Respiratory #2, Gas Transport - Physiology

1. By Professor/ Abd El-Hamid Abou El-Magd Lecturer of physiology Faculty Of Medicine – Ain Shams University Physiology of Respiratory system 2012 - 2013 [email protected]

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 PCO 2 & Low PO 2 ). Air enters alveoli (High PO 2 & Low PCo 2 ). O 2 diffuses from alveoli to blood down its pressure gradient. CO 2 diffuses from blood to alveoli down its pressure gradient.

4. Total & Partial Pressures Partial Pressure

5. O 2 diffusion Alveolar PO 2 = 100 mmHg Pulm. Art. PO 2 = 40 mmHg (venous blood) Pulm. Venous PO 2 = 100 mmHg (arterial blood) O 2 Back to the left atrium

6. CO 2 diffusion Alveolar PCO 2 = 40 mmHg Pulm. Art. PCO 2 = 46 mmHg (venous blood) Pulm. Venous PCO 2 = 40 mmHg (arterial blood) CO 2 Back to the left atrium

7. Alveolar-Capillary membrane (Respiratory membrane)

8. O 2 O 2 ...........................................................

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

10. 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.

11. Important Notes Although CO 2 diffusion is 20 times faster than O 2 , Equilibration of CO 2 (pressure gradient is 6mm Hg) across alveolar-capillary membrane occurs at the same rate as O 2 (pressure gradient is 60 mmHg). In lung diseases that impairs diffusion, O 2 diffusion is more seriously impaired than CO 2 diffusion because of the greater CO 2 diffusion coefficient. This effect is more manifest in patients with lung diseases during exercise.

12. 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 O 2 . = 400 ml / min./ mmHg for CO 2 . Diffusion capacity increases during exercise: = 80 ml/ min./ mmHg for O 2 . = 1600 ml/min./ mmHg for CO 2 . 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.

13. Gas Exchange At Tissue Level Tissue Capillary Arterial Blood Venous Blood PO 2 = 40 mmHg PO 2 = 100 mmHg PO 2 = 40 mmHg PCO 2 = 46 mmHg PCO 2 = 40 mmHg PCO 2 = 46 mmHg 100 mmHg 40 mmHg

14. “ The real reason dinosaurs became extinct …”

15. Gas Transport between Lungs and Tissues O 2 moves under its partial pressure gradient from: The lungs to blood, and then from The blood to tissues to be utilized. CO 2 moves under its partial pressure gradient from: Tissues to blood, and then from Lungs to air be eliminated. So, blood carries O 2 and CO 2 between lungs and tissues. O 2 O 2 O 2 CO 2 CO 2 CO 2

16. O 2 Transport in the Blood O 2 is transported by the blood in 2 forms: Physically dissolved in blood = 1.5% Chemically bound to hemoglobin = 98.5%

17. O 2 in blood Physically dissolved O 2 Only 1.5 % of total O 2 in blood. Dissolved in plasma and water of RBC . (because solubility of O 2 is very low) It is about 0.3ml of O 2 dissolved in 100ml arterial blood (at PO 2 100 mmHg). Its amount is directly proportional to blood PO 2 . Can not satisfy tissue needs. Chemically combined O 2 98.5 % of total O 2 in blood. Transported in combination with Hb . It is about 19.5 ml of O 2 in 100 ml arterial blood . Can satisfy tissue needs.

18. O 2 combined to Hb Hb is formed of 4 subunits. Each subunit contains a heme group attached to a polypeptide chain (α or β). O 2 binds to the ferrous iron atom in the heme group in a rapid oxygenation reaction (HbO 2 ). The connection between iron and O 2 is weak and reversible . The iron stays in the ferrous state . Thus, each Hb molecule can carry up to 4 O 2 molecules.

