Causes
Necrosis may occur due to external or internal factors. External factors may involve mechanical trauma, physical damage to the body (that causes cellular breakdown), any damage to blood vessels (which may disrupt the blood supply to that area); and ischemia. Thermal effects (extremely high or low temperature) can result in necrosis due to the disruption of cells. In frostbite, crystals form, increasing the pressure of remaining tissue and fluid causing the cells to burst. Under extreme conditions tissues and cells die through an unregulated process of destruction of membranes and cytosol.
Internal factors causing necrosis include trophoneurotic disorders; injury and paralysis of nerve cells. Pancreatic enzymes (lipases) are the major cause of fat necrosis. Necrosis can be activated by bacterial toxins and components of the immune system, such as the complement system, activated natural killer cells, and peritoneal macrophages. Pathogen-induced necrosis programs in cells with immunological barriers (intestinal mucosa) may alleviate invasion of pathogens through surfaces affected by inflammation. Toxins and pathogens may cause necrosis; toxins such as snake venoms may inhibit enzymes and cause cell death.
Pathological conditions are characterized by inadequate secretion of cytokines. Nitric oxide (NO) and reactive oxygen species (ROS) are also accompanied by intense necrotic death of cells. A classic example of a necrotic condition is ischemia that leads to a drastic depletion of oxygen, glucose and other trophic factors and evokes massive necrotic death of endothelial cells and non-proliferating cells of surrounding tissues (neurons, cardiomyocytes, renal cells, etc). Recent cytological data indicates that necrotic death occurs not only during pathological events but it is also a component of some physiological process.
Activation-induced death of primary T-lymphocytes, and important constituents of the immune response, are caspase-independent and necrotic by morphology; hence current researchers have demonstrated that the occurrence of necrotic cell death can not only occur during pathological processes but also during normal processes such as tissue renewal, embryogenesis and immune response.
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