Pathogenesis of gallstones

Abstract

Gallstones are composed principally of cholesterol monohydrate crystals (cholesterol stones) or the acid salt of calcium bilirubinate (pigment stones). Cholesterol stones and the black variety of pigment gallstones form in sterile gallbladder bile whereas brown pigment gallstones form in infected bile. Biliary supersaturation is the principal pathophysiological defect and is hepatic in origin. Supersaturation results from excessive secretion of cholesterol or bilirubin conjugates, the precursors of unconjugated bilirubin, and/or, deficient secretion of bile salt and lecithin, the solubilizers of these otherwise insoluble lipids. As has now being clarified for cholesterol stones, an imbalance in pro- and antinucleating biliary proteins, hypersecretion of gallbladder mucin and gallbladder dysmotility possibly from cholesterol "toxicity" to sarcolemma, all interact to promote nucleation. Crystallisation results in suspension of cholesterol crystals or bilirubinate salts in gallbladder mucin gel and is known as "biliary sludge". It is believed today that this stage is essential for evolution of both cholesterol and pigment stones. Brown pigment gallstones form principally in the bile ducts. These stones result from infection of the biliary tree, most commonly due to obstruction from migrating gallbladder stones. Chemical compositions of brown and black pigment stones are different: In black stones, calcium bilirubinate is polymerized and oxidatively degraded but in brown stones, calcium bilirubinate is present as the unpolymerised salt. Brown stones differ also from black stones in containing calcium fatty acid soaps, a result of bacterial phospholipase A1 hydrolysis of biliary lecithin. Both types of pigment gallstones may contain crystalline inorganic calcium salts especially carbonate (gallbladder stones) and phosphate (bile ducts stones). Since a molecular understanding of the multiple defects that lead to cholesterol and pigment gallstones is becoming a reality, the future holds much promise for gallstone prevention.