ROS, ischemia, apoptosis Flashcards

1
Q

oxidation

A

loss of electrons

reduction is the gaining of electrons

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2
Q

does partial reduction of oxygen leads to ROS

A

yes

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3
Q

what is a free radical

A

a species with an unpaid electron

All oxygen radicals are ROS but not other way round

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4
Q

what two ROS are made from partial reduction of oxygen

A

superoxide anion radical

hydrogen peroxide

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5
Q

additionally ROS species can react together to from further ROS such as

A
hydroxyl radicals ( peroxide and iron) 
hypocholorus acid
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6
Q

at low conc of intracellular ROS what effect occur

A

angiogenesis
tissue repair
VEGF induced cell migration
Cell proliferation

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7
Q

at high conc of intracellular ROS what effects occur

A

apoptosis cell death and disease
carcinogenesis and mutagenesis
mitochondrial dysfunction

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8
Q

the production of free radical within the mitochondria may occur in the outer membrane, inner membrane or within the matrix what ROS does it most commonly produce

A

hydrogen peroxide

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9
Q

what do NADPH oxidases do

A

NADPH oxidase catalyzes the production of a superoxide free radical by transferring one electron to oxygen from NADPH. During this process O2 is transported from the extracellular space to the cell interior and the H+ is exported.

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10
Q

ROS and oxidative damage to lipids proteins and DNA

A

lipid- increasemmebrnae fluidity and permeability as well as change breakage

Protein - AA changes, fragmentation of chain, enzyme inactivation and increased susceptibility of proteins to proteolysis

DNA - breakage , removal of nucleotides and modification

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11
Q

necrosis

A

whole cell death and unregulated lacking nutrients or becoming infected indicating a pathologically process

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12
Q

apoptosis

A

programmed cell death

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13
Q

autophagy

A

eukaryotic cell degrade cytoplasmic material in lysomal compartments

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14
Q

in apoptosis what occurs

A

loss of intercellular junctions
condensation of chromatin
shrinkage of cytoplasm and therefore cells
cell blebbing
cell fragments enclosed in apoptotic bodies
recycling of components
phagocytosis of apoptotic bodies by enighborung cells and macrophages

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15
Q

role of cytochrome c in intrinsic mitochondrial apoptosis

A

Mitochondrial cytochrome c (cyt c) has been found to have dual functions in controlling both cellular energetic metabolism and apoptosis. Through interaction with apoptotic protease activating factors (Apaf), cyt c can initiate the activation cascade of caspases once it is released into the cytosol.

activated initiator caps 9

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16
Q

difference between extrinsic and intrinsic apoptotic pathways

A

The extrinsic pathway of apoptosis begins outside a cell, when conditions in the extracellular environment determine that a cell must die. The intrinsic pathway of apoptosis pathway begins when an injury occurs within the cell and the resulting stress activates the apoptotic pathway.

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17
Q

are early stages of necrosis reversible

A

yes

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18
Q

how does necrosis occurs

A

mitochondria hypoxic so swell so sodium oves in and cell explodes as water follow into the cell so everything swells. Autodigestion and lytic enzymes therefore destroy cellular content and release this into extrcelualr space

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19
Q

how many different forms of necrosis are there and what are they

A
6
Coagulative 
liquefactive 
casuous 
fat
fibrinoid 
gangrenous
20
Q

what type of necrosis is the most common type and loss of nucleus with the cellular outline is preserved. This can be associated with schema and is seen in most organs in the body except the brain.

