Jim Pierce Bi 145b Lecture 2, 2008-09
<ul><li>How do we describe the normal flow in and out of the mouth, lung, and alveoli during a respiratory cycle? </li></u...
Inhale Exhale
 
<ul><li>Volumes that go through the mouth: </li></ul><ul><ul><li>Tidal Volume </li></ul></ul><ul><ul><li>Vital Capacity </...
The relationship between these volumes and breathing
<ul><li>We can subdivide the space from the mouth inside: </li></ul><ul><li>Anatomically </li></ul><ul><ul><li>Upper Airwa...
<ul><li>Anatomic Dead Space </li></ul><ul><li>Physiologic Dead Space </li></ul>
 
 
 
<ul><li>Flow: </li></ul><ul><ul><li>Tidal Volume through the mouth per breath </li></ul></ul><ul><ul><li>Total Ventilation...
<ul><li>We can use O 2  and CO 2  to Understand Volumes: </li></ul>
<ul><li>Fowler’s Method – Anatomic Dead Space </li></ul><ul><li>If you inhale a pure gas, you will exhale: </li></ul><ul><...
<ul><li>Fowler’s Method – Anatomic Dead Space </li></ul><ul><li>Approximately 150 cc in a “regular man” </li></ul>
 
<ul><li>Bohr Equation –  Physiologic Dead Space </li></ul><ul><li>All CO2 comes from alveolar gas  (not dead space) </li><...
<ul><li>Bohr Equation –  Physiologic Dead Space </li></ul><ul><li>PV = nRT </li></ul><ul><li>PACO2 * VA = number of mols o...
<ul><li>Bohr Equation –  Physiologic Dead Space </li></ul><ul><li>So: </li></ul><ul><li>PACO2 * VA =  PECO2 * VT = number ...
<ul><li>Bohr Equation –  Physiologic Dead Space </li></ul><ul><li>VA  =  PECO2   VT  PACO2 </li></ul><ul><li>VD  = 1 -  VA...
<ul><li>Bohr Equation –  Physiologic Dead Space </li></ul>
<ul><li>Flow takes Work </li></ul><ul><li>We’ve already minimized work involved to move the chest and lung </li></ul><ul><...
<ul><li>What is the “Residual Volume?” </li></ul><ul><li>The amount of air left in the lung after maximal exhale </li></ul...
<ul><li>At low volumes, alveoli would collapse by: </li></ul><ul><ul><li>Absorbing the last air left behind </li></ul></ul...
 
<ul><li>Surfactants: </li></ul><ul><li>Are amphipathic molecules that forms a phospholipid monolayer lining the alveoli </...
<ul><li>What is surfactant? </li></ul><ul><ul><li>Mainly dipalmitoyl phosphatidylcholine  </li></ul></ul>Protein B Protein D
<ul><li>Surfactant </li></ul>
<ul><li>At low lung volumes: </li></ul><ul><li>In the small alveoli </li></ul><ul><ul><li>The lipophilic tails of surfacta...
<ul><li>At low lung volumes: </li></ul><ul><li>In the large alveoli </li></ul><ul><ul><li>The viscosity of surfactant resi...
<ul><li>Thus, surfactant acts to </li></ul><ul><li>1) keep airways and alveoli open during end expiration. </li></ul><ul><...
Surfactant resists LaPlace
<ul><li>Another mechanism exists to prevent alveolar collapse: </li></ul><ul><ul><li>Without cartilage – bronchioles tend ...
<ul><li>Another mechanism exists to prevent alveolar collapse: </li></ul><ul><ul><li>As the chest wall and lung recoil, th...
<ul><li>Another mechanism exists to prevent alveolar collapse: </li></ul><ul><li>This is called: Small Airway Collapse </l...
<ul><li>This gives lung a special property </li></ul><ul><li>The pressure-volume curve is different during inspiration and...
 
 
<ul><li>There are a variety of factors that influence the pressure-flow curve and cause hysteresis. </li></ul><ul><li>Ther...
 
