View source for Biology:Necrosis

{{Short description|Unprogrammed cell death caused by external cell injury}}
[[File:Structural changes of cells undergoing necrosis or apoptosis.png|thumb|upright=1.6|Structural changes of cells undergoing necrosis and apoptosis]]

'''Necrosis''' ({{etymology|grc|''{{wikt-lang|grc|νέκρωσις}}'' ({{grc-transl|νέκρωσις}})|death}}) is a form of cell injury which results in the premature [[Biology:Cell death|death]] of [[Biology:Cell|cells]] in living [[Biology:Tissue|tissue]] by [[Biology:Autolysis|autolysis]].<ref name="Proskuryakov">{{cite journal | vauthors = Proskuryakov SY, Konoplyannikov AG, Gabai VL | title = Necrosis: a specific form of programmed cell death? | journal = Experimental Cell Research | volume = 283 | issue = 1 | pages = 1–16 | date = February 2003 | pmid = 12565815 | doi = 10.1016/S0014-4827(02)00027-7 }}</ref> The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is often regarded as one of the founders of modern pathology.<ref>{{Cite journal |last1=Gerschenson |first1=L.E. |last2=Geske |first2=F. Jon |date=April 2001 |title=Virchow and Apoptosis |journal=The American Journal of Pathology |language=en |volume=158 |issue=4 |pages=1543 |doi=10.1016/S0002-9440(10)64105-3 |pmc=1891904 |pmid=11290572}}</ref> Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, [[Biology:Apoptosis|apoptosis]] is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.<ref name="Kasper">{{cite book | editor = Stone RM | title = Harrison's principles of internal medicine self-assessment and board review | year = 2001 | publisher = McGraw-Hill, Medical Pub. Division | location = New York | isbn = 978-0071386784 | edition = 15th |vauthors=Kasper DL, Zaleznik DF | chapter = Gas gangrene, antibiotic associated colitis, and other Clostridial infections | pages = 922–927 }}</ref>

Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but rather various receptors are activated and result in the loss of [[Biology:Cell membrane|cell membrane]] integrity<ref>{{cite journal | vauthors = Nirmala JG, Lopus M | title = Cell death mechanisms in eukaryotes | journal = Cell Biology and Toxicology | volume = 36 | issue = 2 | pages = 145–164 | date = April 2020 | pmid = 31820165 | doi = 10.1007/s10565-019-09496-2 | s2cid = 208869679 }}</ref> and an uncontrolled release of products of cell death into the [[Biology:Extracellular space|extracellular space]].<ref name="Proskuryakov" /> This initiates an [[Medicine:Inflammation|inflammatory response]] in the surrounding tissue, which attracts [[Biology:White blood cell|leukocytes]] and nearby [[Biology:Phagocyte|phagocyte]]s which eliminate the dead cells by [[Biology:Phagocytosis|phagocytosis]]. However, microbial damaging substances released by leukocytes would create collateral damage to surrounding tissues.<ref>{{cite journal | vauthors = Rock KL, Kono H | title = The inflammatory response to cell death | journal = Annual Review of Pathology | volume = 3 | pages = 99–126 | year = 2008 | pmid = 18039143 | pmc = 3094097 | doi = 10.1146/annurev.pathmechdis.3.121806.151456 }}</ref> This excess collateral damage inhibits the healing process. Thus, untreated necrosis results in a build-up of [[Medicine:Decomposition|decomposing]] dead tissue and cell debris at or near the site of the cell death. A classic example is [[Medicine:Gangrene|gangrene]]. For this reason, it is often necessary to remove necrotic tissue [[Medicine:Surgery|surgically]], a [[Medicine:Medical procedure|procedure]] known as [[Medicine:Debridement|debridement]].{{citation needed|date=June 2022}}

==Classification==

Structural signs that indicate irreversible cell injury and the progression of necrosis include dense clumping and progressive disruption of [[Biology:Gene|gene]]tic material, and disruption to membranes of cells and organelles.<ref name="Craft">{{cite book |vauthors=Craft J, Gordon C, Tiziani A, Huether SE, McCance KL, Brashers VL | title = Understanding pathophysiology | year = 2010 | publisher = Elsevier Australia | location = Chatswood, N.S.W. | isbn = 978-0729539517 | edition = 1st }}</ref>

