New pathophysiological concepts underlying pathogenesis of pigment gallstones

Abstract

SUMMARY Pigment gallstones, which are much less frequent than cholesterol stones, are classified descriptively as ‘black’ or ‘brown’. They are composed mostly of calcium hydrogen bilirubinate, Ca(HUCB)2, which is polymerized and oxidized in ‘black‘ stones but remains unpolymerized in ‘brown’ stones. Black stones form in sterile gallbladder bile but brown stones form secondary to stasis and anaerobic bacterial infection in any part of the biliary tree, including the gallbladder. Other calcium salts coprecipitate in both stone types; crystalline calcium phosphate and/or carbonate in the case of ‘black’ stones and amorphous calcium salts of long chain saturated fatty acids (‘soaps’) in the case of ‘brown’ stones. Cholesterol is present in variable proportions in ‘brown’ more than ‘black’ stones and, in the latter, the bile sterol may be totally absent. The ‘scaffolding’ of both stone types is a mixed mucin glycoprotein matrix secreted by epithelial cells lining the biliary tree. The critical pathophysiological prerequisite for ‘black’ stone formation is ‘hyperbilirubinbilia’ (biliary hypersecretion of bilirubin conjugates). It is due principally to hemolysis, ineffective erythropoiesis, or pathologic enterohepatic cycling of unconjugated bilirubin. Endogenous biliary β-glucuronidase hydrolysis of bilirubin conjugates in gallbladder bile provides HUCB− molecules that precipitate as insoluble salts with ionized Ca. Putatively, reactive oxygen species secreted by an inflamed gallbladder mucosa are responsible for transforming the initial soft yellow precipitates into hard black [Ca(HUCB)2]n polymers. Despite ‘brown’ gallstones being soft and amenable to mechanical removal, chronic anaerobic infection of the biliary tree is often markedly resistant to eradication.

IL-8 gene polymorphism in acute biliary and non biliary pancreatitis: probable cause of high level parameters?

“…The increase of serum ALT level in the presence of gallstones was shown in biliary etiology, and patients with ALT>150 units/L had a positive predictive value for ABP. Serum total bilirubin value >3 mg is significant for ABP and important for identifier diagnosis 163233343536. In our study, the evaluation of laboratory parameters in patients with ABP and ANBP revealed serum ALT median value in ABP patients with AA genotype was higher than the AT and TT genotypes.…”

Gallstone Classification in Western Countries

“…The ultrastructural analysis with scanning electron microscopy has proved to be useful in the classification and study of pigment gallstones [9,10,[16][17][18][19]. Moreover, the classification of gallstones based on thin-section petrographic microscopy does not consider brown pigment gallstones and should be enriched by the ultrastructural analysis of gallstones [18,19]. In addition, x-ray diffractometry analysis, as well as infrared spectroscopy of gallstones, is of fundamental importance for an accurate stone analysis [9,10,14,16,17].…”

A Study of Correlation Between Total Cholesterol, Total Bilirubin, Calcium and Inorganic Phosphate of Gallstone and Sera of the Stone Formers.

“…An increase in bilirubin, in the serum will subsequently increase the amount of substrate for the endogenous biliary β-glucuronidasae, which in turn will increase the levels of non-polar monohydogenated unconjugated bilirubin in bile, which may precipitate as insoluble salt with calium in bile and thus lead to the formation of pigment gallstones (24). C.S.Pundiretal (25)K.M.Shareefetal (14), both observed in their studies a positive correlation of total bilirubin in serum and pigment gallstone of the patients.…”