1. 2012 - 2013
Physiology of
Respiratory system
By
Professor/
Abd El-Hamid Abou El-Magd
Lecturer of physiology
Faculty Of Medicine – Ain Shams University
Professor.abdelhamid@yahoo.com

2. Gas Exchange
• Sites of Gas exchange:
- At tissues
(between blood & tissues).
- At the lungs
(between blood & air).
• Mechanism of Gas exchange:
- Simple diffusion.
i.e. down partial pressure gradient.
from high to low partial pressure.

3. Gas exchange in the lung
• In the lungs:
- Venous blood enters
pulmonary capillaries
(High PCO2 & Low PO2).
- Air enters alveoli
(High PO2 & Low PCo2 ).
• O2 diffuses from alveoli to blood
down its pressure gradient.
• CO2 diffuses from blood to alveoli
down its pressure gradient.

5. Partial Pressure
Total & Partial Pressures

7. O2 diffusion
Alveolar PO2
= 100 mmHg
Pulm. Art. PO2
= 40 mmHg
(venous blood)
O2
Pulm. Venous PO2
= 100 mmHg
(arterial blood)
Back to the
left atrium

8. CO2 diffusion
Alveolar PCO2
= 40 mmHg
Pulm. Art. PCO2 =
46 mmHg
(venous blood)
CO2
Pulm. Venous PCO2
= 40 mmHg
(arterial blood)
Back to the
left atrium

9. Alveolar-Capillary membrane
(Respiratory membrane)

10. O2
O2

11. Factors affecting
gas diffusion
1)
3)
4)
•
•
Partial pressure gradient of the gas across the alveolarcapillary membrane. (60 mmHg for O2 & 6 mmHg for CO2).
Surface area of the alveolar-capillary membrane. (about 70
m2).
Thickness of the alveolar-capillary membrane. (about 0.5 μ).
Diffusion coefficient of the gas that depends on:
Gas solubility. (CO2 is 24 times soluble than O2).
Molecular weight of the gas. (CO2 M.W. is 1.4 times greater than O2).
•
Net effect: CO2 diffusion is 20 times faster than O2
2)

12. Rate of gas diffusion =
Diffusion coefficient X Pressure gradient x Surface area of the membrane of
Thickness of the membrane
•
The volume of gas transfer across the alveolar-capillary
membrane per unit time is:
Directly proportional to:
-
The difference in the partial pressure of gas between alveoli and capillary blood.
The surface area of the membrane.
The solubility of the gas.
Inversely proportional to:
-
Thickness of the membrane.
Molecular weight of the gas.

13. Important Notes
• Although CO2 diffusion is 20 times faster than
O2, Equilibration of CO2 (pressure gradient is 6mm Hg) across
alveolar-capillary membrane occurs at the same rate as O2
(pressure gradient is 60 mmHg).
• In lung diseases that impairs diffusion, O2 diffusion is more
seriously impaired than CO2 diffusion because of the greater
CO2 diffusion coefficient.
• This effect is more manifest in patients with lung diseases
during exercise.

14. The diffusion capacity of the respiratory
membrane
• Definition:
The volume of gas that diffuses across the alveolar-capillary membrane / min
for a pressure difference of 1 mmHg.
= 20 ml / min./ mmHg for O2.
= 400 ml / min./ mmHg for CO2.
• Diffusion capacity increases during exercise:
= 80 ml/ min./ mmHg for O2.
= 1600 ml/min./ mmHg for CO2.
This is due to opening of pulmonary capillaries
area.
increase of surface
• Diffusion capacity decreases in:
– conditions that increases alveolar-capillary membrane thickness.
e.g. lung fibrosis and pulmonary oedema.
– conditions that decreases the effective area for diffusion.
e.g. collapse, emphysema, and ventilation perfusion mismatch.

15. Gas Exchange At Tissue Level
Tissue
PO2 =
PCO2 =
40 mmHg
46 mmHg
Venous Blood
Arterial Blood
PO2 = 100 mmHg
PCO2 = 40 mmHg
100 mmHg
40 mmHg
Capillary
PO2 = 40 mmHg
PCO2 = 46 mmHg

16. “The real reason dinosaurs became
extinct…”

17. Gas Transport
between Lungs and Tissues
• O2 moves under its partial
pressure gradient from:
-
The lungs to blood, and then from
The blood to tissues to be utilized.
• CO2 moves under its partial
pressure gradient from:
-
O2
O2
O2
CO2
CO2
Tissues to blood, and then from
Lungs to air be eliminated.
• So, blood carries
O2 and CO2 between lungs and tissues.
CO2

