Pathogenesis of Atherosclerosis Flashcards
What is the definition of atherosclerosis?
Hardening of the arteries
In what size vessels does atherosclerosis occur?
Large and medium size muscular arteries
In what layer of the vessel does atherosclerosis begin?
Intima
Is coronary artery disease symptomatic or asymptomatic?
Asymptomatic
What are clinical manifestations of coronary artery disease?
Chronic stable angina
Acute coronary syndrome
Sudden death
Congestive heart failure
What is the key event in the pathogenesis of atherosclerosis?
Focal accumulation of lipid and cells beneath the endothelium
What are the 3 pathologic manifestations of atherosclerosis?
Fatty streak
Fibrous plaque
Complications of plaque
What is the fatty streak and when does it appear?
Area of yellow discoloration on inner surface of artery, does not impede blood flow
Earliest visible lesion of atherosclerosis
When does the fibrous plaque appear?
More advanced lesion
Can project into lumen and may limit blood flow
What are complications related to a plaque?
Rupture or ulceration of the plaque (can cause thrombosis) Weakening of vessel wall Hemorrhage Embolization Calcification of plaque
What antithrombotic and antivasoconstrictive substances are released by the endothelium?
Nitric oxide
Prostacyclin
Bradykinin
What thrombotic and vasconstrictive substances are released by the the endohelium?
Endothelin
Angiotensin II
Norepinephrine
What are 4 functions of normal endothelium?
Barrier function
Antithrombotic activity
Promotes vasodilation
Inhibits smooth muscle migration and proliferation of lipid below endothelium
What happens to the normal functions of endothelium when it gets disrupted?
Endothelium becomes permeable
Lose antithrombotic activity
Reduced vasodilation
Promotes smooth muscle migration
What are the steps of foam cell formation?
LDL enters intima
LDL gets oxidized
Oxidized LDL induces cytokines, which cause increase in adhesion molecules on endothelium
Macrophages attach to endothelium and migrate into intima
Macrophages take up oxidized LDL –> FOAM CELL
Accumulation of foam cells = fatty streak
What are the steps to go from foam cells to formation of atherosclerotic plaque?
Foam cells secrete cytokines and growth factors that attract smooth muscle cells from media
Smooth muscle cells proliferate and secrete collagen, elastin, and growth factors
Foam cells die causing an increase of ECM, cholesterol crystals form, calcification occurs, capillaries grow in = PLAQUE
What is the most common finding in patients with stable angina?
Atherosclerotic plaque in coronary arteries
What happens when a plaque ruptures?
Thrombus forms and can cause MI
Where do plaques often form?
Areas of low shear stress
Branch points
What is the usual progression of plaque formation in terms of location?
Aorta to
Coronary arteries to
Peripheral arteries to
Cerebral arteries
Define the concept of remodeling
As plaque compromises vessel lumen, a compensatory expansion of the outer wall occurs
What can happen with remodeling in diabetics?
Reverse remodeling
Outer wall may actually constrict inward at area of atherosclerosis = narrower lumen = bad
Describe the following characteristics in a STABLE plaque
- Lipid core (small or large)
- Fibrous cap (thick or thin)
In stable plaque:
- Lipid core = small
- Fibrous cap = thick
Describe the following characteristics in a VULNERABLE plaque
- Lipid core (small or large)
- Fibrous cap (thick or thin)
In vulnerable plaque:
- Lipid core = large
- Fibrous cap = thin
What is the common result of a stable plaque?
Narrow lumen limiting blood supply, causing stable angina
What is the common result of a vulnerable plaque?
Rupture resulting in thrombus formation and causing acute MI
What region of the plaque is most likely to rupture and why?
Shoulder region
High stress at margins and “activated” inflammatory cells
Can you predict in which vessel the ruptured plaque and thrombus formed?
No
What is a common result of weakening of vessel wall due to plaque?
Aneurysm
What is a common result of fragmentation of a plaque?
Embolize and cause stroke or renal failure
What is a less common reason for thrombus formation that is often associated with smoking, especially in women?
Plaque erosion
