1. Respiratory Physiology
Jim Pierce
Bi 145a
Lecture 17,

2. Breathing and Ventilation
How do we describe the normal flow in and out of the mouth, lung, and alveoli during a respiratory cycle?
How do we get air in and out of the alveoli?

3. Breathing
Exhale
Inhale

4. Breathing

5. Breath Volumes Volumes that go through the mouth:
Tidal Volume
Vital Capacity
Volumes that exist inside the mouth
Residual Volume
End Expiratory Volume (aka Functional Residual Capacity)
End Inspiratory Volume
Full Lung Capacity

6. Breathing
The relationship between these
volumes and breathing

7. Breathing and Ventilation
We can subdivide the space from the mouth inside:
Anatomically
Upper Airways
Lower Airways
Alveoli
Functionally
Alveolar (Gas Exchanging)
Physiologic Dead Space (Not) }
Anatomic Dead Space

8. Alveolar Ventilation
Anatomic Dead Space
Physiologic Dead Space

9. Breathing

10. Breathing and Ventilation

11. Breathing and Ventilation

12. Breathing and Ventilation
Flow:
Tidal Volume through the mouth per breath
Total Ventilation through the mouth per minute
Alveolar Volume through the alveoli per breath
Alveolar Ventilation through the alveoli per minute

13. Volumes and Gases
We can use O2 and CO2 to Understand Volumes:

14. Volumes and Gases Fowler’s Method – Anatomic Dead Space
If you inhale a pure gas, you will exhale:
Pure Gas
Mixed Gas
Alveolar Gas

15. Volumes and Gases Fowler’s Method – Anatomic Dead Space
Approximately 150 cc in a “regular man”

16. Volumes and Gases

17. Volumes and Gases Bohr Equation – Physiologic Dead Space
All CO2 comes from alveolar gas (not dead space)
Arterial CO2 is almost always equal to Alveolar CO2
There is conservation of mass.

18. Volumes and Gases Bohr Equation – Physiologic Dead Space PV = nRT
PACO2 * VA = number of mols of exhaled CO2
PECO2 * VT = number of mols of exhaled CO2

19. Volumes and Gases Bohr Equation – Physiologic Dead Space So:
PACO2 * VA = PECO2 * VT = number of mols of exhaled CO2

20. Volumes and Gases Bohr Equation – Physiologic Dead Space
VA = PECO2 VT PACO2
VD = 1 - VA VT VT
VD = 1 - PECO2 VT PACO2

21. Volumes and Gases
Bohr Equation – Physiologic Dead Space

22. Alveolar Ventilation Flow takes Work
We’ve already minimized work involved to move the chest and lung
Why waste work opening alveoli?

23. Alveolar Ventilation What is the “Residual Volume?”
The amount of air left in the lung after maximal exhale
It’s purpose: Keep the Alveoli Open

24. Alveolar Ventilation At low volumes, alveoli would collapse by:
Absorbing the last air left behind
Emptying to a larger alveoli (Surface Tension experiment)

25. Alveolar Ventilation

26. Alveolar Ventilation Surfactants:
Are amphipathic molecules that forms a phospholipid monolayer lining the alveoli
The polar heads point at the alveolar wall, the lipophilic side chains point at the lumen

27. Alveolar Ventilation What is surfactant?
Mainly dipalmitoyl phosphatidylcholine
Protein B
Protein D

28. Alveolar Ventilation
Surfactant

29. Alveolar Ventilation At low lung volumes: In the small alveoli
The lipophilic tails of surfactant are crowded and push each other away
This keeps the alveoli open

30. Alveolar Ventilation At low lung volumes: In the large alveoli
The viscosity of surfactant resist overdistension
This keeps the alveoli from expanding

31. Alveolar Ventilation Thus, surfactant acts to
1) keep airways and alveoli open during end expiration.
2) cause even distribution of air during late inspiration.