18. O2 Transport in the Blood
• O2 is transported by the blood in 2
forms:
- Physically dissolved
in blood = 1.5%
- Chemically bound
to hemoglobin = 98.5%

19. O2 in blood
Physically dissolved O2
• Only 1.5 % of total O2 in blood.
• Dissolved in plasma and water of
RBC. (because solubility of O2 is
very low)
• It is about 0.3ml of O2 dissolved in
100ml arterial blood (at PO2 100
mmHg).
• Its amount is directly proportional
to blood PO2.
• Can not satisfy tissue needs.
Chemically combined O2
• 98.5 % of total O2 in blood.
• Transported in combination with
Hb.
• It is about 19.5 ml of O2 in 100 ml
arterial blood.
• Can satisfy tissue needs.

20. O2 combined to Hb
• Hb is formed of 4 subunits.
• Each subunit contains a heme group attached to a
polypeptide chain (α or β).
• O2 binds to the ferrous iron atom in the heme group in a
rapid oxygenation reaction (HbO2).
• The connection between iron and O2 is weak and reversible.
• The iron stays in the ferrous state.
• Thus, each Hb molecule can carry up to 4 O2 molecules.

21. O2 content of the blood
• It is the total amount of O2 carried by blood.
• = dissolved O2 + O2 combined with Hb.
= 0.3 ml/100ml + 19.5 ml/100ml
Plasma (0.3 ml)
Hb of RBCs (19.5 ml)
100 ml blood
= 19.8 ml/100 ml blood.
• It depends mainly on the O2 bound to Hb, as it represents the
main component.

22. O2 carrying capacity
of the blood
• It is the maximum amount of O2 that can be carried by Hb.
• Each gram Hb, when fully saturated with O2, can carry 1.34
ml O2.
• As Hb content = 15 gm/100 ml blood.
So, O2 carrying capacity = 1.34 x 15
Hb = 15 gm
Each gm: 1.34 ml O2
100 ml blood
= 20.1 ml O2/100 ml blood.

23. The percent of Hb saturation with O2 (%
Hb saturation)
• It is an index for the extent to which Hb is combined with
O2.
O2 bound to Hb
• % Hb saturation =
X 100
O2 carrying capacity
• When all Hb molecules are carrying their maximum O2 load,
Hb is said to be fully saturated (100 % saturated).
• PO2 of the blood is the primary factor that determines % Hb saturation.

24. Important notes
• In arterial blood (High PO2 ):
97% of Hb is saturated with O2
• In venous blood (Low PO2 ):
75% of Hb is saturated with O2
• At the lung: high alveolar PO2 (100 mmHg)
Hb automatically loads up (binds) O2.
• At the tissues: low tissue PO2 (40 mmHg)
Hb automatically unloads (releases) O2.

25. Professor.abdelhamid@yahoo.com
• Enumerate sites of gas exchange in the body. Mention
the mechanism of gas exchange.
• Describe the alveolo-capillary membrane. Discuss the
factors that affect gas diffusion through it.
• Discuss oxygen transport in blood.
• Differentiate
between
oxygen
content
of
blood, oxygen carrying capacity and the percent
oxygen saturation of hemoglobin.

27. Oxygen-Hemoglobin
Dissociation Curve
• It is a curve represents the relationship between
blood PO2 (on the horizontal axis) and % Hb saturation
(on the vertical axis) .
Because the % of hemoglobin saturation depends on the PO2 of
the blood.
• It is not linear.
• It is an S-shaped curve that has 2 parts:
- upper flat (plateau) part.
- lower steep part.

29. The upper flat (plateau)
part of the curve
In the pulmonary capillaries (lung, PO2 range of 100-60 mmHg).
- At PO2 100 mmHg
% Hb saturation
- At PO2 60 mmHg
saturation).
97% of Hb is saturated with O2.
90% of Hb is saturated with O2 (small change in % Hb
97 %
90 %
60
PO2
100

30. The upper flat (plateau)
part of the curve
• Physiologic significance:
- Drop of arterial PO2 from 100 to 60 mmHg
little
decrease in Hb saturation to 90 % which will be sufficient to
meet the body needs.
This provides a good margin of safety against blood PO2
changes in pathological conditions and in abnormal situations.
- Increase arterial PO2 (by breathing pure O2)
little
increase in % Hb saturation (only 2.5%) and in total O2 content
of blood.

