Mechanisms of Atheroma and 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
characterized by intimal lesions -atheromas
that impinge on the vascular lumen and can rupture to cause sudden occlusion.
It underlies the pathogenesis of
coronary, cerebral, and peripheral vascular disease
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.
