Editing Necrosis (section)

==Causes==
[[File:Hand necrosis caused by plague.jpg|thumb|right|Hand necrosis from [[bubonic plague]]]]

Necrosis may occur due to external or internal factors.

===External factors===
External factors may involve mechanical trauma (physical damage to the body which causes cellular breakdown), electric shock,<ref>{{cite book | vauthors = Khalid N, Azimpouran M | chapter = Necrosis |date=2023 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK557627/ |title = StatPearls |access-date=2023-09-19 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491559 }}</ref> damage to blood vessels (which may disrupt blood supply to associated tissue), and [[ischemia]].<ref name="Raffray">{{cite journal | vauthors = Raffray M, Cohen GM | title = Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death? | journal = Pharmacology & Therapeutics | volume = 75 | issue = 3 | pages = 153–177 | date = September 1997 | pmid = 9504137 | doi = 10.1016/s0163-7258(97)00037-5 }}</ref> Thermal effects (extremely high or low temperature) can often result in necrosis due to the disruption of cells, especially in bone cells.<ref>{{cite journal | vauthors = Kniha K, Heussen N, Weber E, Möhlhenrich SC, Hölzle F, Modabber A | title = Temperature Threshold Values of Bone Necrosis for Thermo-Explantation of Dental Implants-A Systematic Review on Preclinical In Vivo Research | journal = Materials | volume = 13 | issue = 16 | pages = 3461 | date = August 2020 | pmid = 32781597 | pmc = 7476012 | doi = 10.3390/ma13163461 | doi-access = free | bibcode = 2020Mate...13.3461K }}</ref>  

Necrosis can also result from chemical trauma, with [[Alkali|alkaline]] and [[Acid|acidic]] compounds causing [[Liquefactive necrosis|liquefactive]] and [[Coagulative necrosis|coagulative]] necrosis, respectively, in affected tissues. The severity of such cases varies significantly based on multiple factors, including the compound concentration, type of tissue affected, and the extent of chemical exposure.

In [[frostbite]], crystals form, increasing the pressure of remaining tissue and fluid causing the cells to burst.<ref>{{Cite web |date=2020-08-16 |title=Frostbite |url=https://www.health.harvard.edu/a_to_z/frostbite-a-to-z |access-date=2023-09-19 |website=Harvard Health |language=en}}</ref> Under extreme conditions tissues and cells may die through an unregulated process of membrane and cytosol destruction.<ref name="Nzarian">{{cite journal | vauthors = Nazarian RM, Van Cott EM, Zembowicz A, Duncan LM | title = Warfarin-induced skin necrosis | journal = Journal of the American Academy of Dermatology | volume = 61 | issue = 2 | pages = 325–332 | date = August 2009 | pmid = 19615543 | doi = 10.1016/j.jaad.2008.12.039 }}</ref>

===Internal factors===
Internal factors causing necrosis include: trophoneurotic disorders (diseases that occur due to defective nerve action in a part of an organ which results in failure of nutrition); injury and paralysis of nerve cells. Pancreatic enzymes (lipases) are the major cause of fat necrosis.<ref name="Raffray"/>

Necrosis can be activated by components of the immune system, such as the [[complement system]]; [[bacterial toxin]]s; activated [[natural killer cells]]; and [[peritoneal]] [[macrophage]]s.<ref name="Proskuryakov"/> Pathogen-induced necrosis programs in cells with immunological barriers ([[intestinal mucosa]]) may alleviate invasion of [[pathogen]]s through surfaces affected by inflammation.<ref name="Proskuryakov"/> Toxins and pathogens may cause necrosis; toxins such as [[snake venom]]s may inhibit enzymes and cause cell death.<ref name="Raffray"/> Necrotic wounds have also resulted from the stings of ''[[Vespa mandarinia]].''<ref>{{cite journal | vauthors = Yanagawa Y, Morita K, Sugiura T, Okada Y | title = Cutaneous hemorrhage or necrosis findings after Vespa mandarinia (wasp) stings may predict the occurrence of multiple organ injury: a case report and review of literature | journal = Clinical Toxicology | volume = 45 | issue = 7 | pages = 803–7 | date = 10 October 1980 | pmid = 17952752 | doi = 10.1080/15563650701664871 | s2cid = 11337426 }}</ref>

[[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.<ref name="Raffray"/> A classic example of a necrotic condition is [[ischemia]] which leads to a drastic depletion of [[oxygen]], [[glucose]], and other [[trophic factors]]<ref>{{Cite web|url=http://cellbiology.med.unsw.edu.au/units/science/project2004/Celldeathregulation.htm|title=Cell death regulation: trophic factors|archive-url=https://web.archive.org/web/20071010132549/http://cellbiology.med.unsw.edu.au/units/science/project2004/Celldeathregulation.htm|archive-date=10 October 2007}}</ref> and induces massive necrotic death of endothelial cells and non-proliferating cells of surrounding tissues (neurons, cardiomyocytes, renal cells, etc.).<ref name="Proskuryakov"/> Recent [[Cell biology|cytological]] data indicates that necrotic death occurs not only during pathological events but it is also a component of some [[physiological]] process.<ref name="Raffray"/>

Activation-induced death of primary [[T lymphocyte]]s and other important constituents of the immune response are [[caspase]]-independent and necrotic by morphology; hence, current researchers have demonstrated that necrotic cell death can occur not only during pathological processes, but also during normal processes such as tissue renewal, [[embryogenesis]], and immune response.<ref name="Raffray"/>