Acute Yellow Atrophy

DEFINITION.—By the term acute yellow atrophy is meant an acute affection of the liver, characterized by rapid wasting or degeneration of the organ, accompanied by the systemic symptoms belonging to an acute acholia or cholæmia. It is an acute, diffused inflammation, with atrophy of the proper gland-elements. It has been called icterus gravis, malignant icterus, hemorrhagic icterus, malignant jaundice, etc.

HISTORY.—Cases having a more or less exact resemblance to acute yellow atrophy have been occasionally reported from the earliest period. Amongst English physicians, Bright was one of the first to give an accurate account of the clinical history of some well-defined cases. Rokitansky was really the first to define the disease from the pathological standpoint, and it was he who designated it acute yellow atrophy, this term being intended to signify the nature of the objective changes. The first treatise ever published on the disease as a distinct morbid entity was the monograph of Horaezek, which appeared in 1843. Amongst the French, Ozonam in 1847 was the first to recognize and describe the disease as a distinct affection, although Andral had several years before mentioned an affection of the liver which corresponded in some of its features to this affection. In 1862, Wagner asserted that many of the cases of acute yellow atrophy were only examples of acute phosphorus-poisoning, and that no real distinction exists between the two affections. This statement has been warmly disputed by various German observers, but there is no doubt a close resemblance between the two affections.

Guy's Hospital Reports, 1836, vol. i. p. 621.

Handbook of Pathological Anatomy, Am. ed.

Quoted by Legg, On the Bile, Jaundice, and Bilious Diseases, loc. cit.

Clinique médicale, 1839, tome ii. p. 363.

Archiv der Heilkunde, 1862, p. 364.

CAUSES.—There can be no doubt that acute yellow atrophy is a very rare disease, since so few examples are found post-mortem. In the course of a very large experience in autopsical examinations I have met with but one characteristic example. According to Legg, it is "one of the rarest diseases known to man."

General Field Hospital, December, 1863.

Several theories have been proposed to explain the occurrence of this affection, but without success. It has been ascribed to an excess in the production of bile, to stasis in the bile, and to a sudden saturation of the hepatic cells with biliary matters contained in the portal vein. That these supposed causes are really influential in producing the malady can hardly be entertained. That there is a peculiar poison which has a causative relation to the disease is rendered probable by the fact that a condition closely allied to this disease is produced by phosphorus, antimony, arsenic, and other poisons. Is it not a ptomaine generated under unknown conditions in the intestine? Especially does the morbid anatomy of phosphorus-poisoning nearly agree in all its details with icterus gravis—so nearly that by many German authorities they are held to be identical.

Age has a certain influence in the causation of this disease. It is rarely seen in early life, Lebert in a collection of 63 cases having found only 2 before ten years of age, yet there has been a well-marked case at three, and Hilton Fagge reports one at two and a half years of age. Nevertheless, much the largest number occur between fifteen and twenty-five years of age, and the maximum age may be fixed at sixty.

The influence of sex in the pathogeny is most remarkable. It is true in Lebert's collection of 72 cases there were 44 men and 28 women, but it is now known that he did not properly discriminate in his selection of supposed examples of the disease. The statistics of all other observers are opposed to those of Lebert. Thus, in Frerichs' collection of 31 cases, carefully sifted to eliminate error, there were 22 women and 9 men. Legg has also collected 100 cases of acute yellow atrophy, and of these 69 were women or girls. The most active period of life—from twenty to thirty years of age—is the usual period for the appearance of this disease. More than one-half of Lebert's cases occurred between fifteen and twenty-five; and of Frerichs', two-thirds happened between twenty and thirty years of age. In Legg's collection of 100 cases, 76 were between fifteen and thirty-five years of age. What is the condition of women at this period in life which renders them so susceptible to this malady? There can be no doubt that pregnancy is the great factor. Of 69 cases especially interrogated on this point, examined into by Legg, in 25 pregnancy was ascertained to exist. In Frerichs' collection one-half were women in the condition of pregnancy. The period of pregnancy at which the disease appears varies from the fourth to the ninth month, the greatest number occurring at the sixth month. So long ago as 1848, Virchow drew attention to the remarkable changes in the liver due to pregnancy. Sinety has studied the effect of lactation on the liver, and has ascertained the existence of fatty degeneration. There is a form of jaundice which accompanies menstruation, as shown by Senator, Hirschberg, and others. These facts indicate a certain relationship between the sexual system of the female and the liver, but they do not indicate the nature of the connection, if any exist, between this condition and acute yellow atrophy.

