Diminished Bile Acid Pool Size in Patients with Gallstones

Vlahčevič, Z. Reno; Bell, C. Cooper; Buhac, I; Farrar, John T.; Swell, Leon

doi:10.1016/s0016-5085(19)33757-6

Cited by 335 publications

(48 citation statements)

References 25 publications

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“…Indeed, the small number of subjects studied is probably the explanation for the finding that, although fasting gallbladder bile tended to be supersaturated with cholesterol in our gallstone patients, and unsaturated in our control subjects, this difference was not statistically significant, nor was the difference in total bile acid pool size. Most of our subjects were female, and these appear to have a larger overlap in bile acid pool size (Danzinger, Hofmann, Thistle, and Schoenfield, 1973;Pomare and Heaton, 1973) than do males (Vlahcevic et al, 1970b). Since 10-20% of the population will eventually develop gallstones, any control group will contain patients at high risk for cholelithiasis.…”

Section: Discussion Total Daily Biliary Lipid Outputsmentioning

confidence: 98%

“…The second line of evidence was the demonstration by Vlahcevic, Bell, Buhac, Farrar, and Swell (1970b) that gallstone subjects have a reduced bile acid pool size, yet a normal synthesis rate. The absence of a compensatory increase in bile acid synthesis in response to an inferred decreased return of bile acids to the liver was thus attributed to inappropriate repression of bile acid synthesis, probably due to a hepatic enzyme defect (Schoenfield, 1972).…”

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confidence: 99%

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Biliary lipid output during three meals and an overnight fast. I. Relationship to bile acid pool size and cholesterol saturation of bile in gallstone and control subjects.

Northfield¹,

Hofmann²

1975

Gut

237

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SUMMARY Using a duodenal perfusion technique, the biliary output of bile acids, phospholipid, and cholesterol was measured hourly during three meals and an overnight fast in seven Caucasians with radiolucent gallstones in a functioning gallbladder, and in seven healthy controls without gallstones, closely matched for age, sex, and weight. Before the perfusion, bile acid kinetics were defined by an isotope dilution procedure, and the biliary lipid composition of fasting gallbladder bile was determined. Total daily biliary lipid output was similar in gallstone and control subjects, and was unrelated to cholesterol saturation of fasting gallbladder bile and to bile acid pool size. There was an inverse relationship between the size and recycling frequency of the bile acid pool, so that secretion rate and hepatic return of bile acids remained constant, despite a wide range of pool sizes. The finding of a normal bile acid synthesis rate in subjects with a small pool size therefore indicated normal feedback regulation of bile acid synthesis. Hourly measurements of biliary lipid output showed a linear relationship between bile acid and cholesterol output, with a similar regression line for gallstone and control subjects, but a non-linear relationship between bile acid and phospholipid output. Consequently, samples from all subjects were consistently supersaturated with cholesterol at low bile acid outputs, especially during overnight fasting, but not at high bile acid outputs.These findings indicate that hepatic secretion of bile supersaturated with cholesterol is physiological in man at low bile acid outputs, that bile acid pool size is probably determined in part by its recycling frequency, and that cholesterol cholelithiasis in some Caucasians may be due to an underlying extrahepatic abnormality.

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Section: Discussion Total Daily Biliary Lipid Outputsmentioning

confidence: 98%

mentioning

confidence: 99%

Biliary lipid output during three meals and an overnight fast. I. Relationship to bile acid pool size and cholesterol saturation of bile in gallstone and control subjects.

Northfield¹,

Hofmann²

1975

Gut

237

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“…Supersaturation of gall bladder bile with cholesterol is a precondition for crystallisation 3334 Lithogenic bile may be a result of enhanced cholesterol synthesis, a reduced bile acid pool, or both 3536 The protective effect of ε2 may lie in the metabolic pathways leading to supersaturation, as subjects with the ε2 allele show low cholesterol absorption and a high rate of bile salt synthesis 14.…”

Section: Discussionmentioning

confidence: 99%

The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects

Niemi

Kervinen

Rantala

et al. 1999

Gut

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Background-The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). Aims-To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. Methods-Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography. Results-In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0.28 (95% confidence interval 0.08-0.92). There was no protective eVect in men. The relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8 (1.0-2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. Conclusions-The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD. (Gut 1999;44:557-562)

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“…In nonobese individuals who form cholesterol-rich gallbladder stones, gallstones were associated with a small bile salt pool cycling at a normal frequency within the enterohepatic circulation. 11 Furthermore, it has been suggested that slow intestinal transit increases bacterial degradation of primary to secondary bile salts in the colon. 12 Bile then contains a greater proportion of deoxycholate conjugates which, in turn, increases biliary cholesterol secretion and saturation, thereby enhancing gallstone formation.…”

Section: Cholesterol Gallbladder Stonesmentioning

confidence: 99%