HEMOGLOBIN

By U.Sivakumar

1 PHYSIOLOGY
 OBJECTIVES
• DEFINITION
• STRUCTURE OF HAEMOGLOBIN
• SYNTHESIS OF HAEMOGLOBIN
• FUNCTIONS OF HAEMOGLOBIN
• TYPES OF HAEMOGLOBIN
• FORMS OF HEMOGLOBIN
• VARIATION IN HAEMOGLOBIN LEVELS
• FATE OF HAEMOGLOBIN
• HAEMOLYSIS
2 PHYSIOLOGY
 DEFINE HEMOGLOBIN

• Hemoglobin is the red pigment of blood present in

RBC

3 PHYSIOLOGY
 EXPLAIN WHAT HEMOGLOBIN CONSISTS

• It is a conjugated protein consisting of heme

and goblin
• Heme is an iron protoporphyrin IX complex
• Goblin is a protein consisting of 4 polypeptide
chains
• Porphyrins are tetrapyrroles formed of 4
pyrrole rings joined by 4 methine (-CH-)
bridges.

4 PHYSIOLOGY
 A single molecule of Hemoglobin consists of :-
• 4 protoporphyrin IX molecules + 4 Ferrous iron
atoms (Fe++) + 4 polypeptide chains
MOLECULAR WEIGHT :-
68,000

5 PHYSIOLOGY
Hemoglobin

6 PHYSIOLOGY
 ADVANTAGES OF HEMOGLOBIN REMAINING IN RBC

• It will not be filtered into the urine

• Blood viscosity will increase if Hb is present in the
plasma.
• It will not be destroyed by macrophages easily.

7 PHYSIOLOGY
 SYNTHESIS OF HEMOGLOBIN
• Heme and Globin are required for the
formation of Hemoglobin.
• Heme is formed in mitochondria and globin in
ribosomes.
• Succinyl – CoA, an intermediary product of
TCA cycle, combines with glycine to form α -
amino- β - keto adipic acid with the help of
pyridoxal phosphate which in turn forms
• δ amino - levulinic acid ( ALA ) in the
presence of ALA synthase
8 PHYSIOLOGY
• ALA is converted to porphobilinogen which
forms protoporphyrin – IX.
• Ferrous iron is introduced into protoporphyrin –
IX,and in the presence of heme synthase heme is
formed.
• Globin the Protein component formed by
ribosome combines with heme to form
hemoglobin.

9 PHYSIOLOGY
Succinyl CoA + Glycine
ALA Synthase pyridoxal phosphate
α -amino- β - keto adipic acid.
ALA Synthase
δ amino - levulinic acid ( ALA )
ALA Dehydrogenase
Porphobilinogen

Protoporphyrin - IX
Ferrous iron
Heme synthase
Heme Globin
Hemoglobin
10 PHYSIOLOGY
 FUNCTIONS OF HEMOGLOBIN
Hemoglobin serves three important functions:
• Transport of gases : It Transports oxygen from lungs to
the tissues by forming oxyhemoglobin and carbon
dioxide from tissues to lungs by forming
carbaminohemoglobin.
• Combination of hemoglobin with oxygen is known as
Oxygenation.
• The oxygen molecules combine loosely and reversibly
with hemoglobin to form oxyhemoglobin.
• Hemoglobin returning with carbondioxide from tissues
is called reduced hemoglobin
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• When fully saturated,1g of hemoglobin carries
1.34mL of oxygen .
• Thus oxygen carrying capacity of blood can be
calculated easily if the value of blood
hemoglobin concentration is known
For example, if Hb is 15g%,
100 mL of blood will carry 15 X 1.34 = 20.7mL of
oxygen.
• Hemoglobin buffer: Hb acts as a buffer in
maintaining blood pH

12 PHYSIOLOGY
• It imparts red color to the blood. Erythrocytes
look red due to the presence of hemoglobin in
them, which is a red pigment.

