C H A P T E R 8

1. C H A P T E R 8 RESPIRATORY REGULATION DURING EXERCISE

2. w Discover how your respiratory system regulates your breathing and gas exchange. (continued) Learning Objectives w Find out how the respiratory system brings oxygen to muscles and tissues and rids the body of excess carbon dioxide. w Learn the steps involved in respiration and gas exchange.

3. Learning Objectives w Examine how the respiratory stem functions during exercise and how it can limit physical performance. w Learn how the respiratory system maintains acid-base balance in the body. w Find out why this acid-base balance is important especially during intense physical activity.

5. Respiration Respiration—delivery of oxygen to and removal of carbon dioxide from the tissues External respiration—ventilation and exchange of gases in the lung Internal respiration—exchange of gases at the tissue level (between blood and tissues)

6. External Respiration Pulmonary ventilation—movement of air into and out of the lungs—inspiration and expiration—by decreasing and increasing, respectively, the air pressure (ΔP) in the lungs by contraction and relaxation, respectively, of the respiratory muscles Pulmonary diffusion—exchange of oxygen and carbon dioxide between the lungs and blood by diffusion from high to low gas partial pressures

7. RESPIRATORY SYSTEM

8. Inspiration Rest Expiration Ventilation: Inspiration and Expiration Boyle’s Law: PV = constant Thus, when lung volume increases, air pressure in the lung decreases, and air flows in from the higher atmospheric pressure down the pressure gradient.

9. Ventilation: Inspiration and Expiration Ganong, Review of Medical Physiology, 1997

10. Pulmonary Diffusion w Replenishes blood's oxygen supply that has been depleted for oxidative energy production w Removes carbon dioxide from returning venous blood w Occurs across the thin respiratory membrane with the gas moving from a higher partial pressure to a lower partial pressure down the partial pressure gradient

11. RESPIRATORY MEMBRANE

12. Historical note: pulmonary capillaries Microscopic view of the pulmonary capillaries in a frog published in Opera Omnia (1687). Harvey postulated the existence of capillaries between arterioles and venules, but couldn’t see them. Marcello Malpighi (1628-1694) was the first to see capillaries using a microscope.

13. Laws of Gases Dalton's Law: The total pressure of a mixture of gases equals the sum of the partial pressures of the individual gases in the mixture. Henry's Law: Gases dissolve in liquids in proportion to their partial pressures, depending on their solubilities in the specific fluids and depending on the temperature.

14. Partial Pressures of Atmospheric Air w Standard atmospheric pressure (at sea level) = 760 mmHg w Nitrogen (N2) is 79.04% of air; the partial pressure of nitrogen (PN2) = 600.7 mmHg (760 mmHg ´ 0.7904) w Oxygen (O2) is 20.93% of air; PO2 = 159.1 mmHg w Carbon dioxide (CO2) is 0.03%; PCO2 = 0.2 mmHg

15. ΔP: Mechanism for Gas Diffusion Differences in the partial pressures of gases in the alveoli and in the blood create a pressure gradient (ΔP) across the respiratory membrane. This difference in pressures leads to diffusion of gases across the respiratory membrane. The greater the pressure gradient, the more rapidly the gas diffuses across it.

16. PO2 AND PCO2 IN BLOOD

17. Diffusion of Oxygen into the Pulmonary Capillary from the Alveolus Oxygenation of the blood in the lungs depends on the transit time of the blood in the capillaries: Transit time = capillary volume/blood flow As shown in this graph, transit time is slow enough normally for full oxygenation to occur – the only exceptions are in elite endurance athletes who have exceptionally high maximal cardiac outputs

18. Partial pressure (mmHg) % in Dry Alveolar Arterial Venous DiffusionGas dry air air air blood blood gradient Total 100.00 760.0 760 760 706 0 H2O 0.00 0.0 47 47 47 0 O2 20.93 159.1 105 100 40 60 CO2 0.03 0.2 40 40 46 6 N2 79.04 600.7 568 573 573 0 Partial Pressures of Respiratory Gases at Sea Level

19. Key Points Pulmonary Diffusion w Oxygen diffusion capacity increases as you move from rest to exercise. w The pressure gradient for CO2 exchange is less than for O2 exchange, but carbon dioxide’s diffusion coefficient is 20 times greater than that of oxygen’s, so CO2 crosses the membrane easily.

20. Oxygen Transport wHemoglobin concentration largely determines the oxygen-carrying capacity of the blood (>98% of oxygen transported bound to hemoglobin). The rest is dissolved in the plasma. w Increased H+ (acidity) and temperature of a muscle allows more oxygen to be unloaded there from the hemoglobin. • Training increases oxygen transport to the muscles by increasing muscle blood flow to the active fibers. • Increasing capillarity with training results in an increased capillary volume, which slows the mean transit time, which in turn allows more time for oxygen diffusion from the hemoglobin into the muscle fibers Mean blood transit time = capillary volume/blood flow

21. OXYGEN-HEMOGLOBIN DISSOCIATION CURVE Alveolar PO2 during exercise (at sea level) Bohr Effect Muscle PO2 during exercise

22. Thought Question Under which of the following conditions would you expect the greatest unloading of oxygen from hemoglobin in RBCs in the capillaries in a skeletal muscle: (1) rest, (2) exercise at 50% VO2max, or (3) exercise at 150% VO2max? Explain your answer.

