There is no inflammation in apoptosis because: - Apoptosis is an orderly and controlled process of programmed cell death that does not release intracellular contents into the surrounding tissue. - In apoptosis, the cell shrinks and its contents are packaged into apoptotic bodies which are then phagocytosed by neighboring cells or macrophages in a non-inflammatory manner. - There is no disruption of the cell membrane or release of cytoplasmic enzymes and other inflammatory mediators that would trigger an inflammatory response, as occurs in necrosis. The orderly packaging and removal of dead cells prevents collateral tissue damage and inflammation.

1. CELL DEATH
BY
DR N MANJULA MBBS, MD (PATHOLOGY)

2. CELL
• Cells are the basic units of tissues, which form organs
and systems in the human body.
• Cell injury is the effect of stresses due to variety of
etiological agents on the cell.

3. CELL HOMEOSTASIS
• REVERSIBLE
• IRREVERSIBLE
CELL INJURY
• ATROPHY
• HYPERTROPHY
• HYPERPLASIA
• METAPLASIA
CELL
ADAPTATION • NECROSIS
• APOPTOSIS
CELL DEATH

4. MECHANISM OF CELL INJURY
• DEPLETION OF ATP
• MITOCHONDRIAL DAMAGE
• DEFECT IN CELL MEMBRANE PERMEABILITY
• CALCIUM ION INFLUX
• FREE RADICAL INJURY
• DAMAGE TO DNA AND PROTEINS

8. CELL DEATH
• Cell death is a state of irreversible injury.
• It may occur in the living body as a local or focal change
(i.e. autolysis, necrosis and apoptosis).
• The changes that follow it (i.e. gangrene and pathologic
calcification) or result in end of the life (somatic death).
• Autolysis (i.e. self-digestion) is disintegration of the cell
by its own hydrolytic enzymes liberated from
lysosomes.

9. NECROSIS
• Necrosis is localised area of death of tissue followed
by degradation of tissue by hydrolytic enzymes
liberated from dead cells.
• The damage caused here is irreversible.
• Necrosis is unregulated form of cell death.
• It results from damage to cell membranes and loss of
ion homeostasis.
• The word NECROSIS is derived from Greek word
“NEKROS” meaning corpse.
• It is always pathological.

10. NECROSIS
• It is invariably accompanied by inflammatory reaction.
• It can be caused by various agents - hypoxia, chemical,
physical agents, microbial agents & immunological
injury.
• There are 5 types of necrosis:-
• Coagulative,
• Liquefaction (colliquative),
• Caseous,
• Fat,
• Fibrinoidnecrosis.

11. MECHANISM - NECROSIS
• Necrotic cell – membrane is not intact – contents leak
out.
• Enzymatic digestion of cell / denaturation of proteins.
• Lysosome release enzymes that digest cellular
contents.
• Surrounding it inflammation occurs.
• Debris are removed by phagocytosis.

12. MORPHOLOGY - NECROSIS
• Cytoplasmic Changes
• Increased eosinophilia, glassy and homogeneous
appearance.
• Enzymes digest the cytoplasmic organelles and the
cytoplasm becomes vacuolated - “motheaten”
appearance.
• Nuclear Changes
• Due to the breakdown of DNA and chromatin.

13. NUCLEAR CHANGES IN
NECROSIS
• Pyknosis: Shrinkage of nucleus which appears
shrunken and deeply basophilic (similar to ink drop).
• Karyolysis: Progressive fading of basophilic staining of
the nuclei because of digestion of DNA by Dnase.
• In 1 to 2 days, the nucleus of a dead cell may completely
disappear.
• Karyorrhexis: The pyknotic nucleus undergoes
fragmentation into many smaller fragments.

15. COAGULATIVE NECROSIS
• M/C - type of necrosis.
• Caused by irreversible focal injury.
• Eg:- sudden cessation of blood flow (ischaemic
necrosis).
• Commonly affected organs are the heart, kidney, and
spleen.

16. GROSS - COAGULATIVE NECROSIS
• Focus of coagulative necrosis in the early
stage is pale, firm, and slightly swollen and
is called infarct.
• With progression, the affected area
becomes more yellowish, softer, and
shrunken.

17. MICROSCOPY - COAGULATIVE NECROSIS
• Hallmark - conversion of normal cells into their ‘tomb
stones’ i.e. outlines of the cells are retained and the cell
type can still be recognised but their cytoplasmic and
nuclear details are lost.
• The necrosed cells are swollen and have more
eosinophilic cytoplasm than the normal.
• The necrosed focus is infiltrated by inflammatory cells
and the dead cells are phagocytosed leaving granular
debris.

18. LIQUEFACTIVE NECROSIS
• Occurs commonly due to ischaemic injury and
bacterial or fungal infections.
• But hydrolytic enzymes in tissue degradation have a
dominant role in causing semi-fluid material.
• The common examples are infarct brain and abscess
cavity.

