Respiratory System (Part 2): Gas Exchange and Ventilatory Control

Question 1

Pulmonary Diffusion:
Pulmonary Circulation

Answer 1

Pulmonary Circulation:
- Connected in series with systemic circulation
- Entire cardiac output passes through the
pulmonary circulation
- Low pressure system

• Blood in systemic veins with depleted O2 enters:
  1) Right heart
  2) Pulmonary artery
  3) Pulmonary capillaries
• O2 diffuses across from alveoli

Question 2

Pulmonary Diffusion:
Blood-gas Barrier

Answer 2

• Also called alveolar-capillary membrane:
  1) Alveolar wall (Type I cells)
  2) Capillary wall
  3) Respective basement membranes (‘basal lamina’)

Question 3

Pulmonary Diffusion:
Barometric Pressure (PB)

Answer 3

• Pressure exerted by the weight of gas molecules in the atmosphere above the
  point of measurement
• Measured using a barometer
• Sea level ≈ 101.3 kPa ≈ 760 mmHg ≈ 1 atm
• PB decreases exponentially with altitude,
  with lower density of gas molecules

Question 4

Composition of Air in the Atmosphere

Answer 4

• Conventionally, other inert gases (Argon [Ar], etc.) are categorised under nitrogen (N2) for simplification
• Therefore, N2 composition of air is considered to ≈79%

Question 5

Pulmonary Diffusion:
Partial Pressures of Gases

Answer 5

Air = 79.04% N2 + 20.93% O2 + 0.03% CO2:
- Total air pressure: atmospheric (barometric) pressure
- Individual pressures: partial pressures

Standard atmospheric (barometric) pressure at
sea level = 760 mmHg:
- Dalton’s law: total air pressure = PN2 + PO2 + PCO2

Question 6

Inspired Gas is Modified in the Airways

Answer 6

Partial pressure of inspired O2 (ambient air):
- % concentration x total (barometric) pressure

PO2 in conducting airways:
- The pressure of water molecules in humidified air (PH2O) = 47 mmHg at body temperature (37°C)

PO2 and PCO2 in respiratory airways (alveoli):
- 14.5% O2, 5.5% CO2 (average concentrations)

Question 7

Oxygen Cascade

Answer 7

• Diffusion (movement of gases) depends on partial pressure gradients:
  the greater the gradient, the greater the movement of gas

Question 8

Factors Affecting Diffusion

Answer 8

• So, the partial pressure gradient is an important factor in determining the rate of diffusion of O2 (and CO2) across the alveolar-capillary membrane
• Properties of the diffusion barrier:
  — Surface area
  — Thickness
  — Properties (‘diffusability’) of the gas molecules
  — Dependent on molecular weight (MV) and solubility (sol) of gas molecule
  — Summarised in Fick’s law…

Question 9

Fick’s Law of Diffusion

Answer 9

• Flow of gas (V) across a diffusion barrier proportional to:
  1) d, ‘diffusibility’ of gas
  2) A, area
  3) 1/T, thickness
  4) P1-P2, partial pressure gradient

Fick’s law:
V = d x A/T x (P1-P2)

Question 10

Why is the rate of diffusion important?

Answer 10

Impairment of diffusion can be due to:
1) Lower partial pressures of alveolar oxygen (altitude, COPD, asthma)
2) Loss of alveolar-capillary membrane surface area (COPD)
3) Blood/gas barrier thickening (e.g. pulmonary fibrosis)

Can affect arterial content of oxygen and limit functional capacity

Question 11

Oxygen Carriage in Blood

Answer 11

Haemoglobin:
- 4 Haem groups attached to one of 4 polypeptide chains (globin) to make one Hb molecule
- 4 FE 2+ binding sites each bind to one O2 molecule
- Accounts for ~= 99% of O2 carriage

Dissolved O2:
- Only accounts for ~= 1% of O2 carriage
- But only dissolved O2 exerts a partial pressure
- PO2 plays a role in the regulation of breathing and loading of Hb in lungs and release of O2 in tissues

Question 12

Haemoglobin Saturation

Answer 12

• Depends on PO2, affinity between O2 and Hb

High PO2 (e.g., in lungs):
- Loading portion of O2-Hb dissociation curve
- Small change in Hb saturation per mmHg change in PO2

Low PO2 (e.g., in body tissues):
- Unloading portion of O2-Hb dissociation curve
- Large change in Hb saturation per mmHg change in PO2

Question 13

Oxygen Exchange at the Muscles

Answer 13

Myoglobin has a much greater affinity for O2 than Hb

Question 14

Common Respiratory Condition that Compromises Blood Oxygen-Carrying Capacity?

