Cardiovascular

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when a blood vessel is damaged (ruptured or severed), hemostasis is achieved through these mechanisms:

vascular spasm, formation of a platelet plug, formation of a blood clot, clot organization

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Vascular Spasm

contraction of vessel wall produced by autonomic reflexes, local spasm of vascular smooth muscle, local bioactive molecules (thromboxane A2 from platelets)

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Formation of a platelet plug: endothelial cells

when damaged, they initiate thrombogenesis by exposure of subendothelial collagen which induces platelet adhesion (mediated by von Willebrand factor)

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Patelet adhesion releases

ADP, histamine, seratonin, PDGF

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Platelet aggregation to the endothelial-adhered platelets is due to:

ADP, thrombin, thromboxane A2, platelet activating factor

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Platelet membrane phospholipase is activated with:

liberation of arachidonic acid which is metabolized via cyclo-oxygenase pathway to Thromboxane A2 to induce vasoconstriction and platelet aggregation

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Activation of the coagulation cascade:

d/t exposure of phospholipid complex molecules in platelet membrane after adhesion; the platelet mass is stabilized by fibrin

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Platelet cascade versus coagulation cascade

the platelet plug forms first, if the defect is small, the platelet plug is enough; if the damage is extensive, the clotting cascade is activated for fibrin stabilization

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Activation of clotting cascade

endothelial release of bioactive substances; Platelet release of bioactive substances; Circulating coagulation proteins adhering to exposed collagen of vascular wall

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Activation of the Extrinsic pathway of the clotting cascade is due to vascular injury

initiated by tissue factors from damaged vessels; tissue factors bind circulating factor VII forming activated complex; activated VIIa activates factors X and IX (intrinsic)

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Activated factor X

the common final pathway that initiates: prothrombin (factor II) conversion to IIa w/help from activated co-factor V; thrombin converts fibrinogen to fibrin monomers ( w/factor XIII make fibrin) to stabilize platelet mass into a fxnl clot

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Timing of clot formation

form in <1min; can occlude a med-sized vessel in <few min; after 20min, the clot contracts and closes the defect further; w/in a few hrs growth factors stimulate ingrowth of fibroblasts; in 10-14days the clot is completely fibrous

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Pathophysiology of Shock (circulatory failure/hypotension)

compensation activated by baroreceptors in vessels/heart to stim sympathetics to inc BP and correct hypoxemia (inc HR, contractility, periph constrict, tachypnea); redistribute blood to brain/core; switch to anaerobic glycolysis (metab acidosis)

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Traumatic blood loss

significantly dec volume; hypotension; tachycardic heart unable to maintain bp

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Cardiogenic shock: pump failure

heart becomes an ineffective pump; significantly reduced cardiac output; unable to maintain bp

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Neurogenic shock

usu a/w spinal cord injury; sudden loss of symp tone to systemic circulation (systemic vasodilation, peripheral blood pooling, dec return to heart); dec CO from LV and dec bp

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Pulmonary Thromboembolism

sudden interruption of blood traversing the pulmonary vasculature; dec CO from LV, dec bp

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Sequelae of prolonged HYPOtension

global cerebral hypoxia (brain damage/cerebral edema); global myocardial ischemia; acute respiratory distress syndrome (diffuse alveolar damage); acute tubular necrosis (kidney); centrilobular necrosis (liver); mesenteric bowel infarct

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Pathophysiology of HYPERtension (sys >140 or dias >90)

usu either: 1. inc symp tone (vasoconstriction and inc CO) or 2. inc levels of renin-angiotensin-aldosterone (renin inc AT1 which ACE converts to AT2 for vasoconstriction, inc aldosterone (Na retention inc CO, periph bp) and stim symp (inc CO, vasoconst)

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Increased sympathetics and increased renin levels lead to sustained bp elevations, which cause:

vascular damage in kidneys (a/w reduced renal blood flow; causes kidney to secrete more renin which elevates bp even more via effects on angiotensin and aldosterone) and other end organs

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Pathophysiology of Secondary Hypertension

d/t: 1. Chronic renal failure (mc; dec renal fxn leads to inc plasma vol; dec renal blood flow elevates renin/angiotensin); 2. Renal artery stenosis (mc2; dec flow = inc renin/angiotensin); 3. Conn Syndrome (aka: primary hyperaldosteronism; inc plasma vol

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Sequelae of Hypertension

Malignant hypertension (hypertensive encephalopathy/edema d/t vascular damage; intracerebral hemorrhage; renal failure (fibrinoid vascular necrosis in kidney; malignant nephrosclerosis); LVH & sudden death d/t dysrhythmia; CHF; accelerated atherosclerosis

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More sequelae of hypertension

hyaline arteriosclerosis (brain infarction or nephrosclerosis from inc ECM production that thickens vessel wall); dec renal blood flow; inc renin; chronic renal failure; hyaline arteriosclerosis of retinal vessels and rupture w/bleeds; amblyopia

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Cerebral Aneurysm: Saccular intracerebral

aka: berry aneurysm; usu young people; 1 in 20; usu >1; usu don't rupture; usu anterior cerebral circulation; rupture = subarachnoid bleed; death/morbidity

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Risk factors for intracranial aneurysm formation

abnml/anomalous vessels; coarctation of aorta; polycystic kidney; fibromuscular dysplasia; CT disorder (Marfans; Ehlers-Danlos)

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Pathophysiology of intracerebral aneurysm

origin, growth and configuration influenced by vascular and internal flow hemodynamics; usu at apex of vessel bifurcations; rounded outpouching dt local vascular wall degen or congenital defect in wall; involves only intima and adventitia (thru media)

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Fusiform Intracerebral Aneurysm (atherosclerotic aneurysm)

older pts; vertebrobasilar system; telangiectasias occur; damage to media = arterial stretching over a length; intraluminal clots; thrombosis causes brainstem infarct & mass effect (compress brain/cranial n palsies)

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Aortic aneurysm

d/t: arteriosclerosis (mc), infxn (mycotic aneurysm), aortitis (giant cell, lues (syphilis), A.I. dx), marfan/ehlers-danlos

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Aortic aneurysm pathophysiology

d/t degeneration of tunica media of aorta causing slow and continuous dilation of aortic lumen; artherosclerosis (fibrosis, chronic inflam); elastic fiber fragmentation; cystic medial necrosis; Laplace's Law: luminal dilation results from inc wall tension

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Aortic aneurysm pathology

AAAs are segmental dilations of aortic wall (>1.5x nml diameter); usu btw renal aa and iliac bifurcation; if >5cm in diameter there is a high risk for rupture; thoracic aortic aneurysm (3 grps); usu rupture/dissect

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Thoracic aortic aneurysm

1. ascending aorta (btw aortic valve and innominate artery); 2. aortic arch (btw innominate artery and subclavian artery); 3. descending aorta (btw L subclavian artery and diaphragm

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Mitral valve stenosis

narrowing of inflow tract from LA to LV d/t: Rheumatic heart disease (mc); SLE, RA, infective valvulitis, congenital mitral stenosis

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Pathophysiology of Mitral valve stenosis

ant/post leaflets; flow hindered at when area is red to 2cm (nml 4-6cm); LV filling red; to maintain CO, LA pressure inc; can cause regurgitation and pulmonary hypertension (dec pulm flow into LA/LV, if chronic: pulmonary edema/RHF (cor pulmonale)

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Mitral valve stenosis pathology

valve leaflets thickened; valve commissures may or may not be fused; chordae tendineae are thickened and shortened; enlarged LA

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Mitral valve stenosis: clinical synopsis

usu female; MV Triad: 1. loud S1; 2. mitral valve opening snap; 3. mid-diastolic murmur at apex d/t turbulant flow thru MV (diastolic and systolic murmur w/progression to stenosis and regurgitation)

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Mitral valve stenosis: doppler flow findings

measurement of flow can estimate the pressure gradient (LA pressure minus LV pressure); Normal = 1-2mmHg, Mild stenosis = 5mmHg, Severe stenosis = 10+mmHg

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Mitral valve stenosis: Clinical course and sequelae

Chronic atrial fib (dec CO by 15-20%); Spontaneous LA mural thrombosis (systemic thromboembolism); Pulmonary HT (R-side failure); Infective mitral valvulitis (aggressive antibiotics/prophylaxis); Combo stenosis/regurg; Dec lifespan w/o valve surgery

