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CARDIO & RESPIRATORY phase 1b > 1b Vascular Endothelium > Flashcards

1b Vascular Endothelium Flashcards

1
Q

What are blood vessels lined by?

A

Endothelial cells

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2
Q

What are the three layers of blood vessels, except capillaries and venules?

A

Tunica Adventitia - vasa vasorum and nerves
Tunica Media - external elastic membrane and smooth muscle
Tunica Intima - endothelium - lamina propria

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3
Q

What is contained within the lamina propria?

A

Smooth muscle and connective tissue

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4
Q

What is the site of exchange of nutrients and oxygen between blood and tissues?

A

Capillaries

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5
Q

What 2 features are capillaries and venules supported by?

A

Mural cells (pericytes) - regulate blood vessel diameter

Basement membrane - filter for substances

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6
Q

What properties do endothelial cells have?

A

Organotypic - tissue specific properties with unique gene/protein expression proteins

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7
Q

Why does microvasculature look different in different organs?

A

Endothelial cells are heterogenic

Endothelial cells and microvasculature have organotypic (tissue-specific) properties and expression profiles

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8
Q

What is the surface area thickness diameter and weight of the endothelium?’

A

Surface area > 1000m^2

Weight > 100g

1-2 micrometer thick

10-20 micrometer in diameter

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9
Q

What is contact inhibition?

A

Endothelial cells forming cell-cell junctions signal to one another when they make contact to inhibit each other’s further growth

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10
Q

What is the proliferation rate of endothelial cells?

A

Low proliferation rates, unless new vessels are required = angiogenesis

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11
Q

What are the 6 main functions of blood vessels and tissues that are controlled by endothelium?

A

Permeability
Angiogenesis
Vascular Tone
Inflammation
Tissue homeostasis and regeneration
Haemostasis and Thrombosis

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12
Q

At resting state, what does the endothelium induce with respect to inflammation, thrombosis and proliferation?

A

The endothelium is:

Anti-inflammatory

Anti-thrombotic

Anti-proliferative

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13
Q

When activated, how does the endothelium change to suit a pro-inflammatory environment?

A

The endothelium is:

Pro-inflammatory

Pro-thrombotic

Pro-angiogenic

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14
Q

What different environmental / physiological factors can lead to an activated endothelium?

A

Inflammation

Mechanical stress

Ox LDL

High blood pressure

Smoking

Viruses

High glucose

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15
Q

What is angiogenesis?

A

The formation of new vessels by sprouting from existing vessels

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16
Q

What is the main trigger for angiogenesis?

A

Hypoxia

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17
Q

What three physiological events is angiogenesis needed for?

A

Development
Menstrual Cycle
Wound Healing

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18
Q

What are pathological causes for angiogenesis?

A

Cancer
Retinopathies
Atherosclerosis

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19
Q

What 4 things can an activated endothelium lead to, as implicated in the pathophysiology of atherosclerosis?

A

1) Thrombosis

2) Leukocyte recruitment

3) Senescence - cell stops dividing but does not die

4) Permeability

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20
Q

How do tumours stimulate angiogenesis?

A

Secretes angiogenic factors that stimulate migration, proliferation and neovessel formation by endothelial cells in adjacent established vessels

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21
Q

What is the angiogenic switch?

A

When the amount of angiogenic factors released > the amount of anti-angiogenic, so new vessel formation occurs which then supplies the tumour

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22
Q

Describe the shape of tumour blood vessels?

A

Irregularly shapes, dilated, tortuous

23
Q

How are tumour blood vessels organised?

A

Not into definitive venules, arterioles and capillaries

24
Q

What are two characteristics of tumour blood vessels?

A

leaky and heamorrhagic = due to overproduction of VEGF

25
Q

What is thromboinflammation?

A

Loss of anti-thrombic and anti-inflammation functions of endothelial cells causing thrombosis with associated inflammation

26
Q

How does VWF impact angiogenesis?

A

Controls blood vessel formation and integrity partly by regulating growth factor signalling

27
Q

In response to injury, what is the pathogenesis of atherosclerosis??

A

1 - Endothelial Dysfunction in Atherosclerosis
= Endothelial permeability ↑
= Leukocyte migration ↑ into the subendothelial space
= Leukocyte adhesion = ↑

2 - Fatty Streak Formation in Atherosclerosis
= fatty-Streak Formation

  1. Formation of an advanced lesion
    = Macrohpgae accumulation
    = Formation of necrotic core
    = Angiogenesis
28
Q

Recruitment of blood leukocytes into tissues normally takes place during inflammation, where do leukocytes adhere to?

