12 - Resolution and Repair of Acute Lung Injury

Summary

Introduction

Successful recovery of lung function after acute lung injury requires that the repair process occur in an orderly and controlled sequence similar to that of other injured tissues. First, the excess alveolar fluid and soluble proteins must be removed from the airspaces. Second, the excess soluble and insoluble proteins must be cleared from the alveoli. Third, alveolar epithelial type II cells must repopulate the denuded epithelial barrier. Fourth, the edematous and fibrotic interstitium must shrink and reconstitute its normal matrix. Fifth, the injured and obstructed endothelium must be recanalized to restore normal blood flow to the lung. Sixth, all of the nonessential cells that participated in the repair process must die and their cellular debris must be cleared. Failure of any one of these processes will result in persistent lung injury with fibrosing alveolitis and nonresolving respiratory failure.

This chapter reviews what is known about the recovery of normal lung function after acute lung injury. The first section reviews the mechanisms responsible for removal of alveolar edema fluid. The second section discusses the fibrosing alveolitis that develops as a response to acute lung injury with an emphasis on the role of extracellular matrix proteins in this process. The third section describes the potential contribution of growth factors in remodeling of the vascular endothelium, the interstitium, and the alveolar epithelial barrier. The clinical manifestations and significance of these recovery phases is considered as well.