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, 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

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

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

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

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

The number of calculi which may be present at any time or be produced in the course of years ranges from one to several thousand. The number is in inverse ratio to the size. One case 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.

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

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

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

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

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

Water 4

Solids 96

100

The solids consist of—

Cholesterin 98

Pigment 1

Inorganic or mineral matter 1

100

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

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

Cholesterin 98.1 97.4 70.6 64.2 81.4 84.3 trace. 0

Organic matter 1.5 2.1 22.9 27.4 15.4 12.4 75.2 18.1

Inorganic matter 0.4 0.5 6.5 8.4 3.2 3.3 24.8 91.9

Number of specimens 28 16 580 94 220 16 3 1

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

A calculus consists of three several parts: the nucleus, the body, the rind. A calculus of small or medium size may be a nucleus for the formation of a large one. Usually the nucleus consists of a bit of mucus, casts of the biliary ducts (Thudicum), inspissated bile, a blood-clot, a liver-fluke or other parasite, as a desiccated round-worm, or some foreign body, as a seed, or, as in one reported example, a globule of mercury. The central mass of mucus may contain a large proportion of pigment or crystals of cholesterin or lime-salts, giving it special characteristics. 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.

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

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

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

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

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

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

Bile contains, in 1000 parts,

Water 860

Solids 140

The solids of bile are,

Glycocholate and Taurocholate of soda 90.8

Fat 9.2

Cholesterin 2.6

Mucus 1.4

Pigment and extractive 28.0

Salts 8.0

140.0

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

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

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

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

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, of 91 cases, had 4 in infants; Wolff had 1 in a collection of 45 cases; and Cyr, 2 cases under ten in a group of 558 cases. The following table illustrates the influence of age on the productivity of gall-stones:

AUTHORS.

HEIN. FAUCONNEAU-DUFRESNE. WOLFF. DURAND-FARDEL. CYR.

Whole No. 395 Whole No. 91 Whole No. 45 Whole No. 230 Whole No. 558

From infancy to 30 18 Before 20 10 Before 20 3 Before 20 2 Before 20 20

From 30-70 377 From 20-40 13 From 30-60 42 From 20-30 28 From 21-30 208

From 40-90 68 From 30-60 162 From 31-40 185

From 60-90 38 From 41-50 91

From 51-60 48

Above 60 6

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

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

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

Although there is a general correspondence in the results of the observations on the age most liable, there are differences. Thus, Cyr, whose figures represent the experiences at Vichy, makes the age of maximum liability from twenty to forty years—distinctly earlier than any other observer; and hence it is necessary to bear in mind the extreme latitude of his diagnosis. Of my own collection, 30 in number, all doubtful cases excluded, there were 20 between thirty and fifty years, and 10 between fifty and seventy. Of these, 22 occurred in subjects between forty and sixty. The period of maximum liability is about fifty years of age. Cyr refers the difference of his statistics from those of other observers to the character of the patients. The preponderance in the number of cases of hepatic calculi at or about the fiftieth year is referable to the lessened activity of the nutritive functions at this period, and to the increase in the relative proportion of cholesterin in the blood in advanced life (Luton). Charcot 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.

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

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

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

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

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

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

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

Of all the conditions which favor the production of gall-stones, none are so influential as the bodily state and the associated dietetic peculiarities. Those troubled with these concretions, as they have occurred under my observation, have been either obese or have had a manifest tendency in that direction. They have had a strong inclination for the fat-forming foods, also for starchy, saccharine, and fatty articles, such as bread and butter, potatoes, beans and peas, pork, bacon, and fat poultry, etc. Harley thinks indulgence in bacon (p. 367) is a prime factor. Thudicum rejects this notion on chemical grounds, for obesity and the free consumption of fat cannot be concerned in the production of these bodies, because cholesterin is an alcohol. 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 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.

A Treatise on Gall-stones, p. 214.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

On Diseases of the Liver, p. 354.

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

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

Leçons sur la Maladies du Foie, p. 178.

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

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

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

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

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

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

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

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

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

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

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

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

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

COURSES AND COMPLICATIONS.—Although symptoms cease for the time being when the calculus passes into the duodenum, and although in most instances no after unpleasant effects are experienced, there are cases in which the presence of the concretion in the intestine proves to be fruitful of mischief. Calculi of very large size—from a pigeon's to a hen's egg—are also found in the intestine, without the occurrence of symptoms indicative of their migration. It has been shown that this silent migration of calculi from the liver-passages to the intestinal is not uncommon. Hepatic concretions are distinguishable from the intestinal by their crystalline form and by their composition. The former are usually polyangular, and are composed of cholesterin crystallized about a nucleus of bile-pigment, inspissated bile, or mucus. After entrance into the intestine, lime salts and mucus are deposited in successive layers, so that the form of the calculus is modified and its size increased. The solitary ovoid concretion is most frequently found in the intestine, without previous symptoms of hepatic source, and, although increased in size in the intestine, it retains its original shape. A specimen of this kind now in my possession illustrates these points. It is composed of cholesterin crystallized in radiating lines and concentric rings about a central nucleus of inspissated bile. Around the hepatic concretion there have formed layers of lime and mucus since it has reached the intestine, and after drying this rind became brittle and was readily detached. The polyangular calculus is apt to form the nucleus of a scybala-like mass of feces; hence in the search for these bodies every such mass should be broken up. An example of this has recently come under my own observation. Concretions of all sizes, having reached the intestines, as a rule pass down without creating any commotion, and are silently discharged. But various disturbances occur in some instances. Obstruction of the bowels is one of the results. A great may cases have been collected by Murchison, as many more by Leichtenstern, of impaction of the intestine produced by an accumulation of feces about a biliary concretion. A calculus may be retained in a fold or diverticulum of the small intestine, and may indeed cause a loop to be formed which in turn readily twists, becoming an immovable obstruction. This mode of obstructing the bowels is less common than the simple impaction. It is affirmed by some authorities, especially by Von Schüppel, that obstruction of the bowels—impaction—is more often caused by stones that have ulcerated through into the intestines than by those that have descended by the common duct; and this conclusion must be reached if jaundice has not been present. It is not only the size of the calculus which determines impaction, as has been stated: several may be agglutinated in one mass, and reflex spasm of the muscular layer may be induced by their presence in the bowel. Nevertheless, some enormous concretions have been found in the canal, and others have been discharged without special trouble. Hilton Fagge exhibited to the Pathological Society of London two gall-stones passed with the stools, measuring 2½ by 1/5 inches in long and short diameter, and Fauconneau-Dufresne refers to concretions of the size of a hen's egg. Mention has been made of one in the writer's possession of the size of a pullet's egg, which, until its discharge, caused a train of characteristic symptoms. These immense bodies may have ulcerated through from the gall-bladder or may have grown by successive deposits of carbonate and phosphate of lime after reaching the intestine.

Lectures on Diseases of the Liver, p. 573.

Ziemssen's Cyclopædia, vol. vii.

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

Op. cit.

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

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

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

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

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

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

Leçons.

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

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

Guy's Hosp. Rep., 1875.

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

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

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

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

Cyr, op. cit., p. 185.

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

Lectures on the Pneumogastric, 3d Lecture.

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

Clinique médicale.

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

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

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

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

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

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

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

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

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

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

Clinique médicale de l'Hôtel Dieu de Paris.

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

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

Gazette des Hôpitaux, 1856, June 19.

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

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

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

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

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

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

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

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