Necrosis - WikiHQ

thumb|upright=1.6|Structural changes of cells undergoing necrosis and [[apoptosis]]

Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. 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. 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.

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 and an uncontrolled release of products of cell death into the extracellular space. 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.

Classification

Structural signs that indicate irreversible cell injury and the progression of necrosis include dense clumping and progressive disruption of genetic material, and disruption to membranes of cells and organelles.

Morphological patterns

There are six distinctive morphological patterns of 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,
Liquefactive necrosis (or colliquative necrosis), in contrast to coagulative necrosis, is characterized by the digestion of dead cells to form a viscous liquid mass.
Caseous necrosis can be considered a combination of coagulative and liquefactive necrosis,
Fat necrosis is specialized necrosis of fat tissue,
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.
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.

Causes

thumb|right|Hand necrosis from [[bubonic plague]]

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, damage to blood vessels (which may disrupt blood supply to associated tissue), and ischemia. Thermal effects (extremely high or low temperature) can often result in necrosis due to the disruption of cells, especially in bone cells.

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. Under extreme conditions tissues and cells may die through an unregulated process of membrane and cytosol destruction.

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.

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. and induces massive necrotic death of endothelial cells and non-proliferating cells of surrounding tissues (neurons, cardiomyocytes, renal cells, etc.). However, there are two broad pathways in which necrosis may occur in an organism. 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.

File:4 Bd obs 4 680x512px.tif|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 glioblastoma

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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.

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. In select cases, special maggot therapy using Lucilia sericata larvae has been employed to remove necrotic tissue and infection.
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.
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. In the example of a snake bite, the use of anti-venom halts the spread of toxins whilst receiving antibiotics to impede infection.

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.

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. For example, necrosis of tissue can occur in Arabidopsis thaliana due to plant pathogens.

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.

References

External links

Toxicology Conundrum #018—Life in the Fast Lane
Secondary necrosis of a neutrophil