A system of practical medicine. By American authors. Vol. 2

by Unknown

DISEASES OF THE LIVER.

BY ROBERTS BARTHOLOW, A.M., M.D., LL.D.

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I. FUNCTIONAL DISORDERS.

Biliousness.

DEFINITION.—The term biliousness is used to signify a disturbance of the gastro-intestinal digestion, with coincident excess in the production of bile. According to the popular conception, both lay and medical, the excess of bile is the cause of the symptoms; but when the whole subject is carefully examined it will be found that biliousness is made up of several factors, and that the hepatic disorder, if it exist at all, is a mere incident.

PATHOGENY.—From the time of Galen biliousness has been regarded as a morbid entity and the liver as the organ affected. Stoll, amongst moderns, first revived the Galenical doctrines. Abernethy¹ was amongst English physicians the most conspicuous advocate of the condition called biliousness, and was the apostle of blue pill and black draught. Copland in his great dictionary² more distinctly formulated the views of the English school—especially that portion of it influenced by the results of Indian practice—than had been previously attempted, and hence his work best represents the opinions and practice of the time amongst the English-speaking peoples. In this country the great Rush first promulgated the notions of biliousness which have since so dominated the medical opinion of this continent. A large part of the United States has proved a fruitful soil for the cultivation of theories of biliousness, since the condition known under this name is a frequent accompaniment of malarial poisoning. To this fact must be attributed the preponderating importance of biliary derangements in the practice of the physicians of India also.

¹ Surgical Works, London, 1811, vol. i. p. 36.

² A Dictionary of Practical Medicine, vol. ii. p. 723.

It is a fact which will be hereafter more fully developed that malarial infection may, and often does, derange the hepatic functions without producing fever. The malarial poison irritates the liver, and thus more bile is produced, but the quality deteriorates with the increase in quantity. The functions of the liver are more disturbed during an access of intermittent fever: the organ is swollen, the skin is muddy, the eyes yellow, the tongue coated with a thick yellow fur, and the urine is deeply tinged with bile-pigment.

Many of the metals employed as medicines and as poisons, as gold, silver, antimony, arsenic, phosphorus, etc., irritate the liver both in their entrance and in their exit from the organism, and cause biliousness; and the same fact is true of some vegetable alkaloids and animal poisons. The liver excretes many of these substances, and in their passage out from the blood the hepatic cells are irritated and an increased production of bile is a result. Improper food, indulgence in fats, sweets, condiments, and all kinds of fermented and alcoholic liquors, intestinal indigestion arising from any cause, and gastro-duodenal catarrh, are the most usual and obvious pathogenic factors. In respect to food and indigestion as etiological factors there are several points requiring more explicit statement. When nitrogenous elements (albuminoids) are in excess in quantity or as respects the power to digest and convert them, immature products, of which uric acid is the chief, accumulate in the blood. When the fats, sugars, and starches are in excess of the requirements of the organism or are imperfectly disposed of in the small intestines, a local irritation of the mucous membrane is produced, and various complicated, immature products enter the blood. With these troubles and faults of intestinal digestion a gastro-duodenal catarrh is usually associated. Without the production of catarrhal jaundice, gastro-duodenal catarrh, with the forms of indigestion accompanying it, keeps up a reflex irritation of the liver. Just as the presence of normal chyme induces the flow of bile, so the unhealthy products of intestinal indigestion excite an irritation of the liver. The continued operation of this cause maintains an abnormal activity of the liver, and more bile is produced than is easily disposed of.

SYMPTOMS.—The condition of biliousness, as now understood, is made up of derangement of the gastro-duodenal mucous membrane, with bile-production in excess and bile-absorption probably delayed. The symptoms are the product of these complicated conditions. The complexion is muddy; the conjunctivæ are yellow; the tongue is heavily coated with a yellowish-white fur; a bitter taste persists in the mouth; the breath is heavy in odor, even fetid; the appetite may be keen or there may be complete anorexia; a sensation of nausea, of heaviness, and fulness of the stomach is experienced, especially after eating; the bowels are confined usually, but occasionally the movements are relaxed, bilious in appearance, and cause heat and irritation about the anus; headache is constantly present to some extent, and there is a sense of fulness with more or less dizziness, and singing in the ears; vision is rather blurred, and there is a hebetude of mind; the urine is high-colored, high in specific gravity, and deposits lithates abundantly on cooling. When these symptoms are conjoined with hemicrania, nausea, and vomiting, the case is called bilious sick headache, and when diarrhoea supervenes, the discharges apparently containing much bile, it is bilious diarrhoea. The symptoms which above all others give the character to the morbid complexus are the muddy (bilious) complexion, the yellow-coated tongue, the yellow conjunctivæ, and the high-colored urine. The first departure from the normal may be scarcely observed. Gradually, owing chiefly to errors of diet, to climatic changes, or to malarial influences, or to these several factors combined, the affected person drifts into the condition of biliousness above described. Besides the general malaise, he experiences no little despondency, inaptitude for exertion, and indeed actual weakness. Finally, he is unable to apply himself to business, relinquishes the effort, and seeks advice.

COURSE, DURATION, AND TERMINATION.—Those who are accustomed to experience attacks of biliousness suffer from them at certain intervals which may be tolerably regular—at intervals of a few days, two, three, or four weeks—when the cause is uniform; but they may happen very irregularly when the conditions producing them are variable. The duration of an attack is from two days to a week or more, according to the severity of the symptoms and to the character of the measures instituted for relief. The termination is in a return to the normal state. If the conditions which produced it continue, when one attack is ended the preparations for another begin at once, and at length sufficient derangement of the organs concerned arises to constitute the morbid complexus of biliousness.

TREATMENT.—Prophylaxis has great importance, since the causes of the malady are to a considerable extent, at least, preventable. Errors of diet in respect to the use of condiments, fats, meat, pastry, etc. must be corrected. When there is pronounced gastro-duodenal catarrh and acid fermentation in the duodenum, the saccharine, fatty, and starchy elements of the food must rather be excluded and lean meats allowed. Abundant exercise, bathing, and an open-air life in general should be directed. Whenever a malarial infection is causative a change of climate becomes imperative. Heredity cannot, of course, be excluded, but the tendency to hepatic derangement can be rendered inoperative by an abstemious life.

The remedial management includes the dietetic as well as the medicinal treatment. When the distress has reached sufficient proportions to justify such an extreme measure, the patient should be restricted to a diet exclusively of skimmed milk, of which he is directed to take a gill or more every three hours. This serves a double purpose, as aliment and as a depurative agent, for this considerable quantity of fluid promotes the urinary excretion and the elimination of waste products. If the case is not severe enough to allow of such an expedient, the diet should in any event be restricted to skimmed milk hot, milk and hot water, hot lemonade, a little chicken or mutton broth, a bit of dry toast, etc. As a rule, although not so palatable, hot drinks are more beneficial than cold, but if the preference is decidedly for cold, they may be allowed. After the more severe symptoms have subsided a little lean meat broiled may be added, and as the cure proceeds the succulent vegetables and acid fruits may be permitted. Abstinence from potatoes, hominy, cracked wheat, and oatmeal should be enjoined during the convalescence of those who suffer from habitual attacks.

Medicines may not be necessary to those who have the resolution to adhere to skimmed milk for several days or who can abstain from food altogether for a day. Many experienced sufferers, especially through the South and West and in England, procure rather prompt relief from a blue pill of ten to fifteen grains or from one to five grains of calomel at night, followed by a Seidlitz powder, Rochelle or Epsom salts, or phosphate of soda on the following morning. Such patients find that no other treatment is as serviceable. They get relief from other measures, it is true, but neither as promptly nor as satisfactorily. It is held by the advocates of this practice that the mercurial acts on the liver—that the surplus bile is carried off; and they point to the peculiar stools and to the relief experienced in evidence of the truth of this theory. Without entering on the argument, which would occupy too much space, it must suffice here to state that calomel and blue pill do not increase bile-production,³ but they do stimulate the intestinal glands and increase excretion from them. The peculiar greenish stools produced by these mercurials do not owe their characteristic appearance to the presence of bile, but rather to the chemical transformations of the mercury itself and to the waste products excreted by the intestinal glands. Since the researches of Rutherford have been published, euonymin has been much prescribed in cases of biliousness. From three to five grains are taken at the bed-hour, and a mild laxative in the morning. In the same group of cholagogues are ipecac, iridin, sanguinarin, and especially podophyllin; but the serious objection to their use is that they stimulate the liver when this organ is in an irritable state. As calomel and blue pill have a sedative rather than a stimulant action on the liver, they are more useful in biliousness than are the true cholagogues. It should be borne in mind that one-half of a grain of calomel will have a distinct purgative action on many persons, and that one grain will rarely need to be exceeded.

³ That calomel, the type of a mercurial purgative, does not increase the discharge of bile has been demonstrated on dogs by Röhrig and Rutherford, and confirmed by observation of the effects of 20 grains on Westphalen's case of biliary fistula in man—a case in which, for a time, all the bile escaped externally, and none apparently entered the intestine (Deutsch. Archiv f. klin. Med., 1873, Band xi. pp. 598 and 600).

In general, notwithstanding the unquestionable utility of the mercurial, it is better to relieve cases of biliousness by less objectionable measures. A saline which acts at the same time on the intestines and kidneys, as Rochelle salts, is usually effective in bringing relief. A bottle of solution of magnesia citrate, of Saratoga water (Congress, Hathorn, or High Rock), and of Blue Lick, the famous sulphurous laxative of Kentucky, may remove the disorder in mild cases if at the same time a suitable diet is enjoined. Phosphate of soda in laxative doses, with or without Vichy water, is also a good remedy, if somewhat slow. The warm purgatives, rhubarb, colocynth, aloes, etc., are useful when there is pronounced constipation.

Lithæmia.

DEFINITION.—By the term lithæmia is meant a condition of the system in which uric (lithic) acid is produced in excess, and in which certain derangements occur in consequence of the accumulation of this material in the blood. Uricæmia was the term first suggested by Flint, Sr.,⁴ to express this state, and subsequently lithæmia was employed by Murchison.⁵ The latter has been more generally accepted. In one of the most recent and valuable contributions to this subject by DaCosta⁶ lithæmia is the term used to designate the complex of symptoms produced by uric acid in excess.

⁴ The Principles and Practice of Medicine, Philada., 1882.

⁵ Clinical Lectures on Diseases of the Liver, 2d ed., p. 565.

⁶ The Medical News, vol. ii., 1883.

PATHOGENY.—The ultimate product of albuminoid substances in the organism prepared for final excretion is urea. That this substance is finally formed in the liver, to be excreted by the kidneys, seems now well established.⁷ In acute yellow atrophy of the liver, with the disappearance of the proper structure of the organs urea ceases to be produced, and instead leucin and tyrosin are excreted. In certain states of the system characterized by deficient oxidation urea is not sufficiently formed, and instead uric acid, a lower grade of oxidation and a product of the disintegration of albuminoid substances, results. An excess of urates is not always pathological. Their excretion seems to be in a certain sense a safety-valve function. When albuminoid matters are taken in excess of the power of the system to convert them, or when the supply of oxygen to the blood is deficient from any cause, urea is not formed, but uric acid and urates are abundantly excreted by the urine.⁸ Imperfect digestion of the albuminoids when they are not taken in relatively too large an amount, and limitation below the normal of the oxidation process when the supply of oxygen is not insufficient, will have the same effect: in place of urea, uric acid and urates will be formed and excreted. One of the early results of the persistent presence of an excess of uric acid is the production of lithæmia, the morbid complexus of which this excess is at once the cause and the proof.

⁷ This proposition is not universally accepted. Valmont (Thèse de Paris, Étude sur les Causes des Variations de l'Urée dans quelques Maladies du Foie, 1879) has carefully studied the excretion of urea in several diseases in which the proper structure of the liver is damaged—in atrophic cirrhosis and in cancer. As in these maladies not all the secreting portion of the organ is destroyed, the argument is so far weakened. His conclusions are as follows: "1. Patients with cirrhosis or cancer of the liver who eat little excrete but little urea. If they eat and do not absorb, or vomit or have diarrhoea, the result is the same. When they partake largely of nitrogenous aliment the proportion of urea rapidly increases. 2. In a cachectic or simply anæmic patient the urea falls, apparently in proportion to the state of the general nutrition and of the work done by the organic functions. 3. Absolute immobility of the patient seems to have an influence on the amount of urea excreted. 4. In sclerosis or cancer the quantity of urea falls rapidly on the occurrence of ascites or oedema, when a notable quantity of urea is found in the fluid. 5. The digitalis often used in the treatment also contributed to the loss of urea." If these conclusions are verified, the formation of urea must depend on some other function.

⁸ Genevoix, Essai sur les Variations de l'Urée et de l'Acide urique dans les Maladies du Foie, Paris, 1876.

The persons who suffer from lithæmia are usually those who indulge in the pleasures of the table and habitually consume much meat, pastry, and highly-seasoned and rich food of all kinds. The idle, luxurious, and indolent, literary men of sedentary habits, men who have led active lives, but on retiring from business have continued to indulge in a full diet, are apt to suffer from this malady. Women are less disposed to it, but if subjected to the same conditions may also be similarly affected. Especially do those suffer from lithæmia who indulge in malt liquors or in alcoholic drinks of any kind. These substances act by deranging digestion, and thus preventing the proper conversion of the albuminoids, by inducing congestion of the liver, and also by interfering with the process of oxidation.

SYMPTOMS.—The symptoms of lithæmia include derangements of the digestive organs and of the liver, of the circulation, and of the nervous system. As these subjects suffer from gastric and gastro-duodenal catarrh, they present the usual symptomatology of these affections, as a sense of weight and oppression at the epigastrium, acidity, pyrosis, a capricious—sometimes voracious, sometimes good—appetite, a coated tongue, a bitter taste, etc. The bowels are irregular, sometimes constipated, occasionally relaxed, with scybalæ. The stools may be liquid, almost black or light-yellow and grayish. The motions are apt to be offensive, and a good deal of offensive gas is discharged with them. Hemorrhoids are often present, and there may be heat and irritation about the anus, and not unfrequently intolerable itching. After meals there is much depression, and often an insupportable drowsiness. Irregularity in the rhythm, even intermissions, of the pulse are not infrequent.

The nervous symptoms, as DaCosta has lately insisted on, are the most important and pronounced. The connection between oxaluria and mental despondency has long been known, but the nature of the relation remains undetermined. Headache, frontal and occipital, especially the former, dizziness, tinnitus aurium, suffusion of the eyes, ecchymoses of the conjunctiva, are usually present. Not unfrequently the subjects of this affection experience sudden attacks of vertigo, accompanied by dimness of vision and intense headache, and are supposed to have some organic lesion of the brain. They are irritable, despondent, and often intensely hypochondriacal, almost suicidal—are subject to neuralgic attacks, and have aching in the limbs, a sense of weariness, and more or less burning in the palms and soles.

The skin is rather dry and the complexion muddy. Urticaria is of frequent occurrence, and sudden attacks of nausea, vomiting, and intestinal pain coincide with the appearance of the eruption on the skin.

The urine is usually rather increased in amount, its color heightened, its acidity above normal, and floating in it, usually visible to the naked eye, are reddish masses composed of uric acid. More or less pain in the back, referable to the situation of the kidneys, and sometimes extending along the course of the ureters, is common. The bladder is rather irritable, and the passage of the urine produces heat and scalding. The testicles are apt to feel sore and are somewhat retracted. On standing, the urine may deposit uric acid and the urates copiously, or the acid may be seen to form a cloud which slowly subsides.

COURSE, DURATION, AND TERMINATION.—The course and duration of lithæmia are much influenced by the habits of life of the person affected. When unopposed by treatment and no change is made in the conditions producing it, a gradual increase in the various disturbances takes place. After a time structural changes occur in the liver; the organs of circulation early undergo atheromatous degeneration; various cerebral disorders due to degenerative changes arise; and acute intercurrent affections may terminate life. Amongst the secondary maladies due to lithæmia are gout, diabetes, renal calculi, and nephritic colic. If the cases are subjected to appropriate treatment, curative results may be certainly obtained. The prognosis, then, will be influenced materially by the moral strength of the patient. If he is one who can surrender his appetites and live abstemiously, a cure may be promised. The case is far different with those who will continue the use of malt, vinous, or alcoholic drinks, and will persist in indulging in the pleasures of the table.

DIAGNOSIS.—The differentiation of lithæmia from other affections offers no special difficulties. From gastro-duodenal catarrh it is separated by the excess of uric acid in the urine only, the other symptoms being for the most part the same. The cerebral symptoms—the vertigo, headache, etc.—are to be distinguished from the same due to actual disease of the brain by the previous history, by the absence of changes seen on ophthalmoscopic examination and of other signs of brain disease, and by the subsequent behavior. Cases of cerebral mischief producing such effects would rapidly develop into serious states, whereas in lithæmia there are great fluctuations, but no apparent progress in many months. In lithæmia also there are no changes in the fundus oculi, whereas in brain diseases choked disk, hemorrhage into the retina, white atrophy, etc. are often discovered. Further, in lithæmia there are no disorders of sensibility, of motility, or of intellection, whilst these are ordinary evidences of cerebral mischief.

TREATMENT.—Attention to diet is of the first importance. As uric acid is an intermediate product in the metamorphosis of albumen, it might be supposed that to diminish the quantity of this constituent of the food would be sufficient. In some cases this suffices, but usually attention must be given to the peculiarities of digestion characteristic of each patient. More frequently trouble arises from indulgence in the starchy and saccharine constituents of the diet; in some a very considerable gastro-duodenal catarrh exists, and the mucus, acting as a ferment, sets up an acetic fermentation in the starchy and saccharine substances, with the necessary production of much carbonic acid gas. If the fats disagree, the butyric fermentation also takes place, and very irritating fat acids result. In these cases there is usually much gas formed in the stomach and intestine, and an immediate ratio appears to exist between the degree of mental despondency and the quantity of gas in the intestinal canal. It follows, then, that in cases of lithæmia the saccharine, starchy, and fatty constituents of an ordinary diet should be omitted from the food of such subjects. Bread should be partaken of very sparingly, and the foods containing starch, sugar, and oil ought not to be partaken of at all. The succulent vegetables, as lettuce, spinach, celery, cole-slaw, tomatoes, etc., ought to be substituted. Lean fresh meats, poultry, game (plainly cooked), fresh fish, oysters, eggs, etc. should constitute the basis of the diet. On the other hand, there may be those who do better on a diet of vegetables and fruit, excluding meat. In such we may suppose the fault lies in the stomach digestion, where the albuminoids are converted into peptones, the intestinal digestion being active and normal. All kinds of wine and malt liquors should be prohibited. Coffee and tea must also be relinquished. Without the carefully-regulated diet medicines can accomplish but little; hence he who would obtain curative results must give careful attention to every dietetic detail.

As deficient oxidation is an important factor in developing lithæmia, active exercise must be enjoined. The amount of exercise must be determined by the condition of the individual and the time, regulated as far as may be by the period after meals. As when the food prepared for assimilation is entering the circulation oxygen is needed to perfect the final changes, it seems clear that exercise should be taken three or four hours after the process of digestion has begun. Walking exercise is better than any other for this purpose, but it should not be carried to the point of exhaustion from fatigue. Sea-air and sea-bathing are oxidizing agents of considerable value, and are especially useful to the subjects of lithæmia suffering at the same time from malarial infection.

Medicines are administered with the view to accomplish two purposes: to correct the disorders of digestion, to promote oxidation. One of the most useful remedies is nitric acid, five to ten minims of the official diluted acid being given before meals. It is more especially effective when there is an excessive production of acid. The fermentation which produces acid and the diffusion of acid-forming materials from the blood are alike prevented by it. The injunction to administer it before meals must be borne in mind when these purposes are to be subserved. Nitric acid, as well as the other mineral acids, but in a greater degree, promotes the flow of bile. This well-known clinical fact has been confirmed by experiments. Under the use of nitric acid, as above advised, uric acid and the urates disappear from the urine, being excreted as urea, and hence this remedy accomplishes both of the objects for which medicines are administered in this disorder. No other mineral acid can fill its place in this connection.

Alkalies possess very decidedly the power to promote oxidation. The soda salts are objectionable, for, combining with uric acid, they form the insoluble urate of soda. The salts of potash and lithium, on the other hand, form soluble combinations, and they also increase elimination. Much depends on the time at which they are administered, as Bence Jones,⁹ and since Ralfe¹⁰ especially, has shown. To increase the alkalinity of the blood and urine, they must be taken after meals, for then the acid materials of digestion are pouring into the blood. For the same reason, if alkalies are administered to neutralize the acidity of the intestinal canal, they must be given after meals. The most useful alkaline remedies are liquor potassæ, bicarbonate of potash, Rochelle salts, citrate of lithium, etc. The effervescing preparations of potash and of lithium are elegant and palatable forms in which to administer these remedies. They may also be taken dissolved in Vichy water, in our Saratoga Vichy, or in Carlsbad or Bethesda. When the use of mineral waters is not contraindicated in the state of the digestive organs, great good is accomplished by the persistent use of Vichy, foreign or domestic, of Carlsbad, and the alkaline waters of Wisconsin.

⁹ Lectures on Pathology and Therapeutics, by H. Bence Jones, London, pp. 90, 280.

¹⁰ Physiological Chemistry, by Charles Henry Ralfe, London, 1883.

The so-called cholagogues are unquestionably useful, but they become less and less necessary according to the success achieved in the dietetic course. Phosphate of soda is one of the most effective of this group of medicines. As it acts as a compound, and not as a salt of soda merely, it does not come within the prohibition against the use of soda salts. It promotes the flow of bile and appears to remove the catarrhal state of the mucous membrane. A teaspoonful three times a day is the quantity usually required. Under some circumstances it may be advantageously combined with arseniate of soda. Mercurials were formerly almost universally used, but they have been largely supplanted by podophyllin, euonymin, baptisin, etc., and by the phosphate of soda above mentioned. Podophyllin is indicated when constipation is a symptom. An efficient mode of giving it is in the form of granules, but it must be continued without intermission for some time or during the existence of the lithæmia. The quantity given should be sufficient to maintain the evacuations in a soluble state. Good results are obtained from a combination of podophyllin with extracts of physostigma, nux vomica, and belladonna. When distinct torpor of the liver without constipation exists, euonymin, combined with physostigma, may be advantageously used. For the vertigo and hypochondriasis no remedy is more beneficial than arsenic (Fowler's solution) in small doses kept up for some time, and it is also distinctly curative of the catarrhal state of the mucous membrane. When malarial infection is the cause of lithæmia, quinine becomes indispensable.

Topical agents in some cases render important aid to the other curative measures. A daily sponge-bath, the water made more stimulating by the addition of sea-salt, is very useful in the absence of sea-bathing. Friction of the hepatic region with the official ointment of the red iodide of mercury unquestionably stimulates the hepatic functions. General faradization and faradic and galvanic excitation of the chylopoietic system promotes activity of the digestive apparatus and of the organic functions in general.

Hepatic Glycosuria (Temporary).

DEFINITION.—By the term hepatic glycosuria in this connection is meant a temporary glycosuria due to excessive formation of glycogen. The liver, unduly stimulated, produces more glycogen than can be disposed of, and hence it is excreted by the kidneys as grape-sugar.

PATHOGENY.—In the normal condition it is supposed that the glycogen produced by the liver is converted into grape-sugar, and soon oxidized and thus consumed. One theory of diabetes maintained that in some way the conversion of glycogen into grape-sugar was excessive and beyond the oxidizing power of the blood, and hence this substance was discharged in the urine. The recent discovery by Pavy¹¹ of glycogen in considerable amount in the blood of all parts of the body renders it certain that there are peculiar conditions necessary to the formation of grape-sugar in sufficient quantity to constitute diabetes. It is tolerably certain that an excess of acid in the intestinal canal, diminishing thus the alkalinity of the blood, will have as a symptom sugar in the urine. Persons disposed to the accumulation of fat, and eating freely of sugar and starchy food, are apt to have intestinal indigestion, and the acid produced by the fermentation of these substances will, after its absorption, hinder the conversion of any food-sugar. In such subjects also there may be an increased conversion of the glycogen of the blood into sugar under the same conditions. Such a glycosuria must necessarily be temporary and a purely functional disorder.

¹¹ The Lancet, vol. ii., 1883.

SYMPTOMS.—The subjects of the malady under consideration are of full habit, even obese. They habitually consume considerable quantities of malt liquors and a diet composed largely of the starchy and saccharine foods. If not in malt liquors, they at least indulge freely in bread, potatoes, pastry, cakes—in all forms of farinaceous food, fats, and sweets. They have a keen appetite, eat largely, and drink freely of fluids. As a rule, these subjects are but little disposed to physical exercise and lead rather sedentary lives. Indulgence in such a mode of life tends to increase the accumulation of fat, weakens the muscles, and with them the heart-muscle, and slowly induces a gastro-intestinal catarrh accompanied by stomachal and intestinal indigestion. At first, heaviness, oppression, and drowsiness after meals are experienced; then acidity, pyrosis, and eructations follow; and ultimately the evidences of intestinal indigestion—flatulence, pain, irregular and unhealthy evacuations, etc.—come on. Meanwhile, the appetite is not usually impaired, and the disposition to drink fluids increases; the amount of urine voided is greater, and to rise during the night for the purpose of emptying the bladder comes to be a fixed habit. The urine under these circumstances is copious, high-colored, acid, and deposits on cooling abundantly of uric acid and urates. The amount passed in twenty-four hours will reach sixty, eighty, or more ounces, and the specific gravity will range from 1025 to 1035. On testing in the usual way, traces of sugar, more or less distinct, will appear,¹² but not constantly, and hence repeated examinations are necessary to determine the quantity. As a rule, the evidence of the presence of sugar in small amount is satisfactory.

¹² In testing for sugar, when the urine contains the urates in such abundance there is danger of error. In using Trommer's, Fehling's, or Moore's test, on heating, the urates will effect a reduction of the copper or bismuth. It is necessary, therefore, to separate them before applying the test. This is accomplished as follows: The urine is evaporated to dryness on a water-bath; the sugar in the evaporated residue is dissolved out by absolute alcohol, and then an aqueous solution is prepared, to which the test is applied. An experienced operator will not need to take such precautions, for, familiar with the reactions, he can readily judge of the results.

Various affections of the skin appear in the subjects of this malady, and urticaria, prurigo, eczema, and boils are the forms most usual.

COURSE, DURATION, AND TERMINATION.—Slow in developing, this temporary glycosuria is also slow in its course. It remains nearly stationary for months, even years. Meanwhile the degenerative changes associated with it slowly develop on all sides. The quantity of sugar does not greatly increase, for its amount, being apparently dependent on the quantity of acid entering the blood from the intestinal canal, must continue nearly at the same standard. It is comparatively rare for true diabetes to develop out of this state, although such a termination must be regarded as a natural outcome. One reason, it may be, why such a conclusion is not often reached is because of intercurrent maladies. It is an important fact that acute serous—less often parenchymatous—inflammations are very apt to occur during the existence of even temporary glycosuria. Under appropriate management this disorder is readily amenable to treatment. Hence the prognosis will be favorable or not according to the skill exhibited in its treatment.

DIAGNOSIS.—This malady offers no special difficulty in diagnosis. From gastro-duodenal catarrh and from lithæmia it is distinguished by the saccharine condition of the urine. From diabetes it is separated by the rate of progress, by the protracted duration of the case without any distinct advance, and by the temporary and fugitive character of the glycosuria.

TREATMENT.—To carefully regulate the diet is the first consideration. The traces of sugar and the excess of urates rapidly disappear when the starches, sugar, and fats are withdrawn from the diet. Indeed, the rule as to alimentation must be as rigidly enforced as in true diabetes, but after the gastro-intestinal catarrh has subsided the ordinary mixed diet—that before the disturbance began—may be returned to gradually. Active exercise must be enjoined under the same conditions and for the same purpose as in the treatment of lithæmia. In these obese subjects, unaccustomed to movement, exercise must be cautiously undertaken; beginning with short excursions, it must be gradually increased. Horseback riding is an excellent expedient, but should not take the place of walking.

The merely medical measures have a twofold direction: to remove the gastro-duodenal catarrh; to promote oxidation of the sugar in the blood or prevent the conversion of glycogen into grape-sugar. Vichy water, the potash salts, and alkalies generally serve to accomplish the latter, and phosphate and arseniate of soda, tinctures of nux vomica, and of physostigma, bismuth, and carbolic acid, relieve the former. Small doses of Fowler's solution (two drops ter in die), and a minim three times a day of a mixture in equal parts of tincture of iodine and carbolic acid, are effective remedies in gastro-duodenal catarrh.

Jaundice (Icterus).

DEFINITION.—The term jaundice has its origin in the French word jaune, yellow. Icterus, which has come to be a more technical word, is of uncertain Greek origin, and is much employed by French writers as ictère. The common German name is Gelbsucht, a highly expressive designation. Jaundice signifies a yellow discoloration of the skin caused by the presence of bile. It is a symptom rather than a disease. As a symptom it will receive much consideration in the pages to follow, but there is also a functional disorder—a jaundice due to a disturbance in the biliary functions, without evidences of structural change—which must be discussed here. This preliminary statement of our present knowledge of jaundice will facilitate the comprehension of it as a symptom, and will render unnecessary explanations that will be merely a repetition of previous ones.

CAUSES.—The theories of the causation of jaundice may be reduced to three: 1, that it is due to a disorganization of the blood in which the coloring matter is set free, and hence is known as hæmatogenous; 2, that the materials of the bile, which it is the office of the liver to remove from the blood, are not so disposed of; 3, that the bile, after being formed by the liver, is absorbed into the blood because of an obstacle to its escape, and hence this is called hepatogenous jaundice.

The modern view of hæmatogenous jaundice had its origin in the supposed discovery of the identity of hæmatoidin with bilirubin. If the pigment of the blood has the same composition as the pigment of the bile, hæmatogenous jaundice will be produced whenever hæmatoidin is set free in the blood. Virchow¹³ was the first investigator to show the close resemblance between these two pigments. Since his observation was made an identity of hæmatoidin and bilirubin has been maintained by Zenker, Valentiner, Kühne, and others, and as strenuously denied by Städeler, Preyer, Young, and others. At the present time it appears to be established that although the blood- and bile-pigments are closely related, they are not identical.¹⁴ Nevertheless, a hæmatogenous jaundice is still admitted to exist by Leyden,¹⁵ Immermann,¹⁶ Gubler,¹⁷ Ponfick,¹⁸ and some others. The existence or non-existence of this form of jaundice is, however, of little importance in this connection, since, if it ever occur, the malady of which it is a symptom is not an affection of the liver, but of the blood, as phosphorus-poisoning, pyæmia, etc.

¹³ Archiv für path. Anat., etc., Band i. p. 370, 1847.

¹⁴ Legg, J. Wickham, On the Bile, Jaundice, and Bilious Diseases, p. 243.

¹⁵ Beiträge zur Pathologie des Icterus, Berlin, 1866, p. 6.

¹⁶ Deutsch. Archiv für klin. Med., Band xii. p. 502.

¹⁷ Union médicale, 1857, p. 503.

¹⁸ Ziemssen's Cyclopædia, vol. ix. p. 24.

The second theory, that the bile is preformed in the blood and separated by the liver, and that jaundice results because of the failure of the liver to perform this office, is no longer entertained, although largely held down to within a very recent period. As the bile acids and bile-pigments are not to be found in the blood, chemistry lends no support to the theory of jaundice by suppression of the hepatic function. As they do not exist in the blood and are found in the secretion of the liver, there can be no other view held than that they are formed by this organ.¹⁹

¹⁹ The old doctrine of jaundice by suppression, which has always been maintained by Harley (On Jaundice, London, 1863, p. 20 et seq.), has been again restated and strongly advocated by him in his treatise on The Diseases of the Liver, p. 83, which was issued in 1883. In the two following postulates he formulates his view:

"1. The biliary secretion can be actually retarded, and even totally arrested, without alteration of hepatic tissue.

"2. When the liver strikes work and secretes no bile, the animal body becomes jaundiced as a direct consequence thereof."

This view, he affirms, "can be made comparatively easy of absolute proof."

The evidence on which he chiefly relies is exceedingly fallacious. It rests on two facts: the existence of a case of jaundice in which the ducts and gall-bladder contain no bile, but only ordinary mucus; the appearances presented by a liver in a case of jaundice due to obstruction of the common duct. The evidence afforded by the former is entirely fallacious, because in an old case of jaundice with catarrh of the bile-ducts such changes take place in the bile that it loses all of its distinctive characteristics. This may be seen in an ancient example of obstruction of the cystic duct, where the bile which the gall-bladder contained is ultimately transformed into a whitish or colorless mucus. The changes which occur in the so-called cysts of the arachnoid are comparable, and exhibit the entire transformation of blood-pigment, which is closely allied to bile-pigment.

The third theory of jaundice—that which refers the disease to an absorption of the bile into the blood after it has been formed by the liver—is the one now most generally held, and, indeed, as one of the causes is universally held. The bile is absorbed into the blood because an obstacle to its passage by the bile-ducts exists at some point in their course. This is the principal, but not the only, cause of absorption. When the pressure in the vessels falls below that in the ducts, bile will pass toward and into the vessels. Again, it sometimes happens that a considerable part of the bile discharged into the intestines is reabsorbed unchanged, and enters the portal vein and the general circulation, thus causing jaundice.

The disturbances of the liver causing jaundice are various. It sometimes occurs without cause, and the first intimation of it is the peculiar tint of the skin. It is certainly true that powerful emotions are causative; thus, a violent anger has brought on an attack. In such a case we must suppose a depression of the vaso-motor system, and such a lowering of the blood-pressure as to favor the passage of bile into the veins rather than into the bile-ducts. Thus, it has been abundantly shown that a slight difference in pressure will divert the bile in either direction. Heidenhain²⁰ has demonstrated that the bile passes in the direction of least resistance, and in the case of the considerable vaso-motor depression caused by extreme emotion the least resistance is in the direction of the vessels. More frequently than moral emotion is catarrh of the bile-ducts. It is not necessary for the catarrhal swelling of the mucous membrane to close the ducts to have the bile pass into the veins; such a degree of swelling as to make the passage of the bile somewhat difficult suffices. A simple hyperæmia of the mucous membrane may cause sufficient obstruction of the bile-ducts to give rise to jaundice. Gastro-intestinal catarrh plays an important part in the production of simple jaundice. Frerichs²¹ ascertained that of 41 cases, gastro-duodenal catarrh existed in 34. Ponfick²² considers catarrh of the ducts the principal factor. In fact, at the present time there is but one dissenting voice on this point.²³

²⁰ Quoted by Legg, supra, p. 253.

²¹ Diseases of the Liver, Syd. Soc. ed., by Murchison.

²² Ziemssen's Cyclopædia, vol. ix., supra.

²³ Harley, Diseases of the Liver, 1883, p. 440 et seq.

Gastro-duodenal catarrh extends by contiguity of tissue to the mucous lining of the bile-ducts. The catarrhal state of the mucous membrane is produced by errors of diet, acid indigestion, indulgence in condiments, wines, and rich foods in general. Climatic changes, malarial infection, exposure to cold and dampness, etc. are indirectly causative of jaundice through the intermediation of gastro-duodenal catarrh.

Formerly, obstruction of the gall-ducts was supposed to be caused sometimes by a spasmodic contraction of the organic muscular fibre assumed to exist in the walls of the ducts. Although the presence of these muscular elements has been denied, Heidenhain has lately, apparently, demonstrated them. Audigé has made observations confirmatory of those of Heidenhain, and Dujardin-Beaumetz²⁴ has verified the statements of Audigé. It seems, therefore, in a high degree probable that organic muscular elements exist in the walls of the hepatic ducts, and that spasmodic icterus may therefore occur.

²⁴ Bull. gén. de Thérapeutique, vol. lxxxv. p. 385, 1873.

SYMPTOMS.—Simple icterus may exist without any other obvious symptoms than the yellow discoloration of the skin. In most cases, however, the yellowness is preceded for a week or more by the symptoms of a gastro-intestinal catarrh, or these symptoms accompany the jaundice. There is much mental depression and a general malaise is experienced. Headache, mental hebetude, a total loss of appetite, a furred tongue, and a bitter taste, nausea and sometimes vomiting, constipation or diarrhoea, precede or accompany the jaundice. When these symptoms precede for some time the appearance of yellowness, it is probable that the biliary derangement is secondary to the gastro-duodenal catarrh, but when they occur with the jaundice it is probable that they are due to the absence of bile from the intestine.

The yellowness first appears in the conjunctiva for a day or two before the skin is tinted, and within forty-eight hours after the flow of bile into the intestine has ceased. The face next becomes yellow, then the body, and afterward the limbs, but in some cases the limbs remain free from discoloration. The lips do not exhibit any change of color, but the roof of the mouth, the palate, and the mucous membrane under the tongue are yellow. The saliva does not, as a rule, contain bile-pigment or exhibit any changes of color unless mercurial salivation is caused, when it becomes greenish in color and has a bitter taste.²⁵ A yellow tint of the sweat, especially under the arm-pits, is common. The milk very often contains bile-pigment or is changed in color in some way.

²⁵ Legg, On the Bile, etc., supra.

The feces are colorless or have a grayish or clay-colored tint, and are semi-solid, although sometimes hard and dry. In simple jaundice diarrhoea is very often present. There may be considerable flatulence, and more or less pain in consequence about the umbilicus, and the gas when discharged is very offensive. The stools also, in some cases, have an odor of decomposition, and if carefully examined particles of food, undigested and decomposing, will be found. The feces may have a parti-colored appearance—part whitish or grayish or clay-colored, and part of a normal color. This condition is not difficult of explanation. The obstruction to the flow of bile may be in a part, and indeed in a small part comparatively, of the liver, and hence there may be sufficient bile flow down to color the feces to a greater or less extent. But a small amount of bile-pigment in the blood suffices to tint the whole surface of the body.

The urine may exhibit changes in appearance before the conjunctiva becomes yellow. It is colored in all possible degrees, from a merely high normal hue to a deep brownish almost black tint. It may be deep red and clear like dark brandy or brown like porter, and thick with urates. Usually, the urine of jaundice deposits abundantly of urates, but this fact is more especially true of those patients retaining appetite or having a voracious appetite and indulging in a full diet without restraint. The reaction of the urine is acid, and the specific gravity does not often descend below 1010, and may be 1030. The amount passed in twenty-four hours varies, but does not differ materially from the normal. Toward the termination of some fatal cases the quantity of urine has greatly diminished, and in a few instances was suppressed, but in such examples other factors than hepatic disease were concerned. More or less albumen is nearly constantly present in the urine of jaundice, but the detection of a trace is very difficult when the urine, as is so often the case, is cloudy. The urine should be carefully filtered before applying the test, and a specimen for comparison should be placed alongside of that being examined. If on boiling no haze appears, it may be developed by dropping in some nitric acid. The nitric-acid test, so often employed by allowing some drops of urine to trickle down the test-tube and observing the reaction at the point of contact, is, in the writer's experience, very fallacious. The source of the albumen in jaundiced urine is obviously the blood-globules. As Von Dusch first demonstrated, and Kühne²⁶ afterward clearly confirmed, the bile acids dissolve the red corpuscles. As the quantity of albumen in the urine is small, it is reasonable to conclude, as suggested by Legg, that the bile acids are not present in the blood in any considerable amount.

²⁶ Archiv für path. Anat., Band xiv. p. 333.

