Integrative Physiology III: Exercise

Transcription

1 Integrative Physiology III: Metabolism and Hormones Regulate Metabolism During Oxygen Consumption Is Related to Intensity Several Factors Limit Ventilatory Responses to Cardiovascular Responses to Cardiac Output Increases During Muscle Blood Flow Increases During Blood Pressure Rises Slightly During The Baroreceptor Reflex Adjusts to Feedforward Responses to Temperature Regulation During One fascinating aspect of the physiology of the human being at work is that it provides basic information about the nature and the range of the functional capacity of different organ systems. and Health Lowers the Risk of Cardiovascular Disease Type 2 Diabetes Mellitus May Improve with Stress and the Immune System May Be Influenced by Per-Olof Åstrand and Kaare Rodahl, Textbook of Work Physiology, 1977 Background Basics Aerobic and anaerobic metabolism Feedforward reflexes Muscle metabolism Isometric and isotonic contraction Control of heart rate and contractility Control of blood pressure Local control of blood flow Alveolar ventilation Respiratory chemoreceptors Dehydration Insulin Thermoregulation Each dot of a microarray represents one gene. Genes that are active show up in bright colors. From Chapter of Human Physiology: An Integrated Approach, Sixth Edition. Dee Unglaub Silverthorn. Copyright 2013 by Pearson Education, Inc. All rights reserved. 883

2 Integrative Physiology III: In July 2008 the world watched with great anticipation as Michael Phelps swam his way to a record eight gold medals at the 2008 Olympics. The work done by Phelps and the hundreds of other Olympic athletes from around the world represents one of the most common challenges to body homeostasis: exercise. comes in many forms. Distance running, swimming, and cycling are examples of a dynamic endurance exercise. Weight lifting and strength training are examples of resistance training. In this chapter we examine dynamic exercise as a challenge to homeostasis that is met with an integrated response from multiple body systems. In many ways, exercise is the ideal example for teaching physiological integration. Everyone is familiar with it, and unlike high-altitude mountaineering or deep-sea diving, it involves no special environmental conditions. Moreover, exercise is a normal physiological state, not a pathological one although it can be affected by disease and (if excessive) can result in injury. In addition to being an excellent teaching example, exercise physiology is a very active area of integrative physiology research. The coordinated functioning of multiple body systems is still not well understood in many instances because of complex interactions between neural and local control mechanisms. Researchers use a combination of animal models and studies with human subjects, including elite athletes, in their quest to explain how the body adapts to the metabolic demands of exercise. Note that this chapter is not intended to be a complete discussion of exercise physiology. For further information, readers should consult an exercise physiology textbook. Metabolism and begins with skeletal muscle contraction, an active process that requires ATP for energy. But where does the ATP for muscle contraction come from? A small amount is in the muscle RUNNING PROBLEM Heat Stroke Dangerous heat continues for fifth straight day, reads the morning headline. Had Colleen, 19, taken time to scan the story, she might have avoided the life-threatening health emergency she faced a few hours later. But Colleen overslept and rushed off to field hockey practice. The weather this week had been unbearably hot and humid, just as it had been all summer. The forecast today was for a high of 105 F, with high humidity. In her haste, Colleen forgot her water bottle. No big deal, she thought as she hopped on her bike to pedal two miles to the practice field. fiber when contraction begins ( Fig..1 4 ). As this ATP is used for muscle contraction and transformed into ADP, another phosphate compound, phosphocreatine (PCr), transfers energy from its high-energy phosphate bond to ADP. The transfer replenishes the muscle s supply of ATP. Together, the combination of muscle ATP and phosphocreatine is adequate to support only about 15 seconds of intense exercise, such as sprinting or power lifting. Subsequently, muscle fibers must manufacture additional ATP from energy stored in nutrients. Some of these molecules are contained within the muscle fiber itself. Others must be mobilized from the liver and adipose tissue and then transported to muscles through the circulation. Th e primary substrates for energy production are carbohydrates and fats. The most efficient production of ATP occurs through aerobic pathways such as the glycolysis-citric acid cycle pathway. If the cell has adequate amounts of oxygen for oxidative phosphorylation, then both glucose and fatty acids can be metabolized to provide ATP ( Fig..1 1, 2 ). If the oxygen requirement of a muscle fiber exceeds its oxygen supply, energy production from fatty acids decreases dramatically, and glucose metabolism shifts to anaerobic pathways. In low-oxygen conditions, when the cell lacks oxygen for oxidative phosphorylation, the final product of glycolysis pyruvate is converted to lactate instead of being converted to acetyl CoA and entering the citric acid cycle. In general, exercise that depends on anaerobic metabolism cannot be sustained for an extended period. Cells that obtain their ATP by anaerobic metabolism of glucose to lactate are said to be carrying out glycolytic metabolism. Anaerobic metabolism has the advantage of speed, producing ATP 2.5 times as rapidly as aerobic pathways do ( Fig..2 ). But this advantage comes with two distinct disadvantages: (1) anaerobic metabolism provides only 2 ATP per glucose, compared with an average of ATP per glucose for oxidative metabolism, and (2) anaerobic metabolism contributes to a state of metabolic acidosis by producing H +. (However, the CO 2 generated during exercise is a more significant source of acid.) Where does glucose for aerobic and anaerobic ATP production come from? The body has three sources: the plasma glucose pool, intracellular stores of glycogen in muscles and liver, and new glucose made in the liver through gluconeogenesis. Muscle and liver glycogen stores provide enough energy substrate to release about 2000 kcal (equivalent to about 20 miles of running in the average person), more than adequate for the exercise that most of us do. However, glucose alone cannot provide sufficient ATP for endurance athletes such as marathon runners. To meet their energy demands, they rely on the energy stored in fats. In reality, aerobic exercise of any duration uses both fatty acids and glucose as substrates for ATP production. About 30 minutes after aerobic exercise begins, the concentration of free fatty acids in the blood increases significantly, indicating 884

