Necrosis

Necrotic leg wound (arachnogenic).

Severe necrosis following Bothrops asper envenomation. The victim was an 11-year old boy, bitten two weeks earlier in Ecuador, but treated only with antibiotics.^[1]

Necrosis (in Greek Νεκρός = "dead") is the name given to premature or unnatural death of cells and living tissue. Necrosis is caused by external factors, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death. While apoptosis often provides beneficial effects to the cells host organisms, necrosis is almost always detrimental, and can be fatal.

Cells which die due to necrosis do not usually send the same chemical signals to the immune system that cells undergoing apoptosis do. This prevents nearby phagocytes from locating and engulfing the dead cells, leading to a build up of dead tissue and cell debris at or near the site of the cell death. For this reason, it is often necessary to remove necrotic tissue surgically.

Causes

Cellular necrosis can be induced by a number of external sources, including injury, infection, cancer, infarction, poisons, and inflammation. For example, an infarction (blockage of blood flow to muscular tissue) causes necrosis of muscle tissue due to lack of oxygen to the affected cell, such as occurs in a myocardial infarction -- a heart attack. Certain spider (brown recluse and snake (rattlesnake, Bothrops) venins can cause necrosis of the tissue near the bite wound, as can a Group A streptococcus infection (one of the "flesh-eating" bacteria).

Necrotic tissue does not undergo the same chemical reactions that "normally" dying apoptotic tissue does. The sudden failure of one part of the cell triggers a so-called "cascade of events". In addition to the lack of chemical signals to the immune system, cells undergoing necrosis can release harmful chemicals into the surrounding tissue. In particular, cells contain small organelles called lysosomes, which are capable of digesting cellular material. Damage to the lysosome membrane can trigger release of the contained enzymes, destroying other parts of the cell. Worse, when these enzymes are released from the non-dead cell, they can trigger a chain reaction of further cell death. If a sufficient amount of contiguous tissue necrotizes, it is termed gangrene. Proper care and treatment of wounds or animal bites plays a key role in preventing this type of widespread necrosis. During a surgical biopsy, this necrosis chain-reaction is halted by fixation or freezing.

Necrosis typically begins with cell swelling, chromatin digestion, disruption of the plasma membrane and organelle membranes. Late necrosis is characterized by extensive DNA hydrolysis, vacuolation of the endoplasmic reticulum, organelle breakdown, and cell lysis. The release of intracellular content after plasma membrane rupture is the cause of inflammation in necrosis.

Morphologic patterns

There are seven distinctive morphologic patterns of necrosis:

• Coagulative necrosis is typically seen in hypoxic (low oxygen) environments, such as an infarction. Cell outlines remain after cell death and can be observed by light microscopy.
• Liquefactive necrosis is usually associated with cellular destruction and pus formation (e.g. pneumonia). This is typical of bacterial or, sometimes, fungal infections because of their ability to stimulate an inflammatory reaction. Curiously, ischemia (restriction of blood supply) in the brain produces liquefactive, rather than coagulative, necrosis, due to the lack of any substantial supportive stroma.
• Gummatous necrosis is restricted to necrosis involving spirochaetal infections (e.g. syphilis).
• Haemorrhagic necrosis is due to blockage of the venous drainage of an organ or tissue (e.g. in testicular torsion).
• Caseous necrosis is a specific form of coagulation necrosis typically caused by mycobacteria (e.g. tuberculosis), fungi, and some foreign substances. It can be considered a combination of coagulative and liquefactive necroses.
• Fatty necrosis results from the action of lipases on fatty tissues (e.g. acute pancreatitis, breast tissue necrosis).
• Fibrinoid necrosis is caused by immune-mediated vascular damage. It is marked by deposition of fibrin-like proteinaceous material in arterial walls, which appears smudgy and eosinophilic on light microscopy.

Arachnogenic necrosis

Spider bites are cited as causing necrosis in some areas, but such claims are widely disputed. In the US, only brown recluse spiders (genus Loxosceles) have been proven to consistently cause necrosis.^[2] Other spiders of the same genus, such as the Chilean recluse in South America, have similarly been shown to cause necrosis in other countries.^[3][4]

Claims of necrosis caused by other spiders' bites are common, but supporting evidence is lacking. Conclusive evidence is difficult to obtain, partly because many spider bites are initially painless and thus the species goes unidentified, and partly because many doctors will preemptively remove even possibly necrotic flesh rather than risk further tissue damage. A few spiders commonly suspected (but not conclusively proven) of having necrotic venom include:

• White-tailed spiders in Australia and New Zealand^[5]

• Hobo spider in northwestern USA^[6]

• Sac spider in United States and Australia^[7]

Treatment

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. For example, a snake or spider bite victim will receive anti-venin to halt the spread of the toxins, while an infected patient will receive antibiotics.

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, the automatic breaking down and recycling of the cell material, is not triggered by necrotic cell death.

The standard therapy of necrosis (wounds, bedsores, burns etc.) is surgical removal of necrotic tissue. 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, via an enzymatic debriding agent, is another option. In selected cases, special maggot therapy has been utilized with good results.

See also

• Avascular necrosis
• Gangrene
• Necrotizing fasciitis
• Osteonecrosis of the jaw

External links

• Necrosis causes, details and definition
• Undersea and Hyperbaric Medical Society. "Necrotizing Soft Tissue Infections". Retrieved on 2008-07-25.

References