1. © 2007 McGraw-Hill Higher Education. All rights reserved. Chapter 11 Oxygen Transport

2. © 2007 McGraw-Hill Higher Education. All rights reserved. Introduction Pathway for oxygen Determinants of maximal O 2 transport Limitations to oxygen transport –Normal conditions –Pathological states

3. © 2007 McGraw-Hill Higher Education. All rights reserved. Maximal vs. Submaximal exercise A to B: submaximal B to C: Maximal Below B –Capacity to move O 2 from air to mitochondria NOT fully utilized –Supply can meet demand –Demand sets supply B to C: –Different –Mitochondria maxed out (metabolic limitation) –Or –Supply is maxed out (O 2 supply limitation)

4. © 2007 McGraw-Hill Higher Education. All rights reserved. Maximal vs submaximal exercise Why doesn’t muscle venous Po 2 fall to zero at maximal exercise? –Either an oversupply compared to metabolic capacity –Or –Something else limits the transfer of oxygen Diffusing capacity: Finite Venous Po 2 is a reflection of capillary Po 2 and this is ncessary to provide the gradient into the cell Thus, muscle Vo 2 is determined by O 2 delivery AND diffusive flux of O 2

5. © 2007 McGraw-Hill Higher Education. All rights reserved. Requires integrated function of several tissue and organ systems in an interdependent manner –Interdependent Function of one affects the other(s) –Heart, lungs, vasculature and musculature Oxygen transport pathway

6. © 2007 McGraw-Hill Higher Education. All rights reserved. Oxygen transport pathway: in series or parallel? The pathway is arranged in series, NOT parallel –O 2 goes from air to alveoli (ventilation) to blood (diffusion) to hemoglobin through circulation to musculature (blood flow) to cells to mitochondria (diffusion) –Function of the total system is strongly influenced by the weakest step

7. © 2007 McGraw-Hill Higher Education. All rights reserved. So, O 2 transport is limited in the following: –COPD: pulmonary diffusing capacity –CHF: circulatory limitations –Anemia: reduced O 2 carrying capacity –Mitochondrial myopathies: ability to utilize O 2 Enhancement of one step alone provides little if any benefit Oxygen transport pathway; a pathway in series

8. © 2007 McGraw-Hill Higher Education. All rights reserved. Critical structure and functional elements Lungs –Bring air to the alveoli; ventilation –O 2 then diffuses from the alveolar gas into the pulmonary capillaries and is transported to L heart Ventilation –Air that reaches alveoli is always ~ 150 mL less that V T (anatomical dead space) –V A = Fb * (V T -V D ) –Amount of O 2 reaching the alveoli determined by V A and inspired Po 2 (or FiO 2 ) –This sets the absolute limit of Vo 2

9. © 2007 McGraw-Hill Higher Education. All rights reserved. Vo 2 = (V A x F I o 2 ) – (V A x F A o 2 ) –Thus, Vo 2 is the product of alveolar oxygen delivery minus the amount left in the alveoli after diffusion is complete –V A =100 L/min and FiO 2 =.21 and F A O 2 =.17 Vo 2 = 21 – 17 or 4 L/min If all oxygen were diffused into capillary blood, then Vo 2 would be 21 L/min –V A rises linearly with workrate until La - starts to rise (lactate threshold), afterwards, V A rises at a greater rate (as evidenced by falling PaCO 2 ) Critical structure-function elements

10. © 2007 McGraw-Hill Higher Education. All rights reserved. Diffusion O 2 constantly moved across blood-gas barrier into capillary blood by diffusion This demands an elevated P A O 2 (100 mmHg) compared to PcapO 2 (40 mmHg) Disadvantage: requires high ventilation Advantage: requires no energy input At rest PaO 2 is essentially the same as P A O 2 as transit time is not limiting

11. © 2007 McGraw-Hill Higher Education. All rights reserved. During exercise –Qc increases –So does capillary blood vol. (Vc) Transit time: Vc÷Qc –Rest: 75ml÷100ml/s=0.75s –Exercise: 200÷416=0.48s –As PvO 2 falls during exercise, takes longer than 0.25s for complete equilibration Diffusion Exercise

12. © 2007 McGraw-Hill Higher Education. All rights reserved. Diffusion Adjustments during exercise –V A increases P A O 2 often rises above 100 mmHg PvO 2 is reduced (due to increased O 2 extraction by the muscles Thus, Gradient is increased –Rest: 100-40=60 mmHg –Ex.: 110-20=90 mmHg Factors that determine whether or not diffusion process is complete –Transit time –Alveolar and mixed venous Po 2 –Pulmonary diffusing capacity –O 2 -Hb dissociation curve

13. © 2007 McGraw-Hill Higher Education. All rights reserved. Fick’s law: –Vgas=A/T x (P 1 -P 2 ) x d –So, Vo 2 = A/T X (P A O 2 – PcO 2 ) –As area is huge and thickness is minute; Vo 2 is dominated by the pressure gradient However, PcO 2 changes along the capillary –Thus, PaO 2 = P A O 2 – (P A O 2 -PvO 2 ) x exp[-D/( βQ)] D=diffusing capacity of lung Q=cardiac output Β=slope of O 2 -Hb dissociation curve Thus, how quickly the diffusion of O 2 is complete depends upon –Diffusing capacity –Cardiac output –The slope of the O 2 -Hb dissociation curve Diffusion

