Cellular injury, adaptation and death Flashcards
What does cell injury lead to? (4)
- ATP depletion
- Cell membranes of increased permeability
- Disruption of biochemical pathways
- DNA damage
How can the injured cell react to damage?
- adaptation
- degeneration
- death
Describe the mechanisms of oxygen deficiency (often ultimate cause of injury)
- inadequate oxygenation of blood e.g. cardiac or respiratory failure
- reduced vascular perfusion (ischaemia)
- reduced oxygen transport e.g. anaemia
- inhibition of respiratory enzymes in the cell e.g. cynaide
What are the physical agents leading to cell injury?
- trauma
- temp extremes
- ionising radiation
- electric shock
What are the infectious agents leading to cell injury?
- prions
- viruses
- bacteria
- fungi
- parasites
What are the nutritional imbalances leading to cell injury?
- dietary deficiencies
- long term starvation
- caloric excess
- dietary toxicities
What are the genetic derangements leading to cell injury?
- Inherited diseases
- metabolic disease
- neoplasia
- autoimmune diseases
- susceptibility to infection
- congenital defects
How can workload imbalances lead to cell injury?
- Increased workloads
- respond by hypertrophy or hyperplasia (cell dependent)
- if excessive- leads to cell degeneration and death - Reduced workload
- loss of innervation, hormones or growth factors
- lead to atrophy
- excessive cells can be removed by apoptosis
How do chemicals, drugs and toxins lead to cell injury?
- alter homeostasis
- toxicity depends on cell tolerance
What does cell susceptibility to chemical, drugs and toxins depend on?
- mitotic rate
- ability to:
- take-up
- bind
- concentrate
- metabolise
How does immunological dysfunction lead to cell injury?
- failure to respond
- overreaction
- reaction to self
How does ageing lead to cell injury?
-accumulated damage to cells (proteins, lipids, nucleic acids) (depends on the ability to replicate/ repair)
Pneumonic to remember causes of disease?
V - vascular
I - iatrogenic, idiopathic
T - trauma, toxicity
A - autoimmune, allergy, ageing
M - metabolic
I - infectious, inflammatory
N - nutritional, neoplasia
D -degenerative, developmental
E- endocrine
When is cell injury reversible?
- if the cell can regain homeostasis
- and can then return to normal structure and function
- injury isn’t too severe or prolonged
What happens when the injury is reversible?
(MITOCHONDRIAL DAMAGE)
- reduced oxidative phosphorylation
- reduced ATP
- increased glycolysis
- dysfunction of membrane ion pumps
- reduced protein synthesis
- dysfunction of chromatin based processes
- cell swelling
- ER swelling
- loss of microvilli
- membrane blebs
- clumped chromatin
- lipid accumulation
- myelin figures
What happens in irreversible cell injury?
(UNREPAIRABLE DAMAGE TO INFRASTRUCTURE)
- mitochondrial dysfunction
- cell membrane damage
- production of ROS
- release of lysosomal enzymes
What happens in cell death?
(CELL WIDE SYSTEMS BREAK DOWN)
- cytocavitary system
- cytoskeleton
- chromatin
- oncotic necrosis
- apoptosis
- pyknosis
- karyorrhexis
- karyolysis
- absence of nucleus
- cytoplasmic eosinophilia
What is acute cell swelling?
- initial response to loss of homeostasis
- caused by influx of water
What are the other names for acute cell swelling?
- hydropic degeneration - hepatocytes
- ballooning degeneration-keratinocytes
- cytotoxic oedema - CNS
Describe the molecular mechanism of acute cell swelling
- in homeostasis: N-K-ATP pump maintains electrochemical gradient (NaOUT, Kin) -water follows Na
- when you lose homeostasis: Na floods in, water follows
- so disruption results in the disruption of electrochemical gradient and the influx of water leads to swelling
What are the gross morphological changes when acute cell swelling occurs?
- increase vol and weight of parenchymal organs
- may impart pallor
What does this show?
- white dots are uniform (all around a central vein)
- show acute cell swelling in liver
What microscopic morphological changes would you see in acute cell swelling?
- dilutes the cytosol
- separates organelles
- distends the cell
- swollen, pale, finely vacuolated appearance
If the injury is sublethal and chronic what can the cell do?
- adapt
- accumulate normal or abnormal substances
what is autophagy?
- self eating
- protection mechanism
- eats its own proteins and carbs for nutrients until more can be sourced
- consumes organelles
- limits inflam if the cell does die - factors to promote heterophagy and stops bits of cells lying around
- heterophagy - when a cell phagocytoses another cell or a part of a cell
What is atrophy?
- decrease in tissue mass due to decreased number/size of cells after reaching normal size
What are the causes of atrophy?
- nutrient deprivation
- compression
- decreased workload
- decreased hormore stimulation
- reduced innervation
What does this show?
- mammary atrophy in a spayed dog
What is hypertrophy?
- increase in tissue mass due to increase size of cells (parenchymal cells)
- increase in number of organelles in cells
What are the causes of what is seen?
- hypertrophy
- increased workload
- increased hormonal stimulation
What is hyperplasia?
- increase in tissue mass due to increased number of cells
What are the causes of hyperplasia?
- increased workloadd
- increased hormonal stimulation
- inflammation
- physical trauma
- precursor to neoplasia
