Necrosis
Necrosis (from
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 cell membrane integrity[4] and an uncontrolled release of products of cell death into the extracellular space.[1] This initiates an inflammatory response in the surrounding tissue, which attracts leukocytes and nearby phagocytes which eliminate the dead cells by phagocytosis. However, microbial damaging substances released by leukocytes would create collateral damage to surrounding tissues.[5] This excess collateral damage inhibits the healing process. Thus, untreated necrosis results in a build-up of decomposing dead tissue and cell debris at or near the site of the cell death. A classic example is gangrene. For this reason, it is often necessary to remove necrotic tissue surgically, a procedure known as debridement.[citation needed]
Classification
Structural signs that indicate irreversible cell injury and the progression of necrosis include dense clumping and progressive disruption of
Morphological patterns
There are six distinctive morphological patterns of necrosis:[7]
- 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]
- 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]
- amorphous granular debris enclosed within a distinctive inflammatory border.[7] Some granulomas contain this pattern of necrosis.[10]
- 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]
- antibodies, referred to as immune complexes deposited within arterial walls[7] together with fibrin.[7]
Other clinical classifications of necrosis
- There are also very specific forms of necrosis such as gummatous necrosis (due to spirochaetal infections) and hemorrhagic necrosis (due to the blockage of venous drainage of an organ or tissue).[citation needed]
- 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).[11]
- Some yellow sac spiders and hobo spiders possess necrotic venom have not been substantiated.[citation needed]
- In blind mole rats (genus
Causes
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,[14] damage to blood vessels (which may disrupt blood supply to associated tissue), and ischemia.[15] Thermal effects (extremely high or low temperature) can often result in necrosis due to the disruption of cells, especially in bone cells.[16]
In frostbite, crystals form, increasing the pressure of remaining tissue and fluid causing the cells to burst.[17] Under extreme conditions tissues and cells may die through an unregulated process of membrane and cytosol destruction.[18]
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.[15]
Necrosis can be activated by components of the immune system, such as the
Activation-induced death of primary
Pathogenesis
Pathways
Until recently, necrosis was thought to be an unregulated process.[20] However, there are two broad pathways in which necrosis may occur in an organism.[20]
The first of these two pathways initially involves
The second pathway is a secondary form of necrosis that is shown to occur after apoptosis and budding.[20] In these cellular changes of necrosis, the nucleus breaks into fragments (known as karyorrhexis).[20]
Histopathological changes
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.[21] It is seen as a darker stain of the cytoplasm.
- The microvilli.[7]
On a larger histologic scale, pseudopalisades (false palisades) are hypercellular zones that typically surround necrotic tissue. Pseudopalisading necrosis indicates an aggressive tumor.[22]
-
Pyknosis in a bile infarct
-
Cytoplasmic hypereosinophilia (seen in left half of image)
-
Pseudopalisading seen around necrosis in glioblastoma
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]
- Lucilia sericata larvae has been employed to remove necrotic tissue and infection.[24]
- In the case of 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.[25]
- Wounds caused by physical agents, including physical antibiotics and anti-inflammatorydrugs 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 antibiotics to impede infection.[27]
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.[28]
In plants
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.[29] For example, necrosis of tissue can occur in Arabidopsis thaliana due to plant pathogens.[citation needed]
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.[citation needed]
See also
References
- ^ PMID 12565815.
- PMID 11290572.
- ISBN 978-0071386784.
- S2CID 208869679.
- PMID 18039143.
- ^ ISBN 978-0729539517.
- ^ ISBN 978-1416031215.
- ^ ISBN 978-0781753173.
- ISBN 978-0-9832246-2-4.
- ^ ISBN 978-0443070013.
- ^ "Medical Definition of Myonecrosis; Doctor Written". RxList. Retrieved 2023-06-09.
- Society for Science and the Public. Archivedfrom the original on 19 June 2013. Retrieved 27 November 2012.
- PMID 23129611.
- PMID 32491559. Retrieved 2023-09-19.
- ^ PMID 9504137.
- PMID 32781597.
- ^ "Frostbite". Harvard Health. 2020-08-16. Retrieved 2023-09-19.
- PMID 19615543.
- S2CID 11337426.
- ^ PMID 18846107.
- ISBN 978-0-323-32299-7. Archived from the originalon 2020-08-04.
- PMID 17110662.
- PMID 11899913.
- S2CID 7861732.
- PMID 17490613.
- PMID 22855079.
- S2CID 6827421.
- PMID 15530778.
- ISBN 978-1-60469-095-8.
External links
- Life In The Fast Lane: toxicology Conundrum #018
- Undersea and Hyperbaric Medical Society. "Necrotizing Soft Tissue Infections". Archived from the original on 5 July 2008. Retrieved 25 July 2008.
- Secondary necrosis of a neutrophil