Induced Alterations in Composition of Bile of Persons Having Cholelithiasis

Abstract

Bile acids and lecithin are the major solubilizing agents for cholesterol in bile. The enterohepatic circulation of bile acids may be important in the regulation of the proportions of individual bile acids and of the total amount and relative proportions of bile acids, lecithin, and cholesterol in bile. Experiments were designed to determine the effect on duodenal bile composition of administering or sequestering bile acids. Samples were obtained using a double lumen tube and cholecystokinin stimulation of gallbladder contraction. In bile from subjects with cholelithiasis, the proportion of chenodeoxycholic acid, with respect to total bile acids, was significantly less than that in bile from normal subjects. Administration of cholic, chenodeoxycholic, or hyodeoxycholic acid, clofibrate (Atromid-S) plus cholic acid, or cholestyramine (Questran) to women with cholelithiasis induced significant alterations in duodenal bile composition. In response to cholic acid with or without clofibrate, cholic acid plus deoxycholic acid virtually replaced chenodeoxycholic acid in bile, whereas, after chenodeoxycholic acid administration, this acid comprised 95% of bile acid in bile. Hyodeoxycholic administration induced a small but significant increase in the percentage of chenodeoxycholic acid in bile. Cholestyramine administration removed deoxycholic acid from bile and resulted in a significant increase in cholic acid and a decrease in chenodeoxycholic acid. The ratio of the cholesterol-solubilizing agents in bile—bile acids plus lecithin—to cholesterol was significantly increased by the administration of chenodeoxycholic acid and significantly de­creased by administering clofibrate plus cholic acid. Among the other four groups, no changes in this ratio were observed after 4 months. No significant changes in gallstone size were detected by cholecystography and no adverse reactions to the administered agents were noted. Mechanisms whereby the lithogenic potential of bile was decreased by chenodeoxycholic acid and increased by clofibrate plus cholic acid may involve effects on synthesis, pool size, or secretion of bile acids, lecithin, or cholesterol.