Role of alveolar epithelium during pulmonary edema

The specific role of alveolar epithelium during the constitution and the re solution of alveolar edema has been the subject of numerous studies during the past decade that have conducted to complete reappraisal. Three notions that received general agreement have been reconsidered:the absence of lesio ns of the alveolo-capillary barrier during hemodynamic edema, the retrograd e pathway taken by the edema fluid to flood alveoli and the role of Starlin g forces in governing alveolar liquid resorption. Extensive electron micros copy studies have shown that large increases in transmural capillary pressu re may completely disrupt the alveolo-capillary barrier, a phenomenon calle d "stress failure". Stress failure may explain the occurrence of alveolar h aemorrhage during heavy exercise in thoroughbred horses and the microvascul ar permeability alterations observed in some forms of pulmonary edema such as that produced by high volume ventilation. Recent works suggest that stre ss failure may reflect a preservative cellular response rather than a direc t mechanical injury. The way alveolar edema develops has been clarified usi ng a refined histological preparation. Edema fluid appears to make irruptio n into airspaces directly through the alveolar epithelial barrier, first ac cumulating in zones of low pressure such as the alveolar corners before com pletely filling distal airspaces. Alveolar epithelial type I cells display considered plasticity during this transfer of liquid between the interstiti al and alveolar compartments epithelial type I cells detach by places from their basement membrane; their plasma membrane is deformed by huge expansio ns that confine edema fluid. This may be a way to delay the irruption of pl asma proteins in the alveolar-airway lumen and to preserve surfactant activ ity. The mechanisms of alveolar edema resolution have received considerable attention. Alveolar liquid is absorbed following active transepithelial so dium transport by alveolar cells. In most species, the main pathway taken b y sodium to enter cells at the apical membrane is constituted by epithelial sodium channels. Inactivation of these channels in a knock-out mouse model results in respiratory distress and early death. Transepithelial sodium tr ansport and the clearance of alveolar fluid is positively modulated by horm ones such as beta-adrenergics, cytokines such as tumour necrosis factor-alp ha and growth factors such as keratinocyte growth factor. Maintenance of al veolar epithelial barrier integrity is also a key factor. The efficiency of active transepithelial sodium transport in driving water depends on the pr eservation of the epithelium barrier properties. There is evidence that the ability of the alveolar epithelium to concentrate proteins within airspace s is correlated with clinical improvement in patients suffering from variou s forms of pulmonary edema.