Pulmonary gas exchange and acid-base balance during exercise

Abstract

As the first step in the oxygen-transport chain, the lung has a critical task: optimizing the exchange of respiratory gases to maintain delivery of oxygen and the elimination of carbon dioxide. In healthy subjects, gas exchange, as evaluated by the alveolar-to-arterial PO2 difference (A-aDO2), worsens with incremental exercise, and typically reaches an A-aDO2 of approximately 25 mmHg at peak exercise. While there is great individual variability, A-aDO2 is generally largest at peak exercise in subjects with the highest peak oxygen consumption. Inert gas data has shown that the increase in A-aDO2 is explained by decreased ventilation-perfusion matching, and the development of a diffusion limitation for oxygen. Gas exchange data does not indicate the presence of right-to-left intrapulmonary shunt developing with exercise, despite recent data suggesting that large-diameter arteriovenous shunt vessels may be recruited with exercise. At the same time, multisystem mechanisms regulate systemic acid-base balance in integrative processes that involve gas exchange between tissues and the environment and simultaneous net changes in the concentrations of strong and weak ions within, and transfer between, extracellular and intracellular fluids. The physicochemical approach to acid-base balance is used to understand the contributions from independent acid-base variables to measured acid-base disturbances within contracting skeletal muscle, erythrocytes and noncontracting tissues. In muscle, the magnitude of the disturbance is proportional to the concentrations of dissociated weak acids, the rate at which acid equivalents (strong acid) accumulate and the rate at which strong base cations are added to or removed from muscle.

Figures

Figure 1

Schematic diagram showing equilibration of a gas in the pulmonary capillary of a homogeneous lung. The top half of this figure represents a schematic alveolus and pulmonary capillary, the bottom half the corresponding changes of gas partial pressure in the pulmonary capillary. X represents the distance along the pulmonary capillary from X0, the start of the contact point with the diffusion barrier to X’, the end of the point of contact with the diffusion barrier. Fresh gas is delivered to the alveolus by the process of alveolar ventilation (V˙A). The alveolus is perfused by a pulmonary capillary, with a partial pressure of mixed venous gas (Pv¯) at X0 which rises to a maximum end-capillary partial pressure (Pc’) at X’. Consider a tiny increment of distance along the pulmonary capillary (dX). The flux of gas across the alveolar wall into the blood (dM˙) is described by Fick’s law of diffusion and is given by the product of the diffusing capacity (D) of the element of the barrier corresponding to dX and difference between the partial pressure in alveolar air (PA) and the partial pressure of the gas in capillary blood (Pc), PA–Pc. The uptake of gas into the blood at point dX results in a change in the content of gas in capillary blood (dPc). Under steady-state conditions, this is also equal to dM˙ and is described by the Fick equation and is calculated as the product of the steady-state perfusion (Q˙) and dPc. The content of gas in blood is related to the partial pressure in blood by β the effective solubility of the gas (the slope of the dissociation curve, i.e., dcontent/dPc).

Figure 2

The effect of a nonlinear dissociation curve on the effective solubility (β) and diffusion equilibrium. Here dP is considered to be the change in partial pressure in the blood of a gas required for diffusion equilibrium. When β is relatively large (the steep slope seen in β1) there must be a large change in content (dcont1) for dP whereas when β is relatively small (β2) the same partial pressure change is accomplished with a much smaller change in content (dcont2). Thus, a large β (i.e., β1) means that there is a large sink for a gas, more molecules must be transferred before the partial pressure rises, compared to the situation where β is relatively small (i.e., β2).

Figure 3

The relationship between oxygen and carbon dioxide as a function of differing V˙A/Q˙ ratios [adapted, with permission, from Fahri (67)]. When the V˙A/Q˙ ratio is low, the composition of alveolar gas approaches that of mixed venous blood. When the V˙A/Q˙ ratio is high the PO2 and PCO2 of alveolar gas approaches that of the inspired gas.

Figure 4

Temperature corrected arterial blood gas data and calculated A-aDO2 obtained from 32 healthy normal subjects (15 male, 17 female) during progressive cycle exercise to V˙O2max. Arterial PO2 falls and the A-aDO2 increases with increasing exercise intensity. In this data set, the samples at “rest” are obtained with the subject sitting upright on the cycle ergometer, breathing through a mouthpiece and anticipating maximal exercise. Thus, the PaO2 is somewhat elevated and PaCO2 reduced over true resting values.

