Give the structure and steps of synthesis of Hb.
Give normal values & list functions of Hb.
List physiological & pathological alterations in Hb conc.
describe the fate of Hb.
2. objective
Give the structure and steps of synthesis of Hb.
Give normal values & list functions of Hb.
List physiological & pathological alterations
in Hb conc.
describe the fate of Hb.
3. Factor necessary for haemoglobinization-
1)Role of protein- first class proteins are
required for globin part of Hb.
a) liver, spleen, kidney, heart most valuable.
b) muscle – intermediate value.
c) bread, cereals, dairy products, vegetables ,
fruits- least value.
4. 2) Role of iron- necessary for synthesis of Haem.
-dietary iron and iron released from degradation of
RBCs is reused.
3) Role of other metals-
-copper- essential for absorption, mobilization,
utilization of iron.
-Cobalt- is required for synthesis of vit B12 by bacterial
action.
-Calcium – required indirectly for conserving iron.
5. 4) Role of vitamins- vit B12, folic acid, vit C
required for maturation. Vit C help in
absorption of iron from gut.
5) Role of bile salts- required for absorption
of copper and nickel which in turn essential
for haemoglobin synthesis.
6. Structure of Hb
Globin is made of 4 polypeptide
chains 2 α-chains (141 AA)
and 2 β-chains (146 AA)
Globin is synthesized in ribosome.
Oxygen-binding protein is
called haemoglobin.
7. Haem is made of 4 pyrrole
ring joined by 4 methine bridges
with a central iron atom
(ferrous form)
It is called iron protoporphyrin
Haem is synthesized in the
mitochondria.
9. - Normal count
- after birth- 16 - 23gm%
-At end of 3 month – 9 - 12gm%
-At 10 year of age-12 – 14gm%
-In adult male- 14 – 18gm%
-In adult female- 12 – 15gm%
-clinically – 14.5gm% is considered as 100%
-One gram Hb carries 1.34ml of oxygen.
10. Function of Hb-
1)Transport of O2 from lungs to tissues- O2 combine
loosely & reversibly with each iron atom –
oxyhaemoglobin.
2) Transport of Co2 from tissues to lungs- Co2
combine with amino acids of globin part of Hb –
carbamino-haemoglobin.
11. 3) Control pH of the blood – Hb has 6 times the
buffering capacity as compared to plasma protein.
4) Hb binds with nitric oxide (NO) in lungs to form
nitrosohemoglobin and prevent vasodilation, inhibition of
platelet aggregation and macrophage cytotoxicity.
5) It imparts red colour to blood.
12. Types of Hb
Normal Hb
Adult Hb
Fetal Hb
Embryonic Hb
Hemoglobin Bart’s
Abnormal Hb
Hb S
Hb C
Hb E
Hb D
Unstable Hb
13. Normal Hemoglobins
-Adult haemoglobin - two types
Haemoglobin A –HbA(α2 β2)
appear 8th week of IU life.
Fully formed in 6 months.
Haemoglobin A2 - HbA2(α2 δ2)
minor form of Hb in adult. (3 % in 1st yr of life)
δ chain - last 10 amino acids are different from β chain.
.
14. -Fetal haemoglobin– Hb F(α2 γ2)
γ chain - last 37 amino acids are different from β chain.
major Hb in IU life, disappear by 2-3 mths afterbirth.
Adult level is 1%
shows resistance to action of alkalies.
has more affinity for O2 than Hb A.
↑ in some anemia, hemoglobinopathies, leukemia.
16. HbA1c :-
- glucose attached to valine in β chain.
- Used as an index of control of DM.
- It measures degree of oxidative stress.
17. Abnormal Hemoglobins –
Unstable Hb –
Hb undergo denaturation & precipitate in RBC as
Heinz bodies.
Found in congenital spherocytic hemolytic anemia.
HbS- valine replaces glutamic acid at 6th position
HbC- lysine replaces glutamic acid at 6th position
HbE- glutamic acid replaces lysine at 26th position
HbM- tyrosine replaces histidine at 63rd position
18. Haemoglobinopathies-
Sickle cell haemoglobin -
- (HbS) valine substitute
for glutamic acid at 6th
position in β chain.
HbS is reduced in
hypoxia and RBCs change
to sickle-shaped cell.
19. -Sickle-shaped cells ↑ blood viscosity and ↓ blood flow to
tissues.
- Cells are more fragile, under go haemolysis to produce
sickle cell anaemia (normocyctic normochromic)
Hyposplenism due to micro infarctions in spleen.
∆: sickle test, Hb solubility test
T/t - Bone marrow transplantation
- drugs like hydroxyurea, 5- azacytidine.
20. Thalassemia
Genetically determined
Two types –
α thalassemia (Failure to synthesize α chain )
β thalassemia (Failure to synthesize β chain)
(major & minor)
Anaemia develops in first few months of life & later
becomes severe (microcytic hypochromic)
Hepatosplenomegaly and skeletal defects are
common.
21. Thalassaemia (Mediterranean anaemia) -
β Thalassaemia major β Thalassaemia minor
Less common More common
Complete absence of β
chain
Partial absence of β chain
Moderate to severe
anaemia, HbF level is
increased.
Mild anaemia, HbF level is
normal or slightly
elevated.
Short life span(dies young
17-18 yrs)
Survive longer(up to adult)
22. ∆:
1. Hb electrophoresis
2. Hb-H (aggregates of alpha & beta chains)
3. Alkali denaturation test
4. Acid elution test
23. Fate of RBCs-
-After 120 days cells become fragile, while squeezing
through spleen capillaries are destroyed.
-Hb released is taken by tissue macrophages.
26. Jaundice (icterus) –
yellow appearance of the skin, sclera
and mucous membranes because of
increased Bilirubin.
Normal sr bilirubin – 0.3-1mg/100ml
clinically in jaundice bilirubin exceeds 2-3mg/100ml.
brain is not coloured yellow, as bilirubin does not cross
BBB in adults.
27. Mechanism producing jaundice
1) Excessive (haemolysis) of RBCs - haemolytic
jaundice or pre-hepatic jaundice.
2) Damage to the liver cells - hepatic or hepatocellular
jaundice .
3) Obstruction to bile duct - obstructive or post-hepatic
or cholestatic jaundice .
28. SAQ:-
1. Sickle cell haemoglobin,
2.Factors controlling Hb synthesis,
3. Jaundice
LAQ:-
1. Describe synthesis of Hb and add note on
haemoglobinopathesis.
2. Describe fate of RBCs and add note on jaundice.