Term
| what are the antithrombotic molecules that reside on the endothelial surface? |
|
Definition
| heparan sulfate, thrombomodulin, plasminogen activators |
|
|
Term
| what are the antithrombotic molecules that are created by the endothelium and released into circ? |
|
Definition
|
|
Term
| what are the vasodilators released by the endothelium? vasoconstrictors? |
|
Definition
| dilators: NO and prostacyclin; constrictors: endothelin |
|
|
Term
| what do smooth muscle cells synthesize? |
|
Definition
| collagen, elastin, proteglycans (ECM); vasoactive and inflammatory mediators (IL-6 TNFa --> promote leukocyte proliferation and induce endothelial expression of leukocyte adhesion molecules) |
|
|
Term
| what inhibits smooth muscle cell proliferation in vitro? |
|
Definition
|
|
Term
| what are the key components that contribute to the atherosclerotic inflammatory process |
|
Definition
| endothelial dysfunction; accumulation of lipids in the intima; recruitment of leukocytes and smooth muscle cells to the vessel wall; formation of foam cells; deposition of ECM |
|
|
Term
| what are the 3 pathologic stages of atherosclerosis? |
|
Definition
| fatty streak, plaque progression, plaque disruption |
|
|
Term
| how is the fatty streak created? (earliest visible lesion of atherosclerosis) |
|
Definition
| stressors --> endothelial dysfunction --> entry and modification of lipids within the subintima --> serve as proinflammatory mediators that initiate recruitment of leukocytes --> foam cell formation |
|
|
Term
| how does laminar flow protect against atherosclerosis? |
|
Definition
| favors endothelial expression of NO (vasodilator, antithrombotic, anti-inflam); also increases expression of antioxidant enzyme superoxide dismutase (protects against reactive oxygen species produced by chemical irritants or transient ischemia) |
|
|
Term
| what are examples of "toxic" chemicals that cause endothelium dysfunction upon exposure? |
|
Definition
| cigarettes, abnormal circulating lipid levels, diabetes (increase endothelial production of reactive oxygen species, cells skewed toward proinflammatory processes) |
|
|
Term
| describe lipid trapping in atherosclerosis |
|
Definition
| endothelial dysfunction --> decreased function as a barrier --> LDL gets into intima --> LDL binds to proteoglycans |
|
|
Term
| how does HTN promote retention of lipids in the intima? |
|
Definition
| accentuating production of LDL-binding-proteoglycans by smooth muscle cells --> increases trapping |
|
|
Term
| what are the 2 kinds of chemical modification that LDL undergoes once trapped in the subintima? |
|
Definition
| oxidation (local action of ROS and pro-oxidant enzymes); glycation of LDL in diabetics with sustained hyperglycemia --> LDL antigenc and proinflam --> modified LDL = promotes leukocyte recruitment and foam cell formation |
|
|
Term
| what 2 things are needed for leukocyte recruitment to the vessel wall? |
|
Definition
| 1. leukocyte adhesion molecules (VCAM1, ICAM1, E and P selectins) 2. chemoattractant signals (chemokines) --> mainly attract monocytes and some T lys |
|
|
Term
| what 2 things induce expression of leukocyte adhesion molecules and chemokines? |
|
Definition
| mLDL and proinflammatory cytokines, (IL1, TNFa); mLDL also potently stimulates endothelial and smooth muscle cells to produce proinflam cytokines --> reinforce direct action |
|
|
Term
| how are foam cells made from monocytes and lipids? |
|
Definition
| monocytes attracted to vessel by leukocyte adhesion molecules and chemokines --> adhere to and penetrate intima --> differentiate into phagocytic macrophages --> imbibe lipoproteins to form foam cells |
|
|
Term
| how are mLDL molecules taken up to form foam cells (receptor?) ? |
|
Definition
| not by classic LDL receptors (they do not recognize mLDL); SCAVENGER receptors preferentially bind and internalize mLDL (these cells evade negative fb inhibition and allow themselves to become engorged with lipids --> foam cells) |
|
|
Term
| how is creation of foam cells supposed to be beneficial? where does it go wrong? |
|
Definition
| beneficial by sequestering proinflammatory mLDL particles, but they have impaired efflux --> local accumulation in the plaque and serving as a source of proinflammatory cytokines that fuel atherosclerotic plaque progression |
|
|
Term
| describe the morphology of a typical atherosclerotic plaque? |
|
Definition
| thrombogenic lipid core underlying a protective fibrous cap |
|
|
Term
| in a nutshell how does the transition from fatty streak to fibrous atheromatous plaque happen? |
|
Definition
| migration of smooth muscle cells from arterial media to intima --> proliferation of smooth muscle cells within intima --> secretion of ECM macromolecules by smooth muscle cells |
|
|
Term
| what are 3 things that foam cells secrete that contribute to plaque progression? |
|
Definition