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Mitral Valve Regurgitation

backwards leak during systole d/t: Papillary dysfxn d/t ischemic heart dx (mc); Mitral valve prolapse d/t myxomatous degen of MV (mc2); Senile degen (fibrocalcification); Rheumatic HD; (uncommon: tendinous cord rupture, infective valvulitis, post-balloon

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Mitral valve regurgitation: Pathophysiology

during systole, a large portion of CO is directed back thru mitral valve into left atrium; enlarged LA, CO mildly red (inc HR/strength); larger vol enters LV in diastole causing LV dilation/inc LV end-diastolic vol/pressure; CHF; pulm edema; R-heart fails

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Mitral valve regurgitation: clinical synopsis, course, sequelae

dyspnea on exertion, nocturnal dyspnea, orthopnea, chronic fatigue, holosystolic murmur at apex; chronic atrial fibrillation, recurrent pulmonary edema, congestive heart failure

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Aortic valve stenosis

d/t: Senile fibrocalcific degen (mc); congen bicuspid aortic valve; Rheum HD; infective aortic valvulitis

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Aortic valve stenosis: pathophysiology

nml area: 3-4cm; blood flow red w/area of 1.5cm; LV ejection pressure inc to maintain CO; LV outflow tract obstruction; dilated/hypertrophied LV; LV failure

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Aortic valve stenosis: pathology

valve thickening and distrotion d/t fibrocalcification; only 2 leaflets (bicuspid) rather than 3; cusp fusion usu only if d/t rheum HD or other inflam etiologies

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Aortic valve stenosis: clinical synopsis, course, sequelae

effort angina; syncope on effort; dyspnea; fatigue; systolic murmur; delayed S2; GI bleed; recurrent pulmonary edema; CHF

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Aortic Valve Regurgitation

d/t: Degen of aorta leading to valve annulu expansion (idiopathic, atherosclerosis, lues, giant cell, CT dx); RheumHD; infxn; Uncommon: (severe HTN, bicuspid aorta, dissection, AI dx, quadricuspid aorta, myxomatous degen (rare))

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Aortic valve regurgitation: pathophysiology

if wall dilates, the valve annulus dilates = valve incompetency; blood pumped out LV flows back across aortic valve into LV; dilated/hypertrophied LV; cardiomegaly; inc LV pressure --> LA --> pulm circulation

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Aortic valve regurgitation: pathology

stiffening of valve leaflets; fusion of cusps; thickening and retraction of cusps; commonly a/w markedly enlarged heart (cor bovinum)

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Aortic valve regurgitation: clinical synopsis, course, sequelae

usu clinically silent for yrs; effort dyspnea, angina pectoris; chronic fatigue; pandiastolic murmur; slightly dec diastolic bp; laterally displaced apicul impulse; congestive heart failure w/recurrent pulmonary edema

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Tricuspid valve stenosis

Very RARE; d/t RheumHD (mc, a/w MV stenosis); infective valvulitis; blood cannot get thru 1st valve of R heart; dec pulm blood flow; dec CO; (if w/MV stenosis, effects of pulm HTN and R-side failure are reduced)

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Tricuspid valve stenosis: pathology, clinical synopsis, DDx, clinical course, sequelae

enlarged RA, valve thickening, shrinkage, deformity; fatigue, peripheral edema, ascites, hepatomegaly, anasarca, acrocyanosis; chronically dec CO and systemic hypoxemia (FTT in peds); chronic hepatic congestion --> hepatic cirrhosis ("cardiac cirrhosis")

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Tricuspid Valve Regurgitation

Very RARE; d/t: congen dysplasia, infxn valvulitis, mysomatous degen, pulm valve stenosis, pulm HTN, primary cardiomyopathy; RV SV only partly sent to pulm circulation (d/t backflow thru incompetent valves); thick, shrunk retracted leaflets

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Tricuspid valve regurgitation: clinical synopsis, course, sequelae

fatigue, dec CO, acrocyanosis, hepatomegaly, ascites, anasarca, systolic murmur; progressive RV dilation/hypertrophy leading to RV failure

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Pulmonary valve stenosis

isolated is 2nd mc congenital heart defect; (others: non-syndromatic heart defects; Noonan syndrome; Tetralogy; congen rubella; williams syndrome); RheumHD

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Pulmonary valve stenosis: pathophysiology

causes RV outflow obstruction leading to: inc RV pressures, RV dilation/hypertrophy; dec pulm blood flow leads to: red CO, systemic hypoxia

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Pulmonary valve stenosis: pathology

failure in development of leaflets/separation of commissures leading to dysplastic dome-shaped valve (may have fusion or dysplasia); bicuspid valve is more fxnl; severe stenosis = RV dilation, RVH, RA dilation, tricuspid insufficiency

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Pulmonary valve stenosis: clinical synopsis

pts w/mild or moderate stenosis will be relatively asymptomatic; exertional dyspnea; easy fatigability; acrocyanosis, hepatomegaly, ascites, anasarca, systolic murmur; if pressure gradient across valve is >40mmHg, surgery is needed (RVH/lifespan ok after)

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Pulmonary valve stenosis: Clinico-pathological typology

Valvular (mc); Subvalvular/Infundibular (usu occurs w/VSD, noonan syndrome or tetralogy); Supravalvular (usu a/w congen rubella or williams syndrome)

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Pulmonary valve regurgitation

Senile (trace PV regurgitation); Primary, Secondary (mc); d/t: dilation of pulmonic valve ring, congen malformation of valve (tetralogy), congen absence of PV, acquired PV dx (bacterial, RheumHD, etc); senile d/t structural deterioration of thin valve;

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Pulmonary valve regurgitation: pathology

valve dysplasia (Primary PV regurg); Fenestrations in leaflets (congen or acquired d/t bacterial endocarditis d/t IVDA, immune defic, dysplastic valve); RVH

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Pulmonary valve regurgitation: Clinical synopsis

easy fatigue, dizziness, light-headed, syncope, peripheral edema, chest pain, palpitations, ascites, diastolic murmur, hepatomegaly d/t chronic hepatic congestion, inc jugular venous pressure; inc RV end-diastolic vol/pressure;

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Pulmonary valve regurgitation: common causes of secondary

CHF d/t primary cardiomyopathy; pulm HTN; bacterial valvulitis, RheumHD; carcinoid heart disease; marfans (d/t dilated PV ring);

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Pulmonary valve regurgitation: clinical course and sequelae

highly variable based on cause of regurgitation; pts w/pulm HTN or congen absence of PV have worse prognosis d/t rapid development of RVH and RV failure

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Mitral valve prolapse

idiopathic (mc); marfan or ehler's danlos syndromes; d/t MV regurgitation (CO returns to LA ; LA hypertrophy; pulm HTN; pulm edema; R-heart failure; inc vol entering LV = dilation; CHF)

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Mitral valve prolapse: pathology and clinical course

myxomatous (mucoid degeneration) of valve leaflets; grossly thickened and expanded like a balloon; tendinous cords are thickened and fused; cardiac dysrhythmias, mitral valve regurgitation and complications, sudden death (rare)

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Venous thromboembolism

if inflammation is present, it is called thrombophlebitis; if infection is also present, it is called pyelothrombosis; originates in deep vv of limbs (DVT); mc d/t bed rest or prolonged inactivity; pelvic vv postpartum; usu embolizes to pulm circulation

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Pulmonary embolism

acute decrease in pulmonary blood flow and oxygenated blood to left heart (acute dec CO and generalized hypoxemia); acute inc in pulm artery pressure (acute RHF)

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Arterial Thromboembolism

originates in arterial system (mc from endocardial surface of heart d/t atrial fib, MI, infective endocarditis); ruptured/ulcerated atherosclerotic plaque in large vessel (aorta, common carotid at jxn, iliac aa)

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Arterial thromboembolism: embolization sites

brain (middle cerebral a infarct), internal organs (mesenteric a small bowel infarct OR renal a wedge-shaped cortical infarct), extremities (gangrene digits)

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Arterial thromboembolism: clinical course, sequelae

Dissolution (fibrinolytic system); Partial dissolution (recanalization in coronary aa); Tissue/organ infarction (infarct size depends on size of thromboembolism and presence of collateral circulation); Sudden death (if large embolism in brain or lungs)

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Monckeberg Arteriosclerosis

idiopathic (mc), metabolic bone dx (1* or 2*-CCsteroid), diabetes mellitus; areas of necrosis/dystrophic calcification of tunica media (small-med aa in lower leg; NOT tunica intima); usu asymptomatic; dysfxn rare (chronic distal ischemia &/or thrombosis)

