HEMOGLOBIN

AND
O2 & CO2 TRANSPORT

By Professors
Dr. Ahmed ElGendy Dr.Ahmed Agamy
 Objectives
Haemoglobin
❑ Haemoglobin content
❑ Structure
❑ Types normal and abnormal
❑ Reactions normal and abnormal
O2 Transport
❑ Forms of O2 transport
❑ O2 content, O2 capacity and O2 percentage saturation
❑ O2 dissociation curve
❑ Factors shifting the curve to right and left
CO2 Transport
❑ Forms of CO2 transport Prof. Ahmed ElGendy
❑ Chloride shift phenomenon Prof.Ahmed Agamy
 Haemoglobin
❑ Haemoglobin content
❑ Structure
❑ Types normal and abnormal
❑ Reactions normal and abnormal

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
Nature :
*O2 carrying pigment
*Chromoprotein
*MW = 64 - 450 dalton
*It represents 34% of
RBCs weight(RBCs are Hb
sacs)
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
4 subunits

Each subunit formed of 4 pyrrole rings +

one polypeptide chain

Hb is formed of 4 polypeptide chains (

globin )

4 atoms of iron ( Fe ) in each molecule

Prof. Ahmed ElGendy
Prof.Ahmed Agamy
O2 is carried on Fe++

CO2 is carried on amino acids of polypeptide chain =

carbamino compound

Hb , The more binding with O2 , The less binding to

CO2 ( at lung) and The more CO2 binding The Less
binding with O2 ( at tissues) and amount of O2
delivered to tissue is directly proportional to tissue
activity ( due to increase CO2 , temperature , acids ,
DPG which dissociate O2 from Hb)although they are
carried on different sites with no overcrowding =
computerized process
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
O2   O2

O2   O2

Oxyhaemoglobin
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
*Glycine + Acetic acid Succinyl
Co A
*2 Succinyl CoA + 2 Glycine
Pyrrole ring
*4 Pyrrole rings Protoporphyrin
*Protoporphyrin + Fe Heme
*Heme + Polypeptide Hb chain
( α or B )
*2 α chains + 2 B chains Hb – A (
Adult Hb )
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
1- Adult Hb ( HbA-I ) = 2 α + 2 B polypeptide
chains . HbA-2 represent 2% of adult Hb(2 α +
2 delta polypeptide)
2- Fetal Hb ( HbF ) = 2 α + 2 Y polypeptide
chains
HbF is replaced by HbA soon after birth
HbF has high affinity to O2 than HbA →
Facilitates transport of O2 from mother to
fetus
3- Embryonic Hb ( Gower Hb : I & II ) = 4
Epsilon polypeptide chains
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
Fetal Hb ( HbF ) = 2 α +2Y
polypeptide chains

Some believes that HbF is replaced by

HbA at 4th month after labor not during
intrauterine life not at birth not at adult

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
Adult Hb ( HbA-I ) contain 2 B polypeptide
which bind with DPG to release O2

Fetal Hb ( HbF ) contain 2 Y polypeptide

chains which not bind with 2,3 DPD making
HbF has high affinity to O2 than HbA→
Facilitates transport of O2 from mother to
fetus
N.B: 2,3 DPG =2,3 Diphosphoglycerate

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
*One Hb molecule bind with 4O2 & the
reaction is loose , rapid & reversible
*Iron in Hb is ferrous ( Fe ++ ) in reduced Hb &
remain Fe ++ when it combine with O2
( Oxy-Hb )
*So the reaction is oxygenation not oxidation
*Combination of Hb with O2 occurs in steps ,
each step stimulate next one
Hb + O2 HbO2 ( 25% saturation )
Hb + 2O2 HbO4 ( 50% saturation )
Hb + 3O2 HbO6 ( 75% saturation )
Hb + 4O2 HbO8 ( 100% saturation )
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
1- Factors increase combination :
- Increase pH ( decrease H )
- Decrease CO2
- Decrease temperature
- Decrease 2,3 DPG ( Di-Phosph-
Glycerate )
2- Factors decrease combination :
- Vice Versa
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
B-Abnormal (pathological) types (hemoglobinopathies):
Many types, but the most common are
(1) Hemoglobin-S (Hb–S):-
Contain 2 abnormal  chains (amino acid sequence is abnormal) but normal  chains, this
lead to precipitation of hemoglobin and make RBCs sickle in shape  sickle cell anemia
(2) Hemoglobin–H (Hb-H):-
No  chain but contain 4 chains thalassemia.
In -thalassemia the  chains are absent and Hb contain 4  chains only.

