Mechanism of Atheroma and Infarction Flashcards
Define atheroma.
- 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.
Define infarction
-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.
What is the link between atherosclerosis and inflammation?
Atherosclerosis is a complex inflammatory process.
What are some common sites for atherosclerosis?
- carotid arteries
- coronary arteries
- iliac arteries
- aorta
ESSENTIALLY - any large arteries
What is atherosclerosis mediated by?
LDLs and Angiotensin II
Describe the steps for atherosclerosis initiation. PART 1
- 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.
Describe the steps for atherosclerosis initiation. PART 2
- 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.
Describe the steps for plaque formation.
- 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.
Describe the steps of the maturation of the plaque. PART 1
- 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.
Describe the steps of the maturation of the plaque. PART 2
- 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.
Describe the steps of the maturation of the plaque. PART 3
- 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.
Describe plaque calcification (and the role of calcium) and instability.
- 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.
What is the evidence for calcium deposits forming around atheroma?
Visible on CT scans
Describe the timeline of the formation of these atheroma between birth and 10 years old.
Development of macrophages foam cells
Describe the timeline of the formation of these atheroma during puberty.
- Development of smooth muscle foam cells
- Foam cells accumulate more lipids.
Describe the timeline of the formation of these atheroma between 30-40 years old.
- Maturation of fibrous cap
Describe the rupture of the plaque.
- Can occur if the central core becomes too large
- Causes exposure of subendothelium
- Endothelium is an anticoagulant surface
What is the result of plaque rupture?
- 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.
List some consequences of an atheroma.
- OCCLUSIVE THROMBOSIS
- THROMBOEMBOLISM
- ANEURYSM DUE TO WALL WEAKNESS
Give an example of occlusive thrombosis
Myocardial infarction
When does occlusive thrombosis occur?
- When blood flow decreases or stops to a part of the heart, causing damage to the heart muscle.
Give an example of thromboembolism
Ischaemic stroke
When does thromboembolism occur?
- Obstruction due to an embolus in the body (usually the carotid artery)
- This blocks the blood supply to part of the brain.
Give an example of an aneurysm
Aortic aneurysm
What part of the aorta does an aortic aneurysm weaken?
Walls of aorta
What may happen if the aortic aneurysm were to rupture?
- Massive internal bleeding
- Shock and death if not treated immediately
Where can arterial occlusions occur?
Cardiac and carotid arteries
What is the consequence of an arterial occlusion?
- Tissues downstream from arterial occlusion becomes ischaemic
- Reduced blood flow can lead to symptoms such as angina on exercise.
What may happen if a thrombus in the arteries were to detach?
- Can block the cardiac arteries (cause MI) or cerebral arteries (stroke)
What are the consequences of venous occlusions?
Pain and swelling due to oedema formation.
What may happen if a thrombus in veins were to detach?
- Return to the right side of the heart.
- Enter the pulmonary circulation and cause a pulmonary embolism.
What is the difference between angina and a myocardial infarction?
- 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
List some complications of a myocardial infarction.
- acute cardiac failure
- conduction problems - arrhythmia
- papillary damage - valve dysfunction
- chronic heart failure - myocardial scarring
What is the significant change in an ECG with a myocardial infarction?
- ST segment is slightly raised higher than the baseline since damaged heart tissue won’t depolarise properly
- Known as STEMI (ST Elevated MI)
What can cause a stroke due to thromboembolism? PART 1
Thrombus from a carotid plaque rupture travels into smaller cerebral vessels.
What can cause a stroke due to thromboembolism? PART 2
- 85% are from carotid atheroma ruptures
- 15% are from stasis in the left atrium due to arrhythmia
What can cause non-thromboembolic strokes?
Hypo-perfusion
What is an embolus?
- A lodged blood clot that has come from somewhere else
In general, what are the negative consequences of clots, atheroma and embolus?
- Ischaemia
- Reduced blood supply to tissues
- Death of tissue i.e necrosis
What is the historical view of atheroma?
- WIth age, fat would be laid down in the artery walls
- At some point, they would detach and cause thrombosis
What are the role of lipoproteins?
- Transfer lipids (fats) around the body in the extracellular fluid so they can be taken up by the cells via receptor-mediated endocytosis.