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Arteriosclerosis

obstruction of blood flow leading to end-organ ischemia & infarction; usu tunica intima; d/t HTN w/intimal hyalinization, medial hypertrophy, endothelial hyperplasia; kidneys (a/w generalized glomerular sclerosis/CRF); Brain (sm infarcts in basal ganglia)

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Arteriosclerosis: clinical course and sequelae

increased incidence of chronic renal failure and cerebrovascular accident (aka: stroke)

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Hyperplastic arteriosclerosis

fibrointimal proliferation creating "onion skin" appearance; common in kidneys; usu a/w severe chronic HTN or malignant HTN; inc incidence of chronic renal failure

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Atherosclerosis

mc type of arteriosclerosis; Risks (male, age, postmenopausal, fam hx, smokers, HTN, diabetes mellitus, high LDL, high homocysteine, overweight, sedentary, high TGs)

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Atherosclerosis: pathophysiology

inflam disease; degeneration of med-large muscular aa (tunica INTIMA); "response to injury theory" - endothelial dysfxn allows lipids/WBCs into subendothelial space (inc permeability of lipoptns, dec NO prod, inc leukocyte migration/adhesion)

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Artherosclerosis: "Response to Injury" theory: 1

endothelial injury (infection) is initiating event, mild predisposition to occur at anatomical branching pts in med-sized vessels (vulnerability of these areas d/t variations in shear stress and blood flow)

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Artherosclerosis: "Response to Injury" theory: 2

infiltration by inflam and phagocytic cells; deposition of LDL (oxidized by free radicals from inflam; ox LDL is tissue toxic, more inflam; phagocytosis by MQs produce "foam cell" fatty streak), cholesterol, calcium, cell debris w/in intima;

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Artherosclerosis: "Response to Injury" theory: 3

chronic/progressive inflam; repair initiated as fibroepithelial prolif and fibrosis; final lesion is combo of fibrosis and lipid ("Atheroma"); elevated homocysteine promotes atherosclerosis (coverted to reactive sulfur compound; promotes LDL chol deposit)

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Atherosclerosis and the Positive Repair Reaction

intramural plaque growth buldges wall outward rather than in; usu does not cause angina (a/w progressive growth over yrs which finally causes luminal narrowing); accounts for most vulnerable plaques (more prone to result in plaque rupture and thrombosis)

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Atherosclerosis and C-Reactive Protein

undergoes 100x increase during acute inflammation; pts w/ >1mg/dL have slight inc risk of atherosclerosis; those w/ levels >3mg/dL exhibit significant inc risk of atherosclerosis-related complications (AMI, mortality rate, dec response to statins)

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Atherosclerosis: clinical synopsis 1

Coronary aa (angina pectoris; begins w/exertion, a/w dyspnea, blood flow to aa red 30% to cause pain; at rest w/high-grade stenotic lesion; AMI, chronic ischemia leads to ischemic cardiomyopathy); Aorta (wall weakens/aneurysm; distal infarct d/t rupture)

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Atherosclerosis: clinical synopsis 2

Ilio-femoral aa (ischemia, fatigue, aches w/exertion d/t intermittant claudication; chronic ischemia (thin skin, hair loss, atrophy, distal infarction); Subclavian aa (ischemia on exertion, tiredness, aching in extremity, skin/hair/muscle change, infarct)

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Atherosclerosis: clinical synopsis 3

CVA (stroke; d/t either luminal narrowing/dec blood flow OR plaque thrombosis and acute dec in flow, OR plaque rupture/embolism & distal infarct (single or many))

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Atherosclerosis: clinical synopsis 4

Renal aa (usu unilat dec blood flow/chronic renin elevation and renovascular HTN; unilat chronic ischemia leading to atrophy of kidney; Renal infarct (plaque thrombosis/acute blood flow red OR plaque rupture/embolism and distal infarction)

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Coronary artherosclerosis: modifiable risk factors

smoking, dyslipidemia (HDL <35, LDL >160, TGs >250), HTN, obesity, physical inactivity, elevated circulating homocysteine, diabetes mellitus, heavy ethanol use

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Pathophysiology of Coronary Atherosclerosis in Cigarette Smoking

exact mechinism unknown, but likely d/t injury to endothelium by carbon monoxide and/or nicotine; altered platelet adhesion properties; altered LDL chemistry (inc ability to become oxidized)

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Pathophysiology of Homocysteinemia and Coronary Atherosclerosis

homocysteine converted to very reactive sulfur that reacts w/ LDL-C; promoting LDL-C deposition in vessel wall; also inc circulating LDL levels, inc angiotensin II levels (inc systemic vasoconstriction), inc platelet adhesiveness (thrombogenesis)

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Pathophysiology of Hyperlipidemia and Coronary Atherosclerosis; the anti-atherosclerotic effects of HDL are exerted by

prevent/correct endothelial dysfxn (endothelial prolif & dec apoptosis); promote vasodilation d/t release of NO and prostacyclin thru expression of endothelial NO synthase & coupling COX2 w/prostacyclin synth; dec platelet adhesion, inc antiox activity

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Clinical Synopsis of Coronary Atherosclerosis Lesions

dx is progressive thru life & most pts are asymptomatic (esp if diabetic b/c cardiac sensory nn are damaged); angina pectoris/SOB on exertion, dec exertional capacity, abnml fatigue, dizziness, palpitations (inc PVCs)

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Clinical Course and Sequelae of Coronary Atherosclerosis Lesions

plaques grow slowly over 10-15yrs; distribution of lipid/CT determines stability/risk of rupture, thrombosis, and sequlae; "vulnerable plaques" w/thin fibrous cap will rupture and thrombose;

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Thrombogenesis in atheroma

denudation of overlying endothelium or rupture of fibrous cap d/t chronic inflam results in exposure of thrombogenic contents, platelet adhesion, activation of clotting cascade, thrombosis (occlusive and non); 48% of AMI/CAD occur w/nml cholesterol levels

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Blood supply to SA node in right atrium

either the left coronary artery soley, the right coronary artery soley, or a combo of both

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blood supply to the AV node

supplied by the right coronary artery in most people

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FLAP gene

mutations result in higher chronic levels of circulating leukotrienes; significantly increases risk of AMI

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Acute Myocardial Infarction: risk factors

same as atherosclerosis; positive fam Hx (any 1st degree male relative <45yo or female <55yo who had AMI; diabetes mellitus (esp type I: IDDM); hypercholesterolemia; chronic stumulant use (cocaine, meth)

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Pathogenesis of Myocardial Infarction

plaque rupture triggers event; usu from an area of atherosclerosis with <50% occlusion; leads to embolization of fragments, distal occlusion and subsequent infarct; thrombosis leads to coronary a occlusion and infarct

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Pathophysiology of Myocardial Infarction 1

heart m has no glycogen stores; after occlusion anaerobic glycolysis generates only sm amt of ATP; intracellular ATP creatine-P levels drop w/in min; interaction btw actin&myosin w/Ca influx is altered; ischemic area stops contracting d/t no mitoch oxphos

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Pathophysiology of Myocardial Infarction 2

Cardiocytes in ischemic area have hydropic change and Na/Ca enter cell; myocardium becomes pale; ejection fraction dec proportional to infarct area; electrical instability of heart = risk for re-entry impulses/dysrhythmias

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Pathophysiology of Myocardial Infarction 3

contraction band necrosis (if present, d/t re-O2 in reversible injury causing extreme contraction); coagulative necrosis of coronary aa, neutrophil infiltration 8-12hrs, MQs w/in days; repair begins at 7th day (fibroblasts, angiogen); non-contractile scar

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Pathophysiology of Myocardial Infarction 4: enzymes released during necrosis

troponin I, troponin T, creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST)

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Myocardial Infarction: Subendothelial

located only in subendothelial area (interior 33% of LV wall thickness); area is most vulnerable d/t lack of blood supply (furthest distance from coronary aa and prolonged compression during systolic contraction)

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Myocardial Infarction: Transmural

full thickness of the myocardium (from endocardium to epicardium)

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Myocardial Infarction: Clinical Synopsis

acute chest pressure/squeezing discomfort (anterior precordium, radiates to jaw, neck, arms (L>R), back, epigastrium); actue SOB, nausea or epigstric pain (a/w inf or post wall infarcts); syncope, diaphoresis; no symptoms if diabetic or old

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Myocardial Infarction: Laboratory Diagnosis of Serum Markers

Specific: Creatine phosphokinase (elevated total CPK w/specific elevation in MB fraction; 4hrs after injury, peak 24hrs, nml 72hrs); Troponin-I (3-4hrs after injury, nml w/in wks); Troponin-T (onset after troponin-I); Non-specific (myoglobin, LDH)