19. O 2 content of the blood It is the total amount of O 2 carried by blood. = dissolved O 2 + O 2 combined with Hb. = 0.3 ml/100ml + 19.5 ml/100ml = 19.8 ml/100 ml blood. It depends mainly on the O 2 bound to Hb, as it represents the main component. Plasma (0.3 ml) Hb of RBCs (19.5 ml) 100 ml blood

20. O 2 carrying capacity of the blood It is the maximum amount of O 2 that can be carried by Hb. Each gram Hb, when fully saturated with O 2 , can carry 1.34 ml O 2 . As Hb content = 15 gm/100 ml blood. So, O 2 carrying capacity = 1.34 x 15 = 20.1 ml O 2 /100 ml blood. 100 ml blood Hb = 15 gm Each gm: 1.34 ml O 2

21. The percent of Hb saturation with O 2 (% Hb saturation) It is an index for the extent to which Hb is combined with O 2 . O 2 bound to Hb % Hb saturation = X 100 O 2 carrying capacity When all Hb molecules are carrying their maximum O 2 load, Hb is said to be fully saturated (100 % saturated). PO 2 of the blood is the primary factor that determines % Hb saturation.

22. Important notes In arterial blood (High PO 2 ): 97% of Hb is saturated with O 2 In venous blood (Low PO 2 ): 75% of Hb is saturated with O2 At the lung: high alveolar PO 2 (100 mmHg) Hb automatically loads up (binds) O 2 . At the tissues: low tissue PO 2 (40 mmHg) Hb automatically unloads (releases) O2.

23. [email protected] 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.

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

25. The upper flat (plateau) part of the curve PO 2 % Hb saturation 100 60 97 % 90 % In the pulmonary capillaries (lung, PO 2 range of 100-60 mmHg). - At PO 2 100 mmHg 97% of Hb is saturated with O 2 . - At PO 2 60 mmHg 90% of Hb is saturated with O 2 (small change in % Hb saturation).

26. The upper flat (plateau) part of the curve Physiologic significance: - Drop of arterial PO 2 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 PO 2 changes in pathological conditions and in abnormal situations. - Increase arterial PO 2 (by breathing pure O 2 ) little increase in % Hb saturation (only 2.5%) and in total O 2 content of blood.

27. The steep lower part of the curve PO 2 % Hb saturation 100 60 97 % 90 % In the systemic capillaries (tissue, PO 2 range of 0-60 mm Hg). - At PO 2 40 mmHg (venous blood) 70 % of Hb is saturated with O 2 (large change in % Hb saturation). At PO 2 20 mmHg (exercise) 30 % of Hb is saturated with O 2 . 30 % 70 % 20 40

28. The steep lower part of the curve Physiologic significance: - In this range, only small drop in tissue PO 2 rapid desaturation of Hb to release large amounts of O 2 to tissues. - If arterial PO 2 falls below 60 mmHg desaturation of Hb occurs very rapidly release of O 2 to the tissues. This is important at tissue level.

29. Factors affecting O 2 -Hb dissociation curve Factors that shift O 2 -Hb Curve to the right = decreased affinity of Hb to O 2 & increase O 2 release to tissues. Factors that shift O 2 -Hb Curve to the left = increased affinity of Hb to O 2 & decrease O 2 release to tissues.

30. Factors affecting O 2 -Hb dissociation curve Factors that shift O 2 -Hb Curve to the right Decreased PO 2 . Increased blood PCO 2 . Increased blood H + concentration. Increased blood temperature. Increased concentration of 2,3 DPG. Factors that shift O 2 -Hb Curve to the left Increased PO 2 . Decreased blood PCO 2 Decreased blood H+ concentration. Decreased blood temperature. Decreased concentration of 2,3 DPG

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

32. P 50 It is the PO 2 at which 50% of Hb is saturated with O 2 . It is an index for Hb affinity to O 2 . Normally, P 50 is 27 mmHg (At PCO 2 =40mmHg, pH=7.4, 37°C). 27

33. Increased P 50 = - decreased affinity of Hb to O 2 - shift of O 2 -Hb dissociation curve to the right. Decreased P 50 = - increased affinity of Hb to O2 - shift of the curve to the left. So, The P 50 is an inverse function of the Hb affinity for O 2 . 27

34. Bohr's Effect Represents the effect of PCO 2 and H + (acidity) on the O 2 -Hb dissociation curve. - At tissues: Increased PCO 2 & H + concentration shift of O 2 -Hb curve to the right. - At lungs: Decreased PCO 2 & H + concentration shift of O 2 -Hb curve to the left. So, Bohr's effect facilitates O 2 release from Hb at tissues. O 2 uptake by Hb at lungs.

