Exchange of gases at respiratory membrane 2023.pptx

Physiology MBBS

1. Exchange of gases at respiratory membrane Anjana Talwar Professor of Physiology All India Institute of Medical Sciences New Delhi

2. Bulk Flow : Movement of gas en-masse due to pressure difference Diffusion : Movement of gas due to difference of partial pressures Bulk flow moves the air between environment and conducting airways up to transition zones Diffusion is responsible for movement of gas molecules from alveolar duct to alveolar-capillary interface Terminologies

3. Flow of gases in respiratory tree Bulk flow Diffusion Linear velocity(cm/s) of bulk flow = Flow(cm 3 /s) / Cross-sectional area (cm 2 )

4. Diffusion The constant random thermal motion of molecules, in gaseous or liquid phases, which leads to the net transfer molecules from a region of higher concentration to a region of lower concentration

5. Pulmonary Diffusion: Blood Flow to Lungs at Rest At rest, lungs receive about 4 to 6 L blood/min RV cardiac output = LV cardiac output Pulmonary blood flow = Systemic blood flow Lungs - Low pressure circulation Lung MAP = 15 mmHg vs Aortic MAP = 95 mmHg Small pressure gradient (15 mmHg to 5 mmHg) Resistance much lower due to thinner vessel walls

6. Respiratory Membrane Fluid and surfactant layer Alveolar epithelium Epithelial basement membrane Interstitial space Capillary basement membrane Capillary endothelium Dimensions 0.2 - 0.6 μ 50-100 m 2 Gas exchange is determined by the quantum of Alveolar Ventilation (V) and pulmonary capillary perfusion of blood (Q) or the V/Q ratio

7. Stress failure Hoop stress Longitudinal stress John B. West, Am J Physiol Regul Integr Comp Physiol,2009

8. Stress failure John B. West, Am J Physiol Regul Integr Comp Physiol,2009 First, there is a hoop or circumferential stress: results from the difference of pressure between the inside and the outside of the capillary in accordance with the Laplace relationship. capillary is a thin-walled cylindrical tube, the stress S is given by Pr /t, where P is the transmural pressure, r is the radius of the capillary, and t is the thickness of the load-bearing structure. Second cause of wall stress is if the lung is inflated to high volumes. The increased longitudinal tension of the alveolar wall is partly transmitted to the capillaries that basically make up the wall. for a given capillary transmural pressure, inflating the lung to the high volumes causes ultrastructural damage to the wall. Because the parabronchial structures do not change volume during respiration, this potential cause of increased stress in the blood-gas barrier is avoided.

9. Ultrastructure of Blood-Gas Barrier John B. West, Am J Physiol Regul Integr Comp Physiol,2009

10. Ultrastructure of Blood-Gas Barrier John B. West, Am J Physiol Regul Integr Comp Physiol,2009

11. Ultrastructure of Blood-Gas Barrier Type I collagen cable traverses one side of each capillary, the wall is thickened in this region, and this interferes with the diffusion of gas. J. B. West et.al, Annu . Rev. Physiol. 1999

12. Diffusion of gase s Through Gases: When gases diffuse through other gases in the alveoli, rate of diffusion is defined by Graham’s Law: It is 1/α to √ molar mass with P and T being constant The lighter a gas, more rapidly it diffuses - O 2 being smaller than CO 2 would diffuse faster 1.176 times . Through Fluids: When gases diffuse through liquids across the alveolar membrane into the capillary blood, the solubility of the gases is important. The more soluble a gas, the faster it diffuses - CO 2 diffuses much faster than O 2 as it is much more soluble.

13. Gas Phase to Liquid Phase transition Henry’s Law Amount of a gas absorbed by a liquid with which it does not combine chemically is directly proportional to the partial pressure of the gas to which the liquid is exposed and the solubility of the gas in the liquid

14. Determinant - Characteristics of the Gas Solubility coefficient - Henry's Law Relative solubility of CO 2 & O 2 in water = 24:1 Combining this with Graham's Law , relative rates of diffusion from alveolus to RBC for CO 2 :O 2 = 20.7:1 So, diffusion of CO 2 is rarely a clinical problem

15. Vgas = volume of gas diffusing through the tissue barrier per time, mL/min A = surface area of the barrier available for diffusion (50 – 100 m 2 potential area) D = diffusion coefficient, or diffusivity, of the particular gas in the Barrier T = thickness of the barrier or the diffusion distance P1- P2 = partial pressure difference of the gas across the barrier MW = Molecular weight Diffusion across respiratory membrane Fick’s Law of Diffusion  MW ratio of CO 2 to O 2 = 1.17 Solubility ratio of CO 2 to O 2 = 24 Diffusivity ratio of CO 2 to O 2 = 24 x (1/1.17) = 20 Problems with oxygen appear before problems with carbon dioxide

16. What can limit the amount of diffusion? Diffusion will occur as long as there is gradient from Alveoli to Capillary and will stop once the equilibrium is achieved. To allow more diffusion Option 1 : have an absorber in the capillaries that keeps the Pa gas low Option 2 : move the blood fast so that once the equilibrium is reached, new blood comes in quickly Option 1 : amount of gas transfer is limited by ability to diffuse Option 2 : amount of gas transfer is limited by ability to perfuse

