Cell Death (Necrosis)

Individual Cell Death

● Common event in some regenerating
tissues: such as skin and gut epithelium
and during embryogenesis
● Not a typical event in developed tissues
such as brain
● becomes a serious occurrence when
many cells are involved in such organs as
the liver
● Programmed cell death: Apoptosis
 What are the important factors on
the outcome of injury on cells?
Severity of injury and duration
have a major effect on the outcome
of injury
 Etiology of Tissue Necrosis
1) 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
 Mechanisms of Necrosis

Basic mechanisms:
1) Impaired oxidative phosphorylation
2) Membrane dissolution
3) Osmotic regulation
 Major Signs of Necrosis Similar to
Apoptosis
1) Nuclear degeneration
‑ Chromatin clumping
‑ Karyopyknosis (shrinking)
‑ Karyolysis (dissolution of chromatin)
‑ Karyorrhexis (fragmentation of chromatin)
2) Cytoplasmic changes
 Types of Necrosis
● Liquefactive necrosis: Necrosis in brain,
abscesses
● Coagulative necrosis: Necrosis of kidney,
liver, or heart muscle
● Caseous necrosis: Infection with
Mycobacterium tuberculosis
● Gangrene: Necrosis of an appendage,
usually limbs
● Fat necrosis
 Coagulative necrosis

● Caused by ischemia. Ischemia results in

decreased ATP, increased cytosolic Ca++,
and free radical formation, which each
eventually cause membrane damage.
● Example: Infarct: localized area of
ischemic necrosis as in myocardial
infarct.
 Liquefactive Necrosis
● Usually caused by focal bacterial infections,
because they can attract polymorphonuclear
leukocytes. The enzymes in the polys are
released to fight the bacteria, but also dissolve
the tissues nearby, causing an accumulation of
pus, effectively liquefying the tissue (hence, the
term liquefactive).
● Example: Abscess
 Caseation Necrosis
● Caseous: A distinct form of coagulative
necrosis seen in mycobacterial infections (e.g.,
tuberculosis), or in tumor necrosis, in which the
coagulated tissue no longer resembles the cells,
but is in chunks of unrecognizable debris.
Usually there is a giant cell and granulomatous
reaction, sometimes with polys, making the
appearance distinctive.
● Example: Tuberculosis.
 Fat necrosis

● Fat Necrosis: A term for necrosis in fat, caused either by

release of pancreatic enzymes from pancreas or gut
(Enzymatic fat necrosis) or by trauma to fat, either by a
physical blow or by surgery (Traumatic fat necrosis).
● The effect of the enzymes (lipases) is to release free
fatty acids, which then can combine with calcium to
produce detergents (soapy deposits in the tissues).
● Histologically, one sees shadowy outlines of fat cells
(like coagulative necrosis), but with Ca++ deposits,
foam cells, and a surrounding inflammatory reaction.
 Consequences of Necrosis

● Healing vs. permanent damage

● Local vs. systemic effects.
1) Type of tissue
2) Size of lesion
3) Location of lesion
 AUTOLYSIS

● Lysis of tissues by their own enzymes, following

the death of the organism. Therefore, the key
difference is that there is no vital reaction (i.e.,
no inflammation). Autolysis is essentially rotting
of the tissue.
● Early autolysis is indistinguishable from early
coagulative necrosis due to ischemia, unless
the latter is focal.