Endothelial Cell Function & Hemostasis

Question 1

prothrombotic

Answer 1

promote clot formation

Question 2

antithrombotic

Answer 2

inhibit clot formation

Question 3

Normal Hemostasis major role

Answer 3

-Maintain blood in fluid state & prevent thrombi
formation in healthy state
-Rapidly produce localized and controlled thrombus at site of vessel injury; remove as quickly as possible once vessel heals

Question 4

thrombus is

Answer 4

a clot that forms “in vivo”-so in animal and contains fibrin, platelets and other blood cells

Question 5

What forms first after vascular injury?

Answer 5

Primary hemostatic plug

Question 6

What is not directly involved in the formation of a primary hemostatic plug?

Answer 6

Tissue factor

Question 7

What role does von Willebrand factor play in
hemostasis?

Answer 7

Tethers platelets to collagen in subendothelial matrix

Question 8

What role do platelets play in coagulation?

Answer 8

Provide phospholipid surface for coagulation factors

Question 9

What is the physiologically most important activator of coagulation?

Answer 9

Tissue factor

Question 10

What factor is activated by collagen in the subendothelial matrix at the start of the intrinsic pathway?

Answer 10

Factor XII

Question 11

What is the primary role of the intrinsic pathway in coagulation in vivo?

Answer 11

Amplification

Question 12

What roles do thrombin play in hemostasis?

Answer 12

A. Activate factor XI
B. Activate platelets
C. Breakdown fibrinogen to fibrin

Question 13

Which is the physiologically most important inhibitor of coagulation?

Answer 13

Antithrombin (AT; AKA ATIII) it inhibits not just thrombin but all enzymes in the coagulation cascade

Question 14

What is the role of fibrinolysis in hemostasis?

Answer 14

Break down clots after they form

Question 15

Which is the physiologically most important activator of the fibrinolytic pathway?

Answer 15

Tissue plasminogen activator (TPA)

Question 16

Endothelial cells line

Answer 16

the lumen of heart, blood vessels, and lymphatic
vessels

Question 17

Endothelial cells are a specific type of

Answer 17

simple squamous epithelial cell

Question 18

What links endothelial cells together

Answer 18

Are linked to together (= cohesive) by cell junctions

Question 19

What do tight junctions do

Answer 19

Most arteries and veins endothelial cells have tight junctions that limit flow of cells and other blood constituents into tissue

Question 20

Role of endothelial cells in health; gatekeepers

Answer 20

• Regulate interactions between components in the blood (cells, proteins, fluids) and underlying extravascular tissue
• Selective permeability barrier to control the
  movement of molecules from the blood to the
  tissues and vice versa

Question 22

____ ______ soluble molecules (e.g., oxygen, carbon dioxide) readily pass through endothelial cell membranes via ______ diffusion

Answer 22

Small lipid, simple

Question 23

Which cells prevent inappropriate blood clotting in health & promote blood clotting following vessels injury

Answer 23

Endothelial cells in health

Question 24

Endothelial cells regulate _____ _____ and vacular resistance by ……..

Answer 24

Regulate blood flow and vascular resistance by the production, conversion or inactivation of substances that cause vasoconstriction or
vasodilation

Question 25

Examples of vasodilators

Answer 25

nitrous oxide (NO) and prostacyclin (PGI2)

Question 26

Examples of vasocontrictors

Answer 26

thromboxane A2 (TxA2) and endothelin-1

Question 27

Endothelial cells mediate changes in the expression of

Answer 27

surface adhesion molecules

Question 28

Endothelial cells produce

Answer 28

mediators that regulate the interaction between circulating leukocytes (WBCs like lymphocytes and neutrophils) and the vessel wall

Question 29

Endothelial cells produce and secrete various growth factors or growth inhibitors that regulate

Answer 29

the production and function of other cells

Question 30

Endothelial cells promote

Answer 30

wound healing and new vessel growth in tissue following injury.

Question 31

Endothelial cells vary according to the type of _____ and the _____ the vessel is in

Answer 31

Endothelial cells vary according to the type of vessel (artery vs vein vs capillary) and the tissue the vessel is in (e.g. brain vs lung)

Question 32

Contributors to variety of endothelial cells is

Answer 32

force of blood flow, amount of smooth muscle in the wall, size of lumen

Question 33

Endothelial cells in arteries (high pressure and flow) play major role in

Answer 33

regulating vascular tone

Question 34

Endothelial cells in veins (low pressure and flow) play major role in

Answer 34

cell trafficking and immune function

Question 35

Phenotypes (eg.,receptors expressed on membrane) vary depending on ______ - help the cells perform maximally in specific environments and allow for a

Answer 35

location, a different response to the same stimulus depending on their phenotype

Question 36

True/ False; Endothelial cells express a variety of adhesion molecules and receptors on their surface membranes

