pathology
TRANSCRIPT
By : Ahmed Elshahat Saied
Supervisor :DR,AZZA ATIA
Necrosis
Apoptosis
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
DEFINITION OF NECROSIS
Spectrum of morphologic changes that follows cell death in living
tissues.
CAUSES OF NECROSIS
ISCHEMIA
PHYSICAL AGENTS
CHEMICAL AGENTS IMMUNOLOGICAL INJURY
PATHOGENESIS OF NECROSIS
Denaturation of intracellular proteins.
Enzymatic digestion of the cell.
MORPHOLOGY
Increased eosinophilia of cytoplasm
Glassy form
Cytoplasm is vacuolated
Appearance of myelin figures
Generation of calcium soaps
TYPES OF NECROSIS
Coagulative necrosis
Liquefactive necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
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.
LIQUIFACTIVE NECROSIS
The tissue becomes liquid viscous mass Material is creamy yellow in color Seen in
brain, abscess
GANGRENOUS NECROSIS
Wet gangrene
Dry gangrene
Gas gangrene
WET GANGRENE
Occurs in moist tissues like mouth, bowel, lung, cervix Diabetic foot Bed sores
DRY GANGRENE
Toes and feet due to arteriosclerosis Thromboangitis obliterans Raynaud disease
Trauma
GAS GANGRENE
Wet gangrene caused by gram positive anaerobic bacteria Seen in muscle and
in colon
CASEOUS NECROSIS
Type of coagulative necrosis Seen in tuberculous infections
Tissue is cheesy white in appearance The tissue architecture
is preserved
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
FIBRINOID NECROSIS
Deposition of fibrin like material Seen in immunologic
cell injury, hypertension ,peptic ulcer
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.
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]
Apoptosis,
programmed cell death, is a naturally occurring process in the body
APOPTOSIS
Apoptosis in physiologic situations
Apoptosis in pathologic situations
APOPTOSIS
Apoptosis in physiologic situations
Vaux and Korsmeyer, 1999,Cell
Formation of free and
independent digits
Development of the brain
Development of
reproductive organs
Apoptosis in physiologic situations
Programmed cell death during embryogenesis
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.
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.
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.
The death receptor pathway
• Extrinsic pathway
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.
Inhibition of apoptosis
can result in
a number of cancers,
autoimmune diseases,
inflammatory diseases,
and viral infections.
Tretment
To stimulate apoptosis, one can increase the number of death receptor ligands (such as TNF or TRAIL),
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
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),