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Module 1 > The role of the endothelium > Flashcards

The role of the endothelium Flashcards

1
Q

Define endothelium

A

Vascular endothelium - a layer of thin flat cells which line the interior surface of the blood vessels and form an interface between the circulating blood in the lumen and the vessel wall

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2
Q

What are the humoral factors which regulate the endothelial function?

A

Acetylcholine

Bradykinin

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3
Q

What are the inflammatory mediators that regulate the endothelial function?

A

Histamine
Thrombin TNFalpha
Traffics blood cells to the sites of injury

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4
Q

What are the physical factors that affect the endothelium?

A

Shear stress

Stretch hypoxia

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5
Q

How is vascular tone maintained?

A

It is a balance between vasodilatory molecules and constricting ones
NO, PGI2, Natriruretic peptides are relaxing
ET1 contraction of smooth muscle surrounding

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6
Q

How is NO synthesised and what are its effects?

A

It is synthesised from L-arginine in the endothelium by NO synthase, increased cGMP by activating sobule guanylyl cyclase
Inhibits thrombosis, inflammation and coagulation

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7
Q

What is NO synthesis responsive to?

A

Bradykinin and acetylcholine

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8
Q

How is PGI synthesised and what are its effects?

A

It is synthesised by the ECs and Sm by COX from AA
It cause SM relaxation by increasing cAMP
This has a anticoagulant effect as it inhibits platelet aggregation and SMC proliferation

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9
Q

How is PGI synthesised and what are its effects?

A

It is synthesised by the ECs and Sm by COX from AA
It cause SM relaxation by increasing cAMP
This has a anticoagulant effect as it inhibits platelet aggregation and SMC proliferation

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10
Q

how are naturietic peptides synthesised and what are the effects?

A

Different types synthesised by different places: Brain, Heart etc
release is in response to atrial and ventricular distension
They act as transmembrane guanylyl cyclases and catalyse the synthesis of cGMP and induce vasorelaxation to counteract RAAS

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11
Q

What are the 3 vasoconstrictors?

A

Endothelin - 1
Angiotensin II
Thromboxane

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12
Q

What are the 2 types of endothelin-1 and what are its effects?

A

There is ETa and ETb and they have different effects based on location
The ETa mediates vasoconstriction
The ETb mediates vasodilation in the EC and vasocontriction in SM

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13
Q

How does Endothelin 1 have its effects? and what are they stimulated by?

A

They activated the ETA and ETb receptors in response to hypoxia, stretch, cytokines and endotoxin
In EC - activated NO and vasodilates
in SM - causes vasoconstriction

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14
Q

Wha is angiotensin II and what are its effects? What receptors does it act on?

A

Peptide hormone that causes vasoconstriction and increase in BP
AT1R and AT2R are expressed in the endothelium and proportion determines the vascular effects of ATII

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15
Q

What are the effects of AT1R stimulation?

A

Vasoconstriction by enhanced ET1 , ROS production by NADPH that mop up NO, increased thromboxane and increase TF leading to increased coagulation

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16
Q

What are the effects of AT2R stimulation?

A

Bradykinin release and vasodilation, increased prostacyclin production

17
Q

How does thromboxan mediate the endothelium tone?

A

Produces ROS, this inhibits NO synthesis leading to vasoconstriction and promotes platelet activation

18
Q

How does thromboxan mediate the endothelium tone?

A

Produces ROS, this inhibits NO synthesis leading to vasoconstriction and promotes platelet activation

19
Q

What is the role of the transcellular pathway?

A

they must cross the cell but only small molecules

20
Q

What is the role of the paracellular route?

A

These are larger molecules and they pass through interendothelial junctions

21
Q

What are the 3 types pf endothelial junctions in the paracellular pathway?

A

Adherens
Tight
Gap

22
Q

What do the adherens junctions associate with?

A

They associate with actin cytoskeleton on the cytoplasmic side providing additional support for junctions

23
Q

What is an important distinction between angiogenesis and vasculogenesis?

A

Angiogenesis is growth of blood vessels from existing vasculatutre
Vasculogenesis defines de novo formation of vascular network of precursor cells

24
Q

Give an example of a mediator of angiogenesis

A

VEGF

25
Q

How is coagulation regulated by the endothelium?

A

It produces many more anticoagulants than procoagulants and balance changes can occur in pathology

26
Q

What are some examples of things that can influence the pro/anti coagulant balance?

A

Inflammation
Mechanical injury of the endothelium
Metabolic stress leading to endothelial activation
Oxidative stress

Module 1 (25 decks)

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