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cellular necrosis

Saturday 4 February 2006

Necrosis refers to a spectrum of morphologic changes that follow cell death in living tissue, largely resulting from the progressive degradative action of enzymes on the lethally injured cell (cells placed immediately in fixative are dead but not necrotic).

As commonly used, necrosis is the gross and histologic correlate of cell death occurring in the setting of irreversible exogenous injury. Necrotic cells are unable to maintain membrane integrity and their contents often leak out. This may elicit inflammation in the surrounding tissue.

The morphologic appearance of necrosis is the result of denaturation of intracellular proteins and enzymatic digestion of the cell.

The enzymes are derived either from the lysosomes of the dead cells themselves, in which case the enzymatic digestion is referred to as autolysis, or from the lysosomes of immigrant leukocytes, during inflammatory reactions.

These processes require hours to develop, and so there would be no detectable changes in cells if, for example, a myocardial infarct caused sudden death. The only telling evidence might be occlusion of a coronary artery.

The earliest histologic evidence of myocardial necrosis does not become manifest until 4 to 12 hours later, but cardiac-specific enzymes and proteins that are released from necrotic muscle can be detected in the blood as early as 2 hours after myocardial cell death.


Necrotic cells show increased eosinophilia attributable in part to loss of the normal basophilia imparted by the RNA in the cytoplasm and in part to the increased binding of eosin to denatured intracytoplasmic proteins.

The necrotic cell may have a more glassy homogeneous appearance than that of normal cells, mainly as a result of the loss of glycogen particles. When enzymes have digested the cytoplasmic organelles, the cytoplasm becomes vacuolated and appears moth-eaten. Finally, calcification of the dead cells may occur.

Dead cells may ultimately be replaced by large, whorled phospholipid masses called myelin figures. These phospholipid precipitates are then either phagocytosed by other cells or further degraded into fatty acids; calcification of such fatty acid residues results in the generation of calcium soaps.

By electron microscopy, necrotic cells are characterized by overt discontinuities in plasma and organelle membranes, marked dilation of mitochondria with the appearance of large amorphous densities, intracytoplasmic myelin figures, amorphous osmiophilic debris, and aggregates of fluffy material probably representing denatured protein.

Nuclear changes appear in the form of one of three patterns, all due to nonspecific breakdown of DNA. The basophilia of the chromatin may fade (karyolysis), a change that presumably reflects DNase activity.

A second pattern (also seen in apoptotic cell death) is pyknosis, characterized by nuclear shrinkage and increased basophilia. Here the DNA apparently condenses into a solid, shrunken basophilic mass.

In the third pattern, known as karyorrhexis, the pyknotic or partially pyknotic nucleus undergoes fragmentation. With the passage of time (a day or two), the nucleus in the necrotic cell totally disappears.

Once the necrotic cells have undergone the early alterations described, the mass of necrotic cells may have several morphologic patterns:
- coagulative necrosis (denaturation is the primary pattern)
- liquefactive necrosis (dominant enzyme digestion)
- caseous necrosis (tissular infection by mycobacterias or fungi)
- fat necrosis (cytosteatonecrosis)

Ultimately, in the living patient, most necrotic cells and their debris disappear by a combined process of enzymatic digestion and fragmentation, followed by phagocytosis of the particulate debris by leukocytes. If necrotic cells and cellular debris are not promptly destroyed and reabsorbed, they tend to attract calcium salts and other minerals and to become calcified (post-necrotic calcification or so-called dystrophic calcification).


- Robbins