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Yellow skin pigmentation caused by elevation in serum bilirubin level (also termed icterus); often more easily discernible in sclerae. Scleral icterus becomes clinically evident at a serum bilirubin level of ≥51 µmol/L (≥3 mg/dL); yellow skin discoloration also occurs with elevated serum carotene levels but without pigmentation of the sclerae.


Bilirubin is the major breakdown product of hemoglobin released from senescent erythrocytes. Initially, it is bound to albumin, transported into the liver, conjugated to a water-soluble form (glucuronide) by glucuronosyltransferase, excreted into the bile, and converted to urobilinogen in the colon. Urobilinogen is mostly excreted in the stool; a small portion is reabsorbed and excreted by the kidney. Bilirubin can be filtered by the kidney only in its conjugated form (measured as the “direct” fraction); thus, increased direct serum bilirubin level is associated with bilirubinuria. Increased bilirubin production and excretion (even without hyperbilirubinemia, as in hemolysis) produce elevated urinary urobilinogen levels.


Hyperbilirubinemia occurs as a result of (1) overproduction; (2) impaired uptake, conjugation, or excretion of bilirubin; (3) regurgitation of unconjugated or conjugated bilirubin from damaged hepatocytes or bile ducts (Table 44-1).

TABLE 44-1Causes of Isolated Hyperbilirubinemia


The initial steps in evaluating the pt with jaundice are to determine whether (1) hyperbilirubinemia is conjugated or unconjugated, and (2) other biochemical liver tests are abnormal (Figs. 44-1 and 44-2, Tables 44-2 and 44-3). Essential clinical examination includes history (especially duration of jaundice, pruritus, associated pain, risk factors for parenterally transmitted diseases, medications, ethanol use, travel history, surgery, pregnancy, presence of any accompanying symptoms), physical examination (hepatomegaly, tenderness over liver, palpable gallbladder, splenomegaly, gynecomastia, testicular atrophy, other stigmata of chronic liver disease), blood liver tests (see below), and complete blood count.


Evaluation of the pt with jaundice. ALT, alanine aminotransferase; AMA, antimitochondrial antibody; ANA, antinuclear antibody; AST, aspartate aminotransferase; CMV, cytomegalovirus; EBV, Epstein-Barr virus; ERCP, endoscopic retrograde cholangiopancreatogram; MRCP, magnetic resonance cholangiopancreatography; SMA, smooth-muscle antibody; SPEP, serum protein electrophoresis.


Algorithm for evaluation of abnormal liver tests. α1AT, α1 antitrypsin; AlkP, alkaline phosphatase; ALT, alanine aminotransferase; AMA, antimitochondrial antibody; ERCP, endoscopic retrograde cholangiopancreatogram; GGT, γ-glutamyl transpeptidase; HAV, hepatitis A virus; HBc, hepatitis B core; HBsAG, hepatitis B surface antigen; HCV, hepatitis C virus; MRCP, magnetic resonance cholangiopancreatography; p-ANCA, perinuclear antineutrophil cytoplasmic antibody; SMA, ...

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