Diffusing Capacity and Limitation

Explain perfusion-limited and diffusion-limited transfer of gases

Define diffusing capacity and its measurement

Describe the physiological factors that alter diffusing capacity

Rate of diffusion of gases is given by Fick's Law:
, where:

  • is the pressure gradient across the membrane
  • is the area of the membrane
  • is the solubility of the substance
  • is the thickness of the membrane
  • is the molecular weight of the substance

These can be divided into pressure, lung factors, and substance factors:

  • Pressure gradient
    In the lung, this is a function of:
    • Partial pressure of the gas in the alveolus
      This is affected by:
      • Atmospheric pressure
      • Ventilation
        Alveolar hypoventilation will:
        • Increase PACO2
        • Decrease PAO2
    • Partial pressure of the gas in blood
      This is affected by:
      • Solubility of the gas in blood
        CO2 is ~20 times as soluble as O2 in blood.
      • Binding of gas to protein:
        • Particularly haemoglobin
          Affects the rate of uptake of O2 and CO, and is why calculated DLCO is corrected for haemoglobin.
          • The shape of the oxy-haemoglobin dissociation curve allows a large volume of oxygen to be bound before PaO2 begins to rise substantially.
        • Formation of carbamino compounds
        • Anaesthetic agents to plasma contents
          e.g. albumin, cholesterol.
  • Lung factors
    • Surface Area
      Affected by:
      • Parenchyma volume
        • Body size
        • Pathology
          Many lung diseases will reduce surface area for gas exchange.
      • V/Q mismatch
        Both shunt and dead space reduce the surface area available for gas exchange.
      • Pulmonary blood volume
        Vascular distension and recruitment also affects surface area. Factors affecting pulmonary blood volume include:
        • Cardiac output
          • Increased recruitment of vasculature in high output states
          • Decreased recruitment and increased V/Q mismatch in shock states.
        • Posture
          Increased surface area when supine relative to sitting or standing.
    • Thickness
      Increasing alveolar-capillary membrane thickness impedes gas exchange. Causes of this include:
      • Pathology
        e.g. Pulmonary oedema and cardiac failure.
  • Substance factors
    • Solubility
      More soluble substances will diffuse more quickly.
    • Molecular weight
      Smaller substances will diffuse more quickly.

Diffusion and Perfusion Limitation

Limitation refers to what process limits gas uptake into blood:

  • Gases which are diffusion limited fail to equilibrate, i.e. the partial pressure of a substance in the alveolus does not equal that in the pulmonary capillary
    • e.g. Carbon Monoxide
  • Gases which are perfusion limited have equal alveolar and pulmonary capillary partial pressures, so the amount of gas content transferred is dependent on blood flow
    • e.g. 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

Other Gases

  • Carbon monoxide
    Diffusion limited due to:
    • High affinity for haemoglobin
      Continual uptake into Hb results in a low partial pressures in blood.
  • Nitrous oxide Perfusion limited as equilibrium between alveolus and blood is rapidly reached as it is:
    • Not bound to haemoglobin
    • Relatively insoluble

Diffusion Capacity

  • Measurement of the ability of the lung to transfer gases
  • Measured as DLCO or diffusing capacity of the lung for carbon monoxide
    Carbon monoxide is used as it is a diffusion limited gas.
  • Process:
    • Vital capacity breath of 0.3% CO
    • Held for 10s and exhaled
    • Inspired and expired CO are measured
    • Difference is the amount of CO which is now bound to Hb
    • DLCO is corrected for:
      • Age
      • Sex
      • Hb
  • DLCO is decreased in:
    • Thickened alveolar-capillary barrier
      • Interstitial lung disease
    • Reduced surface area
      • Emphysema
      • PE
      • Lobectomy/pneumonectomy
  • DLCO is increased in:
    • Exercise
      Recruitment and capillary distension.
    • Alveolar haemorrhage
      Hb present within the lung binds CO.
    • Asthma (may be normal)
      Potentially due to increased apical blood flow.
    • Obesity (may be normal)
      Potentially due to increased cardiac output.


  1. Brandis K. The Physiology Viva: Questions & Answers. 2003.
  2. Lumb A. Nunn's Applied Respiratory Physiology. 7th Edition. Elsevier. 2010.
  3. ANZCA March/April 1999
  4. Deranged Physiology - Carbon Dioxide Storage and Transport
Last updated 2017-10-04

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