De l'État du Foie chez les Femelles en Lactation, Paris, 1873 (pamphlet).

Berliner klinische Wochenschrift, 1872, p. 615, "Ueber Menstruelle Gelbsucht."

The influence of depressing emotions has been supposed to be effective in producing this disease, but it is more than doubtful if such a relationship exists. Lebert, however, refers 13 of his cases to this cause, but Legg, who bases his statements on the study of 100 carefully-recorded cases, is sceptical regarding the effect of such influences. Syphilis has in some instances appeared to be the principal, if not the only, pathogenetic factor, and Legg compares the action of the virus of syphilis to the effect of phosphorus, mercury, etc.

On the Bile, Jaundice, and Bilious Diseases, loc. cit.

PATHOLOGICAL ANATOMY.—The anatomical changes occurring in this disease indicate the existence of a systemic condition: the lesions are not limited to the liver, but involve various other organs. The changes in the liver should be first described, since the name of the disease is derived from the alterations in this organ. As the name indicates, the lesions are atrophic, but not all examples show this. In some cases there is little change in the size of the organ; in others the wasting is extreme; certainly in all typical examples the liver is reduced in size. The variations in size observed are probably due to the stage at which the inspection is made: if early, the organ may not be reduced in size, may be even somewhat enlarged by the deposition of new material; if later, the atrophic changes will be more or less pronounced. When the atrophy has taken place, the size of the liver is reduced to one-half, even to one-third, of its original dimensions; it is then soft, almost like pulp, and cannot maintain its shape, but flattens out on the table. The capsule is much wrinkled and the color of the organ is yellowish, variegated by islets of reddish or brownish-red color, these spots being somewhat depressed below the general surface and having a firm texture. On section the boundaries of the lobules are either lost or have become very indistinct, the line of section being bloodless. The knife with which the sections are made becomes greasy. In some instances ecchymoses are discovered under the capsule, and rarely hemorrhagic extravasations in the substance of the liver. The bile-ducts are found intact, as a rule. The greatest change in the size of the liver is observed in the left lobe. The duration of the disease, as has been indicated above, has a marked influence over the size and condition of the liver. The atrophic shrinking of the liver occurs more decidedly after the ninth day. In general, the tissue of the liver is soft and pulpy in consistence. On microscopic examination the most important alterations are seen to have occurred in the hepatic cells; ultimately, these cells disappear, being replaced by fatty and connective-tissue detritus; but before this stage is reached important alterations have taken place in the form and structure of these bodies: the cells become granular and fatty, and lose their sharpness and regularity of contour, especially at the periphery of the lobule, but ultimately all the cells within the lobule undergo atrophic degeneration. In this atrophic degeneration of the hepatic cells, in their fatty degeneration, and ultimately entire disappearance, consist the real proofs of the disease. The red islets of tissue already alluded to consist of the fatty detritus mixed with crystals of hæmatoidin.

More or less increase of the connective tissue is noted in many of the cases—increase of connective tissue with numerous young cells formed around the vessels and the bile-ducts (Waldeyer). The changes in the liver would surely be incomplete without some references to the minute organisms which play so important a part in modern pathology. Waldeyer was the first to demonstrate the presence of bacteria in the pigment-remains of the hepatic cells. Other observers have been unable to detect them, so that at present the parasitic origin of this affection remains sub judice.

Arch. für path. Anat., 1868, p. 536, Band xliii.

