topic 3: cell damage and response

Question 1

injurious stimuli for cell membrane

Answer 1

physical agents (cuts,heat)
chemcial agents (poison, toxins)
immunologival reactions (MAC complex)

Question 2

injurious stimuli for mitochondria

Answer 2

oxygen deprivation

Question 3

injurious stimuli for DNA

Answer 3

genetic defects
aging

Question 4

injurious stimulus that can affect all parts

Answer 4

infectious agents
nutritional imbalances

Question 5

what does cell injury mean (FYI)

Answer 5

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

Question 6

cause of membrane damage

Answer 6

loss of selective membrane permeability (cell memrbane cannot control molecules moving and out of the cell)

Question 7

how does cell membrane loose its selective membrane permeability

Answer 7

1. 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)

Question 8

how disruption of membrane (plasma, mitochondria, lysosomal) leads to injury/death; (impact of damaged cell membrane on the cell)

Answer 8

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)

Question 9

causes of mitochondria damage

Answer 9

Free radicals disrupt mitochondrial membrane permeability.
➢Oxygen deprivation – mitochondria are sites of aerobic respiration. (no oxygen-> cannot produce atp)

Question 10

how does disruption (damage) to mitochondria cause (cell) injury/death

Answer 10

➢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)

Question 11

impacts of ATP depletion (causes by loss of mitochondrial function) -> impacts critical functions of the cell

Answer 11

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)

Question 12

causes of DNA damage

Answer 12

Free radicals can cause DNA strand breaks, cross-linking (form links between the strands- affects during transcription) → results in DNA fragmentation

Question 13

what happens when DNA is damaged/how does it cause cell injury/death

Answer 13

1. repair
2. repair incorrectly/fail (eg high dose of harmful stiumuls such as ionising radiation/chemotherapy)-> consequences can be severe for continious regenerating cells
3. if damage/rfail repair is too severe-> apoptosis (cell inititaed suicide programme)

Question 14

what happens when the stimulus causing cell injury is removed

Answer 14

cells can recover , regain structure and function. cell degeneration occurs (cell trying to fox itslef) -> intracellular changes

Question 15

what are the intracellular changes when cellular degenration occurs

Answer 15

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)

Question 16

what causes fluid accumulation in the cell when the cell undergoes degenration

Answer 16

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

Question 17

how does accumulation of cellular components occur when cell under goes degeneration

Answer 17

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

Question 18

how does fat get accumulated when cell goes through degenration during reversable injury

Answer 18

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)

Question 19

how does pigment accumulate in the cell when cell goes through degeneration

Answer 19

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)

Question 20

how does protein accumulate in the cell when cell goes through degeneration

Answer 20

cell damage caued by virus-> viral protein accumulate in cell (useful for diagnosis of viral infection)

Question 21

what is irreversable cell injury

Answer 21

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

Question 22

what is the intracellular changes to cell for a irreversable cell injury

Answer 22

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)

Question 23

what is apoptosis and what happens during it

Answer 23

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.

Question 24

what is necrosis and what happens during it

Answer 24

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)

Question 25

what are the extracellular changes that occur outside/around injured cells

Answer 25

1. mineralisation
2. crystals
   3, protiens

Question 26

what are examples of the stimulus that cause minerlisation (stimulus cause cell injury-> cause minerlisation)

Answer 26

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

Question 27

explain crystal formation in response to different stimulus , how do crystals form

Answer 27

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

Question 28

explain proteins formation in response to different stimulus

Answer 28

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.