What happens during exercise?
Metabolism during exercise - aerobic vs. anaerobic
PaCO2 during exercise
The exercise test
Physiologic changes during exercise
Normal exercise parameters
Clinical use of physiologic exercise testing
Clinical interpretation of physiologic exercise testing
Tables and Boxed Information are this color
Clinical Problems are this color
Line figures are surrounded by this color
The pulmonary physiology discussed so far deals largely with patients at rest. Many patients complain of dyspnea only during exercise or during minimal exertion, such as stair climbing. Their resting pulmonary function tests many be normal or, if abnormal, not reduced enough to explain the degree of exercise intolerance. Why does exercise either bring out or exacerbate dyspnea in some patients? How does exercise testing help diagnose the cause of dyspnea'?
Exercise physiology, a relatively new field for clinical study, helps to answer these questions. Exercise physiology encompasses aspects of pulmonary, cardiac, and sports medicine, plus cellular metabolism and biochemistry. This chapter will concentrate on exercise physiology in the diagnosis of cardiopulmonary disease.
WHAT HAPPENS DURING EXERCISE?
At this point it will be useful to review basic lung volumes and ventilations. The most visible change in any subject during exercise is the increased in minute ventilation; this manifests as increases in rate and depth of breathing. Study the following figure (from Chapter 4) to familiarize yourself with lung volumes and ventilations. (Shown is a thumbnail of the larger image; if you view the larger image, use the back button on your browser to return to this point.)
The reason for increased minute ventilation during exercise is because much more oxygen and carbon dioxide are exchanged than at rest. This single metabolic fact accounts for the profound changes in not only respiration, but also in cardiac and circulatory physiology during exercise. Increased oxygen supply is provided by increases in both arterial oxygen delivery and tissue oxygen extraction; at the same time there is increased carbon dioxide transport on the venous side. The need for increased gas exchange by exercising muscles leads to the following general physiologic changes.
Metabolic changes. Increased oxygen consumption (VO2) and carbon dioxide production (VCO2) occur immediately with exercise. During aerobic metabolism, glucose and fats utilize oxygen to form adenosine triphosphate (ATP), the ultimate source of energy. There is very little oxygen stored in the body, so aerobic metabolism requires continuous delivery of oxygen from the atmosphere to the blood. Without oxygen, glucose is metabolized anaerobically, and the yield of ATP per glucose molecule is much less; in addition, lactic acid is generated as a by-product. Anaerobic metabolism is sufficient for short bursts of activity, but prolonged exercise requires oxygen as energy substrate.
Cardiac changes. Oxygen consumption (VO2) is related to cardiac output by the Fick equation:
Both SV and HR increase immediately with exercise, but stroke volume plateaus early. Further increases in cardiac output are largely due to increases in heart rate.
Systemic circulation changes. The extra cardiac output delivers more oxygen to exercising muscles. There is a redistribution of the systemic circulation, including vasodilation in the skin and working muscles and vasoconstriction in the visceral organs and nonworking muscles. The net effect of vascular redistribution is a decrease in systemic vascular resistance.
Oxygen extraction changes. Apart from increased cardiac output and vascular redistribution, a third mechanism to meet oxygen requirements is increased oxygen extraction from the arterial blood; this results in an increased arterial-venous oxygen content difference (Equation 1).
Pulmonary circulation changes. Pulmonary circulation also increases immediately with exercise. Unperfused alveoli become perfused (through recruitment of pulmonary capillaries), and underperfused units receive an increased blood supply. As a result, both pulmonary blood volume and the pulmonary diffusing capacity for oxygen increase.
Ventilation changes. As pulmonary blood flow increases, both minute ventilation (VE) and alveolar ventilation (VA) increase; in this way the lungs transfer more oxygen and carbon dioxide and keep pace with metabolic demands. Although both tidal volume (VT) and respiratory rate increase with exercise, in the early stages an increase in VT accounts for most of the rise in VE and VA. At a point where VT approaches approximately 60% of the vital capacity, further increases in ventilation come from increasing respiratory rate.
Hematologic changes. Although most of the increase in oxygen delivery is accounted for by increased cardiac output, in some individuals hemoglobin concentration may rise. This can occur by red cells entering the circulation from splenic and marrow reservoirs, as well as by reduction of plasma volume. The rise in hemoglobin does not occur in well-trained athletes, who tend to have higher resting blood volume than the general population. In any case the magnitude of hemoglobin increase is small, approximately 10%, and does not play a significant role in augmenting oxygen delivery during exercise.
