1. Unit 1 Gas Exchange 2 Dr. Douglas McKim MD Professor of Medicine 737-8899 ext. 75318 dmckim@ottawahospital.on.ca

2.  Explain the factors determining the rate of diffusion across the alveolar-capillary membrane  Describe how the alveolar PO2, diffusing capacity, transit time and venous PO2 have an effect on pulmonary end- capillary PO2  Describe the regional differences in ventilation and perfusion in the lung, why they occur and how they affect PO2  Understand the difference between arterial oxygen content and oxygen delivery  Describe the CO2 dissociation curve and the effect of oxygen Objectives Respiratory Block – Gas Exchange 2 – Dr. Doug McKim

3. The Perfect Lung - Gas Exchange 1) Anatomically efficient, well-matched ventilation and perfusion 2) Ideal oxygen carrying system 3) Built-in reserve for exercise or disease

4. Topics Diffusion – flow (rate) of gases across a tissue interface Oxygen Carriage and Delivery – the transportation of oxygen to the body (concentration x flow) Ventilation Perfusion Relations – the relative proportions of ventilation and blood flow

5. Abnormal CXR ?? PO2 55, PCO2 27 SaO2 88% Give O2 100% PO2 60, PCO2 33 Unable to correct PO2 (much) with oxygen V/Q abnormalities Shunt

6. Abnormal CXR [Unit name – Lecture title – Prof name]

7.  PO2 45, PCO2 66, SaO2 80%  Supplemental O2 30% …  PO2 75 mmHg, PCO2 75, SaO2 95%  Marked improvement in PO2 (compared with 100% in 1 st case) but significant increase in CO2 as well Abnormal CXR [Unit name – Lecture title – Prof name]

8.  Bilateral diffuse airspace disease  Cardiomegaly  Peri-bronchial cuffing  Pulmonary venous congestion  PO2 45, PCO2 50, SaO2 80%  Supplemental O2 100%  PO2 60, PCO2 50 Unable to correct PO2 (much)  Shunt plus low cardiac output Abnormal CXR [Unit name – Lecture title – Prof name]

9. Intro: Ventilation/Perfusion Relationship; V/Q 14.6 16.6 V/Q = Amount of ventilation (L/min) Blood Flow (L/min) Low V/Q High V/Q Lowest V/Q = “Shunt”, i.e;.V = 0 Venous Return Arterial Blood

10. Hypoxemia: Shunt > Low V/Q 150 170 Can still hyperventilate normal or high V/Q units lower CO 2 PO 2 40 PO 2 60 PO 2 100 PO 2 40PO 2 70 PCO 2 70 150 170 200 Normal is 200 ml O2/L ml O2/L

11. Diffusion 14.6 16.6 Venous Return Arterial Blood What properties determine how much gas can be transferred across the alv. cap. membrane “ Perfusion”; Cardiac Output x Oxygen Concentration = O2 Delivery

12. Diffusion

13. Alveolar Diffusion Properties

14. 1) Surface Area for diffusion 2) Thickness of the membrane for diffusion 3) Pressure gradient of the gas across membrane 4) Properties of the gas; ie. Molecular weight, Solubility in the exchange membrane Determinates of Diffusion Capacity [Unit name – Lecture title – Prof name]

15. Diffusion and Perfusion Limitations CO2 diffuses more easily than O2 (more soluble)

16. Diffusion and Perfusion Limitations Why/How do we assess the capacity of the lung to transport gas? (Diffusion) What properties would a gas have in order to most accurately measure the diffusion capacity of the lung? “Escape” analogy… Such a gas would not exert a partial pressure once it entered the capillary

17. Diffusion in Alveolus Capillary Pulm Art PO2 40 Pulm Vein PO2 100 Alveolus PO2 100 PO2 55, SaO2 88% PO2 50, SaO2 80% Time (Sec) Capil. PO2 40 O2 SaO2 75%

18. Diffusion in Alveolus Capillary Pulm Art PO2 40 Pulm Vein PO2 100 Alveolus PO2 100 PO2 55, SaO2 88 PO2 50, SaO2 80 Time (Sec) Capil. PO2 40 O2 PO2 100, SaO2 98% Diseased Lung Exercise SaO2 75 0.25 0.75 Sec.

19. Gas moves from the alveolus into the capillary TIME Alveolus Capillary Alveolar concentration Time O2O2 N2ON2O CO O2O2 N2ON2O Capillary Concentration Partial pressure (eg. PO 2 ) only unbound fraction PO2 40 PO 2 100 Capillary StartCapillary End Partial Pressure

20. “Fire Escape” Analogy [Unit name – Lecture title – Prof name] Alveolus Diffusion Barrier Capillary & RBCs

21. Gas moves from the alveolus into the capillary TIME Alveolus Capillary Alveolar concentration Time O2O2 N2ON2O CO O2O2 N2ON2O Capillary Concentration Partial pressure (eg. PO 2 ) only unbound fraction Partial Pressure

22. Abnormal Alveolar Diffusion of Oxygen Venous

23. Reserve for Alveolar Diffusion of Oxygen e.g. low CO 1) Diseased lung 2) Low Venous PO2

24. Oxygen (and CO2) Transport

25. Oxygen Transport 0 2 carried in two forms in blood: – Bound to hemoglobin – Dissolved (the portion that contributes partial pressure) Bound: This is the O 2 bound to Hb as determined by the O 2 dissociation curve. Normally about 200 ml/L at 100% SaO2 Dissolved: There are.03 ml O 2 /1000 ml blood for each mmHg PO 2. (ie: normal blood with a PO 2 of 100 carries 3.0 ml O 2 /1000 ml) – [this is a small amount compared with ~ 200 ml O2/L of blood bound to Hb]

