PATHOLOGY 425/401

NECROSIS - 1
Dr. D. F. Hardwick

Individual cell death is a common event in some regenerating tissues such as skin and gut epithelium and during
embryogenesis. It is also a phenomenon under genetic control in certain circumstances. When programmed cell death occurs,
it is termed APOPTOSIS. Cell death is certainly not a typical event in developed tissues such as brain and becomes a serious
occurrence when many cells are involved in such organs as the liver. Cell death may also be a serious event when it involves
strategically located cells such as those in essential nuclei and tracts of the brain. This lecture does not deal with the genetice
mechanism of apoptosis.

NECROSIS (Necro - death, osis - state)

This is the term applied to the state of cell death. Essentially this means death of a tissue (cell death on a large scale)
or part of a tissue with cellular reaction to the dead cells.

ETIOLOGY OF TISSUE NECROSIS

l) Hypoxia
2) Physical injury
a) trauma
b) radiation - U.V., Cosmic, X-ray
3) Chemicals - variable
4) Biological toxins - endotoxins
5) Immunological reactions
6) Inborn genetic disorders
7) Nutritional
8) Age

MECHANISMS OF NECROSIS
Basic mechanisms
l) Impaired oxidative phosphorylation
2) Membrane dissolution
3) Osmotic regulation
These, of course, are the same mechanisms basic to cell injury. They differ, in necrosis, only in that the insult was
sufficiently massive to force the degradative process beyond the point of return to viability.

COMMON EXAMPLES OF NECROSIS

l) Heart attack - myocardial infarction
The coronary arteries that supply the heart muscle are frequently occluded. Such occlusions lead to death of
the myocardial tissue distal to the obstruction. This is on an anoxic basis (#l). Such a dead area is said to
be infarcted, a term used for areas of necrosis due to vascular obstruction.
2) Strokes - similarly areas of the brain become infarcted and necrotic due to occlusion of cerebral arteries.
How such a cerebral vascular accident (C.V.A.) manifests itself, of course, depends on which part of the
brain is affected.

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 3) Hepatic necrosis - Liver cells are susceptible to many agents and drugs. A common cause, in the past, of
hepatic cell death was carbon tetrachloride, an agent that leads to peroxidation and disruption of cell
membranes (similar to the way butter becomes rancid). More recently hepatitis, a viral disease of the liver,
has led to hepatic necrosis with massive cell death. The shared drug-culture needle facilitates this.
4) Pancreatic necrosis - Through a complex series of events, likely related to membrane destruction from
enzymes, the pancreas may auto-digest itself. This process, when massive, leaves a scene of devastation
such as is seen only in severe traumatic injury. The auto-digestive process leads to leakage of intravascular
fluids out of vessels (edema), disruption of vessels and subsequent bleeding into the tissues (hemorrhage),
destruction of adjacent fat by pancreatic lipase (fat necrosis), to mention only a few of the more obvious
results. The name 'acute hemorrhagic pancreatic necrosis' fits the disease well.
5) Ulceration - Disruption of any epithelial surface (skin, gut genito- urinary, respiratory tract, etc.) is ulceration.
An ulcer is characterized by an edge, a base and a margin.
Aphthous ulcers of the mouth (canker sores) represent such an area of viral induction of superficial necrosis
leading to ulceration. The Curies developed skin ulcers from radium exposure. Other ulcers, such as the
peptic ulcer of the stomach or duodenum, are due to a chemical ulceration.
6) Apoptotic cell death - Huntingtons disease is an important example of this phenomenon.

PATHOLOGY OF NECROSIS
The types of necrosis are identified by their gross (eye-ball vision) or light microscopic appearance. Typically, changes
do not occur quickly unless the causative agent was excoriative. More usually, the subtle chemical events associated with cell
injury have been operative and only after some length of time has enough actual tissue structure degeneration taken place for it
to be seen with such insensitive tools as the eye and light microscope. For example, an individual may suffer the excruciating
pain of myocardial ischemia (lack of blood), live for 6-12 hours, then die, and the dead area of the heart muscle may show little
evidence of necrosis by visual or light microscope examination, compared to the rest of the heart and muscle.
However, when necrosis is evident, two major sign posts are noted which have similarities to apoptosis:
l) Nuclear degeneration
- chromatin clumping
- pyknosis (shrinking)
- karyolysis (dissolution of chromatin)
- karyorrhexis (fragmentation of chromatin)
2) Cytoplasmic changes - cytoplasmic coagulation with cell edema are the most common manifestations.

TYPES OF NECROSIS
l) Liquefactive necrosis - the tissue becomes liquefied - seen in brain where there is little connective tissue, and
where proteolytic enzymes are present in excess, tissue structure unfirm, e.g. abscesses.
2) Coagulative necrosis - few proteolytic enzymes are present and the tissue seems to coagulate, probably by
protein denaturation, considerable collagen is present, e.g. kidney, liver, or heart muscle.
3) Caseous necrosis - Infection with mycobacterium tuberculosis leads to a hypersensitivity state. In people
with such hypersensitivity state Tb. is accompanied by a peculiar balance of coagulative lytic effects leading
to a cheezy (caseous) appearance to the infected and necrotic tissues.
4) Gangrene - A term relating to necrosis of an appendage usually it is applied to limbs, however, it may also be
used to describe an appendix or gall bladder too. This form of necrosis applies to ischemic necrosis
(embarrassed blood supply) usually with superimposed bacterial action (wet gangrene) but sometimes in
toes without bacterial effects - (dry gangrene or mummification).

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 5) Fat necrosis - This merely refers to a peculiar degeneration of fat. It may be enzymatic (pancreas) or
traumatic (skin) in origin.
Grossly, the fat is a chalky-white lump, microscopically necrotic fat and scavenger cells (leukocytes) and
inflammation are noted.

AUTOLYSIS
This change takes place when dead tissue is allowed to degenerate at temperatures much higher or much lower than
body temperatures.