<ul><li>Thus, surfactant causes the inspiratory portion of the hysteresis loop. </li></ul><ul><li>And collapse of airways ...
<ul><li>Just as total muscle force is a function of average sarcomere length </li></ul><ul><li>Alveolar Compliance and fun...
<ul><li>So is alveolar ventilation even  across different regions of the lung? </li></ul><ul><li>No. </li></ul>
 
<ul><li>Findings: </li></ul><ul><ul><li>Decreased flow to the upper lung </li></ul></ul><ul><ul><li>Increased flow to the ...
 
<ul><li>Thus, net differences in ventilation are based on differences in intrapleural pressure. </li></ul><ul><li>These di...
 
<ul><li>Atmospheric Air has mostly nitrogen </li></ul><ul><li>Air that has been sitting in the nose, mouth, or trachea has...
One of the challenges is Mixing:
<ul><li>Thus – Alveolar Ventilation is affected by: </li></ul><ul><ul><li>Total Flow in and out </li></ul></ul><ul><ul><li...
<ul><li>To understand it you can: </li></ul><ul><li>1) Think about the gas composition at each level (mouth, trachea, etc)...
 
<ul><li>Atmospheric Pressure is 760 mmHg </li></ul><ul><ul><li>(at sea level) </li></ul></ul><ul><li>Atmospheric Fraction ...
<ul><li>When Air goes through our upper airways, it becomes humidified and heated. </li></ul><ul><li>The partial pressure ...
 
<ul><li>P IO2  = (760 mmHg - 47 mmHg) * FIO 2 </li></ul><ul><li>P IO2  = Inspired O 2  Partial Pressure </li></ul><ul><li>...
 
<ul><li>P AO2  = P IO2  – Pressure lost by displacement </li></ul><ul><li>P AO2  = Alveolar O 2  Partial Pressure </li></u...
<ul><li>The body uses oxygen to harness energy from reduced carbon. </li></ul><ul><li>Depending on the carbon source (suga...
<ul><li>The Respiratory Quotient, R, is the number of moles of CO 2  produced per mole of O 2  consumed. </li></ul><ul><li...
<ul><li>P AO2  = P IO2  - P ACO2  / R </li></ul><ul><li>R = Respiratory Quotient </li></ul><ul><li>P AO2  = 150 - P ACO2  ...
P AO2  = (760 mmHg - 47 mmHg) * FIO 2  - P art CO 2  / 0.8
<ul><li>In a similar fashion, we can watch Carbon Dioxide </li></ul><ul><li>Pulmonary Artery brings in CO 2 </li></ul><ul>...
<ul><li>Capnogram = measurement of exhaled pCO 2 </li></ul>
<ul><li>Already we’re seeing one of the differences between these gases: </li></ul><ul><li>Carbon Dioxide Equilibrates Qui...
<ul><li>When we start to look more closely at oxygen, we discover: </li></ul><ul><li>The alveolar pO 2  is higher  than th...
In Mouth Atmosphere
<ul><li>Thus, the things that reduce oxygen: </li></ul><ul><ul><li>Barometric Pressure </li></ul></ul><ul><ul><li>Initial ...
<ul><li>The things that reduce carbon dioxide: </li></ul><ul><ul><li>Rate of Production of carbon dioxide </li></ul></ul><...
<ul><li>How does gas get from air to blood and back again? </li></ul><ul><li>It must cross the membrane which divides the ...
<ul><li>Is Described by Fick’s Law </li></ul><ul><li>(yes, you’ve seen it before) </li></ul><ul><li>Flow is proportional t...
 
<ul><li>Thus, to maximize gas flow: </li></ul><ul><li>1) the lung increases cross sectional area by extensive branching </...
 
 
<ul><li>Each Gas (O 2  , CO 2  , CO, NO 2  , N 2 O, Halothane) diffuses at a different rate. </li></ul><ul><li>Blood flows...
 
 
 
<ul><li>As a result, in general:  </li></ul><ul><ul><li>Gases are  PERFUSION LIMITED  in health  </li></ul></ul><ul><ul><l...
<ul><li>Gas flows down its pressure gradient. </li></ul><ul><li>In general, the reservoir of gas will not be depleted. </l...
<ul><li>The ability to maximize flow  is the ability to make the recipient reservoir as empty as possible. </li></ul><ul><...
<ul><li>When we use mechanical ventilation, we can only control ventilation.  </li></ul><ul><li>Thus, we can affect blood ...
<ul><li>The ways we effect oxygenation  by breathing is: </li></ul><ul><li>Increase the inspired oxygen </li></ul><ul><ul>...
 
