Biliary calcium secretion in the dog occurs primarily by passive convection and diffusion and is linked to bile flow

Despite the importance of biliary calcium in the pathogenesis of gallstones, little is known about the sites or modes of entry of calcium into bile. We here examine the mechanisms of calcium entry into canine bile by comparing the entry of calcium, over a wide range of bile flows (2.4 to 38.0 microliters/kg per minute), with that of potassium, a small ion that is passively distributed throughout the biliary tract and that is also subject to alteration by Gibbs-Donnan forces. It is shown that (1) the concentrations of free ionized calcium, [Ca++], increases in an apparently linear fashion with increasing total bile salt concentration at low bile flow, whereas the rise in [Ca++] is strongly blunted at high rates of flow; (2) the entry of both calcium and potassium into bile is tightly linked to bile flow; and (3) calcium outputs are linearly related to potassium outputs with an intercept at the origin. These results indicate that the canaliculus is permeable to Ca++ ions, and that Ca++ enters bile primarily by passive convection and diffusion. Calcium entry is thus tightly linked to the water flux generated by bile salt secretion. Such passive entry and distribution indicate that calcium will always be present in bile and that possible therapeutic reduction of biliary [Ca++] for treatment, and possibly prevention of calcium-containing gallstones, will require sustained chelation of calcium within the lumen of the biliary tract.