Jaundice

Overview

Jaundice is a clinical term referring to yellowing of body tissues due to deposition of bilirubin. Because bilirubin has a high affinity for the sclera of the eye, the most sensitive indicator of Jaundice is yellowing of the sclera, termed scleral icterus, which occurs when plasma biliruin levels are greater than 3.0mg/dl. At higher concentrations of bilirubin the skin and tissue underneath the tongue will also gain a yellowish hue.

Pathogenesis

The overarching pathogenesis of jaundice is actually quite simple and results from either an over-production or impaired clearance of bilirubin, leading to large elevations of plasma bilirubin (i.e. hyperbilirubinemia). Recall that bilirubin is the biochemical byproduct of heme degradation which is part of the processes of erythrocyte degradation. The bilirubin metabolite is then eliminated from the body through hepatobiliary clearance as described in Heme Degradation. Therefore, Jaundice will either occur due to increased degradation of erythrocytes or hepatobiliary derangements which impair bilirubin clearance. Although the basic pathogenesis is simple, a large number of inherited or acquired etiologies can derange the balance of either bilirubin synthesis or clearance in such a way as to produce jaundice.

Clinical Consequences

The tissue deposition of bilirubin itself is of little clinical significance in adults and largely serves as an indicator of the primary disease which is often clinically serious.

Etiologies

Jaundice can be caused by a large variety of etiologies that can affect any step of bilirubin metabolism and transport. Below we have tried our best to organize the etiologies of jaundice to correspond with the steps outlined in Heme Degradation which the reader should review if unfamililar. Only etiologies which can lead to overt jaundice are discussed below whereas those which typically lead to isolated hyperbilirubinemia without clinical jaundice are left out.

Unconjugated Hyperbilirubinemias

Unconjugated hyperbilirubinemias occur due to increased production of unconjugated bilirubin or impairment of hepatic bilirubin conjugation. Increased production of unconjugated bilirubin is typically the result of derangements in erythrocytes. In contrast, unconjugated hyperbilirubinemias due to impaired conjugation occur due to focal hereditary or acquired biochemical defects in the molecular conjugation machinery and are not the result of large disease processes with overt hepatic pathologies. The links below are not subtopics of this page and will take you to potentially distant sites within the Table of Contents.

Conjugated Hyperbilirubinemias

Conjugated hyperbilirubinemias occur either due to impairments in hepatocytic excretion of conjugated bilirubin, impairment of bile transport, or due to hepatocyte injury resulting in release/regurgitation of conjugated bile. When highly elevated, conjugated bilirubin, which has a dark color, is excreted in the urine; thus, conjugated hyperbilirubinemias are often characterized by the presence of tea- or cola-colored urine. Outside of two highly rare hereditary disorders of hepatocytic bilirubin excretion, the other causes of conjugated hyperbilirubinemia are due to inflammatory damage to hepatocytes or defects in bile transport. In these latter disorders, evaluation of additional liver functions tests is highly informative. Generally, elevations of serum aminotransferases out of proportion to serum alkaline phosphatase suggests hepatocytic injury, whereas the reverse suggests impairment of intra-hepatic or extra-hepatic bile transport. However, it should be pointed out that many hepatic diseases cast a wide histological net of pathology and thus lead to impairments in both hepatocyte and biliary function. The links below are not subtopics of this page and will take you to potentially distant sites within the Table of Contents.

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