Jaundice, a yellowish discoloration of the skin, sclerae, and mucous membranes, results from hyperbilirubinemia (breakdown of hemoglobin) and the deposition of bile pigments. Etiologies include disorders of bilirubin metabolism (eg, hemolysis) and hepatocellular causes due to infections, drugs and toxins, metabolic disease, granulomatous disease, and bile duct obstruction. Hyperbilirubinemia can be divided into 2 types. The unconjugated form results from increased bilirubin production or a liver defect in its uptake or conjugation. The conjugated form occurs in the setting of intra- or extrahepatic cholestasis, resulting in decreased excretion of conjugated bilirubin.
Sudden onset of jaundice in a previously healthy young person and a prodrome of fever, malaise, myalgias, and a tender enlarged liver point to hepatitis (probably viral) as a likely cause. Heavy ethanol use suggests alcoholic hepatitis. In the setting of alcoholic liver disease and cirrhosis, jaundice usually develops gradually. A family history of jaundice or a history of recurrent mild jaundice that spontaneously resolves usually accompanies inherited causes of jaundice such as Gilbert syndrome. Cholecystitis may not cause jaundice unless there is acute biliary obstruction present, such as with a retained common bile duct gallstone. Painless jaundice in an older patient classically suggests pancreatic or hepatobiliary malignancy. Patients with a known prior malignancy and a hard, nodular liver accompanied by jaundice are likely to be found to have liver metastases. Biliary tract scarring or strictures always must be suspected as a cause of jaundice in patients with a prior history of biliary tract surgery, pancreatitis, cholangitis, or inflammatory bowel disease. Hepatomegaly with jaundice, accompanied by pedal edema, jugular venous distention, and a gallop rhythm suggest chronic heart failure.
Diagnosis and Differential
Initial laboratory tests that should be obtained in the workup of a jaundiced patient include serum bilirubin level (total and direct fractions; indirect fraction can be deduced by simple subtraction), serum aminotransferases and alkaline phosphatase levels, urinalysis to check for bilirubin and urobilinogen, and a complete blood count (CBC). Additional laboratory tests may be indicated based on the clinical setting (serum amylase and lipase levels, prothrombin time [PT], INR, electrolytes and glucose levels, blood urea nitrogen [BUN] and creatinine levels, viral hepatitis panels, drug levels, and pregnancy test). With normal liver enzyme levels, the jaundice is more likely to be caused by sepsis or systemic infection, inborn errors of metabolism, or pregnancy, rather than by primary hepatic disease. With abnormally elevated liver enzymes, the pattern of abnormalities may suggest the etiology. Aminotransferase elevation, if predominant, suggests hepatocellular diseases such as viral or toxic hepatitis or cirrhosis, whereas markedly elevated alkaline phosphatase levels (2 to 3 times that of normal levels) and gamma-glutamyl transferase (GGT) points to intra- or extrahepatic obstruction (gallstones, stricture, or malignancy). A Coombs test and hemoglobin electrophoresis may be useful if anemia is present in addition to normal liver aminotransferase levels (hemolysis and hemoglobinopathy). If clinical features and initial laboratory results indicate conjugated hyperbilirubinemia, ultrasound ...