Exam #2: Hemodynamics II Flashcards Preview

General Pathology > Exam #2: Hemodynamics II > Flashcards

Flashcards in Exam #2: Hemodynamics II Deck (53):
1

What balance must be maintained in hemostasis? What is the function of hemostasis?

The balance between prothrombosis & antithrombosis

Function is to maintain blood in a fluid fluid state in the blood, while allowing for the rapid formation of a hemostatic clot in response to vascular injury

2

What are the three general components that contribute to hemostasis?

1) Endothelium/ vascular wall
2) Platelets-- bricks
3) Coagulation cascade & fibrin--mortar/ cement

3

Describe the sequence of clot formation.

1) Injury= transient vasoconstriction (endothelin mediated)
2) Endothelial damage= exposure of ECM causing platelet activation
3) Tissue factor + Factor VII-->Thrombin-->Fibrin
4) Fibrin & platelets from a clot, plugging the defect and preventing blood loss

4

What are the four stages of normal hemostasis following vascular injury?

1) Vasoconstriction
2) Primary hemostasis
3) Secondary hemostasis
4) Thrombus & antithrombotic events

5

Outline the molecular events that cause transient vasoconstriction.

Injury causes the release of "endothelin" from the injured blood vessel, which causes a reflex vasoconstriction

6

Outline the molecular events that occur in primary hemostasis.

- Injury exposes the ECM
- Exposed ECM--> platelet activation & extravasation to the site of injury forming a "hemostatic plug"

7

Outline the molecular events that occur during secondary hemostasis.

- Tissue Factor i.e. Factor III or "Thromboplastin" is exposed during injury
- Tissue Factor + Factor VII--> activation of coagulation cascade & thrombin formation
- Thrombin cleave Fibrinogen to Fibrin

8

Outline the molecular events that occur during thrombus formation and antithrombosis.

- Fibrin + activated platelets form a "permanent plug"
- With the permanent plug formed, antithrombic mechanisms are set in motion to limit the thombus ONLY TO THE SITE OF INJURY
- Limiting thrombus is "tissue plasminogen activator" i.e. "t-PA" mediated

9

What factors activate the endothelium and shift the function to the procoagulant state?

Trauma obviously, but additionally:

1) Infectious agents
2) Hemodynamic forces i.e. HTN
3) Cytokines
4) Plasma mediators

10

What are the antithrombic mechanisms of the endothelium?

Normally, endothelial cells function in an anticoagulant fashion. This state is maintained by three general mechanisms:
1) Anti-platelet: blocking platelet activation & aggregation
- Barrier to thrombogenic subendothelial ECM
- Secretion of prostacyclin (PGI2) & NO inhibit platelet
aggregation
- Secretion of adenosine diphosphatase, breaksdown ADP that causes platelet aggregation

2) Anti-coagulant: blocking coagulation cascade
- Heparin-like molecules= cofactors for antithrombin
- Thrombomodulin= converts thrombin to an anticoagulant

3) Fibrinolytic: lysing clots
- Production of tPA, a protease the degrades fibrin

11

What are the prothrombic mechanisms of the endothelium?

Trauma, inflammation, and other events can cause the endothelium to transition to a prothrombic state. These mechanisms are opposite of the antithombic mechanisms:
1) Platelet effects
- vWF, a cofactor for platelet binding to the ECM

2) Procoagulant
- Cytokine or bacterical endotoxin induced production of
Tissue Factor, that activates the extrinsic clotting cascade

3) Anti-fibrinolytic
- Secretion of t-PA inhibitors, called plasminogen activator inhibitors (PAIs)

12

What are platelets? What produces platelets?

Platelets are anucleate fragments of megakaryocytes produced in the bone marrow; they contain
- alpha granules
- dense granules

13

What are the three steps of platelet activation?

1) Adhesion
2) Secretion of granules and activation
3) Aggregation

14

What is the moleular mechanism that mediates platelet adherence?

ECM vWF + Platelet glycoprotein Ib receptors= firm adherence

*****This is where the genetic defect is in Von Willebrand's Disease that leads to the bleeding disorder (Mom)*****

15

What does platelet adhesion lead to?

Secretion i.e. release of platelet granules (alpha & dense)

16

What are the important mediators released by platelets? What are the functions of these mediators?

1) Ca++= critical for coagulation cascade
2) ADP= platelet aggregation
3) Serotonin-->vasoconstriction

4) Platelet Factor IV-->inactivation (part of maintaining a local response?)

