Question 22

Outline the physiological factors that affect the diffusion of oxygen and carbon 
dioxide within the lung.

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College Answer

Good answers to this question were those that included a definition of diffusion; an outline of 
Fick’s Law of Diffusion and then a further description how each of the variables in the this Law 
affect the diffusion of oxygen and carbon dioxide in the lung; and an outline of the other factors 
that affect diffusion not covered by the above. Most candidates included Fick's Law in their 
answers and at least briefly expanded on the associated variables. 
Few candidates defined the process of diffusion. The other common omissions were the 
factors that affect diffusion that aren't directly encompassed in Fick's Law, such as cardiac 
output, capillary transit time, carbonic anhydrase (conversion of HCO3 to CO2) and 
combination of oxygen with haemoglobin


Diffusion of a gas is a process by which a net transfer of molecules takes place from a zone in which the gas exerts a high partial pressure to a zone in which it exerts a lower partial pressure.

Diffusion of respiratory gases through the alveolar membrane is determined by

  • Physical laws which describe the diffusion of gases through membranes (Fick's Law and Graham's law)
  • The capillary transit time of red blood cells.
  • The rate of protein-binding reaction (eg. oxygen-haemoglobin association)

Factors which influence the diffusion of gases in the lung are:

  • Diffusion coefficient of the gas, which is influenced by:
    • molecular size (stable and predictable for respiratory gases)
    • temperature (stable in most normal human lungs)
    • fluid viscosity/chemical properties of the membrane (altered by disease, eg. pulmonary fibrosis)
    • density of the gas (insofar as it factors into Graham's law)
  • Partial pressure gradient between the capillary and the alveolus, which is influenced by
    • Alveolar gas mixture
    • Solubility of the gas, which influences the relationship of its partial pressure and concentration
    • Mixed venous blood gas content
  • Blood-gas barrier thickness
    • influenced by age and disease (eg. pulmonary fibrosis)
    • Normally about 300 nm (0.3 μm)
  • Surface area of the pulmonary gas exchange surface
    • Alveolar membrane surface area 
      • Maximum available surface area is around 140m2
      • influenced by age and disease (eg. emphysema)
    • Capillary surface area
      • Maximum available surface area is around 125m2
      • influenced by the degree of pulmonary capillary recruitment, pulmonary blood flow and blood volume
    • V/Q matching describes the interplay between these factors, as both shunt and dead space result in a reduced gas exchange surface area
  • Capillary transit time: 
    • Transit time of blood in the alveolar capillaries is normally ~0.75-1.0 seconds
    • A minimum of 0.25 seconds is theoretically enough to fully oxygenate capillary blood
    • In healthy adults, the minimum capilary transit time is probably about 0.45 seconds
    • With disease affecting the blood-gas barrier, even a normal transit time may be insufficient for adequate gas diffusion
  • Chemical reactions and gas-protein binding
    • The binding of haemoglobin and oxygen has a finite reaction rate
    • This reaction rate is much faster than the diffusion rate
    • Diffusion alone is insufficient to account for the rate of oxygen uptake in the pulmonary capillaries
    • Other gases (eg. volatile anaesthetics) also bind to serum proteins and triglycerides
    • Carbon dioxide also binds serum and erythrocyte proteins, but the most important chemical reaction which influences its diffusion is the conversion of bicarbonate into CO2 by carbonic anhydrase



Worth, Heinrich, Walter Nüsse, and Johannes Piiper. "Determination of binary diffusion coefficients of various gas species used in respiratory physiology." Respiration physiology 32.1 (1978): 15-26.

Åberg, Christoffer, et al. "A theoretical study of diffusional transport over the alveolar surfactant layer." Journal of The Royal Society Interface 7.51 (2010): 1403-1410.

Lambertsen, C. J., and J. K. Clark. "The pulmonary oxygen diffusion coefficient.The American journal of the medical sciences 218.6 (1949): 715.

Sharan, Maithili, and M. P. Singh. "Numerical simulation of pulmonary O2 and CO2 exchange." International journal of bio-medical computing 16.1 (1985): 59-80.

Staub, N. C., J. M. Bishop, and R. E. Forster. "Importance of diffusion and chemical reaction rates in O2 uptake in the lung." Journal of applied physiology 17.1 (1962): 21-27.

Lindstedt, Stan L. "Pulmonary transit time and diffusing capacity in mammals." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 246.3 (1984): R384-R388.

Cain, Stephen M., and Arthur B. Otis. "Carbon dioxide transport in anesthetized dogs during inhibition of carbonic anhydrase." Journal of applied physiology 16.6 (1961): 1023-1028.