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Myocardial Infarction: Clinical Course and Sequelae: Early

Cardiac arrhythmias (mc; PVCs, supraventricular tach, bradycardia (post wall infarct; AV node is supplied by R), v-tach, v-fib); Acute mitral regurgitation (ant papillary m ruptur/infarct); Cardiogenic shock (pump failure d/t large LV infarct)

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Myocardial Infarction: Clinical Course and Sequelae: Late

Ventricular aneurysm (d/t transmural infarcts, wall replace w/fibrous tissue); LV wall rupture (a/w transmural w/in 4-7d; necrotic wall can't withstand LV pressure; acute tamponade d/t hemopericardium); 30% mortality (rest have dec life expectancy)

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Myocardial Infarction: Clinical Course and Sequelae: uncommon

infarction of mitral valve papillary m (MV incompetence); Endocardial (mural) thrombosis at site of infarction (may impede LV filling and dec CO); IV septum rupture (acute L--> R shunt, dec CO, acute RVF, acute pulm HTN)

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Non-atherosclerosis-related Myocardial Infarction

d/t: severe LVH (asymmetric, aortic stenosis); Hypoxia (COPD); Microvascular MI; Coronary a. spasm (Prinzmetal's angina; cocaine, meth); Coronary a emboli (mycotic, aneurysm-related, atherosclerotic); Vasculitis (kawasaki, polyarteritis nodosa); dissectio

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Non- atherosclerosis-related Myocardial Infarction: Pathophysiology

coronary aa have minimal or absence atherosclerosis; myocardial O2 demands temporarily exceed supply of coronary aa leading to necrosis of portions of myocardium (commonly subendocardial)

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Causes of ischemic heart disease

mc: coronary artery atherosclerosis; coronary artery spasm (aka: Prinzmetal's angina); chronic anemia; chronic hypoxemia d/t chronic lung dx; valvular heart dx; cardiomyopathy

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Ischemic heart disease: Pathophysiology

imbalance btw blood/O2 requirements of heart & coronary aa ability to meet it (dysfxn begins in 1min of dec; 1sec if obstructed; cell death w/in 30min)

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Factors INCREASING the blood/oxygen demands of the myocardium

systemic HTN, LV hypertrophy; inc HR; LV outflow obstruction; inc LV end-diastolic blood vol

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Factors DECREASING the blood/oxygen supply to the myocardium

narrowing of coronary aa; valvular heart dx; cardiac dysrhythmias; systemic HTN; chronic anemia; chronic hypoxia d/t chronic lung dx

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Cocaine-induced myocardial ischemia: Pathophysiology

cocain induces coronary artery spasm which is especially harmful if coronary artery disease is also present; chronic use is a/w accelerated coronary artery atherosclerosis and chronic myocarditis (followed by myocardial fibrosis)

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Cocaine-induced myocardial ischemia: clinical course/sequelae

inc bp/hr, chest pain; inc risk of AMI, cardiac dysrhythmia and sudden cardiac death

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Prinzmetal's Angina

myocardial ischemia unrelated d/t spont coronary a. spasm; polymorphisms in stromelysin-1 5A/6A gene = impaired NO synth, dec availability, inc basal vascular tone, spont vasospasm, platelet activ/thrombosis, inc thromboxane A2 & other vasoconstrictor

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Prinzmetal's Angina: pathophysiology

elevated LDL chol (esp in oxid form) inhibit NO synthase and inc free O2-radical prod which inactivates NO; genetic polymorphs (common in Japanese) dec NO levels; spasm usu occurs in areas where atherosclerosis has begun d/t higher LDL levels; M8x>W

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Prinzmetal's Angina: clinical synopsis, course, sequelae

inc incidence of AMI, inc incidence of dysrhythmias, inc incidence of sudden cardiac death

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Microvascular Angina

presence of angina pectoris, ischemic changes on ECG during stress testing, but arteriographically normal arteries; usu post-menopausal women; related to DM, chronic HBP, systemic inflam dx (SLE, polyarteritis nodosa, etc)

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Microvascular Angina: Pathophysiology

unknown etiology; ;poor coronary vasodilatory response; inc sensitivity of microcirculation to vasoconstrictor stimuli a/w abnml smooth muscle; dec flow d/t narrowing of intramyocard vessels; LVH inc intramyocard resistance; hypersensitive to heart pain

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Microvascular Angina: Clinical synopsis, coarse, sequelae

chest pain on effort or at rest; poor response to sublingual nitroglycerin; prognosis better than coronary artery atherosclerosis (only a minority suffer progressive myocardial ischemia or AMI); **not a/w inc risk of arrhythmia or sudden cardiac death**

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Hereditary Homocystinuria: Genetics of Classic Type

auto rec; clinical variability d/t multiple genes and mutational polymorphs; classic d/t def of cystathionine synthase (21q22.3); heterozygoes have mildly elevated homocysteine, but usu asymptomatic till late childhood

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Hereditary Homocystinuria: Genetics of other types

mehtylene tetrahydrofolate reductase (MTHFR) on 1q36.3 (normally involved in methionine met and single-carbon transfer); C677T homo (1 in 11 people w/dec MTHFR activity); C677T/A1298C hetero (1 in 6 people; dec MRHFR activity)

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Hereditary Homocystinuria: General Pathophysiology

hyperhomocysteinemia is atherogenic & thrombogenic d/t effects on vasclar endothelium (free-radical chronic damage/dec NO levels); highly reactive sulfur promotes LDL deposition; also interferes w/collagen x-linking in soft tissue

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Hereditary Homocystinuria: Pathophysiology of Cystathionine Synthase

def leads to a block in the metabolic path for homocysteine leading to elevated circulating levels of homocysteine

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Hereditary Homocystinuria: Pathophysilogy of MTHFR deficiency

dec MTHFR activity leads to chronically low folate levels and chronically elevated homocysteine (hyperhomocysteinemia)

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Hereditary Homocystinuria: Clinical synopsis

symptoms present over time; Marfanoid habitus (dolichocephalia, arachnodactyly, kyphoscoliosis, eye lens dislocation); pale skin (dec melanin formation); mild cognitive defect w/behav & psych probs (autistic-like)

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Hereditary Homocystinuria: Lab diagnosis

positive urine cyanide-nitroprusside rxn (homocysteine reacts = red/purple color); elevated serum: methionine, homocysteine, and dec cystathionine synthase in cultured fibroblasts or hepatocytes

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Hereditary Homocystinuria: DDx, clinical course and sequelae

Marfan syndrome; generally dec lifespan d/t thromboembolic complications; inc incidence of: pancreatitis, atherosclerosis, and spont thrombosis (CVA, PE, AMI)

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Thromboangiitis Obliterans (Buerger's Disease)

non-atherosclerotic segmental inflam vasoocclusive disease that affects sm-med sized vessels in upper and lower extremities (mc in lower); d/t smoking or chewing tobacco or pot

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Thromboangiitis Obliterans: Pathophysiology

tobacco-related antigen provoke immunopath rxn & vascular injury, spasm, thrombosis; autoantibodies detected against: type I & III collagen, elastin; *integrity of vessel wall incl elastic lamina is maintained - diff from atherosclerosis & vasculitis*

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Thromboangiitis Obliterans: Acute phase

occlusive inflam thrombosis w/min inflam in vessel walls; PMNs form microabscess w/dep of IgG, IgM, IgA, C3d, C4d in inner aspect of internal elastic membrane

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Thromboangiitis Obliterans: Subacute phase

intraluminal thrombosis organizes; vascular recanulization

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Thromboangiitis Obliterans: End-stage

vascular fibrosis and lumen obliteration; **pathologic characteristics of atherosclerosis (foam cells, chol clefts, fibrous intimal prolif, hyaline degen, calcification) are ABSENT**

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Thromboangiitis Obliterans: Lab diagnosis

elevated ESR, elevated CRP, red levels of total complement and C3

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Thromboangiitis Obliterans: Clinical course and sequelae

most develop ischemia of extremities leading to skin ulceration, "spontaneous gangrene" and surgical amputation; coronary artery narrowing leads to myocardial infarction

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Dilated Cardiomyopathies: General Pathophysiology

dep systolic fxn and systolic pump failure; dec LV contractile forces = dec CO & inc residual vol in end-systole/end-diastole; low CO upreg SNS & RAA-axis, releasing ADH & ANP to inc vol, but vasoconstriction further dec CO...vicious cycle!

