1. CS 2014 Respiratory Partial Pressures and Blood Gasses Christian Stricker Associate Professor for Systems Physiology ANUMS/JCSMR - ANU Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au/PP&BG.pptx Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au/PP&BG.pptx THE AUSTRALIAN NATIONAL UNIVERSITY

2. CS 2014

3. Aims The students should be familiar with the concepts of atmospheric, barometric and partial pressures; be cognisant of the approximate composition of air; know how water vapour affects partial pressures; be able to describe the O 2 cascade from inspired air to blood; understand physiological principles involved in formulating the alveolar gas equation; recognise the concept of ‘shunt’; and be familiar with standard values for blood gases.

4. CS 2014 Contents Basic terms and concepts Partial pressures of N 2, O 2 and CO 2 Air saturated with water: Partial pressures at following locations: 1.Nose 2.Trachea 3.Alveolus 4.Lung capillary / Artery Blood gas values

5. CS 2014 Gasses & Pressures [kPa] 1 kPa ≈ 10.2 cm H 2 O ≈ 7.5 torr 1 kPa = 1000 N / m 2 1 torr = 0.1333 kPa

6. CS 2014 Atmospheric Pressure (P b ) P atm at sea level = 101.325 kPa = 760 torr. ≡ barometric pressure (P b ) “Force per m 2 exerted against a surface by weight of air above that surface in the atmosphere.” = hydrostatic pressure caused by weight of air above measurement area. A column of air of 1 m 2 in cross- section, measured from sea level to the top of the atmosphere has a mass of about 10 4 kg and a weight of 63·10 4 N.

7. CS 2014 Altitude and P b P b drops exponentially with altitude = density of air drops with altitude. Variable with weather conditions (highs and lows). At 8’848 m, it is ~⅓ of that at sea level. Plane cabins are pressurised to about 2’100 m; ~ 80 kPa.

8. CS 2014 Composition of Air GasVol % N2N2 78.03 O2O2 20.99 CO 2 0.04 H2OH2O~ 0.50 Ar 0.94 Air created over a long time period by bacteria/algae. O 2 has been constant over the last 10 million years. Water content variable, depending on weather (in rain clouds saturated). –Omitted for respiratory conside- rations (small change) as air will become fully saturated in airways. Noble (Ar, He, etc.) and inert gasses (N 2 ) are not metabo- lically relevant.

9. CS 2014 1. Ambient Gas Pressures [kPa] Since 1 mol of gas takes identical volume (22.4 L) irrespective of type of gas, pressure affects all gases identically: concentrations ∞ volume content (F X ) norma- lised to P b (barometric pressure) = partial pressure (P X ). In medical physiology, only N 2 and O 2 are “important”; under normal conditions, CO 2 in inspired air is too small. Partial pressures in ambient air:

10. CS 2014 Water Vapour Pressure Upon inhaling, H 2 O vapour becomes part of air/gas mixture → reduces partial pressures of all inspired gasses (O 2, N 2, CO 2, etc.). In a gas mixture saturated with H 2 O, water vapour pressure equals its partial pressure,. At 37°C, is 6.3 kPa is only dependent on temperature. is NOT dependent on ambient pressure. – is the same at sea level as well as on top of Mt. Everest… –At 19’200 m, P b = 6.3 kPa; therefore = 0 at this altitude (and likewise for any other gas…): Armstrong limit/line. –At 19’200 m, water boils at 37°C.

11. CS 2014 2. Tracheal Gas Pressures In trachea, air gets H 2 O saturated at 37°C. Therefore, some partial pressure stems from H 2 O. Therefore, and are smaller than P b ; i.e. 101.3 - 6.3 kPa = 95 kPa Partial pressures in trachea: Due to H 2 O saturation, drops (21.3 → 20.0 kPa). What happens in alveoli?

12. CS 2014 Conventions for Volume Reporting Measured lung volumes and flows in laboratory: ATPS (ambient temperature & pressure, saturated): not for reporting –Conditions not standardised: ambient T and P; = 6.3 kPa –Reason for saturation: typically ambient T < body T Standard reporting of lung volumes and flow: BTPS (body temperature & pressure, saturated) –Conditions standardized to 37°C; 101.3 kPa and = 6.3 kPa –Reasons: to have a physiologically meaningful measure in regard to lung volume; allows comparisons between patients. Standard reporting of gas volumes (in blood): STPD (standard temperature and pressure, dry) –Conditions standardized to 0°C; 101.3 kPa and = 0 kPa –Conversion to BTPS: V BTPS = 1.21 V STPD.

13. CS 2014 Gas Transport to and from Periphery Total gas volume transport is dependent on cardiac output /venous return (~ 5 L/min). Relationship between O 2 uptake and CO 2 elimination. –More O 2 is taken up than CO 2 is breathed off. –Respiratory quotient (at rest, mixed food intake): Rhoades & Pflanzer 2003

14. CS 2014 Gas Exchange in Alveoli So far, no gas exchange was considered. In alveoli, O 2 is taken up into blood → ↓. At same time, CO 2 is exchanged → ↑. For equimolar exchange, ↓ matched with ↑. As less CO 2 produced than O 2 consumed, something has to “patch” the drop in partial pressure: dissolved N 2 in blood.

