How can a thicker alveolar-capillary membrane limit oxygen diffusion?

In the human respiratory system, the alveolar-capillary membrane is normally extremely thin—approximately 0.5 μm—which facilitates the efficient diffusion of gases between the alveoli and the pulmonary capillaries.1

When this membrane thickens, it creates a physical barrier that increases the distance oxygen molecules must travel to reach the blood. According to the principles of diffusion, the rate of gas transfer is inversely related to the thickness of the membrane through which the gas must pass. As the membrane thickens, the efficiency of oxygen transfer decreases, potentially leading to incomplete gas exchange and a reduction in arterial blood oxygen content. This phenomenon is categorized as a "diffusion limitation," where the increased distance prevents oxygen from reaching equilibrium between the alveolar air and the pulmonary capillary blood during the time available for exchange.23