When any large quantity of bile is contained in the urine, its detection is not difficult. A strip of muslin dipped in the urine will be stained, and the underclothing of the patient will have the yellowish spots caused by bile. Gmelin's test is the most convenient. This is applied as follows: Some nitric acid containing nitrous—which is the case of the ordinary commercial article—is put into a test-tube, and some of the suspected urine is allowed to trickle down the side of the tube to come in contact, but not mix, with the acid. At the point of contact, when the urine contains bile-pigment, first a zone of green, then blue, violet, and finally red color, develops. As this play of colors takes place on the instant, the attention must be sharply fixed to see the changes. Rosenbach²⁷ suggests this test be applied by filtering some urine containing bile through filtering-paper and touching the paper with a drop of nitric acid. The result is, a green circle forms at the point of contact. The usual mode of applying Gmelin's test is to place on the bottom of a common white plate or on a porcelain dish a thin film of the urine, and carefully bring in contact with it a thin film of nitric acid. The color reaction mentioned above takes place at the margin of contact.

²⁷ Centralblatt für die medicin Wissenschaft, 1876, p. 5.

Besides the presence of bile and albumen, and some fatty epithelium from the tubules, there is no material change in the composition of the urine. At one time it was supposed that the amount of urea was greatly lessened, but later and more accurate investigations have shown that this excretion is in greater or less quantity according to the food taken, and bears no relation to the jaundice. On the other hand, Genevoix²⁸ maintains that the quantity of urea is increased in spasmodic icterus, and in the same ratio the uric acid declines. As regards the chlorides and other salts, there seems to be a tolerably constant ratio in their variations with the changes of quantity of urea and uric acid—are therefore nearly related to the amount of food taken.

²⁸ Essai sur les Variations de l'Urée et de l'Acide urique dans les Maladies du Foie, Paris, 1876, p. 59 et seq.

As regards the condition of the liver, there is no apparent change. In topography, in the area of hepatic dulness, and in the dimensions of the right hypochondrium the local condition does not deviate from the normal in simple jaundice. There may be more or less tenderness over the epigastrium and along the inferior margin of the liver, but there is rarely any actual pain.

The circulation of bile in the blood and the action of the bile acids on the red corpuscles must have an influence on the functions of various organs. In some cases of jaundice, but by no means in all, the pulse is slow, in a few instances descending as low as 40 per minute, and, according to Frerichs,²⁹ as low as 21 per minute. Usually, the pulse-rate is not lower than 60. To observe the slowing of the heart the patient must be recumbent, for the pulse rises to the normal or above on assuming the erect posture and moving about. The occurrence of fever also prevents the depression of the circulation. The slowing of the heart is found to be due to the action of the bile acids on the cardiac ganglia. The other elements of the bile were ascertained to have no influence on the circulation. As the heart may be slowed by an increase of inhibition through stimulation of the vagi or by a paralyzing action on the cardiac muscle, it was necessary to eliminate these effects to establish the influence of the bile acids on the ganglia. By exclusion, and by ascertaining the effects of the bile acids on a properly prepared Stannius heart, Steiner and Legg have succeeded in demonstrating this important point.³⁰

²⁹ Diseases of the Liver, Syd. Soc. ed., supra.

³⁰ Archiv f. Anat. u. Physiol., 1874, p. 474; Legg, On the Bile, etc., loc. cit.

The temperature of jaundice is normal usually, sometimes below. When a febrile affection occurs during the course of jaundice, the rise of temperature belonging to it is prevented in considerable part, sometimes entirely. The depression of temperature is referred by Legg to the lessened activity of the hepatic functions; but it seems to the writer more satisfactory to refer it to the action of the bile acids on the red corpuscles, the conveyors of oxygen. Röhrig³¹ has shown experimentally that the injection of bile acids has this effect on the temperature of animals.

³¹ Archiv der Heilkunde, 1863, p. 418.

The nutrition of the body early suffers in jaundice; more or less loss of flesh soon occurs, and debility and languor are experienced. There are several factors concerned in this result. The diversion of the bile from the intestine interferes in the digestion of certain materials; when jaundice occurs, glycogen ceases to be formed—and this substance has an important office in nutrition and force-evolution—and the injury done to the red blood-globules interferes with oxidation processes.

The functions of the nervous system are variously disturbed in jaundice. Headache, frontal, occipital, or general, is present in most cases to a greater or less extent. Hebetude of mind and despondency are nearly if not quite invariable, although it is not unusual to see men with jaundice engaged in their ordinary avocations. Drowsiness is a common symptom. More or less wakefulness at night, or sleep with disturbing dreams, not unfrequently coincide with drowsiness during the waking moments. In severe cases of icterus dependent on structural changes the cholæmia may produce stupor, delirium, convulsions, etc., but such formidable symptoms do not belong to the simple and merely functional jaundice.

Vision is sometimes colored yellow, or, rather, white objects appear yellow, but this must be a rare symptom, since Frerichs never met with an example. Murchison³² narrates a case, and the writer has seen one. It is a fugitive symptom, rarely continuing longer than two or three days. The term xanthopsy has been applied to it.

³² Clinical Lectures on Diseases of the Liver, New York, 1877, p. 321.

A nervous symptom of common occurrence is pruritus of the skin. This may be so severe as to prevent sleep, and in any case is a disagreeable and persistent affection, always worse at night. It may appear before the jaundice so long a period as ten days, as in a case mentioned by Graves,³³ and two months in a case narrated by Flint.³⁴ It is most severe at the beginning of the jaundice, and usually disappears before the jaundice ceases, but it may continue to the end. It is not limited to any particular part of the body. Pruritus is sometimes accompanied by urticaria, and the irritation caused by the friction of the skin may set up an eczema. Occasionally boils, and more rarely carbuncles, appear during the course of jaundice. Another curious affection of the skin which occurs during chronic jaundice is xanthelasma or vitiligoidea. First mentioned by Rayer, this disease was afterward well described by Addison and Gull³⁵ under the name vitiligoidea, and they recognized two varieties, v. plana and v. tuberosa. The plane variety is found on the mucous membrane of the mouth, the eyelids, the palms of the hands, and the flexures of the joints, and consists of a yellowish-white soft eruption slightly raised above the surrounding skin and varying in size from a pin's point to a dime in size. The color is described as like that of a dead leaf or chamois-skin. The tuberose variety consists of small tubercles from a millet-seed to a pea in size. They have a yellowish color, are tense and shining, and are placed on the ears, neck, knuckles, elbows, knees, and other parts. Whilst the plane variety gives little if any uneasiness, the tuberose is apt to become irritated and painful. From the pathological point of view this eruption consists of proliferating connective-tissue corpuscles, some of which have undergone fatty degeneration.³⁶ The morbid process tends to occur symmetrically, as on the eyelids, to which it may be confined, but it usually develops in patches, and may indeed extend over the whole body, when it is called xanthelasma multiplex.

³³ Clinical Lectures on the Practice of Medicine, 2d ed., by Neligan, p. 637.

³⁴ Philada. Med. Times, 1878, p. 507.

³⁵ Guy's Hospital Reports, 1851, p. 265.

³⁶ Waldeyer, Archiv für path. Anatomie, etc., vol. lii. p. 318.

The disorganization of the blood caused by jaundice sets up a hemorrhagic diathesis. This result, however, is not usual in simple jaundice, but belongs rather to acute yellow atrophy, sclerosis, and other chronic affections of the liver. It will therefore be more appropriately considered in connection with those maladies.

COURSE, DURATION, AND TERMINATION.—When jaundice is a symptom merely, it pursues a course determined by the peculiarities of the disease. The duration of simple jaundice varies from one to four weeks, the average being about three weeks. If it continues longer than two months, suspicions may well be entertained that the case is of a more formidable character than simple jaundice. The termination of this form of the disease is always in health. A favorable prognosis can be given only in the case of an accurate diagnosis. Those cases may terminate more speedily which, being of malarial origin, are treated by efficient doses of quinine. If delirium and coma come on, the apparently mild case means, probably, acute yellow atrophy, which cannot at the onset be distinguished from simple jaundice. If any nervous symptoms occur or if hemorrhage appears, the case will prove to be serious. A rise of temperature usually indicates mischief. When the stools begin to exhibit the normal appearance from the presence of bile, a satisfactory termination of the case may be soon expected. The yellowness of the skin disappears slowly after the natural route of the bile has been restored, and the urine is the last to lose the pigment, as it was the first to exhibit its presence.

DIAGNOSIS.—The diagnosis of jaundice as a symptom is usually easy. It should be remembered that jaundice cannot be detected at night by any ordinary light, and when it is disappearing the tint varies, now being distinct, again absent. Mental emotion when the color is fading develops it. Browning by the sun's rays causes an appearance which might be mistaken by a superficial observer for jaundice, but it is only necessary to look at the parts protected and at the urine to discover the true state of the case. The detection of bile in the urine and the ocular evidence of its absence from the stools will be conclusive. In some cases of jaundice the stools are golden yellow, and in many instances they are offensive.

It is important to mark out the limits of the gall-bladder, if it is of sufficient size to do so, for any accumulation of bile in this sac signifies an obstruction of the ductus communis choledochus. If the jaundice has come on after the symptoms of gastro-duodenal catarrh, is recent, continues but two or three weeks, and then subsides without any nervous symptoms or hemorrhage, it is a case of simple jaundice, probably due to catarrh or spasm of the bile-ducts. If the jaundice be preceded by attacks of severe pain, nausea, and vomiting, and disappears after a week or two, the case is one of hepatic calculi. If the jaundice persists months after such an attack of acute pain, and does not disappear after a year or more, it is probably due to an impacted calculus. The other diagnostic relations of jaundice are more properly considered in connection with the malady of which jaundice is a symptom.

TREATMENT.—For jaundice the symptom the treatment is included in that of the disease. Here the treatment of simple jaundice, the functional disorder, is to be discussed. If there is much nausea, the tongue is heavily coated, and, especially if the seizure has followed dietetic excesses, an emetic of ipecac may be highly serviceable. Recent experiments have proved the accuracy of the clinical observations which recognized the cholagogue property of ipecac, and hence the emetic effect of this remedy is aided by its power to promote the discharge of bile. Emetics are of course contraindicated when jaundice is due to an impacted calculus, to malignant disease, to echinococci or other kinds of tumor. If there is much irritability of the gastro-intestinal mucous membrane, as shown in vomiting and diarrhoea, small doses of calomel (¹/12 to ¼ grain) three or four times a day are highly useful. If calomel possessed the property ascribed to it of stimulating the liver, it would be injurious; it is beneficial here because it has a sedative effect at first, followed, when a sufficient amount has accumulated, by an eliminant action. Such hepatic stimulants as euonymin, sanguinarin, podophyllin, jalap, colocynth, rhubarb, etc. have long been used in cases of jaundice with the view that the liver is torpid and needs stimulating. It may be inquired, however, If the bile already formed has no outlet by the proper route, what utility can there be in making the organ produce more? The true reason for the administration of such remedies in any case of obstructive jaundice is to cause such downward pressure as to force out of the duct an obstructing plug of mucus. The writer has known this result to be accomplished by a dose of compound jalap powder when a great variety of remedies had been employed in vain. One of the most efficient remedies—in the writer's considerable experience the most efficient—is phosphate of sodium, of which a drachm or more is administered three times a day. This remedy liquefies mucous plugs and promotes the flow of bile without harshly and rudely forcing the biliary secretion, and it also has a marked curative effect in gastro-duodenal catarrh. It may be given advantageously with arseniate of soda—the latter in dose of ¹/20 grain—and dissolved in a tumblerful of Vichy water or Saratoga Vichy water, or preferably in a wineglassful of hot water. Free use of alkaline and laxative mineral waters is desirable, for a double purpose—to act on the liver and on intestinal digestion, and to promote the excretion of biliary matters by the kidneys. In this country we have a number to select from—the Saratoga, Bethesda, Michigan, and others. Certain sulphurous waters, as the Blue Lick of Kentucky, are highly useful in the more chronic cases. Sulphur baths may be conjoined to the internal administration of the waters.

Nitric and nitro-muriatic acids have long been celebrated for their good effects in jaundice. It is the presence of the acid chyme in the duodenum which excites the normal flow of bile, and Bernard found that applying acid to the orifice of the common duct in the intestine has the same effect. There is then a rational reason for the administration of this remedy. A nitro-muriatic bath, both local and general, was formerly more used than now. Its utility is questionable, and the difficulties in the way of applying it great.

Recently, Gerhardt³⁷ has proposed to faradize the gall-bladder, and by compression with the fingers to empty it, forcing the bile into the intestine, and thus clearing out obstructions. This seems to be very questionable if not dangerous practice, but repeated successes will justify it.

³⁷ Sammlung klinische Vorträge, Volkmann, p. 112.

Regulation of the diet is of the first importance. Fats, starches, and sweets cannot be well digested when no bile enters the small intestine, where they undergo conversion. These substances fermenting, much acid results, and hence if a catarrh exist it is increased. An exclusive diet of skimmed milk, kept up for two weeks or as long as possible, is the best mode of alimentation for this part of the treatment. Afterward, the diet should be composed of milk, meat-broth, lemonade, and subsequently of the succulent vegetables, acid fruits, and fresh meat. Indulgence in malt liquors, wines, and spirits should be strictly prohibited.

A new method of treating jaundice has been lately proposed by Krull,³⁸ which has the merit that no injury is done by it if no good is accomplished. It consists in injecting into the rectum from two to four pints of water at 60° F., which is retained as long as possible. Each time the injection is repeated the temperature is raised a little. Krull reports that he has uniformly succeeded, and has never found it necessary to repeat the injection more than seven times. It may be given twice or thrice a day.

³⁸ Berliner klinische Wochenschrift, 1877, p. 159.

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II. STRUCTURAL DISEASES OF THE LIVER.

Hyperæmia of the Liver.

DEFINITION.—An abnormal quantity of blood in the liver, constantly present, constitutes hyperæmia or congestion. During the period of repose there is less, but during the period of activity more, blood circulating in the liver, but the physiological hyperæmia is not, nor does it contribute to, a diseased state unless abnormal conditions continue it beyond the proper limits. The term hyperæmia, here used, applies to a pathological state in which various structural alterations grow out of the continual congestion of the blood-vessels of the organ.

CAUSES.—A physiological congestion of the liver ensues when the process of digestion is going on. The afferent vessels dilate, and not only more blood, but various materials taken up from the foods and products of digestion, many of them having directly stimulating effects, also pass to the organ. Frequent and large indulgence in food, especially if rich in quality and highly seasoned with spices, mustard, etc., the consumption of malt liquors, wines, and alcoholic fluids in general, the habitual use of strong coffee and tea, gradually induce a state of hyperæmia. If to the consumption of a large quantity of highly-stimulating food there is added the mischief of insufficient waste, the danger of congestion of the liver is the greater. Persons addicted to the pleasures of the table are apt to pursue sedentary lives, and hence, besides the inappropriation of the material digested, the process of oxidation is insufficient to burn off the surplus. A sedentary life further tends to make the circulation in the hepatic veins sluggish by lessening the number and depth of the respirations, and with the obesity developed under these conditions the propelling power of the heart is diminished by fatty degeneration or fatty substitution of the cardiac muscle. Disease of the semilunar ganglion, the solar plexus, and of the splanchnics under circumstances and of a nature not now well understood may cause dilatation of the hepatic vessels.

Suppression of a long-existing hemorrhage from piles and from the uterine system has caused hyperæmia of the liver. Evidences of hepatic congestion are comparatively common about the menstrual period in consequence of the tardy appearance of the flow, of its insufficiency, or of its sudden suppression. There is a form of jaundice known as icterus menstrualis, and attacks of hepatic congestion are not uncommon at the climacteric period.

The most important causes of hyperæmia of the liver are mechanical, and consist in obstruction to the circulation in the ascending vena cava from disease of the heart or lungs. Dilatation of the right cavities, incompetence of the tricuspid, and stenosis of the mitral orifice are the usual cardiac changes leading to congestion of the liver. The same effect, to a much less extent, however, is produced by any cause which weakens the propelling power of the heart, as myocarditis, pericarditis, etc. Amongst the pulmonary lesions obstructing the venous circulation are emphysema, interstitial and croupous pneumonia, effusions into the pleura, intrathoracic aneurisms or tumors, etc. It should not be forgotten that effusions into the left pleura, as was demonstrated by Bartels³⁹ and confirmed by Roser,⁴⁰ so push over the mediastinum toward the right and bend the vena cava in the same direction, just as it emerges from the opening in the diaphragm, that the circulation in this vessel is impeded, and consequently congestion of the liver induced.

³⁹ Deutsches Archiv für klin. Medicin, Band iv. p. 265.

⁴⁰ Archiv der Heilkunde, Band vi. p. 40.

The influence of climate, especially of long-continued high temperature, has been warmly disputed. On the whole, it seems probable that in warm climates congestion of the liver is much more common. Malarial infection is an unquestionable cause. In the section on Jaundice it was stated that this symptom may occur without the phenomena of fever, and, indeed, without any other disturbance of the system. In a large proportion of cases of intermittent fever, probably in all, more or less congestion of the liver occurs.

PATHOLOGICAL ANATOMY.—Congestion may take place in the portal system, and be due to conditions of the gastro-intestinal mucous membrane, or in the hepatic vein and radicles, due to obstructive troubles in the heart or lungs. The appearances vary accordingly. Restricting the observations to the hyperæmia, and not including subsequent lesions, it suffices to say that the liver is somewhat enlarged, rather darker in color than the normal, and uniformly so; the radicles and branches of the portal vein in the liver, the trunk of the vein itself, and the veins of the spleen, stomach, intestines, mesentery, etc. are distended with black blood, and the tissue of the liver rather wet, inclined to soften, and here and there marked by minute hemorrhages from rupture of small vessels. The extravasations of blood accompany the hepatic congestion of hot climates, and probably are the preludes to suppurative inflammation. The portal system the more readily suffers from a passive congestion because of the provision for the alternate expansion and contraction of the tunics of the vessel, scantily supplied with contractile elements. An acute congestion of the liver produced by sudden dilatation of the capillaries of the hepatic artery has not been described, but it would appear to be possible.

The most important form of hepatic congestion is the mechanical, arising from obstruction of the circulation in the heart or lungs. In consequence of this obstruction the blood accumulates on the venous side, and there is in consequence an ischæmia of the arterial side. The hepatic vein becomes distended, and its terminal radicle in the centre of each acinus—the central vein—enlarges with the increased pressure. It follows that the minute capillaries emptying into the central vein are also distended with blood, and finally the portal vein and its radicles throughout are similarly affected. The same condition of the hepatic circulation was long ago observed by Virchow⁴¹ as a result of weakness of the muscular tissue of the heart, and consequently diminished propelling power of the organ. On section of the liver much black blood flows out; each central vein is a distinct dark object in the centre of each acinus, and contrasts strongly with the surrounding paler substance, whence the common term for this appearance is nutmeg liver. The long-continued distension of the central vein leads to sclerosis of its walls,⁴² and the neighboring hepatic cells undergo atrophy in consequence of the greater pressure. A relatively increased quantity of connective tissue seems to result, but whether hyperplasia occurs is disputed. By Talamon⁴³ such increase of the connective tissue is denied, but Thierfelder⁴⁴ admits that there is an apparent and also in some cases a real increase. The atrophy of the cells induces more or less shrinking and consolidation of the liver; it is therefore smaller in size and firmer in texture, and presents a brownish-red color. The atrophic change in the hepatic cells is represented finally by some brownish or black pigment, but it is rare, indeed, for all the cells of an acinus to disappear. To this change has been applied the term cyanotic atrophy. In some instances Liebermeister⁴⁵ has found an increase of the connective tissue of the liver; and this opinion is confirmed by Legg.⁴⁶ When this multiplication of the connective tissue occurs, the condition of the liver is entitled cyanotic induration. The sclerosis originating in this way is distinguished from true cirrhosis by its less extent, irregularity, situation, and the marked degree of hepatic congestion.

⁴¹ Archiv für path. Anat., etc., Band v. p. 289.

⁴² Talamon, Recherches anatomo-pathologiques et cliniques sur le Foie cardiaque, Paris, 1881 (pamphlet).

⁴³ Ibid.

⁴⁴ Atlas.

⁴⁵ Beiträge zur path. Anat. u. Klinik der Leberkrankheiten, Tubingen, 1864, p. 209 et seq.

⁴⁶ Medico-Chirurgical Transactions, vol. lviii. p. 345.

SYMPTOMS.—Hyperæmia of the liver is usually one of the complex conditions of a morbid state, and hence is associated in its symptomatology with the connected maladies. On the one hand associated with gastro-intestinal disorders, on the other with cardiac and pulmonary diseases, the symptoms must be varied accordingly. It is necessary, however, to indicate as clearly as may be those belonging to the hepatic circulation.

Congestion of the portal circulation is a condition to which frequent references are made, but which is rarely clearly defined. As seen in the West and South, it signifies a gastro-intestinal catarrh more or less acute, with an obvious condition of biliousness, as manifested in a faint jaundiced tint of the skin and of the conjunctivæ, uneasiness in the right hypochondrium, with enlargement of the area of hepatic dulness, the evacuations from the bowels being either grayish or clay-colored, or more frequently bilious, acrid, and offensive.

The gastro-intestinal disorder which initiates the hepatic disturbance should not be confounded with that which succeeds to congestion of the hepatic veins. The latter invariably comes on after the obstruction at the heart or lungs has continued for some time. There occurs in this state very extensive hyperæmia of the gastro-intestinal mucous membrane, and consequent disorders of stomachal and intestinal digestion. The former is a reflex cause of disturbance, probably through the intermediation of the solar plexus. The gastro-intestinal irritation, by depressing the functions of the hepatic through the solar plexus, induces a paresis of the muscular layer of the portal system, and thus congestion ensues. Such a result is aided by high temperature, but especially by the constitutional tendencies of some subjects to hepatic disturbances. In such examples of hyperæmia the symptoms consist of those belonging to gastro-intestinal catarrh, succeeded by those referable to the liver, consisting in uneasiness, heaviness, and fulness of the right hypochondrium, increase in the area of hepatic dulness, soreness on pressure along the inferior margin of the ribs and over the epigastric region, yellowness of the conjunctivæ, a fawn color of the skin generally, and high-colored rather scanty urine, depositing abundantly uric acid and urates. A liver considerably enlarged and projecting one or two fingers' breadths below the ribs may be quickly relieved and return to the normal size on the occurrence of hemorrhage from piles or after free watery evacuations produced by a hydragogue cathartic.

The form of hepatic congestion most usually observed is that of the hepatic vein, caused by obstructive troubles of the heart or lungs, and known as the nutmeg liver. The increase of size of the liver under these circumstances may be very considerable. To determine an increase in the area of hepatic dulness the position of the organ must be ascertained with reference to the position of the body, whether recumbent or erect. In the former position the liver gravitates toward the thorax; in the latter, downward into the abdomen. If palpation only were employed to detect an increase in the size of the organ, an error might readily be committed in this respect. Some congestion may doubtless exist without an actual increase of size recognizable by our means of investigation; there may be merely some distension manifested by a sense of increased resistance; the liver may project a hand's breadth below the ribs; and between these extremes there may be all possible degrees of enlargement. When the liver, in consequence of hyperæmia, projects below the ribs, it offers to the sense of touch the impression of a smooth, elastic, rather rounded surface, and not the hardness and nodular character of sclerosis, and not the sharpness of border and hardness of texture belonging to amyloid disease. The enlargement of the liver due to hyperæmia is further distinguished by the fact that it varies much in size at different times, and may be much reduced by hemorrhage from the portal system, and increased suddenly by an attack of dyspnoea.

When the liver is enlarged by hyperæmia the patient usually has a distinct appreciation of the fact, feels a sense of weight, tenderness, and oppression in the right hypochondrium, and experiences a painful dragging from the right toward the left when turned on the left side. In some cases pain is felt in the shoulder, or, if not pain, a feeling of weight. A slight icteroid hue of the conjunctiva, face, upper extremities, and trunk is often present, but the stools are not wanting in bile and the urine contains but little pigment—facts indicating that the obstruction is limited to a small number of ducts. If the jaundice is decided, the stools clay-colored, and the urine loaded with pigment, a catarrhal swelling of the common or hepatic duct exists.

As nutmeg liver is an incident in the course of the venous stasis from cardiac or pulmonary obstructive disease, it is not unusual to find ascites and general dropsy occur. When ascites precedes the other manifestations of dropsy, and is relatively more important, the hepatic congestion has led to atrophy of the cells and contraction of the organ, or to cyanotic induration, as it has been designated in contradistinction to cirrhotic induration.

The subjects of hepatic congestion, especially of that form of the malady due to gastro-intestinal irritation, are apt to experience no little mental depression, even hypochondriasis, as, indeed, is usual in most cases of hepatic disease.

COURSE, DURATION, AND TERMINATION.—The behavior of any case of hyperæmia of the liver is determined, first, by the character of the cause, and, secondly, by the extension of the mischief and the atrophic changes which ensue. The congestion arising from gastro-intestinal irritation is comparatively short-lived, since the causal conditions may usually be promptly removed. It is far different in the cases due to pulmonary or cardiac disease. If caused by a left pleuritic exudation, the congestion will disappear as soon as the bend in the ascending vena cava is removed by paracentesis. If, however, produced by a permanent pulmonary obstruction, the course of the hepatic disease is toward cyanotic induration. The same is true of obstructive cardiac lesions. If compensation—as, for example, of a mitral regurgitation—is not effected, the continual congestion must lead to the ultimate lesions of the liver; but if compensation can be brought about, the liver will be saved the irremediable changes. The prognosis, therapeutical and pathological, must necessarily be dependent on the lesions of which the hyperæmia of the liver is merely a symptom.

DIAGNOSIS.—The decision in any case of hyperæmia of the liver must rest on the determination of the gastro-intestinal, pulmonary, or cardiac diseases causative. When, for example, to the gastro-intestinal disturbance or cardiac disease there are added heaviness, uneasiness, increased area of dulness of the right hypochondrium, a hyperæmia of the liver may be concluded to exist. The extent to which the organ is damaged may be judged from its size, the duration of the congestion, and the character of the determining cause. If the area of hepatic dulness declines steadily after having been increased, the causative conditions continuing, the shrinking is due to atrophy. This view is confirmed if ascites has appeared and increased out of proportion to the general dropsy.

TREATMENT.—Those cases of hyperæmia dependent on excesses in eating and drinking require the substitution of a diet composed of lean meat, skimmed milk, acid fruits, and such succulent vegetables as lettuce, tomatoes, celery, etc. When there is a high degree of gastro-intestinal catarrh, an absolute milk diet may be enforced with great advantage. The diet, exercise, bathing, etc. enjoined in the section devoted to lithæmia are equally applicable here. Amongst the special plans of diet sometimes advocated in the condition of abdominal plethora or portal congestion are the grape cure, the whey cure, etc. Great good is accomplished by a simple diet and a course of the Saratoga saline laxative waters—the Congress, Hathorn, Geyser, etc. The alkaline waters of Wisconsin and Michigan, the White Sulphur of Virginia, and others having similar properties in this country may be employed for the same purpose. The saline laxatives, Pullna, Friedrichshall, and other purgative salines, may be used in robust, plethoric subjects with much portal congestion, hemorrhoids, etc. Phosphate of soda, given in sufficient quantity to maintain a soluble state of the bowels, is also a useful remedy. The resinous cathartics, podophyllin, jalap, rhubarb, aloes, euonymin, iridin, baptisin, etc., are all useful when the indication is to unload the portal circulation. The mercurials, formerly so much used, are now discredited to an unwarranted degree. In an irritable state of the gastro-intestinal mucous membrane calomel in small doses is remarkably useful.

The treatment of congestion of the hepatic vein is included in that of the lesion causing it. In some rather exceptional cases the liver enlarges considerably in consequence of incompetence of the mitral, without there being any other conspicuous evidence of the lesion. Remarkable relief is afforded to the hepatic symptoms by the administration of digitalis. The important point in all cases due to cardiac disease is to bring about compensation, and thus obviate the consequences of the lesion. Remediable pulmonary affections should be cured as promptly as possible, and the evil results of incurable affections lessened by efforts to remove the hepatic hyperæmia. Careful alimentation, saline laxatives, and diuretics are the most efficient measures. It would be encroaching on the subjects of pulmonary and of cardiac diseases to enter more minutely into the therapeutical questions connected with a symptom of these affections.

Perihepatitis.

DEFINITION.—By the term perihepatitis is meant an acute inflammation of the serous envelope of the liver. It may be acute or chronic, very rarely the latter, and it is usually a secondary affection, although primary cases are not uncommon.

PATHOGENY.—Inflammation of the hepatic portion of the peritoneum may arise by an extension of the morbid process from neighboring parts, as in perforation of the stomach or duodenum, pleuritis of that part of the membrane reflected from the diaphragm, etc. More frequently it arises by contiguity from some disease of the liver itself, as chronic interstitial hepatitis, abscess, echinococci cysts, cancer, etc. The author has frequently (comparatively) seen perihepatitis follow the passage of gall-stones. It is usual to find considerable organized exudation at the hilus of the liver in the case of those who have had several attacks of hepatic colic, and attachments to various neighboring parts also. In those instances of secondary hepatitis there may be more or less extensive connective-tissue formation and compression of the hepatic substance (Budd).⁴⁷

⁴⁷ Diseases of the Liver; also, Bamberger, Krankheiten des Chlylopoietic Systems, p. 495, 2d ed.

Direct perihepatitis arises from traumatic causes—from contusions of the right hypochondrium by spent balls, blows and falls, etc. Tight-lacing and wearing a strap to support the trousers are supposed to excite a slow, chronic hepatitis, but the latter is more certain to bring about such a result than the former.

SYMPTOMS.—Acute perihepatitis, if of sufficient extent, causes more or less fever; pain is felt in the right hypochondrium, and is increased by pressure and by deep inspirations, and in some rare instances a friction murmur is audible synchronous with the respiratory movements. These symptoms succeed to attacks of hepatic colic, perforation of the stomach or intestine, and contusions of the abdominal wall. The chronic form is not febrile; there is a feeling of soreness instead of acute pain; pressure, the movements of the body, respiration, etc. increase the distress, and on turning on the left side a painful dragging is experienced. A slight degree of icterus may be present in both acute and chronic cases.

COURSE, DURATION, AND TERMINATION.—The course of the acute cases is toward recovery. In two or three days the inflammation reaches the maximum, adhesions form, and then the morbid process declines. The whole course of an acute perihepatitis caused by external injury or by the passage of gall-stones is terminated in a week or ten days. The mischief done may not be limited to the adhesions formed. The large quantity of newly-organized connective tissue may, in its subsequent contraction, compress the common, cystic, or hepatic duct, or the portal, or both ducts and vein. The course of the chronic cases is determined by the causative lesion. The contraction of the new-formed connective tissue may compress the organ and lead to sclerotic changes which cannot be distinguished from cirrhosis. In some instances contusions set up suppurative inflammation, and an abscess forms between the parietal and glandular layer of the peritoneum. Such a case will then present the phenomena of hepatic abscess.

DIAGNOSIS.—The determination of the character of the case will be largely influenced by the history. If the attack has followed a blow on the side or a paroxysm of hepatic colic or the symptoms of perforation, there will be no difficulty in determining its seat and character. In the absence of the history the differentiation must be made between perihepatitis and pleuritis. The distinction consists in the fact that in the former the pain and soreness are below the line of respiratory sounds, although synchronous with them. In chronic perihepatitis the symptoms come on in the course of the hepatic disorder, or are consequent on a local injury, as the pressure of stays or a band.

TREATMENT.—If the symptoms are acute and the subject robust, the local abstraction of blood by leeches affords relief and diminishes the violence of the disease. A bandage should be tightly applied around the body at the level of the hypochondrium to restrain the movements of the affected organ. A turpentine stupe may be confined in this way, or a compress of water may be utilized to serve the same purpose. If the pain is acute and the peritonitis due to perforation or to the passage of calculi, the hypodermatic injection of morphia is the most important resource.

Interstitial Hepatitis; Sclerosis of the Liver; Cirrhosis.

DEFINITION.—The terms interstitial hepatitis and sclerosis of the liver express the nature of the malady: they signify an inflammation of the intervening connective tissue, resulting in a sclerosis—an induration of the organ. The term cirrhosis, now so largely in use, was originally proposed by Laennec⁴⁸ because of the yellowish tint of the granulations, from the Greek word, [Greek: chirros], yellow. As Laennec's theory of cirrhosis was erroneous, having regarded these granulations as new formations, the word is a very faulty one, and hence it would be preferable to use the term sclerosis, since a similar change in other organs is thus designated, as sclerosis of the kidney, sclerosis of the lungs, etc. It is also called in England gin-drinker's liver, hobnail liver. Carswell⁴⁹ first described the anatomical changes with accuracy, and illustrated them with correct drawings. The following year Hallmann⁵⁰ confirmed the truth of Carswell's descriptions, and contributed a good account of the morbid anatomy; and subsequently French, German, and English authorities added new facts, which will be set forth in the further discussion of the subject.

⁴⁸ Traité de l'Auscultatlon médiate, tome ii. p. 501.

⁴⁹ Illustrations of the Elementary Form of Diseases, fasciculus 10, plate 2.

⁵⁰ De Cirrhosi hep., Diss. Inaug., Berolini, 1839, quoted by Thierfelder.

CAUSES.—Sclerosis of the liver is, conspicuously, a disease of adult life and onward. Except the congenital example mentioned below, the earliest age at which the disease has occurred, so far as I am able to ascertain, is four years—a case reported by Wettergreen⁵¹ of hypertrophic sclerosis, in which neither a syphilitic nor paludal cause could be ascertained. Cayley⁵² reports a case in a child of six; Murchison,⁵³ Frerichs,⁵⁴ Griffith,⁵⁵ one each at ten. After this period the increase relatively to age is rapid. The majority of cases occur between thirty and fifty years. Yet Virchow⁵⁶ has given the details of a congenital example. According to Förster, of 31 cases of cirrhosis, 16 were between forty and sixty years. The preponderance of cases in the male sex is very decided. Of Bamberger's 51 cases, 39 were men, 12 were women; of Frerichs' 36 cases, 20 occurred in men and 16 in women—a larger proportion of women than any other author records; of 12 cases observed by myself, only 1 was a woman. Nationality does not affect the production of cirrhosis, except as regards the personal habits of the people. This disease is comparatively uncommon in wine- and beer-drinking countries, and frequent amongst a spirit-drinking people.⁵⁷ The great etiological factor is the abuse, the habitual use, of spirits, and hence the number of cases observed in North Germany, England, Scotland, and the United States. Murchison affirms that he has never seen a case produced in any other way. Even in children of tender years the abuse of spirits can usually be traced. Nevertheless, there are instances of the disease the origin of which cannot be referred to alcoholic excess. The congenital cases, as that narrated by Virchow, and the instances occurring in children and adults not given to spirits in any form, indicate that there are other pathogenetic influences which may bring about a sclerosis of the liver. Virchow⁵⁸ was one of the first to illuminate the subject of visceral syphilis and to demonstrate the occurrence of sclerosis of the liver from syphilitic infection. Very often the syphilitic cachexia coincides with alcoholic excess. There can be no doubt that chronic malarial poisoning causes, or powerfully predisposes to, cirrhosis. I have submitted elsewhere pathological evidence on this point,⁵⁹ and the Italian physicians, who have the opportunity to obtain accurate data, maintain that malarial toxæmia does bring about this state. It is probable that the overgrowth of connective tissue is induced by the repeated congestions of the malarial attacks, and by the obstruction due to catarrh of the bile-ducts which so often occurs in the febrile paroxysms.

⁵¹ Hygeia, 1880, quoted by London Medical Record, March 15, 1881.

⁵² Transactions of the Path. Society of London, vol. xxvii., 1876, pp. 186, 194.

⁵³ Clinical Lectures, loc. cit.

⁵⁴ Clinical Treatise, etc., Syd. Soc. ed., by Murchison.

⁵⁵ Clinical Lectures, loc. cit.

⁵⁶ Archiv f. path. Anat., Band xxii. p. 426.

⁵⁷ Baer, Der Alcoholismus, Berlin, 1878, p. 62 et seq.

⁵⁸ Virchow's Archiv, vol. xv. p. 281; also, Lancereaux, A Treatise on Syphilis, Syd. Soc. ed.

⁵⁹ Memoirs of the Sanitary Commission, medical volume.

J. Wickham Legg⁶⁰ and Charcot⁶¹ nearly simultaneously discovered that obstruction of the bile-ducts, if continued a sufficient length of time, sets up a hyperplasia of the connective tissue of the liver. The evidence is pathological and experimental. Thus, Legg has seen a liver markedly cirrhotic in a case where a small cancer of the duodenum completely obstructed the flow of bile into the intestine.⁶² By tying the common duct in dogs it was found that a hyperplasia of the connective tissue very soon occurred, and this was followed, of course, by contraction of the new tissue and atrophy of the hepatic cells. Closure of the hepatic vein has the same effect, and also, as Solowieff⁶³ has asserted, closure of the portal vein; on the other hand, by Frerichs and others the closure of the portal is attributed to the sclerosis.

⁶⁰ On the Bile, Jaundice, etc., loc. cit., p. 351 et seq.

⁶¹ Leçons sur les Maladies du Foie, etc., p. 231 et seq.

⁶² On the Bile, Jaundice, etc., loc. cit., p. 355.

⁶³ Arch. f. path. Anat., etc., Band lxii. p. 195.

Certain poisons, as antimony, arsenic, notably phosphorus, have the power to set up an irritative hyperplasia of the connective tissue of the liver. These metals accumulate in the liver in preparation for excretion. Wegner,⁶⁴ in the study of the action of phosphorus on dogs, rabbits, and other animals, has induced a marked degree of sclerosis, but such results have not been observed in cases of poisoning by phosphorus in man, except in an instance reported by Küssner.

⁶⁴ Virchow's Archiv, Band lv. p. 18.

Finally, a condition of the liver corresponding in all respects to cirrhosis has been induced by perihepatitis, by the organization of the exudation and its subsequent contraction, and by the extension of the morbid process from the capsule to the interlobular connective tissue (Poulin⁶⁵).

⁶⁵ Étude sur les Atrophies viscérales consécutives aux Inflammations chroniques du Sereuses, etc., Thèse de Paris, 1880.

