium, we find a very peculiar, thin, 
flat, plats-like epithelial lining the ultimate air sacs of the lung. Many of 
these large flat plates are devoid of nuclei. This epithelium varies very 
much in size. The blood supply of the lung you will remember is particularly 
rich.' in this respect, resampling the liver. You will not forget that the lung 
has a double blood supply; one derived from the pulmonary artery, whose cap- 
illaries completely cover the exterior of the air sacs, forming one of the 2 
closest capillary networks to be found in the body, intended for purposes of 
respiration- the true function of the lungs- and the other supply derived from 
the bronchial artery- intended for the nutrition of the lung substance. The 
amount of connective tissue found in the parenchyma of the lung is small. $e 
find along the alveolar walls only a little connective tissue, and this is not 
rich in nuclei. Between the lobules we do find a moderate amount of connective 
•yu, 
tissue, and as we approach the of the lung the quantity along the blood- 
vessels and the bronchial tubes increases in amount; so that the principal part 
of the connective tissue of the lung is that part which lies between the lob- 
ules and the perivascular or peribronchial connective tissue. On account of 
its peculiar structure, the diseases of the lung have oeen said to resemble, 
somewhat, those of the skin ana of mucous membranes or serous membranes rather 
than the diseases of the other glandular structures of the body. In ether 
words, many of the diseases of the lung are of a more superficial character, 
that is, attacking the inner lining, the. inner surfaces of the alveoli. 1'hese 
diseases characterized by this exudate into the alveoli, of one form or another 
are by far the most important of those affecting the lung. I do not mean to 
say that there are no diseases affecting the connective tissue structure of 
the lung, for there are such. Another matter to be borne in mind is that the 
lung is very richly supplied with lymphatics. The most important lymphatic 
system of the lung begins between the epithelial plates lining the ultimate 
air sacs, the open mouths of the lymphatics lying between the junction of these 
ceils. Another system begins at the pleural surface of the lungs, and still 
another carries away the lymph from the bronchial mucous membrane. Ail of 
these lymphatics converge into the glands at the root of the lung and bron-  glands. Again, the fact that the lung is supplied with certain resist- 
ant air channels, the bronchial tubes, is of considerable importance, as far 
as the causation of lung diseases are concerned. If we do not completely dis- 
tend the air saos with every inspiration; if there is suoh a thing as tidal 
air flowing in and out ana suoh a thing as residual air remaining behind after 
i i 
one most forced expiration, although this the case, yet t-he current of air is 
■P -F • * i , 
suiiioient to. carxy the lung various harmful partioies. It is haraly 
necessary for me to tell you that we are coming to believe more and more in the 
injuriousness of certain small boaies, micro-organisms, and although we do not 
know under all circumstances how these enter the body, we do know that many of 
them enter the lung by way of the bronchial rubes. A considerable number of 
them are deposited in the nostrils, others in the trachea and larger bronchial 
tubes, but a certain number of them reach the ultimate or terminal bronchial 
tubes and even their sir-sacs. So I say, this peculiar sturoture of the lung- 
certain resistant air channels entering the lung- has a very important bearing 
upon the causation of lung diseases. You see then that things with 
which the lung is well supplied, air and blood, and it is of considerable im- 
portance that there should be some balance between the lesser circulation 
(which we call pulmonary), and the larger circulation (or general circulation). 
It is true that the lung may contain temporarily a lesser amount of blood than 
normal, or a greater amount of blood than normal without any particular damage, 
but this condition osnnot last long without bringing about diseases of the 
lungs- this want of balance between the lesser and greater circulation. And 
St 
then the fact that there are large veins bringing blood to the right of the 
heart, and may bring along with it various bodies dislodged from parts of the 4 
venous system, and that these bodies can pass directly into the pulmonary artery 
is of considerable importance as regaras the causation of diseases of the lung. 
That we will especially touch upon at the next lecture. One other point which 
is of general bearing: if a part of a lung or if any entire lung is temporarily 
put out of use, it is of importance to know that the other part of the lung, 
or the other lung can act in its place, act vicariously as we say, take the 
place of the parts of the lung which may have been temporarily put out of ac- 
tion. 'Ibis occurs by greater distension of the air sacs of the healthy lung, 
and, if temporary, does no harm, but if prolonged it may bring about serious 
structural change (disease) of the lung. Now let us turn to the circulatory 
disturbances which are founa in the lung: We need not say very much as to 
anaemia of the lung. There is such a condition as anaemia of the lungs or an- 
aemia of one lung. The amount of blood in both lungs may be very much lessen- 
ed in general anaemia. Bere the lungs share the reduction in the number of 
blood cells with the other organs of the body, A patient with general anaemia 
is very easily put out of breath as we say, simply because the number of red 
ceils circulating in the capillaries of the lung is reduced, and the oxygen 
carrying capacity of the blood is below the average. At autopsy the lungs of 
a patient who has died of general anaemia may appear exceedingly pale, very 
much blanched. Remember that at autopsy the anterior margins of tbs lung and 
the apex of the lung may contain much less blood tnan other parts of the lung 
without involving s condition of anaemia of the lungs; that is simply from 
gravitation. Then again, we may have one lung rendered decidedly anaemic by 
compression, from an accumulation of fluid in the pleural cavity. This is 
anaemia by pressure. The amount of blood in such a lung is very much reduced. 5 
It is interesting to know that for purposes of health the lung should be 
well supplied with blood, therefore an anaemic condition of any portion of 
the lung is favorable for the production of disease. It has been claimed that 
those human beings who are born with stenosis of the pulmonary artery, and 
whose lungs have notfhe normal blood supply, are quite prone to the develop- 
ment of tuberculosis, i'here is seme ground for tnis belief. 
Now let us turn to the opposite condition- hyperaemia of the lung- this may 
be looal or it may he general, affecting only s small part of the lung or va- 
rious areas in the lung, or affecting both lungs throughout. Every inflamma- 
tion of the lung is accompanied by a certain amount of congestion immediately 
around the focus of inflammation. This is designated “inflammatory congestion” 
or “collateral congestion”. Se are constantly meeting with examples of this 
form of hyperaemia of the lungs. Then again, there is such a thing as acute 
general hyperaemia of the lungs. The amount of blood contained in the lung is 
markedly increased by active muscular exercise. The same condition is brought 
about by alcoholic stimulants, and if the patient chances to have st the same 
time some obstruction of the left side of the heart, we may have a marked gen- 
eral acute hyperaemia of both lungs as a consequence. I recall a case occurr- 
ing in this city about three years ago in a man 56 years of age who, in the 
midst of e driving snow storm, accompanied by a very strong Northerly wind 
undertook to walk a certain distance in the city, and did cover the distance, 
but upon reaching his friends house fell in the hallway, and died in a few 
minutes. At autopsy the lungs entirely filled the thoracic cavity and were 
intensely engorged. Opon section there was an abundant flow of olood. In 
other words, this patient presented at autopsy ail of the signs of an acute 6 
congestion of the lungs, a oondition which at autopsy is not often met with, 
though it may occasionally be seen. There was also found a marked mitral 
stenosis with Quite a marked hypertrophy of the left ventricle. This partic- 
ular individual, 1 had occas.ion.to believe afterwards, was not aware that there 
was any affection whatever of his heart, and would not have suffered this fatal 
acute congestion of the lungs had not there been this marked mitral stenosis; 
the active exercise taken under these circumstances being sufficient to bring 
about this acute fatal congestion of the lung, not often seen. 
There is another form of congestion of the lung, known as hypostatic con- 
gestion- found especially in the posterior parts of the lower iooes of the - 
lung. This is that form of congestion which we find when the patient is com- 
pelled to lie in one position- the back- for a considerable time, and in which 
there is at the same time some lack of propulsive power in the heart muscle. 
Take typhoid fever for instance; in this disease, especially in the middle and 
later stages of the disease, when the patient is not very sensitive as to his 
i 
surroundings, and where not only the propulsive power of the heart muscle, 
<0. 
but of the diaphragm and of the abdominal muscles are all lessened, we have a 
case in which hypostatic congestion of the lung frequently arises. You under- 
stand that the blood really reaches the posterior parts and bases of the lungs 
by gravity and remains there, gradually accumulating until the vessels of the 
alveolar walls are exceedingly engorged. This is one of the important forms 
I 
of congestion of the lung. 
Then we say have what is knqwjq as “atelectic" congestion. If, for instance 
one of the smaller bronchial tabes becomes plugged with mucus-so that no more 
air enters the portion of the lung parenchyma supplied by that minute bronchus, 
then the air is slowly absorbed and the alveoli 9«oa • Trj 
1 fc0il QOiiapses, giving rise to the 7 
d 
condition known as “atelectasis”. This freauently occurs in the bronchial 
affections of children. The parts no longer supplied with air very 
much engorged with blood, the vessels become considerably distended, the olood 
taking the place of the air which was present before, the pressure of air being 
withdrawn. Ateleotic congestion, as it is called, is especially important in 
Uj 
diseases of children affeoti#fr the bronchial tubes. 
There is another form of congestion of the lung, the so-called “compen- 
satory conges tion77. Suppose there is a considerable effusion in one of the 
pleural cavities, compressing the lung and nature does not remove this large 
exudate or transudate, the physician concludes to remove it by aspiration, end 
proceeds to rapidly remove it. Under these circumstances there may be a most 
in.tenS* engorgement of the lung. The capillaries which have been compressed for 
* 
a long time become rapidly filled with blood, and very often hemorrhage occurs 
into the parenchyma. So called- compensatory congestion. The important fact 
to be drawn from this is that an old pleural- effusion snouid be withdrawn very 
slowly, a small amount at first, then a second withdrawal and perhaps a third. 
Ail of these forms of congestion of the lung are of minor importance as com- 
pared with that from which effects.both lungs generally, and which is of mere 
permanent character- chronic passive congestion of the lungs- the most import- 
ant form of congestion of the lungs for you to taKe into consideration. This 
may be due in considerable part to destruction of the lung substance. In 
chronic substantial emphysema a.great many of the bloodvessels of the lung 
may.be destroyed and both lungs may be in a state of chronic cassive congestion 
1 think you will have sections demonstrating that later. The most important 
cause of this condition is valvular disease of the heart, affecting the left 
side of the heart. It is necessary tor Purposes of health that the blood which 8 
reaches the lung from the right ventricle should leave the lung through the 
left side of the heart. Any obstruction on the left side of the heart which 
interferes with this proper outflow of blood may give rise to a chronic pas- 
sive congestion. Microscopically we find the capillaries in the walls of the 
air sacs considerably dilated (engorged) with,blood. Sot only that, we find 
that-hemorrhage has taken place here and there into the alveoli. In certain 
sections we find many red blood cells present in the alveoli. These hemorr- 
hages take place from time to time into the lungs of a.patient suffering with 
chronic passive congestion and as you know red blood cells under these circum- 
stances very soon undergo disintegration we find that the remains of the red 
blood cells are taken up in a considerable degree by the epithelial cells lin- 
ing the alveoli, also by emigrated leucocytes. In examining a section of long 
standing chronic congestion you expect to find in the alveoli a certain number 
of what are known as “pigment bearing cells", ceils which contain a brown or 
brownish red pigment. This is one of the microscopic appearances which is gen- 
erally met with. These cells are raised with the sputum and can be found in 
the scutum of patients with advanced chronic passive congestion of the lung. 
Inasmuch as the amount of congestion depends very closely upon the action of 
the left ventricle, if this became temporarily weakened the amount of chronic 
passive congestion of course becomes greater. The Germans have applied to 
these cells the term “heart failing cells", and look upon them as being quite 
diagnostic of heart disease when found in the sputum. If the congestion lasts 
for a considerable time, the amount of connective tissue in the lung is in- 
creased, sometimes markedly increased and as there is considerable blood pig- 
ment often deposited in the connective tissue here and there in the lung the 9 
term “brown induration” has been applied to this condition of the lung. 
Closely associated with chronic passive congestion of the lung is oedema of 
the lung, which I intended to take up tonight, but we will defer that until 
Monday evening. One of the sections which will be given you tonight is of 
chronic passive congestion ana the other of oedema of the lungs. Both of these 
sections could come very' well under chronic passive congestion of the lungs, 
and no doubt both show to some extent oedema. Compare them with normal lung 
and I think you will be impressed with the increased amount of blood in the 
capillaries of the lung as compared with the normal sections which you have 
studied (in histology)- the alveoli being much reduced in capacity. PATHOLOGY KO. 16 
Feb. 21,1898. 
PULMONARY OfiOiMA .8fcflSr-feBis3. 
Tonight I wish to invite your attention first to that condition of the 
lungs which is known as “Pulmonary Odessa”. This is not to be considered as 
a primary affection, but is always dependent upon some other pathological con— 
dition. It is a condition of frequent occurence, sometimes arising very rapid- 
ly and quickly leading to a fatal result. We mean by oedema of the lungs, a 
transudate of sew serous fluid, the alveolar walls feat nioj.oi o«»eautffl 
\ 
into the adr sacs. Mow as to the various forms of pulmonary oedema: Just as 
we have inflammatory congestion we may have inflammatory oedema. This being 
preceded of course, by inflammatory congestion. Around any focus of inflamma- 
tion of the lung we may have a certain amount of oedema involving the parts 
not actually concerned in the inflammation. When I was speaking to you on the 
subject of oedema and dropsy I called attention to the fact that in '.nflamma- 
tory oedema the transudate contained considerably more albumen than in tbs 
transudate resulting from cachectic oedema. You will probably have at the 
next meeting a section showing very well inflammatory oedema. You may have 
oedema associated with that form of congestion known as hypostatic congestion. 
In addition to the dilatation of the bloodvessels in the lower lobes of the 
lung there may be considerable escape of serous fluid, thus rendering the part j 
of the lung quits solid- so-called splenization or the lung. Inflammatory 
oedema, hypostatic oedema and ataiectio oedema are some of toe minor varieties! 
of oedema of trie lungs. When we sneak, however, of “pulmonary oedema” we generally have reference to an oedema affecting both lungs throughout their 
ex cent, under these circumstances there is ft-ftftr4=si=n acou?nulation of serous 
fluid in the alveoli of the lungs filling them more or less, and of course, in 
proportion to the fluid transudation displacing the air from the alveoli. 
Lungs which are the seat of pulmonary oedema, do not retract when tie chest is 
opened. They present a reddish appearance or may be decidedly pale. They are 
ooggy to the feel, pit on pressure and when an incision is made into the lung, 
a serous fluid, or. ten tinged with blood and mixed with air bubbles, flows from 
the cut surface and can be squeezed out very readily. Generally the part of 
the lung which is the seat of oedema, does not sink in water. It generally con- 
tains sufficient air to float. Pulmonary oedema of this variety frequently 
occurs during the death agony, at t e last few moments of life when the heart 
is siting very weakly. It is also associated with a number of diseases; indeed 
there is hardly any disease in which we may not have pulmonary oedema, and I 
might say that it is not a necessary concomitant of any disease. The most im- 
portant of the diseases with which it is associated are acute and chronic 
Bright s disease and obstructive lesions on the left side of the heart; croup- 
ous pneumonia, various fevers of a low type and cerebral hemorrhage. The ac- 
tion of the heart is always weakened before we have pulmonary oedema, Hydraem- 
ic conditions of tbs blood and obstructive lesions on the left side of the 
heart leading to chronic passive congestion, are, however, only predisposing 
oausss to general pulmonary oedema, fie know that in many instances where there 
is marked chronic passive congestion of the lung or general anaemia of the pa- 
tient from some chronic disease, pulmonary oedema is most often absent, so that 
there must be some other factor added as the immediate cause of pulmonary oedema. We believe that this oedema is of the mechanical variety, just as the 
majority of dropsies are. Cohnheim taught that the important factor in pul- 
monary oedema was weakening of toe left side of the heart.; partial paralysis 
of the left ventricle while the right ventricle continued to beat with its or- 
dinary vigor. Welsh, from a series of carefully conducted experiments was 
able to confirm Gohnheim’s theory as to the immediate cause of general pulmo- 
if 
nary oedema. He found thatAthe right side of the heart was weakened while the 
left beat with its usual vigor, (these were animal experiments) there was no 
pulmonary oedema. Be also found that he could obstruct the blood flowing from 
the lungs to such an extent that we could scarcely cslieve that this could ever 
arise in human beings, without oedema- but without obstruction to the outflow 
of blood, if be lamed the left heart, this, was followed by general pulmonary 
oedema in the dog. In other words the essential factor seems to be an unequal 
action between the two sides of the heart- the right heart acting more vigors 
ousiy than the left, the right heart pumping blood into the pulmonary capil- 
laries, the left heart failing to remove the blood and in consequence, the ten- 
sion reaching such a point that there is an excessive transudation of serous 
fluid from the capillaries. You see that the most important form of oedema 
is general pulmonary oedema, often called “stagnation oedema”, which is due to 
mechanical causes and is often associated with chronic passive congestion of 
the lungs. This is a condition which may arise suddenly and may suddenly dis- 
appear. . In treating pulmonary oedema, therefore, you should not forget the 
very rich lymphatic supply of the lungs. You should remember hew readily 
large Quantities of fluid may be absorbed and should always look to the heart 
and sustain its action. It is surprising bow readily sometimes this alarming condition subsides. Always bear in mind the hearts condition and treat it 
accordingly. Certain authorities refer to the So-called “toxic” oedema espe- 
cially occurring in connection with Bright's disease ana certain of the acute 
affections and believe that this occurs- without any defective action of the 
heart. It is more than likely that even under these circumstances there is 
added the mechanical obstruction, a mechanical factor. We are not able to 
present to you the section showing general pulmonary oedema. If we could show 
you such a lung you would simply see the alveoli filled with granular looking 
contents, perhaps a few red Diood cells and a few epithelial cells washed from 
the walls of the alveolus, ihe forms 'which you have seen are those of pulmo- 
nary oedema especially associated with chronic passive congestion of the-lungs 
and one of this form associated with inflammation will be shown you when we 
take un acute inflammations. 
Now I wish to say a*few words to you gentlemen, on the subject cf hemorr- 
hagic infarction of the lung. There are various forms of hemorrhage occurring 
in the lung: may have hemorrhage from traumatic causes (injuries to the 
lung from external violence), hemorrhages occurring in scattered areas in the 
lung during some cf the acute infections, smallpox, for instance* extensive 
hemorrhages o®ourMr&& beneath the pleura and scattered throughout the lung sub- 
stance in purpura hemorrhagica, especially that form which is known as fulmi- 
nating purpura. I have only seen one instance of this at autopsyfthe patient 
having died on the third day;) the lungs presented numerous and extensive super- 
ficial hemorrhages beneath the pleura and throughout their substance. In the 
forms of which I have been speaking we conclude that there is some unknown 
change which takes place in the capillary wall which admits of this extensive, 5 
diapedesis of red blood oelis. The most common cause of hemorrhage of the 
lung is tuberculosis. We may have a certain amount of tinging of sputum with 
blood in chronic passive congestion (which I have already mentioned) and in 
connection with the acute inflammatory diseases of the lung we find the ex- 
*> * 
pectoration decidedly tinged with blood- we do not speak of tnese as hemorr- 
hages from the lung, -but in tuberculosis we have hemorrhages slight and severe 
and sometimes rapidly fatal. At autopsy we may find blood located in one part 
of the lung, the hemorrhage having taken place in another part of the lung. 
k hemorrhage taking place into a bronchial tube may be aspirated and carried 
into various parts of the bronchial tree far removed from the point of hemorr- 
hage. In tuberculosis when a patient has hemorrhage you may know that there is 
some focus of disease which has undergone softening (caseation) and- broken into 
the bronchial tube involving the rupture of small bloodvessels. Severe pulmo- 
nary hemorrhage is due to the rupture of the bloodvessels in a pulmonary cav- 
ity. The form of hemorrhage to which I want to draw your attention tonight is 
that known as hemorrhagic infarction and is due to the plugging of one or more 
of the terminal arteries of the lungs. 
In order that you may understand this subject 1 will oooupy a little time 
with tile subject thrombosis and embolism. A tbrombijsss- is a clot of blood 
formed in the heart or the bloodvessels during life. A may be 
eluding (closing the entire vessel) or it may only partially close the vessel,, 
form on one wall of s vessel, this being the so-called“parietal* thrombus. 
The most important cause of the formation of thrombi in vessels, or throm- 
bosis, is some change affecting the endothelium lining the vessel. It may be 
from inflammation involving the wall of the vessel,, from atheroma, calcare- 
ous degeneration of the wail of the vessel pressure from a tumor or from an 6 
injury- all of these being causes of the clotting of blood within the vessels. 
I should say that thrombi may form either in the veins or the arteries, 
but they form more frequently on the venous side. An important secondary 
cause of thrombosis is retardation of the blood current. The retardation may 
also interfere with the proper nutrition of the endothelial ceils. You see 
the effects of retardation of the blood current in the formation of thrombi, 
coagulation of blood- in those dilatations of blood vessels which are known as 
aneurisms. Thrombi also form in the vessels of patients whose circulation is 
very weaV. Under these circumstances we find them forming in little pockets 
behind the valves of the veins, at the apex of the right auricle; in the cere- 
bral sinuses, especially of children, and in the veins of the extremities and 
pelvis. Thrombi forming in the vessels under these circumstances are desig- 
nated “Marantic” thrombi. Thrombi are divided into several varieties, red, 
white and mixed thrombi. If a blood vessel should be tied at two points, then 
the clot forming between those two points will of course, be of just the same 
composition as the blood itself and will give you a typical thrombus. Red 
thrombi form when the blood is at rest, and white or grayish white thrombi form 
while the blood is in motion. Many thrombi form very slowly, the disease orig- 
inating at one side of the vessel and the thrombi or blood clot being formed | 
slowly until finally the vessel is occluded. Other thrombi form suddenly, very 
rapidly, espeoislly by inflammation involving the wall of the vessel and so 
occlude the vessel quickly. The thrombus continues to grow, when once formed, 
generally until it reaches the next branch given off, the next anastamosing 
branch. One of the dangers from the presence of thrombi is the fact that the 
terminal part of it may be broken off and swept away by the blood current. 7 
Before I refer to this let me call your attention to what takes place in the 
thrombus after it has thus formed. You may have organization of the thrombus 
or you may have a softening, these being the two most frequent changes; or 
calcification of the thrombus which is rare. In organization of the thrombus, 
which is the most fortunate change which can take place, connective tissue pre- 
ceding from the wails of the bloodvessel gradually invades the thrombus, new 
bloodvessels enter the thrombus and the place of the former thrombus is- taken 
by new richly vascular connective tissue. This organization of the thrombus 
is a fortunate occurence. Ibis is what the surgeon expects when he be lig- 
ates a bloodvessel- that a thrombus snail form and afterwards undergo organ- 
ization. Sometimes a thrombus which has formed in the continuity of the vessel 
and which has undergone organization may open up the channel and sc the cur- 
rent be partially or completely restored through the bloodvessel. The thrombi 
may also, as I have said before, undergo softening, if this softening is due 
simply to the breaking down of the central part of the thrombus (which occurs 
especially in large thrombi on the wails of the heart), a simple softening, 
the contents of the thrombus being composed of albuminous or fatty granules or 
leucocytes which have undergone fatty degeneration, this is one of the harm- 
less forms of softening, hs the thrombus softens fragments of it may be swept 
away and carried to other parts of the circulatory system, but they are of a a 
as * 
bland character and so do not doAmuch harm as if the thrombus bad undergone 
septic softening. In inflammation due to bacteria invading the walls of the 
bloodvessels and causing thrombosis, if these organisms undergo multiplication, 
the thrombus will often under go a septic softening, or infectious softening. 
