Chapter II: Structural Diseases of the Liver (1)

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 {984} 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 Bartels[39] 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.

[Footnote 39: _Deutsches Archiv für klin. Medicin_, Band iv. p. 265.]

[Footnote 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.

{985} 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 Virchow[41] 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 Talamon[43] such increase of the connective tissue is denied, but Thierfelder[44] 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 Liebermeister[45] {986} 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.

[Footnote 41: _Archiv für path. Anat., etc._, Band v. p. 289.]

[Footnote 42: Talamon, _Recherches anatomo-pathologiques et cliniques sur le Foie cardiaque_, Paris, 1881 (pamphlet).]

[Footnote 43: _Ibid._]

[Footnote 44: _Atlas_.]

[Footnote 45: _Beiträge zur path. Anat. u. Klinik der Leberkrankheiten_, Tubingen, 1864, p. 209 _et seq._]

[Footnote 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 {987} 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 {988} 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.

{989} 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]

[Footnote 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 {990} 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 Laennec[48] 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. Carswell[49] first described the anatomical changes with accuracy, and illustrated them with correct drawings. The following year Hallmann[50] 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.

[Footnote 48: _Traité de l'Auscultatlon médiate_, tome ii. p. 501.]

[Footnote 49: _Illustrations of the Elementary Form of Diseases_, fasciculus 10, plate 2.]

[Footnote 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 Wettergreen[51] of hypertrophic sclerosis, in which neither a syphilitic nor paludal cause could be ascertained. Cayley[52] 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 {991} and fifty years. Yet Virchow[56] 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. Virchow[58] 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.

[Footnote 51: _Hygeia_, 1880, quoted by _London Medical Record_, March 15, 1881.]

[Footnote 52: _Transactions of the Path. Society of London_, vol. xxvii., 1876, pp. 186, 194.]

[Footnote 53: _Clinical Lectures_, _loc. cit._]

[Footnote 54: _Clinical Treatise, etc._, Syd. Soc. ed., by Murchison.]

[Footnote 55: _Clinical Lectures_, _loc. cit._]

[Footnote 56: _Archiv f. path. Anat._, Band xxii. p. 426.]

[Footnote 57: Baer, _Der Alcoholismus_, Berlin, 1878, p. 62 _et seq._]

[Footnote 58: _Virchow's Archiv_, vol. xv. p. 281; also, Lancereaux, _A Treatise on Syphilis_, Syd. Soc. ed.]

[Footnote 59: _Memoirs of the Sanitary Commission_, medical volume.]

J. Wickham Legg[60] and Charcot[61] 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 Solowieff[63] 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.

[Footnote 60: _On the Bile, Jaundice, etc._, _loc. cit._, p. 351 _et seq._]

[Footnote 61: _Leçons sur les Maladies du Foie, etc._, p. 231 _et seq._]

[Footnote 62: _On the Bile, Jaundice, etc._, _loc. cit._, p. 355.]

[Footnote 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 {992} 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.

[Footnote 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 (Poulin[65]).

[Footnote 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 Beale[70] even maintained that the change began in {993} 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 Litten[71] 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.

[Footnote 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.]

[Footnote 67: Förster, _Lehrbuch der pathologischen Anatomie_, Jena, 1873, p. 264.]

[Footnote 68: Cornil, "Note sur l'État anatomique des Canaux biliaires et des Vaisseaux sanguins dans la cirrhose du foie," _Gaz. méd. de Paris_, 1883.]

[Footnote 69: Charcot, _Leçons sur les Maladies du Foie, etc._, p. 226.]

[Footnote 70: _Archives of Medicine_, vol. ii. p. 82.]

[Footnote 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 {994} 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 {995} 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's[72] 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.

[Footnote 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 {996} 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, Hoffmann[74] 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.

[Footnote 73: _Krankheiten des Chylopoiet. Syst._, _loc. cit._]

[Footnote 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 Jackson[75] 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.

[Footnote 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 {997} 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's[76] 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.

[Footnote 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. Graves[77] 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 {998} 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.

[Footnote 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.

[Footnote 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.

{999} 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 Müller[82]) 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.

[Footnote 79: Quoted by Legg, p. 233.]

[Footnote 80: Quoted by Krusenstern.]

[Footnote 81: _Virchow's Archiv_, Band lxv. p. 412.]

[Footnote 82: _Archiv für experimentelle Pathologie und Pharmakologie_, Band i. p. 213.]