Volume 2 — DISEASES OF THE DIGESTIVE SYSTEM. (continued 25)

TREATMENT.—The poison should be evacuated as quickly as possible by emetics and proper diluents. The best emetics are sulphate of copper, apomorphia, and ipecacuanha, the antimonial and mercurial emetics being unsuited, since their effects are similar to those of phosphorus. Oleaginous protectives do not prevent, but really favor, the absorption of phosphorus. Decoctions of flaxseed, slippery elm, acacia, etc. are suitable demulcents and protectives. The fatty matter in food, eggs, etc. will have an injurious effect by promoting the solution and absorption of the phosphorus, and should hence be excluded from the diet. The most effective antidote is oleum terebinthinæ, and the most suitable preparation is the French acid oil. Freshly-distilled turpentine appears to be almost if not entirely useless. It is probable that the American oil which is old and has been exposed to the air for many months will answer the purpose, but it cannot be too strongly insisted on that the turpentine which has proved to be efficient in phosphorus-poisoning is the French acid oil. Turpentine when exposed to the air absorbs oxygen as ozone, and to this principle are probably due the curative effects of old turpentine. Phosphorus when acted on by this agent is converted into a spermaceti-like substance entirely devoid of toxic power. As rapidly as possible the poison should be acted on by the antidote, and then the stomach should be evacuated, using, cæteris paribus, the sulphate of copper, since this forms an insoluble phosphide with any portion of free phosphorus, whilst at the same time it empties the stomach of its contents. Although the immediate results of the poison may be thus removed, the damage to the red corpuscles and to the whole mass of the blood requires special management. The success of transfusion, as practised by Jürgensen,¹³⁹ proves that the substitution of fresh blood may save life when the existing blood-supply is inadequate to the performance of its proper functions. It follows that if the toxic effects of phosphorus have continued for several days, blood-transfusion will be necessary in those cases characterized by an inability to recuperate notwithstanding the successful removal of the poison.

¹³⁹ Berliner klinische Wochenschrift, No. 21, 1871.

For the inflammatory symptoms produced by the local action of phosphorus, opium in some form is indispensable. This remedy is equally valuable as a means of maintaining the vital resources and to prevent the evil results of shock and inflammation.

Carcinoma of the Liver.

DEFINITION.—Under the term carcinoma of the liver are included primary and secondary cancer of the liver. The malady with which we are now concerned is the primary affection, occurring in the organ proper or in some pathological new formation connected with it.

ETIOLOGY.—Heredity is the most important factor. A careful investigation of the reported examples demonstrates that from 15 to 20 per cent. owe their origin to hereditary influence clearly, and probably considerably more are indirectly derived in this way when the immediate connection may not be demonstrable. Next to heredity, age must be regarded as the most important pathogenetic influence, much the largest number occurring at from forty to sixty years of age. It is a malady of advanced life, therefore, rather than of youth or middle age. Excluding the female organs from consideration, it is quite certain that sex has little special influence, and that males and females are affected about equally.

Primary cancer of the liver is comparatively infrequent, occurring in not more than one-fourth of the cases. Frerichs collected 91 cases, and of these 46 were secondary to cancer in organs having vascular communication with the liver.

PATHOLOGICAL ANATOMY.—Under the term cancer of the liver are included several distinct forms of morbid growth, but united in the characteristic of malignancy. From the merely clinical standpoint this characteristic is the most decisive bond of union between them, and serves as the point of departure in the study of this affection. Primary cancer of the liver is divisible into two forms: 1, as a single, defined tumor; 2, as an infiltration through the whole mass of the organ.¹⁴⁰ Secondary cancer occurs in nodular masses, and with extreme rarity as an infiltration. The form of cancer is really the same; the differences in structure are only apparent, the variations being due to the relative proportion of cells, fibres, and vessels. If the fibrous stroma is abundant and the cells small in quantity, the form of structure approaches scirrhus; on the other hand, if the cells largely preponderate, the type is encephaloid; if vessels predominate, it is called telangiectatic. The usual form in cancer of the liver is the soft, cellular variety, encephaloid or medullary. When the cancerous new formation is nodular, the masses vary in size from a pea to a child's head,¹⁴¹ and are numerous inversely as their size. When the cancer occurs as a solitary tumor, it may attain to enormous dimensions. It has a spherical shape usually, protrudes from the surface of the organ somewhat irregularly, and the overlying peritoneum is thickened, cloudy, and adherent from a local inflammation. The central portion, whether there be one, several, or many nodules, is depressed, giving an umbilicated appearance to the tumor; and this central depression is found to be soft, almost diffluent, and full of juice. The fibrous stroma which extends through this central soft material has a reticulated arrangement and a shining, fibrous appearance. The cancerous masses are not confined to these nodules, but extend into the surrounding hepatic structure, push their way into the portal (especially the hepatic) veins, block the ducts, and invade the lymphatic glands in the fissure of the liver.

¹⁴⁰ Virchow, Krankhaften Geschwülste, loc. cit.; Perls, Virchow's Archiv für path. Anat., etc., Band lvi. p. 448 et seq.; Frerichs, A Clinical Treatise, etc., Syd. Soc. ed., loc. cit., vol. ii. p. 281 et seq.

¹⁴¹ Förster, Lehrbuch der Pathologischen Anatomie, by Seibert, Jena, 1873.

When the cancerous new formation takes the form of an infiltration of the organ instead of distinct nodules, the liver is usually uniformly enlarged and its outlines preserved.¹⁴² The peritoneum is opaque, thickened, and adherent. The organ is traversed by fibrous bands, and the intervening portion is a soft, juicy pulp, stained by the imbibition of bile. In extreme cases hardly any portion of the proper hepatic tissue remains, but is replaced by a cancerous new formation having the same shape.

¹⁴² Perls, Virchow's Archiv, Band lvi. p. 448 et seq.

As regards the minute structure of cancer of the liver, it may be regarded as a degeneration (cancerous) of the proper gland-cells and of the epithelium of the bile-ducts. As cancer develops in the liver it is to be noted that the cellular elements preponderate over the fibrous or the stroma, and hence the new formation presents the characteristics of softness, rapid growth, and a multitudinous cellular hyperplasia. As regards the form of the new cells, it cannot now be doubted that they are descendants of the secretory gland-cells and of the epithelial lining of the ducts. According to some observers, it is to the proliferation of the proper gland-cells that the new formations owe their origin; according to others, to the hyperplasia of the cells lining the ducts. As the growth of the new formation can take place only through an adequate blood-supply, it becomes very important to ascertain its source. There can be little doubt that primary cancer of the liver receives its nutrient supply through the hepatic artery, in connection with which new capillaries form in the pathological tissue.

Secondary cancer of the liver is the usual form of the specific manifestation. From the merely clinical standpoint the primary affection is the more important. From the pathological point of view the secondary implication of the liver may be a true metastasis or a mere communication by contiguity of tissue. The most usual metastasis occurs from epithelial cancer of the face (Schüppel), but the ordinary communication of the new formation is from primary cancer of the stomach, intestine, pancreas, mesentery, etc. The cancer elements, as the author has several times verified, crowd the lymphatics and veins, and through these channels reach the liver and other parts. As the cancer elements in the case of secondary implication of the liver are distributed chiefly by the portal vein, it follows that there must be numerous secondary foci and multiple nodes. Cancerous infiltration under these circumstances is the rarest possible form for the new growth to take. The size and number of nodes forming in these cases of secondary implication of the organ vary greatly—from two or three to twenty, or a hundred, or even more. As regards the form, structure, and ultimate behavior of the secondary formation, they do not differ from the primary. As respects the relative proportion of stroma and cellular elements—fibres and cells—they vary greatly, some presenting the firm texture of a predominating fibrous stroma, others the softness and ready diffluence of the excessive cellular production. The latter is undoubtedly the usual condition, and when the nodular masses are incised an abundant creamy juice exudes. With the development of these nodules an increase in the size of the liver takes place and the organ has an uneven and indurated feel. As the cancerous masses develop the proper hepatic structure undergoes atrophy, and finally little is left of the organ but the cancerous new formation. The blood-vessels, lymphatics, and peritoneal investment are invaded, the first mentioned most decidedly; and especially are organized exudations the favorite seats of cancer new formations, those, for example, about the gall-bladder and cystic duct resulting from repeated attacks of passage of calculi.

