PART 2

. THE LIVER

A consideration of the liver is anatomically and physiologically the next step in the discussion of diseases of the alimentary tract. While this organ may participate in most of the pathological states of the tubal part of the system, it is comparatively seldom the primary seat of change and when damaged seems to be possessed of great accommodative and reconstructive power. This must be true, and fortunately so, since we ascribe to it the major detoxicating function of the body. Nevertheless it is noteworthy that the largest solid organ of the animal body shows a relatively low percentage of changes threatening to life. In the sense of Pearl’s method of statistics, it does not “break down” easily. In pathology it is the custom to list with great care all the changes, gross and minute, in the liver, but with a few exceptions they are secondary or incidental. They do however reflect many things, especially referable to diet and to chronic infection from the intestinal drainage area. It is in these directions that the organ will be studied in the following pages.

Anatomically the liver is situated in the right upper part of the abdomen subjacent to the diaphragm in both mammals and birds, being held in position by attachment to this transverse partition, by ligaments or folds of peritoneum, and by the other abdominal viscera. Its general relationships do not offer great variations since in all animals means are afforded for a dual blood supply and an outlet for the hepatic secretion, the bile, into the higher intestines. Naturally variations in the size of the lobes are observed and there has been considerable speculation as to their independence and association. From the standpoint of comparative pathology, little can be ascertained to assist in this matter unless the position of abscesses and hepatitis relative to cholecystitis have a bearing; some discussion of this will appear later. We have not observed any peculiar pathology of the lobes of Spigelius and Riedel. In so far as the size and arrangement of the organ is concerned a few general facts of significance may be mentioned.

It was formerly thought that the liver varied inversely as the size of the animal but Magnan[23] and others have shown that the matter is not so simple. In the first place if there be an actual mathematical formula it is that the liver varies in size inversely as the surface area of the body, but this is not the whole story. It seems that the relation of size of the organ to its weight is not constant and that it is better to judge of the organic capacity by the latter. In herbivorous animals, both birds and mammals, the liver is lightest per kilo of body weight; next in weight are in order, fisheaters, meateaters, insectivora, seedeaters, fruiteaters and omnivora. There is besides this a roughly inverse ratio between the size of the liver and the length of the intestine and in the class Aves inversely as the size of the lungs also. From the immediately foregoing statements it is apparent that a bewildering variation occurs and that only rough measurements of the relative volume of the liver are available. An attempt was made in the Marsupialia, which present all the variations given, to discover if any peculiar pathology corresponded with the above groups; as it was fruitless, no change from our zoological treatment will be made.

Lobar arrangement varies from the relatively simple double avian type to the manifold lobulations of the seal or the marsupial but I can find no literature to indicate that lobes or lobulations have a direct effect upon functions. There must be a difference of blood supply for in certain infectious diseases like enterohepatitis and amœbiasis, the cystic and extreme right lobes are more affected than the left parts of the organ. In the bird this is not so difficult to follow since the three divisions of the portal vein, while they combine at times in an ampulla within the hilum of the liver, seem directed to certain lobes, that from the left portal seeming to point toward the right side. The avian portal system differs from the mammalian in having a large branch from the renal area, the so-called renal-portal system, pass to the liver, and by having a free anastomosis between the portal area and the caudal vena cava whereby blood from the pelvic district may pass into the general circulation without going through the liver. There is no unanimity of opinion as to the function or importance of this connection[24] and from the data collected here there is no peculiar renohepatic pathology.

The gall-bladder is not a constant organ in either mammals or birds and indeed it may be absent or present in very closely related species (Two- toed Sloth present, Three-toed Sloth absent). When present in mammals it is usually a dependent bag while in birds it commonly lies upon the cystohepatic duct, between the liver and the last curve of the duodenum, in some varieties filling from the bottom, the inlet being guarded by a valve. This cystic duct in nearly all birds, comes exclusively from the right lobe while the hepatic duct, with which the cystic has no connection, is formed by combination within the liver of radicles from both sides. It passes to the duodenum well in advance of the cystic duct, in some birds, _e.g._, the Struthiones, very near the pylorus, that is on the descending limb of the duodenal loop. By this means obstruction to the biliary stream is rendered difficult. The common duct combines with one of the pancreatic outlets in most mammals but the abdominal salivary gland in lower animals has more often patent separate ducts or multiple ducts than it does in man. Birds have one to four pancreatic ducts separate from the biliary openings.

