Amyloid Liver

DEFINITION.—By amyloid liver is meant a deposit in the cells of the organ, in its vessels and interstitial tissue, of a peculiar albuminoid matter called amyloid because of a superficial resemblance to starch-granules. Various designations have been applied to this condition of the organ; thus it has been entitled waxy liver and lardaceous liver, because of the apparent resemblance to wax and lard respectively.

CAUSES.—There exists in the blood a peculiar material, albuminoid in form, applied in the normal state to the structure of tissue—dystropodextrin, as it is called by Seegen—which, when precipitated under certain conditions not now known, assumes the peculiar appearance with which we are now familiar under the term amyloid. The character of the amyloid matter was first distinctly set forth in 1858 by Virchow, who also discovered the characteristic reaction by which it can always be detected. The reaction to iodine gave to the material the designation amyloid, or starch-like, by which it is chiefly known. The circumstances inducing the deposit of this material are by no means clearly understood. It has long been known that suppuration, especially in connection with bone, has had a distinct influence. Syphilis, especially the tertiary lesions accompanied by pus-formation, has an evident causative relation. Chronic malarial infection has a more distant and doubtful, but still recognized, power to develop this morbid state. Of the various causes above mentioned, the most frequent is the suppuration of pulmonary cavities. In regard to the influence of this, however, it must be remembered that no form of suppurative disease is so common. The relative frequency of the association between suppurating cavities and amyloid disease is not greater than long-standing necrosis with an extensive sequestrum is with the same state; but the actual number of the former is greater. Amyloid disease of the liver is most frequent between the ages of ten and thirty, but it may occur at any age, the period in life being determined by the operation of the causes. Thus, Frerichs' statistics are: under ten there were 3 cases, from ten to twenty there were 19, and from twenty to fifty there were 37 cases. Men are, relatively to sex, more frequently attacked, and in the proportion of three-fourths, but this difference means, of course, the character of men's occupations and their greater liability thereby to the accidents and diseases incident to such employments.

Besides the pathogenetic factors above mentioned, it may be well to refer in this connection to the effect of long-standing neoplasms. It has been found that amyloid disease is produced in some subjects by the cachexia resulting from the slow development and persistence of such a new formation. The special character of the neoplasm is of less importance in respect to this condition than the constitutional condition—the cachexia—induced by its slow growth and interference with nutrition. Although long-standing disease, especially of a suppurative kind, is known to be necessary to cause amyloid disease, Cohnheim has lately published some facts which seem to prove that the degeneration may occur more speedily than has been heretofore supposed. He has shown, contrary to the previously-accepted view, that amyloid degeneration may follow in three months after the reception of a gunshot wound. He records three cases in which the amyloid deposits ensued in six, five, and three months, respectively.

Virchow's Archiv, vol. liv. p. 271 et seq., "Zur Kentniss der Amyloidentartung."

According to the author's observation, a peculiar somatic type is either necessary to, or at least is greatly promotive of, the amyloid degeneration. If, for example, the same suppurative process occurs in a person of a blond and lymphatic type and in another of brunette and nervo-muscular type, the former will be much more likely to suffer from amyloid change than the latter. "The gelatinous progeny of albuminous parents" is the mode of expression used to designate this particular type.

PATHOLOGICAL ANATOMY.—To use the term amyloid liver is rather misleading, since this indicates the restriction of the morbid process to the liver, whereas it is perfectly well known to be rather widely distributed through various organs and tissues of the body. The term amyloid is itself confusing, since the albuminoid material so designated is not really starch-like. The corpora amylacea, so called, differ materially from starch-granules, and still more from the amyloid matter. According to Wagner, these substances "have nothing in common." In the study of the amyloid deposit it has not been possible to separate it from the tissue in which it is imbedded; hence the published analyses of this peculiar material are probably far from correct. However, it has been rendered probable that the amyloid deposit has close affinities with fibrin. One of the theories—that of Dickinson of London—assumes that this material is fibrin deprived of the potash associated intimately with it. According to Seegen, dystropodextrin, a material existing in normal blood, agrees with amyloid matter in its most essential characteristics. Although Dickinson's theory is not tenable, it has served a useful purpose in showing the close affinity of fibrin with this pathological product. What view soever may be entertained of its nature, it is certain that the material to which we apply the term amyloid is of albuminous origin. Under circumstances with which we are now unacquainted this material is deposited from the vessels, and, instead of undergoing organization and contributing to the structure of tissues, remains unorganized and unappropriated. It is known that this deposition of the amyloid material is related to the process of suppuration and to certain cachexiæ, but the intermediate steps remain unknown and inexplicable.