• Transport of No (Nitric oxide) from lungs to

the tissues where it causes vasodilation

13 PHYSIOLOGY
 TYPES OF HEMOGLOBIN
• Hb A – This is the normal adult hemoglobin.
The globin consists of 2 α and 2 β chains.
α1 and β 1 α2 β 2 act as units

• Hb F – This is present and normal for the fetus-

disappears after birth – Globin consists of 2 α and 2 γ
chains .
• It has more affinity to oxygen than Hb A .Hb F has less
affinity to 2,3 Diphosphoglycerate than Hb A due to lack
of β chains
• HbA2 – This is present in thalasaemia and in the fetus to a
small extent 14 PHYSIOLOGY
• Hemoglobin Bart’s (HB BART’S): This is the minor
hemoglobin present in fetal life.
• It consists of 4 gamma chains.
• Hb Bart’s concentration increases in fetal life in
thalassemia.
Embryonic Hemoglobins :
These hemoglobins are confined to the very early
stages (Embryonic stage) of development.There
are three embryonic hemoglobins:
1.Gower Hb 1: It consists of 2 Zeta and 2epsilon
chains

15 PHYSIOLOGY
2. Hb Gower 2 : It consists of 2 alpha and 2
epsilon chains.
3.Hb Portland : It consists of 2Zeta and 2 gamma
chains.
• There are clinically five important abnormal
hemoglobin's: HbS,HbC,hbD,HbE, and HbM
• Present in different hereditary
hemoglobinopathies.
• HbS: Consists of 2 α and 2 β chains β chains
are abnormal .Valine aminoacid is substituted
for glutamicacid at the sixth position.
16 PHYSIOLOGY
• HbS is present in sickle cell anemia.
• Valine replaces glutamic acid at 6th position causes
sickling of red cells on exposure to hypoxia.
• HbC : Lysine replaces glutamic acid at 6th position
shortens RBC survival.
• HbE : Glutamic acid replaces lysine at 26th position
produces microcytosis.
• HbM : Tyrosine replaces histidine acid at 63rd
position (methemoglobin formation)

17 PHYSIOLOGY
• Unstable hemoglobins :Unstable hemoglobins
are hemoglobin variants that undergo
denaturation and precipitate in the red cells as
Heinz bodies. Unstable hemoglobin's are
present in some form of congenital non-
spherocytic hemolytic anemia.

18 PHYSIOLOGY
 HEMOGLOBIN Ligands (Complexes)
Hemoglobin binds with oxygen to form
oxyhemoglobin and release of oxygen from
hemoglobin to form reduced or deoxygenated
hemoglobin apart from Hb combines with other
chemicals and gases to form Hb-complexes,some
normally and some abnormally .

19 PHYSIOLOGY
1. Methaemoglobin – Stable compound A
compound of Hb+ O2 .This compound is produced
after treating the blood with potassium
ferricyanide . The iron is in the ferric form.
2. Carbaminohaemoglobin –Binding of CO2 with
Hb leads to formation of Carbaminohemoglobin.
It helps in transport of CO2 from tissues to lungs.

20 PHYSIOLOGY
3. Carboxy haemoglobin : Carbon monoxy haemoglobin is a
compound of Hb with Co
4. Sulphaemoglobin : Formed by the combination of Hb with H2S
5. HbA1C (glycosylated HbA): Glucose is attached to terminal
valine in βchain.
In normal individuals,glycosylated Hb (HbA1c) is present in less
concentration,lessthan 4% of total Hb.
The normal HbA1c level is less than4%
As per WHO criteria if HbA1c is more than 6.5% it is considered
abnormal
Its concentration increases in conditions in which blood glucose
is chronically elevated like diabetes mellitus,
Cushing syndrome, hyperthyroidism etc.
21 PHYSIOLOGY
As per ADA (American Diabetic Association)
Criteria :
HbA1c : 4-5.6% :Normal
HbA1c:5.7-6.5% :Prediabetes
HbA1c: > 6.5% :Diabetes