The gall-bladder is missing in most varieties of the following groups: pigeons, parrots, wrens, ostriches, rheas, cuckoos, toucans among the birds; most odd-toed ungulates, hyraces, Indian elephants, all deer, peccaries, three-toed sloth, and many rodents. The varieties lacking this reservoir are herbivorous in the main, true carnivores seeming always to be possessed of such a structure. Among the important herbivorous ungulates, Bovidæ, Tragulidæ, Camelidæ and Suidæ have this bile reservoir almost without exception. Because of the interest now being shown in the pathology of the gall-bladder and its passages and of the pancreas, it was hoped that evidence of definite practical value for human pathology would be at hand in our study if we divided the animals into groups with and without a bile reservoir. The result is not unequivocal but worthy of note; it is discussed on pages 238 and 255.

Microscopically the well known lobular arrangement of the liver is rather faithfully carried out among the mammals albeit the most systematic and complete architecture is to be found in the pig while the marsupial seems the most disorderly, thus resembling the avian organ. In the latter class all the parts are indistinct, the cells having an unclear outline, the tubules being intricately wound and the interlobular connective tissue being scanty and not anastomosing in a definite framework. The intralobular reticulum is especially difficult to detect. Groups of cells are often found at portal spaces; these are large and small mononuclears and granular cells, probably of the hematopoietic system. It is possible that blood formation is performed in the liver and spleen in some adult birds but such a function is denied for the mammal except under very unusual conditions of bone marrow atrophy.

Glycogenic and fatty conservation is a function possessed by both zoological classes as are the detoxicating and bile-producing powers. However it is highly probable that urea and creatin in metabolism is not cared for by the avian liver as it is by the mammalian, judging by the researches of Paton and of Richet.

FAT DEPOSITS.

The care of fat by the liver is very well shown by examining the incidence of fatty metamorphoses through the various orders. In the first place Mammalia show a slightly higher percentage of fatty change than do Aves and should show a greater difference were it not for the large number of cases in two orders of the latter. Among mammals, lemurs, rodents and marsupials store fat in the liver more than other orders but in the second and third, it is chiefly the carnivorous varieties that have this property. Just why the slothful herbivorous lemurs should be first on the list is not evident especially since the grain-eating Ungulata are least apt to present fatty livers. With this exception, mammals with plentifully available hydrocarbons in their diet are most apt to show its deposit in the organ under discussion. Among the birds the gallinaceous varieties stand far ahead of all others, the passerines following next. Galli show the condition in association with acute infections, chronic diseases and in health. Unless there be distinct reason for it at autopsy, it may almost always be said to be normal. Passeres, especially the smaller forms, frequently come to autopsy with such excessively large livers, and indeed with a very large pad of abdominal fat, and nothing else, that one is compelled to look upon this overburdened organ as incapacitated by the deposit. These two orders increase the percentage value for the birds. Striges, Anseres, and Accipitres also show a good number of cases but there is among the Aves no such clear relationship between food fat and fat infiltration as may be found in the Mammalia.

AMYLOID DEPOSITS.

Amyloid deposit is reported with reasonable frequency in domesticated animals, causing in them a fairly definite entity, being as usual related to the effects of long continued or repeated infectious disease. Wild animals suffer from this condition but rarely and therefore to our few cases will be given a short discussion separately. An Indian Paradoxure (_Paradoxurus niger_) had patches of amyloid irregularly distributed through the organ. The animal had a carcinoma of the head of the pancreas, an obstructive biliary cirrhosis in a state of atrophy and a chronic nephritis with arteriosclerosis. There was nothing peculiar about the distribution of the deposit as there was in the next case, a Badger (_Meles meles_) where amyloid was found around the interlobular vessels and extending in the lobules along their canaliculi. This latter case seemed without cause and we have considered it a primary amyloidosis, the spleen, heart muscle, kidneys, intestines and other structures being affected. (See Fig. 7.) A third mammalian case concerned a Dasyure (_Dasyurus viverrinus_) which showed distinct intralobular collections. Its cause was a chronic suppurative process in the jaw bone.

Avian livers are somewhat more prone to show amyloid deposits, eight cases being on record. Four occurred in the Passeres, one each in Columbæ and Impennes and two in Anseres. Three were associated with chronic infectious disease and two with well established nematode parasitism. The remaining three, classed as primary, were not related to any other lesions, in two the amyloid liver being the only finding.

The next abnormal deposition related to the physiology of the organ is blood pigmentation. Normally hemic pigment is dispensed with very rapidly but under unnatural conditions it accumulates. In only one order is there any noteworthy percentage of hemosiderosis, the carnivores, the remainder showing a very trifling incidence.

