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The Biochemistry of Jaundice

The Biochemistry of Jaundice. A collaborative effort of Group 3 Section 1C2 Members: Animations by: Gerald Fuentes. Formation of Bilirubin. Bilirubin Metabolism. Heme = planar; Others = not anymore. Heme Oxygenase. Bilirubin Diglucoronide. Heme. Urobilinogen. Stercobilin. Urobilin.

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The Biochemistry of Jaundice

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  1. The Biochemistry of Jaundice • A collaborative effort of Group 3 Section 1C2 • Members: • Animations by: Gerald Fuentes

  2. Formation of Bilirubin

  3. Bilirubin Metabolism Heme = planar; Others = not anymore Heme Oxygenase Bilirubin Diglucoronide Heme Urobilinogen Stercobilin Urobilin Biliverdin Bilirubin

  4. Circulation Red Blood Cells

  5. 120 days Circulation

  6. Hemoglobin globin globin globin globin heme heme heme heme

  7. I IV II Fe2+ III Heme Oxygenase C NADP H O O O O 2 2

  8. IV III II I Biliverdin

  9. H Bilirubin NADP H

  10. Processing of Bilirubin

  11. Excretion of Bilirubin

  12. 3 Steps of Biliverdin Metabolism • Hepatic Uptake • Conjugation • Excretion • Unconjugated bilirubin is presented in the liver cell • The albumin associated with it is dissociated • Ligandin is delivered to prevent efflux of bilirubin back to plasma

  13. 3 Steps of Biliverdin Metabolism • Hepatic Uptake • Conjugation • Excretion • Unconjugated bilirubin is presented in the liver cell • The albumin associated with it is dissociated • Ligandin is delivered to prevent efflux of bilirubin back to plasma • Unconjugated bilirubin (water insoluble) is converted to bilirubin diglucoronide (water soluble) • Takes place in the smooth endoplasmic reticulum of the liver • Catalyzed by glucoronyl transferase • Bilirubin which is now water soluble can now be excreted from the liver cell to the biliary system.

  14. COOH COOH Methyl Propionate Propionate Vinyl Methyl Vinyl Conjugation with Glucoronates Glucoronyl transferase BILIRUBIN DIGLUCORONIDE

  15. Albumin Bilirubin Role of Blood Proteins in the Metabolism of Bilirubin Sparingly soluble in Blood 1. Albumin Dissolved in Blood

  16. Albumin Albumin Bilirubin Bilirubin Ligandin (-) charge Ligandin (-) charge Blood Liver Ligandin Prevents bilirubin from going back to plasma

  17. Different Causes of Jaundice • Excessive Production of Bilirubin • Reduced Hepatocyte Uptake • Impaired Bilirubin conjugation • Impaired Bile Flow

  18. Diagnosis of Jaundice • Urine Examination • Qualitative measurement of bilirubin • Either Ictotest or Dipstick method • Foam Test method • Normal Urine – foam is absolutely white • Hyperbilibirunemia – foam is yellow

  19. Diagnosis of Jaundice • Stool Examination • Special Blood Test • Radiological

  20. Classification of Hyperbilirubinemia • Retention – due to overproduction of bilirubin • Regurgitation – reflux of bilirubin into blood

  21. Acholuric Vs. Choluric • CHOLURIC – presence of bile derivatives in the urine • Occurs in regurgitation hyperbilirubinemia • Obstructive type • ACHOLURIC – absence of bile in urine • Retention hyperbilirubinemia • Hemolytic type

  22. Hemolytic vs. Hepatocellular vs. Obstructive

  23. Hemolytic Jaundice CLINICAL Defect in uptake of bilirubin by liver cells Immature hepatic conjugating system BIOCHEMICAL Slight change in liver cells Severe increase of Alkaline Phospholipase (APL)

  24. Obstructive Jaundice CLINICAL • Presence of tumors, structures BIOCHEMICAL • Mild to severe increase of APL

  25. Hepatocellular Jaundice CLINICAL • Liver damage (hepatitis, cirrhosis) BIOCHEMICAL • With marked biochemical change in liver cells • Marked increase in APL

  26. Clinical Conditions Related to Increased Unconjugated Hyperbilirubinemia • Gelbert’s Syndrome • Crigler-Najjar Syndrome (Type I) • Crigler-Najjar Syndrome (Type II) • Neonatal Jaundice

  27. Clinical Conditions Related to Increased Conjugated Hyperbilirubinemia

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