===Morphological patterns===

There are six distinctive morphological patterns of necrosis:<ref name="Kumar">{{cite book|vauthors=Kumar V, Abbas AK, Aster JC, Fausto N | title = Robbins and Cotran pathologic basis of disease | year = 2010 | publisher = Saunders/Elsevier | location = Philadelphia, PA | isbn = 978-1416031215 | pages = 12–41 | edition = 8th }}</ref>

# [[Biology:Coagulative necrosis|Coagulative necrosis]] is characterized by the formation of a gelatinous (gel-like) substance in dead tissues in which the architecture of the tissue is maintained,<ref name="Kumar"/> and can be observed by light microscopy. Coagulation occurs as a result of protein [[Biology:Denaturation (biochemistry)|denaturation]], causing [[Biology:Albumin|albumin]] to transform into a firm and opaque state.<ref name="Craft"/> This pattern of necrosis is typically seen in [[Medicine:Hypoxia (medical)|hypoxic]] (low-oxygen) environments, such as infarction. Coagulative necrosis occurs primarily in tissues such as the kidney, heart and adrenal glands.<ref name="Craft"/> Severe [[Medicine:Ischemia|ischemia]] most commonly causes necrosis of this form.<ref name="McConnell">{{cite book | author = McConnell TH | title = The nature of disease: pathology for the health professions | year = 2007 | publisher = Lippincott Williams & Wilkins | location = Baltimore, Mar. | isbn = 978-0781753173}}</ref>
# [[Biology:Liquefactive necrosis|Liquefactive necrosis]] (or colliquative necrosis), in contrast to coagulative necrosis, is characterized by the digestion of dead cells to form a viscous liquid mass.<ref name="Kumar"/> This is typical of bacterial, or sometimes fungal, infections because of their ability to stimulate an inflammatory response. The necrotic liquid mass is frequently creamy yellow due to the presence of dead leukocytes and is commonly known as [[Medicine:Pus|pus]].<ref name="Kumar"/> [[Medicine:Hypoxia (medical)|Hypoxic]] infarcts in the brain presents as this type of necrosis, because the brain contains little connective tissue but high amounts of digestive enzymes and lipids, and cells therefore can be readily digested by their own enzymes.<ref name="Craft"/>
# Gangrenous necrosis can be considered a type of coagulative necrosis that resembles mummified tissue. It is characteristic of ischemia of lower limb and the gastrointestinal tracts. Both dry gangrene and gas gangrene can lead to this type of necrosis. If superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene).<ref>{{cite book| author = Sattar | title = Fundamentals of Pathology | year = 2015 | publisher = Pathoma LLC | location = Chicago, IL | isbn = 978-0-9832246-2-4| pages = 5 | edition = 2015th }}</ref>
# [[Medicine:Caseous necrosis|Caseous necrosis]] can be considered a combination of coagulative and liquefactive necrosis,<ref name="Craft"/> typically caused by mycobacteria (e.g. [[Medicine:Tuberculosis|tuberculosis]]), fungi and some foreign substances. The necrotic tissue appears as white and friable, like clumped cheese. Dead cells disintegrate but are not completely digested, leaving granular particles.<ref name="Craft"/> Microscopic examination shows [[Physics:Amorphous|amorphous]] granular debris enclosed within a distinctive inflammatory border.<ref name="Kumar"/> Some [[Medicine:Granuloma|granuloma]]s contain this pattern of necrosis.<ref name="Stevens">{{cite book|vauthors=Stevens A, Lowe JS, Young B, Deakin PJ | title = Wheater's basic histopathology: a colour atlas and text |year = 2002 | publisher = Churchill Livingstone | location = Edinburgh | isbn = 978-0443070013 | edition = 4th }}</ref>
# [[Medicine:Fat necrosis|Fat necrosis]] is specialized necrosis of fat tissue,<ref name="Stevens"/> resulting from the action of activated [[Biology:Lipase|lipase]]s on fatty tissues such as the pancreas. In the pancreas it leads to acute [[Medicine:Pancreatitis|pancreatitis]], a condition where the pancreatic enzymes leak out into the peritoneal cavity, and liquefy the membrane by splitting the [[Chemistry:Triglyceride|triglyceride]] esters into fatty acids through fat [[Chemistry:Saponification|saponification]].<ref name="Kumar"/> Calcium, magnesium or sodium may bind to these lesions to produce a chalky-white substance.<ref name="Craft"/> The calcium deposits are microscopically distinctive and may be large enough to be visible on radiographic examinations.<ref name="McConnell"/> To the naked eye, calcium deposits appear as gritty white flecks.<ref name="McConnell"/>
# [[Biology:Fibrinoid necrosis|Fibrinoid necrosis]] is a special form of necrosis usually caused by immune-mediated vascular damage. It is marked by complexes of [[Biology:Antigen|antigen]] and [[Biology:Antibodies|antibodies]], referred to as [[Biology:Immune complex|immune complex]]es deposited within [[Biology:Artery|arterial]] walls<ref name="Kumar"/> together with [[Biology:Fibrin|fibrin]].<ref name="Kumar"/>

