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Jaundice is a yellowish discoloration of skin, sclera, and mucous membranes resulting from the elevated levels of bilirubin in the circulation, usually presents at levels of >2.5 mg/dL. Hyperbilirubinemia occurs as a result of (1) overproduction (e.g., hemolysis), (2) inadequate cellular processing (e.g., infections, drugs, toxins), or (3) decreased excretion of bilirubin (e.g., pancreatic tumor, gallstone in the common bile duct). The causes of jaundice can also be classified as prehepatic, hepatic, and posthepatic.

Hyperbilirubinemia can be divided into two types: Unconjugated form results from the increased production of bilirubin or the impaired liver's ability to conjugate bilirubin. Conjugated form occurs as a result of impaired excretion of conjugated bilirubin in the setting of intrahepatic or extrahepatic cholestasis.

Clinical Features

Previously healthy young patients with acute hepatitis typically presents with a sudden onset of jaundice and a prodrome of fever, malaise, nausea, vomiting, and right upper quadrant abdominal pain resulting from the enlarged liver.

History of excessive alcohol consumption suggests alcoholic hepatitis. Jaundice usually develops gradually in the setting of alcoholic liver disease and cirrhosis.

Symptoms of anorexia, weight loss, and malaise associated with painless jaundice in older patients classically suggest hepatobiliary or pancreatic malignancy.

Liver metastases are suspected in patients with primary tumors and an enlarged, hard, tender, nodular liver accompanied by jaundice.

Inherited diseases such as Gilbert syndrome, glucose-6-phosphate dehydrogenase (G6PD) deficiency, can be the cause of jaundice when a family history of jaundice or a history of recurrent mild jaundice that spontaneously resolves or seen in response to a number of triggers such as certain foods, illness, or medication is present.

Jaundice can be seen in patients with the clinical signs and symptoms of cholecystitis in the setting of a retained gallstone in the common bile duct.

Patients with a history of biliary tract surgery, pancreatitis, cholangitis, or inflammatory bowel present with jaundice due to the development of biliary tract scaring or strictures.

Jaundice can be seen in patients with hepatomegaly, pedal edema, jugular venous distention, and a gallop rhythm due to the passive congestion of liver or acute ischemic hepatitis in patients with chronic heart failure.

Diagnosis and Differential

A detailed history, a carefully conducted physical examination, and routine laboratory tests lead to accurate diagnosis in 85% of patients with jaundice. Initial laboratory tests include serum bilirubin level (total and direct (conjugated) fractions; indirect (unconjugated) fraction can be calculated by subtraction), serum transaminases and alkaline phosphatase (ALP) levels, a complete blood count (CBC), and urinalysis to check for bilirubin and urobilinogen. Additional laboratory tests are ordered according to the clinical features to diagnose specific causes. These include serum lipase or amylase levels, prothrombin time (PT), electrolytes and glucose levels, blood urea nitrogen (BUN) and creatinine levels, γ-glutamyl ...

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