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Respiratory Physiology

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Respiratory Physiology

  1. 1. Jim Pierce Bi 145b Lecture 2, 2008-09
  2. 2. <ul><li>How do we describe the normal flow in and out of the mouth, lung, and alveoli during a respiratory cycle? </li></ul><ul><li>How do we get air in and out of the alveoli? </li></ul>
  3. 3. Inhale Exhale
  4. 5. <ul><li>Volumes that go through the mouth: </li></ul><ul><ul><li>Tidal Volume </li></ul></ul><ul><ul><li>Vital Capacity </li></ul></ul><ul><li>Volumes that exist inside the mouth </li></ul><ul><ul><li>Residual Volume </li></ul></ul><ul><ul><li>End Expiratory Volume (aka Functional Residual Capacity) </li></ul></ul><ul><ul><li>End Inspiratory Volume </li></ul></ul><ul><ul><li>Full Lung Capacity </li></ul></ul>
  5. 6. The relationship between these volumes and breathing
  6. 7. <ul><li>We can subdivide the space from the mouth inside: </li></ul><ul><li>Anatomically </li></ul><ul><ul><li>Upper Airways </li></ul></ul><ul><ul><li>Lower Airways </li></ul></ul><ul><ul><li>Alveoli </li></ul></ul><ul><li>Functionally </li></ul><ul><ul><li>Alveolar (Gas Exchanging) </li></ul></ul><ul><ul><li>Physiologic Dead Space (Not) </li></ul></ul>} Anatomic Dead Space
  7. 8. <ul><li>Anatomic Dead Space </li></ul><ul><li>Physiologic Dead Space </li></ul>
  8. 12. <ul><li>Flow: </li></ul><ul><ul><li>Tidal Volume through the mouth per breath </li></ul></ul><ul><ul><li>Total Ventilation through the mouth per minute </li></ul></ul><ul><ul><li>Alveolar Volume through the alveoli per breath </li></ul></ul><ul><ul><li>Alveolar Ventilation through the alveoli per minute </li></ul></ul>
  9. 13. <ul><li>We can use O 2 and CO 2 to Understand Volumes: </li></ul>
  10. 14. <ul><li>Fowler’s Method – Anatomic Dead Space </li></ul><ul><li>If you inhale a pure gas, you will exhale: </li></ul><ul><ul><li>Pure Gas </li></ul></ul><ul><ul><li>Mixed Gas </li></ul></ul><ul><ul><li>Alveolar Gas </li></ul></ul>
  11. 15. <ul><li>Fowler’s Method – Anatomic Dead Space </li></ul><ul><li>Approximately 150 cc in a “regular man” </li></ul>
  12. 17. <ul><li>Bohr Equation – Physiologic Dead Space </li></ul><ul><li>All CO2 comes from alveolar gas (not dead space) </li></ul><ul><li>Arterial CO2 is almost always equal to Alveolar CO2 </li></ul><ul><li>There is conservation of mass. </li></ul>
  13. 18. <ul><li>Bohr Equation – Physiologic Dead Space </li></ul><ul><li>PV = nRT </li></ul><ul><li>PACO2 * VA = number of mols of exhaled CO2 </li></ul><ul><li>PECO2 * VT = number of mols of exhaled CO2 </li></ul>
  14. 19. <ul><li>Bohr Equation – Physiologic Dead Space </li></ul><ul><li>So: </li></ul><ul><li>PACO2 * VA = PECO2 * VT = number of mols of exhaled CO2 </li></ul>
  15. 20. <ul><li>Bohr Equation – Physiologic Dead Space </li></ul><ul><li>VA = PECO2 VT PACO2 </li></ul><ul><li>VD = 1 - VA VT VT </li></ul><ul><li>VD = 1 - PECO2 VT PACO2 </li></ul>
  16. 21. <ul><li>Bohr Equation – Physiologic Dead Space </li></ul>
  17. 22. <ul><li>Flow takes Work </li></ul><ul><li>We’ve already minimized work involved to move the chest and lung </li></ul><ul><li>Why waste work opening alveoli? </li></ul>
  18. 23. <ul><li>What is the “Residual Volume?” </li></ul><ul><li>The amount of air left in the lung after maximal exhale </li></ul><ul><li>It’s purpose: Keep the Alveoli Open </li></ul>