Metabolically, there are two types of exercise, aerobic and anaerobic. Aerobic exercise uses oxygen as energy substrate to metabolize food to adenosine triphosphate (ATP) (see box below, METABOLIC CHANGES DURING AEROBIC AND ANAEROBIC EXERCISE). When the supply of oxygen is no longer sufficient to meet the needs of exercising muscles, anaerobic metabolism begins. In anaerobic metabolism, glucose is converted to ATP without oxygen, and lactic acid is generated as a by-product. A healthy person can perform aerobic exercise for several hours; in contrast, pure anaerobic exercise can only be sustained for a few minutes before severe dyspnea and fatigue set in.
During short bursts of activity, such as sprinting, energy may be obtained only anaerobically. Otherwise, anaerobic metabolism occurs in addition to ongoing aerobic metabolism. Typically, anaerobic metabolism begins approximately midway between resting and maximal oxygen consumption. The point at which anaerobic metabolism begins is called the anaerobic threshold (AT). AT can be identified by a typical pattern of changes in the blood and in expired gases (see the next section).
METABOLIC CHANGES DURING AEROBIC AND ANAEROBIC EXERCISE
During aerobic exercise, both glucose and fatty acids are metabolized. One molecule of glucose utilizes 6 molecules of oxygen and produces 6 molecules of carbon dioxide, for a metabolic respiratory quotient (RQ) of I.O. For fatty acids, 23 molecules of oxygen are used for every 16 molecules of carbon dioxide produced, giving an RQ of 0.71. The average RQ during mild to moderate exercise (before anaerobic threshold) is approximately 0.85.
By contrast, anaerobic metabolism produces only 2 molecules of ATP per molecule of glucose; at the same time 2 molecules of lactic acid are produced, which, when buffered, generate carbon dioxide in excess of that from aerobic metabolism.
C6H12O6 + 6 02
----> 6 CO2 + 6 H2O + 36 ATP (RQ = 1.0)
C16H32O2 + 23 02
----> 16 CO2 + 16 H2O
+ 130 ATP (RQ = 0.71)
Glucose + 2 ADP ----> 2 H+ lactate + 2 ATP (Lactic acid)
H+ lactate- + Na+HCO-3 ---> Na+ lactate- + H2CO3
H2CO3 ---> H2O + CO2
Clinical problem 1
Concerning carbon dioxide production, what is the distinction between aerobic and anaerobic metabolism'?
A common misconception is that respiratory effort during exercise indicates hyperventilation, i.e., low arterial partial pressure of carbon dioxide PaCO2). In fact, PaCO2 is kept remarkably constant during mild to moderate exercise before anaerobic threshold is reached. The constancy of PaCO2 can be explained by the PaCO2 equation (Chapter 4):
During aerobic exercise, carbon dioxide production (VCO2) and alveolar ventilation (VA) increase proportionately, resulting in an unchanged PaCO2 (Fig. 12-1). Only with anaerobic exercise does PaCO2 fall and then only as compensation for the lactic acidosis.
Take a jog around the block but do not push to your limit. After 5 to 10 minutes you will be huffing and puffing, but not hyperventilating.
Clinical problem 2
In the resting steady state, a well-trained jogger has an RQ of 0.8, end-tidal PCO2 of 40 mm Hg, and a minute ventilation of 6 L/min. After 5 minutes on a treadmill at 2.5 mph, the following expired gas measurements are obtained: VCO2 of 800 ml/min, VO2 of 1000 ml/min, end-tidal PCO2 of 39 mm Hg, and minute ventilation of 30 L/min. What are alveolar and arterial PCO2 at this point?
Fig. 12-1. Changes in minute ventilation (VE), alveolar ventilation (VA), metabolic carbon dioxide production (VCO2), and arterial partial pressure of carbon dioxide PaCO2) during exercise. VCO2 represents the total metabolic load of carbon dioxide presented to the lungs for excretion, including carbon dioxide produced from buffering lactic acid. VE, VA, and VCO2 rise proportionately during submaximal exercise, so PaCO2 stays constant. After anaerobic threshold (AT) is reached, VE and VA rise proportionately more than VCO2, so PaCO2 falls; this hyperventilation occurs as compensation for the lactic acidosis.
THE EXERCISE TEST
Exercise testing requires measuring one or more physiologic parameters during a supervised, graded exercise test. Typically these measurements are performed as the patient either walks on a treadmill or cycles on a bicycle ergometer. The test is usually "graded'' in that the work necessary to continue exercising is progressively increased, either by making the treadmill go faster (and raising its angle from the floor) or by increasing the resistance of the bicycle wheel as the subject pedals.
