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 HemeBiliverdinBilirubinBilirubin DiglucoronideUrobilinogenUrobilinStercobilin Heme = planar; Others = not anymore

6. globin Hemoglobin heme

8. I II III IV Fe 2+ NADPH C O 2 O O 2 Heme Oxygenase O

9. IIIIIIIV Biliverdin

10. NADPH H Bilirubin

11. Processing of Bilirubin

12. Excretion of Bilirubin

14. 3 Steps of Biliverdin Metabolism  Hepatic Uptake -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  Conjugation  Excretion

15. 3 Steps of Biliverdin Metabolism  Hepatic Uptake -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  Conjugation -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  Excretion -Bilirubin which is now water soluble can now be excreted from the liver cell to the biliary system.

16. Conjugation with Glucoronates BILIRUBIN DIGLUCORONIDE

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

18. Blood Liver Ligandin (-) charge Ligandin (-) charge Ligandin Prevents bilirubin from going back to plasma

19. Different Causes of Jaundice  Excessive Production of Bilirubin  Reduced Hepatocyte Uptake  Impaired Bilirubin conjugation  Impaired Bile Flow

20. 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

21. Diagnosis of Jaundice  Stool Examination  Special Blood Test  Radiological

22. Classification of Hyperbilirubinemia  Retention – due to overproduction of bilirubin  Regurgitation – reflux of bilirubin into blood

23. 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

24. Hemolytic vs. Hepatocellular vs. Obstructive HemolyticHepatocellularObstructive Urine/Fecal Urobilinogen IncreasedDecreased Absent/ fluctuates BilirubinAbsentPresentPresent ConjugatedNoYesYes

25. 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)

26. Obstructive Jaundice CLINICAL  Presence of tumors, structures BIOCHEMICAL  Mild to severe increase of APL

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

28. Clinical Conditions Related to Increased Unconjugated Hyperbilirubinemia 1.Gelbert’s Syndrome 2.Crigler-Najjar Syndrome (Type I) 3.Crigler-Najjar Syndrome (Type II) 4.Neonatal Jaundice

29. Clinical Conditions Related to Increased Conjugated Hyperbilirubinemia Duben-Johnson Syndrome Rotor Syndrome Defect (hepatocytes) SecretoryTransport Presence of Pigmentation YesNo Metabolism Abnormal Porphyrin Metabolism None