1. Respiratory tract anatomy
fig 13-1

2. Conducting zone vs. respiratory zone
fig 13-2

3. Conducting zone functions
Regulation of air flow
trachea & bronchi held open by cartilaginous rings
smooth muscle in walls of bronchioles & alveolar ducts
sympathetic NS & epinephrine  relaxation ( receptors)  air flow
leukotrienes
(inflammation & allergens  leukotrienes  mucus & constriction)
Protection
mucus escalator (goblet cells in bronchioles & ciliated epithelium)
inhibited by cigarette smoke
Warming & humidifying inspired air
expired air is 37 & 100% humidity (loss of ~400 ml pure water/day)
Phonation
larynx & vocal cords

4. Alveolar structure 1
fig 13-3b

5. Alveolar structure 2
fig 13-4a

6. Alveolar structure 3
fig 13-4b

7. Alveolar structure (notes)
Type I epithelial cells
thin, flat; gas exchange
Type II epithelial cells
secrete pulmonary surfactant  pulmonary compliance (later)
Pulmonary capillaries
completely surround each alveolus; “sheet” of blood
Interstitial space
diffusion distance for O2 & CO2 is less than diameter of red blood cell
Elastic fibers
secreted by fibroblasts into pulmonary interstitial space
tend to collapse lung

8. Lung pressures Lungs are inflated by being “pulled” open
Transmural/transpulmonary pressure = Palveolar – Ppleural = 0 – (-5) = 5 mm Hg

9. Lung pressures during quiet ventilation

10. Lung pressures during ventilation
Purple line:
alveolar pressure (Palv)
-1 mm Hg during inspiration
+1 mm Hg during expiration
Green line:
pleural pressure (Pip)
-4 mm Hg at functional residual capacity
-7 mm Hg after inspiration
Ptp is transpulmonary (transmural) pressure
i.e. Palv – Pip (e.g. at “2”, -1 – (-5) = 4 mm Hg
Lower curve (black):
labeling accidentally omitted
x axis should read “4 sec” i.e. time
y axis is tidal volume = 500 ml

11. Pleural pressure during ventilation
Quiet ventilation:
pleural pressure (Pip) always negative
as lung expands, Pip becomes more negative because recoil (collapsing) force increases as lung stretches
Forced ventilation:
Pip negative during inspiration; more negative as lung expands
Pip can be positive during forced expiration (e.g. FEV1 measurement)

12. Airway resistance Transpulmonary pressure
as lungs expand, pleural pressure becomes more negative
transpulmonary pressure (alveolar pressure – pleural pressure) increases
alveoli expand, bronchioles expand  airway resistance
result: inhalation lowers resistance, exhalation increases resistance
Lateral traction
alveoli & bronchioles all interconnected
expansion of lungs stretches alveoli & bronchioles  resistance
net stocking metaphor

13. Lung compliance Definition: ease of expansion
e.g. balloon is compliant, auto tire is less compliant
i.e. tire requires much greater pressure increase to expand
compliance = Δ volume / Δ pressure
Factors that decrease compliance
surface tension of fluid lining alveolar surface
elastic tissue in alveolar walls
expansion of lungs (stretched lungs are less compliant)
Factors that increase compliance
pulmonary surfactant secreted by type II alveolar cells
reduces surface tension of alveolar fluid
mixture of phospholipid and protein
low levels in premature infants (respiratory distress syndrome)

14. Airway resistance Epinephrine
relaxes bronchiolar smooth muscle (2 receptors)
Leukotrienes
released during the inflammatory response
contract bronchiolar smooth muscle
important in asthma & bronchitis

15. Lung volumes Learn in laboratory:
*tidal volume, *inspiratory reserve volume, *expiratory reserve volume, residual volume, functional residual capacity, *vital capacity, total lung capacity
*can be measured with a spirometer
FEV1: forced vital capacity in 1 second (~80%)
Functional residual capacity:
lung volume when all muscles are relaxed (or subject is dead)
lung volume at the end of quiet expiration
tendency of lungs to collapse = tendency of thoracic cavity to expand
pleural pressure is negative (~ -4 mm Hg)

16. Alveolar ventilation Minute ventilation
tidal volume (ml/breath) x respiratory rate (breaths/min)
Anatomic dead space
space in respiratory tract where no gas exchange occurs
fig 13-20

17. Alveolar ventilation
fresh air entering lung with each breath = tidal volume – dead space
Alveolar ventilation rate
(tidal volume – dead space) x respiratory rate
Example calculations
respiratory rate
tidal volume
dead space
alveolar
ventilation rate
14 /min
500 ml
150 ml
4.9 L/min
24 /min
300 ml
3.6 L/min
see also table 13-5

18. Partial pressures Dalton’s law
In a mixture of gases, each gas behaves independently and exerts a pressure proportional to its concentration in the gas mixture
For example:
Air is 79% N2, 21% O2, 0.4% CO2
Air pressure = 760 mm Hg (dry air at sea level)
P.N2 = 600 mm Hg, P.O2 = 160 mm Hg, P.CO2 = 0.3 mm Hg
Partial pressure in solution
= partial pressure in gas mixture after equilibration with solution
Why use partial pressures?
because gases diffuse down their partial pressure gradients
(in gas or in solution)

19. Partial pressures at various sites
fig 13-22

20. Partial pressure & solubility
because P.O2 plasma = P.O2 blood, putting them in contact, separated by O2 permeable membrane  no net diffusion

21. Alveolar gas composition as AVR varies
Hypoventilation:  alveolar ventilation rate
Hyperventilation:  alveolar ventilation rate

