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HAEMOGLOBIN AND ANAEMIA
1. DR NILESH KATE
MBBS, MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
HAEMOGLOBIN
AND
ANAEMIA.
2. At the End of Class
Haemoglobin
Structure, function,
variations
Derivatives, synthesis and
degradation of
hemoglobin.
Anemia – Types with
example, c/f , treatment
4. HAEMOGLOBIN
It is a Red pigment
Present in RBC of Blood.
It is a conjugated protein,
& Chromoprotein.
It is made up of Iron and
Protein
It’s molecular weight is
68000.
5. Disadvantages if haemoglobin
present in plasma.
Increase viscosity.
Increase osmotic
pressure.
Rapid destruction by
reticuloendothelial
system.
Haemoglobinuria
( excretion through
kidney)
Tuesday, December 8, 2015
6. NORMAL VALUES OF
HEMOGLOBIN
The Normal Hb level:
Fetus – 16-18 gm/dl
Newborn – 20-24
gm/dl.
Transfusion from
placenta
Haemoconcentration
7. NORMAL VALUES OF
HEMOGLOBIN
1 year – 10-12 gm/dl
Males - 14 – 17
gm/100ml
Females- 12 – 15
gm/100ml
Tuesday, December 8, 2015
8. STRUCTURE OF HAEMOGLOBIN.
Iron containing pigment
called Haem attached
with protein – Globin.
Haeme is Iron –
porphyrin complex
called IRON-
PROTOPORPHYRIN IX.
Globin – Protein.
Tuesday, December 8, 2015
9. 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.
Tuesday, December 8, 2015
11. Structure of Globin.
Made up of 4
polypeptide chains.
Globin is HbA
2 alpha chains ( ) –
141 amino acids
2 Beta chains ( ) – 146
amino acids.
Tuesday, December 8, 2015
12. 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.
Tuesday, December 8, 2015
13. 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.
14. Succinyl-CoA Glycine
Pyridoxal phosphate
αAmino -β-ketoadipic acid
ALA synthetase
α amino-δ-Laevulinic acid
ALA dehydrogenase.
Porphobilinogen
Protoporphyrin IX
ferrous
Haem globin
haemoglobin
Tuesday, December 8, 2015
15. 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.
Tuesday, December 8, 2015
16. ROLE OF IRON.
Important for formation of Haeme part of
Haemoglobin.
Sources of iron – Dietary iron
Other sources – Iron released from degradation of
RBC.
Tuesday, December 8, 2015
17. 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.
Tuesday, December 8, 2015
18. Functions of Haemoglobin
Transport oxygen to tissues
Transport Co2 to lungs
Maintains acid base balance ( As a Buffer)
19. 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.
Tuesday, December 8, 2015
20. 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.
Tuesday, December 8, 2015
21. Shift of Oxygen – Haemoglobin
Dissociation curve.
Shift to left. Shift to right.
Tuesday, December 8, 2015
23. 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.
Tuesday, December 8, 2015
24. 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.
Tuesday, December 8, 2015
25. EFFECTS OF SICKLE CELL SHAPE.
Less flexible – blockage
of microcirculation.
Increases blood
viscosity.
More fragile – More
Hemolysis – Anaemia.
Tuesday, December 8, 2015
26. TREATMENT
Drugs – leads to
formation of HbF which
decreases
polymerization of
deoxygenated Hb.
Azacytidine
Hydroxyurea
Bone Marrow
Transplantation.
Tuesday, December 8, 2015
27. 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
Tuesday, December 8, 2015
28. 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.
Tuesday, December 8, 2015
29. 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)
31. ANAEMIA
Definition:
Anemia is defined as a
decreased O2 carrying
capacity due to quantitative
and qualitative Reduction in
RBC counts and Hemoglobin
levels.
32. ANAEMIA
ANAEMIA is labelled
when Hb is less than
13gm/dl in Males
11 gm/dl in Females
15gm/dl in Newborn.
Tuesday, December 8, 2015
36. 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
Tuesday, December 8, 2015
37. 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%
Tuesday, December 8, 2015
38. 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.
Tuesday, December 8, 2015
40. IRON
ABSORPTION
Mainly in duodenum &
upper jejunum.
MECHANISM
Transport across brush
borders
Haeme iron
Non-haeme iron.
Fate in Enterocytes.
Transport in plasma.
Tuesday, December 8, 2015
41. IRON ABSORPTION
Transport across brush
borders.
Absorption of Haeme
form
Absorption of Non-
haeme form
Fate in Enterocytes.
Transport in plasma.
Tuesday, December 8, 2015
42. 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.
Tuesday, December 8, 2015
43. STORAGE OF IRON
As ferritin
As haemosiderin.
Tuesday, December 8, 2015
44. 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.
Tuesday, December 8, 2015
47. APPLIED ASPECTS.
Iron deficiency- iron
deficiency Anaemia
Iron excess –
Haemosiderin
accumulation –
Haemosiderosis –
damages tissue –
Haemochromatosis.
Tuesday, December 8, 2015
48. CAUSES OF IRON DEFICIENCY
ANAEMIA.
Inadequate dietary
intake.
Increased loss of iron.
Increased demand of
iron.
Decreased absorption.
Tuesday, December 8, 2015
49. Megaloblastic Anaemia
Megaloblast –
abnormally large cells
of Erythroid series.
Caused by defective
DNA synthesis due to
deficiency of Vit B12 &
Folic acid.
50. 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.
Tuesday, December 8, 2015
51. 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.
Tuesday, December 8, 2015
52. 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.
Tuesday, December 8, 2015
53. Folic Acid
Folic acid –
Pteroylglutamic acid.
Daily requirement –
100 μg.
Sources – leafy veg,
pulses, yeasts, liver.
From breakdown of
Polyglutamate to
Monoglutamates.
Tuesday, December 8, 2015
54. Aetiology.
Due to vit B12
deficiency
Causes –
Inadequate dietary
intake
Malabsorption due to
gastric cause
Intestinal Cause.
55. 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)
Tuesday, December 8, 2015
56. 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.
58. 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
Tuesday, December 8, 2015
59. 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.
Tuesday, December 8, 2015
60. 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
Tuesday, December 8, 2015
61. MANAGEMENT
General – correction
of causative factor if
possible.
Special – oral
administration of fe
salts, FSFA TAB,
Intramuscular inj.
Tuesday, December 8, 2015