Haemglobin
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abhishekgowdar2006HAEMOGLOBIN
INTRODUCTION
Definition: Is the red coloured
pigment, a conjugated protein
present in the RBC
Constitutes > 90% of dry weight
of RBC
Basis for transport of gases by
RBCs
If Hb was outside the
RBC…..?
Increase blood viscosity rise in
BP
Increase osmotic pressure
Rapid destruction of Hb by RES
Excretion of Hb by kidneys
( Hemoglobinurea)
Normal Value
Fetus: 16.5-18.5gm/dl
At birth: 23gm%
Males: 14 -18gm%
Females: 12 -14gm%
Normal Hb 100% saturated when
blood is equilibrated with 100%
oxygen (760mmHg)
1 gm of Hb when fully saturated
carries 1.34ml of Oxygen
Eg: Male with 15.5 gm of Hb carries=
21ml% (15.5 X 1.34)
STRUCTURE
Hb is a chromoprotein, consists of
two parts
Globin (96%)- protein component
Haem (4%)- iron containing
pigment
STRUCTURE
Globin – a protein substance consisting
of 4 polypeptide chains.
Globin helps haem to keep iron in
ferrous state & also to combine loosely
& reversibly with molecular oxygen
Adult Hb(HbA)
2 α chains: 141 AA, 2 β chains: 146AA
STRUCTURE OF HAEM-
Iron protoporphyrin IX complex
Porphyrin nucleus + Iron
Porphyrin nucleus : 4 pyrrole rings I, II, III, IV
Pyrrole rings are joined by 4 methine bridges(=CH-)
Eight side chains are attached to the pyrrole ring at
positions labelled 1 to 8
Methyl 1,3,5,8 (H3C)
Vinyl 2,4 (CH.CH2)
Propionic acid 6,7 (CH2.CH2.COOH)
PYRROLE ring
Iron…
Ferrous (Fe2+)
Attached to nitrogen atom of pyrrole
ring
On the iron, a bond is available for
loose union,
- In oxyhaemoglobin, O2 is attached
- In carboxyhaemoglobin,CO is attached
STRUCTURE OF HAEM-
iron protoporphyrin IX
1 molecule of Hb contains 4 units of
haem
Each attached to one of 4 polypeptide
chains constituting globin
So 4 iron atoms in one molecule of Hb,
which carry 4 molecules of Hb (8
atoms) of oxygen
Condensation of Haem & Globin
1 molecule of Hb=4 units of haem
SYNTHESIS OF HB
Begins from the stage of intermediate
Normoblast in the process of erythropoiesis
Haem
- Synthesized in mitochondria
- Succinyl-CoA and Glycine are starting
substances
Globin synthesized in ribosome
Factors necessary for Hb
synthesis
Protien
Iron
Metals : copper, cobalt, calcium
Vitamins : vit B12, folic acid, vit c
Bile salts: absorption of metals
Functions of Hb
Transport Oxygen
Transport carbondioxide
Control of pH of blood
Hb estimation…….
Visual method: Sahli, Dare, Haden,
Wintrobes, Haldane, Tallquist
Gasometric method
Spectrophotometric method
Automated method
Others: alkaline hematin, specific gravity,
comparator methods.
Varieties/ Types of Hb
Physiological
Adult Hb: Hb A α2β2 , Hb A2: α2δ2
Fetal Hb: α2ȣ2
Embryonic Hb: Gower Hb I: ε2ζ2
Gower Hb II: α2ζ2
(ε - epsilon), (ζ- Zeta)
Fetal Hb-α2ȣ2
Usually present in fetal RBC
Gradually disappears 2-3 months after birth
Special features:
1) Affinity of oxygen is more than HbA - Movement of
oxygen from maternal to fetal circulation is facilitated.
2) Resistance to action of alkalies
3) Life span less 1-2 weeks
Pathological:
Haemoglobinopathies
Abnormal formation of Hb occurs due to
disorders of globin synthesis.
Abnormal peptides: HbS, HbC,
HbI, HbJ, HbM, HbE
Suppression of synthesis of
polypeptide chain : Thalassaemia
Sickle cell Hb (HbS)
Most common, Mendelian dominant
Gene originated in Africa
Substitution of valine for glutamic acid at
position 6 in beta chain of HbA
HbS : less soluble & precipitates into crystals
within the RBC, elongates to form sickle cell
RBC
Genetics of Sickle Cell Anemia
Genetics of Sickle Cell Anemia
HbS………
Less flexible block of microcirculation
↑ blood viscosity ↓ blood flow
More fragile hemolysis
Sickle cell trait :
resistance to one type of malaria.
Treatment
Presence of HbF in RBCs decreases the
polymerization of deoxygenated HbS
Drugs: 5 Azacytidine
Hydroxyurea
↑ formation of HbF
Bone marrow transplantation
Thalassaemia……………
Mediterranean anaemia
Cause: defect in synthesis of
polpeptide chain α, β of HbA
Types: α Thalassaemia, β Thalassaemia
Major : complete absence
Minor : partial deficient
β Thalassemia major β Thalassemia minor
1 Mediterranean anaemia/ More common
Cooley’s anemia
2 -Homozygous transmission -Decreased synthesis
-Complete absence of β -Mild anemia
chains-severe anemia -HbF normal/slightly
- HbF level increased elevated
3 Short life span: 17-18yrs Longer life
Derivatives of Hb
Oxyhaemoglobin : + O2
Reduced Hb: -O2
Carbamino Hb: CO2
Carboxy Hb: CO
Methaemoglobin: ferric form
Glycosylated Hb: HbA1C derivative of HbA, glucose is
attached to terminal valine in β chains, level increases in
poorly controlled diabetic patients
Fate of Hb
Haemoglobin
Choleglobin
Globin Biliverdin
Iron
Aminoacids
Aminoacids pool Iron BilirubinIn blood circulation
Reutilized Stored as Taken up by
in bone marrow ferritin the liver
For Hb synthesis In other tissues