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