To delineate relationships between biliary outputs of bile acids, phospholipids, and cholesterol, studies were carried out in 18 subjects with intact gallbladders and in six with cholecystectomy. Hepatic secretions of three biliary lipids were determined using an intestinal perfusion technique. In studies on subjects with normal gallbladders (study A), continuous infusion of liquid formula was given to stimulate gallbladder contraction, so that gallbladder storage was eliminated and duodenal outputs were equal to hepatic secretion rates. Bile acid pool size and bile lipid outputs were determined under steady-state conditions (intact EHC). Secretion rates of bile acids were then reduced by progressively withdrawing large amounts of bile from the EHC over a 12-hr period, during which biliary lipid secretions were measured continuously. In study B, six subjects without gallbladders ingested three meals of liquid formula during the day and had an overnight fast. Measurements of biliary lipid outputs were made hourly over the 24-hr period. A wide range of bile acid secretion rates occurred under these physiological conditions owing to the lowering of bile acid outputs during fasting. In both studies A and B, bile saturation with cholesterol increased as EHC became interrupted. However, the magnitude of this increase was variable from subject to subject and appeared to depend on two related factors. First, bile saturation was markedly increased in subjects who exhibited a severe reduction of bile acid output on interrupting the EHC. Second, the degree of uncoupling of cholesterol and phospholipid secretion in the lower range of bile acid outputs was also variable. When secretion of cholesterol was well-maintained in the face of decreasing bile acid and phospholipid outputs, bile became supersaturated. Subjects with high biliary cholesterol during intact EHC were especially prone to cholesterol-phospholipid dissociation. However, even at relatively low outputs of cholesterol, interruption of the EHC sometimes caused marked dissociation of secretions of cholesterol and phospholipids causing super-saturated bile at low rates of bile acid flux. Thus, the degree of coupling of cholesterol and phospholipids at low secretion of bile acids was variable from patient to patient and was a major determinant of the extent of increase in bile saturation.
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