Neonatal Jaundice and Liver Disease

Neonatal Jaundice and Liver Disease

Bilirubin is one of three biologically active end-products of heme catabolism. Its clinical significance in the neonate relates to its propensity for deposition in the skin and mucous membranes, producing easily identifiable jaundice (French jaune, yellow) or icterus (Greek ikteros, jaundice). The yellow color, or the total serum (or plasma) bilirubin concentration at any point in time, represents the combined processes of bilirubin production and bilirubin elimination from the body, the latter process being comprised of bilirubin uptake into hepatocytes, bilirubin conjugation, and excretion of the conjugated product. As long as these functions remain in balance, a moderate degree of jaundice may develop but should not endanger an otherwise healthy, non-hemolyzing infant. However, an imbalance between bilirubin production and its elimination may result in increasing jaundice or hyperbilirubinemia. In rare cases, the degree of bilirubin production relative to its elimination may be so great that bilirubin may deposit in the brain, where it may cause dysfunction in the form of acute bilirubin encephalopathy. Although some cases of acute bilirubin encephalopathy may be transient and reversible, chronic bilirubin encephalopathy, known classically as kernicterus, with resultant permanent neuronal damage manifesting as a form of cerebral palsy, may ensue. As many as eighty percent of otherwise healthy, term newborns develop some degree of elevated total serum bilirubin levels. In contrast, severe hyperbilirubinemia (total serum bilirubin greater than twenty-five milligrams per deciliter) with its potentially devastating sequelae is rare. It is therefore nonetheless important to distinguish between and have a thorough understanding of the normal and pathologic processes of bilirubin physiology and the potential complications of severe hyperbilirubinemia.

Bilirubin Metabolism

Bilirubin Biochemistry Overview

Throughout life, there is a continuum of bilirubin production and elimination from the body. Ongoing lysis of red blood cells, whether physiologic or at increased rates (e.g., due to hemolysis), releases iron protoporphyrin (heme), the oxygen-carrying component of hemoglobin. Catalyzed by heme oxygenase, heme is then converted to biliverdin and subsequently to bilirubin, which in its unconjugated form is transported to the liver bound to albumin. Once in the hepatocyte, bilirubin is conjugated to glucuronic acid by the enzyme uridine diphosphate glucuronic acid-glucuronosyltransferase one A one. Water-soluble conjugated bilirubin can be now excreted into the bile from which it reaches the bowel and is ultimately eliminated from the body. This simplified overview of bilirubin biochemistry will be reviewed in greater detail later in this chapter.