Atherosclerosis

Question 1

What is the etymology of atherosclerosis?

Answer 1

• Athere = gruel; Sclerosis = hardness

Question 2

Where does atherosclerosis occur?

Answer 2

Elastic and medium to large muscular arteries

Question 3

What is an atheroma?

Answer 3

(fibro-fatty plaques)
• Intimal fibrous cap
• Central core rich in lipids

Question 4

What is the clinical significance of atherosclerosis?

Answer 4

A fuckton of people die of it, in fact the most

• Symptomatic atherosclerosis
  
  • Contributes 1⁄2 of all deaths (Western world)
• . MI, Stroke, Aneurysms, Peripheral vascular disease

Question 5

How has the rate of symptomatic atherosclerosis changed through the years?

Answer 5

• 1963 (peak) –> 2000
  
  • 50% decreased death rate heart attack
  • .70% decreased death rate stroke

Due to

1. Prevention of atherosclerosis
2. Improved methods of treatment
3. Prevention of recurrences

Question 6

What are the risk factors of atherosclerosis?

Answer 6

• Age
• Sex
• Genetics
• Hyperlipidaemia
• Hypertension
• Smoking
• Diabetes mellitus

Question 7

What are the different stages of the pathogenesis of atherosclerosis?

Answer 7

Initiation/formation stage (subclinical)

Adaptation stage (subclinical)

Clinical stage

Question 8

Describe the pathogenesis of atherosclerosis

Answer 8

Precursor lesions (fatty streak, internal hyperplasia) undergoes atherogenic injury and so forms:

Fibroinflammatory lipid atheroma which then undergoes atheroma and wall remodelling forming an atheroma

At this stage and henceforth it may destabilise and so cause acute complications

The atheroma will undergo plaque enlargement, lumen stenosis then become a complicated plaque

Through further lumen stenosis the complicated plaque will cause occlusion, though this can also occur due to thrombosis as an acute complication of the atheroma

Question 9

What are the different processes involved in atherosclerosis pathogenesis?

Answer 9

• Chronic endothelial injury / dysfunction
• Role of lipids
• Role of macrophages
• Smooth muscle proliferation
• Formation of a fibro-lipid plaque
• Injury to the plaque – thrombus formation

Question 10

What may cause chronic endothelial injury / dysfunction?

Answer 10

• Haemodynamic disturbances
• Hypercholesterolemia
• Hypertension
• Smoking
• Toxins
• Viruses
• Immune reactions

Question 11

What effects do chronic endothelial injury / dysfunction have on the artery wall?

Answer 11

• Increase in Endothelial permeability
• Increase in Leukocyte adhesion
  
  • Vascular cell adhesion molecule 1 (VCAM-1)
  • Intercellular adhesion molecule- 1 (ICAM-1)
  • P-selectin
  • E-selectin
• Increase in Monocyte adhesion and migration

Question 12

What is the role of lipids in the arterial wall during atherosclerosis?

Answer 12

The lipid involved is hyperlipidaemia (LDL cholesterol)

• Impairs endothelial function
• Accumulates within intima
• Causes oxidative modification of LDL:
  
  • Ingested by macrophages via SCAVANGER receptors = foam cells
  • Chemotactic for monocytes
  • Inhibit the motility of macrophages
  • Stimulates release of cytokines
  • Cytotoxic to endothelial and smooth muscle cells

Question 13

What is the role of macrophages in the arterial wall during atherosclerosis?

Answer 13

• Engulf oxidised LDL = foam cells

• Secrete:
    • IL1 (interleukin 1)
    • TNF (tumour necrosis factor)
    • MCP1 (monocyte
chemotactic protein 1) and
    • growth factors (PDGF, FGF, TNF)
    • Interferon α, TGFβ 

• FATTY streak

Question 14

What is the role of smooth muscles proliferation in the arterial wall during atherosclerosis?

Answer 14

• Collagen and Extracellular matrix deposition
• Fatty streak
 I
 I
 v
• Mature fibro-fatty Atheroma

Question 15

What is the morphology of the atheromatous plaque?

Answer 15

It is a fibro-fatty, fibro-lipid plaque
• Patchy and raised white to yellow 0.3-1.5cm
• Core of lipid
• Fibrous cap
It also has a necrotic centre between the media and the fibrous cap

Found in:
• Abdominal aorta
• Coronary arteries
• Popliteal arteries
• Descending thoracic aorta 
• Internal carotid arteries
• Vessels of the circle of Willis

Question 16

What is the morphology of complicated lesions?

Answer 16

• Calcification
• Rupture or ulceration
• Haemorrhage
• Thrombosis
• Aneurysmal dilatation

Question 17

What is the morphology of fatty streaks?

Answer 17

• Fatty dots < 1 mm
• Elongated streaks 1cm or longer
• Foam cells + T lymphocytes
• In aorta age <1 year
• In coronary artery form in adolescence
• May be precursors of plaques

Question 18

What causes clinical features of atherosclerosis to present?

Answer 18

• Only if complications:
• Thrombosis
• Calcification
• Aneurysmal dilatation
• Ischaemic events:
  
  • Heart
  • Brain
  • Lower extremities
  • Other organs

Question 19

What does ischaemia actually refer to?

Answer 19

An inadequate blood supply to organs/muscles

Question 20

What are the clinical features of atherosclerosis?

Answer 20

Mural thrombosis, embolisation and wall weakening -> aneurysm and rupture

Plaque rupture, erosion and haemorrhage + mural thrombosis and embolisation -> occlusion by thrombus

Progressive plaque growth -> Critical stenosis

Question 21

What primary prevention methods may be used to prevent clinical presentation of atherosclerosis?

Answer 21

• Stop smoking
• Control hypertension
• Weight reduction
• Lowering total LDL
• Reduce calories intake

Question 22

What secondary prevention methods may be used to prevent clinical presentation of atherosclerosis?

Answer 22

• Prevent complication
• Antiplatelet drugs in thrombosis
• Lower blood lipid levels