| PDGF (stimulates migration of smooth muscle cells across internal elastic lamina where they replicate); cytokines/growth factors (TNFa, IL1, TGFb--> further stimulate smooth muscle cell proliferation and synthesis of ECM proteins); tissue factor (with small, subclinical breaches in plaque integrity) --> activates coag and microthrombus formation --> activated platelets within microthrombi release PDGF and heparinase that contribute to smooth muscle cell migration and proliferation (heparinase degrades heparan sulfate, which normally inhibits smooth muscle cell migration and prolif) |
|
|
Term
| what cell contributes the most to matrix desposition? what influences this cells action? |
|
Definition
| smooth muscle cells = dominant collagen-synthesizing cell type. PDGF and TGF-b stimulate smooth muscle cell production of interstitial collagens. IFN-g from T lymphocytes inhibits this |
|
|
Term
| what are the main contributing factors to matrix degradation? |
|
Definition
| MMP secreted by foam cells. inflammatory cytokines stimulate foam cells to secrete MMPs (IL1, TNFa, MCP1, CD40L) |
|
|
Term
| how does the tug of war between matrix synthesis and deposition lead to growth of the plaques lipid core? |
|
Definition
| smooth muscle cells and foam cells die --> release their contents --> contribute lipids and debris to the growing lipid core-->increasing size and protrusion into lumen --> increased hemodynamic stress on the plaque border --> rupture at shoulder? |
|
|
Term
| what is the main determinant of whether or not a plaque will rupture? |
|
Definition
| balance between competing processes of coagulation and fibrinolysis. person's propensity toward coagulation may be enhanced by genetics, coexisting conditions, lifestyle factors |
|
|
Term
| what are the 5 complications of atherosclerotic plaques? |
|
Definition
| calcification (pipelike rigidity, increases fragility of vessel wall); rupture/ulceration (exposes procoagulants --> create thrombus, occludes vessel, infarction; or can simply incorporate into lesion and add to bulk); hemorrhage (intramural hematoma, narrowed lumen even more); embolization; weakening of vessel wall (atrophy and loss of elastic tissue --> aneurysm) |
|
|
Term
| modifiable risk factors for atherosclerosis |
|
Definition
| lipid level, tobacco, htn, diabetes, lack of physical activity, obesity |
|
|
Term
| nonmodifiable risk factors for atherosclerosis |
|
Definition
|
|
Term
| "novel" risk factors - biological markers associated with atherosclerosis |
|
Definition
| increased homocysteine, Lp(a), markers of inflammation like C-reactive protein |
|
|
Term
| what would cause an elevated LDL (correlate with increased incidence of atherosclerosis)? |
|
Definition
| high fat diet, abnormalities in LDL-receptor clearance, genetic defects in LDL receptor (familial hypercholesterolemia) |
|
|
Term
| what's the harm in smoking tobacco? |
|
Definition
| increases modification of LDL decreases HDL, tissue hypoxia --> endothelial damage, increased oxidant stress, increased platelet adhesion, increased leukocyte adhesion molecules, inappropriate stim of sympathetic nervous system; not only accelerates atherosclerosis but increases propensity to thrombosis |
|
|
Term
| how does HTN contribute to atherosclerosis? |
|
Definition
| injures vascular endothelium by hemodynamic stress, increases # of scavenger receptors --> increases # of foam cells, enhances smooth muscle cell production of proteoglycans that bind and trap LDL particles, angiotensin II acts as proinflam cytokein, contriubtes to inflammatory state |
|
|
Term
| what is the metabolic syndrome? |
|
Definition
| clustering of risk factors that is associated with a high risk of atherosclerosis (HTN, hyper-TG, insulin resistance, obesity) 44% of americans have it |
|
|
Term
| how does physical activity decrease chances of atherosclerosis? |
|
Definition
| beneficial effects on lipid profile and BP, enhances insulin sensitivity and endothelial production of NO |
|
|
Term
| what does physiologic estrogen do to protect pre-menopausal women against atherosclerosis? |
|
Definition
| raises HDL and lowers LDL, antioxidant, antiplatelet, improves vasodilation |
|
|
Term
| how does elevated homocysteine contribute to atherosclerosis? |
|
Definition
| promote oxidative stress, vascular inflammation and platelet adhesiveness |
|
|
Term
| how does Lp(a) contribute to atherosclerosis? |
|
Definition
| competition with normal plasminogen activity |
|
|
Term
| what are the 2 things that affect myocardial oxygen supply? |
|
Definition
| oxygen content of the blood (more stable, unless anemia or lung disease present) and coronary blood flow rate (more dynamic); coronary blood flow then determined by perfusion pressure (diastolic) and coronary vascular resistance (forces that compress coronary arteries and factors that alter intrinsic coronary tone) |
|
|
Term
| when are coronary arteries most perfused? |
|
Definition
|
|
Term
| what part of the heart is subjected to greater force than the outer muscle layers? |
|
Definition
|
|
Term
| what are 3 factors that participate in regulation of coronary vascular resistance and why is this important? |
|
Definition
