topic 3: cell damage and response Flashcards
injurious stimuli for cell membrane
physical agents (cuts,heat)
chemcial agents (poison, toxins)
immunologival reactions (MAC complex)
injurious stimuli for mitochondria
oxygen deprivation
injurious stimuli for DNA
genetic defects
aging
injurious stimulus that can affect all parts
infectious agents
nutritional imbalances
what does cell injury mean (FYI)
damage to any cell component, cell membrane, DNA, mitochondria are critical to cell cell vervival and function so thats why we focus of them only
cause of membrane damage
loss of selective membrane permeability (cell memrbane cannot control molecules moving and out of the cell)
how does cell membrane loose its selective membrane permeability
- Decreased synthesis or increased breakdown of phospholipids. (make up the cell membrane)
➢Products that can disrupt phospholipid bilayer (insert into bilayer or exchange with membrane phospholipids). (disrupt the tight arangement of the phospholipid layer-> bigger holes-> anything can go in/out)
➢Free radicals – chemicals that are extremely unstable, reacts readily with other
chemical. (to find electron for its unpaired electron) Can attack membrane lipids, as well as nucleic acids (DNA,RNA) and cellular proteins (creates holes in them)
how disruption of membrane (plasma, mitochondria, lysosomal) leads to injury/death; (impact of damaged cell membrane on the cell)
Plasma membrane damage → loss of osmotic balance, influx of fluids & ions, loss of cellular contents.
* Mitochondrial membrane damage → decreased ATP production. (function of mitochondria)
* Lysosomal membrane damage → leakage of enzymes into cytoplasm, enzymes may digest cell components. (enzymes will digest anything they see)
causes of mitochondria damage
Free radicals disrupt mitochondrial membrane permeability.
➢Oxygen deprivation – mitochondria are sites of aerobic respiration. (no oxygen-> cannot produce atp)
how does disruption (damage) to mitochondria cause (cell) injury/death
➢Loss of mitochondrial membrane potential results in failure of oxidative phosphorylation (the ATP generating pathway) and ATP depletion. (cannot produce ATP through the pathway-> less ATP produced)
➢Mitochondria contain proteins that are essential for ATP generation, but will activate apoptotic pathways if leaked into the cytoplasm (eg mitochondria membrane damage-> leave of this protein-> will cause apototic pathway-> cell death)
impacts of ATP depletion (causes by loss of mitochondrial function) -> impacts critical functions of the cell
Reduced activity of sodium-potassium pump on the plasma membrane → cell swelling due to inability to maintain osmotic gradient. (without ATP the pump cannot work-> sodium remains in the cell,water follows sodium-> cell swelling)
➢Increase in anaerobic glycolysis to maintain energy sources, compensate for reduced aerobic respiration → deplete glycogen stores, lactic acid accumulates, pH decreases. (if there is O2, aerobic glycolysis causes glucose-> atp, in anaerobic glycolysis: glycogen-> atp and lactic acid-> decrease in pH)
➢Reduced protein synthesis. (ribosomes need energy to produce protein)
causes of DNA damage
Free radicals can cause DNA strand breaks, cross-linking (form links between the strands- affects during transcription) → results in DNA fragmentation
what happens when DNA is damaged/how does it cause cell injury/death
- repair
- repair incorrectly/fail (eg high dose of harmful stiumuls such as ionising radiation/chemotherapy)-> consequences can be severe for continious regenerating cells
- if damage/rfail repair is too severe-> apoptosis (cell inititaed suicide programme)
what happens when the stimulus causing cell injury is removed
cells can recover , regain structure and function. cell degeneration occurs (cell trying to fox itslef) -> intracellular changes
what are the intracellular changes when cellular degenration occurs
Clumping of chromatin (can see the threads in the nuclues under the microscope-> usually cannot see)
ii. Membrane blebs (protrutions)
iii. Swelling of endoplasmic reticulum and mitochondria
iv. Histologically: Increased eosinophilic staining
v. Intracellular accumulations (of fluid/ cellular components/fats/pigments/proteins)
what causes fluid accumulation in the cell when the cell undergoes degenration
membrane daamage-> acculmulation of fluid (recall: membrane damage-> loss of selective membrane permeability-> retention of na-> retnetion of wate-> swelling)
fluid accumulation is usally the first manifestation of almost all forms of cell injury
how does accumulation of cellular components occur when cell under goes degeneration
old non functional organelles shrivel up and break down. if not removed from the cytoplasm, tend to accumulate as fatty, protein or cyrstal deposit) can be seen microscopically
how does fat get accumulated when cell goes through degenration during reversable injury
