ROS, ischemia, apoptosis Flashcards
oxidation
loss of electrons
reduction is the gaining of electrons
does partial reduction of oxygen leads to ROS
yes
what is a free radical
a species with an unpaid electron
All oxygen radicals are ROS but not other way round
what two ROS are made from partial reduction of oxygen
superoxide anion radical
hydrogen peroxide
additionally ROS species can react together to from further ROS such as
hydroxyl radicals ( peroxide and iron) hypocholorus acid
at low conc of intracellular ROS what effect occur
angiogenesis
tissue repair
VEGF induced cell migration
Cell proliferation
at high conc of intracellular ROS what effects occur
apoptosis cell death and disease
carcinogenesis and mutagenesis
mitochondrial dysfunction
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
hydrogen peroxide
what do NADPH oxidases do
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.
ROS and oxidative damage to lipids proteins and DNA
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
necrosis
whole cell death and unregulated lacking nutrients or becoming infected indicating a pathologically process
apoptosis
programmed cell death
autophagy
eukaryotic cell degrade cytoplasmic material in lysomal compartments
in apoptosis what occurs
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
role of cytochrome c in intrinsic mitochondrial apoptosis
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
difference between extrinsic and intrinsic apoptotic pathways
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.
are early stages of necrosis reversible
yes
how does necrosis occurs
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
how many different forms of necrosis are there and what are they
6 Coagulative liquefactive casuous fat fibrinoid gangrenous
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.
Coagulative
which type of necrosis is caused by enzymatic destruction of cells and can have access formation, pancreatic and pneumonia as well as brain hypoxia
liquefactive
what type of necrosis is caused by a combination of coagulative and liquefactive necrosis , characteristic of TB and cheese like appearance
caseous
what type of necrosis is action of lipase on fatty tissue, acute pancreatic affecting peritoneal adipose tissue and breast trauma necrosis
fat
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
fibrinoid
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
gangrenous
define ischemia
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
early changes of MI
loss of ATP
accumulation of lactate
necrosis usually 6 Horus
what is reperfusion
the reopening of a coronary artery
what are the major ROS
superoxide amino hydrogen peroxide hdyroxyl radical nitric oxide peroxynitrate
what are the major sources of ROS during IRI
xanthine oxidase system activated neutrophils mitochondrial electron transport chain arachidonic acid metabolism auto-oxidation of catecholamines
what are the major effect of calcium overload and the development of hypercontracture
increased cytosolic calcium so endonuclease to chromatin damage
protease cause disruption of membrane
phophlipase caused decreased phospholipids
ATpase so decreased ATP
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.
true
what is apoptosis
genetically programmed cell suicide, normal physiological cells death
what is necrosis
messy, unregulated, un programmed, pathological cell death, cell lysis
under what circumstances does apoptosis occur
normal development and tissue homeostasis but can also be pathological if not properly activated like in a neurodegenerative disease.
under what circumstances does necrosis occur
pathological - infection, trauma or ischaemia
how many cells at a given time in both apoptosis and necrosis can die
individual for apoptosis
multiple and even whole tissue regions in necrosis
which process apoptosis or necrosis needs ATP
apoptosis
apoptosis causes DNA fragmentation by DNAase Enzyme and necrosis causes random degeneration true or false
true
Necrosis causes lysis of organelle membranes and plasma membranes releasing cellular contents into the surrounding tissue what impact does apoptosis have on cell membranes
the cell membrane remains intact - this helps to minimise the effect on surrounding and neighbouring cells
what is blebbing
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.
what are the distinctive features of apoptosis
blebbing of the plasma membrane
condensation of the nucleus ( pyknosis)
formation of apoptotic bodies
what is pyknosis
irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis
what are the distinctive cell morphologies of necrosis
pyknosis
karyorrhexis and karyolysis( fragmented lysis of nucleus )
cell structure lost
in apoptosis there is near to no inflammatory response, does an inflammatory response occur in necrosis
yes due to attrition of inflammatory cells by release of cellular content by necrotic cells
what happens to the dead cells in apoptosis
apoptotic bodies are engulfed by neighbouring cells or infiltrating macrophages
what happens to the dead cells in necrosis
cellular debris is eventually removed by phagocytic cells