22. Ventilation (air flow) & perfusion (blood flow) matching
If air flow to an alveolus is blocked:
alveolar gas = venous blood (P.O2 40 mm Hg, P.CO2 45 mm Hg)
The  P.O2 signals constriction of blood vessels (hypoxic vasoconstriction)
i.e. don’t send blood to an alveolus with no air flow
If blood flow to an alveolus is blocked:
alveolar gas = atmospheric air (P.O2 160 mm Hg, P.CO2 ~0 mm Hg)
The  P.CO2 signals constriction of bronchioles
i.e. don’t send air to an alveolus with no blood flow

23. Ventilation (air flow) & perfusion (blood flow) matching

24. Alveolar O2  pulmonary capillary blood
fig 13-24
Diseased lung: pulmonary edema, interstitial fibrosis

25. Hemoglobin structure 4 subunits (left) form 1 hemoglobin
Iron is ferrous form (Fe++)
Hb + 4 O2  Hb(O2)4 (saturated)
deoxyHb oxyHb
fig 13-26

26. Oxygen-hemoglobin dissociation curve
fig 13-27

27. Oxygen-hemoglobin dissociation curve (notes)
100% saturation is when every Hb has 4 O2’s bound
Sigmoid (S-shaped) curve indicates that binding of the 1st O2 increases the affinity of the other Hb binding sites for O2 (an allosteric effect technically known as “positive cooperativity”)
Sigmoid curve means that the curve is steepest in the region of unloading O2 i.e. in the tissues where P.O2 is < 40 mm Hg
A steep curve means that a small reduction in P.O2  O2 unloaded
Curve is flattest in the lung where P.O2 is ~100 mm Hg
A flat curve means that a large reduction in P.O2  reduction in O2 saturation of Hb (e.g. at high altitude or in diseased lung)
Also, flat curve means breathing 100% O2 adds little O2 to the blood

28. O2-Hb curve; effect of pH, CO2, DPG, temperature
In working tissue,  pH,  P.CO2,  temperature,  DPG
DPG is diphosphoglycerate (now known as bisphosphoglycerate)
DPG is  in hypoxic tissue (and in stored blood in blood banks)

29. O2 from alveolus  red blood cell in the lung
all O2 movement is by simple diffusion down its partial pressure gradient
fig 13-29

30. O2 from rbc Hb  cells
all O2 movement is by simple diffusion down its partial pressure gradient
highest P.O2 in alveolus
lowest P.O2 in mitochondria
fig 13-29

31. CO2 from tissues  blood CO2 transport: 60% plasma HCO3-
30% carbamino hemoglobin
10% dissolved CO2
CA = carbonic anhydrase
H2O + CO2  H2CO3
fig 13-31a

32. CO2 from pulmonary blood  alveolus
CO2 transport:
60% plasma HCO3-
30% carbamino hemoglobin
10% dissolved CO2
CA = carbonic anhydrase
H2O + CO2  H2CO3
fig 13-31b

33. Hemoglobin as a buffer
Notes on next slide
fig 13-32

34. Hemoglobin as a buffer (notes)
In tissues:
CO2 (produced by metabolism) + H2O  H2CO3  H+ + HCO3-
Hemoglobin becomes more basic when it is deoxygenated, i.e. it binds H+ more tightly
In the lung:
Hemoglobin is oxygenated, becomes more acidic, (i.e. it is a more powerful H+ donor), and releases its H+
H+ + HCO3-  H2CO3  H2O + CO2 (released into alveolus)

35. Rhythmical nature of breathing
Respiratory rhythm generator
located in medulla oblongata of brainstem
During quiet breathing
Inspiration: action potentials burst to diaphragm & inspiratory intercostals
Expiration: no action potentials; elastic recoil of lungs (passive process)
During forced breathing (e.g. exercise, blowing up a balloon)
Active inspiration & expiration
Expiration with expiratory intercostals & abdominal muscles
Breathing is also modulated by centers in pons of brainstem & lungs

36. Control of ventilation (chemoreceptors)
peripheral chemoreceptors
in carotid & aortic bodies
Central chemoreceptors:
in medulla (brain interstitial fluid)
Stimulated by:
1.  P.CO2 (via  pH: most important)
Peripheral chemoreceptors:
see left (arterial blood)
1.  P.CO2 (via  pH)
2.  P.O2
3.  pH
fig 13-33

37. Control of ventilation ( arterial P.O2)
fig 13-34
Acts on peripheral chemoreceptors
( P.O2 depresses central chemoreceptors)
relatively insensitive (potentiated by  P.CO2)
responds to P.O2, not O2 content (i.e. not to anemia or CO poisoning)

38. Control of ventilation ( arterial P.O2)
fig 13-35

39. Control of ventilation ( P.CO2)
Acts on central & peripheral chemoreceptors
central chemoreceptors are the most important regulators of ventilation
acts via  [H+] (pH)
note sensitivity
fig 13-36

40. Control of ventilation ( P.CO2)
fig 13-37

41. Control of ventilation ( pH)
fig 13-38
 P.CO2 acts via  pH, but this is  pH from other sources (e.g. lactic acid)

42. Control of ventilation ( pH)
fig 13-39

43. Increased ventilation & exercise
You would think that exercise  AVR by  CO2,  O2, or  pH
However:
fig 13-41

44. Increased ventilation & exercise; possible mechanisms
fig 13-43
Also:
axon collaterals from descending tracts to respiratory centers
feedback from joints & muscles