Molecular basis of hyperbilirubinemia and phototherapy

Hyperbilirubinemia in the newborn results not only in visible yellow discoloration of the skin but, in high concentration, may cause bilirubin encephalopathy. Such damage to the central nervous system may be subtle and not apparent for several years, as with visual-motor perceptive defects; or it may cause severe neurologic damage (Kernicterus)--even death. Sick and immature infants are the most vulnerable to bilirubin toxicity. Although this condition affects nearly half of all newborns to some degree, only about 10% require treatment. Two methods of treatment are really effective in correcting hyperbilirubinemia, exchange blood transfusions, and/or phototherapy with light radiation in the blue part of the visible spectrum. If the rate of production of bilirubin is excessive or an infant's capacity to conjugate and excrete the pigment is deficient, bilirubin will accumulate in plasma, and will be taken up by other lipid-containing tissues, collagen, and (unless firmly bound to albumin) brain tissue. Many factors combine to raise plasma levels of bilirubin to toxic levels; for example, acidosis, sepsis, hypoxia, hemolysis, hypoalbuminemia, and certain competitive albumin binders. Bilirubin is photolabile in vivo, and if the whole body is irradiated with visible light in the absorption band (450-490 nm) of bilirubin, the pigment will undergo photocatabolism. Under phototherapy bilirubin undergoes photoisomerization at the meso double-bond to conformations less lipophyllic. It is now known that the major photo products of bilirubin IX-alpha are an unresolved mixture of its E, Z and Z, E isomers, easily excreted by the liver. Thus, phototherapy will reduce the accumulation of bilirubin in skin and other tissues and in circulating plasma.