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.
Venneman
Niels Gerard
NG
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
van Erpecum
Karel Johannes
KJ
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D001647:Bile Acids and Salts / Q000378:metabolism*; D001657:Biliary Dyskinesia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D001692:Biological Transport / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D003460:Crystallization; D018450:Disease Progression; D016473:Gallbladder Emptying / Q000502:physiology*; D042882:Gallstones / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis; D013261:Sterols / Q000378:metabolism*
C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D008074:Lipoproteins; D013261:Sterols; D002784:Cholesterol