08-02-22 - Atherosclerosis

Question 1

Learning outcomes

Answer 1

• To identify the risk factors for atherosclerosis
• To explain the pathogenesis of atherosclerosis
• To identify and explain the morphology of atheroma
• To discuss about clinical features and prevention of atherosclerosis

Question 2

Learning outcomes

Answer 2

• To identify the risk factors for atherosclerosis
• To explain the pathogenesis of atherosclerosis
• To identify and explain the morphology of atheroma
• To discuss about clinical features and prevention of atherosclerosis

Question 3

What are 7 risk factors of atherosclerosis?

Answer 3

• Risk factors of atherosclerosis:
• Age
• Sex
• Genetics
• Hyperlipidaemia
• Hypertension
• Smoking
• Diabetes mellitus

Question 4

What are the 6 steps in the pathogenesis (development) of atherosclerosis?

Answer 4

• Steps in the pathogenesis of atherosclerosis:

1) Chronic endothelial injury / dysfunction
2) Role of lipids
3) Role of macrophages
4) Smooth muscle proliferation
5) Formation of a fibro-lipid plaque
6) Injury to the plaque – thrombus formation

Question 5

What do haemodynamic disturbances cause?

What 6 things causes haemodynamic disturbances?

What are 3 consequences of endothelial injury?

Answer 5

• Haemodynamic disturbances cause endothelial injury
• Cause of haemodynamic disturbances:

1) Hypercholesterolemia
2) Hypertension
3) Smoking
4) Toxins
5) Viruses
6) Immune reactions

•	Consequences of endothelial injury:
1)	Increase in endothelial permeability 
2)	Increase in leukocyte adhesion 
3)	Increase in monocyte adhesion and migration 
 

Question 6

What is hypercholesterolaemia?

How does this affect endothelial function?

Where does LDL accumulate in this condition?

What does this cause?

What happens when Macrophages ingest LDL?

What are these chemotactic for?

What happens to the motility of macrophages?

What does this stimulate the release of?

How do these effect endothelial and smooth muscle cells?

Answer 6

• Hypercholesterolaemia is a form of hyperlipidaemia, where there is too much bad LDL cholesterol in the blood
• This impairs endothelial function
• In this condition, LDL cholesterol accumulates in the tunica intima, which causes oxidative modification of LDL
• When macrophages in the tunica intima ingest LDL cholesterol via scavenger receptors, they become foam cells
• These foam cells are very chemotactic for monocytes, which come into the tunica intima and become macrophages
• Ingesting the LDL cholesterol will inhibit motility in the macrophages
• This stimulates the release of cytokines, which are cytotoxic to endothelial and smooth muscle cells

Question 7

What are the 3 roles of macrophages in the development of atherosclerosis?

Answer 7

• Role of macrophages in development of atherosclerosis:

1) Macrophages engulf oxidised LDL to from Foam cells
2) The secret various factors, such as Interleukin 1 and Growth factors, which will be chemotactic for more monocytes
3) Macrophages can form a fatty streak, which the first grossly visible (to the naked eye) lesion in the development of atherosclerosis

Question 8

Role of smooth muscles in the development atherosclerosis.

What does the fatty streak mature into?

What 3 steps is this done in?

Answer 8

• The fatty streak matures into fibrofatty atheroma
• Steps of this process:

1) The smooth muscle enters the tunica intima, which help in formation of collagen on the surface of fibrous tissue, causing a fibrous cap
2) In the centre of the atheroma, foam cells will eventually die, the LDL cholesterol will crystalise and will group together in the centre forming a lipid necrotic debris
3) It is now a full formed fibrofatty atheroma

Question 9

What is morphology?

What is the morphology of atherosclerosis?

What are the 6 sites atheromas can occur from most likely to least likely?

What are 5 complications that can rise due to atheroma?

Answer 9

• Morphology is the visual study of anomalies caused by diseases
• Morphology of atherosclerosis is an atheromatous (fibrofatty, fibro-lipid) Plaque which:

1) Is patch and raised white to yellow 0.3-1.5cm
2) Has a core of lipid
3) Has a fibrous cap

• 6 sites atheromas can occur from most likely to least likely:

1) Abdominal aorta
2) Coronary arteries
3) Popliteal arteries
4) Descending thoracic aorta
5) Internal carotid arteries
6) Vessels of the circle of Willis

• 5 complications that can rise due to atheroma:

1) Calcification
2) Rupture or ulceration
3) Haemorrhage
4) Thrombosis
5) Aneurysmal dilation (when the ascending aortic diameter reaches or exceeds 1.5 times the expected normal diameter)

Question 10

Atherosclerosis morphology pictures

Answer 10

Question 11

What do fatty streaks consist of?

What might they be precursors to?

Answer 11

• Fatty streaks consist of foam cells + T lymphocytes

* Fatty streaks may be precursors to plaques

Question 12

When does the clinical phase of atherosclerosis occur?

What 3 things can this be characterised by?

Answer 12

• The clinical phase of atherosclerosis usually occurs in the middle age to the elderly
• This can be characterized by:
1) Aneurysm (ballooning at weak spot) and rupture
2) Occlusion (closing of hollow organ or vessel) by thrombus
3) Critical stenosis (narrowing)

Question 13

What are 5 primary methods of prevention of atherosclerosis?

What are 3 secondary methods?

Answer 13

• 5 primary methods of prevention of atherosclerosis:

1) Stop smoking
2) Control hypertension
3) Weight reduction
4) Lowering total LDL
5) Reduce calories intake

• Secondary prevention methods:

1) Prevent complications
2) Antiplatelet drugs in thrombosis
3) Lower blood lipid levels