Atherosclerosis pathology Flashcards
Name 3 types of arteriosclerosis
- medial calcific sclerosis
- arteriolosclerosis
- atherosclerosis
what is medial calcific sclerosis
- hardening of tunica media, not intima, of vessels especially at the lower extremities
because it spares intima, there’s not narrowing of lumen
what is arteriolosclerosis and who is susceptible
- hardening of arterioles… characteristic of renal disease, especially for kidney failure and DM
- DOES narrow the lumen
What is atherosclerosis due to?
- accumulation of lipid, inflammatory cells (not neutrophils), and ECM (collagen especially) within intima TO NARROW LUMEN
What two vessels are commonly involved in atherosclerosis
- large elastic arteries in systemic circulation (particulary at bifurcations/bends/branch points, where you would see turbulent flow like aorta nad common carotid)
- muscular arteries – coronoray, Icarotid, cerebral arteries, lOWER EXTREMITY arteries
what arteries are spared for atherosclerosis
arteries of upper extremities
What are 3 significant complications of atherosclerosis
- stenosis of muscular arteries
- provides sites for development of thrombosis (in arteries, atherosclerotic plaques help for stasis and clot formation)
- aneurysm formation (weakening of media due to sclerosis, which can lead to aneurysm)
What is the commonly thought of initiator of atherosclerotic lesions
ENDOTHELIAL DYSFUNCTION
Give Factors that cause endothelial dysfunction
- localized flow abnormalities (aka turbulence) – which gets rid of normal laminar flow (and allows platelets to bounce against wall and injure vessel) as well as losing normal endothelial shear stress
- ***Increase in LDL in the intima of artery
- Hypertension – increases risk of atherosclerosis at any age by increasing permeaebility of endothelial cells, decreasing proper NO levels
- smoking – associated with decreased HDL levels, easier platelet activation, increased fibrinogen
- diabetes – goes with other factors (most DM’s have high cholesterol, low HDL, hypertension);
what is normal laminar flow
cellular components travel through middle of vessel, while acellular plasma is what bathes the endothelial cell
why is normal endothelial stress good?
- triggers release of NO and prostaglandins, so you modulate laminar flow and vasodilation
What is the result of the risk factors of endothelial dysfunction on the artery environment?
- Increased ROS
2. Decreased NO availability
What are the consequences of endothelial dysfunction
- Overexpression of adhesion molecules and chemoattractants
- increase permeability of endothelium to lipids and inflammatory cells
- decrease synthesis and release of NO
Describe what happens later on with endothelial dysfunction
- LDL is coming through endothelial cell via transcytosis and is oxidized to become oxidized LDL
- LDL Ox and ROS increase expression of VCAM-1 (adhesion molecules) – attract monocytes so they’re stuck on surface and go through endothelial layer to intima
- When monocytes get into tissues, they transform to tissue macrophages via M-CSF
- These macrophages are increased in size and has scavenger receptors that allow them to take in LDL, making htem even bigger until they become FOAM CELLS
Describe the steps and pathophys of fullblown atherosclerosis
- Hyperlipidemia causes accumulation of foam cells, which get into the intima (looks like yellow streaks)
- In intima, the macrophage dies, causing a release in cytokines, and also release their lipids (called extracellular lipids) that contain cholesterol crystals
- Cytokines released are going to stimulate growth factors on the smooth muscle cells, which causes smooth muscle to produce ECM collagen
- The collagen now accumulates in the media, which sets the stage for accumulation of lipids and collagen
