Pathogenesis of Gallstones

Cholesterol gallstone formation is a complex process and involves phase separation of cholesterol crystals from supersaturated bile. In most cases, cholesterol hypersecretion is considered the primary event in gallstone formation. The sterol is transported through the hepatocytic canalicular membrane by ABCG5-G8. Expression of this transport protein is regulated by transcription factor Liver X Receptor-alpha, which may be responsible for biliary hypersecretion. Hydrophobic bile salt pool, bile concentration, excess pronucleating mucin, and impaired gallbladder and intestinal motility are secondary phenomena in most cases but nevertheless may contribute to gallstone formation.