A

Coagulative

21
Q

which type of necrosis is caused by enzymatic destruction of cells and can have access formation, pancreatic and pneumonia as well as brain hypoxia

A

liquefactive

22
Q

what type of necrosis is caused by a combination of coagulative and liquefactive necrosis , characteristic of TB and cheese like appearance

A

caseous

23
Q

what type of necrosis is action of lipase on fatty tissue, acute pancreatic affecting peritoneal adipose tissue and breast trauma necrosis

A

fat

24
Q

what type of necrosis causes complexes of antigens and antibodies are deposited in vessel wall with leakage of fibrinogen out of vessels
RA and malignant hypertension

A

fibrinoid

25
Q

what type of necrosis is a surgically used term and dry gangrene is similar to coagulative necrosis
wet gnagrene is similar to liquefactive necrosis due to the secondary infection

fournies gangrene seen in scrotum

A

gangrenous

26
Q

define ischemia

A

Ischemia is damage or dysfunction of oxygen sensitive tissues due to reduction of blood supply

causes reduction in oxidative phosphorylation so less ATP which causes 3 things

  • less sodium pump so bigger influx in calcium and water and sodium and efflux of K and ER swelling and loss of microvilli
  • increased anaerobic glycolysis so decreased glycogen and increased lactic acid so lowers ph and clumping of the nuclear chromatin occurs
  • detachment of ribosomes so protein synthesis decreases
27
Q

early changes of MI

A

loss of ATP
accumulation of lactate
necrosis usually 6 Horus

28
Q

what is reperfusion

A

the reopening of a coronary artery

29
Q

what are the major ROS

A
superoxide amino 
hydrogen peroxide 
hdyroxyl radical 
nitric oxide
peroxynitrate
30
Q

what are the major sources of ROS during IRI

A
xanthine oxidase system 
activated neutrophils 
mitochondrial electron transport chain 
arachidonic acid metabolism 
auto-oxidation of catecholamines
31
Q

what are the major effect of calcium overload and the development of hypercontracture

A

increased cytosolic calcium so endonuclease to chromatin damage
protease cause disruption of membrane
phophlipase caused decreased phospholipids
ATpase so decreased ATP

32
Q

during reperfusion , activated neutrophils adhere to the activated endothelium and subsequently extravasate into surrounding tissue, resulting in proteolytic degradation of basement membranes. Activated neutrophils also generate toxic ROS from molecular oxygen, contributing to tissue degradation during reperfusion.

A

true

33
Q

what is apoptosis

A

genetically programmed cell suicide, normal physiological cells death

34
Q

what is necrosis

A

messy, unregulated, un programmed, pathological cell death, cell lysis

35
Q

under what circumstances does apoptosis occur

A

normal development and tissue homeostasis but can also be pathological if not properly activated like in a neurodegenerative disease.

36
Q

under what circumstances does necrosis occur

A

pathological - infection, trauma or ischaemia

37
Q

how many cells at a given time in both apoptosis and necrosis can die

A

individual for apoptosis

multiple and even whole tissue regions in necrosis

38
Q

which process apoptosis or necrosis needs ATP

A

apoptosis

39
Q

apoptosis causes DNA fragmentation by DNAase Enzyme and necrosis causes random degeneration true or false

A

true

40
Q

Necrosis causes lysis of organelle membranes and plasma membranes releasing cellular contents into the surrounding tissue what impact does apoptosis have on cell membranes

A

the cell membrane remains intact - this helps to minimise the effect on surrounding and neighbouring cells

41
Q

what is blebbing

A

Blebbing is one of the defined features of apoptosis.

During apoptosis (programmed cell death), the cell's cytoskeleton breaks up and causes the membrane to bulge outward. 
These bulges may separate from the cell, taking a portion of cytoplasm with them, to become known as apoptotic blebs.
42
Q

what are the distinctive features of apoptosis

A

blebbing of the plasma membrane
condensation of the nucleus ( pyknosis)
formation of apoptotic bodies

43
Q

what is pyknosis

A

irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis

44
Q

what are the distinctive cell morphologies of necrosis

A

pyknosis
karyorrhexis and karyolysis( fragmented lysis of nucleus )
cell structure lost

45
Q

in apoptosis there is near to no inflammatory response, does an inflammatory response occur in necrosis

A

yes due to attrition of inflammatory cells by release of cellular content by necrotic cells

46
Q

what happens to the dead cells in apoptosis

A

apoptotic bodies are engulfed by neighbouring cells or infiltrating macrophages

47
Q

what happens to the dead cells in necrosis

A

cellular debris is eventually removed by phagocytic cells