Heme catabolism
Learning objectives
• Steps of heme degradation
• Types of jaundice and its clinical condition
• List of investigations for jaundice
HYDROXYLATION OF HEME
HEME OXYGENASE
OPENING OF PYRROLE
HEME OXYGENASE 1 : 14 : 99 : 3
REDUCTION OF BILIVERDIN
EC 1 : 3 : 1 : 24
TRANSPORT&UPTAKE
Noncovalent binding to albumin
Uptake of Bilirubin by liver parenchyma
cells Facilitated transport system
Bind to certain cytosolic proteins
CONJUCATION OCCURS IN LIVER
Bilirubin properties
Unconjugated Conjugated
Insoluble Water soluble
Complexed Loosely bound
Toxic Nontoxic
Cannot be excreted Can be excreted
VAN DENBERG REACTION
UNCONJUCATED CONJUCATED
DIAZO REAGENT
ACCELERATORS
AZODIPYRROLES
JENDRASSIK GROF METHOD
TOTAL BILIRUBIN = (UC/ID + C/D)
VAN DENBERG REACTION
• PRE HEPATIC POSTHEPATIC
UC HEPATIC C
MIXED
DIAZO REAGENT
(ACCELERATOR) 15 mns 30 S
I/D BIPH
D/I
AZO DIPYRROLES
What is jaundice ? its causes
Causes of jaundice
• JAUNDICE OCCURS WHEN THE EQUILIBRIUM BETWEEN
BILIRUBIN PRODUCTION AND CLEARANCE IS DISTURBED
• EXCESSIVE PRODUCTION OF BILIRUBIN.
• REDUCED HEPATOCYTEUPTAKE.
• IMPAIRED CONJUGATION.
DECREASED HEPATOCELLULAR EXCRETION.
• IMPAIRED BILE FLOW.
CASE HISTORY 1
A 26 year old girl admitted to the hospital with yellow
discoloration of the sclera .On examination patient is pale,and
spleen palpable.Biochemical investigation given below
BILIRUBIN
Total 12.8 mg/dL
Conjugated 0.4 mg/dL
Unconjugated 12.4 mg/dL
URINE
Bile salt Absent
Bile pigment Absent
Urobilinogen +ve
FAECES High coloured
PRE HEPATIC/HEMOLYTIC JAUNDICE
• RED CELL MEMBRANE DEFECT.
• INEFFECTIVE ERYTHROPOIESIS.
• CONGENITAL.
• PHYSIOLOGICAL JAUNDICE OF NEWBORN
• HEMOLYTIC DISEASE OF NEWBORN.
UNCONJUGATED
CONGENITAL UNCONJUGATED
Neonatal jaundice
• Breast feeding jaundice
• Breast milk jaundice
• Dubin Johnson syndrome – MOAT
/MRP2defect
• Rotor syndrome – OATP1B1/OATP1B3 defect
Treatment
1. phototherapy
2. phenobarbitone
3. blood exchange
Case history 2
• A 45 year old male who is a known alcoholic admitted to the
hospital with yellow discoloration of the sclera, vomiting had
the following laboratory values.
SERUM BILIRUBIN
Total 6.8 mg/dL
Conjugated 3.6 mg/dL
Unconjugated 3.2 mg/dL
URINE
Bile salt Absent
Bile pigment Absent
Urobilinogen +ve
HEPATIC
HEPATIC JAUNDICE
HEPATIC
• Damage to liver cells results of decreased
conjugation.
• The bilirubin that is conjugated is not efficiently
secreted into the bile
• Urobilinogen is increased in the urine because
hepatic damage decreases the enterohepatic
circulation
• Urine Urobilinogen : Decreased if micro-
obstruction is present
• Urine Bilirubin: Present if micro-obstruction
occurs
CASE HISTORY 3
• A 62 year old male admitted to the hospital with yellow
discoloration of the sclera, abdominal pain had the following
laboratory values. On examination gall bladder is palpable.
SERUM BILIRUBIN
Total 8 mg/dL
Conjugated 7.2 mg/dL
Unconjugated 0.8 mg/dL
URINE
Bile salt Present
Bile pigment Present
Urobilinogen Absent
FAECES Clay colored
CONJUGATED
• DECREASED CANALICULAR SECRETION
INFECTION
DUBIN JOHNSON
ROTAR
DRUGS
• DECREASED DRAINAGE
INTRA HEPATIC OBSTRUCTION
EXTRA HEPATIC OBSTRUCTION
Post hepatic/obstructive
INVESTIGATION
BLOOD: BILIRUBIN Total Direct Indirect
ENZYMOLOGY
VAN DENBERG REACTION
URINE: BILE SALT (HAY’S)
BILE PIGMENT (FOUCHET’S)
UROBILINOGEN (EHRLICH)
CASE SPECIFIC
NORMAL VALUES
• SERUM BILIRUBIN: Total 0.1-0.8 mg/dL
Direct: 0.1–0.4 mg/dL
Indirect: 0.2–0.7
mg/dL
• URINE UROBILINOGEN: 0–4 mg/24 h
• FECAL UROBILINOGEN: 40–280 mg/24 h
CAUSES OF ISOLATED HYPERBILIRUBINEMIA
LIVER FUNCTION TESTS
• 1.The rate limiting enzyme for heme
synthesis?
• 2.unconjugated bilirubin is raised in mostly in
• a.hemolytic jaundice
• b.obstructive
• C.carcinoma of pancreas
• d.stone in gallbladder
• The end product of catabolism of heme is
• A. bile acids
• B.bile salts
• C.bile pigment
• D.uric acid
• The normal brown red color of feces results
from the presence of
• A.stercobilin
• B.bilirubin
• C.biliverdin
• D.bilirubin diglucuronide
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