Perfusion Versus Diffusion Limitation

Expansion

• Perfusion limited - the gas equilibrates across the membrane early in the capillary, so uptake depends only on blood flow. Example: nitrous oxide
• Diffusion limited - the gas never equilibrates because it is avidly bound, so uptake depends on the membrane. Example: carbon monoxide

Oxygen is normally perfusion limited: equilibration is complete in about 0.25 seconds, a third of the resting capillary transit time of 0.75 seconds. There is therefore a large reserve.

That reserve is eroded when:

• Transit time shortens in exercise, as cardiac output rises
• The membrane thickens in fibrosis
• The driving gradient falls at altitude

Combine them, as in an athlete exercising at altitude or a patient with fibrosis exercising, and oxygen becomes diffusion limited, producing exercise-induced desaturation. This is why desaturation on exertion with normal resting gases is an early sign of interstitial lung disease.