===Other clinical classifications of necrosis===

# There are also very specific forms of necrosis such as [[Medicine:Gangrene|gangrene]] (term used in clinical practices for limbs which have had severe hypoxia), gummatous necrosis (due to [[Biology:Spirochaete|spirochaetal]] infections) and hemorrhagic necrosis (due to the blockage of venous drainage of an organ or tissue).{{citation needed|date=May 2023}}
# Myonecrosis is the death of individual muscle fibres due to injury, hypoxia, or infection. Common causes include spontaneous diabetic myonecrosis (a.k.a diabetic muscle infarction) and clostridial myonecrosis (a.k.a [[Medicine:Gas gangrene|gas gangrene]]).<ref>{{Cite web |title=Medical Definition of Myonecrosis; Doctor Written |url=https://www.rxlist.com/myonecrosis/definition.htm |access-date=2023-06-09 |website=RxList |language=en}}</ref>
# Some spider bites may lead to necrosis. In the United States, only spider bites from the [[Biology:Brown recluse spider|brown recluse spider]] (genus [[Biology:Loxosceles|Loxosceles]]) reliably progress to necrosis. In other countries, spiders of the same genus, such as the Chilean recluse in South America, are also known to cause necrosis. Claims that yellow sac spiders and [[Biology:Hobo spider|hobo spider]]s possess necrotic [[Biology:Venom|venom]] have not been substantiated.{{citation needed|date=May 2023}}
# In blind mole rats (genus ''[[Biology:Spalax|Spalax]]''), the process of necrosis replaces the role of the systematic [[Biology:Apoptosis|apoptosis]] normally used in many organisms. Low oxygen conditions, such as those common in blind mole rats' burrows, usually cause cells to undergo apoptosis. In adaptation to higher tendency of cell death, blind mole rats evolved a mutation in the [[Biology:Tumor suppressor|tumor suppressor]] protein [[Biology:P53|p53]] (which is also used in humans) to prevent cells from undergoing apoptosis. Human cancer patients have similar mutations, and blind mole rats were thought to be more susceptible to cancer because their cells cannot undergo apoptosis. However, after a specific amount of time (within 3 days according to a study conducted at the University of Rochester), the cells in blind mole rats release interferon-beta (which the immune system normally uses to counter viruses) in response to over-proliferation of cells caused by the suppression of apoptosis. In this case, the interferon-beta triggers cells to undergo necrosis, and this mechanism also kills cancer cells in blind mole rats. Because of tumor suppression mechanisms such as this, blind mole rats and other spalacids are resistant to cancer.<ref>{{cite web| vauthors = Saey TH |title=Cancer cells self-destruct in blind mole rats|url=http://www.sciencenews.org/view/generic/id/346267/description/Cancer_cells_self-destruct_in_blind_mole_rats|website=Science News|publisher=Society for Science and the Public|access-date=27 November 2012|date=5 November 2012|archive-date=19 June 2013|archive-url=https://web.archive.org/web/20130619171046/http://www.sciencenews.org/view/generic/id/346267/description/Cancer_cells_self-destruct_in_blind_mole_rats|url-status=live}}</ref><ref name="pmid23129611">{{cite journal | vauthors = Gorbunova V, Hine C, Tian X, Ablaeva J, Gudkov AV, Nevo E, Seluanov A | title = Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 47 | pages = 19392–19396 | date = November 2012 | pmid = 23129611 | pmc = 3511137 | doi = 10.1073/pnas.1217211109 | doi-access = free | bibcode = 2012PNAS..10919392G }}</ref>

==Causes==
[[File:Necrotic leg wound.png|thumb|right|Necrotic leg wound caused by a brown recluse spider bite]]

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=http://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 [[Medicine:Ischemia|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>

