Session 6 ILO's Atheroslerosis

Question 1

Define arteriosclerosis, atherosclerosis and atheroma

Answer 1

Atheroma = accumulation of intracellular and extracellular lipid in intima and media of medium and large sized arteries

Arteriosclerosis = thickening and hardening of arterial walls usually due to hypertension or diabetes

Atherosclerosis = thickening and hardening of arterial walls due to atheroma

Question 2

Describe the variable macroscopic appearances of atherosclerosis

Answer 2

1. Fatty streak (3)
   - Lipid deposits in the intima
   - Yellow and slightly raised
   - Relationship to atherosclerosis is somewhat debatable
2. Simple plaque (4)
   - Yellow/white and raised
   - Irregular outline
   - Widely distributed
   - Enlarge and coalesce
3. Complicated plaque (4)
   - Thrombosis
   - Haemorrhage into the plaque
   - Calcification
   - Aneurysm formation

Question 3

Describe the microscopic appearances of atherosclerosis

Answer 3

Early stage: (3)

• Proliferation of smooth muscle cells
• Foam cells accumulate (macrophages carrying lipid)
• Extracellular lipid (so lipid inside and outside cells)

Larger stage: (7)

• Fibrosis
• Necrosis
• Cholesterol clefts
• +/- inflammatory cells (lymphocytes, neutrophils)
• Disrupts internal elastic lamina
• Damage extends into media
• Plaque fissuring

Question 4

Identify modifiable and non-modifiable risk factors for the development of atherosclerosis

Answer 4

Modifiable:

• Smoking
• Alcohol
• Hypertension
• Hyperlipidaemia
• Diabetes Mellitus

Non-modifiable:

• Age
• Gender
• Geography
• Ethnicity
• Genetic predisposition/family history

Question 5

Identify interventions to prevent and manage atherosclerotic disease

Answer 5

• Stop smoking
• Manage diabetes mellitus
• Control hypertension
• Reduce fat intake
• Lipid lowering drugs
• Increase exercise and weight management

(6)
However, some people will still develop atherscleorsis!

Question 6

Describe and understand the cells involved in the formation of an atherosclerotic plaque.

Answer 6

Endothelial cells, platelets, smooth muscle cells, macrophages, lymphocytes, neutrophils.

Question 7

Recognise the common sites of atherosclerosis and the sequelae/complications of atheroma at these sites.

Answer 7

• ischaemic heart disease (heart)
• Cerebral ischaemia (brain)
• Mesenteric ischaemia (intestines)
• Peripheral vascular disease (peripheries)
• Abdominal aortic aneurysm (stomach)

5 common sites of atherosclerosis:

• Aorta (especially abdominal)
• Coronary arteries
• Carotid arteries
• Cerebral arteries
• Leg arteries

Question 8

Explain the cellular events and proposed theories that lead to the formation of atherosclerotic lesions LEARN

Answer 8

4 OLD theories for atherosclerosis pathogensis:

1. Thrombogenic theory
   - Plaques formed by repeated thrombi
   - Lipid derived from thrombi
   - overlying it, a fibrous cap developed
2. Insudation theory
   - endothelial injury
   - leads to inflammation
   - increased permeability to lipids from plasma to get into arterial walls
3. Reaction to injury
   - plaque forms due to endothelial injury
   - increases permeability and allows for platelet adhesion
   - monocytes enter endothelium
   - smooth muscle cells proliferate and migrate
4. Monoclonal hypothesis = generally not accepted
   - Smooth muscle proliferation is needed for formation of APL
   - each plaque is monoclonal
   - Each plaque represented a single clone of cells
   is each plaque a benign tumour, might represent abnormal growth control?
   - could atherosclerosis have a viral aetiology?

3 NEWER theories!

1. Unifying hypothesis 1
   Endothelial injury due to:
   - Toxins, hypertension, haemodynamic stress
2. Unifying hypothesis 2
   Endothelial injury causes:
   - Platelet adhesion, PDGF release, smooth muscle proliferation, migration
   - Accumulation of lipid, LDL oxidation, uptake of lipid by smooth muscle and macrophages
   - Migration of monocytes into the intima
3. Unifying hypothesis 3
   - Stimulated smooth muscle cells produce matrix material
   - Foam cells secrete cytokines (causes further smooth muscle proliferation and inflammation cell recruitment)