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

Formation of Bilirubin

Bilirubin Metabolism HemeBiliverdinBilirubinBilirubin DiglucoronideUrobilinogenUrobilinStercobilin Heme = planar; Others = not anymore

globin Hemoglobin heme

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

IIIIIIIV Biliverdin

NADPH H Bilirubin

Processing of Bilirubin

Excretion of Bilirubin

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

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.

Conjugation with Glucoronates BILIRUBIN DIGLUCORONIDE

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

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

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

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

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

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

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

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

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)

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

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

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

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