1. Unit 1 Gas Exchange 1 Dr. Shawn Aaron Professor, Division of Respirology The Ottawa Hospital saaron@ohri.ca

2.  To review:  1) Principles of gas diffusion  2) Ventilation and gas exchange in the lung  3) Concept of dead space  4) V/Q mismatch  5) Shunt Objectives [Unit name – Lecture title – Prof name]

3. Physics 101: The Gas Laws Gas molecules are continuously in motion, they randomly collide with each other and with surrounding surfaces. Barometric pressure: The earth’s atmosphere exerts a total pressure of 760 mm Hg at sea level.

4. Partial Pressures: In a mixture of gases: Total pressure = sum of the partial pressures of its components Barometric pressures: The earth’s atmosphere exerts a total pressure of 760 mm Hg at sea level. Air is 79% N 2 and 21% O 2 : So: Partial pressure of O 2 in air =.21 x 760 mm Hg = 160 mm Hg.

5. Gas Diffusion: When gas is above a liquid it moves from an area of high pressure  low pressure. This is called diffusion. Each gas moves according to its own pressure gradient without regard to what other gases in the mixture are doing.

6. The lungs work to help us oxygenate our blood and get rid of CO 2  Diffusion of these gases occurs across the alveolar capillary membrane  For diffusion to occur, the partial pressure of O 2 in the alveolus must be > than in the pulmonary capillary so that O 2 can move from the alveolus to the capillary. And…the partial pressure of CO 2 in the alveolus must be < than in the pulmonary capillary so that CO 2 can move out of the capillary to the alveolus. The Movement of Gases

8. The Lungs have 2 functions: 1.Conduction of Air- this occurs in the conducting airways- the trachea, mainstem bronchi, and the segmental bronchi down to the level of the terminal bronchioles. 2.Exchange of Gases- occurs distal to the terminal bronchioles- ie. in the respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli.

9. Movement and Exchange of Gases Conducting airways Gas exchange units of the lung

10. The Alveolar-Capillary Membrane Alveolus

11. Diffusion Oxygen diffuses across the alveolar-capillary membrane into the capillaries and is then bound to HgB. Carbon dioxide diffuses across the alveolar capillary membrane into the alveoli Normally, this process is completed the time time blood has traveled 1/3 the length of the alveolar capillary If the membrane is abnormally thick (pulmonary edema) or transit time is abnormally fast (race horses), process may not be completed and pulmonary venous blood may be deoxygenated

12. Diffusion Diffusion is proportional to the: – Pressure gradient – Surface area available for diffusion 1000 pulmonary capillaries wrap around each alveolus to create a sheet available for diffusion. Each pulm capillary is 10 um- permits a single RBC to pass. Typical RBC is fully saturated with oxygen once it’s gone 25-33% through the pulm capillary. Diffusion does not typically limit gas exchange.

13. Measuring Diffusing Capacity Single-breath Diffusing capacity of CO. Patient takes a vital capacity breath of 0.3% CO and 10% He, holds his breath for 10 seconds, and then exhales. If one inhales a breath of CO- the amount of CO uptaken into the blood will depend on the partial pressure of CO in the alveoli and the diffusion capacity of the alveolar- capillary apparatus. Thus, VCO= PACO * DCO, or….. DCO = VCO/PACO

14. Cause of a low Diffusion Capacity: Loss of surface area for gas exchange= emphysema, pulmonary fibrosis, pneumonectomy. Loss of pulmonary capillaries = emphysema, pulmonary vascular disease (such as chronic PE’s, pulmonary hypertension, etc). Anemia Smoking (because of decreased partial pressure gradient for CO to diffuse into the pulm caps).

15. Ventilation: The lungs and chest wall serve as a vacuum to suck air into the alveoli. Inspiration is an active process  1) Diaphragm descends – “piston” 2) Lower ribs flare out – “bucket handle” 3) Sternum swings out – “pump handle” These 3 movements expand the thoracic cavity and create negative pressure which sucks air in from the mouth  alveoli.

