1.Dr. Vijay Marakala, MBBS, MD. Assistant professor BIOCHEMISTRY SIMS & RC

2. NADPH + H+ NADP+ O2 Fe+3 NADPH + H+ NADP+ Haem degradation Haem oxygenase Bilirubin reductase 3. FATE OF BILIRUBIN ? 4. Fate of bilirubin Further metabolism and excretion of bilirubin occurs in the liver and intestine Uptake of bilirubin by liver Conjugation of bilirubin in liver Secretion of conjugated bilirubin into bile Excretion of bilirubin through faeces and urine 5. BLOOD CELLS LIVER Bilirubin diglucuronide (water-soluble) 2 UDP-glucuronic acid via bile duct to intestines Urobilinogen formed by bacteria KIDNEY CO Biliverdin Heme oxygenase O2 Bilirubin (water-insoluble) NADP+ NADPH Biliverdin reductase Heme Globin Hemoglobin reabsorbed into blood Bilirubin (water-insoluble)via blood to the liver INTESTINE 6. Disorder of Hb catabolism Disease or conditions that interfere with bilirubin metabolism may cause a rise in its serum concentration of bilirubin Total bilirubin 0.1 to 1mg/dl Conjugated 0.1 to 0.4mg/dl Unconjugated 0.2 to 0.7mg/dl NORMAL LEVELS 7. Hyperbilirubinaemia When serum bilirubin exceeds 1mg/dl HYPERBILIRUBINAEMIA >2.2 to 5mg/dl - JAUNDICE Yellowish discoloration of skin and sclera due to deposition of bilirubin in the tissues. The condition is called jaundice or icterus 8. INCREASED HAEMOLYSIS breakdown of Hb JAUNDICE LIVER DAMAGE Excretion of bilirubin JAUNDICE BILE DUCT OBSTRUCTION Excretion of bilirubin JAUNDICE CAUSES OF JAUNDICE 9. Jaundice Classification Prehepatic Hepatic Posthepatic 10. Prehepatic or Haemolytic Jaundice Increased breakdown of haemoglobin to bilirubin. Excess haemolysis may be due to Sickle haemoglobin Deficiency of G- 6PD enzyme Incompatible blood transfusion 11. Hepatic/hepatocellular/intrahepatic Disorder of the liver cells or the bile passages within the liver. Viral hepatitis Toxic chemicals Drugs Cirrhosis 12. Posthepatic or Obstructive Jaundice Obstruction in the passage of conjugated bilirubin from liver to intestine. Gallstones Ca of head of pancreas Ca of common bile duct 13. Lab findings in three types of jaundice 14. Neonatal or physiological Jaundice Mild jaundice in the first few days after birth is common. Results from an accelerated haemolysis and immature liver enzyme system Deficiency of UDP-glucuronyl transferase 15. Congenital Hyperbilirubinemia Crigler-Najjar syndrome Gilberts disease Dubin-Johnson syndrome Rotor syndrome 16. Crigler-Najjar syndrome Deficiency of Type I & II Type I is Fatal Unconjugated bilirubin increases more than 20mg/dl Children die because of Type II is milder form 17. Gilberts disease Partial conjugation defect Reduced activity of Asymptomatic and mild Unconjugated bilirubin increases - 3mg/dl 18. Dubin-Johnson syndrome Mutation in the responsible for transport of conjugated bilirubin into bile Black liver jaundice 19. Rotor syndrome Similar to Dubin-Johnson syndrome Exact defect is not identified No staining of liver