Secondary changes take place in the cancerous nodes. As the cells develop pressure is brought to bear on the vessels supplying them and on each other, with the result of fatty degeneration of the central portion, which effects the change in the form of the nodules and in their consistence, already mentioned. The blood-supply to the cancerous nodes in the liver is derived from the hepatic artery, as Frerichs has determined by carefully-made injections; they also are new formations of exceedingly delicate structure, and form a network about the periphery of each mass or node. By reference to these anatomical considerations it is easy to understand the failure of nutrition of the central portions of the nodes.

Pigment cancers of the liver are rare as secondary formations, and excessively infrequent as primary formations. They are, properly speaking, melano-sarcomas (Schüppel). They are more often metastatic than merely secondary—that is, transferred from different parts, as in the case of melanotic sarcoma of the choroid—than due to neighboring disease transferred by contiguity of tissue. This variety of cancer, so called, takes the form of multiple nodes or of diffused infiltration, the former more frequently; but both modes of development may go on at the same time. The nodes vary in size from a pea to a child's head, have a grayish, brownish, or blackish tint, and exude on section a fluid not creamy like true cancer-juice, but rather watery and containing black particles floating in it. In the case of diffuse infiltration the pigment masses are thoroughly distributed through the original hepatic tissue. In both forms the size and weight of the organ are enormously increased. In the case of the melanotic infiltration the whole organ is uniformly enlarged, reaching in a few months the enormous size of twelve to twenty pounds.

Sarcomas also occur very rarely as primary growths in the liver, but secondary sarcomas are more frequent. There are fibro-sarcoma, lympho-sarcoma, and osteo-sarcoma as secondary deposits, the first being very firm in consistence, the second soft and medullary, and the last of hard, bony consistence.

SYMPTOMS.—We are especially concerned here with primary cancer of the liver. The secondary disease is so obscured by the main and primary lesion that a diagnosis may be impossible. Furthermore, the progress of the original disease is that which demands immediate consideration. As, therefore, the secondary implication of the liver is of relatively trifling importance, and only an incident in the course of the main disease, the matter for consideration now is primary cancer of the liver.

It is the fact that in some, even a considerable proportion, of the cases the onset and progress of cancer of the liver are very obscure. For some time the symptoms may be of the vaguest description. The usual history is this: A person of forty to sixty years begins to fail in flesh and strength, becomes sallow, has disorders of digestion, pain and uneasiness in the right hypochondrium, and the bowels are now confined, now relaxed. The abdomen, notwithstanding the general loss of flesh, increases in size, and the superficial veins are enlarged; very considerable pain is experienced in the right hypochondrium, and often extreme tenderness to pressure is a pronounced symptom. The pains are not limited to the hepatic region, out extend widely from this point in all directions. On palpation the liver is found to be enlarged, its texture indurated, and its outline irregular and nodular, and pain—often, indeed, quite severe—is developed by pressure.

The condition of the liver on palpation is best ascertained by suddenly depressing the abdominal wall with the tips of the fingers arranged in a line. Displacing thus the movable bodies in the cavity, the liver is quickly reached, and nodules, if they exist, are readily felt. If the new formation has developed from exudations about the gall-bladder and cystic duct, it may be felt by suddenly depressing the walls of the abdomen over this organ in the usual position of the fissure.

In the case of general cancerous infiltration of the organ, with the remarkable enlargement which occurs in such cases, there will be present an obvious distension of the right hypochondrium; the intercostal spaces will be forced outward and the arches of the ribs rendered more prominent; the area of hepatic dulness, both vertical and transverse, will be increased; and the limits of dulness will move with a full inspiration downward, and with a full expiration upward. This mobility of cancer-nodules of the liver with the inspiratory and expiratory changes serves to distinguish them from tumors of the abdominal walls. Seen early, the changes in the size of a nodule or of the liver itself may be noted from week to week,¹⁴³ especially in cases of rapidly-growing cancer.

¹⁴³ Murchison, Clinical Lectures, p. 187.

As the cancerous new formations extend into the portal system within the liver, obstruction to the portal circulation results from the blocking of the blood-current. Also, interference in the portal circulation arises by compression of the vessels from without, either through the accumulation of cancer-products in the liver or by the enlargement of the lymphatics in the fissure of the organ. In what way soever it may be produced, the practical fact remains that ascites is a frequent symptom, occurring in somewhat more than one-half of the cases. The character of the fluid varies. It may be a clear serum containing a small proportion of albumen; it may be colored by bile or be of a deeper greenish or reddish hue; it may contain flocculi of lymph and numerous leucocytes floating in it; and the ordinary serum may be rendered cloudy and be filled with shreds of exudation in consequence of peritonitis, or bloody because of hemorrhage from a softening nodule. When the fluid is considerable in amount the difficulty of ascertaining the condition of the liver is greatly enhanced, and symptoms due to the interference of the fluid with the action of various organs are introduced into the complexus of morbid signs. Especially is the upward pressure of the ascitic fluid, and the consequent interference in the movements of the lungs and heart, a source of considerable distress. First, a local and afterward a general peritonitis ensues as a consequence of the extension outwardly of the new formations to the peritoneal layer, and its implication by contiguity of tissue or the rupture of a spreading fungous growth and hemorrhagic extravasation into the cavity. The peritoneal complication is not only a serious addition to the sufferings experienced by the patient, but it adds to the difficulties of a diagnosis. In the case of a celebrated savant who died of cancer of the liver (seen by the writer) there was such a pronounced peritonitis that the diagnosis made by the attending physician was chronic peritonitis. When this complication occurs, there takes place a decided increase in the local tenderness, and this increased sensibility to pressure quickly extends over the abdomen, causing a general exquisite tenderness. Besides this tenderness characteristic of most cases of peritonitis, distension of the abdomen and the decubitus peculiar to this state are obvious symptoms. It is therefore clear that the occurrence of peritonitis not only contributes to the severity and painfulness of the case, but seriously complicates the diagnosis.

It has been already stated that pain in the right hypochondrium is a nearly constant symptom in cancer of the liver. With the initial symptoms, uneasiness, heaviness, a sense of pressure in the hepatic region are experienced, and as the case progresses more or less acute pain develops as a rule. But there are exceptions. In cases of cancer involving the deeper portion of the liver there may be little pain, and in some rare cases of cancer involving the external part of the liver—the capsule and peritoneum—but little pain is experienced. In much the largest proportion of cases the pain is severe, and the production of any considerable pain means the implication of the hepatic plexus of nerves or the hepatic peritoneum. It follows, then, that the pain in the former case is not limited to the locality of the disease, but is more or less widely distributed through the anatomical relations of the hepatic plexus, being felt in the epigastrium, the walls of the chest, the shoulders, etc.

In secondary cancer of the liver, following cancer of the stomach, vomiting is a constant symptom, but also in those cases of primary disease in which the left lobe is especially enlarged, relatively, are nausea and vomiting pronounced symptoms. At the onset of the malady the appetite fails and a gastro-intestinal catarrh is set up. More or less catarrh of the bile-ducts also ensues. The interference with nutrition thus occasioned is enhanced in those cases in which the obstruction of the ducts is sufficient to prevent the escape of bile into the intestine. Jaundice is not a constant symptom, occurring in little more than one-third of the cases. When it occurs, the peculiar stools are present and the intestinal digestion is deranged, as in cases of ordinary obstruction to the ducts. In two cases of cancer of the liver occurring in the writer's practice, and examined by post-mortem, there were calculi present in the gall-bladder; in one case the principal calculus was egg-shaped and the size of a pullet's egg.

The nutrition rapidly fails from the beginning of cancer of the liver. The downward pace is accelerated when the gastro-intestinal digestion fails and vomiting occurs after taking food. The skin becomes dry and wrinkled, and if not jaundiced has a peculiar tint, varying in depth of color from an earthy or fawn-like hue to a deep bronze. Failure of strength is a pronounced symptom from the beginning, and is out of proportion to the loss of flesh. As the wasting advances the decline of strength is accounted for, but the feeling of weakness and the distaste for exertion which occur so early are very significant signs of internal cancer, although they do not indicate the position of the neoplasm. Emaciation finally becomes extreme.

