The continuing importance of bile acids in liver and intestinal disease

Bile acids, the water-soluble, amphipathic end products of cholesterol meta bolism, are involved in liver, biliary, and intestinal disease. Formed in t he liver, bile acids are absorbed actively from the small intestine, with e ach molecule undergoing multiple enterohepatic circulations before being ex creted. After their synthesis from cholesterol, bile acids are conjugated w ith glycine or taurine, a process that makes them impermeable to cell membr anes and permits high concentrations to persist in bile and intestinal cont ent. The relation between the chemical structure and the multiple physiolog ical functions of bile acids is reviewed. Bile acids induce biliary lipid s ecretion and solubilize cholesterol in bile, promoting its elimination. In the small intestine, bile acids solubilize dietary lipids promoting their a bsorption. Bile acids are cytotoxic when present in abnormally high concent rations. This may occur intracellularly, as occurs in the hepatocyte in cho lestasis, or extracellulary, as occurs in the colon in patients with bile a cid malabsorption. Disturbances in bile acid metabolism can be caused by (1 ) defective biosynthesis from cholesterol or defective conjugation, (2) def ective membrane transport in the hepatocyte or ileal enterocyte, (3) defect ive transport between organs or biliary diversion, and (4) increased bacter ial degradation during enterohepatic cycling. Bile acid therapy involves bi le acid replacement in deficiency stales or bile acid displacement by ursod eoxycholic acid, a noncytotoxic bile acid. In cholestatic liver disease, ad ministration of ursodeoxycholic acid decreases hepatocyte injury by retaine d bile acids, improving liver tests, and slowing disease progression. Bile acid malabsorption may lead to high concentrations of bile acids in the col on and impaired colonic mucosal function; bile acid sequestrants provide sy mptomatic benefit for diarrhea. A knowledge of bile acid physiology and the perturbations of bile acid metabolism in liver and digestive disease shoul d be useful for the internist.