cell injury + cell death

Question 1

what are the different ways a cell responds to injury?

Answer 1

1. cell adapts
2. cell remains injured then returns to normal
3. cell dies

Question 2

what are the different causes of cell injury?

Answer 2

environmental:
* hypoxia
* toxins
* immune mediated
* physical agents
* infection
* nutritional/dietary

non-environmental:
* genetic
* ageing

Question 3

how does hypoxia cause cell injury?

Answer 3

cells undergo oxygen deprivation

Question 4

what are the different types of hypoxia?

Answer 4

1. hypoxaemic hypoxia: arterial content of oxygen is low
2. anaemic hypoxia: decreased ability of haemoglobin to carry oxygen
3. ischaemic hypoxia: interruption to blood supply
4. histotoxic hypoxia: inability to utilise oxygen due to diabled oxidative phosphorylation enzymes

Question 5

how are different cells/tissue affected by hypoxia?

Answer 5

different tissues are affected in different ways by hypoxia:
* brain can only go a few mins vs skeletal muscle can go a few hours

cause of hypoxia needs to be adressed

Question 6

what are immune mediated causes of cell injury?

Answer 6

Hypersensitivity reactions:
* injury secondary to excessive immune reaction to “non-self” antigen

Autoimmune reactions:
* immune system reacts to self antigens

Question 7

how do physical agents cause cell injury?

Answer 7

trauma
extreme temps
electric currents
radiotherapy

Question 8

how do infections cause cell injury?

Answer 8

bacterial
fungi
virus
parasites

Question 9

how do genetics/ageing cause cell injury?

Answer 9

inborn errors in metabolism
non functional enzymes
cells are more prone to injury as they age

Question 10

what are the different mechanisms of cell injury?

Answer 10

• depletion of ATP
• direct mitochondrial damage
• direct membrane damage
• disruption to calcium homeostasis
• oxidative stress
• direct damage to DNA and proteins

Question 11

how does ATP depletion cause cell injury?

Answer 11

(varying causes reduce ATP prodction, whats important is the issues which arise from low ATP levels)
* anaerobic glycolysis - increase lactic acid production which lowers pH and denatures cellular enzymes
* affects energy dependent Na+/K+ pump - Na+ and water enter cell, cell swells, Ca2+ enters cell
* causes ribosomes to detach from ER - altered protein synthesis, proteins cant function

Question 12

why does calcium influx cause irreversible cell injury?

Answer 12

activates following:
1. ATPases - increases ATP consumption
2. phospholipases - break down cell and organelle membranes
3. proteases - breaks down proteins
4. enodnucleases - breakdown DNA in cell

Question 13

how does production of free radicals cause cell injury?

Answer 13

free radical formation can be pathological or physiological
free radicals damage the following:
1. lipids - target unsaturated fatty acids, cell membrane and organelles damaged, resulting in Ca2+ influx
2. proteins - promotes protein-protein cross-links and protein fragmentations form
3. DNA - nuclear DNA and mitochondrial DNA is broken down

Question 14

how does the body control free radicals?

Answer 14

free radicals are unstable and decay spontaneously
body removes free radicals by:
1. anti-oxidants
2. transport proteins
3. enzymes

Question 15

what are examples of anti-oxidants which control free radicals?

Answer 15

• lipid soluble vitamins
• ascorbic acid
• glutathione

Question 16

what are examples of transport proteins which control free radicals?

Answer 16

metals produce free radicals so its dangerous for them to just exist in body
* iron binds to transferrin
* copper binds to ceruloplasmin

Question 17

what are examples of vitamins which control free radicals?

Answer 17

• superoxide dismutases
• glutathione peroxidase

Question 18

what are mechanisms which repair free radical damage?

Answer 18

heat shock proteins (ubiquitin):
* repair and re-fold damage proteins
* if they can’t repair proteins they label them for degradation
* in times of stress cells reduce normal protein synthesis and increase heat shock protein synthesis

Question 19

what does an injured cell look like?