PATHOLOGICAL ANATOMY.—Several forms of cirrhosis are recognized by the modern French school of pathologists. According to Sabourin,⁶⁶ there is an annular, a monolobular, and a multilobular form. These differ merely in regard to the arrangement of the new connective tissue. At the outset of the disease the liver is increased in size and hyperæmic. Its consistence is also greater than normal. The outer surface is at this period smooth, but on section the islets of the parenchymatous tissue, yellowish in color, are distinctly visible between the grayish or pale-rose tint of the intervening or proliferating tissue. This reddish-gray material consists of fine connective-tissue elements containing spindle-shaped cells.⁶⁷ The development of this material is such as to even exceed in quantity the proper glandular structure. The bands of newly-formed connective tissue extend between individual lobules (monolobular cirrhosis) or between groups of lobules (multilobular cirrhosis). A portion of the spindle-shaped cells form new vessels communicating with the branches of the hepatic artery.⁶⁸ Coincidently with the formation of the new connective tissue ensues its contraction. The enlarged organ diminishes in size from a slight degree to one-half its original volume; especially in the left lobe is the diminution of size most marked. On the surface it exhibits a knobbed or nodular aspect (hobnail liver), and these knobs present through the capsule a yellow appearance. The granulations, so called, consist of small prominences corresponding to lobules or groups of lobules, and hence vary in size from that of a pinhead to that of a pea.⁶⁹ Between these are the sharply-defined masses of connective tissue. On section the organ is found to be of firm almost cartilaginous hardness, and between the interlacing bundles of connective tissue are the small islands of parenchymatous tissue projecting above the cut surface and having a yellowish or brownish-yellow color. As the terminal branches of the portal are compressed in the process of shrinking undergone by the new connective tissue, they are destroyed. The result of this obliteration of the portal radicles is the impaired nutrition of the lobules and atrophy of the cells. Formerly it was held that the atrophy of the hepatic cells was due to the compression exercised by the contracting connective tissue, and Beale⁷⁰ even maintained that the change began in the cells, the connective tissue contracting as the cells receded before them. This view has been reaffirmed by Ackermann in a paper read last year before the Congress of German Naturalists and Physicians, but without any acknowledgment, so far as I can ascertain, of Beale's long-before expressed opinions. In the discussion which followed the reading of Ackermann's paper the position of its author was supported by Aufrecht, Küssner, and others, but controverted by Rindfleisch. It has been demonstrated by Cohnheim and Litten⁷¹ that the lobule is nourished not only by the portal radicles, but by the branches of the hepatic artery, which enter, by the interlobular vein, the capillaries of the lobule, and hence the nutrition of the cells suffers in consequence of the lessened blood-supply; but it is probable also that more or less compression is exercised. When the cells are destroyed, their remains may be discerned in the mass of connective tissue as fine fat-granules or masses of pigment yellowish or brownish in color. The peculiar appearance to which the name cirrhosis is applied is due to the lobules or groups of lobules which project on section above the divided surface, and are colored yellowish by the bile-pigment, which here exists in an exaggerated quantity. The cells themselves are not normal: they are enlarged by compensatory hypertrophy, and they contain much bile-pigment and a considerable quantity of fat. The compression of the capillaries, especially their obliteration, leads to stasis of the blood and its consequences in the whole chylopoietic system.

⁶⁶ Ch. Sabourin, "Du Rôle que joue le Système veineux sus-hépatique dans la topog. de la cirrhose du foie," Revue de Médecine, June, 1882.

⁶⁷ Förster, Lehrbuch der pathologischen Anatomie, Jena, 1873, p. 264.

⁶⁸ Cornil, "Note sur l'État anatomique des Canaux biliaires et des Vaisseaux sanguins dans la cirrhose du foie," Gaz. méd. de Paris, 1883.

⁶⁹ Charcot, Leçons sur les Maladies du Foie, etc., p. 226.

⁷⁰ Archives of Medicine, vol. ii. p. 82.

⁷¹ Archiv für path. Anat. (Virchow), Band lxvii. p. 153 et seq.

SYMPTOMS.—The development of sclerosis is usually very insidious. After some years' indulgence in spirit-drinking or affected for a length of time with the other causes of the malady, a gradual decline of vigor occurs. The complexion takes on a fawn color, stigmata slowly form on the face, there is more or less yellowness of the conjunctiva, and attacks of headache, giddiness, and even severe vertigo, are experienced. An increasing indisposition to mental effort, some hebetude of mind, and a gradually deepening despondency are felt. The appetite gradually fails, becomes capricious, and only highly-seasoned, rather odd, or unusual articles of food can be taken. Such subjects acquire a taste for condiments, for such uncooked vegetables as onions, celery, raw cabbage, etc., for fruits, and get a distaste for plainly-cooked meats and vegetables, for sweets, etc. The digestion is as capricious as the appetite: at first there are times of appetite, again of indifference, then of disgust; some heaviness is felt after meals; gaseous eructations, acidity, pyrosis, nausea, occur day after day as the case advances; and ultimately morning vomiting is regularly experienced. Nausea is felt on rising; then with much straining and distress a little glairy mucus and a teaspoonful of bile are brought up; after which, it may be, a little food can be taken. It is only after the case is fully declared that these troubles of stomach digestion become constant; previously they occur now and then in a paroxysmal way, whilst between there is only labored digestion.

As the compression of the portal radicles maintains, by reason of the obstruction, a constant hyperæmia of the intestinal mucous membrane, a catarrhal state, with fermentation of the fatty, starchy, and saccharine constituents of the food, and hence complicated products of an irritating kind, must result therefrom. Hemorrhoids, varying in size according to the degree of obstruction, form, sometimes bleeding more or less profusely, again being merely troublesome or painful. Fissures of the anus and fistula in ano not unfrequently complicate the case. The bowels are necessarily rather relaxed than confined, but at the onset of the malady they may be confined, afterward assuming more or less of the characteristics of diarrhoea. The stools may be offensive with the products of decomposition, rather clay-colored or golden, or brownish and almost black from the presence of blood. In some cases the stools are parti-colored—clay-colored in part, brownish in part—and in exceptional examples continue normal or nearly so until near the end. As the transudations from the portal vessels increase, the mucous membrane of the intestinal canal becomes oedematous, and, the normal secretions being arrested, the discharges finally consist of a watery fluid, whitish or grayish, dark-brown or blackish, and very offensive. The decomposition of foods instead of their proper digestion and solution, and especially the fermentation of the starchy and saccharine constituents of the aliment taken, produce a great quantity of gas; hence meteorism comes to be an ordinary symptom. The accumulation of gas is greatly promoted by the paretic state of the muscular layer and by the relaxation of the abdominal walls consequent on the oedema of the muscular tissue. A high degree of distress is sometimes caused by the great accumulation of flatus; the abdomen is greatly distended and the diaphragm is pushed up against the heart and lungs, compelling the patient at length to sit up to breathe with ease. Of course the accumulation of fluid may be greater, and the gas only add to the discomfort.

A very common symptom is hemorrhage. Sometimes it happens, indeed, that this is the only evidence of the portal obstruction at first observed. Hæmatemesis is more common than intestinal hemorrhage. Now the blood may be large in quantity, appear little changed from its usual coagulated state, and be brought up promptly with slight effort of vomiting; now it is passed by stool, is in coffee-colored, granular masses or in a tar-like, semifluid state; and again it appears in coffee-grounds mixed with the contents of the stomach. These variations are due to the character, seat, and extent of the hemorrhage and to the condition of the mucous membrane. Merely-distended capillaries, yielding, may furnish a little blood, which, acted on by the gastric juice, forms coffee-grounds, or, if not acted on in consequence of the failure of the gastric glands to functionate, appears as bloody streaks mixed with mucus. Enlarged veins, giving way, may furnish a large quantity of partly-coagulated venous blood, charred or not as the state of the juices will determine. In some cases hemorrhages into the submucous tissue or thromboses of the submucous veins lead to solution of the membrane thus deprived of its nutritional supply, and ulcers form. Two admirable examples of this kind have been seen by the writer in which large hæmatemesis occurred from ulcers near the pylorus. They were round, smooth ulcers, containing coagula, and the eroded vessels (veins) were readily seen opening into the cavity of each.

The obstruction to the portal circulation results also in an enlargement of the spleen. There may be a simple enlargement due to the hyperæmia merely; there may be an enlargement due to the hyperæmia and to a resulting hyperplasia of the connective tissue; there may be also, in addition to the second form of enlargement, amyloid degeneration, syphilitic hyperplasia, etc. The increased dimensions of the spleen are by no means always made out, and authorities differ greatly as to the proportion of cases in which the enlargement can be detected. The organ may indeed be considerably enlarged whilst pushed upward into the left hypochondrium by the effusion, and yet the attempt to measure and define its dimensions may be fruitless. From a slight increase due to the hyperæmia up to the enormous dimensions acquired by the added amyloid material there are all possible variations in size.

Partly in consequence of the increased blood-pressure in the vessels of the peritoneum, and partly in consequence of the watery condition of the blood itself, effusion takes place into the sac of the peritoneum. Such an accumulation is known as ascites, or dropsy of the abdomen. The time at which the effusion begins, the amount of it, and the degree of contraction of the liver necessary to produce it, vary in each case. Ascites may be the first symptom to announce the onset of cirrhosis; it is more frequently amongst the later symptoms, and is the evidence of much interference in the portal circulation. However, it is not due wholly to hepatic disease. The blood in cirrhosis is much reduced and watery, hence slight causes suffice to induce an outward diffusion. Given a certain obstacle to the passage of the blood through the liver, transudation will be the more prompt to appear the greater the anæmia. In some cases an enormous quantity of fluid collects: from ten to thirty pounds may be regarded as usual, and forty to sixty pounds as exceptional, although the highest amount just given is not rare. The fluid of ascites nearly represents the serum of the blood. It has a straw color and is clear, but it may have a reddish tint from the presence of blood, a greenish-yellow or brown from bile-pigment. The solids of the serum are in the proportion of from 1 to 3 per cent., and consist of albumen chiefly and salts, of which sodium chloride is the principal. Hoppe's⁷² analysis gives this result: 1.55 to 1.75 solids, of which 0.62 to 0.77 is albumen. According to Frerichs, the amounts of solids ranges from 2.04 to 2.48, and of these albumen constitutes 1.01 to 1.34.

⁷² Virchow's Archiv für path. Anat., etc., Band ix.

Oedema of the inferior extremities comes on after, usually—rarely with—the ascites. If the mechanism of this oedematous swelling be as supposed, the effusion into the areolar tissue necessarily succeeds to the abdominal effusion. The pressure of the fluid in the cavity on the ascending vena cava and iliac veins seems to be the principal factor; but to this must also be added the intestinal gas, which in some instances exerts a powerful force. The ankles have in rather rare cases appeared swollen before the abdomen, but the detection of fluid in the peritoneal cavity when in small quantity is not always easy. Obese women, with much accumulation of fat in the omentum and flatus in the intestines, have swollen feet and legs if erect for some time, the effusion being due to pressure on the vena cava. The legs may become enormously distended. The scrotum and penis in the male, the vulva in the female, the buttocks and the abdominal wall, also become oedematous, sometimes immensely. Walking grows increasingly difficult. Warmth and moisture and the friction of the sensitive surfaces excite vesicular and pustular eruptions where the scrotum and labiæ come in contact with the thighs. Urination may be impeded by the oedema of the prepuce.

An attempt at compensation for these evils growing out of the obstruction in the portal system is made by the natural powers. Anastomoses of veins through minute branches are made use of to convey the blood of the obstructed portal circulation into the general venous system, and to this end become greatly enlarged. The interlobular veins being obliterated by the contracting connective tissue, the pressure in the branches and trunk of the portal vein is much increased. Hence an outlet is sought for in the veins which communicate between the portal and the ascending vena cava. One of the most important of these is a vein in the round ligament, at one time supposed to be the closed umbilical vein, but proved by Sappey to be an accessory portal vein. Bamberger,⁷³ however, has found the umbilical vein pervious, and since, Hoffmann⁷⁴ has demonstrated the same fact. It is probable, indeed, that Sappey's observation is correct for some cases. In either event, the veins of the abdominal wall about the umbilicus communicating with the epigastric become enormously distended, and in some advanced cases of cirrhosis form a circle known as the caput Medusæ. Further communication between the portal and the veins of the diaphragm takes place by means of the veins in the coronary and suspensory ligaments. In some instances a new route is established between the veins of the diaphragm and the portal by means of new vessels formed in the organized connective tissue resulting from perihepatitis. Still another channel of communication exists between the inferior oesophageal veins, the azygos, and the coronary, and finally between the inferior hemorrhoidal and the hypogastric. The more completely can communication be established between these anastomosing veins the less severe the results of portal obstruction.

⁷³ Krankheiten des Chylopoiet. Syst., loc. cit.

⁷⁴ Quoted by Thierfelder, op. cit.

Besides these indirect evidences of portal obstruction and a contracting organ, there are direct means of ascertaining the condition of the liver. By the methods of physical diagnosis we may acquire much information. On auscultation, as our Jackson⁷⁵ was the first to show, a grating or creaking like leather, or friction sound, is audible over the right hypochondrium synchronously with the respiratory movements or when produced by moving with the fingers the abdominal wall on the liver. This sound is caused by the bands of false membrane which extend between the two surfaces, and hence indicates a secondary perihepatitis.

⁷⁵ The American Journal of the Medical Sciences, July, 1850.

To ascertain the dimensions of the liver—to mark out the area of hepatic dulness—with accuracy is a most necessary procedure. The period of the disease is an important element in the problem. When the new material is deposited and the congestion of the portal system first occurs, an increase in the dimensions of the organ is observed. This enlargement, of brief duration, must not be confounded with the hypertrophic sclerosis, another form of the malady. So considerable is the increase in the size of the liver that there is an evident enlargement of the right hypochondrium, and the whole abdomen seems fuller. The organ may be felt, on palpation, projecting one, two, or even three fingers' breadths below the margin of the ribs, and the left lobe extends well across the epigastrium, increasing the sense of resistance and the area of dulness in this direction. The enlarged liver, as felt below the ribs, appears firmer than is natural, is yet smooth, and the margin is sharply defined. The duration of this period of enlargement is indefinite, but it is rather brief, and is followed by the contracting and atrophic stage. It is not often, indeed, that the patient presents himself during the period of enlargement. Sometimes a perihepatitis or an unwonted tenderness in the right side compels attention during this stage, but more frequently it escapes notice. If perihepatitis occur, there will be fever, pain, and tenderness, a slight icterode hue of the skin, and possibly Jackson's⁷⁶ friction sound. These symptoms, taken in conjunction with the history of the case and the obvious enlargement of the organ, will indicate the existence of the first stage of sclerosis.

⁷⁶ The American Journal of the Medical Sciences, July, 1850, supra.

The contraction of the liver, or, as it may be expressed, the atrophy of the hepatic cells and the consequent shrinking of the interlobular connective tissue, goes on slowly. Several months may be occupied in an amount of atrophy distinct enough to be recognized by the narrowing of the area of hepatic dulness. Especially difficult is the recognition of the contraction when ascites has fully distended the abdomen. It may be necessary under such circumstances to postpone a decision until tapping has removed the fluid. If the organ can be felt by depressing the walls of the abdomen, more or less unevenness of surface may be detected, and the inferior margin may give the impression of hardness and sharpness of outline. At the same time, the increased dulness of the epigastric region observed during the hypertrophic stage will have gradually ceased because of the shrinking of the left lobe. The liver may be undergoing the atrophic degeneration to a marked extent and yet remain large—larger even than normal. Such a state of things may be due to conjoint amyloid or fatty degeneration of the organ, and, indeed, more or less fatty change occurs in all cases of cirrhosis. The shrinking of the liver persists until the area of dulness is not greater in area than two or three ribs.

The disturbances of function in sclerosis of the liver are not limited to the chylopoietic system. As the secreting structure of the liver is continually lessened in extent by the atrophy, symptoms result from the necessary interference in the hepatic functions. These symptoms are concerned with the liver, with the nutrition of the tissues of the body, and with the kidneys. As regards the biliary function of the liver, the quantity of bile acids and pigment is reduced below the normal in proportion to the damage done to the organ. As a rule, there is little jaundice in sclerosis, and very little bile-pigment present in the urine. Hence there must be little produced. Instead of a jaundiced hue of the skin, it has a fawn color—an earthy, sallow tint eminently characteristic of a chronic affection in which the power to produce bile is much impaired. Occasionally it happens, particularly in the early stages of cirrhosis, that a well-marked jaundice appears in the face and body, but this probably is due to a catarrh of the bile-ducts. In most cases the integument presents the earthy and sallow hue above mentioned. Graves⁷⁷ appears to have been the first to interpret aright the greater significance of this appearance of the skin than the purely jaundiced tint. The glycogenic function of the liver must be impaired in the same ratio as the biliary. The nutrition of the body suffers; the skin becomes dry and harsh; the fat disappears; the temperature of the body, unless the conditions for producing fever are present, is barely up to normal, if not somewhat below; a marked degree of anæmia supervenes; and the action of the heart becomes feeble and rapid after a period of slowness. The blood is altered in quality, and hence hemorrhages—epistaxis especially—occur, petechiæ and ecchymoses appear in the skin, and stigmata are numerous about the face and nose.

⁷⁷ Clinical Medicine, op. cit.

The urine in cirrhosis is high-colored because of the abundance of pigment, and in the early stages of the disease is increased in amount, although of lower specific gravity. When much effusion takes place into the peritoneal sac, the compression of the renal veins by the fluid lessens the activity of the kidneys and diminishes the urinary flow. Much discussion has taken place over the quantity of urea present in the urine in cases of cirrhosis, but it has been established that the relative quantity of urea lessens in proportion to the damage suffered by the liver.⁷⁸ The urates are in excess.

⁷⁸ Charcot, Leçons sur les Maladies du Foie, loc. cit., p. 252; also, Essai sur les Variations de l'Urée dans les Maladies du Foie, par F. Genevoix, Paris, 1876; Des Rapports de l'Urée avec le Foie, par A. Martin, Paris, 1877; Sur l'Urée et ces Variations dans la Cirrhose, Thèse de Paris, Audiguier; Contribution à l'Étude du Rôle du Foie dans la Product. de l'Urée, Reufflet.

COURSE, DURATION, AND TERMINATION.—There are enormous variations in the course of the disease as respects the rate of its progress. In general, it may be said that the whole duration is from three months to six years. The onset is often insidious, and little distress is occasioned until effusion begins in the abdomen. In other cases there is considerable pain in the right hypochondrium, severe disorders of digestion and intestinal derangements, rapid emaciation, ascites, and some intercurrent malady which terminates them, often quite unexpectedly. The usual course is as follows: After the protracted use of alcoholic stimulants the symptoms of gastro-intestinal catarrh appear; there occur acidity, pyrosis, morning vomiting, and distress after meals; the bowels are irregular, the stools rather dark and offensive; the bodily vigor declines and the mental condition is depressed and hypochondriacal; emaciation progresses; the skin becomes dry, harsh, and fawn-colored; stigmata appear on the face; some uneasiness is felt in the abdomen, through the right hypochondrium, and about the umbilicus; presently the abdomen enlarges and the feet and legs swell; after a time the abdominal enlargement is extreme and the walls become thin, the genitals and thighs are greatly distended, and the prepuce is so swollen that urination grows more and more difficult, the penis almost disappearing in the surrounding oedema; notwithstanding the immense size of the abdomen and lower extremities, the chest, face, and upper extremities are wasted away; to lie down is impossible, and only snatches of disturbed sleep are procured in the upright sitting posture; breathing grows more and more difficult, and a sense of suffocation is imminent; and, thus worn out by suffering and want of sleep, the patient at last sinks into a soporose state and dies comatose, if not cut off before by some acute serous inflammation—pleuritis, peritonitis, peri- or endocarditis, pneumonia, etc.

The course of any case of cirrhosis is much influenced by the amount of damage to the hepatic cells and by the extent of the compensatory changes in the circulation. Ulcers of the stomach or intestine, opening vessels, or hemorrhages from the mucous membranes may have a pronounced effect on the progress of any case. A fatal result was determined in a case under the writer's charge by hemorrhage from ulcers near the pylorus, which were caused by thromboses of the stomach veins at that point. Occasionally, the occurrence of thrombosis of the portal vein adds an embarrassing and dangerous complication. The liver, besides the change due to cirrhosis, may be affected by amyloid or fatty degeneration, or by both combined. It should not be forgotten that more or less fatty change takes place in the hepatic cells undergoing atrophy, whence the appearance called cirrhosis. Sclerosis may be a general condition in which several organs participate, the kidneys notably. These organs are changed by a hyperplasia of the connective tissue, and especially by fatty degeneration of the epithelium. In the brain the sclerosis consists in chronic pachymeningitis, adhesions of the dura, etc., and with these connective-tissue changes are often associated extravasations of blood. These lesions are probably due to chronic alcoholism rather than to the cirrhosis—are simultaneous lesions, instead of consecutive.

The duration of cirrhosis must necessarily depend largely on the occurrence of the complications above mentioned and on the appearance of intercurrent diseases. The most usual intercurrent maladies are peritonitis, pleuritis, and other serous inflammations. An attack of cerebral (meningeal) hemorrhage may occur. Failure of the heart may be due to fatty degeneration of its muscular tissue. Stupor, coma, and insensibility may come on toward the close in consequence of the retention of excrementitious matters. By Flint, Jr., these cerebral symptoms were referred to the retained cholesterin, and hence he designated this state cholesteræmia. Numerous experimentalists (Pagès,⁷⁹ Chomjakow,⁸⁰ Von Krusenstern,⁸¹ Koloman Müller⁸²) have studied this question, and only Müller has been able to confirm Flint's theory. The condition is more suitably designated cholæmia, which signifies blood-poisoning from the excrementitious biliary matters retained in the system.

⁷⁹ Quoted by Legg, p. 233.

⁸⁰ Quoted by Krusenstern.

⁸¹ Virchow's Archiv, Band lxv. p. 412.

⁸² Archiv für experimentelle Pathologie und Pharmakologie, Band i. p. 213.

Any fully-developed case of cirrhosis can only terminate in one way, for we possess no means of restoring the hepatic cells when once destroyed. At the outset of the disease, before any serious changes have taken place, it is probable it may be arrested. Proceeding to its natural termination without complications or intercurrent affections, death finally occurs from exhaustion. The emaciation becomes extreme, the stomach gets to be excessively irritable, and an exhausting diarrhoea consumes the last remains of strength. Then an oedema of the lungs or failure of the heart or a deep coma ends the scene.

DIAGNOSIS.—Cirrhosis in its first stage is to be distinguished from diseases which cause enlargement of the liver, and in its second or contracting stage from diseases that induce contraction of the organ. The history of alcoholic excess is an important means of differentiating this from other affections. The enlargement belonging to alcoholism is distinguished from that due to amyloid disease by the permanent character of the latter and by its history of chronic suppuration, in addition to, it may be, alcoholic excess; from cancer, by the character of the enlargement, by its permanence, by the secondary deposits in the mesentery and elsewhere, by the severe and persistent pain; from hydatids or echinococci cysts by the painless enlargement of the latter, by the absence, usually, of any interference with the hepatic functions, by the purring thrill, and by the presence of the characteristic hooklets in the fluid withdrawn. From the maladies characterized by the contraction of the organ it is distinguished by the rapidity with which the case is developed in acute yellow atrophy, and by the profound constitutional disturbance characteristic of this form of contraction. When the liver is lessened in size in consequence of the compression exercised by the contracting exudation of a local peritonitis, there is a history of pain and soreness of the right hypochondrium, followed by the symptoms of contraction—a very different history from that of cirrhosis, in which the local attacks of pain and distress succeed to or accompany the symptoms of contraction. Occlusion of the gall-ducts by a calculus may set up a slow atrophy having some points of resemblance to cirrhosis; but in this malady attacks of hepatic colic precede the signs of obstruction, the jaundice, and gray evacuations, and the evidences of contraction succeed to these very characteristic symptoms; whereas in cirrhosis paroxysms of pain followed by jaundice are not known. Occlusion of the portal vein may also be followed by atrophy, but this is usually due to some other affection of the abdominal organs, and the change in the condition of the liver occurs very promptly, there being neither the history nor the course of symptoms belonging to cirrhosis.

TREATMENT.—As the abuse of alcoholic liquors—even their habitual use in moderation—is the chief pathogenetic factor, they should be entirely given up. Condiments, coffee and tea, highly-seasoned animal foods, are of less importance as causes, but are sufficiently injurious to require them to be discontinued. The food of such subjects should not contain fat, because the bile is necessary to its right assimilation, and should have but a small proportion relatively of starch and sugar, since these articles readily ferment in the presence of an excess of mucus and in the absence of the bile. The succulent vegetables, as lettuce, celery, spinach, etc., should be substituted for the starchy and saccharine. A diet largely composed of skimmed milk renders an important service both as a nutrient and a diuretic and depurant. Lean meats, acid fruits, and the weak alkaline mineral waters should be the basis of a proper system of alimentation.

As malarial intoxication is a cause now distinctly recognized, patients should be removed from such influences. If this be impracticable, the effects of the poison should, as far as possible, be removed, especially the glandular complications. To this end, such remedies should be employed as will affect the overgrowth of the connective tissue, as the compound solution of iodine, the bichloride of mercury, and the chloride of gold (or gold and sodium). Quinine will be necessary, according to circumstances.

Do we possess any means to check the overgrowth of connective tissue in cases of sclerosis? The writer believes that those remedies have this power to a less or greater extent which are separated by the liver from the blood. These are chiefly the salts of gold, silver, copper, arsenic, and mercury (chloride), and phosphorus. The most useful of these are the chloride of gold and sodium and the chloride of mercury, and some phosphates. The writer has had, he thinks, curative results in the commencement of the disease from the chloride of gold and sodium and the phosphate of sodium. German practitioners believe that the chloride of ammonium is a powerful alterant and deobstruent, and prescribe it in this affection to stop the overgrowth of connective tissue. That it does have this effect can hardly be disputed, but the daily quantity necessary is large, the taste very disagreeable, and the stomachal effect that of an irritant. Hence it is by no means so effective as the chlorides above mentioned. The chloride of gold and sodium (¹/10 grain) can be given at the same time with chloride of mercury (¹/20 grain) if it is desirable to combine their effects. The writer has seen what appeared to be cases of cirrhosis in the first stage yield to the persistent administration of phosphate of sodium—drachm j ter in die—and the chloride of gold and sodium.

When contraction of the liver has ensued, and hemorrhages, effusion into the cavity of the peritoneum, and a high degree of gastro-intestinal catarrh have occurred, the relief of the secondary symptoms takes the first place in importance. There are but three modes by which an effusion into the abdomen can be removed: by the skin, by the kidneys, by the intestinal canal. Each of these may be employed in turn. By the skin warm baths, vapor baths, digitalis stupes, and especially the subcutaneous injection of pilocarpin, may be employed. These alone may be sufficient in some cases—rather rarely, however. They may all be used simultaneously or in turn to effect the purpose. A digitalis stupe may be made to have the effect of a vapor bath: a large one is placed on the abdomen and the body is covered with blankets, which results in the production of abundant sweating. The vapor bath is applied in the ordinary way, so that no explanation is needed. If there be no contraindication in the state of the heart, pilocarpin salts can be injected in sufficient quantity to induce active diaphoresis. These measures proving inadequate, an attempt should be made to dispose of the fluid by acting on the kidneys and promoting diuresis. Amongst the diuretics in ascites, Wilks places the resin of copaiba first. The dose ranges from two to five grains, and it may be given in combination with gold or mercury chloride. When this remedy increases the flow of urine, it does good, but if the quantity of urine remains unchanged, it does no good, and should be discontinued.

As the effusion of fluid is due to the portal obstruction, it follows that depletion of the terminal radicles of this system will act most directly on the origin of the troubles. Hydragogue cathartics have, therefore, an important place in the treatment of ascites of hepatic origin. One of the most generally efficient of these remedies is the compound jalap powder, for whilst it produces free watery evacuations, it also stimulates the kidneys somewhat. It is generally better to give a full dose—one or two teaspoonfuls—in the early morning, so that the disturbance caused by it will subside before the time for taking food. Several free watery evacuations should be produced by it. Sometimes the resin or extract of podophyllin is added to the compound jalap powder to increase its activity. Purgative combinations of colocynth, gamboge, and resin of podophyllin are also occasionally employed, but the most efficient hydragogue is elaterium. The last-mentioned may act very efficiently without causing any considerable depression, but the results obtained by it are usually fleeting. After even a very free discharge of fluid the effusion quickly increases, and further purgation is required. Tapping is a palliative expedient which must sometimes be considered. With the present improved aspirator and the antiseptic method the fluid may be withdrawn with ease and safety. It is not necessary in any case to remove all the fluid—merely that quantity which will relieve the pressure on the diaphragm and on the renal vessels. The author has seen general peritonitis result from tapping. As such a complication will increase all the difficulties of a case, it is very desirable to prevent it by careful application of the antiseptic method and sealing of the punctured orifice to prevent the entrance of germs.

In the protracted cases of cirrhosis there ensues, finally, a highly catarrhal state of the mucous membrane, the bowels become very irritable, and frequent offensive and watery discharges occur. If under these circumstances the abdominal effusion increases, the remedies must consist of diuretics and diaphoretics rather than purgatives. Indeed, an exhaustive colliquative diarrhoea may require bismuth, copper, and other astringents, combined with opium, to prevent the patient passing into the condition of collapse. Hemorrhage by vomiting or by stool will demand ice, subsulphate of iron, ipecac, ergotin in the form of subcutaneous injection especially, and other remedies which have been found useful in gastric or intestinal hemorrhage.

Topical remedies are not without utility if used early. When the changes in the liver are secondary to peritonitis of the hepatic portion, the application of leeches and cups renders an important service. At any time during the course of cirrhosis wet or dry cups may be used with advantage whenever local pain, tenderness, and a catching respiration indicate the extension of mischief to the peritoneum. The tincture of iodine or flying blisters, or both in turn, may be applied over the right hypochondrium after cups and leeches, or at any time when local distress indicates the need of counter-irritants. Probably the most efficient topical application during the hypertrophic stage of cirrhosis is the official ung. hydrarg. iodidi rubri. A piece the size of a large pea should be thoroughly rubbed in over the hepatic region daily until some irritation of the skin is produced. When this irritation has subsided the applications should be renewed.

Suppurative Hepatitis; Abscess of the Liver.

DEFINITION.—Suppurative hepatitis is an acute inflammation of the hepatic parenchyma, terminating in suppuration. The inflammation may be primary or due to local conditions entirely, or it may arise from morbid processes occurring in parts or organs in anatomical relation to the liver.

CAUSES.—Climate exercises an unquestionable influence in the production of hepatic abscess. Those warm countries visited by dysentery, says Lombard,⁸³ are almost exclusively affected by this disease. Hirsch,⁸⁴ whilst recognizing the influence of climate, shows that the natives are not affected to the same extent as are Europeans. Both writers maintain that hepatic abscess does not occur frequently in the corresponding parallels of latitude in the United States; which is true of the Atlantic border, but is not correct for the interior continent, the valley of the Mississippi, and its tributaries. In this vast region the conditions for the production of hepatitis exist abundantly. The mean annual temperature, the malaria-breeding soil, the social and personal habits of the people (males), combine to favor the production of hepatic abscess. As the native population and females in tropical countries are not affected, there must be other influences to the action of which the high temperature contributes. The rich and highly-seasoned food in which Europeans indulge and the large consumption of alcoholic drinks are doubtless responsible in a large measure for the occurrence of this malady in such excessive proportions amongst them.

⁸³ Traité de Climatologie médicale, tome iv. p. 386.

⁸⁴ Handbuch der historisch-geographischen Pathologie, Band ii. p. 300.

Sex has a remarkable influence in securing immunity against hepatic abscess. According to the statistics of Rouis,⁸⁵ of 258 cases of hepatic abscess, only 8 were in women. He rightly enough attributes this exemption rather to the difference in habits of the two sexes than to any merely sexual peculiarity. In 12 cases observed by the writer, only 1 was in a woman. In Waring's⁸⁶ collection of 300 fatal cases of tropical dysentery, only 9 occurred in women. These facts are most conclusive regarding the relatively greater frequency of the affection in men. As might be expected, the age at which this disease occurs is the period of adult life, when exposure to the conditions developing it is most likely to happen. In general, then, hepatic abscess may be referred to the period mentioned by Rouis—from twelve to seventy-five years of age. In my own cases the youngest was eleven years and the oldest fifty-four years of age. It is not the broken-down subject of mature age or the weakling of youth who is attacked by hepatic abscess, but the more vigorous and able-bodied, who have, because of their strength and activity, been exposed to the manifold conditions producing it.

⁸⁵ Recherches sur les Suppurations endémiques du Foie d'apres des Observations recueilles dans le Nord de l'Afrique, par J. L. Rouis, Paris, 1860, p. 189.

⁸⁶ An Inquiry into the Statistics and Pathology of Some Points connected with Abscess of the Liver, by Ed. John Waring, Resident Surgeon of Travancore, 1854, p. iii.

Rouis finds that a combination of the lymphatic and nervous temperaments seems most favorable to the production of this malady. It is certain that those who have the bodily conditions influential in the formation of gall-stones are not unfrequently attacked by abscess. The passage of the calculi may induce a local peritonitis of considerable severity; their arrest in the duct, with the result of ulcerating through, producing peritonitis and adhesions, are conditions eventuating in the formation of an abscess always large and sometimes of enormous size. Under such circumstances the element of temperament has a secondary place in the aggregate of causes.

Not very often hepatic abscess results from external blows, contusions, and from penetrating wounds. The liver is so placed as to glide aside when a blow is inflicted on the right hypochondrium, and thus escapes direct compression. An injury which elsewhere would have but little effect may excite suppurative inflammation in the tropical—or, as it may be entitled, the hepatic—abscess zone. Climatic conditions, or the changed habits of Europeans in tropical and subtropical regions, exert a distinct influence in traumatic cases.

The most important causes of hepatic abscess exist in the state of the portal vein, hepatic artery, and the hepatic veins. In the valley of the Mississippi and its tributaries, where abscess of the liver is a comparatively common disease, it has been found that in a large proportion of the cases the initial stage is an affection of the rectum—a form of dysentery properly entitled proctitis. So far as this vast region is concerned, the intestinal disease which precedes abscess of the liver, and stands in a causative relation to it, is an affection of the mucous membrane from which the inferior hemorrhoidal veins arise. This disease, although having a dysenteric form, is not ordinary dysentery. The onset of the disease and its symptomatic expression are those of a mild affection of the mucous membrane of the rectum—so insignificant in some cases as to be recalled with difficulty. In tropical countries abscess of the liver may be associated with dysenteric ulcerations. This relation has been frequently observed, but is far from constant. In Waring's⁸⁷ cases, which occurred in India, 31 per cent. of the fatal cases of hepatic abscess arose during the course of acute or chronic dysentery. De Castro of Alexandria⁸⁸ finds that dysentery is the most frequent cause of abscess in that region, especially in the Greek hospital. Murchison⁸⁹ considers tropical abscess of the liver as secondary to dysentery in a considerable proportion of the cases, but by no means in all. In non-tropical countries abscess of the liver is found to succeed to ulcerations of the stomach, the intestines, the bile-ducts, etc. In the case of ulceration of any part of the mucous membrane from which the portal vein receives branches a morbific material may be conveyed to the liver. This morbific material may be some unknown septic principle the presence of which in the liver will excite suppurative inflammation; it may consist of an embolus having septic power or a merely mechanical irritant; it may be micrococci or some other living organisms, which, arrested in the portal radicles, set up inflammatory foci, etc. There are many examples of hepatic abscess connected with dysenteric ulcerations of the intestine in which no embolus can be found. Admitting the presence of the embolus originally, its disappearance is readily understood by reference to the changes induced by suppuration. Excepting these cases there must be many in which no embolus can be found, because none existed; an unknown septic substance has excited the suppurative inflammation. Emboli may be lodged in the liver from thrombi formed in the peripheral distribution of the portal vein, or from distant parts of the systemic circulation, as in bone diseases. There has been no satisfactory explanation of the manner in which such emboli pass the pulmonary capillaries to be lodged in the liver. At one time there was supposed to be a special relation between injuries of the bones of the head and hepatic abscess, but it is now known that these cases are not more numerous than those due to osteo-myelitis in any situation. Abscesses in the lungs are greatly more frequent than in the liver in cases of this kind. According to Waldeyer,⁹⁰ whilst in two-thirds of the cases of death from surgical diseases and injuries there were abscesses in the lungs, in only 6 per cent. were there abscesses of the liver. It is evident that the emboli entering the systemic circulation are usually arrested in the pulmonary capillaries. Klebs maintains that such emboli consist of parasitic organisms.

⁸⁷ On Abscess of the Liver, supra.

⁸⁸ Des Abcès du Foie des Pays chauds, et de leur Traitement chirurgical, par le Dr. S. V. Castro (d'Alexandrie d'Egypte).

⁸⁹ Clinical Lectures, loc. cit., p. 178.

⁹⁰ Virchow's Archiv für path. Anat., etc., Band xl. pp. 380, 408.

Dilatation and ulceration of the bile-ducts were the principal causes of hepatic abscess, as ascertained by Von Baerensprung, in the Berlin Pathological Institute. Duodenal catarrh involving the orifice of the common duct, catarrh of the biliary passages leading to obstruction, and plugging with a gall-stone have resulted in abscess, the initial lesion being probably rupture of one or more of the finer tubes or inflammation leading to suppuration.⁹¹

⁹¹ Grainger Stewart, The Edinburgh Medical Journal, January, 1873.

Finally, a considerable proportion of cases of hepatic abscess arise under unknown conditions. In such cases, however, it is usually found that there has been more or less indulgence in alcoholic drinks, or the liver has been taxed by excesses in the use of rich foods and condiments, or exposure to extreme degrees of temperature has occurred. In the interior valley of this continent, where hepatic abscess is comparatively common, the causes are to be found in malarial influences, in alcoholic indulgence, in dysenteric attacks the product of climatic variations and improper alimentation, and in the formation and arrest in transitu of hepatic calculi also the result of long-continued gastro-duodenal and biliary catarrh.

PATHOLOGICAL ANATOMY.—Great differences of opinion have been expressed as to the initial lesions in hepatic abscess. It is probable, however, that these differences are due to the character of the abscess. Some have their origin in the hepatic cells, others in the connective tissue, and others still in the vessels. There may be a number of points at which the suppurative process begins, or it may be limited to one. Virchow⁹² describes the initial lesion as beginning in the cells, which first become coarsely granular, then opaque, and finally soften, and pus appears. Klebs, who maintains the constant agency of septic micrococci, affirms that the changes in the cells are due to compression exerted by the mass of these organisms distending the neighboring vessels, and then suppuration begins on the portal side of the lobules. Liebermeister originally held that the initial lesion is in the connective tissue; and this view is also supported by Köster, who brings to bear experimental data. In the walls of the vessels of the connective tissue and about them, between the hepatic cells, great numbers of lymphoid cells accumulate. The intercellular spaces are also distended with plasma and round cells, and in the vicinity of the central vein the swollen hepatic cells are pressed together; soon pus-corpuscles appear, and the proper anatomical elements are broken up into a diffluent mass composed of fat-granules, pus-corpuscles, and disintegrating hepatic cells.

⁹² Archiv für path. Anat., etc., Band iv. p. 314.

When suppurative hepatitis arises from an embolus, or emboli, the first step is the change in the appearance of the acini, which are enlarged and grow softer by disintegration of their cells; then at the centre a yellowish spot appears, and is made up of the detritus, granules of fat, and pus. Surrounding such softening portions of the hepatic tissue is a zone of congestion. When the morbid processes are excited by emboli, there will be as many centres of pus-formation as there are particles distributed by the vessels—from two or three to fifty or more. They may be uniformly distributed through the organ or be collected in one part. Emboli conveyed by the portal vein will be arranged with a certain regularity and through the substance of the liver, whilst those coming from some part of the systemic circulation tend to form at the periphery under the capsule. Small abscesses in close proximity unite ultimately by the softening and disintegration of the intervening tissue.

