The Biochemistry of Jaundice

 A collaborative effort of Group 3 Section

1C2

 Members:

 Animations by: Gerald Fuentes

Formation of Bilirubin
 Bilirubin Metabolism
Heme = planar; Others = not anymore

Bilirubin
Urobilinogen
Stercobilin
Biliverdin
Bilirubin
Urobilin
Heme
Diglucoronide
 Hemoglobin

globin globin globin globin

heme heme heme heme

 Heme Oxygenase

I
C NADPH
IV Fe2+ II

O2 O2
III
IV III II I

Biliverdin
 H

Bilirubin
NADPH
Processing of Bilirubin
Excretion of Bilirubin
 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
 3 Steps of Biliverdin Metabolism
 Hepatic Uptake  Conjugation
 Excretion
-Bilirubin
Unconjugated
which bilirubin
is now water
is presented
(watersoluble
insoluble)
in
can the
is
now
liverexcreted
converted
be cell tofrom
bilirubin
the liver
diglucoronide
cell to the(water
biliary
soluble)
system.
-The albumin associated with it is dissociated
-Takes place in the smooth endoplasmic
-Ligandin is delivered to prevent efflux of
reticulum of the liver
bilirubin back to plasma
-Catalyzed by glucoronyl transferase
Conjugation with Glucoronates

BILIRUBIN DIGLUCORONIDE
Role of Blood Proteins in the
Metabolism of Bilirubin

Sparingly soluble in
Blood

1. Albumin

Dissolved in Blood
Blood

Liver
Ligandin Ligandin

(-) charge (-) 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

Hemolytic Hepatocellular Obstructive

Urine/Fecal Absent/
Increased Decreased
Urobilinogen fluctuates

Bilirubin Absent Present Present

Conjugated No Yes Yes

 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
Rotor Syndrome
Syndrome
Defect
Secretory Transport
(hepatocytes)
Presence of
Yes No
Pigmentation
Abnormal
Metabolism Porphyrin None
Metabolism