Title:Mechanistic Considerations on the Development of Lung Edema: Vascular, Perivascular and Molecular Aspects from Early Stage to Tissue and Vascular Remodeling Stage
VOLUME: 8 ISSUE: 2
Author(s): Giuseppe Miserocchi and Ilaria Rivolta
Affiliation:Department of Experimental Medicine, University of Milano Bicocca, Via Cadore, 48, 20900 Monza (MB), Italy.
Keywords:Air-blood barrier, edema, interstitial matrix, matrix remodelling, microvascular permeability, pulmonary hypertension, vasomotion
Abstract:The purpose of this article is double, to review the mechanisms allowing to control the volume of the
extravascular lung water and then to trace a pathophysiological basis for the development of lung edema when such
control is lost. Efficient gas diffusion in the air-blood barrier is guaranteed by an extremely low volume of extravascular
water, assuring a minimum barrier thickness, and by a perfect matching between alveolar perfusion and ventilation. Low
microvascular permeability and dynamic remodeling of the interstitial matrix and of microvessels maintain this
equilibrium. Lung cells play a crucial role by acting as early sensors of the dysregulation of lung water balance. When
capillary filtration increases due to an increase in microvascular permeability (e.g as in hypoxia), interstitial pressure rises
substantially due to the rigidity of the interstitial compartment. This triggers mechano-transduction in lung cells through
the expression of lipid microdomains that represent specific signaling platforms. Severe edema occurs as a result of
yielding/fragmentation of important link proteins (matrix proteoglycans) to excessive tissue stress. The reparative matrix
remodeling is stimulated by FGF&bgr; (Fibroblast Growth Factor &bgr;) and KGF (Keratinocyte Growth Factor). In edematous
regions the increase in tissue pressure may cause compression of microvessels and associated marked precapillary
vasoconstriction, thus resulting in an increase in pulmonary vascular resistances. Vascular remodeling decreases blood
flow in edematous regions and favors blood redistribution to normal regions. Pulmonary hypertension is common to all
conditions of severe lung edema and is proportional to the extension of the edematous process. In conclusion, it appears
tempting to think of pulmonary hypertension as the consequence, rather than the cause, of lung edema which would lead
to hypothesize that an excessive fibro-proliferative process in the lung might be interpreted as the response to a chronic
condition of high microvascular permeability.
