Role of bulk fluid flow in protein permeability of the dog lung alveolar membrane.

In five anesthetized, closed-thorax dogs, we measured net tracer albumin (RISA) uptake rate from an isosmotic buffer-filled lung lobe for 6 h; 3 h at each of two different alveolar RISA concentrations. We calculated the permeability coefficient assuming a two-compartment (alveolar fluid and plasma) diffusional model. In every dog the permeability coefficient decreased after the alveolar RISA concentration was increased. After freezing the lungs terminally, we found the fluid-filled lobes had extensive free interstitial fluid perivascular cuffs, indicating a third compartment filled by bulk flow. In separate experiments, we filled isolated lung lobes with buffer containing RISA and microsampled free interstitial fluid. The free interstitial fluid RISA concentration averaged 90% of airway concentration. The interstitium appears to fill by bulk flow through low-resistance channels. Tracer protein uptake from a fluid-filled lung lobe involves three fluid compartments. We postulate fluid and protein enter the interstitium by bulk flow along a hydrostatic pressure gradient, and protein then diffuses into plasma from the interstitium.