The urine declines in amount as the case progresses. It is usually very high-colored, contains bile-pigment when jaundice is present, and other forms of pigment produced by conditions not at present known. Sometimes albumen is present, and leucin and tyrosin rarely.

COURSE, DURATION, AND TERMINATION.—As has been already set forth, cancer of the liver may present so few really distinctive symptoms as to escape recognition. Under favorable circumstances the diagnosis may be comparatively easy. In forming an opinion it is useful to review the whole course of the malady and draw conclusions not only from the characteristic signs, but from the development of the symptoms as a whole.

A case of cancer of the liver occurs usually after the middle period of life. The person so affected begins to decline in flesh and strength, has uneasiness in the right hypochondrium, disorders of digestion, and begins to have a pallid or earthy hue of the countenance. Presently, much pain is felt in the hepatic region, the organ distinctly enlarges, and some effusion of fluid and much flatus increase the dimensions of the abdomen. Much tenderness, often exquisite sensibility, is produced by pressure over the liver, and often over the whole abdomen. By careful palpation nodules can be made out and their growth noted in those cases free from peritoneal inflammation. The abdominal swelling and tenderness incommodes the lungs, and a semi-erect decubitus is assumed to relieve the pressure on them; the breathing becomes short, catching, hurried, and painful, and sometimes a most distressing hiccough is superadded to the other sufferings. Great wasting and weakness ensue. Jaundice appears, or the earthy hue of the skin deepens into a bronze discoloration. The case may be terminated by some intercurrent disease—by an attack of pleuritis, pneumonia, by peritonitis from rupture or perforation, by intra-peritoneal hemorrhage, by an exhausting diarrhoea. The natural termination is by gradual failure of the powers, by marasmus, the immediate cause of death being due to cerebral anæmia, to failure of the heart from fatty degeneration of the cardiac muscle, from thrombosis of the portal vein, from the development of a hemorrhagic state, and hemorrhages from the various mucous surfaces, etc. The duration is much influenced also by the character of the cancer, whether scirrhous or medullary. The latter are not only more rapidly growing, more destructive of the hepatic tissue, and more rapidly distributed to neighboring organs, but more quickly perforate the capsule and excite a fatal result by hemorrhage or by peritonitis. The average duration of cancer of the liver is variously stated. Having reference to my own personal observation, controlled by the experience of other observers, the duration is from three to nine months, one year being exceptional. There are cases in which the symptoms are very acute, the progress rapid, the whole course from the initial symptoms to the termination being completed in from two to three months. It need hardly be observed that no case of cancer of the liver has been cured. The invariable termination is in death. If any case has seemed to be cured, it may be asserted with confidence that cancer of the liver did not exist.

DIAGNOSIS.—The differential diagnosis is concerned, first, with the existence of cancer; second, with its form. As cancer causes enlargement of the liver in two textural conditions—namely, uniformly smooth, and nodular—it must be differentiated from other diseases producing similar results. Amyloid disease and echinococcus cysts present us types of the former; cirrhosis and syphilis, of the latter. The history of the amyloid disease and of the echinococcus cyst is very different, and both develop much more slowly. Amyloid disease of the liver arises simultaneously with the same form of degeneration in other organs, and is connected with suppurative disease of some kind, with syphilis, with chronic malarial poisoning, etc., and may occur at any age. Echinococcus cysts enlarge painlessly and do not impair the vital forces; the liver is elastic, and under favorable circumstances presents by palpation the purring-tremor symptom. Cirrhosis may have to be differentiated at two periods—during the time of enlargement, which, however, is rather brief; and during the stage of contraction and nodulation. The history in cancer and in cirrhosis is different: the age, the habits of life, the rate of hepatic change, are opposed in the two diseases; the diminution in size with nodulation is characteristic of cirrhosis; enlargement with nodulation belongs to cancer. The rapid progress of cancer, the wasting, the debility, the cachexia, serve to distinguish it from all other affections of the liver except acute yellow atrophy and phosphorus-poisoning; both, however, are so different in history and development as not to require differentiation. It may be quite impossible in latent cases to distinguish primary cancer of the liver from secondary, but in those examples of the disease occurring in the stomach, intestines, and pancreas there is usually an antecedent history of the primary malady which distinctly separates it in point of time and the character of the symptoms from the secondary implication of the liver. Cancer of the gall-bladder, and especially of the organized exudation about it, may not be readily separated from cancer of the pancreas or of the duodenum. In doubtful cases the history of attacks of hepatic colic becomes an important element in making the differentiation.

TREATMENT.—As we are not in possession of a cure for cancer, the treatment of cancer of the liver must be palliative. Anodynes to relieve pain, paracentesis of the abdomen to remove accumulation of fluid which causes distress, carbolic acid to check nausea and vomiting, and the usual hæmostatics for hemorrhage, are the measures most necessary. In fact, the treatment must be throughout symptomatic—for the relief of symptoms as they arise.

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, Cohnheim¹⁴⁴ 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.

¹⁴⁴ 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,¹⁴⁵ 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.

¹⁴⁵ 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. Orth¹⁴⁶ 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.

¹⁴⁶ 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,¹⁴⁷ 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.

¹⁴⁷ 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.

Fatty Liver; Fatty Degeneration of the Liver (Hepar Adiposum).

DEFINITION.—By the term fatty liver is meant a change in the organ characterized by the excessive quantity of fat- or oil-globules contained in the cells of the parenchyma.

CAUSES.—The liver acts, under normal conditions, as a reservoir for the surplus fat, which it gives out as the demand is made. It is not only the fat brought to the liver by the blood which accumulates in the organ, but it apparently possesses the power to transform certain substances—albumen, for example—into fat. An important causative element, therefore, is the quantity of fat present in the food habitually consumed. This has been proved by the investigations of Radziejewsky¹⁴⁸ and others, who have shown that the fat in the food is stored up in the normal places of deposit, one of which, of course, is the liver. Another causative element is the formation of fat from the albumen of the hepatic cells in consequence of diminished oxidation. In respect to both causes the consumption of oxygen is an important factor. The insufficient supply of oxygen which is a necessary result of a sedentary life leads thus, directly, to the accumulation of fat in the liver-cells. A constitutional predisposition is also an important factor. There are those who under certain conditions of daily life store up large supplies of fat, and others who under the same conditions continue lean. Women more than men are subject to such inherited predispositions.

¹⁴⁸ Virchow's Archiv für path. Anat., etc., Band lvi. p. 211.

Again, fatty liver occurs in the course of certain cachexiæ, notably phthisis. In this case the obstructive pulmonary lesions interfere with the process of oxidation, and also maintain a constant hyperæmia of the portal system. This condition of the liver also occurs in the cancerous cachexia, in anæmia and chlorosis of long standing, in chronic suppurative diseases, etc. The dyscrasia of chronic alcoholism is a very common cause of fatty liver. At the same time that hyperplasia of the connective tissue is taking place the fat is accumulating in the hepatic cells. So great is the accumulation of fat in the blood that the serum presents a milky appearance. This excess in the quantity of fat is rather due to diminished oxidation, to lessened combustion, than to increased production. Another causative element of the fat-production in cases of alcoholism is the interference of alcohol with the process of digestion and assimilation.

Poisoning by phosphorus, antimony, arsenic, and other metals sets up an acute fatty degeneration of the liver. Pregnancy, lactation, and suppuration also have the same effect, but to a slighter and less permanent extent.

PATHOLOGICAL ANATOMY.—Fatty liver agrees with amyloid liver in that the fatty deposits increase the size and weight of the organ. The surface is smooth, the peritoneal investment unaltered, and the margins rounded. Sometimes the organ is merely increased in thickness, sometimes in diameter. It has a greasy feel and cuts like a mass of fatty tissue. Examined at a low temperature—below freezing—it seems like a mass of suet, the proper structure being almost extinguished in the fatty metamorphosis. The outline of the lobules remains distinct even in cases far advanced in the fatty degeneration, but in the extreme cases it is obliterated, the cut surface presenting a uniformly yellowish or grayish-yellow tint. The fatty liver is also wanting in blood; it is dry, and on section only the largest vessels contain any blood. When cardiac disease of a kind to produce congestion of the venous system exists—for example, mitral or tricuspid lesions—the same relative decrease in the quantity of blood in the liver is observable after death, although during the life of the subject the opposite condition may have been present. The cause of this bloodlessness of the fatty liver is to be sought in the pressure exerted by the growing fat-cells.