"When particles of such a thrombus are swept away wherever they are carried 
they give rise to all the effects which pyogenic bacteria can produce. The 8 
most important lesions in pyemia are due to the septio softening of thrombi 
followed by the transference of these septic particles to various parts and 
organs of the body. I want tc call your attention to the fact that one of the 
causes of miliary abscess of the liver are the formation of thrombi in some 
part of the general circulation or of the portal circulation, and I mentioned 
the fact that while the septic particles were frequently small enough to pass 
through the lung, they rarely caused trouble at that point, but more frequent- 
ly caused trouble in the liver. Row it is of importance to distinguish between 
thrombi and the so-called “postmortem clots”, especially as thrombi often form 
in the heart. The thrombus you understand is intimately attached to the ves- 
sel wall or to the heart wall, it is more granular in appearance, generally 
stratified, whereas the postmortem taken to be the immediate 
cause of death, is composed of red layer and an upper white or yellowish white 
gelatinous layer,, and the whole mass is easily removes from the wall of the 
heart. So that one should not fail into error of confounding a postmortem 
clot and a thrombus. Now if a thrombus or a part of a thrombus is broken away 
from its original location and carried to some other part of the circulatory 
system, we designate it as an embolus, and we speak of this as embolism, if 
an embolus is of sufficient size it may be sufficient to plug a large vessel 
such as the pulmonary artery and lead to immediate death, or an embolus of 
ficient size to plug one of the coronary arteries would lead to the like re- 
sult. Whether an embolus would have any effect or not would depend in the 
first place upon whether it was af a bland or an infectious character. If an 
embolus has resulted from simply softening of a thrombus then its presence 
may absolutely do no harm unless it lodges in one of the terminal arteries of 
an organ. If, however, it is a septio (infectious) embolus, then wherever it 9 
lodges it will probably give rise to suppuration. A.bland emolus affecting a 
muscular artery with free anastomoses would give rise to no disturbance what- 
ever. An embolus lodging in a terminal artery, such as those of the spleen, 
heart, brain, kidney, lung i 11 be followed by certain definite results. In 
other words, the part beyond the obstruction is suddenly deprived of its blood. 
8© speak of these arteries as being terminal arteries which do not have any 
anastamcses except through their capillaries, and I have already told you the 
most important organs having arteries of this character. Cobnheim designated 
them terminal arteries—those of the spleen, the heart, the brain, the kidney, 
the lung. When the vessels become occluded the part beyond must either oe re- 
supplied with blood or else it must undergo necrosis, The usual result is that 
the pert undergoes coagulation necrosis (death), so that the essential or most 
important factor in infarction is the necrosis which takes, place, because this 
is the constant phenomenon that goes with infarction. 
Hemorrhagic. infsection of the lung-, obstruction of the terming! arteries 
in the lung is often caused.by emboli swept from some other part of the body, 
often from the right side of the heart, especially in the last days of life. 
These as a rule,* when the circulation is normal, ao not give rise to any trou- 
* 
ble whatever. It is important to. bear in mind thAt emboli obstructing the ter- 
minai arteries of the lung has e double blood supply do not bring about anv 
?h \ ; 
result unless the circulation is disturbed, is weakened in some, way, end hence 
we have infarctions forming in the lungs especially during the last days of 
life when the circulation is interfered with. These infarctions are always 
hemorrhagic in character and this is.brought about by the flowing in of blood 
from the surrounding capillaries into the capillaries of the obstructed dis- 
trict, distending them, the force of the circulation not being sufficient to 10 
oarry the blood on to the veins. The result is that the oapillaries suffer 
in their nutrition.and permit the red cells to rapidly pass through their walls 
so that we have a most marked diapodesis of the red cells in the part inf arc ted. 
This especially in the lungs. Whether an infarction be hemorrhagic or anaemic 
depends upon the part in which it occurs, if the structure is loose such as 
that of the lungs, then toe capillaries become filled with blood and the red 
blood cells pass through in large numbers, filling the alveoli. If the in- 
farction is in an organ such as the.kidney for instance, it will.as a rule.be 
a pale infarction or an anaemic infarction, simply because the substance of th 
the kidney is comparatively solid,, necrosis takes place quickly and hemorrhage 
cannot take place as there is no place for the blood to go. The hemorrhagic 
area in the kidney would be at the margin of the infarct. In examining your 
section of infarction of the lung, in the first piece you will expect to see 
the alveoli crowded with red blood ceils, and next you will expect to see the 
walls of the alveoli undergoing necrosis throughout the inf arc ted area. If 
the infarction is a fresh one (a few days old) you see nothing.else; later 
there is an emigration of white blood ceils (polynuclear leucocytes) into the 
necrotic tissue, ;just as there would be in any other part of the body. The 
result of an infarction in the first place is the necrosis of the tissue; if 
the.patient lives long.enough the place of the inf arc ted area is taken by a 
growth of connective tissue from the surrounding parts. In other words, fi- 
brous tissue takes the place of infarction; the red.blood cells undergo dis- 
integration, granulation tissue forms at the margin, slowly grows into the 
point and finally the place where the infarct was, is taken by fibrous tissue, 
which shows a depression on the lung surface. Inhere do you expect to find 
infarcts of the lung f £t tre surface, if you are examining the lung, the 11 
seat of infarction (and these may be numerous, generally more in the right 
than in the left lung, more apt to affect the the lower lobe than the upper) 
you will notice certain slightly elevated dark red or blackish areas just un- 
der the pleura. They may be the size of a pea or up to the size of a walnut 
or larger. When you make your incision into them, expect to find them wedge- 
shaped, the vessels being at the apex. You will of course find that the in- 
farcted area is firmer than the rest.of the lung, because the air has been ex- 
pelled and the red.blood cells have filled the whole part, you may.be able to 
squeeze out a little biooa from the infarct, .but as a rule it is quite dry. 
With the edge of the knife you can of course scrape sways blood fluid. This is 
the bland infarction of the lung and it occurs at the periphery of the organ 
where the arteries terminate. -If the embolus was a septic embolus then you 
would have suppurative inf 1 affixation taking place at the point of lodgment, and 
that we expect to show you when we take up embolic pneumonia. 
On Wednesday evening we will take up part of the time in a quiz, in order to 
see just vfhers we stand in aiseases of the lung, as these are of such great 
importance. I would ask you to review especially thrombosis and embolism in 
connection with the various forms of infarction. PATHOLOGY No. 18 
F‘eb. 33, 1898. 
PNEUMONIA. 
Synonyms: 
Aoute inflammation of the lung. 
Croupous inf 1 animation of the lung 
Croupous pneumonia 
Aoute pneumonia 
Aoute pneumonitis 
Aoute fibrinous inflammation of the lung 
Aoute lobar pneumonia. 
1 want to speak to you this evening concerning inflammatory disturbance 
of the lung. Inflammation of the lung substance may affect a very small part 
of the organ, a very small area, or it may involve a considerable ccrtion of 
the lung substance. In that form of pneumonia which we designate broncho- pneu- 
monia the inflammation is limited in extent- we have various scattered small 
foci of inflammation. In another form of acute inflammation of the lung, one 
of tbs most important that you can study, because it is of such frequent occur- 
rence, and which is designated "acute inf I animation” of toe lung ( which has 
various synonyms, as indicated above) a considerable portion of the lobe of the 
lung is affected- often an entire lobe. Sometimes two or more lobes are af- 
fected, and occasionally a lobe of each lung, or both lungs may be affected. 
Ibis inflammation of the lung, like all other Inf laminations of the lung has 
certain stages: 
In tbe first stage we have an active byperaenia of the part affeotef. Re- 
calling the vascular phenomena of inf i animat] on, we have in the lung first a 
marked dilatation of tbe capillaries with increased rapidity of tbe current, 
more blood brought to the part, more carried away- a stage which may last 24 to 
4S tours, s stage tbioh »e rarely see at eutocsy; patent* rarely die in this 2 
stage of the disease- the first stage cr that of acute byperaemia of the lung. 
Id the next( the second) stage, we have what you ail are prepared for- an 
exudation of lymph rich in albumen, quite a marked diapedesis of the red cells, 
and commencing emigration of white blood cells. The blood vessels are very 
muoh dilated, and the exudate, suoh as I have described, flows into the alve- 
oli, completely displacing the air. So that whereas in tne first stage (that 
of hyperaemia) the inflamed part or the lung still contains air, in the second 
stage the part of the lung affected is solid. If we make and incision into the 
lung during the second stage, we find that it is not only solid, resembling the 
liver, but that it has a distinctly red color. Since it resembles the liver in 
solidity, it is called “hepatization- red hepatization” of the lung. This 
stage lasts 2 to 5 days- on an average about 3 days. The lung is red because 
the bloodvessels are engorged (distended) and besides the air vesicles contain 
quite a number of red blood cells. 
In the next (the third) stage, that of “gray hepatization”, we find the 
leucocytes very much increased, as compared with the red blood ceils, the al- 
veoli being packed with polymorphonuclear leucocytes. This exudate exerts a 
certain amount of pressure upon the capillary walls, lessening the amount of 
blood in them, and perhaps more important still, the weakened action of the 
heart has a good deal to do with the diminution of the blood in the alveolar 
walls in this stage (gray hepatization), which also lasts 2 or three days. 
Upon examining sections ,qf the lung during the stage of red hepatization 
you will find, in addition to the red cells, a few polynuclear cells, and in 
addition an abuundance of threads of fibrin radiating through the alveoli, 
running from 'wall to wall, stained brightly with cesin- a typical fibrinous 
exudate. In other words, we have here an ex«-Dip of t 
■“ ie ot tbe nost exauisite infxa!B_ 3 
mation that any tissue can show, giving all of the elements that characterize 
an inflammatory exudate- red blood cells, fibrin, emigrated white cells- and 
because of the presence of the florin in the exudate in the alveoli, a section 
of the lung in the stage of red hepatization or gray hepatization, presents a 
granular appearance, the plugs of fibrinous exudate projecting a little above 
toe out surface; so that the surface is not smooth in croupous pneumonia of 
adults, bj*t presents a granular appearance. In addition to the inflammation of 
lung tissue, you also have inflammation of the pleura covering the inflamed 
part, not only of the pleura covering the inflamed part considerably, so that 
we have a pi euro-pneumonia, or a pleurisy in addition to the inflammation of 
the lung substance proper. This pleurisy also gives you a very good example of 
a fibrinous exudate. If you examine a section of an acutely inflamed pleura, 
you find in abundance fibrin and polynuclear leucocytes constituting the exu- 
date, with the subpleural vessels very much injected. 
If all goes well, the next stage (fourth stage) is that of resolution. The 
red cells have already begun to break down and to be absorbed and the contents 
of the alveoli- on enormous exudate weighing several pounds- must undergo some 
change in order to be absorbed. A part of it is raised through the bronchial 
tubes by the patient in the expectoration by coughing, but a very small part 
of it. The greater part of it by far is removed by means of the lymphatics- 
the absorbents of the lungs. White blood cells undergo fatty degeneration 
(disintegrate), the threads of fibrin become loosened from the alveoli walls, 
becomes granular, and this liquid exudate is readily taken up by the lymphat- 
ics of the lung, so that in a few days this enormous quantity of exudate is 
completely removed, and the alveoli restored to their former integrity. 4 
This is the ordinary course in oroupous pneumonia going on to recovery. This 
disease affects more frequently (so statistics show) the right lung than the 
left, and the lower lobes of the lung much more frequently than the upper lobes 
of the lung. You already know the specific cause of this disease- the diplo- 
coccus lanceolatus. Cruopous pneumonia belongs to one of the acute infectious 
Co 
diseases caused by Frenkel's diploccus. Just bow the organism is brought to 
the lung we cannot say. It may be by way of the bronchial tubes, but in cer- 
tain cases it seems to be by way of the circulation. The lungs seem to be the 
o 
favorite organ for the action of the diploqpus lanceolatus. Certain bacteria 
seem to find in certain organs conditions more favorable for their growth; cer- 
tainly the dipioccccus lanceolatus finds in the lung a very favorable seat for 
its growth, and as you all know it is one of the organisms which causes a most 
remarkable exudate of fibrin. Cultures from the lung during the stage, es- 
pecially of red hepatization (2nd stage) are, as a rule,positive- with few ex- 
ceptions the dipiococous lanceolatus is recovered, and in some cases, the or- 
ganism is also recovered from the blood and from the liver and the kidney, so 
that under these circumstances we not only have a iooai inflammation of the 
lung, but a genuine septicaemia, due to this microorganism. During the stage 
of gray hepatization (3rd stage) cultures often fail, the diplooo&us being 
present still in the exudate on stained sections in large numbers but failing 
to grow upon media- probably on account of its having perished. I have stated 
that the usual result was a perfect resolution of the lung, complete obsorptior 
of the exudate if the patient goes on to recovery. In certain cases the ter- 
mination is less fortunate. Occasionally the exudate in a considerable por- 
tion of the lung is not absorbed promptly, its place being slowly taken by the 
formation of vascular connective tissue proceeding from the walls of the alve- 5 
oil, gradually invading the exudate, and giving us what is known as one of the 
forms of ‘’interstitial pneumonia” The patient dying several weeks after the 
original attack, post mortem examination may show a portion of the lung still 
deprived of air, quite injected, and solid- oarnified as we say, resembling 
flesh, and it is in suoh lungs that we find that the exudate instead of being 
absorbed is supplanted by a new growth of connective tissue. This is a rather 
rare termination. Another unfortunate oooursnoe of oroupous pneumonia especial 
ly accompanies cases of chronic bronchial disturbance, where there is some di- 
latation of the bronchial tubes and a rather fitid expectoration. In these 
oases putrefactive bacteria, which are already in the dilated bronchial tubes, 
reach the inflamed area end there set up their destructive action, producing 
a localized gangrene of the lung, which one recognises at once from the ex- 
tremely repulsive odor whioh the patient’s breath gives. Gangrene of the lung 
though an extremely serious condition, does not always lead to tile death of 
the patient- it may be recovered from. Another termination is in certain lo- 
calized abscess areas in the lung; the polynuclear leucocytes gather in such 
large numbers, so infiltrating the alveolar wails, as to give rise to neorosis 
of certain of the alveolar walls. This is a rather rare- termination of croup- 
ous pneumonia. Patients who die of croupous pneumonia during the aouter stages 
of the disease, aie from heart failure. The dipioooccus lanceoiatus produces 
a toxin which acts unfavorably anon the heart muscle, and, as a rule death is 
by asthenia and not by apnoea. 1 have already told you that a sudden oedema 
may occur in inf arc ted Darts of the lung during an attaok of croupous pneu- 
monia. That is one of the diseases in which oedema of the lungs sometimes 
suddenly appears and carries off the patient. 6 
Under those circumstances, unquestionably the left side of the heart is not 
acting as strongly as the right side, and often in this way a quick oedema of 
the lungs is produced, which is an exceedingly serious complication. Beyond 
the inflamed area as the inflammation advances, of course we have an inflam- 
matory oedema. A section (No, 55) taken from a part of the lung of a child 
who died from croupous pneumonia will be shown you tonight. It is taken from 
a part a little distant from the solid area, end not only shows acute pleurisy, 
which you want to study, but gives you a good picture of inflammatory oedema. 
THe sections showing red hepatization{No. 54) of the lung will be shown you 
when we next convene. PATHOLOGY, SO. 19. 
Feb. 25, 1898. 
ACUTE CROUPOUS PNEUMONIA. 
Red hepatization (8na stage) 
3ray hepatization (3rd stage): 
Miorosoopio appearanoe. 
On examination oi the section of red hepatization, you will notice that 
there is a very marked engorgement of the vessels in the walls. In the alve- 
oli you see the vessels distended with red blood cells, so that the wails are 
three or four times thicker than they are normally. In the walls you can get 
the vessels out in various directions- transversely, obliquely, and longitudi 
nelly- and everywhere distended with red stood ceils, which are stained of a 
bright yellow or orange color by the oesin. The vessels also contain large 
numbers of polymorphonuclear leucocytes. Ifithin the alveoli you get a deli- 
cate mesbwork of fibrin, a large number of red blood cells, and some polymor- 
phonuclear leucocytes, and a few disquamated epithelial cells are present. 
Irt the stage of gray hepatization, the vessels in the walls of the alveoli 
are less engorged, the polymorphonuclear leucocytes and red blood cells have 
passed out of the vessels into the air cells, the alveoli are more distended 
than in the red stage, and their contents are sore cellular; they contain about 
the same amount of fibrin, a great many more polymorphonuclear leucocytes, 
also many more desquamated epithelial ceils. Many of the* epithelial cells are 
seen to be swollen and undergoing fatty degeneration, prior to their breaking 
down- in readiness for absorption. The fibrin filaments lose their smooth 
contour, become more or less granular, swollen, and vacillated. The polymor- 
phonuclear leucocytes may show no nucleus, or may be entirely broken up, so that one only gets fragments of the nuclei. In this stage the leucocytes and 
the epithelial cells degenerate and become fatty; the fibrin liquefies, and 
all is gotten ready for rapid absorption by way of the lymphatics. PATHOLOGY HO. 20. 
Feb. 28, 18S8. 
Broncho-pneumonia 
Lobular pneumonia 
Catarrhal pneumonia. 
At our last meeting , gentlemen, I spoke to you concerning that form of 
acute inflammation of the lung which involves a good part of a lobe of the 
lung; sometimes two or or more lobes of the same lung, and it may be a lobe of 
both lungs- the disease showing different stages in the different lobes. 
While one lobe is in a stage of advanced hepatization the inflammation will 
be just commencing another. Your attention was called to the fact that in this 
lobar inflammation of the lung we neve an inflammatory exudate taking place in 
all of-the alveoli of the inflamed part, involving them uniformly. Not only 
being present in the alveoli, but in the minuter bronchial tubes; an exudate 
which you will recall was rich in fibrin, and in the earlier stage contained 
numerous red blood cells which bad escaoed from tbe vessels by diapedesis, and 
in the later stages especially, a vast number of emigrated white blood oelis. 
In other words, an exudate to which the term “fibrinous” or “croupous” has been 
applied, ‘this form of inflammation of tbe lung is described especially by the 
German authors as “croupous inflammation of the lung”. 
Tonight I invite your attention to another form of inflammation of the lung, 
in which the inflammation is limited in its extent. Instead of an entire lobe 
being involved in the inflammation we find here and there throughout the lobe 
foci of inflammation, and when we come to examine into the pathology carefully 
we find that the inflammation has its starting point in the terminal bronchial 
tubes, just where the terminal bronchial tubes end in the so-called alveolar duots; just where the mucous membrane of the tube loses its ciliated cylin- 
drical epithelium, and takes on a low cuboidal epithelium. At this point we 
have the starting place for this form of inflammation of the lung, and hence 
it is designated “broncho pneumonia”. In this form of inflammation of the 
lung, the inflammation first involves the walls of the terminal bronchioles, 
ttrerM>h€' w-alls of khe bronchus ■ and invades the surrounding alveoli in fewer or 
greater numbers. Perhaps it may be only a few of these that are involved, and 
perhaps the inflammation may be confined to the lobule which this terminal 
; bronchus supplies, or it may pass from one lobule to the adjacent lobule, in- 
volving several lobules. As toe inflammation is often confined to a few lo- 
bules, the disease is sometimes spoken of as “lobular pneumonia”, whereas croup 
■ ous pneumonia is spoken of as “lobar pneumonia”-that form which involves the 
entire lobe. It has been found that those who are compelled to breathe an 
. atmosphere of dust during their occupations, such as stone cutters, millers, 
I jute spinners, cigar makers, coal heavers, frequently have localized points of 
inflammation originating about the terminal bronchioles. Of course, the small- 
; er particles reaching this point are taken up by the lymphatics 8nd carried to 
the glands; larger particles which remain behind serve as irritating 
agents to bring about a localized inf 1 animation.. at this point. In stone cutters 
a localized fibrous change takes place about the terminal bronchioles, causing 
certain distinct dense fibrous nodules at this point. Ordinarily they do not 
appear to interfere with the function of the lung. If they are numerous, they 
must necessarily do so. in this way a chronic hyperplasia (increase of con- 
I 
nective tissue), is brought about. Again, experimentation has been made upon 
animals, causing them to breath various irritating particles reduced to a spray. Liquids undergoing putrefaction, for example, have been sprayed, and 
the animal oaused to breathe the atmosphere loaded with such spray. Under 
these circumstances a broncho pneumonia is produced- foci of inflammation lim- 
ited around about the terminal bronohiai tubes. The tuberole baoillus, or 
rather the sputum of patients with tuberculosis has been reduced to a spray in 
this way, and animals compelled to breathe it, and under these circumstances 
we find a typical tubercular broncho—pneumonia produced. Then again it has 
been found that if the vagus nerve is divided the animal develops broncho- 
pneumonia after a while. Later it was found that section of the recurrent 
laryngeal nerve would have the same effect. At first this was designated tro- 
phic inflammation of the lung; afterwards it was found out that it was a gen- 
uine inflammation having nothing to do with certain nerves of nutrition; that 
it was a genuine broncho pneumonia brought about by the entrance of particles 
of food and saliva into the larynx of the animal end so down to the bronohiai 
tubes, the larynx being deprived of its usual sensitiveness by division of the 
vagus or its recurrent laryngeal branch, and the animal being no longer sens- 
ible of the fact that these particles were entering the respiratory channels. 
This is a form of lobular pneumonia which occurs in patients who are camatose. 
Where patients suffer with coma for many days, it is apt to be followed by 
lobular pneumonia, which is designated “aspiration pneumonia”. Inasmuch as 
the particles inspired generally contain the bacteria of putrefaction, such as 
broncho- pneumonia is apt to spread rapidly, involving lobule after lobule: 
this is a serious form of broncho-pneumonia. This form of inf1ammation-Bron- 
oho pneumonia- is most often met with in infancy and childhood. It especially 
I c 
aoompanies certain diseases of young chiiaren, and very frequently complicates 
a 
measels, diphtheria, hooping cough and infleuenza, and is responsible forAoon- siderable mortality in these diseases of childhood. In the adult, broncho- 
pneumonia occasionally complicates typhoid fever; though genuine lobar pneu- 
monia occurs more frequently in the adult as a complication. Now, I have 
said that the starting point was the mucous membrane of the terminal bronchio- 
les, and that the inflammation spreads to wail of the bronchus, and then 
involves the walls of a certain number of alveoli surrounding the bronchus; 
now, what is the appearance of a section of a lobe in which there is broncho- 
pneumonia, what would one expect to find ? You recall that in croupous or 
lobar pneumonia when an incision is made into the lung, we find the lung uni- 
formly involved, presenting generally quite a uniform appearance, red or gray 
or yellowish, and in addition having a more or less granular appearance due to 
the projection of minute fibrinous particles from the air sacs. In broncho- 
pneumonia, on the other hand, the cut section of the lung does not present a 
uniform appearance. One finds scattered areas (pea sized- larger or smaller), 
perhaps red or grayish in color, and presenting a different appearance from 
the intervening lung substance, these points being a little bit elevated. 
