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134 Cards in this Set
- Front
- Back
what can hypotension lead to
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inadequate organ perfusion then dysfunction or death
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what can hypertension lead to
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vessel and end-organ damage
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BP above what limits is considered as increased risk of atherosclerosis
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sustained diastolic above 89 mmHg and systolic above 139 mmHg
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when are lower thresholds for BP applicable
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in patients with other risk factors like diabetes
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what causes essential hypertension
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unknown; combined effects of multiple genetic polymorphisms and interacting environmental factors
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If untreated, what is the clinical outcome of half od hypertensive patients
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die of ischemic heart disease or CHF (another 1/3 of stroke)
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accelerated/malignant hypertension
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rapidly rising BP, when untreated leads to death in 1-2 years
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characteristics of accelerated hypertension
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BP >200/120; renal failure, retinal hemorrages and exudates; generally superimposed on pre-existing benign hypertension
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What is peripheral vascular resistance affected by
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neural and horonal factors
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humoral vasoconstricting influences
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angiotensin II, catecholamines, endothelin
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vasodilators
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kinins, prostaglandins, NO
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what does the renin-angiotensin system affect
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peripheral resistance and sodium homeostasis
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when and where is renin secreted
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by the JG cells of kidney in response to fall in BP
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3 actions of angiotensin II
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vascular smooth muscle contraction, aldosterone secretion stimulation, distal tubular reabsorption of Na
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why does decreased blood volume cause increased reabsorption of Na by proximal tubules
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glomerular filtration rate falls (basically blood goes slower allowing more time for Na to be reabsorbed)
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What do atrial and ventricular myocardium release in response to volume expansion
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natriuretic factors
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what are the actions of natriuretic factors
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inhibit Na reabsoption in distal tubules and induce vasodilation (endogenous inhibitors of renin-angiotensin system)
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What reabsorbes 98% of Na in kidneys
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ion channels, exchangers, and transporters constitutively active and not subjet to regulation
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Where is the remaining 2% reabsorbed?
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epithelial Na+ channel (ENaC) in the cortical collecting tubule (tightly regulated by renin-angiotensin system)
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Where are genetic defects affecting aldosterone metabolism and increasing aldosterone secretion
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aldosterone synthase, 11B-hydroxylase, 17a-hydroxylase; all cause hypertension
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Liddle syndrome
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mutations in epithlial Na+ channel protein that leads to increased distal tubular reabsorption of Na+ induced by aldosterone; causes hypertension
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exogenous factors in hypertension
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stress, obesity, physical inactivity, heavy consumption of salt
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one of the most common causes of secondary hypertension
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primary aldosteronism
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2 forms of small blood vessel disease associated with hypertension
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hyaline arteriolosclerosis and hyperplastic arteriolosclerosis
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hyaline arteriolosclerosis
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plasma protein leakage across injured endothelial cells and increased smooth muscle cell matrix synthesis in response to chronic hemodynamic stress
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what other common disease causes hyaline arteriolosclerosis and what causes it
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diabetic microangiography; hyperglycemia induced endothelial cell dysfunction
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nephrosclerosis due to chronic hypertension
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arteriolar narrowing of hyaline arteriolosclerosis causes diffuse impairment of renal blood supply and causes renal scarring
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hyperplastic arteriolosclerosis
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occurs in malignant hypertension; vessels exhibit 'onion-skin' lesions-consist of smooth muscle cells with thickened, reduplicated basement membranes
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necrotizing arteriolitis
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fibrinoid deposits and vessel wall necrosis, particularly in the kidney
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arteriosclerosis
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generic term describing arterial wall thickening and loss of elasticity
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3 general patterns of arteriosclerosis
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1) arteriolosclerosis 2) Monskeberg medial sclerosis 3) atherosclerosis
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arteriolosclerosis
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affects small arteries and arterioles (hyaline and hyperplastic variants)
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Monskeberg medial sclerosis
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calcific deposits in muscular arteries; generally in patients >50; deposits may undergo metaplastic change into bone; do not encroach on vessel lumen and are usually not clinically significant
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Atherosclerosis
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most frequent and clinically important pattern
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atheromas
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intimal lesions that protrude into vessel lumens
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increased risk of atherosclerosis with 2 or 3 risk factors
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4 times, 7 times increased risk
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modifiable risk factors in IHD
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hyperlipidemia, hypertension, cigarette smoking, diabetes
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what are dietary sources high in cholesterol and saturated fats
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egg yolks, animal fas, butter
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what raises/lowers HDL levels
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exercise and moserate ethanol consumption; obstiry and smoking
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what class of drugs lowers cholesterol
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statins
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mechanism of statins
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inhibit hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (the rate limiting enzyme in cholesterol biosynthesis)
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other risk factors for cardiovascular events
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inflammation, hyperhomocystinemia, metabolic syndrome, lipoprotein (a), factors affecting hemostasis, others
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C-reactive protein
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circulating marker of inflammation that correlates with IHD risk
