14) Mechanisms of atheroma and infarction

Question 1

What is atheroma (atherosclerosis)?

Answer 1

• A degeneration of the arterial wall caused by fatty deposits which leads to restriction of circulation.
• They can burst to form the site where a blood clot can form and so it increases the risk of thrombosis
• Formation of atheroma begins when we are very young

Question 2

What is infarction?

Answer 2

• Obstruction of blood supply to an organ or region of tissue (typically through a thrombus) causing local tissue death

Question 3

What is an embolus?

Answer 3

• A lodged blood clot that has come from somewhere else

Question 4

What is the historical view of atheroma?

Answer 4

• When we are young there is no fatty deposits and hence the lumen is at its widest and least restricted
• As we grow older the fat gets laid down in the arterial wall causing it to restrict blood flow
• This can happen until it eventually infarcts where the fat stores detach and cause thrombosis
• This is because people thought that it was through this mechanism that LDLs, cholesterol and phospholipids were taken in by cells

Question 5

How is inflammation mediated?

Answer 5

• It is mediated by LDL, angiotensin II and various inflammatory substances
• Ongoing systemic inflammatory diseases make it worse
• Common sites for inflammation are large arteries such as carotid arteries, coronary arteries, iliac arteries and the aorta

Question 6

Describe the formation of a plaque

Answer 6

• Oxidation of LDLs on the surface of the endothelium leads to inflammatory reactions which activates these endothelial cells
• These activated LDLs and inflammatory cells express cytokines and adhesion molecules
• This activates circulating monocytes which binds to the endothelium and start to express adhesion molecules.
• They undergo diapedesis (movement through the tissue) and they differentiate into tissue macrophages
• These tissue macrophages reside in the intimal layer and release inflammatory mediators.
• As Macrophages are activated they engulf LDLs from circulation and become foam cells
• These activated foam cells release growth factors which cause smooth muscle cells (from the medial layer) to cross the internal elastic lamina to enter the intima
• These muscle cells are activated and release growth factors
• They also being synthesising collagen and elastin in the intima layer
• The elastin and collagen secreted by the smooth muscle forms a fibrous plaque and causes the cells underneath it to become oxygen starved as they are too far away from the available oxygen.
• These cells start to die and undergo apoptosis where they release globules of fat.
• This results in the formation of a lipid core underneath the fibrous plaque.

Question 7

How does a plaque lead to embolism?

Answer 7

• Along with lipids, metalloproteases and other enzymes are released which can break down the matrix causing the fibrous plaque to burst releasing the lipid core.
• The lipid core can then block another vessel leading in an embolism or could even form a blood clot

Question 8

Describe the calcification process in atheroma formation

Answer 8

• If the lipid core does not burst calcium deposits may form around the atheroma (visible on a CT scan)
• The role of calcium deposits is unknow however some say it may help stabilise the plaque
• Although considered a bad thing, a lot of calcium deposits rather than a few can be an advantage

Question 9

How does plaque rupture result in coagulation

Answer 9

• If the lipid core becomes too large it will rupture and expose the sub-endothelium
• The endothelium is normally an anticoagulant surface
• However collagen along with other factors and proteins found in the intima forms very good bases for clotting and gives a pro-coagulant surface in the artery.
• The lipid core that breaks off forms the thrombus which may block the artery or other arteries down stream

Question 10

What are the consequences of atheroma?

Answer 10

• Occlusive thrombosis: e.g. a myocardial infarction/heart attack, when blood flow decreases or stops to a part of the heart causing damage to myocardium (necrosis)
• Thromboembolism: e.g. ischaemic stroke, obstruction due to an embolus from elsewhere in the body blocking blood supply to the brain. Other type of ischaemic strokes can occur
• Aneurysm (due to wall weakness): Weakness in the wall of the aorta increases the risk of aortic rupture. When this rupture takes place, massive internal haemorrhage occurs which can lead to shock and death if left untreated

Question 11

What happens when arterial occlusion occurs?

Answer 11

• As we go downstream in the arteries, they got more and more narrow
• This means if an embolus were to break off it may get lodged somewhere downstream before it reaches the capillaries.
• Once it gets lodged anything downstream of this occlusion will be ischaemic and hypoxic.
• This reduced blood flow can lead to symptoms such as anginas when exercising if it blocks a minor artery (i.e. away from the heart and brain)
• It may even go on to block cardiac arteries (leading to myocardial infarction) or cerebral arteries (causing strokes) which can cause serious damage and even death.

Question 12

What happens when venous occlusions occur?

Answer 12

• It will not cut off blood/oxygen supply to the tissues as it carries deoxygenated blood
• If it does not detach it will cause pain and swelling as hydrostatic pressure will increase leading to oedema
• However a thrombus may detach and return to the right side of the heart.
• This is because veins get bigger as we go downstream. Hence when a thrombus breaks off it is less likely to get lodged in a vein downstream
• This can cause it to block chambers within the heart causing serious problems
• If it does not get lodged in the chambers of the heart it would come out of the right ventricle and enter the pulmonary circulation
• It enters the pulmonary artery (arteries getting smaller) so will get dislodged in the lungs causing a pulmonary embolism.

Question 13

What causes the three types of angina?

Answer 13

• Stable cardiac angina: Due to permanent flow limitation and not necessarily infarction. At rest the person will be alright however when oxygen demand increases (e.g. exercise) it will not be able to adequately perfuse the tissues downstream.
• Unstable cardiac angina: Due to transient (short lasting) thrombosis and not necessarily infarction
• Myocardial infarction: Due to complete occlusion as tissues downstream are not perfused and hypoxic leading to cell necrosis.

Question 14

How can a thrombus cause a stroke?

Answer 14

• A plaque may rupture in the carotid artery causing a thrombus to form
• This thrombus can travel into smaller cerebral vessels and get lodged
• This will lead to ischaemia in the brain and even necrosis

Question 15

How do haemorrhagic/ non-thromboembolic stroke occur?

Answer 15

• A plaque can form in the brain and can even lead to an aneurysm.
• When this occurs blood leaks into the brain which causes damage to the brain.
• Haemorrhage can occur when we block the blood supply or bleed into the brain