3 Integrative Physiology III: OVERVIEW OF MUSCLE METABOLISM ATP for muscle contraction is continuously produced by aerobic metabolism of glucose and fatty acids. During short bursts of activity, when ATP demand exceeds the rate of aerobic ATP production, aerobic glycolysis produces ATP, lactate, and H +. Intestine Liver Lungs Amino acids Adipose tissue Glucose absorbed Liver glycogen Glucose Pyruvate Lactate Glycerol + fatty acids Lipids stored in adipose tissue Gas exchange at the lungs: O 2 1 Blood Glucose Lactate Fatty acids 2 O 2 CO 2 Muscle tissue Lactate Fatty acids Triglycerides Glycogen Rest 3 Glycolysis (anaerobic) Pyruvate Acetyl CoA Oxidative phosphorylation and citric acid cycle (aerobic) 4 Contraction ADP + P i ATP + creatine ~ Rest Creatine P (PCr) + ADP Contraction Myosin ATPase Ca-ATPase Relaxation CO 2 1 Glucose comes 2 Fatty acids can be 3 Lactate from anaerobic 4 from liver glycogen used only in aerobic metabolism can be converted or dietary intake. metabolism. to glucose by the liver. Both aerobic and anaerobic metabolism provide ATP for muscle contraction. Fig..1 AEROBIC VERSUS ANAEROBIC METABOLISM Anaerobic metabolism produces ATP 2.5 times faster than aerobic metabolism, but aerobic metabolism can support exercise for hours. 4 Hours KEY ATP produced (moles/min) 3 2 Endurance time for maximal muscle activity ATP production Muscle endurance 1 1 min Phosphocreatine can sustain only 10 seconds of maximal exercise. Anaerobic metabolism produces ATP 2.5 times faster than aerobic metabolism but can support only 1 minute of maximal exercise. Aerobic metabolism supports exercise for hours. Fig

4 Percent substrate used by muscle Integrative Physiology III: that fats are being mobilized from adipose tissue. However, the breakdown of fatty acids through the process of b-oxidation is slower than glucose metabolism through glycolysis, so muscle fibers use a combination of fatty acids and glucose to meet their energy needs. At lower exercise intensities, most of the energy for ATP production comes from fats ( Fig..3 ), which is one reason walking is a good way to lose weight. As exercise intensity increases and ATP is consumed more rapidly, the muscle fibers begin to use a larger proportion of glucose. When exercise exceeds about 70% of maximum, carbohydrates become the primary source of energy. Aerobic training increases both fat and glycogen stores within muscle fibers. Endurance training also increases the activity of enzymes for b -oxidation and converts muscle fibers from fast-twitch glycolytic to fast-twitch oxidative-glycolytic. Hormones Regulate Metabolism During Several hormones that affect glucose and fat metabolism change their pattern of secretion during exercise. Plasma concentrations of glucagon, cortisol, the catecholamines (epinephrine and norepinephrine), and growth hormone all increase during exercise. Cortisol and the catecholamines, along with growth hormone, promote the conversion of triglycerides to glycerol and fatty acids. Glucagon, catecholamines, and cortisol also mobilize liver glycogen and raise plasma glucose levels. A hormonal environment that favors the conversion of glycogen into glucose is desirable, because glucose is a major energy substrate for exercising muscle. ENERGY SUBSTRATE USE DURING EXERCISE At low-intensity exercise, muscles get more energy from fats than from glucose (CHO). During high-intensity exercise (levels greater than 70% of maximum), glucose becomes the main energy source. 100% 80% 60% 40% 20% Fat CHO 0% Rest intensity (% maximum) Data from G. A. Brooks and J. Mercier, J App Physiol 76: , 1994 Fig..3 RUNNING PROBLEM By the time Colleen reached the practice field, she was already sweating and her face was flushed. At 9:00 A.M. the air temperature was 80 F and the humidity was 54%. Colleen took a quick drink of water from the large water container and ran out to the field. Q1: Humidity is the percentage of water vapor present in air. Why is the thermoregulatory mechanism of sweating less efficient in humid environments? Curiously, although plasma glucose concentrations rise with exercise, the secretion of insulin decreases. This response is contrary to what you might predict, because normally an increase in plasma glucose stimulates insulin release. During exercise, however, insulin secretion is suppressed, probably by sympathetic input onto the beta cells of the pancreas. What could be the advantage of lower insulin levels during exercise? For one thing, less insulin means that cells other than muscle fibers reduce their glucose uptake, sparing blood glucose for use by muscles. Actively contracting muscle cells, on the other hand, are not affected by low levels of insulin because they do not require insulin for glucose uptake. Contraction stimulates the insulin-independent translocation of GLUT4 transporters to the muscle membrane, increasing glucose uptake in proportion to contractile activity. Oxygen Consumption Is Related to Intensity Th e activities we call exercise range widely in intensity and duration, from the rapid and relatively brief burst of energy exerted by a sprinter or power lifter, to the sustained effort of a marathoner. Physiologists traditionally quantify the intensity of a period of exercise by measuring oxygen consumption 1V O2 2. Oxygen consumption refers to the fact that oxygen is used up, or consumed, during oxidative phosphorylation, when it combines with hydrogen in the mitochondria to form water. Oxygen consumption is a measure of cellular respiration and is usually measured in liters of oxygen consumed per minute. A person s maximal rate of oxygen consumption 1V O2 max2 i s an indicator of the ability to perform endurance exercise. The greater the V O2 max, the greater the person s predicted ability to do work. A metabolic hallmark of exercise is an increase in oxygen consumption that persists even after the activity ceases ( Fig..4 ). When exercise begins, oxygen consumption 886

