The O2 required for oxidative metabolism by exercising muscle travels from the atmosphere to the muscle mitochondria in three discrete steps:
1. Uptake of O2 by the lungs, which depends on pulmonary ventilation
2. O2 delivery to muscle, which depends on blood flow and O2 content
3. Extraction of O2 from blood by muscle, which depends on O2 delivery and the gradient between blood and mitochondria
Maximal O2 uptake by the lungs can exceed resting O2 uptake by more than 20-fold
The respiratory and cardiovascular systems can readily deliver O2 to active skeletal muscle at mild and moderate exercise intensities. As power output increases, the body eventually reaches a point at which the capacity of O2 transport systems can no longer keep pace with demand, so the rate of O2 uptake by the lungs () plateaus (Fig. 60-6). At rest, is typically 250 mL/min for a 70-kg person (see p. 647), which corresponds to 3.6 mL of O2 consumed per minute for each kilogram of body mass (mL O2/[min × kg]). Maximal oxygen uptake measured at the lungs () is an objective index of the functional capacity of the body's ability to generate aerobic power. In people who have a deficiency in any part of the O2 transport system (e.g., chronic obstructive pulmonary disease or advanced heart disease), can be as low as 10 to 20 mL O2/(min × kg). The range for mildly active middle-aged adults is 30 to 40 mL O2/(min × kg); for people in this category, a 3-month program of aerobic conditioning can increase by >20%. In elite endurance athletes, may be as high as 80 to 90 mL O2/(min × kg), more than a 20-fold elevation above the resting . Lowering of the O2 content of the blood by hemorrhage or high altitude decreases , whereas blood transfusion or aerobic conditioning increases it.
FIGURE 60-6 Dependence of O2 consumption on mechanical power output. Aerobic training increases the maximal O2 uptake by the lungs ().
The typical method for determining is an incremental exercise test on a stationary cycle ergometer or treadmill. Such tests assess training status, predict performance in athletes, and provide an index of functional impairment in patients. During the test, the technician monitors the and of the subject's expired air, as well as total ventilation. The criteria for achieving include (1) an inability to continue the pace at the prescribed power requirement, (2) a leveling off of as the power requirement increases (see Fig. 60-6), and (3) a respiratory exchange ratio () > 1.15. Such a high is a transient/non–steady-state occurrence (i.e., not a real respiratory quotient; see p. 681) and indicates that a significant hyperventilation, triggered by low blood pH (see p. 710), is reducing the body's CO2 stores.
O2 uptake by muscle is the product of muscle blood flow and O2 extraction
The body's total store of O2 is ~1 L (mainly in the form of O2 bound to hemoglobin), a volume that (if used completely) could support moderate aerobic exercise for 30 seconds at best, heavy aerobic exercise for not more than 15 seconds, and maximal aerobic exercise for less than 10 seconds. If activity is to persist, the body must continually transport O2 from the ambient air to the muscle mitochondria at a rate that is equivalent to the O2 utilization by the muscle. This increased O2 transport is accomplished by increasing alveolar ventilation to maintain alveolar levels that are sufficient to saturate arterial blood fully with O2 (see p. 681) and by increasing cardiac output to ensure a sufficiently high flow of oxygenated blood to the active muscles (see p. 464). The integrated organ-system response to the new, elevated metabolic load involves the close coupling of the pulmonary and the cardiovascular O2-delivery systems to the O2-acceptor mechanisms in the muscle; the response includes sophisticated reflexes to ensure matching of the two processes.
The convective O2-delivery rate is the product of cardiac output (i.e., heart rate × stroke volume) and arterial O2 content:
The rate of O2 uptake by skeletal muscle depends on both the O2 delivery to skeletal muscle and the extraction of O2 by the muscle. According to the Fick equation (see p. 423), is the product of blood flow to muscle (F) and the arteriovenous (a-v) difference for O2:
The , established by the rate of oxidative phosphorylation in muscle mitochondria, requires an adequate rate of O2 delivery to the active muscle. Exercise triggers a complicated series of changes in the cardiovascular system that has the net effect of increasing F and redistributing cardiac output away from the splanchnic and renal vascular beds as well as from inactive muscle to better supply the active musculature (see p. 581). Increased O2 extraction from the blood by active skeletal muscle occurs at the onset of exercise in response to elevated mitochondrial respiration and the attendant fall in intracellular , which increases the gradient for O2 diffusion from blood within the microcirculation (see Fig. 24-5) to mitochondria within active muscle fibers.
At the onset of exercise, the content of O2 in the arterial blood (; see Fig. 29-3) actually increases slightly (e.g., from 20.0 to 20.4 mL O2/mL blood) secondary to the increase in alveolar ventilation triggered by the CNS (see p. 350). Also as a consequence of the anticipatory hyperventilation, actually falls with the onset of exercise. Possible mechanisms of this ventilatory increase include a response to mechanoreceptors in joints and muscles, descending cortical input, and resetting of peripheral chemoreceptors by a reduction in their blood supply (see pp. 711–712). The increase in ventilation in anticipation of future needs is enhanced in well-trained athletes.
O2 delivery by the cardiovascular system is the limiting step for maximal O2 utilization
For years, exercise and sports scientists have debated over the factors that limit and thus contribute to performance limitations. As noted above, the transport of O2 from atmosphere to muscle mitochondria occurs in three steps: uptake, delivery, and extraction. A limitation in any step could be rate limiting for maximal O2 utilization by muscle.