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Pathophysiology & Pathology of Idiopathic Dilated Cardiomyopathy

unknown etiology w/inc genetic association; cardiomegaly - LV wall thickness, mitral valve regurg &/or tricuspid (d/t chamber dilation) & valve leaflet thickening; mitral regurg leads to more LV overload...vicious cycle!

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Dilated cardiomyopathy: Clinical synopsis

dyspnea on exertion, exercise intolerance, fatigue, chronic tachycardia (compensatory tachycardia to maintain CO); *systolic heart murmur (usu d/t mitral valve regurgitation)*

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Dilated cardiomyopathy: Lab diagnosis

hypernatremia (d/t hyperaldosteronism) OR hyponatremia (d/t plasma vol expansion) may be present; *elevated serum B-type natriuretic peptide (BNP) --> most sensitive indicator of natriuretic peptides for CHF*

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Common causes of secondary dilated cardiomyopathy

chronic HTN, ischemia, chronic alcoholism, cocaine, meth, mitral/aortic valve dx; post-viral myocarditis, chaga's, anemia, sarcoidosis, drug-related (doxorubicin), peripartum CM, thyrotoxicosis, amyloidosis, GSDs, Muscular dystrophy, thiamine def

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Dilated cardiomyopathy: Clinical course

most progress to chronic CHF; inc incidence of sudden cardiac death d/t dysrhythmia; 5YS 50% (better prognosis for women)

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Dilated cardiomyopathy: Variants - Familial

aka; hereditary DC; may account for 40% of all idiopathic dilated cardiomyopathies; may be sporadic, auto dom, auto rec, or X-linked

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Hypertrophic Cardiomyopathy: Genetics

most auto dom w/variable expressivity; some sporatic; heterogenous w/>6genes on 4 chromosomes (sarcomeric ptns - myosin heavy beta chains, actin, tropomyosin)

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Hypertrophic Cardiomyopathy: General Pathophysiology

several mechanisms; diastolic dysfxn d/t impaired LV filling; systolic dysfxn d/t abnml Ca kinetics & subendocardial ischemia; asymmetric septal hypertrophy a/w LV outflow obstruction & dec CO

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Hypertrophic Cardiomyopathy: General Pathology

disorganized cardiocytes & myocardial muscle bundles (whorled pattern); interstitial/myocardial fibrosis; abnml intramural coronary aa w/dec lumen & thickening of vessel wall (intramyocardial sm vessel dx; usu ventricular septum a/w myocardial fibrosis)

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Hypertrophic Cardiomyopathy: clinical course and sequelae

inc risk of death d/t strenuous exercise; **mc cause of sudden cardiac death in kids/teens*; CHF, chronic cardiac dysrhytmia

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Hypertrophic Cardiomyopathy: variants - obstructive primary HCM

(aka: asymmetric septal hypertrophy, idiopathic subaortic stenosis, idiopathic hypertrophic subaortic stenosis); **systolic dysfxn predominates (LV outlfow obstruction dec CO, abnml Ca kinetics, subendocardial ischemia)*; diastolic dysfxn w/dec LV filling

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Hypertrophic Cardiomyopathy: variants - Non-obstructive Primary HCM

(aka: concentric hypertrophic cardiomyopathy); more common than obstructive HCM; **predominately a diastolic dysfxn d/t impaired LV filling**

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Secondary Hypertrophic Cardiomyopathy: common causes, course, sequelae

athletic training, hypertension, coarctation of aorta, aortic stenosis; course is similar to primary HCM (sudden cardiac death, CHF, dysrhytmia); changes d/t training are physiologic and will return to nml if training stops

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Restrictive cardiomyopathy: common causes

idiopathic (primary); Acute/chronic myocarditis (idiopathic, infectious - chagas; sarcoidosis, loeffler's endomyocarditis); LVH; LV infiltrative disease (amyloidosis, glycogen storage dx, hemochromatosis); endocardial fibroelastosis

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Restrictive cardiomyopathy: Pathophysiology

excessive rigidity of LV walls resulting in inability of LV to stretch during diastole leading to dysfxn in contraction & dec CO; bilat dilation; endomyocardial Bx shows thick endomyocardial fibroelastosis, chronic myocarditis or non-specific fibrosis

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Restrictive cardiomyopathy: Clinical course and sequelae

progressive cardiac dysfxn ending in CHF (more rapid in younger pts); inc incidence of thromboembolic events in pts w/significant endomyocardial pathology; 5YS ~25%

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Restrictive cardiomyopathy:Pathophysiology

replacement of portions of myocardial wall usu RV by fibrofatty tissue w/loss of cardiocytes; pulm circulation maintained by RA contraction (aka: Fontan heart); electrical instability, V-arrhythmias (PVCs, V-tach, V-fib)

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Restrictive cardiomyopathy: Pathology

very characteristic gross features: large areas of RV wall are thinned and replaced w/pale, yellow-white fibroadipose tissue ("parchment change"); areas of smooth muscle may also be present in the areas of dysplastic myocardium; mc in RV (rare in LV)

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Restrictive cardiomyopathy: Clinical synopsis and course

onset of symptoms usu in teens/young adult; palpitations, syncope, inverted T waves in anterior chest leads over RV; most pts (if they live thru abnml heart rhythms) develop various degrees of heart failure; inc incidence of tricuspid regurgitation

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WHO Criteria for Obesity: Grade I

overweight; BMI: 25-29.9kg/m2

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WHO Criteria for Obesity: Grade 2

obesity; BMI of 30-39.9kg/m2

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WHO Criteria for Obesity: Grade 3

severe morbid obesity; BMI >40kg/m2

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Obesity Cardiomyopathy: Pathophysiology

probably related to elevated metabolic requirements and inc blood volume; possible mechanism for chronic hypoxia d/t chronic respiratory insufficiency d/t inhibition of respiratory movement from obesity (Pickwickian syndrome)

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Obesity Cardiomyopathy: Pathology and Clinical course

cardiomegaly, LVH, dilated ventricular chambers, may be a/w fibrofatty change in SAN and AVN; inc incidence of primary cardiomyopathy, CHF, sudden cardiac death

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Peripartum Cardiomyopathy

dilated cardiomyopathy leading to symptomatic systolic dysfxn in 3rd trimester of pregnancy or immediately postpartum w/o evidence of other caue; may occur in 1/1500 pregnancies; usu >30yo, inc in blacks; a/w *systolic dysfxn*

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Peripartum Cardiomyopathy: Clinical course and sequelae

inc incidence of CHF d/t uterine contraction of 3-500mL blood into circulation; sudden cardiac death d/t dysrhythmia, thromboembolism d/t myocarditis & hypercoagulable blood; 40% return to nml; 1YS 60%; **avoid future pregnancy**

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Common causes of Congestive Heart Failure

mc: coronary artery disease/ischemic cardiomyopathy; HTN (mc2); cardiomyopathy, aortic stenosis, coarctation of aorta, primary pulmonary HTN, pulm valve stenosis, myocarditis, cardiac dysrhythmia (atrial fib (mc)); anemia

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Cardiac output and compensatory mechanism: Sympathetic Nervous System

inc HR (chronotropic) - inc CO; inc contractile strength (inotropic) - inc SV d/t inc shortening of myofibrils; stim peripheral vasculature (aa vasoconstrict in skin, skeletal mm, bowel, kidneys to shift blood to CNS, heart, lungs) & vv constrict to heart

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Cardiac output and compensatory mechanism: Inc levels of circulating catecholamines

inc HR, inc contractility of heart, systemic vasoconstriction

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Cardiac output and compensatory mechanism: Activation of renin-angiotensin-aldosterone system

effects of angiotensin II: vasoconstriction inc BP & slightly inc peripheral resistance; inc circulating aldosterone (causes kidneys to retain Na & water to expand blood plasma/vol)

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Cardiac output and compensatory mechanism: Net result

increase CO back to normal; BUT...in diseased heart these mechanisms need to work on a min-min basis to maintain CO; they inc the heart's workload which is detrimental and produces further heart failure

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Pathophysiology of the Compensatory Mechanisms in Heart Failure: effects of chonically elevated catecholamines and SNS stimulation

chronic vasoconstriction (chronic inc total peripheral resistance and elevated afterload; LVH); alteration in Ca metabolism in myocardium (depressed contractility, inability of myocardium to relax during diastole)

