Term
| Hemostasis involves 3 processes |
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Definition
1) of platelet adhesion (mediated by von Willebrand factor, collagen and specific platelet receptors)
2) platelet aggregation (mediated by fibrinogen or von Willebrand factor and platelet receptor glycoprotein IIb,IIIa (alpha2b,beta3),
3)and fibrin formation mediated by the coagulation cascade |
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Term
| what is platelet adhesion mediated by |
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Definition
| von Willebrand factor, collagen and specific platelet receptors |
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Term
| what is platelet aggregation mediated by |
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Definition
| fibrinogen or von Willebrand factor and platelet receptor glycoprotein IIb,IIIa (alpha2b,beta3), |
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Term
| what is fibrin formation mediated by |
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Definition
| coagulation cascade. This results in the formation of a “plug” comprised of platelets, insoluble fibrin and cellular elements of the blood (WBC and RBC) “trapped” in the clot |
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Term
| Active processes mediated by _______ cause degradation of the blood clot. |
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Definition
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Term
| There is ordinarily a delicate balance between ______ and ________ factors in the blood such that vessel integrity and flow is maintained. |
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Definition
| procoagulant and anticoagulant |
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Term
| The endothelium plays an active role by |
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Definition
1) providing a barrier between the flowing blood and the subendothelium
2) synthesizing a number of factors that that can inhibit or activate platelets, inhibit or activate blood coagulation, inhibit or activate fibrinolysis; or
3) effect vascular tone. |
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Term
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Definition
| small (2um) anucleate cytoplasmic fragments derived from bone marrow megakaryocytes that mediate the process known as primary hemostasis; these circulate in an 'inactive'state and their interactions with the endothelium and blood proteins does not cause disruption of normal blood flow. |
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Term
| The platelet surface expresses many receptors, some of which are linked to ________ and others are surface receptors acting as ____________ |
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Definition
g proteins
adhesion molecules |
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Term
| Protease activated receptors (PARs) |
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Definition
| a class of receptors that exist of the surface of platelets that are g protein coupled. |
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Term
| Granules in platelets contains substances such as these that upon release can aid in platelet activation |
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Definition
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Term
| Phospholipid metabolism is critical to normal platelet function fore what two reasons |
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Definition
1) thromboxane synthesis and release
2) phosphatidyl serine exposure |
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Term
| upon injury to endothelium, platelets stick to exposed collagen by 2 different mechanisms: |
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Definition
1) via collagen receptors on the platelet surface (there are several)
by the action of von Willebrand factor (vWF) binding to collagen and the platelet surface glycoprotein Ib,IX,V complex. |
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Term
| VWF (von Willebrand factor) |
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Definition
| large, circulating, adhesive glycoprotein critical for platelet adhesion (defined as platelets sticking to collagen and other non platelet surfaces) especially in conditions of high shear stress |
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Term
| Activating a platelet leads to: |
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Definition
| mediated receptor engagement, second messenger generation followed by platelet shape change, thromboxane synthesis from membrane lipids, granule secretion, surface phospholipid exposure (to support coagulation reactions) and exposure of the integrin, glycoprotein IIb,IIIa (alpha2b,beta3). Exposure of this integrin in a form that allows interaction with plasma proteins (fibrinogen and vWF) causes platelet aggregation to occur. This is the process of platelets sticking to one another. |
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Term
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Definition
| places an important function in platelet activation allowing rapid platelet shape change |
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Term
| glycoprotein alpha2bbeta3 |
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Definition
| an integrin, that when exposed in a certain form, allows interaction with plasma proteins (fibrinogen and vWF) causing platelet aggregation to occur. |
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Term
| once in the cell, iron can do two things |
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Definition
1) be stored in ferritin (globular protein can hold thousands of iron molecules)
2) can transport iron out of cell and into blood |
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Term
