Composition of Basal and Stimulated Hepatic Bile in Baboons, and the Formation of Cholesterol Gallstones (original) (raw)
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Disorders of bile acid metabolism in cholesterol gallstone disease
Journal of Clinical Investigation, 1992
The aim of the study was to evaluate the metabolism of individual bile acids in patients with cholesterol gallstone disease. Therefore, we determined pool size and turnover of deoxycholic (DCA), cholic (CA), and chenodeoxycholic acid (CDCA) in 23 female gallstone patients classified according to their gallbladder function and in 15 healthy female controls. Gallstone patients had normal hepatic bile acid synthesis, but, depending on gallbladder function, differed with respect to turnover and size of the bile acid pools: Patients with wellemptying gallbladder (group A, n = 9) had enhanced turnover and reduced pools of CA (-46%; P less than 0.01 vs. controls) and CDCA (-24%; P less than 0.05), but normal input and size of the DCA pool. With reduced gallbladder emptying (less than 50% of volume; group B, n = 6), turnover and pools of CA, CDCA, and DCA were similar as in controls. Patients with loss of gallbladder reservoir (group C, n = 8) had increased input (+100%; P less than 0.01) and pool size of DCA (+45%; P = 0.07) caused by rapid conversion of CA to DCA, while the pools of CA (-71%; P less than 0.001 vs. controls) and CDCA (-36%; P less than 0.05) were reduced by enhanced turnover. Thus, in patients with cholesterol gallstones, the pools of primary bile acids are diminished, unless […]
Altered gallbladder concentration of biliary lipids during early cholesterol gallstone formation
Digestive Diseases and Sciences, 1987
Whether gallbladder absorptive function is altered during formation of cholesterol gallstones is unclear. We tested the hypothesis that alterations in biliary lipid composition present during early cholesterol gallstone formation enhance gallbladder absorption, as manifested by an increase in the ratio of gallbladder to hepatic bile lipid concentrations. Prairie dogs received either control or a 0.4% cholesterol-enriched chow for two or six weeks. The bile acid pool of each animal was labeled with [14C]cholic acid. Gallbladder and hepatic bile were analyzed for lipid composition with calculation of indices for cholesterol saturation, gallbladder stasis, and gallbladder absorption. Animals maintained on cholesterol-enriched chow for two weeks had a significant increase, as compared to controls, in the ratio of gallbladder to hepatic bile concentrations of cholesterol (8.66±1.09 vs 5.76±0.48), phospholipids (4.76±0.42 vs 3.21±0.34), bile acids (6.42±2.20 vs 3.54±0.46), and total lipid content (6.22±0.94 vs 3.64±0.43). These changes occurred at a time when gallbladder stasis is present and cholesterol crystals are forming but prior to stone formation. Similar findings were noted in six-week cholesterol-fed prairie dogs. We propose that the uniformly increased ratios of biliary lipids result from enhanced gallbladder absorption of water and sodium. The resulting increase in solute concentration may promote nucleation and, therefore, may be an important etiologic factor in cholesterol gallstone formation.
Quantification of cholesterol nucleation promoting activity in human gallbladder bile
Clinica Chimica Acta, 1987
We have developed a simple method to quantitate cholesterol nucleation promoting activity in bile. The method makes use of the fact that gallbladder bile of cholesterol gallstone patients contains potent nucleation promoting activity. Gallbladder bile samples were serially diluted, routinely from l/25 to l/6400. The diluted samples were mixed with a supersaturated model bile and the nucleation time (NT) of the mixtures was determined. The greatest dilution that resulted in a significant shortening of the NT was called the nucleation promoting activity titre (NPAT). The determination is independent of the original lipid content of the bile sample. The NPAT was measured in 14 gallbladder bile samples derived from patients with cholesterol gallstones and 9 controls. In all samples promoting activity was found. In the samples from the stone patients the NPAT was significantly elevated as compared to the patients without cholesterol stones (p = 0.01). Our results suggest that the cholesterol saturation index and the activity of cholesterol nucleation promoting factors are the most important factors in the pathogenesis of cholesterol gallstone disease. Assessment of the NPAT allows the differentiation of groups of patients with a normal cholesterol saturation index who are at risk for gallstone formation due to a high NPAT.
Gastroenterology, 1995
Background/Aims: Impaired postprandial gallbladder emptying may provide time for progressive bile concentration with formation of instable cholesterol-rich vesicles and fast nucleation of cholesterol crystals. The aim of this study was to assess postprandial gallbladder emptying, bile composition, and nucleation of cholesterol crystals in the same patient. Methods: In 30 patients with cholesterol gallstones, postprandial gallbladder emptying was measured ultrasonographically. In each patient, gallbladder bile composition (obtained at cholecystectomy) and nucleation of cholesterol crystals was determined. Patients were divided in 22 strong contractors (>50% postprandial gallbladder emptying) and 8 weak contractors. Results: In weak contractors, bile salt and phospholipid concentrations were much higher than in strong contractors (234.6 _+ 24.7 vs. 130.3 +_ 10.8 mmol/L [P < 0.001] and 44.5 _+ 3.5 vs. 30.2 _+ 3.1 mmol/L [P < 0.05], respectively). Cholesterol concentrations were comparable in strong and weak contractors. Consequently, total lipid concentration was significantly higher (15.5 _+ 1.4 and 9.2 _+ 0.7 g/dL; P < 0.001) and cholesterol saturation index significantly lower (0.90 + 0.08 and 1.61 ___ 0.17; P < 0.001) in weak contractors. Nucleation time, percentage of cholesterol in vesicles, bile salt species, and molecular species of phosphatidylcholine were not significantly different. Conclusions: Differences in bile composition can be linked to different patterns of postprandial gallbladder emptying and may point to two different pathways of gallstone formation.