14. © 2007 McGraw-Hill Higher Education. All rights reserved. Heart and circulation Strong linear relationship between Cardiac output and Vo 2 –5-6 to 1 ratio of Qc and Vo 2 –Fick principle Vo 2 = Q x (CaO 2 - CvO 2 ) Cardiac output (L/min)Oxygen uptake (L/min)

15. © 2007 McGraw-Hill Higher Education. All rights reserved. CaO 2 = 1.39 x Hb xSaO 2 –This ignores the small amt dissolved in the blood Thus, Vo 2 = Qx(CaO 2 -CvO 2 ) represents the difference between O 2 delivery (QxCaO 2 ) to the tissue and O 2 return (QxCvO 2 ) to the lung Thus Qo 2 = Qx 1.39 x Hb x SaO 2 –O 2 delivery is dependent upon the integrated function of: CV system Blood Lungs Heart and circulation 5 ml o 2 /100 ml blood

16. © 2007 McGraw-Hill Higher Education. All rights reserved. Very different at rest –Qc: 5 L/min –Qm: 1 L/min Maximal exercise –Qc: 20-25 L/min –Qm: 17-22 L/min Blood –Carries O 2 –O 2 -Hb dissociation curve determines how O 2 and blood interact Cardiac output and muscle blood flow

17. © 2007 McGraw-Hill Higher Education. All rights reserved. O 2 -Hb dissociation curve Non-linear –Loading of O 2 at lung fairly rapid –Unloading at the tissues is slower Why? –When loading, large changes in saturation because you are on the steep portion of the curve. –When unloading begins curve is flat Very little change in saturation for a large change in Po 2 By the time that the Po 2 is quite low (smaller gradient) –Thus, the off-loading of O 2 is slower than the loading process in the lungs because of the shape of the O 2 -Hb dissociation curve

18. © 2007 McGraw-Hill Higher Education. All rights reserved. Loading and unloading O 2 So, in same amount of time (0.3s in figure 11.4) –P A O 2 = PcapO 2 –But PcapO 2 ≠ PiO 2 –Thus, most muscles have an intrinsic diffusion limitation –Diffusing capacity Measured in mL O 2 /mmHg/min As gradient is smaller in muscle, diffusion limitations occur more often

19. © 2007 McGraw-Hill Higher Education. All rights reserved. The O 2 -Hb dissociation curve shifts to the right during exercise (this effect occurs at the muscle level) –Temp –pH –Pco 2 Curve remains mostly normal at the lung as Co 2 is exhaled, pH rises and temperature is reduced P 50 of the O 2 -Hb dissociation curve

20. © 2007 McGraw-Hill Higher Education. All rights reserved. The Muscles Diffusive flux out of the capillary into the muscle follows the same laws as described previously –Vo 2 = A/T (PcapO 2 -PiO 2 ) –PvO 2 = PiO 2 + (PaO 2 -PiO 2 ) x exp[- Dm/ βQ] –PiO 2 is essentially “0”, so PvO 2 = PaO 2 x exp[-Dm/βQ] Thus, –Muscle O 2 diffusion is determined by »Blood flow (time) »Shape of O 2 -Hb dissociation curve »Diffusing capacity of the muscle

21. © 2007 McGraw-Hill Higher Education. All rights reserved. Other factors that may limit O 2 transport Pulmonary heterogeneity –Ventilation-perfusion mismatch (V A /Q) –Can also cause hypoxemia and reduced O 2 delivery –Measure of the matching of alveolar ventilation to capillary blood flow Tissue heterogeneity –Vo 2 -perfusion mismatch (Vo 2 /Q) –Impacted by muscle fiber type

22. © 2007 McGraw-Hill Higher Education. All rights reserved. Integrated function of the lungs, heart, vasculature, blood and tissue Many ways to describe Vo 2 –Lung: –Vo 2 =V A (P I O 2 -P A O 2 ) –Tissue: –Vo 2 =Qm(PcapO 2 -PiO 2 ) –Integrated: –Vo 2 =Q(CaO 2 -CvO 2 ) Thus, FiO 2, V A, Q, β, D L and D M ALL play a role in the determination of Vo 2 max Note how a reduction in the above factors has a much greater effect on Vo 2 max than an increase; why?

23. © 2007 McGraw-Hill Higher Education. All rights reserved. System integration in determining maximal O 2 transport Two ways to describe muscle O 2 flux –Fick Principle: Convective O 2 transport –Vo 2 =Q(CaO 2 -CvO 2 ) –Fick’s law Diffusive –Vo 2 =D M (PcapO 2 -PiO 2 )

24. © 2007 McGraw-Hill Higher Education. All rights reserved. As PiO 2 is essentially a constant (and close to zero at max exercise) –Vo 2 =D M x PvO 2 (or PcapO 2 ) If you plot both the convective and diffusive O 2 flux equations on one graph (Fig. 11.8) –Intersection is Vo 2 max System integration in determining maximal O2 transport

25. © 2007 McGraw-Hill Higher Education. All rights reserved. System integration A: If Diffusive conductance is reduced; Vo 2 max is reduced B: If Convective conductance is reduced; Vo 2 max is reduced C: Hypoxia reduces convective conductance Thus, muscle blood flow, oxygen carrying capacity, muscle diffusing capacity, pulmonary diffusing capacity can all impact Vo 2 max