2. Jim Pierce Bi 145a Lecture 16, 2009-10 Respiratory Physiology [the Ins and Outs]

3. The Lungs

5. Pulmonary Tree

6. Trachea and Esophagus

7. Trachea

8. Respiratory Epithelium

9. Respiratory Epithelium Explained

10. Brush Border and Goblet Cells

11. Structure of the Distal Airway

12. Alveoli

13. Terminal Bronchioles, Respiratory Bronchioles, and Alveoli

14. Blood Supply of the Distal Airway

15. Alveolar Membrane (TEM)

16. Pulmonary Circulation

17. Lungs in situ

18. Bronchial Arteries

19. The Diaphragm

20. Accessory Muscles

21. Upper Airway Development

24. Airway Budding

27. Growing into the Pleural Cavity

28. Lower Airway Development

30. Airway Maturation

34. Capillary Blood Flow

35. Lung Physiology The Lung has three jobs Absorb Oxygen Excrete Carbon Dioxide (and affect pH) Neurohormal and Hematopoetic Function (Remember - it’s a filter that all of the blood must traverse)

36. Lung Physiology It’s not surprising to find Neurohormonal Function (note that 100% of the Cardiac Output must cross the lung) Thus, the body has placed a variety of enzymes on the vascular endothelium.

37. Metabolic Roles

38. Lung Physiology Do Not Forget that the lung is a Neurohormonal Organ People do because the gas exchange physiology is very interesting. Perhaps the role of the lung in immunologic dysfunction is more interesting.

39. Lung Physiology Furthermore, Multipotent Stem Cells, Reticulocytes, and Megakaryocytes sometimes escape from the bone marrow and wedge into the lung microvasculature. They finish differentiation because of the presence of Reticular Fibers

40. Pulmonary Physiology So we need to ask: 1) How do we BREATHE? That is, get air in and out of the lungs What are the parts of the airway and lungs that allow us to move the air? What are the muscles that move the air in and out? What controls them?

41. Pulmonary Physiology 2) How do we VENTILATE? That is, how do we get air to the alveoli? What causes the movement of air to get to the terminal respiratory tract? What are the volumes of air that are breathed that make it there? How does the air distribute in the lung? What factors affect the distribution of air in the lungs?

42. Pulmonary Physiology 3) How do we PERFUSE the lung? That is, how does blood flow in the lung? What brings the blood to the lungs? How is the blood flow distributed around the lungs? Where does the blood go? Where does the interstitial fluid go? What factors affect the regulation of blood flow?

43. Pulmonary Physiology 4) How do we EXCHANGE GASES? That is, how do we get the O 2 in and the CO 2 out? What factors affect diffusion from the alveoli to the capillary? How does blood flow affect the balance of gases? How does ventilation affect the balance of gases? When is the exchange blood flow limited? When is the exchange ventilation limited?

44. Pulmonary Physiology 5) How do we match VENTILATION and PERFUSION? That is, how do we make the blood and air go to the same place? What regulatory factors insure that ventilated lung are perfused? What factors insure that perfused lung is ventilated? How do we turn off perfusion or ventilation when the lung is not ventilating or perfusing?

45. Pulmonary Physiology 6) How do we adjust pulmonary function to compensate for changes in the periphery? Increase in Oxygen Demand Increase in Carbon Dioxide Production Change in pH

46. Breathing In the medulla, there is a respiratory center This center takes “respiratory inputs” Then it produces “respiratory outputs” Thus, it is directly responsible for controlling breathing (rate and depth)

47. Breathing The medullary respiratory assesses Local (i.e. brain) pH Local pCO 2 Afferent signals from the brain (thinking) Afferent signals from the periphery carotid bulb Heart, Lung The primary force on breathing is pCO 2

48. Breathing The medullary respiratory center indicates: Frequency of Initiation of inspiration Duration of inspiration Force of inspiration Inspiratory / Expiratory pause Expiratory duration Expiratory force

49. Breathing The respiratory cycle: Inspiration Inspiratory Pause (usually zero) Expiration Expiratory Pause

50. Breathing How do we inspire? How do we expire?

51. Breathing The brain controls the muscles of breathing indicating the respiratory rate. C3, C4, C5 nerve roots innervate the diaphragm via the phrenic nerve Other Cervical and Thoracic roots innervate the accessory muscles.