| accumulation of local metabolites, endothelium-derived substances, neural innervation (important bc heart removes as much oxygen as possible from blood supply, so any additional oxygen requirement must be met by an increase in blood flow which is determined by mediators of coronary vascular resistance) |
|
|
Term
| what is the primary local metabolite that affects coronary vascular tone? and how does it accumulate? |
|
Definition
| ADENOSINE (vasodilator); hypoxemia --> aerobic metabolism and oxidative phosphorylation in mit inhibited --> ATP cannot be regenerated --> ADP and AMP accumulate --> degraded to adenosine |
|
|
Term
| NO is released in response to endothelium exposure to... |
|
Definition
| acetylcholine, thrombin, products of aggregating platelets (seratonin, adp), shear stress of blood flow |
|
|
Term
| describe how endothelial-dependent vasodilators cause vasodilation (i.e. AcH, seratonin, histamine). |
|
Definition
| endothelial-dependent vasodilator binds to endothelial cell --> increase in intracellular free Ca --> activates nitric oxide synthase (L-arginine --> NO) --> NO diffuses into smooth muscle --> activates G-cyclase (GTP --> cGMP) --> increased intracellular cGMP results in smooth muscle relaxation and is also associated with antimigratory effects of the smooth muscle cells |
|
|
Term
| how does administration of AcH in a normal person and a person with endothelial dysfunction differ? |
|
Definition
| normal person: vasodilation; endothelial dysfunction: causes vasocinstriction bc reduced NO production by dysfunctional cells and unopposed direct vasoconstriction of smooth muscle by AcH. |
|
|
Term
| what are the 3 major determinants of myocardial oxygen demand? |
|
Definition
| ventricular wall stress, heart rate, contractility |
|
|
Term
| what is la place's relationship |
|
Definition
| wall stress = (pressure x radius)/(2 x wall thickness) |
|
|
Term
| in ischemia, reduction in blood flow to myocardium results from a combination of? |
|
Definition
| fixed vessel narrowing and abnormal vascular tone (contributed by atherosclerosis-induced endothelial cell dysfunction) |
|
|
Term
| hemodynamic significance of a stenotic lesion (as interpreted from poiseuilles law) depends on what 2 factors? |
|
Definition
| the length of the lesion and the degree of vessel narrowing (much more impt) |
|
|
Term
| describe the anatomy of coronary arteries |
|
Definition
| large, proximal epicardial segments (subject to overt atherosclerosis); distal segments free of flow-limiting plaques and can adjust their vasomotor tone in response to metabolic needs |
|
|
Term
| if a stenosis narrows the lumen by less than 60%...? |
|
Definition
| maximal potential blood flow through artery is not significantly altered. in response to exertion, resistance vessels can dilate to provide adequate blood flow |
|
|
Term
| if a stenosis narrows the lumen by ~70%...? |
|
Definition
| resting blood flow is normal; maximal blood flow REDUCED even with full dilation of resistance vessels (when oxygen demand increases during exertion, coronary flow reserve is inadequate --> ischemia) |
|
|
Term
| if a stenosis narrows the lumen by ~90%...? |
|
Definition
| even with maximal dilation of resistance vessels, blood flow may be inadequate to meet basal requirements at REST --> ischemia |
|
|
Term
| how does adrenergic stimulation result in vasodilatioN? |
|
Definition
| activation of sympathetic nervous system (alpha adrenergic constrictor effect of catecholamines on smooth muscle) vs. increased blood flow and shear stress causing increase in release of NO. NO>constriction. |
|
|
Term
| what do we observe in people with risk factors for CAD before visible atherosclerotic lesions have developed? |
|
Definition
| impaired endothelial-dependent vasodilation |
|
|
Term
| aside from atherosclerotic CAD, what else can cause decreased myocardial oxygen supply? |
|
Definition
| decreased perfusion pressure d/t hypotension; severely decreased blood oxygen content |
|
|
Term
| what causes an increase in myocardial oxygen demand? |
|
Definition
| rapid tachycardias, profound acute HTN, severe aortic stenosis |
|
|
Term
| what are the consequences of ischemia? |
|
Definition
| reduced generation of ATP impairs interaction of contractile proteins --> transient reduction in ventricular systolic contraction and diastolic relaxation (energy dependent); pulmonary congestion with dyspnea; accumulation of metabolic products (lactate, seratonin, adenosine) --> peripheral pain receptors --> angina; transient abnormalities in ion transport --> arrhythmias |
|
|
Term
| quickly define stunned myocardium |
|
Definition
| tissue, after suffering ischemia (not necrosis) --> prolonged systolic dysfunction even after return of normal myocardial blood flow |
|
|
Term
| what is hibernating myocardium? |
|
Definition
| tissue with chronic ventricular contractile dysfunction in the face of a persistently reduced blood supply |
|
|
Term
|
Definition
| pattern of chronic, predictable, transient angina during exertion or emotional stress (occlusion ~70%) |
|
|
Term
| differences in vascular tone over the sites of fixed stenosis can result in 2 different kinds of angina. what are they? |
