Causes[edit]

Necrotic leg wound caused by a brown recluse spider bite

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), damage to blood vessels (which may disrupt blood supply to associated
tissue), and ischemia.[12] Thermal effects (extremely high or low temperature) can result in
necrosis due to the disruption of cells.
In frostbite, crystals form, increasing the pressure of remaining tissue and fluid causing the cells
to burst.[12] Under extreme conditions tissues and cells die through an unregulated process of
destruction of membranes and cytosol.[13]

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. [12]
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.
[12]
 Necrotic wounds have also resulted from the stings of Vespa mandarinia.[14]
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.[12] A
classic example of a necrotic condition is ischemia which leads to a drastic depletion
of oxygen, glucose, and other trophic factors 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.[12]
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.[12]
Pathogenesis[edit]
Pathways[edit]
Until recently, necrosis was thought to be an unregulated process.[15] However, there are two
broad pathways in which necrosis may occur in an organism. [15]
The first of these two pathways initially involves oncosis, where swelling of the cells occurs.
[15]
 Affected cells then proceed to blebbing, and this is followed by pyknosis, in which nuclear
shrinkage transpires.[15] In the final step of this pathway cell nuclei are dissolved into the
cytoplasm, which is referred to as karyolysis.[15]
The second pathway is a secondary form of necrosis that is shown to occur after apoptosis and
budding.[15] In these cellular changes of necrosis, the nucleus breaks into fragments (known
as karyorrhexis).[15]

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.[6]
 Karyorrhexis: the shrunken nucleus fragments to complete dispersal. [6]
 Pyknosis: the nucleus shrinks, and the chromatin condenses. [6]
Other typical cellular changes in necrosis include:

 Cytoplasmic hypereosinophilia on samples with H&E stain.[16] 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.[6]
On a larger histologic scale, pseudopalisades (false palisades) are hypercellular zones that
typically surrounds necrotic tissue. Pseudopalisading necrosis indicates an aggressive tumor. [17]

Pyknosis in a bile infarct

 

Cytoplasmic hypereosinophilia (seen in left half of image).

 

Pseudopalisading seen around necrosis in glioblastoma.