Atherosclerosis

Question 1

Define atherosclerosis (2 definitions)

Answer 1

-Atherosclerosis is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

-The thickening and hardening of arterial
walls as a consequence of atherosclerosis

Question 2

Define arteriosclerosis

Answer 2

The thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus

Question 3

Describe the macroscopic features of atherosclerosis

Answer 3

Fatty streak
Simple plaque
Complicated plaques

Question 4

What is a fatty streak?

Answer 4

Lipid deposits in intima. Yellow, slightly raisde. Relationship to atherosclerosis somewhat debatable.

Question 5

What is a simple plaque?

Answer 5

Raised yellow/white. Irregular outline. Widely distributed. Enlarge and coalesce.

Question 6

What is a complicated plaque?

Answer 6

Formed from:

• Thrombosis
• Haemorrhage into plaque
•  Calcification
•  Aneurysm formation

Question 7

What are common sites of atherosclerosis?

Answer 7

Aorta - especially abdominal
 Coronary arteries
 Carotid arteries
 Cerebral arteries
 Leg arteries

Question 8

How may atherosclerosis appear microscopically?

Answer 8

Early changes:
- proliferation of smooth muscle cells
- accumulation of foam cells
- extracellular lipid

Later changes:

•  fibrosis
•  necrosis
•  cholesterol clefts
•  +/- inflammatory cells
• disruption of internal elastic lamina
•  damage extends into media
•  ingrowth of blood vessels
•  plaque fissuring

Question 9

What are the potential clinical effects of ischaemic heart disease?

Answer 9

- sudden death
- myocardial infarction
- angina pectoris
- arrhythmias
- cardiac failure

Question 10

What are the potential clinical effects of cerebral ischaemia?

Answer 10

• transient ischaemic attack
• cerebral infarction (stroke)
• multi-infarct dementia

Question 11

What are the potential clinical effects of mesenteric ischaemia?

Answer 11

• ischaemic colitis
• malabsorption
• intestinal infarction

Question 12

What are the potential clinical effects of peripheral vascular disease?

Answer 12

• intermittent claudication
• Leriche syndrome
• ischaemic rest pain
• gangrene

Question 13

What are risk factors for atherosclerosis?

Answer 13

• Age
• Gender
• Hyperlipidaemia
• Cigarette smoking
• Hypertension
• Diabetes mellitus
• Alcohol
• Infection
• Genetics
• Familial Hyperlipidaemia

Question 14

What is the role of endothelial cells in atheroma?

Answer 14

-Key role in haemostasis
-Altered permeability to lipoproteins
-Production of collagen
-Stimulation of proliferation and migration
of smooth muscle cells

Question 15

What is the role of platelets in atheroma?

Answer 15

-Key role in haemostasis
-Stimulate proliferation and migration of
smooth muscle cells (PDGF)

Question 16

What is the role of smooth muscle cells in atheroma?

Answer 16

• Take up LDL and other lipid to become foam cells

- Synthesise collagen and proteoglycans which are present in excess in atheromatous plaques

Question 17

What is the role of macrophages in atheroma?

Answer 17

• Oxidise LDL
• Take up lipids to become foam cells
• Secrete proteases which modify matrix
• Stimulate proliferation and migration of smooth muscle cells

Question 18

What is the role of lymphocytes in atheroma?

Answer 18

• TNF may affect lipoprotein metabolism

- Stimulate proliferation and migration of smooth muscle cells

Question 19

What is the role of neutrophils on atheroma?

Answer 19

-Secrete proteases leading to continued local damage and inflammation

Question 20

Give a unifying hypothesis for atheroma formation

Answer 20

1) Endothelial injury due to:

• raised LDL
• ‘toxins’ e.g. cigarette smoke
• hypertension
• haemodynamic stress

2) Endothelial injury causes:

-platelet adhesion, PDGF release, SMC proliferation and migration
-insudation of lipid, LDL oxidation, uptake of
lipid by SMC and macrophages
-migration of monocytes into intima

3)

• Stimulated SMC produce matrix material
• Foam cells secrete cytokines causing further SMC stimulation
• recruitment of other inflammatory cells