Abstract
The authors of this interesting article (Calbet and Lundby, 2009) conclude in the abstract that “hypoxia reduces Vo2max because it limits O2 diffusion in the lung.” In my opinion they ascribe too little importance to convectional pulmonary transport and too much to the diffusion pressure gradient from the lungs to the mitochondria. A main effect of altitude is the reduction of molecule number in each liter of inspired air. For simplification, consider an ascent to 5500 m that reduces barometric pressure to one-half. To transport an equal amount of oxygen into the alveoli as at sea level, the ventilation at BTPS conditions has to be doubled, corresponding to unchanged Ve at STPD. This is clearly impossible at high performance levels, such as Vo2max. Even if possible, the oxygen pressure in inspired air remains halved, while Pio2 − Pao2 must be equal to that at sea level for unchanged oxygen uptake. Only an increased ventilation at STPD can increase the mass transport of this gas, increasing again Pao2 to partly reestablish the pulmonary diffusion pressure. This is possible only at very moderate altitudes during hard exercise. The next step, oxygen diffusion from the alveoli into blood, depends on the difference between Pao2 and mean capillary Po2 times diffusion capacity. Since the lower limit of venous Po2 at exhausting exercise (∼10 mmHg; Sutton et al., 1988) can hardly be reduced, only an increase in diffusion capacity, either by increasing lung capillary or erythrocyte area, improves oxygen transport. All additional acclimatization effects in the rest of the body are mitigating deleterious consequences of lung failure, but cannot compensate for them. Blunting of peak Q is not “contributing to the limitation of Vo2max,” (Calbet and Lundby, 2009) if all oxygen diffused into the blood can be transported.
Acclimatization changes in oxygen affinity are more complex than described. The standard oxygen dissociation curve (ODC: Pco2 40 mmHg, pH 7.4, 37°C) is right-shifted because of a rise in 2,3-diphosphoglycerate concentration in Caucasians and Amerindians, but with intense hyperventilation this is compensated or even overcompensated for, improving the loading of O2 but attenuating unloading. To my knowledge, the ODC has never been studied in Ethiopians, who have the longest adaptation time at altitude and an astonishingly high Sao2 (Beall et al., 2002). The steepness of the curve is also important. The best acclimatization effect would be a rise in slope, improving loading in the lungs and unloading in the tissues. Only minimal changes in Hill's n were observed in residents of Bogotá (Schmidt et al., 1990). Interestingly, an increase in hemoglobin concentration leads to a rise not in ΔSo2/ΔPo2, but in the physiologically decisive oxygen extraction Δ[O2]/ΔPo2. An increase of [Hb] by 20% increases Δ[O2] by 20% for a given ΔPo2. Also, the Bohr effect (Bohr coefficient times ΔpH) steepens the in vivo curve because of lower venous than arterial pH. The Bohr coefficients are not consistently changed at altitude (Schmidt et al., 1990). The increased [Hb] even buffers pH changes; conversely, Pco2 differences at low Pco2 and [
The statement “that increasing [Hb] … could make more difficult the diffusion of O2 from the red cells to the muscle mitochondria since the O2 may tend to remain bound to the haemoglobin, particularly without the in vivo right shift of P50” (Calbet and Lundy, 2009) is not correct. At constant oxygen uptake, Svo2 and therefore also Pvo2 are higher with increased [Hb], thus compensating for a lacking right shift of the curve. Additionally, an increased [Hb] corresponds to an enlarged red cell number and thus diffusion area.