Gastroenterology

Gastroenterology

Volume 118, Issue 5, May 2000, Pages 912-920
Gastroenterology

Liver, Pancreas, and Biliary Tract
Impaired human gallbladder lipid absorption in cholesterol gallstone disease and its effect on cholesterol solubility in bile

https://doi.org/10.1016/S0016-5085(00)70177-6Get rights and content

Abstract

Background & Aims: The role of the gallbladder in gallstone pathogenesis is still unclear. We examined the effects of gallbladder mucosal lipid absorption on lipid composition and cholesterol crystallization in bile. Methods: The in vitro–isolated, intra-arterially perfused gallbladder model was used (1) to compare the absorption rates of lipids from standard bile by gallbladders obtained from 7 patients with cholesterol gallstones and 6 controls; and (2) to measure the microscopic cholesterol crystal detection time in cholesterol-enriched pig bile before and after lipid absorption by the pig gallbladder. Results: Control gallbladders, but not cholesterol gallstone gallbladders, significantly reduced cholesterol (P < 0.02) and phospholipid (P < 0.01) and increased bile salt (P < 0.01) molar percentages in bile over a 5-hour period by efficient and selective cholesterol and phospholipid absorption. A histomorphometric study of the epithelial cells showed significantly higher values for nuclear density (P < 0.01) and nuclear (P < 0.05) and cytoplasmic (P < 0.05) areas in the cholesterol gallstone than the control group. Sequential microscopy of cholesterol-enriched pig bile showed significantly shorter cholesterol filament (P < 0.01) and typical cholesterol plate (P < 0.02) detection times before than after exposure of bile to the gallbladder lipid absorption. Conclusions: In cholesterol gallstone disease, the human gallbladder epithelium loses its capacity to selectively and efficiently absorb cholesterol and phospholipids from bile, even if it is hyperplastic and hypertrophic. This epithelial dysfunction eliminates the positive effect that the normal gallbladder exerts on cholesterol solubility in bile and might be a pathogenetic cofactor for cholesterol gallstone formation.

GASTROENTEROLOGY 2000;118:912-920

Section snippets

Materials and methods

The study protocol complied with our institute's ethical guidelines for animal and human studies, and consent was obtained from the patients.

Native gallbladder bile lipid composition in controls and cholesterol gallstone patients

The mean age (55.9 ± 11.2 vs. 58.2 ± 5.3 years [mean ± SD]) and sex distribution (men/women, 3/3 vs. ¾) were comparable in the control and cholesterol gallstone groups. For native gallbladder bile composition, the cholesterol molar percentage was significantly higher in the cholesterol gallstone group than in the control group (10.3% ± 3.3% vs. 6.6% ± 2.3%, respectively [mean ± SD]; P < 0.05). The cholesterol saturation index (CSI) was also higher in the cholesterol gallstone group than in

Discussion

The main finding of this study, performed using the isolated, intra-arterially perfused gallbladder model, was that gallbladder cholesterol absorption and phosphatidylcholine absorption from standard bile were markedly reduced in organs obtained from cholesterol gallstone patients compared with those from controls, whereas bile salt absorption was less affected. Consequently, over the experimental period of 5 hours, the control gallbladders induced a significant reduction of cholesterol and

Acknowledgements

The authors thank Giuseppe Di Lullo for technical assistance in electron microscopy, Marina Pines for revising the English text, and the veterinary surgeons of the Tor Cervara abattoir of Rome, Italy, for providing the pig gallbladders.

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    Address requests for reprints to: Stefano Ginanni Corradini, M.D., Ph.D., Via Asmara 9-B, 00199 Rome, Italy. e-mail: [email protected]; fax: (39) 06-4453319.

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