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Pathophysiology of the Compensatory Mechanisms in Heart Failure: effects of chronic Renin-Angiotensin-Aldosterone Stimulation

chronic vasoconstriction (inc TPR afterload, LVH (dec angiogenesis, loss of cardiocites/gain of fibrosis; dysrhytmias: atrial-fib); Chonic inc blood vol (inc preload, inc TPR, inc afterload, LVH)

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Pathophysiology of the Compensatory Mechanisms in Heart Failure: Effects of Left Ventricular Hypertrophy

failure of capillary ingrowth to support hypertrophied heart, leads to dec cardiocytes and inc fibrosis; predisposition to cardiac dysrhythmias (atrial-fibrillation)

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Congestive Heart Failure: Clinical Synopsis

Dyspnea on exertion that can progress to dyspnea at rest; exercise intolerance, fatigue, chronic tachycardia to maintain CO, angina pectoris, peripheral edema

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Congestive Heart Failure: Lab diagnosis

hypernatremia d/t hyperaldosteronism (more common than hyponatremia which is d/t volume expansion); elevated serum B-type natriuretic peptide (BNP); CXR: cardiomegaly; Echocardiography: dilated LV & LA, LV wall dysfxn, dec LV ejection fraction (<50%)

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Congestive Heart Failure: Clinical course and sequelae

progressive debility leading to inability to walk or exercise; inc incidence of cardiac dysrhythmias, inc incidence od sudden cardiac death, 5YS 50%

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Cor pulmonale

alteration in structure and fxn of RV d/t primary disorder of the respiratory system (ex: COPD (mc); pulmonary interstitial fibrosis, chronic bronchial asthma)

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Cor pulmonale: Pathophysiology

elevated pulm arterial pressure (pulm HTN) leads to chronically inc work for RV, leading to RVH; progressive inc in pulm circulation pressures, RV fails d/t dec pulm blood flow, dec CO, systemic hypoxia, systemic edema)

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Cor pulmonale: pathology and clinical synopsis

RVH, w/ or w/o RV dilation; excessive fatigue, SOB on exertion, near-syncope or syncope, ankle/pedal edema; hepatomegaly, *split S2, JVD, (uncommon: pleural effusions, ascites)

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Cor pulmonale: Lab findings

EKG (RVH, P-pulmonale enlarged P wave d/t RA dilation); CXR (prominent hilar vessels-pulm aa; cardiomegaly; RV shadow); 2-D echocardiogram (RVH, paradoxical motion if IV septum - buldge into LV during sytole; doppler - inc R IV/pulm outlfow press, RV dil)

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Cor pulmonale: clinical course and sequelae

dec RV cardiac output leads to dec pulm blood flow & systemic hypoxia; Inc systemic venous pressure leads to ascites, chronic passive liver congestion, cardiac cirrhosis; peripheral edema; 5YS 30%

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Dysrhythmias: common causes

hypoxia, ischemia, electrolyte imbalances, drug side effects

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Disorders of impuls origination: Common Causes of Ectopic Pacemakers

damaged/dysfxnl sinus node; emergence of excitable focus in atria or ventricles (PVCs, PACs, premature nodal contractions); HTN, hypoxia, electrolye imbalance (K, Ca, Na, Mg), drug-related

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Pathophysiology of sinus node dysfxn

usu d/t ageing or atherosclerosis of nodal artery; if sinus node is damaged, the AV node (40-60bpm) or Purkinje fibers (15-40bpm) take over; these escape rhythms are slower and lead to dec CO

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Pathophysiology of ectopic foci

enhanced or localized depolarization of segments of conduction system or myocardium; ectopic beats (atrial or ventricular) are common and alone do not imply underlying disease; inc risk of initiating sustained re-entry tachycardias

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Disorders of Impulse Conduction: Pre-excitation syndromes

Wolf-Parkinson-White: 1 in 400; accessory tract links atria w/ventricles (Kent/Mahaim fibers) bypasses AV node w/diff conduction properties & refractory periods, facilitates reentry; abnml tahyarrhythmias d/t dual conduction; *recurrent A-fib, A-flutter*

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Disorders of Impulse Conduction: Common Causes of Re-entry Dysrhytmias

ischemic heart disease (mc); cardiomyopathy w/cardiomegaly; electrolyte imbalances, drug effect; *loss of atrial contribution to ventricular filling, dec ventricular filling, dec CO*

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Disorders of Impulse Conduction: Pathophysiology of Re-entry Dysrhythmias

d/t circular electrical impulse w/in heart; conduction system is slow & part of impuls arrives late so heart treats it as new impulse that spreads abnml paths, leading to re-entry circuits; originate from border zone btw scarred & active myocardial tissue

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Disorders of Impulse Conduction: Clinical Course of Re-entry Dysrhythmias - Atrial Fibrillation

loss of 15% of diastolic filling of ventricles d/t loss of atrial contraction; has a propensity to from atrial thrombosis that embolizes in pulmonary or systemic circulation

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Disorders of Impulse Conduction: Clinical Course of Re-entry Dysrhythmias - Ventricular Tachycardia and V-Fib

lack of an "atrial kick"; dec CO, often degenerates to ventricular fibrillation (the complete absence of cardiac output)

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Thrombophlebitis: Risk Factors

prolonged bed rest, vascular injury (IV cannulation, IV diagnostic procedures, traumatic injury, IVDA); Malignancy (lung, ovary, brain); Thrombophilia (Factor V Leiden, Antithrombin III Def, Ptn C or Ptn S Def)

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Thrombophlebitis: General Pathophysiology

"Virchow's Triad" - flow stasis, hypercoagulability, vessel wall injury; w/o endothelial injury it will rarely occur; endothelial injury initiates inflam and platelet adhesion; pts w/superficial thrombophlebitis often have deep vein too

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Superficial Venous Thrombophlebitis

most have associated deep vein thrombophlebitis; leg pain, localized erythema and edema a/w palpable venous induration

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Deep Vein Thrombophlebitis - Clinical synopsis

low grade fever, unilat leg edema, soft tissue tenderness, Homan's Sign (tenderness w/dorsiflexion of foot); superficial thrombophlebitis

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Deep Vein Thrombophlebitis - Lab findings and clinical course

elevated serum D-dimer (fibrin degredation product indicating active thrombolysis); few calf vein infxns progress to DVTs of upper leg; 1 in 6 pts w/DVT of upper leg veins develop pulmonary thromboembolism

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Deep vein thrombophlebitis: Sequelae

1. Pulm embolism does NOT occur w/superficial cases; 2. Postphlebitis Syndrome - occurs in 50%, valvular damage in vv causes peripheral venous insufficiency (chronic edema, discoloration, ulceration)

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Venous Thromboembolism: Pathophysiology

originates in deep vv of lower extremities; mc d/t bed rest or prolonged inactivity; pelvic vv - commonly postpartum; embolizes to pulmonary circulation

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Venous Thromboembolism: Pathology

gritty, may or may not have lines of Zahn, adherent to luminal endothelium (esp if thrombophlebitis inflam is present); higher [ ] of RBCs than arterial thromboemboli (darker and more homogenous)

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Arterial Thromboembolism: Pathophysiology

originates in arterial system on endocardial surfaces (atrial fibrillation, mitral stenosis, MI) or Luminal surfaces of carotid aa; embolize to middle cerebral a, mesenteric or renal aa, gangrene of digits

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Arterial Thromboembolism: Pathology

lines of Zahn are common; adherent to luminal endothelium, gritty in consistency

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Clinical Course and Sequelae of Thromboembolism

1. dissolution (d/t fibrinolysis); 2. Partial dissolution, organization or recanulization (freq in coronary aa, new lumen is narrower); 3. Tissue/organ infarct (size of infarct depends on size of thromboembolus & collateral flow); 5. death (lung) or CVA

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Paradoxical Thromboembolism

originates in venous (Right heart circulation) and embolizes thru a R-->L shunt (atrial septal defect (mc), or VSD) causing damage in systemic arterial circulation; (normally, thromboemboli originate in venous circulation and lodge in lungs as PE)

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Atherosclerotic Plaque Embolism (cholesterol embolism syndrome): Common Causes

vascular diagnostic/surgical procedure (mc) (aortic aneurysm repair, carotid endarterectomy, diagnostic ateriography, coronary a. angioplasty, renal a. angioplasty); aortic aneurysm, aortic dissection

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Atherosclerotic Plaque Embolism (cholesterol embolism syndrome): Pathophysiology

chol crystals break off from atherosclerotic plaques & enter downstream organs, occlude arterioles & sm arteries; induce inflam rxn, adventitial fibrosis that occludes lumen; local inflam rxn (vasospastiv mediators & tissue ischemia = organ damage/infarct

