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17 Cards in this Set
- Front
- Back
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Define atherosclerosis.
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• Multifactorial, chronic inflammation
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Describe the role of LDL in atherosclerosis.
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• Accumulation of LDL in walls of medium size & larger muscular arteries
• Leads to hardening & calcium deposition, plaque accumulation, restriction of blood flow and clot formation • LDL levels increase with aging due to diminished LDL receptor functioning |
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Describe the role of HDL in atherosclerosis.
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protective
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Tangier's Disease.
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low levels of the anti-atherogenic HDL-cholesterol
o defect in the ABCA1 cholesterol transporter, essential for HDL formation leading to accum. Of intracellular cholesterol |
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Outline the pathogenesis.
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1. initial endothelial lesions leads to impaired endothelial cells functioning, inflame. And altered permeability
2. Transcytosis of ox-LDL cholesterol & the migration of platelets & monocytes into the intimal space increases 3. Monocyte-derived macs deposite in the tunica intima & media accum. lipid into foam cells 4. These foam cells express scavenger receptors that take up ox-LDL (not subject to negative feedback) 5. Foam cells stretch & underlying Macs are exposed = advance lesion 6. Tear can widen from pressure leading to thrombus formation, artery occlusion and vascular damage 6. Platelets liberate growth factor that cause proliferation of smooth muscle which release collagen leading to further enlargement of the plaques (possible rupture) |
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Explain the synthesis of NO via NOS.
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• Local hormone produced in mammalian cells (endothelial)
• Maintains vascular homeostasis & atherosclerosis actions • NADPH-dependent NO synthase (eNOS) [requires calcium and tetrahydrobiopterin] reduces the arg to citruline forming NO |
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Evaluate the role of NO atherosclerosis.
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• Mediates vasodilation for inhibiting platelet adherence and aggregation to endothelial cells, inhibiting smooth muscle proliferation and lowers oxidation of LDL
• Atherosclerosis = dysfunctional eNOS |
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List the dietary risk factors for atherosclerosis.
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• Diet= high in saturated fat or cholesterol
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List the life style risk factors for atherosclerosis.
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• Smoking = oxidative damage to LDLs, reduce protective HDL, increase platelet aggregation & elevate plasma fibrinogen
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Describe the infective agents.
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• Pathogen free chicken infected with MDV develop visible plaques & feeding chicken cholesterol rich diet potentiated this process
• MDV presence in affected arteries • CMV infection of arterial smooth muscle may initiate atherosclerosis • Endothelial cells express viral glycoproteins & increase adherence of polymorphonuclear leukocytes (initial phase) |
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Describe familial Hypercholesteremia.
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• Defective LDL receptors
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Heterogenous Hypercholesteremia.
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• Missing single gene of LDL-receptor
• Entry of LDL & IDL into the liver is reduced and circulations LDL are elevated to 300mg/dL • Leads to xanthomas and formation of atheroma • Suffer from cardiovascular event before 30 & treatment aimed towards lowering circulating LDL |
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Homozygous Hypercholesteremia.
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• Almost no LDL receptors
• Plasma cholesterol exceed 700 • Usually die in childhood of CAD since liver transplant is the only treatment |
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Describe the clinical events involved with atherosclerosis.
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Ischemic stroke/ aneurysm
aoritc aneurysm ischemic bowel intermittent claudication Heart attack/angina |
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Describe the role of Cholestyramine.
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• bile acid binding resins, prevent reabsorption of negatively charged bile acids thus reducing circulating LDL
• Also, expression of LDL receptors is increased • Should be mixed with other foods and low initial doses • Side effects; constipation or bloating, circulating Tag levels should be monitored (may rise by 10-15%) |
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Describe the role of Statins.
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• Inhibitors of HMG CoA reductase
• Can block cholesterol biosynthesis • Increase LDL receptor on the liver = reduce LDL & increase HDL • HDL = reduce inflammation (COX-2) • Lipitor; widely prescribed, some benefits in Alzheimer’s & sickle cell • Statins are contradicted in liver & kidney disease, tolerated but may cause hepatitis |
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Describe the role of Niacin.
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• Reduce Tags and increase HDL
• Low doses associated with gastritis & GI bleeding • Contradicted in peptic ulcer disease, gastritis, diabetes an liver disease • Gemfibrozil (lopid); derivative of fibric acid, activates peroxisomes proliferator activated receptor alpha o agent of choice w/ elevated tags (little effect on LDL) o metabolized in the kidney (avoid w/ renal disease) • if agents fail, gradually increase doses or use in combination with other lipid lowering agents (lower LDL by 50-60%) |