Not all cases of fatty liver are advanced to the degree indicated in the above description. From the normal size up to the maximum attained by the most advanced fatty liver there are numerous gradations in the quantity of fat and in the dimensions of the organ. Fatty degeneration may accompany cirrhosis, in which the liver is contracted. The deposits of fat may take place in particular areas. In cases of fatty liver per se the deposit occurs within the liver-cells, as may be demonstrated on microscopic examination, the initial change consisting in the formation of granules in the protoplasm which ultimately coalesce, thus producing fat-globules or cells. The fatty change in the hepatic cells proceeds in a certain methodical manner from the cells at the periphery of each lobule to the centre. The quantity of fat deposited in the liver in cases of fatty change is very great. In the normal condition of the organ fat exists, according to Perls,¹⁴⁹ in the proportion of 3 per cent. of the weight of the liver. When the condition of fatty liver exists the quantity of fat rises to 40, even 45, per cent.—almost one-half. It is important to note, as was pointed out by Frerichs, that in an inverse ratio with the increase of fat was the quantity of water.

¹⁴⁹ Virchow's Archiv, supra.

That more or less fatty change in the liver is not incompatible with a normal functional activity is quite certain, but the boundary between health and disease is by no means well defined in respect to the quantity of fatty change in the liver-cells. The liver, within certain limits, is a mere reservoir of the surplus fat of the body, and hence a variable, but not excessive, amount of accumulation of fat is not incompatible with a normal functional performance of the organ. The limits of a merely functional state and of a diseased state are not, therefore, very clearly defined. In certain inferior animals, as Frerichs has shown, a fatty condition of the liver is normal.

SYMPTOMS.—The signs and symptoms of fatty liver are by no means well defined. This state of the organ, as a rule, accompanies the general tendency to fatty metamorphosis and deposit in the body. It is a symptom in the course of phthisis, of chronic alcoholism, and of various forms of metallic poisoning, but under these circumstances there is no material change in the course of the symptoms produced by this complication. As an independent affection it rarely, if ever, exists alone. So far as its symptoms can be defined, they are referable to the organs of digestion and assimilation and to the liver itself.

The appetite is generally good, but distress after eating, acidity and heartburn, eructations of acid liquid and of certain articles of diet, are experienced. The stools are usually rather soft or liquid, wanting in color, whitish or pasty, and occasionally dark, almost black, owing to the presence of blood. Hemorrhoids are usually present. The discharges are often offensive from the decomposition of certain constituents of the food, acid and burning because of the presence of acetic, butyric, and other fat acids, or merely offensive because of the formation of hydrogen compounds with sulphur and phosphorus. Notwithstanding the derangement of the stomachal and intestinal digestion, the deposition of fat continues in an abnormal ratio. With the increase in body-weight a decline in muscular power takes place. The respiration is hurried on the slightest exertion, and dyspnoea is produced by any prolonged muscular effort. The circulation is feeble and the pulse slow in the state of repose, but on active exertion the pulse becomes rapid and at the same time feeble. The sleep is disturbed by horrifying dreams, and only on assuming a nearly sitting posture can the patient sleep with any degree of quietude.

In these cases of fatty liver a very considerable mental inquietude, despondency, even hypochondria and melancholia, result. The relation of insufficient hepatic excretion to the mental state is yet sub judice, but there can be no doubt that some connection exists. From the earliest period hepatic derangements—as the term hypochondria denotes—have been associated with certain disorders of the mind. This relation certainly holds good in respect to the mental perturbation occurring in cases of fatty liver. With a rotund countenance and a well-nourished body there is associated very considerable mental despondency.

Without distinct jaundice the skin has an earthen or tallow-like hue, the conjunctiva is muddy or distinctly yellow, and now and then well-defined jaundice appears.

The urine is rather scanty, high-colored because of the presence of bile-pigments, and deposits urates abundantly. When jaundice accompanies fatty liver the urine will be very dark, muddy, thick, and will react to the usual tests for bile, urates, etc.

The area of hepatic dulness is, as a rule, enlarged in cases of fatty liver. The deposition of fat in the cells adds to the gross size of the organ, and hence the inferior margin extends below the border of the ribs to a degree determined by the amount of increase in its substance. If the liver can be felt, it is smooth, not hard and resisting, and is free from nodules. Usually, however, owing to deposits of fat in the omentum and in the abdominal walls, the outlines and condition of the liver cannot be ascertained, and must remain merely conjectural. Rather, therefore, by implication than by direct examination can the condition of the liver be ascertained.

COURSE, DURATION, AND TERMINATION.—The course of fatty liver, as an element in a general change not of a toxic character, is essentially of a chronic character. The fatty liver of acute phosphorus, antimonial, and other forms of poisoning is acute and fatal, but it is not these forms with which we are here concerned. Acting the part of a reservoir of the surplus fat stored up in the body, which may be disposed of under normal and physiological conditions, the fatty liver becomes by careful management a normal organ again. The course, duration, and termination will therefore largely depend on the nature of the management pursued. A fatty liver cannot, then, be regarded as fatal, or even as dangerous to life per se. The course and termination will therefore be those of the associated condition.

DIAGNOSIS.—The determination of the existence of fatty liver will not be difficult in all those cases in which this condition may properly be suspected; for example, in phthisis, in chronic alcoholismus, in obesity, and in cases of habitual indulgence in eating and drinking. If in these cases the organ is distinctly enlarged, is smooth, and is flabby in outline; if at the same time the digestion is deranged, the stools are light in color, there are hemorrhoids, flatulence, acid indigestion, and torpid bowels,—a fatty liver may be reasonably suspected. The subjects of fatty liver are usually obese, and present the characteristics typical of that condition, or they are the victims of alcoholismus or present the evidence of habitual indulgence in the pleasures of the table. The differentiation of fatty liver from amyloid degeneration, from cystic disease, and from other maladies causing enlargement of the organ is made by reference to these points in the etiological history—by a careful study of the condition of the organ itself and of the organs associated with it in function. As the amyloid liver is more likely to be confounded with the fatty liver, it should be noted that the former is an outgrowth of the process of suppuration, that the organ is hard in texture, and that amyloid change occurs at the same time in other organs—conditions opposed to those characteristic of the fatty liver. Cancer of the liver is accompanied by a peculiar cachexia; the body wastes, and the enlarged liver is hard and nodular instead of being smooth and flabby.

TREATMENT.—When fatty liver is a symptom merely, its treatment is merged into that of the primary condition. Thus, in phthisis and in the various forms of metallic and phosphorus-poisoning the condition of the liver is quite secondary. There are cases of obesity, however, in which the fatty change in the liver is a part of the general morbid process, and must be treated accordingly. There are still other cases in which, without a decided tendency to obesity, the food habitually consumed is of a fatty or fat-forming nature. The first requisite in the treatment of fatty liver is to amend the diet. From the time of Hippocrates down to Mr. Banting it has been recognized that the starchy and saccharine constituents of the food, as well as the fatty, contribute to the formation of fat. In arranging a dietary in cases of fatty liver this fact should be regarded. Besides excluding the fats, saccharine and starchy substances should be cut off. The diet should be composed of fresh animal foods, game, fish, oysters, and such succulent vegetables as lettuce, celery, spinach, raw cabbage (cole-slaw), etc. Amongst the articles excluded should be bread, but the greatest difficulty is experienced in its withdrawal, many patients declaring themselves unable to live without it. In such instances a small biscuit (water-cracker) may be allowed, but, as far as may be accomplished, bread should be cut off from the diet.

