The pathogenesis of cholesterol gallstones is multifactorial. A number of key processes, however, appear to interact closely in the formation of cholesterol gallstones. These include:

a. Cholesterol supersaturation

b. Gallbladder stasis

c. Accelerated nucleation

The development of gallstones is a complex multifactorial process. Although a number of factors may contribute to gallstone formation, a number of steps are considered critical in the formation of gallstones. These include cholesterol supersaturation whereby the amount of cholesterol present is in excess of the ability of the micelles and vesicles to transport cholesterol in a soluble state. In addition, the process by which cholesterol crystals form and agglomerate is referred to as nucleation. It is likely that the process of nucleation is altered by a number of biliary proteins or other compounds which may promote or inhibit the nucleation process. Gallbladder stasis provides the proper environment for gallbladder crystal precipitation and stone formation. The stagnant pool of bile within the gallbladder may facilitate both cholesterol supersaturation, the nucleation process, as well as altering the gallbladder’s absorptive or secretory functions. Although bilirubin has been suggested to play a small role in cholesterol gallstone formation, perhaps in either nucleation or solubilization of cholesterol, excessive production of bilirubin as seen in hemolytic disorders is associated primarily with the formation of pigment gallstones.