Pathophysiology of Atheroma

Question 1

What is an atheroma?

Answer 1

A focal elevated lesion in the intima of large and medium sized arteries

Question 2

What happens when an atheromatous plaque forms in the coronary arteries?

Answer 2

The lumen becomes narrowed and the heart becomes ischaemic

Question 3

What cause angina

Answer 3

An atheroma in a coronary artery causing ischaemia

Question 4

List the constituents of a normal artery wall

Answer 4

1. Intima (made of endothelium and internal elastic lamina)
2. Media (made of elastic tissue)
3. Adventitial (made of the external elastic lamina)

Question 5

What is the most important risk factor associated with atheroma?

Answer 5

Hypercholesterolaemia

Question 6

describe the pathogenesis of the genetic mutation which causes hypercholesterolaemia

Answer 6

A lack of adequate LDL receptors on the surface of cells means that LDL remains in the blood

Question 7

Describe the major clinical signs of hyperlipidaemia

Answer 7

• Corneal arcus (premature)
• Tendon xanthomata (knuckles, Achilles)
• Xanthelasmata

Question 8

Other than hypercholesteraemia, list 5 significant risk factors for atheroma

Answer 8

• Smoking
• Hypertension
• Diabetes mellitus
• Male
• Elderly

Question 9

Describe the three steps of atheroma development

Answer 9

1. Development of a fatty streak in young children
2. Development of an early atheromatous plaque in young adults
3. Fully developed atheromatous plaque

Question 10

What does the fatty streak and the early atheromatous plaque comprise?

Answer 10

masses of lipid laden macrophages

Question 11

Describe the structure of a fully developed atheromatous plaque

Answer 11

a central lipid core with a fibrous tissue cap. The whole structure will be covered by the arterial endothelium.

Question 12

What 2 constituents make up the fibrous cap of atheromas and where do they come from?

Answer 12

Collagens produced by smooth muscle cells
Inflammatory cells (macrophages, T-lymphocytes and mast cells) recruited from the arterial endothelium

Question 13

What is the lipid core of an atheroma made of?

Answer 13

Cellular lipids/debris derived from the lipid laden macrophages which died in the plaque

Question 14

What is the lipid core surrounded by (underneath the fibrous cap)?

Answer 14

a rim of foamy macrophages

Question 15

Why are the macrophages foamy?

Answer 15

they are “foamy” due to the uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor

Question 16

What happens to the plaque structure later in developement?

Answer 16

It is subject to extensive dystrophic calcification

Question 17

What can be used as a marker for atheromas in angiograms/CT scans?

Answer 17

Dystrophic calcification

Question 18

Where in a blood vessel network do atheromas form and why?

Answer 18

They form at arterial branching points/bifurcations due to the turbulent nature of the blood flow in these regions

Question 19

Which three events can result in a complicated atheroma?

Answer 19

1. Haemorrhage into the plaque
2. Plaque rupture
3. Fissuring and thrombosis

Question 20

List the 2 steps in the process os atheromatic plaque development (with regards to the vessel wall)

Answer 20

1. Injury to the endothelial lining of an artery occurs (accumulation of LDL in the vessel wall, monocyte adhesion to the endothelium and migration into the intima and transformation into foamy macrophages)
2. Chronic inflammation and healing response of the vascular wall causes further injury (Platelet adhesion, a factor released from activated platelets and macrophages cases smooth muscle cell recruitment and proliferation, extracellular matrix production and T cell recruitment. lipids accumulate)

Question 21

Name the two main causes of endothelial injury (the fist step in the development of an atheromatic plaque)

Answer 21

1. haemodynamic disturbance (e.g. turbulent flow)

2. Hypercholesteraemia

Question 22

Explain how hypercholesteraemia causes endothelial injury

Answer 22

Chronic hypercholesterolaemia can directly impair endothelial cell function by increasing local production of reactive oxygen species.
lipoproteins aggregate in the intima and are modified by the free radicals produced by inflammatory cells. The modified low density lipoprotein is then accumulated by macrophages but not completely degraded which results in foamy macrophages. These foamy macrophages are toxic to endothelial cells and release of growth factors & cytokines

Question 23

Explain the process by which injured endothelial cells become highly permeable to LDL

Answer 23

Injured endothelial cells are functionally altered which results in them producing an abnormally high quantity of cell adhesion molecules (ICAM-1, E-selectin), which makes the endothelia highly permeable to LDL and increases thrombogenicity

Question 24

Explain the process by which an atheromatic plaque increases in size over time

Answer 24

Small areas of endothelial loss cause microthrombi to form at the denuded areas of the plaque surface
This happens over and over again which slowly increases the size of the plaque

Question 25

List the 4 pathologies caused by atheromous plaques which have serious clinical consequences

Answer 25

1. Progressive lumen narrowing (stenosis)
2. Acute atherothrombotic occlusion
3. Embolisation of the distal arterial bed
4. Ruptured atheromatous abdominal aortic aneurysm

Question 26

Carotid artery atheromatous debris is a common cause of ______

Answer 26

Stroke

Question 27

Aneurysms > ____cm diameter are considered to be at high risk of rupture

Answer 27

5cm

Question 28

What is a mural thrombus and where can it embolise to?

Answer 28

Mural thrombus = thrombi that attach to the wall of a blood vessel and cardiac chamber

can embolise to the legs

Question 29

Name the three features of an atheromatous plaque that is vulnerable to rupture

Answer 29

1. Thin fibrous cap
2. Large lipid core
3. Prominent inflammation

Question 30

List the ways in which an atheromatous plaque can be prevented

Answer 30

• Stop smoking
• Control blood pressure
• Weight loss
• Regular exercise
• Dietary modification
• Cholesterol lowering drugs
• Aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)
• Surgical management (removal or bypass of atheromatous vessels)