You see at once that there is no uniform invoivment of the lung. These areas 
are firmer than the intervening lung substance, and if pressed upon generally 
a drop of muco-puruient exudate is forced from the center of the area- from 
the Dronchiai tube which is the central point. In this form of inflammation 
of the lung, you may find these diseminated small areas of inflammation in a 
lobe of one lung, or they may be scattered over ail the lobes of both lungs. 
Now what is the appearance of a section under the microscope? The most strik- 
ing difference between the exudate here and in croupous pneumonia is the lack 
of fibrin, the lessened amount of fibrin present in the exudate. In many oases of broncho-pneumonia there does not seem to be any fibrin present. In 
other oases there is fibrin, but, as s rule, not very muoh, a much less quan- 
tity than in croupous pneumonia, fie find the bronchial tube filled with an 
accumulation of white blood cells ana perhaps a few red blood ceils, fie find 
in the involved alveoli a few polynuclear leucocytes, occasionally an alveolus 
quite packed with them, fie find also some epithelial ceils which have come 
from the wall of the alveolus. You may find a considerable number of red blood 
ceils in addition to the leucocytes and epithelial cells, and in many of the 
alveoli you see a granular material which presents a certain amount of oedema 
in thse alveoli, but you do not see much fibrin. In other words, the exudate 
resembles a good deal that of mucous membrane, ana hence is referred to as a 
■catarrhal exudate, and this form of pneumonia is called "catarrhal pneumonia”. 
You see at once that here we have a different exudate and that this exudate 
is limited in its extent. Between the foci of inflammation one may find the 
alveoli involved in mere or less inflammatory oedema. If everything goes 
well, this exudate is very much more quickly absorbed than the enormous exu- 
date in croupous pneumonia. The patient recovering there is no difficulty 
about the absorption of the exudate. Dr. Carroll will tell you as to the 
means of diagnosing broncho-pneumonia from croupous pneumonia, that is, as to 
some of the best helps in that regard. 
Concerning the etiology of the disease; it is found that in many oases the 
microorganism concerned in the diplocoocus ianceoiatus, in this case entering 
certainly by way of the respiratory tract and not by way of circulation, as 
we believe is the case in many croupous inflammations of the lung. Another 
organism which is frequently found is the streptococcus pyogenes. In broncho- 
pneumonia complicating diphtheria, the diphtheria bacillus Loeffler) has been fonud in numerous instances, sometimes in pure culture, though more 
often associated with the streptoooooous pyogenes. In other oases the staph- 
ylococcus aureaus has been isolated in pure culture. In the majority of oases 
of broncho pneumonia complicating la grippe, the diplocooccus lanceolatus is 
the causative agent, though in a few instances the infleuenza bacillus has 
been alone found, or in such enormous numbers as to lead to the belief that it 
was the causative agent. Rarely the anthrax bacillus has been found. Of 
course there is such a thing as invasion of the lung by the anthrax bacillus. 
the 
I would say regardingAbroncho-pneumonia of measels, diphtheria and influenza, 
that the dipioccocus lanceolatus is the organism most often isolated. One way 
in which broncho pneumonia sometimes originates I did not mention. It occasion- 
ally takes place in this way, A child has a bronchitis and a terminal bron- 
chiole or several terminal bronchioles become plugged with mucus drawn down 
deeply while coughing into the terminal bronchi, effectually plugging them like 
a stopper in a bottle. Under these circumstances the air of the occluded alve- 
oli is absorbed, and as I have told you congestion sets in these ataleotio air 
cells. Now the very muco-pus which obstructed the bronchus contains the in- 
flammatory agent-the bacteria-some of these microorganisms which I have al- 
ready mentioned- and you see that you have at once a most favorable condition 
for broncho-pneumonia. As regards the broncho pneumonia of hooping cough, I 
think it very likely that tRe bacillus of hooping cough will be found frequent- 
ly to be the causative factor. A section of lung which shows a bronchitis due 
to another form of parasite, which is interesting in the study of the subject 
of broncho pneumonia, especially to the veterinary students, is due to the 
ova of a certain worm, affecting hogs and sheep, a form of so-called pulmo- 
nary ? bronchitis, occurs in sheep and hogs, due to the ova of the Strongylus paradoxus in the bog, will also be shown you. 
Let me say just a word in studying this subject of broncho- pneumonia and 
oroupous pneumonia- do not be bothered with the thought of whether you are 
able to diagonise the two microscopically; whether they will be sprung upon 
you, so to speak, in an examination. We cannot get very often lungs which 
show the typical broncho-pneumonia that a student wants to see, in other words, 
half a dozen alveoli involved around the bronchiole, one that would delight 
one’s heart- we find that the inflammation has gone further. The case which 
we have tonight is of broncho pneumonia of a patient who died from diphtheria. 
Tbs section shows with Gram the diphtheria bacillus, the streptococcus py- 
ogenes and the stapbylocoooous. You won’t be able always to locate a focus of 
inflammation, unless you look very closely. You will observe though, as com- 
pared with the lung of oroupous pneumonia that the alveoli present quite a dif- 
ferent appearance. I never give out broncho-pneumonia on an examination, be- 
cause I do not think it is exactly fair, and 1 do not want the class to be 
r 
worried thinking that they are going to get a section of broncho pneumonia. 
Understand the pathology ana do not worry about the microscopical appearances. PATHOLOGY HO. 22. 
Interstitial 
Vesioul ar 
Marsh 4, 18S8. 
Emphysema 
Vicarious or compensatory 
chronic substantive 
Emphysema, 
ft'hen we were on the subject of oroupous pneumonia, gentlemen, I think I 
mentioned some of the terminations of this affection, the most common one 
being resolution, the exudate being absorbed and the lung structure return- 
ing to its normal condition. I think that 1 referrea to the fact that occa- 
sionally tha inflammation terminated in some part of the inflamed lung in a 
local accumulation of pus, known as an abscess; also, that if putrefactive 
bacteria reached the inflammed long by means of the bronchial tubes another 
I termination was gangrene- due®the action of putrefactive bacteria, known by 
I its extremely repulsive odor given to the breath of the patient. 1 also re- 
f ferred to another termination, viz: that of organization of the exudate, re- 
suiting in what is designated interstitial pneumonia. A section of the lung 
in this condition will be shown you tonight. This is one of the rare termin- 
ations of oroupous pneumonia, and may take two forms; one in which the new 
connective tissue is largely interlobular (i.e.extending from the alveolar 
wall into the exudate within the air sacs, gradually replacing it by rich 
vascular connective tissue). The other forms which this interstitial change 
takes is in the thickening and growth, especially of the interlobular wails 
(walls of the airsaos); so that we have radiating bands of connective tissue 
through and through the lung structure. You often see a combination of both- 
the interlobular growth along with the interlobular growth of connective tis- 
sue, which is the most common form. The lung in this condition becomes quite solid (as I have already told you), and in the fresh condition resembles a 
piece of flesh, hence it is called oarnified lung, carnification of the lung. 
This is of course an incurable affection, that part of the lung affected by 
being permanently disabled. It may involve a part or the whole of a lobe 
or even a greater portion of the lung than the lobe may be affected. You have 
' 
had a section showing another form of pneumonia, the so-called “embolic pneu- 
monia”. (1 should have reminded you, however, while on the subject of croup- 
ous pneumonia, that another rare termination is known as “purulent infiltration| 
of the lung”, in which the accumulation of polynuclear leucocytes becomes so 
extensive that the alveolar walls are compressed, indeed the alveolar walls 
themselves become infiltrated with polynuclear leucocytes, so that in exam- 
ining a section you are scarcely able to make out the divisions between the 
separate alveoli. This is one of the rare terminations of croupous pneumonia,\ 
the lung under these circumstances having the appearance of advanced gray hepa- 
tization. Of course when this condition takes place it is very unfortunate 
for the patient. Then another form of pneumonia as I was going to say, is em- 
bolic pneumonia, of which you have already bade, section and the condition ex- 
plained to you. You know that it is due to septic material reaching the lung 
from some infected area on the surface of the body or in the interior of the 
body. These are minute metastatic abscesses in the lung, occasionally hun- 
dreds scattered through each lobe, and each abscess having in its center the 
bacteria transported from some other part of the body- a septic infarct. A 
septic embolus may be of sufficient size to plug a terminal artery producing, 
if the circulation is enfeebled, a hemorrhagic infarct. This infarct, if the 
patient lives long enough, is invaded by leucocytes from all sides, so much so that it becomes separated from the sound lung tissue, just as a slough 
tfould become separated in any other part of the body. The infarct breaks 
down into a purulent material and you quickly have an abscess in the lung, 
fhe usual condition found though is that of miliary abscess. I think in the 
section which you had you were able to see colonies of micrococci. The mi- 
croscopic section explains itself easily in the embolic pneumonia. There is 
also a form of consolidation of the lung, associated with chronic obstructive 
valvular disease of of the heart which is designated by American authors often 
as catarrhal pneumonia. I merely touch upon this: other authors especially 
the German authors, refer to this condition as Heart Pneumonia. We will not 
show you a section of this as it is not of sufficient importance. Microscopi- 
cally, the alveoli are filled with disquamated epithelium from the walls of 
the alveolus, many of these containing blood pigment, and the lung is generally 
in a condition of chronic passive congestion, often designated “heart pneumo- 
nia”. Of course it is not really a pneumonia; it is not a true inflammatory 
condition. This brings us to the end of the acute inflammations of the lung, 
and before we take up the subject of tuberculosis, which is one of the most 
important affections of the lung, I want to call your attention to one of the 
degenerations of the lung, designated as emphysema. By the term emphysema 
we understand the presence of sir in the connective tissue of the body, which 
is the general meaning of the term emphysema (generally in the subcutaneous 
connective tissue.) 
Emphysema of the lungs is divides into two principal forms: interstitial 
emphysema, in whiob the air has escaped from one or more ruptured air cells 
into the interlobular connective tissue or the subpleurai connective tissue; / 
and vesoular emphyseum (whioh refers to an entirely different form) in which 
the air cells have undergone an increase in size, due to an abnormal accumu- 
lation of air within the air ceils proper of the lung, leaning to distention 
of these and to atrophy of their walls, Mow there are two forms of vesoular 
A 
emphysema, generally designated acute vesicular emphysema and chronic vesicular 
emphysema, or chronic substantive emphysema, sometimes chronic idiopathic em- : 
physema; sometimes chronic diffuse emphysema. To return a moment to intersti- ] 
tial emphysema, this is an acute form of emphysema, and occurs frequently in 
children who are the subjects of diseases attended with severe paroxysmal coughi 
ing such as hooping cough. In a paroxysm of whooping cough the air cells along; 
the anterior border of the lung toward the apex of the lung may become sudden- 
ly so distended with air that their walls give way, admitting air into the in- 
terlobular or subpleurai connective tissue. At autopsy, beneath the pleura, 
numerous little or pea-sized blebs, pearly looking blebs, are seen, 
which represent the air which has escaped from ruptured air cells, iven dur- 
ing life the air may reach the connective tissue of the anterior mediastinum 
(that connective tissue just beneath the sternum) and may pass along this 
connective tissue into the cervical connective tissue, giving you emphysema of 
the side of the nook and over the shoulder- not necessarily fatal at all. A 
child may present such symptom as that in whooping cough and make a perfectly 
good recovery. Now to return to vescuisr emphysema; when one lung for in- 
stance is compressed by a pleural effusion, the air cells of the lung undergo 
considerable distention. In other words, they undergo a compensatory disten- 
tion- vicarious distention. I called your attention to this fact when we 
were considering the lung in a general way, and I told you that sometimes this over distention, this vicarious action of the lung, leads to structural changes 
in the lung. 'He may have in this way, where the effusion is of long standing, 
an emphysema of the vesoular variety produced in the other lung- vicarious or 
compensatory emphysema. Then again, where a number of terminal bronchi are 
obstructed we may have a compensatory emphysema in other lobules of the lung. 
While a certain number of the lobules are the seat of collapse ( atalectasis), 
in order to supply the necessary respiratory surface, others undergo sufficient 
enlargement to constitute the condition of acute compensatory emphysema. In 
chronic substantive emphysema- tne form which is generally understood when one 
speaks of emphysema of the lungs- the entire parenchyma of both lungs may be 
involved. As a rule the apices, the upper lobes, the anterior border of the 
middle and lower lobes and the lateral borders of the lower lobe are gener- 
ally the points involved ey'en in chronic substantive emphysema. Now first as 
regards the gross appearance of the lungs the seat of this disease: You can 
diagnose emphysema of the lungs by examining the body of the cadaver, finding 
prominent, rounded chest, the projection at the upper part of the chest one 
may see before opening the thorax. Gdod opening the thorax the lungs do not 
collapse. They are found to meet in the center and perhaps to entirely 
bide tne pericardium. They are pale and and do not give the ordinary 
signs of crepitation when pressed upon or when out- toey give the sensation of 
a soft, doughy feel. If you grasp the lobe of a healthy lung between your 
thumb and index finger and approximate the finger and thumb, you find that you 
have considerable substance between the fingers, something which dis- 
tinctly feel as lung parenchyma. If you grasp in the same way a lung which 
is the seat of chronic substantive emphysema you will be surprired to find 
that your fingers almost touch each other. In other words there is a marked atrophy of the lung substance here, quite obarsoteristio when pressed between 
the fingers. The heart extends further to the right than in the healthy conA 
dition, due to the hypertrophy and dilatation of the right ventricle. You 
can see the air vesicles of such a lung with the necked eye, pinhead sized- 
the dilated vesicles showing distinctly as pinhead sized areas or even larger. 
Microscopically, it is seen that the ind/fundibula are very much dilated and 
that the individual air sacs are also dilated ana have broken one into the 
other. Suppose we take a cut (see fig) of an ordinary bronchiole-(this fig.l) 
you understand is the infundibulum of a terminal bronchial tube or terminal 
duct with a certain number of air sacs surrounding it. Now in emphysema of 
course the ultimate bronchioles also have a certain number of air sacs sur- 
rounding them. The first change which takes place (microscopically) is in the 
alveolar duots and in the indifundibuium- these become much distended and the 
interspaces between the alveoli can hardly be seen. You will see by the sec- 
tion that the figures are not exaggerated. Not only that; adjoining indifundi- 
o 
buia may break into each Either, sc that you get an enormous vacancy in the 
\ 
lung substance. This dilatation is due to atrophy of the structure proper of 
the alveolar walls. You know in the healthy lung the alveolar wall has a 
Quantity of fine elastic fibers, which give it support. When atrophy of these 
elastic fibers takes place small openings are formed from one alveolus to an- 
other where they join, here a rupture occurs, this growing larger until sev- 
eral alveoli are converted into the common sac. You will readily understand 
that while this atrophy is going on in the alveolar wails, the capillary net 
work, which is very fine becomes much coarser, many of the capillaries become 
obliterated- fortunately without hemorrhage as they undergo atrophy by pres- sure. Now one of the results of this obliteration of so many of the capillar- 
iss of the lung, rm an interference df the proper circulation of the blood 
through the lungs. I think I gave you emphysema as one of the causes of chron- 
ic passive congestion of the liver. You now understand how it is that this di- 
sease causes chronic passive congestion of the liver- more work is thrown upon 
the right heart in emphysema and this hypertrophies, or at least it should 
hypertrophy if this disease continues. The hypertrophy is often followed by 
dilatation- compensation is broken, the right heart dilates, and gives rise to 
passive congestion of the liver, stomach, kidneys, spleen, etc. Microscopical- 
ly one frequently finds, generally finds,disease of the bronchial tubes which 
are the seat of inflammation,—bronchitis is present, frequently their walls 
* 
are also involved- much thickened. Now as the causation of emphysema of the 
lungs- there has been a good deal of discussion on this point. The majority 
of authors have attributed emphysema to the accompanying bronchitis, or to the 
presence of a chronic bronchitis. Laenneo (the great french Physician) believ- 
ed that the presence of bronchitis was the most important element in the pro- 
duction of emphysema of the lungs. Be believed that the air during inspire*- 
tion was carried into the alveoli, but during expiration was preventid from 
leaving the aiveoli by the plugs of mucus in the bronchial tubes. In this 
case the air cooped up in the alveoli underwent ratification by heat and sc 
distended the aiveoli of the lungs. Another physician, Gsdner, also attrib- 
uted the emphysema largely to bronchitis, but he believed that it brought 
about emphysema of certain lobules by causing a dilatation of certain lobules; 
in other words, be believed that when certain lobules were distended by the 
products of the bronchitis, these collapsed, as I have already told you they will do (the air being absorbed) and other obstructed lobules underwent by 
vicarious or compensatory emphysema. These were two prominent defenders of 
the inspiratory theory of emphysema. The objection to this theory, as far as 
the lungs are concerned, is that the expiratory act is stronger by a third than 
the inspiratory; so of the air succeeded in entering the air cells it should 
also succeed in leaving them, especially when the full expiratory force is 
brought into play. Gainer's theory certainly accounts for the compensatory 
emphysema found in broncho-pneumonia. But in chronic substantive emphysema 
thet requires some explanation, and it is now believed that in this disease, 
the air cells become ever distended as the result of expiratory force and not 
as the result of inspiratory force. For example, a child has hooping cough, or 
a patient has ohronio bronchitis with spasmodic coughing, now, during a par- 
oxysm of coughing the glottis is suddenly closed and the respiratory muscles 
acting on the base of the chest force the sir suddenly into the upper parts 
of the lung and as it cannot escape through the glottis, it over distends the ! 
air cells. Again, in an individual by reason of bis employment, blowing upon 
a wind instrument, when that requires a good deal of expiratory effort, will 
under these circumstances we have, just as in paroxysmal coughing, distend 
the air ceils t- the lung. The fact that the left lung is more effected than 
the right would also bear cut the expiratory theory, because the presence of 
the liver on the right side interferes with the compression on that side of 
the chest, consequently the left lung is more affected than the right in em- 
physema. The expiratory theory even does net fully explain the permanent over- 
distention of the sir ceils of the lung: there is something else required here, 
hot every individual who blows an instrument or who is a glass blower develops 
emphysema,nor every child who has whooping cough, by any means, in other words, giver this employment in certain individuals and you have emphysema, 
given the same employment in others and you have nothing of the kind. 
Cohnheim believed, as the result of his studies of the histological elements 
of the lung, that in individuals who developed emphysema as the result of in- 
creased expiratory force, there was a congenital lack of development of the 
elastic tissue of the lung. Bearing on this point, it has been ascertained 
that emphysema is largely a hereditary disease. Dr. Jackson of Boston, in 28 
i oases found well marked heredity in 18 of these where several members of the 
: family were affected with emphysema, and their ancestors, etc. So that in 
addition to the expiratory force we must take into consideration some congeni- 
tal defect, some vice, some error in nutrition in order to bring about emphy- 
: serna. Bronchitis may either precede or accompany it and a bronchitis in some 
individuals may be the starting point for a chronic emphysema. You will ap- 
preciate that the destruction of the alveolar walls and of the capillaries 
leads to the diminution in the respiratory surface of the lung, in other words 
whereas a healthy individual, any of us or ail of us, have a certain amount of 
reserve lung, which we can call into pi ay when we take a slight amount of ex- 
ercise without showing any distress. Most of us can go up two or three flights 
of stairs without showing any respiratory distress. Not so with the emphyse- 
matous individual; he has no reserve supply of lung, and hence very slight ef- 
forts bring about labored respiration. If there is much bronchitis, then his 
respiration is labored all the while. 1’hese are the individuals who are com- 
paratively free from pulmonary distress during the summer months, but when the 
winter months come on, they are at once overtaken with this labored form of 
respiration. Of course it is an incurable disease, but one cannot even treat 
an incurable disease unless he has some conception of its pathology. On Monday evening we will take up the subject of tuberculosis, provided 
there is sufficient time after the Quiz. PATHOLOGY NO. 24. 
March 7, 1898. 
TOBERCOLOSIS. 
‘Tonight, gentlemen, I want to just briefly call your attention to the sub- 
ject of tuberculosis of the lungs, by way of introduction. Tuberculosis is 
one of the most important diseases of these organs, because it is more fre- 
quently met with in practice than perhaps snyotber disease of the lungs- a 
disease which you all know is due to the presence of the tubercle bacillus. 
¥ou can form no idea of the confusion that foraieriy prevailed concerning va- 
rious lesions 'which appeared in the lungs as the result of the action of tu- 
bercle bacillus, prior to Koch's discovery of this bacillus. The whole sub- 
ject has been wonderfully cleared up since we know the causative agent. Let 
me say that the tubercle bacillus may reach the lungs through three different 
channels: The respiratory channels, the bloodvessels (circulatory system), and 
through the lymphatics. The ordinary channel is unquestionably the respira- 
tory- the tubercle bacilli being taken in with the air breathed into the lungs. 
Now wherever the tubercle bacillus lodges ( it makes no difference in what 
tissue of tie body, whether In the lungs, liver, kidneys, in the connective 
tissue, mucous membrane, serous surface, it matters net where) it brings about * 
nearly always- scarcely an exception- certain quite distinctive changes; chang- 
es which are quite to be contrasted with those produced by ether bacteria. If 
the pyogenic organisms reach an organ you have certain changes; you have an 
emigration of polynuclear leucocytes and you have e suppuration taking place; 
not so with the tubercle bacillus. This organism causes certain definite 
changes which partake of the proliferative character. Long ago Laenneo called 
attention to certain minute, miliary-sized, grayish, somewhat translucent, little masses that were to be found in the lungs, and in other tissues, which 
if . 
be designated as tubercle, or “tubercles” (not tuberou-1 es). He had no idea 
what the origin of these was, but called attention to the fact that they en- 
larged and underwent certain changes in their Interior. In recent ye&rs these 
have been carefully studied microscopically, end when seen at different stages 
present certain quite different appearances. If the tubercle bacilli lodge in 
a tissue, let us say in the lungs- let us say that they are brought by the way 
of the bronchial tubes to the alveoli, or by way of the bloodvessels into the 
alveolar wails- wherever they lodge the tissues begin to undergo proliferation 
(multiplication of the fixed cells of the part), and we find in the center 
large, vesoular looking nuclei, certain large stained nuclei, you see nothing 
but the nuclei. These are designated on account of their resemblance to the 
nuclei of the epithelial cells, “epithelioid” cells. These epithelioid ceils 
are derived from the multiplication of the connective tissue cells of the part. 
