Gallstones cholic acid

Galls tone-solubilizing (gallstone-dissolving) drugs, such as ursodiol (Actigall), suppress die manufacture of cholesterol and cholic acid by die liver. The suppression of die manufacture of cholesterol and cholic add may ultimately result in a decrease in die size of radiolucent gallstones. 

In the bile cholesterol is kept soluble by fats, phospholipids like lecithin and by bile acids. The important bile acids in human bile are cholic acid, chen-odeoxycholic acid or chenodiol and ursodeoxycholic acid or ursodiol. Bile acids increase bile production. Dehydrocholic acid, a semisynthetic cholate is especially active in this respect. It stimulates the production of bile of low specific gravity and is therefore called a hydrocholeretic drug. Chenodiol and ursodiol but not cholic acid decrease the cholesterol content of bile by reducing cholesterol production and cholesterol secretion. Ursodiol also decreases cholesterol reabsorption. By these actions chenodiol and ursodiol are able to decrease the formation of cholesterolic gallstones and they can promote their dissolution. 

Part of the cholesterol newly synthesized in the liver is excreted into bile in a free non-esterified state (in constant, amount). Cholesteiol in bile is normally complexed with bile salts to form soluble cholic acids, Free cholesterol is not readily soluble and with bile stasis or decreased bile salt concentration may precipitate as gallstones. Most common gallstones are built of alternating layers of cholesterol and calcium bilirubin and consist mainly (80-90%) of cholesterol. Normally. 80% of hepatic cholesterol arising from blood or lymph is metabolized to cholic acids and is eventually excreted into the bile in the form of bile salts. 

Bile Salts Enable the Digestion of Lipids Cholesterol is the precursor of both steroids and bile salts and is an integral component of cell membranes. It is eliminated from the body via conversion to bile salts and direct secretion into the bile. In fact, the word cholesterol (from the Greek chole (bile) and stereos (solid)) was used originally to describe the material of which gallstones are made. In the process of degradation, it is converted to the primary bile acids cholic acid and chenodeoxycholic acid in approximately equal amounts. The salts of these acids are excreted in bile. They perform two important functions in the digestive tract ... 

Derivation From bile and gallstones, from deoxy-cholic acid or cholic acid. 

Mosbach and Bevans (134) showed that cholestanol-induced cholecystitis and cholelithiasis could be inhibited by the simultaneous administration of dehydrocholic acid and that the extent of inhibition depended on the relative concentrations of the two steroids. Similar observations were made by Ricci et al, (135). Deoxycholic and cholic acids were also effective inhibitors (136), but hyodeoxycholic acid did not suppress gallstone formation and appeared to increase biliary tract inffammation. Several non-bile acid choleretics were without inhibitory effects (136). Lindelof and van der Linden (32) found that intravenous injections of cholecystokinin every 8 hr did not suppress and may actually have enhanced gallstone formation. The inhibition of cholelithiasis by dehydrocholic, deoxycholic, and cholic acids was not accompanied by a decrease in cholestanol absorption but did result in increased tissue cholestanol levels, suggesting a decrease in the conversion of this sterol to bile acids (134,136). Conversely, methyl testosterone apparently inhibited stone formation by interfering with cholestanol absorption, since tissue and serum levels of cholestanol were reduced (137). Olive oil has been shown to facilitate stone formation (138), perhaps by enhancing cholestanol absorption (137). 

By 1900, only deoxycholic acid and cholic acid had been obtained in pure crystalline form. In 1911, Fischer (30) isolated lithocholic acid from a gallstone in the course of his classical studies on the bile pigments. Hyodeoxy-cholic acid was purified by Windaus and Bohne in 1923 (31) and chenodeoxy-cholic acid was rediscovered almost simultaneously by Wieland and Reverey (32) and by Windaus et al. (33) in 1924. 

Lithocholic acid was first isolated from a gallstone by Fischer in 1911 (30). It was later isolated from ox bile (1 g from 100 kg of bile) (64) from rabbit bile (0.4 g from 900 ml) (65) and subsequently from monkey, human, pig, and guinea pig bile (2, 66, 67). Lithocholic acid has been identified as one of the bile acids in human blood (68) and as a principal fecal bile acid. Moset-tig et al. (69) isolated lithocholic acid from human stool and estimated its concentration to be 3 g/100 kg of fresh stool. Lithocholic acid is particularly insoluble, is not hydroxylated to an appreciable extent in man (70), and may be the cause of liver disease (4). In early studies lithocholic acid was not available in sufficient amounts from natural sources and was prepared from cholic acid. Lithocholic acid was particularly valuable in establishing the correspondence of the B/C ring structure between bile acids and cholesterol (71). 

The natural occurrence of the 5a-epimer of deoxycholic acid was first demonstrated by Danielsson, Kallner, and Sjovall (62). The original isolation of this compound was probably by Kishi (61) who named the unidentified acid lagodeoxycholic acid from rabbit bile. In addition to its occurrence in rabbit bile, allodeoxycholic acid is present in rabbit feces (62) and accumulates as the glycine conjugate in gallstones of rabbits fed cholestanol (168). Allodeoxycholic acid may be synthesized from cholic acid by reactions similar to the preparation of allocholic acid (62,168). 

Nevertheless, having shown that the senun cholesterol concentration can be exchanged by the type of carbohydrate eaten the possible mechanisms whereby this is achieved must be considered. One possibility that has been explored is that the rate of secretion and composition of bile is affected. In 1919 it was discovered that sucrose, in the diet of dogs with a bile fistula, suppressed bile acid excretion (Foster et al., 1919) and this was found to be true in rats where both sucrose and dextrose decreased cholic acid in the bile whereas cornstarch did not affect the level (Portman et al., 1955). The half-life of cholic acid was also influenced by the type of dietary carbohydrate (Portman and Murphy, 1958). In a series of experiments on hamsters it has been shown that young animals on a fat-free diet have a marked tendency to form cholesterol gallstones when the dietary carbohydrate was dextrose and showed no such tendency when the carbohydrate was starch (Dam and Christensen, 1961). 

Vlahcevic, Z. R., Bell, C. C., Buhac, I., Farrar, J. T., and Swell, L., Diminished bile acid pool size in patients with gallstones. Gastroenterology 59, 165-173 (1970). Vlahcevic, Z. R., Juttijudata, P., Bell, C. C., and Swell, L., Bile acid metabolism in patients with cirrhosis Cholic and chenodeoxycholic acid metabolism. Gastroenterology 62, 1174-1181 (1972). 

Enteroliths are concretions of precipitated bile acids which form in the intestinal tract and thus differ from gallstones, which consist mainly of cholesterol, bilirubin, or both. All but two enteroliths of which the composition has been determined have been found to be composed of choleic acid, a molecular coordinate complex of deoxycholic acid, and usually a fatty acid in a proportion of about 8 1. Of the remaining two, one enterolith was found in an afferent gastroenterostomy loop (84) and the other in a diverticulum of the second portion of the duodenum (85). Both of these enteroliths consisted of a mixture of unconjugated primary bile acids, cholic and chenodeoxycho-lic acids. 

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