  19. 24. <ul><li>At low volumes, alveoli would collapse by: </li></ul><ul><ul><li>Absorbing the last air left behind </li></ul></ul><ul><ul><li>Emptying to a larger alveoli (Surface Tension experiment) </li></ul></ul>
  20. 26. <ul><li>Surfactants: </li></ul><ul><li>Are amphipathic molecules that forms a phospholipid monolayer lining the alveoli </li></ul><ul><li>The polar heads point at the alveolar wall, the lipophilic side chains point at the lumen </li></ul>
  21. 27. <ul><li>What is surfactant? </li></ul><ul><ul><li>Mainly dipalmitoyl phosphatidylcholine </li></ul></ul>Protein B Protein D
  22. 28. <ul><li>Surfactant </li></ul>
  23. 29. <ul><li>At low lung volumes: </li></ul><ul><li>In the small alveoli </li></ul><ul><ul><li>The lipophilic tails of surfactant are crowded and push each other away </li></ul></ul><ul><ul><li>This keeps the alveoli open </li></ul></ul>
  24. 30. <ul><li>At low lung volumes: </li></ul><ul><li>In the large alveoli </li></ul><ul><ul><li>The viscosity of surfactant resist overdistension </li></ul></ul><ul><ul><li>This keeps the alveoli from expanding </li></ul></ul>
  25. 31. <ul><li>Thus, surfactant acts to </li></ul><ul><li>1) keep airways and alveoli open during end expiration. </li></ul><ul><li>2) cause even distribution of air during late inspiration. </li></ul>
  26. 32. Surfactant resists LaPlace
  27. 33. <ul><li>Another mechanism exists to prevent alveolar collapse: </li></ul><ul><ul><li>Without cartilage – bronchioles tend to collapse </li></ul></ul><ul><ul><li>During inhalation, lung expansion opens bronchioles </li></ul></ul><ul><ul><li>During exhalation, bronchioles can (and do) collapse </li></ul></ul>
  28. 34. <ul><li>Another mechanism exists to prevent alveolar collapse: </li></ul><ul><ul><li>As the chest wall and lung recoil, the pressures in the lung increase </li></ul></ul><ul><ul><li>These increased pressures start to start to force bronchioles closed </li></ul></ul><ul><ul><li>By the end of exhalation, almost all bronchioles are collapsed </li></ul></ul>
  29. 35. <ul><li>Another mechanism exists to prevent alveolar collapse: </li></ul><ul><li>This is called: Small Airway Collapse </li></ul>
  30. 36. <ul><li>This gives lung a special property </li></ul><ul><li>The pressure-volume curve is different during inspiration and expiration. </li></ul><ul><li>This is known as Hysteresis </li></ul>
  31. 39. <ul><li>There are a variety of factors that influence the pressure-flow curve and cause hysteresis. </li></ul><ul><li>There are TWO main factors: </li></ul><ul><ul><li>Surfactant </li></ul></ul><ul><ul><li>Collapse of Airways </li></ul></ul>
  32. 41. <ul><li>Thus, surfactant causes the inspiratory portion of the hysteresis loop. </li></ul><ul><li>And collapse of airways causes the expiratory portion of the hysteresis loop </li></ul>
  33. 42. <ul><li>Just as total muscle force is a function of average sarcomere length </li></ul><ul><li>Alveolar Compliance and function is a function of average alveolar volume </li></ul><ul><li>These same mechanisms lead preferentially to isovolumetric alveoli </li></ul>
  34. 43. <ul><li>So is alveolar ventilation even across different regions of the lung? </li></ul><ul><li>No. </li></ul>
  35. 45. <ul><li>Findings: </li></ul><ul><ul><li>Decreased flow to the upper lung </li></ul></ul><ul><ul><li>Increased flow to the lower lung </li></ul></ul><ul><li>How do we explain regional differences in air flow to the lung? </li></ul>
  36. 47. <ul><li>Thus, net differences in ventilation are based on differences in intrapleural pressure. </li></ul><ul><li>These differences lead to different TRANSMURAL pressures, which lead to different flow rates. </li></ul>