A Manual of General Pathology, by Prof. Dr. E. Wagner, p. 325 et seq.

The amyloid matter is first exuded into the coats of the finest ramifications of the hepatic artery, and therefore the first appearance of the disease is in the middle zone of the lobules. In this respect pathologists are agreed: that the amyloid deposits first appear in the walls of the vessels. Wagner maintained, in opposition to Virchow, that the exudation is limited to the vessels and does not extend to the hepatic cells, which perish by pressure and consequent atrophy. This point has not yet been decided. It seems most probable, however, that the ramifications of the hepatic artery and all the capillaries of the lobule are affected, and that the deposits in them lead to atrophic degeneration of the cells.

In consequence of this extensive implication of the vascular system of the liver important changes occur in the size, density, and appearance of the liver. The organ is greatly enlarged in all its diameters. When felt through the walls of the abdomen its outline is distinct, it is firm, even hard, to the sense of touch, and it projects from a finger's breadth to a hand's breadth below the margin of the ribs. The increase of size of the amyloid liver is very great, attaining in weight, on the average, twice that of the normal organ; but this size may be largely exceeded in exceptional instances. In respect to shape and outline the amyloid liver does not differ from the normal organ; for although its dimensions are increased, its relations to the parts adjacent are not altered. The weight of the amyloid liver may reach ten, twelve, even sixteen pounds avoirdupois. The color of the amyloid liver is very different from that of the normal organ: instead of having the reddish-brown tint, it becomes grayish, yellowish, or reddish-gray. In consistence the amyloid liver is firm and rather elastic and doughy, and on section the margins of the incision are well defined, even sharp. A very characteristic feature of the cut surface is its paleness, anæmia, or bloodlessness, and scarcely any blood is exuded, even from the large vessels. The appearance of the incised surface of the liver has been described by comparison with various substances: according to one, it is waxy; according to another, it is lardaceous. A thin section of a part of the liver far advanced in the amyloid change is distinctly translucent, almost transparent; but a marked difference is observable between the amyloid matter and the lobules proper, even in the cases of extreme deposit. The lobules are separated by an opaque yellow border, and the centre of each is marked by a spot of a similar yellow color.

The amyloid material is remarkable for its power to resist the action of chemical agents and putrefactive decomposition. The test originally proposed by Virchow—iodine—continues to be the most characteristic. Orth suggests a method of applying it which is very excellent in respect to the clearness with which the reaction is shown: A large, thin section of the affected liver is placed in a saucer of water containing some iodine, and after the reaction has taken place is laid on a white plate. Iodine tincture, diluted or the compound solution, is brushed over the affected region, when the amyloid matter assumes a deep mahogany tint and the normal tissues a merely yellowish hue. The distinctness of the reaction may be increased by brushing over the iodized surface some dilute sulphuric acid, when the amyloid matter takes a deep violet, almost black, color.

Diagnosis in Pathological Anatomy, Riverside Press, 1878, p. 321.

Only a part of the organ—namely, the smaller vessels—may be involved in the degeneration, and this may be restricted to patches or parts of the organ. With the amyloid change there may be associated syphilitic gummata, or the liver may be more or less advanced in fatty degeneration or in cirrhosis. Those parts of the organ not invaded by the disease are not often entirely normal; they are more or less darkened in color by venous congestion, distinctly softer, etc. The amyloid change is not limited to the liver, but extends to the kidneys, lymphatic glands, the intestinal mucous membrane, etc.

SYMPTOMS.—As the amyloid change in the liver is usually coincident with a simultaneous alteration of other organs, and as the deposits characteristic of the affection are dependent on long-previous disease of an exhausting kind, it is not surprising that the subjects of this affection present the evidences of a cachexia. To the effects of a chronic malady we have added the complications growing out of the amyloid change in the liver, associated, as it usually is, with amyloid degeneration of other important organs.

