Past Papers · SAQ

Pulmonary Gas Diffusion

Current · V5 (2025) → C7.vi Historical · V4 (2023) → F7.iii 3 exam appearances

2023B Q06

Exam question

Explain perfusion limited and diffusion limited transfer of gases in the alveolus.

CICMWrecks answer

Master answer

Fick’s law of diffusion

Describes Diffusion through tissues
Rate of movement of solute across semi-permiable membrane J is

J\;={{D\;A\;\Delta C}\over{T}}

where

D=Diffusion\;constant\;\propto\;{{Solubility}\over{\sqrt{Molecular\;Weight}}}

C = concentration (or partial pressure for gasses)
A = cross-sectional area
T = thickness of the membrane or distance over which diffusion takes place.

The rate of diffusion of a gas through a tissue is:

Directly ∝:

Surface area of the barrier
Affected by:
- Parenchyma volume: Changes with Body size and in disease states
- V/Q mismatch: reduced in shunt and dead space
- Pulmonary Blood Volume: changed with vascular distension and recruitment
  - Cardiac output: increased recruitment in high output states, decreased recruitment and increased V/Q mismatch in shock states
  - Posture: Increased surface area while supine (compared to sitting or standing)
Solubility of the gas
- CO₂ is ~20 times as soluble as O2 in blood
Concentration gradient (partial pressure difference)
- Rate of blood flow through lungs
  - Transit time of blood across capillary (not part of Fick’s Equation) – based on HR
  - alters total gas exchange across alveolus
  - Can potentially change perfusion limited gas exchange to diffusion limited
- Alveolar partial pressure affected by:
  - Atmospheric pressure
  - Ventilation: Alveolar hypoventilation → ↑ P_ACO₂ , ↓ P_AO₂
- Partial pressure in blood affected by:
  - Binding of gas to protein:
  - Rate of oxygenation of reduced Hb:
    - Shift of oxygen dissociation curve (pH, temperature, PCO2, 2,3-DPG)
    - Haematocrit
    - Abnormalities of haemoglobin
  - Formation of carbamino compounds
  - Anaesthetic agents to plasma contents, e.g Albumin, cholesterol
  - Enzymatic Action
    - carbonic anhydrase (conversion of HCO3 to CO2)

Inversely ∝:

Membrane thickness
- Increased thickness impedes gas exchange – Pathological states like pulmonary edema and cardiac failure
Square root of Molecular Weight
- smaller substances diffuse more quickly

Diffusion vs. perfusion limited

Transfer of gases can be diffusion or perfusion limited dependent on the rate limiting step

Diffusion Limited

Occurs in gases which do not reach equilibration of P_a and P_A
The rate of gas diffusion across the alveolar membrane limits its transport away from the lung
Rate limiting step = rate of diffusion
E.g. CO
- CO binds so avidly to Hb (250x that of O2) → virtually no CO dissolved in plasma → P_aCO rises only slightly
- Even when RBC traversed entire length of pulmonary capillary, there is still substantial partial pressure difference across alveolar-capillary barrier → equilibrium of P_aCO and P_ACO never reached

Perfusion Limited

Characterized by complete equilibration i.e. P_a = P_A
amount of gas transferred between alveolus and capillary = dependent on amount of blood passing through the capillary
rate limiting step = rate of blood flow
E.g. N₂O
- N2O rapidly diffuses across alveolar-capillary barrier
- Insoluble; does not bind to Hb; only carried in plasma in dissolved form
- P_aN₂O = P_AN₂O (<0.07sec); well before RBC has traversed pulmonary capillary
- ↑ diffusion rate will not ↑ blood transport away from the lungs → limiting factor = rate of blood flow / perfusion
- e.g. CO₂ (ventilation limited i.e. perfusion limited in reverse)

Is the transfer of O2 perfusion or diffusion limited?

Can behave as both perfusion and diffusion limited
O₂ diffusion takes 0.25s; pulmonary capillary transit time is 0.75s
Normal conditions
- Transfer of O₂ across the alveolar capillary barrier is perfusion limited
- Equilibrium is reached between alveolar and capillary PO2 before the RBC has traversed the pulmonary capillary
Conditions where transfer of O₂ may become diffusion limited
- Disease of the alveolar capillary barrier
  - Pulmonary fibrosis: thickening of alveolar-capillary barrier → ↓ rate of diffusion
  - Exercise: ↑ CO → ↓ RBC transit time
  - Altitude: ↓ PaO2

Diffusion of O2 and CO2

Oxygen

Oxygen diffusion takes ~0.25s
Pulmonary capillary transit time is 0.75s
Therefore, under normal conditions oxygen is a perfusion limited gas
However, oxygen may become diffusion limited in certain circumstances:
- Alveolar-capillary barrier disease
  Decreases the rate of diffusion.
  - Decreased surface area
  - Increased thickness
- High cardiac output
  Decreases pulmonary transit time.
- Altitude
  Decreases PAO2

Carbon Dioxide

Carbon dioxide is ventilation limited, rather than diffusion or perfusion limited
This is because it is:
- 20x more soluble in blood than oxygen
- Rapidly produced from bicarbonate and carbamino compounds
- Present in far greater amounts than oxygen
  1.8L.kg^-1 exist in the body (though 1.6L^-1 of this are in bone and other relatively inaccessible compartments).
Impairment of diffusion capacity causes type 1 respiratory failure as oxygen is affected to a much greater extent than carbon dioxide

Kerr / JC 2020

Reusable content

Formulae used in this answer

Diffusion coefficient — solubility and molecular weight

Diffusion coefficient

CWF-0046

D=Diffusion\;constant\;\propto\;{{Solubility}\over{\sqrt{Molecular\;Weight}}}

Fick diffusion flux

CWF-0047

J\;={{D\;A\;\Delta C}\over{T}}

Answer by JC, Kerr

Past papers

Exam appearances

3 appearances

Exam	Exact exam wording	Candidate success
2023B Q06	Explain perfusion limited and diffusion limited transfer of gases in the alveolus.	48%
2021A Q15	Explain perfusion limited and diffusion limited transfer of gases in the alveolus.	36%
2016B Q22	Outline the physiological factors that affect the diffusion of oxygen and carbon dioxide within the lung.	43%