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.
  • Reduced diffusion capacity leads to Type 1 respiratory failure as oxygen is affected to a greater extent than carbon dioxide

Carbon Dioxide

  • Carbon dioxide is an exception to these categories and limited by ventilation, rather than diffusion or perfusion.
  • This is because CO2 is constantly being produced by the body, and needs to be removed - it therefore moves in the opposite direction to the other gases.
  • There is a large amount of carbon dioxide in venous blood, present in various forms:
    • Dissolved in plasma (CO2 is 20x more soluble in blood than oxygen)
    • Bicarbonate ions (part of the CO2 and pH buffer system)
    • Carbamino compounds (largely bound to Hb for carriage to the alveolus)
  • This means that although CO2 readily diffuses into the alveolus, the partial pressure in the blood does not change because it is constantly being replenished both from the above stores, and ongoing production by cellular metabolism.
  • If equilibrium is reached across the alveolar-capillary membrane, CO2 transfer will stop regardless of speed of diffusion or ongoing perfusion.
  • Therefore, the only way to ensure ongoing removal of CO2 from the blood is to clear it from the alveolus i.e. by maintaining alveolar ventilation.

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. Yartsev, A. Carbon Dioxide Storage and Transport.
Last updated 2021-08-23

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