5 Integrative Physiology III: O 2 consumption (L/min) OXYGEN CONSUMPTION AND EXERCISE Oxygen supply to exercising cells lags behind energy use, creating an oxygen deficit. Excess postexercise oxygen consumption compensates for the oxygen deficit Fig..4 Cellular energy use exceeds oxygen uptake (oxygen deficit) Resting level of O 2 consumption increases so rapidly that it is not immediately matched by the oxygen supplied to the muscles. During this lag time, ATP is provided by muscle ATP reserves, phosphocreatine, and aerobic metabolism supported by oxygen stored on muscle myoglobin and blood hemoglobin. The use of these muscle stores creates an oxygen deficit because their replacement requires aerobic metabolism and oxygen uptake. Once exercise stops, oxygen consumption is slow to resume its resting level. The excess postexercise oxygen consumption (EPOC; formerly called the oxygen debt) represents oxygen being used to metabolize lactate, restore ATP and phosphocreatine levels, and replenish the oxygen bound to myoglobin. Other factors that play a role in elevating postexercise oxygen consumption include increased body temperature and circulating catecholamines. Several Factors Limit Excess postexercise oxygen consumption Time (min) begins ends What factors limit a person s exercise capacity? To some extent, the answer depends on the type of exercise. Resistance training such as strength training depends heavily on anaerobic metabolism to meet energy needs. The situation is more complex with aerobic or endurance exercise. Is the limiting factor for aerobic exercise the ability of the exercising muscle to use oxygen efficiently? Or is it the ability of the cardiovascular system to deliver oxygen to the tissues? Or the ability of the respiratory system to provide oxygen to the blood? One possible limiting factor in exercise is the ability of muscle fibers to obtain and use oxygen. If muscle mitochondria are limited in number, or if they have insufficient oxygen supply, the muscle fibers are unable to produce ATP rapidly. Data suggest that muscle metabolism is not the limiting factor for maximum exercise capacity, but muscle metabolism has been shown to influence submaximal exercise capacity. This finding explains the increase in numbers of muscle mitochondria and capillaries with endurance training. The question of whether the pulmonary system or the cardiovascular system limits maximal exercise was resolved when research showed that ventilation is only 65% of its maximum when cardiac output has reached 90% of its maximum. From that information, exercise physiologists concluded that the ability of the cardiovascular system to deliver oxygen and nutrients to the muscle at a rate that supports aerobic metabolism is a major factor in determining maximum oxygen consumption. One goal of training is to improve cardiac efficiency. Next we examine the reflexes that integrate breathing and cardiovascular function during exercise. Ventilatory Responses to Think about what happens to your breathing when you exercise. is associated with both increased rate and increased depth of breathing, resulting in enhanced alveolar ventilation. hyperventilation, or hyperpnea, results from a combination of feedforward signals from central command neurons in the motor cortex and sensory feedback from peripheral receptors. When exercise begins, mechanoreceptors and proprioreceptors in muscles and joints send information about movement to the motor cortex. Descending pathways from the motor cortex to the respiratory control center of the medulla oblongata then immediately increase ventilation ( Fig..5 ). VENTILATION AND EXERCISE Ventilation rate jumps as soon as exercise begins, despite the fact that neither arterial P CO2 nor P O2 has changed. This suggests there is a feedforward component to the ventilatory response. Ventilation (L/min) begins Time (min) ends Modified from P. Dejours, Handbook of Physiology (Washington, D.C.: American Physiological Society, 1964). Fig

