Chapter III: Affections of the Biliary Passages (1)

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, Virchow[150] was the first to treat of this condition systematically. Amongst recent writers, Harley[151] 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.

[Footnote 150: _Archiv für path. Anat._, Band xxxii. p. 117 _et seq._]

[Footnote 151: _Diseases of the Liver_, _supra_.]

[Footnote 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 {1052} 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, {1053} 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, {1054} 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; {1055} 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 {1056} 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, {1057} 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.

{1058} 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

[Footnote 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 {1059} 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 case[154] 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.

[Footnote 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 {1060} 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] {1061} 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.

[Footnote 155: Thudicum, J. L., _On Gall-stones_, London, 1863; also Frerichs, _op. cit._, vol. ii. p. 503.]

[Footnote 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: {1062}

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.
Salts 8.
-----
140.

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 {1063} 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 Ord[157] 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.

[Footnote 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; Wolff[159] 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.
Whole No. 395
From infancy to 30 18
From 30-70 377

FAUCONNEAU-DUFRESNE.
Whole No. 91
Before 20 10
From 20-40 13
From 40-90 68

WOLFF.
Whole No. 45
Before 20 3
From 30-60 42

DURAND-FARDEL.
Whole No. 230
Before 20 2
From 20-30 28
From 30-60 162
From 60-90 38

CYR.
Whole No. 558
Before 20 20
From 21-30 208
From 31-40 185
From 41-50 91
From 51-60 48
Above 60 6

[Footnote 158: _Traité de l'Affection calculeuse du Foie_, Paris, 1851.]

[Footnote 159: _Virchow's Archiv f. path. Anat., etc._, Band xx., 1861, p. 1.]

[Footnote 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 {1064} 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 (Luton[161]). Charcot[162] 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.

[Footnote 161: Jaccoud's _Dictionnaire encyclopéd._, art. "Voies Biliaires;" _idem._, _Bull. gén. de Thérap._, March 15, 1866.]

[Footnote 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 {1065} 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. Beneke[164] 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.

[Footnote 163: _A Treatise on Gall-stones_, p. 214.]

[Footnote 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, Frerichs[165] 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. {1066} 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).

[Footnote 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 {1067} 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]

[Footnote 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.