17. Normally, with each breath, we pull in about 500-600 ml of air (10 mL/kg) = Tidal volume (V T ). Normally, we take 16 breaths/minute = Respiratory Rate (RR). Minute ventilation (V E ) = RR * V T = 16/min * 500 ml = 8 1itres/min. Does all 8 litres of V E participate in gas exchange? NO…some is wasted ventilation. Ventilation in People

18. Wasted ventilation = Dead Space Dead space = ventilation to an area of lung, but no perfusion.

19. Alveolar ventilation (V A ) = Minute ventilation – dead space ventilation. Alveolar ventilation (VA) = V E – V D V A = (500*16) – (150*16) = 5600 ml NB: Small, shallow breaths are wasteful  proportionally more dead space ventilation Trachea + upper airway = Anatomic dead space = 150 ml (3 mL/kg) If VT = 500 ml, then 350 ml gets to lungs trachea lungs Dead Space and Ventilation

20. Physiologic Dead Space = anatomic dead space + alveolar dead space (alveoli that are ventilated but not perfused) No perfusion  No gas exchange  Wasted Ventilation The Physiologic Dead Space

21. Clinical Example: Massive Pulmonary Embolism Example of dead space: Massive pulmonary embolism – complete blockage of R pulmonary artery, R lung is still ventilated, but no perfusion What happens to V A ? Assume RR = 16 and V T = 500 ml Anatomic dead space = 150 ml Physiologic dead space = (500-150)/2 = 175 ml V A = V E – V D = 16 (500 – 150 – 175) = 2.8 litres

22. In summary: 1.Alveolar hypoventilation  Failure of gas exchange  Build-up of CO 2 2.Causes of alveolar hypoventilation: RR Tidal volume Dead space ie.minute ventilation

23. Determinants of alveolar pO 2 (p A O2): 1.pO 2 in air = 760 * 0.21 = 160 mm Hg 2.Air gets into trachea and is humidified. The partial pressure of H 2 O in tracheal air is 47 mm Hg. So…partial pressure of O 2 in trachea = (760-47) * 0.21 = 150 mm Hg 3.When air gets to alveoli, it mixes with the gas already in the alveolus which contains CO 2.

24. Alveolar air normally contains about 5.5% CO 2 and 15% O 2. P A O 2 = (760-47) * 0.15 = 100 mm Hg P A CO 2 = (760-47) * 0.55 = 40 mm Hg Gradients

25. The Respiratory Quotient The Respiratory Quotient is the ratio of CO 2 production relative to O 2 consumption by the body – RQ = VCO 2 /VO 2 Humans on a regular diet consume more O 2 than they produce CO 2, so RQ is usually 0.8 The different rates of movement affect gas tensions in the alveoli – excess removal of O 2 elevates the CO 2 tension in the alveoli

26. The Alveolar Air Equation: Allows us to calculate the composition of alveolar gas. P A O 2 = FiO 2 (P B – P H2O ) – P A CO 2 /RQ Assume RQ = 0.8 Assume P A CO 2 = PaCO 2 = 40 mm Hg If breathing room air: P A O 2 = 0.21 (760-47) – (40/0.8) = 150 – 50 = 100 mm Hg So, when breathing room air at sea level  alveolar PO 2 is 100 mm Hg  arterial PO 2 should be 100 mm Hg.