26. O2 Dissociation Curve 200ml/L 180 ** **Note: need to convert to ml/L (x 10) Gases on 100% O2 in Case #1

27. Anemia, Polycythemia and Effect of Carbon Monoxide

28. 1 gm of fully saturated (SaO 2 100%) Hb carries approx. 1.34 ml O 2 Normal Hb is ~ 150 gm per 1000 ml 150 gm x 1.34 ml O 2 /gm = ~ 200 ml O 2 per 1000 ml of blood, also referred to as: (Ca O2 = “arterial concentration” = ~ 200 ml/L) 100 gm of fully saturated (SaO 2 100%) Hb (eg. Anemia) would carry ~ 134 ml O 2 /1000 ml of blood Oxygen Transport

29. O2 Concentration at Different Hb Levels: 200, 150, 100 gm/L 200 150 100 300 200 100 ml/L

30. O 2 Concentration at Different Hb Levels; 200, 150, 100 gm/L 200 150 100 300 200 100 ml/L 180

31. The CO2 Dissociation Curve [Unit name – Lecture title – Prof name]

32. “Shunt”

33. Measurement of Shunt- definitions Q t = total blood flow, Q s = shunted flow Ca O 2, Cv O 2, Cc’ O 2 Concentration of arterial, mixed venous and end-capillary oxygen The total amount of oxygen carried to the alveoli is the O2 concentration per litre X number of litres of blood per minute – ml O2/L x L/min = ml O2/min (= O2 delivery)

34. Measurement of Physiologic Shunt Cv O 2 Q t – Q s 100% Oxygen

35. Measurement of Physiologic Shunt PO2 55, PCO2 27 100% Oxygen; PO2 60 Cao 2 = 180 ml/L (arterial O2 by ABG and O2 dissociation curve) Cco 2 = 200 ml/L Cvo 2 = 150 ml/L Therefore; Qs 200-180 Qt 200-150 = 2/5 = 40% shunt = Cv O 2 Q t – Q s 100% Oxygen

36. Effect of Shunt on PO 2 Venous O2 200 150 100 ml/L 50

37. Ventilation – Perfusion Relationships (V/Q)

38. Ventilation-Perfusion Relationships

39. Normal Shunt Dead Space Extreme low V/Q Extreme high V/Q

40.  Dead space contributes to hypoxemia through “wasted ventilation”  Imagine a Pulmonary Embolism occluding the entire left pulmonary artery…  While perfusion (total cardiac output) is only going to one lung half the ventilation is wasted (no perfusion in the embolized lung)  Unless Ve increases to compensate for dead space, alveolar CO2 rises (more venous blood flow) and O2 falls as a result Dead Space and Hypoxemia [Unit name – Lecture title – Prof name] PE; blood clot Wasted Ve (no perfusion) V A = Ve – V D ; increased V D = lower V A

41. Regional Gas Exchange in the Lung On Room Air

42. Alveolar Gases at Different Heights of the Lung

43. VA/Q Ratios in Different Levels of the Lung

44. Upper alveoli: little volume change per unit pressure change

45. Perfusion matched to ventilation Distending Pleural Pressure – 10 cm H 2 O – 2 cm H 2 O

46. High V/Q, lower Ventilation Low V/Q, higher Ventilation

47. Ventilation-Perfusion Relationships

48. Can hyperventilate…but… Can add O 2 150 170

49. Pneumonia: Low V/Q, Shunt 150 170 Can still hyperventilate normal or high V/Q units lower CO 2 150 160 200 ml O2/L

50.  Decreased surface area  Decreased pressure gradient for oxygen (low alv O2)  Increased membrane thickness  Alveolar filling  Areas of lower ventilation; stiffness, edema  Adaptations to optimize V/Q  Why gas exchange more affected than an upper lobe pneumonia? [Unit name – Lecture title – Prof name] Questions??

52. Changes in O 2 Dissociation with: Temp, PCO 2, pH

53. O 2 delivery (ml/min) is equal to the amount of O 2 carried on Hb plus dissolved (-negligible) multiplied by the volume of blood delivered per minute. ie: O 2 delivered = O 2 per unit volume x volume/minute = ml O 2 /1000 ml x C.O. L /min = 200 ml O 2 / L of blood x 5 L/min = 1000 ml O 2 / min However, not all O2 delivered is utilized. Amount used equals the difference between the arterial and the venous values. Venous O 2 150 ml per Litre ( 75% Sat ) and Arterial 200 ml / Litre. Difference: 200 – 150 = 50 ml O 2 /L Oxygen consumption at 50 ml O 2 /L and 5L/min CO = 250 ml/min Oxygen Delivery

54. Oxygen Delivered = C.O. x arterial O 2 Content (O 2 content = gms Hb x % saturation, eg. 150gm Hb @ 100% Sat = 200 ml O 2 ) eg. O 2 delivery = 5.0 L/min x 200ml / L = 1000 ml/min Only about 25% of the O 2 delivered to the periphery is utilized leaving the blood approx. 75% saturated, ie; 750 ml O 2 / min is returned to the heart. 50 ml O 2 / L x 5.0 L / min = 250 ml O 2 to the tissues.