|
Definition
| fixed-threshold and variable-threshold angina |
|
|
Term
|
Definition
| sudden increase in the tempo and duration of ischeic episodes occurring with lesser degrees of exertion and even at rest |
|
|
Term
| describe variant angina (prinzmetal angina) |
|
Definition
| coronary artery spasm in the absence of overt atherosclerotic lesions --> reduces coronary oxygen supply --> angina (may involve increased sympathetic activity with endothelial dysfunction and may be a sign of early atherosclerosis) occurs at REST (pathophys = reduction of supply, not increase in demand) |
|
|
Term
| which demographic is affected the most by silent ischemia? |
|
Definition
| diabetics - impaired pain sensation from peripheral neuropathy |
|
|
Term
|
Definition
| patients with typical angina symptoms but no evidence of atherosclerotic coronary stenoses on angiograms, may show definite signs of ischemia during exercise testing. (could be that there is inadequate vasodilator reserve of the coronary resistance vessels, microvascular dysfunc, vasospasm and hypersensitive pain perception) better prognosis than those with actual atherosclerotic disease |
|
|
Term
| describe the duration of angina |
|
Definition
| lasts a few minutes (rarely more than 5-10 mins, always more than a few seconds) |
|
|
Term
| accompanying symptoms of chronic stable angina |
|
Definition
| tachycardia, diaphoresis, nausea, dyspnea, transient fatigue and weakness |
|
|
Term
| what might we find on physical examination of someone having an anginal attack? |
|
Definition
| increased HR and BP, mitral regurgitation, abnormal bulging impulse on palpation of left chest, s4 gallop, may be no abn cardiac physical findings |
|
|
Term
| what do we find on the EKG of a patient with acute ischemia? |
|
Definition
| transient ST depression (horizontal or downsloping), T wave inversion or flattening |
|
|
Term
| what would we find on the EKG of someone having a more severe transmural myocardial ischemia? |
|
Definition
| ST elevation (can also be seen with the intense vasospasm of variant angina) |
|
|
Term
| stress test is considered positive when... |
|
Definition
| chest discomfort reproduced, EKG abnormalities consistent with ischemia develop (>1mm horizontal or downsloping ST segment depressions) |
|
|
Term
| stress test is considered MARKEDLY positive if.... |
|
Definition
| ecg changes within first 3 mins; ecg mins persist for 5 mins after exercise stopped; magnitude of st segment depression >2mm; systolic bp decreases; ventricular arrhythmias develop; pt cannot exercise at least 2 min |
|
|
Term
| under what circumstances do we do nuclear imaging studies/radionuclide exercise tests? |
|
Definition
| patients with baseline ecg abnormalities that preclude interpretation of standard exercise test; improvement in test sensitivity when standard stress test results are discordant with the clinical suspicion of CAD |
|
|
Term
| what drug do we use for pharmacologic stress testing when exercising is not possible? |
|
Definition
| dobutamine (stimulates HR and FOC); dipyridamole (vasodilates by blocking destruction of adenosine --> ischemic regions are already maximally dilated, so drug induced vasodilation increases flow to the myocardium perfused by healthy arteries and "steals" blood away from diseased segments) --> after either drug is administered, do nuclear imaging and look for cold spots (can also be done with echo instead of nuclear imaging_) |
|
|
Term
| what is the gold standard for identifying a coronary artery stenosis? |
|
Definition
| coronary angiography; inject radio-opaque contrast |
|
|
Term
| the predictors of mortality with CAD (and the predictors that help guide therapy) are? |
|
Definition
| extent of impaired LV contractile function; poor exercise capacity; magnitude of clinical anginal symptoms |
|
|
Term
| how do nitrates help to relieve angina? |
|
Definition
| venodilation --> reduces venous return to the heart --> subsequent decline in LV volume; also, dilates coronary vasculature (may be of min value in patients who have already dilated maximally from accumulation of local metabolites, but may be helpful when coronary vasospasm is playing a role in development of ischemia) |
|
|
Term
| what are the uses for nitrates? |
|
Definition
| symptomatic relief (angina); acute attacks use sublingual tablets, sprays (rapid); longer acting prevention - use oral tablets or patches once a day (patient can become tolerant, provide nitrate-free intervals for several hours each day) |
|
|
Term
| how do beta blockers help prevent recurrent ischemic episodes? |
|
Definition
| decrease myocardial oxygen demand by slowing HR, also increases amt of time spent in diastole and therefore helps coronary perfusion (not just symptomatic relief, been proven to actually decrease rates of recurrent infarction and mortality following an acute MI) FIRST LINE therapy in CAD tx |
|
|
Term
| use beta blockers with caution in which patients? |
|
Definition