Figure 5

Individual subject PaO2, PaCO2, and A-aDO2 for the same 32 subjects whose data appears in Figure 2, plotted as a percentage of V˙O2max. Here, the wide variation in the blood gas responses to exercise can be appreciated.

Figure 6

Temperature corrected arterial blood gases obtained at near maximal and maximal exercise (cycle ergometer or treadmill running) in normal subjects [(A) n = 198; (B) and (C) n = 175)]. Data are, with permission, from references (15, 45, 76, 93, 94, 118, 121, 124, 219, 231, 251, 328, 357). The horizontal line in A and B defines the normal value and in C the limits of the expected increase in A-aDO2 with exercise as defined by Dempsey and Wagner (47). The arterial PO2 is lower and the PaCO2 and A-aDO2 higher with increasing aerobic capacity. Above a V˙O2max of 65 to 70 mL/kg/min the majority of individuals have significant gas exchange impairment although it is uncommon in individuals with a V˙O2max<50mL/kg/min.

Figure 7

The Relationship between PaO2 and PaCO2 during maximal exercise for the subjects from Figure 6. PaCO2 is an index of alveolar ventilation and it can be seen that limited hyperventilation explains only approximately 20% of the variance in PaO2.

Figure 8

The effect of exercise on the V˙A/Q˙ distribution and PaO2. Data are shown for a healthy normal subject at rest and during heavy near-maximal exercise (V˙O2~4.1 liter/min). The closed circles represent perfusion (plotted on the right-hand y-axis in liter/min) and the open squares represent the arterial PO2 (plotted on the left-hand y-axis in mmHg) from a lung unit with the V˙A/Q˙ ratio given on the x-axis. Data in red are resting data; blue are exercising data. Exercise results in an alteration in the PO2 versus V˙A/Q˙ relationship because of the lower mixed venous PO2 entering the lung and also because of changes in the oxygen-hemoglobin dissociation curve in the blood. There is an increase in cardiac output in this subject from 6.2 liter/min at rest to 25.0 liter/min during heavy exercise, and alveolar ventilation is increased from 6.2 liter/min to 170 liter/min, thus the plot of Q˙ versus V˙A/Q˙ ratio moves to the right with exercise. V˙A/Q˙ inequality is also increased during exercise and the blood flow distribution is broader (LogSDQ˙=0.45 rest, 0.53 exercise). Despite these changes the increased V˙A/Q˙ inequality with exercise does little to lower PaO2. This is because the lowest perfused V˙A/Q˙ units occur at a higher V˙A/Q˙ ratio with exercise (arrows).

Figure 9

Estimation of pulmonary diffusion limitation during exercise using the multiple inert gas elimination technique. The measured ventilation-perfusion inequality and shunt are used to calculate the expected A-aDO2 under the measurement conditions. The results are compared to the measured A-aDO2. At rest, the two sets of data overlie one another but as exercise intensity increases, the measured A-aDO2 exceeds that expected from the amount of V˙A/Q˙ inequality and shunting. This indirect index is a measure of pulmonary diffusion limitation although a contribution from the bronchial circulation and thebesian veins cannot be excluded. Data, with permission, from references (121, 124, 251)

Figure 10

The alveolar-arterial difference at rest and during exercise to near maximal at different barometric pressures. There is no systematic relationship between A-aDO2 and barometric pressure. This is likely due to a combination of factors including individual subject variability and the relative contributions of diffusion limitation, V˙A/Q˙ inequality and shunt to the A-aDO2 within a subject at different elevations. See text for details. Data are, with permission, from references (15, 46, 300, 302, 327, 334).

Figure 11

Response to progressive exercise in age- and height-matched men and women. Based on prediction equations, women have a smaller forced vital capacity (FVC), and peak expiratory flow (PEF). With incremental exercise there is expiratory flow-limitation (EFL) observed in the woman, and hyperinflation as demonstrated by an increase in end-expiratory lung volume (EELV). Figure, with permission, from Sheel and Guenette (276).

Figure 12

Relationships showing the dependence of plasma pH, [H+], and [HCO3−] on plasma [SID] when PCO2 is held constant at 40 mmHg and [Atot] is held constant at 16 mEq/L. Note the decreasing slope in the [SID]: [H+] relationship with increasing [SID], indicating increased ability to remove (buffer) H+ from solution. For comparison, the dashed—dotted line extrapolates a linear decrease in [H+] with increasing [SID]; increasing [SID] from 39 to 45 mEq/L has the effect of buffering approximately 3 mEq/L of H+.

