The Biochemistry of Jaundice

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The Biochemistry of Jaundice

• A collaborative effort of Group 3 Section 1C2
• Members
• Animations by Gerald Fuentes

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Formation of Bilirubin
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Bilirubin Metabolism
Heme planar Others not anymore
Heme Oxygenase
Heme
Biliverdin
Bilirubin
Bilirubin Diglucoronide
Urobilinogen
Urobilin
Stercobilin
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Circulation
Red Blood Cells
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120 days
Circulation
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Hemoglobin
globin
globin
globin
globin
heme
heme
heme
heme
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Heme Oxygenase
C
NADP
H
O
O
O
O
2
2
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I
II
III
IV
Biliverdin
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H
Bilirubin
NADP
H
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Processing of Bilirubin
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Excretion of Bilirubin
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3 Steps of Biliverdin Metabolism

• Conjugation

• Hepatic Uptake

• 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

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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.

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Conjugation with Glucoronates
Glucoronyl transferase
BILIRUBIN DIGLUCORONIDE
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Role of Blood Proteins in the Metabolism of
Bilirubin
Sparingly soluble in Blood
1. Albumin
Dissolved in Blood
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Blood
Liver
Ligandin Prevents bilirubin from going back to
plasma
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Different Causes of Jaundice

• Excessive Production of Bilirubin
• Reduced Hepatocyte Uptake
• Impaired Bilirubin conjugation
• Impaired Bile Flow

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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

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Diagnosis of Jaundice

• Stool Examination
• Special Blood Test
• Radiological

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Classification of Hyperbilirubinemia

• Retention due to overproduction of bilirubin
• Regurgitation reflux of bilirubin into blood

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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

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Hemolytic vs. Hepatocellular vs. Obstructive
Hemolytic Hepatocellular Obstructive
Urine/Fecal Urobilinogen Increased Decreased Absent/ fluctuates
Bilirubin Absent Present Present
Conjugated No Yes Yes
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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)

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Obstructive Jaundice

• CLINICAL
• Presence of tumors, structures
• BIOCHEMICAL
• Mild to severe increase of APL

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Hepatocellular Jaundice

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

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Clinical Conditions Related to Increased
Unconjugated Hyperbilirubinemia

1. Gelberts Syndrome
2. Crigler-Najjar Syndrome (Type I)
3. Crigler-Najjar Syndrome (Type II)
4. Neonatal Jaundice

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Clinical Conditions Related to Increased
Conjugated Hyperbilirubinemia
Duben-Johnson Syndrome Rotor Syndrome
Defect (hepatocytes) Secretory Transport
Presence of Pigmentation Yes No
Metabolism Abnormal Porphyrin Metabolism None