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.
What is toxic epidermal necrolysis and how is it diagnosis histologically?
How is it different from Steven Johnson Syndrome?
Full thickness necrosis of the skin and mucous membrane due to CYTOPTOXIC LYMPHOCYTES attacking epidermis (associate with ACUTE DRUG REACTION)
Diagnosis= skin biopsy to shown full thickness epidermis necrosis
TEN= effects <30% body SJS= effects >30% body