| in an enterocyte, what is the port that inron exits the cell through |
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Definition
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Term
| in the enterocyte, this is the protein that oxidizes iron once it exits the cell |
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Definition
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Term
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Definition
| in the blood, iron is bound to this when it wants to enter the cell |
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Term
| the three types of transferrin |
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Definition
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Term
| out of the 3 transferrins, whuch one does the transferrin receptor have the highest affinity for? |
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Definition
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Term
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Definition
| this oxidizes iron when it is leaving the macrophage cells; contains a copper molecule |
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Term
| What are the three things that regulate iron transfer |
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Definition
1) if RBC is deficient in iron it then makes more TFr's
2) cells at bottom of crypt
3) protein hepcidin |
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Term
| Iron Response Elements (IRE) |
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Definition
| short stem loop bound by iron response protein (IRP) found in UTRs (untranslated regions of mRNA) whose products are involved in iron metabolism |
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Term
| Explain how IRE for ferritin works |
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Definition
| mRNA of ferritin (iron storage) has IRE in 5' UTR ; when iron is low, IRP binds to IRE in ferritin mRNA leading to reduced translation rate |
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Term
| Explain how IRE for transferrin receptor works |
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Definition
| mRNA of transferrin receptor (iron acquisition) has IRE bind to 3' UTR and this leads to increased mRNA stability |
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Term
| Iron Response Proteins exist in 2 forms |
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Definition
1) if lots of iron is in the cell, it occupies that space
2) if there is not a lot of iron in the cell, then space is unoccupied.
if in 5', it prevents translation
if in 3', it stabilizes message from being degraded |
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Term
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Definition
this explains that intestinal cells have vili and crypts; intestine cells are born in crypt and move up to vilus tip and then die/slough off
the base of the crypt is bathed in blood (gives nutrients to cells)
iron gets into these cells (either will make DMT-1 or not)
if there is no iron, mRNA for DMT-1 stabilized and makes lots of DMT-1 so iron can be absorbed |
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Term
| all the things that regulate the amount of hepcidin produced in the liver |
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Definition
1) 2 TFr's on cell membrane
2) HFE protein
3) BMP
4) HJ (hemojuvelin) |
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Term
if iron is low, how will this effect:
1) hepcidin
2) DMT-1
3) ferroportin
4) ferritin |
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Definition
1) decrease
2) increase
3) won't be degraded
4) you will make less |
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Term
| the ______ senses the amount of iron in blood, and this controls the amount of hepcidin made in the cell |
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Definition
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Term
| does hepcidin increase or decrease during inflammation? |
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Definition
increases
(inflammatory cytokines (IL-6) creases this increase) |
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Term
| two ways to decrease iron levels in body |
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Definition
1) Proton pump inhibitor- (decreases person's ability to absorb iron (bc your body's acid is decreased)
2) increased hepcidin production from inflammation (iron trapped in macrophages and iron doesnt get absorbed; iron can't go to RBC's and creates anemia |
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Term
| after an injury, what is the general process that occurs? |
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Definition
| 1) platelet receptor, glycoprotein 1b95 sticks to collagen by circular protein vWF secreted in blood and made by megakaryocytes, then firm adhesion occurs (when PLT binds to receptors and then PLTs aggregate (express integrin on cell surface) and circulate plasma protein Fibrinogen binding dependent on alpha2bbeta3 |
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Term
| explain glycoprotein 1b95 |
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Definition
| Platelet glycoprotein IX (GP9) is a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib (GP Ib), a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor (VWF). The main portion of the receptor is a heterodimer composed of 2 polypeptide chains, an alpha chain and a beta chain, that are linked by disulfide bonds. The complete receptor complex includes noncovalent association of the alpha and beta subunits with GP9 and platelet glycoprotein V . |
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Term
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Definition
| when platelet binds to receptors (VWF must bind collagen first before PLT's) |