Answer 19

reversible changes:
* swelling - due to damage to Na+/K+ pump
* clumped chromatin - due to reduced pH
* ribosome dispersion- lack of ATP which normally holds them together
* cytoplasmic blebs - symptomatic of cell swelling

irreversible changes:
* nuclear changes -
* lysosome ruptures
* membrane defects - reflects membrane damage
* lysis of ER - due to membrane defects

Question 20

what is the difference between apoptosis + necrosis?

Answer 20

apoptosis:
* individual cells death
* programmed cell death
* cell shrinks
* plasma membrane is preserved
* organelles contract
* DNA is cleaved between nucelosomes
* dead cells taken up by phagocytosis

necrosis:
* grouped cell death
* cells swell
* plasma membrane destroyed
* organelles swell and break down
* DNA is degraded randomly
* dead cells start inflammatory process

Question 21

what happens in apoptosis?

Answer 21

individual programmed cell death
* cells shrink
* no inflammation
* physiological or pathological

Question 22

what are physiological causes of apoptosis?

Answer 22

• embryogenesis
• involution of hormone dependent tissue

Question 23

what are pathological causes of apoptosis?

Answer 23

• cell death in viral infection
• cells with damaged DNA

Question 24

what are the 2 pathways for apoptosis?

Answer 24

intrinsic pathway (mitochondrial):
* mitochondria release cytochrome C which activate caspases which induce apoptosis

Extrinsic pathway (death receptor):
* death receptors are released by T killer cells and attach to the cell membrane which then activate caspases which leads to cell death

Question 25

what are the basics of necrosis?

Answer 25

• cells swell
• disorganised and messy

characteristic nuclear changes:
* pyknosis (nuclear shrinkage)
* karyorrhexis (fragmentation)
* karyolysis (dissolution)

Question 26

what are the different types of necrosis?

Answer 26

• coagulative
• liquefactive
• caseous
• fat necrosis
• fibrinoid necrosis

Question 27

when is coagulative necrosis seen?

Answer 27

• tissue retains ghost outline of cells and tissue architecture
• protein denaturation is prominent cause of cell injury/death
• occurs in solid organs

Question 28

when is liquefactive necorsis seen?

Answer 28

• damage of loose tissue (seen in brain)
• complete loss of architecture
• release of enzymes which break down tissue

Question 29

when is caseous necrosis seen?

Answer 29

• seen in the lung in tuberculosis
• ‘cheese’ like

Question 30

when is fat necrosis seen?

Answer 30

• direct trauma to fatty area
• acute pancreatitis

Question 31

what molecules are released by injured cells?

Answer 31

tested for in blood:
potassium
myoglobin
enzymes

Question 32

what molecules accumulate in cells post injury?

Answer 32

1. normal cell components
2. abnormal cell components
3. pigment

Question 33

what is gangrene?

Answer 33

necrosis visible to naked eye

Question 34

what is infarction?

Answer 34

necrosis caused by reduction in arterial blood supply

Question 35

what is the difference between wet, dry and gas gangrene?

Answer 35

dry gangrene:
* necorsis + exposure to air = coagulative necrosis (black)

wet gangrene:
* necrosis and infection = liquefactive necrosis (green)

gas gangrne:
* necrosis + infected with anaerobic bacteria = swollen

Question 36

what is the difference between a white and red infarct?

Answer 36

white infarct:
* no associated haemmorhage
* seen in solid organs
* occlusion of end artery

red infarct:
* associated haemmorhage
* occurs in organs with dual blood supply
* previous vascular congestion

Question 37

what is pathological calcification?

Answer 37

abnormal deposition of calcium within tissues, 2 types:
1. localised in dying tissue (dystrophic)
2. generalised (metastatic)

Question 38

what is the difference between localised and general pathological calcification?

Answer 38

Localised:
* most common
* nothing to do with calcium metabolism

generalised:
* depositon in otherwise normal tissue
* metabolic errors cause high levels of circulating calcium
* can be fatal