27. Determinants of alveolar PO2: Can figure this out from the alveolar air equation: P A O 2 = FiO 2 (P B – P H2O ) – P A CO 2 /RQ 1.Inspired oxygen fraction (FiO 2 ) 2.Barometric pressure (PB) 3.Alveolar pCO 2 : a) depends on metabolic rate ( metabolic rate CO 2 production) b) depends on alveolar ventilation ( ventilation CO2)

28. Examples: Climb Mt. Everest: At 27,000 feet P B = 282 mm Hg P A O 2 = 0.21 (282-47) – (40/0.8) = 49-50 = -1 mm Hg!!! So how can anyone climb Everest?! 1.Climb Everest with oxygen: Example: Wearing 40% oxygen P A O 2 = 0.40 (282-47) – (40/0.8) = 94 – 50 = 54 mm Hg

29. 2.Or…hyperventilate: Breathe pCO 2 down to 15 mm Hg: P A O 2 = 0.21 (282-47) – (15/0.8) = 49 – 15 = 30 mm Hg So…we’ve seen that hyperventilation will decrease the P A CO 2 and increase the P A O 2. What about hypoventilation? p A CO 2 P A O 2 Effects of Hyper- and Hypo- Ventilation

30. Example of Hypoventilation: Patient A RR = 16 V T = 500 ml PGY1 gives him morphine overdose 5 minutes later… RR = 4 V T = 300 ml…YIKES ! What’s his minute ventilation? What’s his alveolar ventilation? His PCO 2 shoots up to 80 mm Hg What’s his P A O 2 ? More on Hypoventilation

31. One important point: The effects of hypoventilation on PO 2 can be overcome by giving supplemental oxygen. Example: Patient given morphine, PCO 2 = 80 mm Hg P A O 2 = 0.21 (760-47) – (80/0.8) = 50 But, if patient is placed on 28% O 2 : P A O 2 = 0.28 (760-47) – (80/0.8) = 100 NB: He is still acidotic though! Hypoventilation in the presence of supplemental O 2

32. Ventilation-Perfusion Matching Last important concept: V/Q matching Normally in the alveolus V=Q and V/Q=1 (ie. ventilation to the alveolus = blood flow to the alveolus) Normally, this is tightly regulated by the body – if ventilation to the alveolus decreases, the pulmonary arteriole will vasoconstrict, proportionally reducing perfusion to the alveolus Extremes: 1.Dead space = ventilation but no perfusion, V/Q = infinity Gas delivered to the alveoli won’t participate in gas exchange (delivering oxygen to the body and removing CO 2 ) 2.Shunt: perfusion but no ventilation V/Q = 0 Blood traveling to the alveoli won’t pick up oxygen or release CO 2

33. Normal V/Q matching 1 unit ventilation 1 unit perfusion pO2 = 100 pCO2 = 40 pO2 = 40 pCO2 = 46 pO2 = 100 pCO2 = 40

34. Even a small change in Ventilation matching will cause hypoxemia: 0.5 unit ventilation 1.5 units ventilation 1 unit perfusion pO2 = 55 O2 sat = 85% pCO2 = 50 pO2 = 40 pCO2 = 46 pO2 = 55 pCO2 = 50 pO2 = 110 pCO2 = 30 pO2 = 110 O2 sat = 100% pCO2 = 30 Final O2 sat = 92%, PO2= 62, PCO2=40

35. V/Q Matching in Real Life V/Q matching goes on all the time – when you stand up the dependent portions of lung (ie. the bases of the lung) are less ventilated. The associated pulmonary arteries vasoconstrict, to maintain V/Q matching and arterial PO 2 When 1 part of lung is diseased (ie. mucous plug blocking an airway and an area of lung), the pulmonary arteries will vasoconstrict to this area, and less blood will flow to the pulmonary capillaries feeding the diseased poorly ventilated area. V/Q matching prevents most people from getting hypoxic

36. V/Q Mismatch: The Main Cause of Hypoxemia Most diffuse lung diseases cause V/Q mismatch Even a little V/Q mismatch cause hypoxemia The ultimate V/Q mismatch is called a Shunt = Section of lung that’s perfused, but not ventilated

37. RLL Pneumonia PO2 55, PCO2 27 Give O2 50% PO2 60, PCO2 33 Unable to correct O2 Because of: Shunt