Session 6 ILOs - Atherosclerosis

Question 1

Define atheroma, arteriosclerosis and atherosclerosis

Answer 1

Atheroma = accumulation of intracellular and extracellular lipid in intima and media of medium/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

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

Answer 2

4 OLD theories for atherosclerosis pathogensis:

1. Thrombogenic theory
   - plaques formed by repeated thrombi, lipid derived from thrombi
   - overlying fibrous cap
2. Insudation theory
   - endothelial injury
   - inflammation
   - increased permeability to lipids from plasma
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
   - each plaque is monoclonal, 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)

Question 3

Describe the variable macroscopic appearances of atherosclerosis e.g. fatty streak, simple plaque and complicated plaque

Answer 3

1. Fatty streak
   - Lipid deposits in the intima
   - Yellow and slightly raised
2. Simple plaque
   - Yellow/white and raised
   - Irregular outline
   - Widely distributed
3. Complicated plaque
   - Thrombosis
   - Haemorrhage into the plaque
   - Calcification
   - Aneurysm formation

Question 4

Describe the microscopic appearances of atherosclerosis e.g. early changes including accumulation of foam cells and later changes with cholesterol clefts and disruption of internal elastic lamina

Answer 4

Early stage:

• Smooth muscle proliferates
• Foam cells accumulate (macrophages carrying lipid)
• Extracellular lipid (so lipid inside and outside cells)

Larger stage:

• Fibrosis
• Necrosis
• Cholesterol clefts
• +/- inflammatory cells (lymphocytes, neutrophils)
• Disrupts internal elastic lamina and damage extend into media
• Ingrowth of blood vessels

Question 5

Identify modifiable and non-modifiable risk factors for the development of atherosclerosis e.g. age, gender, geography,

Answer 5

Modifiable:

• Smoking
• Hypertension
• Alcohol
• Hyperlipidaemia
• Diabetes Mellitus

Non-modifiable:

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

Question 6

Identify interventions to prevent and manage atherosclerotic disease

Answer 6

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

However, some people will still develop atherscleorsis!