Atheroma - Revision

Question 1

What are the 3 layers of an arterial vessel?

Answer 1

1. Intima
2. Media
3. Outer adventitia

Question 2

Which layer of the arterial vessel is located closest to the arterial lumen?

Answer 2

Intima

Question 3

What is the intima composed of?

Answer 3

A single layer of endothelial cells (endothelium)

Question 4

Effect of NO and prostacyclin?

Answer 4

Relax blood vessels (vasodilation) and inhibit platelet activation (limit thrombosis)

Question 5

What are NO and prostacyclin released by?

Answer 5

Endothelial cells

Question 6

In normal endothelium, describe and explain the;

a) smooth muscle cells?
b) net coagulant or anticoagulation?
c) adhesion molecules?

Answer 6

a) relaxed - due to release of NO and prostacyclin
b) net anticoagulant properties
c) no expression of leucocyte adhesion molecule

Question 7

How does the endothelium modulate contraction of smooth muscle cells in the media?

Answer 7

By releasing substances such as vasodilators and vasoconstrictors

Question 8

Examples of vasodilators?

Answer 8

NO and prostacyclin

Question 9

Example of vasoconstrictor?

Answer 9

Endothelin

Question 10

What does ‘endothelial cell activation’ refer to? What could this be caused by?

Answer 10

Endothelium undergoes changes to allow it to contribute in the inflammatory response.

Caused by e.g: common stresses (e.g. shear stress and mild changes in temperature), transient infections and minor trauma.

Question 11

What are the five core changes of endothelial cell activation?

Answer 11

1. Loss of vascular integrity
2. Expression of leucocyte adhesion molecules
3. Change from antithrombotic to prothrombotic
4. Cytokine production
5. Vasoconstriction

Question 12

What characterises the normal arterial endothelium?

Answer 12

1. Net anticoagulant properties
2. Net relaxation of smooth muscle cells
3. Anti-inflammatory characteristics

Question 13

What is the elasticity of a vessel regulated by?

Answer 13

The lamina elastica

Question 14

Purpose of lamina elastica?

Answer 14

Provide elasticity and prevent the vascular wall from collapsing

Question 15

Why is lamina elastica important in atherosclerosis

Answer 15

it prevents the weakening of the vessel wall that can prevail as a complication of atherosclerosis

Question 16

Where is lamina elastica found?

Answer 16

Between intima and media

Question 17

Normally, what do smooth muscle cells synthesise that contributes to connective tissue matrix of the vessel wall?

Answer 17

Collagen, elastin and proteoglycans

Question 18

What inflammatory and vasoactive mediators do smooth muscle cells synthesis

Answer 18

E.g. IL-6 and TNF-a

Question 19

Effect of IL-6 and TNF-a?

Answer 19

Stimulate leukocyte migration and induce the endothelial cells to express leukocyte adhesion molecules

Question 20

What is an atheroma?

Answer 20

An abnormal accumulation of material in the intima

Question 21

What are the 5 key stages of atheroma formation?

Answer 21

1. Endothelial dysfunction
2. Formation of lipid layer or fatty streak within theintima
3. Migration of leukocytes and smooth muscle cells into the vessel wall
4. Foam cell formation
5. Degradation of extracellular matrix

Question 22

What 3 main stages can the formation of the plaque be divided into?

Answer 22

1. Fatty streak
2. Plaque progression
3. Plaque disruption

Question 23

Does a fatty streak protrude substantially into the artery wall or impede blood flow?

Answer 23

No (people over 20 tend to have)

Question 24

What allows circulating LDLs into the intima?

Answer 24

Disruption of endothelial barrier due to endothelial dysfunction

Question 25

What does entry of lipids into the intima stimulate?

Answer 25

Creates a proinflammatory environment and initiates the migration of leukocytes and formation of foam cells

Question 26

What are factors associated with endothelial dysfunction?