6 Integrative Physiology III: As muscle contraction continues, sensory information feeds back to the respiratory control center to ensure that ventilation and tissue oxygen use remain closely matched. Sensory receptors involved in the secondary response probably include central, carotid, and aortic chemoreceptors that monitor P CO2, ph, and P O2 ; proprioceptors in the joints; and possibly receptors located within the exercising muscle itself. Pulmonary stretch receptors were once thought to play a role, but recipients of heart-lung transplants display a normal ventilatory response to exercise even though the neural connections between lung and brain are absent. hyperventilation maintains nearly normal arterial P O2 a n d P CO2 by steadily increasing alveolar ventilation in proportion to the level of exercise. The compensation is so effective that when arterial P O2, P CO2, and ph are monitored during mild to moderate exercise, they show no significant change ( Fig..6 ). This observation means that the once- accepted causes of increased ventilation during mild to moderate exercise reduced arterial P O2, e l e v at e d a r t e r i a l P CO2, a n d d e - creased plasma ph must not be correct. Instead the chemoreceptors or medullary respiratory control center, or both, must be responding to other exercise-induced signals. Several factors have been postulated to be these signals, including sympathetic input to the carotid body and changes in plasma K + concentration. During even mild exercise, extracellular K + increases as repeated action potentials in the muscle fibers allow K + to move out of cells. Carotid chemoreceptors are known to respond to increased K + by increasing ventilation. However, because K + concentration changes slowly, this mechanism does not explain the sharp initial rise in ventilation at the onset of activity. It appears likely that the initial increase in ventilation is caused by sensory input from muscle mechanoreceptors combined with parallel descending pathways from the motor cortex to the respiratory control centers. Once exercise is under way, sensory input keeps ventilation matched to metabolic needs. BLOOD GASES AND EXERCISE Arterial blood gases and ph remain steady with submaximal exercise. Gas partial pressure (mm Hg) ph O 2 consumption (% of maximum) FIGURE QUESTIONS Arterial P O2 Arterial ph Venous P O2 Ventilation Arterial P CO2 Adapted from P. O. Astrand, et al. Textbook of Work Physiology, 4th ed. New York: McGraw Hill, Fig Ventilation increases with exercise. Why doesn't arterial P O increase as well? 2 2. What happens to O 2 delivery to cells with increasing exercise? 3. Why does venous P O 2 decrease? 4. Why doesn't arterial P CO2 increase with exercise? 5. Why does arterial P CO2 decrease with maximum exercise? Total pulmonary ventilation (L/min) Concept Check Answers: End of Chapter 1. If venous P O decreases as exercise intensity increases, what do you 2 know about the P O of muscle cells as exercise intensity increases? 2 Cardiovascular Responses to When exercise begins, mechanosensory input from working limbs combines with descending pathways from the motor cortex to activate the cardiovascular control center in the medulla oblongata. The center responds with sympathetic discharge that increases cardiac output and causes vasoconstriction in many peripheral arterioles. Cardiac Output Increases During During strenuous exercise, cardiac output rises dramatically. In untrained individuals, cardiac output goes up fourfold, from 5 L>min to 20 L>min. In trained athletes, it may go up six to eight times, reaching as much as 40 L>min. Because oxygen delivery by the cardiovascular system is the primary factor determining exercise tolerance, trained athletes are therefore capable of more strenuous exercise than untrained people. Cardiac output is determined by heart rate and stroke volume: Cardiac output (CO) = heart rate * stroke volume 888

7 Integrative Physiology III: If the factors that influence heart rate and stroke volume are considered, then C O = (SA node rate + autonomic nervous system input) * (venous return + force of contraction) Which of these factors has the greatest effect on cardiac output during exercise in a healthy heart? Venous return is enhanced by skeletal muscle contraction and deep inspiratory movements during exericse, so it is tempting to postulate that the cardiac muscle fibers simply stretch in response to increased venous return, thereby increasing contractility. However, overfilling of the ventricles is potentially dangerous, because overstretching may damage the fibers. One factor that counters increased venous return is increased heart rate. If the interval between contractions is shorter, the heart has less time to fill and is less likely to be damaged by excessive stretch. Th e initial change in heart rate at the onset of exercise is due to decreased parasympathetic activity at the sinoatrial (SA) node. As cholinergic inhibition lessens, heart rate rises from its resting rate to around 100 beats per minute, the intrinsic pacemaker rate of the SA node. At that point, sympathetic output from the cardiovascular control center escalates. Sympathetic stimulation has two effects on the heart. First, it increases contractility so that the heart squeezes out more blood per stroke (increased stroke volume). Second, sympathetic innervation increases heart rate so that the heart has less time to relax, protecting it from overfilling. In short, the combination of faster heart rate and greater stroke volume increases cardiac output during exercise. Muscle Blood Flow Increases During At rest, skeletal muscles receive less than a fourth of the cardiac output, or about 1.2 L>min. During exercise, a significant shift in peripheral blood flow takes place because of local and reflex reactions ( Fig..7 ). During strenuous exercise in highly trained athletes, the combination of increased cardiac output and vasodilation can increase blood flow through DISTRIBUTION OF BLOOD FLOW DURING EXERCISE Blood flow is distributed differently at rest than during exercise. Vasoconstriction in nonexercising tissuses combined with vasodilation in exercising muscle shunts blood to muscles. CARDIAC OUTPUT AT REST 5.8 L/min CARDIAC OUTPUT DURING VIGOROUS EXERCISE.6 L/min Brain 13% Brain 3% Cardiac output = 5.8 L/min Cardiac output =.6 L/min 4% 4% Kidney 19% Kidney 1% GI 24% GI 1% Skin 9% Skin 2.5% Other tissues 10% Other tissues 0.5% Skeletal muscles 21% Skeletal muscles 88% FIGURE QUESTION The percentage of cardiac output to all tissues except muscle falls with exercise. In which tissues does actual blood flow decrease? Fig