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Atherosclerotic Plaque Embolism (cholesterol embolism syndrome): Clinical Triad

renal failure (or multi-organ dysfunction), HTN, distal ischemic injury (CVA, extremity ischemia (livedo reticularis on skin or focal gangrene)

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Atherosclerotic Plaque Embolism (cholesterol embolism syndrome): Lab findings

peripheral blood eosinophilia; elevated BUN and creatinine, hematuria, dec total complement, elevated C-reactive ptn

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Atherosclerotic Plaque Embolism (cholesterol embolism syndrome): Clinical course and sequelae

emboli don't reach lung, but inflam mediators released from ischemic tissue may result in acute lung injury causing Diffuse Alveolar Damage and manifestation of Acute Respiratory Distress Syndrome; mortality: 20-90%

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Vasculitis: Polyarteritis Nodosa Pathophysiology

big inc circulating alpha-interferon & IL-2; mild inc TNF-a, IL-1b; 30% w/HBV, HCV Ab-Ag complexes; develops from immune complex deposition (type III hypersensitivity); few w/anti-ANCA (antineutrophil cytoplas); multiorgan dysfxn from systemic vasculitis

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Organs affected by Polyarteritis Nodosa

renal system (60%) - progressive renal failure; Skin (40%) - purpura, nodules, cut infarcts, livido reticularis, non-spec rashes, Raynaud; CNS (25%) - vasculitis & CVA; CV system (25%) - myocarditis; Musculoskeletal system

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Polyarteritis Nodosa: Clinical Synopsis, course, sequelae

fever, wt loss, diffuse myalgias, HTN, livedo reticularis, renal failure; Inc incidence of: med-large artery aneurysms, renal failure, CVA, bowel infarcts, myocardial infarct; mortality 25% w/aggressive Rx

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Churg-Strauss Syndrome: Pathophysiology

pulm sm vessel inflam (vasculitis) a/w necrosis, granulomatous inflam in & around blood vessels & w/in lung parenchyma; inflam of sm-med non-pulm vessels (systemic vasculitis) esp in kidneys (glomerulonephritis)

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Churg-Strauss Syndrome: Clinical synopsis, course, sequelae

fever, myalgias, wt loss, recurrent bronchospasm (asthma), chronic sinusitis, hemoptysis, renal failure, cut purpura, livedo reticularis; coronary arteritis in minority a/w AMI, high mortality w/o Tx; 5YS 65% w/Rx

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Wegener Granulomatosis: Pathophysiology

autoimmune inflam w/anti-ANCA (antineutrophil cytoplasmic antibodies) directed at neutrophil proteinase 3 (PR-3); activated PMNs target endothelium, damage = inflam mediators, monocyte, Tcell recruitment and more damage

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Wegener's Granulomatosis: Pathology

necrotizing granulomatous lesions of upper or lower respiratory tract; necrotizing vasculitis w/acute and chronic inflam cells and vessels destruction (sinuses, upper airways, necrotizing glomerulonephritis; pulm dx can occur w/o renal-"Regional Wegeners"

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Wegener's Granulomatosis: Clinical Synopsis

fever, wt loss, arthralgias, chronic sinusitis, chronic nasal discharge, recurrent otitis media, recurrent oropharyngeal ulcerations, chronic cough, livedo reticularis, recurrent cut purpura/ulceration on lower extremities, renal failure

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Wegener's Granulomatosis: Lab findings

anti-ANCA; elevated ESR, elevated BUN and creatinine; X-ray: pulmonary infiltrates and sinusitis

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Wegener's Granulomatosis: Clinical course and sequelae

progressive renal failure, inc incidence of infectious pneumonia, inc incidence of tracheal stenosis d/t chronic inflam; w/o Tx 1YS 20%; immune suppressive Rx allows high 5YS

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Wegener's Granulomatosis: On the Boards!!

Wegener granulomatosis, Churg-Strauss Syndrome and Microscopic Polyangiitis often manifest antibodies to neutrophil cytoplasmic antigens: ANCA

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Temporal Arteritis: Pathophysiology

chronic inflam in temporal aa (other vessels such as aorta & intracerebral aa); mononuclear cell infiltration often a/w multi-nucleate giant cells; *thickening/sclerosis of tunica intima & media* d/t cell-mediated response to Ag near elastic arterial wall

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Temporal Arteritis: Clinical Synopsis

unilat headache, onset of amblyopia w/compromise of ophthamlic a circulation; palpatory tenderness over temporal a; few have polymyalgia rheumatica as prodrome or associated disease

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Temporal Arteritis: lab findings

markedly elevated ESR; elevated C-reactive ptn, elevated liver enzymes (ALT, AST)

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Temporal Arteritis: Clinical course, sequelae

most develop visual loss w/o Rx; inc incidence of aortic aneurysm; inc incidence of CVA

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Kawasaki's Disease: Pathophysiology

probably d/t infectious etiology d/t periodic epidemics w/geographic spread; systemic vasculitis of med sized arteries d/t immune system hyper-reaction (infiltrate of CD4 cells); proinflam cell-med rxn triggered by unknown antigen or superantigen

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Kawasaki's Disease: Clinical synopsis

abrupt onset of fever, edematous and cracked lips, bilat conjunctivitis, exanthem & desquamation, cervical adenopathy, acral erythema and swelling

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Kawasaki's Disease: Lab findings

elevated ESR, liver enzymes (ALT, AST), platelet count after several wks

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Kawasaki's Disease: Clinical course, sequelae

most resolve spontaneously; 25% develop acquired heart disease (coronary artery aneurysm (mc); myocarditis, valvulitis); **it is the most common cause of acquired heart disease in children**; there in an inc incidence of chronic non-specific arthritis

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Raynaud's Disease

(idiopathic or primary); recurrent vasospasm of sm arteries/arterioles followed by vasodilation; usu young women initiated by cold exposure; period of pallor/pain in digits followed by erythema

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Raynaud's Phenomenon

secondary raynaud's disease; vasospasm/vasodilation of small arteries/arterioles; occurs in a/w underlying disease, usu autoimmune (SLE, Scleroderma (PSS))

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Immune Complex Vasculitis: Pathophysiology

type III immune complex deposition; vasculitis d/t deposition in sm vessels and capillaries (IgA and activated C3); >95% resolve spontaneously; few develop chronic renal failure d/t glomerulonephritis

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Serum Sickness: common causes

meds (act ast haptens that bind to endogenous ptns which invoke antibody formation and immune complex deposition); IV antitoxin Rx (anti-rabies, anti-tetanus, anti-snake venom)

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Serum sickness: Pathophysiology

antibodies bind to foreign ptns leading to immune complex formation; vascular deposition of immune complexes (type III hypersensitivity) leads to complement fixation, recruitment of PMNs, cytokine production, tissue damage from inflammtion

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Serum sickness: clinical synopsis, course, sequelae

fever, urticaria, erythematous rash, generalized lymphadenopathy, arthritis, erythema multiforme, glomerulonephritis; almost all resolve spontaneously, inc incidence of renal failure d/t glomerulonephritis

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Non-cyanotic Congenital Heart Disease

mc: aortic stenosis and coarctation of the aorta; no significant L-->R or R-->L shunts

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Occurance of Congenital Heart Disease

Ventricular septal defect (40%); Patent Ductus Arteriosus (12%); Atrial Septal Defect Ostium Secundum type (8%); Atrial Septal Defect Ostium Primum type (8%); Coarctation of Aorta (8%); Aortic Stenosis (8%); Pulmonary Stenosis (8%)

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Ventricular Septal Defect: Pathophysiology

any part of ventricular septum fails to close after 7th wk gestation; large or small; L-->R shunt may or may not present (CHF delayed to 2nd-3rd mo of life); Inc pressure in R heart/pulm vasculature R heart overload and pulm HTN; inc vol to LV & dec CO

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Ventricular Septal Defect: Clinical Synopsis

symptoms depend on size of L-->R shunt; cyanosis depends on size of shunt; FTT; tachypnea; diaphroesis; dyspnea on exertion progressing to fatigue; *holosystolic murmur may not present if VSD is very large*

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Ventricular Septal Defect: Clinical Course and Sequelae

inc incidence of pulm HTN leads to RV failure; Eisenmenger complex (acute onset of R-->L shunting; reversal of L-->R when pressure of pulm circulation excedes the LH pressure; acute systemic hypoxia & cyanosis d/t deO2 blood in LV); LHF; good Px w/surgery