Answer 26

``` Increased age Male sex Family history of CHD Smoking Elevated cholesterol Low HDL-cholesterol Diabetes mellitus Hypertension Obesity High fat consumption ```

Question 27

How does NO function as an anti-atherosclerotic substance?

Answer 27

1. Vasodilation 2. Inhibition of platelet aggregation 3. Anti-inflammatory effects

Question 28

Why are atheromas more likely to occur at sites of bifuraction?

Answer 28

Disturbed flow can impair protective functions

Question 29

How can smoking lead to atheromas?

Answer 29

Exposure to chemical irritants promotes endothelial dysfunction by increasing endothelial production of reactive oxygen species. This leaves the endothelium become inclined to exhibit pro-inflammatory processes, such as secreting inflammatory cytokines.

Question 30

How do macrophages become foam cells?

Answer 30

Macrophages adhere to dysfunctional endothelial cells and transmigrate into the intima. These macrophages are called ‘foam cells’ after they have taken up LDLs.

Question 31

What hypothesis can explain the recruitment of inflammatory cells after injury?

Answer 31

Response to injury hypothesis

Question 32

How do foam cells encourage the plaque progression?

Answer 32

Serving as a source of proinflammatory cytokines.

Question 33

What are the 2 features of an atherosclerotic plaque?

Answer 33

1. Lipid-rich necrotic core | 2. Fibrous cap

Question 34

What does the fibrous cap contain?

Answer 34

Dead foam cells, macrophages, smooth muscle cells, lymphocytes and extracellular matrix

Question 35

How can the vessel compensate during the early stages of the atherosclerotic plaque?

Answer 35

a compensatory outward remodeling of the plaque wall (preserves the diameter of the vessel lumen)

Question 36

Progressive vessel narrowing may result in ischaemia. What are some ischemic symptoms?

Answer 36

angina pectoris or intermittent claudication

Question 37

During the phase of transition from fatty streak to plaque formation, where do the smooth muscle cells migrate from/to?

Answer 37

From the media to the intima

Question 38

Once in the intima, what do smooth muscle cells do?

Answer 38

proliferate within the intima and secrete extracellular matrix molecules

Question 39

What do foam cells release that directly contribute to the migration and proliferation process of SMCs?

Answer 39

platelet derived growth factor (PDGF), cytokines and growth factors

Question 40

What predisposes a plaque to rupture? What influences this process?

Answer 40

Metabolic processes in extracellular matrix weaken the fibrous cap. This process is influenced by the balance of matrix deposition synthesis by smooth muscle cells and degradation by matrix metalloproteinases (MMP)

Question 41

What is MMP secreted by?

Answer 41

Foam cells that are stimulated by inflammatory cytokines

Question 42

How does MMP weaken the fibrous cap?

Answer 42

degrades collagen and elastin of the fibrous cap

Question 43

What causes the lipid core to grow?

Answer 43

Cell death leads to release of cellular contents, whereby more lipids and cellular debris is absorbed to the dynamic lipid core

Question 44

What is released when the fibrous cap is ruptured? What does this lead to?

Answer 44

The highly thrombogenic components of the necrotic core are in direct contact with the circulating monocytes in the blood Will lead to the formation of thrombus at the rupture site.

Question 45

What does inflammatory stimuli in the plaque environment iniciate?

Answer 45

smooth muscle cells, endothelial cells, and foam cells to release tissue factor that initiates the extrinsic coagulation pathway also stimulate expression of antifibrinolytics

Question 46

How can activated endothelial cells contribute to thrombosis?

Answer 46

depositing fibrin at the vascular wall

Question 47

What are the most common locations of atherosclerosis?

Answer 47

1. Dorsal section of the abdominal aorta 2. Proximal coronary arteries 3. Popliteal arteries 4. Descending thoracic aorta 5. Internal carotid arteries 6, Renal arteries

Question 48

What is angina pectoris?

Answer 48

chest pain or discomfort due to coronary heart disease --> when the heart muscle doesn't get as much blood as it needs

Question 49

What are the 2 ways in which atherosclerosis can cause occlusion?

Answer 49

1. Growing plaque/thrombus occluding vessel | 2. Embolisation

Question 50

What are the 4 major clinical consequences of atherosclerosis?

Answer 50

1. Acute narrowing of vessel lumen 2. Chronic occlusion 3. Embolism 4. Aneurysm

Question 51

If the thrombus formed after plaque rupture causes a complete occlusion, what can it result in? What can this manifest as?

Answer 51

results in ischemic necrosis (infarction) of the tissue manifested as stroke, MI, gangrene of several possible organs such as intestine, spleen or lower extremities

Question 52

What characterises chronic occlusion?

Answer 52

When the occlusion is gradual and incomplete, it may chronically disturb the blood supply to tissues

Question 53

What can chronic occlusion lead to? What are the clinical manifestations?

Answer 53

This can result in chronic ischemia of those tissues Manifestations: - angina pectoris - intermittent claudication - organ atrophy (atrophy due to impairment of blood flow )

Question 54

What is embolisation?

Answer 54

The transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites.

Question 55

Fragments of thrombi in abdominal aorta may transfer to the popliteal artery. What may this result in?

Answer 55

Gangrene of the leg

Question 56

How can a plaque lead to an aneurysm?

Answer 56

Atherosclerotic lesion may extend into the medial layer, resulting into atrophy and loss of elastic tissue. This can subsequently cause dilatation and weakness of the artery, forming aneurysm.

Question 57

What are dangers of aneurysms?

Answer 57

may suddenly rupture

Question 58

Purpose of expression of leucocyte adhesion molecules in endothelial activation?

Answer 58

Facilitates the recruitment and attachment of circulating leukocytes to the vessel wall.

Question 59

What is endothelial cell activation typically induced by?

Answer 59

Endothelial cell activation is typically induced by proinflammatory cytokines, such as TNF-α and IL-6