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73 Cards in this Set
- Front
- Back
2 types of cell death
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necrosis and apoptosis
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does necrosis require ATP?
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no
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does apoptosis require ATP?
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yes
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which type of cell death causes inflammatory response?
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necrosis
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why doesn't apoptosis make inflammatory response?
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no loss of membrane integrity/ no release of cell contents
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why does necrosis occur?
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cell doesn't have time to adapt --> dies
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initiators of necrosis
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1) ischemia
2) membrane damaging agents 3) mitochondrial poisons |
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ischemia
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restriction of blood supply
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ischemia series of events
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mitochondria get loss oxygen --> low ATP --> lose ion gradients --> increase Ca++ --> activates lots of -ases
anaerobic glycolysis --> generates lactic acid --> pH drops --> ribosomes stop working |
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name a mitochondrial poison
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cyanide
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what does increased cytoplasmic Ca++ do?
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activates phospholipases, proteases, endonucleases --> promotes injury
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what is the irreversible step of cell injury, making it's death inevitable
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loss of IMM integrity
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what is a clinical example of ischemia/hypoxia
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myocardial infarction (MI)
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ischemia-reperfusion injury
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the restoration of circulation results in inflammation and oxidative damage
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2 pathways of apoptosis
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1) death receptor (extrinsic)
2) mitochondrial (intrinsic) |
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describe death receptor apoptosis pathway
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lymphocyte fas ligand --> bind to cell's fas receptor --> forms DISC complex --> cleaves procaspases --> chop up everything
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describe mitochondrial (intrinsic) apoptosis pathway
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cell notices things are going awry --> increase in BH3 proteins --> attach to BCL2 proteins --> move off Bax/Bac pores --> Cytochrome C escapes --> cleaves procaspases --> chop up everything
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transglutaminase
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cross-links all the junk that was chopped up in apoptosis caspase thing
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phosphatidylserine
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usually on cytoplasmic side, but with apoptosis flips to outer, screams "eat me" and alerts neighbors
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if you see cytoplasmic blebs...
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apoptosis!
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when does apoptosis happen in normal physiology
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webbing between digits
neuronal remodeling selecting immune cells post-pregnancy |
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ischemic injury can cause
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necrosis and apoptosis:
1) no blood --> necrosis 2) some blood --> apoptosis |
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2 important free radicals
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OH
superoxide anion O2- |
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which is the most damaging of ROS?
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OH-
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what is a non-FR ROS?
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H202
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why is H202 dangerous
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can diffuse --> spread ROS
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some key ROS reactions
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O2- --> H202
H202 --> OH- (fenton and haber-weiss) |
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how do ROS affect proteins?
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1) bind S-S together --> affects tertiary structures
2) sticks shit on 3) unfolds 4) splits apart |
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how do ROS affect lipids?
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lipids propagates the oxidation!!
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how do ROS affect DNA?
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base changes induce apoptosis
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how do we eliminate ROS?
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1) glutathione
2) vitamine E 3) vitamine C |
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glutathione
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quenches FRs
ratio of GSSG / GSH --> more GSSG = more stress = close to depleting this buffer |
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what metal helps glutathione?
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selenium
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vitamin E
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quenches lipid FRs
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vitamin C role with ROS
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replenishes Vitamin E
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how do we repair/remove molecs damaged by ROS?
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repair = chaperones try to help
remove = if too damaged, chaperones ubiquinate the molec = gets chewed up |
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UPR response
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ER membrane detects lots misfolded proteins --> activates tranx of UPR part of promoters --> turns on protective genes
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how directly detect ROS?
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Nrf2 pathway
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how directly detect hypoxia?
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HIF pathway
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Nrf2 pathway
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normally, Nrf2 bound by Keap --> SH part of keap oxidized --> unbinds --> Nrf2 free to be a tranx factor --> turn on protective genes
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HIF pathway
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normally, OH onto HIF --> no oxygen --> HIF free to be a tranx factor --> turns on protective genes
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how can you tell which cells in petri dish are in mitosis?
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rounded up --> because of microtubules breaking down to make spindle
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interphase
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period between 2 mitoses
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H-TdR
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radioactive thymidine --> will only incorporate into replicating DNA
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what phase do we find when put H-TdR in?
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S phase
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colchicine
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prevents spindle formation --> therefore blocks in mitosis
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using H-TdR and colchicine elucidates
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G2
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which phase of cell cycle has twice the amount of DNA
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G2
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mitogen
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stimulates Go cells to enter G1 and continue cycle
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histone synthesis occurs...
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only during S phase
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histone phosphorylation occurs...
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at end of G2
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RB protein
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regulates progression through restriction point
binds to, and so inhibits, tranx factors that would allow cycle to continue |
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phosphorylated RB
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unbinds from tranx --> cycle go
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de-phosphrylated RB
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bind to tranx --> cycle stop
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MPF
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M-phase promoting factor
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how do we regulate cell cycle?
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cyclins --> CDKs
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how can you regulate CDK?
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1) phosphorylate it
2) add CKI 3) degrade cyclin |
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are we the same as yeast re: # of CDKs?
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no, we have multiple cyclins and CDKs
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regeneration requires
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intact tissue scaffold
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what are the phases of fibrosis?
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1) hemostasis and inflammation
2) angiogenesis and fibrogenesis 3) remodel / scar formation 4) re-epithelialization |
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tissue repair entails either or both of:
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regeneration
scarring (fibrosis) |
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hemostasis happens how?
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clotting = caspases --> factor 10a --> fibrin = scab
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function of hemostasis
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1) stop bleeding
2) keep microorgs out 3) scaffold for cell migration |
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PDGF
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secreted by platelets
recruit fibroblasts to scene |
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fibrogenesis
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replacing fibrin matrix with connective tissue matrix
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what is tissue resulting from fibrogenesis?
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granulation tissue (transitional)
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what happens in remodel phase of wound repair?
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remodel blood vessels and collagen
collagen: 3 --> 1 |
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contracture
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scar briding a joint
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adhesion
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organized exudate bridging serosal surfaces
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stricture
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circumferetial scar in a tubular structure
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keloid/hypertrophic scar
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excessive collagen production
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fibrotic disorders most often caused by
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chronic inflammation
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examples of fibrotic disorders
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1) cirrhosis
2) pulmonary fibrosis 3) scleroderma |