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),