In the so-called tropical abscess, which is the variety so frequently met with in the interior of this country, the mode of development is different from the embolic, above described. Owing to the deposit of some morbific matter whose nature is now unknown, the vessels dilate and hyperæmia of the part to become the seat of suppuration ensues. The cells become cloudy, granular, and opaque from the deposit of an albuminous matter in them. Within the area of congestion a yellowish spot soon appears, surrounded by a translucent, pale-gray ring, and here suppuration begins; the neighboring cells disintegrate and a purulent collection is formed, which enlarges by the destruction in succession of the adjacent portions of hepatic tissue. Whilst this process is going on there is a border of deep congestion about the abscess, fading off gradually into the normal tint of the hepatic parenchyma; the walls of the abscess are rough and irregular from projections of tissue just beginning to disintegrate, and the pus burrows in various directions more or less deeply into the softening parts. The size to which such purulent collections attain is largely determined by the condition of the liver as a whole. If the organ attacked is healthy otherwise and the general health is not deteriorated, the area of the abscess may be limited by a well-defined membrane and continue inactive for a long time. This limiting membrane is of inflammatory origin, developed from the connective tissue, and varies in thickness from a mere line to several. It was formerly called a pyogenic membrane, because the pus discharged was supposed to be formed by it. When such a limiting inflammation cannot take place, the abscess continually enlarges by the softening and destruction of the adjacent hepatic tissue, and may finally attain to enormous proportions. The embolic abscesses vary in size from that of a pea to that of an orange. The so-called tropical abscesses are usually single—in three-fourths of the cases, according to Rouis;⁹³ in 62.1 per cent., according to Waring.⁹⁴ Of the fatal cases collected by the latter author, 285 in number, a single abscess existed in 177, and multiple abscesses in 108. In 11 per cent. there were two abscesses; in 3.6 per cent., three; and in 5.6 per cent. there were four abscesses. As regards the part of the liver in which abscess occurs, the statistics show a great preponderance in favor of the right lobe. In Waring's collection of 300 cases the right lobe was the seat of the abscess in 163, or 67.3 per cent.; the left lobe was affected in 16, or 6.6 per cent.; and both lobes in 35, or 14.4 per cent. The preponderance of cases affecting the right lobe is the more striking when it is understood that, other parts being invaded, the right is included with them in the morbid process. In my own cases the right lobe was the seat of the abscess in 70 per cent.

⁹³ Recherches sur les Suppurations endémiques du Foie, loc. cit., p. 146.

⁹⁴ An Inquiry into the Statistics and Pathology, etc. connected with Abscess of the Liver, loc. cit., p. 125.

The contents of the abscesses are affected in character by the form of the disease, whether embolic or tropical, by its rate of development, by the condition of the hepatic parenchyma, by the formation of a limiting membrane, etc. In the more chronic cases, surrounded by a dense membrane, the pus is usually laudable or dry and cheesy; in the acute embolic cases the pus is dark brown, ichorous or grumous, and contains a good deal of detritus of the hepatic parenchyma; and in the tropical cases it is of a sanguinolent, dark color, or more frequently of a grayish purulent fluid; and in the acute forms contains much broken-down tissue, whilst in the chronic cases, in direct ratio to their duration, the pus approaches the laudable character. The source of an abscess discharging from the neighborhood of the liver may be ascertained by a microscopical examination and the discovery of the hepatic elements (the cells) in the fluid. Bile may also be present in the pus.

The abscesses not confined by a limiting membrane constantly enlarge by the softening and disintegration of the adjacent liver substance, and those enclosed or encysted after a period of quiescence of variable duration begin active efforts to establish communication outwardly. The point to which a purulent collection in the liver tends becomes an important element in diagnosis and in treatment. As the abscess approaches the surface of the liver the capsule inflames, and if adhesions are not formed more or less sloughing occurs, and the contents are discharged into the abdominal cavity. Adhesions may form to the parietes, an external swelling appear, and after a time discharge take place in the right hypochondrium at some point. Pus may escape at the umbilicus, in the right inguinal region, posteriorly at the sacro-iliac junction, and in other situations. Adhesions may form to the stomach, duodenum, the ascending vena cava, to the diaphragm opening the thoracic cavity, the pericardium, or the mediastinum; and the accumulated pus may thus find a vent. According to Waring,⁹⁵ the termination of hepatic abscess is as follows: Of 300 cases, 169, or 56.3 per cent., remained intact—that is, had not advanced beyond the liver; 48 were evacuated by operation, or 16 per cent.; 14, or 4.6 per cent., entered the thoracic cavity; 28, or 9.3 per cent., opened into the right lung; 15, or 5 per cent., entered the abdominal cavity; 7, or 2.3 per cent., opened into the colon; 1 entered the stomach; 3 entered the hepatic vein near the vena cava; 1 communicated with the hepatic ducts, 2 with the right kidney, etc. The termination of 162 fatal cases, according to Rouis,⁹⁶ was as follows: 125 proved fatal in consequence of the extent of the abscess or of the severity of the accompanying dysentery; 3 terminated by gangrene of the walls of the abscess; 3 by peritonitis; 12 by opening of the abscess; 2 by rupture of adhesions; 11 by opening of the abscess into the pleura; 2 by intercurrent and 3 by secondary pneumonia. Notwithstanding the differences in the mode of expressing the conditions, the general results are the same.

⁹⁵ An Inquiry into the Statistics and Pathology, etc. of Abscess in the Liver, loc. cit.

⁹⁶ Recherches sur les Suppurations endémiques, etc., p. 149.

An abscess of the liver having discharged in a favorable way, healing may take place. There may be such an extent of injury—the whole secreting structure of the liver being destroyed—that repair is beyond the power of the organism. The best results are attained when discharge occurs by the most direct route externally; the next, by way of the right lung; the third, by the stomach or intestine. Repair cannot be hoped for when a large part of the normal hepatic structure is destroyed. When the pus escapes the walls of the abscess approximate, and union takes place by connective tissue, leaving a radiated or a merely linear cicatrix to mark the site of the purulent collection. So perfectly does repair take place in suitable subjects that no trace of the lesion may remain.

Those portions of the liver outside the borders of the abscess, and beyond the vascular derangements produced by it, may be entirely healthy. In the cases terminating in recovery the portion of the liver unaffected by abscess continues to functionate normally. More or less of the liver may be destroyed; hence it follows that recovery may be partial. According to the damage done to the proper secreting structure of the organ will the recovery be partial, limited, or complete.

SYMPTOMS.—The existence of an abscess of the liver is determined by systemic or general and by local symptoms, and they may be acute or chronic.

Systemic.—In acute cases the beginning of mischief may be announced by a rigor, but more frequently this indicates the onset of suppuration, and is one of the phenomena of the chronic form. As the disease occurs in this country, a chill takes place suddenly in a case which presents the usual symptoms of proctitis (dysentery) during the course of this affection or soon after its apparent cure; then a febrile movement occurs, and subsequently an irregular intermittent, the rise of temperature being preceded by rigors or mere transient chilliness. With these febrile symptoms there may be associated uneasiness in the right hypochondrium, acute pain, or a feeling of weight and pressure, with jaundice, etc. The fever is septicæmic, intermittent, or remittent if it have any special type. In the septicæmic form the rigors are severe, occur irregularly, sometimes daily, sometimes twice a day, and at intervals of two or three days or longer; the fever rises to a high point—104°, 105°, or higher—and the sweats are profuse. In the intermittent form the fever usually has the quotidian type; some slight chilliness is experienced in the early morning as a rule, and the exacerbation occurs in the afternoon and evening, the sweating being slight toward the morning. More frequently, in the writer's observation, the type of fever has been remittent, with periodical, but not regularly so, exacerbations. In such cases the morning temperature has been at 99° or 100°, and the evening 102° or 103°. Such a range of temperature may be present during three or four weeks or even longer, the abscess gradually making its way outwardly. Conclusions may be drawn from the behavior of the febrile movement as to the character of the local affection, with the limitations imposed by the necessary uncertainty of the data. If the chills are decided rigors, the fever high, and the sweats profuse, either pyæmic abscesses or large tropical abscesses implicating neighboring organs exist. The simple intermittent, especially the remittent, form of fever suggests abscesses of medium size making their way outwardly, with only partial injury to the parts traversed. In a certain portion of the cases the type of fever changes when a large accumulation of pus takes place; after several weeks of a mild remittent the fever becomes irregularly intermittent with rigors, strong exacerbations, and profuse sweats. In protracted cases the fever assumes the typhoid aspect; there is profound adynamia, dry tongue, sordes, diarrhoea, and the usual symptoms of this state. When the secreting structure of the liver is destroyed to a large extent, the condition of acholia is superadded to the typhoid state.

The pulse is irritable and quick from the beginning of the symptoms. In a few instances a slow pulse, such as occurs in jaundice, has been observed, but generally the number of cardiac contractions is in a direct ratio with the body temperature. When typhoid symptoms supervene in advanced cases the pulse becomes weak and dicrotic.

Not every case presents the symptom sweating. The chronic cases with mild remittent fever have little more than slight moisture of the surface, whilst the acute and pyæmic cases are characterized by profuse sweats. If to an irregular febrile movement, preceded by chills and followed by sweats, there is added the tendency to sweat on all occasions—on slight exertion, on sleeping, under any excitement—suppuration may be suspected.

General malaise, a sense of fatigue and exhaustion, and progressive decline in flesh and strength occur. It is remarkable, however, how some obese subjects preserve their roundness and apparent fulness of habit. Usually, however, emaciation advances pari passu with the progress of the suppuration. The more acute the symptoms, the more rapid the wasting. When an encysted abscess develops in the course of a chronic dysentery, there may be no appreciable change in the condition of the patient properly attributable to the additional lesion. The loss of appetite, the frequent vomiting, and often the dysenteric troubles, contribute materially to the exhaustion and the wasting of the tissues. The stomachal derangements may be present with the initial symptoms, but they are usually more pronounced when the abscess attains to considerable size.

A peculiar tint of the skin, especially of the face, is observed in those cases without jaundice. There is an earthy or sallow hue, which to the practised eye signifies suppuration. Jaundice is present in a less proportion of cases. In 13 of Waring's cases the skin is said to be sallow. In Rouis's collection icterus was present in 17 per cent., or 26 times in 155 patients. According to Waring, jaundice is rarely present. In the 12 cases in my own hands actual jaundice was not present in one, but 9 had an earthy hue or presented some yellowness of the conjunctiva. In fact, jaundice does not have the importance as a symptom which might, a priori, have been expected.

The mental condition of these subjects is that of depression. They sleep poorly, are disturbed by vivid dreams of a horrifying character, and the nocturnal sweats increase the tendency to wakefulness. Hypochondria, or at least marked symptoms of mental depression, as Hammond⁹⁷ has shown, are present in many cases. So frequent, indeed, seems to be the association of a depressed mental state with hepatic abscess that in every case of the former the liver should be carefully explored. Hammond goes so far as to say that in every case of hypochondriasis puncture of the liver with the aspirator needle should be practised when any symptom, however indefinite, indicates the existence of an abscess. Besides the condition of hypochondriasis in many cases, there may be stupor, hebetude of mind, confusion due to acholia, cholæmia (Flint's cholesteræmia), when a large part of the liver structure is destroyed.

⁹⁷ Neurological Contributions, vol. i. No. 3, p. 68: "On Obscure Abscesses of the Liver, their association with Hypochondria and other Forms of Mental Derangement, and their Treatment."

Sweating has already been referred to as a phenomenon connected with the febrile movement. It is necessary to state further that this may vary in amount from a mere moisture of the surface connected with sleep, or it may be a profuse diaphoresis with which the febrile paroxysm terminates. As a systemic symptom, sweating is strongly suggestive of suppuration, and may therefore be extremely significant, in this connection, of suppuration in the liver. According to Waring, of 75 cases specifically interrogated on this point, 72 presented this symptom. Rouis refers (p. 123) to it as very constantly present, coming on chiefly at night—sometimes generally over the body, sometimes limited to the head, and always accompanied by an accelerated pulse.

The urine in cases of hepatic abscess varies; it is never normal. There may be merely an excess of urates—a symptom common enough in all febrile affections and in suppuration. It is usually high-colored, deficient in urea, and contains leucin and tyrosin, and not often bile-pigment, except when jaundice is present, which, as we have seen, is rather uncommon.

It should be borne in mind that whilst the above-described mental and cerebral and other symptoms are often present, they are by no means invariably so. There are cases, usually of encysted abscess, in which no functional disturbance of any kind exists. But the systemic symptoms are by no means so important as the local. To these we must now direct attention.

Local.—The position, size, and shape of the liver are not without significance, but it is strictly correct to say that an abscess of the liver may exist without any change in the size of the organ or in its relations to the surrounding organs. In 2 of 12 cases in the hands of the writer there was no evidence of enlargement of the right hypochondrium, but a difference in circumference of half an inch was ascertained in favor of the left side. In 4 cases there was no appreciable change in the size of the hepatic region; in one-half there was an increase in the area of hepatic dulness. In one of the cases in which the left side was the larger the abscess was of enormous extent, and discharged by the stomach and intestine. The enlargement of the liver may be very great. In one instance observed by the author the abscess reached to the upper border of the third rib. Rarely does the dulness extend more than two fingers' breadth below the inferior margin of the ribs, although cases are reported in which the enlarged organ reached to the crest of the ileum. As a rule, the diaphragm is pushed up and the lung displaced, rather than the dulness is extended downward. When the first tumefaction due to the initial congestion takes place, the organ may be much larger than subsequently, the pus becoming encysted and the normal state outside of the area of suppuration being restored. The purulent collection in a large proportion of the cases taking place in the right lobe, the extension of dulness is in the same lines as the normal. When, however, the right lobe is the seat of abscess, or a purulent collection forms around an impacted calculus, the swelling may appear in the outer border of the epigastrium next the ribs, and the increased area of dulness will be across the epigastrium and occupying the superior portion of this region. The general experience on these points corresponds to my own. Thus, according to Waring, there was an evident enlargement of the liver in 90 cases, and no enlargement in 11. In most cases the increase in size gives the impression of a fulness or hardness of the liver or of a diffused swelling or tumor of the epigastrium. In some instances the right hypochondrium is bulged out, the intercostal spaces widened, and the side appears to be or is actually elevated, and occasionally enlarged veins form, as in cases of the obstructed portal circulation of cirrhosis. In a case recently presented at Jefferson College Hospital clinic by the author, a globular swelling formed in the walls of the abdomen just below the inferior margin of the ribs near the site of the gall-bladder, and was held by an eminent surgeon to be a tumor of this locality; but it had the history of an hepatic abscess, and ultimately proved to be one. Rouis furnishes statistical evidence of the time when the increase in size of the liver occurs with respect to the other symptoms. He has noted an enlargement of the organ 73 times in 122 cases. Of 51 cases, the liver was enlarged in 12 before suppuration, in 22 at the onset of suppuration, and in 17 after suppuration was established. In 49 examples the liver was enlarged in 2 before any other symptom was manifest, in 8 at the onset of symptoms, and in 39 after the symptoms were well declared.

Fluctuation is not referred to by the writers in general, and there are no statistical data on this symptom, so far as our observation extends. No symptom could be more uncertain in all doubtful cases. When a large accumulation has taken place and the parietes of the sac are thin, fluctuation may be detected, but it cannot then be regarded as decisive. When an abscess in the interior of the right lobe is encysted, no fluctuation can be effected. The best mode of eliciting fluctuation, according to Hammond, is to place the extremities of the fingers of the left hand in the depression between the ribs over the most prominent part of the right hypochondrium, and gently tap with the fingers of the right hand the right border of the epigastrium. In 3 out of 12 cases this method has apparently elicited fluctuation in my own experience. The elasticity of the hepatic structure is such that the method of palpation, however practised, must return a sensation nearly allied to that of fluctuation in a purulent accumulation. It is certain, therefore, that errors of observation are liable to occur, and hence conclusions based on an apparent fluctuation should be accepted with caution; under any circumstances it should be very distinct, and even then should not be acted on unless supported by other suggestive evidence.

The uneasiness or pain felt in the right hypochondrium varies greatly according to the position of the abscess, the degree and kind of pressure exerted on neighboring organs, and the period of its development. When the peritoneal layer of the liver is involved, there will usually be acute pain, and this happens at two periods—when the abscess first forms from an impacted calculus or from any cause which includes the peritoneum, and subsequently when the pus, making its way from the liver, excites inflammation in the peritoneal investment of the liver, of the diaphragm, or affects ultimately the pleural membrane. In the so-called pyæmic abscesses there is very little pain, and in the case of the large single abscess in the interior of the right lobe there is rather a sensation of weight or of heaviness, of dragging than of acute pain. When the capsule of the liver is put on the stretch or the peritoneal investment is inflamed, then acute pain may be felt. More or less pain or local distress is, on the whole, a usual symptom. According to Rouis,⁹⁸ local pain is present in 141 out of 177 cases, or in 85 per cent. The statistics of Waring⁹⁹ closely correspond, for of 173 patients affected with this malady, in 153 there was more or less pain referable to the affected organ. The position of the pain has some influence in determining the seat of the malady, and often indicates the position of the abscess. As respects the character of the pain, there is little uniformity; in general it is a tensive, heavy, throbbing sensation, but under the circumstances above mentioned this may have an acute or lancinating character, as when the capsule or the peritoneal investment of the organ becomes involved.

⁹⁸ Recherches, etc., loc. cit.

⁹⁹ An Inquiry, etc. into Abscess of the Liver, loc. cit.

Besides the pain directly referable to the liver there are painful sensations felt in the neighboring parts, of very considerable significance. These are often described as sympathetic pains, and are referred to the shoulder—to the right shoulder when the right lobe is the seat of mischief, and to the left shoulder when the abscess forms in the left lobe of the liver. Although this statement has many limitations, it is not without diagnostic importance. Rouis ascertained the existence of the shoulder pain in 17 per cent. of the cases, or in 28 in a total of 163. Waring reports that this symptom was observed in 52 in a total of 76 cases. The right shoulder seems to be affected in about the same ratio as the right lobe of the liver in 25 times out of 26 cases, according to Rouis. The shoulder pain appears at the same time, in a majority of cases, as the hepatic pain, but it is very capricious. It is most frequently at the top of the shoulder, but it may be at the end of the clavicle, in the scapula, or extend down the arm. Its duration is very irregular, appearing occasionally during the existence of the disease, coming on at the outset, and lasting weeks or months, or only felt on pressure over the liver, on coughing, or on taking a full inspiration. The character of the pain is equally uncertain. It is usually heavy, tensive, stinging, or may be merely a sensation of soreness or of uneasiness or of weariness. The behavior of the shoulder pain is partly explicable by reference to the path by which the reflex is conveyed. As Luschka¹⁰⁰ has shown, the filaments of the phrenic nerve supplied to the suspensory ligament and capsule of the liver, put on the stretch or irritated, convey the impression to the cord, and it is reflected over the sensory fibres of the fourth cervical distributed to the shoulder. Rouis reports an instance in which the deltoid was wasted.

¹⁰⁰ Quoted by Thierfelder, op. cit.

The decubitus of patients affected with hepatic abscess is often extremely characteristic. To obviate the pressure on the swollen and inflamed organ the position assumed is right lateral-dorsal, the body inclined to the right, the right thigh flexed on the pelvis, and the spinal column so curved as to relax the abdominal muscles of the right side. When the pain and tenderness are not great there may be frequent changes of position, but in repose the lateral-dorsal decubitus is assumed. When the suppuration is well advanced and the accumulation large, the patient keeps in that position nearly constantly. If pressure interferes with the normal play of the lungs, and dyspnoea is produced on assuming the recumbent posture, the attitude taken expresses this state also: then the decubitus is lateral and partly dorsal, but the body is raised to a half-upright. There are many exceptions to these rules. Some lie easiest on the back, some on the left side; but it is quite certain that much the largest number, when uninfluenced by special circumstances, naturally place themselves as above described.

Jaundice is amongst the rarer symptoms. Rouis finds it to be present in 17 per cent. of the cases, Thierfelder in 16 per cent., and Waring in somewhat less than 6 per cent. Referring to my own observation, jaundice has rarely been present, but some yellowness of the conjunctivæ and a faint yellow tint of the skin generally have been evident. The peculiar aspect of the countenance connected with suppuration has rarely been wanting. When jaundice does occur, it is referable to two conditions—to a catarrhal swelling of the bile-ducts, which may be coincident with the onset of the suppurative inflammation; to the pressure of the abscess on the hepatic or common duct, which must happen at a late period.

As an abscess of the liver forms and enlarges, pressure is exerted on neighboring organs, producing very decided disturbances. Nausea and vomiting, anorexia, a coated or glazed tongue, diarrhoea or dysentery, are amongst the disorders of this kind involving the digestive apparatus. Each of these symptoms will require examination.

There is nothing characteristic in the condition of the tongue which does not belong to suppuration in any situation. Nevertheless, there are some appearances that have a certain value in conjunction with other diagnostic signs. At the onset of the suppurative inflammation the tongue is more or less heavily coated, but as the case proceeds it becomes dry and glazed in parts, whilst covered with a well-defined membrane-like crust at the base and margins. This appearance is very characteristic of the cases of suppuration, the abscess enlarging. In a very important case observed by me lately there was a well-marked diphtheritic-like exudation of the tongue and fauces toward the termination of the case, the membrane forming as the pus accumulated. This appearance was coincident with a typhoid state.

Nausea and vomiting appear with the beginning of symptoms, are associated with the general signs of systemic disturbance, and are especially prominent when an accumulation of pus takes place, being due under these circumstances to pressure on the hepatic and solar plexuses or to direct encroachment on the stomach—probably to both causes. The frequency and persistence of the vomiting are points of much diagnostic importance, according to Maclean¹⁰¹ and Fayrer,¹⁰² which I am able to fully confirm from my own experience. The matters ejected by vomiting consist of the contents of the stomach—glairy mucus, the accumulation in the gall-bladder, altered blood (coffee-grounds)—and the contents of the abscess if it discharge by the stomach. The vomiting is most apt to occur during the febrile exacerbation or at the time of sweating. The statistics are conclusive as to the frequency of vomiting as a symptom. Of 84 cases in which special reference was made to this point, in 74 nausea or vomiting existed. In my own experience this symptom has never been wanting.

¹⁰¹ "The Diagnostic Value of Uncontrollable Vomiting," by W. C. Maclean, Brit. Med. Journ., August 1, 1873.

¹⁰² Ibid., September 26, 1873.

The relation between abscess of the liver and dysentery has been much discussed. Under the head of Causes the influence of dysentery as a pathogenetic factor has already been examined. We have now to study its symptomatic relations. A considerable proportion of the cases occurring in this country have been preceded by proctitis—simple, sporadic dysentery affecting the rectum. In India a close relationship has been traced between ulcerations of the intestinal canal and abscess. According to Waring, 75 per cent. of the cases have occurred in those who were actually suffering from dysentery or recent or old ulcerations. As observed by Rouis in Algiers, out of 143 cases there were 128 with dysentery, or 90 per cent. Budd¹⁰³ long ago maintained that a peculiar poison generated at an open ulceration in the intestine was the true cause. Moxon,¹⁰⁴ Dickinson, and others have lately reaffirmed this explanation. A case by the latter¹⁰⁵ casts a strong light on this question: A patient had extensive dysenteric ulceration of the intestine and an abscess of the liver, without any symptoms indicating their existence. Such a case teaches the instructive lesson that dysenteric ulcerations may escape detection, and hence the connection between abscess and the intestinal lesion remains unknown. In a small proportion of cases—about 5 per cent.—dysentery is a result, apparently, of hepatic abscess. Whether the relation is admitted to exist or not, it is a curious fact that in so many cases ulcerative disease of the intestinal canal accompanies the hepatic affection. Hemorrhoids, prolapse of the rectum, gastro-intestinal catarrh, etc. are produced by the pressure of an enlarging abscess on the portal vein.

¹⁰³ Diseases of the Liver, 3d ed., p. 82.

¹⁰⁴ Pathological Transactions, 1862 and subsequently. Numerous cases are recorded in the various volumes up to 1880.

¹⁰⁵ Ibid., vol. xiii. p. 120.

The urine contains bile-pigment when jaundice is present, is usually loaded with urates, and the amount of urea may be deficient when much of the hepatic tissue is destroyed.

From the beginning of symptoms some cough is experienced: it is short and dry, but after a time in many cases the cough is catching and painful, and finally may be accompanied by profuse purulent expectoration. The breathing is short and catching when by the upward extension of the mischief the diaphragm is encroached on, and may become very painful when the pleura is inflamed. Ulceration of an abscess into the lungs is announced by the signs of a local pleuro-pneumonia—by the catching inspiration, the friction sound, the crepitant râle, the bronchophony and bronchial breathing, and bloody sputa usually, etc. Some time before the abscess really reaches the diaphragm, preparation is made in the lung for the discharge through a bronchus. The author has seen many examples of this, and a very striking illustration of the same fact is afforded in a case by Dickinson,¹⁰⁶ in which an abscess holding about four ounces was contained in the upper part of the right lobe; its walls were irregular and not lined by a limiting membrane. It is further stated that the "right pleura was coated with flocculent lymph, and the cavity contained serous fluid," etc. Here, in advance of the abscess, preparation was made for its discharge through the lung. The tendency of an abscess of the abdomen to external discharge is manifested in two directions: those of the upper part tend to discharge through the lungs, those of the lower part through the natural openings below. Abscesses of the liver come within the former rule, but it is not of invariable application, since some discharge by the stomach or intestine, some externally; yet a large proportion make their way through the lungs. Another symptom referable to the pulmonary organs in cases of hepatic abscess is singultus, or hiccough. This is a symptom of the period of discharge rather, and is often extremely protracted and exhausting. Pericarditis occurs in those cases in which discharge takes place in this direction, and it may develop, as does pleuritis, in advance of any change in the diaphragm. This preparation of the thoracic organs for external discharge seems almost like a conscious purpose, as if an intelligent supervision of these processes were exercised.

¹⁰⁶ Transactions of the Pathological Society, vol. xxxii. p. 127.

COURSE, DURATION, AND TERMINATION.—As the facts already given have sufficiently shown, the course of abscess of the liver is extremely uncertain. From the beginning to the end there may not be a single indication of its presence. On the other hand, a well-marked case is perfectly characteristic. Abscesses of the liver are acute and chronic—the former of short duration, accompanying pyæmia, portal phlebitis, and similar conditions; the latter, arising in the course of chronic dysentery or from unknown causes, especially if encysted, remaining latent for weeks or months. The course of an abscess is much influenced by the direction taken by the pus in the attempt at discharge. This portion of the subject requires careful statement and thorough treatment, and we therefore present it somewhat in detail. Beginning with his individual observations, the abscess in the author's 12 cases discharged—3 externally, 5 by the lungs, and 4 by the stomach or intestines. In Waring's¹⁰⁷ collection of 300 fatal cases, 169 remained intact at death, 48 were operated on; consequently, only 83 are left for the purpose of this comparison. Of 83 cases of hepatic abscess discharging spontaneously in some direction, 42 escaped into the thoracic cavity or by the right lung (in 28); into the abdominal cavity (15) or stomach (1) or intestine (7), 23; externally 2, besides in special directions to be hereafter referred to. Rouis¹⁰⁸ has tabulated the results in 30 cases of abscess fatal without an operative influence. Of these, 2 discharged externally, 17 by the thorax (15 by the lung), 5 by the stomach, 4 by the intestine, and 2 by the biliary canals.

¹⁰⁷ An Inquiry, etc. into Abscess of the Liver, loc. cit., p. 131.

¹⁰⁸ Recherches sur les Suppurations endémiques du Foie, etc., loc. cit., p. 148.

The appearances presented when the discharge takes place through the external parts are by no means uniform. When the epigastric or umbilical region is the point of discharge, a globular tumor forms, which may be mistaken for a fibroid or fatty growth; softening in the centre of the mass occurs, and ultimately the pus is discharged. If the pus makes its way outwardly through the right hypochondrium, the tumor formed is furrowed by the attachment to the ribs, and several openings usually occur. The pus may burrow under the skin for some distance and point in the axilla, or, making its way along the suspensory ligament, emerge at the navel, or, descending, appear in the lumbar region or under Poupart's ligament.

As the statistics prove, the most usual route for discharge to take place is by the thoracic cavity, especially the right lung. Some time in advance of an opening in the diaphragm a localized pleuro-pneumonia occurs, adhesions form between the pulmonary and costal pleura, and a channel is tunnelled out for the passage of the pus to a bronchus. The discharge of pus suddenly occurs after some days of cough and bloody expectoration. Even in favorable cases the amount is so large that the patient has extreme difficulty in disposing of it, and in unfavorable cases, the quantity being large, the patient's life is ended by apnoea. In still other cases an extensive purulent accumulation may form in the pleural cavity, the lung is compressed, and all the phenomena of an empyema superadded to those of a hepatic abscess. In a case reported by Westphalen¹⁰⁹ all the bile secreted by the patient came out by an opening in the fifth intercostal space. The empyema thus induced may indeed be the principal lesion, as in the case of the late Gen. Breckenridge, on whom thoracentesis was performed by Sayre of New York, and in a case reported by Löwer.¹¹⁰ So far from this being uncommon, as asserted by Thierfelder, when an abscess of the liver approaches the diaphragm inflammatory symptoms begin on the pleural side, and thus pyothorax may occur in advance of the perforation of this septum.

¹⁰⁹ Deutsches Archiv für klin. Med., 1873, Band xi. p. 588.

¹¹⁰ Berliner klinische Wochenschrift, 1864, p. 461.

The opening of an hepatic abscess into the pericardium is rare, since in Waring's collection of 300 fatal cases there was not one. When it does occur, pain is experienced about the heart; the action of the organ becomes irregular; præcordial anxiety and oppression are felt; suffocative attacks occur; and very soon the symptoms of pericarditis arise. Perforation of the ascending vena cava or of the hepatic vein happens in about 2 per cent. of the cases. When a quantity of pus is thus turned into the circulation, disastrous results follow, not so much from the infective nature of the pus as from the sudden increased pressure within the vascular system and the labor imposed on the heart, already failing.

The escape of the pus into the peritoneal cavity occurs in about 11 per cent. of the cases of spontaneous evacuation, according to Waring. Of the 162 fatal cases collected by Rouis, 14 opened into the peritoneum—about the same proportion as Waring gives. When discharge takes place into the peritoneum, the patient passes into a condition of collapse, or peritonitis is excited and rapidly proves fatal. In rare instances the inflammatory reaction is restricted to a small area, ulceration takes place through the abdominal parietes, and thus discharge is effected.

An opening may be made into the intestine or into the pelvis of the kidney. In the former case pus is discharged by stool or by vomit, and often in enormous quantity; in the latter by the urine, frequent and painful micturition, with much pus, being the evidence of the accident. In either case communication may be kept up with the abscess, and the patient be worn out with the exhausting discharge maintained by the intercommunication between the abscess and the canal through which discharge takes place.

Cases of hepatic abscess prove fatal without perforation. In Waring's collection of 300 cases, 169 remained intact, in the words of the author—that is, did not extend beyond the boundaries of the liver. Of 203 cases collected by Rouis, 96 did not extend beyond the liver. According to Thierfelder, about one-half of the cases of hepatic abscess perforate the liver. These statistics therefore closely correspond, and the general conclusion is very nearly expressed in the formulated statement of Thierfelder.

The duration of hepatic abscess cannot readily be expressed in figures. The acute cases terminate early by reason of the various complicating conditions. The chronic cases are much influenced in their duration by the presence of a limiting membrane, for if this be formed the duration will be protracted over weeks or months; and those cases not thus confined are necessarily of shorter duration. A period of latency may result when the extension of the morbid process is thus hindered. Forming a conclusion from the general conduct of the cases, it may be said that the duration of hepatic abscess is from two weeks to six months. Of 220 cases collected by Waring, the average duration was 39 days. Rouis fixes the average duration in 179 cases at 60 days. Of Waring's cases, the largest number (59) terminated in from 10 to 20 days; whilst Rouis places the maximum number (104) at from 11 to 60 days, the shortest duration of any case being 10 days, and the longest 480 days.

The termination may be accelerated by the manner of discharge, as when the abscess opens into the ascending vena cava, into the sac of the pericardium, or into the peritoneal cavity. In my own cases, carefully selected for these observations, death occurred in one during discharge by the right lung, one within twelve hours after discharge by the intestine, and one within ten days after discharge by the stomach and intestine, the mortality of the whole being 75 per cent. In Waring's collection of 300 fatal cases, 169 died whilst the abscess was still intact—that is, in the liver.

The mortality from abscess of the liver is very large. In Rouis's collection of 203 cases, 162 died, 39 recovered entirely, and 2 improved; 80 per cent., therefore, proved fatal. According to De Castro,¹¹¹ whose observations were made at Alexandria, Egypt, 93 in 208 cases died, this being 72.5 per cent. According to Ramirez,¹¹² of 11 cases of which an account is given in his memoir, 10 died and 1 recovered—a mortality of 90 per cent. De Castro (p. 40) also gives the results arrived at by the Medico-chirurgical Society of Alexandria, who collected 72 cases of abscess, of which 58 died, making the percentage of deaths 80.5. Various circumstances besides the abscess affect the result. An early successful operation, the mode of discharge, the amount of hepatic tissue destroyed by the suppuration, the extent of pre-existing lesions—especially ulcerations of the intestinal canal—are important factors in the result. In respect to some of these we have valuable statistical data. The discharge through the lungs is the most favorable route, next by the parietes of the abdomen, and lastly by the intestinal canal. One-half of those cases in which discharge is effected by the right lung get well. This is my own experience, and it accords with the observations of Rouis, of De Castro, and others. Rouis gives the result in 30 cases of hepatic abscess discharging by the right lung; of these 15 recovered. Of 25 cases observed by De Castro, discharging by the lungs, 19 recovered. Next to the discharge by the bronchi, the most favorable mode of exit is externally, through the parietes of the abdomen; much less favorable is by the stomach or intestine; but still more fatal is the discharge into the cavity of the peritoneum. When the abscesses are multiple and due to pyæmia, the termination is always in death. The numerous lesions besides the hepatic accelerate the fatal issue. In the case of large single abscesses the result is in a great measure due to exhaustion from protracted suppuration. When in addition to the formation of a great quantity of pus there is frequent vomiting and rejection of aliment, the failure of strength is proportionally rapid. In favorable cases, after an abscess is evacuated through the right lung, recovery takes place promptly. When the discharge occurs through the abdominal wall, the process is much slower, and often fistulous passages with several orifices, very slow to heal, are formed. Complete recovery may ultimately take place. The recovery will be incomplete in those cases with large loss of hepatic substance, especially when this coincides, as it usually does, with catarrh, ulceration, and other lesions of the intestinal tube. Again, the recovery will be incomplete in those cases where there are imperfect healing of the abscess site and a fistulous communication with the exterior.

¹¹¹ Des Abcès du Foie des Pays chauds, et de leur Traitement chirurgical, loc. cit., p. 40, Paris, 1870.

¹¹² Du Traitement des Abcès du Foie, Observations receuilles à Mexico et en Espagne, par Lino Ramirez, M.D., Paris, 1867, loc. cit.

It is possible for the arrest and healing of a suppurative inflammation of the liver to take place without discharge. Under such circumstances the watery part of the pus is absorbed, the solid constituents undergo a fatty metamorphosis, are emulsionized, and thus absorbed, and gradually closure of the damaged area is effected by a connective-tissue formation. We must, however, accept with caution those examples of this process which are supposed to have occurred because radiating cicatrices are discovered on the surface of the liver. In a case of hepatic abscess discharging through the lung, known to the writer, after death, which occurred fifteen years subsequently, there was no trace of the mischief, so perfectly had repair been effected. Radiating cicatrices are so often of syphilitic origin that they cannot be accepted as proof of the former existence of an abscess.

DIAGNOSIS.—He who finds the diagnosis of abscess of the liver easy under all circumstances can have had but little experience with the numerous difficulties in the way of a correct opinion. There are cases so plain that the most casual inspection suffices to form a conclusion; there are cases so difficult that the most elaborate study fails to unravel the mystery. The maladies with which hepatic abscess may be confounded are echinococcus of the liver, dropsy of the gall-bladder, cancer, abscess of the abdominal wall, empyema, or hydrothorax, etc. As regards echinococcus, the difference consists in the slow and painless enlargement characteristic of echinococcus, and the absence of any symptoms other than those due to the mere pressure of the enlarging mass. In abscess there may be no apparent enlargement, or the increase in the area of dulness may be very great, or after a period of increase of size there may be contraction due to the formation of pus, and hence limitation of the inflammation; finally, the accumulation of fluid may be sufficient to cause dulness up to the inferior margin of the second rib. There are no corresponding changes of size in the echinococcus cyst. Furthermore, abscess of the liver large enough to be recognized by the increased dimensions of the organ will be accompanied by more or less pain in the right hypochondrium and by a septicæmic fever. On the other hand, an echinococcus tumor is not accompanied by fever, pain, or tenderness, and it has that peculiar elastic trembling known as the purring tremor. The most certain means of differential diagnosis is the use of an aspiration-needle and the withdrawal of a portion of the fluid. The presence of pus with hepatic cells will be conclusive of abscess, whilst a serous fluid with echinococci hooklets will prove the existence of the echinococcus cyst.

In cases of dropsy of the gall-bladder there are no febrile symptoms, no chills, and the tenderness when present is limited to the pyriform body, the seat of the accumulation of fluid, and no general enlargement of the liver can be made out. At the point of swelling fluctuation may be detected, or if the gall-bladder is filled with calculi the sensation imparted to the touch is that of a hard, nodular body of an area and position corresponding to that of the gall-bladder. Tapping the gall-bladder, an easy and safe procedure, will resolve all doubts. When an impaction of a gall-stone is the cause of abscess, the clinical history is eminently characteristic: there are attacks of hepatic colic, after one of which the chills, fever, and sweats belonging to hepatic abscess occur.

The differentiation of cancer of the liver from abscess rests on the following considerations: In cancer there is slow enlargement, with pain; a more or less nodular state of the organ without fluctuation; usually ascites; no rigors; no fever and sweats. In abscess the liver may or may not be enlarged; there are rigors, fever, and sweating, and the surface of the organ, so far as it can be reached, is smooth and elastic, and it may be fluctuating. Cancer happens in persons after middle life, develops very slowly, and is accompanied by a peculiar cachexia; abscess occurs at any period, very often succeeds to or is accompanied by dysentery and by the usual phenomena of suppuration.

It is extremely difficult to separate an abscess in the abdominal wall, in the right hypochondrium, or a tumor in this region, from an abscess of the liver. The history of the case, the existence of a dysentery or of an apparent intermittent or remittent fever before the appearance of a purulent collection, will indicate the liver as the probable source of the trouble. Attention has already been called to a case in which an abscess of the liver was supposed by an eminent surgeon to be a tumor of the abdominal wall. The history in this case of an obstinate remittent fever, followed by the appearance of a tumor of the hypochondrium and by a preliminary discharge at the umbilicus, clearly indicated the nature of the trouble. In the absence of any history of the case it is extremely difficult to fix the origin of a suppurating tumor originating, apparently, in the depth of the right hypochondrium.

Mistakes are frequently made in the case of an abscess developing in the convexity of the right lobe of the liver and pushing the diaphragm up to the third, even to the second, rib, and thus producing conditions identical with empyema of the right thorax. Such instances of hepatic abscess are peculiarly difficult of recognition, because, the physical signs being the same as those of empyema, the differentiation must rest on the clinical history. In cases of empyema proper the effusion in the chest is preceded by pain and accompanied by an increasing difficulty of breathing; in hepatic abscess there are, as a rule, symptoms of disturbance in the hepatic functions, fluctuation in the hepatic region, dysentery, etc., long anterior to any disturbance in the thoracic organs. Again, empyema may be a latent affection, without any symptom except some obscure pain and a progressive increase in the difficulty of breathing; on the other hand, abscess of the liver is preceded by symptoms of liver disease and of associated maladies. A dry, purposeless cough is present in many cases of abscess; a painful cough with bloody expectoration occurs when preparation is making for discharge through the lungs.

Errors of diagnosis are liable to occur in the consideration of symptoms unquestionably hepatic in origin. Thus, the intermittent fever accompanying some cases of hepatic colic, like the shivering fits and fever which occur in cases of nephro-lithiasis, may be confounded with the septicæmic fever of hepatic abscess. An attentive examination of the attendant circumstances, especially a careful survey of the right hypochondrium, can alone determine the nature of the symptoms. In all doubtful cases the experimentum crucis of puncture with the exploring-needle becomes a measure of necessity. When all diagnostic indications are at fault, the needle of the aspirator may decide the issue. An abundant experience has shown that a needle of suitable size may be introduced into the right lobe without any ill result—often, indeed, with distinctly good effects when there is no suppuration or when pus cannot be detected. In the present state of our knowledge it cannot be determined why puncture of the organ should be beneficial in cases having the symptomatic type of hepatic abscess when none exists; but of this fact there is no doubt.