Limited O2 Uptake by the Lungs
One view is that the lungs limit . An inability of alveolar O2 diffusion to saturate arterial blood fully (see Fig. 30-10C) occurs in a subset of elite athletes (including race horses). Thus, a decrease in occurs at maximal effort on an incremental test. The inability of the lungs to saturate arterial blood in athletes could be the consequence of a ventilation-perfusion mismatch at very high cardiac outputs (see p. 698). N60-7
Exercise-Induced Arterial Hypoxemia in Women
Contributed by Emile Boulpaep, Walter Boron
It has been well established that young male athletes can develop arterial hypoxemia when exercising near their maximal rate of O2 consumption (). Thoroughbred horses can also exhibit exercise-induced arterial hypoxemia (EIAH). The study cited below shows that many healthy and active young women experience a significant EIAH, even when well below . The alveolar-arterial (A-a) gradient (see Box 31-1) rises with , reaching values 3- to 10-fold higher than the resting value when is at . The anatomical basis of this effect may be smaller lung volumes (corrected for height and age), reduced diffusing capacity (DL; see p. 668), smaller-caliber airways, and reduced hematocrit. Physiologically, the mechanism could involve a significant mismatch.
Harms CA, McClaran SR, Nickele GA, et al. Exercise-induced arterial hypoxaemia in healthy young women. J Physiol. 1998;507:619–629.
Limited O2 Delivery by the Cardiovascular System
According to the prevalent view, a limitation in O2 transport by the cardiovascular system determines . That is, maximal cardiac output, and hence O2 delivery, is the limiting step according to the convective flow model. Support for this view comes from the observation that training can considerably augment maximal cardiac output and muscle blood flow (see the following section). Moreover, largely increases in parallel with these adaptations (Fig. 60-7).
FIGURE 60-7 Dependence of maximal oxygen utilization on oxygen delivery. The graph illustrates the relationship between maximal O2 delivery to the peripheral tissues () and maximal O2 uptake by lungs () for five individuals with different lifestyles. Training increases both O2 delivery and O2 uptake. (Data from Saltin B, Strange S: Maximal oxygen uptake: old and new arguments for a cardiovascular limitation. Med Sci Sports Exerc 24:30–37, 1992.)
Limited O2 Extraction by Muscle
A third point of view is that, with increasing demand, O2 extraction by muscle from blood becomes inadequate despite adequate O2 delivery. According to this diffusive flow model, a major limitation in O2transport is the kinetics of O2 diffusion from hemoglobin in the red blood cell to the muscle mitochondrial matrix. Thus, anything that lowers either the muscle's diffusing capacity for O2 or the gradient between hemoglobin and mitochondria reduces .
Effective circulating volume takes priority over cutaneous blood flow for thermoregulation
When we exercise in the heat, our circulatory systems must simultaneously support a large blood flow to both the skin (see p. 1195) and contracting muscles, which taxes the cardiac output and effective circulating volume (see pp. 554–555). During exercise, the ability to maintain both arterial blood pressure and body core temperature (Tcore) within acceptable physiological limits depends on maintaining an adequate effective circulating volume. Effective circulating volume depends on total blood volume, which in turn relies on extracellular fluid (ECF) volume and overall vasomotor (primarily venomotor) tone, which is important for distributing blood between central and peripheral blood vessels.
Effective circulating volume tends to fall during prolonged exercise, especially exercise in the heat, for three reasons (Fig. 60-8).
FIGURE 60-8 Effect of exercise on central blood volume.
First, exercise causes a shift in plasma water from the intravascular to the interstitial space. This transcapillary movement of fluid during exercise primarily reflects increased capillary hydrostatic pressure as arterioles dilate (see p. 469). In addition, increased osmolality within muscle cells removes water from the extracellular space. When exercise intensity exceeds 40% of , this loss of plasma water is proportional to the exercise intensity. In extreme conditions, the loss of plasma water can amount to >500 mL, or ~15% of the total plasma volume.
Second, exercise causes a loss of total-body water through sweating (discussed in the next subchapter). If exercise is prolonged without concomitant water intake, sweat loss will cost the body an important fraction of its total water. A loss of body water in excess of 3% of body weight is associated with early signs of heat-related illness, including lightheadedness and disorientation, and it constitutes clinical dehydration. N40-10
Third, exercise causes a redistribution of blood volume to the skin because of the increase in cutaneous blood flow in response to body heating (see Fig. 60-8). Venous volume in the skin increases as a result of the increased pressure in the compliant veins as blood flow to the skin rises. No compensatory venoconstriction occurs in the skin because of the overriding action of the temperature
In response to this decrease in effective circulating volume that occurs during exercise, the cardiopulmonary low-pressure baroreceptors (see pp. 546–547) initiate compensatory responses to increase total vascular resistance (see Fig. 60-8). The sympathetic nervous system increases this resistance by (1) increasing the splanchnic vascular resistance, which directs cardiac output away from the gut; (2) offsetting some of the thermoregulatory system's vasodilatory drive to the skin; and (3) offsetting some of the vasodilatory drive to the active skeletal muscles.
With heavy heat loads, the restriction of peripheral blood flow has the benefit of helping to maintain arterial blood pressure and effective circulating volume, but it carries two liabilities. First, it reduces convective heat transfer from the core to the skin because of the reduced skin blood flow (see p. 1195), which contributes to excessive heat storage and, in the extreme, heat stroke (see Box 59-1). Second, the limitation of blood flow to active muscle may compromise O2 delivery and hence aerobic performance.
With low thermal and metabolic demand, no serious conflict arises among the systems that regulate effective circulating volume, arterial blood pressure, and body temperature. The cutaneous circulation is capable of handling the heat-transfer requirements of the temperature-regulatory mechanism without impairing muscle blood flow or cardiac filling pressure.