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Term
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Definition
they express integrins on cell surface
(in resting state, they can't bind to ligand)
-circulating plasma protein involved is fibrinogen (binding is dependent on alpha2bbeta3 |
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Term
| General short hand summary of PLT activation |
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Definition
1) shape change
2) ADP
3) TXA2
4) PL(theta) exposure
5) alpha2bbeta3 |
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Term
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Definition
this is in the dense tubular system
-if intercellular calcium increases, then this is released and coverted to thromboxane A2
cyclo-oxygenase1 targets |
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Term
| receptors on surface of platelet that bind collagen directly |
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Definition
alpha2beta1
glycoprotein 6 |
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Term
| True or false: platelet activation involves tyrosine inositol phosphate reaction |
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Definition
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Term
| Platelet maturation process/steps: |
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Definition
1) early stem cell
2) committed stem cell
3) early megakaryocyte
4) late megakaryocyte
5) platelets |
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Term
| what proteins are involved in platelet maturation? |
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Definition
-IL3
-thrombopoietin
-KL
-IL-6 |
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Term
| overview of platelet activation |
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Definition
1) resting
2) adhesion
3) activation ( shape change, granule release, TXA2 synthesis, PL exposure, IIBIIIA exposure)
4) aggregation |
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Term
| Glycoprotein Ib,IX,V complex |
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Definition
binds to vWF
constitutively present on cell surface |
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Term
| glycoprotein IIb,IIIa (alpha2bbeta3) |
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Definition
a platelet receptor
-present on surface but inaccessible to its ligand
-needs to be converted to state where it can bind to its ligand
-primary ligands are fibrinogen and vWF |
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Term
| types of platelet receptors: |
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Definition
-Glycoprotein Ib,IX,V complex
-Glycoprotein IIb,IIIa (alpha2bbeta3)
-G protein coupled receptors such as
----Thrombin-protease activated receptor
----Thromboxane A2
----ADP
----Prostacyclin
-Collagen receptors
----GPVI, alpha2beta1 |
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Term
| what are the 4 types of g-protein coupled platelet receptors? |
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Definition
-Thrombin-protease activated receptor
-Thromboxane A2
-ADP (P2Y1 stimulatory g protein and P2Y12 inhibitory g protein that inhibits adenylate cyclase)
-Prostacyclin (stimulates adenylate cyclase) |
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Term
| Protease activated receptors (PAR) |
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Definition
These receptors are members of the seven transmembrane G-protein-coupled receptor superfamily; these are activated by the action of serine proteases such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR 2).[2] These enzymes cleave the N-terminus of the receptor, which in turn acts as a tethered ligand. In the cleaved state, part of the receptor itself acts as the agonist, causing a physiological response. once cleaved, it becomes active.
ex. thrombin |
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Term
| reasons for platelet assymmetry |
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Definition
-negatively charged Phospholipids are sequestered inside the membrane (PS, PE)
- numerous enzymes responsible for this asymmetry (floppases, flippases, scramblases) |
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Term
PLT surface receptors include:
and most of these use GTP bind proteins and phospholipase C (converting PIP into IP3 and DAG) |
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Definition
ADP receptors
Thromboxane receptors
alpha2beta1 receptors
GP6 receptors
thrombin receptors |
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Term
| what is the role of phospholipase C? |
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Definition
it converts PIP into:
1) IP3--> increasing calcium concentrations
2) DAG --> creating more protein kinase C |
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Term
when PLT's adhere to collagen receptors, what happens to intracellular
1)calcium levels
2) thromboxane A2 levels
3) phosphliase C levels |
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Definition
1) increases
2) increases
3) increases
they can act in autocrine or paracrine way |
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Term
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Definition
ADP synthesis recruits other PLT's to neighborhood,
enzymes that sequest negative charge are then althered so neg. charge in membrane is exposed. coagulation on surface of PLT as neg. phospholipid gets exposed. |
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Term
| what two things inhibit platelet aggregation? |
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Definition
1) if ADP is inhibited
2) if there is aspirin present
keep in mind, inhibiting parts of the pathway is not nearly as bad as inhibiting alpha2beta3 (final part of pathway) |
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