1

Respiratory tract anatomy

fig 13-1

2

Conducting zone vs. respiratory zone

fig 13-2

3

Conducting zone functions

Regulation of air flowtrachea & bronchi held open by cartilaginous ringssmooth muscle in walls of bronchioles & alveolar ductssympathetic NS & epinephrine relaxation ( receptors) air flowleukotrienes

(inflammation & allergens leukotrienes mucus & constriction)

Protectionmucus escalator (goblet cells in bronchioles & ciliated epithelium)inhibited by cigarette smoke

Warming & humidifying inspired airexpired air is 37 & 100% humidity (loss of ~400 ml pure water/day)

Phonationlarynx & 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 cellsthin, flat; gas exchange

Type II epithelial cellssecrete pulmonary surfactant pulmonary compliance (later)

Pulmonary capillariescompletely surround each alveolus; “sheet” of blood

Interstitial space diffusion distance for O2 & CO2 is less than diameter of red blood cell

Elastic fiberssecreted by fibroblasts into pulmonary interstitial spacetend 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) pressurei.e. Palv – Pip (e.g. at “2”, -1 – (-5) = 4 mm Hg

Lower curve (black):labeling accidentally omittedx axis should read “4 sec” i.e. timey 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 complianti.e. tire requires much greater pressure increase to expandcompliance = Δ volume / Δ pressure

Factors that decrease compliance

surface tension of fluid lining alveolar surfaceelastic tissue in alveolar wallsexpansion of lungs (stretched lungs are less compliant)

Factors that increase compliance

pulmonary surfactant secreted by type II alveolar cellsreduces surface tension of alveolar fluidmixture of phospholipid and proteinlow 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 150 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 rateHyperventilation: 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

fig 13-26

4 subunits (left) form 1 hemoglobin

Iron is ferrous form (Fe++)

Hb + 4 O2 Hb(O2)4 (saturated)

deoxyHb oxyHb

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

fig 13-29

all O2 movement is by simple diffusion down its partial pressure gradient

30

O2 from rbc Hb cells

fig 13-29

all O2 movement is by simple diffusion down its partial pressure gradient

highest P.O2 in alveolus

lowest P.O2 in mitochondria

31

CO2 from tissues blood

fig 13-31a

CO2 transport:

60% plasma HCO3-

30% carbamino hemoglobin

10% dissolved CO2

CA = carbonic anhydrase

H2O + CO2 H2CO3

32

CO2 from pulmonary blood alveolus

fig 13-31b

CO2 transport:

60% plasma HCO3-

30% carbamino hemoglobin

10% dissolved CO2

CA = carbonic anhydrase

H2O + CO2 H2CO3

33

Hemoglobin as a buffer

fig 13-32

Notes on next slide

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)

fig 13-33

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)

Stimulated by:

1. P.CO2 (via pH)

2. P.O2

3. pH

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)

fig 13-36

Acts on central & peripheral chemoreceptors

central chemoreceptors are the most important regulators of ventilation

acts via [H+] (pH)

note sensitivity

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

fig 13-41

You would think that exercise AVR by CO2, O2, or pH

However:

44

Increased ventilation & exercise; possible mechanisms

fig 13-43

Also:

axon collaterals from descending tracts to respiratory centers

feedback from joints & muscles