8 Integrative Physiology III: RUNNING PROBLEM By 10:00 A.M. the temperature had risen to 93 F, with 50% humidity. Colleen felt dizzy and nauseated, but she pressed on. She had made the team by the skin of her teeth and felt she had to prove herself to her teammates. She took only a short drink of water during a break and hustled back onto the field. At 10:07 A.M. Colleen collapsed on the field. One of her teammates with training in first aid felt Colleen s skin. It was hot and dry. A call went in to emergency medical services. Q2: Individuals with a heat emergency called heat exhaustion have cool, moist skin. Hot, dry skin indicates a more serious emergency called heat stroke. Why is heat exhaustion less serious than heat stroke? (Hint: How does skin temperature relate to the body s ability to regulate body temperature?) exercising muscle to more than 22 L>min! The relative distribution of blood flow to tissues also shifts. About 88% of cardiac output is diverted to the exercising muscle, up from 21% at rest. The redistribution of blood flow during exercise results from a combination of vasodilation in skeletal muscle arterioles and vasoconstriction in other tissues. At the onset of exercise, sympathetic signals from the cardiovascular control center cause vasoconstriction in peripheral tissues. As muscles become active, changes in the microenvironment of muscle tissue take place: tissue O 2 concentrations decrease, while temperature, CO 2, and acid in the interstitial fluid around muscle fibers increase. All these factors act as paracrines causing local vasodilation that overrides the sympathetic signal for vasoconstriction. The net result is shunting of blood flow from inactive tissues to the exercising muscles, where it is needed. Blood Pressure Rises Slightly During What happens to blood pressure during exercise? Peripheral blood pressure is determined by a combination of cardiac output and peripheral resistance: Mean arterial blood pressure = cardiac output * peripheral resistance Cardiac output increases during exercise, thereby contributing to increased blood pressure. The changes resulting from peripheral resistance are harder to predict, however, because some peripheral arterioles are constricting while others are dilating. Skeletal muscle vasodilation decreases peripheral resistance to blood flow. At the same time, sympathetically induced vasoconstriction in nonexercising tissues offsets the vasodilation, but only partially. Consequently, total peripheral resistance to blood flow falls dramatically as exercise commences, reaching a minimum at about 75% of V O2 max ( Fig..8 a). If no other compensation occurred, this decrease in peripheral resistance would dramatically lower arterial blood pressure. However, increased cardiac output cancels out decreased peripheral resistance. When blood pressure is monitored during exercise, mean arterial blood pressure actually increases slightly BLOOD PRESSURE AND EXERCISE (a) Peripheral resistance decreases due to vasodilation in exercising muscle. (b) Mean arterial blood pressure rises slightly despite drop in resistance. Peripheral resistance (mm Hg/L/min) GRAPH QUESTION If peripheral resistance falls as exercise intensity increases, but peripheral blood pressure rises only slightly, what must be happening to cardiac output? Arterial pressure (mm Hg) Systolic Mean Diastolic % VO 2max % VO 2max Fig

9 Integrative Physiology III: as exercise intensity increases ( Fig..8 b). The fact that it increases at all, however, suggests that the normal baroreceptor reflexes that control blood pressure are functioning differently during exercise. Concept Check Answers: End of Chapter 2. In Figure.8 b, why does the line for mean blood pressure lie closer to diastolic pressure instead of being evenly centered between systolic and diastolic pressures? ( Hint: What is the equation for calculating mean blood pressure?) The Baroreceptor Reflex Adjusts to Normally, homeostasis of blood pressure is regulated through peripheral baroreceptors in the carotid and aortic bodies: an increase in blood pressure initiates responses that return blood pressure to normal. But during exercise, blood pressure increases without activating homeostatic compensation. What happens to the normal baroreceptor reflex during exercise? Th ere are several theories. According to one, signals from the motor cortex during exercise reset the arterial baroreceptor threshold to a higher pressure. Blood pressure can then increase slightly during exercise without triggering the homeostatic counter-regulatory responses. Another theory suggests that signals in baroreceptor afferent neurons are blocked in the spinal cord by presynaptic inhibition at some point before the afferent neurons synapse with central nervous system neurons. This central inhibition inactivates the baroreceptor reflex during exercise. A third theory is based on the postulated existence of muscle chemoreceptors that are sensitive to metabolites (probably H + ) produced during strenuous exercise. When stimulated, these chemoreceptors signal the CNS that tissue blood flow is not adequate to remove muscle metabolites or keep the muscle in aerobic metabolism. The chemoreceptor input is reinforced by sensory input from mechanoreceptors in the working limbs. The CNS response to this sensory input is to override the baroreceptor reflex and raise blood pressure to enhance muscle perfusion. The same hypothetical muscle chemoreceptors may play a role in ventilatory responses to exercise. RUNNING PROBLEM While they waited for the ambulance, Colleen s coaches began to try to cool her down by misting her with cool water and using a fan to blow air across her body. When the paramedics reached Colleen on the field, they took her blood pressure, and it was extremely low. Her body temperature was 104 F. The paramedics rushed Colleen to the hospital. Q3: Why was Colleen s blood pressure so low? Q4: Why would misting and fanning help lower Colleen s body temperature? experience, ventilation rates jump as soon as exercise begins ( Fig..5 ), even though experiments have shown that arterial P O2 and P CO2 do not change (Fig..6 ). How does the feedforward response work? One model says that as exercise begins, proprioceptors in the muscles and joints send information to the motor cortex of the brain. Descending signals from the motor cortex go not only to the exercising muscles but also along parallel pathways to the cardiovascular and respiratory control centers and to the limbic system of the brain. Output from the limbic system and cardiovascular control center triggers generalized sympathetic discharge. As a result, an immediate slight increase in blood pressure marks the beginning of exercise. Sympathetic discharge causes widespread vasoconstriction, increasing blood pressure. Once exercise has begun, this increase in blood pressure compensates for decreases in blood pressure resulting from muscle vasodilation. As exercise proceeds, reactive compensations become superimposed on the feedforward changes. For example, when exercise reaches 50% of aerobic capacity, muscle chemoreceptors detect the buildup of H +, lactate, and other metabolites, and send this information to central command centers in the brain. The command centers then maintain changes in ventilation and circulation that were initiated in a feedforward manner. Thus, the integration of systems in exercise probably involves both common reflex pathways and some unique centrally mediated reflex pathways. Feedforward Responses to Interestingly, there is a significant feedforward element in the physiological responses to exercise. It is easy to explain physiological changes that occur with exercise as reactions to the disruption of homeostasis. However, many of these changes occur in the absence of the normal stimuli or before the stimuli are present. For example, as you may know from your own Temperature Regulation During As exercise continues, heat released through metabolism creates an additional challenge to homeostasis. Most of the energy released during metabolism is not converted into ATP but instead is released as heat. (Efficiency of energy conversion from 891

