Mechanics of atheroma and infarction Flashcards
Define 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.
Define 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.
Define Thrombus
Blot clot
Define embolus
A blot clot that moves around the body and then lodges in a vessel
Give a historical overview of atheroma
- Young
- Older - fat laid down in artery wall
- Infarct - Fat stores detach and cause thrombosis
How are fats transported round the body and what lipids are carried round the body?
Lipoproteins transfer fats around the body, so they are available to be taken up by the cells via receptor-mediated endocytosis. The lipids carried by LDLs include cholesterol, phospholipids, and triglycerides.
Atherosclerosis and inflammation
What is it caused by, what makes it worse and where does it occur?
A complex inflammatory process
• Mediated by low-density lipoprotein (LDL) & angiotensin II
• An ongoing systemic inflammatory disease makes it all worse (eg. rheumatoid arthritis).
Commons sites are larger arteries • Carotid arteries & circle of Willis • Coronary arteries • Iliac arteries • Aorta
Describe the formation of plaque in a blood vessel: initiation
- Inflammatory triggers active arterial endothelial cells. 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 the formation of plaque in a blood vessel: 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
Describe the formation of plaque in a blood vessel: Maturation of the plaque
- 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 he edge of the plaque leaving a large lipid core covered by a fibrous plaque that may be vulnerable to enzymatic digestion.
Describe the process of 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 slight advantage.
How does atheroma begin when we are young?
On image
How does a 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 3 main 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.
What is the difference between an arterial and venous occlusion?
Arterial Occlusion
• Particularly cardiac and carotid arteries. Anything downstream from arterial occlusion becomes starved of oxygen ie. Ischaemia. 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.
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.
