pediatrics
Perinatal Physiology
Neonatal Bilirubin Metabolism
(See also Liver Structure and Function and Aged or damaged fetal red blood cells are removed from the circulation by reticuloendothelial cells, which convert heme to bilirubin (1 g of hemoglobin yields 35 mg of bilirubin). This bilirubin binds toalbuminand is transported to the liver, where it is transferred into hepatocytes. Glucuronyl transferase then conjugates the bilirubin with uridine diphosphoglucuronic acid (UDPGA) to form bilirubin diglucuronide (conjugated bilirubin), which is secreted actively into the bile ducts. Bilirubin diglucuronide makes its way into meconium in the gastrointestinal tract but cannot be eliminated from the body because the fetus does not normally pass stool. The enzyme beta-glucuronidase, present in the fetus’ small-bowel luminal brush border, is released into the intestinal lumen, where it deconjugates bilirubin glucuronide; free (unconjugated) bilirubin is then reabsorbed from the intestinal tract and re-enters the fetal circulation. Fetal bilirubin is cleared from the circulation by placental transfer into the mother’s plasma following a concentration gradient. The maternal liver then conjugates and excretes the fetal bilirubin. At birth, the placental connection is terminated, and although the neonatal liver continues to take up, conjugate, and excrete bilirubin into bile so it can be eliminated in the stool, neonates lack proper intestinal bacteria for oxidizing bilirubin to urobilinogen in the gut; consequently, unaltered bilirubin remains in the stool, imparting a typical bright-yellow color. Additionally, the neonatal gastrointestinal tract (like that of the fetus) contains beta-glucuronidase, which deconjugates some of the bilirubin. Feedings invoke the gastrocolic reflex, and bilirubin is excreted in stool before most of it can be deconjugated and reabsorbed. However in many neonates, the unconjugated bilirubin is reabsorbed and returned to the circulation from the intestinal lumen (enterohepatic circulation of bilirubin), contributing to physiologic hyperbilirubinemia and jaundice. Increased hematocrit and shorter life span of red blood cells in the neonate result in increased bilirubin production and also contribute to physiologic hyperbilirubinemia. 