Bilirubin Metabolism and Excretion

Bilirubin Metabolism and Excretion

• The liver is the primary site of bilirubin metabolism and excretion.
• Glucuronic acid is the major conjugating group in the glucuronidation of bilirubin.
• The enzyme UDP-glucuronyl-transferase catalyzes the glucuronidation of bilirubin.
• Conjugated bilirubin is excreted into the bile.

Fate of Bilirubin in the Body

• Urobilinogen is yellow.
• Stercobilin is brown.
• The main clinical laboratory test used to measure serum bilirubin is the Van den Bergh assay.
• The Van den Bergh assay measures direct bilirubin.
• Direct bilirubin is water-soluble (conjugated) and reacts rapidly in the Van den Bergh assay.

Organ Involvement in Bilirubin Removal

• The spleen is primarily responsible for the removal of senescent erythrocytes from circulation.
• The liver is primarily responsible for the conversion of heme to bilirubin.

Heme Catabolism

• The molecule biliverdin is used in the catabolism of heme to yield bilirubin.
• Bilirubin is normally processed by the liver through glucuronidation.

Enzyme Role in Heme Catabolism

• UDP-glucuronyl-transferase is involved in the conjugation of bilirubin.

Conjugation and Deconjugation

• Conjugated bilirubin is converted back into unconjugated bilirubin through deconjugation.

Bilirubin Measurement

• Direct bilirubin is measured directly using the Van den Bergh assay.
• Indirect bilirubin is measured indirectly through the difference between total bilirubin and direct bilirubin.

Neonatal Jaundice

• The biochemical basis for problems associated with neonatal jaundice is the inability of the newborn to efficiently conjugate bilirubin.

Genetic Disorders of Hyperbilirubinemia

• The genetically inherited disorders of hyperbilirubiemia mentioned are Crigler-Najjar syndrome and Gilbert-Meulengracht syndrome.
• These disorders affect bilirubin lab values, leading to elevated levels of bilirubin in the blood.

Characteristics of Unconjugated Hyperbilirubinemia

• Unconjugated (indirect) hyperbilirubinemia is characterized by elevated levels of indirect bilirubin in the blood.

Treatment of Neonatal Jaundice

• The most common treatment for neonatal jaundice is phototherapy.

Characteristics of Gilbert Syndrome

• Gilbert syndrome is NOT characterized by an inherited deficiency of the MRP2 transporter.
• It is characterized by a mild, chronic unconjugated hyperbilirubinemia.

Characteristics of Dubin-Johnson Syndrome

• Dubin-Johnson syndrome is characterized by an inherited deficiency of the MRP2 transporter.
• It is characterized by a conjugated hyperbilirubinemia.

Characteristics of Obstructive Jaundice

• Obstructive jaundice is characterized by a conjugated hyperbilirubinemia.

Hepatocellular Jaundice

• The characteristic feature of hepatocellular jaundice is a mixed pattern of unconjugated and conjugated hyperbilirubinemia.
• The genetic basis of Gilbert-Meulengracht syndrome is a deficiency in the UDP-glucuronyl-transferase enzyme.
• The prognosis of Dubin-Johnson syndrome is generally good.