1. Breathing and Exercise

2. Ventilation (1) Gas Exchange (2) Gas Transport (3) Gas Exchange (4) Cell Respiration (5) Respiration Requires the Interaction of Physiological Systems Respiration Requires the Interaction of Physiological Systems

4. Conducting Zone: Structure-Function Nasal Cavity is rich in blood supply which warms inspired air. Moist lining humidifies. Upper airways are mainly cartilaginous plates that are ‘stiff’ and conduct air efficiently. Lower airways contain more smooth muscle which can regulate airflow by relaxing and expanding. Mucociliary ‘elevator’ filters.

5. Respiratory Zone - Structure- Function Type 1 epithelial cells are thin (0.1 to 0.5 µm) making gas exchange with blood efficient. Type 2 epithelial cells make surfactant which keep alveoli ‘open’. Alveolar macrophages remove bacteria and other contaminants. Highly branched allows for great surface area for gas exchange.

8. (P atm - P alv ) Airway Resistance Flow = End-Expiration

9. (P atm - P alv ) Airway Resistance Flow = Inspiration

10. (P atm - P alv ) Airway Resistance Flow = Expiration

11. Inspiration

12. Inspiratory Muscle Action

13. Expiration

15. Volume (liters) 0 2 4 6 Time

16. Lung Volumes and Capacities in Healthy Subjects Males Females Measures (20-30 yrs) (20-30 yrs) VC 4800 3200 RV 1200 1000 FRC 2400 1800 TLC 6000 4200 RV/TLC x 100 20% 24% Measurements are in ml except where indicated.

17. Lung Volumes and Capacities in Healthy Subjects Males Females Males Measures (20-30 yrs) (20-30 yrs) (50 to 60 yrs) VC 4800 3200 3600 RV 1200 1000 2400 FRC 2400 1800 3400 TLC 6000 4200 6000 RV/TLC x 100 20% 24% 40% Measurements are in ml except where indicated.

18. Dead Space Anatomical Dead Space (ADS) is the volume of air needed to fill the conducting zone. Physiological Dead Space (PDS) is ADS + nonfunctional alveoli. Healthy people: ADS = PDS Some pulmonary diseases: ADS < PDS

19. Ventilation of Dead Space and Alveoli V T is volume required to fill dead space (V D ) + alveoli (V A ). In healthy subjects: V T = ~500 ml V D = ~150 ml V A = ~350 ml

22. Ventilatory Adjustments and Respiratory Efficiency Increase tidal volume –alveolar ventilation increases –dead space ventilation is unchanged Increase respiratory frequency –alveolar ventilation increases –dead space ventilation increases Increasing tidal volume more efficient!!!

23. What Determines the Work of Breathing? Lung and Chest Wall Compliance Tissue and Airway Resistance

24. Elastic Properties of the Lung are a Determinant of Compliance Elastic Properties of the Lung are a Determinant of Compliance Lung Volume Transpulmonary Pressure Compliance = y/x

25. Lung Volume is a Determinant of Compliance Lung Volume (% Total Lung Capacity) Transpulmonary Pressure (cm H 2 O) Total Lung Capacity (elastic elements are stretched) Functional Residual Capacity Residual Volume (airways are compressed)

26. Resistance Tissue resistance (~20% of total resistance) Airway resistance (~80% of total resistance) –Airway dimensions –Smooth muscle contraction –Intrapleural pressure

27. Regulation of Airway Smooth Muscle Airways constricted by: Parasympathetic stimulation Acetylcholine Histamine Leukotrienes Thromboxane A2 Serotonin  -adrenergic agonists Decreased PCO 2 Airways dilated by: Sympathetic stimulation (  2 receptors) Circulating  2 agonists Nitric oxide Increased PCO2 in small airways Decreased PO2 in small airways

28. Lung Volume is Invesrsely related to Airway Resistance Lung Volume Airway Resistance High Intrapleural Pressures Compress Airways Low Intrapleural Pressures Distend Airways

