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f protein denaturation causing albumin to transform into a firm and opaque state 6 this pattern of necrosis is typically seen in hypoxic low oxygen environments such as infarction coagulative necrosis occurs primarily in tissues such as the kidney heart and adrenal glands 6 severe ischemia most commonly causes necrosis of this form 8 liquefactive necrosis or colliquative necrosis in contrast to coagulative necrosis is characterized by the digestion of dead cells to form a viscous liquid mass 7 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 pus 7 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 6 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 9 caseous necrosis can be considered a combination of coagulative and liquefactive necrosis 6 typically caused by mycobacteria e g 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 6 microscopic examination shows amorphous granular debris enclosed within a distinctive inflammatory border 7 some granulomas contain this pattern of necrosis 10 fat necrosis is specialized necrosis of fat tissue 10 resulting from the action of activated lipases on fatty tissues such as the pancreas in the pancreas it leads to acute pancreatitis a condition where the pancreatic enzymes leak out into the peritoneal cavity and liquefy the membrane by splitting the triglyceride esters into fatty acids through fat saponification 7 calcium magnesium or sodium may bind to these lesions to produce a chalky white substance 6 the calcium deposits are microscopically distinctive and may be large enough to be visible on radiographic examinations 8 to the naked eye calcium deposits appear as gritty white flecks 8 fibrinoid necrosis is a special form of necrosis usually caused by immune mediated vascular damage it is marked by complexes of antigen and antibodies referred to as immune complexes deposited within arterial walls 7 together with fibrin 7 other clinical classifications of necrosis edit there are also very specific forms of necrosis such as gangrene term used in clinical practices for limbs which have had severe hypoxia gummatous necrosis due to spirochaetal infections and hemorrhagic necrosis due to the blockage of venous drainage of an organ or tissue 11 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 gas gangrene 12 some spider bites may lead to necrosis in the united states only spider bites from the brown recluse spider genus 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 hobo spiders possess necrotic venom have not been substantiated 13 14 in blind mole rats genus spalax the process of necrosis replaces the role of the systematic 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 tumor suppressor protein 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 15 16 causes edit hand necrosis from bubonic plague necrosis may occur due to external or internal factors external factors edit external factors may involve mechanical trauma physical damage to the body which causes cellular breakdown electric shock 17 damage to blood vessels which may disrupt blood supply to associated tissue and ischemia 18 thermal effects extremely high or low temperature can often result in necrosis due to the disruption of cells especially in bone cells 19 necrosis can also result from chemical trauma with alkaline and acidic compounds causing liquefactive and 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 20 under extreme conditions tissues and cells may die through an unregulated process of membrane and cytosol destruction 21 internal factors edit 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 18 necrosis can be activated by components of the immune system such as the complement system bacterial toxins activated natural killer cells and peritoneal macrophages 1 pathogen induced necrosis programs in cells with immunological barriers intestinal mucosa may alleviate invasion of pathogens through surfaces affected by inflammation 1 toxins and pathogens may cause necrosis toxins such as snake venoms may inhibit enzymes and cause cell death 18 necrotic wounds have also resulted from the stings of vespa mandarinia 22 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 18 a classic example of a necrotic condition is ischemia which leads to a drastic depletion of oxygen glucose and other trophic factors 23 and induces massive necrotic death of endothelial cells and non proliferating cells of surrounding tissues neurons cardiomyocytes renal cells etc 1 recent cytological data indicates that necrotic death occurs not only during pathological events but it is also a component of some physiological process 18 activation induced death of primary t lymphocytes 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 18 pathogenesis edit pathways edit until recently necrosis was thought to be an unregulated process 24 however there are two broad pathways in which necrosis may occur in an organism 24 the first of these two pathways initially involves oncosis where swelling of the cells occurs 24 affected cells then proceed to blebbing and this is followed by pyknosis in which nuclear shrinkage transpires 24 in the final step of this pathway cell nuclei are dissolved into the cytoplasm which is referred to as karyolysis 24 the second pathway is a secondary form of necrosis that is shown to occur after apoptosis and budding 24 in these cellular changes of necrosis the nucleus breaks into fragments known as karyorrhexis 24 histopathological changes edit further information myocardial infarction diagnosis 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 karyolysis the chromatin of the nucleus fades due to the loss of the dna by degradation 7 karyorrhexis the shrunken nucleus fragments to complete dispersal 7 pyknosis the nucleus shrinks and the chromatin condenses 7 other typical cellular changes in necrosis include cytoplasmic hypereosinophilia on samples with h e stain 25 it is seen as a darker stain of the cytoplasm the cell membrane appears discontinuous when viewed with an electron microscope this discontinuous membrane is caused by cell blebbing and the loss of microvilli 7 on a larger histologic scale pseudopalisades false palisades are hypercellular zones that typically surround necrotic tissue pseudopalisading necrosis indicates an aggressive tumor 26 pyknosis in a bile infarct cytoplasmic hypereosinophilia seen in left half of image pseudopalisading seen around necrosis in glioblastoma treatment edit 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 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 amputation of affected limbs or organs chemical removal of necrotic tissue is another option in which enzymatic debriding agents categorised as proteolytic fibrinolytic or collagenases are used to target the various components of dead tissue 27 in select cases special maggot therapy using lucilia sericata larvae has been employed to remove necrotic tissue and infection 28 in the case of ischemia which includes myocardial infarction the restriction of blood supply to tissues causes hypoxia and the creation of reactive oxygen species ros that react with and damage proteins and membranes antioxidant treatments can be applied to scavenge the ros 29 wounds caused by physical agents including physical trauma and chemical burns can be treated with antibiotics and 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 30 in the example of a snake bite the use of anti venom halts the spread of toxins whilst receiving antibiotics to impede infection 31 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 32 in plants edit if calcium is deficient 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 33 for example necrosis of tissue can occur in arabidopsis thaliana due to plant pathogens 34 cacti such as the saguaro and cardon in the sonoran desert experience necrotic patch formation regularly a species of dipterans called 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 35 see also edit avascular necrosis frostbite gangrene necroptosis necrotizing fasciitis osteonecrosis of the jaw toxic epidermal necrolysis necrotizing arteriolitis references edit 1 2 3 4 5 proskuryakov sy konoplyannikov ag gabai vl february 2003 necrosis a specific form of programmed cell death experimental cell research 283 1 1 16 doi 10 1016 s0014 4827 02 00027 7 pmid 12565815 gerschenson l e geske f jon april 2001 virchow and apoptosis the american journal of pathology 158 4 1543 doi 10 1016 s0002 9440 10 64105 3 pmc 1891904 pmid 11290572 kasper dl zaleznik df 2001 gas gangrene antibiotic associated colitis 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