mechanism of atheroma and infarction Flashcards
what is an 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.
what is an infarction ?
Obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue.
describe initiation of atherosclerosis
- Inflammatory triggers active arterial endothelial cells. this leads to Oxidation of LDL particles, chiefly stimulated by presence of necrotic cell debris and free radicals in the endothelium.
- LDL and inflammation - 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. It is an appropriate immunological response to inflammation but in the wrong place here.
describe plaque formation
- Macrophages then begin to accumulate LDL 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 plaque maturation
- Smooth muscle cells accumulate LDL becoming a second type of foam cell but they continue to make extracellular matrix of elastin and collagen which forms a fibrous plaque.
- Cells underneath this plaque become oxygen starved they begin to undergo apoptosis and 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 matrix 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 calcification and instability
- Later on in life calcium deposits may form around the atheroma and these are visible on a CT scan.
- 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 could be a sight advantage.
give a summary of the development of atheroma
Endothelial Dysfunction:
* Triggered by factors like oxidative stress, hypertension, smoking, diabetes, and high LDL cholesterol.
* The endothelium becomes permeable, allowing LDL to enter the arterial wall.
LDL Oxidation & Inflammatory Response:
* LDL gets oxidized by free radicals in the subendothelial space.
* Oxidized LDL (oxLDL) attracts monocytes, which differentiate into macrophages.
Foam Cell Formation (Fatty Streaks):
* Macrophages engulf oxLDL, forming foam cells, which accumulate and create fatty streaks (early atherosclerotic lesions).
Plaque Growth & Fibrous Cap Formation:
* Repeated inflammation leads to smooth muscle cell migration and deposition of collagen, forming a fibrous cap over the lipid core.
* The growing plaque narrows the artery, restricting blood flow.
Plaque Rupture & Thrombosis:
* If the fibrous cap ruptures, exposed lipids and cell debris trigger platelet aggregation and clot formation (thrombosis).
* This can cause heart attacks (myocardial infarction) or strokes if a clot blocks a critical artery.
describe plaque 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 very good bases for clotting along with other proteins and factors in the intima. This gives us a pro-coaguant surface in an artery.
- A thrombus now forms which may occlude the artery.
what are the consequences of atheroma
Occlusive thrombosis:
* eg. myocardial infarction
* Commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle.
Thromboembolism:
* eg. ischaemic stroke
* In this case obstruction due to an embolus from elsewhere in the body (usually carotid artery) blocking blood supply to part of the brain. Other types of ischaemic strokes occur.
Aneurysm due to wall weakness:
* eg. aortic aneurysm
* Cause weakness in the wall of the aorta and increase the risk of aortic rupture. When rupture occurs, massive internal bleeding results and, unless treated immediately, shock and death can occur.
is atherosclerosis inevitable ?
what is aterial occlusion ?
- Particularly cardiac and carotid arteries. Anything downstream from arterial occlusion becomes starved of oxygen. 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 death or serious damage very quickly.
what is venous occlusion ?
- We tend to think of 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 causes oedema.
- However a thrombus may detach and return to the right side of the heart and could enter the pulmonary circulation causing a pulmonary embolism.
what are the complications of myocardial infarctions ?
- acute cardiac failure
- conduction problems - arrhythmia
- valve dysfunction
- stroke
- wall rupture
- chronic heart failure
describe the types of stroke
Stroke due to thromboembolism:
* Ischaemic
* Thrombus at carotid plaque rupture travels into smaller cerebral vessels.
* 85% from carotid atheroma rupture, 15% from stasis in left atrium due to arrhythmia.
Non-thromboembolic stroke:
* Haemorrhagic
* Due to hypoperfusion, loss of blood pressure (eg. heart failure, haemorrhage, shock), or aneurysm rupture and bleeding in the brain
