Fibrinolysis

Question 1

plasminogen is produced where?

Answer 1

liver

Question 2

when is fibrinolysis activated?

Answer 2

When coagulation cascade is activated

Question 3

Main components of fibrinolysis are

Answer 3

plasminogen
plasminogen activators
plasmin
inhibitors of plasminogen activators/plasmin

Question 4

Activators of plasminogen

Answer 4

intrinsic factors
extrinsic factors
urokinase
lipoprotein a
exogenous activators

Question 5

intrinsic activators of plasminogen

Answer 5

12a, 11a, Kallekrein

Question 6

how does kallekrein activate plasminongen?

Answer 6

converts urokinase to a more active form;
releases bradykinin from HK which stimulates release of tissue plasminogen activator (tPA)

Question 7

extrinsic factors that activate plasminogen

Answer 7

tPA, uPA

Question 8

where is urokinase plasminogen activator found?

Answer 8

plasma and urine

Question 9

what is uPA major function?

Answer 9

in tissues it digests cellular maxtrix allowing cells to migrate

Question 10

what allows tPA efficiency to increase?

Answer 10

when it is bound to fibrin along with plasminogen

Question 11

where is tPA produced?

Answer 11

endothelial cells

Question 12

when is tPA released?

Answer 12

in response to stimuli: thrombin, bradykinin, exercise, venous stasis, and DDAVP (drug therapy for VW disease)

Question 13

what activates uPA?

Answer 13

plasmin
kallikrein

Question 14

what effect does lipoprotein a have on plasminogen?

Answer 14

It is similar in structure to plasminogen and competes w/ plasmin for biding fibrin
It also inhibits activation of plasminogen by tPA and uPA

Question 15

exogenous activators of plasminogen

Answer 15

streptokinase
staphylokinas
Y.pestis

Question 16

how do exogenous activators affect plasminogen?

Answer 16

they assume enzymatic activity when bound to plasminogen
Streptokinase has no preference for bound plasminogen
Stapylokinase has a preference for bound plasminogen

Question 17

examples of inhibitors of fibrinolysis

Answer 17

PAI (1,2,3)
TAFI
AP (alpha 2 antiplasmin)
alpha 2 macroglobulin

Question 18

PAI

Answer 18

plasminogen activator inhibitors
form complex with plasminogen activators and inhibits their activity

Question 19

PAI 1 inhibits…

Answer 19

inhibits tPA

Question 20

PAI 2 inhibits…

Answer 20

inhibits uPA

Question 21

PAI 3 inhibits…

Answer 21

inhibits protein c

Question 22

TAFI

Answer 22

thrombin activatable fibrinolysis inhibitor

Question 23

TAFI is activated by what?

Answer 23

thrombin-thrombomodulin complex

Question 24

How does TAFI inhibit plasminogen?

Answer 24

removes lysine and arinine residues from fibrin eliminating binding sites for plasminogen

Question 25

AP

Answer 25

alpha 2 antiplasmin

Question 26

how does Alpha 2 antiplasmin inhibit plasminogen?

Answer 26

crosslinks fibrin by f13a which increases resistance of fibrin to action of plasmin binds circulating unbound plasmin inhibiting it

Question 27

how does alpha 2 macroglobulin function as an inhibitor?

Answer 27

it neutralizes plasmin if AP cannot neutralize all the plasmin present

Question 28

FDP

Answer 28

fibrin degradation products fragments x, y, d, e

Question 29

fragment x

Answer 29

competes with fibrinogen for thrombin===less fibrin is formed

Question 30

fragment y & d

Answer 30

interferes with polymerization of fibrin monomers

Question 31

fragment e

Answer 31

inhibits thrombin

Question 32

FSP inhibits

Answer 32

platelet aggregation

Question 33

plasmin degrades what factors?

Answer 33

5, 8, 12

Question 34

liver function

Answer 34

produces most coagulation factors, activators, and inhibitors removes activated coagulation factors, plasmin, and FSP

Question 35

Positive feedback

Answer 35

thrombin activates plts thrombin activates factors 5, 8 f10a activates f7, 8

Question 36

negative feedback

Answer 36

thrombin inactivates factors 5, 8, 10a (thru TF pathway inhibitor), &7 fibrin slows thrombin release FDP interferes w/ fibrin monomer polymerization

Question 37

biochemical inhibitors

Answer 37

soluble naturally occurring proteins that inhibit enzymes by forming a complex at active site

Question 38

AT

Answer 38

antithrombin prod. by liver, endothelial cells, megakaryocytes

Question 39

what does Anti Thrombin inhibit?

Answer 39

all serine proteases: thrombin, 12a, 11a, 9a, 10a, kallekrein, & plasmin by forming a 1:1 complex acts slowly w/o heparin

Question 40

Anti thrombin activity is increased with what?

Answer 40

heparin 3-4x increase

Question 41

heparin must have what to work as an anticoagulant?

Answer 41

Anti Thrombin

Question 42

Where is heparin located?

Answer 42

granules of basophils and mast cells

Question 43

heparin cofactor 2

Answer 43

inhibits thrombin 1000x more effective bound to heparin

Question 44

protein c

Answer 44

produced in liver activated by thrombomodulin:thrombin complex w/ protein s inactivated f5a &8a

Question 45

protein s

Answer 45

on phospholipid surface w/ protein c inactivates f5a & 8a

Question 46

APC

Answer 46

activated protein C

Question 47

Activated protein C is inactivated by what?

Answer 47

protein c inhibitor PAI 3, alpha 1 antitrypsin, and alpha 2 macroglobulin

Question 48

tissue factor pathway inhibitor

Answer 48

inhibits f7a-TF complex, f10a, & plasmin

Question 49

alpha 2 macroglobulin inhibits...

Answer 49

thrombin, f10a, plasmin, kallekrein

Question 50

how does alpha 2 macroglobulin inhibit?

Answer 50

binds enzyme undergoing a conformation change preventing enzyme from binding w/ substrate

Question 51

alpha 1 antitrypsin

Answer 51

inhibit proteases at tissue level

Question 52

c-1 inhibitor

Answer 52

inhibits complement system inhibits f12a, 11a, kallekrein, and plasmin