ESSENTIALS OF DIAGNOSIS
Jaundice results from accumulation of bilirubin in body tissues; the cause may be hepatic or nonhepatic.
Hyperbilirubinemia may be due to abnormalities in the formation, transport, metabolism, or excretion of bilirubin.
Persistent mild elevations of the aminotransferase levels are common in clinical practice and caused most often by nonalcoholic fatty liver disease (NAFLD).
Evaluation of obstructive jaundice begins with ultrasonography and is usually followed by cholangiography.
Jaundice (icterus) results from the accumulation of bilirubin—a product of heme metabolism—in body tissues (eFigure 16–1). Hyperbilirubinemia may be due to abnormalities in the formation, transport, metabolism, or excretion of bilirubin. Total serum bilirubin is normally 0.2–1.2 mg/dL (3.42–20.52 mcmol/L). Mean levels are higher in men than women, higher in Whites and Hispanics than Blacks, and correlate with an increased risk of symptomatic gallstone disease and inversely with the risk of stroke, respiratory disease, cardiovascular disease, and mortality, presumably because of antioxidant and intestinal anti-inflammatory effects. Jaundice may not be recognizable until serum bilirubin levels are about 3 mg/dL (51.3 mcmol/L).
Jaundice. (Reproduced, with permission, from Sherlock S, Summerfield JA. Color Atlas of Liver Disease. Mosby, 1991.)
Jaundice may be caused by predominantly unconjugated or conjugated bilirubin in the serum (Table 16–1). Unconjugated hyperbilirubinemia may result from overproduction of bilirubin because of hemolysis; impaired hepatic uptake of bilirubin due to certain drugs; or impaired conjugation of bilirubin by glucuronide, as in Gilbert syndrome, due to mild decreases in uridine diphosphate (UDP) glucuronyl transferase, or Crigler-Najjar syndrome, caused by moderate decreases (type II) or absence (type I) of UDP glucuronyl transferase. Hemolysis alone rarely elevates the serum bilirubin level to more than 7 mg/dL (119.7 mcmol/L). Predominantly conjugated hyperbilirubinemia may result from impaired excretion of bilirubin from the liver due to hepatocellular disease, drugs, sepsis, or hereditary hepatocanalicular transport defects (such as Dubin-Johnson syndrome, progressive familial intrahepatic cholestasis syndromes, and intrahepatic cholestasis of pregnancy) or from extrahepatic biliary obstruction. Features of some hyperbilirubinemic syndromes are summarized in Table 16–2. The term “cholestasis” denotes retention of bile in the liver, and the term “cholestatic jaundice” is often used when conjugated hyperbilirubinemia results from impaired bile formation or flow. Mediators of pruritus due to cholestasis have been identified to be lysophosphatidic acid and autotaxin, the enzyme that forms lysophosphatidic acid.
Table Graphic Jump Location Table 16–1.Classification of jaundice. ||Download (.pdf) Table 16–1. Classification of jaundice.
|Type of Hyperbilirubinemia ||Location and Cause |
|Unconjugated hyperbilirubinemia (predominantly indirect bilirubin) || |
Increased bilirubin production (eg, hemolytic anemias, hemolytic reactions, hematoma, pulmonary infarction)
Impaired bilirubin uptake and storage (eg, posthepatitis hyperbilirubinemia, Gilbert syndrome, Crigler-Najjar syndrome, drug reactions)
|Conjugated hyperbilirubinemia (predominantly direct bilirubin) ||Hereditary Cholestatic Syndromes (see also Table 16–2) |
|Faulty excretion of bilirubin conjugates (eg, Dubin-Johnson syndrome, Rotor syndrome) or mutation in genes coding for bile ...|