TREATMENT.—As the formation of pus is coincident with or causative of the first symptoms, it is obvious that treatment directed to prevent an abscess can rarely succeed. Yet it is probable that now and then an abscess just forming has been arrested and healing effected. At the onset of symptoms some large doses of quinine, with a little morphine (scruple j of the former and ¹/8 gr. of the latter), every four or six hours, may have a decided curative effect. During the course of the septicæmic fever, with its chills and febrile exacerbations, quinine in full doses and alcohol according to the conditions present are necessary remedies. As the symptoms develop saline laxatives are useful until the formation of pus becomes evident, when all perturbating treatment of the intestinal canal should cease. If dysentery be present when the hepatic symptoms arise, it should be cured as promptly as possible; and of all remedies for this purpose, ipecac given in the usual antidysenteric quantity offers the best prospect of relief. For the dysentery which succeeds to abscess, and is probably, in part at least, dependent on portal obstruction, the mineral astringents, as copper sulphate, are the most effective remedies. As far as practicable, after an abscess has formed the intestinal canal should be kept quiet, for any considerable disturbance will endanger the escape of pus into the peritoneal cavity. Persistent vomiting is very significant of pressure by an enlarging abscess in the stomach, and usually signifies an abscess associated with impacted calculus. It is important in such cases to maintain, as far as can be done, a quiescent condition of the stomach, for the purpose of preventing rupture into the peritoneal cavity and to favor the nutrition which is seriously endangered by the repeated vomiting. Effervescent soda powders are very useful; carbolic acid in solution, or creasote-water with or without bismuth, is beneficial; champagne, very dry and highly effervescent, has been, in the writer's hands, remarkably efficient. As food becomes a most important need in such cases, milk and lime-water, wine-whey, egg-nog, and similar aliments must be given in small doses and frequently. Nutrient enemata, prepared from eggs, milk, and beef-juice, with the materials for digestion—acid and pepsin—may be made to supplement the stomach, but such efforts have a very limited utility, owing to the state of the hepatic functions and to the obstruction of the portal circuit. In all cases it is necessary to maintain the strength by suitable aliment and the judicious use of stimulants. The long-continued and profuse suppuration makes an enormous demand on the vital resources of the patient, and this must be compensated by suitable food-supplies.

As the formation of pus has taken place in most cases when symptoms have begun, the question of highest importance is, Shall the pus be evacuated? The statistical evidence relating to this question becomes then an extremely valuable guide. As in almost all cases of puncture of the liver for the evacuation of an abscess some part of the liver substance must be passed through, it is necessary to note how far this can be done without inflicting permanent injury on the organ. Hammond has punctured the liver in eight cases without the presence of an abscess, and of these not one has presented any unfavorable symptom. The author has punctured the liver, penetrating well into the interior, in two cases in which no abscess was discovered, but the symptoms of hepatitis existed, with the effect to improve the symptoms. In Condon's¹¹³ collection of 11 cases there were 8 of abscess evacuated by the trocar, and 3 of acute hepatitis in which abscess had not formed, but in which the puncture procured the most decided amelioration of the symptoms. We have heretofore referred to Hammond's experience in the puncture of the liver in cases of hypochondriasis, this condition appearing to depend in some instances on the presence of abscess. In a number of instances abscesses did exist, but in many others there was no apparent lesion of the liver, but in these cases the puncture of the organ was without any ill result. Testimony to the same effect is given by Ramirez,¹¹⁴ who asserts that he had not known a single instance in which any ill result followed puncture of the liver. It may therefore be regarded as certain that exploratory puncture of the organ for the purpose of diagnosis as well as for treatment can at any time be performed with suitable precautions in respect to the size, condition, and character of the instrument.

¹¹³ "On the Use of the Aspirator in Hepatic Abscess," Dr. E. H. Condon, The Lancet (London), August, 1877.

¹¹⁴ Du Traitement des Abcès du Foie, Observations recueilles à Mexico et en Espagne, par Lino Ramirez, M.D., Paris, 1867, p. 65.

The authorities of most experience are agreed that, provided with the aspirator, the abscess may be punctured as soon as a purulent collection can be ascertained to exist. The obvious reason for tapping the abscess is its tendency to extend in various directions, destroying the hepatic substance. In those examples confined by a limiting membrane, after a time of inactivity ulceration begins, and the pus seeks an outlet in some direction. The early evacuation by a suitable aspirator becomes then a measure of the highest necessity. The good effects of puncture with even such a crude instrument as the trocar is well exhibited in the statistics collected by Waring.¹¹⁵ In a collection of 81 cases opened by the knife or trocar there were 66 deaths, making the percentage of recoveries 18.5. In these cases the operative procedure was a final measure, and the mischief had been done almost if not quite in its entirety. The statistics of Waring are concerned with a period anterior to 1850. Although they demonstrate the value of the trocar and evacuation of the abscess, as compared with the results of the natural course of the disease, the far greater success of the treatment by the aspirator is shown by the statistics of recent times. Thus in McConnell's¹¹⁶ 14 cases, also of India, in which the aspirator was used to empty the sac, 8 recovered and 6 died. The statistics of Waring may also be profitably compared with those of Condon,¹¹⁷ in which, of 8 cases of abscess evacuated by the aspirator, 4 recovered, or 50 per cent. They may also be compared with Sach's¹¹⁸ cases, 21 in number, of which 8 recovered, or 38 per cent., and with the cases of De Castro¹¹⁹ of Alexandria, who reports 22 large abscesses operated on, the proportion of cures being 31.8 per 100, and 10 small abscesses, the proportion of cures being 70 per 100. In a case seen in consultation with Collins, in this city, last year, the aspirator was used by us about three months after the symptoms of abscess declared themselves. About a quart of bloody pus was drawn off at once, the opening sealed, and no subsequent accumulation occurred, the patient entirely recovering, for after a year he was seen (December, 1884) in complete health. From these data we draw the important conclusion that early operation is desirable. This fact may be formulated in the expression: In all cases of hepatic abscess use the aspirator whenever the presence of pus is made out. When the abscess is large, and especially when communication is established with the parietes of the abdomen, a free opening, followed by the insertion of a drainage-tube, is the proper method to pursue. If the pus reaccumulates, it is good practice to inject the cavity with tincture or compound solution of iodine after the pus is drawn off, provided the dimensions of the abscess are not too great.

¹¹⁵ An Inquiry into the Statistics of Abscess of the Liver, loc. cit.

¹¹⁶ "Remarks on Pneumatic Aspiration, with Cases of Abscess of the Liver treated by this Method," Indian Annals of Medical Science, July, 1872, quoted.

¹¹⁷ Lancet, supra.

¹¹⁸ Ueber die Hepatitis der heissen Länder, etc., von Dr. Sachs in Cairo.

¹¹⁹ Des Abcès du Foie des Pays chauds, et de leur Traitement chirurgical, par le Docteur S. V. de Castro (d'Alexandrie d'Egypte), Paris, 1870, p. 59.

As regards the mode of proceeding, the following are useful rules: Ascertain, if possible, the existence of fluctuation; locate the point where the walls of the abscess are thinnest; insert an exploring-needle, and if the dépôt of pus is reached substitute a trocar having a sufficient calibre to evacuate the contents of the abscess; observe antiseptic precautions in respect to each detail of the operative procedure, and after the removal of the canula or needle, if a drainage-tube is not necessary, close the wound antiseptically. If drainage is necessary, keep the cavity empty and use proper solutions to prevent septic decomposition. When an abscess of the liver is pointing, the best place to puncture is where the abscess is most prominent and it walls thinnest, but if the accumulation of pus is encysted and there is no attempt at effecting an exit, the exploring-needle should be passed into the interior of the right lobe, the most usual site of suppuration. If pus be reached, a larger trocar may be inserted to evacuate the cavity thoroughly. Repeated insertion of the needle-trocar is preferable when the abscess is small, but when the accumulation is large and sufficiently firm attachments to the abdominal parietes exist, a drainage-tube will be necessary.

In what direction soever discharge of an abscess may take place, the general indications are to support the powers of life by food and stimulants. The utmost quietude should be maintained. It is useful, by the application of a firm flannel bandage, to keep the liver in its proper position and maintain it there. When pointing of an abscess occurs, a large flaxseed poultice is a soothing and a mechanically supporting application.

Acute Yellow Atrophy.

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

HISTORY.—Cases having a more or less exact resemblance to acute yellow atrophy have been occasionally reported from the earliest period. Amongst English physicians, Bright¹²⁰ was one of the first to give an accurate account of the clinical history of some well-defined cases. Rokitansky¹²¹ was really the first to define the disease from the pathological standpoint, and it was he who designated it acute yellow atrophy, this term being intended to signify the nature of the objective changes. The first treatise ever published on the disease as a distinct morbid entity was the monograph of Horaezek,¹²² which appeared in 1843. Amongst the French, Ozonam in 1847 was the first to recognize and describe the disease as a distinct affection, although Andral¹²³ had several years before mentioned an affection of the liver which corresponded in some of its features to this affection. In 1862, Wagner¹²⁴ asserted that many of the cases of acute yellow atrophy were only examples of acute phosphorus-poisoning, and that no real distinction exists between the two affections. This statement has been warmly disputed by various German observers, but there is no doubt a close resemblance between the two affections.

¹²⁰ Guy's Hospital Reports, 1836, vol. i. p. 621.

¹²¹ Handbook of Pathological Anatomy, Am. ed.

¹²² Quoted by Legg, On the Bile, Jaundice, and Bilious Diseases, loc. cit.

¹²³ Clinique médicale, 1839, tome ii. p. 363.

¹²⁴ Archiv der Heilkunde, 1862, p. 364.

CAUSES.—There can be no doubt that acute yellow atrophy is a very rare disease, since so few examples are found post-mortem. In the course of a very large experience in autopsical examinations I have met with but one characteristic example.¹²⁵ According to Legg, it is "one of the rarest diseases known to man."

¹²⁵ General Field Hospital, December, 1863.

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

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

The influence of sex in the pathogeny is most remarkable. It is true in Lebert's collection of 72 cases there were 44 men and 28 women, but it is now known that he did not properly discriminate in his selection of supposed examples of the disease. The statistics of all other observers are opposed to those of Lebert. Thus, in Frerichs' collection of 31 cases, carefully sifted to eliminate error, there were 22 women and 9 men. Legg has also collected 100 cases of acute yellow atrophy, and of these 69 were women or girls. The most active period of life—from twenty to thirty years of age—is the usual period for the appearance of this disease. More than one-half of Lebert's cases occurred between fifteen and twenty-five; and of Frerichs', two-thirds happened between twenty and thirty years of age. In Legg's collection of 100 cases, 76 were between fifteen and thirty-five years of age. What is the condition of women at this period in life which renders them so susceptible to this malady? There can be no doubt that pregnancy is the great factor. Of 69 cases especially interrogated on this point, examined into by Legg, in 25 pregnancy was ascertained to exist. In Frerichs' collection one-half were women in the condition of pregnancy. The period of pregnancy at which the disease appears varies from the fourth to the ninth month, the greatest number occurring at the sixth month. So long ago as 1848, Virchow drew attention to the remarkable changes in the liver due to pregnancy. Sinety¹²⁶ has studied the effect of lactation on the liver, and has ascertained the existence of fatty degeneration. There is a form of jaundice which accompanies menstruation, as shown by Senator,¹²⁷ Hirschberg, and others. These facts indicate a certain relationship between the sexual system of the female and the liver, but they do not indicate the nature of the connection, if any exist, between this condition and acute yellow atrophy.

¹²⁶ De l'État du Foie chez les Femelles en Lactation, Paris, 1873 (pamphlet).

¹²⁷ Berliner klinische Wochenschrift, 1872, p. 615, "Ueber Menstruelle Gelbsucht."

The influence of depressing emotions has been supposed to be effective in producing this disease, but it is more than doubtful if such a relationship exists. Lebert, however, refers 13 of his cases to this cause, but Legg, who bases his statements on the study of 100 carefully-recorded cases, is sceptical regarding the effect of such influences. Syphilis has in some instances appeared to be the principal, if not the only, pathogenetic factor, and Legg¹²⁸ compares the action of the virus of syphilis to the effect of phosphorus, mercury, etc.

¹²⁸ On the Bile, Jaundice, and Bilious Diseases, loc. cit.

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

More or less increase of the connective tissue is noted in many of the cases—increase of connective tissue with numerous young cells formed around the vessels and the bile-ducts (Waldeyer¹²⁹). The changes in the liver would surely be incomplete without some references to the minute organisms which play so important a part in modern pathology. Waldeyer was the first to demonstrate the presence of bacteria in the pigment-remains of the hepatic cells. Other observers have been unable to detect them, so that at present the parasitic origin of this affection remains sub judice.

¹²⁹ Arch. für path. Anat., 1868, p. 536, Band xliii.

Important changes also take place in the spleen, but the opinions on this point are somewhat contradictory. Frerichs found the spleen enlarged in most of his cases; Liebermeister, on the other hand, and Legg,¹³⁰ find that the spleen is enlarged in about one-third of the cases. When the atrophic changes occur in the liver, more or less swelling of the splenic veins must occur in consequence of portal obstruction. The peritoneum, especially the omental part, is the seat of multiple ecchymoses, and the endothelium is fatty. The mesenteric glands are usually swollen. More or less blackish or brownish fluid, consisting of altered blood, is usually found in the stomach, and the same, assuming a tar-like consistence, in the large intestine. Ecchymoses of rather small size are distributed over the stomach and intestines. The epithelium of the stomach-glands is found granular and disintegrating, and a catarrhal state of the gastro-intestinal mucous membrane exists throughout. The secretions are never normal, and the stools are wanting in bile or present a tarry appearance, due to the presence of blood.

¹³⁰ On the Bile, Jaundice, and Bilious Diseases, supra.

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

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

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

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

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

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

Various divisions have been proposed to mark the type of the symptoms: thus, the icteric period embraces the prodromal symptoms with jaundice; the toxæmic period is that stage characterized by profound nervous disturbances. Ozonam has divided the symptoms into those of the prodromal period and those of the serious stage, the latter being subdivided into the symptoms of excitation and those of collapse. There may be no prodromal period, however; without any preliminary symptoms the patient is suddenly seized with delirium and passes into a condition of coma and insensibility, or the first evidence of serious illness may be convulsions. It is probable, however, that in even the most sudden cases mild prodromal symptoms had occurred, but were overlooked. There is much variability in the symptoms of the toxæmic period. There are three symptoms: excitement with delirium, sometimes delirium ferox; coma, less or more profound; and convulsions. Legg has numerically expressed the relative frequency of these symptoms thus: Of 100 cases of unquestionable acute atrophy, 76 had become comatose, 59 were delirious, and 32 had suffered convulsions.¹³¹ According to the same authority, delirium and coma were associated together in about one-half of the cases, but in pregnant women coma often occurs alone (Legg). Usually, when convulsions happen there has been either coma or delirium. With these cerebral symptoms there are often present various disturbances of motility and sensibility, such as local convulsions, jactitations, hiccough, extreme restlessness, paralysis of the sphincters, and incontinence of urine and feces or retention, grinding of the teeth, exalted sensibility of the skin, or it may be complete anæsthesia, severe itching of the surface, etc.

¹³¹ On the Bile, Jaundice, and Bilious Diseases, loc. cit.

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

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

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

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

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

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

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

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

DIAGNOSIS.—George Harley¹³² maintains the singular doctrine that acute yellow atrophy is only the "sporadic form of the contagious jaundice of the tropics," or yellow fever. He bases his opinion on the identity of their symptoms, pathological anatomy, mortality, and contagious character; for he affirms that acute yellow atrophy may exhibit contagious power in temperate climates.

¹³² Diseases of the Liver, Amer. ed., 1882, p. 255.

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

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

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

TREATMENT.—It was formerly supposed that a case of acute yellow atrophy must necessarily prove fatal, but this opinion must now be modified, since examples of cure of supposed cases have been reported from Oppolzer's clinic,¹³³ by Lebert,¹³⁴ by Harley,¹³⁵ and others. As at the onset the symptoms cannot be distinguished from a bilious attack or from catarrhal jaundice, the treatment must be appropriate to these states. When the serious symptoms begin, a large dose (scruple j) of quinine should be at once administered, and half the quantity at regular intervals to keep up the cinchonism. Phosphate of soda, with some arseniate and such mild hepatic stimulants as euonymin, iridin, etc., should be given to maintain a gentle aperient action. Experience has proved that active or drastic cathartics do harm rather than good; on the other hand, mild laxatives, especially those having cholagogue action, seem to do good.

¹³³ Thierfelder, op. cit.

¹³⁴ Ibid.

¹³⁵ Diseases of the Liver, Amer. ed., supra.

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

The Liver in Phosphorus-Poisoning.

DEFINITION.—Poisoning by phosphorus may seem to be a toxicological question rather than a merely hepatic disease, but as the morbid complexus thus induced is so similar to acute yellow atrophy that the conditions are regarded as identical by many of our German colleagues, it is necessary to enter into some details regarding it.

PATHOGENY.—Phosphorus-poisoning occurs at any period from youth to old age, but is most common from twenty to thirty years of age. Women seem more inclined to effect self-destruction in this way than are men, probably because phosphorus matches are so readily obtained. Children may munch match-heads in a spirit of mischief. That form of chronic poisoning seen in workmen in match-factories, and consisting in necrosis of bone, etc., does not come within the scope of the present inquiry.

A body poisoned by phosphorus does not exhibit a tendency to putrefactive decomposition within the usual period. The tissues are more or less deeply stained by bile-pigment, and this coloration extends to pathological fluids as well. The serous and mucous membranes contain points of blood-extravasation, but they are especially numerous in the serous membranes. Hemorrhages of this kind are due to two causes—to the disorganization of the blood, and to fatty degeneration of the arterioles. The heart is also more or less advanced in fatty degeneration, the muscles granular, the striations obscure or obliterated, and the whole soft and easily torn. The spleen is usually enlarged—often, indeed, to twice its natural size. The liver presents highly-characteristic alterations. When death occurs early the organ is generally enlarged, infiltrated with fat, the connective tissue undergoing hyperplasia; but in more advanced cases atrophy has taken place, the cells have disappeared and are replaced by fat-granules, crystals of leucin and tyrosin, connective tissue, etc.—in fact, the changes characteristic of acute yellow atrophy. The jaundice has been variously interpreted. As the bile-ducts in advanced cases are found to contain no bile, but only a colorless mucus, the advocates of a hæmatogenic jaundice hold that the jaundice is due to a failure of the liver to excrete the biliary principles in the blood; whilst the opponents of this view maintain the existence of an obstruction in the ultimate ducts. Harley¹³⁶ has recently brought forward some strong facts and arguments—which we believe can be successfully controverted—maintaining the former view. The jaundice of phosphorus-poisoning, if Harley's opinion prove to be correct, must be regarded as a hæmatogenic jaundice.

¹³⁶ Diseases of the Liver, loc. cit.

The mucous membrane of the stomach, as might be supposed, is more or less ulcerated or in an advanced state of catarrh, and the gastric glands are affected by fatty degeneration.

The kidneys are affected in a similar manner to the liver; the epithelium is fatty and sometimes detached, and the same process is found to occur in the vessels and epithelium of the cortex.

SYMPTOMS.—Not only in the morbid anatomy, but in the symptoms, do we find that a very remarkable resemblance exists between acute yellow atrophy and phosphorus-poisoning. As phosphorus is usually swallowed in bulk, some hours may elapse before the local symptoms begin, for the contents of the stomach and the tough mucus lining the mucous membrane may, and usually do, prevent immediate contact of the poison with the mucous membrane. When the stomach is entirely empty the symptoms may begin in an hour or two. The symptoms produced may be arranged in two groups—those due to the local irritation excited by the poison; those due to its systemic impression. In the first group belong burning in the gullet, pain, nausea, and vomiting. According to Lewin,¹³⁷ who has collected a number of cases for analysis, vomiting occurs in 26 out of 32 instances of poisoning. Some hours—often, indeed, three or four days—then elapse before the systemic symptoms begin. Vomiting, which was for the time being suspended, occurs again, and instead of the mere contents of the stomach, containing more or less phosphorus, blood, somewhat changed by the gastric juice—chocolate-colored or as coffee-grounds—appears in the vomited matters. The evacuations from the bowels may at first, as the contents of the stomach, appear phosphorescent, and afterward exhibit the appearances due to the presence in them of altered blood. At this time, if the liver be examined it will be found somewhat enlarged and tender to pressure, and on or about the third day jaundice appears; but it should not be overlooked that jaundice, as Bamberger¹³⁸ has shown, may be postponed to the second or third week after the phosphorus has been taken.

¹³⁷ Virchow's Archiv für path. Anat., etc., Band xxi. p. 514 et seq.

¹³⁸ Legg, On the Bile, Jaundice, and Bilious Diseases, loc. cit.

In favorable cases the area of hepatic dulness decreases and the jaundice declines. In the fatal cases certain nervous phenomena become prominent. There occur drowsiness, developing into coma, with intercurrent attacks of delirium which may be of a maniacal character; convulsions, spasmodic attacks, dilated pupils, and involuntary evacuations. The disorganization of the blood and the fatty change in the vessels are exhibited in the hemorrhages from the gastro-intestinal mucous membrane. The nervous phenomena are due chiefly to the retention in the blood of various excrementitious matters which it is the function of the liver to separate from the blood. Flint's theory of cholesteræmia has been so abundantly disproved that no one upholds it at the present time, but the cerebral symptoms are properly referred to the retention of all hepatic excrement.

The temperature in phosphorus-poisoning rises from 99° to 102° F., but it may reach in severe cases to 103° to 105° F., and at death or immediately afterward to 105°, even to 107° F. The same fact is true of acute yellow atrophy. With the jaundice the pulse declines, but in the further progress of the case, especially toward the close, the pulse becomes rapid and small.

The changes occurring in the urine are highly significant. The amount of urea decreases as the symptoms increase in severity, and leucin and tyrosin take its place. If the case tends to recovery the urea again increases in amount, but if the tendency is in the opposite direction the quantity of urea steadily diminishes. Bile acids and bile-pigment are found in quantity, and albumen is present in small amount.

COURSE, DURATION, AND TERMINATION.—Phosphorus-poisoning is necessarily an acute affection, but the duration of cases is much influenced by the form in which the poison is taken. If in a liquid and diffusible form, as oleum phosphoratum, the local and systemic symptoms will develop in a few hours, but if in solid masses, as particles of match-heads, many hours (six to ten) may elapse before the local irritation begins. The proportion of cures in phosphorus-poisoning varies from one-fourth to one-half of the cases. Much depends, however, on the promptness and efficiency of the treatment. The prognosis is the more favorable the earlier proper measures of relief have been instituted. If the case has proceeded to jaundice, hemorrhages, black vomit, etc. without the administration of suitable antidotes, little can be expected from any kind of treatment.

DIAGNOSIS.—The history of any case involved in doubt is indispensable to a correct conclusion. The phosphorescent appearance of the matters vomited or passed by stool may make the differentiation comparatively easy; but if the case has passed beyond this stage, phosphorus-poisoning can be separated from acute yellow atrophy only by the history of the case. If the fact of the administration of phosphorus is successfully concealed, no differentiation can be made, since even the best authorities hold to the identity of the toxic symptoms produced by this poison and of the morbid anatomy, with the symptoms and lesions of acute yellow atrophy.

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.

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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.

A by no means infrequent combination is that of bilirubin with calcium; and this may constitute the nucleus or form a part of the body or the crust of a calculus. The mechanism of its formation is not unlike that of the cholesterin concretion. Bilirubin is soluble in alkalies, and is precipitated from its solution by acids. It follows that when acid fermentation takes places under the influence of mucus, bilirubin may be precipitated in combination with calcium. The salts of sodium and potassium are much more abundant in bile than those of lime, but the latter much more often enter into the formation of calculi because of their slighter solubility. Other combinations of bile-pigments, mucus, and the salts of the bile take place, but they are relatively less frequent. The principal lime salt is the carbonate, and this combines in varying proportions with the bile acids, the fat acids, and bile-pigment.

Certain physical conditions are not less important than the chemical in the production of hepatic calculi. Accumulation of bile in the gall-bladder, stasis, and concentration are essential conditions. If bile remains long in the gall-bladder, it becomes darker in color and more viscid, its specific gravity rises, and the relative proportion of solids increases, doubtless because of the absorption of a part of the water. The reaction—which, as has been stated, is in the fresh state neutral or alkaline—becomes acid in consequence of a fermentative change (Von Gorup-Besanez) set up by the mucus. If a catarrhal state of the mucous membrane exist, the mucus, epithelium, and lymphoid cells cast off play the part of a ferment. The lime which is so important a constituent of biliary concretions is not present even in concentrated bile in sufficient amount to account for its agency in the formation of these bodies, is furnished by the diseased mucous membrane (Frerichs). Indeed, numerous crystals of carbonate of lime have been seen in situ in contact with the mucous membrane in cases of chronic catarrh. It follows, then, that catarrh of the biliary passages has an important causative relation to that pathological condition of the bile which precedes the formation of calculi. In this connection we must not lose sight of the researches made by Ord¹⁵⁷ on the action exerted by colloids on the formation of concretions. The mucus is the colloid; cholesterin, lime, and soda salts are the crystalloids. These latter diffusing through the colloid medium, the resulting combinations assume spheroidal forms. The union of bilirubin and lime salts illustrates the same principle.

¹⁵⁷ On the Influence of Colloids upon Crystalline Forms and Cohesion, with Observations on the Structure and Mode of Formation of Urinary and other Calculi, by W. Miller Ord, M.D., F.R.C.P. Lond., etc., London, 1879.

CAUSES.—We have here to consider the external conditions and the general somatic influences which lead to the formation of biliary concretions. Age has an important causative action. Besides other agencies due to advancing life, the increase of cholesterin is an influential factor. The less active state of the functions in general, diminished oxidation, loss of water, and concentration of the bile are influential factors in determining the formation of hepatic calculi in advancing life, as the opposite conditions oppose their production in early life. Although not unknown in infancy, at this period in life and until twenty years of age they occur but rarely. Fauconneau-Dufresne,¹⁵⁸ of 91 cases, had 4 in infants; Wolff¹⁵⁹ had 1 in a collection of 45 cases; and Cyr,¹⁶⁰ 2 cases under ten in a group of 558 cases. The following table illustrates the influence of age on the productivity of gall-stones:

AUTHORS.
HEIN.		FAUCONNEAU-DUFRESNE.		WOLFF.		DURAND-FARDEL.		CYR.
Whole No.	395	Whole No.	91	Whole No.	45	Whole No.	230	Whole No.	558
From infancy to 30	18	Before 20	10	Before 20	3	Before 20	2	Before 20	20
From 30-70	377	From 20-40	13	From 30-60	42	From 20-30	28	From 21-30	208
		From 40-90	68			From 30-60	162	From 31-40	185
						From 60-90	38	From 41-50	91
								From 51-60	48
								Above 60	6

¹⁵⁸ Traité de l'Affection calculeuse du Foie, Paris, 1851.

¹⁵⁹ Virchow's Archiv f. path. Anat., etc., Band xx., 1861, p. 1.

¹⁶⁰ Traité de l'Affection calculeuse du Foie, Paris, 1884, p. 53.

Although there is a general correspondence in the results of the observations on the age most liable, there are differences. Thus, Cyr, whose figures represent the experiences at Vichy, makes the age of maximum liability from twenty to forty years—distinctly earlier than any other observer; and hence it is necessary to bear in mind the extreme latitude of his diagnosis. Of my own collection, 30 in number, all doubtful cases excluded, there were 20 between thirty and fifty years, and 10 between fifty and seventy. Of these, 22 occurred in subjects between forty and sixty. The period of maximum liability is about fifty years of age. Cyr refers the difference of his statistics from those of other observers to the character of the patients. The preponderance in the number of cases of hepatic calculi at or about the fiftieth year is referable to the lessened activity of the nutritive functions at this period, and to the increase in the relative proportion of cholesterin in the blood in advanced life (Luton¹⁶¹). Charcot¹⁶² maintains that after sixty biliary calculi are more frequent, but owing to the physiological conditions then existing the migration of these bodies is effected without notable inconvenience.

¹⁶¹ Jaccoud's Dictionnaire encyclopéd., art. "Voies Biliaires;" idem., Bull. gén. de Thérap., March 15, 1866.

¹⁶² Leçons sur les Maladies du Foie, etc., p. 145.

According to most authorities, females are more liable to the formation of gall-stones than are men. Thudicum, after an analysis of the statistics given by the most experienced and celebrated authorities, places the proportion at 3 to 2. Von Schüppel gives the same figures. Cyr, whilst recognizing this estimate as true of the great mass of observations on this point, finds that in his own cases the preponderance of females over males was even greater, being 4 to 1—inversely to the liability of the sexes to gout; but this excess is to be explained by the character of the subjects falling under his observation. Women are subjected to influences which favor the formation of these concretions, such as pregnancy, sedentary habits, diet of a restricted character, the use of corsets, and the somatic changes at the climacteric period.

The social state, by reason of the conditions associated with a good position in life, has an influence in the production of calculi. Luxurious habits and indulgence in the pleasures of the table are important factors, and hence this malady is encountered amongst the better class of patients in private practice rather than amongst laboring people in the hospitals.

As the somatic conditions which exert a predisposing action, and the social circumstances also favoring the formation of hepatic calculi, are transmitted, heredity is by some classed among the etiological factors, but it can only be regarded as indirect.

Malarial influences unquestionably exert a very powerful influence as this malady occurs in this country. Paroxysms of intermittent either induce or accompany the seizures of hepatic colic, and chronic malarial poisoning exerts a direct causative influence through the hepatic disturbances and the gastro-duodenal catarrh which are associated with it. Attacks of hepatic colic are extremely frequent in the malarial regions of the West and South. It may be, however, that this malady is frequent rather in consequence of the diet of pork than of climatic causes, for it is probable that indulgence in such food plays an important part in the formation of biliary concretions (Harley). Due allowance made for diet, climate is yet, no doubt, an influential factor. In warm, especially in malarial, regions the functions of the liver are taxed to compensate for the increased action of the skin and lungs; but this organ is, besides, affected by the poison of malaria, and to the congestion caused by it is superadded a catarrhal state of the bile-ducts and of the duodenum. A pathological condition of the bile itself is first induced; then the fermentative changes set up by the mucus cause the separation and crystallization of pigment and cholesterin.

Certain seasons favor the formation of biliary concretions, because then the special influences which operate at all times are more active and persistent. These seasons are fall, winter, and early spring, and gall-stones are more numerous then in consequence of the activity of the malarial poison, the character of the diet then employed, and the lessened oxidation due to the more sedentary life. Climate is a factor of some consequence, but not in the direction that might have been supposed. Gall-stones are more common in temperate than in tropical climates—a statement confirmed by the observation of the physicians of India. They are, according to Harley, quite common in Russia, where also they attain to extraordinary dimensions; but these circumstances are not due to the climatic peculiarities of that country, so much as to the diet habitually consumed, consisting so largely of fatty substances.

Of all the conditions which favor the production of gall-stones, none are so influential as the bodily state and the associated dietetic peculiarities. Those troubled with these concretions, as they have occurred under my observation, have been either obese or have had a manifest tendency in that direction. They have had a strong inclination for the fat-forming foods, also for starchy, saccharine, and fatty articles, such as bread and butter, potatoes, beans and peas, pork, bacon, and fat poultry, etc. Harley thinks indulgence in bacon (p. 367) is a prime factor. Thudicum rejects this notion on chemical grounds, for obesity and the free consumption of fat cannot be concerned in the production of these bodies, because cholesterin is an alcohol.¹⁶³ The agency of a fatty diet has been so strongly indicated in clinical observations, and the relation of cholesterin to the fats so obvious, that it can hardly be doubted the free consumption of fat in food contributes directly to the formation of calculi. An indirect relation may also be traced. A catarrhal state of the duodenal mucous membrane existing, and the bile excluded by swelling and obstruction of the bile-ducts, fats are decomposed, and the fat acids, absorbed into the portal blood, contribute to those chemical changes in the bile which result in the precipitation of cholesterin. Beneke¹⁶⁴ traces a connection between atheromatous degeneration of the vessels and the formation of biliary concretions. A general increase in the amount of fat in the body is usually coincident with the atheromatous change, and at the same time the relative proportion of cholesterin in the bile becomes greater.

¹⁶³ A Treatise on Gall-stones, p. 214.

¹⁶⁴ Deut. Archiv für klin. Med., Band xviii.

Indulgence in the starchy and saccharine foods plays a part in the formation of gall-stones not less, if not more, important than the consumption of fats. A diet of such materials is highly fattening, and if the necessary local conditions exist they readily undergo fermentation, and thus cause or keep up a catarrh of the mucous membrane.

Too long intervals between meals, Frerichs¹⁶⁵ thinks, is more influential than errors of diet in causing concretions. The bile accumulates in the gall-bladder, and the condition of repose favors the occurrence of those changes which induce the separation and crystallization of cholesterin. Obstacles to outflow of every kind have the same effect. The largest calculus in my possession was obtained from a case of cancer of the gall-bladder which compressed, and finally closed, the cystic duct. Sedentary habits have the same mechanical effect, but, as already pointed out, insufficient air and exercise act by lessening oxidation. Corpulent persons indulging in rich food and avoiding all physical exertion, those of such habits confined to bed by illness or injury, the literary, the well-to-do, self-indulgent, lazy, are usual subjects of this malady. Any condition of things which causes a considerable retardation in the outflow of bile will have a pathogenetic importance, especially if the causes of chemical change, the lessened quantity of taurocholic and glycocholic acid, and an increased quantity of cholesterin, coexist. Moral causes, as fear, anxiety, chagrin, anger, etc., have seemed to exercise a causative influence in some instances (Cyr).

¹⁶⁵ A Clinical Treatise on Disease of the Liver, Syd. Soc. ed., vol. ii. p. 511.

To the causes of retardation of the bile-flow mentioned above must be added catarrh of the bile-ducts. This acts in a twofold way—as an obstruction; a plug of mucus forming the nucleus. It has already been shown that fermentative changes may be set up by the mucus, which plays the part of a ferment, an acid state of the bile resulting.

Situation of Gall-stones, and their Destiny.—The gall-bladder is, of course, the chief site for these bodies, but biliary concretions and masses of inspissated bile may be found at any point in the course of the ducts. Single stones may be impacted at any point in the cystic, hepatic, or common duct, or masses composed of numerous small calculi may take the form of a duct and branches, making a branching calculus of the shape and size of the mould in which it is cast. Such casts may be hollow, thus permitting an outlet to the bile, or they may completely close the tube, and a cyst form, the walls of which grow thicker with connective-tissue deposits. Stones of very large size may be thus enclosed, Frerichs having seen one the size of a hen's egg formed about a plum-seed, which was the nucleus. In some rare instances the major part of the larger tubes have been filled with inspissated bile, through which the fluid bile could only be slowly filtered.

Calculi are not often found in the hepatic duct, since they can only lodge there in descending from the smaller tubes, and hence are too small to become wedged in. The usual site, as has been sufficiently explained, is the gall-bladder. At the entrance to the cystic duct and at the terminus of the common duct in the duodenum are the points where migrating calculi are most apt to be arrested.

Spontaneous disintegration of gall-stones sometimes occurs. Cholesterin being dissolved off of the corners and edges, the cohesion of the mass is impaired and it falls apart in several fragments. By very slight mechanical injury air-dried calculi will be broken up. In the gall-bladder two factors are in operation to effect the disintegration of the contained calculi: the movements of the body, by which the corners and the borders are crumbled; the solvent action of the alkaline bile on the cholesterin. When, however, these concretions are made up of lime and pigment, their integrity can be impaired only by the process of cleavage; no solvent action can take place.

Various changes occur in the ducts or in the gall-bladder in consequence of the presence of these concretions. Whilst a catarrhal state of the mucous membrane of the ducts is an element of much importance in the process by which concretions are formed, on the other hand the presence of these bodies excites catarrh, ulceration, perforation, and, it may be, abscess of the liver. When concretions form or are deposited in the ducts, they cause inflammatory reaction, the walls yield, and the neighboring hepatic structures may also be affected by contiguity. The dilatation of the tube is usually cylindrical, much more rarely sacciform. The neighboring connective tissue may undergo hyperplasia and a more or less extensive sclerosis occur. More frequently the calculus ulcerates through, and an abscess is produced which will take the usual course of that malady. Very rarely a calculus is found enclosed in a separate sac and surrounded by healthy hepatic tissue (Roller).¹⁶⁶

¹⁶⁶ Berliner klin. Wochensch., No. 42, 1879; ibid., Nos. 16, 17, and 19 for 1877, Fargstein.

As the gall-bladder is the usual place for the formation and storage of gall-stones, the changes in connection with this organ are the most important. The calculi may be so numerous or so large as to distend the gall-bladder and cause it to project from under the inferior border of the liver, so as to be felt by palpation of the abdominal wall. The stones may be few in number and float in healthy bile, or they may fill the bladder to the exclusion of fluid, the cystic duct being closed permanently; or there may be, with one or more concretions, a fluid composed of mucus, muco-pus, serum, and bilious matter. The mucous membrane may be in a normal state, but this is rare; usually it is affected by the catarrhal process, and atrophic degeneration has taken place to a less or greater extent; the rugæ are obliterated, the muscular layer hypertrophied. When attacks of hepatic colic have occurred, more or less inflammation of the peritoneal layer of the gall-bladder and cystic duct is lighted up, and organized exudations form, changing the shape and position of the organs concerned. It is usual in old cases of hepatic colic to find the gall-bladder bound down by strong adhesions, the cavity much contracted or even obliterated, the cystic duct closed, and the neighboring portion of the liver the seat of sclerosis. Such inflammatory exudations about the gall-bladder may become the seat of malignant disease—of scirrhus. Several examples of this have been reported, and one has occurred in my own practice.

The contact of a gall-stone, especially of a polyangular stone, may cause ulceration of the mucous membrane. This is the more apt to occur if the muscular layer of the gall-bladder is hypertrophied, especially if certain fasciculi are thickened and overacting, leaving intervening parts weak and yielding to the pressure of the stone forced in by the spasmodically contracting muscles. Finally yielding, the stone and other contents of the gall-bladder escape into the cavity of the abdomen. Adhesions to neighboring parts may prevent rupture. Such adhesions are contracted with the colon, the duodenum, the stomach, and other organs. In some rare instances the closed gall-bladder has undergone a gradual process of calcification, the mucous membrane losing its proper structure, the muscular layer degenerating, and a slow deposit of lime salts taking place, the ultimate result being that the biliary concretions are enclosed in a permanent shell.

