Basic science of acute lung injury

Acute lung injury results from direct or indirect insult to the lung and manifests clinically as severe hypoxaemia and stiff lungs; mechanical ventilation is usually indicated. A set of diagnostic criteria must be met, within which the degree of hypoxaemia distinguishes acute lung injury from acute respiratory distress syndrome (the latter is more severe). The pulmonary oedema is non-hydrostatic. The course of the disease can be divided into inflammatory, proliferative and fibrotic phases lasting on average 4–6 weeks. During this time, the alveolar walls are damaged, allowing protein and fluid to leak in. Surfactant (essential for lung compliance) is inactivated. The major inflammatory mediators are neutrophils, which release multiple mediators, including cytokines, free radicals, histotoxic enzymes and other proteases. Vascular tone is reduced by nitric oxide and cyclooxygenase-2, thus preventing hypoxic pulmonary vasoconstriction and contributing to worsening hypoxia. The body counteracts by manufacturing inhibitors of inflammatory cytokines and upregulating anti-inflammatory cytokines. In most cases, the lung attempts to restore normal architecture by apoptosis of neutrophils followed by removal of proteinaceous fluid from the alveoli and proliferation of type-II pneumocytes, which are integral to structure and production of surfactant, respectively. Collagen can be laid down as part of the fibrotic phase; the finding of procollagen peptide at the onset of respiratory failure confers a poor prognosis.