Cell death.ppt at isamic university in Uganda

its g00d

1. Cell deathCell death
DR.KATONGOLE FAUZ KDR.KATONGOLE FAUZ K
Pathology dept.Pathology dept.
20222022

2. Cell deathCell death
Overview: There are two forms of cell death,
apoptosis and necrosis.
Apoptosis is controlled (programmed)
breakdown of cells occurring in response to
damage to DNA or as part of normal growth
and development.
Necrosis is uncontrolled breakdown of cells
in response to injurious stimuli.

3. ApoptosisApoptosis
Basic description: Programmed cell death. (single-cell
suicide)
Derived from Greek "falling off " (as for autumn leaves)
It can be physiologic or and pathologic
Energy is expended in this cell death.
The cells activate their own enzymes to degrade their
own nuclear DNA, nuclear proteins and cytoplasmic
proteins.
It does not elicit an inflammatory reaction in the host
Apoptosis and necrosis sometimes co-exist.

4. Patterns of occourance of apoptosisPatterns of occourance of apoptosis
During growth and development, some cells serve a
function in the growth phase but need to be removed
after their purpose is fulfilled.
In neonates, a rapid cell growth rate is necessary; in
adults, however, unrestrained cell growth can lead to
cancer.
When DNA sustains irreparable damage (e.g., after low-
dose radiation exposure), the cell must be destroyed so
mutations that have developed will not be propagated.
In this manner, apoptosis serves as a safety step by
removing damaged cells from the body.

5. Phases of apoptosisPhases of apoptosis
Initiation is the phase in which caspases
(cysteine aspartic acid proteases) become
catalytically active.
Execution is the phase in which the action of
caspases causes death of cell.

6. Mechanism of apoptosisMechanism of apoptosis
There are multiple pathways by which apoptosis is
initiated, including the extracellular and intracellular
pathways.
Both pathways share similar endpoints, culminating
with the use of caspases and prevention of
inflammatory reaction.
1.Initiation of extracellular pathway: In Fas-Fas ligand
binding, the Fas ligand binds to a member of the
tumor necrosis factor family known as the Fas
receptor.

7. MMechanism of apoptosis..echanism of apoptosis..
The activated Fas receptor in turn activates FADD
(Fas-associated death domain), which in turn
activates caspases.
2. Initiation of intracellular pathway: The
mitochondria release cytochrome c, which
combines with Apaf-1 (apoptosis activating factor-
1) to activate caspases.
Caspases, which cleave DNA, are activated. DNA is
cleaved in a coordinated manner so the
fragments, if analysed on a gel, will form a ladder.

8. Mechanism of apoptosis..Mechanism of apoptosis..
In contrast, in necrosis (an uncoordinated
breakdown of DNA), the gel will be a smear.
Apoptosis does not generate an
inflammatory reaction as necrosis does.
Fragments of cells express phosphatidyl
serine, which is recognized by macrophages;
therefore, fragments can be engulfed
without generating an inflammatory
reaction.

9. Examples of apoptosis..Examples of apoptosis..
1. Programmed destruction of cells during
embryogenesis.
2. Hormone-dependent involution in the adult e.g.
endometrial cell breakdown during the menstrual
cycle, the regression of the lactating breast after
weaning and prostatic atrophy after castration.
3. Death of host cells that have served their useful
purpose, such as neutrophils in an acute
inflammatory response and lymphocytes at the end
of an immune response.

10. MMorphology of apoptosisorphology of apoptosis

11. NecrosisNecrosis
Basic description: Necrosis is a term used to
describe uncontrolled death of cells due to one of
the various causes of cellular injury.
Necrosis may be defined as the morphology of cell
death in living body.
1.Gross morphology of necrosis: Necrosis is typically
manifested by softening and discoloration of the
organ. Other processes can have a similar
appearance, so the gross appearance of necrosis
is not specific.