As above indicated, biliary concretions may remain where deposited for an indefinite period. Very often they migrate from the point of formation, the gall-bladder, into the duodenum, producing characteristic symptoms called hepatic colic. As the size of the ducts increases from above downward, obviously but little vis a tergo is needed to propel the concretions onward. The chief agency in the migration of these bodies is the discharge of bile. Common observation shows that the symptoms of hepatic colic usually declare themselves in two or three hours after a meal—at that time when the presence of the chyme in the duodenum solicits the flow of bile. The gall-bladder contracts on its contents with an energy in direct ratio to the amount of bile present, and with the gush of fluid the concretion is whirled into the duct. Once there, the cystic duct being unprovided with muscular fibres, the onward progress of the stone must depend on the flow of bile; and, as the canal is devious, this may not always carry the concretion into the common duct. Just behind the neck of the gall-bladder the duct makes an angle somewhat abrupt, and here also its folds project into the canal, so that at this point the stone is apt to lodge; but much depends on the size and shape of the calculus. If it pass through the cystic duct, the inflammation resulting may close the canal, several instances of which have fallen under my observation. The next point where stoppage of the migrating calculus may, and frequently does, occur is the orifice of the common duct in the duodenum. This orifice has a funnel shape, the smaller extremity toward the intestine, the object of this being to prevent the entrance into the duct of foreign bodies from the intestine. A diverticulum is thereby made (Vater's) in which a concretion may lodge, partly or wholly preventing the escape of bile into the bowel. The various forces concerned in the propulsion of the concretion onward from the common duct into the intestine are the discharges of bile, the contraction of the few muscular fibres in the walls of the duct, the respiratory movements, especially forced expiration, coughing, sneezing, vomiting, defecation—in fact, all of those acts in which the abdominal muscles, the diaphragm, and the sphincters are simultaneously brought into strong contraction. The symptoms produced by the migration and stoppage of a concretion will vary according to the size and shape of the stone, and the consequent diminution in the amount of bile discharged or its complete arrest. In other words, the stone may be firmly wedged in, completely closing the canal against the passage of bile, or it may lie loosely in the diverticulum Vateri, acting as a sort of ball valve, now permitting a gush of bile, and now stopping the passage-way more or less tightly.

The migration of calculi may take place by ulcerating through into neighboring hollow organs. Usually the first step consists in stoppage of the bile. To the accumulating bile mucus is added, and the gall-bladder or the duct—usually the common or cystic duct—dilates, often to a considerable extent, and, adhesions forming, discharge ultimately takes place through some neighboring hollow organ. The routes pursued by such fistulous communications are various. The organs most frequently penetrated are the stomach, duodenum, and colon, less often the urinary passages, and very rarely the portal vein. Numerous examples of external discharge of calculi have been reported. The most usual, as it is the most direct, is the fistulous connection of the gall-bladder or common duct with the duodenum. Solitary stones of immense size have been thus discharged. Murchison¹⁶⁷ gives references to many interesting examples, and the various volumes of Transactions of the Pathological Society are rich in illustrative cases. The symptoms produced by the migration of calculi by the natural route and by ulceration into other organs will be hereafter considered.

¹⁶⁷ Clinical Lectures on the Diseases of the Liver, 2d ed., p. 487 et seq.

SYMPTOMS DUE TO THE PRESENCE OF GALL-STONES AT THEIR ORIGINAL SITE.—Very large calculi or numerous small ones may be present in the biliary passages without causing any recognizable symptoms. The migration of these bodies by the natural channel and by ulceration into the duodenum may also be accomplished without any local or systemic disturbance.¹⁶⁸ That the retention of calculi may not induce any characteristic reaction by which they may be recognized is probably due to the fact that the gall-bladder, in which they chiefly form, possesses but slight sensibility, and as it is in a constantly changing state of distension or emptiness according to the amount of bile present, it is obvious that a foreign body made up of the biliary constituents, and having nearly the same specific gravity as the bile, is not likely to cause any uneasiness or recognizable functional disturbances. Furthermore, the slowness with which biliary concretions form enables the organ to accommodate itself to the new conditions. The lack of sensibility which is a feature of the gall-bladder, and which I have had the opportunity to ascertain by actual puncture in an individual not anæsthetized, is in some instances supported by a general state of lowered acuteness of perception. There are great differences in respect to readiness of appreciation and promptness of response to all kinds of excitation in different individuals. To what cause soever we may ascribe the lack of sensibility, the fact remains that in not a few cases of gall-stones in the gall-bladder there are no symptoms to indicate their presence. On the other hand, there are some disturbances that have a certain significance.

¹⁶⁸ Amongst the numerous examples of this kind to be found recorded may be mentioned the case reported by M. L. Garnier, Agrégé à la Faculté de Médecine de Nancy (Archives de Physiologie normale et pathologique, No. 6, 1884, p. 176): An hepatic calculus, weighing 24.5 grammes, was discharged without any symptoms or even consciousness on the part of the patient, a man of sixty years. He had had colic and jaundice, but these subsided entirely, and there was no further disturbance. As has happened in so many instances, this stone must have ulcerated through into the bowel without causing any recognizable symptoms.

The subjective signs are uneasiness—a deep-seated sensation of soreness—felt in the right hypochondrium, increased by taking a full inspiration and by decubitus on the left side. Pain or soreness, sometimes an acute pain, is experienced under the scapula near the angle, at or about the acromion process, and sometimes at the nape of the neck. In one case under my observation within the past year a patient who had had several attacks of hepatic colic, the usual polyangular stones having been recovered, had from time to time severe pain over the right side of the neck, shoulder, and scapula, accompanied by a severe herpes zoster in the district affected by the pain. This is of course an extreme example, but it is very suggestive of the relation which may exist between hepatic disturbances and shingles. Attacks of gastric pain coming on some time after food, and not soon after, as is the case in true gastralgia, are usual in the early stage of the disease—are constant, according to Cyr,¹⁶⁹ who quotes approvingly an observation of Leared on this point. Migraine or sick headache and vertigo occur in many cases, but it may well be doubted whether these symptoms are not due to the accompanying gastro-duodenal catarrh, which is a nearly constant symptom. Acidity, flatulence, epigastric oppression, a bitter taste, a muddy rather bilious complexion, and constipation are symptoms belonging to catarrh of the gastro-duodenal mucous membrane. Most of these symptoms are rather indefinite. Some additional information may be supplied by palpation. When the gall-bladder is distended with gall-stones, or is in the enlarged state which occurs when the common duct is obstructed, it may project beneath the inferior border of the liver far enough to be felt. In thin persons a grating sound, produced by the friction of the calculi, may be heard, the stethoscope being applied as palpation is made over the hypochondrium. It is rare that these symptoms can be elicited, since the calculous affection of the liver occurs for the most part in persons of full habit, in whom the abdominal walls are too thick to allow of the necessary manipulation. There may be also some tenderness on pressure along the inferior margin of the ribs, especially in the region of the gall-bladder.

¹⁶⁹ Traité de l'Affection calculeuse du Foie, p. 71.

SYMPTOMS DUE TO THE MIGRATION OF GALL-STONES BY THE NATURAL CHANNELS.—A calculus passing into the cystic duct from the gall-bladder causes the disturbance known as hepatic colic or bilious colic, because of the jaundice which accompanies the major part of these seizures. But jaundice is not a necessary element in these cases; it is not until the concretion reaches the common duct that the passage of bile into the intestine is interfered with. The gall-bladder has a function rather conservative than essential, for its duct may be permanently closed without apparently affecting the health.

The time when an attack of hepatic colic is most likely to occur would seem to be determined by the flow of bile; for this, as has been stated, is the chief factor in moving calculi along the ducts. As, no doubt, the presence of the chyme in the duodenum is the stimulus for the production of bile and also for the contractions of the gall-bladder, it follows that a few hours after meals is the time when the attacks of hepatic colic would a priori be expected. This is in accord with experience, but there are exceptions. In one of the most formidable cases with which the writer has had to deal—the diagnosis confirmed by the recovery of the calculi—the most severe attacks occurred in the early morning. According to Harley,¹⁷⁰ colic from the passage of inspissated bile occurs when the stomach and duodenum are most nearly empty—from ten at night until ten in the morning—and this he relies on as a means of diagnosis, but the exceptions are too numerous to assign much importance to this circumstance.

¹⁷⁰ On Diseases of the Liver, p. 354.

The onset of pain is usually sudden, but it may develop slowly from a vague uneasiness in the region of the gall-bladder; or after some pain and soreness at this point, accompanied by nausea, even vomiting, the paroxysm will begin with very acute pain. The situation of the pain is by no means constant, and usually varies in position in the same case. The point of maximum intensity is near the ensiform cartilage, outward and downward two or three inches, about the point of junction of the cystic and common duct. From or about this region the pain radiates through the epigastrium, the right hypochondrium, upward into the chest, backward under the scapula, and downward and inward toward the umbilicus. In some instances under my observation the most acute suffering was located in the right iliac region, in others in the lumbar region, and in still others in the epigastrium. The position of the pain may be such as to draw attention from the liver, and thus greatly confuse the diagnosis. In a well-defined attack the pain is intense, shooting, and boring, irregularly paroxysmal; the patient writhes in agony, screams and groans, rolls from side to side, or walks partly bent, holding the part with a gentle pressure or rubbing with an agonized tension of feeling. Meanwhile the countenance is expressive of the intensest suffering, is pallid and drawn, and the body is covered with a cold sweat. Nausea presently supervenes, and with the efforts to vomit a keen thrust of pain and a sense of cramp dart through the epigastrium and side. Very considerable depression of the vital powers occurs; the pulse becomes small, feeble, and slow, or very rapid and feeble. The patient may pass into a condition of collapse, and, indeed, the pain of hepatic colic may cause death by sudden arrest of the heart's action. The cases which prove fatal in this way are doubtless examples of fatty heart, the degeneration of the cardiac muscle being a result of the action of the same factors as those which cause gall-stones to form, if the relation of general steatosis to these bodies which I have set forth prove to be true. The pain is not continuously so violent as above expressed: it remits from time to time, and seems about to cease altogether when a sudden access of anguish is experienced and the former suffering is renewed, and, it may be, more savagely than before. The pain of an attack of hepatic colic has no fixed duration. It will depend on the size of the calculus, on the point where impacted, and on the impressionability of the subject. The severity of the seizures varies within very wide limits. The attack may consist in a transient colic-like pain, in a mere sense of soreness, in epigastric uneasiness with nausea, or it may be an agony sufficient to cause profound depression of the powers of life—to destroy life, indeed. The usual attack of hepatic colic is one in which severe suffering is experienced until relief is obtained by the exhibition of anodynes. Under these circumstances the subsidence of the pain may be rather gradual or it may be sudden: in the former case, as the effects of the anodyne are produced, we may suppose that the spasm subsides and the stone moves onward, at last dropping into the intestine: an enchanting sense of relief is at once experienced. Very serious nervous disturbances may accompany the pain. Paroxysms of hysteria may be excited in the hysterical; convulsions occur in those having the predisposition to them from any cause, and in the epileptic.

The onset of a severe seizure is announced by chilliness, sometimes by a severe chill. Now and then the paroxysms commence with the chill, and the pain follows. It occasionally happens that the attacks in respect to the order in which the symptoms occur, and in their regularity as to time, behave like an ordinary ague. In fact, there appear to be two modes or manifestations of the attacks of hepatic colic in malarious localities: those in which the phenomena are merely an outcome of the passage of the calculi; those in which an attack of intermittent fever is excited by the pain and disturbance of hepatic colic. To the first Charcot¹⁷¹ has applied the phrase fièvre intermittente hépatique. It is supposed to correspond pathogenetically to urethral fever produced by the passage of a catheter. On the other hand, the second form of intermittent can occur only under the conditions producing ague. A calculus passing in a subject affected with chronic malarial poisoning, the latent malarial influence is aroused into full activity, and the resulting seizure is compounded of the two factors. The truly malarial form of calculus fever differs from the traumatic in its regular periodicity and the methodical sequence of the attacks, which occur in the order of an intermittent quotidian or tertian. During the attacks of hepatic colic, when protracted and severe, a sense of chilliness or distinct chills occur, sometimes with the regularity of an intermittent; but these differ from the seizures which the chill inaugurates at distinct times, the intervening period being free from disturbance.

¹⁷¹ Leçons sur la Maladies du Foie, p. 178.

The fever which accompanies some severe paroxysms of hepatic colic has a distinctly intermittent character, hence the name applied to it by Charcot. There are two forms of this calculus fever as it occurs in malarious localities: one intermittent, coming on during a protracted case, and immediately connected with and dependent on the passage of the stone; the other a regular intermittent quotidian or tertian, which determines and accompanies the paroxysm of colic. A case occurring under my observation very recently, in which these phenomena were exhibited and the calculi recovered, proves the existence of such a form of the malady. In this case with the onset of the pain a severe chill occurred; then the fever rose, followed by the sweat, during which the pain ceased, but much soreness and tenderness about the region of the gall-bladder, and jaundice, followed in the usual way. At the so-called septenary periods also attacks come on in accordance with the usual laws of recurrence of malarial fevers.

Not all cases are accompanied by fever. In many instances, probably a majority, the pulse is not accelerated, rather slowed, and the temperature does not rise above normal. The inflammation which follows an attack of hepatic colic will be accompanied by some elevation of the body-heat, and fever will occur when ulceration of the duct and perforation cause a local peritonitis; but these conditions are quite apart from those which obtain in the migration of calculi by the natural channel.

Nausea and vomiting are invariable symptoms of hepatic colic. First the contents of the stomach are brought up, then some glairy mucus only, with repeated and exhausting straining efforts; and with the sudden cessation of the pain there may appear in the vomit a quantity of bilious matter, the contents of the gall-bladder liberated by the passage of the stone into the intestine. If bile is present in the vomit from the beginning, it may be concluded that the obstruction is not complete.

Constipation is the rule. The abdomen may be distended with gas—is usually, indeed, when constipation exists. Free purgation gives great relief. The stools are composed of scybalæ chiefly at first, afterward of a brownish offensive liquid, and when jaundice supervenes they become whitish in color, pasty, and semi-solid. Now and then it happens that a copious movement of the bowels takes place as the attack is impending, but during the paroxysm no action occurs.

Jaundice is an important, but not an invariable, symptom. It comes on within the first twenty-four hours succeeding the paroxysm, and appears first in the conjunctiva, thence spreading over the body generally. The intensity of the jaundice depends on the amount of the obstruction: if complete, the body is intensely yellow; and if partial, the tint may be very light. The very slight degree of obstruction which suffices to determine the flow of bile backward has been already stated. There may be no jaundice, although all the other symptoms of the passage of gall-stones may be present. Such is the state of the case when a calculus enters and is arrested in the cystic duct. Under these circumstances the natural history differs from that which obtains when the obstruction is in the common duct and ends abruptly by the discharge of the calculus into the intestine. After the persistence of the symptoms of hepatic colic for a variable period without jaundice, this sign of obstruction may appear, indicating the removal of the stone from the cystic into the common duct. The symptoms accompanying the jaundice—the hebetude of mind, the slow pulse, the itching of the skin, the dark-colored urine—have been sufficiently detailed in the section on that topic in another part of this article.

The duration of the jaundice is different in different cases, and is influenced by the degree and persistence of the obstruction. When the obstruction is partial and the stone is soon removed, the jaundice will be slight and will disappear in a day or two; on the other hand, when the stone completely blocks the passage and is slowly dislodged, the jaundice will be intense and will persist for ten days to two weeks.

After the paroxysm has passed, if severe, the liver will be swollen, more or less tenderness will be developed by pressure, and in some instances, a local peritonitis coming on, there will occur the usual symptoms of that condition.

Although all the symptoms produced by the passage of biliary calculi may be present, some uncertainty will always be felt unless the body causing the disturbance is recovered from the feces. A properly-conducted search is therefore necessary. As this is so often done inefficiently and the calculus not found, an error of diagnosis may seem to have occurred. Every stool should be examined in the mode hereinafter described for a number of days after the attack until the calculus is found. It should be remembered that only air-dried calculi float on water. The stool, as soon as passed, should be slowly stirred up in water sufficient to make a thin mixture, and all solid particles removed for further examination, the thinner portion poured off, and more water added from time to time until only solids remain at last. It should not be forgotten that masses of inspissated bile, biliary sand, may produce symptoms not unlike those due to gall-stones proper, and hence all particles having the appearance of this material should be examined chemically. Place some of the supposed bile on a white plate and pour over it some drops of strong sulphuric acid, when the biliverdin will take on a brilliant scarlet color.

The discharge of particles of inspissated bile causes symptoms not unlike those due to the migration of biliary calculi, but there are points of difference. A strongly-marked case diagnosticated biliary calculi, and in which masses of inspissated bile were discharged in great quantity, will furnish the symptomatology to be now described. The onset of the paroxysms of pain is less abrupt than is the case with gall-stones, and the attacks may occur at any time; the pain also subsides more gradually, and hardly ceases at any time, but revives every now and then, so that several days, even weeks, may be occupied with one seizure. Jaundice is less apt to follow, and indeed well-defined jaundice rarely occurs in this affection. There is much swelling of the liver, also considerable tenderness, and relief is most certainly afforded by free purgation, anodynes seeming rather to keep up the disturbance, probably by checking the hepatic secretions.

Attacks of hepatic colic may be expected to recur when a calculus with multiple facets migrates, but the time when its associates may be expected to move cannot be predicated on any data now available. Single attacks may happen at intervals of weeks, months, or years. The migration of one large stone may so dilate the ducts as to facilitate the passage of those that remain behind, thus ensuring a recurrence of the seizures at an early period.

IMPACTION OF CALCULI AND MIGRATION BY ARTIFICIAL ROUTES.—The point at which impaction takes place is an element of great importance. The size of the calculus is far from being decisive as to the certainty of impaction or as to the untoward results. A not unfrequent accident is the blocking of the cystic duct at its opening, thus preventing the influx or outgo of bile from the gall-bladder. If the stone does not ulcerate through, in this position it does no damage, for the gall-bladder, as has been stated, may be closed without any apparent detriment. Just at the bend of the cystic duct, near its origin, is the point where arrest of a calculus is most likely to take place. The next most likely point is the duodenal end of the common duct. When impaction occurs a local inflammation comes on, an exudation is poured out, ulceration begins, and presently the peritoneum is reached. Adhesions usually form with the neighboring organs, but now and then perforation takes place, and bile, pus, and the calculus are precipitated into the peritoneal cavity. A fatal peritonitis follows, as a rule; but rarely the inflammation is localized, and an abscess forms which pursues the usual course of such accumulations; or adhesions may take place about the site of the perforation and prevent a general inflammation of the peritoneum. In this way a very large sac may be produced, with the ultimate result of rupture into the general cavity, although a fistulous communication may be established with some neighboring organ, permitting safe discharge in this direction.

A gall-stone impacted in one of the hepatic ducts or in the main duct, ulcerating through, may form an abscess not distinguishable from other solitary hepatic abscesses except by the presence of the concretion causing the mischief and the absence of the usual conditions giving rise to these accumulations of pus. It is probable that fatal abscesses of the liver not infrequently are caused in this way in extra-tropical countries. Adhesions forming to neighboring hollow organs or to the external integument, such abscesses discharge, carrying out the calculus with them. In this way may be explained the discharge by the intestine of calculi much too large to have passed by the natural route and unattended by the usual symptoms of hepatic colic. These gastro-intestinal biliary fistulæ extend from the gall-bladder and the larger ducts to the stomach, to the duodenum, and to the transverse colon; but of these the communication with the stomach is the least common. The adhesion of the gall-bladder or common duct to the duodenum or colon may be direct, exudations uniting the two parts without the intervention of an abscess cavity, or such a sac or cavity may be interposed. In some cases the discharge of biliary calculi is effected through these routes with so little disturbance as to escape notice, or the symptoms may be only vague indications of a local inflammation in the neighborhood of the liver.

Biliary fistulæ communicating externally, caused by the migration of calculi, are comparatively common. They have the clinical history, and are usually treated as cases, of hepatic abscess. Sometimes hundreds of calculi are thus discharged. In such instances it may be assumed that communication has been established with the gall-bladder. Hepatic abscess thus due to the migration of calculi may discharge into the pelvis of the kidney, into the ascending vena cava, or through the lung, but these places of outlet are comparatively uncommon.

COURSES AND COMPLICATIONS.—Although symptoms cease for the time being when the calculus passes into the duodenum, and although in most instances no after unpleasant effects are experienced, there are cases in which the presence of the concretion in the intestine proves to be fruitful of mischief. Calculi of very large size—from a pigeon's to a hen's egg—are also found in the intestine, without the occurrence of symptoms indicative of their migration. It has been shown that this silent migration of calculi from the liver-passages to the intestinal is not uncommon. Hepatic concretions are distinguishable from the intestinal by their crystalline form and by their composition. The former are usually polyangular, and are composed of cholesterin crystallized about a nucleus of bile-pigment, inspissated bile, or mucus. After entrance into the intestine, lime salts and mucus are deposited in successive layers, so that the form of the calculus is modified and its size increased. The solitary ovoid concretion is most frequently found in the intestine, without previous symptoms of hepatic source, and, although increased in size in the intestine, it retains its original shape. A specimen of this kind now in my possession illustrates these points. It is composed of cholesterin crystallized in radiating lines and concentric rings about a central nucleus of inspissated bile. Around the hepatic concretion there have formed layers of lime and mucus since it has reached the intestine, and after drying this rind became brittle and was readily detached. The polyangular calculus is apt to form the nucleus of a scybala-like mass of feces; hence in the search for these bodies every such mass should be broken up. An example of this has recently come under my own observation. Concretions of all sizes, having reached the intestines, as a rule pass down without creating any commotion, and are silently discharged. But various disturbances occur in some instances. Obstruction of the bowels is one of the results. A great may cases have been collected by Murchison,¹⁷² as many more by Leichtenstern,¹⁷³ of impaction of the intestine produced by an accumulation of feces about a biliary concretion. A calculus may be retained in a fold or diverticulum of the small intestine, and may indeed cause a loop to be formed which in turn readily twists, becoming an immovable obstruction. This mode of obstructing the bowels is less common than the simple impaction. It is affirmed by some authorities, especially by Von Schüppel, that obstruction of the bowels—impaction—is more often caused by stones that have ulcerated through into the intestines than by those that have descended by the common duct; and this conclusion must be reached if jaundice has not been present. It is not only the size of the calculus which determines impaction, as has been stated: several may be agglutinated in one mass, and reflex spasm of the muscular layer may be induced by their presence in the bowel. Nevertheless, some enormous concretions have been found in the canal, and others have been discharged without special trouble. Hilton Fagge exhibited to the Pathological Society¹⁷⁴ of London two gall-stones passed with the stools, measuring 2½ by 1¹/5 inches in long and short diameter, and Fauconneau-Dufresne¹⁷⁵ refers to concretions of the size of a hen's egg. Mention has been made of one in the writer's possession of the size of a pullet's egg, which, until its discharge, caused a train of characteristic symptoms. These immense bodies may have ulcerated through from the gall-bladder or may have grown by successive deposits of carbonate and phosphate of lime after reaching the intestine.

¹⁷² Lectures on Diseases of the Liver, p. 573.

¹⁷³ Ziemssen's Cyclopædia, vol. vii.

¹⁷⁴ Transactions of the London Pathological Society, vol. xix. p. 254.

¹⁷⁵ Op. cit.

The symptoms caused by the presence of concretions in the intestines are, when pronounced, sufficiently characteristic. At a variable period after an attack or attacks of hepatic colic the disturbance begins. The condition of impaction above referred to does not differ from ordinary fecal accumulation. It is true that occasionally the intestinal irritation due to the presence of these bodies in some instances preceded the symptoms of impaction, but usually there is no evidence to indicate that the stoppage of the bowel is due to anything else than feces. The irritability manifested by the intestinal mucous membrane when gall-stones are present varies remarkably. There may be only some ill-defined pain which, as a rule, indicates the position of the calculus, or it may be pain with a feeling of soreness, or it may take the form of violent colic, with nausea, vomiting, and depression. In my own cases pain was experienced at or near the ileo-cæcal valve, where one was lodged, and along the descending colon, where the others were; the pain and soreness ceased when these bodies were discharged.

In a few instances gall-stones are brought up by vomiting. The most remarkable example of this is a case to be found in the Transactions of the Pathological Society (vol. xii. p. 129): A woman ninety-four years of age vomited a stone the size of a nutmeg. In the reported examples violent pain, nausea, and much vomiting preceded the discharge of the calculus.

Like other foreign bodies, a gall-stone may ulcerate through the intestine, producing fatal peritonitis.

Many conditions due to the presence of biliary concretions, and which arise during their migrations, may be viewed as complications. Many of those produced directly have been described as a part of the proper course of the malady; others are local and reflex, and these may with propriety be considered as complications. First in importance are those due to obstruction and the local inflammation.

The passage of a calculus along the duct excites an inflammation of the mucous membrane, which by contiguity of tissue invades the peritoneal layer if the stone is retained for a sufficient time, and especially if it is immovably lodged. The stoppage in the flow of bile leads to dilatation of the ducts, and a change takes place in the character of that fluid, owing to the admixture of mucus with the bile and to the pouring out of a pathological secretion: it loses the bilious appearance and becomes a merely sero-purulent fluid. Serious changes ensue in the structure of the liver, as was first suggested by O. Wyss and Leyden, and afterward more especially by Wickham Legg¹⁷⁶ and Charcot.¹⁷⁷ A ligature to the common duct in animals is followed in so short a time as two weeks by hyperplasia of the connective tissue and atrophy of the gland-elements. It has been ascertained that similar changes ensue in man from the impaction of a calculus in the common duct. Under these circumstances the size of the liver, as indicated by the area of hepatic dulness, at first enlarges, and subsequently more or less contraction, coincident with the atrophy, ensues. When the cystic duct is obstructed the contents of the gall-bladder increase, and become ultimately sero-purulent (dropsy). In some instances, the walls of the abdomen being thin, a globular elastic tumor may be felt projecting from beneath the liver.

¹⁷⁶ St. Bartholomew's Hospital Reports for 1873. See also Treatise on Diseases of the Liver, by the same author, loc. cit.

¹⁷⁷ Leçons.

Angiocholitis, or inflammation of the duct, is caused by the passage, especially by the impaction, of a calculus. The inflammation may extend by contiguity of tissue and involve the surrounding parts. Several cases have been examined by the writer in which the gall-bladder and the cystic and common duct were imbedded in a mass of organized exudation. An extension of inflammation may take place, and be confined to the hepatic peritoneum. Heavy organized exudations will form, adhesions be contracted to the diaphragm, to the parietal peritoneum, and to the neighboring organs, and the capsule, thickened and contracting, will ultimately induce changes in the structure of the adjacent part of the liver. When the inflammation extends to the peritoneum there are the usual systemic symptoms, and locally acute pain, increased by the respiratory movements and by pressure, and assuming a constrictive character; nausea and frequent vomiting, and often a very troublesome hiccough, caused, doubtless, by implication of some branches of the phrenic nerve; constipation, etc.

The relation of biliary colic to cancer of the biliary passages was first noted by Frerichs, who ascertained the occurrence of gall-stones in 9 out of 11 cases of cancer of these parts. Hilton Fagge¹⁷⁸ reports a case of the kind, and the writer can add another from his own observations.

¹⁷⁸ Guy's Hosp. Rep., 1875.

The most important of the reflex symptoms are those pertaining to the circulatory system. The action of the heart becomes irregular in rhythm and diminishes in force. The circulation of the bile acids in the blood causes slowing of the heart's action, as has been set forth in the section on jaundice; but that is a direct consequence, and is not a reflex impression. Potain was the first to show that the structure of the heart is affected. A mitral murmur is a recognized symptom in the icterus of gall-stones, but Potain¹⁷⁹ has shown that the real seat of this murmur is the tricuspid, and that the affection of the heart is a dilatation of the right cavities. The physiological reason for this condition of the heart is the rise of tension in the pulmonary artery, which is secondary to irritation of the splanchnic nerves; and to this factor is also due the reduplication of the first sound and the accentuation of the second sound—characteristic signs of the cardiac change in these cases.

¹⁷⁹ Cyr, Traité de l'Affec. calc. de Foie, loc. cit.

There are certain reflex nervous troubles in cases of hepatic colic, some of them of great importance. One of the lesser troubles is herpes zoster. A very violent attack in the course of the distribution of the first, second, and third cervical nerves has happened in a case under the writer's observation. There have been reported from time to time cases of sudden death during the paroxysms of hepatic colic, in which a calculus lodged in Vater's diverticulum, at the intestinal extremity of the common duct, was the cause of the accident. An explanation of this result is to be found in the intimate nervous communications between the liver and the heart through the solar plexus and the large number of ganglia contained in Vater's diverticulum. The most severe pain is felt as the calculus is passing through the orifice of the common duct into the intestine, and here also the spasm of the muscular fibre is most tense. The so-called crushing-blow experiment of Goltz illustrates how intense suffering, such as the passage of a gall-stone, can paralyze the heart through the solar plexus. The depression of the heart's action does not always occur on the instant, but it may be gradual—several hours, even a day or two, being occupied in the suspension of activity. Leigh of Liverpool¹⁸⁰ has reported an example of death in six hours in a female of thirty, previously in good health; Cornillon,¹⁸¹ another in a female of fifty-three, who died in twelve hours from the beginning of the paroxysm; Williamson,¹⁸² a female of fifty-one years, who expired on the fourth day; Habershon,¹⁸³ two, who died during the paroxysms at a period not stated; and Brouardel, one which was the subject of a medico-legal investigation. In the first case the calculus was yet in the gall-bladder, the appearances indicating that persistent spasms had occurred to force the calculus into the cystic duct; in the others in which the position of the stone is mentioned, it was engaged in the orifice of the common duct or had reached the intestine.

¹⁸⁰ Medical Times and Gazette, 1867, vol. i. p. 248.

¹⁸¹ Cyr, op. cit., p. 185.

¹⁸² The Lancet (London), vol. ii. p. 780.

¹⁸³ Lectures on the Pneumogastric, 3d Lecture.

In several instances sudden death has resulted from uncontrollable vomiting induced by the paroxysms of hepatic colic. Trousseau¹⁸⁴ mentions a case in which strangulated hernia and death ensued in consequence of the violent vomiting brought on by the passage of a calculus.

¹⁸⁴ Clinique médicale.

DIAGNOSIS.—Unless the distension of the gall-bladder is sufficient to cause a recognizable tumor, gall-stones in that organ do not produce symptoms by which they can be diagnosticated. If sudden attacks of violent pain in the right hypochondrium, accompanied by nausea and vomiting and followed by jaundice, have occurred from time to time, then the presence of biliary concretions may be suspected if the symptoms belonging to them are present in the intervals between the seizures. The migrations of calculi produce symptoms so characteristic that error is hardly possible. The only disorders with which an attack of hepatic colic may be confounded are gastralgia and hepatalgia. As regards the first, the distinction is made by the seat of pain, by the absence of after jaundice, and by the lack of a concretion passed by stool. As the diagnosis may depend on the finding a concretion, the writer must again affirm the importance of a properly-conducted search of all the stools passed for several days after the paroxysm.

Hepatalgia is diagnosticated with great difficulty, for the pain has the same seat, the same character, but as a rule it does not terminate so abruptly, is not accompanied by such severe vomiting and depression, jaundice is absent, and no stone can be found in the evacuations. Both gastralgia and hepatalgia occur in the subjects of neurotic disturbances—in the pale, delicate, and hysterical—whereas, as a rule, hepatic colic happens to the obese, to the persons of active digestion addicted to the pleasures of the table.

The passage of calculi may be confounded with flatulent colic, with the pain caused by lead and other mineral poisons, with impaction, internal strangulation, local peritonitis, and similar causes of sudden and violent pain. The differentiation is made by attention to the seat and character of the pain, by the previous history, and especially by the absence of jaundice and of a concretion. From renal colic the hepatic is separated by the position of the pain, by the direction taken by it, and by the retraction of the testicle, the irritability of the bladder, and the appearance of blood in the urine—all characteristic symptoms of the renal affection.

TREATMENT.—The treatment of biliary concretions includes the remedial management for the calculi in position, for the paroxysms of hepatic colic caused by the migration of these bodies, and for the results and complications.

Treatment of the Calculus State: Of Inspissated Bile.—As the particles of inspissated bile are deposited along the larger hepatic ducts, and form in consequence of a deficiency in the amount of glycocholate and taurocholate of soda, two methods of treatment are to be carried out: free purgation by an active cholagogue to wash out the offending substance, and the exhibition of a soda salt to promote the alkalinity of the bile and the consequent solution of the bile-pigment. Harley's method, which he strongly urges, consists in the administration of "one or two drachms of sulphate of soda in a bitter infusion every morning before breakfast, or from twenty to thirty grains of bicarbonate of soda, along with a drachm of taraxacum-juice in a bitter infusion, every night at bedtime at regulated intervals for a month or so, according to the constitution of the patient and the severity of the symptoms."

As persons who suffer from inspissation of the bile are naturally bilious, it is of the first importance in the prophylactic treatment to regulate the diet. Indulgence in malt liquors, in fatty and saccharine articles of food, must be forbidden. Acid fermentation in the course of duodenal digestion should be prevented by withholding the starches and sugars. Peptonized foods, given with an alkali, are highly useful. Milk, fresh meat, and the succulent vegetables are the proper constituents of a diet for these subjects. Bread is one of the most offending articles, and should be restricted in amount as much as possible.

Next to a suitable diet, systematic exercise is a measure of the highest utility in these cases. A daily morning sponge bath of a weak alkaline water not only maintains the skin in a healthy state, but also promotes the oxidation processes of the body. The alkaline mineral waters of Wisconsin, Michigan, Virginia, and other States, especially of the Bethesda Spring of Wisconsin, may be drunk with great advantage to accomplish the same purpose.

We possess direct means for preventing inspissation of the bile—remedies which act in the physiological way by increasing the proportion of glycocholate and taurocholate of soda. Harley prefers the sulphate and bicarbonate for this purpose, but my experience is in favor of the cholate and phosphate of sodium, especially the latter; for, whilst it plays the part of a soda salt, it exerts a decided cholagogue action, thus effecting the results achieved by the combined use of sulphate of soda and taraxacum. A cure may be confidently looked for in this malady by the persistent use of sodium phosphate—drachm j ter in die. It seems to act more efficiently when given dissolved in hot water.

The paroxysms of hepatic colic due to the passage of inspissated bile are to be treated in the same way as when this condition of things is caused by the migration of formed calculi. The action of cholagogue purgatives is more decidedly beneficial in the attacks due to the passage of inspissated bile.

Biliary Calculi in Situ.—Notwithstanding their crystalline form and firmness of texture, it is possible to effect the gradual solution of biliary calculi. Outside of the body it is easy to dissolve a calculus in chloroform, in Durande's remedy, etc., if time enough be given, but the problem is a far more difficult one when the calculus is in position in the gall-bladder or in a hepatic duct. As Trousseau¹⁸⁵ has wisely observed, it is not safe to apply to conditions within the body conclusions reached by experiments in the laboratory. Nevertheless, facts are known which justify the belief that an impression may be made on concretions in the gall-bladder. The motion of respiration and the voluntary actions of the abdominal muscles cause more or less attrition and breaking off of the angles and margins of the crystals, thus permitting the solvent action of the bile. If, however, the bile continues in the state in which it was at the time of the crystallization of the cholesterin, it will make no impression on this substance. We have now the means of restoring its power to dissolve crystallized cholesterin. As a necessary preliminary, fracture of the crystals must be effected. This may be accomplished, when the natural forces have failed to effect it, by manipulation of the gall-bladder through the walls of the abdomen, but especially by faradization. Excellent results have been achieved by this last-mentioned expedient, but no satisfactory explanation has been made of its methodus medendi, unless we accept the mechanical effect of the muscular movements. In applying the faradic current an electrode is introduced into the rectum, and the other, a sponge well moistened, is placed over the gall-bladder. An interrupted galvanic current is indicated, the electrodes in the position just mentioned, when a migrating calculus is stopped on its way. Such an application has rendered important service in a few cases.

¹⁸⁵ Clinique médicale de l'Hôtel Dieu de Paris.

Except that calculi have been found in a state of decay, their angles and edges broken, divided by cleavage, there is no evidence that they have undergone solution when in situ, except the clinical evidence which consists in a disappearance of the symptoms. The remedy of Durande, which consists in a mixture of ether and turpentine—three parts of the former and two of the latter—has been celebrated since the close of the last century, and is yet much employed in France, notably at Vichy. It is preferred by Cyr,¹⁸⁶ who advises its administration in capsules taken immediately before meals. Chloroform readily dissolves calculi out of the body, and hence it has been proposed, and indeed much used, for the purpose of effecting their solution in the gall-bladder; but, as Trousseau urges, there is no warrant for the belief. Corlieu,¹⁸⁷ who first proposed its use, and afterward Bouchut,¹⁸⁸ maintained that chloroform does exert this solvent action, and reported cases in confirmation; but there are so many sources of fallacy that such evidence must be viewed with suspicion. It has usually been administered in small doses (five minims) three times a day for a long period. That it is beneficial by stimulating the flow of pancreatic secretion and by allaying spasms is probably true, but that any quantity which can be administered in safety will act as a solvent of cholesterin concretions cannot be believed.

¹⁸⁶ Traité de l'Affection calculeuse du Foie, p. 287.

¹⁸⁷ Gazette des Hôpitaux, 1856, June 19.

¹⁸⁸ Bullétin gén. de Thérap., vol. lxi. p. 49.

If solution of hepatic calculi is possible under any circumstances, the most rational mode of effecting it would seem to be to restore that condition of the bile which in the normal state maintains cholesterin in the state of solution. Cholesterin is precipitated and crystallizes about a nucleus when the glycocholate and taurocholate of soda are deficient in amount. The agents most effective in restoring the solvent power of the bile are the salts of soda, of which the sulphate is preferred by Harley. In 1873 the cholate of soda was brought forward by Schiff, who prescribed it in doses of 50 centigrammes (8 grains nearly) three times a day, to be gradually increased until digestive or circulatory troubles arose. This remedy, which is eminently rational from the point of view above indicated, has apparently been of decided service in many published cases and in the writer's experience. It will be found, however, that five grains three times a day is as large a quantity as can be easily borne.

Another soda salt which in my own hands has proved in a high degree effective is the phosphate. As has been explained when referring to its use in cases of disorders due to inspissated bile, it has a distinct cholagogue action, but the chief sources of its utility in this affection are its chemical and resolvent powers. The usual quantity is one drachm three times a day, dissolved in sufficient warm water.

Bile itself, in the form of inspissated ox-gall, was formerly much used, a scruple to a drachm being given three times a day, and not without good results. It was also prescribed with chloride of ammonium. For the gastro-duodenal catarrh and the accompanying catarrh of the bile-ducts this combination is sometimes useful.

I have recently proposed a new expedient for effecting the solution of hepatic calculi. This method consists in puncture of the gall-bladder with a fine exploring-trocar, and the injection through the canula, after withdrawing the stylet, of a suitable solvent. Durande's remedy, chloroform, and other solvents can be introduced in this way without injury to the parts. I have punctured the gall-bladder, removed its contents, and explored its interior without damaging the organ in any way and without leaving after traces. The measure proposed offers no special difficulties in its execution.

The Paroxysms of Hepatic Colic.—The pain of hepatic colic being the most acute suffering known to man—in its severest form at least—the most powerful anodynes are required. The measures employed for relief of pain happen to be the most efficient for promoting the expulsion of the calculus and for limiting, if not preventing, the subsequent inflammation. As soon as the character of the seizure is manifest a hypodermatic injection of morphine and atropine—¹/8 to ½ grain of the former and ¹/200 to ¹/80 grain of the latter—should be given; ether administered by inhalation if necessary; and by the stomach chloroform, chlorodyne, or chloral. As the stomach is usually exceedingly irritable, the subcutaneous injection of remedies is a precious resource: this failing or contraindicated, relief may be given by the rectal injection of laudanum or chlorodyne. As relief is often afforded by the act of vomiting, the attempts to empty the stomach should be encouraged, and to this end large draughts of warm water should be given. Hot fomentations and mustard plaster should be applied over the right hypochondrium, and an entire warm bath may be used if available.

