• Dubin-Johnson syndrome results from an autosomal recessive defect in the transport protein responsible for hepatocellular excretion of bilirubin glucuronides across the canalicular membrane. Affected individuals exhibit conjugated hyperbilirubinemia. Other than having a darkly pigmented liver (from polymerized epinephrine metabolites, not bilirubin) and hepatomegaly, patients are normal.
Cholestasis is a condition caused by extrahepatic or intrahepatic obstruction of bile channels or by defects in hepatocyte bile secretion. Patients may have jaundice, pruritus, skin xanthomas (focal accumulation of cholesterol), or symptoms related to intestinal malabsorption, including nutritional deficiencies of the fat-soluble vitamins A, D, or K. A characteristic laboratory finding is elevated serum alkaline phosphatase and γ-glutamyl transpeptidase (GGT), enzymes that are present on the apical membranes of hepatocytes and cholangiocytes.
MORPHOLOGYThemorphologicfeaturesofcholestasisdependonitsseverity,duration,andunderlyingcause.Commontobothobstructiveandnonobstructivecholestasisistheaccumulationofbilepigmentwithinthehepaticparenchyma(
Fig.16.23 ).Elongatedgreen-brownplugsofbilearevisibleindilatedbilecanaliculi.Ruptureofcanaliculileadstoextravasationofbile,whichisquicklyphagocytosedbyKupffercells.Dropletsofbilepigmentalsoaccumulatewithinhepatocytes,whichcantakeonafine,foamyappearancereferredtoasfeathery degeneration. Occasionalapoptotichepatocytesalsomaybeseen.
The most common cause of bile duct obstruction in adults is extrahepatic cholelithiasis (gallstones, discussed later), followed by malignant obstructions, and post-surgical strictures. Obstructive conditions in children include biliary atresia, cystic fibrosis, choledochal cysts (a cystic anomaly of the extrahepatic biliary tree), and syndromes in which there are insufficient intrahepatic bile ducts (paucity of bile duct syndromes). The initial morphologic features of cholestasis have been discussed and are entirely reversible with correction of the obstruction. Prolonged obstruction can lead to biliary cirrhosis, discussed later.
Fig. 16.23 Cholestasis.(A)Morphologicfeaturesofcholestasis(right) andcomparisonwithnormalliver(left). Cholestatichepatocytes(1)areenlargedandareassociatedwithdilatedcanalicularspaces(2).Apoptoticcells(3)maybeseen,andKupffercells(4)frequentlycontainregurgitatedbilepigments.(B)Cholestasis,showingthecharacteristicaccumulationofbilepigmentsinthecytoplasm.
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Ascending cholangitis, secondary bacterial infection of the biliary tree, may complicate duct obstruction. Enteric organisms such as coliforms and enterococci are common culprits. Cholangitis usually presents with fever, chills, abdominal pain, and jaundice. The most severe form of cholangitis is suppurative cholangitis, in which purulent bile fills and distends bile ducts. Since sepsis rather than cholestasis tends to dominate this potentially grave process, prompt diagnostic evaluation and intervention are imperative.