week 4- coagulation part 2

Question 1

what are some regulators of hemostasis:

Answer 1

1. anticoagulant proteins
2. endothelial cell
3. fibrinolysis

Question 2

what is a major anticoagulant

Answer 2

antithrombin

Question 3

what does antithrombin degrade

Answer 3

IIa (thrombin) , IXa, Xa
stimulated by heparin and heparin-like proteoglycans

Question 4

where is antithrombin made

Answer 4

liver

Question 5

protein C

Answer 5

-made in liver
-vitamin K dependent
-activated when bound by thrombin: thrombomodulin = forms APC complexes

Question 6

what does protein C inactivate

Answer 6

Va, VIIIa

Question 7

Tissue factor pathway inhibitor (TFPI)

Answer 7

produced by the endothelial cell and inactivates the tissue factor VIIa complex

Question 8

healthy endothelial cell is

Answer 8

anti thrombotic

Question 9

how do endothelial cells prevent platelets from sticking to endothelial cells and limiting secondary hemostasis

Answer 9

1. expression of heparin -like molecules that inhibit coagulation
2. production of factors that reduce platelet activation
3. enzymes that degrade ADP (ADP activates platelets)
4. thrombomodulin (binds thrombin and activates protein C)
5. Protein S (cofactor for Protein C)
6. tissue factor pathway inhibitor
7. tissue type plasminogen activator (promotes fibrinolysis)

Question 10

what is fibrinolysis

Answer 10

removal of clots , set into motion by coagulation

Question 11

plasmin is formed by cleavage of

Answer 11

plasminogen

Question 12

active plasmin can

Answer 12

break down fibrin and also inhibits its polymerization

Question 13

activation of plasminogen occurs via

Answer 13

factor XII dependent pathway
or action of plasminogen activators

Question 14

2 main types of plasminogen activators

Answer 14

tissue type (t-PA)
urokinase (u-PA)

Question 15

main source of t PA

Answer 15

endothelial cells

Question 16

where is u-PA present

Answer 16

plasma

Question 17

where is tPA most active vs uPA

Answer 17

t-PA most active when bound to fibrin
u-PA can activate plasminogen in fluid phase

Question 18

fibrinolysis regulators act to limit production of ______

Answer 18

active plasmin

Question 19

examples of regulators of fibrinolyssi

Answer 19

1. plasminogen activator inhibitors (PAI-1, PAI-2)
2. antiplasmins
3. C1 inhibitor

Question 20

what is thrombosis

Answer 20

pathologic blood clot formation

Question 21

thrombosis causes (virchow’s triad)

Answer 21

1. endothelial cell activation
2. changes in blood composition
3. altered blood flow

Question 22

what might cause endothelial injury/activation of vessel wall?

Answer 22

1. inflammation
2. infectious agents
3. toxins
4. trauma
5. cancer cells

Question 23

changes in blood composition is also known as

Answer 23

hypercoagulability

Question 24

what may change blood composition ?

Answer 24

changes in plasma proteins , accumulation of metabolites that can alter fibrinogen structure

Question 25

protein losing nephropathy

Answer 25

-glomerulus leaks protein into urine -antithrombin is about the same size as albumin -animals lose antithrombin in urine -at risk of developing blood clot

Question 26

altered blood flow

Answer 26

-turbulence and stasis -very turbulent blood flow can mechanically damage the cell -increases in stress can cause flow induced changes in gene expression -stasis promotes interaction between platelets and vessel wall

Question 27

fate of thrombi

Answer 27

1. propagation 2. embolization 3. dissolution 4. organization and recanalization

Question 28

what is a downstream consequence of thrombus

Answer 28

infarts

Question 29

what is an infarct

Answer 29

-area of ischemic necrosis caused by occulusion or significant reduction in blood flow to tissue

Question 30

what is immunothrombosis

Answer 30

a blood clot that forms to entrap infectious agents and prevent their dissemination in the body

Question 31

mechanism of cytokine mediated expression of TF and activation of coagulation proteins

Answer 31

1. bacterial infection produces cytokines that stimulate membrane expression or inc. synthesis of TF * in any disease state with cellular activation or damage, there is potential for activation of coagulation

Question 32

what is bacterial polyphosphates (polyP) initiation of the contact pathway

Answer 32

-polyp are negatively charged phosphorus polymers that are an important source of energy in prokaryotes -released by activated platelets and mast cells -large amounts can activate FXII -can also generate thrombin independently of FXI activation

Question 33

thrombin mech:

Answer 33

-thrombin binds to PARs (protease activated receptors) -signaling pathways triggered by thrombin: PAR promote activation of platelets - results in all platelet changes associated with coagulation

Question 34

once a PAR is activated ____

Answer 34

it is endocytosed

Question 35

______ can activate specific PARs

Answer 35

TF-VIIa complex and Xa

Question 36

What are NETs

Answer 36

meshes of chromatin and proteins that are spit out onto a cell -bacteria is trapped in the meshes

Question 37

DIC: disseminated intravascular coagulation

Answer 37

when inflammation triggers excessive activation of coagulation or dampens fibrinolysis, clots form in an unregulated, disseminated manner

Question 38

important points of DIC

Answer 38

- always secondary -animals can be in the state where they are showering their microcirculation with small thrombi or they can be bleeding because they are no longer able to clot

Question 39

when clots dont form

Answer 39

hemorrhage

Question 40

hemorrhage defined as

Answer 40

extravasation of blood

Question 41

petechiae

Answer 41

pinpoint size hemorrhages into skin, MM, or serosal surfaces

Question 42

ecchymoses

Answer 42

subcutaneous hemorrhage at least 1 cm

Question 43

hematoma

Answer 43

accumulation of blood within tissue

Question 44

causes of bleeding

Answer 44

1. defects in primary hemostasis 2. defects in secondary hemostasis 3. trauma 4. toxins 5. vessel wall

Question 45

why might animals with liver disease/failure bleed?

Answer 45

-no coagulation factors -coagulation factors not carboxylated -secondary to whatever is causing liver disease

Question 46

severity of infarcts depends on:

Answer 46

-if there are alternative routes to supply tissue -the needs of the cell population -if there was advance warning

Question 47

steps in wound healing: