Atherosclerosis

Question 1

What % of patients with new incidence angina die or have an MI in the next year?

Answer 1

10%

Question 2

What is atherosclerosis?

Answer 2

• The build up of cholesterol rich plaques
• A progressive disease affecting the intima of elastic and muscular arteries characterised by focal atheroma (fibrofatty plaques) consisting of a lipid core covered by a fibrous cap

Question 3

What does atherosclerosis cause?

Answer 3

Stenosis (narrowing) of coronary arteries

Question 4

What does the fibrous cap of plaque contain?

Answer 4

Smooth muscle cells and CT

Question 5

What is the atheroma?

Answer 5

A soft pool of extracellular lipid, cell debris and activated immune cells → progressively calcifies over time

Question 6

Where do plaques generally form?

Answer 6

In the proximal region of the coronary arteries, within 6cm of the aorta

Question 7

How many directions can plaque develop in?

Answer 7

2

Question 8

What can one direction of plaque development lead to?

Answer 8

Acute coronary syndrome which causes a big blood clot to form

Question 9

Describe the fibrous cap

Answer 9

Thin and vulnerable to rupture

Question 10

How does (stable) plaque cause ischaemia?

Answer 10

Patient cannot get enough blood to region of the heart

Question 11

What is arteriosclerosis?

Answer 11

A group of disorders that have in common thickening and loss of elasticity of material walls = hardening of arteries

Question 12

What are the 3 types of arteriosclerosis?

Answer 12

1) Atherosclerosis
2) Monckeberg’s medial sclerosis
3) Arteriolosclerosis

Question 13

What is Monckeberg’s medial sclerosis?

Answer 13

Disease characterised by calcification fo the media of muscular arteries

Question 14

What is arteriolosclerosis?

Answer 14

Disease characterised by the proliferative or hyaline thickening of the walls of small arteries and arterioles

Question 15

What might the layers of a blood vessel with arteriosclerosis look like?

Answer 15

Fragmented

Question 16

Describe atherosclerosis in the aorta

Answer 16

• Area of bifurcation is an area of turbulence so would look here for fatty streaks and plaque
• Can become extremely calcified

Question 17

What do the edges of atheromatous plaques look like?

Answer 17

They are calcified

Question 18

What are major predisposing factors for atherosclerosis?

Answer 18

1) Diet and hyperlipidaemias
2) Hypertension (systolic and diastolic)
3) Cigarette smoking esp. women
4) Diabetes

Question 19

What are minor predisposing factors for atherosclerosis?

Answer 19

Obesity, physical inactivity, male gender, increasing age, family history, stress, oral contraceptives (?), high carb intake (?)

Question 20

What happens to atheroma in small arteries?

Answer 20

In small arteries, atheroma are occlusive, compromising blood flow to distal tissues and causing ischaemic injury

Question 21

What sits between the media and intima in an atherosclerotic vessel?

Answer 21

Macrophages containing lipid which occlude the vessel

Question 22

What does endothelial injury lead to?

Answer 22

Thrombus

Question 23

What is acute coronary syndrome?

Answer 23

Transient occlusion of the coronary artery precipitated by a sudden decrease in coronary flow → chest pain that comes and goes, doesn’t occur with exertion

Question 24

What are the 4 stages in the development of an atheromatous plaque/lesion?

Answer 24

1) Lipid is present in macrophages in the intima of the blood vessels
2) Lipid is present in both macrophages and (proliferating) smooth muscle cells
3) Fibrous plaque
4) Complex plaque (fibrous cap overlying a lipid core) incl. cholesterol clefts

Question 25

In response to what are the lesions of atherosclerosis initiated?

Answer 25

To some form of injury to arterial endothelium

Question 26

What mechanisms of pathogenesis lead to atherosclerosis?

Answer 26

1) Endothelial injury 2) Macrophages and other inflammatory and immunological mechanisms 3) Smooth muscle cell proliferation 4) Hyperlipidaemia 5) Thrombosis

Question 27

How does endothelial injury lead to atherosclerosis?

Answer 27

- Endothelial damage is a major risk factor in atherogenesis but early lesions develop at sites of intact endothelium - Endothelial dysfunction (increased permeability, increase blood monocyte adhesion and increased EC replication) starts the process - Risk factors e.g. HTN and smoking increase endothelial permeability - Increased expression of the vascular cell adhesion molecules ICAM-1 and VCAM-1 increase monocyte adhesion

Question 28

How do macrophages and other inflammatory immunological mechanisms lead to atherosclerosis?

Answer 28

- Monocytes migrate into the intima and then accumulate LDL to produce foam cells - Monocytes/macrophages express the LDL receptor and a specific receptor (scavenger) for oxidised LDL (oxidised by EC< platelet or WBC enzymes) - T cells are found in plaques (uncertain role)

Question 29

How does smooth muscle cell proliferation lead to atherosclerosis?

Answer 29

With lipid accumulation, smooth muscle cell proliferation and ECM deposition in the intima are the major processes for the progressive growth of plaques

Question 30

How does hyperlipidaemia lead to atherosclerosis?

Answer 30

- Hyperlipoproteinaemia is the abnormality common to most syndromes of premature atherosclerosis - Can be primary (genetic) or secondary to e.g. nephrotic syndrome, alcoholism, hypothyroidism, diabetes - Increases in the plasma level of LDL may increase the level of lipid penetration in the arterial wall - Hyperlipoproteinaemia may also directly alter EC function

Question 31

What is the effect of atherosclerosis on the legs?

Answer 31

1) Slow, insidious narrowing of the vascular lumina results in ischaemia of the tissues perfused by the involved vessels 2) This is seen as intermittent claudication in the legs → atherosclerosis of iliac trunk and femoral arteries leading to angina of legs 3) V narrow iliac and femoral arteries lead to ischaemia in legs, causing leg pain

Question 32

How does atherosclerosis lead to infarct?

Answer 32

Sudden occlusion of the lumen by super-imposed thrombosis or haemorrhage into an atheroma produces ischaemia and if severe and prolonger, infarction of the tissues in the perfusion zone

Question 33

How does atherosclerosis lead to embolism?

Answer 33

Provides a site for thrombosis → embolism

Question 34

How can atherosclerosis cause aneurysm even in the heart and what can this lead to?

Answer 34

- Weakening the wall of a vessel can cause aneurysm or rupture - This can happen in the heart itself → ventricles burst or blood is released between the heart and pericardium → tamponade (no room for heart to beat) - This can happen 10-15 days after infarct → death

Question 35

What is thrombosis?

Answer 35

A complication of late-stage atherosclerosis

Question 36

What may organisation of thrombi contribute to?

Answer 36

Plaque formation and luminal encroachment

Question 37

What substance can be detected (immunohistologically) in up to 40% of plaques in an individual person at any given time?

Answer 37

Fibrin

Question 38

When is there a significant risk of sudden death and occlusion with plaque?

Answer 38

Once an atheromatous plaque occludes 70% of the cross sectional area of the coronary artery

Question 39

Describe a rupture abdominal aortic aneurysm

Answer 39

- In distal aspect of abdominal aorta before bifurcation - Catastrophic → can't be saved - Even leaking aneurysm v difficult to solve