Diffusion and perfusion limited gas exchange—what's the difference?

The flux (or movement) of gasses across the alveolar-capillary membrane is not an instantaneous process. It is dependent on the principles of perfusion and diffusion. Applying Fick’s law to the alveolar-capillary membrane we can see that the flux of gases—or the diffusion of oxygen and carbon dioxide—is influenced by the area and thickness of the membrane, the molecular weight and solubility of the gas molecules, and the pressure gradient across the membrane. For an alveolar gas at nearly constant partial pressure, the pressure gradient for diffusion is determined by the gas’s partial pressure in the capillary blood.

But, the rate and efficiency of gas transfer is also dependent on blood flowing through the pulmonary capillaries—or, perfusion. And the speed of blood flow (or the rate of perfusion) is important—it determines the amount of time blood is available in the capillary for diffusion to take place. Under normal, resting circumstances, a red blood cell spends about 0.75 seconds in a pulmonary capillary.

The physiology of two gases highlights these principles: carbon monoxide (CO) and nitrous oxide (N₂O).

As inspired carbon monoxide (CO) diffuses across the alveolar-capillary membrane, it rapidly enters red blood cells, avidly binding to hemoglobin. Consequently, there is essentially no increase in the partial pressure of carbon monoxide in the plasma. The partial pressure difference across the alveolar-capillary membrane (P1 – P2) remains maximal.

The amount of carbon monoxide taken up in the pulmonary circulation depends on the diffusion characteristics of the alveolar-capillary membrane, not the amount of pulmonary capillary blood flow. The uptake of carbon monoxide is said to be diffusion limited.

In contrast to carbon monoxide, inspired nitrous oxide (N₂O) does not combine with hemoglobin. Rather, it remains dissolved in plasma causing the partial pressure of nitrous oxide in the pulmonary capillary to increase, and the pressure gradient falls to zero. Consequently, additional uptake of nitrous oxide is dependent on it being carried away from the site of diffusion—in other words, it is dependent on pulmonary capillary blood flow.

The amount of nitrous oxide taken up in the pulmonary capillaries depends entirely on the rate of pulmonary blood flow, not on the diffusion characteristics of the alveolar-capillary membrane. Hence, nitrous oxide transfer is described as perfusion limited.

The physiology of oxygen movement across the alveolar-capillary membrane is intermediate to that of carbon monoxide and nitrous oxide. Oxygen combines with hemoglobin, although much less avidly than does carbon monoxide. The partial pressure of oxygen in blood flowing through the pulmonary capillaries equals the partial pressure of oxygen within the alveolus by the time the red blood cell travels along about one third of the capillary length.

Diffusion of oxygen across the alveolar capillary membrane is normally perfusion limited.

However, in a variety of disease states, equilibration of alveolar and blood partial pressures of oxygen may be delayed relative to red blood cell capillary transit time, with resultant diffusion limitation, as well.