Important changes also take place in the spleen, but the opinions on this point are somewhat contradictory. Frerichs found the spleen enlarged in most of his cases; Liebermeister, on the other hand, and Legg, find that the spleen is enlarged in about one-third of the cases. When the atrophic changes occur in the liver, more or less swelling of the splenic veins must occur in consequence of portal obstruction. The peritoneum, especially the omental part, is the seat of multiple ecchymoses, and the endothelium is fatty. The mesenteric glands are usually swollen. More or less blackish or brownish fluid, consisting of altered blood, is usually found in the stomach, and the same, assuming a tar-like consistence, in the large intestine. Ecchymoses of rather small size are distributed over the stomach and intestines. The epithelium of the stomach-glands is found granular and disintegrating, and a catarrhal state of the gastro-intestinal mucous membrane exists throughout. The secretions are never normal, and the stools are wanting in bile or present a tarry appearance, due to the presence of blood.

On the Bile, Jaundice, and Bilious Diseases, supra.

Important changes take place in the kidneys. They consist essentially in a granular and fatty degeneration of the tubular epithelium, whence the altered appearance of the cortex. Multitudes of bacteria crowd the pyramids. Ecchymoses also are found in the mucous membrane of the pelvis of the kidney, in the bladder, and indeed all along the genito-urinary tract.

The muscular tissue of the heart is in a state of acute fatty degeneration, beginning with a granular change which may at the outset be of very limited extent and involve but few fibres. The endo- and pericardium are studded with ecchymoses or marked by hemorrhagic extravasations, and the pleura presents similar appearances, but not to the same extent.

The brain does not always show evidences of change, but in many instances there are ecchymoses of the meninges; the walls of the vessels are affected by fatty degeneration.

The tissues of the body are more or less deeply stained with bile. The pathological change on which the jaundice depends has been variously stated, but the most probable explanation is that which refers it to mechanical obstruction of the bile-ducts, either by catarrhal swelling or fatty degeneration of the epithelium. Notwithstanding the prominence of the hepatic symptoms, acute atrophy of the liver is probably only one element in a constitutional morbid complexus.

SYMPTOMS.—Acute yellow atrophy begins in two modes—the grave symptoms preceded by mild prodromes, or the most serious symptoms appear at the onset. The former mode is the more common. The usual prodromes are referable to the gastro-intestinal canal, and consist of loss of appetite, nausea, vomiting, a bitter taste in the mouth, headache, and general malaise. Indeed, the opening attack may be much like an ordinary bilious seizure or acute gastro-duodenal catarrh or a sick headache. In some cases the initial symptoms—nausea and diarrhoea—appear to be induced by an indigestible article of food. Jaundice never fails to be present at some period, but is usually one of the prodromic symptoms. It has no special characteristics by which the gravity of the approaching seizure may be measured. It is usually rather deep, and all parts are deeply stained, but the coloration may be limited to the body and upper extremities. No change in pulse or temperature, except the usual depression of both functions, is to be observed; the urine is deeply stained with pigment, and the feces are grayish, colorless, or parti-colored.

The period of time elapsing before the serious symptoms come on is not constant; from one week to several months have been the variations observed. In a minority of the cases no prodromes have occurred, but the grave symptoms have declared themselves at once. From the appearance of the jaundice up to the onset of severe symptoms the time has varied from two weeks to several months, but has rarely exceeded three months. During this time there may be nothing to indicate the gravity of the approaching symptoms; in fact, the case then, as at the onset, seems to be one of simple gastro-duodenal catarrh associated with catarrhal jaundice. The onset of serious symptoms is most usually announced by dilatation of the pupil. If, therefore, in a case of apparently simple catarrhal jaundice, especially in a pregnant female, there should occur without apparent reason a marked and persistent dilatation of the pupil, the possibility of the case being one of acute atrophy should be apprehended. This symptom is not, alone, of sufficient value to decide the character of the case, but then an obstinate insomnia comes on, violent headache is experienced, there is more or less confusion of mind, and jactitations or an extreme restlessness occurs. When such pronounced nervous symptoms appear the character of the attack is explained.