31. The steep lower part
of the curve
In the systemic capillaries (tissue, PO2 range of 0-60 mm Hg).
% Hb saturation
- At PO2 40 mmHg (venous blood)
(large change in % Hb saturation).
At PO2 20 mmHg (exercise)
70% of Hb is saturated with O2
30% of Hb is saturated with O2.
97 %
90 %
70 %
30 %
20
40
60
PO2
100

32. The steep lower part
of the curve
• Physiologic significance:
- In this range, only small drop in tissue PO2
rapid
desaturation of Hb to release large amounts of O2 to tissues.
- If arterial PO2 falls below 60 mmHg
desaturation of
Hb occurs very rapidly
release of O2 to the
tissues.
This is important at tissue level.

33. Factors affecting O2-Hb dissociation curve
Factors that shift O2-Hb
Curve to the right =
decreased affinity of Hb to O2 & increase
O2 release to tissues.
Factors that shift O2-Hb
Curve to the left =
increased affinity of Hb to O2 & decrease
O2 release to tissues.

34. Factors affecting O2-Hb dissociation curve
Factors that shift O2-Hb
Curve to the right
• Decreased PO2.
• Increased blood PCO2.
• Increased blood H+
concentration.
• Increased blood
temperature.
• Increased concentration of
2,3 DPG.
Factors that shift O2-Hb
Curve to the left
• Increased PO2.
• Decreased blood PCO2
• Decreased blood H+
concentration.
• Decreased blood
temperature.
• Decreased concentration of
2,3 DPG

36. During exercise
There will be:
•
•
•
•
•
Decreased PO2 in capillaries of active muscles.
Increased temperature in active muscles.
Increased CO2
Decreased pH due to acidic metabolites.
Increased 2, 3 DPG in RBCs by anaerobic glycolysis.
All these factors lead to:
• Shift of O2-Hb dissociation curve to the right.
• Decrease affinity of Hb to O2.
• More release of O2 to tissues.

37. P50
• It is the PO2 at which 50% of Hb is saturated with O2.
• It is an index for Hb affinity to O2.
• Normally, P50 is 27 mmHg
(At PCO2=40mmHg, pH=7.4, 37°C).
27

38. • Increased P50 =
- decreased affinity of Hb to O2
- shift of O2-Hb dissociation curve to the right.
• Decreased P50 =
- increased affinity of Hb to O2
- shift of the curve to the left.
So, The P50 is an inverse function of the Hb affinity for O2.
27

40. Bohr's Effect
• Represents the effect of PCO2 and H+ (acidity) on the
O2-Hb dissociation curve.
- At tissues: Increased PCO2 & H+ concentration
shift of O2-Hb curve to the right.
- At lungs: Decreased PCO2 & H+ concentration
shift of O2-Hb curve to the left.
So, Bohr's effect facilitates
i) O2 release from Hb at tissues.
ii) O2 uptake by Hb at lungs.

41. Important Notes
• CO2: combine reversibly with Hb (at sites other than O2 binding sites)
change in the molecular structure of Hb
O2.
decrease in affinity of Hb to
• H+: combine reversibly with Hb (at sites other than O2 binding sites)
change in the molecular structure of Hb
O2.
decrease in affinity of Hb to
• 2,3 DPG:
- Produced by anaerobic glycolysis inside RBCs.
- Binds reversibly with Hb (at β polypeptide chain) decrease Hb affinity to O2.
- Increased by: exercise, at high altitude, thyroid hormone, growth hormone
and androgens.
- Decreased by: acidosis and in stored blood.

42. O2 dissociation curve
of fetal Hb
• Fetal Hb (HbF) contains 2 and 2 polypeptide chains
and has no  chain which is found in adult Hb (HbA).
• So, it cannot combine with 2, 3 DPG that binds only to
 chains.
• So, fetal Hb has a dissociation curve to the left of that
of adult Hb.
• So, its affinity to O2 is high
uptake by the fetus from the mother.
increased O2

44. O2 dissociation curve
of myoglobin
• One molecule of myoglobin has one ferrous atom (Hb has 4
ferrous atoms).
• One molecule of myoglobin can combine with only one
molecule of O2 .
• The O2–myoglobin curve is rectangular in shape and to the left
of the O2-Hb dissociation curve.
• So, it gives its O2 to the tissue at very low PO2.
• So, it acts as O2 store used in severe muscular exercise when
PO2 becomes very low.

47. Professor.abdelhamid@yahoo.com
• Discuss with diagram oxygen-hemoglobin associationdissociation curve.
• List the factors that affect oxygen-hemoglobin curve.
• Explain effects of CO2, H+ and 2,3DBG on oxygenhemoglobin curve.
• Compare the fetal hemoglobin and myoglobin
dissociation curves to that of adult hemoglobin.

