Role of gallbladder mucus in the pathogenesis of cholesterol gallstones

Recent observations indicate that the hepatic secretion of lithogenic bile, gallbladder mucus hypersection, and gallbladder stasis are all critical factors in the pathogenesis of cholesterol gallstones. Using the prairie dog gallstone model, we investigated the interaction of these factors and the sequence in which they develop. The results of this study indicated that (1) gallbladder bile mucus concentration is elevated before cholesterol precipitation and increases progressively with the formation of cholesterol crystals, (2) cystic duct resistance increases in the presence of cholesterol crystals, but not fine, sonicated crystals increase cystic duct resistance. We conclude that these alterations trigger a self-perpetuating cycle of mucus hypersecretion, cholesterol crystallization, and gallbladder stasis which culminates in the formation of cholesterol gallstones.