29. Airway Compression and Intrapleural Pressure

30. Ventilation (1) Gas Exchange (2) Gas Transport (3) Gas Exchange (4) Cell Respiration (5) Respiration Requires the Interaction of Physiological Systems Respiration Requires the Interaction of Physiological Systems

31. Regulation of Pulmonary Vascular Blood Flow Pulmonary artery pressure Extravascular events Chemical regulation of pulmonary vascular smooth muscle Gravity

32. Pulmonary Vascular Resistance Mean Pulmonary Artery Pressure (mmHg) Increased Pressure decreases Vascular Resistance in the Pulmonary Circulation

33. Recruitment Distension

34. Ventilation-Perfusion Matching Regional Ventilation –Increased by high CO 2 Regional Circulation –Decreased by low O 2 Ensures regions of the lung that are well ventilated are also well perfused

36. Ventilation (1) Gas Exchange (2) Gas Transport (3) Gas Exchange (4) Cell Respiration (5) Respiration Requires the Interaction of Physiological Systems

37. Diffusion of Gases O2O2 CO 2 T P1P1 P2P2 A ()V AD T PP gas    12

38. Surface Area for Pulmonary Gas Exchange is Influenced by: Body position Body size Exercise Some pulmonary diseases

39. Atmospheric Air (mmHg) Humidified Air (mmHg) Alveolar Air (mmHg) Expired Air (mmHg) N2N2 597.0 (78.6%)563.4 (74.1%)569.0 (74.9%)566.0 (74.5%) O2O2 159.0 (20.8%)149.3 (19.7%)104.0 (13.6%)120.0 (15.7%) CO 2 0.3 (0.04%) 40.0 (5.3%)27.0 (3.6%) H2OH2O 3.7 (0.5%)47.0 (6.2%) Total 760 (100.0%) Partial Pressures of Respiratory Gases as they Enter and Leave the Lungs at Sea Level Partial Pressures of Respiratory Gases as they Enter and Leave the Lungs at Sea Level

40. Gas Pressure Gradients in the Lung Values are PO 2 and PCO 2 in mmHg Pulmonary Capillary Alveoli Environment Tissue Metabolism Air-Blood Barrier Artery Vein O2O2 CO 2 0.03 159 40 104 40 104 45 40

41. Gas Pressure Gradients in the Lung: Light to Moderate Exercise Gas Pressure Gradients in the Lung: Light to Moderate Exercise Values are PO 2 and PCO 2 in mmHg Pulmonary Capillary Alveoli Environment Tissue Metabolism Air-Blood Barrier Artery Vein O2O2 CO 2 0.03 159 40 104 40 104 60 25

42. l5 O 2 molecules are dissolved in solution on both sides of the semi-permeable membrane (no net movement). Dissolved O 2 = 5 Dissolved O 2 = 5 Hemoglobin as an O 2 Carrier

43. lHemoglobin now binds 4 O 2 molecules, leaving only one in solution. There is now a 5:1 dissolved O 2 ratio (O 2 now moves from left to right). Hb Dissolved O 2 = 5 Dissolved O 2 = 1 Hemoglobin as an O 2 Carrier

44. l5 O 2 molecules are dissolved in solution on both sides of the semi-permeable membrane (no net movement). Dissolved O 2 = 5 Dissolved O 2 = 5 Hemoglobin as an O 2 Carrier

45. RBC transit in pulmonary capillary at rest is 1.0 sec RBC transit in pulmonary capillary during exercise is as little as 0.5 sec

46. RBC transit in pulmonary capillary at rest is 1.0 sec RBC transit in pulmonary capillary during exercise is as little as 0.5 sec

47. Diffusion - Limited Transfer in the Lung Presence of an end capillary to alveolus partial pressure difference

48. Perfusion-Limited Transfer in the Lung Absence of an end capillary partial pressure difference An increase in blood flow increases gas exchange with air by sending more blood through pulmonary capillaries.

