Cell Death (Apoptosis and Necrosis) Flashcards
1
Q
What is apoptosis
A
- Programmed / targeted cell death
- Normal and necessary event of development
- Triggered by variety of signals
- No inflammation, cell shrinkage
- Fragmentation / condensation of chromosomes / cytoplasm / nucleus
- Enzymatically degrades DNA and proteins
- Organelle disruption
- Depolymerisation of cytoskeleton
- Release membrane bound fragments in apoptotic bodies
- Blebbing of plasma membrane
2
Q
What is physiological apoptosis
A
- Maintenance of constant number of cells in tissues
- Elimination of cells that served their useful purpose
- Programmed destruction of cells during embryogenesis
- Elimination of infected / tumour cells by cytotoxic T cells
- Involution of hormone dependent tissues upon hormone deprivation
- Cell loss in proliferating cell populations
- Elimination of auto-reactive cells
3
Q
What is pathological apoptosis
A
- Eliminates cells that are genetically altered or injured beyond repair without severe host reaction
- DNA damage, accumulation of mis-folded proteins in ER
- Cell injury in infections
- Pathologic atrophy in parenchymal organs after duct obstruction
4
Q
What are the nuclear changes of apoptosis
A
- Karyolysis (nuclear fading)
- Pyknosis (nuclear shrinkage)
- Karyorrhexis (nuclear fragmentation)
5
Q
What are the phagocytic effects of apoptosis
A
- Very limited host reaction as dead are cleared quickly
- Prevents further tissue damage by stimulating production of anti-inflammatory cytokines and chemokines
- Recruitment of macrophages for phagocytosis
6
Q
What is the mitochondrial (intrinsic) pathway of apoptosis
A
- Caused by GF withdrawal, DNA damage, protein misfolding
- Inhibition of BAX (inter mitochondrial membrane)
- Movement of cytochrome C to outer mitochondrial membrane
- Release of pro-caspase 9 and caspase 9 to cytoplasm
- Bind with pro-caspase 3 which activates caspase 3
- Initiates cell death / apoptosis
7
Q
What is the death receptor (extrinsic) pathway of apoptosis
A
- Killer T cells
- FAS ligand binds FAS receptor and pro-caspase 8 on cell membrane
- Assembly of adaptor proteins into a “death-inducing signalling complex”
- Binds pro-caspase 3 to activate caspase 3 and cell death / apoptosis
8
Q
What is necrosis
A
- Premature death due to unexpected and accidental cell damage
- Toxins, radiation, heat, trauma, hypoxia
- Swelling, loss of cell membrane integrity, pathological
- Intracellular materials spill into surrounding environment
- Causes tissue damage, inflammation, oedema, recruitment of WBC’s
- Passive, pathological, inflammation, cell / mitochondrial swelling
- DNA degradation, loss of cell membrane integrity, loss of ion transport, cell lysis / dissipation
9
Q
What are the 7 morphological subgroups of necrosis
A
- Coagulative
- Liquefactive
- Caseous
- Enzymatic Fat
- Gangrenous
- Fibrinoid
- Ischemic Necrosis
10
Q
What is coagulative necrosis
A
- Most common
- Cell is dead but basic tissue architecture is initially preserved
- Tissues exhibit firm texture, leukocytes recruited into area
- Homogeneous, glassy eosinophilic appearance (loss of cytoplasmic RNA / glycogen)
- Characteristic of hypoxic death of cells (infarcts) in all solid organs except the brain
11
Q
What is liquefactive necrosis
A
- Loss of organ cellular architecture
- Enzymatic breakdown of tissue, complete cell digestion
- Tissues with focal bacterial or fungal infection (renal abscess)
- Hypoxic death of cells in CNS evokes liquefactive necrosis
- If initially inflammation creamy yellow = pus
12
Q
What is caseous necrosis
A
- Loss or organ cellular architecture
- White yellow colouring
- Tissue architecture is obliterated
- Infections (myo-bacterial / fungal / tuberculous)
13
Q
What is enzymatic fat necrosis
A
- Focal areas of fat destruction
- Results from hydrolytic action of release of activated lipase’s on fat cells
- Seen in and around pancreas / fatty areas of body (trauma)
- Fatty acids released via hydrolysis react with Ca to form chalky white areas / “fat saponification”
14
Q
What is gangrenous necrosis
A
- Seen on extremities
- Lack of BF due to ischemic necrosis or trauma / physical injury
- Dry Gangrene: No bacterial superinfection, tissue appears dry (“black and dead”)
- Wet Gangrene: Bacterial superinfection, tissue appears wet / liquefactive
15
Q
What is fibrinoid necrosis
A
- Caused by immune reactions
- Complexes of antigens and antibodies deposited in arterial walls
- Fibrin leaks out of vessels
- Complexes react with fibrin and form eosinophilic (bright pink) areas