Various divisions have been proposed to mark the type of the symptoms: thus, the icteric period embraces the prodromal symptoms with jaundice; the toxæmic period is that stage characterized by profound nervous disturbances. Ozonam has divided the symptoms into those of the prodromal period and those of the serious stage, the latter being subdivided into the symptoms of excitation and those of collapse. There may be no prodromal period, however; without any preliminary symptoms the patient is suddenly seized with delirium and passes into a condition of coma and insensibility, or the first evidence of serious illness may be convulsions. It is probable, however, that in even the most sudden cases mild prodromal symptoms had occurred, but were overlooked. There is much variability in the symptoms of the toxæmic period. There are three symptoms: excitement with delirium, sometimes delirium ferox; coma, less or more profound; and convulsions. Legg has numerically expressed the relative frequency of these symptoms thus: Of 100 cases of unquestionable acute atrophy, 76 had become comatose, 59 were delirious, and 32 had suffered convulsions. According to the same authority, delirium and coma were associated together in about one-half of the cases, but in pregnant women coma often occurs alone (Legg). Usually, when convulsions happen there has been either coma or delirium. With these cerebral symptoms there are often present various disturbances of motility and sensibility, such as local convulsions, jactitations, hiccough, extreme restlessness, paralysis of the sphincters, and incontinence of urine and feces or retention, grinding of the teeth, exalted sensibility of the skin, or it may be complete anæsthesia, severe itching of the surface, etc.

On the Bile, Jaundice, and Bilious Diseases, loc. cit.

During the toxæmic period, and directly dependent on the retention of excrementitious matters in the blood, hemorrhages occur from the mucous surfaces, from wounds, and into the various serous membranes. A changed state of the blood being present in all cases of this disease, the proportion in which extravasations take place is high—in about 71.3 per cent. according to Liebermeister, and 80 per cent. according to Legg. The latter author regards these estimates as rather low. When hemorrhage occurs in the stomach in small amount, it presents itself as coffee-grounds or as black vomit, and in the intestine in the form of black, tarry stools or melæna. Hemorrhage may also occur from the surface of an ulcer, from a fresh wound, a leech-bite, etc.; but the most usual form of extravasation of blood after the gastro-intestinal is epistaxis or bleeding from the nose. Women who abort, as they are very apt to do when this disease comes on, may suffer from frightful hemorrhage, and deaths have been thus caused. Various opinions have been expressed as to the cause of the hemorrhagic condition—by some attributed to the changes in the composition of the blood; by others to the alterations of the vessel walls; both factors are doubtless concerned.

During the prodromic period the temperature of the body, as in the case of ordinary uncomplicated jaundice, is rather depressed below normal, sometimes as much as two degrees; but when the toxæmic stage comes on the body-heat rises to a variable extent, but usually over 100° F. In some cases no febrile movement can be detected; in others a very considerable elevation of temperature occurs, but very rarely attains to 105° or 106° F. The pulse becomes very rapid, in some instances rising to 140; but without any apparent cause it may fall suddenly to 70 or 80, and these fluctuations may take place several times a day. The rise of temperature and a very rapid pulse may come on in the final coma only; and immediately after death, as Legg points out, the body-heat may attain the maximum elevation.

As the toxæmic period develops the tongue becomes dry, glazed, fissured, sordes form on the teeth and lips, the breath becomes fetid, and the breathing may assume the Cheyne-Stokes type. The nausea and vomiting of the prodromal period persist, and the ominous coffee-grounds appear in the rejected matters, or grumous masses—clots acted on by the gastric juice—are brought up. Black, pitch-like, or tarry stools, the result of hemorrhage, are passed toward the end—involuntarily when liquid. When no blood is present the stools are grayish and without bile. Constipation may be the condition instead of diarrhoea in about one-third of the cases.

Various eruptions have been observed on the skin, such as petechiæ, roseola, eczema, etc., but their very variety, as their occasional appearance, indicates their accidental relationship to the disease.

The urine is much altered in character, but it is usually acid in reaction, although it has been observed neutral or alkaline. The specific gravity is at or nearly normal, and it has a deep-brownish or bilious hue due to the presence of bile-pigment. The most important change in the composition of the urine is the diminished quantity of urea or its entire disappearance; the phosphates, and especially the chlorides, are also usually diminished in amount; and albumen and leucin and tyrosin appear to a lesser or greater extent, together with hyaline, fatty, and granular casts.

Although the observations are somewhat contradictory, it seems pretty definitely established that the blood is more or less altered in composition, morphological and chemical. The red corpuscles are diminished in amount, and often deformed; the white corpuscles are increased; and excrementitious products—urea, leucin, tyrosin, and cholesterin—are found in greater or less quantity.

