Trotman B W
State University of New York Health Science Center, Brooklyn.
Gastroenterol Clin North Am. 1991 Mar;20(1):111-26.
Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease. The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates. At the pH of bile, this results in two monohydrogenated bilirubin anions that precipitate with calcium ions. Bilirubin monoconjugates that are increased in several conditions, such as Gilbert's syndrome and chronic hemolysis, may play a pivotal role in black stone formation as a source of unconjugated monohydrogenated bilirubin and as a possible co-precipitant with calcium. The precipitation of calcium carbonate and phosphate is influenced by local gallbladder factors. Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts. We used nb/nb mice with a chronic hemolytic anemia as a model of hemolysis-induced black stone disease. The presence of 40% bilirubin monoconjugates in mouse gallstones indicated the importance of this moiety in the pathogenesis of black stones. Other data obtained by marrow transplantation experiments in mice revealed the relative importance of genotype versus the hemolytic anemia on determinants such as biliary bile acid composition and mucin secretory glands in the mouse gallbladder neck. Additional physical chemical studies of the interaction of unconjugated bilirubin in model bile solutions will be helpful in further delineating the pathogenesis of both black and brown pigment gallstones.
黑色和棕色色素胆结石在形态、成分和临床方面都有所不同。黑色结石主要在胆囊内无菌胆汁中形成，与高龄、慢性溶血、酗酒、肝硬化、胰腺炎及全胃肠外营养有关。棕色结石不仅在胆囊内形成，也在肝内和肝外胆管内形成；它们均被肠道细菌感染，通常与化脓性胆管炎有关。棕色结石与十二指肠乳头旁憩室有关，是新生胆总管结石的主要类型。胆囊切除术通常可治愈黑色色素结石病，而棕色结石病在胆囊切除术后结石常复发。黑色结石的发病机制可能与胆红素结合物的非细菌性、非酶性水解有关。在胆汁的pH值条件下，这会产生两个与钙离子沉淀的单氢化胆红素阴离子。在几种情况下（如吉尔伯特综合征和慢性溶血）增加的胆红素单结合物，可能作为未结合单氢化胆红素的来源以及可能与钙的共沉淀剂，在黑色结石形成中起关键作用。碳酸钙和磷酸钙的沉淀受局部胆囊因素影响。棕色色素结石在被肠道细菌感染的胆汁中形成，这些细菌能产生水解酶：β-葡萄糖醛酸酶、磷脂酶A和结合型胆汁酸水解酶。产生的胆红素和脂肪酸阴离子形成不溶性钙盐。我们使用患有慢性溶血性贫血的nb/nb小鼠作为溶血诱导的黑色结石病模型。小鼠胆结石中40%胆红素单结合物的存在表明该部分在黑色结石发病机制中的重要性。通过小鼠骨髓移植实验获得的其他数据揭示了基因型与溶血性贫血在诸如小鼠胆囊颈部胆汁胆汁酸组成和粘蛋白分泌腺等决定因素上的相对重要性。对模型胆汁溶液中未结合胆红素相互作用的额外物理化学研究将有助于进一步阐明黑色和棕色色素胆结石的发病机制。