Great relief is usually afforded by the action of purgatives. The irritability of the stomach forbids the employment of drastic purgatives, yet podophyllin resin is warmly commended by Dobell. It must be given in small doses, and preferably dissolved in spirit. Calomel in one-grain doses, every four hours until it purges, allays nausea and lessens the after-uneasiness in the right hypochondrium, but mercurial treatment given with a view to a supposed cholagogue effect only does evil by prolonged administration, especially if ptyalism is induced. If evidences of portal congestion are present, such remedies as euonymin, iridin, baptisin, and others of the cholagogue group give good results. The most effective of the remedies of this kind is ipecacuanha, given in purgative doses: the emesis induced by it favors the extrusion of the stone, and the powerful cholagogue effect relieves the portal congestion. Twenty grains at once, and repeated if need be in three hours, is a suitable quantity.

The various complications which may occur, and the results which follow the migration of the calculus, require treatment adapted to the conditions existing, and will be mentioned in the sections devoted to these topics.

Occlusion of the Biliary Passages; Stenosis of the Ductus Communis Choledochus.

DEFINITION.—By occlusion of the biliary passages is meant an obstruction, internal or external, of the hepatic, cystic, or common duct. The causes of the obstruction are various, but the results are quite uniform; hence the term includes a complexus of symptoms of a very distinctive type. Occlusion may be congenital or acquired: it is the latter with which we have especially to deal.

Stenosis signifies a narrowing which in its extremest form produces a nearly complete obstruction; when the canal is entirely closed the term occlusion is applied. Stenosis also may be congenital or acquired.

PATHOGENY.—The conditions producing narrowing of a hepatic duct or its complete obstruction are numerous, and some of them complex in their relations. As regards the ducts themselves, the interference may be entirely within the canal, or it may affect the walls, or it may be wholly extraneous; as, for example, when a cancer of the pancreas encroaches on the common duct. It will be convenient to consider the causes of stenosis and obstruction from these points of view: 1, internal; 2, of the duct walls; 3, extraneous.

The most usual situations for the occurrence of those changes that lead to occlusion by inflammatory adhesions are the beginning of the cystic duct, obstruction of which is of little moment, and the end of the common duct, which finally proves fatal.

The passage of a large polyangular calculus may cause such irritation, abrasion of the epithelium, and subsequent inflammatory exudation as to effect a direct union of the opposing sides of the canal. This takes place at the beginning of the cystic duct especially, since, owing to the spasm of the gall-bladder and the absence of muscular fibres in the walls of the duct, the stone crushes into, without passing through, the canal. The inflammatory exudation thus excited may close the duct. Not unfrequently the gall-bladder, full of calculi, is thus shut off from the liver permanently. In one instance the writer has seen a calculus wedged into the orifice of the cystic duct, whilst just beyond the lumen was permanently obstructed by an organized exudation. Permanent closure of the cystic duct is of far less consequence than of the common duct, and may, indeed, be a conservative condition, as in the case above mentioned, where numerous polyangular calculi may have migrated, except the closure of the passage.

The most usual point of obstruction in the course of the common duct is the intestinal end, but various processes are employed to effect it. The first in importance is catarrhal inflammation. This seems the more credible when it is remembered that to a simple catarrh of the mucous membrane is due the temporary stoppage of the duct, producing jaundice in much the largest proportion of cases. When the epithelium is detached and granulations spring up from the basement membrane, adhesions of the surfaces will readily take place, and the union may be so complete as that all traces of the duct will disappear. It is probable that in many, if not in most, of these cases the initial condition of the canal is that of simple catarrh, the more positive changes in the mucous membrane arising from peculiarities in the tissues of the individual affected, or from local injury caused by the passage of a concretion or irritation of pathological secretions of the duodenum.

Stenosis, and finally occlusion, of the common duct may arise from the cicatrization of an ulcer. Such ulcers may occur in several modes. They may result from catarrhal inflammation of a chronic type, much new connective-tissue material forming, and in the process of cicatrization, with the contraction belonging to it, the lumen of the canal is so far filled up that the passage of bile is effectually prevented. They may be produced in that state of the tissues which accompanies certain cachectic and profoundly adynamic conditions, as in severe typhoid fever. Such ulcers may also be due to the mechanical injury effected by the migration of a gall-stone. In cicatrizing, a tight stricture, impermeable to the passage of bile, may result, or the lumen of the canal be entirely obliterated. In the latter case the duct itself may disappear and leave no trace. An ulcer situated at the duodenal end of the common duct and extending into the duodenum may also in the process of healing so contract as to render the orifice impermeable to bile. The same effect may follow the cicatrization of an ulcer of the duodenum in the immediate vicinity of the orifice of the common duct.

Without the intervention of an ulcer as a means of explaining closure of the common duct, this accident may be caused by a catarrhal inflammation which effects denudation of the basement membrane, and thence union may be produced by the mere contact of the freshly-granulating surfaces. Congenital occlusion of the bile-ducts or obstruction occurring in a few days after birth, it is probable, is effected in this way, but no direct evidence of the process has thus far been offered. During intra-uterine life, as at any period in after-life, it seems necessary to the production of such changes that a peculiar constitutional state must exist; otherwise, such a result might happen to every case of catarrhal inflammation of the bile-ducts. The extent of the changes is further evidence in the same direction; for not only are the walls of the duct in permanent apposition and adhesion, but the duct degenerates into a mere fibrous cord, and in some instances is nearly, even entirely, obliterated.¹⁸⁹

¹⁸⁹ Ziemssen's Cyclopædia, p. 589.

The cystic or common duct—the latter to be chiefly considered—may be occluded by the retention in its lumen of some foreign body. The impaction of a biliary calculus has already been repeatedly referred to, but there are some additional points demanding consideration. The larger concretions may be stopped in the neck of the gall-bladder; those small enough to enter the canal may be arrested at its bend behind the neck, and the very entrance of the cystic duct may be blocked, as in a case examined by the writer.

The hepatic duct is very rarely permanently occluded. As the calibre of this canal continuously enlarges downward, there is no point at which a stone is likely to be arrested; nevertheless, it occasionally happens that such an obstruction does occur. An example has occurred under the observation of the writer, but the cause was a gunshot wound of the liver.

The most usual, and for very obvious reasons the most important, of the sites where occlusion occurs is the common duct and at the termination of the duct in the small intestine, the intestinal orifice. Just behind and to the right of its orifice the duct is dilated into a fossa—the diverticulum Vateri; and here concretions of a size to pass along the common duct are stopped. It is not essential that the stone fit the canal: it may do so and prevent any bile passing into the duodenum; it may be a polyangular body, and, though wedged in, leave spaces through which more or less can slowly trickle. The symptoms will be modified accordingly. Again, the diverticulum may contain numerous concretions, which distend the canal greatly, but through the interstices of which some bile can flow.

Other foreign bodies very rarely close the intestinal end of the ductus communis; thus, for example, a cherry-seed, a plum-seed, a mass of raisin-seeds, may slip into the orifice after the passage of a gall-stone has stretched it sufficiently. A much more common cause of occlusion is an intestinal parasite, which crawls in and is fastened. The common round-worm is the most frequent offender, and much less often liver-flukes find a lodgment there.

The ductus communis choledochus may be closed by agencies acting from without. They are various, but the most common are the carcinomata. Primary cancer of the gall-bladder and gall-ducts, although not of frequent occurrence, is by no means rare. It develops in connection with the connective-tissue new formations produced by the inflammation following the migration of large calculi. A very instructive example has been examined by the writer. The patient, a woman aged forty-eight, had had numerous paroxysms of hepatic colic, and after death, which followed a protracted stage of jaundice by obstruction, a large ovoid calculus, filling the gall-bladder, was found, and an extensive organized exudation of inflammatory origin was the seat of carcinomatous disease involving the cystic and common ducts and closing the lumen of both. Cancer of the pylorus, of the duodenum, of the pancreas, of the right kidney, and of the liver itself, not unfrequently by exterior pressure permanently occlude the common duct. To this category of obstructing causes must be added enlarged lymphatic glands of the transverse fissure, large fecal accumulations, tumors of the ovaries and uterus, aneurisms of the abdominal aorta, and especially aneurism of the hepatic artery, several examples of which have been reported, and one has occurred in a case seen by the writer.

The effects of obstruction are much less important when the cystic duct is closed. The contents of the gall-bladder accumulate, constituting the condition known as dropsy of the gall-bladder. A catarrhal state of the mucous membrane is set up; the muco-pus formed mixes with the bile, and the mixture undergoes fermentative changes which further alter its character and impart to it irritating qualities, in consequence of which the mucous membrane becomes more decidedly inflamed, and a still more purulent fluid forms, so that ultimately the contents of the gall-bladder are entirely purulent, and that organ may attain to enormous size. Instead of a catarrhal inflammation leading to suppuration, the mucous membrane may pour out serum abundantly, the biliary contents and mucus disappear by absorption, and finally the gall-bladder will be moderately distended by a serous-like fluid. No further disturbance ensues, and the gall-bladder, thus shut off from participation in the hepatic functions, ceases to give trouble.

The results are far different when the obstruction occurs in the hepatic or common duct, for then the bile can no longer perform its double function of secretion and excretion—of contributing materials necessary to digestion and assimilation, and excreting substances whose removal is necessary to health. The liver continuing to functionate after closure of the duct is effected, obviously the secretion of bile continues to accumulate, and the irritation of the mucous membrane causes a catarrhal state; mucus is poured out, and serum escapes from the distended vessels. If the hepatic duct only is obstructed, the dilatation will not involve the cystic duct and gall-bladder, but as the common duct at its termination is occluded, usually the whole system of tubes will be affected by the ensuing changes. The alterations already described as occurring in the gall-bladder take place in all the hepatic ducts. The bile-elements are absorbed, and the fluid distending the whole system of hepatic tubes becomes finally a semi-transparent serum or a very thin sero-mucus, having in bulk a pale sea-green color. Although an intense jaundice coexists with the obstruction, no portion of the bile escapes into the ducts. At the beginning of the obstruction more or less bile is in the tubes, and then the fluid will have a distinct biliary character; but as it accumulates, first the bile-constituents disappear, then the mucus—which at the outset was formed freely—is absorbed, and at last only a colorless serum remains. This fluid, which has been examined chemically by Frerichs, is found to be slightly alkaline, to have only 2 per cent. of solids, and to present no trace of any biliary constituent. As the fluid accumulates the gall-bladder and ducts dilate, sometimes to an enormous extent, the fluid they contain amounting to several pints. The walls of the ducts grow thinner, and may finally give way with the pressure or from external violence, the fluid exciting an intense and quickly-fatal peritonitis. Important changes occur in the structure of the liver also. With the first retention of bile the liver conspicuously enlarges, and may indeed attain to twice its normal size, but it subsequently contracts, and may lessen in as great a degree as it had enlarged. Changes begin in the glandular structure as pressure is brought to bear on the cells by the enlarging ducts. The liver-cells become anæmic and the protoplasm cloudy, but granular and fatty degeneration does not take place. Even more important as an agency affecting the condition of the hepatic cells is the hyperplasia of the connective tissue, which ensues very promptly when an obstruction to the flow of bile arises from any cause, as has been shown by Legg¹⁹⁰ and Charcot.¹⁹¹ The liver on section has a rather dark olive-green color, and is firmer in texture, owing to the increased development of the connective tissue; the cells are bile-stained and contain granules of coloring matter and crystals of bilirubin, and although they are at first not altered in outline, subsequently more or less atrophy is produced by the contraction of the newly-formed connective tissue and the pressure made by the dilated hepatic ducts.

¹⁹⁰ On the Bile, Jaundice, and Bilious Diseases, p. 352 et seq.

¹⁹¹ Leçons sur les Maladies du Foie, etc., p. 205 et seq.

SYMPTOMS.—The symptoms produced by occlusion of the cystic duct are not sufficiently characteristic to be diagnosticated with any certainty. When an attack of hepatic colic has slowly subsided without jaundice, and an elastic tumor, globular or pyriform in shape, has appeared from under the inferior margin of the liver in the position of the gall-bladder, dropsy of that organ may then be suspected. As paracentesis of the gall-bladder may be performed with ease, safety, and little pain, the diagnosis may be rendered more certain by the use of the exploring-trocar.

Obstruction of the hepatic or common duct is accompanied by symptoms of a very pronounced and distinctly diagnostic character. Without referring now to the antecedent symptoms or to those belonging to the obstructing cause, the complexus of disturbances following the obstruction is the subject to which our attention must be directed. The great fact dominating all other considerations is the stoppage of the bile, whether this has occurred suddenly or slowly. Jaundice begins in a few hours after the canal is blocked. At first there is yellowness of the conjunctiva, then diffused jaundice, deepening into the intensest color in two or three weeks, or, when the obstruction is sudden and complete, in a few hours. At first the color is the vivid jaundice tint, a citron or salmon or yellow-saffron hue, but this gradually loses its bright appearance, grows darker, and passes successively into a brownish, bronze-like, and ultimately a dark olive-green, which becomes the permanent color. Under some moral emotional influences there may be a sudden change to a brighter tint, lasting a few minutes, but otherwise the general dark olive-green hue persists throughout. In a few instances, after some weeks of jaundice, the abnormal coloration entirely disappears, signifying that the liver is too much damaged in its proper glandular structure to be in a condition to produce bile. Such a cessation of the jaundice is therefore of evil omen.

Pruritus, sometimes of a very intense character, accompanies the jaundice, in most cases appears with it, and in the supposed curable cases it has persisted after the cessation of the discoloration. The irritation may become intolerable, destroying all comfort, rendering sleep impossible, and so aggravating as to induce a highly nervous, hysterical state. The scratching sets up an inflammation of the skin, and presently a troublesome eczema is superadded. In some of the cases a peculiar eruption occurs on the skin and mucous membranes, entitled by Wilson¹⁹² xanthelasma. It has been carefully studied by Wickham Legg,¹⁹³ who has ascertained the character of the changes occurring in the affected tissues, and also by Mr. Hutchinson.¹⁹⁴ As a rule, this eruption appears after several months of jaundice, and manifests itself first on the eyelids, then on the palms of the hands, where it makes the most characteristic exhibit, and after a time on the lips and tongue. It occurs in irregular plaques of a yellowish tint slightly elevated above the general surface, and rarely assumes a tubercular form. As was shown by Hilton Fagge, xanthelasma occurs more especially in the milder cases of catarrhal icterus that had been protracted in duration, but it is also occasionally seen in the jaundice of obstruction.

¹⁹² Diseases of the Skin, 6th ed., Lond., p. 773.

¹⁹³ On the Bile, Jaundice, and Bilious Diseases, p. 317 et seq.

¹⁹⁴ Medico-Chirurgical Transactions, vol. liv. p. 171.

According to the stage of the disease during which the examination is made the liver will be enlarged or contracted; more or less tenderness may be developed by pressure in the area occupied by the ducts, and a tumor in a position to effect compression may possibly be detected. The area of hepatic dulness will be increased in the beginning of all the cases in which the obstruction is complete, but will remain normal so long as the flow of bile persists despite the obstruction. When enlarged, the liver can be felt projecting below the inferior margin of the ribs, and with it, in most cases, the elastic globular body, the gall-bladder. The state of the hepatic secretion, and in consequence the duration of the obstruction, may be ascertained by puncture of the gall-bladder and withdrawal of some of its contents for examination. The presence of unaltered bile will indicate recent obstruction; of serum, will prove long-standing interruption of bile-production. The presence of concretions in the gall-bladder will indicate the character of the obstructing cause, and an increased amount of bile of a normal or nearly normal kind will be conclusive evidence that the obstruction is in the course of the common duct. In a fatal case of permanent occlusion examined by myself the cystic duct was closed by inflammatory adhesions and the common duct was stopped up by a calculus.

The enlarged area of hepatic dulness will, in a protracted case, not continue. The proper secreting structure, the hepatic cells, undergo atrophy, and the increased connective tissue—to the development of which enlargement of the organ is mainly due—contracts. The ultimate result is that the liver becomes sclerosed, and is distinctly smaller, the area of hepatic dulness diminishing to a greater relative extent than the area of dulness due to hypertrophic enlargement. The contraction of the liver goes on at the rate that several months are required to make the result evident on percussion and palpation. Not unfrequently, the contraction is too slight to affect the percussion note of the right hypochondrium, and then, to realize the condition of the organ, the history and rational signs must be closely studied.

Whilst the liver thus varies in size, the gall-bladder remains enlarged and projects from the under surface of the organ, elastic, globular, and distinctive. The shrinking of the liver from around it makes the impression of growing size; it may be increasing, indeed, but more frequently the enlargement is merely apparent.

Whether the liver be enlarging or diminishing in size, its functions are impaired, or indeed entirely suspended. As the digestive canal receives the bile immediately on its production, it will be best to begin with the gastro-intestinal disorders which accompany occlusion of the bile-ducts. The appetite is either wanting entirely and food is loathed, or an excessive or canine appetite is experienced. The latter belongs rather to an early stage of the disorder, and comes on after the first disturbance of the stomach belonging to the immediate effects of the occlusion. The former is the result of long-standing interference with the primary assimilation. The tongue is coated with a thick yellowish fur, which, drying, is detached in flakes, leaving the mucous membrane beneath red, raw, fissured, and easily bleeding. The taste is bitter, and the mouth has a pasty, greasy, and unclean feeling. There is much thirst, and as a rule the patient experiences a keen desire for acid drinks and for fresh fruits. The stomach is rather intolerant of food, and nausea comes on as soon as it enters the stomach. The mucus and stomach-juice accumulating over night, in the morning there is much retching and nausea until the acid and rather foul contents of the organ come up. When food is retained it causes much distress, gases of decomposition accumulate, distending the stomach and giving prominence to the epigastrium, and eructations of offensive gas, with some acid liquid, occur from time to time. Similarly, in the intestines the foods undergo decomposition instead of normal digestion; gases of putrefaction are evolved, the abdomen generally is swollen, and flatulent colic results. Very irritating fat acids are liberated by the decomposition of the fatty constituents of the food, which, with the acid products of the fermentation occurring in the starch and sugar of the diet, cause a sensation of heat and distress through the abdomen. Usually, the bowels are torpid, but in some cases the stools are relaxed, having the consistence and presenting somewhat the appearance of oatmeal porridge. They may be firm, moulded, even hard. The gas discharged and the stools are offensive, with a carrion-like odor. Sometimes decomposing articles of food can be detected in the stools by very casual inspection—always, indeed, when the examination is intimate. An excess of fat is also a characteristic of the condition induced by occlusion of the ducts, especially when the pancreatic duct is closed, as does happen in cancer of the head of the pancreas.

A significant change in the color of the stools takes place. They lose their normal brownish-red tint and become yellowish or clay-colored or white, pasty, or grayish. Sometimes the stools are very dark, tar-like in color and consistence, or more thin like prune-juice, or in black scybalæ. The most usual appearance of the stools in occlusion is grayish, mush-like, and coarsely granular. The very dark hue assumed at times or in some cases signifies the presence of blood. A dark tint of the evacuations may be caused by articles of food, as a greenish hue may be due to the use of spinach; a clay-colored tint to the almost exclusive use of milk; a grayish tint to the action of bismuth; a bilious appearance to the action of rhubarb; and many others. When the occlusion is partial, although it be permanent, sufficient bile may descend into the duodenum to color the stools to the normal tint, and yet all the other signs of obstruction be present.

The bile-pigment, not having an outlet by the natural route, by the intestine, passes into the blood; all the tissues of the body and the various secretions and excretions, notably the urine, are stained by it, constituting the appearance known as jaundice or icterus. This malady has been described (see anté), but it is necessary now to give a more specialized account of those conditions due more especially to the prolonged obstruction of the biliary flow. These are a morbid state of the blood; changes in the kidneys and in the composition of the urine; a peculiar form of fever known as hepatic intermittent fever; and a group of nervous symptoms to which has been applied the term cholæmia.

It has already been shown that but little pressure is required to divert the flow of bile from the ducts backward into the blood. Changes consequently ensue in the constitution of the blood and in the action of the heart and of the vessels. The bile acids lower the heart's movements and lessen the arterial tension; hence the pulse is slower, softer, and feebler than the normal. Should fever arise, this depressing action of the bile acids is maintained; and hence, although the temperature becomes elevated, the pulse-rate does not increase correspondingly. There are exceptions to this, however, in so far that the heart and arteries are in some instances little affected, but it is probable under these circumstances that there are conditions present which induce decomposition of the bile acids.

The most important result of the action of the bile on the constitution of the blood is the hemorrhagic diathesis. Soon after the occlusion occurs in very young subjects—at a later period in adults—the occlusion having existed for many months, in some cases only near the end, the disposition to hemorrhagic extravasations and to hemorrhages manifests itself. From the surface of the mucous membranes, under the serous, in the substance of muscles, the hemorrhages occur. Epistaxis, or nasal hemorrhage, is usually the first to appear, and may be the most difficult to arrest. The gums transude blood, and wherever pressure is brought to bear on the integument ecchymoses follow. The conjunctiva may be disfigured and the eyelids swollen and blackened by extravasations, and the skin of the cheeks and nose marked by stigmata. Hæmatemesis sometimes occurs, but the extravasations into the intestinal canal more frequently—indeed, very constantly—take place in a gradual manner, and impart to the stools a dark, almost black, tar-like appearance. In the same way the urine may contain fluid blood and coagula, or it may have a merely smoky appearance from intimate admixture with the blood at the moment of secretion.

Both the bile-pigment and bile acids exert an injurious action on the kidneys. In cases of prolonged obstruction not only are the tissues of the organ stained by pigment in common with the tissues of the body, but the epithelium of the tubules, of the straight and convoluted tubes, are, according to Moebius,¹⁹⁵ infiltrated with pigment. In consequence of the size and number of the masses of pigment, the tubes may become obstructed and the secretion of urine much diminished. Other changes occur, due chiefly to the action of the bile acids, according to the same authority. These alterations consist in parenchymatous degeneration. The urine contains traces of albumen in most cases, and, according to Nothnägel,¹⁹⁶ always casts of the hyaline and granular varieties stained with pigment. As the alterations in the structure of the kidneys progress, fatty epithelium is cast off, and thus the tubules come finally to be much obstructed and the function of the organ seriously impaired. To cholæmia then are superadded the peculiar disturbances belonging to retention of the urinary constituents.

¹⁹⁵ Archiv der Heilkunde, vol. xviii. p. 83.

¹⁹⁶ Deutsches Archiv für klin. Med., vol. xii. p. 326; also, Harley, op. cit., p. 503.

One of the most interesting complications which arises during the existence of obstruction of the bile-ducts is the form of fever entitled by Charcot¹⁹⁷ intermittent hepatic fever. Although its character was first indicated by Monneret,¹⁹⁸ we owe the present conception of its nature and its more accurate clinical history to Charcot. It does not occur in all cases. As has already been pointed out, the passage of a gall-stone may develop a latent malarial infection or a febrile movement comparable to that caused by the passage of a catheter, and known as urethral fever. Charcot supposes that true intermittent hepatic fever is septicæmic in character, and can therefore arise only in those cases accompanied by an angiocholitis of the suppurative variety—such, for example, as that which follows the passage of calculi. Illustrative cases of this fever, one of them confirmed by an autopsy, have been recently reported by E. Wagner,¹⁹⁹ who is rather inclined to accept Charcot's view of the pathogeny. A remarkable case has been published by Regnard,²⁰⁰ in which the angiocholitis was induced by the extension of echinococcus cysts into the common duct. Whilst there are some objections to Charcot's theory, on the whole it is probably true that this intermittent hepatic fever is produced by the absorption from the inflamed surface of the ducts of a noxious material there produced. It may be likened to the fever which can be caused by the injection of putrid pus into the veins of animals.

¹⁹⁷ Leçons sur les Maladies du Foie, etc., p. 178 et seq.

¹⁹⁸ Cyr, Traité de l'Affection calculeuse du Foie, p. 193.

¹⁹⁹ Deutsches Archiv für klin. Medicin, vol. xxxiv. p. 529.

²⁰⁰ Gazette méd. de Paris, No. 49, 1873, quoted by Wagner, supra.

Intermittent hepatic fever, as its name implies, is a paroxysmal fever, having a striking resemblance to malarial fever, but differs from it in less regularity of recurrence, in the fact that urea is below the normal amount instead of increased, and in the effect of quinine, which in the case of malarial fever is curative, but not curative in hepatic fever. The paroxysms are sometimes quotidian, rarely double quotidian, tertian, quartan, and even longer, and in the same case all of these varieties may occur; on the other hand, there may be entire regularity of the seizures. The severity of the chill, the maximum temperature, and the amount of sweating vary within considerable limits; there may be merely a slight sense of chilliness or a severe rigor; the temperature may rise to 101° or to 104° F., and there may be a gentle moisture or a profuse sweat. There does not seem to be any relation between the extent and severity of the local mischief and the systemic condition.

The period of onset of intermittent hepatic fever, and its duration and mode of termination, are by no means readily determined. Cyr fixes on the paroxysms of colic as the beginning, but he obviously confounds the chill and fever caused by the passage of a calculus with the true intermittent hepatic fever. In a carefully-observed case, the facts confirmed by an autopsy, E. Wagner²⁰¹ gives the clinical history of a typical example of this malady: Gall-stones were found in the duodenum, in the common and cystic ducts, but the most important one was a polyangular stone obstructing the hepatic duct. There was an ulcer with thickened margin at the entrance to the gall-bladder, and the mucous membrane of the common duct near the intestinal orifice had a smooth, cicatricial aspect of recent origin, indicating inflammatory ulceration. The conditions favorable to the production of a morbid material of a kind to induce septicæmic fever were therefore present. The onset of fever occurred ten days after the last seizure, time being thus afforded for the local changes necessary. The duration of the fever in this case was five months, but the existence of pulmonary phthisis with cavities will explain this apparently protracted hepatic intermittent fever. The duration of the disease in its usual form is uncertain, and ranges between a week and two months, or even three months, according to Charcot.²⁰²

²⁰¹ Deutsches Archiv für klinische Medicin, Band xxxiv. p. 531, 1884.

²⁰² Leçons sur les Maladies du Foie, p. 180.

Suspension of work by the liver necessarily involves retention in the blood of various excrementitious matters. The attempt of Flint²⁰³ to establish the doctrine of cholesteræmia has not been supported by the evidence of contemporary or subsequent physiologists. This theory denies to the other constituents of the bile any morbific action, and concentrates those disturbances known as cholæmia on the effects of cholesterin. As uræmia signifies not merely the presence of urea in the blood, but of all of the toxic substances excreted by the kidneys, so the word cholæmia comprehends all the constituents of bile having power to derange the organism by their presence in the blood.

²⁰³ The American Journal of the Medical Sciences, 1862, p. 349 et seq.

By cholæmia is meant those disturbances, chiefly nervous, which are due to the presence of biliary excrementitious matters in the blood, and not less to the effect on nutrition of the absence of bile from the process of digestion in the intestine. As the atrophic changes proceed in the liver, the quantity of urea and uric acid in the urine diminishes, and presently leucin and tyrosin appear. Amongst the means of differential diagnosis of hepatic intermittent fever from malarial fever Charcot mentions the quantity of urea present—in the former greatly lessened, in the latter much increased. There is, however, a source of fallacy here not mentioned by Charcot: that is, the variations in the amount of urea due to destruction of the hepatic secreting structure. It follows that as changes occur in the kidneys, to the condition of cholæmia is superadded the derangements belonging to uræmia.

When the occlusion has existed for some time—a variable period, partly due to peculiarities of individual structure—there come on certain characteristic symptoms of nervous origin: headache, hebetude of mind, dull hearing, obscure or hazy vision, xanthopsia; somnolence and greatly increasing stupor, leading into coma; rambling and incoherence of mind, passing into delirium; muscular twitching, subsultus; muscular weakness, deepening into paralysis; and finally, it may be, general convulsions. As these derangements of the nervous system develop, a light febrile movement supervenes, so that the whole complexus has the typhoid type, or, as it can be more definitely expressed, the patient thus affected lapses into the typhoid state.

COURSE, DURATION, AND TERMINATION.—Occlusion of the gall-ducts is an essentially chronic malady in the greatest number of cases. As a rule, the causes of obstruction operate slowly, but to this rule there are exceptions. Permanent occlusion may take place suddenly, as when a gall-stone is impacted immovably in the common duct, or when a round-worm makes its way into the duct and is firmly fixed there, incapable of further movement.

When occlusion is once effected the gradual changes occurring in the liver lead to slow decline of the nutrition; the bile-elements circulating in the blood poison it and set up alterations in the structure of the kidney, and ultimately, the brain becoming affected, the end is reached by convulsions and coma. Although permanent occlusion, if unrelieved, terminates in death, a small proportion of cases get well, either in consequence of giving way of the obstructing cause or from the opening of a new route to the intestine. Thus, a calculus lodged in the fossa of Vater may suffer such injury to its outer shell as to yield to the action of solvents, or, suppuration occurring around it, the stone may be loosened and forced onward, or ulceration may open a channel into the bowel. An incurable malady causing the occlusion, the termination in death is only a question of time. The duration of any case must be indefinite. There are several factors, however, whose value can be approximately estimated. When the obstructing cause is merely local—as, for example, a gall-stone or the cicatrix of a simple ulcer—the duration of the case is determined by the mere effect of the suspension of the hepatic functions. As the eliminating action of the liver and the part played by the bile in the intestinal digestion are necessary to life, it follows that the complete cessation of these functions must lead to death. The rate at which decline takes place under these circumstances varies somewhat in different subjects. Probably two years may be regarded as the maximum, and three months the minimum, period at which death ensues when no other pathogenetic factor intervenes.

DIAGNOSIS.—To determine the fact of occlusion is by no means difficult: the persistent jaundice, the absence of bile in the stools, and the appearance of the bile-elements in the urine are sufficient. It is far different when the cause of the occlusion is to be ascertained.

The ease and safety with which the exploring-trocar can be used in cases of supposed obstruction of the cystic duct enable the physician to decide with confidence points which before could only be matters of mere conjecture. The writer of these lines was the first to puncture the gall-bladder and to explore, by means of a flexible probe passed through the canula, the course of the duct.²⁰⁴ It is possible in this way to ascertain the existence of gall-stones in the gall-bladder, to find an obstruction at the entrance of the cystic duct, to demonstrate the presence of echinococci cysts, and to remove for microscopical examination pathological fluids of various kinds. More recently, Whittaker and Ransohoff²⁰⁵ of Cincinnati have attempted the detection of a gall-stone impacted at any point by the introduction of an exploring-needle; and this practice has been imitated by Harley²⁰⁶ of London, but without any reference to the pioneer and prior investigation of his American colleagues. The case of Whittaker and Ransohoff survived the exploratory puncture, but Harley's case proved fatal from traumatic peritonitis. Notwithstanding this untoward result, Harley persists in the advocacy of this method. It must appear to any one familiar with the intricate arrangement of the parts composing the anatomy of this region a most hazardous proceeding, and hardly to be justified in view of the superior safety and certainty of my method. To explore the interior of the gall-bladder an aspirator-trocar is introduced; any fluid intended for microscopical examination is then withdrawn, and through the canula a flexible whalebone bougie is passed.

²⁰⁴ The Cincinnati Lancet and Clinic for 1878-79; also, W. W. Keen, M.D., "On Cholecystotomy," The Medical News, Sept., 1884.

²⁰⁵ Lancet and Clinic, 1884.

²⁰⁶ Lancet (London), July, 1884.

When icterus comes on in a few days after birth and persists until death ensues by convulsions and coma, there can be no doubt regarding congenital absence or impermeability of the common duct. Permanent retention-jaundice, accompanied by the characteristic symptoms of that condition immediately succeeding an attack of hepatic colic, is probably due to impaction by a calculus. When, at or after middle life, in a patient with a history of former attacks due to gall-stones, there begins a fixed pain in the right hypochondrium, and subsequently retention-jaundice, the existence of a malignant growth in connection with the cicatricial tissue and ancient organized exudation should be suspected; and this suspicion will be confirmed if subsequently a tumor can be felt. If with a localized pain slowly-developing jaundice, intestinal indigestion, fats and oils appearing unchanged in the stools, and a condition of prostration more than is properly referable to the derangement of the hepatic functions, come on in a man or woman after thirty-five, cancer of the head of the pancreas should be suspected; and this suspicion will be confirmed if a tumor can be detected in that situation. It should not be forgotten, however, that in emaciated subjects the head of the pancreas may be so prominent as to be mistaken for a scirrhous growth.

A pulsating tumor of the right hypochondrium, accompanied by jaundice, may be an aneurism of the hepatic artery. Pulsation may be communicated to a bunch of enlarged portal lymphatic glands, which will compress the common duct, but in this case, as the increase in the size of the glands is due to caseous, amyloid, or cancerous deposits, there will be found a source whence these morbid products are derived, and will explain the nature of a tumor thus constituted.

The differentiation of hypertrophic cirrhosis from occlusion of a slowly-forming character is by no means easy. In both jaundice gradually appears; in both the liver is enlarged, but in hypertrophic cirrhosis much more than in occlusion; and in the latter the gall-bladder is full—may indeed be distended—whilst in the former it is empty or contains but little bile. The history of the case may indicate the nature of the symptoms. Previous attacks of hepatic colic, and the symptoms of occlusion supervening on the last, are highly significant of calculous occlusion.

TREATMENT.—To ascertain the nature of the occlusion is a necessary preliminary to any exact treatment. In many cases this must remain a mere conjecture, when, of course, the treatment is only symptomatic. When it is probable or certain that the duct is obstructed by a calculus, two methods may be resorted to for its removal: one method is to break up the calculus by mechanical means; the other is to effect its solution by chemical agents.

Fracture of an impacted calculus is not a merely fanciful expedient. If the site of the obstruction is ascertained, an attempt may be made to penetrate the calculus by an aspirator-needle passed through the abdominal walls, according to the method of Whittaker and Ransohoff. The dangers attendant on this mere puncture are great, and a fatal result has occurred in one of the very few cases in which it has been done. Less severe and dangerous methods for attempting the disintegration of a calculus should be first tried, as follows: Make firm friction with the fingers along the inferior margin of the ribs and toward the epigastrium and umbilicus, whilst the opposite side posteriorly is supported by the hand spread out and applied firmly. A strong faradic current sent through the region of the gall-bladder and ducts has in several instances seemed to do good—indeed, to remove obstructions. A calculus impacted may be dislodged either by the fracture of its surfaces or by the strong muscular contractions of the abdominal walls and of the muscular layer of the duct. Most calculi are easily broken, and when the smallest breach is made in the external crust disintegration follows; and some calculi are so friable as to yield to slight pressure. Furthermore, the slightest solution in the continuity of the rind disposes the whole mass to dissolve in suitable menstrua. Mechanical rupture is so important a step in the process of disintegration of an impacted calculus that so serious an operation as section of the abdomen as a preliminary to it should be considered. The cavity exposed, the obstructed duct is found, and its retained calculus is mashed without section of the duct. I find one instance²⁰⁷ in which this was done as a subordinate part of a cholecystotomy, and the breaking up of the stone proved to be easy of accomplishment. It is also the method of Tait, who proposes to mash the calculus by means of suitable forceps fitted with padded blades.

²⁰⁷ Harley's case, op. cit.

I have suggested a means of effecting solution of an impacted calculus which seems, on further reflection, well worthy of consideration. The proposal is to inject, through a canula introduced into the gall-bladder, one of the solvents of the cholesterin calculus before mentioned. I have already used the canula as a duct for the passage of an exploring-sound, and have by means of it explored the interior of the gall-bladder. It is quite as feasible to inject through the canula a solvent, successive charges of which can be thrown in and withdrawn by the aspirator.

That the usual solvents introduced by the stomach can effect the solution of impacted calculi has been declared impossible by Trousseau;²⁰⁸ and with this conclusion I unhesitatingly agree. I have already discussed this part of the subject, and need now only refer the reader to that section.

²⁰⁸ Clinique médicale, loc. cit.

The various causes of obstruction besides calculi do not offer an inviting field for the exercise of therapeutical skill. Each case must be treated according to the nature of the obstructing cause; hence to make an accurate diagnosis is an essential preliminary to suitable treatment.

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IV. DISEASES OF THE PORTAL VEIN.

Thrombosis and Embolism of the Portal Vein; Stenosis; Pylephlebitis.

DEFINITION.—By the terms at the head of this section are meant the various pathological processes which induce coagulation of the blood in some part of the portal system. As the portal vein is made up of many branches coming from the various organs of the abdominal cavity except the kidneys, and as it empties, so to speak, into the liver, it is obvious that various and complex derangements will ensue on the formation of thrombi.

CAUSES.—Thrombosis of the portal vein occurs under three general conditions: the blood is in a readily coagulable state; the action of the heart is weak and the blood-current sluggish; the circulation through the vein is impeded by external pressure. The coagulability of the blood is increased in diseases characterized by an excess of its fibrin-producing constituents, of which cirrhosis of the liver may be mentioned as one having this peculiarity. In chronic maladies of a depressing kind there may be simply a weak action of the heart, or the muscular tissue of the organ may be affected by a fatty and atrophic degeneration. The external pressure by which the blood-current through the vein is impeded may be caused by the newly-formed connective tissue of Glisson's capsule, by enlarged lymphatics in the hilus of the liver, or by tumors of various kinds. The first named of these causes of compression—atrophic cirrhosis—is most frequently acting. Very rarely, organized exudations of the peritoneum may be so situated as to compress the portal vein. This result can only happen when the hepatic portion of the peritoneum is involved.

Pylephlebitis exists in two forms: the adhesive and suppurative. The former results in changes not unlike those of simple thrombosis. The blood coagulates in the affected part of the vessel, the clot is organized, and the vessel ultimately forms a solid rounded cord which is permanently occluded. The suppurative variety is so different in its origin and in its results that it requires separate treatment, and I therefore postpone the consideration of it to the next section.

SYMPTOMS OF THROMBOSIS AND ADHESIVE PYLEPHLEBITIS.—It is a remarkable fact that the biliary function of the liver is not necessarily affected in cases of occlusion of the portal vein. It is true, in advanced cases of cirrhosis, when the interlobular veins are obliterated by the pressure of the contracting newly-formed connective tissue, the functions of the liver are arrested in so far as the damage thus caused extends. Notwithstanding the blocking of the portal, sufficient blood reaches the hepatic cells by the anastomosis between the hepatic artery and the interlobular veins—an anatomical connection demonstrated by Cohnheim and Litten.²⁰⁹ So long as this anastomosis continues bile will be formed, although the portal vein is occluded.

²⁰⁹ Virchow's Archiv, Band lxvii. p. 153, "Ueber Circulationsstörungen in der Leber."

The most significant symptoms of thrombosis of the portal vein are the sudden formation of ascites, which quickly assumes a very high grade, and equally sudden passive congestion of the gastro-intestinal mucous membrane, enlargement of the spleen, and distension of the superficial veins of the abdominal parietes. When these symptoms succeed to cirrhosis of the liver, or appear after the formation of a tumor in the hepatic region, or come on in the course of phthisis or chronic inflammation of the hepatic peritoneum, the existence of thrombus of the portal vein may be reasonably suspected.

Coincidently with the occlusion of the portal vein the gastro-intestinal mucous membrane becomes the seat of a catarrhal process, and to the fluid thus produced is added a much more abundant transudation from the distended capillaries. Nausea, vomiting, and diarrhoea result, the rejected matters being serous, watery, and in many cases tinged with blood. Now and then quite a severe hemorrhage takes place, and the blood is brought up by vomiting (hæmatemesis) or is discharged by stool. Hemorrhoids form, and, in large masses protruding, much pain is experienced, and free bleeding may result from rupture of a distended vein.