In [[Medicine:Frostbite|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 [[Biology:Complement system|complement system]]; bacterial toxins; activated natural killer cells; and peritoneal [[Biology:Macrophage|macrophage]]s.<ref name="Proskuryakov"/> Pathogen-induced necrosis programs in cells with immunological barriers (intestinal mucosa) may alleviate invasion of [[Biology:Pathogen|pathogen]]s through surfaces affected by inflammation.<ref name="Proskuryakov"/> Toxins and pathogens may cause necrosis; toxins such as [[Chemistry:Snake venom|snake venom]]s may inhibit enzymes and cause cell death.<ref name="Raffray"/> Necrotic wounds have also resulted from the stings of ''[[Biology:Vespa mandarinia|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 = 803–807 | date = 10 October 1980 | pmid = 17952752 | doi = 10.1080/15563650701664871 | s2cid = 11337426 }}</ref>

Pathological conditions are characterized by inadequate secretion of cytokines. [[Chemistry:Nitric oxide|Nitric oxide]] (NO) and [[Biology:Reactive oxygen species|reactive oxygen species]] (ROS) are also accompanied by intense necrotic death of cells.<ref name="Raffray"/> A classic example of a necrotic condition is [[Medicine:Ischemia|ischemia]] which leads to a drastic depletion of [[Chemistry:Oxygen|oxygen]], [[Chemistry:Glucose|glucose]], and other [http://cellbiology.med.unsw.edu.au/units/science/project2004/Celldeathregulation.htm trophic factors] and induces massive necrotic death of endothelial cells and non-proliferating cells of surrounding tissues (neurons, cardiomyocytes, renal cells, etc.).<ref name="Proskuryakov"/> Recent [[Biology: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 lymphocytes and other important constituents of the immune response are [[Biology:Caspase|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, [[Biology:Embryogenesis|embryogenesis]], and immune response.<ref name="Raffray"/>

==Pathogenesis==
===Pathways===
Until recently, necrosis was thought to be an unregulated process.<ref name="Kroemer">{{cite journal | vauthors = Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G | display-authors = 6 | title = Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009 | journal = Cell Death and Differentiation | volume = 16 | issue = 1 | pages = 3–11 | date = January 2009 | pmid = 18846107 | pmc = 2744427 | doi = 10.1038/cdd.2008.150 }}</ref> However, there are two broad pathways in which necrosis may occur in an organism.<ref name="Kroemer"/>

The first of these two pathways initially involves oncosis, where swelling of the cells occurs.<ref name="Kroemer"/> Affected cells then proceed to blebbing, and this is followed by [[Biology:Pyknosis|pyknosis]], in which nuclear shrinkage transpires.<ref name="Kroemer"/> In the final step of this pathway cell nuclei are dissolved into the cytoplasm, which is referred to as [[Biology:Karyolysis|karyolysis]].<ref name="Kroemer"/>

The second pathway is a secondary form of necrosis that is shown to occur after apoptosis and budding.<ref name="Kroemer"/> In these cellular changes of necrosis, the nucleus breaks into fragments (known as [[Biology:Karyorrhexis|karyorrhexis]]).<ref name="Kroemer"/>

===Histopathological changes===
{{Further|Biology:Myocardial infarction diagnosis}}
{{Anchor|Pseudopalisade|Cytoplasmic hypereosinophilia}}[[Image:MI_with_contraction_bands_very_high_mag.jpg|thumb|'''Karyolysis''' (and contraction band necrosis) in myocardial infarction (heart attack)]]

The nucleus changes in necrosis and characteristics of this change are determined by the manner in which its DNA breaks down:
* '''[[Biology:Karyolysis|Karyolysis]]''': the [[Biology:Chromatin|chromatin]] of the nucleus fades due to the loss of the DNA by degradation.<ref name="Kumar"/>
* '''[[Biology:Karyorrhexis|Karyorrhexis]]''': the shrunken nucleus fragments to complete dispersal.<ref name="Kumar"/>
* '''[[Biology:Pyknosis|Pyknosis]]''': the nucleus shrinks, and the chromatin condenses.<ref name="Kumar"/>

Other typical cellular changes in necrosis include:
* '''Cytoplasmic hypereosinophilia''' on samples with H&E stain.<ref>{{cite book | chapter = Frozen Section Diagnosis | chapter-url = https://books.google.com/books?id=n8AtBQAAQBAJ&pg=PA320 | page = 320 | archive-url = https://web.archive.org/web/20200804105603/https://books.google.se/books?id=n8AtBQAAQBAJ&pg=PA320 | archive-date=2020-08-04 | vauthors = Marchevsky AM, Balzer B, Abdul-Karim FW |title=Intraoperative Consultation E-Book | series = Foundations in Diagnostic Pathology |year=2014|publisher=Elsevier Health Sciences|isbn=978-0-323-32299-7 }}</ref> It is seen as a darker stain of the [[Biology:Cytoplasm|cytoplasm]].
* The '''[[Biology:Cell membrane|cell membrane]]''' appears discontinuous when viewed with an [[Engineering:Electron microscope|electron microscope]]. This discontinuous membrane is caused by cell blebbing and the loss of microvilli.<ref name="Kumar"/>