If there are acidity, heartburn, pyrosis, and regurgitation of acid liquid, much good may be expected from the administration of diluted nitric acid before meals, especially if there be considerable uric acid in the urine. The simultaneous administration of tincture of nux vomica will prove useful if the appetite is poor and the digestion feeble. When the complexion is muddy, the conjunctivæ yellow, and the tongue coated, excellent results are had from the persistent use of phosphate of sodium. Under these circumstances also arsenic is very beneficial. Even better results may be had from a combination of the two agents, a teaspoonful of the pulverized phosphate being given with one-fortieth of a grain of the arseniate of sodium. Alkalies, as lithium citrate, solution of potassa, etc., are unquestionably useful as remedies for obesity and fatty liver, but they must be administered with a proper caution. Also, the permanganate of potassium has seemed to the author to be especially valuable as a remedy for these states.

Remedies to increase the activity of the portal circulation and diminish congestion of the hepatic vessels are useful at the outset, but the anæmia which succeeds renders their use improper at a later period. Amongst the hepatic stimulants of great use in those cases characterized by whitish, pasty stools, yellow conjunctivæ, etc., are resin of podophyllin, euonymin, baptisin, and others having the same powers. Saline laxatives are also useful, but to a less extent. It must be remembered, however, that these subjects are wanting in bodily vigor, often suffer from weak heart, and always have flabby muscles, so that they bear all depleting measures badly. The hepatic stimulant of greatest utility in these cases is sulphate of manganese. The writer has had excellent results from a combination of quinine and manganese. For the general state, which denotes insufficient oxidation according to the chemical pathologists, permanganate of potassium is a remedy of value, as above mentioned. The best form in which to administer this is the compressed tablet, and the dose usually is two grains. As chalybeate tonics are indicated, the oxidizing power of the succinate of the ferric peroxide, the remedy so warmly advocated by Buckler, may be utilized with advantage. The combination of quinine, iron, and manganese in pill form, or the syrup of the iodides of iron and manganese, or the phosphate of iron, quinine, and strychnine, are tonics adapted to the relief of the depression accompanying this malady.

III. AFFECTIONS OF THE BILIARY PASSAGES.

Catarrh of the Bile-Ducts.

HISTORY AND DEFINITION.—Although catarrh of the bile-ducts had been incidentally referred to by some previous writers, notably by Stokes of Dublin, Virchow¹⁵⁰ was the first to treat of this condition systematically. Amongst recent writers, Harley¹⁵¹ appears to be the only one disposed to question the importance of catarrh of the bile-ducts as a factor in the production of jaundice. Even in phosphorus-poisoning the appearance of jaundice, at one time supposed to be hæmatogenic in source, has been referred to a catarrh of the bile-ducts.¹⁵² It seems probable that opinions have too decidedly veered toward the importance of this condition as a factor in the production of jaundice.

¹⁵⁰ Archiv für path. Anat., Band xxxii. p. 117 et seq.

¹⁵¹ Diseases of the Liver, supra.

¹⁵² Wyss, Archiv der Heilkunde, 1867, p. 469 (Legg).

CAUSES.—Catarrh of the bile-ducts has been referred to all those causes which can excite a catarrhal process in any situation. These are systemic and local. Amongst the systemic may be placed peculiarities of constitution or idiosyncrasy. A tendency to hepatic disorders is a feature in certain types of constitution, and, as such types are transmitted, the hepatic disorders seem to be inherited. In such persons, possessing the so-called bilious nature, catarrh of the biliary passages is not uncommon, and a special susceptibility to it apparently exists. The atmospherical and other causes which in some subjects will set up a catarrh of the bronchi will in the bilious type induce a catarrh of the duodenum and bile-ducts. The malady is not inherited; only the character of bodily structure which favors it under the necessary conditions.

Climatic changes and certain seasons, especially the autumn, are influential causes. Exposure to cold and dampness, the body warm and perspiring, will set up a catarrhal process in the bile-ducts and intestine, especially in those having the special susceptibility which belongs to certain bodily types. Malarial miasm is an especially active cause in malarial regions. The writer has seen many examples in various parts of the United States within the malaria-breeding zone. Other miasmatic agencies are not without importance. The exhalations from the freshly-upturned soil of some cities, the gases from cesspools and sewers, and illuminating gas exert a causative influence. The bad air thus made up has been happily called civic malaria.

The most influential causes of catarrh of the biliary passages are local in origin and in action: they are the agencies which induce catarrh of the duodenum. Disturbances of the portal circulation should be first named. Whenever obstructive lesions of the cardiac orifices exist, whenever the pulmonary circulation is impeded by disease of the lungs, the portal vein is kept abnormally full, and as a necessary result of the stasis a catarrh of the mucous membrane follows. Congestion of the portal system may be a result of vaso-motor paresis. The abdominal sympathetic may be the seat of various reflex disturbances: those of a depressing kind induce stasis in the portal system. Certain medicinal agents have this effect, and prolonged and severe cutaneous irritation, it is probable, may act on the portal circulation in the same way. The action of cold on the peripheral nerves may be similarly explained.

Catarrh by contiguity of tissue is the most frequent factor. Catarrh of the duodenal mucous membrane is the initial condition, and from thence the process extends to the bile-ducts. Although the duodenum may be alone affected, the usual state of things is a gastro-intestinal catarrh, the stomach and the whole length of the small intestine being simultaneously diseased. When the catarrhal process is thus diffused the duodenal mucous membrane is most deranged, probably because the acid and fermenting chyme is first received here, and what acridity soever it may possess attacks this part in its greatest strength. It must be remembered that the secretion of the duodenal glands and of the pancreas and liver must also have an abnormal character; hence those foods which in the healthy condition of things are digested in this part of the canal undergo ordinary putrefactive decomposition and furnish very irritating products. This observation is especially true of the fats: the fat acids are in the highest degree irritating. The digestive fluid of the duodenum has a more or less pathological character, because the catarrhal process not only interferes with the habitually easy flow of the gland secretions, but, extending to the gland elements themselves, gradually alter their structure.

Gastro-intestinal catarrh results from the misuse of foods and the abuse of certain condiments and of spirits. Excess in the quantity of starchy, saccharine, and fatty foods which undergo conversion and absorption in the intestine, habitually consumed, decomposition of such portions as escape proper digestion ensues, and the products of this decomposition exercise an irritant influence on the mucous membrane. The daily consumption of sauces and condiments and of highly-seasoned foods has a constant irritating action; but more influential than any other causative agency is the abuse of malt liquors and spirit. Whilst the latter acts more on the stomach and the liver proper, the former affect more the duodenal mucous membrane and the bile-ducts.

To these causative agencies must be added a pathological state of the bile itself. Under conditions not now known the bile seems to acquire acrid properties and set up a catarrh in passing along the ducts.

PATHOLOGICAL ANATOMY.—The area affected by the catarrhal process varies greatly. The termination of the common duct for a short space may be the only part affected, but with this there is always more or less, sometimes most extensive and severe, duodenal catarrh, followed by jaundice. The extent to which the common duct is affected may be exactly indicated by the staining with bile, which extends down to the point of obstruction. The catarrhal process may invade the whole extent of the common duct, the cystic duct, gall-bladder, and the ramifications of the tube throughout the organ. The resulting appearances will vary accordingly.

The first change observable is a more or less considerable hyperæmia of the mucous membrane; but this is rarely seen, because the examination cannot be made at the time when this condition is present. The epithelial layer is swollen, sodden, the cells cloudy, undergoing rapid multiplication and desquamating. The cast-off cylindrical epithelium, mucous cells, and serum make up a turbid mixture, which, with bile, fills the smaller ducts, and may in places, especially at the orifice of the common duct, form an obstruction sufficient to prevent the passage of the bile; which may, however, be readily pressed out with a little force. Especially near the end of the common duct the mucus is apt to accumulate, and a plug of it, often tenacious and somewhat consistent, obstructs the orifice. It is probable that whilst catarrh is the chief cause of jaundice, it may also, by a merely intermittent activity, cause the condition of biliousness—now so far relieved as to permit the bile to descend into the intestine, now so much obstruction as to prevent the escape of any considerable part of that formed. When the common duct is the seat of the catarrhal process, and the outflow of bile thus prevented, it accumulates in the gall-bladder, which may be so far distended as to present a recognizable tumor of pyriform shape through the abdominal parietes.

