Altered gallbladder concentration of biliary lipids during early cholesterol gallstone formation

Whether gallbladder absorptive function is altered during formation of cholesterol gallstones is unclear. We tested the hypothesis that alterations in biliary lipid composition present during early cholesterol gallstone formation enhance gallbladder absorption, as manifested by an increase in the ratio of gallbladder to hepatic bile lipid concentrations. Prairie dogs received either control or a 0.4% cholesterol-enriched chow for two or six weeks. The bile acid pool of each animal was labeled with [14C]cholic acid. Gallbladder and hepatic bile were analyzed for lipid composition with calculation of indices for cholesterol saturation, gallbladder stasis, and gallbladder absorption. Animals maintained on cholesterol-enriched chow for two weeks had a significant increase, as compared to controls, in the ratio of gallbladder to hepatic bile concentrations of cholesterol (8.66 +/- 1.09 vs 5.76 +/- 0.48), phospholipids (4.76 +/- 0.42 vs 3.21 +/- 0.34), bile acids (6.42 +/- 2.20 vs 3.54 +/- 0.46), and total lipid content (6.22 +/- 0.94 vs 3.64 +/- 0.43). These changes occurred at a time when gallbladder stasis is present and cholesterol crystals are forming, but prior to stone formation. Similar findings were noted in six-week cholesterol-fed prairie dogs. We propose the uniformly increased ratios of biliary lipids result from enhanced gallbladder absorption of water and sodium. The resulting increase in solute concentration may promote nucleation and, therefore, may be an important etiologic factor in cholesterol gallstone formation.