Part 177

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 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.

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. 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

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). 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.

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. 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.

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. {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).

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).