When the catarrhal process invades the finer ducts the appearances are somewhat different. There are no bile-stains along the course of the common and cystic ducts, and the gall-bladder is empty, or at most contains only some mucus, with altered bile. The tubes at or near their ultimate ramifications contain a turbid mucus composed of cylindrical epithelium and lymphoid cells, and tenacious enough to close them firmly. More or less hyperæmia of the liver-structures proper, and consequent increased dimensions of the organ, a more or less active catarrhal condition of the duodenal mucous membrane, accompany the changes in the finer ducts.

SYMPTOMS.—There are marked differences in the behavior of the more acute cases of catarrh of the bile-ducts and the chronic examples of the same disorder. The former is held to be the most frequent cause of jaundice, whilst the latter is an important element in the so-called bilious state, in lithæmia, and as a secondary condition in some cardiac and pulmonary diseases. Also, the morbid complexus of catarrh of the bile-ducts includes the symptoms of duodenal and gastro-duodenal catarrh.

The acute form of this disease sets in with the symptoms of gastro-duodenal catarrh. Usually, after indulgence in too highly stimulating food or in some article having a specially irritating character, an attack of acute indigestion supervenes. The tongue is more or less heavily coated, the breath heavy, the taste bitter, pasty, or sourish, the appetite poor or actual repugnance to food, especially to the offending articles, is experienced, and nausea, not unfrequently vomiting, ensues. The epigastrium and the hypochondriac regions have a heavy, overloaded, distressed, and sore feeling; there is some tenderness to pressure; sometimes the gall-bladder, abnormally full, may be detected by careful palpation; and the area of hepatic dulness will usually be increased. The abdomen is more or less distended by gases, and eructations of offensive gases (hydrogen and sulphur compounds, volatile fat acids, etc.) occur. Constipation exists when the catarrhal process is limited to the duodenum, and the stools consist of hard lumps having a light yellow, clay-colored, or whitish appearance. When the whole extent of the small intestine is affected, the stools will be soft, liquid, or watery, and will vary in color from yellow to gray or white. In some cases the fecal matters will have an offensive odor—the odor of decomposition—and considerable discharges of very foul-smelling gas will attend the evacuations. This symptom will occur when the intestinal digestion is suspended and the contents of the bowel in consequence undergo putrefactive decomposition.

During the initial period of the disorder the urine will simply be high-colored and loaded with urates and uric acid, but when jaundice supervenes the pigment will convert the urine into a dark, coffee-colored, and somewhat thick liquid.

With the onset of the malady symptoms referable to the nervous system appear. Headache, dizziness, and hebetude of mind are present, and now and then an attack of catarrh of the bile-ducts will have the objective signs of an ordinary migraine or sick headache. Usually, however, as the intestinal and hepatic troubles develop, headache and some mental hebetude come on, but when jaundice supervenes the headache becomes more severe, and very considerable mental depression, irritability of temper, and moroseness are experienced. Chilly sensations, with flashes of heat, are felt at the outset, but with the appearance of jaundice the sensation of coldness predominates. In some cases, the intestinal catarrh being extensive, there will be, after some preliminary chilliness, a febrile movement, but this is never of a pronounced character, and in the slighter cases of the disease or when the catarrhal process is limited to the bile-ducts, there is no elevation of temperature. With the first symptoms the pulse is somewhat quickened, but as the bile acids accumulate in the blood they effect a decided slowing of the heart's action, the pulse falling as low, it may be, as 50 per minute. This lessened activity of the circulation is accompanied by corresponding reduction of temperature, the body-heat falling a degree or more.

The most distinctive symptom of catarrh of the bile-ducts is jaundice. In the acute or quickly-developing form above described of catarrhal icterus the symptoms of gastro-intestinal disturbance precede the first indication of jaundice from five to eight days. Yellowness of the conjunctiva and of those parts of the body exposed to the air is the first manifestation; afterward the jaundice hue becomes general. The tint varies in depth from a faint gamboge-yellow, only discernible in a favorable light, to a deep greenish- or brownish-yellow.

In the more chronic cases of catarrh of the bile-ducts the symptoms are simply those of a gastro-duodenal catarrh, to which some hepatic disturbances are superadded. Some abdominal uneasiness felt in the epigastrium and in the right hypochondrium, especially in two to three hours after meals; flatulence, sometimes accompanied by colic; constipation, persistent or alternating with diarrhoea—in the one case in hard lumps with more or less mucus adherent, in the other soft or liquid, and in both cases having a rather golden-yellow color, grayish or black and tar-like appearance,—such are the symptoms referable to the intestinal canal. The disturbances in the hepatic functions produced by the catarrhal swelling of the mucous membrane of the ducts are further exhibited in a somewhat sallow, earthy, or muddy complexion, yellowish tint of the conjunctiva, high-colored, acid urine loaded with urates and phosphates. Such subjects, although having, it may be, a keen appetite, rather lose than gain in weight: they experience lassitude, headache, much depression of spirits, and the mental symptoms are most pronounced during the time intestinal digestion is going on. In fact, the morbid complexus is rather that of intestinal catarrh; nevertheless, the slight degree of obstruction to the outflow of bile occurring in these cases has an influence both in the intestinal digestion and in the nutritive functions. Any degree of obstruction, as has already been pointed out, leads to serious structural change of the liver, and this in turn produces well-defined symptoms.

Disturbances of the hepatic functions, even jaundice, accompany the paroxysms of malarial fever. Without the occurrence of fever, catarrhal jaundice may come on during the course of chronic malarial poisoning. Catarrh of the bile-ducts is the pathogenetic factor in these cases. More especially in malarial regions, but also in temperate and warm climates, paroxysmal attacks, with or without jaundice, are comparatively frequent. These acute seizures occur in those having the chronic form of the malady, and are excited by sudden climatic changes, by excesses in eating, especially by the use of improper articles of diet. Considerable nausea, flatulence, and constipation or diarrhoea, weight, tension, and soreness in the right hypochondrium and sometimes in the shoulder, chilliness, general malaise, headache, and an increasing icterode tint of the skin, constitute the complexus of symptoms belonging to these cases.

COURSE, DURATION, AND TERMINATION.—Acute catarrh of the bile-ducts with jaundice has a well-defined course—in its mildest form, with little gastric or gastro-intestinal disturbance—lasting ten days or two weeks; in the ordinary form, with the accompanying gastro-duodenal catarrh, running its course in a month to six weeks. In the chronic form, with acute exacerbations due to indiscretions in diet or to climatic influences, the course of the disease is chequered by vicissitudes, the result of the causes just mentioned, and its duration must therefore be indefinite and, as a rule, protracted. Catarrh of the bile-ducts, or catarrhal jaundice, usually terminates in health after a period of functional derangement of the intestines and liver. Without exhibiting any features of a special character, some cases do not pass through this benign course: the intestinal catarrh sets up an ulcerative process at one or more points in the duodenum; but more especially the obstruction to the free course of the bile caused by the catarrhal swelling of the mucous lining of the ducts induces structural changes in the liver—an hypertrophy of the connective-tissue elements, a sclerosis.

DIAGNOSIS.—There are but two signs which indicate the nature of the disorder, and only one that is really distinctive. Intestinal indigestion with slight coincident biliary derangement is one, and jaundice is the other. When, after the signs and symptoms of gastro-duodenal catarrh have declared themselves, jaundice appears, there can be no question as to the nature of the case. The diagnosis is more difficult in the chronic cases with exacerbations due to the exciting causes above mentioned, for the persistence of the jaundice will suggest the occurrence of some permanent organic lesion. The differentiation of the various kinds of jaundice has already been made.

TREATMENT.—Regulation of the diet is of the first importance. Those foods requiring the intestinal juices for their solution and absorption, and which cannot be properly digested when a duodenal catarrh exists or when bile is absent, should of course be excluded from the diet. These articles are the fats, starches, and sweets. The mucus playing the part of a ferment, these substances are converted into various secondary products of an irritating character. Flatulence is caused by the evolution of carbonic acid gas and the hydrogen compounds of sulphur and phosphorus; and acetic, butyric, and other acids not only change the reaction of the intestinal juices, but are directly irritating to the mucous membrane. In the acute cases a diet of skimmed milk, taken hot and at three hours' interval, and after the acute symptoms have subsided, in conjunction with some other aliment, is the most appropriate mode of alimentation. Meats, fish, eggs, and oysters are the chief articles of diet, besides the milk, during the whole course of the more chronic cases; and to these may be added the succulent vegetables, as lettuce, spinach, celery, raw cabbage, and tomatoes. If, in consequence of irritability of the mucous membrane or of idiosyncrasy, any article occasions distress, it should be omitted from the diet.

