Cell Injury,Necrosis and Apoptosis

8/3/2019 Cell Injury,Necrosis and Apoptosis

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Moderator : Dr Raj Mehrotra

By : Dr Mustafa Ali


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Stress ,increased demand

ADAPTATION

Inability to adapt

` Injurious stimulus

` CELL INJURY

CELL DEATH


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` If the limits of adaptive responses to a stimulusare exceeded , or when the cell is exposed to aninjurious agent or stress , a sequence of events

follows that is loosely termedcell

injury.

` It is reversible up to a certain point , but ifstimulus persist , the cell reaches to a point of no

return and suffer irreversiblecell injury andultimately cell death.


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` Oxygen deprivation

` Physical agents

` Chemical agents and drugs

` Infectious agents` Immunologic reactions

` Genetic derangments

` Nutritional imbalance


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` Cell injury results from functional andbiochemical abnormalities in one or more ofseveral essential cellular components.

1. Depletion of ATP:` Activity of Na-K pump is reduced

` Switch to anaerobic metabolism , increasedanaerobic glycolysis and accumulation of lactic

acid.` Failure of Ca pump

` Misfolding of proteins


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2. Mitochondrial damageMitochondrial permeability transition

3. Influx of intracellular Ca2+ and loss of calciumhomeostasis

Enzyme known to be activated by Ca2+ includeATPase, phopholipases , proteases and endonucleases.

4. Accumulation of oxygen derived free radicals(oxidativestress)

An imbalance b/w free radical generating and scavengingsystems results in oxidative stress.

5. Defect In membrane permeability.


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1. Reversible cell injury:

A. Vacuolar/hydropic degeneration

B. Fatty change

2. Irreversible cell injury:

A. Necrosis

B. Apoptosis


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Reversible Irreversible

Characterised by

1.Generalized swelling of celland its orgenelles

2.Blebbing of the plasmamembrane

3.Detachment of ribosomes

from ER4.Clumping of nuclearchromatin

5. Loss of microvilli andformaion of myelin figures

` Characterised by

1.Increasing swelling of cell2.Swelling and disruption

of lysosomes3.Presence of large

amorphous densities inswollen mitochondria4.Profound nuclear

changes


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` Necrosis is death ofcellleading to itsdisintegration and lysis.

It is of mainly four types:

1.Coagulative necrosis: outlineofcells arepreserved.

Ex: renaland myocardial infarction

2.Caseous necrosis: distinct typeofcoagulativenecrosis,term is restricted to the necrosis due toTB.


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3. Liquefactive necrosis: tissue is completelydigested and changed into liquid mass.

Ex: bacterial & fungal infection

infarction of CNS4. Fat necrosis: fatty acid produced by lipases

combines with calcium to cause saponification.

Ex: acute pancreatitis


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Apoptosis is a pathway of cell death induced byregulated intracellular program which isgenetically determined.

Initiation of apoptosis occurs principally by signalfrom two distinct but convergent pathways-

1.the extrinsic , or death receptor initiated pathway

2.The intrinsic , or mitochondrial pathway


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` Intrinsic pathway is activated by withdrawal ofgrowth signals while extrinsic pathway is initiatedby engagement of cell surface death receptors on

variety of cells.` Once initiated , both pathways converge to

activate caspases and they complete executionphase.

` Executioner caspases cleave cytoskeletal andnuclear matrix proteins and lead to breakdown ofthe nucleus.


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Necrosis Apoptosis

1. Due to irreversible injury

2. Involves large area

3. Accompanied by inflammation

4. Plasma membrane ruptured

5. This is brought about byleakage of fluid ,ion ,proteinsand enzymes

1. Programmed cell deathmay be physiological orpathological

2. Involves single cell or fewcluster of cells

3. Not accompanied byinflammation

4. Plasma membrane intact

5. This is brought about by a

chain reaction of differentcaspases


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Necrosis Apoptosis

6. The cytoplasm becomesvacuolated and moth eaten

7. Nucleus shows pyknosis,karyorrhexis and karyolysis.

8. No apoptotic body is formed

9. DNA electrophoresis shows asmearing effect

10. TUNEL staining is negative

6. The cells are shrunken withdense eosinophilic cytoplasm

6. Nuclear chromatin fragmentsand condenses peripherally

7. Formation of apoptotic bodies

8. DNA laddering is seen

9. TUNEL staining is positive


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` Cellular aging is the result of a progressive declinein the proliferative capacity and life span of cellsand the effect of continuous exposure to

exogenous influences that result in progressiveaccumulation of cellular and molecular damage.


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Cell Injury,Necrosis and Apoptosis

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