Necrosis

Apoptosis
 Types of Cell Death - NECROSIS

• Focal cell death

occurring in a living
body is called
necrosis.
• In necrosis, damage
to cell membrane
causes leakage of
lysosomal enzymes
that produce
dissolution of the cell
 Microscopic Appearance of
Necrosis
Light microscopic changes Electron microscopic changes

Cytoplasmic changes 1. Destruction of cell

1. Increased eosinophilia
membrane
2. Homogenous or moth
eaten appearance 2. Mitochondrial swelling
3. Sometimes calcium
3. Deposition of amorphous
deposition
material
Nuclear changes
1. Pyknosis 4. Myelin figures
2. Karyolysis
3. Karyorrhexis
 TYPES OF NECROSIS
1. Coagulative necrosis
2. Liquefactive necrosis
3. Gangrenous necrosis
4. Caseous necrosis
5. Fat necrosis
6. Fibrinoid necrosis
 COAGULATIVE NECROSIS
• Follows hypoxic cell
death

• Gross: Tissue is firm

• M/E: Preservation of
basic outline of cells

• Cause: Increasing
acidosis within cells
denatures lysosomal
enzymes
Infarct Of Kidney
Infarct of Brain
Myocardial Infarction
COAGULATIVE NECROSIS OF HEART
 LIQUEFACTIVE NECROSIS
• There is complete digestion
of cells due to action of
various enzymes.

• Usually follows bacterial

infections

• Provokes intense collection

of inflammatory cells

• Gross: tissue appears

viscous and pus may be
present

• M/E: Only necrotic debris is

seen
ABSCESS (LIQUEFACTIVE NECROSIS) OF LIVER
 GANGRENOUS NECROSIS
• In this there is coagulative
necrosis along with
superimposition of
saprophytic organisms
that produce putrefaction

• It is called wet gangrene if

there is concurrent
liquefaction

• In absence of liquefaction
it is called dry gangrene

• Gross: Tissue appears

black
 CASEOUS NECROSIS
• It is a form of coagulative
necrosis produced most
often by bacteria M.
tuberculosis.

• Gross: Necrotic area

appears cheesy

• M/E: Presence of
amorphous granular
eosinophilic material
that is surrounded by
characteristic
granulomatous
inflammation.
TB LUNG WITH AREAS OF CASEOUS NECROSIS
 FAT NECROSIS
• It represents focal
areas of necrotic
adipocytes due to
activation of enzymes

• Seen most commonly

in pancreas and
breast

• Lipid is converted to
fatty acids that may
combine with calcium.
Calcified lipid is
deposited in tissues
as chalky streaks
Fat Necrosis
 Fibrinoid Necrosis
• Seen more often
in context of
malignant
hypertension
and
immunological
injuries

• Characterized by
outpouring of
fibrin rich
exudate
 Types Of Cell Death - APOPTOSIS
• It is the form of cell
death that is initiated
by activation of a
programmed and
coordinated series
of events within a
cell.
• These events are
under control of
certain genetic
influences.
PHYSIOLOGICAL APOPTOSIS – FEW EXAMPLES
1. During embryogenesis:-

 Large number of neurons produced. Many get deleted to form

synapses.

2. Formation of roof of mouth: -

 Palatine processes fuse. Redundant tissue removed. When abnormal

- cleft palate.

3. Maturation of immune system:-

 Inappropriate clones of immunocytes removed

4. Cells that are dependant on a trophic stimulus for survival involute

when the stimulus is withdrawn, as seen during menstrual cycle

5. Size of tissues having continuously proliferating cells is kept in

check by apoptosis – intestinal tissue.
 PATHOLOGICAL APOPTOSIS
1. Cell injury during viral diseases like hepatitis and AIDS.

2. Cell death seen in tumors due to the action of cytotoxic

lymphocytes

3. Use of injurious agents like radiation and cytotoxic drugs

4. Duct obstruction producing atrophy of the organ

5. Many auto-immune diseases .

6. Neurodegenerative disorders.

7. Failure of normal apoptotic process can result in tumor

formation.
 MORPHOLOGICAL FEATURES OF APOPTOSIS
 Death of single cells: - intensely eosinophilic,
dense fragmented chromatin.

 Nuclear and cytoplasmic fragmentation.

 On EM -
 Peripheral condensation of chromatin,

 Cell organelles remain intact,

 Cell shrinkage.

 Phagocytosis of apoptotic cell by adjacent cells.

 Absence of surrounding inflammation.

Apoptotic bodies in Liver
 BIOCHEMICAL FEATURES OF APOPTOSIS
• Protein cleavage:

– Caspases are activated, which activate DNAases.

– Fragmentation of DNA and cytoplasmic proteins occurs.

• DNA fragments are further broken down by

endonucleases into 180 to 200 bps fragments.

• Phosphatidyl serine and thrombospondin molecules

are expressed on these cells.

• These molecules promote phagocytosis of these

cells
 MECHANISM OF APOPTOSIS
• Apoptosis is a dynamic process and is energy dependant

• Activation of specific genes initiate apoptosis.

• Extrinsic and intrinsic pathways activated by withdrawal of

GFs, hormones, viruses, FAS, TNF, radiation, toxins, free
radicals etc.

• Both pathways result in activation of initiator caspases.

• Apoptosis is an autocatalytic process.

• Caspase 3 and 6 are final executioner caspases.

• Caspases have proteolytic activity.

• They degrade proteins involved in transcription, DNA repair

and replication along with cytoskeletal proteins.
 Necrosis versus Apoptosis
Feature Apoptosis Necrosis

Induction May be induced by Invariably due to pathological

physiological or pathological injury
stimuli

Extent Single cells Multiple cells

Biochemical Events Energy dependent Cell membrane integrity lost

fragmentation of DNA enzyme leakage from
lysosomes

Cell membrane integrity Maintained Lost

Morphology Formation of apoptotic bodies Cell swelling and lysis

Inflammatory response None Often present

Fate of dead cells Ingested by neighboring cells Ingested by polymorphs and

macrophages