49. Diffusion of O 2 to Tissues Diffusion-Limited

50. Diffusion of CO 2 from Tissues Perfusion-Limited

51. Transport of O 2 in the Blood

53. O 2 Carrying Capacity of Blood

54. Capacity of Blood to Transport O 2 is determined by Characteristics of the Hb-O 2 Dissociation Cure Capacity of Blood to Transport O 2 is determined by Characteristics of the Hb-O 2 Dissociation Cure

55. ‘S’ Shape of Hb-O 2 Dissociation Curve Caused by interaction of 4 Hb subunits as they bind O 2. Hb subunits associate with O 2 sequentially with each successive binding facilitating the next. Flat upper portion insures consistent and adequate O 2 delivery over a broad range of alveolar and arterial PO 2. Steep portion permits rapid unloading of O 2 from Hb during times of need, when PO 2 is low.

56. Hb-O 2 Binding Affinity is Influenced by Many Factors Hb-O 2 Binding Affinity is Influenced by Many Factors

57. Venous Blood has a Decreased O 2 Carrying Capacity Venous Blood has a Decreased O 2 Carrying Capacity

58. Bohr Effect Tissues: High CO 2 or reduced pH decrease Hb affinity for O 2 and facilitates O 2 unloading from blood. Lungs: Reduced CO 2 or increased pH increase Hb affinity for O 2 and facilitate O 2 uptake by the blood.

59. Transport of CO 2 in the Blood

60. Blood CO 2 Transport CO 2 ~ 7% HbCO 2 ~ 23% HCO 3 - ~ 70%

62. Haldane Effect describes the Reduced Capacity of Arterial Blood to Transport CO 2 Haldane Effect describes the Reduced Capacity of Arterial Blood to Transport CO 2 Blood CO 2 (ml/dl) Blood PCO 2 (mmHg)

63. Haldane Effect Tissues: Deoxygenated Hb affinity for CO 2 is higher than Hb-O 2 affinity for CO 2. This results in an increased capacity of blood to carry CO 2. Lungs: Hb-O 2 has decreased affinity for CO 2 and is more acidic than deoxygenated Hb. This facilitates CO 2 removal from the pulmonary capillaries.

64. Control of Breathing Requires Three Elements: One that Senses the 'Internal Climate', One that Integrates Sensory Info and Central Commands, One that Carries Out the Order Central Controller pons, medulla, other parts of brain Sensors Effectors Negative Feedback chemical, mechanical, and other receptors inspiratory and expiratory muscles InputOutput

65. Medullary Respiratory Centers Figure 22.25

66. Depth and Rate of Breathing: P CO2

67. Peripheral and Central Chemoreceptors have different Response Characteristics Breathing is stimulated by: Peripheral -  PCO 2,  pH,  PO 2 Central -  pH,  PCO 2 (indirect) Central response to arterial PCO 2 is of greater magnitude. Peripheral response to arterial PCO 2 is faster.

68. Ventilation (liters/min) Time (sec) Sole Source of Ventilatory Drive to Hypoxia Comes from Peripheral Chemoreceptors Sole Source of Ventilatory Drive to Hypoxia Comes from Peripheral Chemoreceptors Hypoxia Peripheral Chemoreceptor afferent nerves intact or denervated

69. Respiratory adjustments are geared to both the intensity and duration of exercise During vigorous exercise: –Ventilation can increase 20 fold –Breathing becomes deeper and more vigorous, but respiratory rate may not be significantly changed (hyperpnea) Exercise-enhanced breathing is not prompted by an increase in P CO2 or a decrease in P O2 or pH –These levels remain surprisingly constant during exercise Respiratory Adjustments: Exercise

70. As exercise begins: –Ventilation increases abruptly, rises slowly, and reaches a steady state When exercise stops: –Ventilation declines suddenly, then gradually decreases to normal Respiratory Adjustments: Exercise

71. Pulmonary Response to Constant Load Exercise

73. Exercise-Induced Lactic Acidosis H 2 0 + C0 2 H 2 C0 3 H + + HC0 3 - CA

74. Incremental Exercise Test

76. Acclimatization – respiratory and hematopoietic adjustments to altitude include: –Increased ventilation – 2-3 L/min higher than at sea level –Chemoreceptors become more responsive to P CO2 –Substantial decline in P O2 stimulates peripheral chemoreceptors Respiratory Adjustments: High Altitude