12. Morphology of necrosis..Morphology of necrosis..
Microscopic morphology of necrosis: Necrotic
cells are going to show;
1. Increased eosinophilia with a glassy
homogeneous appearance.
2. Vacuolated and moth-eaten cytoplasm
3. Calcification of the dead cells may occur

13. Nuclear changes in necrosisNuclear changes in necrosis
Nuclear changes show one of three patterns:
1- Pyknosis, (also in apoptosis) – nuclear
shrinkage and increased basophilia.
2-Karyolysis: basophilia of the chromatin may
fade (dissolution or disintegration of the
nucleus).
3- Karyorrhexis: destructive fragmentation of
the nucleus.

14. Microscopic morphology..Microscopic morphology..

15. Patterns of tissue necrosis..Patterns of tissue necrosis..
1. Coagulative necrosis
2. Liquefactive (colliquative) necrosis
3. Fat necrosis
4. Caseous necrosis
5. Gangrenous necrosis
• Dry gangrene
• Moist gangrene
• Gas gangrene
6. Fibrinoid necrosis

16. 1.Coagulative necrosis1.Coagulative necrosis
Basic description: Coagulative necrosis is the type of necrosis
in which protein denaturation is more prominent than
enzymatic breakdown.
Microscopic morphology of coagulative necrosis
 There is increased eosinophilia of the cytoplasm and
decreased basophilia of the nucleus; both are associated
with preservation of the general cellular architecture (the
organ type is identifiable).
Organs affected by coagulative necrosis: Coagulative necrosis
may occur in any organ. In organs with a high fat content,
such as the brain, coagulative necrosis is followed rapidly by
liquefactive necrosis.

17. Gross morphology..Gross morphology..

18. 2.Liquefactive necrosis2.Liquefactive necrosis
Basic description: Liquefactive necrosis occurs in
situations in which enzymatic breakdown is more
prominent than protein denaturation or in organs
that lack a substantial protein-rich matrix (e.g., lipid-
rich organs such as the brain).
Microscopic morphology of liquefactive necrosis
 There is loss of organ cellular architecture. In
liquefactive necrosis of the brain, there are sheets of
lipid-laden macrophages that replace the dead
tissue. (see figure below)

19. Patterns of necrosis..Patterns of necrosis..
Organs affected by liquefactive necrosis: Liquefactive
necrosis is most commonly associated with organs
that have a high fat and low protein content (e.g. the
brain), or those with a high enzymatic content (e.g.
the pancreas).
3.Fat necrosis: Fat necrosis is a term applied to a
change in adipose tissue due to trauma or the release
of enzymes from adjacent organs (e.g., the pancreas).
The trauma or enzymatic action causes a breakdown of
lipid and a release of fatty acids, which combine with
calcium to form chalky deposits.

20. Morphology of liquefactive Morphology of liquefactive
necrosisnecrosis

21. Patterns or types of Patterns or types of
necrosis..necrosis..
4. Caseous necrosis (See fig A and B below):
Caseous necrosis is a “cheesy-looking” necrosis
associated with tuberculosis infections and
other granulomatous disease processes.
Granulomas are a form of chronic inflammation
due to some infections (e.g., mycobacterial),
foreign bodies and other chronic stimuli.

22. Morphology of caceous necrosisMorphology of caceous necrosis

23. Important points on Important points on
necrosisnecrosis
Cell death involves the release of intracellular
enzymes into blood. These enzymes in the blood can
be measured and used clinically to detect disease.
Cell death affects morphology (the shape of the cell)
and function. Morphologic changes (both gross and
microscopic) can develop over a period of time, while
loss of function may occur almost immediately.
Because of this immediate loss of function, the
clinical manifestations of cellular injury may be
present before the morphologic changes occur.

24. Further reading/ SDLFurther reading/ SDL

Read in detail all other types of Read in detail all other types of
necrosisnecrosis

Differences between apoptosis & Differences between apoptosis &
necrosisnecrosis
Ubiquitination
Ischemia-reperfusion injury.
White and red infarcts?

25. Thank you!Thank you!