HAEMOGLOBIN AND ANAEMIA

DR NILESH KATE

MBBS, MD

ASSOCIATE PROF

DEPT. OF PHYSIOLOGY

HAEMOGLOBIN AND

ANAEMIA.

At the End of Class Haemoglobin

Structure, function,

variations

Derivatives, synthesis and

degradation of

hemoglobin.

Anemia – Types with

example, c/f , treatment

Haemoglobin(C712H1130O245N214S2Fe)4

HAEMOGLOBINIt is a Red pigment Present in RBC of Blood.It is a conjugated protein,

& Chromoprotein.It is made up of Iron and

ProteinIt’s molecular weight is

68000.

Disadvantages if haemoglobin present in plasma.

Increase viscosity. Increase osmotic

pressure. Rapid destruction by

reticuloendothelial system.

Haemoglobinuria

( excretion through kidney)

Tuesday, May 2, 2023

NORMAL VALUES OF HEMOGLOBIN

The Normal Hb level: Fetus – 16-18 gm/dl Newborn – 20-24

gm/dl. Transfusion from

placenta Haemoconcentration

NORMAL VALUES OF HEMOGLOBIN

1 year – 10-12 gm/dl Males - 14 – 17

gm/100mlFemales- 12 – 15 gm/100ml


STRUCTURE OF HAEMOGLOBIN. Iron containing pigment

called Haem attached with protein – Globin.

Haeme is Iron – porphyrin complex called IRON-PROTOPORPHYRIN IX.

Globin – Protein.


STRUCTURE OF HAEME IRON-PROTOPORPHYRIN IX.

IRON Ferrous form (Fe2+). Iron attached to

nitrogen atom of each pyrrole ring.

On iron loose bond for Oxygen Carbon monoxide.


STRUCTURE OF HAEME IRON-PROTOPORPHYRIN IX.

Porphyrin nucleus. 4 Pyrrole Rings

(Tetrapyrrole) Bridges – Methine (CH) Side chains – 8

Methyl (CH3) - 4 Vinyl (CH.CH2) - 2 Propionic acid - 2

(CH2.CH2.COOH)


Structure of Globin. Made up of 4

polypeptide chains. Globin is HbA 2 alpha chains ( ) –

141 amino acids 2 Beta chains ( ) – 146

amino acids.


Attachment of Haeme to Globin.

4 units of Haeme attached to 1 unit of Globin.

So 1 Haemoglobin molecules contains 4 Iron Atoms which carry 4 molecules of oxygen.


Synthesis of Hemoglobin

i) 2 succinyl – CoA + 2 glysine Pyrrole

ii) 4 Pyrrole Protoporphyrin IX

iii) Protoporphyrin IX + Fe2+ Heme

iv) Heme + Polypeptide Hemoglobin chain (α or β)

v) 2 α chains + 2 β chains Haemoglobin A.

Succinyl-CoA GlycinePyridoxal phosphate

αAmino -β-ketoadipic acid ALA synthetase

α amino-δ-Laevulinic acid ALA dehydrogenase.

Porphobilinogen Protoporphyrin IX

ferrous Haem globin

haemoglobin


Factors controlling Haemoglobin formation.

Role Of Proteins – First class proteins provide amino acids.

Most imp – food of animal origin, liver, spleen, kidney & heart

Intermediate value – muscles Least – cereals, dairy products, veg & fruits.


ROLE OF IRON. Important for formation of Haeme part of

Haemoglobin. Sources of iron – Dietary iron Other sources – Iron released from degradation of

RBC.


Role of other metals Copper – Promotes

Absorption, Mobilization & Utilization of iron.

Cobalt – Increases production of Erythropoietin.

Calcium – conserve iron & subsequent utilization.

Role of vitamins. Vit B12, Folic acid help in

synthesis of nucleic acid. & vit C helps in absorption

of iron from gut. (Fe3+ to Fe2+)

Role of bile salts. Imp for proper absorption

of copper & nickel.


Functions of Haemoglobin Transport oxygen to tissues Transport Co2 to lungs Maintains acid base balance ( As a Buffer)

Haemoglobin – Oxygen Binding.

O2 is attached with haemoglobin reversibly at 6th covalent bond.

Oxygenation of 1st haem increases affinity for 2nd in turn 3rd & 4th.

Reason for O2-Hb dissociation curve Sigmoid shape.


