Mechanisms of Atheroma and Infarction

Question 1

Define what an atheroma and what an infarction is.

Answer 1

• ATHEROMA:
  
  • The degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, leading to the restriction of the circulation and a risk of thrombosis.
• INFARCTION:
  
  • The obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing a local death of the tissue.

Question 2

What is the link between atherosclerosis and inflammation? What are some common sites for atherosclerosis?

Answer 2

• Atherosclerosis is a complex inflammatory process.
• It’s mediated by low-density lipoproteins (LDLs) and Angiotensin II.
• An ongoing systemic inflammatory disease makes the effects much worse (eg. rheumatoid arthritis).
• Common sites for atherosclerosis are larger arteries: -
  
  • carotid arteries and the Circle of Willis
  • coronary arteries
  • iliac arteries
  • aorta

Question 3

Describe the steps for atherosclerosis initiation.

Answer 3

1. Inflammatory triggers activate arterial endothelial cells. The oxidation of LDLs occurs, chiefly stimulated by the presence of necrotic cell debris and free radicals in the endothelium.
2. Endothelial cells start to become activated and express cytokines and adhesion molecules.
3. Circulating monocytes bind to the activated endothelium. They start expressing adhesion molecules and begin to move through the tissue and reside in the intima layer.
4. Monocytes differentiate into tissue macrophages which release their own inflammatory mediators. It is an appropriate immunological response to inflammation, but here, it is in the wrong place.

Question 4

Describe the steps for plaque formation.

Answer 4

1. Macrophages then begin to accumulate and engulf LDLs from the circulation and become foam cells.
2. 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.
3. The activated smooth muscle cells also release growth factors and may also begin synthesising collagen and elastin in the intima layer.

Question 5

Describe the steps of the maturation of the plaque.

Answer 5

1. Smooth muscle cells start to accumulate LDLs, becoming a second type of foam cell. However, they continue to make the extracellular matrix of elastin and collagen, which forms a fibrous plaque.
2. Cells underneath this plaque become oxygen-starved, so they begin to undergo apoptosis and release their fat into a globule of fat that is accumulating in the intima known as the lipid core.
3. The dying cells release their matrix metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque. This leaves the large lipid core covered by a fibrous plaque that may be vulnerable to enzymatic digestion.

Question 6

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

Answer 6

Later on in life, calcium deposits form around the atheroma. These are visible on CT scans. The role of calcium deposits remains uncertain; there have been arguments that calcification may actually stabilise the plaque, as it may make it less likely to rupture. Calcium may be a bad thing, but paradoxically, a lot of calcium deposits rather than a few could be a slight advantage.

Question 7

We know that atheromas start to occur from youth. Describe the timeline of the formation of these atheromas.

Answer 7

BETWEEN BIRTH AND 10 YEARS OLD: development of macrophages foam cells BY PUBERTY: development of smooth muscle foam cells The foam cells then accumulate more lipids. BETWEEN 30 AND 40 YEARS OLD: maturation of the fibrous cap

Question 8

Describe the rupture of the plaque.

Answer 8

If the central core becomes too large, plaque rupture can occur and the sub-endothelium is exposed. The endothelium is normally an anticoagulant surface. Collagen forms a very good base for clotting along with other proteins and factors in the intima. This gives us a pro-coagulant surface in the artery. A thrombus now forms which may occlude the artery.

Question 9

List some consequences of an atheroma.

Answer 9

OCCLUSIVE THROMBOSIS: eg. myocardial infarction Commonly known as a heart attack; it occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. THROMBOEMBOLISM: g. ischaemic stroke In this case, there’s an obstruction due to an embolus from elsewhere in the body (usually the carotid artery) blocking the blood supply to part of the brain. Other types of ischaemic strokes can occur. ANEURYSM DUE TO WALL WEAKNESS: eg. aortic aneurysm Causes weakness in the wall of the aorta and increases the risk of aortic rupture. When the rupture occurs, massive internal bleeding results and, unless treated immediately, shock and death can occur.

Question 10

What is an arterial and venous occlusion?

Answer 10

ARTERIAL OCCLUSION: It occurs particularly in cardiac and carotid arteries. Anything downstream from arterial occlusion becomes starved of oxygen (ie. ishaemia). The reduced blood flow can lead to symptoms such as angina on exercise. A thrombus becoming detached can block the cardiac arteries (MI) or cerebral arteries (stroke) and cause serious damage very quickly, or death. VENOUS OCCLUSION: We tend to think of this as happening in the legs, but here an occlusion doesn’t cut off the oxygen supply. It will cause pain and swelling as hydraulic pressure cause oedema. However, a thrombus may detach and return to the right side of the heart. It could then enter the pulmonary circulation, causing a pulmonary embolism.

Question 11

What is the difference between angina (plus both kinds of anginas) and a myocardial infarction?

Answer 11

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 12

List some complications of a myocardial infarction.

Answer 12

• acute cardiac failure - conduction problems - arrhythmia - papillary damage - valve dysfunction - mural thrombosis - stroke - wall rupture - chronic heart failure - myocardial scarring

Question 13

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

Answer 13

In the ECG of a person with ST Elevated Myocardial Infarction (STEMI), their ST segment is slightly raised higher than the baseline (as indicated by the name). Recognising the STEMI is one of the most fundamental things in interpreting an ECG. Damaged heart tissue doesn’t depolarise properly, so this section is elevated above the baseline.

Question 14

What are the types of strokes?

Answer 14

STROKE DUE TO THROMBOEMBOLISM: A thrombus from a carotid plaque rupture travels into smaller cerebral vessels. 85% are from carotid atheroma ruptures 15% are from stasis in the left atrium due to arrhythmia NON-THROMBOEMBOLIC STROKE: Due to hypo-perfusion, there is a loss of blood pressure (eg. heart failure, haemorrhage, shock), or an aneurism rupture and bleeding in the brain.