| obstructive airway disease; acutely decompensated LV dysfunction; marked bradycardia; heart block; insulin-treated diabetic patients (masks tachy and other catecholamine-mediated responses that can warn of hypoglycemia) |
|
|
Term
| how do calcium channel blockers protect against ischemic attack? |
|
Definition
| dihydropyridines = potent vasodilators (decrease oxygen demand via venodilatation and arterial dilatation and increasing myocardial oxygen supply by increasing coronary dilatation, potent agents for relief of coronary artery vasospasm); nondihydropyridine = vasodilators but not as potent, more potent cardiac depressant actions (reduce FOC and slow HR) |
|
|
Term
| calcium channel blockers: how good of drugs are these? |
|
Definition
| ONLY long-acting blockers recommended as SECOND-LINE drugs if symptoms not controlled by beta blockers and nitrates |
|
|
Term
| care should be taken in combining a beta blocker with nondihydropyridine calcium channel blocker, why? |
|
Definition
| nondihydropyridine calcium channel blocker is a potent cardiac depressant and so are beta blockers --> could cause excessive bradycardia and precipitate heart failure in patients with LV contractile dysfunction |
|
|
Term
| what antiplatelet therapy is helpful in patients with CAD? |
|
Definition
|
|
Term
| when is coronary revascularization pursued? |
|
Definition
| angina sx do not respond adequately to antianginal drug therapy; unacceptable side effects of medications; high risk CAD for which revascularization is known to improve survival |
|
|
Term
| what is the major downside of percutaneous coronary interventions? how have we tried to improve this? |
|
Definition
| recurrent symptoms in 1/3 of patients within 6 months of procedure --> require additional coronary interventions; now we do coronary stents (need oral antiplatelet agents) |
|
|
Term
| stents were developed in response to frequent recurrent symptoms associated with PCIs. stents are still associated with in-stent restenosis caused by smooth muscle migration and proliferation, what have we developed to help that? |
|
Definition
| drug-eluting stents - polymer coat, incorporates anti-proliferative meds that are released over 2-4 weeks to prevent neointimal proliferation and clinical restenosis. antiplatelet therapy still needed |
|
|
Term
| have PCI been shown to reduce the risk of MI or death? |
|
Definition
|
|
Term
| what is the most common artery and vein used in bypass grafts? |
|
Definition
| vein: saphenous; artery: internal mammary |
|
|
Term
| use of what adjunctive drug can help improve the patency of bypass grafts? |
|
Definition
| aggressive lipid lowering therapy |
|
|
Term
| in general, what do we use noninvasive testing for (stress test, echo, nuclear imaging)? |
|
Definition
| in people with angina, use to identify those patients with HIGH-RISK disease becasuse the long-term prognosis for such patients can be improved by coronary revascularization |
|
|
Term
| who's a good candidate for PCI? |
|
Definition
| persistent episodes of angina, significant stenoses in 1 or 2 coronary arteries + certain low risk patients with 3 vessel disease |
|
|
Term
| CABG indicated for people with... |
|
Definition
| significant (>50%) stenosis of the left main coronary artery, multi-vessel disease, reduced LV contractile function or diabetes |
|
|
Term
| what are the 3 most important natural inhibitors of clot formation that maintain blood fluidity (antithrombus)? |
|
Definition
| antithrombinIII, proteins C&S, tissue factor pathway inhibitor |
|
|
Term
| describe how antithrombin III works as an antithrombotic |
|
Definition
| irreversibly binds thrombin and other clotting factors, inactivating them and facilitating their clearance from circulation. the effectiveness is increased 1000x by binding to heparan sulfate (present on luminal surface of endothelial cells) |
|
|
Term
| describe how protein C&S work as antithrombotics |
|
Definition
| protein C (once activated) synthesized in the liver, inactivates/degrades factors Va and VIIIa ("acceleration factors" of the coagulation pathway) --> inhibiting coagulation; presence of protein S in circ enhances the inhibitory function of protein C |
|
|
Term
| what does thrombomodulin do? |
|
Definition
| thrombomodulin is a thrombin binding receptor normally present on endothelial cells --> cannot convert fibrinogen to fibrin, but instead the complex activates protein C from inactive circulating plasma form into active form that can degrade factors Va and VIIIa |
|
|
Term
| describe how tissue factor pathway inhibitor acts as an antithrombotic |
|
Definition
| activated by coagulation factor Xa --> complex binds to and inactivates the complex of tissue factor with factor VIIa that normally triggers the extrinsic coagulation pathway |
|
|
Term
| how does tissue plasminogen factor work to lyse clots? |
|
Definition
| secreted by endothelial cells in response to many triggers of clot formation --> cleaves plasminogen to plasmin --> enzymatically degrades clots |
|
|
Term
| how does prostacyclin work as an inhibotor of platelets? |
|
Definition