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What is CRP
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acute-phase reactant synthesized primarily by liver; role in innate immune response
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what role does CRP play in innate immune response
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opsonizing bacteria and activating complement
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How does CRP contribute to atherosclerosis
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can activate local endothelial cells and induce a prothrombic state and increase adhesiveness of endothelium for leukocytes
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what can cause high homocysteine levels
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low folate and vitamin B12 intake
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what is lipoprotain (a)
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modified LDL that contains apolipoprotein B-100 portion of LDL linked to apolipoprotein A
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2 hypotheses of artherosclerosis mechanism
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1) intimal cellular proliferation 2) repetative formation and organization of thrombi
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atherosclerosis is produced by (7 steps)
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1) endothelial injury 2) accumulation of lipoproteins 3) monocyte adhesion 4) platelet adhesion 5) factor release 6) smooth muscle proliferation and ECM production 7) lipid accumulation
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where do early atheromas begin
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sites of morphologically intact endothlium; thus endothelial dysfunction underlies human artherosclerosis
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two most important causes of endothelial dysfunction
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hemodynamic disturbances and hypercholesterolemia
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why do plaques tend to occur at ostia of existing vessels
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1) disturbed flow patterns 2) endothelial gene products (like antioxidant superoxide dimutase)
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common lipoprotein abnormalities in the general population
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1) increased LDL cholesterol levels 2) decreased HDL cholesterol levels 3) increased levels of lipoprotein (a)
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what are the dominant lipids in atheromas
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cholesterol and cholesterol esters
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how does hypercholesterolemia cause atheroscerosis
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directly impair endothelial cell fxn by increasing local oxygen free radical producation (injure tissues and accelerate NO decay)
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how does LDL become oxidized
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via free radicals generated by macrophages or endothelial cells
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what does oxidized LDL stimulate
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release of GFs, cytokines, chemokines by endothelial cells and macrophages and increase monocyte recruitment
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LDL oxidation cycle
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oxidized LDL recruits monocytes, monocytes arrive and engulf potentially harmful oxidized LDLs, monocytes secrete factors that recruit more monocytes and cause oxidation of more LDL
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growth factors implicated in smooth muscle cell proliferation and ECM synthesis
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PDGF, FGF, TGF-alpha
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what is PDGF released by
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locally adherent platelets, macrophages, endothelial cells, and smooth muscle cells
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what is the main ECM product smooth muscle cells synthesize
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collagen; stabilizes plaques
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fatty streaks
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earliest lesions in atherosclerosis; lipid-filled foamy macrophages
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most extensively involved vessels in atherosclerosis
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lower abdominal aorta, coronary arteries, cicle of Willis
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vessels ususally spared by atherosclerosis
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upper extremities, mesenteric, and renal arteries (except at ostia)
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3 components of atherosclerotic plaques
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1) cells including smooth muscle cells, macrophages, and T cells 2) ECM including collagen, elastic fibers, and proteoglycans 3) intra and extracellular lipid
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what are plaques susceptable to?
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rupture, ulceration, erosion…thrombosis
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what percent occlusion generally occurs before demand exceeds supply
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~70%
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intermittent claudication
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diminished extremity perfusion
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intrinsic factors that trigger abrupt changes in plaque configuration
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structure and configuration
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extrinsic factors that trigger abrupt changes in plaque configuration
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BP, platelet reactivity
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what affects cap stability
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balance of collagen synthesis to degradation
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what determines collagen turnover
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metalloproteinases (MMPs) elaborated by macrophages
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inhibitors of MMPs (TIMPs)
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produced by endothelial cells, smooth muscle cells, and macrophages
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statin affect on plaques
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may stabilize plaques in addition to lowering cholesterol levels
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what does aadrenergic stimulation do
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increase BP, induce local vasoconstriction
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peak onset of MI
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6 am and 12 pm
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what can cause vasoconstriction
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1) circulating adrenergic agonists 2) locally released platelet contents 3) impaired secretion of endothelial cell relaxing factors relative to contracting factors 4) mediators from perivascular inflammatory cells
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vascular pathology results via what 2 principle mechanisms
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1) narrowing or complete obstruction (either progressive or acute) 2) weakening of vessel walls (dilation and rupture)
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arterial wall
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thickness gradually diminishes as vessels become smaller, but ratio of thickness to diameter become greater
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what separates the intima from the media
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internal elastic lamina
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what generaaly separates arterial media from adventicia
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external elastic lamina
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what is in the adventicia
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CT with nerve fibers and vasa vasorum
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Three categories of arteries
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1) large/elastic arteries 2) medium/muscular arteries 3)small arteries (less than 2mm) and arterioles (20-200 um)
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where are most structural variations in arteries due to local adaptations
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in the media and ECM
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ectatic
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dialated
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how are resistance and arteriole diameter related
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halving diamter increases resistance 16 fold