Figure 13

The dependence of plasma [H+] on [Atot] and [SID] when PCO2 is constant at 40 mmHg.

Figure 14

The dependence of plasma [H+] on PCO2 and [SID] when [Atot] is constant at 16 mEq/L.

Figure 15

Diagram showing interrelationships between ventilation, acid-base variables, and cellular processes. The dashed arrows indicate pathways through peripheral and central chemoreceptors that drive ventilation according to the acid-base status of the individual.

Figure 16

(A) Relationships between the dependent acid-base variables and [Atot] in resting muscle. The hatched bar indicates a normal range for resting muscle. (B) Relationships between the dependent acid-base variables and [Atot] in muscle with high intensity exercise. The hatched bar indicates a normal range for very high intensity exercise.

Figure 17

(A) Relationships between the dependent acid-base variables and PCO2 in resting muscle. The hatched bar indicates a normal range for resting muscle. (B) Relationships between the dependent acid-base variables and PCO2 in muscle with high intensity exercise. The hatched bar indicates a normal range for very high intensity exercise.

Figure 18

(A) Relationships between the dependent acid-base variables and [Atot] in resting muscle. The hatched bar indicates a normal range for resting muscle. (B) Relationships between the dependent acid-base variables and [Atot] in muscle with high intensity exercise. The hatched bar indicates a normal range for very high intensity exercise.

Figure 19

Schematic of whole body acid-base interactions during high intensity exercise.

Figure 20

The relationships between muscle [H+] and each of the independent variables PCO2, [Atot], and [SID] in response to 30 s of very high intensity exercise and subsequent 0.5 min of recovery. The time course of change is indicated by the arrows. R = resting; 0.5 = 0.5 min of recovery; 3.5 = 3.5 min of recovery; 9.5 = 9.5 min of recovery. The solid lines indicate [H+] isopleths at resting [SID] of 100 mEq/L (with KA of 1.64 × 10−7 Eq/L) and [SID] of 60 mEq/L which occurred at 3.5 min of recovery (with Ka of 1.98 × 10−7 Eq/L. The dashed line indicates the resting [H+] isopleth but using the exercise KA of 1.98 × 10−7 Eq/L.

Figure 21

Arterial—antecubital venous (∎) and arterial—femoral venous (•) PCO2 (top panel) and [H+] (bottom) differences during four repeated, 30 s bouts of very high-intensity exercise interspersed with 4 min rest periods, followed by 90 min of recovery. Data, with permission, from Lindinger et al. (179, 180).

Figure 22

Plasma [Atot] as functions of PCO2 and [SID] (top) and [Atot] and [SID] bottom. The arrows show the time course of change going from rest (R) to 0.5 min after 30 s of very high intensity exercise, then to 3.5 and 9.5 min of recovery. Experimental data from Kowalchuk et al. (163).

Figure 23

The time course of plasma [lactate−] and negative change in plasma [HCO3−] from preexercise (time = −1 min) at the end of 30 s of very high intensity exercise (time 0) and during 9.5 min of resting recovery. Using data, with permission, from Kowalchuk et al. (162, 163).

Figure 24

Time course of erythrocyte [lactate−] in blood sampled from two sets of subjects performing four 30 s bouts of high intensity exercise interspersed with 4 min rest periods (shaded area), and subsequent recovery. Data are a composite from the arterial and femoral venous data of Lindinger et al. (180) and the arterial and antecubital venous data of McKelvie et al. (204).

Figure 25

Time course of muscle and plasma [lactate−] in humans that performed 30 s of very high intensity leg bicycling exercise. Data, with permission, from Kowalchuk et al. (162, 163).

Figure 26

Time course of plasma [H+] in humans that performed 30 s of very high intensity leg bicycling exercise. Data, with permission, from Kowalchuk et al. (162, 163).

Figure 27

Time course of plasma PCO2 and [HCO3−] in humans that performed 30 s of very high intensity leg bicycling exercise. Data, with permission, from Kowalchuk et al. (162, 163).

Figure 28

Time course of V˙E and V˙CO2 in humans that performed 30 s of very high intensity leg bicycling exercise. Data, with permission, from Kowalchuk et al. (162, 163).