That is, proliferative changes give rise to epithelioid cells, ceils with 
large oval palely stained nuclei. Then outside of these ceils we find certain 
smaller ceils, the round nucleus staining quite deepiy, ceils which in all re- 
spects resemble the ceil s seen in tie normal lymthc t-0 gland, and anich on this 
account are designated "lymphoid” ceils. These lymphoid ceils completely sur- 
round the larger epithelioid cells in the center of the tubercle. At times 
the multiplication of these lymphoid ceils is so great that they completely 
cover up the epithelioid cells, which you may not see at all, hence you can 
readily understand that if a section passed through the outer edge it woulci 
only show the lymphoid cells. Another thing, it is hard to find tubercles 
■just at tte stage which will give you a true histological picture, though the : picture which I have giver you is the one that you must become acquainted with, 
we find in the early stages of tue tubercle that the bloodvessels (capillaries) 
in the part are entirely destroyed- so that the miliary tubercle is devoid of 
vessels, a nonvascular structure. $ow, as I said, it is difficult to find tis- 
sue (we had such lest year but they were ouiokiy used up) showing miliary tu- 
bercles in granulation tissue in which we could demonstrate easily the epithel- 
ioid cells and the surrounding lymphoid cells, but whether we find these or 
not, you know that is what takes place. After long discussion as to the or- 
igin of the epithelioid cells, all admit, even BaumgsrJten, who has a special 
theory as to the small round lymphoid cells, that these ere proliferated cells, 
due simply to the proliferation of the connective tissue ceils, or tissue 
cells of the part. Concerning the lymphoid cell there has been some dispute. 
Baumgarten, 'who has especially investigated the histology of tubercles or the 
formation of young tubercles, believes that these are the smell emigrated leu- 
cocytes from the bloodvessels. Very many share the same opinion with Baum- 
garten- others contend that these also are small proliferated connective tis- 
sue cells. It is impossible to say which is true- probably they are connective 
tissue ceils and not emigrated 1-euoooytes; it seems more probable that they 
are connective tissue cells. Now you may also find at the center of the tuber-j 
ole a ceil of an entirely different character, ana upon which a good deal of 
stress has been laid, which has often been called the characteristic tuber- 
cular cell. I refer to the giant ceil. You may find certain large cells, 
which when stained in the section give you an oesin stained center especially, 
a cell without any distinct limiting membrane, which contains s number of 
oval nuclei, generally scattered aroiind its periphery- sometimes 18 to 24 nu- 
clei in this one protoplasmic mass- a large cell with a granular center and about its periphery a considerable number of oval, rather palely (?) stained, 
somewhat vesicular nuclei- the so.oalied giant cell. This ceil was formerly 
considered characteristic of tuberculosis. We know that it is not at all. 
Giant cells are found in chronic inflammatory conditions' of the tissues, they 
are found around foreign bodies which are introduced purposely into the tis- 
sues of animals; they occur in the nodules of leprosy, etc., but they especial - 
the 
iy occur in tubercular lesions. Sometimes the giant cell isAcentrai cell of 
the tubercle, and around it will be the epithelioid cells, and around these 
the lymphoid cells, or the giant cells may be located somewhere in the per- 
iphery of the tubercle. Now, these are generally considered to be giant con- 
nective tissue cells, some believe from the fusion of epithelioid cells; some 
believe that the cell not undergoing division and its nuclei continuing to 
undergo division gives this peculiar picture (the nuclei being scattered around 
the margin- of course sometimes the nuclei may be gathered at the two poles 
of the ceil.) As to the origin of the giant cell, nothing is positively known. 
We only know that they occur in various conditions other than tuberculosis. 
Always be prepared to see giant ceils in miliary tubercles- do not be disap- 
pointed if you do not find them. Sometimes upon a stained section the tuber- 
cle bacilli are found located in the center of the giant ceil, so that many 
authors consider the giant cell as having undergone coagulation necrosis. 
Now what changes does tubercle undergo? In answer to that 1 will say, cer- 
tain definite characteristic change, due possibly in part to its being a non- 
vascular structure, but due in greater pert to the specific action of the 
tubercle bacillus. In other words the center of the tubercle undergoing ne- 
3 3? 0 5? j F 
--—-—(underscore that about six times), tost form of necrosis which t'eigert has designated “coagulation necrosis”, and to which we apply the term 
“caseation”. It becomes converted into a cheesy-like material, and hence 
you are prepared to hear that stained with cesin you get what? all the epithel- 
ioid cells obliterated, a somewhat homogeneous often granular center, quite 
deeply stained with oesin, necrotic tissue, in the center, and this necrotic 
tends to spread and involve not only the miliary tubercle, but all the products 
of the miliary tubercle. While the lymphoid cells are being proliferated arounc 
■ 
the margin, the necrosis, (the caseation) in the center is advancing. Indeed 
when you examine the majority of your sections of miliary tuberculosis, you 
find that the epithelioid cells have undergone necrosis; you get simply the 
lymphoid cells surrounding the tubercle. So, remember, gentlemen, that the 
tubercle bacillus, wherever it lodges causes a definite, characteristic pro- 
liferation of the fixed cells of the part, which is followed by caseation (ne- 
crosis) of the center. Observe that 1 have said nothing about the entrance 
of polynuclear leucocytes, ihey take no part in it. Remember though that 
when caseation takes place, when necrotic tissue is formed, then we have a 
tissue which attracts the polymorphonuclear leucocytes. The tubercle bacillus 
very rarely exerts any positive chemotaotic action on the polymorphonuclear 
cells. Councilman, however, has reported two cases of tubercslosis of the 
lung in which there was formation of pus at a very early stage. They are the 
only two cases on record that I am aware of. If any one asks you if the tu- 
bercle bacillus is pyogenic, say MG. It is not at all, as we understand it. 
fie only have migration of the leucocytes into the tubercle after necrosis has 
taken place in the lungs of children very early, and it is in such that we 
find the early migration of polymorphonuclear leucocytes into the caseation. PATHOLOGY SO. 25. 
TUBERCULOSIS, (continued) 
Marob S, 1898. 
During the course on bacteriology, gentlemen, I think 1 mentioned to you 
some of the biological characteristics of the tubercle bacillus; calling 
your attention to the fact that it grew best at body temperature, and that it 
was rather resistant to drying; that the tubercle bacillus maintained its vi- 
tality for a long time in the dry sputum. At the last lecture I mentioned 
the ways by which the tubercle bacillus entered the body putting the respiral- 
tory tract as the first and most important portal of entry; also mentioning 
the digestive tract, the genito-urinsry passages, and by wounds of the skin. 
Infection through the skin is less frequent, though there are numerous instan- 
ces on record of such infection. Children have been infected in this way 
following the operation for circumcision, the mouth of an individual having 
tuberculosis being applied to the raw surfaces sometimes, as the Jewish opera- 
tors do. In this way the wound' becomes infected with the tubercle bacillus, 
infecting the nearest lymphatic glands first, then the blood, and the patient 
becomes the subject cf tuberculosis. I think I called your attention to the 
fact that tuberculosis is an infectious disease- not only an infectious di- 
sease, but a contagious disease. I mentioned the. experiments cf Cornet, in 
which he demonstrated the t the tuberoule bacillus could be found in the dust 
of wards and rooms occupied by patients who had pulmonary phthisis. I also 
mentioned to you the observations of Strauss, who made use of the mucus dis- 
, ... and 
cnarge from tne nares ot physicians, nurses, medical students who were especial- 
ly in attendance on tuberculous patients, inoculating this material into the 
abdomen of the Guinea pig, and producing a tuberculosis in a majority of the 
inoculated animals. I emphasized tbs fact that the dangerous zone was the one in close proximity to the patient- the room in which the patient is living; 
that the tubercle bacillus is not spread everywhere; that we fail to find it 
in unoccupied rooms; that we failed to find it in the wards of hospitals where 
other classes of patients ace treated, and 1 think following this I recommend- 
ed to you the disinfection of the sputum. I cautioned you against permitting 
the sputum of tuberculosis patients to become dried, so that it might be ground 
under foot or reduced to a condition of powder, and hence easily raised by 
currents of air. As long as the sputum is moist, there is no danger from it- 
the danger is from the dried sputum. 
During the last lecture, cerhaps 1 did not mention to you the very delioate 
£ 
retioului that oan be made out in certain young mid ary tubercles- the re- 
mains as we believe of fibers of connective tissue. As a rule we do not see 
this reticulated structure, sc 1 omitted to mention it at the last lecture, 
having in mind the general appearance of the miliary tubercle. Looked at 
from ots finest histological point, a reticulum is seen in miliary tubercles 
occasionally. I think I also mentioned to you as regards pulmonary tuberculo 
sis, that the bacilli reached the lung in different ways; most often by the 
bronchial tubes (the respiratory channels) also by the lymphatic vessels, and 
also by the general circulation (bloodvessels) Of course the first channel is 
perfectly evident to all. In oases of tuberculous diseases of the vertebrae we 
have the lymphatics of the pleura first affected by the tuberculous virus, and 
thence the bacillus distributed through various parts of the lung. Then again 
we have only few tubercle bacilli reaching the lung by way of the bloodvessels 
(circulation), or we may have an enormous number reaching it by way or the 
bloodvessels. If the number is large, then we have an outbreak of an immense 1 number of miliary tubercles. Under these circumstances we have infection by 
a quantity of tubercle bacilli, such as occurs for instance when a tuberculous 
lymphatic gland ruptures into a bloodvessel, or when the bacilli have come by 
way of the lymphatic channels and the thoracic duct from any tuberculous scusoe 
When in considerable numbers, we not only have tuberculous developed in the 
lungs, but in various organs of the body- we find tuberculosis everywhere ex- 
cept in the muscles and in the skin; in certain organs more frequently than 
in others, the lung, kidney, spleen and liver being especially frequent. Now 
according to these three modes of infection we may have a foous of tuberculo- 
sis in any structure of the lung, involving the wail of the bronchus, within 
the alveoli, on the septum between the alveoli; in the lymphatics; in the in- 
terstitial connective tissue of the lung, affecting the pleura itself. Simply 
because so many of the structures or all the structures of the lung may be 
affected in different cases, and because the process undergoes varying degrees 
of rapidity in different individuals, it results that at autopsy baraly any 
two oases of pulmonary tuberculosis present the same appearance, bet us sup- 
pose for instance, that the tubercle bacilli have entered by way of the res- 
piratory channels, and nave lodged in an ultimate bronchiole. There we have 
miliary tubercles developed; the miliary tubercle may enlarge undergoing ca- 
seation in the center growth at the periphery so that it afterwards forms s 
body sufficiently large to be seen as a yellowish or a yellowish white mass 
in the pulmonary parenchyma. Now wa cave from this central tubercle, numer- 
ous others formed in its immediate vicinity, the bacilli being taken up by the 
lymphatics and by the wandering cells, passing back into the tissues. In this 
way we have a central focus and numerous foci smaller than the central one, scarred around, and then these growing in various directions may finally ap- 
proach each other and form what is known as a "conglomerate tubercle”. If 
caseation takes place in the whole area, then we have quite a large tuberculous 
focus. The large tuberculous nodules found in the brain and in the spleen are 
usually of this formation, starting from a very small center, the tubercles 
forming around this and undergoing enlargement and caseation until they unite. 
Now, under these circumstances, we may , also, at the same time have the bacil- 
li taken up by the lymphatics and carried a considerable distance from that 
point and here and there other foci develop wherever the bacilli lodge, ne 
have tubercles formed in this way in tie perivascular spaces; in the peribron- 
chial connective tissue; we may find them beneath the pleura, and so scattered 
through the lung, each one undergoing this coagulation, necrosis or caseation 
(death) in the center. Now one of the characteristics of a tuberculosis focus 
is that following the caseation in the center, it undergoes softening (lique- 
fioation). Suppose we have an area, s tuberculous focus of this kina, looai-ea 
in the parenchyma proper, of the lung: we will say of infection coming by way 
of the bloodvessels and that it has attained s considerable size in the way L 
I have designated (toe same epithelioid and lymphoid cells) this area in its 
growth reaches a bronchus and the wall.undergoes necrosis until the entire j 
wall of the bronchus becomes effected, undergoing this peculiar softening and 3 
is at last broken through and the tuberculous materiel enters the bronchial 
*»• •• • 
tube. Under these circumstances vre have bacilli appearing in the sputum. 
You do not find bacilli in sputum in pulmonary tuberculosis until some area 
has undergone softening and these softened contents have reached the interior 
of a bronchus; so that in acute miliary tuberculosis affecting the the lungs the absence of baoilli from the sputum in not a basis for the conclusion tbat 
tbe patient has no tuberculosis. In the ordinary forms of tuberculosis, ne- 
crosis takes so quickly and tbe bronchus is perforated so Quickly tbat if 
there is any considerable amount of sputum we find tbe bacillus. Mow is there 
any danger in this infected material reaching tbe bronchial tubes ? Yes, very 
serious danger. In the first place this material is not raised, another part 
of it reaches other branches and is aspirated into other parts of the lung; is 
quickly dissemated by way of the bronchial tubes; and wherever this tuberculous 
jfc * 
material lodges it sets up s&me changes tbat I have already indicated to vou. 
K' 
Mow another important point in connection with tuberculosis of the lung, (this 
is important to remember) is tbat we don't always have miliary tubercles 
formed in the lung. We may have as a result of the tuberculous virus being 
Y 
carried to other bronchial* tubes, we will say a diffuse infiltration of tbs 
parenchyma of the lungs with epithelioid and ly-mpboid cells in enormous num- 
bers, and microscopically get no diagnostic Picture of a tubercle. This we 
speak of as infiltration of- the tissue, and in no tissue does it occur so 
often as in the lung. Another point to bear mind is that these cells ooour- 
ing in s wide spread infiltration have the same tendency to undergo caseation 
as in tbe miliary tubercle. This is what we have taking place in the so-called 
oases of “Galloping consumption”- considerable parts of the lungs, many lobules 
occasionally half of a lobe, sometimes an entire lobe and cases are on record 
where an entire lung has undergone the neouiiar change. First the tissues 
are invaded by the epitbeiiod and lymphoid cells, the alveoli being crowded 
with them. You may see such alveoli in some of your sections, and as a re- 
sult of the action of the tubercle baoilli, all of this mass undergoing oa- seation, producing what was formerly known as osseous (or oheesy) pneumonia 
long before we knew anything of the tubercle bacillus. There were any num- 
ber of theories concerning "caseous pneumonia;;; that was one of the subjects 
on which there was very great confusion in elucidating the pathological changes 
in the lungs prior to Koch's discovery of the tubercle bacillus. Now we know 
that caseous pneumonia is due to the specific action of the tubercle bacillus, 
occurring in individuals who have little resistance to the inroads of this or- 
ganism. Another point to be borne in mind is that wherever the miliary tuber- 
cle occurs, especially in the lungs it acts as an exciter of inflammation. 
It is itself, so to speak, a foreign body, a new the tissues in 
many oases appearing to resent the invasion. So don’t be surprised if you find 
in your section of the lung signs of inflammation about the tuberculous areas- 
you nearly always find them, perhaps the alveoli filled with polymorpho- 
nuclear leucocytes, some red cells, fibrin and oedema; all of these present 
with pulmonary tuberculosis. Only in case you obtained a lung at the earliest 
stage of acute miliary tuberculosis would you miss the inflammatory process. 
This is important to bear in mind. As the result of the softening of tuber- 
culous foci, we have appearing in the lungs certain cavities which we ail as- 
sociate in our minds- or those of us wno have seen many autopsies- pulmonary 
tuberculosis. These represent areas of caseation, where the material was 
broken dov(p,.. being carried away, and has reached the bronchial tube so that it 
could pass out by expectoration or pass to other parts of the lung, rie now 
believe that the pyogenic organisms are important in this connection, that is, j 
that they hasten the process. The staphalooooous and the streptococcus pyoge- 
nes especially having been found in tuberculous cavities. The cavity en- 
larges by this caseous degeneration taking place in its wall. These cavities are irregular as a rule, presenting many projections, and sometimes one sees 
skirting the walls of the cavities enlarged bloodvessels, which are often diT 
lated, little aneurisiai sacs from the withdrawal of the air pressure and the 
bloodvessels may rupture and lead to rapidly fatal pulmonary hemorrhage- though 
I have always told you that as a rule this hemorrhage was due to the breaking 
down of small miliary tubercles and is generally not dangerous, ft here there is 
a large aneurismal bloodvessel iH. the wail of the cavity, then the hemorrhage 
is large, and is sometimes fatal- within a few minutes. If a tuberculous pro- 
cess is to be arrested, it generally takes place by the formation of connective 
tissue around the tuberculous focus. Where patients have considerable resis- 
i 
tanoe to the inroads of this bacillus, we find small and large tuberculous 
foci (upon section) surrounded by a distinct band of quite dense fibrous tis- 
sue, giving rise to the so-called “fibroid tuberculosis". Indeed, the fibrous 
tissue may enter tbs tubercle, displacing the tuberculous tissue, so that We 
have a dense nodule of fibrous tissue in the lung, but' this is one of the rare 
occurrences. So too, we may have the connective tissue of the lung very much 
increased in connection with the presence of tuberculous foci scattered about 
in the substance of the lung, giving rise to the so-called “fibroid phthisis" 
in lungs where the tissues have reacted by the production of large quantities 
of connective tissue (which is very small in the normal lung), then again 
it is possible that lime salts may be deposited, the cheesy material becoming 
dry and healing taking place in this way. fte find in the apex of the lung 
occasionally at autopsy such a mass, which represents a healed tuberculous 
focus. In the majority of oases, however, another of these terminations takes 
place, of which I have already spoken to you, the process slowly and gradu- 
ally advancing. It is not proper to divide chronic tuberculosis into the preoavity stage and into the stage in which cavities are present in the lungs, 
simply because we find areas of tuberculosis in all stages in the lung; one 
just beginning; another already softened, and having given rise to a cavity. 
The tubercle bacilli generally affect lodgment in the apex of the lungs, and 
spread from that point toward the base. In the section this evening showing 
miliary tuberculosis (lungs of child) caseation has taken place rapidly and 
the areas are already invaded by polynuclear leucocytes, (finis) PATHOLOGY, HO. 26 
March 11, 1898. 
TOBiRCOLOSIS (continued) 
The two sections wbioh you have this evening will be the last of the lung. 
There will be an examination on Monday evening. 
There was one thing wbioh Or. xReed forgot to mention in his lecture, and he 
has requested me to oall your attention to it, and that is, that tuberculosis 
is net an hereditary disease. The predisposition to tuberculosis is inherited, 
but not the disease itself. It is very exceptional for tuberculosis to be dis- 
covered in the unborn. A great many observations have been made on children 
born of tuberculosis parents, and few exceptions have been noticed of the diseaj 
sease being inherited. It is a constitutional weakness from the disease of 
the parents. Another thing, the tubercle bacilli may enter the body and remain 
latent for a number of years. Some French investigators, a few years ago, 
made a series of experiments upon healthy individuals. The material, they used 
was from the bronchial lymph glands, perfectly fresh, from persons who died 
from violence.• The bronchial glands were rubbed up in a mortar, and injected 
into Guinea pigs, and more than o0% of the Guinea pigs died of tuberculosis, 
showing that these apparently healthy individuals carried the tubercle bacilli 
in the bronchial lymph glands without manifesting any signs of the disease. 
The tubercle bacilli may enter by way of the respiratory tract, be deposited 
in the lymph glands of the lung and remain there for a number of years; then 
caseation occurs, there is a rupture into a pulmonary vein, and in that way 
the organism gets into the circulation and excites general miliary tuberculo- 
sis, or, the bacilli instead of entering the circsiation direct, may get into the lymph channels, and be carried by the lymph channels to the thoracic duct, 
and in that way enter the circulation and excite general miliary infection. 
The bacilli may enter the body without there being any lesion that can be de-r 
tected. In a number of instances tuberculosis of the retro- peritoneal lymphat- 
ic glands has been found without any lesion in the intestine. 
After the examination (Monday) we will take up the kidney. PATHOLOGY, NO. 27. 
March 18, 1898. 
KIDNEY. 
Histology; Acute Congestion; Chronic Passive Congestion. 
It is hardly necessary for me to state to you gentlemen, that the diseases 
of the kidney- the organ which we will now take up- are of extreme importance. 
I will ask you to recall briefly your knowledge of the histology of the kidney: 
You know that the kidney is very of ten. designated as a'compound tubular gland 
with epithelium of several kinds largely entering into the structure of its 
parenchyma; that it is quite richly supplied with blood vessels; that the epi- 
thelium lines certain tubular structures, and that each of the tubes runs an 
independent course. You recall that the kidney is divided into two areas (two 
parts) the “cortical”, that portion lying under the capsule, and the “pyramidal 
or medulary” part, that portion adjacent to the pelvis of the kidney; and that 
in the cortical part we find the secreting mechanism of the kidney. You recall 
that t,tg,kidney tubules begin with quite a wide, expanded extremity, and that 
the tubule at first runs a somewhat convoluted course in the cortex; then dips 
down into a straight tube entering even the medullary portion of the kidney; 
then turns upon itself and again enters the cortex- quite deeply into the cor- 
tex- again becomes a oonvulated tubule, and finally descends to the pyramidal 
or medullary section of the kidney. The first descending and ascending por- 
tions are designated respectively the descending and ascending limbs of fienle’s 
loop, the loop which is made being described as Henle’s loop, and when it de- 
scends a second time it is termed a straight or collecting tubule. You recall 
that the epithelium varies in character in the several parts of the kidney tu- 
bule; that the epithelium lining the capsule of Bowman (the expanded portion) is quite flat, is soon as tee tubule proper begins- starts on its course from 
this expanded extremity- the epithelium at onoe becomes a medium columnar epi- 
thelium (medium in height); that it continues of this character until the de- 
scending limb of Rente’s loop is reached, when it again takes on a low form 
but not so flat as that in Bowmans capsule. That in the ascending limb of 
: \ 
Rente’s loop it is again slightly higher constituting a low ouboidal epithel- 
ium. Jn the second convoluted portion it takes on a form- a columnar epithet- 
ium of medium hieght- which becomes still higher in the straight or collecting 
tubules. This you will find, of course in your Text book on the histology of 
the kidney. 
flow, let me oail your attention for a moment to the blood s.upply of the kid- 
8 
ney, which is of rather peculiar character. You recall that the vessels enter 
at the hylum of the kidney, and that branching at that point they ascend 
to the district between the medullary end cortical portions where they form 
arches, and from the convex surface of these arches are given off straight 
branches which pass up into the cortex, and are called "interlobular” branches; 
small branches „ . , . , , . . 
and that from these interlobular brenohesAsre given oil on either side which 
go to supply those peculiar structures, tbe“Malpigfaian bodies,;of the kidney. 
