Diffusion Capacity

• 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

• 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

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

• 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

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

or: 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:

• 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 D_L. D_L can then be split into two components, with D_M representing the conductance of the blood-gas membrane, V_C the capillary blood volume, and θ representing the rate of reaction with Hb (in ml/min/ml blood/mmHg):

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