17. Movement of O 2 , N 2 O and CO across the barrier O 2 = Saturable binding to Hb Binding is quick (1/100 th of second) Perfusion Limited CO = un-saturable binding to Hb Diffusion Limited N 2 O= Perfusion Limited

18. Movement of N 2 O across the barrier moves through the alveolar-capillary barrier very easily and it does not combine chemically with the hemoglobin in the erythrocytes. Saturation point (equilibrium) < 0.1 sec Once saturated – no more uptake possible (since ΔP = 0) unless blood flow increases Hence, N 2 O uptake is Perfusion limited

19. Movement of CO across the barrier Diffusion is very fast Has 2 1 0 x affinity for Hb than O 2 most of CO is in combination Gas tension very low in aqueous phase Hence, equilibrium state NOT reached till the time blood in capillary is exposed to CO in alveoli ….. Uptake depends on its diffusivity in the barrier and by the surface area and thickness of the barrier-that is, the diffusion characteristics of the barrier itself Uptake can only be Diffusion limited

20. Movement of O 2 across the barrier Equilibrium between blood and alveolar PO 2 reached in 1/3 rd transit tim e O 2 chemically binds to Hb exerts no partial pressure, so PO 2 difference across the alveolar-capillary membrane is initially well maintained and oxygen transfer occurs chemical combination of O 2 and Hb occurs rapidly (within 1/100 th of a second), and at the normal alveolar partial pressure of O 2 , the Hb gets saturated with O 2 very quickly PO 2 in the blood rises rapidly to that in the alveolus, and from that point, no further oxygen transfer from the alveolus to the equilibrated blood can occur.

21. Movement of O 2 across the barrier transit time decreases to 0.25sec due to increased Cardiac output during exercise Total amount of O 2 transferred increases with exercise because of recruitment of previously unperfused capillaries, which increases the surface area for diffusion, and because of better matching of ventilation and perfusion. Even in severe exercise PO 2 of end-capillary blood is equal to alv PO 2 So, only if diffusion is affected due to change in area or thickness of the membrane it will not reach alv PO 2 Exercise

22. Effect of decrease in diffusivity on O 2 diffusion At resting conditions, even ¼ may not be problem. any decrease in transit will manifest as low O 2 transfer (now the transfer is limited by diffusivities) Perfusion Limited Diffusion Limited

23. Effect of decrease P AO 2 on O 2 diffusion Perfusion Limited, if resting Diffusion Limited, if exercising

24. Effect of decrease in diffusivity on CO 2 diffusion Same time for carbondioxide and Oxygen even though D CO 2 is 20x more than D O 2

25. Diffusion capacity The amount of gas diffusing per minute across an area of 1 cm 2 of the respiratory membrane when the pressure gradient is 1 mmHg Fick’s principle explains the rate of diffusion across a membrane as: Where: V gas = AD (P 2 – P 1 ) / T V = Diffusion capacity of a gas A = surface area for diffusion T = Thickness of membrane; D = Diffusion coefficient P 2 -P 1 = difference in partial pressure

26. Measurement of Diffusion Capacity T, A & D are most difficult to measure in an intact lung. For convenience, Fick’s formula is rearranged into measurable units as under: D L = V gas / ΔP D L = DC of Lung (Includes A, D & T) V gas = volume of gas transferred per minute ΔP = pressure gradient Technique = Single breath test (dilute CO) inhaled and held for 10 sec Alv PCO is measured at the beginning and end of 10 seconds, along with lung volume. Normal value= 20 – 30 mL/min/mmHg Affected by age, sex and body size

27. D L CO = 17ml / min / mmHg D L O2 = 21ml/min/mmHg D L CO2 = 400-450ml / min / mmHg Diffusion capacities of various Gases in Rest and Exercise Increase in surface due to recruitment of capillaries Better Ventilation Perfusion Matching

28. Diffus ing capacity of lungs Diffusion capacity of lungs depends on Respiratory membrane Surface area (decreased in emphysema) Diffusion distance (interstitial diseases, p. edema) Pulmonary capillary blood flow Chemical reaction time for Hb & O 2 Hb concentration (anemia -  diffusion capacity, but supine position or exercise  it)

29. (1) Diffusion of oxygen through the blood-gas barrier, including the plasma and red cell interior (2) reaction of the oxygen with hemoglobin DL = Diffusion capacity of lung DM = Diffusion capacity of membrane Vc = volume of blood in capillary Theta = rate of reaction y = mx + c Steps in oxygen transfer

30. Measurement of Diffusion Capacity single-breath method a single inspiration of a dilute mixture (about 0.3%) of carbon monoxide is made Hold breath for 10 sec. Measure the inspired and expired concentration of CO to get the amount diffused steady-state method Breathe a low concentration of carbon monoxide (about 0.1%) for 0.5 minute to reach a steady state of gas exchange

31. Single breath method Inhale test gas containing 0.3% CO from RV to TLC Hold the breath for 10 seconds Collect alveolar gas sample after discarding dead space DLCO= 60 V A F ACOi T bh (P B -47) F ACOf ln