Diffuse alveolar damage--the role of oxygen, shock, and related factors. A review.

Exposure to high concentrations of oxygen has been demonstrated to cause alterations throughout the respiratory tract in humans and other animals. Changes occur in the airway epithelium, the arterial vascular bed, the alveolar septa, and in the pleural space. Atelectasis, interstitial and alveolar edema, pleural effusions, and changes in cell function and structure occur. The morphologic changes that occur in the lung in response to inhalation of high concentrations of oxygen were first described in 1897-1899 by J. Lorraine Smith (24, 25) who characterized the acute histologic features as including atelectasis, inflammation, and vascular congestion, with death due to con­ solidation of the lungs from congestion and exudation into the alveoli. This has subsequently been defined as the early or exudative phase of severe pulmonary oxygen toxicity. Multiple investigators have confirmed similar morphologic patterns in a wide variety of animal species (6), including primates (19) and man (14, 18, 22). Among the most dramatic effects are those involving the cells of the alveolar septum. Kistler et al (20) used electron microscopy to identify qualitatively and quantitatively many of the changes occurring in rat lungs. The earliest change was a twofold increase in the width of the interstitial space caused initially by edema. Subsequently the number of interstitial cells and interstitial matrix elements increased. The capillary endothelial cell was identified as one of the primary targets of oxygen-mediated cell injury; cytoplasmic changes in these endothelial cells were followed by fragmentation and cell destruction. These changes in the lung microvasculature are those most closely associated with events leading to death of animals given lethal doses of hyperoxia.

Morphologic Changes in Pulmonary Oxygen Toxicity

Prolonged breathing of very high F(IO(2)) (F(IO(2)) ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of F(IO(2)), is usually fatal. The severity of HALI is directly proportional to P(O(2)) (particularly above 450 mm Hg, or an F(IO(2)) of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O(2) species that overwhelms natural anti-oxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when F(IO(2)) exceeds 0.7, and may become problematic when F(IO(2)) exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of F(IO(2)), the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over F(IO(2)), as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies.

http://rc.rcjournal.com/content/respcare/58/1/123.full.pdf

Hyperoxic Acute Lung Injury

For a study of the processes and mechanisms of pulmonary structural remodeling in fibrotic lungs and metaplastic squamous epithelial cells in fibrotic alveoli, immunohistochemical, ultrastructural, and light-microscopic morphometric observations were made of the lungs in acute and proliferative stages of diffuse alveolar damage (n = 40) obtained from biopsies and autopsies. Morphometry showed that intraalveolar fibrosis developed in the early proliferative stage and was more prominent than interstitial fibrosis. In the early proliferative stage, activated myofibroblasts migrated into intraalveolar spaces through gaps in the epithelial basement membrane. They then attached to the luminal side of epithelial basement membrane and produced intraalveolar fibrosis and coalescence of alveolar walls. This intraalveolar fibrosis was the essential factor in the remodeled lungs. Albumin, fibrinogen, immunoglobulins, and surfactant apoprotein were present throughout the hyaline membrane. Fibronectin was not found in hyaline membrane of the lesions in early acute stage but was demonstrated in later stages in outer layers of hyaline membranes and in the areas of intraalveolar fibrosis. Fibronectin may be responsible for the migration and proliferation of myofibroblasts in intraalveolar spaces. Metaplastic single-layered and stratified squamous epithelial cells were keratin-positive and surfactant apoprotein-negative. These metaplastic epithelial cells were frequently found in the alveoli with minimal Type II epithelial cell proliferation and in the grossly scarred alveoli.

The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage.

Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial.

https://journal.chestnet.org/article/S0012-3692(15)39175-3/pdf

Oxygen Pneumonitis in Man: Light- and Electron-Microscopic Morphometric Studies

Oxygen Pneumonitis in Man

The structure of the extracellular alveolar lining layer in 3 human lungs is described. This lining was composed of 2 layers: a) a highly osmiophilic surface layer, b) a base layer.

Jacques Eggermann

Papers

Oxygen Pneumonitis in Man: Light- and Electron-Microscopic Morphometric Studies

Oxygen Pneumonitis in Man

Demonstration of the extracellular alveolar lining layer (surfactant) in human lungs. An ultrastructural study.

Light- and Electron-Microscopic Morphomefric Studies