Answer 36

True, they communicate with soluble factors and cells in the blood

Question 37

Expression of adhesion molecules and receptors change depending on their

Answer 37

environment and state of activation

Question 38

Activation result in changes in membrane receptors and substance produced such as

Answer 38

(e.g. mediators of inflammation, growth factors, vasomodulatory compounds)

Question 39

What signals from other cells change the membrane receptors and substances produced

Answer 39

e.g. vascular smooth muscle cells, blood cells like platelets and leukocytes), soluble molecules in the blood (e.g., hormones, cytokines), oxygen levels in the blood, and mechanical forces (e.g. blood pressure, blood flow)

Question 40

Examples of endothelial cell activators

Answer 40

bacterial and viral antigens, products of the complement cascade, mediators produced by inflammatory cells, decreased tissue oxygen levels and a variety of products of lipid metabolism

Question 41

In health, endothelial cells inhibit

Answer 41

clot formation, platelet activation & binding

Question 42

Endothelial cells inhibit clot formation by producing

Answer 42

PGI2 and an enzyme to break down ADP, an important platelet activator

Question 43

Endothelial cells will also inhibit the coagulation cascade by expressing

Answer 43

Express surface heparin-like molecules (heparan sulfate: cofactor for antithrombin III) * Express receptor called thrombomodulin that binds thrombin → thrombin inhibition & activation of protein C pathway which inhibits coagulation * Release inhibitor of tissue factor pathway

Question 44

Endothelial cells produce what that will them stimulate fibrinolysis?

Answer 44

tissue plasminogen activator (TPA)

Question 45

Endothelial cells have ____ charge to repel

Answer 45

Negative surface charge to repel cells like platelets

Question 46

Platelet Adhesion activation

Answer 46

-release vWF -produce platelet activators -express platelet adhesion molecules -down regulate platelet inhibitors

Question 47

Coagulation Stimulation

Answer 47

-TF expression - decreased TM -decreased Heparin sulfate -decreased inhibitors of TF

Question 48

Endothelial cell becomes prothrombotic following injury or activation and will release

Answer 48

Release substances to cause vasoconstriction to slow blood flow

Question 49

Prothrombotic endothelial cell will inhibit fibrinolysis by

Answer 49

produce PAI to bind to & inhibit tPA

Question 50

Which of the following is not a cause of prolonged CRT in a dog?

Answer 50

Anemia, b/c while it will likely cause the gums to become pale- it should not affect the ability for them to fill.

Question 51

Why does tissue edema occur with endothelial cell damage?

Answer 51

B/c if these cells that create the barrier to keep most fluid out are destroyed then the fluid will come flooding in which is what edema is= extracellular fluid accumulation

Question 52

tight cell junctions limit transfer of

Answer 52

large molecules or cells from blood to tissue

Question 53

Do small hydrophobic molecules (eg, O2, CO2) readily pass through the permeability barrier?

Answer 53

Yes

Question 54

Water soluble molecules (eg, proteins, glucose) must be

Answer 54

transported

Question 55

Based upon your understanding of the structure of blood vessels, why are petechiae( small pinpoint hemorrhages into tissues arising from leakage of blood, typically from capillaries) common in dogs with heatstroke?

Answer 55

Capillaries don't have the same layers of muscle that veins and arteries do and so if you damage capillaries it is much more likely to cause blood leakage than if there was damage to artery or vein

Question 56

Animals with heatstroke are prone to excessive clot formation in the microvasculature which may cause additional cell death and tissue loss due to further impairment of blood flow. Why?

Answer 56

Additional cell death means we are losing endothelial cells and whatever has survived now expresses its prothrombotic activity and produce things that activate platlets and encourage clotting

Question 57

Roles of Endothelial cells in health

Answer 57

* Antithrombotic surface to prevent inappropriate clot formation * Keeps components of blood away from subendothelial tissue

Question 58

Roles of Endothelial cells in injury

Answer 58

* Loss exposes subendothelial tissue that express prothrombotic molecules to activate platelets (e.g. collagen) and coagulation system (e.g. tissue factor) * Surrounding endothelial cells express prothrombotic activities

Question 59

Role of vessels in hemostasis

Answer 59

* Vasoconstriction -Neurogenic reflex in response to injury to decrease blood flow -Response to release of vasoactive substances -Limits blood loss but usually insufficient by itself to prevent blood loss

Question 60

Healthy endothelial cells are prothrombotic or antithrombotic to prevent clot formation?

Answer 60

antithrombotic

Question 61

Loss of endothelium causes exposure of what activator of the coagulation cascade that is not normally found on resting endothelial cells or any unactivated cells in the blood?

Answer 61

Tissue factor

Question 62

What is a prothrombotic activity of endothelial cells?

Answer 62

decrease production of platelet inhibitors