HEMOGLOBIN.

DR. Haroon Rashid.

Lecture-29

Objectives

• Describe in detail the structure, synthesis, and catabolism of hemoglobin• Explain the different forms in which hemoglobin is present in the blood.• Enumerate the functions of hemoglobin• Discuss the various abnormal types of hemoglobin

Hb• Def:The red, oxygencarrying pigmentPresent in RBCs.

HbStructure:• There are about 250 million molecules of haemoglobin in

each RBC !!!!• Each molecule of haemoglobin has: 4 haem moieties + 4 Polypeptide chains ( haem ) ( globin )• Each haem has: 4 pyrol rings + 1 Iron molecule ( ferrous form)• Polypeptide chains are of different types ( Alpha, Beta, Gamma, Delta etc).

HbSynthesis:• Most of Hb( 65 % )is synthesized by nucleated red cell precursors ( ENB to

INB stage) in bone marrow.• 35%of Hb is synthesised in Reticulocyte.Synthesis of Haem: Mainly in mitochondria.Acetoacitic acid Via Kreb’s cycle to Succinyl coA2 Succinyl coA + 2 Glycine = Pyrol4 Pyrol . ProtoporphyrinsProtoporphyrin IX + Iron = HaemSynthesis of Polypeptide chains:• Occurs at Ribosomes with the help of AA• 4haem + 4 Polypeptide chains = 1 molecule of Hb.

Hb

HbQuantity ( Normal value ):• Adult male : 14 – 18 gms%• Adult female : 12 – 16 gms %• New born : 20 – 23 gms%Types of Hb:I. Physiological: HbA (α2 β2 ) HbA2 (α2 δ2) Hb F (α2 γ2)II Pathological: HbS (α2 β2 6glu > Valin) HbC (α2 β2 6glu > Lysiin), Hb H = β4

Adult Hb Vs Fetal Hb Adult Fetal• P chains: α2 β2 / (α2 δ2) (α2 γ2)• With alkali: less resistant more resist.• O2 affinity: less more• Life span 120 days less.• Present in Adult RBCs Fetal life

Adult RBC has: 98.5% HbA + 1.5% HbA2 + 0.5 % HbF.

HbFunctional properties of Hb:• Oxygen affinity: Varies with PO2,• Transport of oxygen from lungs to tissue.• Carbon dioxide from tissues to lungs• It has binding site for nitric oxide, binds with nitric oxide in the

lungs & releases in the tissues where it causes vasodilation.

Regulation of PH ( Bohr)70% of whole blood PH is regulated by Hb.

• It is amphoteric.• It forms reduced Hb when gives O2 and becomes basic and can

combine with acid.• It forms Carbaminohaemoglobin with CO2.

Fate of Hb

Hb

• I gm of Hb can carry 1.34 ml of O2• 1gm of Hb has 3.35 mg of Iron• 1gm of Hb gives 35mg of Bilirubin.• 900 gms of Hb is in circualtion and about 8gms is

catabolized/ day, thus 280 mg of bilirubin ( 8 X 35 ) is formed / day. *0 % is excreted in stool as Stercobilinogen and 20 % in urine as urobilinogen.

Forms of Haemoglobin.

• Oxyhaemoglobin.• Carbamino-haemoglobin.• Reduced Haemoglobin.• Carbon Monoxy Haemoglobin.(Carboxy

Haemoglobin)• Methaemoglobin. (Ferrous oxidised to Ferric)

Hb

Applied aspect:• Porphyrias: defect in haem portion.• Haemoglobinopathies: HbS, HbD, HbC etc.• Thalasemias: alpha thalassemia,

beta thalassemia.

Sickle cell disease

• Most common in Africans• 1:5 west Africans are carriers• Occurs in areas where malaria is common• Increasing numbers in Ireland• Here each Beta polypeptide chain of HbA at

position 6,glutamic acid is replaced by Valine. Therefore when it is exposed low O2 tension or low pH it precipitates into crystals in RBCs.

• It damages cell membrane producing increased fragility of RBCs.

• Crystals elongate & RBCs become sickle shaped, which decreases the blood flow to tissues due to sickling-increases blood viscosity. The above causes produces severe anaemia called Sickle Cell Anaemia.

• Finally,patient dies of anaemia & secondary infection.

Sickle cell disease – clinical features

• Vaso-occlusive crises– Common precipitants are infection, dehydration– Bone pain – Stroke– Visceral infarction – spleen, kidneys– Dactilytis - children

Sickle cell disease – clinical features

• Sequestration crises– Sickling with pooling of red cells in liver or spleen

– severe anaemia, rapid enlarging liver or spleen– Acute chest syndrome – chest pain, hypoxia,

diffuse shadowing on CXR

Sickle cell disease – clinical features

• Aplastic Crises– Usually follows infection with parvovirus B19– Causes a temporary arrest of erythropoiesis– Severe anaemia– Transfusion support

Sickle cell disease – clinical features

• Decreased splenic function – increased susceptibility to infection

• Gallstones• Chronic leg ulcers• Avascular necrosis• Renal papillary necrosis• Proliferative retinopathy

• Other haemoglobins are Haemoglobin C,E,I,J & M. HbC is same as Hbs but it is not associated with sickling. All these abnormal haemoglobins cause hemolytic anaemias.

The Thalassaemias

• Presence of HbF beyond the age of 4-6 months after birth, due to deficient production of a or b-chains of HbA causes a or b Thalassaemia respectively

• Autosomal recessive disorders• Characterised by ineffective haemopoiesis

The Thalassaemias

• a Thalassaemia(Rare)– Severity depends on the number of genes deleted– Trait – 1 or 2genes deleted, mild anaemia, hypochromic

microcytic film– Hb H, 3 genes deleted , splenomegaly, Hb 6-10g/dl,

hypochromic microcytic– Hyrdrops fetalis – 4 gene deletion, death in utero

The Thalassaemias• b Thalassaemia-It is 2 types • 1)Major b Thalassaemia also called Cooleys or

Mediterranean anaemia. • It is less common.• Inheritance-Homozygous (Abnormal genes from both parents

& all haemoglobin is abnormal.)• Trait – mild hypochromic microcytic anaemia, advice re carrier

state• Totally absence of b chain synthesis.• HbF is increased.• Life span is short less 17 yrs.

2) Minor• More common• Heterozygous-Abnormal gene from one parent

formation of abnormal haemoglobin.• Mild anaemia.• Partial synthesis of b chain.• HbF normal or slightly increased.• Patient survives upto adult life & can transmit the

gene to the offsprings.

The Thalassaemias

• Laboratory features– Severe anaemia– Hypochrominc microcytic cells, target cells– BM erythroid hyperplasia– DNA analysis

Refrences

• Guyton.• Ganong.• Internet.