DEGENERATIONS.

Going further into the physicochemical alterations of the liver brings us to consideration of those changes known as degenerations— parenchymatous, fatty, hydropic, hyaline, all of which we shall group under one heading. They occur in a great variety of conditions and do not appear to be specific, nor as the records are analyzed do they appear to occur preëminently in any one disease of the lower animals. The percentages are however higher for orders and families whose diet contains relatively more protein, carnivores, the higher marsupials, accipitrine, and wading birds.

ACUTE ATROPHY.

A very important degenerative disease of the liver is acute yellow atrophy or, better expressed, acute degenerative atrophy for it is a total destruction of the whole or large parts of the parenchyma. It is apparently toxic in origin being related to the toxemias of pregnancy, to certain organic and inorganic soluble poisons; some cases arise without discoverable cause. We have seen no cases in the mammal but two in birds. Both were females, one in active ovulation, while the other had no related pathology and the condition of the ovaries could not be determined since they had been destroyed after death by rats. The macroscopic and minute anatomy offers nothing new. Jaundice was present but not intense.

HEPATITIS.

True inflammatory lesions are to be defined as some form of parenchymatous change to which are added congestion, infiltration of round or polynuclear cells, stagnation in the bile ducts or perhaps actual degeneration of their lining cells. It seems necessary to stipulate these things because in the chronic forms, usually called cirrhosis, it is necessary to have all of them, plus efforts at regeneration, in order to determine it as a chronic progressive process. Acute hepatitis is a rare condition in mammals except when it is combined with septicemia or severe enteritis. In birds on the other hand the liver is, aside from the intestinal wall, perhaps the most frequent seat of pathology in the abdomen. This is because of its almost constant involvement in infective enteritis, and in such conditions as fowl cholera, fowl typhoid, coccidiosis and cecal amœbiasis, all of which we have sporadically. When one searches for special distribution among the orders, only one of them stands out as having a high percentage, the Galli, an order which seems to have a very vulnerable liver.

The macroscopic anatomy of hepatitis in birds is peculiar in showing a definite swelling with spots of gray or yellow color, sometimes coalescing to form irregular areas. These are much more definite than in the mammalian organ where swelling and hemorrhage are the commoner findings. These pale spots are of two origins. They may be focal necroses of the hepatic cells, with or without circumferential congestion or hemorrhage to make them stand out. In amœbic, coccidial and typhoid livers such is the type of change. In septicemia and cholera, the mottlings are made up of increased interstitial mononuclear areas, with blood cells and shadow cells numerously present. I have seen what was in all probability a stage of repair after both these kinds of change. In the former, regeneration seemed to take place from adjoining liver cells, there being in the section no evidence of increased bile ducts to make new hepatic cells. It seemed also that phagocytes were derived from blood cells and not from Kupffer’s cells. In the infiltrative lesion disappearance of the liver cells from the groups leaving compressed and deeply granular remnants was all that could be determined. Regeneration seemed to be progressing in the manner just outlined.

NECROSES.

The degenerative and infiltrative areas of acute hepatitis are simulated by focal necroses in livers not the seat of a general hepatitis from which they can be differentiated only by the microscope. These small areas of local tissue death are quite common in all pathological processes but are most common in the liver, possibly because of its exposure to toxins from the intestine. Their exact origin is not determined, various explanations being given. The somewhat distinct distribution in mammals _versus_ that in birds may help in the final decision. In the former, focal necroses are more often encountered midway in the anatomic lobule and around the central vein whereas a perivascular location seems the usual position in the bird.

Massive necroses of the liver may be of considerable importance in veterinary medicine. They take their origin in several different ways. The commonest in our records are those due to cecal coccidiosis and amœbiasis (quail disease and blackhead) while from the primary seat of these two infectious diseases, the cecum, may originate the virus of nonspecific hepatic necroses. We have observed several birds, passerine, psittacine and gallinaceous, which at autopsy showed a distention of the cloaca, ceca, and lower small intestine with urates and slime but no mural inflammation and a large area of necrosis in the liver. This suggests perhaps a “white diarrhœa” but it did not occur in epizoötics and other morbid anatomy of this specific disease was absent. These frequent instances of association between the colonic area and the liver seem to suggest the transfer of necrotizing organisms, just as amœbæ travel, and to indicate measures to clean out the tract when birds become “plastered.” Massive necroses also arise from mould disease, and from infection with the necrosis bacillus, emanating from nearby infectious foci, or _via_ the normal passageways from the intestine. Massive areas of degeneration may form by the coalescing of numerous foci, in any septicemic disease.