The symptomatic expression of amyloid liver is therefore mixed up with various derangements that occur simultaneously, but especially with the causes inducing the existing cachexia, with chronic suppuration of pulmonary cavities, or in connection with diseased bone, with the syphilitic cachexia, or with chronic malarial toxæmia. With what cause soever the cachexia may be associated, the symptomatology of amyloid liver is secondary to, or ingrafted on, the conditions produced by the cachexia. The liver is enlarged in all well-marked cases from a finger's breadth to a hand's breadth or more below the inferior margin of the ribs; it is also firm to the touch, well defined, elastic, and its margin rounded, but yet well defined. There is usually no tenderness nor pain, and, without any uneasy sensations to indicate the change taking place, the organ is found to have slowly enlarged, sometimes to an extraordinary extent. Careful palpation may also demonstrate an enlargement of the spleen. When the abdominal muscles are relaxed and there is no swelling of the abdomen by flatus or peritoneal effusion, the very considerable enlargement of the liver can be readily ascertained. If the effusion is not so great as to distend the abdomen unduly, the increased consistence and dimensions of the liver can still be made out with comparative ease. The hepatic functions are not always sufficiently disturbed to produce characteristic symptoms. In a small proportion—scarcely one-tenth—of the cases does jaundice appear, and when present it is due, usually, to enlargement of the lymphatics in the hilus of the organ, and thus directly compressing the hepatic duct. In the writer's experience, although jaundice has not occurred, there was present a peculiar dark earthy or bronzed tint of the skin, significant of chronic hepatic troubles. Obstruction of the portal circulation is rather unusual, and the explanation is to be found in the fact that the amyloid degeneration occurs first in the radicles of the hepatic artery. In about one-fourth of the cases ascites is present, but in a somewhat larger proportion hemorrhoids, blackish, tarry stools, and other evidences of portal congestion. When the intestinal arterioles are attacked, an intractable colliquative diarrhoea comes on; the stools are offensive, sometimes light from the absence of bile, sometimes dark from decomposition or the presence of blood. When the stomach arterioles are also involved, which is usual under these circumstances, the blandest and simplest articles of diet will pass unchanged or simply decomposed. Blood may be vomited sometimes in large quantity from thrombic ulcers, but the matter ejected from the stomach when the case is well advanced is a thin, watery fluid, faintly acid or neutral, and greenish or brownish in color.

An enlarged spleen is often present, produced by the same conditions—by amyloid degeneration. The same change taking place in the kidney, the urine becomes pale, abundant, of low specific gravity, and albuminous. General dropsy supervenes in a majority of the cases finally, due largely to the hydræmia; and of this condition ascites is a part. In some cases enlargement of the abdomen is the first step in the dropsical effusion, and may throughout be the most prominent, as the author has seen. In other cases oedema of the feet and legs is the first evidence of dropsy; in still others the dropsy is general from the beginning.

Amyloid liver may coexist with a fairly good state of the bodily nutrition, but if digestion and assimilation be interfered with by any of the causes above mentioned, the strength rapidly declines and emaciation reaches an extreme degree.

COURSE, DURATION, AND TERMINATION.—As amyloid liver is never a substantive affection, but secondary to some constitutional malady or to long-continued suppuration, its course must be considered in relation to the agency producing it. It is very silent in its origin and progress, and causes no pronounced symptoms until it attains considerable size and its functions are interfered with by the extent of the deposits. The history of the affection to which it is secondary therefore precedes the onset of the amyloid change and accompanies it throughout. The enlarged organ, with the results of its enlargement in altered functions of the abdominal organs, is a symptom superadded to existing disturbances. The period elapsing in the course of a chronic suppurative disease before the amyloid change occurs differs greatly in different cases, and may be stated as from three months (Cohnheim's case) to many years. Many of the cases terminate by an intercurrent disease; others by uræmic convulsions; a very few by hemorrhage from the stomach or intestines; and those pursuing their course uninterruptedly, by exhaustion.

