Mechanisms governing the secondary burst of reactive oxygen species (ROS) and basic pathways of cell death from hyperoxia. 1: Loss of plasma membrane integrity from lipid peroxidation by ROS. 2: ROS damage to the mitochondria membranes and deactivation of enzyme systems and cytochrome chain. 3: This results in the release of cytochrome c into the cytoplasm. 4: ROS damage to the nuclear membrane and fragmentation of DNA. 5: Evolving cell trauma from steps 1, 2, and 4 trigger the production and release of pro-inflammatory cytokines and chemokines into the extracellular space and circulation. 6: This attracts and activates platelets, neutrophils, and macrophages, resulting in a secondary burst of ROS from these inflammatory cells. Mechanisms governing the secondary burst of reactive oxygen species (ROS) and basic pathways of cell death from hyperoxia. 1: Loss of plasma membrane integrity from lipid peroxidation by ROS. 2: ROS damage to the mitochondria membranes and deactivation of enzyme systems and cytochrome chain. 3: This results in the release of cytochrome c into the cytoplasm. 4: ROS damage to the nuclear membrane and fragmentation of DNA. 5: Evolving cell trauma from steps 1, 2, and 4 trigger the production and release of pro-inflammatory cytokines and chemokines into the extracellular space and circulation. 6: This attracts and activates platelets, neutrophils, and macrophages, resulting in a secondary burst of ROS from these inflammatory cells. Direct cell trauma results in necrosis or “unplanned” cell death. In addition, the release of cytochrome c into the cytoplasm (A-1) and damage to the plasma membrane (A-2) trigger other cellular processes that instruct the cell to essentially “commit suicide” through the process of apoptosis (programmed cell death). Richard H Kallet, and Michael A Matthay Respir Care 2013;58:123-141 (c) 2012 by Daedalus Enterprises, Inc.