You recall that the artery upon entering the expanded end of the kidney tubule, 
or Bowman’*s capsule, divides into a number of branches (capillaries) and that 
these form quite a capillary net work within the expanded tubule, the blood 
afterwards leaving at the same point by the efferent artery- and that this ef- 
ferent artery breaks up again into another capillary district, so that we have 
two distinct series of capillaries- the first, a very important one forming the 
Malpighian bodies; the second and squally important surrounding the secreting tubules of the kidney. The kidney, therefore, has a double supply of capil- 
laries. The blood which leaves the Malpighian body is still arterial blood. 
Another thing to bear in mind is that the tuft of capillaries within Bowman's 
capsule is of very peculiar kind, it is the queerest, the most peculiar oepil- 
1 ary net work that we know of in the body. In the first place, the branches 
of the efferent artery which enter Bowman's capsule do not anastamose with 
each other; they form loops twisted here and there; the most remarkable body 
which one can wish to see under the microscope, and in which no anastarnoses 
can be made out between the loops. In the next place, although ther< 
are cells within these capillaries, no one has yet made out by nitrate of sil~ 
ver stain that they are distinct endothelial cells. They are cells of a pe- 
culiar kind. Another thing to be borne in mind is that this is the only cap- 
illary system in the body through which albumin does not normally escape. 
You know that through all of the capillaries of the body we have an escape of 
lymph containing more or less albumin; not so with the glomerular capillaries 
in a condition of health- the watery portions of the urine passes out here, but 
unmixed with albumen. It is difficult to explain why in a normal condition 
albumen does not escape from these capillaries in any other portion of the body. 
The amount of connective tissue in the kidney is exceedingly small- found chief- 
ly about the blood vessels. There is very little of it in the cortex of the 
kidney, and that little lies between the tubules around the expanded end of 
the tube known as Bowman’s capsule, a very slight quantity entering Bowman’s 
capsule with the efferent artery, and affording a certain amount of support 
to the capillary net work there present. In the pyramidal portion, however, 
between the collecting tubules there is some connective tissue in the normal state. I think you will get a very good idea of the amount of connective tis- 
sue in the kidney from an examination of the first section which will be given 
to you tonight, and which you may take as a normal kidney barring the acute 
congestion which is there shown* Yon recall that this tuft of blood vessels 
lying with Bowman's capsule is covered with a layer of epithelium (don't forget 
that), so that when you are looking at a Malpighian body under the raicroscoDe, 
most of the nuclei which you see are nuclei external to the capillaries; not 
the nuclei of endothelial cells within the capillaries. A few do consist of 
the nuclei within the blood vessels. The majority are the nuclei of epithelr 
ial cells and here and there a connective tissue nucleus. Of course it is not 
necessary for me to remind you that in the development of the Malpighian body 
it pushes before it the expanded extremity of the urinary tubule, and this is 
what gives it its epithelial layer. In the figure x represents the expanded 
tubuie or Bowman's capsule, lined with very flat epithelial cells. You appre- 
ciate that the bloodvessels do not pierce that- dc not form a loop lying free 
with simply a little of connective tissue about them- but as they enter they 
push this capsule before them- the flat epithelial lining is turned as shown 
in figure, end on the edges of this sac again are epithelium; perhaps s little 
more elevated on the visceral layer than on the peripheral layer. Where the 
vessels enter the tuft, z, they push the capsule y, before it. The kidney 
you recall is the great excretory organ of the body, which is a point to be 
borne in mind. Although the lungs, the skin, and the intestinal tract help to 
get rid of the waste products of the body, the greater part of the result of 
tissue metabolism reaches the kidney and is there excreted. A large portion 
of water which is taken in is" finally eliminated by the kidneys, and we know dow that the watery part passes out through the Malpighian bodies or tufts. 
That is conclusively proven and accepted, and we know further that the solid 
part, such as urea, uric acid, and oreatin (these are the most important) are 
excreted by the secreting epithelium proper and which lines the kidney tubules. 
If the red blood cells, for instance undergo extensive disintegration, the 
hemaglobin is excreted, but we do not find it in Bowman’s capsules- we find 
the granular material within the secreting cells of the tubules proper. Anoth_ 
er important point to be borne in mind in connection with the kidney is the 
fact that the urine is conducted away by a certain channel, the ureter, and 
that this channel serves as one of the sources of infection -bacteria reaching 
the bladder can pass under certain conditions into the ureter and into the pel- 
vis of the kidney and on through the collecting tubules, finally reaching the 
proper secreting structure in the cortex of the kidney, giving rise to pyeione- 
pbretis, or the suppurative form of kidney inflammation. Another point to be 
borne in mind is that the amount of urine secreted depends not so much upon the 
pressure within the bicod vessels in the kidney as upon the amount of blood 
which flows through the kidney capillaries in a given time. We will have oc- 
casion to call your attention to this point further on. 
Tonight I propose to invite your attention especially to the circulatory 
disorders of the kidney. We have three of these: Acute congestion; chronic 
passive congestion; and hemorrhagic infarction of the kidney. It is inter- 
esting to know that in aooute active congestion of the kidney the amount of 
blood passing through the kidney in one minute's time may equal the weight of 
this organ, and that under the stimulation of certain diuretics this may take 
e 
place- such an enormous quantity of blood passing through the kidney in the space of a minute. Now there are various irritants which bring about active 
congestion of the kidneys, and in the early stage of this acute congestion ow- 
ing to the increased amount of blood which passes through the glomeruli, the 
urine 1 should say is very rapidly and very extensively increased. Por instance 
suppose an individual consumes within a short time a given amount of alcohol- 5 
some form of alcoholic liquor- this gives rise to an acute congestion of the 
kidneys- it is there that it must be eliminated, and we know that the effect of 
this alcoholic intake is a prompt filling of the bladder with water. Not only 
alcohol, but various drugs may bring about a serious acute congestion of the 
kidney, which may not stop with the first stage of congestion, but goes on to 
inflammatory disturbance- chlorate of potash in large doses, copaiba, oil of 
cubebs, nitrate of potash, oantbarides, arsenic and various drugs of this char-’ 
acter exercise a particular irritating influence upon the kidney. Oantbarides 
whether taken internally or applied as a blister may give rise to serious sc- 
ute congestion of the kidney. Now if the dose of one of these irritants is 
sufficiently large it may have, as I have said, the effect of bringing about 
not only acute congestion of the kidney, out absolute inflammation of the or- 
gan, so that whereas at first the amount of urine is increased, later it is 
diminishea, and we have even red blood ceils appearing in Bowman's capsule and 
in the urine. The kidney under these circumstances (when one has an oportun- 
ity of examining a kidney during the stage of acute active congestion such as 
the section you will see tonight) is enlarged, the capsule easily tears, the 
surface is deeply congested and dark, red in color, and upon section the whole 
surface, both cortex and medullary portions, is of an intensely red color. 
Blood may drip from the surface; the Malpighian bodies may appear as red points 
scattered over the surface of the-kidney (microscopically). You will have a obance to see what the changes are and where the vessels are most dilated. 
The most important form of congestion of the kidney, however is chronic pas- 
sive congestion. This condition we have taken up in several of the organs al- 
ready, and 1 may here say that the same causes which produce chronic passive 
congestion in the iiVer may bring about chronic passive congestion in the kidney 
Lesions of the heart are most important; are the ones to be looked to when you 
have a patient with symptoms of chronic passive congestion of the kidney. This 
appears only when failing compensation takes place. One may find this condi- 
tion with advanced emphysema of the lungs. Chronic passive congestion of the 
kidney goes with chronic passive congestion of the lungs and of the liver. 
The organ presents at autopsy quite a characteristic appearance. The capsule 
strips easily upon section, or even before you strip away the capsule the stel- 
late (star-shaped) veins seem to be distended. When you incise the organ, al- 
though both areas of the kidney are injected, the pyramidal shows the most 
marked injection. Another point, the kidneys to the feel are very firm, they 
are resistant almost to stony hardness. An organ the seat of ohroniopassive 
congestion is almost of stony hardness. The injection and stony feeling are 
the two characteristic points to be borne in mind. Now just as in acute cond 
gestion of the kidney you may have albumin appearing in the urine in the later j 
stages, so in chronic passive congestion of the kidney you may have a small 
amount of albumin; not only that, but you find here the amount of urine de- 
creased, and you will at onoe appreciate why- owing to the venous stasis, to 
the stagnation of the blood current. Although the pressure is greater in the 
bloodvessels of the kidney, the amount of blood circulating in a given time 
is really lessened- less then in the normal state. Not only this, but you may find in the urine certain oasts in obronio passive congestion of the 
kidney- hyaline oasts derived from the albumin escaping through the glomeruli, 
collecting in the tubules, and assuming a certain shape, appearing in the 
urine as casts of the tubules, larger oe smaller, and which are sometimes con- 
sidered to indicate chronic inflammation of the kidney. Now bear in mind, that 
if you have a patient presenting the symptoms of decreased amount of urine, 
with/a slight amount of albumin and a few pale hyaline casts, perhaps a few 
blood cells, always look to the heart’s condition before you conclude that the 
patient has chronic Bright’s disease. Many of the so-called cures of chronic 
Bright’s disease are simply oases in which a chronic passive congestion of the 
kidney by proper remedies has been somewhat ameliorated- a few doses of digi- 
talis, a purgative or two to relieve the portal circulation, is promptly fol- 
lowed by an increased flow-of urine, a dimunition in the albumin, and a genr 
eral- improvement in the patient’s condition. Unless you appreciate this con- 
dition of chronic passive congestion of the kidneys you cannot treat the symp- 
toms intelligently. The thira disorder of the circulation to which { will call 
your attention is that of infarction of the kidney. I can refer to it in a 
very few words.. You appreciate what infarction is, and I will only say that 
any fragment of material dislodged- generally from the valves of the heart- 
may reach the renal arteries and plug one of its terminal branches. Under 
these circumstances the blood supply is cut off. 'tie do not here have the typ- 
ical hemorrhageic infarct- we have the pale infarct-coagulation necrosis 
promptly follows. It has been shown experimentally that legation of the renal- 
artery or vessel- for a period of two hours leads to extensive destruction of 
the parenchyma of the kidney-so here this is very promptly followed by oosgr uiation necrosis. This infarction is denser than that of the lung. Al- 
though there is a certain amount of distension of the capillaries of the part, 
this is generally limited to the periphery of the infarct, fte have a pale 
infarct with a deep border at the surface and paler towards the interior. This 
infarct undergoes the same changes that an infarct would, in the lungs. Follow- 
ing the necrosis we have the entrance of the polynuclear leucocytes and grad- 
ual breaking down (liquefaction) of the infarcted region, followed by absorp- 
tion and the proliferation of new cells from the connective tissue ceils of 
the kidney to supply the place. In other words a granulation tissue growing 
into the infarct. Finally this undergoes a fibrous change, the bloodvessels 
disappear, and the place of the infarct is taken by connective tissues which 
contracts and leaves deep scar-like marks upon the surface of the kidney, 
showing where the infarct has occurred. This is simply an infarct. We have 
here a septic infarct- under these circumstances we have an abscess which may 
be small or large, may be followed by healing, but more generally leads to 
pyelonephritis. A section of acute and chronic passive congestion will- be 
shown you tonight. One point which 1 omitted in describing chronic passive 
congestion is this: If a chronic oassive congestion lasts for a number of 
years it leads to an increase of connective tissues of the organ, .just as 
chronic passive congestion is followed by this change in other organs of the 
body. In this section we will see that the connective tissue is found between 
the tubules- whereas in the first section you will net find it, in the second 
section you will easily make it cut. This adds somewhat of course tc the densi- 
ty of the kidney, but even in kidneys where there is no incressd connective 
tissue we have the same stony hardness that we have in these kidneys. This is a point to be borne in mind, at the next lecture we will take up parenchy- 
matous degeneration cf the kidney. 
DR. OMRCLL, Ihe most important differences which we have cf the.sections 
tonight is that in acute ocngesticc the organ is enormously reddened {?), 
vessels are congested, epithelium swollen and somewhat cedenrsxous with albu- 
minous material and perhaps a red blood cell or 2 in the capsules- ohrcn. 
pass, increase cf conn. tiss. seme hyaline csts. in tubules, blood in capsules 
and tubules, epithelium swollen & degnratd, e few nuclei fail to appear, cells 
swollen, cloudy, slightly granular, stained brightly with eosin. PATHOLOGY 29. 
Merch 25, 18S8. 
Acute Fyrenchamatous Degeneration 
Granular Degeneration 
Cloudy Swelling 
1. 
£cute Bright’s Disease 
£oute Inflammation of the Kidney 
£oute Diffuse Nephritis 
2. 
It the lest lecture, gentlemen, 1 ceiled ycur attention to some of the 
important points in the histology of the kidney which I thought were worth 
mentioning, especially the difference in the epithelium in various parts of 
the kidney tubules. I also called ycur attention to the blood supply of the 
kidney and especially emphasized the histcicgcoai structure of the first cap- 
illary tuft—of that remarked!e mass of capillary blood vessels found in the 
dilated end of each kidney tubule. I might have described the Malpighian tuft 
with its tubuie really as a gland, as in it we have all the elements of a gland 
blood vessels, epithelium, and tubuie to sot as a duct to carry away the pro- 
duct of secretion. I also invited ycur attention to the second capillary net_ 
work, which is supplied by the blood passing from the Malpighian tufts. This 
is collected first into a single vessel, which leads from Bowman's capsule at 
a point opposite to the commencement of the kidney tubule, and which breaks up 
into a second capillary tuft around the tubules proper of the kidney. I men- 
tioned the fact that the amount of connective tissue in the kidney was very 
slight and that when cne examines a section of the kidney the nuclei found 
between the tubules, are generally the nuclei of the walls of the bloodvessels. 
There is a little connective tissue strengthening the dilated end of the tu- 
bule around Bowman's capsule, end there is still mere in that portion of the kidney at the junction cortical sna the pyramidal structure, srcund tie 
blood vessels which form the arches at that point- where we find the larger 
blood vessels upon sections of the kidney. Of course, e certain amount of 
neotive tissue is found at the surface of the kidney- spread over the kidney 
in the form of a delicate capsule, i then invited your attention to certain 
of the circulatory disorders of the kidney: first, active acute congestion of 
the kidney, and secondly, chronic passive congestion of the kidney, directing 
your attention to the fact that in chronic passive congestion of the kidney 
we often, end generally do, find albumen in the urine, and may find, and gen- 
erally do, hyaline casts in the urine, and that the presence of albumin in 
small Quantities, end of casts, did not warrant the diagnosis of inf 1 animation 
of the kidney or Bright’s disease; that it was due to the obstructive 
aemia, to the increase of pressure in the bloodvessels, and to nutritive dis- 
turbances in the epithelium iu the walls of the capillaries of the Malpig- 
hian tufts- in the glomerular capillary wails and the epithelium covering them;1 
tonight 1 propose to say something to you about scute parenchymatous aegen- 
eration of the kidney first, and afterwards about acute Bright’s disease prop- 
er. Acute pyrenohymeteas degeneration of the kidney is also designated as 
"granular degeneration", and as"cioudy swelling" of the epithelial cells of 
the kidney, ihe term "cloudy swelling" was introduced by Virchow, and he baa 
in view more tten tie cloudy appearance which is seen-with the naked eye upon 
section of the organ, -axui~&€4~~ the appearance which is seen under the micro- 
scope. In this form of degeneration (you have already had a section of the 
kidney showing cloudy swelling) possibly Dr. Garrcli has already told you, 
the epithelial cells become swollen, and whereas they were before finely granular, they become, when the condition is at ail marked, coarsely granular. 
Sometimes they are more distinct, their outline being clearer than it was in 
the normal epithelium, and if the process continues, the nucleus itself may be 
involved, staining very poorly with bematoxylon, or else net staining at all, 
will have disappeared from the granular ceils affecteiby this form of degen- 
eration. Ihe granules which we see are albuminous in composition. £lhis is 
believed to be a disorganization of the protoplasm of the cell, causing its 
albuminous constituents to separate in these coarser particles. 'Ihe condition 
K. 
of cloudy swelling in an organ affected with this degeneration is easier di- 
agnosed with the naked eye than with the microscope, unless the condition is 
auite well marked, in the ceils. The cortex of the kidney under these circum- 
stances appears swollen, of a lighter color, the is lost, indeed, it 
frequently gives you an appearance as if it had been boiled, bad been dipped 
in hot water at least, giving that cloudy appearance which Virchow had in view 
when be designated it as cloudy swelling. Now, we believe that it is better to 
separate these acute degenerative changes from the inflammatory changes proper 
of the kidney. We find cloudy swelling or granular degeneration especially 
associated with acute infections- typhoid fever, croupous pneumonia, scute 
septicaemia, yellow fever, erysipelas; the eruptive fevers, smallpox, measles, 
diphtheria, etc. ihese diseases constitute one important class of the causes 
of cloudy swelling of tie kidney. It is also caused by various poisons, phos- 
phorus, antimony, arsenic, the mineral acids, chlorate of potash, and is also 
found in the kidneys of those who have died from extensive burns on the sur- 
face of the body. New in the last named condition (extensive burns) we be- 
lieve that this degeneration of the kidney is caused by certain toxic products 
circulating in the blood which aie brought to the kidney for the purpose of excretion. Beer in mind thet this cloudy swelling under these circumstances 
does not affect all of the epithelium of the secreting tubules, it is only 
found here and there in scattered patches. One explanation of this is that 
the epithelial cells of the kidney vary in their resistance to the action of 
toxic products. That may or may not be true. Another explanation is thet the 
secretory epithelial cells of the kidney are net all acting, not all function- 
ing at s given time; that at one time a certain number of cells will be carry- 
ing out the function of excretion, ana at another time the ceils in e differr 
ent part of the kidney. That is at least a rational explanation. We do not 
know positively why certain cells should be- affected ana others left undamaged, 
but this is what we find microscopically. New this form of parenchymatous de- 
generation of the kidney, this cloudy swelling, if it has net gmne too far, is 
rapidly recovered from, liven if certain cells are destroyed, their places are 
taken by the proliferation of other epithelial cells- the kidney has a certain 
amount of regenerative action in its epithelium. It is more than likely in the 
normal condition of the human being that portions of kidney epithelial cell 
may break down and be renewed, or a ceil may be disQuamated, or a number of 
cells, and their places taken by regeneration of ctner ceils. It is probable 
that in all cases of acute infection of moderate (medium) severity we have 
this condition of cloudy swelling of the epithelium of the kidney. Icu knew 
it is freouently the case that during an attack of diphtheria,' croupous pneu- 
monia, typhoid fever, erysipelas, etc.,examination of the urine shews a cer- 
tain amount of albumin. It may or may net show albumin. If cloudy swelling 
is at ail marked in tire kidney, we have albumin, pnder those circumstances 
the glomerular vessels are effected sc that they no longer prevent the albumen 
of the blood from passing through their walls. Sc 1 say that in the various acute infections we have every reason to believe, even though the patients 
make a good recovery, there is a certain amount of clcuay swelling, Aside from 
ecu H inflammation of the kidney, we find this in patients who have died from 
another disease- a patient dies of typhoid, not aue to the olcudy swelling of 
his kidney but perhaps from hemorrhage of the bowels, perhaps from the toxic 
effects of the typhoid bsciilus on the hesrt muscles, the patient dying from 
debility, under these circumstances we find olcudy spelling in the kidney, but 
the olcudy swelling did not kill the patient, but was only a part of his di~ 
ssase. So the majority of patients with these disturbances of the epithelium 
can, or readily recover. It is one stage, remember, in the fatty 
tion of the cells, only another step to the fatty degeneration of the epithel- 
ium. Under those circumstances the epithelial cells are of course completely 
destroyed; they do not recover their functioning power. If you have a patient 
with one of the scute infections end you find a certain amount of albumen in 
his urine and a few hyaline oasts, ac not come to the conclusion that the pa_ 
teint has Bright’s disease- just oear in mina the granular degeneration of ep- 
ithelium which goes with those infections so often. Now, as 1 have already 
said, we celieve that these purely degenerative affections of the epithelium 
should be separeted from the inflammatory affections proper of the kidney. 
Ihey should net be called, -as they so often are, acute parenchymatous nephri- 
tis, acuta catarrhal- nephritis, acute desquamative nephritis. You see those 
terms used especially in the milder forms of kidney affection It is better 
to consider ail of those simply as acute degenerations of the kidney epithel- 
ium, which frequently prevents the scouts affections of the kidney, but in 
themselves do net constitute an acute Bright’s disease. Secondly I will call your attention to soute Bright's disease. 1 said that another term which we 
used was “acute inflammation of the kidney" but preferably “acute diffuse ne- 
phritis" to express mere properly the oondition of the kidney found in this di- 
sease. liver sinoe Bright's memorable investigations, published in 1829, in 
which he showed that the condition of the urine attended by albuminuria, or 
dropsy, was associated with certain inflammatory disturbances of the kidney, 
these diseases have been designated “Bright’s disease". He deserves the credit 
of calling the attention of the profession mere than ?0 years ago to these in- 
flammatory affections of the kidney, lou will at once remember end appreciate 
that net every case of eibuminsria, or every case of dropsy, is necessarily a 
case of Bright’s disease. 1 have already told you sufficiently to warn you 
against this conclusion, ft'e style this inf 1 amm atcry affection of the kidney 
as “scute diffuse nephritis." It is universally admitted that there is here 
really an inflammatory disturbance; that while ail of the lesions seen in 
Bright’s disease of the kidney are not inflammatory there are many important 
lesions here tc be found-there are certain proliferative lesions, certain in- 
terstitial changes which are net purely, net wholly inflammatory) but never- 
theless there ere inflammatory lesions present in acute diffuse nepnritis, so 
that it is proper to disignate it nephritis, an inflammation of the kidney. 
Now we say diffuse, and that is meant tc show that no one structure of the kid- 
ney is affected in this disease aside from the ether structures of the kidney. 