Table 12-1 lists many of the measurements obtained during a physiologic exercise test, grouped according to the equipment required. The first group of measurements can be obtained without a mouthpiece but does require continuous monitoring of the patient's ECG. Included in this group is noninvasive measurement of arterial oxygen saturation (SaO2), which can be accomplished with an ear or finger oximeter (Fig. 12-2).
Working down the list in Table 12-1, each group of measurements becomes progressively more "invasive." Measurements in the second group require the collection of expired gases, which means the subject must keep a mouthpiece in place while exercising. The mouthpiece is connected through hoses to instruments that sample and measure expired oxygen and carbon dioxide; a typical setup is shown in Figures 12-2 and 12-3.
The third group of measurements is obtained from arterial blood and requires an indwelling arterial catheter. Finally, the test can be performed with a right heart catheter in place, a technique that is only rarely necessary.
Obviously, not all the measurements listed in Table 12-1 are recorded in every exercise test; measurements must be tailored to the problem being evaluated. However, the one almost universal measurement is pulse oximetry, discussed further below.
Figure 12-2a. A subject exercising on a treadmill, hooked up for Group 1 and Group 2 measurements (see Table 12-1). The poster of the mountain is preferable to looking at a blank wall.
Figure 12-2b. The same subject, showing mouthpiece in place. All expired air goes through tubing to instruments that continuously measure concentration of expired gases, while SpO2 is measured with a pulse oximeter (on her right index finger). (Click on any image for a larger picture; then hit back key on browser to return to this point).
Figure 12-3. Subject on a bicycle
Apart from measurement of heart rate, probably the most commonly measured exercise variable is oxygen saturation by pulse oximetry (SpO2). This is because exercise oximetry is so widely used to assess need for supplemental oxygen in patients with dyspnea, whether or not they are being considered for exercise training. Such a test may consist of nothing more than walking the patient in the hospital corridor while measuring finger pulse oximetry.
Whatever the purpose for exercising a patient, it is essential to screen for exercise-induced hypoxemia, because it may be the cause of symptoms and is treatable. Above 85% true oxygen saturation, SpO2 is accurate to within about +/- 3% of the blood oxygen saturation as measured with a co-oximeter (SaO2) (Escourrou 1990). However, there are several potential pitfalls to using pulse oximetry for exercise testing, including improper capture of pulse, inaccuracy at very low levels of SaO2, intravenous dyes, skin pigment, and poor signal response. In a review of 10 studies utilizing both ear and finger pulse oximetry during exercise, Mengelkoch, et. al. found that only 67% of the pulse oximeters studied were considered accurate when SaO2 was > 85% in non-smokers (Mengelkoch 1995). However, the current generation of finger pulse oximeters appear to be more accurate than the older ear-probe equipped models (Mengelkoch 1995). It is interesting that most of the studies reviewed used cycle ergometry, since it produces less oximetry artifact than a treadmill.
An avoidable pitfall of pulse oximetry can occur when there is excess carboxyhemoglobin. In contrast to blood co-oximeters, which utilize four wavelengths of light to separate out oxyhemoglobin from reduced hemoglobin, methemoglobin (MetHb) and carboxyhemoglobin (COHb), pulse oximeters utilize only two wavelengths of light (Powers 1989; Principles of Pulse Oximetry 1991). As a result, pulse oximeters measure COHb and part of any MetHb along with oxyhemoglobin, and combine the three into a single reading, the SpO2. (MetHb absorbs both wavelengths of light emitted by pulse oximeters, so that SpO2 is not affected as much by MetHb as for a comparable level of COHb). Powers, et. al. showed that in subjects who smoked and had COHb levels of >4%, pulse oximeters significantly overestimated SaO2 (Powers 1989).
Whereas excess methemoglobin is an uncommon finding clinically, excess carboxy-hemoglobin is present in all cigarette and cigar smokers. A resting SpO2 should be correlated with a measured SaO2 and (if a blood co-oximeter is available), COHb and methemoglobin levels. If the measured SaO2 does not agree with SpO2, the fact should be noted, reason(s) sought, and then accounted for during the exercise test. If a measured SaO2 cannot be correlated with SpO2, exercise testing should not be done in current smokers, so as to avoid falsely high SaO2 readings. (The half-life of CO breathing ambient air is about 6 hours, so 24 hours after smoking cessation the CO level should be normal, i.e., less than 2.5%.)
