Cell DeathCell Death (Necrosis) (Necrosis)

Individual Cell DeathIndividual Cell Death

CCommon event in some regenerating ommon event in some regenerating tissuestissues: : such as skin and gut epithelium such as skin and gut epithelium and during embryogenesisand during embryogenesis

NNot a typical event in developed tissues ot a typical event in developed tissues such as brainsuch as brain

becomes a serious occurrence when many becomes a serious occurrence when many cells are involved in such organs as the cells are involved in such organs as the liverliver

PProgrammed cell deathrogrammed cell death: : AApoptospoptosiiss

What are the important factors on What are the important factors on the outcome of injury on cells?the outcome of injury on cells?Severity of Severity of iinjury njury and and ddurationuration

have have aa major effect on the major effect on the outcomeoutcome of injuryof injury

EtEtiiology ology oof Tf Tiissue Necrosssue Necrosiiss

11) Hypoxia) Hypoxia

2) Physical injury2) Physical injury

a)a) T Traumarauma

b) b) RRadiation ‑ U.V., Cosmic, X‑rayadiation ‑ U.V., Cosmic, X‑ray

3) Chemicals ‑ variable3) Chemicals ‑ variable

4) Biological toxins ‑ endotoxins4) Biological toxins ‑ endotoxins

5) Immunological reactions5) Immunological reactions

6) Inborn genetic disorders6) Inborn genetic disorders

7) Nutritional7) Nutritional

MechanMechaniisms sms oof Necrosf Necrosiiss

Basic mechanismsBasic mechanisms::

11) Impaired oxidative phosphorylation) Impaired oxidative phosphorylation

2) Membrane dissolution2) Membrane dissolution

3) Osmotic regulation3) Osmotic regulation

Major Signs of Necrosis Similar to Major Signs of Necrosis Similar to ApoptosisApoptosis

11) Nuclear degeneration) Nuclear degeneration

‑ ‑ CChromatin clumpinghromatin clumping

‑ ‑ KaryoKaryopyknosis (shrinking)pyknosis (shrinking)

‑ ‑ KKaryolysis (dissolution of chromatin)aryolysis (dissolution of chromatin)

‑ ‑ KKaryorrhexis (fragmentation of chromatin)aryorrhexis (fragmentation of chromatin)

2) Cytoplasmic changes2) Cytoplasmic changes

Types Types oof Necrosf Necrosiiss

Liquefactive necrosisLiquefactive necrosis:: Necrosis in brain, Necrosis in brain, aabscessesbscesses

Coagulative necrosisCoagulative necrosis:: Necrosis of Necrosis of kidney, kidney, liver, or heart muscleliver, or heart muscle

Caseous necrosisCaseous necrosis:: Infection with Infection with MMycobacterium tuberculosis ycobacterium tuberculosis

GangreneGangrene:: N Necrosis of an appendageecrosis of an appendage, , usually limbsusually limbs

Fat necrosisFat necrosis

Coagulative necrosisCoagulative necrosis

Caused by ischemiaCaused by ischemia. . Ischemia results in Ischemia results in decreased ATP, increased cytosolic Cadecreased ATP, increased cytosolic Ca++++, , and free radical formation, which each and free radical formation, which each eventually cause membrane damageeventually cause membrane damage..

Example: Infarct: localized area of Example: Infarct: localized area of ischemic necrosis as in myocardial ischemic necrosis as in myocardial infarct. infarct.

Liquefactive NecrosisLiquefactive Necrosis

Usually caused by focal bacterial infections, Usually caused by focal bacterial infections, because they can attract polymorphonuclear because they can attract polymorphonuclear leukocytes. The enzymes in the polys are leukocytes. The enzymes in the polys are released to fight the bacteria, but also dissolve released to fight the bacteria, but also dissolve the tissues nearby, causing an accumulation of the tissues nearby, causing an accumulation of pus, effectively liquefying the tissue (hence, the pus, effectively liquefying the tissue (hence, the term liquefactive). term liquefactive).

Example: AbscessExample: Abscess

Caseation NecrosisCaseation Necrosis

Caseous: A distinct form of coagulative Caseous: A distinct form of coagulative necrosis seen in mycobacterial infections (e.g., necrosis seen in mycobacterial infections (e.g., tuberculosis), or in tumor necrosis, in which the tuberculosis), or in tumor necrosis, in which the coagulated tissue no longer resembles the cells, coagulated tissue no longer resembles the cells, but is in chunks of unrecognizable debris. but is in chunks of unrecognizable debris. Usually there is a giant cell and granulomatous Usually there is a giant cell and granulomatous reaction, sometimes with polys, making the reaction, sometimes with polys, making the appearance distinctive. appearance distinctive.

Example: Tuberculosis.Example: Tuberculosis.

Fat necrosisFat necrosis

Fat Necrosis: A term for necrosis in fat, caused either by Fat Necrosis: A term for necrosis in fat, caused either by release of pancreatic enzymes from pancreas or gut release of pancreatic enzymes from pancreas or gut ((Enzymatic fat necrosisEnzymatic fat necrosis) or by trauma to fat, either by a ) or by trauma to fat, either by a physical blow or by surgery (physical blow or by surgery (TraumaticTraumatic fat necrosisfat necrosis). ).

The effect of the enzymes (lipases) is to release free The effect of the enzymes (lipases) is to release free fatty acids, which then can combine with calcium to fatty acids, which then can combine with calcium to produce detergents (soapy deposits in the tissues). produce detergents (soapy deposits in the tissues).

Histologically, one sees shadowy outlines of fat cells Histologically, one sees shadowy outlines of fat cells (like coagulative necrosis), but with Ca++ deposits, (like coagulative necrosis), but with Ca++ deposits, foam cells, and a surrounding inflammatory reaction. foam cells, and a surrounding inflammatory reaction.

Consequences of NecrosisConsequences of Necrosis

Healing vs. permanent damageHealing vs. permanent damage Local vs. systemic effects.Local vs. systemic effects.

11) Type of tissue) Type of tissue

2) Size of lesion2) Size of lesion

3) Location of lesion3) Location of lesion

AUTOLYSIS AUTOLYSIS

Lysis of tissues by their own enzymes, following Lysis of tissues by their own enzymes, following the death of the organism. Therefore, the key the death of the organism. Therefore, the key difference is that there is no vital reaction (i.e., difference is that there is no vital reaction (i.e., no inflammation). Autolysis is essentially rotting no inflammation). Autolysis is essentially rotting of the tissue. of the tissue.

Early autolysis is indistinguishable from early Early autolysis is indistinguishable from early coagulative necrosis due to ischemia, unless coagulative necrosis due to ischemia, unless the latter is focal.the latter is focal.