17

What causes platelet aggregation?

ADP & thromboxane A2released by platelets

18

Outline the process of platelet aggregation. What is the role of fibrinogen?

1) ADP triggers a conformation change in platelet GpIIb & GpIIIA receptors
2) Conformational change induces binding to fibrinogen
3) Fibrinogen binding to receptors on adjacent platelets= aggregation

19

What is the mechanism of action of plavix?

Inhibition of ADP induced platelet binding

20

What is the end goal of the coagulation cascade?

Formation of thrombin that cleaves circulating fibrinogen to fibrin i.e. the "mortar" that seals platelets & forms the permanent plug

21

What is a coagulation factor complex? Where does it assembly? What is required for its assembly?

A coagulation factor complex is:

Enzyme (activated coagulation factor) + Proenzyme (inactivated coagulation factor) + Ca++ = complex
- Ca++ is the cofactor that holds the two coagulation factors together
- Assembly occurs on a phospholipid surface

22

What is the difference between serum and plasmin?

Serum= blood without clotting factors

Plasmin= blood with clotting factors

23

What is the function of thrombin?

- Conversion of fibrinogen to fibrin monomer
- Fibrin is the "glue" for the platelet plug

24

Draw the coagulation cascade.

N/A

25

What is a Prothrombin time (PT)?

Measurement of the extrinsic pathway

26

What drug will prolong PT?

Warfarin

27

What is a Partial Thromboplastin Time (PTT)?

Measurement of the intrinsic pathway--normally this is longer than the PT

28

What drug prolongs the PTT?

Heparin

29

What is the mnemonic to remember the intrinsic pathway?

TENET

30

List the anticoagulants.

1) Antithrombin III
2) Protein C
3) Plasmin

31

What is the mechanism of antithrombin III?

Direct inactivation of serine proteases:
- IXa
- Xa
- XIa
- XIIa

32

What is the mechanism of Heparin?

Potentiation of antithrombin III

33

What is the mechanism of protein C?

Inhibition of Va and VIIIIa

34

What is the function of Protein S?

Enhancement of protein C

35

What is thrombomodulin?

- Activated by thrombin
- Binds to thrombin and alters its conformation
- Conformational change leads to activation of protein C (anticoagulant)

36

What is tissue pathway factor inhibitor?

A protein produced by the endothelium that inactivates TF- Factor VIIa

37

What inactivates free plasmin?

Circulating alpha-2 antiplasmin

38

What is the function of plasminogen activator inhibitor (PAI)

Inactivation of tPA

39

What activates PAI?

Thrombin & various cytokines

40

What is the function of plasmin? What is the precursor of plasmin?

- Breakdown of fibrin
- Plasminogen

41

What substances activate plasminogen?

1) Urokinase
2) tPA i.e. "Tissue Plasminogen Activator"
3) Streptokinase

42

What is the difference between a thrombus and an embolus?

Thrombus= blot clot that forms abnormally within a blood vessel

Embolus= dislodged blood clot that travels through the bloodstream

43

Where is Heparin produced naturally?

Basophils and mast cells to prevent formation and extension of blood clots

44

How is Heparin administered?

SubQ or IV, NEVER PO

45

What is the mechaism of Heparin?

Potentiation of Antithrombin III

46

What is Warfarin?

Oral medication that is a synthetic derivative of coumarin

47

Why would you put a patient on Warfarin vs. Heparin?

Heparin= starts working immediately; therefore, it is used post-op to prevent DVT, PE...etc.

Warfarin= takes time to start working; therefore, it is used for long-term anticoagulant therapy

48

What are the Vitamin K dependent clotting factors produced by the Liver?

VII
IX
X
II (Prothrombin)

49

Which pathway is inhibited by Warfarin & which pathway is inhibited by Heparin? How are these measured?

Warfarin= Extrinsic & PT

Heparin= Intrinsic & PTT

50

Aside from coumadin and heparin, what are the other classes of anticoagulant drugs?

- Direct Thrombin Inhibitors
- Direct Factor X inhibitors
- Tissue Factor Pathway Inhibitors

51

What is Dabigatran?

Direct Thrombin Inhibitors

52

What is Rivaroxaban & apixaban?

Direct Factor Xa Inhibitors

53

What is the difference between an anticoagulant, anti-platelet, and thrombolytic agent?

Anticoagulant= prevent clot formation & extension

Antiplatelet= interfere with platelet activity

Thrombolytic= dissolve EXISTING thrombi