CVM week 10

Question 0

Which layer of the artery are the majority of the fibroblasts, mast cells located?

Answer 0

Tunica adventitia

Question 1

Which layer of the artery are the majority of the smooth muscle cells located?

Answer 1

Tunica media

Question 2

List some functions of smooth muscle cells?

Answer 2

Normal contractile function, maintain extracellular matrix, contained in the tunica media

Question 3

List some functions of endothelial cells?

Answer 3

Impermeable to large molecules, anti-inflammatory, resist leukocyte adhesion, promote vasodilation, resist thrombosis

Question 4

What is atherosclerosis?

Answer 4

Fibrofatty lesions in the intimal lining of large and medium sized arteries. It is a chronic inflammatory response of the arterial wall initiated because of injury to the endothelium. Inside these lesions are lipids, smooth muscle cells as well as connective tissue

Question 5

What can atherosclerosis lead to?

Answer 5

Progressive narrowing of the arterial lumen which obstructs blood flow- causing ischaemia and promotes thrombus formation

Question 6

Identify five possible changes that can occur in atherosclerosis to altar the integrity of the blood vessel wall and explain their clinical significance?

Answer 6

1. Narrowing of vessel by fibrous plaque- increased wall rigidity
2. Plaque ulceration or rupture - thrombosis
3. Intrapleural haemorrhage -narrowing of lumen, MI,Stroke
4. Peripheral emboli - fragmentation of plaque , emoticons stroke
5. Weakening of vessel walls- aneurysms

Question 7

List some non modifiable risk factors of atherosclerosis?

Answer 7

Male sex,age (over 45 in males, over 55 in females), family history.

Question 8

List some modifiable risk factors for atherosclerosis?

Answer 8

Dyslipidaemia, poor diet (atherogenic), cigarettes smoking, hypertension, diabetes mellitus, metabolic syndrome, obesity, lack of physical activity, thrombogenic state (clotting disorders)

Question 9

What underlies the disease of atherosclerosis?

Answer 9

Abnormal lipid metabolism

Question 10

What is correlated with reduced plaque development?

Answer 10

Dietary restrictions and drug therapy to reduce cholesterol levels

Question 11

What are low density lipoproteins?

Answer 11

They have a role in transporting cholesterol to tissues. High levels of LDL with high cholesterol content are associated with an increased risk of atherosclerosis

Question 12

What are high-density lipoproteins?

Answer 12

They have a role in transporting cholesterol to the liver for excretion. Low levels of HDL are associated with an increased risk of atherosclerosis.

Question 13

True or false : elevated high density lipoprotein particles protect against atherosclerosis?

Answer 13

True

Question 14

What are the three stages in the pathogenesis of atherosclerosis (brief)?

Answer 14

1.fatty streak formation 2.plaque progression 3.plaque disruption

Question 15

Which of the stages of the formation of the atherosclerotic plaque are responsible for that clinically significant manifestations of the disease?

Answer 15

Stages 2.plaque progression and 3.plaque disruption

Question 16

List some factors when in abnormal levels lead to endothelial dysfunction and activation?

Answer 16

Lipoproteins, smoking, cytokines, turbulent flow, oxygen, glucose

Question 17

What are the changes seen in endothelial cells after inflammatory activation?

Answer 17

Increased: permeability, inflammatories cytokines, leukocyte adhesion molecules

Decreased: vasodilatory molecules, antithrombotic molecules

Question 18

What are the changes seen in smooth muscle cells after inflammatory activation?

Answer 18

Increased inflammatory cytokines, extracellular matrix synthesis and migration and proliferation into the sub intima

Question 19

Where do you fatty streaks most commonly occur?

Answer 19

In the aorta and coronary arteries

Question 20

At what age do most people begin to form fatty streaks in their vessels?

Answer 20

By age 20

Question 21

What is the most likely cause of fatty streak initiation

Answer 21

Endothelial dysfunction

Question 22

How is a fatty streak formed?

Answer 22

LDLs leak into intima. They get trapped and oxidised and then increase expression of leukocyte adhesion molecules onto the endothelial cells. This also causes migration of monocytes to the vessel walls

Question 23

Does the fatty streak cause any symptoms?

Answer 23

No

Question 24

How are foam cell formed?

Answer 24

Monocytes enter into the tunica intima and differentiate into macrophages. The macrophages then engulf/imbibe the modified LDL and evolve into a foam cell

Question 25

When foam cells die what did they assist in forming?

Answer 25

The necrotic core

Question 26

what does the accumulation of foam cells in the intima give rise to?

Answer 26

The fatty streak

Question 27

What do foam cells secrete and what does that assist with?

Answer 27

Secrete proinflammatory cytokines, growth factors, interferon (IFN) q, matrix metalloproteinases (MMP), and reactive oxygen species (ROS) that maintain the chemotactic stimulus for leukocytes adhered to the vascular endothelium, increase the expression of scavenger receptors, enhance macrophage replication and regulate SMC accumulation in the intima

Question 28

What are scavenger receptors?

Answer 28

Receptors on macrophages that binds preferentially to oxidised LDL causing macrophages to internalise the LDL

Question 29

Describe stage 2: plaque progression?

Answer 29

Involves smooth muscle migration and proliferation, enhanced lipid accumulation, collagen and other extracellular matrix deposition, lymphocyte infiltration, lipid-rich necrotic core and encapsulation by a fibrous cap Plaque may progress to form stable or unstable plaque

Question 30

What is the necrotic core made up of?

Answer 30

Acellular, lipid rich core including cellular debris from foam cells, endothelial cells and smooth muscle cells

Question 31

What are the predominant factors that affect the stability of an atherosclerotic plaque?

Answer 31

Cell composition and ratio of ECM to lipid content

Question 32

What would a unstable plaque be like?

Answer 32

Thin fibrous cap, large lipid pool,many inflammatory cells, little collagen, large number of macrophages and a small number of smooth muscle cells

Question 33

What would a stable plaque be like?

Answer 33

Small lipid pool, thick fibrous cap, preserved lumen

Question 34

Are stable or unstable plaques more likely to rupture?

Answer 34

Unstable.

Question 35

List some measures that may stabilise an atherosclerotic plaque?

Answer 35

Decreased LDL, increased HDL, decreased angiotensin II, decreased insulin resistance, decreased oxidative stress, decreased blood pressure

Question 36

Describe stage 3: plaque disruption ?

Answer 36

Rupture or erosion of the plaques fibrous cap

Question 37

Where does the rupture most commonly occur in the plaque?

Answer 37

At the shoulder cap of the plaque

Question 38

How does rupture of the plaque lead to thrombosis?

Answer 38

Physical disruption of the atherosclerotic plaque - causes arterial thrombosis as blood coagulant factors contact thrombogenic collagen found in the arterial extracellular matrix and tissue factor produced by macrophage-derived foam cells in the lipid core of lesions.