The pulmonary blood-gas barrier is an extraordinary bioengineering structur
e because of its vast area but extreme thinness. Despite this, almost no at
tention has been given to its mechanical properties. The remarkable area an
d thinness come about because gas exchange occurs by passive diffusion. How
ever, the barrier also needs to be immensely strong to withstand the very h
igh stresses in the capillary wall when capillary pressure rises during exe
rcise. The strength of the thin region of the barrier comes from type TV co
llagen in the basement membranes. When the stresses in the capillary walls
rise to high levels, ultrastructural changes occur in the barrier, a condit
ion known as stress failure. Physiological conditions that alter the proper
ties of the barrier include severe exercise in elite human athletes. Animal
s that have been selectively bred for high aerobic activity, such as Thorou
ghbred racehorses, consistently break their pulmonary capillaries during ga
lloping. Pathophysiological conditions causing stress failure include high-
altitude pulmonary edema and overinflation of the lung, which frequently oc
curs with mechanical ventilation. Remodeling of the capillary wall occurs i
n response to increased wall stress in diseases such as mitral stenosis. Th
e barrier is able to maintain its extreme thickness with sufficient strengt
h as a result of continual regulation of its wall structure. How it does th
is is a central problem in lung biology.