Abstract

The enterohepatic circulation of bile acids in man is reviewed. The chemistry of biliary bile acids is summarized and related to the formation of primary bile acids in the liver and secondary bile acids in the intestinal lumen. New findings showing that lithocholic acid is absorbed in man are presented, and the recent experiments showing that lithocholic acid is extensively sulfated are reviewed. The consistent hepatotoxicity of chenodeoxycholic acid in the rhesus monkey, which contrasts with its non-toxicity in man, is explained by the inability of the rhesus monkey to sulfate abosrbed lithocholic acid; this accumulates in the enterohepatic circulation of the monkey causing liver damage. In man, absorbed lithocholic acid is rapidly sulfated, and the sulfated conjugates are excreted fecally without enterohepatic cycling. The physical chemistry of bile is highlighted, and it is shown that the saturation of bile with cholesterol depends on the amount of bile acids passing through the liver: at low bile acid flow rates, such as occurs during overnight fasting, bile is supersaturated in both gallstone and healthy persons. Chenodeoxycholic acid decreases cholesterol secretion into bile, renders bile unsaturated during most of the day and night, and thus induces gallstone dissolution.