Carbon monoxide can also be measured in exhaled air as ppm (parts per million) and correlated with a blood carboxyhemoglobin level (e.g., 10 ppm roughly equals 2% COHb). Also, if a co-oximeter is available, carboxyhemoglobin can be reliably measured on a venous blood sample; the value is the same as arterial. If venous COHb is elevated, its value can be subtracted from the SpO2 to get a truer reading of the patient's SaO2. Attention to CO is important if one is to obtain accurate estimation of the patient's blood oxygen status.
PHYSIOLOGIC CHANGES DURING EXERCISE
Fig. 12-4 graphs many of the parameters that can be measured during the graded exercise test (see groups presented in the box on p. 242). The abscissa for each group represents increasing work. i.e., a progressive increase in treadmill speed or in bicycle wheel resistance. Work is usually measured in kilopond-meters (kpm); one kpm is the work required to move a one kilogram mass a vertical distance of one meter against gravity. Work per unit time is power or kpm/min, which is often converted into watts (600 kpm/min is roughly equal to 100 watts). For example, a 70-kg person walking on a treadmill at 3 mph, 5% grade, generates approximately 300 kpm/min or 50 watts of power.
Fig. 12-4. Physiologic changes during exercise. A, Group 1 data. B, Group 2 data; C, Group 3 data; and D, Group 4 data. AT = anaerobic threshold.
In clinical practice, actual work rates are not usually stated. Instead, the exercise test is quantitated in terms of the patient's oxygen uptake (VO2). Normal resting VO2 is approximately 3.5 ml/min/kg. Multiples of resting Vo, are called METS so that 10 METS equal 35 ml/min/kg. The intensity or severity of the exercise test is quantitated in terms of either the absolute oxygen consumption (ml O2/min) or the number of METS.
The parameters listed in the box above and graphed in Fig. 12-4 are discussed in the next section. The values displayed represent typical changes for an adult of average physical fitness. The physiologic changes at anaerobic threshold arc also summarized in this box.
Group 1 measurements
Patient response and symptoms can give valuable information about overall exercise capability. Sometimes the patient is so uncoordinated that the test is invalid. Treadmills and bicycles are foreign to many patients, so the examiner has to make sure the test is at least valid before collecting data.
Common reasons for exercise intolerance are dyspnea, fatigue, leg pain, and chest pain. Leg pain may be a clue to developing lactic acidosis but can also be caused by shoe discomfort or orthopedic problems. Careful questioning can reveal the reason. Any chest pain or discomfort should be correlated with the ECG. If a patient quits because of dyspnea or fatigue, the collected data should reveal whether the problem's origin is cardiac, respiratory, or poor fitness (see section Clinical Interpretation of Physiologic Exercise Testing).
Heart rate rises immediately during exercise and continues to increase linearly along with VO2. VO2 reaches a maximal limit and plateaus because heart rate does so. The predicted maximal heart rate declines with age:
Both diastolic and systolic blood pressures increase with increasing exercise, systolic proportionately much more than diastolic. Mean arterial pressure increases from approximately 90 mm Hg at rest to 140 mm Hg at maximal oxygen consumption.
The electrocardiogram normally shows sinus tachycardia without arrhythmia or abnormal ventricular beats.
Arterial oxygen saturation (SaO2) is unchanged during exercise, reflecting the constant arterial partial pressure of oxygen (PaO2).
Group 2 measurements
Minute ventilation (VE) increases linearly along with VO2 until anaerobic threshold (AT) is reached. At AT, VE rises to compensate for the increase in carbon dioxide production. Normally ventilation does not limit exercise. Maximal ventilation achieved during exercise is usually approximately 65% to 75% of the maximal voluntary ventilation (MVV).(1) At low levels of work, increase in VE is caused mainly by an increase in tidal volume; at high work rates, increases in respiratory rate account for most of the rise in VE.
Normally, end-tidal gas measurements (PetO2 and PetCO2) reflect alveolar gas values; end-tidal partial pressure of oxygen (PetO2) and partial pressure of carbon dioxide (PetCO2) are constant until anaerobic threshold, at which point PetO2 rises and PetCO2 falls.
At rest, oxygen uptake (VO2) is approximately 250 to 300 ml/min or approximately 3.5 ml/min/ kg. VO2 increases during aerobic exercise and is the single best measurement of the total exercise effort. The lower the VO2 for a given amount of work, the more aerobically fit is the person. Thus if two people are doing the same work, e.g., walking on a treadmill at 2 mph for 5 minutes, the one with the lowest oxygen uptake is considered more physically fit.
