Volume 4 of the series Hepatology pp 223-249

The Role of the Gallbladder in Gallstone Formation

  • Eldon A. ShafferAffiliated withDivision of Medicine, Faculty of Medicine The University of Calgary

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For many years cholelithiasis was equated with disease of the gallbladder, causally linked through stasis and infection (1). The traditional concept that gallstone disease originated within the gallbladder remained firmly entrenched despite the prescient suggestion over a century ago that the essence of the problem might reside in the liver (2). During the past decade, the exciting developments made in our understanding of cholesterol gallstone formation have tended to de-emphasize the role of the gallbladder (3). The initial breakthrough came when cholesterol solubility in bile was defined by the relative molar proportions of the major biliary constitutents: bile salts, phospholipid and cholesterol. Admirand and Small (4) then proposed that the underlying defect in cholesterol gallstone formation was the production of gallbladder bile containing an excess of cholesterol relative to the solubilizing capacity of bile salts and phospholipid. The source of this abnormal or lithogenic bile was subsequently shown to be the liver, so that gallstone disease evolved into a metabolic disorder (5,6). In this scheme, the gallbladder had a secondary role, providing a passive receptacle for precipitation of cholesterol microcrystals from unstable bile and their subsequent growth into macroscopic stones (7). Commonly overlooked was the fact that the gallbladder is where gallstones form and where the clinical problems associated with gallstones develop. The gallbladder is therefore intimately linked to gallstone disease.