long term fat breakdown (eg diabetes/obeasity)-> (can cause cell damage)-> lipid accumulate in cells (cannot breakdown effectively) (esp in lver cells: major organ invloved in fat metabolsim)
how does pigment accumulate in the cell when cell goes through degeneration
produced by body endogenously (eg. cell injury-> breakdown of RBC result in
bile pigment accumulation & jaundice, or melanin deposits in chronic dermatitis);
or exogenous (eg. carbon in lungs)
how does protein accumulate in the cell when cell goes through degeneration
cell damage caued by virus-> viral protein accumulate in cell (useful for diagnosis of viral infection)
what is irreversable cell injury
alternation/loss of cell function and structureal change to the point of no return (call cannot repair it) -cell cannot rexover even if stimus stops
what is the intracellular changes to cell for a irreversable cell injury
intracelluar chanfes of the injured change PLUS
Loss of ribosomes
ii. Nuclear decondensation, shrinkage, fragmentation (it unwinds, shrinks and breaks apart)
iii. Lysosomal rupture (contains enzymes that can digest cellular components )
iv. Vacuolated cytoplasm (enzymes have digested organelles, cause ‘moth-eaten’ appearance)
v. Myelin figures (phospholipid masses derived from damaged cellular membranes)
vi. Swollen mitochondria with amorphous densities (without clearly defined forms, aka loose its shape)
vii. Histologically: more eosinophilic (eosin stain denatured cytoplasmic proteins)
what is apoptosis and what happens during it
Programmed cell death that is induced by a tightly regulated process.
how it happens:
* Cells that are destined to die activate enzymes that degrade the cells’ own nuclear DNA and cytoplasmic proteins.
what happens during it:
.plasma membrane remains intact (important so that opsonins can attack the cell surface and makr it for phagocytosis)
* Cell and cellular fragments become targets for phagocytes.
* Dead cell is cleared before cellular contents leak out.
* Purpose of apoptosis: eliminates cells that are no longer needed. (can cause cancer)
- Examples: embryogenesis, regression of mammary tissue after weaning, death of immune cells
at the end of immune response.
what is necrosis and what happens during it
Death of cells in a living animal.
* Involves a series of cellular changes that accompany cell death, in response to
irreversible cell injury, largely due to degradative action of enzymes.
what happens during it:
* Loss of membrane integrity,(from cell death causes my extreme/irreverable injuries cuts) contents leak out.
* Cell is digested by enzymes from the cell’s own lysosome or from lysosomes of leukocytes recruited to remove dead cells. (lysomes rupture during cell death-> release enxumes-> enzymes digest)
- Common harmful stimuli that lead to irreversible cell injury, then necrosis: direct
tissue damage or indirect damage due to disruption of blood supply of the tissue. - Direct tissue damage – burns (heat, cold, chemical); trauma, poisons/toxins; infectious agents.
- Indirect tissue damage – ischaemia, pressure (eg. from tumor cell pressing on adjacent tissues,
prolonged pressure of tight bandage/immobility)
what are the extracellular changes that occur outside/around injured cells
- mineralisation
- crystals
3, protiens
what are examples of the stimulus that cause minerlisation (stimulus cause cell injury-> cause minerlisation)
calcium deposit locally at the site of tissue damage (fat necrosus of pancreatcic cell) -known as dystrophic (in cell) calcification
high calcium levels in blood and tissues (eg high parathyroid hormone) calcification at normal tissue- known as metastatic calcification
calcification: deposition of calcium salts in both normal and injured tissues (Made up of cells)
gum inflamation, bacteria in mouth, mineral i saliva-> dental plague
contents of organ becoming thicken by mucous, bacteria (cause the cell injury-> result in minerals getting attracted) and high mineral level-> kidney, bladder and bile stones
explain crystal formation in response to different stimulus , how do crystals form
how they form: certain substance enter via skin,lungs, inestinal tract-> cause formation of crystalline material that accumuate in various tissues
- Eg. when animals drink liquid
antifreeze-> formation of calcium oxalate crystals in kiendy (inside and outisde cell) -> Results in necrosis and renal
failure. - Eg. Excess production or insufficient excretion of
metabolic waste product uric acid-> Uric acid crystals deposit in tissues such as joints and kidneys -> tissue damage
explain proteins formation in response to different stimulus
eg. in some chronic infectious, inflammatory, immune, metabolic or neoplastic diseases, or as part of aging.-> amyloid (dense protein) accumulation
* Amyloids are abnormal protein forms. Once produced and deposited, very resistant to removal by enzymes. )amyloid is so hard that even enzymes cannot digest it)
* Accumulation of amyloids can hinder function of affected tissues and cause cell
death.