A

Adhere to endothelium of post-capillary venules and transmigrate into tissues

29
Q

In atherosclerosis, where do leukocytes adhere to and what happens after it does this?

A

Activated endothelium of large arteries

Gets stuck in the subendothelial space

30
Q

What is a post-capillary venules?

A

Structure similar to capillaries but more pericytes

31
Q

What happens to monocytes when they migrate to the sub-endothelial space?

A

Differentiate into macrophages and become foam cells

32
Q

What is the endothelium important in regulating?

A

The flux of fluids and molecules from blood to tissues and vice verca

33
Q

What is the consequence of increased vascular permeability?

A

Results in leakage of plasma proteins through the junctions into the sub-endothelial space

34
Q

How does the increased permeability of the endothelium lead to atherosclerosis?

A

Lipoproteins enter subendothelium through weaknesses in the endothelium which then bind to proteoglycans and the lipoproteins are oxidated in the environment of the subendothelium

Macrophages come and agglutinate the proteoglycan-lipoprotein complexes which leads it to become a foam cell

35
Q

Where do atherosclerotic plaques preferentially occur?

A

At bifurcations and curvatures of the vascular tree

36
Q

Why do atherosclerotic plaque prefer to occur at bifurcations of blood vessels?

A

The flow patterns and haemodynamics forces are not uniform in the vascular system

37
Q

What is the wall shear stress?

A

Force per unit area exerted by the wall on the fluid in a direction on the local tangent plane

38
Q

In straight parts of the arterial tree what is the wall shear stress described as?

A

high and directional

39
Q

In branches and curvatures, how is blood flow disturbed and what is the resultant effect on wall shear stress?

A

Blood flow is disturbed with non-uniform and irregular distribution of low wall shear stress

40
Q

What four things does laminar blood flow promote?

A

Anti-thrombotic, anti-inflammatory factors
Endothelial survival
Inhibition of SMC proliferation
Nitric Oxide (NO) production

41
Q

What does disturbed blood flow promote?

A

Thrombosis

Inflammation (leukocyte adhesion)

Loss of Nitric Oxide production

Endothelial apoptosis

SMC proliferation

42
Q

What are 6 functions of Nitric Oxide that make it essential for the health of the cardiovascular system?

A
  1. Vasodilation
  2. reduce platelet activation
  3. Inhibits monocyte adhesion
  4. Inhibits proliferation of SMC in the vessel wall
  5. Reduces release of superoxide radicals
  6. Reduces oxidation of LDL cholesterol (major constituent of plaque)
43
Q

What does angiogenesis promote?

A

Plaque growth

Therapuetic angiogenesis prevents damage post-ischemia

44
Q

Is coagulopathy associated with high or low levels of D-Dimers and Fibrinogen?

A

high

45
Q

In severe Covid-19, what could be used as a marker for endothelial injury?

A

Levels of circulating endothelial cells

High D-Dimer levels would be a marker for disease progression

-

46
Q

How are endothelial cells involved in the propagation of COVID-19 infection?

A

SARS-CoV2 Infection = Cytokine storm = endothelial activation = procoagulant switch

47
Q

How would you decrease the increased circulating endothelial cells in COVID-19 patients due to endothelial damage?

A

Give anticoagulants

48
Q

What does a higher than normal D-Dimer level mean?

A

That you have significant blood coagulation

49
Q

High levels of troponin?

A

An issue with the heart as it releases troponin into the blood following an injury such as a myocardial infarction

50
Q

What is the main 2 mechanisms by which COVID can cause activation and damage to the endothelium?

A

Cytokine storm secondary to SARS-CoV2 infection causes endothelial damage

SARS-CoV2 enters endothelial cells and causes direct damage

51
Q

Is ACE2 expressed on epithelial or endothelial cells?

A

Epithelial

52
Q

Does SARS-CoV2 replicate in endothelial cells?

A

no

53
Q

What are the factors which the microvascular endothelial cells produce?

A

Angiocrine factors

54
Q

What are angiocrine factors?

A

Angiocrine factors are factors which can promote the tissue repair of specific tissues - vital for the maintenance of tissue homeostasis and regeneration

CARDIO & RESPIRATORY phase 1b (14 decks)

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