There are two main types of cell death: necrosis and apoptosis. Necrosis is accidental cell death due to external factors like trauma or toxins. It is characterized by cellular contents leaking out and causing inflammation. Apoptosis is programmed cell death that occurs as part of normal development and tissue homeostasis. It is triggered through internal signals or external death ligands binding to receptors. This activates a caspase cascade that breaks down the cell in a controlled, non-inflammatory way. Dysregulation of apoptosis can lead to cancer, autoimmune disease, or neurodegeneration.

1. By : Ahmed Elshahat Saied
Supervisor :DR,AZZA ATIA

2. Necrosis
Apoptosis

3. For every cell, there is a time to live
and a time to die.
There are two ways in which cells
die: They are killed by injurious
agents.
They are induced to commit suicide.
Death by injury
Cells that are damaged by injury,
such as by mechanical damage
exposure to toxic chemicals

4. DEFINITION OF NECROSIS
Spectrum of morphologic changes
that follows cell death in living
tissues.
CAUSES OF NECROSIS
ISCHEMIA
PHYSICAL AGENTS
CHEMICAL AGENTS
IMMUNOLOGICAL INJURY

5. PATHOGENESIS OF NECROSIS
Denaturation of intracellular proteins.
Enzymatic digestion of the cell.

7. MORPHOLOGY
Increased eosinophilia of cytoplasm
Glassy form
Cytoplasm is vacuolated
Appearance of myelin figures
Generation of calcium soaps

8. TYPES OF NECROSIS
 Coagulative necrosis
Liquefactive necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis

9. COAGULATIVE NECROSIS
Coagulative necrosis is a type of accidental
cell death typically caused by ischemia
Denaturation of structural proteins
and enzymatic digestion of cells.
Example
– Heart, kidney,spleen spleen.

14. LIQUIFACTIVE NECROSIS
The tissue becomes liquid viscous mass
Material is creamy yellow in color Seen in
brain, abscess

17. GANGRENOUS NECROSIS
Wet gangrene
Dry gangrene
Gas gangrene

18. WET GANGRENE
Occurs in moist tissues like mouth, bowel,
lung, cervix Diabetic foot Bed sores

21. DRY GANGRENE
Toes and feet due to arteriosclerosis
Thromboangitis obliterans Raynaud disease
Trauma

23. GAS GANGRENE
Wet gangrene caused by gram positive
anaerobic bacteria Seen in muscle and
in colon

25. CASEOUS NECROSIS
Type of coagulative necrosis Seen
in tuberculous infections
Tissue is cheesy white in
appearance The tissue architecture
is preserved

28. FAT NECROSIS
Seen in pancreas, breast In acute
pancreatitis ,activated lipase
causes fat necrosis.
Grossly visible chalky white
areas. Presence of shadowy
outlines of necrotic cells

30. FIBRINOID NECROSIS
Deposition of fibrin like
material Seen in immunologic
cell injury, hypertension
,peptic ulcer

32. Treatment
Debridement, referring to the removal of
dead tissue by surgical
Wounds caused by physical agents,
including direct physical trauma and injury,
can be treated with antibiotics and anti-
inflammatory drugs to prevent bacterial
infection and inflammation. Keeping the
wound clean from infection also prevents
necrosis.

33. Chemical and toxic agents (e.g. pharmaceutical drugs,
acids, bases) react with the skin leading to skin loss
and eventually necrosis. Treatment involves
identification and discontinuation of the harmful
agent, followed by treatment of the wound, including
prevention of infection and possibly the use of
immunosuppressive therapies such as anti-
inflammatory drugs or immunosuppressants.[15] In the
example of a snake bite, the use of anti-venom halts
the spread of toxins whilst receiving antibiotics to
impede infection.[16]

34. Apoptosis,
programmed cell death, is a naturally
occurring process in the body

35. APOPTOSIS
Apoptosis in physiologic
situations
Apoptosis in pathologic
situations

36. APOPTOSIS
Apoptosis in physiologic situations
Vaux and Korsmeyer, 1999,Cell

37. Formation of
free and
independent
digits
Development
of the brain
Development
of
reproductive
organs
Apoptosis in physiologic situations
Programmed cell death during embryogenesis

39. 1. Apoptosis triggered by internal signals: the intrinsic or
mitochondrial pathway
In a healthy cell, the outer membranes of its mitochondria
display the protein Bcl-2 on their surface. Bcl-2 inhibits
apoptosis.
Internal damage to the cell
causes a related protein
, Bax, to migrate to the surface of
the mitochondrion where
it inhibits the protective effect of
Bcl-2 and inserts itself into the outer
causing mitochondrial membrane
punching holes in it and
cytochrome c to leak out.

40. The released cytochrome c binds to the protein Apaf-1
("apoptotic protease activating factor-1"). Using the energy
provided by ATP, these complexes aggregate to form
apoptosomes. The apoptosomes bind to and activate caspase-
9. Caspase-9 is one of a family of over a dozen caspases. They
are all proteases. They get their name because they cleave
proteins — mostly each other — at aspartic acid (Asp)
residues). Caspase-9 cleaves and, in so doing, activates other
caspases (caspase-3 and -7). The activation of these
"executioner" caspases creates an expanding cascade of
proteolytic activity (rather like that in blood clotting and
complement activation) which leads to digestion of structural
proteins in the cytoplasm,
degradation of chromosomal DNA, and
phagocytosis of the cell.

41. 2. Apoptosis triggered by external signals: the extrinsic
or death receptor pathway
Fas and the TNF receptor are integral membrane proteins with their receptor
domains exposed at the surface of the cell
binding of the complementary death activator (FasL and TNF respectively)
transmits a signal to the cytoplasm that leads to
activation of caspase 8
caspase 8 (like caspase 9) initiates a cascade of caspase activation leading to
phagocytosis of the cell.
Example (right): When cytotoxic T cells recognize (bind to) their target, they
produce more FasL at their surface.
This binds with the Fas on the surface of the target cell leading to its death by
apoptosis.
The early steps in apoptosis are reversible — at least in C. elegans. In some
cases, final destruction of the cell is guaranteed only with its engulfment by a
phagocyte.

42. The death
receptor
pathway
• Extrinsic
pathway

43. 3. Apoptosis-Inducing Factor (AIF)
Neurons, and perhaps other cells, have another way
to self-destruct that — unlike the two paths
described above — does not use caspases.
Apoptosis-inducing factor (AIF) is a protein that is
normally located in the intermembrane space of
mitochondria. When the cell receives a signal telling
it that it is time to die, AIF is released from the
mitochondria (like the release of cytochrome c in
the first pathway);
migrates into the nucleus;
binds to DNA, which
triggers the destruction of the DNA and cell death.

44. Inhibition of apoptosis
can result in
a number of cancers,
autoimmune diseases,
 inflammatory diseases,
and viral infections.

45. Tretment
To stimulate apoptosis, one
can increase the number of
death receptor ligands (such
as TNF or TRAIL),

46. Hyperactive apoptosis
On the other hand, loss of control of cell
death (resulting in excess apoptosis) can
:lead to
neurodegenerative diseases,
hematologic diseases,
tissue damage.
The progression of HIV is directly linked
to excess, unregulated apoptosis

47. Treatments
Aiming to inhibit works to block
specific caspases. Finally, the Akt
protein kinase promotes cell
survival through two pathways.
Akt phosphorylates and inhibits
Bas (a Bcl-2 family member),