32. Alveolar Ventilation
Surfactant resists LaPlace

33. Alveolar Ventilation
Another mechanism exists to prevent alveolar collapse:
Without cartilage – bronchioles tend to collapse
During inhalation, lung expansion opens bronchioles
During exhalation, bronchioles can (and do) collapse

34. Alveolar Ventilation
Another mechanism exists to prevent alveolar collapse:
As the chest wall and lung recoil, the pressures in the lung increase
These increased pressures start to start to force bronchioles closed
By the end of exhalation, almost all bronchioles are collapsed

35. Alveolar Ventilation
Another mechanism exists to prevent alveolar collapse:
This is called: Small Airway Collapse

36. Hysteresis This gives lung a special property
The pressure-volume curve is different during inspiration and expiration.
This is known as Hysteresis

37. Hysteresis

38. Hysteresis

39. Hysteresis
There are a variety of factors that influence the pressure-flow curve and cause hysteresis.
There are TWO main factors:
Surfactant
Collapse of Airways

40. Hysteresis

41. Alveolar Ventilation
Thus, surfactant causes the inspiratory portion of the hysteresis loop.
And collapse of airways causes the expiratory portion of the hysteresis loop

42. Alveolar Ventilation
Just as total muscle force is a function of average sarcomere length
Alveolar Compliance and function is a function of average alveolar volume
These same mechanisms lead preferentially to isovolumetric alveoli

43. Alveolar Ventilation
So is alveolar ventilation even across different regions of the lung?
No.

44. Regional Ventilation

45. Regional Ventilation Findings:
Decreased flow to the upper lung
Increased flow to the lower lung
How do we explain regional differences in air flow to the lung?

46. Regional Ventilation

47. Regional Ventilation
Thus, net differences in ventilation are based on differences in intrapleural pressure.
These differences lead to different TRANSMURAL pressures, which lead to different flow rates.

48. Regional Ventilation

49. Alveolar Ventilation Atmospheric Air has mostly nitrogen
Air that has been sitting in the nose, mouth, or trachea has water vapor
Air that has been in the alveoli has water vapor, CO2, and less O2

50. Alveolar Ventilation
One of the challenges is Mixing:

51. Alveolar Ventilation Thus – Alveolar Ventilation is affected by:
Total Flow in and out
Anatomic Dead Space
Functional Dead Space
Gas Mixing

52. Alveolar Ventilation To understand it you can:
1) Think about the gas composition at each level (mouth, trachea, etc)
2) Think about the gas content as it travels “down” its pressure gradient

53. Ventilation

54. Oxygen Atmospheric Pressure is 760 mmHg
(at sea level)
Atmospheric Fraction of Oxygen is 21%

55. Oxygen
When Air goes through our upper airways, it becomes humidified and heated.
The partial pressure of water rises
to 47 mmHg

56. Alveolar Ventilation for Oxygen

57. Oxygen
PIO2 = (760 mmHg - 47 mmHg) * FIO2 PIO2 = Inspired O2 Partial Pressure FIO2 = Fraction of Inspired O2 PIO2 = 713 * 21% = 150 mmHg

58. Alveolar Ventilation for Oxygen

59. Oxygen
PAO2 = PIO2 – Pressure lost by displacement PAO2 = Alveolar O2 Partial Pressure The effect of mixing! Fortunately – CO2 Production is related to O2 Consumption

60. Carbon Dioxide
The body uses oxygen to harness energy from reduced carbon.
Depending on the carbon source (sugar, fat, protein) there are differing amounts of carbon dioxide produced

61. Carbon Dioxide
The Respiratory Quotient, R, is the number of moles of CO2 produced per mole of O2 consumed.
For a person eating a regular diet, it is approximately 0.8
It increases with fat metabolism
It decreases with sugar metabolism

62. Oxygen
PAO2 = PIO2 - PACO2 / R R = Respiratory Quotient PAO2 = PACO2 / 0.8 (just before mixing, arterial CO2 equals alveolar CO2) PAO2 = PaCO2 / 0.8

