Physical and metabolic factors in gallstone pathogenesis

Gallstones are divided into three major types-cholesterol, black pigment, and brown pigment-depending on their composition, and hence, on their pathogenesis. Gallstones form as the culmination of a complex series of events that begin when insoluble lipids and inorganic salts secreted by the liver are not solubilized normally by the detergent properties of bile salts. This occurs when metabolic events produce bile that contains excess amounts of either cholesterol or bilirubin, both of which are relatively insoluble in aqueous solution. Additionally, physical factors must allow rapid nucleation within the residence time of bile in the biliary tree. This article discusses metabolic factors underlying the secretion of supersaturated bile, and physical factors allowing the solubilization and precipitation of the biliary lipids and calcium salts that constitute gallstones.