Adaptation, Injury & Cell Death Flashcards
How do cells adapt to a stressor (5)?
Atrophy Hyperplasia Hypertrophy Metaplasia Dysplasia
What are the causes of atrophy (5)?
Decrease workload
« » neuronal stimulation
« » hormonal « »
Insufficient blood flow
« » nutrition
How atrophy occur (mechanism)?
Decrease in prot synthesis
Increase PROT DEGRADATION
Or AUTOPHAGY
Ingest its own organelles (attempt to conserve energy and survive)
Eg.: lack of nutrients activates UBIQUITIN ligase (E3) to attach multiple ubiquitin mol onto unnecessary prots.
Prots w/ attached ubiquitin mols are transported towards PROTEASOMES.
Proteasome job: degrade prots & recycles aa
In atrophy, which pathway is use for the degradation of prots?
Ubiquitin-proteasome pathway
What are the causes of hypertrophy (2)?
Increase workload
« » hormonal stimulation (growth factor, anabolic steroids)
What are the 2 types of hypertrophy and explain it
Physiological = n d/t increase demand
Pathological = compensatory following a disease (eg.: myocardial infarct)
How hypertrophy occurs (mechanism) (3)?
Increase prot and cell synthesis
Optimization of cell fct
Enzymatic induction (liver)
Optimization: muscle hypertrophy, some myosin chains are replaced by more energetically efficient chains.
Increase metabolism via MECHANICAL: stress TROPHIC: growth factor Trigger induce gene transcription Induce prot/c synthesis Increase functionnality
Give an example of hypertrophy of functional enzymes (enzymatic induction in the liver).
Chronic alcoholics
Become + tolerant to higher dose of alcohol
Because they have a GREATER NMB of liver ENZYMES & they work FASTER
Liver enzymes: responsible for breakdown and metabolism of alcohol.
What is the difference b/w pathological hyperplasia and cancer?
Hyperplasia occurs in response to ABNORMAL STIMULUS
It STOPS if the stimulus is REMOVED
Cancer: proliferation despite absence of stimulus
What is metaplasia?
A substitution of cell from one type to another.
Give an example of metaplasia
Substitution of normal COLUMNAR epithelium into SQUAMOUS metaplasia in airways of SMOKERS
(From ciliated to squamous)
Squamous cells: survival advantage in presence of smoke
BUT
Decrease in ciliary mvt increase ACCUMULATION of TOXIC particles in the lung
Cause LUNG CANCER in long term
How metaplasia occur (mechanism)
Reprogramming of STEM CELLS to differentiate into a different phenotype.
What is dysplasia?
Metaplasia cells w/ ABNORMAL structure and fct
New fct can be unrelated to any of the know cell types
If exposed for a long time to a stressor CAN become PERMANENT
What part of the cell are more vulnerable to cell injury (5)?
Mitochondria
Plasma membrane
ER
Protein synthesis
Nucleus/DNA
What type of cells are more vulnerable to ischemia?
Neurons
What are the major causes of cell injury(9)? Pense aux cours de la session jusqu’à présent
Hypoxia
Free radical
Physical
Chemical
Biological
Immune reactions
Genetic abnormalities
Nutritional imbalance
Aging
What is hypoxia?
Oxygen deficiency
Define ischemia
Inadequate blood supply to cells
Major cause of hypoxia
Name 4 causes of ischemia
Atherosclerosis
Thrombus
Embolism
Vessel spasm
Compression
Name 2 types of cell death d/t ischemia
Myocardial infarct
Stroke
Name 3 types of hypoxia caused by poor oxygenation of the blood
Severe anemia
Carbon monoxide poisoning
Pneumonia
Explain the mechanism of hypoxic injury
Decrease of 02
Decrease ATP prod (via oxidative phosphorylation)
Voir p.10
Severe ischemia lead to which ion influx?
Calcium
In severe ischemia calcium influx activates which enzymes?
ATPase
Protease
Phospholipase
Nuclease
Damage plasma membrane/nuclear membrane (d/t an increase in phospholipid & membrane prot breakdown)
If cell dies = necrosis
Free radicals react with what (3)?
Nucleic acid
Lipid
Prots
Free radicals initiate the formation of what?
