I.

Mechanism of bilirubin formation

1. Bilirubin catabolism starts from the catabolism of hemoglobin in the reticuloendothelial
system and ineffective erythropoiesis in the newborn.
2. Enzyme heme oxygenase acts on heme from hemoglobin, giving rise to biliverdin and carbon
monoxide.
3. Biliverdin is converted to bilirubin by the enzyme biliverdin reductase. This form is called
indirect-reacting, unconjugated bilirubin and is insoluble in water and can cause toxicity in the
central nervous system. The unconjugated bilirubin binds to the albumin so that it will not enter
the CNS.
4. The metabolism continues with the uptake of bilirubin into hepatocytes. The non-polar, fat
soluble bilirubin crosses the hepatocyte plasma membrane and is bound mainly to cytoplasmic
ligandin or Y protein for transport to the smooth endoplasmic reticulum.
5. The unconjugated (indirect) bilirubin is converted into water-soluble conjugated (direct)
bilirubin by the enzyme uridine diphosphogluconurate glucuronosyltransferase (UGT).
6. Most of the conjugated bilirubin is excreted through the bile into the small intestine and
eliminated in the stool.
7. Some may undergo hydrolysis and is converted into the unconjugated fraction by the intestinal
enzyme beta-glucoronidase and is returned to the enterohepatic circulation.

Three main mechanisms in the development of neonatal jaundice:

1. Erythrocytes of a newborn has a shorter life span of 70-90 days compared to that of an adult.
Normally, newborns produce about 6-8mg/kg of bilirubin a day due to the short life span of their
red blood cells. This rate is 2.5 times higher than that of adults.
2. Neonates have low number of intestinal bacteria that converts bilirubin into urobilinogen and
stercobilinogen, which are excreted in urine and stool respectively. There is also a decrease
activity of beta-glucoronidase, a conjugating enzyme. Therefore, unconjugated bilirubin is
reabsorbed in the enterohepatic circulation resulting in an increase the bilirubin load of the liver.
3. Newborns have deficient ligandin enzymes which promotes entry of free bilirubin into the
hepatocytes for conjugation causing in a reduced clearance of bilirubin from the plasma.
II. Difference between physiologic and pathologic jaundice
PARAMETER PHYSIOLOGIC
Onset > 24 hours of life
Type of Bilirubin Unconjugated
Rise of Bilirubin per day < 5mg/dL/day
Resolution of Jaundice Less than 1 week, or
sometimes 2 weeks
Treatment Observation or sometimes
phototherapy
PATHOLOGIC
< 24 hours of life
Unconjugated or conjugated
> 5mg/dL/day
Persistent for more than 2
weeks
Phototherapy or exchange
transfusion