Mechanisms of atheroma and infarction

Question 1

Explain heart attacks (myocardial infarction) in the UK

Answer 1

-in the UK around 100, 000 hospital admissions each year are due to heart attacks

Question 2

Describe what atheroma and infarction is

Answer 2

atheroma- degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, leading to restriction of the circulation and a risk of thrombosis

Infarction- obstruction of the blood supply to an organ or region of tissue by a thrombus or embolus (causing local death of the tissue)

Question 3

Explain the historical view of atheroma

Answer 3

It is believed that in young people, there is no fat stored in the artery walls, however in older people fat is laid down in artery walls.

In infarction, the fat stores detach and cause thrombosis which prevents blood from getting to the heart and can lead to myocardial infarction

Question 4

Explain atherosclerosis

Answer 4

atherosclerosis is a complex inflammatory process.
This is mediated by low density lipoprotein, angiotensin II and various inflammatory substances

Question 5

What are common sites of atherosclerosis

Answer 5

common sites are:
-carotid arteries and circle of Willis
-coronary arteries
-iliac arteries
-aorta

Question 6

Explain the process of initiation

Answer 6

Initiation:

1) inflammatory triggers active arterial endothelial cells. Oxidation of LDL particles, this is stimulated by the presence of necrotic cell debris and free radicals in the endothelium

2) LDL and inflammation, endothelial cells start to become activated and express cytokines and adhesion molecules

3) Circulating monocytes bind to the activated endothelium. They start expressing adhesion to the molecules and begin to move through the tissue and reside in the intimal layer

4) Monocytes differentiate into tissue macrophages—-> release their own inflammatory mediators

Question 7

Explain plaque formation

Answer 7

plaque formation:

1) Macrophages then become to accumulate LDL from the circulation and become foam cells

2) Activated foam cells release growth factors which cause smooth muscle cells to leave via the medial layer and cross the internal elastic lamina— entering the intima

3) The activated smooth muscle cells also release growth factors- may begin synthesising collagen and elastin in the intima layer

Question 8

Explain maturation of the plaque

Answer 8

Maturation of the plaque:

1) Smooth muscle cells accumulate LDL- becoming a second type of foam but continues to make extracellular matrix of elastin and collagen (forms fibrous plaque)

2) Cells underneath this plaque become oxygen starved. Apoptosis occurs and they release their fat which forms a globule of fat thats accumulating in the intima

3) the dying cells release matrix metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque leaving a large lipid core.
This lipid core is covered by fibrous plaque that may be vulnerable to fibrous digestion

Question 9

explain calcification and instability

Answer 9

when we get older, calcium deposits may form around the atheroma and these are visible through a CT skin.

Although the role of calcium deposits are uncertain, arguments suggest that calcification may stabilise the plaque

Question 10

Explain the stages from how atheroma begins when we are young

Answer 10

1) development of a macrophage from foam cells release growth
2) development of smooth muscle foam cells and accumulation of more lipids all occurs between 0-10 years old

3) maturation of fibrous cap occurs between the ages of 30 and 40 years old

Question 11

Explain 3 consequences of atheroma

Answer 11

3 consequences of atheroma:

1) Occlusive thrombosis- commonly known as a heart attack, occurs when blood flow decreases causing damage to the heart muscle

2) Thromboembolism- obstruction is due to an embolus from elsewhere in the body- blocking blood supply to part of the brain

3) Aneurysm due to wall weakness- causes weakness in the wall of the aorta and increase risk of aortic rupture. When rupture occurs + massive internal bleeding shock and death can occur

Question 12

Is atherosclerosis inevitable

Answer 12

-mummified remains suggest that atheroma is as old as modern man and is found in hunter-gatherer societies

Question 13

Which factors contribute atheroma formation?

Answer 13

-systemic inflammation
-wood fire smoke
-parasite infections
-genetic and environmental factors

Question 14

Explain arterial occlusion

Answer 14

arterial occlusion:
-anything downstream from arterial occlusion becomes starved of O2. The reduced blood flow can lead to symptoms such as angina on exercise

-a thrombus becoming detached can block the cardiac arteries or cerebral arteries and can cause death or serious damage

Question 15

Explain venous occlusion

Answer 15

• occlusion doesnt cut off oxygen supply
• it will cause pain and swelling as hydraulic pressure causes oedema.
  -a thrombus may detach and return to the right side of the heart and could heart.

Question 16

Explain stable cardiac angina and unstable cardiac angina

Answer 16

Stable cardiac angina:
-due to permanent flow limitation, not necessarily infarction

Unstable cardiac angina:
-due to transient thrombosis, not necessarily infarction

Question 17

Explain myocardial infarction

Answer 17

Myocardial infarction due to complete occlusion

Question 19

Explain complications of MI

Answer 19

Complications of MI:
-acute cardiac failure
-conduction problems (arrhythmia)
-papillary damage (valve dysfunction)
-mural thrombosis (stroke)
-wall rupture
-chronic heart failure (myocardial scarring)

Question 20

Explain a stroke due to thromboembolism

Answer 20

Thrombus at carotid plaque rupture travels into smaller cerebral vessels.

85% from carotid atheroma rupture, 15% from stasis in left atrium due to arrhythmia

Question 21

Explain non thromboembolic stroke

Answer 21

-due to hypoperfusion, loss of blood pressure or aneurysm rupture and bleeding in the brain