Bilirubin metabolism

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BILIRUBIN METABOLISM

Transcript of Bilirubin metabolism

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BILIRUBIN METABOLISM

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Bilirubin

Bilirubin is the degradation product of hemeproteins.

Heme is an iron-containing porphyrin, found in hemoglobin of the red blood cells.

Bilirubin

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Formation of bilirubin

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Uptake of Bilirubin by the liver

Bilirubin is only slightly soluble in plasma thus transported to the liver by binding non-covalently to albumin. Bilirubin dissociates from the carrier albumin molecule and enters a hepatocyte and binds to intracellular proteins; ligandin and Z protein.

Note: drugs, such as salicylates and sulfonamides can displace bilirubin from albumin, permitting bilirubin to enter the central nervous system. This causes the potential for neural damage in infants.

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Formation of Bilirubin diglucuronide (conjugated bilirubin)

The solubility of bilirubin is increased by the addition of two molecules of glucuronic acid.This conjugation process is catalyzed by bilirubin (UDP) glucuronyltransferase.UDP (uridine diphosphate)-glucuronic acid is the glucuronate donor.

Varying degrees of deficiency of this enzyme result in Crigler-Najjar I and II and Gilbert syndrome, with Crigler-Najjar I being the most severe deficiency.

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Excretion of bilirubin

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Excretion of Bilirubin

Enterohepatic urobilinogen and urobilin excretion in the urine: Some of the urobilinogen is reabsorbed from the gut and enters the portal blood. A portion participates in the enterohepatic urobilinogen cycle, i.e. taken up by the liver, and then resecreted into the bile.The remainder is transported by the blood to the kidney, where it is converted to yellowand excreted, giving urine its characteristic color.

urobilin

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Summary of Bilirubin Metabolism

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ADDITIONAL INFO

• In newborns, the normal hemoglobin level is 15-18 mg/dl so the physiologic rate of RBC destruction is proportionately high. Excessive bruising from birth trauma or abnormal blood collections such as in a cephalohematoma may further add to the rate of RBC destruction and bilirubin formation.

• The level of glucoroynl transferase is low in the newborn and any increase in the rate of bilirubin formation can overwhelm the capacity to conjugate.