As work increases, VO2 increases in a linear fashion and eventually plateaus. This plateau, which for a healthy person occurs only after the onset of anaerobic threshold (very heavy exercise), is called the maximal VO2 (VO2 max). The level of exercise (work rate) can increase beyond VO2 max, but the rate of oxygen uptake will remain flat because cardiac output cannot increase further. For a given type of exercise (e.g., bicycle or treadmill), work intensity, and level of training, there is a constant VO2 max for each individual. VO2, max increases as fitness improves (Fig. 12-5). For most adults without cardiopulmonary disease, Vo, max is between 2 and 3 L/min, which is approximately 10 times the resting VO2. World class athletes can reach a VO2 max of over 4 L/min.
The following equations predict VO2 max, in L/min, for men and women (Jones and Campbell,1982):
O2-pulse is VO2/heart rate and is another useful index of fitness. O2-pulse increases with increasing exercise. In healthy patients O2-pulse ranges from 2.5 to 4 ml O2/heart beat at rest to 10 to 15 ml O2/heart beat at maximal exercise. At any given work rate, O2-pulse is higher in the fit person than in the unfit.
Carbon dioxide production increases immediately during exercise. Below AT, the extra carbon dioxide presented to the lungs for excretion comes from food metabolism. Above AT, additional carbon dioxide enters the blood from buffering of lactic acid (see the box on p. 241).
Respiratory quotient (RQ), measured as carbon dioxide elimination over oxygen uptake by the lungs, increases as the AT is approached. On a regular diet, RQ during mild to moderate exercise is approximately 0.85. At AT, RQ goes above 1.0. The rise above 1.0 is caused by the increase in VCO2 compared to VO2, as extra carbon dioxide enters the blood from the buffering of lactic acid, (see box on p. 241). This RQ does not reflect the metabolic exchange of oxygen and carbon dioxide, which cannot go higher than 1.0 (1.0 is the value when only carbohydrates are metabolized).
Group 3 measurements
PaO2 and P(A-a)O2. The alveolar-arterial oxygen pressure difference (P(A-a)O2) does not change at low work levels but increases at AT, caused mainly by an increase in alveolar partial pressure of oxygen (PAO2); generally arterial partial pressure of oxygen (PaO2) stays fairly constant throughout exercise. Part of the increase in PAO2 is caused by hyperventilation after AT is reached. However, at rest an increase in PAO2 would also increase PaO2, and this does not occur during exercise; constant Pao, may be caused by a reduced mixed venous oxygen content counterbalancing the effect of an increased PAO2.
Arterial partial pressure of carbon dioxide (PaCO2) stays remarkably constant below AT. Above AT, PaCO2 and end-tidal PCO2 (PetCO2) normally fall, largely as a result of compensation for the developing lactic acidosis.
Lactate, pH, and HCO3- are fairly constant until AT, at which point lactate increases from the anaerobic metabolism of glucose; also at this point, pH and HCO3- begin to fall as the lactic acid is buffered in the blood.
VD/VT. Calculation of VD/VT (ratio of dead space to tidal volume) requires measurement of both the expired and the arterial PCO2 (see Equation 9, Chapter 4). VD/VT normally falls with exercise. Initially the decrease is rapid as a result of the large increase in tidal volume. As respiratory rate begins to account for most of the increase in the minute ventilation, the decline in VD/VT slows.
Group 4 measurements
Cardiac output may increase severalfold and is the single most important mechanism for satisfying the increased oxygen uptake during exercise. In early exercise the cardiac output increases as a result of both an increase in stroke volume and in the heart rate. Stroke volume plateaus early so that further increases are caused by the heart rate.
Pulmonary artery pressures rise only slightly during exercise despite the enormous increase in cardiac output sent through the pulmonary circulation. Mixed venous PO2 and oxygen saturation fall because of increased oxygen extraction by the exercising tissues.
In any state of impaired exercise tolerance, one or more of the previous physiologic parameters are abnormal, either its absolute value or its value relative to the work rate achieved. For example, a cardiac patient might produce lactic acid after walking only 2 minutes at I mph a work rate well below the normal anaerobic threshold.
NORMAL EXERCISE PARAMETERS
Like most effort-dependent tests, there is a wide range of normal values for exercise testing. Care should be taken to use the normal values appropriate to the patient being studied, particularly regarding age and sex. Table 12-2 shows normal values for a group of 77 healthy middle-aged men who were evaluated because of a history of asbestos exposure (Hansen, Sue, and Wasserman, 1984). These men had no evident cardiopulmonary disease (except for pleural thickening evidenced on chest x-ray in some subjects) and were considered representative of middle-aged men in general. All had normal resting pulmonary function tests.