Classification and pathogenesis of pigment gallstones

Abstract

Pigment gallstones contain a variety of insoluble calcium salts. Calcium bilirubinate is usually the major component while cholesterol accounts for less than 50% by weight. There are two types of pigment stones, identifiable by epidemiological, clinical, morphological and compositional features. The pathogenesis of each is conjectural. Black stones have a glass-like featureless appearance on fracturing. They form in the gallbladder and do not recur after cholecystectomy. They are found in 60–80% of patients with haemolysis, but are usually found in the general population in elderly, thin patients without haemolysis. Calcium phosphate and carbonate are frequently also present and may predominate. The remainder consists primarily of a protein network, mostly glycoprotein, which may slowly trap and interdigitate with a network of microcrystalline calcium salts. Brown stones have a rough surface and on cross-section demonstrate alternating brown and tan layers containing predominantly calcium bilirubinate and calcium salts of fatty acids respectively. Glycoproteins are much less prominent. Brown stones are associated with stasis, bacterial infection and parasites, whereas black stones are found in sterile bile. The female:male ratio for both types is 1.25:1. In the West, brown stones usually form in the common duct, more than a year after cholecystectomy for cholesterol or black stones. In the Orient, brown stones form de novo anywhere within the biliary tract and are the major cause of intrahepatic stones, cholangiohepatitis and liver failure. They are believed to form by rapid non-crystalline precipitation of calcium salts of bilirubin and fatty acids following enzymatic hydrolysis of bilirubin glucuronide and lecithin. These enzymes could originate from bacteria and/or from damaged biliary epithelium. Thus, aside from being pigmented and containing calcium bilirubinate, there are no common features in the pathogenesis of black and brown pigment stones, and they form in mutually exclusive circumstances.

The epidemiological data presently available support the hypothesis that the conditions under which pigment stones form are not only separate from those for cholesterol stones but prevent the simultaneous formation of cholesterol stones. Similarly the conditions for formation of the two subtypes of pigment stones — black and brown stones — preclude simultaneous formation of the other. This presentation will provide a classification of pigment stones and summarize the available chemical, structural and epidemiological data, all of which support the above hypotheses.