Oxygen – Haemoglobin Dissociation curve.

As affinity of Hb for O2 falls graph shifted to right.

As affinity of Hb for O2 rise graph shifted to left.

H+ ion conc, Pco2 temp & 2,3-DPG affects shift.


Shift of Oxygen – Haemoglobin Dissociation curve.

Shift to left. Shift to right.


VARIETIES OF HAEMOGLOBIN. Pathological

(Haemoglobinopathies) Sickle Cell Haemoglobin. Hb C Thallasemia.

Physiological. Adult

Haemoglobin A --

4 polypeptide chains

2 α (alpha) & 2 β (Beta) Haemoglobin A2 -- 2 α

(alpha) & 2 δ (Delta) Fetal.

FETAL HAEMOGLOBIN. Present in fetal RBC & disappear

in 2-3 months

after birth. Structure

4 polypeptide chains

2 α(alpha) & 2 γ (gamma) Characteristics.

Affinity for oxygen – more Resistance to action of alkalies Life span – less.


PATHOLOGICAL (HAEMOGLOBINOPATHIES)

Sickle cell haemoglobin.(HbS) Substitution of Valine

for Glutamic Acid at 6th position in beta chain.

When HbS is reduced (in low O2 tension) precipitate into crystals in RBC changes shape become Sickle shaped.


EFFECTS OF SICKLE CELL SHAPE. Less flexible – blockage

of microcirculation. Increases blood

viscosity. More fragile – More

Hemolysis – Anaemia.


TREATMENT Drugs – leads to

formation of HbF which decreases polymerization of deoxygenated Hb. Azacytidine Hydroxyurea

Bone Marrow Transplantation.


Pathological (Haemoglobinopathies)

Haemoglobin C.

Similar to HbS but not associated with Sickling.

Other varieties are HbE, HbI, HbJ, HbM

Thalassaemia Defect in synthesis of

polypeptide chain. Types Major Minor


DIFFERENCE IN THALASSAEMIA MAJOR & MINOR.

β Thalassaemia Major Less common Homozygous transmission Complete absence of beta

chain synthesis. Anemia – moderate to

severe HbF – markedly increased Life span – short Cooley’s Anaemia

β Thalassaemia Minor. More common. Heterozygous

transmission. Partial Absense. Anemia- mild. HbF – slightly elevated. Life span – comparatively

longer.


DERIVATIVES OF Hb 1. Hb + O2 HbO2 (Oxyhaemoglobin) Iron in ferrous state)

2. Hb + Cyanide Methaemoglobin Iron in ferric state.

3. Hb + CO2 Carbamino hemoglobin

4. Hb + CO Carboxy hemoglobin

5. Hb + H2S Sulphemoglobin.

6. Hb + Glucose Glycosylated ( attached to terminal

Valine)

FATE OF HAEMOGLOBIN


Tetra pyrrole straight chain with Globin & Iron

ANAEMIADefinition:

Anemia is defined as a decreased O2 carrying capacity due to quantitative and qualitative Reduction in RBC counts and Hemoglobin levels.

ANAEMIA ANAEMIA is labelled

when Hb is less than 13gm/dl in Males 11 gm/dl in Females 15gm/dl in Newborn.


MORPHOLOGICAL CLASSIFICATION:

normochromic

Etiological Classification

DUE TO DECREASED RBC PRODUCTION.

IRON DEFICIENCY ANAEMIA.

Most common in India. In women of reproductive

age group (20-45 yrs) In periods of active

growth of infancy, childhood & adolescence


IRON METABOLISM Total body contains 4-5 gms Forms –

Haemoglobin 70% Storage iron 20-23% 2/3rd

Ferritin & 1/3rd Haemosiderin.

Myoglobin in red muscles 5% Intracellular enzymes 2-3%


DAILY REQUIREMENTS & SOURCES

5-10 mg/day in Males 20 mg/day in

Females. 40 mg/day in

Pregnant & lactating women.

Meat, liver, egg, green leafy veg, Jaggery & whole wheat.


IRON ABSORPTION

Mainly in duodenum & upper jejunum.

MECHANISM Transport across brush

borders Haeme iron Non-haeme iron.

Fate in Enterocytes. Transport in plasma.


IRON ABSORPTION Transport across brush

borders. Absorption of Haeme

form Absorption of Non-

haeme form Fate in Enterocytes. Transport in plasma.