63. Alveolar Gas Equation
PAO2 = (760 mmHg - 47 mmHg) * FIO2 - PartCO2 / 0.8

64. Carbon Dioxide In a similar fashion, we can watch Carbon Dioxide
Pulmonary Artery brings in CO2
CO2 rapidly equilibrates with alveolar CO2
During exhale alveolar gas mixes with dead space gas displacing CO2
By end exhale, dead space gas is gone and CO2 is equivalent to alveolar CO2

65. Carbon Dioxide
Capnogram = measurement of exhaled pCO2

66. Oxygen versus Carbon Dioxide
Already we’re seeing one of the differences between these gases:
Carbon Dioxide Equilibrates Quickly
Oxygen Equilibrates Slowly

67. A-a Gradient
When we start to look more closely at oxygen, we discover:
The alveolar pO2 is higher than the arterial pO2
A-a gradient = PAO2 - PaO2

68. Alveolar Ventilation for Oxygen
Atmosphere In
Mouth

69. Alveolar Ventilation Thus, the things that reduce oxygen:
Barometric Pressure
Initial Inspired Fraction of Oxygen
Humidification (before and after)
Alveolar Mixing
Diffusion Limits
Mixing with Deoxygenated Blood
Extraction by Tissue

70. Alveolar Ventilation The things that reduce carbon dioxide:
Rate of Production of carbon dioxide
Total Buffer of carbon dioxide
Diffusion (not very limited)
Alveolar Mixing
Dead Space Mixing

71. Pulmonary Gas Exchange
How does gas get from air to blood and back again?
It must cross the membrane which divides the alveoli and the capillary.

72. Diffusion of Gases Is Described by Fick’s Law
(yes, you’ve seen it before)
Flow is proportional to
Cross sectional area,
Diffusion constant,
Pressure gradient,
The inverse of the thickness of the membrane.

73. Diffusion of Gases

74. Diffusion of Gases Thus, to maximize gas flow:
1) the lung increases cross sectional area by extensive branching
2) the lung makes the membrane as thin as possible
3) the blood has mechanisms to increase rates of uptake or removal of gas

75. Diffusion of Gases

76. Diffusion of Gases

77. Diffusion of Gases
Each Gas (O2 , CO2 , CO, NO2 , N2O, Halothane) diffuses at a different rate.
Blood flows by at a (relatively) constant rate.
Thus, the total flow can be limited by either blood flow or diffusion.

78. Diffusion of Gases

79. Diffusion of Gases

80. Diffusion of Gases

81. Diffusion of Gases As a result, in general:
Gases are PERFUSION LIMITED in health
But can become DIFFUSION LIMITED in disease.

82. Carbon Dioxide versus Oxygen
Gas flows down its pressure gradient.
In general, the reservoir of gas will not be depleted.
There will always be O2 in the air (atmospheric and both inhaled (21%) and exhaled (18%))
There will always be CO2 in the blood (arterial at about 40 mmHg, venous at about 45 mmHg)
Furthermore, these pressures are relatively unchanged between pre and post exchange

83. Carbon Dioxide versus Oxygen
The ability to maximize flow is the ability to make the recipient reservoir as empty as possible.
As a result
Oxygenation is based on PERFUSION
Carbon dioxide excretion is based on VENTILATION.

84. Carbon Dioxide versus Oxygen
When we use mechanical ventilation, we can only control ventilation.
Thus, we can affect blood carbon dioxide with ease.
Nevertheless, no changing in breathing will affect oxygenation

85. Carbon Dioxide versus Oxygen
The ways we effect oxygenation by breathing is:
Increase the inspired oxygen
To increase the alveolar oxygen
Which will increase the diffusion gradient
Which will increase the flow of oxygen
Fix the underlying problem (perfusion)

86. Questions?