Hb-H (α thalassemia)
Hb-S (Sickle cell anemia) β thalassemia
(No α Chains)
Abnormal beta chain (No β Chains)
Prof. Ahmed ElGendy Prof.Ahmed Agamy
 O2 Transport
❑ Forms of O2 transport
❑ O2 content, O2 capacity and O2 percentage saturation
❑ O2 dissociation curve
❑ Factors shifting the curve to right and left

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
Forms of O2 transport:-
(1) O2 in physical solution (Dissolved):-
- Nature:- Free O2 molecules dissolved in blood
- Volume:- 0.3 ml /100 ml arterial blood (PO2= 100 mmHg)
0.13ml/100ml venous blood (PO2=40mmHg)
It depends on O2 tension in alveoli
- Importance:- It determines PO2 in blood. The PO2 in turn determines:-
a-The rate and direction of O2 diffusion
b- Percentage saturation of hemoglobin with O2 i.e. O2 in chemical
combination is determined by O2 in physical solution
(2) O2 in chemical combination :- (Chemical form):-
- Nature:- O2 combines with the iron of hemoglobin, while still in ferrous state
HbO4, HbO6 and HbO8
- Volume:- 19ml/ 100 ml arterial blood 14ml/100ml venous blood
Depends on O2 tension
- Importance:- It constitute the main supply of O2 to tissues. Tissues utilize first O2 in
physical form, this leads to drop of PO2 in arterial blood. Then O2 is dissociated from
Hb to supply tissues. Prof. Ahmed ElGendy
Definitions:-
1- O2 capacity:-
- It is the volume of O2 in ml present in 100ml blood when Hb is fully saturated with O2 .
- Normal value:- 20 ml O2 / 100ml blood
O2 capacity = 1.33ml O2 x Hb content = 1.33ml O2 x 15= 20 ml O2.
Prof. Ahmed ElGendy
- Depends on (affected by) Hb content only but not O2 tension. Prof.Ahmed Agamy
2- O2 content:-
- It is the volume of O2 in ml present in 100 ml blood
- Normal value:- Arterial blood 19 ml/100 ml blood (at PO2 100 mmHg)
Venous blood 14 ml/100ml blood (at PO2 40mmHg).
- Depends on (affected by) both tension and Hb content.
3- O2 percentage saturation (O2 %saturation):-
- O2 % saturation = percent of Hb saturated with O2 in 100mlblood

=
19
- Normal value:- Arterial blood = 20 x 100 = 95%

Venous blood = x 100=70%

- Depends on O2 tension only. Prof. Ahmed ElGendy

Prof.Ahmed Agamy
 Oxyhemoglobin dissociation curve
- Aim of the curve:- To study the affinity of Hb to O2 at different O2 tensions. This is done
by studying the relation between PO2 (O2 tension) and O2 % saturation at different O2 tensions.
O2 % saturation is used as an evaluation of Hb affinity for O2 (but not O2 content or O2
capacity) because it is affected only by O2 tension (and not Hb content) while O2 content and
O2 capacity are affected by Hb content.
- Description of the curve:-
It is sigmoid shape (s-shaped) composed of 3 parts:-
(1) First slope part (slowly descending part) (right half of the curve):-
❑ Occurs at high O2 tension at the lungs) (at lungs O2 tension during rest is 100 mm Hg and at
high altitudes is 70 mm Hg).
❑ In this part marked  in PO2 →only slight  in O2 % saturation e.g.  PO2by 30mm Hg (from

100 to 70). → only 5%  in O2 % saturation (from 95 to 90%)

❑ This means at high PO2 (at lungs) the affinity of Hb to O2 is high this allows easy and
complete saturation of Hb with O2 at lungs
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
(2) Steep part (rapidly descending part) from PO2 50 to 20 mmHg):-
❑ Occur at low O2 tension (at tissues) (at tissues PO2 is 40 mmHg at rest and 30mmHg during
exercise).
❑ In this part slight  in PO2 → marked  in O2 % saturation e.g.  PO2 by only 10mmHg (from

40 to 30 mm Hg) → O2 % saturation by 30% (from 70 to 40%).