23. Carbon Dioxide Transport w Dissolved in blood plasma (7% to 10%) • As bicarbonate ions resulting from the dissociation of carbonic acid (60% to 70%) Carbonic anhydrase CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3− w Bound to hemoglobin (carbaminohemoglobin) (20% to 33%)

24. a-vO2diff and Arterial O2 Content w Hemoglobin (Hb)—1 molecule of Hb can carry 4 molecules of O2, and 100 ml of blood contains ~14-18 g of Hb in men and ~12-14 in women (1 g of Hb combines with 1.34 ml of oxygen in both genders). w There are ~20 ml of O2 per 100 ml of arterial blood (15 g of Hb  1.34 ml of O2/g of Hb) in men and ~17 ml of O2 per 100 ml of arterial blood (13 g  1.34) in women. w Low iron leads to iron-deficiency anemia, reducing the body’s capacity to transport oxygen—this can lower the aerobic capacity, and is more common in women than in men

25. – The a-vO2 diff at rest and during exercise Rest – Maximal exercise – (R. Venticle) (L. Ventricle)

26. – The increase in a-vO2 diff during strenuous exercise reflects increased oxygen use by muscle cells. This use increases oxygen removal from arterial blood, resulting in a decreased venous oxygen concentration. However, in normal individuals, the lungs fully oxygenate the blood even at maximal exercise. In addition,

27. Factors that Determine Oxygen Delivery to the Muscles 1. Oxygen content of blood 2. Amount of blood flow 3. Local conditions within the muscle: Bohr effect (e.g., PO2, pH, and temperature)

28. Neural Control of Pulmonary Ventilation Two general central neural control systems: (1) voluntary control – cerebral cortex; (2) automatic control – pons and medulla – set the basic respiratory rhythm Activation of motor units stimulates respiration – “feed-forward” system Muscle mechanoreceptors – “exercise reflex” stimulates ventilation – “feed-back” system Chemoreceptors: (1) brain chemoreceptors (mainly in the medulla) - ↑ PCO2 and ↓ pH (↑ H+) stimulate ventilation; (2) peripheral chemoreceptors (large arteries) - ↑ PCO2, ↓ PO2, and ↓ pH stimulate ventilation

29. Neural Control of Ventilation

30. . Ventilation (VE) is the product of tidal volume (TV) and breathing frequency (f): . VE = TV ´ f Both TV and f increase during exercise Ventilation increases from about 15 l/min at rest to above 120 l/min at maximal exercise Elite athletes may go above 180 l/min at maximal exercise. Pulmonary Ventilation

31. VENTILATORY RESPONSE TO EXERCISE Chemoreceptor “fine-tuning” Feed-forward control and mechano-receptor feed-back

32. Terminology Dyspnea—shortness of breath. Hyperventilation—increase in ventilation that exceeds the metabolic need for oxygen. Voluntary hyperventilation, as is often done before underwater swimming, reduces the ventilatory drive by increasing blood pH. Valsalva maneuver—a breathing technique to trap and pressurize air in the lungs to allow the exertion of greater force; if held for an extending period, it can reduce cardiac output. This technique is often used during heavy lifts and can be dangerous in certain people under certain conditions.

33. . . w The ratio between VE and VO2 . . . w At rest—VE/VO2 = ~25 L of air breathed per L O2consumed per minute . . . w At max exercise—VE/VO2 = ~30 L of air per L O2 consumed per minute Ventilatory Equivalent for Oxygen w Indicates breathing economy

34. . w When work rate exceeds 55% to 70% VO2max, increasing amounts of lactic acid are formed in the muscle fibers and released into the blood. Ventilatory Breakpoint w The point during intense exercise at which ventilation increases disproportionately to the oxygen consumption. • w Because of the carbonic anhydrase reaction, increased lactic acid levels result in both increased PCO2 and H+ levels in the blood, triggering an increase in ventilation by stimulation of the chemoreceptors. Remember: • Carbonic anhydrase • CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3−

35. . . VE AND VO2 DURING EXERCISE

36. . . w Identified by noting an increase in VE/VO2 without a concomitant increase in the ventilatory equivalent for carbon dioxide (VE/VCO2) . . “Anaerobic” Threshold w Point during intense exercise at which metabolism becomes increasingly more anaerobic w Reflects the lactate threshold under most conditions, though the relationship is not always exact

37. . . . . VE/VCO2 AND VE/VO2

38. Respiratory Limitations to Performance w Respiratory muscles may use up to 11% of total oxygen consumed during heavy exercise and seem to be more resistant to fatigue during long-term activity than muscles of the extremities. w Respiration is usually not a limiting factor for performance, even during maximal effort, though it can limit performance in highly trained people. The best measure of a limitation in the lungs is a decrease in oxygen content in the arterial blood leaving the lungs (hypoxemia). w Also, airway resistance and gas diffusion usually do not limit performance in normal healthy individuals, but abnormal or obstructive respiratory disorders can limit oxygenation of the blood and performance.

39. Thought Question Why might an extremely well-trained endurance athlete experience hypoxemia during intense exercise, i.e., what is the physiological reason?

40. Respiratory Regulation of Acid-Base Balance w Excess H+ (decreased pH) impairs muscle contractility and ATP formation w The respiratory system helps regulate acid-base balance by increasing respiration when H+ levels rise. Because of the carbonic anhydrase reaction, increased acid results in higher PCO2, and the resulting increase in ventilation allows a “blowing off” of excess CO2, which raises the pH. w Thus, whenever H+ levels begin to rise, from carbon dioxide or lactate accumulation, bicarbonate ions buffer the H+ to prevent acidosis.

41. ARTERIAL BLOOD AND MUSCLE pH

42. Thought Question A large decrease in pH causes a reduction in the activities of most enzymes. With this in mind, why can’t a 100 meter sprinter maintain the 10 sec/100 m pace for longer distances?

43. RECOVERY AND BLOOD LACTATE LEVELS The more rapid removal of lactate from the blood during active recovery results from lactate being taken up and oxidized in the active heart and muscles.