19. LIQUEFACTIVE NECROSIS
• Grossly, the affected area is soft with liquefied centre containing necrotic
debris.
• Later, a cyst wall is formed.
• Microscopically, the cystic space contains necrotic cell debris and
macrophages filled with phagocytosed material.
• The cyst wall is formed by proliferating capillaries, inflammatory cells, and
gliosis.

20. CASEOUS NECROSIS
• Caseous (caseous= cheese-like) necrotic material.
• Structural outline is not preserved.
• Caseous necrosis = coagulative + liquefactive.
• Eg:- Tuberculosis.

21. GROSS - CASEOUS
NECROSIS
• Foci of caseous necrosis resemble cheese which is
soft, granular and yellowish.

22. MICROSCOPY - CASEOUS
NECROSIS
• Centre of the necrosed focus contain structureless,
eosinophilic material.
• The surrounding tissue shows characteristic
granulomatous inflammatory reaction consisting of
epithelioid cells (modified macrophage having slipper-
shaped vesicular nuclei).
• It is seen admixed with giant cells of Langhans’ and
foreign body type and peripheral rim of lymphocytes.

23. MICROSCOPY - CASEOUS NECROSIS

24. FAT NECROSIS
• Special form of cell death - in fat-rich anatomic
locations.
• Examples:-
1. Traumatic fat necrosis of the breast,
2. Mesenteric fat necrosis due to acute pancreatitis.

25. MECHANISM - FAT NECROSIS
ACUTE
PANCREA
TITIS
Liberation
of
pancreatic
lipases
Necrosis of
the
pancreas
and peri
pancreatic
fat
Hydrolysis
of fat into
free fatty
acids
Free fatty
acid +
calcium
Calcium
soaps
Saponificat
ion

26. GROSS - FAT NECROSIS
• Yellowish-white and firm deposits.
• Formation of calcium soaps imparts the necrosed foci
firmer and chalky white appearance.

27. MICROSCOPY - FAT
NECROSIS
• The necrosed fat cells have cloudy appearance and are
surrounded by an inflamatory reaction.
• Formation of calcium soaps is identified in the tissue
sections as amorphous, granular and basophilic
material.

28. FIBRINOID NECROSIS
• It is characterized by deposition of fibrin-like material.
• It is encountered in various examples of immunologic
tissue injury (e.g. in immune complex vasculitis,
autoimmune diseases, Arthus reaction etc), arterioles
in hypertension, peptic ulcer etc.

29. MICROSCOPY - FIBRINOID NECROSIS
• It is identified by brightly
eosinophilic, hyaline-like
deposition in the vessel wall.
• Necrotic focus is surrounded by
nuclear debris of neutrophils.
• Local haemorrhage may occur
due to rupture of the blood
vessel.

30. APOPTOSIS –
programmed
cell death
NECROSIS –
pathological
killing of cells

31. APOPTOSIS
• Apoptosis - coordinated and internally programmed
cell death.
• Apoptosis = falling off or dropping off.
• It is a physiological as well as pathological process.
• When the cell is not needed, pathway of cell death is
activated (‘cell suicide’).
• Unlike necrosis, apoptosis is not accompanied by any
inflammation and collateral tissue damage.

32. PHYSIOLOGIC CAUSES OF
APOPTOSIS
Organised cell destruction in sculpting of tissues during
development of embryo.
Physiologic involution of cells in hormone-
dependent tissues. Eg:- endometrial shedding,
regression of lactating breast after withdrawal of
breast-feeding.
Involution of the thymus in early age.
Normal cell destruction followed by replacement
proliferation such as in intestinal epithelium.

33. PATHOLOGIC CAUSES OF
APOPTOSIS
• Cell death of tumor cells on exposure to
chemotherapeutic agents.
• Cell death by cytotoxic T cells in immune mechanisms
such as in graft-versus-host disease and rejection
reactions.
• Cell death in viral infections e.g. formation of
Councilman bodies in viral hepatitis.
• Pathologic atrophy of organs and tissues on
withdrawal of stimuli e.g. prostatic atrophy after
orchiectomy.
• Degenerative diseases of CNS e.g. in Alzheimer’s
disease.

34. MORPHOLOGIOCAL
CHANGES IN APOPTOSIS
• Cell shrinkage: Size of the cell decreases with dense eosinophilic cytoplas
• Chromatin condensation and fragmentation– Chromatin material aggregates
below the nuclear membrane initially, later fragmentation of nuclear material
occurs.
• Formation of cytoplasmic blebs & apoptotic bodies – Cell surface shows
blebbing. Condensed cytoplasm, fragmented nuclear material and organelles
are packed into the blebs which are separated from the cell forming apoptotic
bodies
• Phagocytosis of apoptotic cells or cell bodies usually by macrophages which
degrade them by lysosomal enzymes

38. GANGRENE
• It is massive necrosis with superadded putrefaction.
• TYPES:- dry and wet gangrene.
• A variant of wet gangrene - gas gangrene is caused by
clostridia (Gram-positive anaerobic bacteria).

41. WHY THERE IS NO INFLAMMATION IN
APOPTOSIS?
• IF YOU ANSWER THIS THEN THE PURPOSE OF THIS CLASS IS FULFILLED.