The medicinal management includes the administration of remedies for gastro-intestinal catarrh. The treatment of catarrhal jaundice has been discussed. When constipation exists, saline laxatives, especially phosphate of sodium and Rochelle salt, are useful. If there be diarrhoea, the most appropriate remedies are bismuth, with or without carbolic acid, Hope's mixture, oxides of zinc and silver, and other mineral tonic astringents.

The propriety of the administration of special hepatic stimulants—cholagogues—has been much disputed. When the disorder consists merely in an obstruction to the outflow of bile, the utility of stimulating the production of this secretion seems more than doubtful. Much harm has been done by the indiscriminate use of mercury. Its power to increase the production of bile having been assumed, and the quantity of bile present in the feces being manifestly less in cases of catarrhal jaundice, it followed that mercury should be employed in this disorder. Modern experience has quite demonstrated its inutility in the mode and for the purpose to which it was formerly devoted. Nevertheless, good effects are had from calomel in small doses as a sedative to the mucous membrane. When there are nausea, headache, vertigo, and constipation present, excellent results may be had from the ¹/20 gr. to ¹/10 gr. of calomel, exhibited at short intervals until the bowels are moved. If calomel possessed the property formerly ascribed to it, of stimulating the hepatic functions, it would be contraindicated in catarrh of the bile-ducts. This contraindication exists in respect to all hepatic stimulants.

If there be decided irritability of the stomach and constipation, Seidlitz powders may be given at regular intervals. Phosphate of sodium in drachm doses is highly useful for the double purpose of a laxative effect and to prevent the tendency to inspissation of the bile, which is one of the most important results of catarrh of the bile-ducts and gall-bladder. In the more chronic cases the persistent use of sodium phosphate is to be highly commended.

In this disease, especially as it occurs in gouty subjects, sulphate of manganese is often decidedly serviceable. If anæmia and debility coexist, this remedy can be combined with sulphate of iron and sulphate of quinine—a combination which the writer has found peculiarly effective under such circumstances. When oxidation is deficient and the urates are present in the urine in excessive quantity, good effects are had from the permanganate of potassium, a tablet containing two grains being given four times a day. In the more chronic cases the salts of silver, copper, and zinc are really very useful, especially the oxides of silver and zinc; and of these the former is more efficient. Better than any of those mentioned is arsenic, as arseniate of sodium or as Fowler's solution, but the best results are had from small or medium doses persistently used. If there be much intestinal catarrh and consequent diarrhoea, bismuth and aromatic powder, oxide of silver, Fowler's solution with a little opium, Hope's mixture, etc. are appropriate remedies.

It is in catarrh of the bile-ducts that nitric and nitro-muriatic acids have proved useful, rather than in cirrhosis and other diseases of the liver-tissues. They prevent fermentation, promote oxidation, and increase the activity of the assimilative functions. When there occurs active fermentation of certain foods, and consequently considerable flatulence, excellent results are obtained from the members of the antiseptic group—from creasote or carbolic acid, salicylic acid, biborate of sodium, the benzoates, etc. To these may be added quinine, the dose of which will be determined by the purpose for which it is prescribed. So often is catarrhal jaundice of malarial origin that quinine becomes a remedy of high importance in the cases occurring in the malarial-forming zone.

Certain special plans of treatment have been proposed for the cure of catarrhal jaundice. One of the most effective of these is enemata of cold water. By means of an irrigating apparatus the large intestine is well distended with water once a day for several days. The first enema has a temperature of 60° F., and subsequent injections are a little warmer. The increased peristalsis of the bowels and the reflex contractions of the gall-bladder dislodge the mucus lining and obstructing the gall-ducts. When the bile flows into the intestine, digestion is resumed and the catarrhal inflammation subsides. But with the irrigation method may be employed other remedies, as above indicated.

Faradization of the gall-bladder has been used successfully for the expulsion of the stored-up bile and the removal of the mucus obstructing the ducts. It is applied by means of one moistened sponge electrode placed directly over the gall-bladder, and the other on the opposite side of the body and posteriorly. A slowly-interrupted faradic current is then passed. This expedient is not suitable when the case is acute in character.

Biliary Concretions; Gall-Stones; Hepatic Calculi; Hepatic Colic.

DEFINITION.—There are two classes of concretions which may occasion symptoms: inspissated bile and regularly-formed gall-stones. Slowly-developing symptoms of jaundice from obstruction may arise from the deposit of particles of inspissated bile in the hepatic ducts, or sudden attacks of hepatic colic be due to the passage of concretions. When biliary calculi reach the intestines, certain kinds of disturbance may be caused by their presence there. Under the term biliary concretions must be considered, therefore, the mechanism of their production, their composition, the symptoms caused by their passage through the ducts (hepatic colic), and the intestinal disturbance due to their retention in the bowel.

Formation: Inspissated Bile.—Those concretions consisting of inspissated bile are irregularly-shaped masses of a brownish, greenish-brown, or reddish-brown color, friable and crumbling into a gritty dust with slight pressure of the fingers. When recent and before drying, they are softer, almost pultaceous, and may take the form of the canal through which pressed. But as seen after drying they present the appearance of a dark vegetable extract, dried and partly pulverized. When examined as found in the gall-bladder or lodged in the larger hepatic ducts or distributed in irregular fragments (gall-sand) in the various hepatic passages, they present the shape, color, and general characteristics of a partly-dried vegetable extract roughly broken up, but still soft enough to take any shape from pressure. The writer has seen them thus in situ accompanying regularly-formed gall-stones in a case of gunshot wound of the liver. These masses of inspissated bile differ from gall-stones in composition; they consist of bile, but with a preponderance of the coloring matter. According to Harley,¹⁵³ who has given a more correct account of these bodies than any other systematic writer, their composition is as follows:

Water 5.4

Solids 94.6

The contents of the solids are—

Bile-pigment 84.2

Cholesterin 0.6

Salts (iron, potash, soda) 15.2

¹⁵³ The Diseases of the Liver, with and without Jaundice, etc., by George Harley, M.D., F.R.S., Philada., 1883, p. 349.

Some years ago, before I was aware of the nature of such concretions. I detected a number in examining the stools of a patient who had in quick succession many attacks of hepatic colic, but as the usual form of concretion was looked for and not found, the relation of these bodies to the symptoms in the case was not understood. I now recognize the value of Harley's observations on these bodies.

The biliary concretion which is properly a gall-stone has a definite form and a more or less well-defined crystalline structure. The forms taken are various. The most usual form is octagonal or hexagonal or polyangular, with smooth facets, corresponding to points of contact of other calculi. Instead of smooth facets and sharp angles, the concretion may be studded with irregularly-shaped masses. When there are numerous calculi present, they have smooth surfaces and rather sharp angles, made, not by attrition, as has been supposed, but by deposition of the new material under pressure. When they have this form there are many present, but the number of facets does not indicate the number of calculi, and the absence of facets is not proof of the absence of other calculi. The smooth opposing surfaces are not always plane, but may be convex or concave to fit the shape of the adjacent bodies.

Calculi may be globular, ovoid, cylindrical, and truncated cones. The largest in my collection is egg-shaped, and nearly filled the gall-bladder which contained it, a little mucus free from bile-elements only being present. If a concretion forms in a duct or a single one is present in the gall-bladder, the shape is determined by the pressure of the walls of the duct or of the gall-bladder, respectively. As found in the stools, and still somewhat soft, the shape will represent the form of the common duct through which it has been pressed. Such a soft, recently-formed gall-stone will have the crystalline structure and chemical constitution of these bodies, and will therefore differ from, apparently, similar masses of inspissated bile. Although a round, ovoid, or cylindrical calculus indicates the absence of others because there are no evidences of mutual pressure and adaptation, a positive conclusion cannot be reached in that way, for the gall-bladder may contain numerous calculi of long-standing, and a recent concretion formed in a duct be discharged with the usual symptoms.