10 Integrative Physiology III: organic substrates to ATP is only 20 %.) With continued exercise, heat production exceeds heat loss, and core body temperature rises. In endurance events, body temperature can reach C ( F), which we would normally consider a fever. Th is rise in body temperature during exercise triggers two thermoregulatory mechanisms: sweating and increased cutaneous blood flow. Both mechanisms help regulate body temperature, but both can also disrupt homeostasis in other ways. While sweating lowers body temperature through evaporative cooling, the loss of fluid from the extracellular compartment can cause dehydration and significantly reduce circulating blood volume. Because sweat is a hypotonic fluid, the extra water loss increases body osmolarity. The combination of decreased ECF volume and increased osmolarity during extended exercise sets in motion the complex homeostatic pathways for overcoming dehydration, including thirst and renal conservation of water. The other thermoregulatory mechanism increased blood flow to the skin causes body heat loss to the environment through convection. However, increased sympathetic output during exercise tends to vasoconstrict cutaneous blood vessels, which opposes the thermoregulatory response. The primary control of vasodilation in hairy regions of skin, such as trunk and limbs, during exercise appears to come from a sympathetic vasodilator system. Activation of these acetylcholine-secreting sympathetic neurons as body core temperature rises dilates some cutaneous blood vessels without altering sympathetic vasoconstriction in other body tissues. Although cutaneous vasodilation is essential for thermoregulation, it can disrupt homeostasis by decreasing peripheral resistance and diverting blood flow from the muscles. In the face of these contradictory demands, the body initially gives preference to thermoregulation. However, if central venous pressure falls below a critical minimum, the body abandons thermoregulation in the interest of maintaining blood flow to the brain. The degree to which the body can adjust to both demands depends on the type of exercise being performed and its intensity and duration. Strenuous exercise in hot, humid environments can severely impair normal thermoregulatory mechanisms and cause heat stroke, a potentially fatal condition. Unless prompt measures are taken to cool the body, core temperatures can go as high as 43 C (109 F). It is possible for the body to adapt to repeated exercise in hot environments, however, through acclimatization. In this process, physiological mechanisms shift to fit a change in environmental conditions. As the body adjusts to exercise in the heat, sweating begins sooner and doubles or triples in volume, enhancing evaporative cooling. With acclimatization, sweat also becomes more dilute, as salt is reabsorbed from the sweat glands under the influence of increased aldosterone. Salt loss in an unacclimatized person exercising in the heat may reach 30 g NaCl per day, but that value decreases to as little as 3 g after a month of acclimatization. Concept Check and Health Physical activity has many positive effects on the human body. The lifestyles of humans have changed dramatically since we were hunter-gatherers, but our bodies still seem to work best with a certain level of physical activity. Several common pathological conditions including high blood pressure, strokes, and diabetes mellitus can be improved by physical activity. Even so, developing regular exercise habits is one lifestyle change that many people find difficult to make. In this section we look at the effects exercise has on several common health conditions. Lowers the Risk of Cardiovascular Disease Answers: End of Chapter 3. The active vasodilator nerves to the skin secrete ACh but are classified as sympathetic neurons. On what basis were they identified as sympathetic? As early as the 1950s, scientists showed that physically active men have a lower rate of heart attacks than do men who lead sedentary lives. These studies started many investigations into the exact relationship between cardiovascular disease and exercise. Scientists have subsequently demonstrated that exercise has positive benefits for both men and women. These benefits include lowering blood pressure, decreasing plasma triglyceride levels, and raising plasma HDL-cholesterol levels. High blood pressure is a major risk factor for strokes, and elevated triglycerides and low HDL-cholesterol levels are associated with development of atherosclerosis and increased risk of heart attack. Overall, exercise reduces the risk of death or illness from a variety of cardiovascular diseases, although the exact mechanisms by which this occurs are still unclear. Even such mild exercise as walking has significant health benefits that could RUNNING PROBLEM When Colleen arrived in the emergency room, she was quickly diagnosed with heat stroke, a life-threatening condition. She was immersed in a tub of cool water and given intravenous fluids. Q5: What steps should Colleen have taken to avoid heat stroke? (Start at 9:00 A.M., when Colleen set out for the practice field.) 892