| synthesized and secreted by endothelial cells, increases platelet levels of cAMP --> strongly inhibits platelet activation and aggregation (also indirectly inhibits coagulation by potent vasodilating properties) |
|
|
Term
| what are the 2 ways atherosclerosis contributes to thrombus formation? |
|
Definition
| plaque rupture (exposes circulating blood elements to thrombogenic substances); endothelial dysfunction (loss of normal protective antithrombotic and vasodilatory properties) |
|
|
Term
| what is the major trigger of coronary thrombosis and what causes it to happen? |
|
Definition
| plaque rupture; what causes rupture: chemical factors that destabilize the atherosclerotic lesions, physical stresses (systolic bp, blood viscosity, epinephrine levels) |
|
|
Term
| after a plaque ruptures, what are 4 ways it contributes to thrombosis? |
|
Definition
| 1. exposure of tissue factor from atheromatous core triggers coagulation pathway 2. exposure of subendothelial collagen activates platelets (release their granules, which include facilitators of platelet aggregation, activators of coagulation cascade, and vasoconstrictors) 3. intraplaque hemorrhage --> decreases vessel lumen diameter 4. turbulent blood flow --> shear stress --> further platelet activation |
|
|
Term
| what are a few other causes of ACS other than atherosclerosis? |
|
Definition
| vasculitis, coronary emboli (infected valves), congenital abnormalities, coronary trauma or aneurysm, severe coronary spasm (cocaine induced?), increased blood viscosity, markedly increased oxygen demand (aortic stenosis) |
|
|
Term
| early changes in infarction: what happens as oxygen levels fall in the myocardium supplied by an occluded vessel? (two major things) |
|
Definition
| decrease in the amount of ATP produced, and an increase in anaerobic metabolism |
|
|
Term
| myocardial hypoxia (from ischemia/infarct) --> decrease in ATP. what are the consequences of this? |
|
Definition
| impaired transmembrane Na-K-ATPase --> increased extracellular K (altered membrane potential, predisposing to arrhythmias); increased intracellular Na (altered membrane potential and intracellular edema); increase in intracellular Ca (intracellular edema and contributes to cell death by activation of degradative lipases and proteases) |
|
|
Term
| myocardial hypoxia (from ischemia/infarct) --> increase in anaerobic metabolism. what are the consequences of this:? |
|
Definition
| increaes in intracellular H (lowered pH) --> chromatin clumping and protein denaturation --> cell death |
|
|
Term
| what happens ~1-2 minutes into transmural infarction? |
|
Definition
| ATP levels fall and there is a decrease in myocardial function (cessation of contractility) |
|
|
Term
| what happens 10 minutes into a transmural infarction? |
|
Definition
| 50% depletion of ATP; cellular edema, decreased membrane potential and susceptibility to arrhythmias |
|
|
Term
| what happens 20-24 mins into transmural infarction? |
|
Definition
| irreversible cell injury marked by development of membrane defects |
|
|
Term
| what happens 1-3 hours into transmural infarction? |
|
Definition
| wavy myofibers (early histologic changes of irreversible injury) intercellular edema separates the myocardial cells |
|
|
Term
| what happens 4-12 hours into a transmural infarction |
|
Definition
| hemorrhage, edema, PMN infiltration begins |
|
|
Term
| what happens 18-24 hours in to transmural infarction |
|
Definition
| first gross morphologic changes seen, coagulation necrosis, edema |
|
|
Term
| after 2-4 days, what do we see in transmural infarction? |
|
Definition
| total coagulation necrosis, monocytes appear, PMN infiltration peaks |
|
|
Term
| what are the 2 late pathologic changes seen in infarction? |
|
Definition
| clearing of necrotic myocardium; deposition of collagen to form scar tissue |
|
|
Term
| what happens 5-7 days after a transmural infarction? |
|
Definition
| yellow-softening from resorption of dead tissue by macrophages (phagocytic clearing + thinning and dilation of infarcted zone --> structural weakness of ventricular wall and possibility of myocardial wall rupture) |
|
|
Term
| what happens 7+ days after a transmural infarction? |
|
Definition
|
|
Term
| what happens 7 weeks after transmural infarction? |
|
Definition
| fibrosis and scarring becomes complete |
|
|
Term
| what are the functional alterations that occur after myocardial infarction? |
|
Definition
| systolic dysfunction (decreased CO); loss of synchronous contraction of myocytes (decreased CO); diastolic dysfunction (reduced compliance and elevated filling pressures); hypokinesis, akinesis, dyskinesis of myocytes |
|
|
Term
| briefly describe ischemic preconditioning and what might cause it |
|
Definition
| brief ischemic insults may render that tissue more resistant to subsequent episodes (via ischemia-related activation of adenosine receptors?) |
|
|
Term
| describe how the ventricular tissue remodels after an MI |
|
Definition
