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By
Professor/ Abd El-Hamid Abou El-Magd Lecturer of physiology
Faculty Of Medicine – Ain Shams University
Physiology of
Respiratory system
2012 - 2013
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.
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.
Total & Partial Pressures
Parti
al P
ress
ure
O2 diffusion
Alveolar PO2 = 100 mmHg
Pulm. Art. PO2 = 40 mmHg
(venous blood)
Pulm. Venous PO2 = 100 mmHg
(arterial blood)
O2
Back to the left atrium
CO2 diffusion
Alveolar PCO2 = 40 mmHg
Pulm. Art. PCO2 = 46 mmHg
(venous blood)
Pulm. Venous PCO2 = 40 mmHg
(arterial blood)
CO2
Back to the left atrium
Alveolar-Capillary membrane(Respiratory membrane)
O2
O2
............
............
............
............
...........
Factors affecting gas diffusion
1) Partial pressure gradient of the gas across the alveolar-capillary membrane. (60 mmHg for O2 & 6 mmHg for CO2).
2) Surface area of the alveolar-capillary membrane. (about 70 m2).
3) Thickness of the alveolar-capillary membrane. (about 0.5 μ). 4) 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
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.
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.
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 increase of surface
area.
• 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.
Gas Exchange At Tissue Level
Tissue
Capillary
Arterial Blood Venous Blood
PO2 =
40 mmHg
PO2 = 100 mmHg PO2 = 40 mmHg
PCO2 =
46 mmHg
PCO2 = 40 mmHg PCO2 = 46 mmHg100 mmHg
40 mmHg
“The real reason dinosaurs became extinct”…
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:- Tissues to blood, and then from - Lungs to air be eliminated.
• So, blood carries O2 and CO2 between lungs and tissues.
O2
O2
O2
CO2
CO2
CO2
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%
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.
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.
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
= 19.8 ml/100 ml blood.
• It depends mainly on the O2 bound to Hb, as it represents the main component.
Plasma (0.3 ml) Hb of RBCs (19.5 ml)100 ml blood
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
= 20.1 ml O2/100 ml blood.100 ml blood
Hb = 15 gmEach gm: 1.34 ml O2
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.
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.
• 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.
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.
The upper flat (plateau) part of the curve
PO2
% H
b sa
tura
tion
10060
97 %
90 %
In the pulmonary capillaries (lung, PO2 range of 100-60 mmHg). - At PO2 100 mmHg 97% of Hb is saturated with O2.- At PO2 60 mmHg 90% of Hb is saturated with O2 (small change in % Hb saturation).
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.
The steep lower part of the curve
PO2
% H
b sa
tura
tion
10060
97 %90 %
In the systemic capillaries (tissue, PO2 range of 0-60 mm Hg).- At PO2 40 mmHg (venous blood) 70% of Hb is saturated with O2
(large change in % Hb saturation).At PO2 20 mmHg (exercise) 30% of Hb is saturated with O2.
30 %
70 %
20 40
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.
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.
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
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.
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
• 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
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.
Important Notes
• CO2: combine reversibly with Hb (at sites other than O2 binding sites) change in the molecular structure of Hb decrease in affinity of Hb to O2.
• H+: combine reversibly with Hb (at sites other than O2 binding sites) change in the molecular structure of Hb decrease in affinity of Hb to O2.
• 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.
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 increased O2 uptake by the fetus from the mother.
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.
• Discuss with diagram oxygen-hemoglobin association-dissociation curve.
• List the factors that affect oxygen-hemoglobin curve.
• Explain effects of CO2, H+ and 2,3DBG on oxygen-hemoglobin curve.
• Compare the fetal hemoglobin and myoglobin dissociation curves to that of adult hemoglobin.
CO2 in bloodVenous blood Arterial blood
2.8 ml/100ml 2.4 ml/100ml (5%) Physically dissolved CO2
45.8 ml/100ml 43.2 ml/100ml (90%) Chemically combined CO2 as HCO3
3.4 ml/100ml 2.4 ml/100ml (5%) Chemically combined CO2 as carbamino
52 ml/100ml 48 ml/100ml Total CO2
46 mmHg 40 mmHg PCO2
Tidal CO2: is the amount of CO2 added from tissues to 100 ml arterial blood (about 4 ml) to be changed to venous blood.
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.
Tissue
RBC
Plasma
HCO-3
+H2OPlasma proteins
HbCA
CO2
Cl-
H2O
CO2 HCO3 +H+H2CO3
CO2 +H2O H2CO3 HCO3 +H+
Cl-
H2O
HbO
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.
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.
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.
Lung alveoli
RBC
Plasma
HCO-3
Carbamino proteins
CO2
CO2
Cl-
H2O
CO2
CO2Hb
CO2
+H2O
H2CO3 HCO3 +H+
Cl-
H2O
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.
CO2 dissociation curve
PCO2
CO2 c
onte
nt
4640
52 ml
48 ml
66 ml
60
a
v
Reduced Hb
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.
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.
• 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.
