Gallstone Disease: From Dyspepsia to Biliary Complications

Ten percent to 20% of Americans will develop gallstones. Bile salts and bile acids may be interchangeably used, although their strict physicochemical properties differ [1,2]. The basis for most biliary tract disease, gallstones are a significant health care burden in the United States, where more than 700,000 cholecystectomies are performed annually. The resultant cost from symptoms and complications approach $10 billion [3]. Most (about 85%) gallstones consist of cholesterol. Cholesterol gallstones primarily form because of an imbalance in the composition of bile [4]. Bile is 95% water. Its 3 major organic solids are lipids: bile acids, phospholipids (lecithin), and cholesterol. Cholesterol and lecithin are water insoluble, being predominantly hydrophobic molecules. The remaining constituents are electrolytes plus a rather small amount of pigment (conjugated bilirubin). In the first stage of cholesterol gallstone formation, the liver secretes excess cholesterol relative to the solubilizing components, bile salts and lecithin. This results in supersaturated bile. The next stage is nucleation in which factors like certain proteins in bile hasten the precipitation of the excess cholesterol out of solution, forming microcrystals. Mucin, a glycoprotein secreted in excess by the gallbladder mucosa, then acts as a matrix scaffold to retain these cholesterol microcrystals. An early stage in gallstone formation is the appearance of biliary sludge (“microlithiasis”). Sludge consists of cholesterol microcrystals, mucin, and pigment material (bilirubinate). In the last stage, retention and growth, impaired gallbladder contractility holds on to this precipitated material, allowing the microcrystals to agglomerate and grow into overt gallstones. The interaction of multiple genetic and environmental factors predisposes certain individuals to form gallstones [1,5]. Genes contribute 25% to the phenotype, most evident as the basis for ethnicity and a familial predisposition. A combination is necessary: genetic traits predisposing to stone formation triggered by exogenous and dietary factors, yielding the phenotypic expression. Gallstones reach epidemic proportions in the North and South American Indian populations, in which 60% to 70% develop gallstones. The risk is also Gallstone Disease: From Dyspepsia to Biliary Complications