11 Integrative Physiology III: reduce the risk of developing cardiovascular diseases or diabetes and the complications of obesity in the estimated 40 million adult Americans with sedentary lifestyles. Type 2 Diabetes Mellitus May Improve with Regular exercise is now widely accepted as effective in preventing and alleviating type 2 diabetes mellitus and its complications, including microvascular retinopathy, diabetic neuropathy, and cardiovascular disease. With regular exercise, skeletal muscle fibers up-regulate both the number of GLUT4 glucose transporters and the number of insulin receptors on their membrane. The addition of insulin-independent GLUT4 transporters decreases the muscle s dependence on insulin for glucose uptake. Glucose uptake into the exercising muscle also helps correct the hyperglycemia of diabetes. Up-regulation of insulin receptors with exercise makes the muscle fibers more sensitive to insulin. A smaller amount of insulin then can achieve a response that previously required more insulin. Because the cells are responding to lower insulin levels, the endocrine pancreas secretes less insulin. This lessens the stress on the pancreas, resulting in a lower incidence of type 2 diabetes mellitus. Figure.9 shows the effects of seven days of exercise on glucose utilization and insulin secretion in men with mild type 2 diabetes. Individuals in the experiment underwent glucose tolerance tests, in which they ingested 100 g of glucose after an overnight fast. Their plasma glucose levels were assessed before and for 120 minutes after ingesting the glucose. Simultaneous measurements were made of plasma insulin. The graph in Figure.9 a shows glucose tolerance tests in control subjects (blue line) and in the diabetic men before and after exercise (red and green lines, respectively). Figure.9 b shows concurrent insulin secretion in the three groups. After only seven days of exercise, both the glucose tolerance test and insulin secretion in exercising diabetic subjects had shifted to a pattern that was more like that of the normal control subjects. These results demonstrate the beneficial effect of exercise on glucose transport and metabolism, and support the recommendation that patients with type 2 diabetes maintain a regular exercise program. Stress and the Immune System May Be Influenced by Another health-related topic receiving much attention is the interaction of exercise with the immune system, and exercise immunology has become a recognized scientific discipline. EXERCISE IMPROVES GLUCOSE TOLERANCE AND INSULIN SECRETION The experiments tested normal men (blue line), men with type 2 diabetes who had not been exercising (red line), and those same diabetic men after seven days of exercise (green line). KEY Normal controls Type 2 diabetes, no exercise Type 2 diabetes, after 7 days of exercise (a) Plasma glucose during glucose tolerance test (b) Plasma insulin during glucose tolerance test 0 No exercise Plasma glucose (mg/dl) Control Plasma insulin (μunits/ml) No exercise Control 0 Ingest glucose Time (min) Ingest glucose Time (min) Data from B. R. Seals, et al., J App Physiol 56(6): , 1984; and M. A. Rogers, et al., Diabetes Care 11: , Fig

12 Integrative Physiology III: Epidemiological studies looking at large populations of people suggest that exercise is associated with a reduced incidence of disease and with increased longevity. Moreover, many people believe that exercise boosts immunity, prevents cancer, and helps HIV-infected patients combat AIDS. However, there are few rigidly controlled research studies providing evidence to support those viewpoints. Indeed, other evidence suggests that strenuous exercise is a form of stress that suppresses the immune response. Immune suppression may be due to corticosteroid release, or it may be due to release of interferon- g during strenuous exercise. Researchers have proposed that the relationship between exercise and immunity can be represented by a J-shaped curve ( Fig..10 ). People who exercise moderately have slightly more effective immune systems than those who are sedentary, but people who exercise strenuously may experience a decrease in immune function because of the stress of the exercise. Another area of exercise physiology filled with interesting though contradictory results is the effect of exercise on stress, depression, and other psychological parameters. Research has shown an inverse relationship between exercise and depression: people who exercise regularly are significantly less likely to be clinically depressed than are people who do not exercise regularly. Although the association exists, assigning cause and effect to the two parameters is difficult. Are the exercisers less depressed because they exercise? Or do depressed individuals exercise less because they are depressed? What physiological factors are involved? Many published studies appear to show that regular exercise is effective in reducing depression. But a careful analysis of experimental design suggests that the conclusions of some of those studies may be overstated. The subjects in many of the experiments were being treated concurrently with drugs or psychotherapy, so it is difficult to attribute improvement in their condition solely to exercise. In addition, participation in IMMUNE FUNCTION AND EXERCISE Individuals who exercise in moderation have fewer upper respiratory infections (URIs) than sedentary individuals or those who exercise strenously. % incidence of URIs Moderate exercise enhances immunity, but strenuous exercise is a form of stress that depresses immunity. Sedentary Fig..10 Moderate intensity Strenuous exercise studies gives subjects a period of social interaction, another factor that might play a role in the reduction of stress and depression. The assertion that exercise reduces depression has support from studies showing that exercise increases serotonin in the brain. Drugs that enhance serotonin activity, such as the selective serotonin reuptake inhibitors, are currently being used to treat depression, and a way to achieve the same result without drugs would be desirable. A number of clinical trials that look at exercise effects on depression and health are currently underway. RUNNING PROBLEM CONCLUSION Heat Stroke After a day of treatment, Colleen recovered enough to be sent home. She was unable to practice with the team for the remainder of the season because victims of heat stroke are more sensitive to high temperature for some time after the episode. Heat stroke can occur in athletes who overexert themselves in extremely hot weather, but it is also common in elderly individuals, whose thermoregulatory mechanisms are less efficient than those in younger people. To learn more about the symptoms and treatment of heat stroke, try a Google search. Then check your understanding of this problem by comparing your answers to those in the table below. 894

13 Integrative Physiology III: RUNNING PROBLEM CONCLUSION (continued) Question Facts Integration and Analysis 1. Why is the thermoregulatory mechanism of sweating less efficient in humid environments? Humidity is the percentage of water vapor present in air. Thermoregulation in warm environments includes sweating and evaporative cooling. Evaporation is slower in humid air, so evaporative cooling is less effective in high humidity. 2. Individuals with a heat emergency called heat exhaustion have cool, moist skin. Hot, dry skin indicates a more serious emergency called heat stroke. Why is heat exhaustion less serious than heat stroke? Sweating helps the body regulate temperature through evaporative cooling. As evaporation occurs, the skin surface cools. Cool, moist skin indicates that the sweating mechanism is still functioning. Hot, dry skin indicates that the sweating mechanism has failed. Subjects with hot, dry skin are likely to have higher internal temperatures. 3. Why was Colleen s blood pressure so low? Blood volume decreases when the body loses large amounts of water through sweating. Colleen had been sweating but not replacing the fluid she lost. This caused her blood volume to decrease, with a corresponding decrease in blood pressure. 4. Why would misting and fanning help lower Colleen s body temperature? Evaporation of water creates evaporative cooling. Putting water on Colleen s skin, then using a fan to evaporate the water helps cool the skin. 5. What steps could Colleen have taken to avoid heat stroke? (Start at 9:00 A.M., when Colleen set out for the practice field.) Heat stroke is caused by dehydration resulting from excessive sweating. Dehydration results in a drop in blood pressure. Peripheral blood vessels constrict in an effort to maintain pressure and blood flow to the brain. Constricted blood vessels in the skin cannot release excess heat. In addition, the sweating response is inhibited to prevent further fluid loss. Colleen could have avoided heat stroke by: (1) consuming large amounts of fluid (water plus electrolytes) before and during practice; (2) avoiding unnecessary exercise such as bicycling to practice; (3) stopping activity at the first signs of heat emergency (dizziness and nausea); (4) seeking shade and drinking large amounts of fluid to replenish lost fluids; (5) applying cool wet towels or ice to lower body temperature. Test your understanding with: Practice Tests Running Problem Quizzes A&PFlix TM Animations PhysioEx TM Lab Simulations Interactive Physiology Animations Chapter Summary In this chapter you learned about exercise and the physiological challenges it presents. Integration and coordination between the body s physiological control systems allow the internal environment to remain relatively constant, despite the challenges to homeostasis that exercise presents. 895