More free radicals
What is a free radical?
Very reactive molecule w/ unpaired electrons
2nd most common cause of cell injury
Free radical cell injury is common in what case?
Ischemic reperfusion
Huge prod of ROS when blood supply is restored after being depleted for a while because c is OVERCOMPENSATING
What is the major free radical in cell injury?
Reactive oxygen species (ROS)
Eg.: superoxide anion 02•-
How ROS is produce naturally and give 2 examples?
Prod via REDOX REACTION
Such as
Mitochondrial resp
Within lysosome of immune cells
Mitochondrial damage=high amount of ROS released
Also Radiation UV light Chemical agents (cigarette smoke) Inflammation
Name enzymes and antioxidants that regulate ROS
Enzyme
Superoxide dismutase (SOD)
Glutathione peroxidase (GSH)
Catalase
Antioxidants
Vit A E C
B-carotene
(free radical scavengers)
Explain the 3 mechanism of ROS injury
- LIPID PEROXIDATION of membrane
- membrane damage
- blebs
- formation of more ROS - PROTS DAMAGE
- breakdown
- misfolding - DNA DAMAGE
- mutation leading to cancer
- cell death
- aging
If cell dies=necrosis
Give examples of physical injuries (3)
Trauma
Electric shock
Extreme temperatures
Give example of what causes chemical injuries (6)
Polluants
CO
Insecticides
Asbestos
Ethanol
Therapeutic drugs
Explain how a chemical injury injured cells
Alter
Integrity of plasma membrane
Osmotic homeostasis
Enzymatic/prot fct
Explain how biological agents cause cell injury
Replication
Secreted toxins
Impair w/ normal tissue fct/metabolism
Bacteria
Viruses
Worm
Give example of immune reaction that can cause cell injury (2)
Autoimmune disease
Allergic reactions
-complement cascade
-cell-mediated toxicity
Give examples of genetic abnormalities that can cause cell injuries (4)
Sickle cell anemia
Down syndrome
Huntingdon’s disease
Spinal muscular atrophy
Explain how genetic abnormalities can cause cell injuries (3)
Damage d/t
Impaired prot fct
Accumulation of misfold prot
DNA mutations
Define polymorphism
Genetic variant
Can predispose to certain injury
Or
Dev of diseases
Give an example of polymorphism
Albino’s more vulnerable to UV light damage
What are the risks associate with the accumulation of cell injury/ impaired metabolism d/t nutritional imbalances (3)?
Increase risk of
Infections
Db
Heart diseases
Explain what is cellular senescence
Alteration in replicative capabilities of cells
- diminished adaptation
- increased cell death
Name the different types of necrosis (4)
COAGULATION Scar tissue (eg.: fibroblasts) to avoid having a hole
LIQUEFACTIVE
Leave a hole
CASEOUS
B/w solid/liquid
Mix of hole & scar tissues
GANGRENE
Coagulative + bacterial infection
Give examples for each types of necrosis
Coagulation
Liquefactive
Caseous
Gangrene
Coagulation = myocardial infarct
Liquefactive = abscess lung/brain
Caseous = tb
Gangrene = severe frostbites/ischemia
When does apoptosis occurs?
Tissue turnover
Injury
- DNA/prot damaged beyond repair
- deprived of growth factor
Give examples of apoptosis
Skin shredding
Lining of GIT turnover
Delayed damage to spinal cord
What part of the cell released factor promoting or inhibiting apoptosis?
Mitochondria
What can trigger extrinsic apoptosis?
Viruses
Immune cells
Radiation
Mitochondrial content
How cytotoxic t cells kills infected cells?
Via apoptosis
Death receptor (extrinsic) pathway
In what disease is there a high concentration of caspase?
Neurodegenerative diseases
What causes intracellular accumulation (3)?
Ineffective removal
Inability to remove d/t genetic disease or lack of enzyme
Unable to store
Give examples of intracellular accumulation (5)
SILICIA
Accumulation in the lung of minors
PIGMENTS
Tattoos
MELANIN
Accumulation in freckles
CALCIUM
Heart valves
LIPOFUSCIN
Not harmful
Marker of past free-radical injury/aging/atrophy
(Common in heart/brain/liver)
