Figure 2.

Venn diagram of five primary defects: genetic factors and LITH genes, hepatic hypersecretion, gallbladder hypomotility, rapid phase transitions, and intestinal factors. The hypothesis proposed is that hepatic cholesterol hypersecretion into bile is the primary defect and is the outcome in part of a complex genetic predisposition. The downstream effects include gallbladder hypomotility and rapid phase transitions. A major result of gallbladder hypomotility is alteration in the kinetics of the enterohepatic circulation of bile salts, resulting in increased cholesterol absorption and reduced bile salt absorption that lead to abnormal enterohepatic circulation of bile salts and diminished biliary bile salt pool size. Not only does gallbladder hypomotility facilitate cholesterol nucleation/crystallization, but also it allows the gallbladder to retain cholesterol monohydrate crystals. Although a large number of candidate Lith genes have been identified in mouse models, the identification of human LITH genes and their contributions to gallstones require further investigation. Reproduced with modifications and with permission from [48].