52. Breathing – ACTIVE FORCE Muscles of Breathing: Principle Muscles Diaphragm Intercostal Accessory Muscles There are no skeletal muscles in the lung

53. The Diaphragm

54. Accessory Muscles

55. Breathing – PASSIVE FORCE The connective tissue of the chest wall Determines the minimum and maximum volume of the chest cavity Does not control the minimum or maximum lung volume The connective tissue of the lung Primarily is elastic and tends to collapse Has some stiffness from connective tissue

56. Chest Wall Remember: Chest wall is Separate from Lung

57. Lungs Grew into the Pleural Cavity Chest Wall Lung

58. Chest Wall and Lung The total force from muscles of the chest wall tend to Expand the Chest The lung – with no muscles but lots of elastic tissue – tends to collapse

59. Chest Wall and Lung

60. The “negative” pressure keeps the lungs “stuck” to the chest wall (it’s not truly negative – it’s actually just 5 below atmospheric)

61. Breathing The overall ability of the chest and lung to allow a change in airway pressure based on volume moved is COMPLIANCE

62. Chest Wall and Lung When the muscles relax, the equilibrium is at the end of a comfortable exhale It is possible to contract muscles To exhale more To inhale (We have “exhale” and “inhale” reserve)

63. Chest Wall and Lung Why? It’s like a garage door opener: The balance of the heavy door and powerful spring keeps the “net mass” very low, making it easy to open and close

64. Chest Wall and Lung Like the garage door opener: The balance of the chest wall expansion and lung contraction keeps the “net mass” very low, making it easy to open and close

65. Inspiration When inspiratory muscles contract… The Thoracic Cage expands…

66. Inspiration The thoracic cage expands both anteriorly and laterally

67. Inspiration This is done by rib and sternum movement Ribs move like a bucket handle

68. Inspiration Sternum moves like a water pump

69. Inspiration Together, the thorax expands

70. Breathing When inspiratory muscles contract… The Thoracic Cage expands… Generating a negative pressure On the Pleural Space

71. Breathing As the Chest wall expands, the negative pressure in the pleural space actively expands the lung

72. Breathing Thus, the negative inspiratory force is transmitted from chest wall to lung -TRANSMURAL! This leads to a pressure gradient between the mouth and lung… Which leads to gas flow.

73. Ventilation Once we get negative pressure on the lung, we observe a net flow of air.  P = Q * R Pressure gradient Flow Resistance (of airways)

74. Inspiration All inspiration is active: Force is required to expand the thorax and draw air into the lungs

75. Exhalation Exhalation can be either active or passive Passive exhalation is the “relaxation” of the inspiratory muscles Active exhalation is the contraction of the axial skeletal muscles

76. Passive Exhalation During passive exhalation The inspiratory muscles relax The lung recoil is greater than the chest expansive force Thus, the lung and chest contract. This increases the pressure inside the lung This causes a pressure gradient, leading to airflow out through the airways

77. Passive Exhalation One can prevent passive exhalation without continuous use of force. By closing the epiglottis, the airways are “disconnected” from the environment. Regardless of the pressure gradient, no air will flow

78. Active Exhalation During active exhalation Intercostal, Abdominal muscles Contract This brings the chest to its smallest volume and braces it while the abdominal organs are forced upward into the diaphragm This increases the pressure in the chest cavity as well as in the lungs. As long as the airways remain open, Air will flow down the pressure gradient

79. Active Exhalation

80. During active exhalation As long as the airways remain open, Air will flow down the pressure gradient Active exhalation with a closed epiglottis prepares you for a cough. Active exhalation at the end of passive exhalation produces only a small, slow exhale because the small airways have collapsed

81. Chest Wall and Lung

83. Questions?