Question 20

List the physiological factors affecting the diffusion of oxygen across the alveolar membrane (70% of marks). Describe how this changes with exercise (30% of marks).

[Click here to toggle visibility of the answers]

College Answer

The first section of this question was generally well done, but few really good marks, 
whereas the second section was poorly understood. The diffusing capacity is defined as the 
volume of gas that will diffuse through the membrane each minute for a partial pressure 
difference of 1mmHg. Factors affecting the rate of gas diffusion through the respiratory 
membrane include those related to the Fick equation (e.g. thickness of the membrane, 
surface area of the membrane, diffusion coefficient of the gas in the substance of the 
membrane, partial pressure difference of the gas between the two sides of the membrane, 
gas’s solubility), rate of combination of oxygen with reduced haemoglobin and factors 
affecting surface area (e.g. lung volume, age, posture). 
During strenuous exercise the oxygen diffusion is increased as pulmonary blood flow is 
greatly increased and there is opening up of previously dormant pulmonary capillaries 
increasing the surface area of blood into which oxygen can diffuse. Also, alveolar ventilation 
increases and there is better matching of ventilation and perfusion increases from 
21ml/min/mmHg up to 65ml/min/mmHg.


"The physiological factors affecting the diffusion of oxygen across the alveolar membrane"  does not immediately scream "start the answer with a definition of diffusing capacity". 

  • Diffusing capacity = Net rate of gas transfer / Partial pressure gradient
  • Factors affecting diffusing capacity include:
    • Factors which influence gas properties
      • The density of the gas
      • Size of the molecules
      • The temperature of the medium
    • Factors which influence the gas exchange surface area
      • Age (with increasing age, total available surface area decreases, irrespective of the other factors)
      • Body size: height influences the size of the lungs
      • Lung volume
      • Shunt, dead space and V/Q inequality
    • Factors which influence the membrane characteristics
      • Disease states which increase the thickness of the blood-gas barrier, which include:
        • Pulmonary oedema
        • Interstitial lung disease, eg. pulmonary fibrosis
    • Factors which influence uptake by erythrocytes
      • The affinity of haemoglobin for oxygen
      • Haemoglobin concentration
      • Cardiac output (insofar as it affects capillary transit time)
    • Sources of error in the course of measurement, due to alveolar haemorrhage, carbon monoxide poisoning, anaemia, etc
  • With exercise, both major elements affecting diffusing capacity are altered:
    • Oxygen uptake in the pulmonary capillaries increases because:
      • Surface area increases (larger tidal volumes)
      • Pulmonary blood flow increases (increased cardiac output)
      • V/Q matching improves (areas of high ventilation receive greater blood flow, and dormant capillary beds are recruited)
    • Partial pressure gradient in the pulmonary capillaries increases because:
      • Oxygen extraction ratio increases, decreasing the PO2 of mixed venous blood
      • Increased minute ventilation decreases the alveolar PCO2 (thus increasing the alveolar PO2, all other things remaining equal)
      • Increased delivery of haemoglobin to the absorptive surface acts as an oxygen sink and maintains a low capillary partial pressure


Ogilvie, C. M., et al. "A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide." The Journal of clinical investigation 36.1 (1957): 1-17.

Cotes, J. E., et al. "Standardization of the measurement of transfer factor (diffusing capacity)." (1993) European Respiratory Journal 6: 41-52

Weibel, Ewald R., et al. "Morphometric model for pulmonary diffusing capacity I. Membrane diffusing capacity." Respiration physiology 93.2 (1993): 125-149.

Krogh, Marie. "The diffusion of gases through the lungs of man." The Journal of physiology 49.4 (1915): 271-300.

Turino, G. M., et al. "Effect of exercise on pulmonary diffusing capacity." Journal of Applied Physiology 18.3 (1963): 447-456.

Hsia, Connie CW. "Recruitment of lung diffusing capacity: update of concept and application." Chest 122.5 (2002): 1774-1783.

Ayers, Larry N., et al. "Diffusing capacity, specific diffusing capacity and interpretation of diffusion defects." Western Journal of Medicine 123.4 (1975): 255.