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

36. O 2 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 O 2 is high increased O 2 uptake by the fetus from the mother.

37. O 2 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 O 2 . The O 2 –myoglobin curve is rectangular in shape and to the left of the O 2 -Hb dissociation curve. So, it gives its O 2 to the tissue at very low PO 2 . So, it acts as O 2 store used in severe muscular exercise when PO 2 becomes very low.

38. [email protected] Discuss with diagram oxygen-hemoglobin association-dissociation curve. List the factors that affect oxygen-hemoglobin curve. Explain effects of CO 2 , H+ and 2,3DBG on oxygen-hemoglobin curve. Compare the fetal hemoglobin and myoglobin dissociation curves to that of adult hemoglobin.

39. CO 2 in blood Venous blood Arterial blood 2.8 ml/100ml 2.4 ml/100ml (5%) Physically dissolved CO 2 45.8 ml/100ml 43.2 ml/100ml (90%) Chemically combined CO 2 as HCO 3 3.4 ml/100ml 2.4 ml/100ml (5%) Chemically combined CO 2 as carbamino 52 ml/100ml 48 ml/100ml Total CO 2 46 mmHg 40 mmHg PCO 2 Tidal CO 2 : is the amount of CO 2 added from tissues to 100 ml arterial blood ( about 4 ml ) to be changed to venous blood.

40. 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 CO 2 in the bicarbonate form. It prevents excessive drop of blood pH.

41. Tissue RBC Plasma HCO - 3 + H 2 O Plasma proteins Hb CA CO 2 Cl - H 2 O CO 2 HCO 3 +H + H 2 CO 3 CO 2 + H 2 O H 2 CO 3 HCO 3 +H + Cl - H 2 O HbO

42. Chloride shift phenomenon Mechanism: CO 2 entering the blood diffuses into RBCs rapidly hydrated to H 2 CO 3 in the presence of the carbonic anhydrase enzyme. H 2 CO 3 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.

43. 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 CO 2 with very little change in the pH.

44. 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 CO 2 by lungs.

45. Lung alveoli RBC Plasma HCO - 3 Carbamino proteins CO 2 CO 2 Cl - H 2 O CO 2 CO 2 Hb CO 2 + H 2 O H 2 CO 3 HCO 3 +H + Cl - H 2 O

46. CO 2 dissociation curve It is a curve represents the relationship between the total CO 2 content and CO 2 tension. It is linear, in the physiological range of PCO 2 . The normal PCO 2 range is: 40 mmHg in arterial blood with CO 2 content of 48 ml/100 ml blood 46 mmHg in venous blood with CO 2 content of 52 ml/100 ml blood. This linear relationship means that any change in PCO 2 will produce a great change in CO 2 content of the blood. Also, at any given CO 2 tension, reduced Hb carries more CO 2 than oxyHb .

47. CO2 dissociation curve PCO 2 CO 2 content 46 40 52 ml 48 ml 66 ml 60 a v Reduced Hb

48. Important Notes Bohr's effect: - Increased CO 2 decrease the affinity of Hb to O 2 shift of O 2 -Hb dissociation curve to the right. Haldane effect: - Increased O 2 decrease the affinity of Hb to CO 2 (because binding of O 2 with Hb displacement of CO 2 from the blood). The presence of O 2 or CO 2 carried by Hb interferes with the carriage of the other gas.

49. Carbon monoxide (CO) poisoning CO + Hb carboxyhemoglobin ( HbCO ). CO and O 2 compete for the same binding sites on Hb . The affinity of Hb for CO is 240 times more than its affinity for O 2 . 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 O 2 -Hb dissociation curve to the left. Q: Detect effects of CO poisoning on: PO 2 , O 2 content, HV, % Hb saturation & on color of blood.

50. [email protected] Define P 50 , its normal value and importance . Compare O 2 with CO 2 transport in blood. Explain the changes that occur in blood at tissues due to addition of CO 2 . Describe CO 2 curve. Discuss Bohr’s effect and Haldane effect and their integration.