Cellular Response To Stress Flashcards
How would you differentiate between a live and dead histology sample?
Alive:
Clear cell architecture
No apoptosis or necrosis present
Dead:
Loss of architecture
Lack of nuclei
Cell debris
What are the 4 types of responses to cellular stress or injury?
- Hyperplasia
- Hypertrophy
- Atrophy
- Metaplasia
How is adaptation defined in context of a stress/injury response?
Reversible changes to size/number/phenotype/metabolic activity/function of cells
What occurs in cellular hyperplasia? Give a clinical example, including the signs and treatments available.
Quiescent cells re-entry the cell cycle due to hormonal/chemical changes or due to GF
Benign protastatic hyperplasia
Dihydrotestosterone (DHT) stimulates epithelial and stromal cell hyperplasia leading to nodules forming and COMPRESSING URETHRA.
Signs of urinary obstruction: Increased frequency Nocturia Weak stream Incomplete emptying Dribble
TX
5-alpha reductase inhibits to inhibit DHT prod
What occurs in hypertrophy? Give a clinical example.
Increased size of cells due to mechanical stimuli
LV hypertrophy
What is atrophy and why can it occur?
Decreased number or size of cells= decreased size of tissue or organ
Causes:
- loss of hormonal stimulation in pituitary disease
- disuse
- decreased BS
- de-innervation
- brain atrophy in Alzheimers
What is hypoplasia?
Failure of organ to reach normal size during development
What is the process of metaplasia? Name 3 clinic examples.
Unfavourable environment causes original cell type to be replaced with another by REPROGRAMMING local tissue or COLONISING tissue cells
Bronchial squamous metaplasia
- Cause= cigarette smoke
- Ciliated columnar -> squamous
Barretts
- Cause= GORD/acid reflux
- Squamous -> gastric (columnar lined)
Stomach
- Cause= H pylori (chronic inflammation)
- Gastric -> intestinal
Why does cell injury occur?
Directly due to injury mechanism
Indirectly due to failure of adaptation process
What are the 4 main biochemical mechanisms of cell injury?
- ATP depletion
- leads to cell swelling, clumping of chromatin and decreased protein synthesis - Mitochondria damage
- ATP decrease and apoptosis mediators released - Raised intracellular calcium
- Increased reactive O2 species
What are the features of early cell injury? Is it reversible or irreversible?
- Cell swelling
- membrane dysfunction leads to Na+ and H2O entering - Reduction in cytoplasmic RNA
- cytoplasm appears RED on H+E stain= EOSINOPHILIA
Reversible
What are the 2 types of cell death? What are the major differences between them?
- Necrosis
- energy-independent
- loss of cell integrity
- cell enlarges
- plasma membrane disrupted
- nucleus shrinks, fragments and disappears
- involves a group of cells
- tissue responds with acute inflammation due to lack of macrophage involvement to clear cell debris
- pathological occurrence - Apoptosis
- energy dependent due to mitochondria remaining in-tact
- cells shrinks
- plasma membrane intact
- nuclear fragments/apoptotic bodies present
- involves single cell
- tissue responds with phagocytosis
- physiological and pathological process
What are the 2 signalling pathways involved in apoptosis? What enzyme mediates both pathways?
- Mitochondrial= intrinsic
- BCL2 effectors release intracellular in response to cell injury, which stimulate cytochrome C release from mitochondria= pro-apoptotic - Death receptor
- stimulated by extracellular TNF or Fas ligand
Caspases
What are the 5 types of necrosis and what are the key histological identifiers?
- Coagulative (associated with ischaemic injuries)
- visible dead tissue architecture - Liquefactive
- loss of tissue architecture - Caseous
- granuloma formation with central caseous necrosis (granular eosinophilic material) - Fibrinoid (associated with BV injury)
- fibrin accumulation in SM - Fat (dramatic in acute pancreatitis)
- fat droplets
- foamy macrophages due to phagocytosed fat
What are the 2 other types of cell death. Comment on whether they are caspase dependent or independent and how are they differ from necrosis/apoptosis?
- Necroptosis
-caspase-independent
-morphologically similar to necrosis
-Difference from necrosis:
Triggered by extrinsic TNF - Pyroptosis
-caspase-dependent
-Difference from apoptosis:
Stimulated by intracellular microbial products via INFLAMMASOME COMPLEX.
