Biliary lipid secretion and gallbladder motor function in man, and effects of ursodeoxycholic acid

ABSTRACT The two main aims of the studies reported in this thesis were 1) to obtain a detailed description of gallbladder motor function in man; and 2) to clarify the mechanism whereby ursodeoxycholic acid (UDCA) reduces cholesterol saturation of bile. In order to achieve these aims, seven gallstone subjects were studied. Repeat studies were carried out in six patients during treatment with UDCA, and the methodology was validated in these subjects and in two cholecystectomized patients. A conventional intestinal perfusion technique was used to measure secretory outputs into the duodenum. This was combined with a continuous intravenous infusion of indocyanine green as a hepatic bile marker to derive hepatic secretion rates, and with an intravenous bolus of 99mTC RIDA as a gallbladder bile marker to derive quantitative measurements of absolute gallbladder filling and emptying. Subjects were studied aver a thirteen hour period that included an evening meal followed by an overnight fasto The studies of gallbladder motor function suggested that the canventional concept of the gallbladder as a simple pump that empties postprandially and fills during fasting requires modification. Postprandially, filling always accompanied predominant emptying, and during fasting emptying often accompanied predominant filling. In both phases, the majority of the hepatic bile entered the gallbladder before reaching the duadenum. These findings suggest that gallbladder motor function is more analogous to a "bellows" than to a simple pump, and this may be important in mixing of gallbladder contents. The effect of UDCA on cholesterol saturation of hepatic bile was due to an alteration in bile acid secretory coupling with phospholipid in addition to cholesterol. An additional effect of UDCA, if administered at bedtime, was to maintain hepatic bile acid secretion rate during overnight fasting, thus preventing the nocturnal secretion of supersaturated hepatic bile that occurs at low bile acid secretion rates. The effect of UDCA on cholesterol saturation of fasting gallbladder bile was due to an increase in the total mass of bile acid stored in the gallbladder, without any effect on cholesterol masso UDCA was also shown to inhibit gallbladder emptying and pancreatic enzyme secretion postprandially