14 Integrative Physiology III: Metabolism and 1. Exercising muscle requires a steady supply of ATP from metabolism or from conversion of phosphocreatine. ( Fig..1 ) 2. Carbohydrates and fats are the primary energy substrates. Glucose can be metabolized through both oxidative and anaerobic pathways, but fatty acid metabolism requires oxygen. ( Fig..1 ) 3. Anaerobic glycolytic metabolism converts glucose to lactate and H +. Glycolytic metabolism is 2.5 times more rapid than aerobic pathways but is not as efficient at ATP production. (Fig..2 ) 4. Glucagon, cortisol, catecholamines, and growth hormone influence glucose and fatty acid metabolism during exercise. These hormones favor the conversion of glycogen to glucose. 5. Plasma glucose concentrations rise with exercise, but insulin secretion decreases. This response reduces glucose uptake by most cells, making more glucose available for exercising muscle. 6. The intensity of exercise is indicated by oxygen consumption 1V O2 2. A person s maximal rate of oxygen consumption 1V O2 max2 is an indicator of that person s ability to perform endurance exercise. 7. Oxygen consumption increases rapidly at the onset of exercise. Excess postexercise oxygen consumption is due to ongoing metabolism, increased body temperature, and circulating catecholamines. (Fig..4 ) 8. Muscle mitochondria increase in size and number with endurance training. 9. At maximal exertion, the ability of the cardiovascular system to deliver oxygen and nutrients appears to be the primary limiting factor. Ventilatory Responses to 10. hyperventilation results from feedforward signals from the motor cortex and sensory feedback from peripheral sensory receptors. (Fig..5 ) 11. Arterial P O2, P CO2, and ph do not change significantly during mild to moderate exercise. (Fig..6 ) Cardiovascular Responses to 12. Cardiac output increases with exercise because of increased venous return and sympathetic stimulation of heart rate and contractility. (Fig..7 ) 13. Blood flow through exercising muscle increases dramatically when skeletal muscle arterioles dilate. Arterioles in other tissues constrict. (Fig..7 ) 14. Decreased tissue O 2 and glucose or increased muscle temperature, CO 2, and acid act as paracrine signals and cause local vasodilation. 15. Mean arterial blood pressure increases slightly as exercise intensity increases. The baroreceptors that control blood pressure change their setpoints during exercise. (Fig..8 ) Feedforward Responses to 16. When exercise begins, feedforward responses prevent significant disruption of homeostasis. Temperature Regulation During 17. Heat released during exercise is dissipated by sweating and increased cutaneous blood flow. and Health 18. Physical activity can help prevent or decrease the risk of developing high blood pressure, strokes, and type 2 diabetes mellitus. 19. Studies suggest that serotonin release during exercise may help alleviate depression. Questions Level One Reviewing Facts and Terms 1. Name the two muscle compounds that store energy in the form of high-energy phosphate bonds. 2. The most efficient ATP production is through aerobic/anaerobic pathways. When these pathways are being used, then glucose/fatty acids/ both/neither can be metabolized to provide ATP. 3. What are the differences between aerobic and anaerobic metabolism? 4. List three sources of glucose that can be metabolized to ATP, either directly or indirectly. 5. List four hormones that promote the conversion of triglycerides into fatty acids. What effects do these hormones have on plasma glucose levels? 6. What is meant by the term oxygen deficit, and how is it related to excessive postexercise oxygen consumption? 7. What organ system is the limiting factor for maximal exertion? 8. In endurance events, body temperature can reach C. What is normal body temperature? What two thermoregulatory mechanisms are triggered by this change in temperature during exercise? Level Two Reviewing Concepts 9. Concept map: Map the metabolic, cardiovascular, and respiratory changes that occur during exercise. Include the signals to and from the nervous system, and show what specific areas signal and coordinate the exercise response. 10. What causes insulin secretion to decrease during exercise, and why is this decrease adaptive? 11. State two advantages and two disadvantages of anaerobic glycolysis. 12. Compare and contrast each of the terms in the following sets of terms, especially as they relate to exercise: (a) ATP, ADP, PCr (b) myoglobin, hemoglobin 13. Match the following brain areas with the response(s) that each controls. Brain areas may control one response, more than one response, or none at all. Some responses may be associated with more than one brain area. (a) pons 1. changes in cardiac output (b) medulla oblongata 2. vasoconstriction (c) midbrain 3. exercise hyperventilation (d) motor cortex 4. increased stroke volume 896