Not only are the secretory epithelial cells involved, but also the bloodvessels 
the glomeruli, and the interstitial oonnegtive tissue. Ihe disease is some- 
times called “acute tubal nephritis", thereby implying that the condition in 
the tubes is the most important lesion found in the kidney. It is sometimes called “acute croupous nephritis*5, attention being particularly called to the 
exudate within the kidney tubules, as if that was the most important element to 
be found in this disease, fte do net believe that at all. We do net believe 
that you can separate by any hard and fast lines in acute Bright's disease, 
those oases in which one structure is affected and the other entirely unaffect- 
ed. We will have occasion very scon to point cut to you several varieties of 
acute Bright's disease, but we will emphasize the fact that wiile in these va- 
rieties one structure is more affected than the others, that ail the structures 
are affected in this disease of the kidney. New in the first place, let me 
direct your attention to the appearance of the kidney. Ibe normal kidr 
ney weighs about 32C grams, the normal adult kidney. In acute Bright's disease, 
acute diffuse nephritis, the kidney is enlarged. It will vary in weight up to | 
5C0 grams; it may reach a weight of SOC grams. Ibe kidney as a rule is inject- 
ed- one sees this befare the capsule is removed, ifee capsule leaves the sur- 
face of the kidney readily, does not adhere, strips easily from the surface of 
the kidney, and under those circumstances one will find the greater portion of 
the surface of the organ injected. It may be that these in j eo ted areas are dis-: 
tinctly limited and that they are separated by paler areas, giving you a some- 
what mottled appearance to the kidney. Upon cut section the kidney presents 
no increased resistance to the knife, ana oerhaps in the mere severs inflam- 
mations of the kidney, the acute inf 1 ammatiens, Heed oozes from the surface 
of the organ, though this is net always the case, ihe color of the cortex 
varies; it may be decidedly dark red in color, or may present lighter areas 
showing areas of advanced cloudy swelling or even fatty degeneration of the 
epithelium. ‘Ihe normal striaticn of the cortex is lost, the cortex is thick- 
ened, decidedly increased in thickness as compared with the normal cortex; indeed, the enlargement cf the kidney is almost exclusively in the cortical 
portion. Of course the enlargement of the kidney is due, in great cart, to 
exudation from the bloodvessels, oedema cf the organ- the kidney is moist on 
cut section, moist when tie capsule is stripped away, the glomeruli may appear 
as distinctly red points scattered over the surface cf the cortex, or they may 
£ 
occur as pale, rather transparent points, ihe pyramidal structure i# general- 
ly injected. 1 will mention very scon one variety cf acute Bright's disease 
in which the kidney is but little if at all swollen. The description I have 
given you applies to the great majority cf cases cf acute diffuse nephritis. 
Now when we come to examine such kianeys, microscopically, we do not fina that 
the pathological change is confined to any one structure of the kidney. We 
find that the epithelium is always affected- the same cloudy swelling which we 
find in connection with the acute infections is here present, often in an ad- 
vanced condition, even passing on to tbs stage cf fatty degeneration cf the 
cells- many swollen, coarsely granular and somewhat arcpsical cells are to be 
seen. The glomeruli also present changes: One may find proliferation of the 
epithelium lining Bowman's capsule, one may find the escape cf a few leucocytes 
or many red blood cells into Bowman's capsule, ana one may also find a consid- 
erable collection cf red blood ceils in the tubules cf the kidney. More than 
that, one may find, ana ordinarily dees, where the disease has been cf several 
weeks duration, changes in the interstitial connective tissue, round cell in- 
filtration between tie tubules where normally it does net belong, round cell 
infiltration around Bowman’s capsule. So that in this disease all of the 
structures of the kidney ere affected. Now, having said that much, 1 will 
call your attention to tie fact that we may distinguish two types especially 
in this form of acute diffuse nephritis, viz: - 1. .Acute hemorrhagic nephritis; I 2. Acute glomerular nephritis. These are the two principal divisions of acute 
diffuse nephritis, based simply upon the anatomical changes which one finds in 
the kidney, bearing in mind that in each of these the other structures may be 
effected, we find for instance in certain acute inflammations of the kidney 
following scarlet fever mere often than any other disease, the form which may- 
be designated as acute hemorrhagic nephritis, simply because we find that the 
hemorrhage into the tubules and Bowman’s capsules is such a prominent feature 
and no other reason. If this lasts long enough we find marked interstitial 
changes. The sections which we showed last year were beautiful, showing both 
of these conditions. The specimens which we will show you tonight shows hem- 
orrhage from the same disease- another case. Both ere eauslly good specimens 
of acute hemorrhagic nephritis with granular degeneration of the epithelium. 
In this form also we find cloudy swelling, fatty degeneration of the epithel- 
ium, and you may find in Bowman’s capsule net only remains of red blood cells 
but albumin which has escaped. We believe that in all forms of acute Erigot 
disease the glomeruli are effected. There seems to be no reason for believe 
ing that they are net affected. They permit diapedesis of red bleed cells 
end the escape of albumen, end I have told you that these were the only cap- I 
illaries in the body which in health do not permit albumen to escape. It is 
not due to advance in blood pressure, because the pressure in acute Bright’s 
disease is lower in the renal vessels. It is due to defective nutrition, 
some change brought about by the poison producing the disease and acting upon 
the gicm€ruigr ogpiiXeries and their epithelial covering. Kcw let us take the 
second form (b), acute glomerular nephritis: Again in this disease, scarlet 
fever, or in other diseases especially acute ulcerative endocarditis (end the 
Bright’s disease which goes with it,) we find the most marked change in the glomeruli epithelium. We find changes both within the capillaries in Bow- 
men's capsule, which has led to a glomeruli nephritis being divided into 
“extraoapillary glomerular nephritis" and “intracapillary glomerular nephritis" 
but we find the two going together and it is net proper tc separate them. 
Just as by administrating csntbarides to rats one may produce acute inflamma- 
tion of the kidney, characterized by proliferation of cells in Bowman's cap- 
sule and the same change within tie capillaries, sc we also find in scarlet 
fever both changes. Instead of the flat epithelial ceils which we find in the 
condition of health, these ceils are much swollen; not only that, but we find 
proliferation of the cells, sc that one gets within the glomerulus a distinct 
crescent of cells, accumulating at that point ( y-\ even to such an extent as 
to press upon the glomerular capillaries ponrfeg, interferring with the oirou- 5 
laticn through the tuft, ibis is seen in certain acute inflammations in the 
kidney- in scarlet fever etc. Ccuooilmarm in recent investigations made in 
the Massachusetts General Hospital has shown that this form of glomerular 
nephritis is very often associated with the acute inflammation of the kidney 
caused by the diploocoous ianoeolatus, following acute ulcerative endooarditis. 
Then instead of tie affection being largely outside of the caciilaries, affect 
* 
iag the proliferation cf the epithelium in the capsule, we find the capilla- 
ries just blocked with cells- a few white blcoa cells, e few leucocytes, but 
largely due tc proliferation ef the endothelial cells lining the vessels, so 
that they become stuffed with ceils, ihen we also find that the capillaries 
are closed with masses cf hyaline material, which stains deeply with eosin, 
end which upon staining with fibrin give the exact reaction cf fibrin- fi- 
brinous masses plugging the capillaries cf the glomerulus. And you recall thet any obstruction in tie glomerular capillaries, whether by compression 
by a orescent of epithelium lying outside of the capillaries, or an accumu- 
lation of cells within the capillaries, or this fibrinous plug, will lead to 
a defect in the blood supply in the 2nd capillary district. 
If the epithelial cells are to remain in the normal condition, they must 
have the normal supply of blood, which here they do not get, not only that, 
this blood contains toxic products. So remember that there is one form of ac- 
aoute Bright’s in which extracapillary and intraoapillary glomerular nephritis 
are the important feature, but do not forget that in such kidneys you always 
have a certain amount of hemorrhage, leu may also find, along with this glom- 
erular proliferation, beginning interstitial changes- in certain cases, marked 
interstitial changes. How these are the two most common forms of acute Brights 
disease. I will mention one ether which is occasionally found, and in which 
the amount of parenchymatous degeneration is so extensive that we are almost 
(h- 
compelled to call this an acute generative nephritis. Sometimes I am willing 
K 
to bring it in the class cf acute inflammations, and then again I am net. How- 
ever you do find it when a patient has been poisoned- when some toxic product 
is at work in the blood circulation you do find e most extensive increase of 
the epithelium cf tne kidney in which the secreting epithelium in many places 
and in nearly all the tubes has been destroyed by some toxic product, end if 
you choose, you may call this the 3rd form, and put it “c>; under the head of 
acute diffuse nephritis, and you may call it acute degenerative nephritis. 
I find that Dr. Oounoilmann, the Professor cf pathology at Harvard, who has 
spent as much time as any one else in this country in the study of patholog- 
ical Ofianges occurring in the kidney, mentions this form cf acute Bright’s disease, but I am willing to say that I have never seen but one oase. I did 
not believe until I had a obanoe to examine the kidney of a woman who died in 
Garfield Hospital, and who presented all the symptoms of delusional insanity. 
$ben the autopsy was made the kidneys were found soaroely enlarged- a little 
enlarged- there was a little loss of striation in the oortiosl substance, but 
there was nothing about the organ that would lead one to believe that the pa- 
tient had Bright's disease, ihe diagnosis was in doubt at the time of her 
death, but takinjjinto consideration the fact that she bad this delerium, and 
died in a comatose condition, 1 suggested before the autopsy that she probably 
bad Bright's disease. $hen we examined the kidney the changes were very acute 
and very extensive. Doubtless other oases occur.. In this oase I think there 
is no hemorrhage into the tubules, I think the whole lesion or most of the le- 
sions ere confined to the epithelial cells. Ihe glomeruli if I remember were 
apparently not affected in this kidney, ihere was albumin in the patient's 
urine, and of course the glomeruli were affected, but they did not show any 
chances microscopically. 
Now as tc the cause of scute Bright's disease (divided into acute and chron- 
ic forms- we take up the chronic later), ‘Ihe causes of acute Bright's disease 
may be classed: 1. as the acute infections, and place with these acute ulcer- 
ative endocarditis, in which of course we have infection with various bacte- 
ria. Then you-may put down extensive burns of the surface- which have been 
followed by acute Bright's disease. When I sneak of acute infection I also in-* 
dude the eruptive fevers. The one disease which occasions more acute Bright's* 
disease than any other is scarlet fever. Then you may put down exposure to 
cold. How this acts we do not know, possibly by suppressing the function of the skin, throwing extra work on the kidneys, and in this way inflammatory 
disturbance is begun. H any rate exposure to the cold will bring this about. 
Alcohol alone will hardly cause Bright's disease, but if the individual gets 
drunk end forgets tc go home, lies in the gutter on a odd night, he exposes 
himself to aoute inflammation of the kidney. Ihe late Dr. Flint mentions one 
oase of aoute Bright's disease whiob be believed was due to the excessive in* 
dulgenoe in beer without any exposure. You may also put down pregnancy as a 
cause of acute Bright's disease, although I may here remark that when a preg- 
nant woman has albumen in her urine and a few casts, it does not necessarily 
lead to the conclusion that she has acute Bright's disease, but certain oases 
of acute diffuse nephritis have taken their starting point during pregnancy; 
probably here the effect is toxic, is due tc some toxic product. Mew I will 
remark in addition that the majority of cases of aoute Bright's disease that 
do not terminate fatally end in complete recovery. Very few of the oases go 
on to chronic Bright's disease. Ihe impression among a good many physicians 
is that chronic Bright's disease must first be preceded by aoute Bright's di- 
sease. ihat is not true at ail. Chronic Bright's disease is entirely a dif- 
ferent affection, and although a few oases follow aoute Bright's disease, this 
is exceptional. If the patient does not die, the recovery is permanent. 
Mow as to the condition of the urine., In addition tc the albumen, which is 
present generally in considerable quantity, the urine contains various organ- 
ized constituents, red blood cells sometimes in considerable quantity, present- 
ing that dark smoky appearance (color) which is indicative of blood being pres- 
ent. then it contains also certain oasts of the renal tubules, whiob it is 
well to bear in mind- very pale oasts, very pale elongated bodies, which are known as hyaline oasts, and whioh probably have their origin simply in the 
coagulation of the albumen whioh has escaped from the glomerular capillaries. 
Very pale bodies are found in the urine which have distinctly rounded ends, 
sometimes constricted towards the center or in two or three places- bodies 
which you will find when you reduce your light, pale hyaline casts. Then there 
are casts which are decidedly granular in appearance- the granular casts- but 
you do net find these sc much in this form as in chronic Bright's disease, 
though one may find the finely granular oasts in acute Bright's disease. Anoth- 
er form which we find in epithelial oasts, which consists of the epithelium of 
the kidney separated, dequamsted, in considerable quantity. Of course these 
cells are held together by a homogeneous material. Sometimes these cells are 
decidedly granular, coarsely granular. You also get oasts of polynuclear leu- 
cocytes, whose nuclei have the characteristic irregular shape cf the leucocyte. 
Ihen casts of red blood cells which have become molded in the tubules and 
forced cut by the pressure of the urine. Ihese are very important in the di- 
agnosis cf acute Bright's disease. Hot as much attention, however, is paid 
to the finding of pale hyaline casts as formerly was attended to this, and I 
may here remark that one may find them net only in chronic passive congestion 
cf the kidney, but in the urine in all oases cf marked jaundice- ( put that 
down and underscore it; it may help you in a pinch). If you do find them in 
jaundice, do not conclude that the patient has Bright's disease. Where you 
find epithelial hyaline, and blood casts in the urine, ycu have very good mi- 
v 
orcsoopio evidence that the patient has acute inflammation of the kidney. 
When we come to review this subject next time, I may bring cut one or two new 
points, but these are the most important. I will ask you to read what Csler has tc say on aoute Bright's disease, before next lecture. I do not know bow 
extensive an article he has, but inasmuch as everything he says is good, that 
too will be good, I do net think that those of you who have Green's pathology 
need read the article on acute Bright’s disease. 
DS GARRQLL: 
In the first section (aoute hemorrhagic inflammation) you will find 
degeneration of the epithelium, absence of nuclei, an amount of congestion in 
the capillaries and elsewhere throughout the kidney, casts in the tubules, and 
also the tubules, especially tne convoluted, filled with blood, which stains 
very distinctly, the cells are quite well observed and you cannot mistake them 
for anything else. You will fisc see a tubule out in half, with a thin wall in 
which you get rounded nuclei of the epithelial cells. In the center you get a 
mass of blood, stained deeply with ecsin. In the Malpighian bodies you get 
your capsule with the tuft perhaps compressed, and outside of that the balance 
of the capsule may also be filled with red blood cells. Ibis occurs in every 
instance- hemorrhage into the tubule and into the glomeruli. In the second 
section (the case of delusional insanity- perhaps a case of uremic poisoning) 
there is very marked disintegration of the red blood ceils. Ihe, blood went 
into solution in tne serum end as the fluid transided through the epithelial 
cells it appeared in the tubules (?). You know the convoluted tubules are the 
excretory apparatus of the kidney. As the blood passes through these tubules 
separation of the solid elements takes place, and the blood pigment is in so- 
lution in the serum, this being preceded by the passing cf the cell, chiefly 
through the convoluted tubules. Say a convoluted tubule is cut horizontally: you will find the epithelial cells swollen, almost filling the lumen of the 
tube entirely. You may find opening here and there. Ihe epithelial cells are 
indistinctly outlines, iit the base of the cells just inside of the basement 
membrane you will find little dark pigment granules (hemosiderin), sometimes 
in a considerable amount, and sometimes only a few granules. If the tubule is 
out in cross section you get the same thing, with the arrangement of the pig- 
ment about the periphery of the tubule with the nuclei very distinct. In 
pyrmdi portn (col.tubuls) ere hyaline oasts; prhps u*l see smll tubuls whose 
epithelium is flatnd agnst their wells, won may or may’nt stain; nucli abt walls 
& in ontr may give homogenous mass (coegltd album) shws no nucli but pigs tu- 
bule, onteins no leucocyte & no epithelium. Vsls everywhere dstnded.{finis.) PATHOLOGY No. 3C. 
March 26, 1898. 
Acute suppurative nephritis 
Acute purulent nephritis. 
In bringing tc ycur notice this form cf inflammation of the kidney, acute 
suppurative inflammation, please do not get the idea that this is a form 
cf Bright’s disease, because it is not included under Bright’s disease. 
Ibis form cf inflammation cf the kidney is frequently taken up as a first 
inflammatory affection cf the organ because it is easily studied, easy to 
stain, and the picture under the microscope is more striking in acute sup- 
purative inflammation. In the acute inflammation cf the kidney, of which I 
spoke when we were last together, ycu will recall we bad an inflammation of 
the kidney produced by certain toxic substances, certain solvable chemical 
poisons circulating in the blood and reaching the kidney and sc bringing 
about certain alterations of the secreting epithelium, the interstitial con 
neotive tissue, and especially changes in the glomeruli. These soluable 
chemical poisons are generally the products cf bacterial growth in some 
part cf the body. Icu remember thstl mentioned the acute infectious di- 
seases as being one cf the great sources cf acute inflammation cf the 
kidney, acute Bright’s disease. Now tonight I want to call your attention 
tc a form cf inflammation cf the kidney which is due tc the presence of 
bacteria in the kidney, not the soluable products alone. Cf course there 
is a certain local effect from these last, as you will readily understand, 
but in this form of inflammation cf the kidney the bacteria have reached I 
the kidney as insoluable bodies; and they reach the kidney in two ways, 
CC6 
either through the bloodvessels, when we speak cf the inflammation 
“hematogenous” in origin- brought by the circulatory channels- or else they reach the kidney through the urinary channels- the bladder, the ureter 
the pelvis of the kidney, etc.- in this case you can speak of the origin as 
being urinogenous. Now as regards the first variety, we find bacteria 
reaching the kidney especially -from a local affection of the heart valves. 
In ulcerative endocarditis we have one of the most prominent sources of the 
bacteria which are brought to the kidney. Generally the pyogenic organisms 
are the ones concerned, though you must remember that the diplcccccus lan- 
ceolatus is a frequent cause of ulcerative endocarditis and occasionally 
(exceptionally) brings about this acute suppurative inflammation of the 
kidney, We have had already a very good example of acute purulent inflam- 
mation of the kidney in the section of the rabbit's kidney, ihere you bad 
what we would call the simple metastatic purulent inflammation of the 
kidney; that is, a few bacteria being brought to the kidney. In that case 
the staphylococcus aureus, and this is the organism frequently concerned 
in the hematogenous variety,- perhaps a few organisms being arrested in 
some capillary, not large enough to plug it and create an embolus, increas- 
ing until finally the vessel is closed and then setting up a purulent in- 
flammation in their immediate vicinity. That was a good example of simple 
metastatic purulent inflammation of the kidney of the hematogenous variety. 
We find in cases of pyaemia, in oases of septicaemia (purpural septicaemia) 
this form of inflammation of the kidney, occasionally along with pyaemic 
abscesses in other parts of the body, in the liver especially, iben again, 
the typhoid bacillus in one case reported by P'iexncr was the cause of a 
very exo-ellen-t- purulent inflammation of the kidney- numerous metastatic 
/v 
miliary abscesses being scattered not only Sft through the cortex but the 
pyremidial structure of the kidney, the typhoid bacillus being isolated in pure culture from these. 
Now when we come to the urinogencus variety we find generally other 
organisms involved, this form of inflammation of the kidney generally is 
connected with some obstructive lesion at the neck of the bladder, or in the 
urethra- a stricture, an enlarged prostate, a tumor of the bladder- obstruct- 
ing the outflow of the urine. It is the form which fellows sometimes the in- 
troduction of a catheter, especially an unclean catheter. It used to follow 
quite frequently surgical operations upon the urethra and upon the bladder. 
It occasionally complicates acute gonorrhoea, though this is quite excep- 
tional; buVAis found that instead of the pyogenic bacteria being the occasion 
of the purulent inflammation of the kidney that here very common bacteria ere 
involved. Ibe bacillus ocli communis, lactis aregenes, and occasionally the 
common organism of putrefaction, the preteus vulgaris. In the urinogencus 
variety cultures more often give the coli communis and the proteus vulgaris 
than any other organism. Let us take a patient with some obstruction at the 
neck of the bladder, perhaps enlargement of the prostate in an elderly indi- 
vidual, perhaps an infected instrument is passed- it used to be the case end 
even at the present day it sometimes occurs- net only t4e4* the colon bacil- 
lus may be found in the urethra and may be carried in (deeper down) by the 
catheter, actually into the bladder. In ether oases there is no question 
about it that the colon bacillus passes through tbs wall of the bowel, and 
enters the bladder in that way, New suppose the catheter is infected; then 
we have just the conditions necessary for the establishment of an inflam- 
mation of the bladder. If there is no obstruction at the neck of the blad- 
der, if the urine is easily voided, then the danger from an andean catheter is comparatively slight. Remember that the great danger is in these cases 
where there is seme obstruction tc the outflow of the urine. Those are the 
cases in which you want tc be particular about the introduction of a ceth*r 
eter tc see that the instrument is sterile. Now the organism multiplying in 
the pladder- especially the preteus vulgaris can set up the most intense inr 
f 
flemmaticn of the mucous membrane of the bladder, or even without exciting ? 
inflammation of the bladder it is possible that the organism may creep along 
the ureter, especially if one ureter is pata leus, until they reach the pel- 
vis of the setting up a pyelitis and from that point proceed by the 
collecting tubules until finally the cortex, the labarynth of the kidney, 
is reached by the bacteria. It is worth knowing that an acute pylc- nephri- 
tis of this character may run its course in 10 or 12 days. I have seen two 
or three instances of the kend where the date of infection was well estab- 
lished- where the urine prior to the introduction of the catberter was free 
from albumen or pus, where following it 24, 48 hours or -5 days, these ele- 
ments begun to appear in the urine, perhaps a little bleed passes, then fel- 
low chills, high range of temperature, prostration and death, end at autopsy 
one or both kidneys are found to be affected with-an acute purulent inflam- 
( 
mation of the urincgencus_ vare£ty. New in the first variety, where the bac- 
teria are brought by way of the blood, both kidneys are involved; in the sec- 
ond variety freauently only one kidney. If there is something peculiar about 
one ureter, if it is more pfilulous, if there should be some obstruction at 
the mouth of one ureter and tbs ether patulous, it is possible that the bac- 
teria will pass up one ureter, reaching only cni kidney, there setting up 
these destructive lesions. It is an exceedingly serious form of inflamma- 
tion of the kidney, the symptoms not gt el\ wepl ®srked» many cases of obscure deaths, patients dying from debility and fever following the introduction of 
of a catheter where we do not appreciate the cause, of these 
oases are due to inflammation of this form in the kidney. If one has the 
history of an obstructive lesion at the neck of the bladder and cystitis 
especially, then you have a clue to the disease, otherwise it is exceedingly 
difficult to form an opinion as to this form of kidney inflammation during 
life j 
i:* Now what is the condition of the kidney ? first as seen with the naked 
eye. As a rule the organ is considerably enlarged, one observes beneath the 
capsule before it is stripped away a number of circular areas, whitish or 
yellowish white areas, some cf them point in size, others half the size 
of a pea, though the majority smaller. Now upon making an incision into the 
organ, we find scattered^the cortex and generally through the pyramidal 
structure- if it has proceeded from the pelvis of the kidney- distinct milia- 
ry abscesses in the in the pyramidal portion, often oblong and cf consider- 
able size, the substance of the kidney in between being injected frequently- 
i 
miliary abscesses surrounded by a distingt hyperaemio zone. ‘Ihe surface is 
moist, fluid can be scraped away from the surface with the edge cf the knife, 
and if one makes a ocverslip or slide from the contents cf one cf these whitr 
ish areas, he finds innurable polynuclear leucocytes, sc yen see that it 
really is a condition cf miliary abscess cf the kidney in the majority cf 
oases. Microscopically, this form cf inflammation shows a large number of 
emigrated white blood cells present in the section.. You will recall that 1 
said that in acute Bright's disease, one saw few emigrated leucocytes. In 
this form the striking picture under the microscope is seen in the tubules. 