On a larger histologic scale, '''pseudopalisades''' (false [[Biology:Palisade (pathology)|palisades]]) are hypercellular zones that typically surround necrotic tissue. Pseudopalisading necrosis indicates an aggressive tumor.<ref>{{cite journal | vauthors = Wippold FJ, Lämmle M, Anatelli F, Lennerz J, Perry A | title = Neuropathology for the neuroradiologist: palisades and pseudopalisades | journal = AJNR. American Journal of Neuroradiology | volume = 27 | issue = 10 | pages = 2037–2041 | date = 2006 | pmid = 17110662 | pmc = 7977220 }}</ref>

<gallery>
File:4 Bd obs 4 680x512px.tif|'''[[Biology:Pyknosis|Pyknosis]]''' in a bile infarct
File:Histopathology of cytoplasmic hypereosinophilia in a pituitary adenoma.jpg|'''Cytoplasmic hypereosinophilia''' (seen in left half of image)
File:GBM pseudopalisading necrosis.jpg|'''Pseudopalisading''' seen around necrosis in [[Medicine:Glioblastoma|glioblastoma]]
</gallery>

==Treatment==

There are many causes of necrosis, and as such treatment is based upon how the necrosis came about. Treatment of necrosis typically involves two distinct processes: Usually, the underlying cause of the necrosis must be treated before the dead tissue itself can be dealt with.{{citation needed|date=June 2022}}
* [[Medicine:Debridement|Debridement]], referring to the removal of dead tissue by surgical or non-surgical means, is the standard therapy for necrosis. Depending on the severity of the necrosis, this may range from removal of small patches of skin to complete [[Medicine:Amputation|amputation]] of affected limbs or organs. Chemical removal of necrotic tissue is another option in which enzymatic debriding agents, categorised as proteolytic, fibrinolytic or [[Biology:Collagenase|collagenase]]s, are used to target the various components of dead tissue.<ref name="Anu">{{cite journal | vauthors = Singhal A, Reis ED, Kerstein MD | title = Options for nonsurgical debridement of necrotic wounds | journal = Advances in Skin & Wound Care | volume = 14 | issue = 2 | pages = 96–100; quiz 102–3 | year = 2001 | pmid = 11899913 | doi = 10.1097/00129334-200103000-00014 }}</ref> In select cases, special [[Medicine:Maggot therapy|maggot therapy]] using ''Lucilia sericata'' larvae has been employed to remove necrotic tissue and infection.<ref name="Horobin">{{cite journal | vauthors = Horobin AJ, Shakesheff KM, Pritchard DI | title = Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon the migration of human dermal fibroblasts over a fibronectin-coated surface | journal = Wound Repair and Regeneration | volume = 13 | issue = 4 | pages = 422–433 | year = 2005 | pmid = 16008732 | doi = 10.1111/j.1067-1927.2005.130410.x | s2cid = 7861732 }}</ref>
* In the case of [[Medicine:Ischemia|ischemia]], which includes [[Medicine:Myocardial infarction|myocardial infarction]], the restriction of blood supply to tissues causes [[Medicine:Hypoxia (medical)|hypoxia]] and the creation of [[Biology:Reactive oxygen species|reactive oxygen species]] (ROS) that react with, and damage proteins and membranes. [[Biology:Antioxidant|Antioxidant]] treatments can be applied to scavenge the ROS.<ref name="Eum">{{cite journal | vauthors = Eum HA, Cha YN, Lee SM | title = Necrosis and apoptosis: sequence of liver damage following reperfusion after 60 min ischemia in rats | journal = Biochemical and Biophysical Research Communications | volume = 358 | issue = 2 | pages = 500–505 | date = June 2007 | pmid = 17490613 | doi = 10.1016/j.bbrc.2007.04.153 }}</ref>
* Wounds caused by physical agents, including physical trauma and chemical burns, can be treated with antibiotics and [[Chemistry:Anti-inflammatory|anti-inflammatory]] drugs to prevent bacterial infection and inflammation. Keeping the wound clean from infection also prevents necrosis.
* Chemical and toxic agents (e.g. pharmaceutical drugs, acids, bases) react with the skin leading to skin loss and eventually necrosis. Treatment involves identification and discontinuation of the harmful agent, followed by treatment of the wound, including prevention of infection and possibly the use of immunosuppressive therapies such as anti-inflammatory drugs or immunosuppressants.<ref name="Cooper">{{cite journal | vauthors = Cooper KL | title = Drug reaction, skin care, skin loss | journal = Critical Care Nurse | volume = 32 | issue = 4 | pages = 52–59 | date = August 2012 | pmid = 22855079 | doi = 10.4037/ccn2012340 | doi-access = free }}</ref> In the example of a snake bite, the use of anti-venom halts the spread of toxins whilst receiving antibiotics to impede infection.<ref name="Chrotenimitkhum">{{cite journal | vauthors = Chotenimitkhun R, Rojnuckarin P | title = Systemic antivenom and skin necrosis after green pit viper bites | journal = Clinical Toxicology | volume = 46 | issue = 2 | pages = 122–125 | date = February 2008 | pmid = 18259959 | doi = 10.1080/15563650701266826 | s2cid = 6827421 }}</ref>

