Physiology

Question 1

List the 3 phases of hemostasis

Answer 1

1) Vasoconstriction
2) Platelet plug
3) Fibrin clot

Question 2

Vasoconstriction during hemostasis is initiated by which nerves (1) and mediated by what cells (2)?

Answer 2

1) Initiated by sympathetic nerves
2) Vascular smooth muscle cells

Question 3

Platelets are fragments of?

Answer 3

Megakaryocytes- bone marrow bound WBC

Question 4

List 6 characteristics of platelets

Answer 4

1) lack nuclei in mammals
2) contain contractile proteins (actin and myosin)
3) contain organelles
- mitochondria: releases ADP (important for clotting cascade)
- ER and golgi: storage of Ca, synthesis of enzymes (important for clotting cascade)

4) contain enzyme systems for synthesis of prostaglandins

5) contains growth factors (PDGF, VEGF)

6) contain factor XIII (fibrin-stabilizing factor)

Question 5

Explain how formation of platelet plug occurs during hemostasis. (4 steps)

Answer 5

1) Platelet adhesion to exposed collagen and subsequent activation

2) Release of granules containing platelet agonists

3) Platelets aggregate to form plug and release more platelet attracting substances

4) Intact endothelial cells releases nitric oxide and prostacyclins that inhibits unintentional platelet aggregation/activation (prevent non-specific clotting from occurring)

Question 6

During hemostasis, what mediates platelet adhesion and how does does it eventually leads to the activation of platelets?

Answer 6

Platelet adhesion is mediated by Von-Willebrand’s factor (vWF), a plasma protein produced by the platelets to bind platelets to exposed collagen.

Adhesion activates platelets, leading to a morpholigcal change, which triggers the release of granules containing platelet agonists -> aggregation

Question 7

List 2 examples of platelet agonists released by platelets and how they can lead to platelet aggregation during hemostasis.

Answer 7

Platelet agonists from granules:
1) ADP
2) Thromboxane A2 (Tbx A2)

ADP: acts on ADP P2Y12 receptor, plays a central role in activating glycoprotein (GP) IIb/IIIa receptors an platelet recruitment and aggregation
Tbx A2: promotes aggregation and further vasoconstriction

Question 8

Fibrinogen links platelets through?

Answer 8

Glycoprotein receptors

Question 9

How is thrombin activated in the clotting cascade?

Answer 9

Factor Xa, together with Ca and Factor Va converts prothrombin to thrombin

Question 10

What does thrombin do?

Answer 10

1) Enhances its own generation (positive feedback loop)
2) Activates Factor XIII (stabilization of fibrin mesh)
3) Platelet activation
4) Release of PF3 from platelets (activation of intrinsic pathway)

Question 11

Prothrombin and thrombin is also known as what factor respectively?

Answer 11

Prothrombin: factor II
Thrombin: factor IIa

Question 12

Explain how factor Xa is activated through the extrinsic pathway of the coagulation cascade.

Answer 12

Damaged tissues outside the blood circulation releases tissue factor/thromboplastin (also known as factor III), which activates factor VII to factor VIIa.

In the presence of calcium, factor VIIa activates factor X to Xa.

Question 13

Explain how factor Xa is activated through the intrinsic pathway of the coagulation cascade.

Answer 13

Exposure to collagen fibres inside the circulation or exposure to foreign surfaces causes activation of factor XII to XIIa, which activates factor XI to Xia.

Factor XIa with calcium, activates factor IX to IXa.

Factor IXa, together with Ca and factor XIIIa, activates factor X to Xa.

Question 14

List 2 differences between extrinsic pathway and intrinsic pathway in the coagulation cascade

Answer 14

1) Speed: extrinsic pathway occurs within seconds, while intrinsic occurs within minutes as there are more enzymatic processes

2) Location: tissue damaged outside the blood circulation triggers the extrinsic pathway, while intrinsic pathway occurs inside the blood circulation

Question 15

Explain how PDGF and VEGF assist with repair of damaged blood vessels

Answer 15

PDGF: stimulates vascular smooth muscle cells to build new vessel wall

VEGF: stimulates endothelial cells to multiply and restore inner endothelial lining

Question 16

Explain the role of prostacyclin in regulation of blood clotting

Answer 16

Prostacyclin, a prostaglandin produced by intact endothelial cells, inhibits platelet activation and limits spread of blood clotting

Question 17

Explain the role of serotonin in regulation of blood clotting

Answer 17

Serotonin at high concentrations inhibits ADP activity.

Recall: ADP attracts and activates more platelets

Question 18

List 5 examples of endogenous anticoagulants

Answer 18

1) Smoothness of endothelial surface
2) Antithrombin III
3) Heparin
4) Thrombomodulin
5) Tissue plasminogen activator

Question 19

Explain the fibrinolysis process.

Answer 19

1) During clot formation, plasminogen is trapped inside the clot. Plasminogen is a plasma protein and protease precursor made by the liver

2) The surrounding tissue and vascular endothelial cells slowly release tissue plasminogen activator (tPA) which cleaves the inactive plasminogen to protease plasmin

3) Plasmin digests fibrin thereby dissolving the clot

4) Macrophages remove the remains of the clot

Question 20

Which vitamin is essential for the synthesis of several clotting factors?

Answer 20

Vitamin K