48. CO2 in blood
Arterial blood
Venous blood
Physically dissolved CO2
2.4 ml/100ml (5%)
2.8 ml/100ml
Chemically combined CO2 as
HCO3
43.2 ml/100ml (90%)
45.8 ml/100ml
Chemically combined CO2 as
carbamino
2.4 ml/100ml (5%)
3.4 ml/100ml
Total CO2
48 ml/100ml
52 ml/100ml
PCO2
40 mmHg
46 mmHg
Tidal CO2: is the amount of CO2 added from tissues to 100 ml
arterial blood (about 4 ml) to be changed to venous blood.

49. Chloride shift phenomenon
• Definition: It is the movement of Cl- in exchange
with HCO-3 across RBC membrane.
• It is responsible for carrying most of the tidal
CO2 in the bicarbonate form.
• It prevents excessive drop of blood pH.

50. Tissue
CO2
Plasma
CO2 + H2O
H2CO3
Plasma
proteins
HCO3 +H+
HCO-3
CO2 + H2O
Hb
RBC
CA
H2CO3
HCO3 +H+
HbO
ClH2O
ClH2O

51. Chloride shift phenomenon
• Mechanism:
- CO2 entering the blood diffuses into RBCs
rapidly hydrated
to H2CO3 in the presence of the carbonic anhydrase enzyme.
- H2CO3 dissociates into H+ and HCO-3.
- H+ is buffered by the reduced (not oxygenated) Hb.
- HCO-3 concentration in RBCs increases.
- some of the HCO-3 diffuses out to the plasma.
- In order to maintain electrical neutrality, chloride ions (Cl-)
migrate from the plasma into the red cells.

52. Chloride shift phenomenon
•
-
Net effect:
Increased HCO-3 in both the RBCs and plasma.
Increased Cl- inside the RBCs.
Increased osmotic pressure inside RBCs
water
shift from the plasma.
- Increase RBCs volume
increase in the hematocrit
value.
- Buffering of the tidal CO2 with very little change in the
pH.

53. Reverse chloride shift phenomenon
• Definition: It is the movement of Cl- in exchange
with HCO-3 across RBC membrane.
• It is responsible for removal of the tidal CO2 by
lungs.

54. Lung
alveoli
CO2
Plasma
CO2
Carbamino
proteins
HCO-3
CO2Hb
CO2
CO2
+ H2O
RBC
H2CO3
HCO3 +H+
ClH2O
ClH2O

56. CO2 dissociation curve
• It is a curve represents the relationship between the total CO2
content and CO2 tension.
• It is linear, in the physiological range of PCO2.
• The normal PCO2 range is:
-
40 mmHg in arterial blood with CO2 content of 48 ml/100 ml blood
46 mmHg in venous blood with CO2 content of 52 ml/100 ml blood.
• This linear relationship means that any change in PCO2 will
produce a great change in CO2 content of the blood.
• Also, at any given CO2 tension, reduced Hb carries more CO2 than
oxyHb.

57. CO2 dissociation curve
Reduced Hb
CO2 content
66 ml
v
52 ml
48 ml
a
40
46
PCO2
60

58. Important Notes
• Bohr's effect:
- Increased CO2
decrease the affinity of Hb to O2
shift of O2-Hb dissociation curve to the right.
• Haldane effect:
- Increased O2
decrease the affinity of Hb to CO2 (because
binding of O2 with Hb
displacement of CO2 from the blood).
•
The presence of O2 or CO2 carried by Hb interferes
with the carriage of the other gas.

59. Carbon monoxide (CO) poisoning
• CO + Hb
carboxyhemoglobin (HbCO).
• CO and O2 compete for the same binding sites on Hb.
• The affinity of Hb for CO is 240 times more than its affinity for
O2.
• CO can interfere with both the combination of O2 with Hb in the
lungs and the release of O2 at tissues by:
- Presence of of CO (even in small amounts) bind to a large portion
of Hb
preventing its binding to O2.
- CO shifts O2-Hb dissociation curve to the left.
Q: Detect effects of CO poisoning on: PO2, O2 content, HV, % Hb
saturation & on color of blood.

60. Professor.abdelhamid@yahoo.com
• Define P50, its normal value and importance .
• Compare O2 with CO2 transport in blood.
• Explain the changes that occur in blood at tissues due
to addition of CO2.
• Describe CO2 curve.
• Discuss Bohr’s effect and Haldane effect and their
integration.