❑ This means at low PO2 (at tissues) the affinity of Hb to O2 is low this allow easy and rapid

dissociation of O2 from Hb at tissues.

(3) Second slope part (second slowly descending part):-
❑ Occur at very low PO2 (at sk. ms during sever exercise, PO2 is 20 mm Hg orless)
❑ In this part affinity of Hb to O2 increases again and released amount of O2 is minimal. At this

level of PO2 (20mmHg) an additional source of O2 in muscle (myoglobin) starts to supply

muscles with O2 (steep part of O2 myoglobin curve starts at PO2 20 mmHg).

-Significance of S-shape (sigmoid shape) of the curve:

•At high PO2 (at lungs) the affinity of Hb to O2 is high allowing easy and nearly complete
saturation of Hb with O2.
•At low PO2 (at tissues) the affinity of Hb to O2 is low allowing easy and rapid dissociation of
Prof. Ahmed ElGendy
O2 from Hb to supply tissues.
Slope part Steep part
Slope part (slowly descending part)
(high affinity) Easy & rapid
Easy and complete saturation
needs other dissociation Prof. Ahmed ElGendy
(High affinity)
source(myoglob.) (low affinity) Prof.Ahmed Agamy
 Factors affecting affinity of Hb to O2
(Factors shifting O2 Hb dissociation curve)
Shift t o t h e right Sh ift t o t h e left
M e a n i n g : - t h e affinity o f H b t o O 2 is M e a n i n g : - t h e affinity o f H b t o O 2 is
d e c r e a s e d i.e. a t a n y g i v e n O 2 i n c r e a s e d ( l o a d i n g o f H b ) i.e a t
t e n s i o n H b w ill b e l e s s s a t u r a t e d , a n y g i v e n O 2 t e n s i o n H b w ill b e
t h u s g i vi n g m o r e O 2 t o t i s s u e s m or e saturated w ith O2 thus
(unloading of Hb). g i vi n g l e s s O 2 t o t i s s ue s .
Causes:- Causes:-
1. P C O 2 i n b l o o d ( B o h r ’ s effect.) 1 . PCO2 in blood
2 . H + concentration 2.  H + concentration in blood
3. Temperature 3.  temperature
4 . 2.3 D.P.G in R B C S. 4. 2,3 D.P.G content in R B C s.
5. H b concentration as in 5 .  H b concentration as anemia
pregnancy and polycythemia.
6. Carbon monoxide poisoning
7. Fetal hemoglobin.
Significance:- Increase O2 supply Significance:- Decrease O2 supply
t o a c t i ve t i s s u e s . M o s t o f t h e s e t o i n a c t i ve t i s s u e s
f a c t o r s a r e p r e s e n t a t t h e a c t i ve Prof. Ahmed ElGendy
tissues Prof.Ahmed Agamy
Notes:
1 Iron containing red pigment found in skeletal ms., especially slow ms. (adapted for prolonged
contraction). It contains one heme group and thus can combine with one O2 molecule only.
2 Oxymyoglobin dissociation curve:- is in the form of rectangular hyperbola i.e. it store O2 and
release It only when PO2 reaches very low level (about 20mmHg) (PO2 at ms exercise) i.e.
during exercise it is dissociated and during recovery from exercise it is saturated again. In this
way myoglobin performs complementary function to that of Hb.
3-2,3 diphosphoglycerate (2,3 DPG) is formed in RBCs by anaerobic glycolysis, its concentration
in RBCs is increased in :- 1- At high altitude 2- ms. Exercise.
It combines with Hb in the deoxygenated form thus decreases its affinity for O2
4-Fetal Hb:- has high affinity for O2 than adult Hb. This is because it is composed of 2alpha and
2 gamma chains. Gamma chain can not combine with DPG thus increases affinity of FHb to
O2.