| early post-MI: infarct expansion (thinning and dilatation of the necrotic zone) --> dilatation of overworked noninfarcted segments which are subjected to increased wall stress (initially compensatory to increase CO, but progressive enlargement --> heart failure and predisposition to ventricular arrhythmias) |
|
|
Term
| how do the sx of MI compare to those of angina? |
|
Definition
| discomfort quality resembles angina pectoris, but more severe, lasts longer, radiates more widely, no response to sublingual nitroglycerin (25% of pts asymptomatic, particularly common among diabetics); diaphoresis, tachy, cool/clammy skin; pulm congestion/dyspnea |
|
|
Term
| physical findings of an MI? |
|
Definition
| S4 (atrial contraction into a noncompliant ventricle); S3; friction rub (if inflammation has extended to pericardium); systolic murmur (if ischemia induced papillary muscle dysfunc); low grade fever |
|
|
Term
| unstable angina and STEMI: ecg changes? |
|
Definition
| ST depression, T wave inversion |
|
|
Term
| what are the 2 serum markers of infarction that we'd see in STEMI or NSTEMI? |
|
Definition
| cardiac specific troponins (cTnI, cTnT) - preferred biomarkers to detect necrosis; creatine kinase MB isoenzyme (small amt of this found in non-cardiac tissue, therefore not as sensitive as troponins); elevation of these biomarkers doesnt occur for a few hours, so echo and hx are more relied upon |
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Term
| what is the critical diff in approach to treating patients with STEMI and NSTEMI/UA? |
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Definition
| STEMI patients benefit from immediate reperfusion therapies |
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Term
| acute tx of UA and NSTEMI? |
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Definition
| same; antiischemic meds (b blockers, nitrates, calcium channel antagonists) and antithrombotic therapy (aspirin, clopidogrel, unfractionated heparin, low molecular weight heparins, glycoprotein IIb/IIIa receptor antagonists) |
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Term
| describe how unfractionated heparin and low molecular weight heparin work and why theyre prescribed in patients with UA and NSTEMI |
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Definition
| both are anticoags, bind to antithrombin III and greatly increase its potency in the inactivation of clot-forming thrombin. unfractionated heparin inhibits coag factor Xa while LMWH preferentially inhibits it, therefore LMWH has more predictable pharmacologic response and is easier to use. improves cardiovascular outcomes and reduces likelihood of progression from UA to MI |
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Term
| explain how glycoprotein IIb/IIIa receptor antagonists work and what theyre used for |
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Definition
| antiplatelet agents, block final common pathway of platelet aggregation; effective in reducing cardiac events in patients undergoing percutaneous coronary intervention (benefit in pts with UA or NSTEMI is more modest, only for high risk patients) |
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Term
| what do we use to reperfuse patients with STEMI? |
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Definition
| fibrinolytic drugs or percutaneous coronary vascularization (preferred if it can be performed rapidly or if pt is contraindicated in fibrinolytic therapy, pt presents late or pt is in shock) |
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Term
| how frequent does recurrent ischemia/post-infarction angina occur? |
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Definition
| 20-30% of patients (lower in those who have undergone PCI or stent implantation); poor omen correlates with increased risk for reinfarction, pt usually requires urgent cardiac catheterization followed by revascularization by PCI/stent or bypass surgery |
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Term
| what are 4 mechanisms that contribute to the development of post-MI arrhythmias? (dangerous) |
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Definition
| 1. anatomic disruption of perfusion to struc of conduction pathway 2. accumulation of toxic metabolites and abn transcellular ion concentrations owing to membrane leaks 3. autonomic stimulation (sym and parasym) 4. administration of potentially arrhythmogenic drugs |
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Term
| what is the diff b/w post-MI ventricular fibrillation that occurs during first 48 hours and vfib that occurs after first 48 hours? |
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Definition
| first 48 hours: related to transient elec instability (long term prognosis not affected); after 48 hrs: reflects severe LV dysfunc (assoc with high mortality) |
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Term
| what caues atrial premature beats and a fib post-MI? |
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Definition
| atrial ischemia or atrial distension secondary to LV failure |
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Term
| what causes conduction blocks post-MI? |