You can pick out here and there with your lew power areas in which you not only find the leucocytes within the tubules, filling mere or less a number 
of the tubules but you find that the interlobular bloodvessels are distend- 
ed with polynuclear leucocytes. ‘Ibis is the striking picture. Not only 
that- you find that the wells of certain tubules have broken down, and this 
may involve s number of tubules, the whole area being crowded with polymor- 
phonuclear leucocytes. Ihen again in this mass you usually meet the remains 
of cross sections of tubules where the necrotic epithelium only shows by 
staining with eosin. If in examining the kidney microscopically you find a 
large number of leucocytes occupying the interlobular spaces and leucocytes 
within the tubules, and sometimes 1 may say within Bowmen's capsule in large 
numbers, you may come tc the conclusion that we have here acute nurulent in- 
flammation of the kidney of one of these two varieties. Micrcsoonically it 
is often impossible tc say which variety we have. If one should find the 
glomerular vessels stuffed with white blood cells or emigrated cells; only 
in Bowman's capsule and here and there in the tubes in the cortex and lim- 
ited tc that part- none in the cross section of the collecting tubules, none 
in the zone between the cortex and the pyramidal structure the emigrated 
leucocytes, confined entirely to the cortex, after exsminging several sec- 
tions you could convince yourself- you might say that here was a case of 
purulent inflammation in which the bacteria had reached the kidney through 
the blood vessels; out always examine the pyramidal portion of your section, 
look at the collecting tubules and see if the trouble is not there also. 
You sometimes find the most marked picture in that region, distinct areas 
in which the collecting tubules, one, two, or half a dozen ere stuffed with 
leucocytes, and you may find that they are more prominent at this point than in the cortex proper. Under these circumstances it would be a fair 
inference that the inflammation has extended through the pelvis (of the 
kidney) into the tubules, and was of the urincgencus variety. If you have 
a history of obstruction at the neck of the bladder and if one kidney only 
is involved of course there is no Question about the way in which the di- 
sease originated. it is as I have told you an exceedingly serious form of 
inflammation of the kidney, and as a rule the patient dies- probably always 
from the urincgencus variety. It is probable that a patient with metastatic 
abscesses of the kidney may recover. Occasionally the source of infection 
in the kidnev is an infective embolus, one or several of them washed from 
the mitral valves which first produce distinct infarction of the kidney, 
then give rise to large abscesses, ‘ibis is also a fatal form of inflamma- 
tion. lie now will ask you please to remember that this is not Known as 
Bright's disease of the kidney. Bright had nothing to say on this form of 
inflammation of the kidney, ibis is sometimes called acute interstitial 
inflammation of the kidney, there is interstitial inflammation but do not 
confound it with the chronic interstitial inflammation of the kidney, and 
keep it quite separate in your mind from that form. PMfiOLOGY So. 31. 
March 28, 1898. 
1. Acute Glomerular nephritis. 
2. Chronic Diffuse nephritis. 
1, Ihe first section which we have tonight is one of glomerular nephritis. 
Ihe patient bad an acute inflammation of the joints; also purpuric spots, 
and was critically ill early in the attack, there was a good deal of confu- 
sion regarding the diagnosis in his case however, the physician in examining 
the patient's urine, found that there was albumen in considerable amount, and 
that there was some bled in the urine; also some epithelial casts. The au- 
topsy, as ‘.far as the bacteriological results went, showed that it was a case 
cf streptococcus infection from which the patient diea, but the kidney com- 
plication was certainly the most important immediate cause cf death. Ihe 
section cf which I am now speaking was hardened in Miller’s fluid, and you 
will see hew exquisitely the cells eie preserved, and hew well the nuclei cf 
the kidney epithelium stain with bematexylon. iNhen you examine this section, 
even with low power, you will notice that the nuclei in the glomeruli ere encr 
mously increased. In certain glomeruli you will see that the glomerular epi- 
thelium (that lining Bowman’s capsule) is increased. With a little care you 
can see that certain cf the capillaries are enormously dilated, being crowded 
with nuclei- there are polynuclear cells; there is considerable cloudy swell- 
ing, there is that peculiar material which is designated “hyaline material” in 
the tubes, which occurs from the degeneration cf epithelial cells, leu have 
in this section the appearance that Councilman describes as being sc prominent 
in the kidneys cf those who die cf endocarditis due to the dipiccooous lance- 
clatus. I have examined sections cf bis cases, and this is a repetition cf 
what we get; however, in this case the streptcccoous pyogenes was isolated from the organs sod the blood, as well as from the kidney, and was the only 
organism present. I do not think that it had anything to do with the rheumatic 
symptoms at all, or (?) the purpuric symptoms. 'Ihere may have been some other 
organism which accounted for the purpuric symptoms. At any rate, there was a 
secondary infection by the pyogenes, and that was the the organism responsible 
for the glomerular nephritis. ?cu will not see a more striking case of the in- 
tracapillary and extraospillary varieties than is here shown. Ihere is oonsid- 
erable proliferation of cells in Bowman’s capsule, and the number of connective 
tissue cells throughout the section is increased. You notice that some of the 
nuclei here are seen between the tubules, Kbst I went you to see is the large 
number of epithelial cells within Bowman’s capsule, and proliferation of nu- 
clei within the capillaries of the glomeruli. FAlflOLGGY NC. 52. 
April 1, 1898. 
Chronic Bright's disease 
Chronic diffuse nephritis 
1. Large kidney without amyloid 
2. Large kidney with amyloid 
5. Small contracted kidney 
4. Kidney of arteric-solercsis. 
I have given above Chronic Bright's disease of* chronic diffuse nephritis 
as the general term, and I have placed under that head (1) the large kidney 
without amyloid degeneration; (2) the large kcdney with amyloid degeneration, 
(5) the small contracted kidney, and (4) the kidney of enteric-sclerosis, 
ffle will have occasion to refer to these various form as we go along. 
Op to this time we have considered the acute form of inflammation of the 
kidney- Acute Bright's disease. At the last lecture I spoke to you concern- 
ing acute suppurative inflammation of the kidney, and stated that this did 
not belong properly under the disease (acute Bright's disease). In discuss- 
ing the subject of acute Bright's disease, 1 called ycur attention to the fact 
that the different structures of the kidney are sc intimately related one to 
the other, that we cannot have disease of the one without also having some 
change in the other. Notwithstanding that fact, 1 did call ycur attention to 
certain types of kidney in which, while ail of the structures were.ni ore or less 
A 
involved, one particular structure shewed a greater amount of pathological 
change than the other. 
fhe same author who directed attention to the acute forms of kidney disease 
also in his writings was the first to direct attention to the chronic diseases 
of the kidney. So that in honor of his investigations we speak of acute in- 
flammation of the kidney as “Acute Bright's Disease" and chronic inflammation cf the kidney as “Chronic Bright's Disease." 
When we take up the subject cf the classifioaticn of chronic Bright's di- 
sease we meet with considerable difficulty, le are here indeed entering one of 
the most difficult fields in pathology. It is very easy tc bring about an 
acute inf1smmation of the kidney in animals by means cf certain irritating 
substances given tc t.iem by way cf the digestive system or by way of the 
bloodvessels- to bring about extensive cell death, extensive parenohymatcus 
cnsnges in the kidney. We bring about acute suppurative lesions in the kidney, 
as you already know, by injecting bacteria into the general blood system, but 
up tc the present time no one has succeeded exoerimentaily in producing chronic 
inflammation of the kidney, such as we are about tc study. Ibis is the form 
of inflammation that comes on insiduously. No symptoms mark it in the begin- 
ning, and frequently the patient's kidneys are in an advanced state cf change 
when he first comes under observation. As cur studies and observations have 
multiplied, we have come tc change certain ideas which the profession former- 
ly held, as tc the classificaticn.cf chronic kidney inflammation, formerly 
the views cf frerich, a physician who gave much attention tc the study of in- 
flammation cf the kidney, attracted much attention, fie. believed that in these 
e*4c forms cf 4&e kidney inflammation we had three stages. 1, the stage cf 
A 
inflammation; 2. the stage cf degeneration; and 3 the stage cf atrophy, and 1 
may say that you will meet in a very short day's journey physicians who still 
adhere tc Frerich's classification. 1 dare say that this view of Frerich's 
is one very tenaciously adhered tc by physicians of today. an easy 
simple classification; does away with all complications, makes it perfectly 
plain- tc say that the kidney is in a state of inflammation, or atrophy, that every inflamed kidney is goi.ig tc atrophy, and every atrophied kidney has 
been inflamed. I dc not know that anything I can say tc you will oeuse you 
tc accept any other classification. Now when we have really come tc study 
symptoms in connection with the form of kidney found at autopsy we find that 
Freriob's classification is almost entirely built upon pure theory; it is sup- 
ported by neither clinical symptoms nor pathological study. Probably one rea- 
son why physicians hold tc this classification of Drigbt’s disease is through 
the work of Mr. Granger Stuart on diseases of the kidney, a prominent Scottish 
writer., who wrote one of the most attractive treatises on the kidney, one of 
the easiest tc study and “cram” on I ever met with,* absolutely a finished pro- 
duction. He could from the clinical symptoms tell you .lust what degree of 
degeneration the patient had in bis kidney, or what degree of contraction. I 
studied it 25 years ago end was simply charmed with it. New, when I tell you 
that two patients with the identical clinical symptoms may have entirely dif- 
ferent changes in the kidney, you will understand that ycu'oannct accept Stu- 
art's endorsement of Freriob's classification. 
Another classification which is far better is that suggested by another 
German investigator, Bartels, and which has been adopted very largely by En- 
glish medical men. It locks upon oAPWiic Bright’s disease as including a num- 
ber of distinct affections of the kidney under the head of Bright’s disease. 
* 
For instance, Bartels gives first, “acute Bright’s disease”, secondly paren- 
chymatous inflammation of the kidney- chronic parenchymatous nephritis”. In 
this form the secreting structures of the kidney, the epithelium of the secret- 
ing tubules especially is involved- the parenchyma proper of the kidney- and 
if this be sc, then chronic parenchymatous nephritis is quite correct. 3. “Chronic interstitial nephritis”. In this form the connective tissue 
stroma of the organ is especially increased;and the 4th form "waxy degeneration 
of the kidneyfamyloid disease of the kidney”. New certainly this classifica- 
tion is far more scientific than the first- that of Frerioh. ihe only trouble 
is that we do not meet with examples of purely parenchymatous nephritis. It is 
the rarest thing. You did see that section of the acute change affecting the 
epithelium largely, but I emphasized the point that this was rare in chronic 
Bright's disease. You do not find one kidney with the lesion confined to the 
epithelial structure end another with the lesion confined to the connective 
tissue of the kidney. 
As far as the waxy degeneration- the fourth form- is concerned, if the 
amount of waxy degeneration amounts to anything it is accompanied by a genuine 
inflammation- genuine nephritis. Ferscnally I prefer to accept the classifi- 
cation which Austin Flint suggested, and which Welch of the Johns Bcpkins sup- 
ports. Ihey prefer to embrace chronic Bright’s disease under the general term 
of “Chronic diffuse nephritis and to regard the various forms which we find 
under this as sc many manifestations- sc many varieties- of one £nd the same 
disease- chronic diffuse nephritis. Accepting this classification we propose 
to tell you something about four forms of chronic diffuse nephritis. 1. that 
form which is characterized by the Targe kidney and in which there is no amy- 
loid degeneration present, this is known as the large white kidney of Wilkes- 
Gecrge Rilkes, an Fnglish physician, first having proposed this term. 2. We 
% 
will direct your attention to the large kidney with amyloid degeneration, which 
if you choose you may call amyloid nephritis. 5. the most important form- the 
small contracted kidney, synonym# for it which I will give you 
whenwe take up that special form- 4. Ihe contracted kidney which accompanies a general disease, (general thickening)of the blood vessels, designated “Ar- 
terio sclerosis. Mow, 'ttrr linrtlT5TTW',reiy: The first kidney which we will 
describe under chronic diffuse nephritis is the large white kidney. I have 
already told you that acute Bright's disease, as a rule, does net pass ever 
into chronic Bright's disease. That is the patient either gets well or dies, 
as a rule. Sometimes, however, (exceptionally) the acute disease is prolonged 
into a chronic condition, and then we find the large white kidney but the ma- 
jority of cases of large white kidney without amyloid degeneration do not orig 
inate as acute Bright's disease- the disease is of a slow hidden nature from 
the beginning. In this particular form we find at autopsy the kidney much en- 
larged. Instead of having the normal weight, say of 15C grams which the adult 
kidney weighs, it may be found to weigh £50, 500 or 400 grams. $hile the kid- 
ney , as a rule is pale in odor it may be mottled white and red. The oapsule 
strips away easily, is not adherent. Upon out section the oortex is found to 
be decidedly increased, mere often of a pale color but sometimes reddish 
areas marking hemorrhage into the tubules, or yellowish white areas marking 
fatty degeneration of the epithelium within the tubules. The striaticn of the 
kidney in the oertioal ares is obscure, and the Malpighian bodies, as a rule,- 
pale. The pyramidial structure, just as in all the forms of chronic Bright's 
\4v hr 
disease is congested. microscopical It the oapsule 
is still adherent to the section, it is net found to be thickened, but here 
and there through the section, one finds areas of marked increase in the con- 
nective tissue of the kidney- areas in which the tubules are much compressed, 
or have largely disappeared. Here the tubules are narrowed. In ether areas 
not affected by connective tissue, the tuples are even dilated much larger 
than normal. This connective tissue growth may show numerous cell nuclei or I 
may be poor in oells- present a fribrilated appearance. Bear in mind, just as 
I told you in aoute Bright’s disease you do not find the section of the kidney 
unitcrmly^diffusely affected, but we find scattered areas of disease in one 
ncrticn of the kidney while another portion will scarcely be disturbed. The 
diseased pert shows marked change in the connective tissue growth. 'Ihe con- 
nective tissue round about Bowman’s capsule is generally thickened and tne 
connective tissue of the capsule, of the tuft itself may be considerably in- 
creased. Ihe glomerulus may be converted into a mass of fibrous tissue. Fre- 
quently the glomeruli present a lobulated form, as if they were divided up 
into distinct lobules, and occasionally vessels are seen that have undergone 
a hyalins degeneration Jkd tc the epithelium of the Where the con- 
nective tissue has increased we generally find atrophy as well- cells which 
have undergone atrophic changes. In other sections of the kidney you may find 
oells the seat of hyaline degeneration, peculiar refractive material which 
appears in them as droplets and which is olcsely/the nature of fibrin. He 
/ 
frequently find in fresh sections, that many of the epithelial ceils, the 
secreting oells, have undergone fatty degeneration. We sometimes find that 
the epithelium of Bowman’s capsule end the tuft has undergone considerable pro- 
liferation, and we get moon figures of the proliferated oells. Sometimes we 
find numbers of these cells lying in the tube leading from the tuft. Ihe 
bloodvessels, as a rule, are unaffected, though occasionally one does find 
some increase in the intima of the vessels- seme slight endarteritis. Here 
and there, especially in the mottled kidney, we find red blood cells in 
Bowman’s capsule, but more especially in certain tubules of the kidney. .In- 
deed in seme of the large mottled kidneys the amount of hemorrhage into the tuble is sufficient to constitute what is called "chronic hemorrhagic nephritic 
which is one of the forms of this large white kidney without amyloid degenera* 
ticn. Ibis is the chronic form of Bright’s disease which runs rather a short 
course. Ihe patient generally because we do not cure the in a 
year and a half or two years. You can prolong life, do e good deal of good in 
relieving the patients condition, but you cannot cure the condition. 
Ibe second form to which I will call your attention is the large kidney 
with amyloid degeneration, the waxy kidney- sometimes net classed with chronic 
Bright's disease. I do not know where your text book on the practice of med- - 
ioine places this amyloid degeneration of the kidney, possibly ncx with chronic 
Bright's disease. As I have told yen, you may designate nephritidj 
Ihis is of the frequent forms of chronic inflammations of the kidney- this 
with the small contracted kidney. Ibis is the form that gees as yon already 
knew with amyloid degeneration of the liver, and the diseases with which it is 
associated- syphilis, chronic suppuration of bone,chronic tuberculosis, etc. 
sc that you will net be surprised to bear me state that with this form of 
chronic inflammation of the kidney we have amyloid degeneration of a number 
of the organs, in which amyloid is deposited- spleen, liver, stomach, intestine 
uterus, ovaries etc. 'Ibe kidney microscopically is changed- the capsule strips 
as a rule, easily, though sometimes it is adherent, and we may find, I may 
here remark, that the amyloid kidney is sometimes smaller than the normal size. 
Here we find the capsule adherent, and the surface of the kidney instead of 
being smooth as usual, somewhat granular. Open cut section the cortex is 
found increased, as a rule, and pale in color. Ihe disease may be sc slight; 
the patient having died of some intercurrent affection, that to the naked eye no amyloid change is to be seen. As a rule, though, the amount of amyloid 
degeneration is sufficient to show greyish translucent areas. Ihe markings 
8 P 6 
of the kidney are obscure and the glomeruli are pale, Iber€Aareas of whitish 
or yellowish appearance, marking fatty degeneration of the cells. Ihe pyrami- 
dal portion is congested. 
4s tc the microscopical appearance: One sees in this form very deoeded 
forifis 
changes. It is really cne cf the pleasant A of chronic Bright’s disease to 
get under the microscope, because you can find something without difficulty. 
In the first place the connective tissue stroma cf the kidney is much 
Many tubules are in a state of atrophy. Ihey may have disappeared entirely 
where this increase cf connective tissue has taken place. 
In the next place the glomeruli are decidedly involved by the deposit of this 
peculiar material of albuminous origin, (amyloid material) in the walls of the 
capillaries, leading finally to their obliteration. Net only in the Malpighian | 
tufts do we find this amyloid deposit, but we find it in larger blood vessels* j 
in the straight vessels- of the kidney, and in the vessels especially along 
the vascular zone, the zone of the blood vessels arches between the cortex and i 
the pyramidal portions; and you notice that just as in the liver, the amyloid 
is deposited in the middle coat of the blood vessels. Not only that, but we 
find the basement membrane propria, upon which the epithelial cell are sup- 
ported, thickened by the amyloid deposit; then too you find the most extensive 
change in the kidney epithelium- marked fatty degeneration, hyaline degenera- 
tion, atrophy, etc. Ibis is the form of chronic Bright’s disease which may 
lest many years, end which the patient may have in a well advanced condition 
without being aware of it. Now I think you will appreciate that although we oall one form here the large white kidney without amyloid and the other the 
large kidney without amyloid degeneration, you will now be ready to acknowledge 
that both forms, from what I have told you are really instances of chronic 
diffuse nephritis; that is that all of the structures of the kidney are in- 
volved- interstitial tissue, epithelium and blood vessels. We will speak about 
the other form some other time. PATHOLOGY NO. 33. 
April 6, 1898, 
Small contracted kidney 
11. Chronic Interstitial Nephritis 
2. Cbronio Arterio-Solerotio Kidney 
Synonyms: 
Small granular kidney 
Red atrophy of tbs kidney 
Gouty kidney. 
I have spoken to you already, gentlemen, concerning two of the forms of 
chronic Bright's disease- the large kidney, white or mottled, without waxy 
degeneration, end the large kidney with waxy degeneration, sometimes called 
"amyloid nephritis”, tav Th ere are two important varieties of chronic Bright's 
disease, which are embraced under the small contracted kidney. Amyloid nephri- 
tis and the small contracted kidney embrace the majority of cases of chronic 
Bright's disease. In the form of small contracted kidney we have two distinct 
varieties- 1st chronic interstitial nephritis, which is often referred to as 
the small granular kidney, red granular kidney, red atrophy of the kidney etc. 
“Cyanotic atrophy of the kidney” has occasionally been applied to it. New I 
told you that you could net accept Brerioh's ideas that the large kidney un- 
derwent a change into the small kidney- B'rerich’s idea being that this was the 
rule. Notwithstanding that fact, there are occasional cases which sofem to 
beer cut the idea- these ere the exceptional oases- that the large white kidney 
may later undergo considerable decrease in size with e still more marked in- 
crease of the connective tissue of the kidney. That is quite the exception, 
however. Sc that although there is such a thing as a secondarily contracted 
kidney, 
Awhat we refer to here in the small contracted kidney is an organ which at no 
time has undergone enlargement, but is what may be designated a primarily con- treated kidney. 'Ihere is every evidence tc believe that the kidney from the 
beginning of the disease starts on its way tc atrophy- grows smaller. This is 
the one form of Bright’s disease that, more than any other, has a right to be 
considered a distinct disease of the kidney, target us take the chronic in- 
terstitial nephritis as the first form of the small contracted.kidney. Ibis 
variety constitutes probably half of the oases of small contracted kidney. It 
is the.kidney which English authors have-written a good deal about, designating 
it as the small gouty kidney, others as the small spirit kidney, the writer 
being influenced by his belief that gout or the influence of alcohol was the 
important causative factor in the production ci this variety of kidney disease. 
We here find the kidney much reduced in size- reduced | or even 'i. Ibe kidney 
is not smooth, but rough; the capsule does not peel away when you attempt to 
remove it but is found tc be adherent, and when separated with force carries 
with it portions of the kidney structure. Not only that, before the capsule 
is removed, in s majority of these cases, one observes under the capsule a 
number of little cysts of varying size filled with clear contents, from a pin 
point tc pea size; sometimes many dozen of these cysts scattered under the 
capsule. Like other form of chronic Bright’s disease of course you understand 
that,both kidneys are affected, occasionally one. being in a little more advanc- 
ed stage than the other. When the capsule is removed I say the.kidney is rough, 
it presents a granular, uneven surface. Ibe parts of the.kidney which have not 
undergone the most advanced change present often a yellowish appearance, a 
greenish yellonr appearance, and the depression between these granulations on 
the surface of the.kidney mark the seat of the connective tissue. Just as in 
cirrhosis of the liver, the nodules on the surface of the liver represent the 
the secreting parenchyma of the liver and the depression.between the nodules the new oonneotiwe tissue, so this same condition is seen in the kidney. 
