Cellular and intercellular transport pathways in exchange vessels.

The endothelium of lung alveolar capillaries is of the continuous type, that of airway exchange vessels (capillaries and pericytic venules) includes both continuous and fenestrated types. Water and small lipophilic solutes penetrate via the endothelial cells (cell membrane pathway) as well as through intercellular junctions. Hydrophilic solutes are limited to junctional pathways and cytoplasmic vesicles. Permeation of hydrophilic solutes is progressively restricted with increasing molecular size, as by a sieve, with many openings 8 nm and a few 40 to 60 nm wide. In response to local tissue injury or to certain chemical mediators, larger junctional pathways may be opened, greatly increasing permeability to large molecules. Both alveolar capillaries and airway exchange vessels exhibit this response, but the effective stimuli may differ (e.g., alveolar capillaries are insensitive to histamine and bradykinin). Hydrophilic solutes are transported by diffusion, convection, and vesicular exchange (transcytosis). For small ions and molecules (radii < 2 nm), diffusion is the dominant transport mode; contributions of convection and transcytosis are negligibly small. Because diffusion decreases with increasing molecular size, all three mechanisms may contribute substantially to transport of large molecules (radii > 2 nm). Fenestrated endothelia have higher hydraulic conductivities and are more permeable to small ions and molecules than are continuous endothelia. However, their permeabilities to plasma proteins are about the same. Lung alveolar capillary endothelium has lower hydraulic conductivity and lower solute permeabilities than do other continuous endothelia (heart, skeletal muscle). Airway exchange vessel endothelium has about the same permeability to serum albumin as alveolar capillary endothelium.