Mechanisms of Atheroma & Infarction Flashcards
What is an atheroma?
Degeneration of the walls of the arteries.
What is an atheroma caused by and what does it lead to?
→ Accumulated fatty deposits and scar tissue
→ Leading to restriction of the circulation and a risk of thrombosis.
What is an infarction?
→Obstruction of the blood supply to an organ or region of tissue
What is an infarction typically caused by?
→Typically by thrombus or embolus causing local death of tissue.
What is the historical view of atheroma?
Young - No fatty deposits
Older - Fat laid down in artery wall
Infarct - Fat stores detach and cause thrombosis.
What is Atherosclerosis ?
→A complex inflammatory process
What is Atherosclerosis mediated by?
→Mediated by low density lipoprotein (LDL) & Angiotensin II
What makes atherosclerosis worse?
→An ongoing systemic inflammatory disease makes it worse (e.g rheumatoid arthritis)
What are common sites for atherosclerosis?
→Carotid arteries & circle of Willis
→Coronary arteries
→Iliac arteries
→Aorta
Describe the initiation of plaque formation
→ Inflammatory triggers activate arterial endothelial cells.
→Oxidation of LDL particles stimulated by the presence of necrotic cell debris and free radicals in the endothelium.
→Endothelial cells start to become activated and express cytokines and adhesion molecules.
→Circulating monocytes bind to the activated endothelium.
→They start expressing adhesion molecules and begin to move through the tissue and reside in the intimal layer
→Monocytes differentiate into tissue macrophages which release their own inflammatory mediators.
Describe plaque formation
→Macrophages begin to accumulate LDL from the circulation and become foam cells
→Activated foam cells release other growth factors
→This causes 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
→Begin synthesizing collagen and elastin in the intima layer.
Describe the maturation of the plaque
→Smooth muscle cells accumulate LDL becoming a second type of foam cell
→They continue to make extracellular matrix of elastin and collagen which forms a fibrous plaque.
→ Cells underneath this plaque become oxygen starved and begin to undergo apoptosis.
→They release their fat which forms a globule of fat that is now accumulating in the intima known as the lipid core.
→The dying cells release metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque
→ Leaving a large lipid core covered by a fibrous plaque that may be vulnerable to enzymatic digestion.
describe how a plaque can rupture
→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 good base for clotting along with other proteins and factors in the intima.
→This gives a pro-coagulant surface in the artery.
→A thrombus now forms which may occlude the artery.
What is calcification and how is this seen ?
→Later on in life calcium deposits may form around the atheroma
→ visible on a CT scan.
What is the role of calcium deposits?
→The role of calcium deposits remains uncertain,
→There have been arguments that calcification may actually stabilise the plaque.
→Calcium may be a bad thing but paradoxically a lot of calcium deposits rather than a few may be advantageous.
When was atheroma first found?
→Mummified remains suggest that atheroma is as old as modern man
→found in hunter-gatherer societies.
What % of people have smooth muscle foam cells by puberty?
→65% of people have smooth muscle foam cells by puberty.
When does maturation of the fibrous cap occur? (what age)
→30-40 years old
When do macrophage foam cells develop?
→Macrophage foam cells develop between birth and 10 years of age.
what is occlusive thrombosis and what is an example of it?
e.g Myocardial Infarction
→Occurs when blood flow decreases or stops to part of the heart causing damage to the heart muscle.
What is a thromboembolism and what is an example of it?
→eg. Ischaemic Stroke
→Obstruction due to an embolus from elsewhere in the body (usually carotid artery) blocking blood supply to part of the brain.
What is an example of an aneurysm due to wall weakness?
eg. Aortic Aneurysm
→Cause weakness in the wall of aorta and increases the risk of aortic rupture.
→When rupture occurs, massive internal bleeding results and unless treated immediately shock and death can occur.
What are 5 factors that can cause atheroma?
→Systemic inflammation promotes atheroma formation
→Smoking
→Parasite infections lead to chronic inflammations
→Genetics
→Lifestyle choices
Where does arterial occlusion occur?
→Particulary cardiac and carotid arteries.
What is arterial occlusion?
→Anything downstream from arterial occlusion becomes starved of oxygen.
What can arterial occlusion lead to?
→reduced blood flow can lead to symptoms of angina on exercise.
What can a detached thrombus cause?
→Can block the cardiac arteries (MI) or cerebral arteries (stroke) and cause death or serious damage quickly.
What are the symptoms of venous occlusion and
What can the thrombus then do?
→Occlusion does not cut off the blood supply.
→Causes pain and swelling as hydraulic pressure causes oedema.
→Thrombus may detach and return to the right side of the heart and could enter the pulmonary circulation
→Causing a pulmonary embolism.
What is stable cardiac angina due to?
→Due to permanent flow limitation.
→Coronary artery is no longer capable of dilating and allowing more blood flow.
→Not necessarily infarction.
What is a symptom of stable cardiac angina?
→Chest pain when engaging in physical activity.
What is unstable cardiac angina due to?
→transient thrombosis.
→Not necessarily infarction.
What is a symptom of unstable cardiac angina?
→chest pain occurs without physical activity.
What is Myocardial infarction due to and what happens to muscle tissue?
→Due to complete occlusion.
→Muscle tissue downstream begins to die.
What does STEMI stand for?
→ST Elevated Myocardial Infarction
Why is the ST section elevated?
Damaged heart tissue does not depolarise properly so this section is elevated above the baseline.
how does a stroke due to thromboembolism happen?
Thrombus at carotid plaque rupture travels to smaller cerebral vessels.
How does a non-thromboembolic stroke happen and what happens?
Due to hypo-perfusion
Loss of blood pressure (e.g heart failure, haemorrhage, shock) or aneurysm rupture and bleeding in the brain.