ABSCESS.

In man, amœbæ, flukes, cestodes and biliary tract infection are the commonest causes of purulent collections within the liver. In the lower mammals parasites play practically a solitary rôle at least as the major influence in localizing the collection, bacteria from the intestine doing the rest. We have one case of massive abscess in a porcupine suffering with septic pneumonia, the suppuration in the liver being due to the colon bacillus, the general septicemia probably being from distemper. Monkeys have shown more abscesses than any other order, three being observed. One was due to infestation with trichocephalus which had apparently penetrated from the colonic wall into the liver through adhesions formed between these two structures. Another seems certainly amœbic but these protozoa could not be found, while the third followed an ulcerative enterocolitis of unknown cause. Two cats were seen with parasitic abscesses; one harbored _Distoma_ or _Clonorchis sinensis_, the other a nematode of ascaris type.

The topographic distribution of these six hepatic abscesses was interesting. The position of the abscess is not mentioned in one case but of the remaining five three were entirely in the right lobe, one had the major lesion on the right side and smaller separate abscesses spread over the organ, and one with about equal distribution in all lobes. All three confined to the right side were solitary.

Abscesses of considerable size are not met with in the bird as in the mammal perhaps because the former does not form real pus, necroses developing instead.

Congestion of the liver is a matter of small importance from the standpoint of pathology unless it be of sufficient duration to cause cyanotic atrophy and induration. However the facts that congestion of this organ occurs three times as often in the mammal as in the bird and that vascular cirrhosis has not been seen in the latter class, are interesting and noteworthy. In addition ascites of hepatic origin has not been seen in the birds. The explanation for this lies in the rich anastomosis between the intestinal area and the caudal vena cava so that the blood does not have to pass through the liver to reach the heart. This arrangement would reduce the back pressure in passive congestion and relieve the liver in the congestion due to toxic or inflammatory distention of small vessels.

CIRRHOSIS.

The chronic inflammations or so-called cirrhoses of the liver have been subjected to a great deal of study and many theories have been expounded as to their cause and classification. Here is not the place to discuss the academic question of nomenclature but rather to adopt an acceptable working classification and to analyze our material thereon. A cirrhosis is a chronic inflammation of the liver indicated by increased connective tissue with evidences of degeneration and attempts at regeneration on the part of the hepatic cells. Certain cases of increased connective framework fail to show the last two features and, since they must be grouped near the cirrhoses because of the prominence of connective tissue, they are called _fibroses_, _perilobular in type_. Among the instances carrying out the full stipulations are livers with evidence of a perivascular fibrosis and obstruction, to which are added degeneration and regeneration of the lobular margins; such are PORTAL CIRRHOSES in human medicine associated with passive congestion in the intestinal area, and ascites. In a second variety, fibrosis seems to succeed upon obstruction to the biliary lumina or upon peribiliary inflammation, BILIARY CIRRHOSES. The effects of this are to dam back bile with the production of varying degrees of jaundice and for the inflammation to spread into the lobules, thus distorting their internal architecture; this form is therefore unlike portal cirrhosis which alters the size and shape of lobules as a whole. Fatty change is very prominent in certain cases and it has been a custom, perhaps without warrant, to put such livers into a separate group. It may be that they represent a different chemical process. When there exists for a long time a venous stasis in the liver, necrosis is apt to occur in the cells subjected to pressure and the absence of fresh blood. This gives rise to a “nutmeg” liver upon which may succeed a definite perivenous fibrosis.

This then is a working classification of the hepatic cirrhoses. Perhaps many slightly differing varieties might be constructed but this grouping will permit comparison and contrast with human cases, and with instances in the various orders. Because of the relatively small total, thirty- two, it is perhaps unwise to attempt any conclusions as to distribution but it is certainly noteworthy that twenty-six occurred in mammals. This means 1.6 per cent. in mammalian autopsies against .2 per cent. in avian. Among the former class the carnivores stand at the head of the list, followed in order by the marsupials, ungulates, primates, and rodents.

