mechanisms of atheroma and infarction Flashcards
What is an atheroma?
Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis
What is an 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.
What is MI?
Myocardial infarction; when blood flow decreases to a part of the heart causing a damage in myocardium.
Describe how the arterial wall changes with age and how this can affect the blood flow
Older: more fat laid down in arterial wall which can detach and cause a thrombosis. The thrombosis can then lead to a myocardial infarction
Name 3 lipids transferred around the body via LDL’s and describe how these are taken up
Transferred round the body and taken up by cells via receptor mediated endocytosis 3 types of lipids carried by LDL are: 1. Cholesterol 2. Phospholipids 3. Triglycerides
What is atherosclerosis?
It is a complex inflammatory process mediated by LDL’s and angiotensin II
What can make atherosclerosis worse?
An ongoing systemic inflammatory disease makes the effects much worse (eg. rheumatoid arthritis).
What are the common sites for atherosclerosis?
LARGER ARTERIES: Carotid arteries and circle of Willis Coronary arteries Iliac arteries Aorta
Describe the steps for atherosclerosis initiation
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.
Describe the steps for plaque formation
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 synthesizing collagen and elastin in the intima layer.
Describe the steps of plaque maturation
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.
Describe plaque calcification (and the role of calcium) and instability.
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 stabilize 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.
Describe the rupture of the plaque.
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.
List some consequences of an atheroma.
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. ischemic 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 ischemic 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.
What is arterial occlusion?
It occurs particularly in cardiac and carotid arteries. Anything downstream from arterial occlusion becomes starved of oxygen (ie. ischemia). 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.
