Biochem Final Platelet Plug

Front 1

wht is hemostasis

Back 1

stop bleeding

Front 2

what is a thrombus

Back 2

pathological
stops bleeding (hemostasis)

Platelet plug + fibrin clot

Front 3

what is platelet adhesion

Back 3

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collagen
von Willebrand factor
GP1b/IX
high shear force

Front 4

what is platelet activation

Back 4

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TxA2
Thrombin

Front 5

what is platelet aggregation

Back 5

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GPIIb
Fibrinogen

Front 6

how does PGI2 inhibit platelet plug formation when secreted by healthy endothelium

Back 6

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Front 7

what affect does PGI2 have on platelet function

Back 7

inhibitory

**healthy endothelium secretes PGI2 which decreases Ca

Front 8

what 2 factors are secreted by healthy endothelium so that platet plugs arent formend

Back 8

PGI2: inhibit platelet activation by decreasing Ca

NO: dilation

Front 9

what is primary hemostasis

Back 9

forming platelet plug

Front 10

what are the 3 main events that happen when vascular endothelium is damages

Back 10

1. constrict
2. platlet plug: primary hemostasis
3. fibrin clot: secondary hemostasis

Front 11

what is the name of the process that makes platelets

Back 11

thrombopoiesis

Front 12

how to RBC and platelets compare?

Back 12

Platelets are 1/10 the...
1. size
2. half life
3. prevalence

Front 13

what is thrombocytopemia
what is thrombocytosis

Back 13

low platelet (<10^5)
high platelet (<4X10^5)

Front 14

what do platelets contain, what do they lack

Back 14

1. granules
2. mito
3. lysosomes

NO nucleus

Front 15

what granules are found in platelets

Back 15

1. Dense: store Ca/ADP
2. Alpha: vWF, fibrinogen, V, serotonin, PDGF
3. Dense tubular system, store Ca

Front 16

what do dense granules store. where are they

Back 16

1. Ca
2. ADP

platelets

Front 17

what do alpha granules store? where are they

Back 17

1. vWF
2. Fibroninogen
3. V
4. Serotonin
5. PDGF

Front 18

what is a dense tubular system, who has it and why

Back 18

in platelets to store Ca

Front 19

what prevents platelet plug formation in healthy endothelium

Back 19

PGI2 secreted from the endothelium binds Gs and increases cAMP, cAMP causes Ca to enter the dense tubular system and keeps Ca levels low, this inhibits plug formation

Front 20

what G protein does PGI2 work through

Back 20

Gs
cAMP increases and causes Ca to enter the dense tubular network and cytosolic Ca is low

Front 21

what are the 5 main steps for plug formation

Back 21

1. Adhesion
2. Activation
3. degranulation/secretion
4. Shape change
5. Aggregation
5. agg

Front 22

what initiates plug formation

Back 22

exposure of collagen to the lumen of BV

Front 23

what binds to exposed collagen, then what, what phase of plug formation

Back 23

1. Adhesion

**collagen is exposed and vWF binds to it
**high shear force then makes vWF change shape
**Gb1b/IX on platelets then bind to vWF

Front 24

what receptor is associated with creating a plug? what is associates with inhibiting a plug

Back 24

Agonists bing Gq to activate plug formation and increase Ca (PLC, IP3 adn DAG)

Antagonists (PGI2) bind Gs and to cAMP to keep Ca low

Front 25

what agonist is made by platelets

Back 25

Ax2

Made by platelets, bind Gq to increase Ca and start plug formation

**ca activates PLA2, this frees AA, AA used to make Ax2

Front 26

what is a potent platelet agonist

Back 26

thrombin

**activates plug formation
**thrombin bunds Gq, Ca increases, PLA2 activated, AA freed, Ax2 made

Front 27

when thrombin/Ax2 binds Gq Ca increases. What is activated by Ca

Back 27

PLA2

*activated PLA2 frees AA from PM, AA then is used to make Ax2

Front 28

how does activation occur?

Back 28

Ax2/Thrombin binds to Gq
Ca increases (PLC, IP3 Dag)
Ca binds PLA2)
PLA2 makes AA
AA makes Ax2 and more plateles can be activated

Front 29

what is degranulation

Back 29

when platelets secrete TxA2 and activate other platelets (autocrine) so they skip adhesion (the first step)

Front 30

what are 2 roles TxA2 plays in plug formation

Back 30

1. Autocrine signal to activate other platelets
2. cause granules to secrete their contents

Front 31

what role does ADP play in plug formation

Back 31

1. TxA2 stimulates it release form dense granules in platelets.
2. ADP then acts as an aggregation agonist
Autocrine signal, binds platelet ADP receptor

Front 32

what drug interacts with ADP receptors

Back 32

Plavix

*it binds and blocks ADP receptors on platelets to inhibit plug formation

Front 33

what 2 affects does increase in Ca have on plug formation

Back 33

1. activate PLA2 to increase AA to make TxA2 to activate platelets

2. bind myosin light chains to change shape

**ca is increased by Gq

Front 34

what receptor is only displayed on activated platelets

Back 34

GpIIb/IIIa

*when Ca increases the myosin light chains get Ca and the shape of the platelet changes, this allows GPIIb/IIIa to be expressed

Front 35

what is GP1b/IX
what is GPIIIb/IIIa

Back 35

GPIb/IX: expressed on platelet, allows platelet to bind to vWF

GPIIIb/IIIa: on ACTIVATED platelet (shape is changed)

Front 36

what things are expressed on the activated platelet that has changed shape due to Ca of myosin light chanis

Back 36

1. GPIIb/IIIa
2. Phosphatidylserine moves to outside leaf of PM and makes it negatinve, this lets VIIIa and Va bind

Front 37

when are phosphatidlyserine resudue on outer leaflet of platelet

Back 37

after the platelet has changed shape due to ca

it make the membrane negative and lets VIIIa and Va bind for secondary hemostasis

Front 38

what is aggregation, what allows it"?

Back 38

fibrinogen binds to the GPIIb/IIIa on activated platelets with shape changes this allows 2 plateltes to be linked

**the RGD sequence in fibrinogen is what binds to platelets

Front 39

what does fibrinogen do

Back 39

binds to GPIIb/IIIa on activated chape changed platelets and links to platelets together

**the RGD sequence in fibrinogen is what binds to the platelet

Front 40

what does integrilin do?

Back 40

has the same RGD binding sequence as fibrinogen, it outcompetes fribrinogen for binding to GPIIb/IIIa on the platelet

**inhibits plug formation by blocking fibrinogen from linking platelets

Front 41

how does asprin have an antithrombogenic effect

Back 41

1. blocks Cox 1 (no TxA2 synthesis in platelets)
2. blocks Cox 2 (no PGI2 in endothelium)

**cox 2 is inducible and CAN be overcome so that PGI2 is still made, but platelets dont have nuclei and so cant make more AxT2

** PGI2 is made and inhibits formation
**AXT2 is NOT made and so wont promote plug formation