Carnivora have shown a few typical portal cirrhoses from a pathological standpoint but only one, in a badger (_Taxidea taxus_), was combined with the classical picture of intestinal hyperemia and ascites. Two of the cases were combined with chronic enteritis which may, of course, have been secondary but there was also a hyperplasia of the spleen which bespoke some grade of infection. None of the four showed involvement of the biliary tract. One animal, a skunk (_Mephitis mesomelas_), was jaundiced; it had anemia, nephritis and enlarged spleen but no intestinal inflammation; perhaps the associated anemia may have been responsible for the pigmentation. Biliary cirrhosis occurred in two Carnivora, in both associated with enlarged spleen and nephritis. One showed jaundice and the other, with a huge liver from congestion and interstitial infiltration, had a small ascites. Fatty cirrhosis was diagnosed in a raccoon but this is viewed with some reservation because this animal easily stores fat and in this case it may not have been a part of the process. In none of the foregoing cases did parasitism enter into the causation of the change and I shall always specify when such a factor was probable. The only vascular cirrhosis in our records occurred in a Gray Wolf incident to a longstanding myocarditis (Gray Wolf, _Canis lupus mexicanus_, Myocarditis, Adenomatoid goitre, Chronic gastroenteritis, Vascular cirrhosis of liver, Subacute diffuse nephritis, Edema of lungs, pericardium, and peritoneum). Two examples of perilobular fibrosis appeared in this order, a raccoon (_Procyon lotor_) and a paradoxure (_Trichosurus vulpecular vulpecular_). The only noteworthy feature was, in the former, a very marked biliary stasis on the lobular margins and in the connective tissue; this animal was not jaundiced.

Ungulata are normally well supplied with definite interlobular strands which, in a few varieties, completely encircle the lobule but always show as clear fibrous septa going out from the portal areas. This richness of connective tissue renders more difficult a decision of increase so that unequivocal degenerations and regenerations with inflammatory changes have been demanded as criteria for cirrhosis. It has been recognized that cattle get a definite increase in their interstitial tissue without serious reaction in the parenchyma. With the knowledge of these facts in mind it has been possible to detect two distinct portal cirrhoses, two biliary cirrhoses and three perilobular fibroses. It is however evident by examining the rest of the autopsy notes that the chronic inflammations have had with one exception, little influence on the animal’s life and death and the associated pathology is not instructive in etiology. One old deer with the definite portal type had ascites and intestinal hyperemia which hastened his end.

The type of cirrhosis in the marsupial is progressively inflammatory and of the biliary variety. In two of the three cases there was active infection somewhere in the body, one a long continued streptothricosis, the other and more important a choledochitis with involvement of the pancreatic head. The third case showed a nephritis and a pericholedochitis and pericholecystitis. In all three there was definite evidence of biliary obstruction within the liver and in the occurrence of general jaundice.

Monkeys have presented one portal, two biliary, and one perilobular cirrhoses. The London Garden reports a cirrhosis with gall stones in a Chimpanzee. The case of the Barbary Ape is so good that it is quoted in brief.

Barbary Ape ♀ (_Macacus innuus_). Found dead. Never known to be sick. On exhibition nine years. Acute dilatation of stomach. Acute gastritis. Portal cirrhosis of liver. Acute parenchymatous nephritis. Chronic passive congestion of lungs. Chronic splenitis and perisplenitis. Ascites. Mild passive congestion of abdominal circulation. On opening the abdomen a dilated stomach occupies most of the anterior part, displacing the intestines downward and backward. The upper lobes of both lungs are uniformly deep red, soft, collapsed, subcrepitant. Subclavian vessels—veins distended with red clot, arteries with small amount of chicken fat clot. The heart is dilated on the right side, filled with currant jelly clot. The liver is small, surface hobnailed, edges rough, consistency tough, color brown. Section surface glistening, moist, granular and opaque, mottled by irregular brown areas separated by paler brown intercommunicating bands. Gall-bladder is small, contains viscid yellow bile and duct is patulous. Areolar tissue about the bile ducts is thick and opaque, the duct wall itself is thick and yellow. Gall-bladder tightly attached to capsule of liver. Spleen is slightly enlarged, soft and tough. Capsule is smooth, opaque and thickened on gastric surface. The trabeculæ are prominent, pulp mottled gray-red, few recent hemorrhages. Capsule of the kidneys is smooth, strips easily leaving a smooth brown surface with dilated vessels. Organ is soft. Section surface is glistening, striæ wide and indistinct, glomeruli faintly visible. Microscopic section of liver shows high grade of fibrosis almost entirely confined to portal areas with a marked increase in bile ducts although no place is found where these bile ducts are running into lobules suggesting attempt at regeneration. Liver cells show high grade of fatty degeneration in some places, whole lobules being necrotic. There is no pigmentation and connective tissue is fairly rich in cells. Fibrosis quite well advanced. Cells about equally fibroblasts, round cells and polynuclears. Bile ducts very well preserved and cellular infiltrate rather less directly around them than at other parts of connective tissue. The section of kidney shows moderate congestion, granular and vacuolar degeneration of epithelium generally distributed except in proximal tubules where there is swelling and desquamation. Detritus present in tubules and capsular spaces. Tufts swollen.