The prognosis is very unfavorable. By some a cure at the beginning of the morbid deposits is regarded as possible, and examples of cures have been reported. The writer has seen supposed cases of amyloid liver terminate in recovery. There must always remain an impression that in such instances an error of diagnosis was committed. Those of syphilitic origin are probably more curable, but syphiloma of the liver may be confounded with amyloid disease, and hence the cure may be referred to the latter.

DIAGNOSIS.—Amyloid degeneration of the liver may be confounded with the various non-febrile enlargements of the organ. An important element in making the differentiation is the history of suppuration in connection with bone, with lung cavities, with constitutional syphilis, with chronic malarial toxæmia, etc. From fatty liver, amyloid degeneration is distinguished by the history as just sketched; by the fatty tendencies of the body in the former, emaciation in the latter; by the concomitant changes in the spleen, kidneys, and elsewhere; and by the subsequent history, fatty liver terminating by a weak heart usually, whilst the amyloid disease ends in the modes described in the preceding paragraph. From hydatid disease, amyloid liver is differentiated by the history, by the difference in the physical characteristics of the enlargement, by the presence of the purring tremor in the one, its absence in the other, and especially by the subsequent course. In all doubtful cases the use of an aspirator-needle and the withdrawal of some fluid containing the characteristic hooklets of the echinococcus will serve to determine the nature of the growth. From cancer, amyloid liver is separated by the previous history, by the nodular character of the enlargement, by the pain, and by the cachexia and associated derangements. Whilst amyloid liver is secondary to suppurative diseases, cancer is usually secondary to cancer of the stomach or other organ within the limits of the portal circulation.

TREATMENT.—As amyloid disease owes its origin to syphilis, to chronic malarial toxæmia, to suppuration, these, so far as they are remediable conditions, should be cured as speedily as may be, to prevent the development of the amyloid disease or to arrest it if begun. Unfortunately, the condition of the liver is not recognized until the morbid change is effected, and therefore practically irremediable.

The treatment necessarily involves that of the morbid state to which the amyloid deposits are owing. The syphilitic disease requires iodine and mercury; the malarial, quinine, iodine and the iodides, eucalyptus, iron, etc., according to the state of each case; and surgical diseases, especially necrosis of bone, should be effectively treated by suitable surgical expedients. The cause being removed if possible, what means, if any, can be resorted to to cause the absorption of the amyloid matter? The only specific plan of treatment hitherto proposed is that of Dickinson, based on his theory of the constitution of amyloid matter; according to which the amyloid deposits consist of fibrin altered by the separation of the potash and soda salts, which have been eliminated in the pus. If this theory be admitted, the obvious indication is to supply the alkaline materials. The cases reported by Dickinson in which this theory was practically demonstrated were not sufficiently improved to lend any empirical support to this method.

The Pathology and Treatment of Albuminuria, p. 214 et seq.

The medicinal remedies which do any good are the iodides—notably the iodides of ammonium, of iron, of manganese, etc., the compound solution of iodine, and the double iodide of iron and manganese. As the officinal ointment of the red iodide of mercury, rubbed in over the splenic region, does so much good in chronic enlargement of the spleen, it is probable that it will prove effective in this form of enlargement of the liver. The writer has observed results from it in such cases that justify him in strongly urging its employment. The method of its application consists in rubbing perseveringly a piece of the ointment, a large pea in size, over the whole hepatic area, and repeating it daily until some irritation and desquamation of the skin is produced, when it should be suspended until the parts will bear renewed applications. Besides the topical application of the red iodide, this remedy may be given internally with advantage without reference to syphilitic infection. It seems to the writer probable that bichloride of mercury may be as useful, as it is certainly more manageable. The chloride of gold and sodium, arsenic in small doses, and the metallic tonics, so called, may be useful carefully administered, especially the first mentioned, which the writer believes has some real power over the disease.

Dietetic rules are of great importance. As the hepatic functions are much disturbed, if not entirely suspended, it is necessary to give those foods which are converted into peptones in the stomach. As a rule, fats, starches, and sweets are mischievous, and milk, meats, oysters, and the nitrogenous foods best adapted to nourish the patient. If the diarrhoea should prove exhausting, the mineral acids, with opium, are the best remedies. Nausea and vomiting are best relieved by carbolic acid mixture, and hemorrhages by the solution of the chloride or subsulphate of iron.