COURSE, DURATION, AND TERMINATION.—Although, as a rule, the course of acute atrophy is rapid, it is not invariably so. In some instances the prodromic symptoms have continued through several months, but, according to Thierfelder, one-half of the cases terminate in from three to five weeks, and in only 10 per cent. is the duration continued into eight weeks. The course of the disease is extremely rapid in pregnant females, rarely extending beyond the second week. An extended course of the disease is due to delay in the prodromic stage, the toxæmic period being always absolutely and relatively shorter. In the condition of pregnancy the danger is increased by the hemorrhages, and the early termination is due chiefly to this factor. When the duration of the disease is protracted and its evolution normal, the accumulation of hepatic excrementitious matters sets up cerebral disturbance, which becomes a pronounced feature of the case.

The termination cannot probably be otherwise than fatal. As in the course of the disease the hepatic cells undergo solution and disintegration, their restoration can hardly be regarded as possible, certainly not probable. Any curative result must, then, be wrought in the prodromic period, when the diagnosis must be viewed with some mistrust.

DIAGNOSIS.—George Harley maintains the singular doctrine that acute yellow atrophy is only the "sporadic form of the contagious jaundice of the tropics," or yellow fever. He bases his opinion on the identity of their symptoms, pathological anatomy, mortality, and contagious character; for he affirms that acute yellow atrophy may exhibit contagious power in temperate climates.

Diseases of the Liver, Amer. ed., 1882, p. 255.

As acute yellow atrophy comes on as an ordinary catarrhal jaundice, it is impossible to distinguish it from the latter affection during the prodromal period. When cerebral symptoms, black vomit, and tarry stools appear, the area of hepatic dulness very decidedly diminishes, and leucin and tyrosin replace urea in the urine, acute atrophy may be suspected.

Acute phosphorus-poisoning, as regards its symptomatology and morbid anatomy, does not differ from acute yellow atrophy, and many cases of the latter have been mistaken, it is supposed, for the former. To distinguish between them the history of the case must be carefully ascertained.

When, after the prodromal symptoms, which may not be accurately diagnosticated, there occurs a rapid decline in the area of hepatic dulness, hemorrhages take place from the mucous surfaces, stupor and delirium supervene, and urea disappears from the urine, being replaced by leucin and tyrosin, there can be no difficulty in coming to a conclusion: the case must be one of acute yellow atrophy.

TREATMENT.—It was formerly supposed that a case of acute yellow atrophy must necessarily prove fatal, but this opinion must now be modified, since examples of cure of supposed cases have been reported from Oppolzer's clinic, by Lebert, by Harley, and others. As at the onset the symptoms cannot be distinguished from a bilious attack or from catarrhal jaundice, the treatment must be appropriate to these states. When the serious symptoms begin, a large dose (scruple j) of quinine should be at once administered, and half the quantity at regular intervals to keep up the cinchonism. Phosphate of soda, with some arseniate and such mild hepatic stimulants as euonymin, iridin, etc., should be given to maintain a gentle aperient action. Experience has proved that active or drastic cathartics do harm rather than good; on the other hand, mild laxatives, especially those having cholagogue action, seem to do good.

Thierfelder, op. cit.

Ibid.

Diseases of the Liver, Amer. ed., supra.

Important symptoms arising during the toxæmic period require remedies to combat them. Nausea and vomiting, and also diarrhoea, are best relieved by carbolic acid and bismuth in combination. Hemorrhage requires, when intestinal, the chloride and perchloride of iron; when from other mucous surfaces, ergotin, gallic acid, and other hæmostatics. The depression of the vital forces should be treated by small and frequently-repeated doses of alcohol, by quinine, by iron, and, under some conditions, by digitalis. After the disintegration of the hepatic cells has been produced no remedies can be of any service. Until this occurs, however, it seems to the author well worth while to attempt to stay the destruction by the administration of those remedies which, by their accumulation in that organ, indicate a special affinity for its tissue. These drugs are phosphorus, antimony, gold, silver, and mercuric chloride. By the timely administration of one or more of these would it not be possible to stay the progress of the atrophic degeneration?