Bilirubin Conjugation
Bilirubin – a product of hemoglobin degradation and is toxic once it accumulates in the body.
Unconjugated bilirubin – also termed as indirect bilirubin. This type of bilirubin is soluble in fat but not in water. Because it is fat soluble it may be absorbed by the subcutaneous fat, causing the yellowish discoloration of skin or jaundice.
Conjugated bilirubin – also termed as direct bilirubin. This type of bilirubin is water soluble. It is in this form that bilirubin is excreted out of the body. Conjugated bilirubin is less toxic that the other type.
Factors Contributing to Bilirubin Production
- Excess production
Approximately 6-8 mg/kg of bilirubin is produced in infants each day during the first 2 weeks of life and adults have a rate of 2.5 times than that of neonates.
- Red Blood Cell Life
In adults RBC’s life span is 120 days. In preterm infants the RBCs last only for 60-70 days and 80-100 days in term infants. Neonates’ erythrocytes are more fragile and susceptible to damage and injury than those of adults. Red blood cells break down faster in neonates and thereby producing more amount of bilirubin than adults.
- Liver immaturity
The liver normally produces adequate amounts of the enzyme glucoronyl transferase to conjugate bilirubin and be excreted out of the body. The newborn’s immature liver may not be able to produce adequate amounts of this enzyme resulting to the limited amount of bilirubin that can be conjugated.
- Intestinal factors
Two factors may result to high levels of unconjugated bilirubin:
- Sterile intestines of newborns at birth – conjugated bilirubin cannot be reduced to urobilirubin or stercobilin to be excreted out of the body without the intervention of intestinal flora.
- Large amount of beta-glucuronidase enzyme in the newborn’s intestines – beta-gucuronidase changes bilirubin back to the unconjugated state.
- Delayed Feeding
Feeding the newborn helps to establish a normal intestinal flora and promotes the passage of meconium. Meconium contains high amounts of bilirubin. In cases where feeding is delayed or meconium is not excreted the beta-glucuronidase exposure in the intestine is prolonged thus increasing the chance of converting the unconjugated bilirubin to the conjugated state.
- Trauma
Trauma at birth (e.g. bruising) results to the increased hemolysis of RBC. Hemolysis of RBC results to the production of additional bilirubin.
Bilirubin conjugation
- Unconjugated bilirubin (UCB) is released into the bloodstream and attaches to the albumin binding sites in the plasma to be carried to the liver.
- Once unconjugated bilirubin is already at the liver, the enzyme glucuronyl transferase in the smooth endoplasmic reticulum of liver cells binds the UCB to ligandin and other proteins to become a conjugated bilirubin.
- Conjugated bilirubin (CB) is then excreted into the bile and into the duodenum.
- As CB reaches the intestines, the normal intervenes on conjugated bilirubin and converts it to urobilinogen and stercobilin.
- Urobilinogen and stercobilin are excreted in the stools and some urobilinogen are excreted by the kidneys.
image from ahdc.vet.cornell.edu