Diffusion Capacity

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  • Carbon monoxide - diffusion limited
  • Rapidly taken up by Hb within the cell, therefore a large amount of CO can be taken up with no increase in partial pressure
  • CO partial pressure barely changes, and gas continues to move rapidly across the alveolar wall
  • Therefore, amount of CO getting into blood is limited by diffusion properties of the blood-gas barrier
  • Nitrous Oxide - perfusion limited
  • Does not combine with Hb in blood, therefore partial pressure rises rapidly - reaching equilibrium with alveolar gas in 1/10th of transport time
  • Therefore, amount of N2O taken up by blood depends on amount of available blood flow, not on diffusion properties of blood-gas barrier

Screen shot 2012-09-24 at 10.15.35 AM.png

  • O2:
  • Under resting conditions, mixed venous blood PO2 is 4/10ths of alveolar PO2
  • Capillary PO2 reaches alveolar PO2 by the time the RBC is 1/3rd of the way along the capillary - therefore perfusion limited under these conditions
  • With severe exercise, pulmonary blood flow increased and transit time can be as little as 1/3rd of normal 0.75 seconds, however usually still no fall in end-capillary PO2
  • If diffusion properties of lung are impaired, blood PO2 may not reach alveolar value by the end of the capillary indicating diffusion limitation
  • Combination of exercise and diffusion limitation makes gas end capillary PO2 likely to be much lower
  • Low alveolar PO2 - eg. at altitiude can also cause reduced end capillary PO2 by decreasing the pressure gradient driving diffusion
  • Diffusion limitation or perfusion limitation depends on:
  • Solubility in the blood-gas barrier
  • "Solubility" in the blood - indicated by the slope of this dissociation curve
  • Sheep entering gate analogy - if small gate and big field, limited by gate. If small gate/field or big gate/field, limited by field size.

Measuring Diffusion Capacity[edit]

  • Diffusion of a gas through tissues is described by Fick's law:

Screen shot 2012-09-24 at 10.29.36 AM.png

  • Rate of transfer of a gas through a sheet of tissue is:
  • Proportional to the tissue area A and difference in gas partial pressure between the 2 sides (P1 - P2)
  • Inversely proportional to the tissue thickness T
  • Proportional to the gas constant - which depends on the properties of the tissue and gas:
  • Proportional to the solubility of the gas, inversely proportional to the square root of the molecular weight
  • Area of blood gas barrier in lung is 50-100m, thickness only 0.3μm
  • Carbon monoxide is used to measure diffusing capacity using the Fick equation

Screen shot 2012-09-24 at 10.50.33 AM.png

  • Lung area and blood gas barrier thickness are unable to be measured, therefore instead we use the diffusing capacity of the lung

Screen shot 2012-09-24 at 10.50.40 AM.png or: Screen shot 2012-09-24 at 10.50.48 AM.png where P1 and P2 are partial pressures of alveolar gas and capillary blood. Because there is minimal CO in blood, this can be simplified as: Screen shot 2012-09-24 at 10.50.54 AM.png

  • Or - the volume of CO in mls per minute per mmHg of partial pressure

Reaction Rates with Hb

  • In the case of O2 and CO, uptake is also limited by reaction with haemoglobin.
  • This is also included in DL. DL can then be split into two components, with DM representing the conductance of the blood-gas membrane, VC the capillary blood volume, and θ representing the rate of reaction with Hb (in ml/min/ml blood/mmHg):

Screen shot 2012-09-24 at 11.08.22 AM.png

Single Breath Method

  • Single breath of dilute CO inspired and held for 10 seconds, then measured on expiration.
  • Helium is also added to give a measurement of lung volume by dilution
  • Normal diffusing capacity of CO is 25ml/min/mmHg, increasing 2-3x on exercise due to recruitment and distension of pulmonary capillaries