The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man

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Abstract
The importance of calcium in gallstone formation is increasingly recognized. Calcium carbonate is an important constituent of gallbladder stones and may be present in the nidus of cholesterol stones. Secondary deposition of calcium carbonate on the surface of cholesterol gallstones is an important reason for failure of oral bile acid dissolution therapy. We sought to determine the effects of bile acids on the crystallization conditions of calcium carbonate in bile. We studied 18 patients with choledocholithiasis with a percutaneous or endoscopically placed catheter high in the biliary tree. Samples of bile in the basal state and following replacement of the bile acid pool with cholic acid, chenodeoxycholic acid and ursodeoxycholic acid were analyzed for total calcium, ionized calcium, bicarbonate and carbonate, and the saturation index for calcium carbonate was calculated. Hepatic bile in the basal state was supersaturated with calcium carbonate. Total calcium concentrations rose linearly with rising bile acid concentrations but ionized calcium was maintained in a relatively narrow range. These data are consistent with an important role for bile acids in binding calcium. Extrapolation of the linear regressions between bile acid concentration and calcium concentrations suggested that in the absence of bile acids, biliary calcium concentrations are in passive equilibrium with plasma. Chenodeoxycholic acid and ursodeoxycholic acid caused a bicarbonate-rich choleresis and significantly augmented the saturation index for calcium carbonate, whereas cholic acid caused no change. In contrast with animal models, the apparent choleretic activity of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid was similar, and no hypercholeresis was observed with ursodeoxycholic acid. Chenodeoxycholic acid and ursodeoxycholic acid therefore increase the thermodynamic possibility for calcium carbonate precipitation.