Upon section of the organ it is found that this atrophy affects the cortical 
portion of the kidney; this is reduced from i to I,sometimes to a mere line, 
and the pyramidal portion is, as in other forms of Bright’s, injected. Micro- 
scopically vse find that all parts of the kidney are involved- all of the struc- 
tures of the.kidney, I should say. Possibly the interstitial tissue of the 
organ is more.in creased than in anyother of the forms that we have yet studied] 
This connective tissue may radiate down as distinct large bands from the cap- 
sule, and one may find no remains of tubules in such.bands. In other areas the 
connective tissue is found increased.between the tubules and these very much 
compressed and atrophied. Other tubules are found decidedly dilated; some dilat- 
ed into small cysts owing to the contraction of the connective tissue of the 
kidney, interfering with the escape of the secretion from Bowman’s capsule, 
thus.backing up the urine in the tubules. One finds many cf the glomerular 
tufts completely obliterated- nothing to.be seen but s dense fibrous connective 
tissue. Ground other tufts Bowman’s oapsule is very muoh thickened. Occasion- 
ally one sees that here and there in the section one of the smaller blcodves- 
¥ 
sels is affected, its cal reduced, owing to the increase in the intima of 
the vessel, .but this is in striking contrast in this form of chronic nephritis 
with the bloodvessels in the srterio-sclerotic kidney, as we will see. Now 
in addition to the increase of connective tissue which is very marked in this 
form; in addition to the obliteration of many of the Malpighian tufts by the 
connective tissue increase, in addition to the thickening of Bowman’s capsule 
and to the dilatation of certain tubes, and atrophy of others, we find the 
epithelium here, as a rule, muoh. atrophied. 'Ibis may.be especially in the 
tubules which are surrounded.by quite dense connective tissue. We find other 3 tubules containing epithelium that has undergone hyaline degeneration, fatty 
degeneration. You.know $eigert, a German pathologist, has expressed the view 
that in this form of obrcnio kidney disease, the first change is atrophy of the 
epithelium, and that all of the connective tissue increase is simply compensa- 
tory- to take the place of atrophied epithelium. Be has tried to sustain this 
view with a good deal of acute observation and reasoning, end he does not stani 
alone in this regsrd,.Other pathologists in this country,regard the first 
change in this form of chronic nephritis as affecting the secreting epithelium, 
but we will not stop to consider that this is true or not. It cannot.be posi- 
tively sustained. In the second variety of small contracted kidney- the kid- 
ney of arterio-solerosis, as it is called, we find very much the sameobanges, 
but we find especially the. bloodvessels in the.kidney affected. Kcw the first 
form, the chronic interstitial nephritis, is not associated with s disease of 
the.bloodvessels. I have said that occasionally a.bloodvessel may.be found, 
even in this form of kidney disease, in which the caliber of the vessel is re- 
duced by the thickening of the intima. On the other hand, the chronic arterio- 
sclerotic . kidney is the kidney which we find in connection with a general di- 
sease of the arteries, which was first described.by Gull & Sutton in 1891 un- 
der the title “irteric-Cepillary Fibrosis”- this was the first important arti- 
cle on the subject- Sir William.Gull, the distinguished physician who has con- 
tributed .so.much to.good.solid practical medicine. 
.Under this.general arterial disease they described,a thickening of the walls 
of the arteries.and capillaries which condition affected the arterial system 
generally. 'Ihey described it as a fibroid thickening affecting the outermost 
coats of the vessel- the adventitia as you have been taught to call it. Now 
we have every reason to.believe that the pathological histology of this disease ss interpreted,by Gull & Sutton, is net oorreot. Ihere is suoh a disease as 
general arteriosclerosis, and, it , is a very important disease, a very impor- 
tant affection for the physician to recognize.clinically. Ibis is one of the 
affections which you ere able to diagnose. It is that peculiar disease of 
the .bloodvessels which is accompanied.by an increased pressure in the vessels 
a plus tension as your professor of practice will describe it tc you- a thick- 
ening in the radial arteries, for instance, so that the vessels can be rolled 
under the finger, end the is with difficulty shut off in the vessel. Ibis is 
accompanied by a most marked hypertrophy of the heart and an accentuation of 
the aortic second sound. Ihese are the characteristics of the disease- general 
arterio-solerosis, - a disease which every graduate in medicine should be sc- 
A 
qusinted, because you are apt tc meet with it. It is a disease which is met 
with frequently in this.country, and it occurs not in old people, but , as a 
rule, in the very robust and strong middle aged people- from 4C to 5C years 
of age. Ihese ages embracing most of Councilmans*s oases as observed in this 
country. Ibis disease has.been especially written on from the pathological 
side by Gull and Sutton, by the German Pathologist I horns, who has contributed 
so much tc.cur knowledge of diseases ..of the. bloodvessels, and. in this country 
especially.by Ccunoilmann, the present professor of pathology at Harvard Col- j 
lege. Of course, your professor of clinical medicine will lecture tc you on 
arterio- capillary fibrosis or.general arterio-solerosis. I simply want to cal 
call your attention to the fact that there.are three forms of arterio- sclero- 
sis. First the form which is.known as (I am not speaking now of the kidney 
seen j' 
understand, but of the bloodvessels) :,nodular 3rterio-scierosis;; If you 
many autopsies and have seen the aorta and larger bloodvessels opened, you may have had your attention attracted to certain slightly elevated, light colored 
areas involving the intima of the vessel, and which were doubtless designated 
atheromatous patches- atheroma- this is the nodular variety of arterio-sclero.rr 
sis. Then again there is another variety known as “senile” arterio sclerosis 
“senile endarteritis” in which in elderly people, the walls of the vessels are 
found to be much thickened,elevated, certain exaggerated curves in the artery 
Oi £ 
where normally they do not occur- these arteries becoming quite oalcerous under 
K 
(L 
the disposition of lime salts. Then there is the general srterio-sclerosis, 
affecting all of the bloodvessels, which is found in middle aged individuals, 
the so-called secondary arterio sclerosis- the nodular form being designated 
sometimes as primary arteriosclerosis. This form which accompanies the srte- 
rio sclerotic kidney is the important form. Ail of these forms as Thoma has 
shown us are due directly to the degeneration of the muscular coat of the ves- 
sels, which is the first change, in the nodular variety, and in general arterio 
sclerosis, frequently the muscle cells are found to have undergone fatty de- 
generation. Most often though, the change is a deposit of a hyaline,smooth, 
homogenious material in the middle coat of the vessel, a material which in some 
respects resembles amyloid, but is of a different chemical constitution. This 
deposit follows either fatty degeneration or atrophy of the muscle cells. In 
order that the vessel shall not be weakened, what does nature do ? She 
strengthens the inner coat of the bloodvessels, the intima. That undergoes 
marked thickening, just at the point in nodular sclerosis wherftthe muscular 
coat is weakest, and in the same way in general arterio sclerosis. Here we 
have involving the large vessels and the small vessels, sometimes all of them, 
this peculiar change taking place in the muscle coat of the vessels, followed by a thickening o$ the intima. It is interesting to know that during life 
these atheromatous patches, which we see at autopsy, do not project inside of 
the vessel at all. Thoms hss shown by taking oasts of the vessels with parraf- 
fin that the wall is perfectly smooth and that there is no depression, showing 
that the intima is increased just enough to make the vessel smooth. After 
death, with the pressure removed they appear as elevated patches. 
Now as to the general cause of arterio-fibrosis or sclerosis: Although 
Thoma attributed it to increase of pressure in the smaller vessels, this fol- 
lowed by increased pressure in the larger vessels, we do not aooept this view 
at all. It seems to be some primary change- to be due to some primary oeuse- 
oertainly we find it in syphilitics. Then again arterio-soierosis is found in 
men who are compelled to do extremely hard manual labor, men who are also ex- 
posed to great hardships, and, as Osier says, it is at times unmistakably her- 
editary. He quotes some one as saying “a man is only as old as his arteries7’. 
Nature sometimes, as Osier remarks, makes a body otherwise very well, but puts 
in poor tubing, and this is the oase in this disease known as general arterio- 
sclerosis. For some reason the bloodvessels are s to do their proper 
work- from some general constitutional cause the meaia or muscular ooat of the 
bloodvessels undergoes this peculiar change and is followed by thickening of 
the intima. 
We find in the kidney some of the most striking changes: first the change in 
the bloodvessels; and the kidney symptoms, bear in mind, due to the arterial ' 
changes, are the most prominent symptoms ordinarily found in the disease known 
as arterio-solerosis. The kidney symptoms are often the organs that first oall 
attention to the disease- the faot that the patient has something wrong with the urine, perhaps an increase in the quantity of the urine, small amount of al- 
bumen in it, diminution in the specific gravity, etc. 
In regard to the structural changes in the kidney, we find a very great in- 
crease in the connective tissue of the organ, this change especially takes plac( 
in the oapillaris of the glomeruli, completely obliterating many of these, so 
A 
that they appear just as the glomeruli do in the kidney of chronic interstitial 
nephritis. We find some cystic dilatation. We do not find as marked atrophy- 
In other words, we may have the kidney of arterio-sclerosis not much 
whereas the chronic interstitial nephritis is always a small kidney; this ar- 
terio-solerotic kidney is occasionally a kidney of normal size or perhaps a iitJ 
tie reduced in size. It is extremely resistant to pressure, to tearing and to 
the klife. Upon section the vessels at the hylus of the kidney are found to 
project above the out surface, or in making section of the kidney the vessels 
in the intermediate zone are found to project, their walls being very much 
thickened and very prominent. We find perhaps the oortioal substance markedly 
reduced, or a little reduced- occasionally the change to the eye is extremely 
slight in this form of kidney sclerosis. We have the same changes in the epi- 
thelial structures as I have described to you in the other form; indeed you may 
have just the same picture microscopically in this form that you have in the 
first, except that the bloodvessels are different, and it is important to bear 
in mind that the disease of the arteries is the chief difference between these 
two varieties in kidney disease- one associated with general arterio-sclerosis, 
and the other not associated with it. In both of these forms of Bright’s di- 
sease, gentlemen, we have marked hypertrophy of the heart. Bright believed 
that this hypertrophy was due to an accumulation of urea circulating through the vessels; that it was brought about by spasm of the vessels, the urea act- 
ing either upon the vaso-motor center or upon the walls of the vessels, thus 
reducing their calibre, so putting greater action upon the heart and thus lead- 
ing to this hypertrophy. This is considered even yet one of the good explana- 
tions for the hypertrophy of the heart. Others have attributed the hypertro- 
phy to the obliteration of the bloodvessels in the kidney and other organs of 
the body, especially the general arterio-sclerosis; others still have attrib- 
uted it to the fact that so much blood is required to be carried through the 
kidney in a given time, and hence as many of the bloodvessels are obliterated, 
as many of the glomeruli are obliterated, the heart in order to pump a given 
amount of blood through fewer capillary districts, must increase its power. 
This may have something to do with it. Nature has seme very peculiar ways of 
bringing about adjustments. At any rate, although there is such extensive ob- 
literation of the vessels in the kidney, bear ir mind that in the small con- 
tracted kidney (both varieties) the urine is not diminished, but increased. 
The amount of urine secreted depends not so much upon the pressure as upon the 
quantity of blood that passes through the kidney in a given time, as I have 
already told you. This very much hypertrophied heart manages to send more 
blood through the kidney, consequently we have an increased amount of urine, 
but of low specific gravity. This is one of the important points in diagnosis. 
a 
If you have a patient who passes 55 or 60 ounces of urine, without or with a 
little albumen end doing this daily, and with as low a specific gravity as 
Q. 
1,012, 1.010 or 1.008, be prepared for the small contracted kidney. It is one 
of the forms of Bright's disease- both of these varieties- ‘which stasis upon 
the patient very gradually. Sometimes he may be syphilitic, or a gouty indi- vidual, or a painter who has been working in lead for a number of years. -It 
is one of the insiduous forms of ohronio Bright's disease. I have already 
implied in these remarks something as to its causation. It may be that many 
of the oases, especially of small contracted kidney, has its origin in one of 
the attacks of the acute infectious disease. We do not knew. That view is 
coming into prominence, ihe idea that chronic malaria accounts for this varie- 
ty of kidney disease is sometimes held. I do not attach any particular impor- 
tance tc it. PATHOLOGY HO. 54 
April 8, 1898. 
SPLEEN. 
1. Acute splenic tumor 
2. Chronic passive congestion 
3. Infarction 
4. Amyloid degeneration 
5. Spleen of the leukaemia 
6. Spleen of Malaria 
?. Tuberculosis of Spleen. 
These are the most important pathological conditions of the spleen. 
•Ibe diseases of the spleen are in some respects of less importance than 
those of the liver, lungs and kidneys. Indeed, although the spleen is of im- 
portance in the animal economy, it does not seem to be absolutely necessary 
in order that the individual should have an average degree of health. Occa- 
sionally there is a congenital absence of the spleen. In other oases the 
spleen has been removed by surgical operation, the patient remaining in a fair 
state of health. Nevertheless, there are various diseases of the spleen with 
which you should have some acquaintance. I need not recall to you the histol- 
ogy of the spleen- you knew that it consists largely of lymphoid tissue. It is 
an organ made up of blood spaces, bloodvessels and lymphoid tissue- the largest 
collection of lymphoid or adenoid structures to be found in the body, ibe 
spleen consists largely of what is known as splenic pulp, and scattered through 
this splenic pulp we have certain well,defined localized lymphoid structures 
along the bloodvessels, known as the Malpighian bodies or “Malpighian follicles 
of the spleen. Ibe splenic pulp constitutes the greater part of the splenic 
tissue. It contains blood spaces generally known as venous capillaries or ve- 
nous spaces, whose walls are made up of spindle shaped cells and whose contents 2 
consist of red blood cells and white blood cells. Ihis splenic pulp also con- 
tains a number of lymphoid cells- cells having a single nucleus and correspond 
ing to lymphoid cells of lymphatic glands, then certain larger cells with rela 
tive more protoplasm containing one or more nuclei, which you are already ac- 
quainted with as the "splenic cells" proper. As I have already said the most 
marked collection of lymphoid cells are those that are found around the blood- 
vessels- certain of the bloodvessels and smaller arteries of the spleen- and 
in examining a section of the spleen you will generally notice that the blood- 
vessel is most often deoentrally located; that is, it is not quits in the oen 
ter of the lymphoid cells in the Malpighian follicle- this appearance you are 
already familiiar with. All of this structure is supported by bands of con- 
nective tissue radiating from the capsule and from the hylus of the spleen. 
These are the coarser bands or the so-called trabeculae of the spleen, along 
which the bloodvessels run for quite a distance in the spleen. Then we have 
in addition to these coarser trabeculae, Quite a network of finer fibers which 
course through the splenic pulp in various directions, known as the splenic 
reticulum, ihere is a very delicate reticulum in between the lymphoid cells 
in the Malpighian follicles of the spleen. Mow then, you see that the spleen 
consists largely of blood spaces and of lymphoid cells. 
We first take up the vascular disturbances in the spleen, and I may here 
remark that there is an active congestion of the spleen which accompanies di- 
gestion. Ihe capsule covering the spleen is very distensible and permits of 
considerable enlargement of the organ, this enlargement occurring with each 
act of normal digestion. But thereis another form of active congestion of the 
spleen which is not physiological- it is that quite marked congestion of the spleen which attends certain of the acute infectious diseases; especially 
well marked in relapsing fever, typhoid fever, croupous pneumonia, and in the 
h b 
antrax spleen of animals; and in the antrax spleen of human beings also, al- 
though anthrax is a rare disease in the human being. You know that enlargement 
of the spleen is one of the clinical symptoms which we meet with during the 
course of typhoid fever* ihe educated physician always palpates the spleen in 
in typhoid, notwithstanding the fact that we have various other reliable tests 
for the diagnosis-of this disease. Ihe spleen is found to be much enlarged in 
typhoid, and I will take that as a type of acute splenic enlargement. At autop- 
sy it is found to be dark in color, very friable (soft and friable- easily torn) 
and indeed rupture of the spleen may take place during life, so that I may warn5 
you against being too enthusiastic in puncturing the spleen of typhoid fever or 
croupous pneumonia, (sometimes in bacteriological research the physician may 
want a culture of typhoid bacillus and the spleen of the human being is the 
place to get it ) but it is better to take it after death than during life, be- 
cause the hypodermic needle may cause a rupture of the much softened spleen end 
fatal hemorrhage. Rupture of the spleen seems to be beyond surgical assistance. 
Upon section the spleen is of a very dark color, the splenic pulp being so en- 
gorged that the splenic cells have taken up a number of red blood corpuscles 
and are then known as “corpuscles carrying cells", these you may find in ty- 
phoid fever especially, or in croupous pnemonia for that matter, these cells, 
which are really the splenic cells proper, act as phagocytes and take up the 
red blood cells brought to the spleen. In addition to the blood carrying cells, 
we find in the pulp various areas of necrosis, You will detect those with low 
power. You will notice certain areas stained a little more brightly with eosin than the other parts of the pulp, and in these areas you will see numer- 
ous fragments of nuclei of cells, especially of the polymorphonuclear cells 
that have wandered into the area of necrosis. Now this condition of acute 
splenic tumor, as it is called, in typhoid fever, in croupous pneumonia, in 
septicaemia, in anthrax, is frequently referred to as acute inflammation of the 
spleen, scute splenitis, fie do find in the acute stages a lesger number of 
polymorphonuclear leucocytes in the splenic pulp than normally, and occasional- 
ly a necrosis goes on to absolute abscess formation, which is raer. Occasion- 
ally there are numerous small abscesses scattered through the splenic pulp, so 
that it is generally spoken of as scute splenitis, though it is more properly 
designated as “splenic tumor". The necrosis in the spleen do not contain group: 
of typhoid bacillus. In a section we find clumps of the bacilli scattered here 
and there in the pulp and occasionally in the vascular spaces, but just as we 
do not find them in the necrosis of the liver, we do not find them in the ne- 
crotic areas of the spleen. Probably the necrosis is brought about by the pro- 
duction of emboli in the bloodvessels, or primarily by the presence of the tcx- 
ines io the circulation. .1 think 1 told you when on the subject of the liver 
of typhoid that it was impossible to say whether the necrosis was due to emboli 
or simply to the toxines circulatin through the liver. The same applies to 
their production in the spleen. Seme of these marked necrosis have been de- 
scribed as occurring in relapsing fever, which disease has net been in this 
country for several years. When I was in hospital in New York, some years 
ago, we bad two epidemics and these were due to the spirillum Cbermieri- 
Obermeir being the first to detect these in the blood of the human being. It 
is in this form of splenic tumor (relapsing fever) that the most marked necro- 
sis have been found. They have also been found in in acute splenic fever and fatal oases of diphtheria. If all goes well this splenic tumor undergoes reso- 
lution, and the neorotio areas, which are generally minute, are replaced by a 
regeneration of the cells of the splenic pulp. 
Now as tc the second chronic passive congestion of the spleen. 
This needs only a word. It is caused by obstructive lesions in the heart, lung 
and liver, with which you are already familiar. The spleen in chronic passive 
congestion does not obtain the size that it does in acute splenic tumor. In- 
stead of being a light soft spleen it is a dark resistant spleen, at times it 
is but little increased in size over the normal. The resistance is due to an 
increase in the connective tissue proper of the reticulum of the spleen, which 
gives you a firmer organ to deal with. The cut surface is generally of a dark 
red color. The back pressure of the blood has a remarkable effect in causing 
atrophy of the Malpighian follicles-{hence they are not prominent in the spleen 
of chronic passive congestion. Neither of these conditions can be effected by 
remedies. Chronic passive congestion of the spleen is a permanent oondition- 
if a patient once has it, it remains until he ceases to be of any further par- 
ticular interest. 
Regarding the third condition- infarction of the spleen: This is another 
one of the vascular disturbances of the spleen. Here we have as a rule, the 
anaemic form of infarction. Although the splenic tissue being less resistant 
than the kidney tissue and resembling more closely that of the lung, may fur- 
nish us hemorrhagic infarctions, as a rule, anaemic infarctions are found here. 
They come of course with lesions of the left side of the heart or from masses 
of fibrin torn away from aneurism of the aorta, whether thoracic or sbdominal- 
generally masses of fibrinous exudate with bacteria swept from the left ventri- ole of the heart in ulcerative endocarditis. The splenic artery is a good 
sized vessel, and the spleen ranks about next to the kidney in being the seat 
of infarction. The infarction here undergoes the same change as you already 
have been made acquainted with in the lung and kidney. It sometimes leads to 
the formation of an abscess- a distinct abscess. This abscess may rupture 
through the capsule and cause a fatal peritonitis, or the hemorrhagic infarct 
may undergo resolution, liquefication and softening -its place being taken by 
granulation tissues, just as we saw in the lung-, finally a dense scar tissue 
being formed, which causes a puckering of the spleen- remaining afterwards as a 
distinct puckered depression on the surface of the spleen. Infarcts, as a rule, 
are large in the spleen. 
4th. Amyloid degeneration of the spleen goes with amyloid degeneration of 
other organs, and is met with in two forms. In the firrt form the middle ooat 
of the arteries is the seat of the amyloid deposit. It even invades the Mal- 
pighian follicles, destroying them, and giving you, upon section, distinct, 
translucent, grayish areas, scattered uniformly throughout the spleen, giving 
rise to the so-called “sago” spleen, reminding you of sago scattered over the 
surface of the spleen. This is one form. The other form (the second) the 
reticulum proper or pulp of the spleen is invaded, and you have a general amy- 
loid degeneration of the splenic tissue. This goes with tuberculosis, chronic 
bone disease, syphilis, and diseases of that order. 
5th. The spleen of leukaemia is an interesting spleen to study microscopi- 
cally. Ibis and the spleen of malaria are two of the most resistant forms of 
splenic tumor that we can meet with. In both the spleen is enlarged; in the 
one case (leukaemia) due to the enormous accumulation of white bloodcells in the splenic pulp, snd in the second case (malaria) due to the accumulation of 
malarial parasites, malarial pigment, and degenerated red blood cells,- both 
of these forms of collection of cells serving to cause an increase, to a 
marked extent, of the connective tissue of the spleen. One can better under- 
stand the spleen of leukaemia by studying the section than I could possibly ex- 
plain. You know the spleen is one of the organs which serves, like the lym- 
phatic glands, to filter out various particles in the blood. Degenerated red 
blood cells find their way to the spleen. He used to think the spleen the 
source of the red blood cells, we now consider it the graveyard of the red 
blood cells. In regard to its vascular relations; you know it has never been 1 
decided whether the arteries and veins connect directly or whether the arteries! 
stop and there are oetain large blood spaces in the spleen without walls proper 
from which the vsnious capillaries lead. Others contend that the arterial cap- 
illaries snd the venous capillaries are in connection with each other, which 
is probably the true theory. As I have already said, the splenic pulp.serves 
to filter out various foreign bodies, pigment of all kind, hemosiderin, mala- 
rial blood, degenerated red blood cells, malarial parasites, white blood cells 
when they are in large numbers in the circulation- all of these collecting 
in the spleen. The spleen is one of the sources of the white blood cells 
(the leucocytes), so that in chronic malaria snd in leucaemia (the splenic 
myelogenous leuoaemoa) we find quite a collection of cells that are foreign 
to the normal spleen, which give rise to the swelling end to the connective 
tissue hyperplasia which we find under these circumstances in the spleen. 
7th. The other lesion to which I will call your attention is tuberculosis 
of the spleen. This appears in two forms; 1st Acute miliary tuberculosis, go-