1

Oxygen Transport
Total Body Oxygen Stores
Oxygen in the Lung (~500 ml O
2
).

Oxygen in the Blood (~850 ml O
2
).

Oxygen in the Cells (very little except
Mb-bound).
3
At the Lung Level
At the Tissue Level
Oxygen Is Carried in Blood in 2
Forms
Bound to hemoglobin in red blood cells.

Dissolved in plasma. Normally
insignificant.

7
Hemoglobin
Each heme molecule is capable of binding
with 1 O
2
molecule and each globin
molecule is capable of binding with 1 CO
2

molecule.
So, each molecule of Hb can bind to either 4
molecules of O
2
and 1 molecule of CO
2

100 ml of blood has about 15 gm of Hb, at Hct
= 0.45

8
Binding of O
2
to 4 heme sites given by:
4 2 2 3 2
3 2 2 2 2
2 2 2 2
2 2
) ( ) (
) ( ) (
) (
O Hb O O Hb
O Hb O O Hb
O Hb O HbO
HbO O Hb
+
+
+
+
Equilibrium constants for different reactions
different
Binding of first O
2
relatively low affinity
2nd, 3rd and 4th - much higher affinity
9
Oxygen as Oxyhemoglobin

Each gram of Hb can store about 1.34 ml
of O
2
:
1 L of blood (150 gm of Hb) can store
about 208 ml of O
2
Oxygen Capacity of
Hb.
With normal cardiac output, about 1040 ml
of O
2
can be carried in blood per minute. (4
times of the metabolic demands).

10
11
Oxygen in Dissolved Form
The amount of O
2
carried in blood in dissolved
form obeys Henrys law which states that
C
O2
= o
O2
*P
O2
.
o
O2
is the solubility coefficient of O
2
in plasma:
o
O2
= 1.35E-6 M/mmHg
= 0.03ml of O
2
/(L of plasma*mmHg)
Normal arterial plasma with P
O2
of 100 mmHg
contains 3 ml of O
2
/L of plasma and RBC water.
During a normal cardiac cycle, about 15 ml of O
2

is carried in plasma per minute, where the normal
metabolic demand is about 250 ml O
2
per minute.
12
O
2
Saturation.
Units: percent.

Fraction or percentage of all the
hemoglobin binding sites that are
currently occupied by oxygen.

14
100
Hb of capacity O
Hb with combined O
) saturation (% S
2
2
HbO2
=
Oxygen Saturation of Hb
Four (5-6?) Things Change
Oxyhemoglobin Affinity
1. Hydrogen Ion Concentration, [H
+
]
2. Carbon Dioxide Partial Pressure, PCO
2
3. Temperature
4. [2,3-DPG]

5. Special Case: Carbon Monoxide
6. Hemoglobin variants
16
17
Factors Affecting Hb-O
2
Affinity:
Summary
Hydrogen Ion:
Increased H
+
(decreased pH) increases H
+
binding to
Hb and reduces O
2
affinity (HbO
2
+H
+
HbH
+
+O
2
).

Carbon Dioxide (Bohr effect):
Increased P
CO2
increases CO
2
binding to Hb and
reduces O
2
affinity (increased O
2
delivery to tissue).
Increased P
CO2
increases H
+
and reduces O
2
affinity
(fixed acid Bohr effect).

Temperature and 2,3-DPG (diphosphoglycerate):
Increased temperature and 2,3-DPG reduces O
2
affinity.
Effect of CO & Anemia on Hb-O
2
Affinity
Normal blood with Hb=15 gm/dl, anemia with Hb=7.5 gm/dl,
and normal blood with 50% HbCO (carboxyhemoglobin).
Exercise
Increase temperature

Increased PCO
2
and

Decreased pH (acidosis)
2,3-DPG
2,3-DPG is a glycolytic intermediate
accumulates to uniquely high levels in RBCs
-Increased 2,3-DPG right shift

-Decreased 2,3-DPG left shift

Increased 2,3-DPG associated with
hypoxia.
Conditions with Increased 2,3-DPG
acclimatization to high altitudes.
chronic lung disease; emphysema.
anemia.
hyperthyroidism.
right to left shunt.
congenital heart disease.
pulmonary vascular disease.
23
Carbon Dioxide
Transport
24
At the Tissue Level
25
At the Lung Level
26
Carbon Dioxide Transport
CO
2
is transported in blood in dissolved form, as
bicarbonate ions, and as protein-bound carbamino
compound.

Protein-bound CO
2
(carbamino compounds):

Amount of CO
2
stored as carbamino compounds
is about 21 ml/L (4% of the total art CO
2
).
27
Carbon Dioxide Transport
A majority amount of CO
2
is transported in the
form of bicarbonate ions (HCO
3
-
):

Amount of CO
2
in HCO
3
-
form at P
CO2
=40
mmHg is about 420 ml/L (90% of the total
arterial CO
2
).
-
HCO H CO H O H CO
3 3 2
CA
2 2
+
+
+
28
Carbon Dioxide Transport

Haldane Effect: Increasing O
2
-saturation reduces
CO
2
content and shifts the CO
2
dissociation
curve to right. This is because, increasing P
O2

leads to :

Decrease in the formation of carbamino compound.
Release of H+ ions from the hemoglobin and resulting
in dehydration of HCO
3
-
.
29
Carbon Dioxide Dissociation Curve
Over the normal physiological range (P
CO2
= 30 to 55 mmHg
and P
O2
= 40 to 100 mmHg), the CO
2
equilibrium curve is
nearly linear. But, O
2
equilibrium curve is highly nonlinear.
Bicarbonate in RBCs.
Carbonic anhydrase is present in RBCs
CO
2
forms carbonic acid which
dissociates to H
+
and HCO
3
-



Released H
+
is buffered by histidine
residues (imidazole group)
CO H O H CO H HCO
2 2 2 3 3
+ +
+ Carbonic Anhydrase
Percent of the total PaCO
2
: 70%
Carbamino Compounds in RBCs.
Approximately 30% of RBC contents is Hb

CO
2
forms carbamino hemoglobin

Released H
+
is buffered by histidine
residues (imidazole group)
Percent of the total PaCO
2
: 23 %
CO
2
Formation in Plasma
Carbamino compounds
CO
2
binds the amine groups of plasma
proteins to form carbamino compounds.
R NH CO R NH COO H + +
+
2 2
34
Carbon Dioxide Transport
Three forms of storage, transport & kinetics of CO
2
in blood
Chloride Shift (Hamburger Shift)
Newly formed HCO
3
-
passes out of RBC

Cl
-
diffuses into RBC to maintain
electroneutrality
Chloride shift is rapid
Complete before the RBCs exit capillary

36
Tissue-Gas Exchange: Summary
Gas exchange processes in the peripheral organs
are essentially opposite those in the lungs.
O
2
is released from the capillary blood to the
tissues and diffuses to the mitochondria where O
2

is converted to CO
2
and energy (ATP) through
cellular metabolism.
CO
2
diffuses from the tissues to the blood stream
and is transported to the lungs for elimination.
The exchange of O
2
and CO
2
in the blood-tissue
exchange unit depends on P
O2
, P
CO2
, and also on
O
2
and CO
2
saturation curves.