Lung Interstitial Pressure and Structure in Acute Hypoxia

Abstract

The air blood barrier is a gas exchanger and is well designed to fulfill this task as its main feature is its minimum thickness that in turn reflects a minimum amount of extravascular water. The maintenance of a minimum water volume is due to mechanisms able to control interstitial fluid turnover and to offset transient conditions of increase in this volume. The hydraulic pressure in the lung interstitium is ~ -10 cmH₂O and reflects the equilibrium between the lymphatic absorption pressure and the microvascular filtration through the basement membrane whose hydraulic permeability is kept very low due to the macromolecular organization of heparansulphate proteoglycans (HS-PGs). When microvascular filtration is increased, the increase in extravascular water is minimal in face of a considerable increase in interstitial pressure (up to ~ 5 cmH2O) because of the high elastance of the extracellular matrix thanks to the mechanical role of matrix chondroitin sulphate proteoglycans (CS-PGs). This increase in pressure buffers microvascular filtration. Hypoxia causes fragmentation of CS-PGs of the extracellular matrix and of HS-PGs of the basement membrane: the result is a decrease in tissue elastance and an increase in permeability of the endothelial and epithelial barriers. When the overall PGs fragmentation overcomes a critical threshold, severe lung edema develops. Recovery from severe lung edema requires that extracellular integrity is restored. We provide evidence for a prompt lung cellular response to interstitial edema. We interpret this response as a fine mechanism to detect minor increases in extravascular water and to promote the reparative process.