The veins of the abdominal parietes, which in the normal state are invisible or at least not prominent, and which form anastomoses with the portal, when the obstruction occurs dilate, sometimes to a remarkable extent. The most important anastomosis is that between the femoral and saphena and internal mammary and epigastric veins. When the hepatic branches of the portal are closed, but the trunk remains pervious, the parumbilical vein enlarges greatly, and, communicating with the superficial veins of the anterior part of the abdominal walls, forms a radiating network of tortuous veins to which is given the striking title of caput Medusæ.

The most significant symptom of portal thrombosis is a quickly-forming ascites. It is true, ascites is a common symptom in advanced cirrhosis, but the rapid accumulation of fluid and the prompt filling of the cavity after tapping distinguish that which arises from portal thrombosis from all others. Besides its excessive extent, the ascites presents the usual symptoms.

Due to the same cause as the enlargement of the superficial veins, the hemorrhages, the ascites, etc., there occurs considerable hypertrophy of the spleen in many of the cases. It sometimes happens that the new compensatory circulation and the hemorrhages from some part in the usual route of the portal so dispose of the blood that the spleen does not enlarge sufficiently to be readily made out.

COURSE AND TERMINATION.—It is obvious that a condition such as that induced by thrombosis of the portal must be comparatively quickly fatal; but the cases vary in duration as the compensatory circulation is more or less complete. Whilst the majority of cases terminate within two weeks, instances of several months' duration are not unknown, but a fatal termination, sooner or later, is inevitable in all cases.

Coming on in the course of some chronic affection of the liver or some obstructing cause exterior to the organ, there soon follow ascites, nausea and vomiting, hæmatemesis, bloody stools of a liquid character, enlargement of the spleen, distension of the abdominal veins, and the distressing symptoms produced by an excessive accumulation of fluid in the peritoneal cavity.

DIAGNOSIS.—As there is no symptom of thrombosis of the portal which may not be caused by advanced cirrhosis, the diagnosis rests on the rapid production of the attendant phenomena and their conjoint appearance.

TREATMENT.—A symptomatic treatment is alone possible. The highly irritable and congested intestinal mucous membrane precludes the employment of hydragogue cathartics. Salines which cause outward diffusion from the vessels are the only cathartics which can be used with propriety. Action of the kidneys and of the skin must be maintained. To this end the resin of copaiba in pilular form and pilocarpine subcutaneously may be used. If the strength of the patient will permit, leeches around the anus can be applied, and much relief may be expected from free bleeding. It is probable that opening a swollen hemorrhoid would give the same kind of relief as that caused by a free hemorrhage. In any case the benefit derived from treatment must be merely palliative and temporary.

Suppurative Pylephlebitis.

PATHOGENY.—Primary pylephlebitis rarely if ever occurs. On the other hand, the secondary form is by no means uncommon; it succeeds to ulcerative or purulent inflammation at some point in the circuit of origin of the portal radicles. The most frequently-occurring cause is ulceration and suppuration of some part of the intestinal tube, and hence the most common result is multiple abscess of the liver. Pylephlebitis has often resulted from typhlitis; from ulcers of the large intestine, as in dysentery; from such traumatic injuries as tying hemorrhoids; from proctitis; from ulcers of the stomach and similar morbid processes elsewhere within the range of origin of the portal system. The pathogeny is clear. The inflammatory or ulcerative action extends to and involves the walls of the veins, or some morbid material diffuses through the vein walls. In either case coagulation of the blood in the vessel ensues, and the clot undergoes a series of changes resulting in the formation of emboli, which, carried into the main current, are subsequently lodged in the hepatic capillaries.

There are three steps in the morbid process: the changes in the vein wall; the production and transformation of the thrombus; and the formation of secondary suppurating foci in the liver.

The appearance of the tunics of the inflamed vessels varies with the stage at which they are examined. At first the walls of the vessels are reddish from congestion, succulent, and swollen, infiltrated by leucocytes and inflammatory exudation and the cellular elements undergoing proliferation. The intima especially is much altered in its appearance and structure, becoming thick, opaque, grayish or yellowish in color, and having adherent to it a thrombus passing through its characteristic changes. Ulceration of the intima then occurs, and the purulent elements, with shreds of tissue, mingle with the degenerating blood-clot, and ultimately there remains a purulent dépôt lined with sloughing, even gangrenous, contents. Emboli detached from such decomposing thrombus are arrested in the vessels of the liver, and there set up a suppurating phlebitis, ending in an abscess formation, or a quantity of pus from the original point of ulcerative phlebitis passes into the portal vein, and is generally distributed through the hepatic branches, here and there foci of suppuration being established by the deposit of decomposing emboli. There may be numerous small abscesses irregularly distributed through the liver, or there may be one or two larger collections of pus. Very often the vessel whose occlusion by a suppurating embolus has caused the mischief is destroyed, and hence no communication with the abscess-cavity can then be traced. These abscesses are not limited by a line of inflammatory demarcation or by a limiting membrane, but the hepatic tissue adjacent is congested and infiltrated with pus.

Ulceration, abscesses, or purulent inflammation occurring at any point within the area of origin of the radicles of the portal vein may induce pylephlebitis and consequent hepatic abscess. There are two points at which, suppuration established, secondary pylephlebitis is most apt to occur: the cæcum; the rectum. As respects the former, the symptoms of typhlitis precede the hepatic disturbance; and as respects the latter, usually dysentery, or rather proctitis, is the initial disease. In both sources of the hepatic trouble the inferior hemorrhoidal veins are chiefly concerned—a fact explicable by reference to the sluggishness of the circulation and the distended condition of these veins, whence it is that thrombus is very readily induced. Numerous instances of pylephlebitis following suppurative lesions of the cæcum have been reported. One of the most recent, and at the same time typical, examples of such conditions is that published by Bradbury²¹⁰ of Cambridge, England. The initial lesion was "an ulcer the size of a split pea" situated near "the junction of the vermiform appendix and cæcum." "The hemorrhoidal veins and the inferior mesenteric above were filled with breaking-down clot and pus," and "the liver contained many abscesses of various sizes, the largest about the size of a lemon, which had burst through the diaphragm." As is so often the case, the ulcer of the cæcum produced no recognizable disturbance, and important symptoms were manifest only when the emboli lodged in the liver set up suppuration, when there occurred the usual signs of hepatic abscess. In the West and South hepatic abscess due to pylephlebitis, induced by proctitis, with ulceration of the rectum, is a common incident. Various examples of this kind have fallen under my own observation. The relatively greater frequency of this form of pylephlebitis is due to the fact above stated, that the inferior hemorrhoidal veins are voluminous, have a sluggish current, and are liable to over-distension by pressure of feces and by external abdominal bands and clothing. Cases of a corresponding character arise from suppuration and ulceration elsewhere within the portal circuit. Thus, Bristowe²¹¹ reports a case in which pylephlebitis resulted from an ulcer of the stomach, the neighboring veins becoming implicated and the usual results following.

²¹⁰ The Medical Times and Gazette, Sept. 27, 1884, p. 450, "Proceedings of the Cambridge Medical Society."

²¹¹ Transactions of the Pathological Society of London, vol. ix. p. 278.

When inflammation has begun in a radicle of the portal vein, it may proceed to the liver by contiguity of tissue, the whole intervening portion of the vessel being affected. Probably more frequently the intra-hepatic portion of the portal is inflamed by emboli, and the adjacent hepatic tissue then undergoes suppuration, as has been already set forth.

SYMPTOMS.—There being two points of disease—the primary lesion of the peripheral vessel and the secondary results in the hepatic portion of the portal—the symptomatology must have a corresponding expression. The stomach, the cæcum, or the rectum, or some other organ or tissue, being occupied by a morbid process, there will be a characteristic complex of symptoms. Taking up the most usual primary disturbance, a typhlitis or an ulcer of the cæcum, there will be pain, tenderness, and possibly fever, occupying in point of time the period proper to such a malady and an amount of disturbance of function determined by the extent of the lesion. The symptoms caused by a single small ulcer of the cæcum, as in the example narrated by Bradbury, may present no characteristic features and may have little apparent importance, and yet the lesion is productive of very grave consequences.

When from any of the causes mentioned above a thrombus forms in a vein of the portal system in consequence of the extension of the inflammation about it, the case, what importance soever it previously had, now takes on new characters. The onset of the inflammation of the vein walls and the puriform degeneration of the thrombus is announced by a chill—a severe rigor, or chilly sensations at least. At the time of the chill, and sometimes before it, pain is felt, significant of the lesion in the vein. When proctitis or typhlitis precedes the pylephlebitis, pain appropriate to the malady is a significant symptom; but the pain which comes on with the beginning of the inflammation in the liver is a new sign. The most frequent sites of the pain are the right hypochondrium and the epigastrium, but it may also be felt in the left hypochondrium or in either iliac fossa. Unless there be diffuse peritonitis the pain is accompanied by a strictly-localized tenderness to pressure. The situation of the pain may afford an indication of the vein attacked, and when there are two points at which pain is experienced, one may originate at the first situation of the morbid action; the other will be due to pylephlebitis.

The fever succeeding the chill is decided, and in some cases may attain to extraordinary height—a manifestation indicative of the pyæmic character of the affection. The fever intermits or remits, with a more or less profuse perspiration. The febrile phenomena are similar in their objective expression to malarial fever, but there is an important difference in respect to the periods of recurrence of the chills. The paroxysms are very irregular as to time: there may a daily seizure at different hours, or there may be several chills on the same day. In other words, the paroxysms have the pyæmic characteristics rather than the malarial. After a time the intermittent phenomenon ceases, and there occurs a remission merely, the exacerbation being preceded by chilliness and succeeded by sweating. The sweats are characteristically profuse and exhausting. During the sweating the temperature begins to decline, and reaches its lowest point just before the chilly sensations during the early morning announce the onset of the daily exacerbation of the afternoon and evening. The thermal line exhibits many irregularities until the febrile movement assumes the remittent type, when there occur the morning remission and nocturnal exacerbation. The maxima may be from 103° F. to 105°, even to 106°.

When the pain and chill come on, disturbances of the digestive organs ensue. When a large vein of the portal system is occluded, the remaining veins must be over-distended, and congestion of a part or of all of the digestive tract will be a result. An acute gastric catarrh is set up. The appetite is lost, the stomach becomes irritable, and vomiting is a usual incident. Sometimes the disgust for food is extreme, and the nausea and vomiting are almost incessant. The vomited matters consist of a watery mucus mixed with thin bile after a time, and now and then of a bloody mucus. Thrombosis of a stomach vein may occur, to be followed by an acute ulcer, and from this considerable hemorrhage may proceed, when the vomit will consist of blood. Such an accident, happening to the mucous membrane of the intestine, will be indicated by bloody stools if the ulceration is low down, or by brownish, blackish, or chocolate-colored stools if higher up in the small bowel.

The tongue has usually a characteristic coating in these cases. Large patches of a rather heavy and darkish fur form, and, cast off from time to time, leave a glazed and somewhat raw surface. Sometimes there is a profuse salivary flow, but more frequently the mouth is dry. The lips are fissured or contain patches of herpes, and the buccal cavity may be more or less completely lined by patches of aphthæ.

Diarrhoea is a usual symptom, the stools being dark when mixed with blood, or grayish and pasty or clay-colored when there is jaundice.

Three-fourths of the cases of pylephlebitis are free from jaundice. This symptom may occur at the onset when the common duct is obstructed by a calculus, but in other cases it appears when the formation of pus in the liver exerts sufficient compression of the hepatic ducts to prevent the passage of the bile.

When jaundice occurs, it is accompanied by the usual symptoms. The urine, previously unchanged, is now colored by bile-pigment, and the alterations in the renal structure and function belonging to jaundice also take place.

It sometimes happens that the obstruction of the portal vein is sufficient to cause enlargement of the superficial veins of the abdomen, but the duration of the disease is usually too brief to permit much deviation from the normal, except rarely. In the cases characterized by the occurrence of diffuse peritonitis the abdomen will present a swollen and tense appearance, and there will be acute tenderness to pressure. The area of hepatic and splenic dulness is not increased from the outset, but is evident, as respects the spleen, soon after the obstruction at the liver, and as respects the liver when the formation of abscesses occurs.

COURSE, DURATION, AND TERMINATION.—The course of pylephlebitis is compounded of the disturbance at the original point of disease, and of the secondary inflammation at the several points in the liver where emboli set up purulent inflammation. There are, therefore, two distinct symptom-groups, and a short intervening period in which the first is being merged into the second. The duration is variable, but the extreme limits are not remote from each other, the condition of pylephlebitis terminating in from two weeks to three months, the shorter being the more usual. The termination is death, doubtless invariably; for, as in true pyæmia arising from other causes, the septic changes in the blood are such as to preclude the possibility of a return to the normal condition.

DIAGNOSIS.—The main point in the diagnosis consists in the occurrence of an evident local inflammation, followed by the signs of suppuration in the hepatic region coming on subsequent to ulceration and suppuration at some point in the peripheral expansion of the portal system. Thus, when a proctitis with ulceration of the rectum has been in existence for some time, there occur pain and tenderness in the hepatic region, accompanied by an irregularly intermittent fever and by profuse sweating, it can be assumed with considerable certainty that emboli have been deposited in some one or more of the terminal branches of the portal. The evidences of hepatic trouble—swelling of the organ, jaundice, etc.—and of portal obstruction, which then supervene, indicate with some precision the nature of the case.

TREATMENT.—Although pylephlebitis wears a most unfavorable aspect, the possibility of a favorable result should always be entertained by the therapeutist.

As absorption of medicaments must be slow—indeed, uncertain—by the gastro-intestinal mucous membrane when there is portal occlusion, it is well to attempt treatment by the skin and subcutaneous connective tissue. Gastro-intestinal disturbance—nausea, vomiting, and diarrhoea—should be treated by a combination of bismuth, creasote, and glycerin—remedies acting locally chiefly. Ammonia—the carbonate and solution of the acetate—is indicated, and should be given for the purpose of dissolving thrombi and emboli. Corrosive sublimate, carbolic acid, and quinine can be administered by the subcutaneous areolar tissue. Quinine may also be introduced by friction with lard, and in considerable quantity.

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V. PARASITES OF THE LIVER.

Echinococcus of the Liver; Hydatids of the Liver.

DEFINITION.—The echinococcus is the intermediate or larval stage in the development of the Tænia echinococcus—the completed parasite—whose chief habitat is the intestine of the dog. As the natural and clinical history of parasites is elsewhere treated of, the subject is here confined to the development of echinococci cysts in the liver, its ducts, and vessels.

CAUSES.—The presence of echinococcus vesicles in the liver is due to the migration of the embryo from the intestinal canal. As Davaine²¹² has ascertained by analysis of all the recorded examples previous to the publication of his treatise, echinococci are found in as large a proportion in the liver as in all the other organs combined. This statement is repeated with approval by Cobbold²¹³ and by Heller.²¹⁴ The embryo, set free in the intestine from the food or drink containing the ova, starts on its migration. There are several reasons why the liver is selected for its habitat: it is the largest accessible organ; the common duct and the portal vein offer the most convenient roadway for reaching and penetrating its substance. The exact route or routes of which the parasite avails itself in migrating have not been definitely settled, although Friedreich has shown that the portal vein is the medium of transmission of the Echinococcus multilocularis. The comparative frequency with which the liver is entered indicates that the portal vein is the favorite route of migration.

²¹² Traité des Entozoaires et des Maladies vermineuses, etc., par C. Davaine, Paris, 1877, p. 383.

²¹³ Entozoa, by T. Spencer Cobbold, M.D., F.R.S., London, 1874, p. 275.

²¹⁴ In vol. iii of Ziemssen's Cyclopædia, p. 561.

PATHOLOGY AND SYMPTOMS.—The number of echinococci reaching the liver varies from one to ten or twelve or more. They increase in size from the time of their deposit in the organ, and ultimately attain to large proportions. The rapidity of growth depends somewhat on the character of the tissue in which imbedded, and the amount of disturbance of function is determined by the position of the parasite in the organ. Echinococci may be deposited in any part of the liver—in the substance of the organ, in the ducts, or in the vessels—but the most usual site is near the capsule, and, developing outwardly in the direction of least resistance, impart to the outline of the organ an irregular contour. As the echinococci develop, the adjacent parts of the liver pressed upon undergo atrophy, but the connective tissue of the organ contributes to the formation of the dense capsule which envelops them. But as the increase in size is not rapid, although continuous, if the cysts are situated at the periphery and adjacent to the capsule, they may be present for many months without causing any distinct symptoms. In a case occurring under my own observation last year the only symptom which attracted attention was an enlargement of the hepatic region, and on examination a characteristic elastic, irregular, and painless tumor could be readily detected by sight and touch occupying the right hypochondrium and extending into the epigastric and umbilical regions. When the echinococci cysts impinge on the portal vein or on the hepatic duct, there will be caused the usual results of such pressure—ascites or jaundice, or both conditions may occur simultaneously, with obstruction of both vein and duct. When the cysts develop downwardly, the stomach and intestines will be displaced, and nausea and vomiting, diarrhoea or constipation, and, it may be, considerable pain of a colic-like character, will be caused. An upward development of the cysts gives rise to more pronounced disturbances. The diaphragm is pushed upward, the heart displaced, and the lungs, especially the right, compressed. Occasionally the diaphragm is softened and perforated by the pressure of the enlarging cysts, and the lungs are ultimately tunnelled, the parasites being discharged by the bronchi.

The growth of an echinococcus tumor may spontaneously cease, and then retrograde changes take place, leading to its final disappearance. This arrest of development may occur without any obvious cause, but now and then such a change from the ordinary course of tumors may be effected by an external injury, as a blow on the abdomen, but more frequently the death of the parasite is caused by ulceration into a bile-duct, and the entrance of bile, which is a poison to these hydatids. It sometimes happens that, opening into a duct of large size, the daughter and granddaughter vesicles are slowly discharged through it into the intestine, and thus a cure is effected. Inflammatory action occurring in the cysts, adhesions may form and rupture into a neighboring cavity take place. Direct communication may be established with the intestine, or the cavity of the pleura or peritoneum be entered, with results entirely disastrous.

A necessarily fatal termination must also ensue when the hydatids penetrate the ascending vena cava, but this accident is, fortunately, very rare.

The passage outward through the abdominal wall is an exceedingly uncommon but fortunate issue of echinococcus of the liver, for in this mode the hydatids may be discharged without much difficulty.

The echinococcus vesicle is enveloped in a dense, resisting, and elastic capsule, constructed out of the connective tissue of the part in which it is deposited. The innermost layer of the vesicle is the germinative (endocyst), and from its granular surface are developed the brood-capsules and their scolices—i.e. the head with its suckers and crown of hooklets.²¹⁵ Each vesicle may contain not only daughter, but also granddaughter, progeny, numbering from a dozen up to many thousands, and they will vary in size from the head of a pin to a pullet's egg. It follows that the mother vesicles must also greatly vary in size: they range from a large pin's head to a child's head. The vesicles or sacs contain a clear, faintly yellowish, or opalescent fluid, neutral or slightly alkaline in reaction, and holding in solution a large per cent. of sodium chloride, but free from albumen. The specific gravity of the fluid ranges from 1007 to 1015, according to the quantity of sodium chloride present. Succinic acid and also hæmatoidin are usual constituents, besides the ingredients already mentioned.

²¹⁵ Entozoa, Cobbold, p. 273 et seq., chapter viii.

Although the form of hydatid or echinococcus cyst above described is the usual one, there is occasionally produced an anomalous development of the parasite, which from its resemblance to colloid cancer was supposed to have this character until Virchow²¹⁶ unravelled the mystery by demonstrating its true structure. This form of the parasite is designated Echinococcus multilocularis. Its resemblance to colloid cancer is the more striking because of the tendency of the interior of the mass to undergo degeneration, to disintegrate, and to break up into pus-sacs with greenish, cheesy, and bilious contents. An Echinococcus multilocularis tumor is of almost stony hardness; it has a very dense fibrous structure, intersected by cavities with thick gelatinous contents. These minor cavities²¹⁷ are sacs of echinococci, but they depart widely from the typical form, well-defined scolices being seldom encountered.

²¹⁶ Archiv für Anat., Virchow, vol. xi. p. 80.

²¹⁷ Carrière, quoted by Davaine, op. cit., p. 961.

Echinococci of the liver develop very slowly, and it is characteristic of them to attain to very large proportions in most cases without causing any very pronounced symptoms. There are certain signs common to hydatids in any situation; there are others which are due to particular circumstances.

A hydatid tumor of the liver is smooth but somewhat irregular in outline, and elastic, when it develops downward, extending below the margin of the ribs. If, however, it grows upward, the area of hepatic dulness extends in that direction beyond the usual limits; the diaphragm is pushed up, the lungs forced upward to the left and compressed, and the heart also displaced upward toward the left. The extension of the tumor downward, in the direction of least resistance, is more usual. If the walls of the abdomen are sufficiently thin, the tumor large enough, and if made up of many daughter vesicles, there may be evoked by palpation the very characteristic sign known as hydatid purring. To produce this effect an oscillation must be caused by a sudden impulse communicated to the tumor on one side, the hand resting against the other side. This sensation is likened to the impression on the eye of the vibration of a bowl of jelly. Even when there is a well-defined tumor this symptom is comparatively infrequent, but if present it is pathognomonic, since no other kind of tumor possesses the property of oscillation and elastic collision of its several constituents.

When the tumor is so situated as to occlude the hepatic or common duct, jaundice will be a symptom, and when the stomach is pressed upon there will be epigastric oppression and nausea. If the vena cava is impinged on or the portal vein, the usual results—ascites and oedema of the lower extremities and of the scrotum—will be manifest. There is, of course, nothing distinctive in these results.

The Echinococcus multilocularis, situated in the substance of the liver, causes the usual disturbances of a new formation in such a position. Much of the hepatic tissue is destroyed by its growth, and many of the minor ducts closed. Jaundice is an early symptom—the first, indeed, in many cases—and is also one of the most persistent. It is present, according to Griesinger, in 10 out of 13 cases. The usual gastro-intestinal disorders belonging to jaundice occur under these circumstances; also the nervous disturbances of cholæmia.²¹⁸

²¹⁸ Davaine, op. cit., p. 962.

Enlargement of the spleen is a very frequent symptom, being present, according to Davaine, in 11 out of 13 cases, and, according to Heller, in 25 out of 29 cases, in which this fact was made the subject of direct inquiry.

Pressure on the vena cava causes oedema of the inferior extremities in a small number of cases; and on the vena porta, ascites. There may occur thrombosis of the portal, in which event the ascites will form very quickly, and return as quickly after tapping.

The usually placid course pursued by echinococcus of the liver may be much modified by inflammation and suppuration. Some external injury may develop the inflammation. Having occurred, the clinical history corresponds to other cases of hepatic abscess, and the reader is therefore referred to the section on that topic for fuller information.

DIAGNOSIS.—At the outset of echinococcus of the liver the differentiation of the tumor from other tumors, and of the disturbances produced by it as contrasted with the effects of other morbid growths, becomes exceedingly difficult, if not impossible. The size, painlessness, elasticity, the purring tremor of the echinococcus tumor, afford a sure basis for constructing a diagnosis, and as ultimately developed they become the means of accurate differentiation from other morbid growths of that locality. All doubt as to the nature of a given hydatid tumor of the liver may be set at rest by the use of the aspirator. The discovery of the characteristic hooklets of the scolex in the fluid withdrawn from the tumor will be conclusive as to the presence of echinococci. The hooklets may be absent, as in the case of acephalocysts, but the fluid is characteristic in other respects: it contains a large quantity of chloride of sodium and is free from albumen.

Very great difficulty is experienced in diagnosticating an echinococcus tumor developing from the upper surface of the liver, pushing the diaphragm and lungs upward and displacing the heart to the left. Whilst the physical signs may be, and are, usually alike when the condition calling for diagnosis has existed for some time, there are means of differentiating in the history of the cases and in the initial symptoms.

The origin and growth of the echinococcus tumor are obscure and free from constitutional disturbance; the onset of a pleuritic exudation is marked by pain, fever, and hurried respiration and by physical signs of a characteristic kind. It is true there are cases of so-called latent pleurisy in which a hydrothorax forms without any well-marked indications, but it will usually be found that some local pain, hurried breathing, or other symptoms existed from the beginning. Those cases of hydrothorax accompanying renal and cardiac diseases are readily enough associated with their original cause.

Echinococcus of the liver may be confounded with abscess of the liver, but a differentiation can be readily made by attention to a few considerations, except in the rare condition of the Echinococcus multilocularis which has proceeded to suppuration. In this latter condition there are no means of differentiation, since an abscess-formation has already occurred, nor is there any need to attempt a distinction without the occasion of a difference. Echinococcus differs from abscess in history, in the character of the swelling, and in progress. Abscess of the liver is preceded by paroxysms of hepatic colic, by inflammatory ulceration of some part of the intestinal tract, or by local injury—traumatism. The onset of a hydatid tumor is silent and painless. The swelling of the liver when an abscess forms is not considerable at any time, and appears to be a uniform enlargement of the organ, except when the pus tends to make its way through the walls of the abdomen externally. An enlarging echinococcus tumor is an obvious projection from the surface of the liver at some point, and it does not have the characteristic tenderness, the fluctuation of an abscess matured and ready to discharge, and the constitutional disturbance; but it does have a peculiar elasticity, and now and then may present that eminently characteristic sign, the purring tremor. The use of the exploring-trocar will usually suffice to clear up all doubts by the withdrawal of the characteristic fluid of the hydatid cyst or of pus.

DURATION AND TERMINATION.—The progress of an echinococcus tumor is exceedingly slow, and the development of symptoms produced by its extension is early or late according to its position and to the nature of the parts impinged on. A spontaneous cure may take place under the rather rare circumstances of an opening into the hepatic duct or one of its principal divisions, and the gradual discharge of the cysts by this outlet into the intestine. Next to this mode of termination, the most fortunate direction taken by the enlarging cysts is through the walls of the abdomen externally. When the growth is upward through the lungs, the symptoms belonging to empyema or hydrothorax, with pulmonary abscess, ensue, and the termination is fatal after a protracted course. Rupture into the peritoneal cavity is a fatal event. Ulceration into the intestine, and the discharge of the cysts through the route thus made, may effect a cure, but more frequently the fistulous communication becomes a means of forming a fecal abscess.

The result in any case of hydatids of the liver is much influenced by the mode of treatment adopted and the period at which it is undertaken. As these parasites can be readily reached and destroyed by safe means, obviously the more early the diagnosis is made and the treatment carried out, the less the injury done to the hepatic structures and neighboring parts.

TREATMENT.—Prophylactic.—As the intestine of the dog is the natural habitat of the Tænia echinococcus, and as the hydatid is the first stage in the development of the ovum and the second in the life-history of the parasite, the means of prophylaxis consist in preventing contamination of human food and water with the dog's excrement, which contains the ova of the parasite. In Iceland, where hydatid disease is very prevalent, dogs and human beings living in the same huts and obtaining their water-supply by melting the snow just about them, contamination of food and drink must readily occur. In this country such conditions cannot exist; nevertheless, cases of hydatids are not infrequent. The chief, if not the only, source of contamination is through the consumption of such uncooked vegetables as lettuce, celery, cabbage, etc., in the folds of which the ova may be retained, and from which an ordinary washing does not suffice to detach them. It follows that such articles of food should be minutely inspected and cleansed before being placed on the table.

Boiling and filtration are the means of removing impurities of this kind from potable waters.

Therapeutical.—The remedial management of cases of Tænia echinococcus is necessarily restricted to that stage in their development when by increasing size the functions of organs begin to be affected. Internal medicines given with the view to arrest the growth of the parasite are useless. Formerly, such attempts were made and successes were claimed, but it is now known that no medicine can act on organisms enclosed as these are in a dense capsule. It is needless to occupy space with therapeutical details of this kind, but mention may be made of the agents that were supposed to be effective. Laennec held that baths of a solution of common salt had a distinct curative effect. The internal use of iodide of potassium and the local application of iodine paint were believed to cure a case in St. George's Hospital, London, in the practice of Mr. Cæsar Hawkins. Kameela was, in Iceland, supposed to have a curative effect, but notwithstanding this the physicians of that island resort to very heroical surgical methods in the treatment of this affection.

The one means of relief consists in the removal of the vesicles, either by suitable incisions or by compassing the death of the parasite, after which the power of nature may be adequate to the cure. In Iceland large incisions are made into the tumor at its most prominent part, and, although accidents are not uncommon, the results in many cases are eminently satisfactory. The accidents are shock, hemorrhage, and especially peritonitis. Under favorable circumstances now no procedure is more satisfactory in its results than free incision and drainage. The tumor should be prominent, adherent all round to the peritoneum, and the walls of the abdomen thin to ensure complete success without accident. At the present time, so great have been the advances in abdominal surgery, this operative procedure may be preferable in some few cases presenting the favoring conditions above mentioned.

Very simple expedients, however, suffice in most cases. The most simple is puncture. This is now much practised in Iceland, and, as the statistics show, with considerable success. Thus, Hjaltelin²¹⁹ reports 100 cases cured in this way, and in his own hands this expedient proved successful in 41 out of 50 cases operated on. In Australia, where hydatid disease is also quite common, simple puncture has effected a large proportion of cures,²²⁰ and is the method of treatment usually pursued. In England puncture has the approval of some of the best authorities.²²¹

²¹⁹ Davaine, op. cit., p. 605.

²²⁰ The Medical Times and Gazette, August, 1873, p. 164.

²²¹ Transactions of the Clinical Society for 1872: discussion participated in by Gull, Bryant, Greenhow, etc.

The mode of performing this operation consists in the introduction of an exploring-trocar into the most prominent part of the tumor. It may be withdrawn at once or be permitted to remain for a few minutes to several hours. The dangers are suppuration in the sac and peritonitis; but the former, although sometimes accompanied by severe constitutional symptoms, is not likely to endanger life, and even formidable disturbances due to the latter are usually recovered from. The facts show that puncture very rarely indeed causes dangerous, especially fatal, symptoms. An eruption of urticaria has been observed to follow puncture with the trocar, and also aspiration, in a considerable proportion of the cases, but it has no special significance.

Since the introduction of the aspirateur, puncture and withdrawal of the fluid by means of this instrument has been practised more frequently, and this appears to be a more effective procedure, than simple puncture with an exploring-trocar, although in most cases the escape of the contained fluids suffices to destroy the parasite. The aspirateur is less likely to permit the escape of fluid into the peritoneal cavity or the entrance of air into a vein punctured by accident. If puncture with the trocar or aspiration be practised, shall all the fluid be withdrawn at once? The answer to this question may be decided by the character of the sac. Does it contain daughter and granddaughter vesicles? If so, one puncture may not permit the escape of much fluid; but in any event it is the practice of the most judicious and experienced authorities²²² to withdraw as much as possible of the contents of the cysts at the first operation. Formerly, a method practised by some French surgeons consisted in successive tappings, a small quantity of fluid being drawn off each time.²²³ There is no good reason for this method of treatment now, and it seems to have been discontinued.

²²² Transactions of the Clinical Society, loc. cit.

²²³ Davaine, supra.

Yet another method of treatment, but less effective than puncture or aspiration, consists in injecting into the sac, after the removal of its contained fluid, certain agents toxic to hydatids. A solution of the extract of fern, alcohol, solution or tincture of iodine, and bile, are the chief remedies thus employed. It has long been known that bile is destructive of these parasites, and cases have occurred of spontaneous cure in which the opening of the growing cysts into a bile-duct has secured the entrance of bile and consequent arrest of growth and atrophy of the hydatids. Several successful cases have been reported in which the injection of aspidium (male fern) was the effective agent, but the threatening symptoms produced by it, and the comparative freedom of other methods of treatment from such disturbances, do not recommend the injections of fern. In the case reported by Pavy²²⁴ the extract of fern was mixed with a solution of potassa.

²²⁴ Lancet (London), July, 1865.

Injections of iodine in solution or in the form of tincture have been more frequently practised than of any other material. Davaine,²²⁵ who finds it less successful than simple puncture and aspiration, recommends, as affording the best results, a dilute aqueous solution of iodine. Alcohol, a solution of permanganate of potassium, and various antiseptic agents have been used to some extent, but none of them possess any advantages over more simple measures.

²²⁵ Op. cit., p. 650.

The latest proposal for the treatment of hydatid cysts, and probably the most effective consistent with entire safety, is electrolysis. Originally suggested by Althaus²²⁶ to those who first employed the measure on any considerable scale, it had been mentioned thirty years before by Budd, and appears to have been first practised in Iceland on a single case. The first elaborate attempt to establish electrolysis on a sound basis as a regular procedure was made by C. Hilton Fagge and Mr. Arthur E. Durham.²²⁷ They operated on eight cases, and all were successful. The method consists in the introduction of two needles connected with the negative pole, and the application of the positive—a moistened sponge—on the exterior in the neighborhood of the hepatic region. The strength of current employed by Fagge and Durham was that furnished by a battery of ten cells, and which by previous trial was found to decompose a saline solution. The two electrolytic needles, connected with wires attached to the negative pole, were introduced into the most prominent part of the tumor about two inches apart. The current was allowed to pass about ten minutes usually, sometimes a little longer, the sponge on the exterior—the positive pole—being shifted occasionally. The immediate effects are not considerable. The tumor may be rendered somewhat more tense and appear to be enlarged, but more frequently it becomes softer and is lessened in size, the increase of size being due to the disengagement of hydrogen gas, and the diminution caused by the escape of more or less fluid. The immediate effects of the operation varied. In one case no symptom followed, and in this the result was regarded as doubtful, although a cure was considered probable. In the others more or less constitutional disturbance followed, the symptoms being pain and fever, the temperature ranging between 100° and 103° F. The duration of the fever was from two to nineteen days, the latter in one case only. As has been observed in some of the cases treated by puncture or by aspiration, a rash appeared on the skin—in some instances scarlatinous, in others of urticaria. It is a curious circumstance that an eruption of urticaria is reported to have appeared in one subject in whom a rupture of the sac into the peritoneal cavity is supposed to have occurred.

²²⁶ On the Electrolytic Treatment of Tumors, etc., London, 1867.

²²⁷ Medico-Chirurgical Transactions, 1871, p. 1 et seq.

Although so little change in the tumor occurs immediately after the operation, yet it undergoes slow absorption, and ultimately disappears. The time occupied in the disappearance of the tumor varies from a few weeks to many months, the difference being due probably to the situation of the growth, those occupying the substance of the liver requiring a longer time to fill up.

Fagge and Durham report a case in which simple acupuncture was followed by a result apparently as good as obtained by electrolysis, and other similar experiences have been published. If the simple introduction of a needle suffices to arrest the growth of a hydatid cyst and induce its atrophy, of course the more complex procedures will be abandoned.

The tendency of the treatment of hydatid cysts has constantly been toward simplicity, and the success occurs in a direct ratio thereto. In forming an estimate of the relative value of the methods of treatment, the average of mortality of each plan becomes the most important factor. Simple tapping and paracentesis, the most frequently adopted mode of treatment, is not without immediate and remote danger. Of 46 cases carefully tabulated by Murchison,²²⁸ there were 3 deaths properly attributable to the operation; but the after results—suppuration of the cyst and its consequences, peritonitis, etc.—cannot be measured so accurately. About two-thirds of the cases thus treated result in cure, and in a majority of these a single operation suffices. The injection of the various substances which have been employed for that purpose does not seem to increase the proportion of cures, and their use distinctly enhances the dangers of the treatment. At present, the decision as to the method of treatment to be employed in any case should be made between simple tapping, electrolysis, and acupuncture. Of these, the last mentioned, it can hardly be doubted, is the method which is most desirable, for although it has not been employed so largely as the others, thus far the results have been better: the percentage of recoveries without accident has been higher relatively than by other methods of treatment. As acupuncture presents no special difficulties or dangers, and is but little painful, it may be tried first, reserving more formidable measures for the failures by this simple expedient.

²²⁸ Clinical Lectures on Diseases of the Liver, loc. cit.

Distoma hepaticum and Distoma lanceolatum (Liver-Flukes).

The Distoma hepaticum, entitled by Linnæus Fasciola hepatica, occurs very frequently in herbivorous animals and occasionally in the biliary passages of man.²²⁹ It is, however, less important than the Distoma lanceolatum, which, although much smaller than the former, occurs in much larger numbers.

²²⁹ Davaine, Traité des Entozoaires, Paris, 1877, p. 240 et seq.; also, Cobbold, Entozoa, p. 148.

Distoma hepaticum is a leech-like parasite from 25 to 30 mm. in length, of a brownish color, smooth to the naked eye, but thickly covered with minute spikes or spines to be seen with a low power, and provided with a cephalic (entrance to oral cavity) and an abdominal sucking disk, which are also organs of locomotion. The Distoma lanceolatum owes its name to its lancet shape; it is smaller than D. hepaticum, measuring about 8 mm. in length and half this or less in width; it is unprovided with spines, but contains two suckers at the side. Both parasites are hermaphrodite; the ova, according to Cobbold (p. 166), have "an average longitudinal diameter of ¹/180, whilst their greatest transversal measurement is about ¹/270." These ova are capable of some movement, provided as they are with a ciliated envelope.

The disease known as the rot in sheep, and a peculiar cachexia entitled by Davaine la cachexie aqueuse, are caused by the presence of distoma. The ova gain access to man through the use of unwashed cress, lettuce, and similar vegetables eaten in the raw state, and in drinking-water. Fortunately, this accident is rare. The number of reported examples collected from all sources by the indefatigable Davaine is twelve.²³⁰

²³⁰ Ibid., p. 253 et seq.

The larger distoma passes into the common and hepatic duct and gall-bladder, whilst the smaller (lanceolatum) enters the finer ramifications, and, there multiplying, several consequences may ensue. The irritation caused by their presence and development will excite a more or less severe cholangitis, or, accumulating in sufficient numbers, an actual obstruction will be induced, and jaundice and structural alterations of the liver will in turn be brought on.

The DIAGNOSIS of such a malady is, in the very nature of the case, uncertain at best, and in most cases impossible. Nevertheless, it may be made in rare instances. The existence of the rot may cast suspicion on the mutton and kitchen vegetables so situated as to suggest the possibility of contamination with the ova of distoma. Definite and conclusive information will be afforded by the presence of the ova, still more of the more or less fully-developed parasite, in the feces of a patient effected by the symptoms of catarrhal jaundice or occlusion of the biliary passages. By tapping the gall-bladder parasites may be withdrawn.

The SYMPTOMS are those common to cases of catarrh of the bile-ducts (cholangitis), catarrhal jaundice, or occlusion of the passages, as may be. As these have been detailed under their respective heads, it is not necessary to repeat the observations already made.

As regards the TREATMENT, in addition to the methods of management recommended in such cases it may be stated that the use of certain parasiticides offers a reasonable prospect of good results. Creasote, bichloride of mercury, thymol, eucalyptol, oil of wintergreen (gaultheria), and similar agents are rational remedies and should be fairly tried.

Parasites in the Portal Vein.

The entozoön which by its presence in the blood causes the disease chyluria also inhabits the portal vein. In some parts of the world—Brazil more especially—this disease is exceedingly common. It has occurred also in two or three instances in England, and the writer has had a case within the past year (1884) in Philadelphia. The parasites in this case were found in immense numbers in the urine.

The blood of the portal vein sometimes is actually filled, and the liver substance itself is penetrated, by them, but nothing is known of the alterations they induce in these organs. When cases of hæmaturia or chylous urine due to the Filaria sanguinis hominis occur, the changes are not confined to the urinary organs, but often, doubtless, involve the liver. There are no signs in the present state of our knowledge by which the existence of these parasites in the portal vein and liver can be determined.