Cell/Tissue Injury

Question 1

Causes of cell injury

Answer 1

Hypoxia 
Ischemia (causes hypoxia)
Physical agents
Drugs and chemicals 
Infectious agents 
Immunological rxns 
Nutritional imbalances
Genetic

Question 2

Response of cells to injury

Answer 2

Adaptation
Injury
Death

Question 3

Adaptation

Answer 3

Cell undergoes changes that allow it to deal with stress

Question 4

Injury and 2 types

Answer 4

If cell is unable to adapt to stress

Reversible - if injurious agent removed then it reverts back to normal

Irreversible - Death is inevitable

Question 5

Response of cell to injury depends on

Answer 5

Lenght of time
Dose
Type of cell

Question 6

Example of type of cell adaption

Answer 6

Neuron less able to adapt than muscle cell

Question 7

Ischemia and hypoxia causes

Answer 7

lack of oxygen which decreases ATP

Question 8

Oxygen derived free radicals will cause

Answer 8

Degradation of cellular proteins, membrane phospholipids, and nucleic acids

Question 9

Role of calcium in cell injury

Answer 9

If injury interferes with calcium ATPases, calcium will enter the cell and activate enzymes

Question 10

Calcium activated enzymes and what they do…one other thing it does

Answer 10

Phospholipiases - destroy membrane phospholipids
Proteases - destroy proteins f membrane cytoskeleton
Endonucleases - DNA/chromatin fragmentation
ATPases - ATP depletion

Also causes mitochondrial permeability so no ATP can be generated

Question 11

ATP depletion leads to what and caused by what?

Answer 11

Cause - decreased ATP synthesis or activation of ATPases

Effect - loss of integrity of cell membrane

Question 12

Common themes in cell death

Answer 12

oxygen
calcium
ATP depletion
Defects in membrane permeability

Question 13

Ischemic/hypoxic reversible injury

Answer 13

Decrease or loss of ATP within cell due to decrease in mitochondrial function…decrease in ATP causes increase in anaerobic glycolysis (generates lactic acid and lowers pH…leads to decreased activity and inactivation of intracellular enzymes…also causes failure of sodium pumps of cells membrane…influx of sodium and water causes swelling which impairs function)

Question 14

Hypoxia/ischemic irreversible injruy

Answer 14

Inability to reverse mitochondrial effects
Profoud distrubance to cell membrane due to loss of phospholipids from membrane (because of decrease in production due to lack of ATP and increase in phospholipase activity),
cytoskeletal abnormalities (calcium activated proteases),
reperfusion injury (oxygen free radicals generated…can extend the injury),
lipid breakdown of products that result from phospholipid degradation have detergent effect on membrane,
loss of intracellular amino acids (mostly from glycine…these protect from oxidative damage)

Question 15

Necrosis morphologic changes

Answer 15

Increased eosinophilia (cytoplasm stains deep pink when stained with H and E)…due to more avid binding of eosin to denatured proteins
Vacuolization (due to digestion of organelles)
Calcification

Question 16

Nuclear necrotic changes

Answer 16

1 of 3

Karyolysis - stains pale blue (vs dark blue)…due to DNA degradation by DNA-ases
Pyknosis - Nuecleus shrinks and becomes darker blue…due to chromatin condensation
Karyorrhexis - nucleus undergoes fragmentation

After 2 days of onset, nucleus disappears

Question 17

Morphology of necrotic tissue

Answer 17

Coagulative - outlines of each cell are preserved…occurs when denaturation of cellular proteins predominates…cell does not autolyze…from ischemia/hypoxia

Liquefactive - cells disappear due to digestion and lysis by enzymes that are derived from cells own lysosomes or white blood cells within area (focal bacterial)

Caseous - appears cheesy…fragmented cells and granular debri…tuberculosis

Question 18

Intrinsic activaiton of initiator caspase

Answer 18

Certain stressors activate intracytoplasmic sensor proteins (member of Bcl-2 family (subclassed BH3- only)…sensors activate Bax and Bak which polymerize into oligomers, insert into mitochondrial membrane…create channel that allow proteins normally within inner mitochondrial membrane to leak into cytoplasm (Bax and Bak also inhibit anti-apoptotic proteins Bcl-x and Bcl-2)…because cytochrome c leaks out, will bind to Apaf-1 whcih forms apoptosome hexamer…apoptosome binds to and activates initator caspase 9 which activates caspase 9 molecules

Question 19

Extrinsic pathway of apoptosis

Answer 19

Cell membranes have deathreceptors (like TNFR 1 and Fas)…ligand binds and activates capases 8 and 10…causes activation of other initiator caspases

Question 20

Execution phase of apoptosis

Answer 20

Activated intiator caspase activate executioner caspases (3 and 6)…degrade critical components…cell death

Question 21

Morphologic apoptosis effects

Answer 21

Minimal membrane damage…nuclear chromatin condenses and aggregates to membrane…blebs to form apoptotic bodies…no inflammatory response…involves small numbers of cells

Question 22

Autophagy steps

Answer 22

Autophagic vacuole fuses with lysosome…enzymes digest organelles and move back into cytoplasm

This is good for nutritionally deprived cells

Question 23

Genetic regulation of autophagy

Answer 23

Atg genes

Question 24

Pathologic?
# of cells 
Apoptotic bodies 
Inflammatory response
Membrane damage 

Apoptosis vs. necrosis

Answer 24

Necrosis - always, apop - sometimes 
Necrosis - many cells 
Bodies only in apop
Apop has no inflam resp
Minimal mem damage in apop