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Definition
| ischemia or necrosis of conduction tracts; increased vagal tone d/t stimulation of afferent fibers by inflamed myocardium or d/t generalized autonomic activation in assoc with pain of acute MI |
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Term
| how much of the LV mass has to infarct for cardiogenic shock to ensue? |
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Definition
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Term
| describe the self-perpetuating cycle of cardiogenic shock. |
|
Definition
| 1. MI --> decreased contractility --> hypotension --> decreased coronary perfusion pressure --> increased ischemia --> decreased contractility, etc etc 2. decreased SV increases LV size --> increases oxygen demand |
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Term
| what can we do to treat patients suffering from cardiogenic shock? |
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Definition
| IV inotropic agents (dobutamine) to increase CO, arterial vasodilators to decrease PVR; intra-aortic balloon pump (inflates during diastole to increase perfusion of the coronary arteries and reduce afterload); early cardiac catheterization and revascularization |
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Term
| what happens when ischemic necrosis causes papillary muscle rupture in the LV? |
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Definition
| acute severe mitral regurgitation --> HF/pulm edema |
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|
Term
| what happens when the ventricular septal wall ruptures after an MI? |
|
Definition
| blood shunted L to R --> volume overload of pulm capillaries --> CHF |
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|
Term
| what are the complications of a LV aneurysm? |
|
Definition
| thrombus formation (stagnant flow); ventricular arrhythmias (stretched myofibers); HF from reduced CO |
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|
Term
| what are some clues that a LV aneurysm is happening? |
|
Definition
| persistent ST elevation (weeks after STEMI), bulge at LV border on xray |
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|
Term
| how does an MI result in pericarditis? |
|
Definition
| early post-MI period necrosis and neutrophilic infiltrates extend from myocardium to adjacent pericardium |
|
|
Term
| what is dressler syndrome? |
|
Definition
| uncommon form of pericarditis; caused by an immune process directed against damaged myocardial tissue |
|
|
Term
| what are 2 ways that an MI can result in complete heart block? aka what 2 vessels are most commonly affected? |
|
Definition
| occlude R coronary artery --> knock out AV node; occlude LAD --> knock out septum |
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|
Term
| what fraction of people die with their first infarct? |
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Definition
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|
Term
| sinus bradycardia is a common arrhythmia to occur post-MI, what usually causes this? |
|
Definition
| excessive vagal stimulation or SA nodal ischemia in the setting of an INFERIOR wall MI (n/v, epigastric pain) |
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|
Term
| sinus tachycardia is common post-MI, what causes this? |
|
Definition
| common with acute MI bc pt is scared, anxiety, pain, HF. drug administration (dopamine), volume depletion |
|
|
Term
| whats the most common post-MI arrhythmia? |
|
Definition
| premature ventricular depolarization (don't require treatment) |
|
|
Term
| how do we determine whether shock is due to MI or hemorrhagic shock, sepsis? |
|
Definition
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|
Term
| in cardiogenic shock, what is the mortality rate? |
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Definition
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|
Term
| approx 1/3 of patients with LV infarction develop...? |
|
Definition
| RV infarction (d/t profound hypotension in the setting of impaired LV filling, esp with R coronary artery block) --> HTN, shock (tx: increase fluids, raise venous pressure) |
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Term
| what is the tx for papillary muscle rupture? |
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Definition
| surgery to repair the mitral valve (in the mean time, if BP is ok, use diuretics, if BP is bad use balloon pumps) |
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|
Term
| ventricular free wall rupture results in either? |
|
Definition
| cardiac tamponade or pseudoaneurysm formation |
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|
Term
| who is at an increased risk for ventricular free wall rupture? |
|
Definition
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|
Term
| what post-MI complication always accompanies full-thickness aka transmural MI? |
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Definition
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