EXAM #1: ARTERIOSCLEROSIS Flashcards
What is the definition of arteriosclerosis?
“Hard arteries” due to thickening of the blood vessel wall
What are the three sub-categories of arteriosclerosis?
1) Atherosclerosis
2) Arteriolosclerosis
3) Monckeberg medial calcific sclerosis
What is the definition of Atherosclerosis?
INTIMAL plaque that obstructs blood flow
Describe the composition of an atherosclerotic plaque.
- Necrotic lipid core (cholesterol)
- Fibromuscular cap
*Often undergoes dystrophic calcification
What vessels are most commonly involved in atherosclerosis?
Large and medium sized arteries i.e.
1) Abdominal aorta
2) Coronary artery
3) Popliteal artery
4) Internal carotid artery
What are the modifiable risk factors in atherosclerosis?
1) HTN
2) Hypercholesterolemia (LDL)
3) Smoking
4) DM
- Inactivity
- Stress
- Obesity
Note that these risk factors are synergistic/ additive
What are the nonmodifiable risk factors in atherosclerosis?
1) Age
2) Gender
- Males
- Post-menopausal women (estrogen is protective)
3) Genetics
What total serum cholesterol increases the risk of atherosclerosis?
160 mg/dL
Which familial dyslipoproteinemias are associated with premature atherosclerosis?
1) Familial hypercholesterolemia (increased LDL)
2) Familial combined hypercholesterolemia (Increased LDL and VLDL)
3) Familial Type III Lipoproteinemia (IDL)
4) Familial hypertriglyceridemia (VLDL and TAG)
5) Familial AI/CII (no HDL)
Which of the familial dyslipoproteinemia is associated with the most severe premature atherosclerosis?
Familial AI/CII i.e. lack of HDL
What is the impact of smoking on the etiology of atherosclerosis?
Smoking= 200% risk
Smoking cessation= 1/2 of the prior risk
What are the two “unusual” risk factors associated with atherosclerosis?
1) Homocystine
2) Chlamydia pneumonia
Outline the pathogenesis of atherosclerosis.
1) Endothelial injury:
- Damage to endothelium allows LIPIDS to lead into INTIMA
2) Macrophage response
- Lipids are oxidized and consumed by macrophages–>foam cells
3) INFLAMMATION and healing
- Leads to deposition of ECM and proliferation of smooth muscle
What cellular adhesion molecule is over-expressed in response to endothelial injury in the pathogenesis of atherosclerosis?
Vascular cell adhesion molecule-1 (VCAM-1)
What receptor on macrophages allows them to take up lipids to form foam cells?
Scavenger receptors
What recruits macrophages to sites of intimal injury from accumulated lipids?
Monocyte chemo-attractant protein 1 (MCP-1)
What is the significance of foam cells in the intima?
1) Cause smooth muscle cell emigration from the media to the intima
2) Further secretion of cytokines for inflammatory response
Causes further macrophage activation
What factor is highly implicated in the proliferation of smooth muscle cells in the pathogeneis of athersclerosis ?
PDGF
What are the two morphologic stages of atherosclerosis?
1) Fatty streaks
2) Proliferative lesion
2) Atherosclerotic plaque, or “atheroma”
What is a fatty streak?
Flat yellow lesions of the intima consisting of foam cells/ lipid laden macrophages
What process do atherosclerotic plaques undergo?
Dystrophic calcification i.e. “hardening” of the artery
Where do atherosclerotic plaques begin to develop? Why?
Adjacent to bifurcations b/c of the changes in blood flow in these regions
Shear stress= endothelial injury
What are the major complications of atherosclerotic lesions?
1) Calcification
2) Hemorrhage
3) Rupture or ulceration
4) Thrombosis
Why is rupture of an atherosclerotic plaque dangerous?
Substances exposed by the rupture induces thrombogenesis
What are the implications of the strength of the fibromuscular cap of an atherosclerotic plaque?
Thickness is directly correlated with stability
The thicker the cap, the less likely it is to rupture and thrombose
What is the primary prevention for atherosclerosis?
Prevention with:
1) Statins
2) Anti-hypertensives
3) Aspirin to prevent clotting
Lifestyle modification is key to prevention
What is secondary prevention in atherosclerosis?
Treatment once an atherosclerotic plaque has ruptured i.e:
1) TPa
2) Angioplasty
3) CABG
What is the primary cause of an abdominal aortic aneurysm?
Atherosclerosis
Why does atherosclerosis predipose one to an abdominal aortic aneurysm?
- Atherosclerosis in the media increases the diffusion barrier to the media
- Hypoxia from limited diffusion leads to atropthy and weakness of the vessel wall
- Ballooning of the vessel occurs
What is the ABPI?
Ankle Brachial Pressure Index
*Comparison of ankle BP to arm BP
What ABPI is considered abnormal?
Less than 0.9
*The lower the number, the worse the PVD
What is the major complication of peripheral atherosclerosis? What patient population is this most common in?
Gangrene
*DM
What happens when there is a MI or ischemic CVA?
Atherosclerotic plaque rupture and thrombosis that:
- Occludes coronary artery (MI)
- Occludes the cerebral artery (CVA)
What degree of stenosis must occur for there to be complications?
70%
What is the Glagov coronary remodeling hypothesis?
- As the vessel lumen narrows, it will initially expand to compensate
- Eventually the vessel will not be able to expand further
This point, where the vessel can no longer expand is when severe disease results
