Stress Failure of the Pulmonary Blood–Gas Barrier

Abstract

The ultrastructure of the blood–gas barrier was a mystery for many years because this is beyond the resolution of the light microscope. However, when Frank Low published the first electron micrographs of the human blood–gas barrier in 1953, it was immediately clear that a vanishingly small amount of tissue, only 0.2 µm thick, separated the pulmonary capillaries from the alveolar gas. Astonishingly, however, it was 40 years before the fragility of the barrier was recognized. Two selective forces determine the structure of the barrier. First, it must be exceedingly thin to allow adequate transfer of gases across it by diffusion. Even so, under some physiological conditions, humans develop arterial hypoxemia because the diffusion rate of oxygen through the barrier is insufficient. Next, the barrier must be immensely strong to prevent bleeding into the alveoli. However, again this occurs in humans under some physiological conditions, and it is particularly striking in animals such as the Thoroughbred racehorses that are capable of very high aerobic activity. Mechanical failure of the barrier can occur when it is exposed to high stresses. Failure is seen if the capillary transmural pressure is greatly increased, the lung is inflated to very high volumes, or the type IV collagen that is responsible for the strength becomes abnormal in disease. Remodeling of the barrier is seen if the stresses are increased over a period of time. The basic structure of the barrier has been highly conserved throughout the evolution from the lungfishes through the amphibians, reptiles, mammals, and birds.