Answer 14

Chronic Obstructive Pulmonary Disease (COPD)

Question 15

Ventilation and Acid-Base Balance

Answer 15

CO2 + H2O H2CO3 H+ + HCO3−:

1) Increase in
carbon dioxide
concentration…
2) Increases the concentration of free Hydrogen ions, so decreasing the pH of the blood

Question 16

Alveolar and Cellular Gas Exchange:
Summary

Answer 16

1. Oxygen diffuses into the arterial ends of pulmonary capillaries and CO2 diffuses into the alveoli because of differences in partial pressures
2. As a result of diffusion at the venous ends of pulmonary capillaries, the Po2 in the blood is equal to the Po2 in the alveoli and the Pco2 in the blood is equal to the Pco2 in the alveoli
3. The Pco2 of blood in the pulmonary veins is less than in the pulmonary capillaries because of mixing with deoxygenated blood from veins draining the bronchi and bronchioles
4. Oxygen diffuses out of the arterial ends of tissue capillaries and CO2 diffuses out of the tissue because of differences in partial pressures
5. 5. As a result of diffusion at the venous ends of tissue capillaries, the Po2 in the blood is equal to the Po2 in the tissue and the Pco2 in the blood is equal to the Pco2 in the tissue. Go back to step 1

Question 17

Local Control of Ventilation:
Ventilation and Perfusion Across the Lung

Answer 17

• VA/Q of 1.0 = optimal gas-exchange across the lung
• Decrease in PaO2 explained in part by VA/Q mismatch

Question 18

Neural Control of Ventilation - Overview

Answer 18

• Automatic control can be overridden with cortical involvement
• CNS needed for ventilation
• Respiratory control centres in the brainstem automatically and rhythmically control rate/depth of breathing
• The neural drive to breath is heavily modulated by feedback from a variety of receptors
• Chemoreceptors are sensitive to PaO2 and/or PACO2/pH, it helps maintain blood gas homeostasis by reflexly adjusting ventilation

Question 19

Peripheral Chemoreceptors

Answer 19

• Sensory receptors
  located in carotid arteries (carotid bodies) and aortic arch (aortic bodies)

Involved in blood-gas
and acid-base
homeostasis:
- Sensitive to:
1) ↓ PaO (hypoxaemia)
2) ↑ PaCO (hypercapnia)
3) ↓ arterial pH (acidaemia)

Question 20

Central Chemoreceptors

Answer 20

• Although their importance is clear, their
  anatomical identity is still
  not well defined. Likely
  multiple sites
• Located below surface of medulla
• Respond to changes in PaCO2 (via changes in pH within cerebral spinal fluid)
• Generate ~80% of ventilatory response to CO2
• As PaCO2 is the most tightly regulated variables, central chemoreceptors are critically important

Helpful mnemonic: “The Central Chemoreceptors are Central to the Control of ventilation and respond to changes in the level of PaCO2”

Question 21

Effects of PaO2 and PaCO2 on Ventilation

Answer 21

• Ventilation increases at lower PaO2, but the response becomes substantial at fairly low PaO2 values
• Small changes in PaO2 do not affect ventilation to a great extent
• PaCO2 has a profound effect on ventilation
• Small changes in PaCO2 increase ventilation substantially

Question 22

Effect of PaO2 on Ventilation (Key Terms and Summary)

Answer 22

• Hypoxia: decrease in oxygen levels below normal values
• Hypoxaemia: decrease in blood PO2 below normal values
• Peripheral (carotid) chemoreceptors respond to decreased PaO2 by increasing stimulation of respiratory centre to keep it active despite decreasing O2 levels
• Major regulator of ventilation during rest and exercise
• Hypercapnia: greater-than-normal amount of CO2
• Hypocapnia: lower-than-normal amount of CO2
• Central (medullary) chemoreceptors are most
  important for regulation of arterial PCO2 and pH at rest
• Peripheral (carotid) chemoreceptors respond rapidly to changes in arterial PCO2 and pH during exercise