Atherosclerosis

Question 1

Define Arteriosclerosis

Answer 1

Thickening of the walls of arteries and arterioles usually as a result of hypertension/diabetes mellitus, often associated with loss of elasticity

Question 2

What can Arteriosclerosis result in

Answer 2

Poor tissue perfusion
Inelastic/weak vessels (→aneurysm)
Risk of thrombus formation

Question 3

Define Atherosclerosis

Answer 3

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

Question 4

Define Atheroma

Answer 4

Necrotic core of the atherosclerotic plaque. Thickening of arterial walls as a consequence of atherosclerosis

Question 5

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

Answer 5

Thrombogenic theory:
Plaques formed by repeated thrombi, lipid derived from thrombi, fibrous cap

Insudation theory: Endothelial→Inflammation→Increased permeability to lipid from plasma

Monoclonal hypothesis:
Each plaque is monoclonal, abnormal smooth muscle proliferation

Reaction to injury hypothesis:
(Chronic inflammatory and healing response of the arterial wall to an endothelial injury)
Plaques form in response to endothelial injury→Increases permeability and allows platelet adhesion→Monocytes penetrate endothelium→Smooth muscle cells proliferate

Question 6

Outline the components of atherosclerotic plaque

Answer 6

Cells: Endothelial cells, platelets, neutrophils, macrophages, leucocytes, smooth muscle cells

Lipid: Intracellular (FOAM cells) and extracellular (POOLS)

Extracellular matrix: Collagen, elastin, proteoglycans

Question 7

Describe the roles of these components in atherosclerosis
-Endothelial cells
-Platelets
-Smooth muscle cells
-Macrophages
-Lymphocytes
-Neutrophils

Answer 7

Endothelial cells:
Haemostasis, altered permeability to lipoproteins, production of collagen, stimulation of proliferation & migration of smooth muscle cells

Platelets:
Haemostasis, stimulation & migration of SMC

Smooth muscle cells:
Take up LDL and other lipid to become foam cells, synthesis of collagen & proteoglycans

Macrophages:
Oxidise LDL, Take up lipids to become foam cells, Secrete proteases which modify matrix, Stimulation of proliferation and migration of SMCs

Lymphocytes:
TNF (tumour necrosis factor) may affect lipoprotein metabolism, Stimulation of proliferation & migration of SMCs

Neutrophils:
Secrete proteases leading to local damage and inflammation

Question 8

Microscopic appearance of atherosclerosis

Answer 8

Fatty streak
-proliferation of SMC
-accumulation of foam cells
-extracellular lipid

Stable plaque
-fibrosis
-necrosis
-cholesterol clefts
-inflammatory cells

Unstable plaque
-disruption of internal elastic lamina
-damage extends into media
-new vessels grow into plaque (from adevntitia
-plaque fissuring (laminar cracking)

Question 9

Difference between stable and unstable plaque

Answer 9

Unstable has a thinner fibrous cap and more likely to rupture. It has a higher risk of heart attacks and strokes

Question 10

Macroscopic appearances of atherosclerosis

Answer 10

Check Images

Fatty streaks: yellow, intima

Stable plaque: raised yellow, irregular outline, widely distributed, enlarge and coalesce (come together)

Unstable plaque: yellow&red, irregular, rough, hard, calcified

Question 11

Complications of Atherosclerosis

Answer 11

Ulceration
Thrombosis
Vasospasm (narrowing brain BV)
Embolisation
Calcification
Haemorrhage
Aneurysm formation
Rupture of atherosclerotic artery

Question 12

Common sites of Atherosclerosis

Answer 12

Coronary arteries
Carotid arteries
Abdominal arteries→Mesenteric ischaemia, Acute bowel ischaemia, AAA
Peripheral arteries
Renal arteries

Question 13

Modifiable risks of atherosclerosis

Answer 13

Hyperlipidaemia (high lv. of LDL)
Hypertension
Smoking (predisposition of thrombosis)
Obesity (↑risk of diabetes mellitus, hypertension, hyperlipidaemia)

Question 14

Non-modifiable risks of atherosclerosis

Answer 14

Age (elderly)
Sex (male) oestrogen is protective of atherosclerosis
Post menopause: sudden drop in oestrogen
Family history: genetic conditions such as hypercholesterolemia

Question 15

Sign of hypercholesterolaemia

Answer 15

Corneal arcus: deposition of lipid in the outer edges of cornea forming a white ring
Tendon xanthoma: deposition of lipid in tendons which form lumps under skin
Xanthelasma: Deposition of lipid in the skin around the eyelids

Question 16

Prevention of Atherosclerosis

Answer 16

Decrease total Cholesterol and LDL in diet
Lipid lowering drugs (statin)
Low fat and high fibre diet
Aspirin

Question 17

Management of Athersclerosis

Answer 17

Statins
Anti-hypertensives
CANTOS: Targeting inflammation, Canakinumab (monoclonal Ab targeting IL-1 Beta)
Exercise
Normal BMI
Non smoker
Alcohol consumption (in moderation)
Balanced diet
Diabetic medication

Question 18

Glossary of
1. Fatty streak
2. Fibrous cap
3. Foam cells
4. Intima
5. Intima thickening

Answer 18

1. The first grossly visible lesion in the development of atherosclerosis (foam cells, tunica intima)
2. A layer of fibrous connective tissue in the intima
3. Cells in an atheroma that consist of monocyte macrophages containing numerous lipid inclusions rich in cholesterly esters
4. The innermost layer of a BV
5. Accumulation in the intima of SMCs within a matrix of proteoglycans

Question 19

Which cells can become foam cells in atherosclerotic plaques

Answer 19

Macrophages
Smooth muscle cells

Question 20

In which layer of the arterial wall does atheroma build up occur in

Answer 20

Tunica intima

Question 21

What are the symptoms of Abdominal Aortic Aneurysm

Answer 21

Sudden onset of back/flank pain
Hypotension
Pulsatile abdominal mass

Question 22

What type of lipoprotein is oxidised leading to atherosclerosis? (reason)

Answer 22

LDL (oxidised and turns macrophages into foam cells
Reason: LDLs have the longest half life and is susceptible to oxidative damage

Question 23

Define stable plaque

Answer 23

A raised lesion in the arterial wall that begins to occlude the lumen (doesn’t cause symptoms)