Abstract

The etiology of biliary stone formation in man is poorly understood, but probably involves three phases: (1) the production and secretion of a lithogenic bile, (2) the precipitation and aggregation of cholesterol microcrystals, and (3) the growth of the nidus to form macroscopic stones. This first phase is probably the most essential factor necessary for stone formation. The determinants of cholesterol cholelithiasis involve an alteration in the relative concentrations of bile salts, lecithin, and cholesterol [8]. Although cholesterol and lecithin are insoluble in water, bile salts solubilize these molecules by forming micelles [7]. Micelle formation is also an important mechanism of biliary lipid excretion [ 121. The concentration of lecithin appears to be important in the micelle for increasing bile salt solubilization of cholesterol [23, 241. Bile production with decreased bile salt and/or decreased lecithin secretion relative to an increased cholesterol secretion would potentiate the formation of a lithogenic bile. Bile salts are synthesized in the liver from cholesterol. In the rat and guinea pig, the enzyme, cholesterol-7-a-hydroxylase has been suggested to be the rate-limiting enzyme of bile salt synthesis [5, 9, 151. The biochemical sequence of bile salt anabolism in the human liver is similar to that in the rat [4]. It is possible that an enzyme such as cholesterol-7-cw-hydroxylase may be deficient in individuals with small bile salt pools. Since reduced bile salt pool size occurs in

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