The biliary forms of Primates were associated in one case with an undetermined parasite in the bile channels, in the other with tuberculosis and chronic enteritis. In all the cases the relative inconspicuousness of bile in ducts or in cells is worthy of mention. The perilobular fibrosis in a small cebus was trifling in extent but was associated with considerable round cell infiltration in isolated areas; there was also nephritis, splenitis, and enteritis.

The only representative of the rodents is a capybara (_Hydrochœrus hydrochœrus_), their largest variety. This case was originally described as a typical Lænnec or Pictou cirrhosis but I now class it as a portal form. The distinct insular arrangement of the lobules, the failure of involvement of the bile channels and the ascites are reasons for the present decision. The animal suffered also from tuberculosis (not in liver) and myocarditis.

The Indian Elephant, “Bolivar” (_Elephas indicus_), an old specimen, is the only member of his order to show cirrhosis. It may be considered as a senile process in part but the extreme distortion and compression of the lobules press the conclusion that it was a progressive inflammation.

[Illustration:

FIG. 18.—PORTAL CIRRHOSIS OF LIVER IN ATROPHIC STAGE. BARBARY APE (MACACUS INNUUS). THE DILATATION OF THE STOMACH ALSO SHOWS IN PHOTOGRAPH. ]

[Illustration:

FIG. 19.—ATROPHIC PORTAL CIRRHOSIS OF LIVER. INDIAN ELEPHANT (ELEPHAS INDICUS). ]

Aves fail to show lesions which could be called portal cirrhosis, five of their six cases being biliary and one fatty with signs of continued infection. The macroscopic anatomy of the avian liver with chronic fibrosing hepatitis is fairly uniform and suggestive. In the first place it is grossly nodular, lumpy, not finely granular or “hobnailed.” The sensation to the finger is resilient rather than tough. The color is variable but green and dull purple are the usual shades. On section no peculiarities present themselves unless it be that one can find pale spots on a dark background, which may correspond to the mammalian connective tissue strands. Microscopically the increase of cellular groups at portal spaces and the extensive growth of connective tissue between the liver columns are the noteworthy features. There is nothing in mammalian cirrhoses to compare with the intralobular growth of fibres in birds. There is of course no regularity so that the degree of replacement or necrosis of parenchyma is hard to estimate. Bile ducts do not proliferate but seem, once obstructed and surrounded, to succumb to the inflammation. The six cases in birds are: Psittaci, 3, Galli, Anseres, Struthiones each one. The cases in the last two orders were associated with parasites, to which bacteria or toxin may have been added. It is interesting to note that the two frankly progressive obstructive biliary cases in the parrots showed general jaundice.

It was formerly customary in many quarters to speak of atrophic and hypertrophic cirrhosis. Now it is generally thought that any form will be large or small as growth and regeneration on the one hand, or contraction, atrophy and degeneration on the other, may be predominant at the time the organ is seen. It is perhaps misleading to judge by our notes of what happens, but it is curious that in the thirty-two cases, the pathologist could state only in seventeen instances that the liver was larger or smaller than normal. This means therefore that the liver of cirrhosis need not deviate greatly from its customary size. Nine of the seventeen times the organ was considered smaller than normal, eight times it was greater. These variations did not strictly correspond to type, but the portal form, frequently called atrophic, was more often small than was the biliary form.

Gastrointestinal disease accompanied cirrhosis in fourteen instances. Nephritis was present nineteen times. The spleen was enlarged six times, in all of which definite evidence of infection existed in the body. Choledochitis existed four times, twice with biliary cirrhosis, twice with perilobular fibrosis; cholecystitis existed twice, once in a monkey, and once in a bird with parasites. Pancreatitis was seen in three biliary cirrhoses and once in a perilobular fibrosis.

The relation of the existence of cirrhosis to the presence of a gall- bladder is interesting. Among the thirty-two animals twenty-one have gall-bladders, eleven have not. The exact number of animals in our whole list with and without this structure, unfortunately cannot be given with exactness. As nearly as I can figure it out, sixteen per cent. of our animal posts have been on varieties without a gall-bladder, eighty-four per cent. with it. This would make the absence of this reservoir a factor favoring the development of cirrhosis since one-third of the cirrhoses are in groups devoid of this bag, yet these same groups supplied only one-sixth of the total postmortems.

