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COVER ARTICLE
PROBLEM-ORIENTED DIAGNOSIS

Jaundice in the Adult Patient
SEAN P. ROCHE, M.D., Albany Medical College, Albany, New York REBECCA KOBOS, M.D., University of Nevada School of Medicine, Reno, Nevada Jaundice in an adult patient can be caused by a wide variety of benign or life-threatening disorders. Organizing the differential diagnosis by prehepatic, intrahepatic, and posthepaticcauses may help make the work-up more manageable. Prehepatic causes of jaundice include hemolysis and hematoma resorption, which lead to elevated levels of unconjugated (indirect) bilirubin. Intrahepatic disorders can lead to unconjugated or conjugated hyperbilirubinemia. The conjugated (direct) bilirubin level is often elevated by alcohol, infectious hepatitis, drug reactions, and autoimmunedisorders. Posthepatic disorders also can cause conjugated hyperbilirubinemia. Gallstone formation is the most common and benign posthepatic process that causes jaundice; however, the differential diagnosis also includes serious conditions such as biliary tract infection, pancreatitis, and malignancies. The laboratory work-up should begin with a urine test for bilirubin, which indicates that conjugatedhyperbilirubinemia is present. If the complete blood count and initial tests for liver function and infectious hepatitis are unrevealing, the work-up typically proceeds to abdominal imaging by ultrasonography or computed tomographic scanning. In a few instances, more invasive procedures such as cholangiography or liver biopsy may be needed to arrive at a diagnosis. (Am Fam Physician2004;69:299-304. Copyright© 2004 American Academy of Family Physicians.)

Members of various family practice departments develop articles for “Problem-Oriented Diagnosis.” This is one in a series from the Department of Family and Community Medicine at Albany Medical College. Guest coordinators of the series are Neil C. Mitnick, D.O., and Mary F. Smith, Ph.D.

he word “jaundice” comes from the French wordjaune, which means yellow. Jaundice is a yellowish staining of the skin, sclera, and mucous membranes by bilirubin, a yellow-orange bile pigment. Bilirubin is formed by a breakdown product of heme rings, usually from metabolized red blood cells. The discoloration typically is detected clinically once the serum bilirubin level rises above 3 mg per dL (51.3 µmol per L). Jaundice is not a commonpresenting complaint in adults. When present, it may indicate a serious problem. This article discusses the evaluation of the adult patient with jaundice. A systematic approach is warranted to clarify the cause quickly so that treatment can begin as soon as possible. Pathophysiology The classic definition of jaundice is a serum bilirubin level greater than 2.5 to 3 mg per dL (42.8 to 51.3 µmol per L)in conjunction with a clinical picture of yellow skin and sclera. Bilirubin metabolism takes place in three phases—prehepatic,

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intrahepatic, and posthepatic. Dysfunction in any of these phases may lead to jaundice.
PREHEPATIC PHASE

The human body produces about 4 mg per kg of bilirubin per day from the metabolism of heme. Approximately 80 percent of the heme moiety comes from catabolismof red blood cells, with the remaining 20 percent resulting from ineffective erythropoiesis and breakdown of muscle myoglobin and cytochromes. Bilirubin is transported from the plasma to the liver for conjugation and excretion.1
INTRAHEPATIC PHASE

Unconjugated bilirubin is insoluble in water but soluble in fats. Therefore, it can easily cross the blood-brain barrier or enter the placenta. Inthe hepatocyte, the unconjugated bilirubin is conjugated with a sugar via the enzyme glucuronosyltransferase and is then soluble in the aqueous bile.
POSTHEPATIC PHASE

Once soluble in bile, bilirubin is transported through the biliary and cystic

Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the...
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