♦ Diffusion-limited O2 transport. In certain pathologic conditions (e.g., fibrosis) and during strenuous exercise, O2 transfer becomes diffusion limited. For example, in fibrosis the alveolar wall thickens, increasing the diffusion distance for gases

In diffusion-limited gas exchange scenarios, such as those seen in pulmonary conditions like fibrosis, the mechanics of oxygen (O2) transport are altered significantly. Under normal circumstances, the transfer of O2 from the alveoli into the pulmonary capillary blood is rapid, allowing for efficient equilibration—this is often referred to as perfusion-limited gas exchange. In healthy lungs, O2 equilibrates quickly due to a favorable diffusion gradient created by the high partial pressure of O2 in the alveoli compared to that in the blood. However, in pathological conditions such as pulmonary fibrosis, the thickening of the alveolar wall increases the diffusion distance. This not only reduces the diffusion capacity (DL) but also slows the rate at which O2 can cross into the blood. As a result, while there still exists a partial pressure gradient driving the diffusion of O2, the time available for equilibration is significantly compromised, leading to incomplete transfer by the time blood exits the pulmonary capillary. The unique aspect of diffusion-limited processes is that the partial pressure gradient can remain present along the entire length of the capillary. This means that while there is a gradient favoring O2 diffusion from the alveoli to the blood, the actual amount of O2 that can be transferred is restricted by the limited rate of diffusion associated with the increased thickness of the barrier. In essence, although the gradient still exists and may intuitively suggest that more O2 could be absorbed in the context of ongoing diffusion, the inability to achieve rapid equilibration means that the total O2 transfer is actually impaired, not enhanced. This is in contrast to normal pulmonary function, where the equilibration occurs quickly within the initial portion of the capillary. Thus, the impact of fibrosis in this context ultimately leads to decreased oxygen transfer efficiency, rather than an increase, underscoring the importance of maintaining healthy alveolar structures for optimal gas exchange.