Neonatal jaundice pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Pathophysiology

Bilirubin formation and metabolism

• Bilirubin is the final catabolic product of the heme. The heme is a component of some of the body substances and enzymes but it is mainly incorporated in the hemoglobin which is the main component of the red blood cells.
• Bilirubin is formed mainly in the liver and spleen through two steps which include the following:
  • Heme oxygenase enzyme dysregulates the porphyrin ring of the heme breaking it. A green substance called biliverdin is then formed as a result of the previous reaction. Carbon monoxide is a result of the reaction as well
  • Biliverdin reductase enzyme then forms the bilirubin from the biliverdin.
• Bilirubin is a toxic metabolite so, the body has physiologic processes in order to eliminate the bilirubin. Bilirubin elimination includes the following process:
  • Hepatic uptake:
    • After the formation of the bilirubin and its secretion into the bloodstream.
    • The bilirubin becomes bound to the albumin in order to transport it to the liver.
    • The hepatocytes then reuptake the bilirubin and prepare it for excretion.
  • Conjugation:
    • To excrete the bilirubin into the bile, it must be water soluble first.
    • Conjugation of the bilirubin with the glucuronic acid makes it water-soluble and the final product is bilirubin diglucuronide.
    • The conjugation process occurs by the glucuronosyltransferase enzyme in the liver cells.
  • Clearance and excretion:
    • After conjugation of the bilirubin in the liver, it is secreted into the bile then into the gastrointestinal tract.
    • In the GIT, the conjugated bilirubin is metabolized by the gut enzymes into urobilinogen which is oxidized into urobilin.
    • Metabolism of the conjugated bilirubin occurs properly in the adults. However, the newborns have sterile gastrointestinal canal which impedes the catalyzation of the conjugated bilirubin.
    • The sterile tract will end up with a small amount of excreted bile.
    • The remaining conjugated bilirubin will be unconjugated by the beta-glucuronidase enzyme in the neonatal intestine.
    • The unconjugated bilirubin can be reabsorbed back into the blood and to the liver through the enterohepatic circulation of bilirubin.
    • A small amount of bilirubin is cleared into the urine as urobilinogen.

Pathogenesis

• The main pathogenesis mechanisms of neonatal jaundice include the following:
  • Bilirubin production is elevated because of increased breakdown of fetal erythrocytes. This is the result of the shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates.
  • Hepatic excretory capacity is low both because of low concentrations of the binding protein ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the enzyme responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble (conjugation).