Atherosclerosis

Question 1

What are the 3 layers of the vascular wall (from lumen outwards)?

Answer 1

Tunica Intima
Tunica Media
Tunica Adventitia

Question 2

What are the components of Tunica Intima?

Answer 2

Endothelium (single layer of squamous epithelial cells)
Basal Lamina (made up of collagen, proteoglycans and glycoproteins) 
Sub-endothelial layer (loose connective tissue + internal elastic membrane in arteries and arterioles)

Question 3

What are the components of Tunica Media?

Answer 3

Smooth muscle layers with variable amounts of elastin, reticular fibres and proteoglycans interposed between cells.
External elastic membrane separates Tunica Media from Tunica Adventitia

Question 4

What is the Tunica Adventitia made up of?

Answer 4

Longitudinal collagenous tissue and a few elastic fibres

Question 5

What is the difference in histology between arteries and veins?

Answer 5

Arterial walls are thicker than veins to accommodate pulsatile flow and high pressures

Question 6

What are the 3 different types of artery?

Answer 6

1. Large (or elastic) arteries
2. Medium (or muscular) arteries
3. Small arteries (arterioles)

Question 7

What are the functions of the endothelium lining blood vessels?

Answer 7

Selective permeability barrier
Non-thrombogenic barrier (normally does not support adherence of platelets or formation of thrombi unless damaged) 
Maintenance of blood flow and vascular resistance (through secretion of vasoconstrictors/dilators) 
Immune response (control of lymphocytes) 
Modification of lipoproteins (through oxidation by free radicals released by endothelial cells)

Question 8

What are the functions of smooth muscle within vascular walls?

Answer 8

Mediation of vasoconstriction and vasodilation
Up-regulation of collagen
Proteoglycan production

Question 9

Define arteriosclerosis?

Answer 9

Hardening of the arteries
Generic term reflecting arterial wall thickening and loss of elasticity
3 distinct types: arteriolosclerosis, atherosclerosis and Monckeberg medial sclerosis

Question 10

What is arteriolosclerosis?

Answer 10

Affects small arteries/ arterioles

Can cause downstream ischaemic injury.

Question 11

Who is most likely to develop arteriolosclerosis?

Answer 11

Patients with hypertension and diabetes

Question 12

What is Monckeberg medial sclerosis?

Answer 12

Characterised by the presence of calcific deposits in muscular arteries.
More common in >50
Generally not clinically significant as do not encroach on lumen

Question 13

What is atherosclerosis?

Answer 13

Most common blood vessel abnormality

Endothelial dysfunction caused by endothelial injury in the Tunica Intima

Question 14

What factors predispose you to endothelial injury in atherosclerosis?

Answer 14

LDL cholesterol hyperlipidaemia 
Hyperglycaemia (diabetes) 
Hypertension 
Increased toxin levels (e.g. smoking) 
Some viral or bacterial infections

Question 15

What is the pathogenesis of atherosclerosis?

Answer 15

1. Chronic endothelial “injury” (due to predisposing factors)
2. Endothelial dysfunction (e.g. increased permeability to LDL cholesterol; increased leukocyte and monocyte adhesion)
3. Endothelial injury increases production of reactive oxygen species which oxidise LDL in the Tunica Intima
4. Monocytes from bloodstream enter Tunica Intima and differentiate into Macrophages
5. Macrophages phagocytose oxidised LDL transforming themselves into foam cells
6. Foam cells and infiltrated T lymphocytes form initial atherosclerotic lesion (or fatty streak)
7. Lesion undergoes remodelling and growth into fibrofatty plaque (as smooth muscle cells migrate from the media and fibroblasts form protective capsule of connective tissue)
8. Thick layer of fibrous connective tissue containing smooth muscle cells, macrophages, foam cells, T lymphocytes, cholesterol crystals and cell debris is known as an atheromatous plaque

Question 16

What are the microscopic indicators of an advanced atherosclerotic lesion?

Answer 16

Thrombosis can occlude vessel
Thinning of Tunica Media
Calcification of accumulated extracellular lipids
Necrosis within lesion

Question 17

What are the principle components of atherosclerotic lesions microscopically?

Answer 17

Cells (smooth muscle, macrophages, T cells)
Extracellular Matrix (collagen, elastic fibres, proteoglycans)
Intra- and Extracellular lipids

Question 18

What are the clinical consequences of atherosclerotic disease?

Answer 18

Myocardial infarction  
Cerebral infarction (stroke)  
Aortic aneurysm
Peripheral vascular disease (gangrene) 
Reno-vascular disease