  37. 49. <ul><li>Atmospheric Air has mostly nitrogen </li></ul><ul><li>Air that has been sitting in the nose, mouth, or trachea has water vapor </li></ul><ul><li>Air that has been in the alveoli has water vapor, CO 2 , and less O 2 </li></ul>
  38. 50. One of the challenges is Mixing:
  39. 51. <ul><li>Thus – Alveolar Ventilation is affected by: </li></ul><ul><ul><li>Total Flow in and out </li></ul></ul><ul><ul><li>Anatomic Dead Space </li></ul></ul><ul><ul><li>Functional Dead Space </li></ul></ul><ul><ul><li>Gas Mixing </li></ul></ul>
  40. 52. <ul><li>To understand it you can: </li></ul><ul><li>1) Think about the gas composition at each level (mouth, trachea, etc) </li></ul><ul><li>2) Think about the gas content as it travels “down” its pressure gradient </li></ul>
  41. 54. <ul><li>Atmospheric Pressure is 760 mmHg </li></ul><ul><ul><li>(at sea level) </li></ul></ul><ul><li>Atmospheric Fraction of Oxygen is 21% </li></ul>
  42. 55. <ul><li>When Air goes through our upper airways, it becomes humidified and heated. </li></ul><ul><li>The partial pressure of water rises </li></ul><ul><li>to 47 mmHg </li></ul>
  43. 57. <ul><li>P IO2 = (760 mmHg - 47 mmHg) * FIO 2 </li></ul><ul><li>P IO2 = Inspired O 2 Partial Pressure </li></ul><ul><li>FIO 2 = Fraction of Inspired O 2 </li></ul><ul><li>P IO2 = 713 * 21% = 150 mmHg </li></ul>
  44. 59. <ul><li>P AO2 = P IO2 – Pressure lost by displacement </li></ul><ul><li>P AO2 = Alveolar O 2 Partial Pressure </li></ul><ul><li>The effect of mixing! </li></ul><ul><li>Fortunately – CO 2 Production is related to O 2 Consumption </li></ul>
  45. 60. <ul><li>The body uses oxygen to harness energy from reduced carbon. </li></ul><ul><li>Depending on the carbon source (sugar, fat, protein) there are differing amounts of carbon dioxide produced </li></ul>
  46. 61. <ul><li>The Respiratory Quotient, R, is the number of moles of CO 2 produced per mole of O 2 consumed. </li></ul><ul><li>For a person eating a regular diet, it is approximately 0.8 </li></ul><ul><ul><li>It increases with fat metabolism </li></ul></ul><ul><ul><li>It decreases with sugar metabolism </li></ul></ul>
  47. 62. <ul><li>P AO2 = P IO2 - P ACO2 / R </li></ul><ul><li>R = Respiratory Quotient </li></ul><ul><li>P AO2 = 150 - P ACO2 / 0.8 </li></ul><ul><li>(just before mixing, arterial CO 2 equals alveolar CO 2 ) </li></ul><ul><li>P AO2 = 150 - P aCO2 / 0.8 </li></ul>
  48. 63. P AO2 = (760 mmHg - 47 mmHg) * FIO 2 - P art CO 2 / 0.8
  49. 64. <ul><li>In a similar fashion, we can watch Carbon Dioxide </li></ul><ul><li>Pulmonary Artery brings in CO 2 </li></ul><ul><li>CO 2 rapidly equilibrates with alveolar CO 2 </li></ul><ul><li>During exhale alveolar gas mixes with dead space gas displacing CO 2 </li></ul><ul><li>By end exhale, dead space gas is gone and CO 2 is equivalent to alveolar CO 2 </li></ul>
  50. 65. <ul><li>Capnogram = measurement of exhaled pCO 2 </li></ul>
  51. 66. <ul><li>Already we’re seeing one of the differences between these gases: </li></ul><ul><li>Carbon Dioxide Equilibrates Quickly </li></ul><ul><li>Oxygen Equilibrates Slowly </li></ul>
  52. 67. <ul><li>When we start to look more closely at oxygen, we discover: </li></ul><ul><li>The alveolar pO 2 is higher than the arterial pO 2 </li></ul><ul><li>A-a gradient = PAO 2 - PaO 2 </li></ul>
  53. 68. In Mouth Atmosphere