GALL STONES.

Our experience with concrements in the biliary system is limited to six cases which can be detailed in brief.

American Beaver ♀ (_Castor canadensis_) showed a soft purplish liver with groups of tortuous yellow lines; these prove to be groups of hepaticola with fatty degeneration around them, but successful regeneration is going on; bile ducts are not seriously involved over any great part of the organ; the bladder is distended greatly with thin, yellow-green fluid; duct is not patulous; common duct narrowed at middle and above this constriction lies a small concrement; bladder contains two large and several small pale yellow-green friable stones; mucosa injected and covered with mucopus; the pancreas is not affected.

American Beaver ♂ (_Castor canadensis_) shows a slight bile obstruction and pigmentation through the liver but no pus or cirrhosis; bladder is collapsed containing only a little limpid brown fluid; wall is slightly roughened but not opaque; there is a blue- black stone 1.5 × 1 cm. free in the cavity; duct patulous; pancreas and intestine not affected.

Brant Goose ♂ (_Branta bernicla glaucogastra_) liver shows slight fatty change; bladder much distended, contains twenty-six small, quite hard, greenish stones; one is impacted in the cystic duct which is not patulous.

Pigtailed Macaque ♂ (_Macacus nemestrinus_) shows a normal liver; bladder contains a small black concrement, very hard, no cystitis.

Polar Bear ♀ (_Ursus maritimus_) showed a chronic cholecystitis and cholangitis, the stone (?) in this case consisting of a solitary, black, friable mass, six mm. in diameter.

Mongoose Lemur ♂ (_Lemur mongoz_) showed a normal liver; bladder of about normal size but the duct can be forced only by considerable pressure; there is a small stone and a granule in the tortuous cystic duct; no cholecystitis.

The specimens that are preserved show these to be chiefly inspissated bile, those from the first beaver and the goose being the only ones to rise to the dignity of gall stones; it would seem that there was plenty of opportunity for calculi to form in the bladder of this beaver. In no case is there a cholangitis or cirrhosis dependent upon cholelithiasis.

While stones have been shown as infrequent there is a condition of the bile which may be quite important. In Passeres, Accipitres, and Striges one frequently sees a very dense inspissation of the bile both in the cystic area and in the lesser independent bile duct. This need not be, indeed usually is not, associated with hepatitis or cholecystitis. There is no one thing more common than another in relation with it but the diagnoses most often made are enteritis, distention of the proventricle and gizzard, and constipation.

INFLAMMATION OF THE BILIARY SYSTEM.

The biliary tract from its origin in fine intrahepatic radicles to the bladder and to the end of the common or intestinal ducts is the seat of many inflammations both acute and chronic, but since they are supposed to lead to damage to the liver and pancreas and to the production of gall stones, it is well to consider the system as a whole. As a matter of fact separate analyses of cholangitis, choledochitis and cholecystitis do not reveal different figures for each or for different orders. The vulnerability of this tract is found to be directly as the percentage of cirrhosis, to wit, the carnivores stand first, then the marsupials, ungulates, Primates and rodents; among the birds the order is Accipitres, Anseres, Struthiones, Psittaci, and Galli. It is difficult in most instances to evaluate the various possible etiological factors, but, due caution being exercised, gastrointestinal inflammation could be held responsible in seventeen of the total of fifty cases. In twelve of the seventeen this process was wholly or largely in the duodenum. The next factor was general infection, at the head of which pneumonia and “distemper” occupied about equal places. In marsupials, the streptococcal and streptothrical infections to which these animals are susceptible, was the prime factor. This group almost always has definite signs of stasis both in the liver and, as indicated by jaundice, in the general tissues. Pancreatitis was present in seven of the fifty cases and in five of the seven, enteritis was also found. Common duct stones were not observed. I shall have something to say about pericholangitis and pericystitis under the head of pancreatitis.

TUMORS.

The liver presents a good share of the tumors appearing in solid viscera but, with the exception of a few points, they offer little of interest. In the first place three angiomata have been seen and while they may not be tumors in the accepted sense of the word, may be considered briefly. A single cavernous angioma was seen in a goose. It occupied a large part of the right lobe but did not seem to affect mechanically the function of the organ since conditions wholly foreign to the liver were the cause of death. A leopard presented several small groups of telangiectatic angiomata lying mostly at portal spaces, a few also under the capsule. The liver of a thrush was likewise scatteringly beset with small angiomata. The original notes and recent examination do not reveal parasites or perivascular sarcomatous change.

