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The Biochemistry of JaundiceThe Biochemistry of Jaundice
A collaborative effort of Group 3 Section A collaborative effort of Group 3 Section 1C21C2
Members:Members:
Animations by: Gerald FuentesAnimations by: Gerald Fuentes
Formation of BilirubinFormation of Bilirubin
Bilirubin MetabolismBilirubin Metabolism
HemeBiliverdinBilirubinBilirubin DiglucoronideUrobilinogenUrobilinStercobilin
Heme = planar; Others = not anymore
globin globin globin globin
Hemoglobin
heme heme heme heme
I
II
III
IV Fe2+
NADPHC
O2O O2
Heme Oxygenase
O
IIIIIIIV
Biliverdin
NADPH
H
Bilirubin
Processing of BilirubinProcessing of Bilirubin
Excretion of BilirubinExcretion of Bilirubin
3 Steps of Biliverdin Metabolism3 Steps of Biliverdin Metabolism
Hepatic UptakeHepatic Uptake
-Unconjugated bilirubin is presented in the Unconjugated bilirubin is presented in the liver cellliver cell
-The albumin associated with it is dissociatedThe albumin associated with it is dissociated
-Ligandin is delivered to prevent efflux of Ligandin is delivered to prevent efflux of bilirubin back to plasmabilirubin back to plasma
ConjugationConjugation ExcretionExcretion
3 Steps of Biliverdin Metabolism3 Steps of Biliverdin Metabolism
Hepatic UptakeHepatic Uptake
-Unconjugated bilirubin is presented in the Unconjugated bilirubin is presented in the liver cellliver cell
-The albumin associated with it is dissociatedThe albumin associated with it is dissociated
-Ligandin is delivered to prevent efflux of Ligandin is delivered to prevent efflux of bilirubin back to plasmabilirubin back to plasma
ConjugationConjugation
-Unconjugated bilirubin (water insoluble) is Unconjugated bilirubin (water insoluble) is converted to bilirubin diglucoronide (water converted to bilirubin diglucoronide (water soluble)soluble)
-Takes place in the smooth endoplasmic Takes place in the smooth endoplasmic reticulum of the liverreticulum of the liver
-Catalyzed by glucoronyl transferaseCatalyzed by glucoronyl transferase
ExcretionExcretion-Bilirubin which is now water soluble can now Bilirubin which is now water soluble can now be excreted from the liver cell to the biliary be excreted from the liver cell to the biliary system.system.
Conjugation with GlucoronatesConjugation with Glucoronates
BILIRUBIN DIGLUCORONIDE
Role of Blood Proteins in the Role of Blood Proteins in the Metabolism of BilirubinMetabolism 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 JaundiceDifferent Causes of Jaundice
Excessive Production of BilirubinExcessive Production of Bilirubin Reduced Hepatocyte UptakeReduced Hepatocyte Uptake Impaired Bilirubin conjugationImpaired Bilirubin conjugation Impaired Bile FlowImpaired Bile Flow
Diagnosis of JaundiceDiagnosis of Jaundice
Urine ExaminationUrine Examination– Qualitative measurement of bilirubinQualitative measurement of bilirubin– Either Ictotest or Dipstick methodEither Ictotest or Dipstick method– Foam Test methodFoam Test method
Normal Urine – foam is absolutely whiteNormal Urine – foam is absolutely white Hyperbilibirunemia – foam is yellowHyperbilibirunemia – foam is yellow
Diagnosis of JaundiceDiagnosis of Jaundice
Stool ExaminationStool Examination Special Blood TestSpecial Blood Test RadiologicalRadiological
Classification of HyperbilirubinemiaClassification of Hyperbilirubinemia
Retention – due to overproduction of Retention – due to overproduction of bilirubinbilirubin
Regurgitation – reflux of bilirubin into bloodRegurgitation – reflux of bilirubin into blood
Acholuric Vs. CholuricAcholuric Vs. Choluric
CHOLURIC – presence of bile derivatives in CHOLURIC – presence of bile derivatives in the urinethe urine– Occurs in regurgitation hyperbilirubinemiaOccurs in regurgitation hyperbilirubinemia– Obstructive typeObstructive type
ACHOLURIC – absence of bile in urineACHOLURIC – absence of bile in urine– Retention hyperbilirubinemiaRetention hyperbilirubinemia– Hemolytic typeHemolytic type
Hemolytic vs. Hepatocellular vs. Hemolytic vs. Hepatocellular vs. ObstructiveObstructive
HemolyticHemolytic HepatocellularHepatocellular ObstructiveObstructive
Urine/Fecal Urine/Fecal UrobilinogenUrobilinogen IncreasedIncreased DecreasedDecreased Absent/ Absent/
fluctuatesfluctuates
BilirubinBilirubin AbsentAbsent PresentPresent PresentPresent
ConjugatedConjugated NoNo YesYes YesYes
Hemolytic JaundiceHemolytic Jaundice
CLINICALCLINICAL Defect in uptake of bilirubin by liver cellsDefect in uptake of bilirubin by liver cells Immature hepatic conjugating systemImmature hepatic conjugating system
BIOCHEMICALBIOCHEMICAL Slight change in liver cellsSlight change in liver cells Severe increase of Alkaline Phospholipase Severe increase of Alkaline Phospholipase
(APL)(APL)
Obstructive JaundiceObstructive Jaundice
CLINICALCLINICAL Presence of tumors, structuresPresence of tumors, structures
BIOCHEMICALBIOCHEMICAL Mild to severe increase of APLMild to severe increase of APL
Hepatocellular JaundiceHepatocellular Jaundice
CLINICALCLINICAL Liver damage (hepatitis, cirrhosis)Liver damage (hepatitis, cirrhosis)
BIOCHEMICALBIOCHEMICAL With marked biochemical change in liver With marked biochemical change in liver
cellscells Marked increase in APLMarked increase in APL
Clinical Conditions Related to Clinical Conditions Related to Increased Unconjugated Increased Unconjugated
HyperbilirubinemiaHyperbilirubinemia
1.1. Gelbert’s SyndromeGelbert’s Syndrome
2.2. Crigler-Najjar Syndrome (Type I)Crigler-Najjar Syndrome (Type I)
3.3. Crigler-Najjar Syndrome (Type II)Crigler-Najjar Syndrome (Type II)
4.4. Neonatal JaundiceNeonatal Jaundice
Clinical Conditions Related to Clinical Conditions Related to Increased Conjugated Increased Conjugated
HyperbilirubinemiaHyperbilirubinemiaDuben-Johnson Duben-Johnson
SyndromeSyndrome Rotor SyndromeRotor Syndrome
Defect Defect (hepatocytes)(hepatocytes) SecretorySecretory TransportTransport
Presence of Presence of PigmentationPigmentation YesYes NoNo
MetabolismMetabolismAbnormal Abnormal Porphyrin Porphyrin
MetabolismMetabolismNoneNone