Apoptosis And Necrosis

Question 1

What is apoptosis?

Answer 1

NON INFLAMMATORY programmed cell death without the release of products harmful to the surrounding cells

Question 2

Apoptosis in disease

Answer 2

Cancer: lack of apoptosis - mutated p53 protein
HIV: too much apoptosis - kills the antibodies (helper T cells - CD4)

Question 3

Apoptosis can be triggered by

Answer 3

DNA damage
- Single-strand break
- Base alteration
- Cross-linkage

Question 4

Characteristics of apoptosis

Answer 4

Energy dependant most of cell death
Involved the enzymatic digestion of nuclear and cytoplasmic contents
With phagocytosis of the resultant breakdown products whilst still retained within the cell membrane
Chromatin unaltered, fragmented for easy phagocytosis

Question 5

Regulation of apoptosis

Answer 5

Triggered by both extracellular and intracellular signals
Inhibitors:
- growth factors
- extracellular cell matrix
- sex steroids
- some viral proteins
Inducers:
Growth factor withdrawal
Loss of matrix attachment
Glucocorticoids
Some viruses
Free radicals
Ionising radiation
DNA damage
Ligand-binding at ‘death receptors’

Question 6

Apoptosis pathways

Answer 6

INTRINSIC = uses pro and anti apoptotic members of the Bcl-2 family
- Bax acts on mitochondrial membrane to promote CYTOCHROME C release
- Activates CASPASES = apoptosis
EXTRINSIC - ligand-binding at death receptors on the cell surface e.g. TNFR1
- FasL or TNF-L binds to csm receptors which activate caspases = apoptosis
CYTOTOXIC = CD8+ binding release GRANZYME B from CD8+ cell -> PERFORIN -> CASPASES = apoptosis

All pathways converge upon a final common effector pathway characterised by the activation of proteases and DNAses

Question 7

What is necrosis?

Answer 7

INFLAMMATORY Traumatic cell death in an organ or tissue due to disease, injury or failure of the blood supply which induces inflammation and repair
- CELLS BURST
- Organelles splurge
- CSM damaged
- Chromatin altered

Question 8

Types of necrosis

Answer 8

Coagulative - (MOST COMMON) = caused by ischeamia and occurs in most organs
Liquefactive/Colliquative - happens in brain due to lack of stroma
Caseous - e.g TB
Gangrene - rotting of tissues from bacteria esp CLOSTRIDIA, the effected tissue appears black

Question 9

Clinical examples of necrosis

Answer 9

Toxic spider venom
Frostbite
Cerebral infarction
Avascular necrosis of bone - femur has single arterial supply through the neck of the femoral head
Pancreatitis