Impaired human gallbladder lipid absorption in cholesterol gallstone disease and its effect on cholesterol solubility in bile

Background & Aims: The role of the gallbladder in gallstone pathogenesis is still unclear. We examined the effects of gallbladder mucosal lipid absorp tion on lipid composition and cholesterol crystallization in bile. Methods: The in vitro-isolated, intra-arterially perfused gallbladder model was use d (1) to compare the absorption rates of lipids from standard bile by gallb ladders 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 g allbladders, significantly reduced cholesterol (P < 0.02) and phospholipid (P < 0.01) and increased bile salt (P < 0.01) molar percentages in bile ove r a 5-hour period by efficient and selective cholesterol and phospholipid a bsorption. A histomorphometric study of the epithelial cells showed signifi cantly 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 cont rol group. Sequential microscopy of cholesterol-enriched pig bile showed si gnificantly 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 diseas e, the human gallbladder epithelium loses its capacity to selectively and e fficiently absorb cholesterol and phospholipids from bile, even if it is hy perplastic and hypertrophic. This epithelial dysfunction eliminates the pos itive effect that the normal gallbladder exerts on cholesterol solubility i n bile and might be a pathogenetic cofactor for cholesterol gallstone forma tion.