Mechanism of Atheroma and Infarction

Question 1

Define atheroma.

Answer 1

• Degeneration of the walls of the arteries
• Caused by accumulated fatty deposits and scar tissue
• Leads to the restriction of the circulation and a risk of thrombosis.

Question 2

Define infarction

Answer 2

-Obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus
- Causes a local death of the tissue.

Question 3

What is the link between atherosclerosis and inflammation?

Answer 3

Atherosclerosis is a complex inflammatory process.

Question 4

What are some common sites for atherosclerosis?

Answer 4

• carotid arteries
• coronary arteries
• iliac arteries
• aorta
  ESSENTIALLY - any large arteries

Question 5

What is atherosclerosis mediated by?

Answer 5

LDLs and Angiotensin II

Question 6

Describe the steps for atherosclerosis initiation. PART 1

Answer 6

• Inflammatory triggers activate arterial endothelial cells.
• Oxidation of LDLs occurs, chiefly stimulated by necrotic cell debris and free radicals in the endothelium.
• Endothelial cells start to become activated and express cytokines and adhesion molecules.

Question 7

Describe the steps for atherosclerosis initiation. PART 2

Answer 7

• Circulating monocytes bind to the activated endothelium.
• Monocytes express adhesion molecules and begin to move through the tissue and reside in the intima layer.
• Monocytes differentiate into tissue macrophages which release their own inflammatory mediators.

Question 8

Describe the steps for plaque formation.

Answer 8

• Macrophages accumulate and engulf LDLs from the circulation and become foam cells.
• Activated foam cells release other growth factors which cause smooth muscle cells to leave the medial layer and cross the internal elastic lamina, entering the intima.
• The activated smooth muscle cells also release growth factors and may also begin synthesising collagen and elastin in the intima layer.

Question 9

Describe the steps of the maturation of the plaque. PART 1

Answer 9

• Smooth muscle cells start to accumulate LDLs, becoming a second type of foam cell.
• Smooth muscle cells continue to make the extracellular matrix of elastin and collagen, which forms a fibrous plaque.

Question 10

Describe the steps of the maturation of the plaque. PART 2

Answer 10

• Cells underneath this plaque become oxygen-starved, so they begin to undergo apoptosis
• Fat released into a globule of fat that is accumulating in the intima known as the lipid core.

Question 11

Describe the steps of the maturation of the plaque. PART 3

Answer 11

• Dying cells release their matrix metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque.
• Leaves the large lipid core covered by a fibrous plaque that may be vulnerable to enzymatic digestion.

Question 12

Describe plaque calcification (and the role of calcium) and instability.

Answer 12

• Later on in life, calcium deposits form around the atheroma.
• The role of calcium deposits remains uncertain - possible that calcification may stabilise the plaque, as it may make it less likely to rupture.

Question 13

What is the evidence for calcium deposits forming around atheroma?

Answer 13

Visible on CT scans

Question 14

Describe the timeline of the formation of these atheroma between birth and 10 years old.

Answer 14

Development of macrophages foam cells

Question 15

Describe the timeline of the formation of these atheroma during puberty.

Answer 15

• Development of smooth muscle foam cells
• Foam cells accumulate more lipids.

Question 16

Describe the timeline of the formation of these atheroma between 30-40 years old.

Answer 16

• Maturation of fibrous cap

Question 17

Describe the rupture of the plaque.

Answer 17

• Can occur if the central core becomes too large
• Causes exposure of subendothelium
• Endothelium is an anticoagulant surface

Question 18

What is the result of plaque rupture?

Answer 18

• Collagen forms a base for clotting along with other proteins and factors in the intima. - - Forms a pro-coagulant surface in the artery.
• Thrombus forms which may occlude the artery.

Question 19

List some consequences of an atheroma.

Answer 19

• OCCLUSIVE THROMBOSIS
• THROMBOEMBOLISM
• ANEURYSM DUE TO WALL WEAKNESS

Question 20

Give an example of occlusive thrombosis

Answer 20

Myocardial infarction

Question 21

When does occlusive thrombosis occur?

Answer 21

• When blood flow decreases or stops to a part of the heart, causing damage to the heart muscle.

Question 22

Give an example of thromboembolism

Answer 22

Ischaemic stroke

Question 23

When does thromboembolism occur?

Answer 23

• Obstruction due to an embolus in the body (usually the carotid artery)
• This blocks the blood supply to part of the brain.

Question 24

Give an example of an aneurysm

Answer 24

Aortic aneurysm

Question 25

What part of the aorta does an aortic aneurysm weaken?

Answer 25

Walls of aorta

Question 26

What may happen if the aortic aneurysm were to rupture?

Answer 26

• Massive internal bleeding
• Shock and death if not treated immediately

Question 27

Where can arterial occlusions occur?

Answer 27

Cardiac and carotid arteries

Question 28

What is the consequence of an arterial occlusion?

Answer 28

• Tissues downstream from arterial occlusion becomes ischaemic
• Reduced blood flow can lead to symptoms such as angina on exercise.

Question 29

What may happen if a thrombus in the arteries were to detach?

Answer 29

• Can block the cardiac arteries (cause MI) or cerebral arteries (stroke)

Question 30

What are the consequences of venous occlusions?

Answer 30

Pain and swelling due to oedema formation.

Question 31

What may happen if a thrombus in veins were to detach?

Answer 31

• Return to the right side of the heart.
• Enter the pulmonary circulation and cause a pulmonary embolism.

Question 32

What is the difference between angina and a myocardial infarction?

Answer 32

• STABLE CARDIAC ANGINA: due to permanent flow limitation, not necessarily an infarction
• UNSTABLE CARDIAL ANGINA: due to transient thrombosis
• MYOCARDIAL INFARCTION: due to complete occlusion

Question 33

List some complications of a myocardial infarction.

Answer 33

• acute cardiac failure
• conduction problems - arrhythmia
• papillary damage - valve dysfunction
• chronic heart failure - myocardial scarring

Question 34

What is the significant change in an ECG with a myocardial infarction?

Answer 34

• ST segment is slightly raised higher than the baseline since damaged heart tissue won’t depolarise properly
• Known as STEMI (ST Elevated MI)

Question 35

What can cause a stroke due to thromboembolism? PART 1

Answer 35

Thrombus from a carotid plaque rupture travels into smaller cerebral vessels.

Question 36

What can cause a stroke due to thromboembolism? PART 2

Answer 36

• 85% are from carotid atheroma ruptures
• 15% are from stasis in the left atrium due to arrhythmia

Question 37

What can cause non-thromboembolic strokes?

Answer 37

Hypo-perfusion

Question 38

What is an embolus?

Answer 38

• A lodged blood clot that has come from somewhere else

Question 39

In general, what are the negative consequences of clots, atheroma and embolus?

Answer 39

• Ischaemia
• Reduced blood supply to tissues
• Death of tissue i.e necrosis

Question 40

What is the historical view of atheroma?

Answer 40

• WIth age, fat would be laid down in the artery walls
• At some point, they would detach and cause thrombosis

Question 41

What are the role of lipoproteins?

Answer 41

• Transfer lipids (fats) around the body in the extracellular fluid so they can be taken up by the cells via receptor-mediated endocytosis.