  54. 69. <ul><li>Thus, the things that reduce oxygen: </li></ul><ul><ul><li>Barometric Pressure </li></ul></ul><ul><ul><li>Initial Inspired Fraction of Oxygen </li></ul></ul><ul><ul><li>Humidification (before and after) </li></ul></ul><ul><ul><li>Alveolar Mixing </li></ul></ul><ul><ul><li>Diffusion Limits </li></ul></ul><ul><ul><li>Mixing with Deoxygenated Blood </li></ul></ul><ul><ul><li>Extraction by Tissue </li></ul></ul>
  55. 70. <ul><li>The things that reduce carbon dioxide: </li></ul><ul><ul><li>Rate of Production of carbon dioxide </li></ul></ul><ul><ul><li>Total Buffer of carbon dioxide </li></ul></ul><ul><ul><li>Diffusion (not very limited) </li></ul></ul><ul><ul><li>Alveolar Mixing </li></ul></ul><ul><ul><li>Dead Space Mixing </li></ul></ul>
  56. 71. <ul><li>How does gas get from air to blood and back again? </li></ul><ul><li>It must cross the membrane which divides the alveoli and the capillary. </li></ul>
  57. 72. <ul><li>Is Described by Fick’s Law </li></ul><ul><li>(yes, you’ve seen it before) </li></ul><ul><li>Flow is proportional to </li></ul><ul><ul><ul><li>Cross sectional area, </li></ul></ul></ul><ul><ul><ul><li>Diffusion constant, </li></ul></ul></ul><ul><ul><ul><li>Pressure gradient, </li></ul></ul></ul><ul><ul><ul><li>The inverse of the thickness of the membrane. </li></ul></ul></ul>
  58. 74. <ul><li>Thus, to maximize gas flow: </li></ul><ul><li>1) the lung increases cross sectional area by extensive branching </li></ul><ul><li>2) the lung makes the membrane as thin as possible </li></ul><ul><li>3) the blood has mechanisms to increase rates of uptake or removal of gas </li></ul>
  59. 77. <ul><li>Each Gas (O 2 , CO 2 , CO, NO 2 , N 2 O, Halothane) diffuses at a different rate. </li></ul><ul><li>Blood flows by at a (relatively) constant rate. </li></ul><ul><li>Thus, the total flow can be limited by either blood flow or diffusion. </li></ul>
  60. 81. <ul><li>As a result, in general: </li></ul><ul><ul><li>Gases are PERFUSION LIMITED in health </li></ul></ul><ul><ul><li>But can become DIFFUSION LIMITED in disease. </li></ul></ul>
  61. 82. <ul><li>Gas flows down its pressure gradient. </li></ul><ul><li>In general, the reservoir of gas will not be depleted. </li></ul><ul><ul><li>There will always be O 2 in the air (atmospheric and both inhaled (21%) and exhaled (18%)) </li></ul></ul><ul><ul><li>There will always be CO 2 in the blood (arterial at about 40 mmHg, venous at about 45 mmHg) </li></ul></ul><ul><li>Furthermore, these pressures are relatively unchanged between pre and post exchange </li></ul>
  62. 83. <ul><li>The ability to maximize flow is the ability to make the recipient reservoir as empty as possible. </li></ul><ul><li>As a result </li></ul><ul><ul><li>Oxygenation is based on PERFUSION </li></ul></ul><ul><ul><li>Carbon dioxide excretion is based on VENTILATION. </li></ul></ul>
  63. 84. <ul><li>When we use mechanical ventilation, we can only control ventilation. </li></ul><ul><li>Thus, we can affect blood carbon dioxide with ease. </li></ul><ul><li>Nevertheless, no changing in breathing will affect oxygenation </li></ul>
  64. 85. <ul><li>The ways we effect oxygenation by breathing is: </li></ul><ul><li>Increase the inspired oxygen </li></ul><ul><ul><li>To increase the alveolar oxygen </li></ul></ul><ul><ul><li>Which will increase the diffusion gradient </li></ul></ul><ul><ul><li>Which will increase the flow of oxygen </li></ul></ul><ul><li>Fix the underlying problem (perfusion) </li></ul>
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