Factors affecting iron absorption

Form of dietary iron – haem iron Non-haem iron – ferrous form (Fe2+) > ferric form

(Fe3+) Meat & fish ,Human breast milk ,Acid gastric

juice – enhances absorption. Dietary factors – Phytates , phosphates, calcium,

egg white, phenols, tea, coffe wine reduces. Iron stores in body – Negative feedback effect.


STORAGE OF IRON As ferritin As haemosiderin.


REGULATION OF BODY IRON Mucosal block theory of absorption. Saturation of apoferritin & apotransferrin Decresed rate of apoferritin synthesis. Role of specific iron receptors in brush borders.


APPLIED ASPECTS. Iron deficiency- iron

deficiency Anaemia Iron excess –

Haemosiderin accumulation – Haemosiderosis – damages tissue – Haemochromatosis.


CAUSES OF IRON DEFICIENCY ANAEMIA.

Inadequate dietary intake.

Increased loss of iron. Increased demand of

iron. Decreased absorption.


Megaloblastic Anaemia Megaloblast –

abnormally large cells of Erythroid series.

Caused by defective DNA synthesis due to deficiency of Vit B12 & Folic acid.

Vit B 12 (Extrinsic Factor) Vit B12 –

Cyanocobalamin or extrinsic factor.

Daily need – 1-2 μg. Sources – Milk, Meat,

Liver of Animals Also synthesized by

bacterial Flora.


Vit B 12 (Extrinsic Factor) Absorption – need

Intrinsic Factor Of Castle , a glycoprotein secreted by parietal cells of gastric mucosa.

With it form Intrinsic Factor- Cyanocobalamin complex

Bound to sp receptors in ileum & absorbed by Endocytosis.


Vit B 12 (Extrinsic Factor) Transport – in blood

transported by combining with Transcobalamin-II

Storage – In liver & Muscle

Role – required for synthesis of DNA & maturation of nucleus & cell.


Folic Acid Folic acid –

Pteroylglutamic acid. Daily requirement –

100 μg. Sources – leafy veg,

pulses, yeasts, liver. From breakdown of

Polyglutamate to Monoglutamates.


Aetiology. Due to vit B12

deficiency Causes –

Inadequate dietary intake

Malabsorption due to gastric cause

Intestinal Cause.

Addisonian Pernicious Anaemia.

Aetiology – vit B12 deficiency due to failure of secretion of Intrinsic Factor by stomach due to Autoimmune Atrophy of Gastric Mucosa.

Features. Features of

Megaloblastic anaemia Anti-intrinsic factor

antibodies. Schilling test.

(abnormal vit B12 absorption test corrected by addition of Intrinsic Factor)


Clinical Features: General features of Anemia

Pallor, Weakness, Lethargy,

Breathlessness on exertion

Palpitations heart failure pedal edema

Special features :

Angular cheilitis, Atrophic glossitis,

Oesophageal atrophy/web Dysphagia,

Koilonychia, brittle nails, gastric atrophy.

Special features :

LAB FINDINGS Blood picture & red cell

indices. Hb Decreased RBC – Microcytic,

Hypochromic in iron deficiency

Megaloblastic in vit B12 & FOLIC ACID deficiency

Red cell indices – MCV,MCH & MCHC Decreases


BONE MARROW FINDINGS. Iron deficiency

anaemia Marrow Cellularity –

Erythroid Hyperplasia. Erythropoiesis –

Normoblastic Marrow Iron –

Deficient.

Megaloblastic anaemia.

Marrow cellularity – Megaloblastic Hyperplasia.

Marrow iron – by Prussian Blue staining increase in size & no of iron granules.


BIOCHEMICAL FINDINGS. Iron deficiency

Anaemia Serum iron decreases

(below 50 mg%) Serum Ferritin – very

low. Total Iron Binding

Capacity – increased.

Megaloblastic Anaemia. serum bilirubin – increases. Urine Urobilinogen –

excretion increases. Serum iron & Ferritin –

increases. Serum vit B12,Folate levels -

decreased


MANAGEMENT General – correction

of causative factor if possible.

Special – oral administration of fe salts, FSFA TAB, Intramuscular inj.


THANK YOU

HAEMOGLOBIN AND ANAEMIA

Health & Medicine

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