Even after the initial cause of the necrosis has been halted, the necrotic tissue will remain in the body. The body's immune response to apoptosis, which involves the automatic breaking down and recycling of cellular material, is not triggered by necrotic cell death due to the apoptotic pathway being disabled.<ref name="Edinger">{{cite journal | vauthors = Edinger AL, Thompson CB | title = Death by design: apoptosis, necrosis and autophagy | journal = Current Opinion in Cell Biology | volume = 16 | issue = 6 | pages = 663–669 | date = December 2004 | pmid = 15530778 | doi = 10.1016/j.ceb.2004.09.011 }}</ref>

==In plants==

If calcium is deficient, [[Chemistry:Pectin|pectin]] cannot be synthesized, and therefore the cell walls cannot be bonded and thus an impediment of the meristems. This will lead to necrosis of stem and root tips and leaf edges.<ref name=Capon_2010>{{cite book| author = Capon B | title = Botany for gardeners | date = 2010 | publisher = Timber Press | location = Portland, OR | isbn = 978-1-60469-095-8 | edition = 3rd }}</ref> For example, necrosis of tissue can occur in [[Biology:Arabidopsis thaliana#Evolutionary aspect of plant-pathogen resistance|''Arabidopsis thaliana'']] due to plant pathogens.{{citation needed|date=June 2022}}

Cacti such as the Saguaro and Cardon in the Sonoran Desert experience necrotic patch formation regularly; a species of Dipterans called [[Biology:Drosophila mettleri|Drosophila ''mettleri'']] has developed a p450 detoxification system to enable it to use the exudates released in these patches to both nest and feed larvae.{{citation needed|date=June 2022}}

== See also ==
{{col div|colwidth=25em}}
* [[Medicine:Avascular necrosis|Avascular necrosis]]
* [[Medicine:Frostbite|Frostbite]]
* [[Medicine:Gangrene|Gangrene]]
* [[Medicine:Necrotizing fasciitis|Necrotizing fasciitis]]
* [[Medicine:Osteonecrosis of the jaw|Osteonecrosis of the jaw]]
* [[Medicine:Toxic epidermal necrolysis|Toxic epidermal necrolysis]]
* [[Biology:Necroptosis|Necroptosis]]
{{colend}}

== References ==
{{Reflist|32em}}

== External links ==
* [https://web.archive.org/web/20091124192117/http://lifeinthefastlane.com/2009/09/toxicology-conundrum-018/ Life In The Fast Lane: toxicology Conundrum #018]
* {{cite web |url=http://www.uhms.org/ResourceLibrary/Indications/NecrotizingSoftTissueInfections/tabid/279/Default.aspx |title=Necrotizing Soft Tissue Infections |author=Undersea and Hyperbaric Medical Society |access-date=25 July 2008 |url-status=dead |archive-url=https://web.archive.org/web/20080705205656/http://www.uhms.org/ResourceLibrary/Indications/NecrotizingSoftTissueInfections/tabid/279/Default.aspx |archive-date=5 July 2008 }}
* [https://www.youtube.com/watch?v=OyHnXEgNL7Q Secondary necrosis of a neutrophil]

{{pathology}}

[[Category:Necrosis| ]]
[[Category:Cellular processes]]

{{Sourceattribution|Necrosis}}