Simple adenomata were observed in a woodchuck (_Arctomys monax_). This diagnosis is made with the appreciation that nodular regeneration of the liver after damage and in cirrhosis sometimes suggests tumor, but with adenomata an increase of supporting framework may occur. The liver of this animal presented numerous .3 to 10. cm. irregularly spherical, encapsulated, firm or slightly resilient, brown masses which under the microscope consisted of large pale vacuolated cells in columns or strands not connected with bile ducts. The last feature speaks in favor of the diagnosis of adenoma. The damage to the organ was probably considerable and the portal circulation must have been impeded since passive congestion and ascites were present. Enteritis and nephritis seemed the causes of death.

Adenomata or fibroadenomata of bile duct origin were seen in four animals, a Red Fox (_Canis vulpes pennsylvanicus_), a Gray Fox (_Canis cinereo argenteus_), a Jaguar (_Felis onca_) and a Common Deer (_Mazama virginiana_). The first two present similar pictures, pinpoint to 8. mm., gray, well outlined areas some of which are clearly cystic, others opaque and more solid. In the first fox a larger mass was found near the hilum. Careful study and consultation has failed to discover parasites in these cases, although their presence was strongly suspected, so that we were forced to conclude, in view of the rather typical microscopic picture, that they are adenomata of bile duct origin. Their scattered distribution, but with a tendency to be more numerous beneath the capsule, corresponds with a human case just brought to my notice. The mass in the liver of the deer was single and resembled an infarct, with cysts exposed by cross section. This tumor was found on the diaphragmatic surface of the right lobe.

Tumors of an atypical, therefore malignant, epithelial variety were found four times, in an Alpaca (_Lama pacos_) and three parrakeets; these birds are very prone to have all kinds of tumors. The records of the first animal could not be as satisfactory as might be desired because of an advanced state of decomposition but there was a carcinoma- like growth of the gall-bladder area and a large hard alveolated tumor occupying one-half of the liver. The colon had been involved by the former, with perforation. Two of the parrakeets showed a simple carcinoma with well developed fibrous tissue bands running in all directions through the large mass. The whole growth was comparable to the usual picture of these massive tumors when they are primary in the liver. All these three cancers seem to take their origin in the liver cells but the third had such an interesting involvement of the connective tissue that its minute anatomy will be given; it was denominated adenocarcinoma sarcomatodes.

Undulated Grass Parrakeet ♂ (_Melopsittacus undulatus_). Section of liver shows organic capsule normal. Nothing remains of the original structure by which it might be recognized, suggestion in places of granular cells resembling liver cells being only occasional occurrences and in small numbers. Where liver cells do occur they are highly granular in various degrees of atrophy and show various grades of nuclear retrogression. Greatest part of section consists of dense, white fibrous tissue in which lymphocytes are rather diffusely placed together with large numbers of epithelium-lined spaces. These spaces are often elongated after manner of imperfect ducts but are of irregular form, have single layer of low cuboidal epithelium and richly staining nuclei. Upon search certain acini are found to have especially hyperchromatic nuclei and penetration of basement membrane. In such localities collections of epithelial cells are to be seen in plug form in lymphatics and acini of imperfect development of lumen are found. In addition to these epithelial lesions connective tissue ones are seen, occurring generally in restricted localities. The interstitial framework is seen to consist of closely placed spindle cells, some of which are especially elongated after manner of imperfect ducts but are of irregular form, directed in a definite, purposeful manner, but interlace in the whorling manner noted in fibromas. Nuclei are, however, entirely too chromatic for a connective tissue tumor. Whenever a vessel occurs in these regions its lining endothelium is always swollen and nuclei in its wall will be proliferated and of embryonic type. This latter condition is apt to occur in patchy manner, part of wall appearing normal and other parts containing these peripherated elongated nuclei.

Secondary tumors were observed in the liver seven times as follows: Red Kangaroo (_Macropus rufus_) from malignant papilloma of the stomach; Spotted tailed Dasyure (_Dasyurus maculatus_) from cancer in the small intestine; Dorcas Goat (_Capra hircus_) from sarcoma in lymph nodes in mediastinum; Raccoon-like Dog (_Canis procyonoides_) from mixed tumor of thyroid; Undulated Grass Parrakeet (_Melopsittacus undulatus_) from a brain tumor probably glioma; another of same species from a sarcoma of pectoral muscle; European Robin (_Erithacus rubeculus_) adenoma of adrenal (_hypernephroma_).

SECTION VII THE ALIMENTARY TRACT,