15. CS 2014 3. Alveolar Gas Pressures In alveoli, as CO 2 is exchanged, O 2 is taken up. Under “normal” conditions corresponds to 5.3 kPa; i.e. is reduced by this amount: Holds if metabolism produces same CO 2 volume as O 2 is utilised / burnt; i.e. for glucose… Correction needed for how CO 2 is made from O 2 : respiratory quotient (“normal” metabolism) i.e. Difference of 1.3 kPa from dissolved N 2 → ↑.

16. CS 2014 Determinants of Gas Exchange Structural elements: –Film on alveolar walls: watery solute. –Cell membrane: lipids. –Blood plasma: watery solute. Gas exchange ( ) via diffusion –scales with membrane surface area (A) and thickness (a), difference in partial pressure ( ) and diffusion capacity of the lung D L (CO to det.), –which is dependent on solubility, »directly ~ to difference in partial pressure; »indirectly ~ to temperature (T). –Solubility of CO 2, O 2 and N 2 in water depends on temperature (T). In fever, less is dissolved in body fluids. In hypothermia much more (avalanche). CO 2 solubility at 37°C is ~23 x better than that for O 2, which is ~ 2 x better than that for N 2.

17. CS 2014 Diffusion from Alveolus to EC Diffusion over many different media. –All steps “resist” free diffusion: ↓. –Membrane diffusion rate (D M ) limited by sum of D 0 + … + D 10 (in series). –Binding of O 2 to haemoglobin takes time and also “resists” free diffusion (D H ). –Normally, D M ≈ D H such that Under normal conditions, O 2 exchange is perfusion limited. –Blood spends sufficient time in pulm. capillary to fully equilibrate with ; –BUT can become diffusion limited in pathology (interstitial fibrosis) or under strenuous exercise / at high altitude. Similar for CO 2, just faster…

18. CS 2014 4. Arterio-Venous Difference O 2 concentration at end of lung capillary: 13.4 kPa (a’). –Practically not possible to measure easily. O 2 concentration in aorta: 12.0 kPa (a). –Practically taken from a peripheral artery (femoral/brachial). O 2 difference is result of venous admixture (heart) –Called shunt. O 2 concentration in right atrium: 5.3 kPa ( ). –Average concentration as venous blood is mixed with different O 2 extraction rates in various parts of body. Arterio-venous difference (a - ): 6.7 kPa. – drops by ~ 60%: extraction from blood. –A large amount of O 2 remains “bound” in blood (partial extraction). –In particular vascular beds, this difference can be much larger (heart muscle; leg muscles in a marathon runner…).

19. CS 2014 Arterial Blood Gas Values AnalyteReference Range 9.3 – 13.3 kPa 4.7 – 6.0 kPa pH7.35 – 7.45 HCO 3 - 22 – 26 mmol/L Total CO 2 25 – 30 mmol/L Values for different analytes are given incl. reference ranges. –not to be known by heart! Arterial values vary considerably. Link to acid-base control via CO 2 (see lecture series by K. Saliba).

20. CS 2014 Review of Changes in Axis along bottom indicates distance from nose. At each step, ↓. Note notation.

21. CS 2014 Overview of Gas Pressures Under resting conditions and with a “normal” metabolism. Values in arteries/veins can be measured directly (blood gas analysis). Without diffusion barriers, can be determined from blood gas. ↑ in alveoli because R is 0.8; i.e. insufficient CO 2 is produced. As a consequence ↑. ↑ in arteries due to venous admixture into arterial blood (shunt). Total pressure in veins ↑.

22. CS 2014 Take-Home Messages P b drops with altitude; it is ~⅓ of normal on Mt. Everest. For purpose here, air consists of 79% N 2 and 21% O 2. Water vapour pressure is 6.3 kPa at all pressures. Reporting of lung and gas volumes in BTPS & STPD, resp. In alveolus, O 2 is exchanged for CO 2 at a relative volume described by respiratory quotient R = 0.8. Alveolar gas equation describes. Gas exchange is via diffusion of dissolved gas, governed by gas solubility ( » > ). Under normal conditions, blood is sufficiently long in alveolar capillary to fully saturate ( ). Arterial O 2 value is smaller due to shunt.

23. CS 2014 MCQ A 25 year-old medical student ascends the summit of Mt. Blanc in France (4810 m). Assuming standard barometric pressure at this altitude (P b = 55.4 kPa), a normal metabolism and a CO 2 concentration of 4.2 kPa, which of the following values best describes the predicted alveolar partial pressure for O 2 on Mt. Blanc? A.8.3 kPa B.7.5 kPa C.6.2 kPa. D.5.1 kPa E.4.7 kPa

24. CS 2014 That’s it folks…

25. CS 2014 MCQ A 25 year-old medical student ascends the summit of Mt. Blanc in France (4810 m). Assuming standard barometric pressure at this altitude (P b = 55.4 kPa), a normal metabolism and a CO 2 concentration of 4.2 kPa, which of the following values best describes the predicted alveolar partial pressure for O 2 on Mt. Blanc? A.8.3 kPa B.7.5 kPa C.6.2 kPa. D.5.1 kPa E.4.7 kPa