Supersaturation of canine gallbladder bile with calcium bilirubinate during formation of pigment gallstones

Analogous to cholesterol gallstones forming in bile supersaturated with cholesterol, pigment gallstones may form in bile supersaturated with calcium bilirubinate. We tested this hypothesis in a dietary model of pigment gallstones. The concentration of ionized calcium (Ca⁺⁺) and unconjugated bilirubin (UCB) was measured in 15 normal dogs and in 15 dogs with pigment gallstones induced by 6 weeks of a methionine-deficient diet. Although there was minimal change in the gallbladder's ability to acidify or concentrate bile, both [Ca⁺⁺]and [UCB]markedly increased. These values were compared with equilibrium concentrations in model bile solutions. In all normal bile, the [UCB]was equal to or lower than the mean [UCB]concentration of model bile solutions with comparable [Ca⁺⁺]. However, in all but one bile sample from dogs with pigment gallstones, the [UCB]exceeded this concentration and was therefore supersaturated with calcium bilirubinate. This supports the hypothesis that calcium bilirubinate precipitation is important in the formation and growth of pigment gallstones.