Necrosis

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Structural changes of cells undergoing necrosis and apoptosis

Necrosis (from

cell injury which results in the premature death of cells in living tissue by autolysis.[1] 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.[2] 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, 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.[3]

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

organelles.[6]

Morphological patterns

There are six distinctive morphological patterns of necrosis:[7]

  1. 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]
  2. 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]
  3. 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]
  4. amorphous granular debris enclosed within a distinctive inflammatory border.[7] Some granulomas contain this pattern of necrosis.[10]
  5. 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]
  6. antibodies, referred to as immune complexes deposited within arterial walls[7] together with fibrin.[7]

Other clinical classifications of necrosis

  1. 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
    ]
  2. 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]
  3. Some
    yellow sac spiders and hobo spiders possess necrotic venom have not been substantiated.[citation needed
    ]
  4. In blind mole rats (genus
    spalacids are resistant to cancer.[12][13]

Causes

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,[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

Vespa mandarinia.[19]

Activation-induced death of primary

embryogenesis, and immune response.[15]

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

blebbing, and this is followed by pyknosis, in which nuclear shrinkage transpires.[20] In the final step of this pathway cell nuclei are dissolved into the cytoplasm, which is referred to as karyolysis.[20]

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

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:

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
    Pyknosis in a bile infarct
  • Cytoplasmic hypereosinophilia (seen in left half of image)
    Cytoplasmic hypereosinophilia (seen in left half of image)
  • Pseudopalisading seen around necrosis in glioblastoma
    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]

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

External links