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Jaundice is a yellowish discoloration of body tissues resulting from the deposition of bilirubin. Tissue deposition of bilirubin occurs only in the presence of serum hyperbilirubinemia and is a sign of either liver disease or, less often, a hemolytic disorder or disorder of bilirubin metabolism. The degree of serum bilirubin elevation can be estimated by physical examination. Slight increases in serum bilirubin level are best detected by examining the sclerae for icterus. Sclerae have a particular affinity for bilirubin due to their high elastin content, and the presence of scleral icterus indicates a serum bilirubin level of at least 51 μmol/L (3 mg/dL). The ability to detect scleral icterus is made more difficult if the examining room has fluorescent lighting. If the examiner suspects scleral icterus, a second site to examine is underneath the tongue. As serum bilirubin levels rise, the skin will eventually become yellow in light-skinned patients and even green if the process is long-standing; the green color is produced by oxidation of bilirubin to biliverdin.
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The differential diagnosis for yellowing of the skin is limited. In addition to jaundice, it includes carotenoderma, the use of the drug quinacrine, and excessive exposure to phenols. Carotenoderma is the yellow color imparted to the skin of healthy individuals who ingest excessive amounts of vegetables and fruits that contain carotene, such as carrots, leafy vegetables, squash, peaches, and oranges. In jaundice the yellow coloration of the skin is uniformly distributed over the body, whereas in carotenoderma the pigment is concentrated on the palms, soles, forehead, and nasolabial folds. Carotenoderma can be distinguished from jaundice by the sparing of the sclerae. Quinacrine causes a yellow discoloration of the skin in 4–37% of patients treated with it.
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Another sensitive indicator of increased serum bilirubin is darkening of the urine, which is due to the renal excretion of conjugated bilirubin. Patients often describe their urine as tea- or cola-colored. Bilirubinuria indicates an elevation of the direct serum bilirubin fraction and, therefore, the presence of liver or biliary disease.
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Serum bilirubin levels increase when an imbalance exists between bilirubin production and clearance. A logical evaluation of the patient who is jaundiced requires an understanding of bilirubin production and metabolism.
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PRODUCTION AND METABOLISM OF BILIRUBIN
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(See Chap. 331) Bilirubin, a tetrapyrrole pigment, is a breakdown product of heme (ferroprotoporphyrin IX). About 80–85% of the 4 mg/kg body weight of bilirubin produced each day is derived from the breakdown of hemoglobin in senescent red blood cells. The remainder comes from prematurely destroyed erythroid cells in bone marrow and from the turnover of hemoproteins such as myoglobin and cytochromes found in tissues throughout the body.
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The formation of bilirubin occurs in reticuloendothelial cells, primarily in the spleen and liver. The first reaction, catalyzed by the microsomal enzyme heme oxygenase, oxidatively cleaves the α bridge of the porphyrin group ...