Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

Question 2

What is arteriosclerosis?

Answer 2

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

Question 3

What are the macroscopic features of atherosclerosis?

Answer 3

Fatty streak
Simple plaque
Complicated plaque

Question 4

What is a fatty streak?

Answer 4

Lipid deposits in intima

Appearance - yellow, slightly raised

Question 5

What is simple plaque?

Answer 5

Appearance

• raised yellow/white
• irregular outline

Question 6

What is complicated plaque?

Answer 6

Abnormality of vessel wall causing problems with flow
- can cause thrombosis

Plaque has a fibrous cap - can cause haemmorhage

Presence of lipid summons calcium
- get calcification

Question 7

What are the early microscopic changes?

Answer 7

Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid

Question 8

What are later microscopic changes?

Answer 8

Fibrosis
Necrosis
Cholesterol clefts

Question 9

What are late microscopic changes?

Answer 9

Internal elastic lamina disruption
Damage into media
Ingrowth of blood vessels
Plaque fissuring - releases thrombolytic agents

Question 10

Risk factors of atherosclerosis

Answer 10

Age
Gender
Hyperlipidaemia
Smoking
Hypertension 
DM
Alcohol

Question 11

Pathogenesis theories for atherosclerosis

Answer 11

Thrombogenic theory
Insudation theory
Monoclonal hypothesis
Reaction to injury hypothesis

Question 12

What is the thrombogenic theory?

Answer 12

Plaques are formed by repeated thrombi

Lipid derived from the thrombi with an overlying fibrous cap

Question 13

What is the insudation theory?

Answer 13

Enothelial injury causes inflammation

So increased permeability to lipid from plasma

Question 14

What is the monoclonal hypothesis?

Answer 14

Each plaque monoclonal - represents abnormal growth

Question 15

What is the reaction to injury hypothesis?

Answer 15

Plaques form in response to endothelial injury

Injury increases permeability to lipid and allows platelet adhesion

Question 16

What cells are involved in atherosclerosis?

Answer 16

Endothelial cells
Platelets
Smooth muscle cells
Macrophages
Lymphocytes
Neutrophils

Question 17

What role do endothelial cells play?

Answer 17

Altered permeability to lipoproteins
Produce collagen
Stimulate proliferation and migration of smooth muscle cells

Question 18

What role do platelets play?

Answer 18

Stimulate proliferation and migration of smooth muscle cells

Question 19

What role do smooth muscle cells play?

Answer 19

Take up LDL to become foam cells

Synthesise collagen and proteoglycans

Question 20

What role do macrophages play?

Answer 20

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

Question 21

What role do lymphocytes play?

Answer 21

TNF - may affect lipoprotein metabolism

Stimulate proliferation and migration of smooth muscle cells

Question 22

What role do neutrophils play?

Answer 22

Secrete proteases - local damage and inflammation

Question 23

How do plaques form?

Answer 23

Endothelial injury

• raised LDL
• toxins
• hypertension

Lipid molecules cross endothelium + accumulate in intima
Formation of foam cells
Foam cells increase = fatty streak

Fibrous cap develops

• smooth muscle cells
• reinforced by collagen, elastin + matrix proteins

Endothelium stretches - platelets fill gaps
Cells in centre die + necrose
Dead cells release cholesterol

Question 24

Complications of plaque

Answer 24

Ulceration
Thrombosis
Calcification
Aneurysm