22 PHYSIOLOGY
 Variation in Hb levels
• Adult males – 14 to 18g/dL
• Adult females – 12 to 16g/dL
• Newborn Hb level – 16- 22g/dL
Conditions that decrease Hb Concentration :
Physiological :
• Children have values lower than that in adults.
• women have values lower than that in males.
• Hb is less during pregnancy due to hemodilution
23 PHYSIOLOGY
Pathological : Hb is less in different types of
anemia .
Relative decrease in Hb concentration occurs in
different Pathological conditions that produce
hemodilution like excess ADH secretion as occurs
in pituitary tumors.
Conditions that increase Hb Concentration :
Physiological : Hb level is high at high altitude that
occurs due to hypoxia.
Hb is more in newborns. In excessive sweating
relative increase in Hb occurs due to
hemococentration. 24 PHYSIOLOGY
Pathological : Hb concentration increases in
conditions that produce hemoconcentration like
severe diarrhea,vomiting,etc and conditions that
produce hypoxia like congenital heart disease,
emphysema etc.

25 PHYSIOLOGY
 FATE OF HEMOGLOBIN

• At the end of the life span of RBCs become senile

and are destroyed mainly in the spleen by reticulo-
enothelial system (RES) .

26 PHYSIOLOGY
 RBC
breakdown
Haemoglobin
Converted into
Haem + globin
aminoacids and
reutilized by the body
WITH IN
With in Porphyrin ring+ Iron
RES
RES - Haemoxygenase
Biliverdin + co
reduction Reutilized for the synthesis of
Bilirubin Hb

(Liver) Bilirubin glucuronide

reduction
(Intestine) Urobilinogen (Stercobilinogen )
Oxidation
(urine or Stools) Urobilin (Stercobilin)
FATE OF RBC AND HEMOGLOBIN
27 PHYSIOLOGY
 HAEMOLYSIS
• The break down of RBC resulting in the release
of Hb is called haemolysis .
• Excess haemolysis leads to anaemias called
haemolytic anaemias .
• In haemolytic anaemias the released Hb is
converted into bilirubin.
• In severe haemolysis which usually takes place
in transfusion reactions the released Hb
precipitates in the renal tubules leading to
either oliguria or anuria .
28 PHYSIOLOGY
HAEMOLYSIS

29 PHYSIOLOGY
 SUMMARY
• Hemoglobin is the red pigment of blood present in RBC
• It imparts red color to the blood. Erythrocytes look red
due to the presence of hemoglobin in them.
• A single molecule of Hemoglobin consists of :
• 4 protoporphyrin IX molecules + 4 Ferrous iron atoms
(Fe++) + 4 polypeptide chains
• Succinyl CoA + Glycine forms the α -amino- β - keto
adipic acid then it forms the δ amino - levulinic acid
gives rise to Porphobilinogen then it forms the
Protoporphyrin - IX

30 PHYSIOLOGY
• With the help of heme synthase then it forms
the heme and globin (Hemoglobin).
• Important function of hemoglobinTransport of
gases : It Transports oxygen from lungs to the
tissues by forming oxyhemoglobin and carbon
dioxide from tissues to lungs by forming
carbaminohemoglobin.
• When fully saturated,1g of hemoglobin carries
1.34mL of oxygen
• There are two types of hemoglobin HbA,HbF

31 PHYSIOLOGY
• There are different forms of hemoglobin
Methaemoglobin, Carbaminohaemoglobin,
Carboxy haemoglobin, Sulphaemoglobin.
• At the end of the life span of RBCs become senile
and are destroyed mainly in the spleen by
reticulo-enothelial system (RES) .
• The break down of RBC resulting in the release of
Hb is called haemolysis.
• Heme part is converted into bilirubin conjugated
in liver enters into intestine excreted through
urine as urobilin and stercobilin in feces.
32 PHYSIOLOGY
 Important Questions
1.Enumerate functions of Hemoglobin ?
- 3 Marks
2.Define hemoglobin and its types, Describe the
fate of hemoglobin ?
- 7 Marks

15 PHYSIOLOGY