The number of calculi which may be present at any time or be produced in the course of years ranges from one to several thousand. The number is in inverse ratio to the size. One case¹⁵⁴ is reported in which 7802 calculi were found in the gall-bladder, but they must have been very minute in size. Of the specimens now in my collection, there are 230 obtained from one gall-bladder, which they entirely filled; they are nearly uniform in size, have an average weight of two grains, and contain four, five, and six smooth facets. Another collection of calculi removed from a closed gall-bladder contains 45, of large size, distending the organ and forming a tumor which projected beyond the margin of the liver. Hepatic calculi are rarely solitary; hence if one attack of hepatic colic occur, others may be expected.

¹⁵⁴ Frerichs, op. cit., vol. ii. p. 499.

In color gall-stones vary from a clear white to a dark-brown, almost black, tint. The most usual tint of the mature calculi in the gall-bladder is that of the ripe chestnut. Long stay in the intestines increases the depth of the color, until it becomes almost black; on the other hand, detention in the gall-bladder has a slightly bleaching action; but the real cause of difference of color is the presence or absence of pigment. If composed of pure cholesterin, the color will be whitish, opaque, or glistening and almost translucent.

In size gall-stones vary from the smallest pea up to a hen's egg. When several hundreds are contained in the gall-bladder, they will usually be of the dimension of a medium-sized pea. Two large solitary concretions in my possession are respectively 2 inches and 1½ inches in long diameter, and 1 inch and ¾ of an inch transversely. Very much larger calculi have, however, been recorded; thus, one mentioned by Frerichs is 5 inches in length and 4 inches in circumference. The most frequently encountered calculus, at least in this country, is polyangular in shape and of the size of a large pea. Globular or ovoid seems to be the prevailing form, and the dimensions that of a small pea, in Germany, according to Frerichs and Von Schüppel, but this statement must refer to the initial shape of these bodies.

Not all hepatic calculi have defined mathematical forms, but may consist of branching cylinders composed of irregular nodular masses, not unlike the concretions of inspissated bile. As a rule, in each case where the calculi are multiple there is uniformity of color, shape, and composition. This feature is well exhibited in my collection. The calculi obtained from each subject are in one case white, polyangular, rather unctuous, and nearly equal in size; in another, chestnut-brown in color, polyangular in shape, and varying slightly in size, but uniformly characteristic in shape; and in a third, singular in number, ovoid in shape, dark-brown in color.

In composition gall-stones vary somewhat. When fresh they contain considerable water, and at all times are hygroscopic. Dried in the air, they are composed of—

Water 4

Solids 96

100

The solids consist of—

Cholesterin 98

Pigment 1

Inorganic or mineral matter 1

100

Such are the constituents, according to Harley, of the usual concretion, the cholesterin calculus. But as other varieties are encountered occasionally, it may be well to give the composition of these. The following table by Ritter, to be found in Robin's Journal for 1872 (p. 60), is a correct representation of the contents of different specimens:

Composition of Different Kinds. 1st. 2d. 3d. 4th. 5th. 6th. 7th. 8th.

Cholesterin 98.1 97.4 70.6 64.2 81.4 84.3 trace. 0

Organic matter 1.5 2.1 22.9 27.4 15.4 12.4 75.2 18.1

Inorganic matter 0.4 0.5 6.5 8.4 3.2 3.3 24.8 91.9

Number of specimens 28 16 580 94 220 16 3 1

The above may be regarded as the average composition, expressed in round numbers. The variations from these figures will be comprehended in two parts.

A calculus consists of three several parts: the nucleus, the body, the rind. A calculus of small or medium size may be a nucleus for the formation of a large one. Usually the nucleus consists of a bit of mucus, casts of the biliary ducts (Thudicum), inspissated bile, a blood-clot, a liver-fluke or other parasite, as a desiccated round-worm, or some foreign body, as a seed, or, as in one reported example, a globule of mercury.¹⁵⁵ The central mass of mucus may contain a large proportion of pigment or crystals of cholesterin or lime-salts, giving it special characteristics.¹⁵⁶ There may be several nuclei. Fauconneau-Dufresne reports an instance in which a pyramidal concretion contained four, and Guilbert a globular stone with five, distinct nuclei. Such examples of calculi having multiple nuclei are produced by the adhesion whilst in a soft state of two or more, and the subsequent addition of material to the conjoint mass, welding it into a single stone. A few calculi are homogeneous throughout, composed of nearly pure cholesterin, mixed intimately with a little coloring matter and lime salts. The cholesterin calculus will have a somewhat translucent appearance, will be a dead white or a yellowish-white, or present a greenish- or brownish-yellow tint through the white. Even the white calculus, apparently composed of nearly pure cholesterin, will be found on section to contain traces of a nucleus. By long detention in a gall-bladder whose duct is permanently occluded, and is therefore free of fluid, the mucus nucleus may so shrivel as to leave a cavity which is merely stained. One of my specimens—a solitary calculus of large size—exhibits this peculiarity.

¹⁵⁵ Thudicum, J. L., On Gall-stones, London, 1863; also Frerichs, op. cit., vol. ii. p. 503.

¹⁵⁶ Cyr, Jules, Traité de l'Affection calculeuse du Foie, Paris, 1884, p. 11 et seq.

The body consists of cholesterin, nacreous or darkened by pigment, deposited in radiating lines or in concentric layers, or in both together. Pigment may be intimately incorporated with the cholesterin or deposited between the layers of this substance, pure or nearly pure, forming an alternating arrangement.

The crust or rind usually is smooth, unctuous to the touch, firm, but when broken with the finger-nail readily crumbles. When composed of lime salts, or when the cholesterin is mixed with varying proportions of these salts and of pigment, the surface is still smooth, but thicker, firmer, and darker in color. The rind may not be smooth, but studded with wart-like projections, or it may consist of several layers of earthy matter separated by pigment. These layers may be very friable, and readily crumble and fall off. In some instances the crust, several lines in thickness, is the body of the calculus, and the cavity contains only a light honeycomb of mucus and pigment.

The specific gravity of gall-stones composed of crystallized cholesterin is nearly that of water. Air-dried calculi will float on water, but the recent ones, full of moisture, sink. The relation of the weight of the calculus to that of the bile is more important. As the specific gravity of bile ranges from 1020 to 1026, it is obvious that on this fluid air-dried calculi will float, but, holding in the recent state much water, ordinary gall-stones will sink. Those containing much mineral matter will have a correspondingly high specific gravity—much higher than bile.

ORIGIN AND FORMATION OF HEPATIC CALCULI.—Certain conditions are necessary to the formation of these bodies on the part of the bile and on the part of the gall-bladder and ducts. Constituted for the most part of cholesterin, which exists in such small quantity in normal bile, there must be some change in the composition of this fluid to increase the quantity or to diminish the solubility of that constituent. It will conduce to a better understanding of the subject to premise the composition of the bile:

Bile contains, in 1000 parts,

Water 860

Solids 140

The solids of bile are,

Glycocholate and Taurocholate of soda 90.8

Fat 9.2

Cholesterin 2.6

Mucus 1.4

Pigment and extractive 28.0

Salts 8.0

140.0

Normal bile is neutral or slightly alkaline in reaction. If the reaction become acid from any cause, the constituent cholesterin is precipitated; and this occurs the more readily the larger the proportion of this substance held in solution. Cholesterin is an excrementitious material found in the blood and excreted by the liver. It represents in part, probably, the waste of nervous matter, but more certainly of the fatty tissues in general. Conditions of the system in which the metamorphosis of the fatty elements occurs more freely—as obesity, advancing life, etc.—are accompanied by an increased production and excretion of cholesterin.

So long as the neutral state or the alkalinity of the bile is maintained, the cholesterin will be kept in solution, although its relative proportion may be in excess of the normal. A lack of the soda constituent of the system is one factor, but the most important is a catarrhal state of the mucous membrane of the bile-ducts and gall-bladder. The mucus formed plays a double rôle: it furnishes a nucleus about which cholesterin crystallizes; it acts as a ferment and inaugurates a process of acid fermentation which results in the precipitation of cholesterin. When all the conditions favorable to the separation and crystallization of cholesterin are present, any foreign body may serve the purpose of a nucleus. The articles which have thus served have been enumerated.