A patient is brought to the emergency depament following carbon monoxide poisoning. Hyperbaric oxygen was given, following which patient developed oxygen toxicity. What is the likely mechanism of the toxicity?
The free radical theory of oxygen toxicity explains the mechanism of oxygen toxicity. According to the theory, various highly reactive and potentially cytotoxic free-radical products of oxygen are generated metabolically in the cell. These sho-lived oxygen metabolites, including superoxide anion, hydroxyl radical, hydrogen peroxide, and singlet oxygen, have been shown to be capable of effects such as inactivation of sulfhydryl enzymes, interaction with and disruption of DNA, and peroxidation of unsaturated membrane lipids with resultant loss of membrane integrity. The cell is also equipped with an array of antioxidant defenses, including the enzymes superoxide dismutase, catalase, glutathione peroxidase, vitamin E, and ascorbate. Under hypoxia, the intracellular generation and influx of free radicals is believed to increase markedly and may overwhelm the detoxifying capacity of the normal complement of antioxidant defenses, with resultant cytotoxicity. The pathology of oxygen toxicity in the lungs is non-specific and consists of atelectasis, edema, alveolar hemorrhage, inflammation, fibrin deposition, and thickening and hyalinization of alveolar membranes. Ref: Yao & Ausio's Anesthesiology: Problem-Oriented Patient Management By Fun-Sun F. Yao, Vinod Malhotra, M.D., 2012, Page 67 ; Pulmonary physiology by Michael G. Levitzkypage, 2007, Page 245
Direct DNA damage
Apoptosis
Nuclear fragmentation
Mediated by free radicals