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
 CO2 Transport
❑ Forms of CO2 transport
❑ Chloride shift phenomenon

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
CO2 content:
CO2 content of arterial blood= 48 ml /100 ml blood
CO2 content of venous blood= 52 ml /100 ml blood
Tidal CO2:-
Definition:- CO2 which is given by the tissues to each 100ml blood each minute during its flow
through the tissues. Normally = 4 ml/100ml blood /min.
Buffering (Carriage) of tidal CO2:-
The 4ml CO2 added by the tissue should be buffered, otherwise they will decrease the PH of
the blood to a dangerous level. They are carried as follows:-
A-In physical solution (dissolved):- about 7% (0.4ml), this decreases PH from 7.4 to 7.34.
CO2+ H2O ⇄ H2CO3 ⇄ H++ HCO -3 occurs in plasma and RBCs
B-In chemical combination:- 93% (3.6ml)as:-
1 Bicarbonate 70% (2.6ml) (main form) in RBCs as KHCO3 and in plasma as NaHCO3 .
2 Carbamino compounds 23% (1ml) mainly with Hb forming carbaminohemoglobin and to
less extent with plasma proteins forming carbaminoproteins.
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
Buffering (Carriage) of tidal CO2

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
 Transport (carriage) of CO2 as HCO-3
(Chloride shift) (Hamburger’s) phenomenon
Definition:- Is the mechanism by which CO2 given by the tissues is buffered (carried) as
bicarbonate.
Mechanism:-
❑ When blood is exposed to high CO2 tension (at tissues) most of CO2 diffuses into RBCs and

70% of it then combine with H2O to form H2CO3 under the effect of carbonic anhydrase
enzyme (C.A). This enzyme accelerates the reaction about 5000 folds or more and it is
present only in RBCs not plasma. For this reason, the reaction is very rapid in RBCs and
very slow in plasma leading to formation of 65% of HCO -3 in RBCs and only 5% inplasma.
❑ H2CO3 dissociates to H+ andHCO-3 :-

1 H+ is buffered primarily by hemoglobin (reduced Hb binds more H+ than oxy Hb)

2-HCO-3:-
- Part of it (about 30%) combines with K+ supplied from Hb to form KHCO3 (oxy Hb
binds more K+ than reduced H+).
- Most of it (about 70%) passes to plasma down concentration gradient.
Prof. Ahmed ElGendy
 3 Cl- passes from plasma to RBCs down electric gradient. This is helped by the presence of a
special HCO-3 - Cl- carrier in RBCs membrane which facilitate the transport of these 2 ions in
opposite directions.
4 With each CO2 molecule added to RBCs there is an increase of one osmotically active
particle (Cl- or HCO-3) and according to osmotic pressure H2O shifts from plasma to RBCs
leading to an increase in RBCs volume. Thus hematocrit value of venous blood is 3%
normally more than that of arterial blood.
Result:-
Results: RBCs Plasma
1- HCO- Increase Increase
3
2- Cl- Increase Decrease
3- Osmotic Pressure Increase →volume Constant
→ Hematocrit by 3%
Significance:-
Enables blood to carry most of tidal CO2 as HCO-3 thus prevents excessive drop in PH of blood
by the carried CO2
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
 Chloride shift
(Hamburger’s)
phenomenon
Reduced Hb:-
-Carry more CO2 (Haldane effect)
-Carry more H+
70%

30%

Oxy Hb carry more K+

Prof. Ahmed ElGendy RBCs Blood Tissues

Prof.Ahmed Agamy
 Bohr and Haldane effects
Haldane effect describes the effect of oxygen concentrations on hemoglobin's affinity for
carbon dioxide (loading of CO2). High oxygen concentrations (at lungs) enhance the unloading
of carbon dioxide (i.e. oxyhemoglobin carries less CO2). The converse is also true: low oxygen
concentrations (at tissues) promote loading of carbon dioxide onto hemoglobin (i.e. reduced
hemoglobin carries more CO2).

Bohr effect describes the effect of carbon dioxide (and hence H+) on the affinity of hemoglobin
for oxygen. High CO2 concentrations (at tissue) decreases the affinity of Hb for oxygen (shift to
right). The converse is also true: low concentrations (at lung) cause high affinity for oxygen.

Prof. Ahmed ElGendy

Prof.Ahmed Agamy
Prof. Ahmed ElGendy
Prof.Ahmed Agamy
Resources
▪ Guyton AC, and Hall JE (2010); Text book
of
medical physiology, 12th ed., W.B.
Saunders Company
▪ Ganong WF. (2012) ; Review of Medical
Physiology, 24th ed., Lange Basic Science
▪ Lauralee Sherwood (2012); Human
physiology, from cell to system, 8th ed.,
Blackwell Press
▪ www.advan.physiology.org
Prof. Ahmed ElGendy
Prof.Ahmed Agamy