Cholesterol stones

The altered composition of bile increases the capacity for cholesterol uptake. Thus, gallstones can be dissolved in the course of a 1- to 2 y treatment, provided that cholesterol stones are pure and not too large (<15 mm), gall bladder function is normal, liver disease is absent, and patients are of normal body weight. UCDA is more effective (daily dose, 8-10 mg) and better tolerated than is CDCA (15 mg/d frequent diarrhea, elevation of liver enzymes in plasma). Stone formation may recur after cessation of successful therapy. 

The cholesterol excreted with the bile is poorly water-soluble. Together with phospholipids and bile acids, it forms micelles (see p. 270), which keep it in solution. If the proportions of phospholipids, bile acids and cholesterol shift, gallstones can arise. These mainly consist of precipitated cholesterol (cholesterol stones), but can also contain Ca " salts of bile acids and bile pigments (pigment stones). 

Contraindications Allergy to bile acids, calcified cholesterol stones, chronic hepatic disease, radiolucent bile pigment stones, radiopaque stones... 

H-12) Gallstones. Most gallstones are composed mainly of cholesterol. Bile salts and phospholipids normally prevent the precipitation of cholesterol, but cholesterol stones may form when the cholesterol/bile salt-phospholipid ratio increases excessively. Cheno-deoxycholate may be used as oral therapy for cholesterol gallstones. It not only provides an extra recirculating source of bile acids but inhibits the rate-limiting step in cholesterol biosynthesis. 

Methyl-tert-butylether and monoctanoin are solvents that are used for the rapid dissolution of cholesterol gallstones in patients who are not considered suitable for surgery. They are given by direct infusion into the gallbladder (1). However, they are suitable only for cholesterol stones, take too long to act, are often not successful, and have high rates of adverse effects (2). 

Intermediate connective tissues, muscle, blood, cartilage, cholesterol stones, uric acid stones. 

Formation of cholesterol stones involves the precipitation of cholesterol from supersaturated bile. 

Chenodiol, a bile acid with cholehtholytic properties (250 mg b.i.d. for 2 weeks), is indicated in dissolution of radiolucent cholesterol stones (gallstones) when systemic disease or age... 

Bile contains cholesterol and bile salts, the latter being important in keeping cholesterol in solution. An increase in cholesterol concenira-Hon ora decrease in bile salts may result in the formation of cholesterol. stones, if they give rise to symptoms, laparoscopic cholecystectomy i.s the treatment of choice. However, smalt non-calcified stones may be dissolved by prolonged oral adniinislration of the bile acid ursodeoxycholic acid, which decreases the cholesterol content of bile by inhibiting an enzyme involved in cholesterol formation. 

During this stage, the stone grows from micro- to macroscopic size by the deposition of the major stone constituents. For cholesterol stones, at least, this appears to require a bile that is supersaturated with respect to cholesterol. The capacity of bile to hold cholesterol in solution varies from species to species (11), and this accounts for the difficulty in producing cholesterol gallstones in some species and the relative ease with which they can be produced in others. 

The importance of the type of carbohydrate was studied in hamsters receiving diets containing 2% lard (60). Glucose (72.3%) gave 100% cholesterol stones, whereas sucrose gave predominantly amorphous pigment stones only two of seven contained cholesterol. Rice starch and lactose (72.3 7o) completely prevented lithiasis. In a second series, when rice starch was sub-... 

In a study on the effects of hormones, testosterone-treated males and estrogen-treated females had a lower incidence of amorphous pigment stones than gonadectomized animals but may have had a higher incidence of cholesterol stones the total incidence was similar (66). Progesterone, on the other hand, lowered the incidence of cholesterol stones in females. Deoxycorticosterone had no clear effect on stone formation. Desiccated thyroid lowered and methyl thiouracil raised the ratio of cholesterol/amorphous pigment stones. 

Shioda (82) investigated the effect of dietary constituents on gallstone formation in golden hamsters. Like Dam, he found that hamsters on a low-fat diet frequently formed cholesterol gallstones. The addition of unsaturated fats (codliver oil, sesame oil) prevented cholesterol stones but allowed the development of amorphous pigment stones. Cholesterol stones correlated well with increased cholesterol and decreased bile acids and phospholipids in hepatic bile that was consequently supersaturated with respect to cholester-... 

Raw starch (/5-starch) protected against gallstones, but when predigested with enzymes (83) or cooked (84) the starch (a-starch) became absorbable and the incidence of cholesterol stones was as great as in animals on the glucose, fat-free diet. The addition of neomycin to the a-starch, butterfat, 1 % cholesterol diet protected completely against cholesterol stones but resulted in a 100% incidence of amorphous pigment stones (84). 

Hikasa et al. (76) interpreted the results of these studies as indicating that cholesterol stone formation in hamsters is related to a relative deficiency in the supply of linoleic acid or its conversion to arachidonic acid and other unsaturated derivatives by pathways dependent on pyridoxal phosphate. Nonabsorbable carbohydrates were thought to favor growth of elements of the bacterial flora that produce vitamin Be and thus prevent stone formation. Diets high in saturated and short-chain fats, and low in linoleic acid, may also inhibit conversion of pyrisoxine to pyrisoxal phosphate and so favor stone... 

Complete analyses of these stones have not been published. However, in view of the low cholesterol content reported in the stones, it is doubtful that these stones can be considered to be primarily cholesterol stones. The major constituents have not been identified, but rabbits form stones of various types readily, as shown by work on cholestanol-induced cholelithiasis and the early work on stasis and infection as etiological factors. 

It is of interest that the diet used in dogs resembles that used by Dam and Christensen (46) to produce gallstones in hamsters in being high in carbohydrate and low in protein and fat. The low protein resulted in an increased glycine/taurine ratio of biliary bile salts in both dogs (113) and hamsters (61). Furthermore, addition of 1 % cholesterol to the hamster diet decreased the incidence of cholesterol stones and increased the incidence of... 

Calcium has been recognized as a constituent of gallstones since the earliest chemical studies (see reference 118). It occurs as calcium carbonate (either calcite or aragonite), calcium phosphate (apatite), calcium bilirubinate, or the salts of bile acids and fatty acids. In normal hepatic bile, the calcium concentration is about 21 mg %. It is about 45 mg % in normal gallbladder bile and about twice that in the gallbladder bile of patients with cholesterol stones (119). The concentration of calcium is said to vary with the concentration of bile salts (3). Apparently, calcium in bile is bound in part to bile salt micelles, and under normal conditions this complex remains stable and soluble (120). However, under appropriate conditions of pH, calcium concentration, and anion concentration, calcium salts may precipitate. 

These results raise the question of whether these amorphous stones containing calcium bile salts could be related to the pathogenesis of the cholesterol stones. Glycine-conjugated bile salts, particularly of the less soluble compounds such as chenodeoxycholate and lithocholate, have been found in greater proportions in the centers of human gallstones (167), and it would be of interest to know whether this is the case in the cholesterol stones that frequently coexisted in these animals. 

As is often the case for biological products, the term pure is a misnomer no stones are made of pure cholesterol or concentric layers of pure cholesterol and calcium bilirubinate. Stones often contain other components such as iron, proteins, and mucopolysaccharides. In fact, even the purest cholesterol stones seem to contain small amounts of protein or polysaccharide at their center, a finding that is in keeping with the concept that gallstones, like kidney... 

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