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diffusion of oxygen become ineffecient at what distance
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100 um
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What layers are present in capillaries
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endothelial cell lining, NO media
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Where does vascular leakage and leukocyte exudation occur in general
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postcapillary venules
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what vessels does atherosclerosis generally affect
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elastic and muscular arteries
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what vessels does hypertension generally affect
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small muscular arteries and arterioles
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what 3 processes characterize blood vessel formation and remodeling
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vasculogenesis, angiogenesis, arteriogenesis
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vasculogenesis
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formation of blood vessles during embryogenesis
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angiogenesis
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new vessel formation in maature organism; aka neovascularization
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arteriogenesis
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remodeling of existing arteries
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significant congenital vascular anomalies (no necessarily common)
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1) developmental or berry aneurysms 2) arteriovenous fistula 3) fibromuscular dysplasia
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fibromuscular dysplasia
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foal irregular thickening of wall of medium and large muscular arteries (renal, carotid, etc)
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Weibel-Palade bodies
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intracellular membrane-bound storage organelles for von Willebrand's factor in endothelial cells
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activities of vascular endothelium
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maintain nonthrombogenic blood-tissue interface, modulate vascular resistance, metabolize hormones, regulate inflammation, affect growth of other cell types
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how can the tight jxns btwn endothelial cells be loosened
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high BP, vasoactive agents (histamine),
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where can you find fenestrated capillaries
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liver sinusoids or renal glomeruli
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promoters of vascular smooth muscle cells
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PDGF, endothelin-1, thrombin, FGF, interferon-gamma, IL-1
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inhibitors of vascular smooth muscle cells
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heparan sulfates, NO, TGF-B
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neointima
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a new or thickened layer of arterial intima
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true aneurysm
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innvolves intact attenuated arterial wall or thinned ventricular wall of the heart
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what are examples of true aneurysms
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atherosclerotic, syphilitic, congenital vascular, ventricular that follow trasmural Mis
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false aneurysm
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defect in the vascular wall leading to extravascular hematoma that freely communicates with the intravascular space
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saccular aneurysm
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spherical outpouching (often contain thrombus)
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Fusiform aneurysm
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diffuse, circumferential dilation along a vascular segment (not specific for any disease or clinical manifestations)
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Marfan syndrome
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defect in fibrillin causing aberrant TGF-B activity and progressive weakening of elastic tissue
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LoeysDietz syndrome
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mutations in TGF-B receptors lead to abnormalities in collagen I and III
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Ehlers-Danlos syndrome (vascular forms)
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type III collagen mutation
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example of nutritional basis for aneurysm formation
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vit C deficiency (lack of cross-linking)
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What degrades ECM components
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MMPs
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cystic medial degeneration
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ischemia of media causing scarring, inadequate ECM synthesis, producation of GAGs
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two most important disorders that predispose to aortic aneuryms
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atherosclerosis and hypertension
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most common atherosclerosis aneurysm sites
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abdominal aorta
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most common hypertension aneurysm site
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ascending aorta
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mycotic aneurysm
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caused by infections
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why does the media become ischemic in atherosclerosis of abdominal aorta
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plaque in intima compresses on underlying media and comprises nutrient and waste diffusion from vascular lumen into arterial wall
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Major influence that leads to aneurysm formation is
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production of MMP by inflammatory cell infiltrates
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Inflammatory AAA (abdominal aortic aneurysm)
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dense periaortic fibrosis containing abundant lymphoplasmacytic inflammation with many macrophages and often giant cells (cause uncertain)
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Mycotic AAA
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lesions that become infected by lodging of microorganisms in wall
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common bacteria causing mycotic AAA
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from Salmonella gastroenteritis bateremia
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how do AAA present
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abdominal mass, often palpably pulsating, that simulates a tumor
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how quickly do aneurysms expand
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0.2-0.3 cm per year
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when should a aneurysm be managed aggresively
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greater than 5cm; surgical bypass
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signs and symptoms of thoracic aneurysm
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encroachment causing repiratory difficulties, swallowing issues, persistent cough (irritation of recurrent laryngeal nerve), pain from bone erosion, cardiac disease
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aortic dissection
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blood splays apart the laminar planes of the media to form a blood-filled channel within the aortic wall
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iatrogenic
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induced inadvertently when trying to fix problem or by diagnotic procedure
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proximal lesions in aotic dissections
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more common, involve both ascending and descending or just ascending (type I and II)
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distal lesions in aortic dissection
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doesn't involve ascending aorta, usually distal to subclavian artery (type III)
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clinical symptoms of aotic dissection
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sudden onset excruciating pain in anterior chest
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