Ischemic cell death, or oncosis, is a form of accidental cell death. The process is characterized by an ATP depletion within the cell leading to impairment of ionic pumps, cell swelling, clearing of the cytosol, dilation of the endoplasmic reticulum and golgi apparatus, mitochondrial condensation, chromatin clumping, and cytoplasmic bleb formation. Oncosis refers to a series of cellular reactions following injury that precedes cell death. The process of oncosis is divided into three stages. First, the cell becomes committed to oncosis as a result of damage incurred to the plasma membrane through toxicity or ischemia, resulting in the leak of ions and water due to ATP depletion. The ionic imbalance that occurs subsequently causes the cell to swell without a concurrent change in membrane permeability to reverse the swelling. In stage two, the reversibility threshold for the cell is passed and the cell becomes committed to cell death. During this stage the membrane becomes abnormally permeable to trypan blue and propidium iodide, indicating membrane compromise. The final stage is cell death and removal of the cell via phagocytosis mediated by an inflammatory response. Etymology Although ischemic cell death is the accepted name of the process, the alternative name of oncosis was introduced as the process involves the affected cell(s) swelling to an abnormally large size in known models. This is thought to be caused by failure of the plasma membrane's ionic pumps. The name oncosis (derived from ónkos, meaning largeness, and ónkosis, meaning swelling) was first introduced in 1910 by pathologist Friedrich Daniel von Recklinghausen. Comparison to Apoptosis Oncosis and apoptosis are distinct processes of cellular death. Oncosis is characterized by cellular swelling caused by a failure in ion transporter function. Apoptosis, or programmed cell death involves a series of cell shrinking processes, beginning with cell size reduction and pyknosis, followed by cell budding and karyorrhexis, and phagocytosis by macrophages or neighboring cells due to size decrease. The phagocytic disposal of apoptotic cells prevents the release of cellular debris that could induce an inflammatory response in neighboring cells. In opposition, the leakage of cellular content associated with membrane disruption in oncosis often incites an inflammatory response in neighboring tissue, causing further cellular injury. Additionally, apoptosis and the degradation of intracellular organelles is mediated by caspase activation, particularly caspase-3. Oligonuclosomal DNA fragmentation is initiated by caspase-activated deoxyribonuclease following caspase-3 mediated cleavage of the enzyme’s inhibitor, ICAD. In contrast, the oncotic pathway