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Patent Ductus Arteriosus: Pathophysiology

delay or failure in closure of ductus arteriosus; prolonged patency at higher altitudes and a/w congenital rubella infxn; few have L-->R shunt leading to: inc vol/pressure in RV & pulm circulation & inc vol to LV

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Patent Ductus Arteriosus: Clinical Synopsis

varies w/size of L-->R shunt (few are asymptomatic); may be cyanotic depending on size of shunt; FTT, tachypnea, *continuous (machine-like) systolic murmur* that can involve diastole

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Patent Ductus Arteriosus: CXR

prominence of pulmonary trunk; cardiomegaly

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Patent Ductus Arteriosus: Clinical course, sequelae

inc incidence of pulm HTN leading to RVF; inc incidence of LVF; excellent Px w/surgery; significant morbidity and dec lifespan w/o surgery

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Atrial Septal Defect: Pathophysiology

atrial setum forms btw 4th and 5th wk; w/any AST a L-->R shunt can develop d/t inc LA pressure as pulm resistance falls and RV becomes more compliant after birth; L-->R shunt presence depends on size of defect and may not show till 6-8wks old w/CHF

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Atrial Septal Defect: Anatomic typology - Ostium Secundum

mc & least serious type; located in central portion of interarterial septum in area of fossa ovali; usu not a/w significant probs; most pts do not require surgery; can account for paradoxical embolization in adults

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Atrial Septal Defect: Clinical Synopsis

most are asymptomatic; systolic ejection murmur may be present; if significant L-->R shunt pt may have: FTT, slowly progressive dyspnea --> pulm HTN and RV failure

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Atrial Septal Defect: Clinical Course, Sequelae

1 in 6 pts w/ ASD-OS undergo spontaneous closure by 5yo; inc incidence of cardiac dysrhythmias d/t abnml conduction system; few develop significant L-->R shunts w/progressive pulm HTN

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Atrial Septal Defect: Note

in severe congenl heart defects, survival is dependent on open fossa ovalis (ASD, secundum) or ductus arteriosus (tricuspid atresia or mitral valve atresia); when both avenues of R-->L shunting are closed, the pt has sudden loss of CO & terminal hypoxemia

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Coarctation of the Aorta: Pathophysiology

narrowing of aorta mc distal to L subclavian a (abnml development of L-4th/6th aortic arches); causes inc pressure for LV to pump against (inc afterload); dec flow to systemic circulation esp limbs; ductus arteriosus is bypass till closure/decompensation

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Coarctation of the Aorta: Pathology

d/t marked ridgelike thickening of aortic wall media; opposite to insertion of PDA/ligamentum arteriosum (becomes obstruction when patent ductus involutes); defect in vessel media = posterior infold (post shelf) that may extend around entire aorta

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Coarctation of the Aorta: Clinical Synopsis in Neonates

cyanosis depends on degree of stenosis (differential: upper limbs pink. lower blue); dec peripheral pulses; tachycardia; tachypnea; lethargy d/t hypoxemia; systolic ejection murmur in L chest area

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Coarctation of the Aorta: Clinical Synopsis in Childhood

usu presents during childhood; dyspnea (during exertion if mild stenosis or at rest if severe); angina pectoris, chronic HTN, marked BP differences btw upper & lower limbs if coarcted segment is aortic arch; systolic ejection murmur diminishes w/LVF

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Coarctation of the Aorta: Clinical Course, Sequelae

if prox to ductus arteriosus neonatal acute CHF w/closure; inc LHF & CHF; chronic systemic HTN (d/t RAA-activity d/t dec renal flow); inc aortic/cerebral aneurysm; inc spinal cord infarct/paraplegia; Turners; dec life w/o surgery; excellent w/surgery

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Aortic Stenosis: Pathophysiolgoy

obstruction to LV outflow leading to low CO and dec perfusion thru coronary aa; enlargement d/t combo of dilation & compensatory LVH

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Aortic Stenosis: Clinical Synopsis in Neonates

may be cyanotic depending on severity of stenosis; dec peripheral pulses; tachycardia; tachypnea; lethargy d/t hypoxemia; *systolic ejection murmur at L upper sternal border*

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Aortic Stenosis: Clinical Synopsis in Childhood

usu presents in childhood; dyspnea on exertion or at rest depending on severity; angina pectoris; systolic ejection murmur at L upper sternal border dec w/development of LVF; CXR shows cardiomegaly

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Aortic Stenosis: Clinical Course, Sequelae

if severe, CHF develops after birth when ductus arteriosus closes (leads to acute drop in blood reaching aorta); most progress to severe stenosis but depends on pressure gradient across aortic valve; inc incidence of sudden cardiac death

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Pulmonary Stenosis: Pathophysiology/Pathology

valvular type (mc); d/t fusion of leaflet commissures = thick, domed valve; dec RV output to pulm circulation; inc RV pressure; RV dilation; RA dilation

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Pulmonary Stenosis: Clinical Synopsis

**usu acyanotic** but can be cyanotic if stenosis is severe; dyspnea (depends on severity); systolic ejection murmur at L upper sternal border; CXR: prominent pulmonary trunk

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Pulmonary Stenosis: Clinical Course, Sequelae

variable depending on pressure gradient across pulm valve (as measured via cardiac catheterization: No probs if <25mmHg; Unpredictable if 26-40mmHg; Progression to RVF if >41mmHg); excellent prognosis w/Rx

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Eisenmenger's Syndrome

sudden change from a L-->R to a R-->L shunt; reversal thru a PDA, ASD or VSD d/t pathological changes of prolonged pulmonary hypertension

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Genetic Diseases Commonly a/w Congenital Heart Defects

Trisomy 18, 13 and 21; Cri du chat syndrome (Chrom 5 deletion); Monosomy X (Turner);

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Genetic Diseases and Congen Heart Defects: On the Boards!!

VSD is mc type of defect in genetic disease pts EXCEPT Turner, with is Coarctation of the Aorta!!

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Pericardial Effusion: Hydropericardium

accum of serous fluid in pericardial sac d/t Transudate [(mc) low cell & ptn content; ultrafiltrate of plasma d/t imbalance of hydrostatic forces usu d/t CHF) or Exudates (high cell & ptn content; indicative of pericardial dx such as infxn, AI or cancer)

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Pericardial Effusion: Hemopericardium

accumulation of blood in pericardial sac; d/t ventricular rupture (mc); aortic dissection, angioplasty; trauma; may progress to cardiac tamponade depending on volume of accumulation

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Cardiac Tamponade: Pathophysiology

fluid fills pericardial sac; slow filling stretches sac to accomodate 12oz; pressure rises and constricts heart; impairs ventricular filling (dec CO, dec systemic BP, generalized hypoxia)

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Cardiac Tamponade: Clinical Synopsis

Beck Triad (hypotension, inc JVD, diminished heart sounds); Pulsus Paradoxus (exaggerated, >12mmHg, of nml inspiratory dec in systolic bp); Kussmaul sign (inc JVD w/inspiration)

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Cardiac Tamponade: Echocardiography Findings, Clinical Course, Sequelae

fluid distending the pericardial sac, collaps of ventricular walls during diastole; significant risk of sudden death unless pericadial fluid is removed!

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Acute Pericarditis: Comon Causes

idiopathic (primary, mc); Uremia (mc2); metastatic (mc3); Infectious (mc4; bacterial, viral, TB, fungal, parasitic - protozoan/metazoan)

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Acute Pericarditis: General Pathophysiology

commonly a/w hydropericardium (exudative type); rich in fibrin, ptn and inflam cells; (infrequently a/w hemorrhage)

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Acute Pericarditis: Selected Pathophysiologies - Acute uremic Pericarditis

elevated levels of circulating urea cause an inflam pericarditis in addition to being toxic to other tissues

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Acute Pericarditis: Selected Pathophysiologies - Acute Bacterial Pericarditis

usu lymphatic or hematogenous spread in the context of sepsis

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Acute Pericarditis: Clinical synopsis, course, sequelae

chest pain, pericardial friction rub; most resolve spontaneously; few develop cardiac tamponade, few evolve into chronic pericarditis

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Constrictive Pericarditis: Pathophysiology/Pathology

evolution of pericarditis from acute to chronic to constrictive; severe fibrous thickening of pericardium; venous return to heart is dec; dec diastolic filling, inc ventricular end-diastolic & pulm vascular pressure; dec CO (CHF d/t inability to inc SV)

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Constrictive Pericarditis: Clinical Synopsis

elevated JVD, compensatory tachycardia; acral cyanosos (d/t low CO and chronic hypoxemia)

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