CVS Pathology Flashcards

Question

Progression of myocardial necrosis: first site, "at risk" area, earliest detectable feature

Answer 1

Necrosis begins in myocardium beneath endocardial surface i.e. subendocardium (coronary arteries run an epicardial course) --> wavefront of cell death move through myocardium with extended ischaemia Area that depends on occluded vessel = "at risk" myocardium The very narrow zone of myocardium immediately beneath endocardium is spared because it can be oxygenated by diffusion from ventricle Earliest detectable feature of myocyte necrosis is disruption of sarcolemmal membrane --> leakage of intracellular macromolecules --> basis of blood tests to detect irreversible myocyte damage

Answer 2

Following occlusion, contractile function is lost within 2 minutes as aerobic metabolism ceases and lactic acid accumulates (ultrastructural changes e.g. glycogen depletion, cellular and mitochondrial swelling) ***Gross changes not apparent for the first 12 hrs Microscopic changes not apparent until 12-18 hrs <30 minutes - reversible ischaemia - histology: normal - clinically: angina relieved by nitroglycerin, fast and weak pulse, sweating, ST depression, cardiac enzymes normal >30 minutes - irreversible ischaemia - histology: wavy fibres at edges of infarct - clinically: AMI, chest pain not received by nitroglycerin, ST elevation, cardiac enzymes elevated 1 hr - histology: edema - clinically: cardiogenic shock (if massive >40% infarcted) --> hypotension and dyspnea due to pulmonary edema; sudden cardiac death 4 hrs - triphenyl tetrazolium chloride (TTC) fails to stain infarcted myocardium because of LDH leakage --> area of infarct unstained and old scars appear white and glistening - histology: typical features of coagulative necrosis

Answer 3

12 hrs - grossly: myocardial mottling (red-blue discolouration) because of trapped blood - histology: pyknosis, karyorrhexis, myocyte HYPEREOSINOPHILIA, loss of cytoplasmic cross striations 1 day - histology: neutrophil infiltration (acute inflammation) 3-7 days: - grossly: pale firm well defined region with hyperaemic rim - histology: inflammatory infiltrates (neutrophils peak at 5-6 days), macrophages and granulation tissue first appear at margins on day 4 - clinically: ventricular rupture --> haemopericardium --> cardiac tamponade --> papillary muscle tear --> mitral regurgitation with new murmur 7 days - histology: macrophage infiltration 2 weeks - grossly: yellow, soft, sunken area with red-purple hyperaemic rim (progressive replacement by granulation tissue) by day 10 - histology: fibrosis, compensatory myocyte hypertrophy 2 months - gross: scarring complete -- thin firm greyish white dense fibrous tissue --> unable to distinguish age of scar (healing occurs from borders towards the centre as it requires migration of inflammatory cells and ingrowth of new vessels from margins)

Answer 4

``` Sudden cardiac death (arrhythmia, cardiogenic shock, thromboembolism (cerebral), ventricular rupture) Uncomplicated cases (10%) Complicated cases (90%) ``` Heart conduction: - lethal arrhythmias most common - 75% cases (VF as most common cause of SUDDEN CARDIAC DEATH) Cardiac muscle/wall: - progressive LVHF with pulmonary oedema (remaining viable muscles have increased workload - chronic IHD) - 60% - cardiogenic shock - 10% - ventricular rupture causing haemopericardium and cardiac tamponade Pericardium: - pericarditis - Dressler's syndrome (post-infarction fever, pericarditis, pleurisy, pneumonitis due to auto Ab against damaged pericardial Ag - Type II HSR or viral infection; can occur between 10 days to 2 years post MI) - 1-4% Blood: - thromboembolism (reduced contractility causing stasis and endocardial damage exposing thrombogenic surface) - up to 40% Papillary muscle: - papillary muscle/chordae tendinae rupture (acute mitral regurgitation --> acute heart failure) - 1-5% (SUDDEN DEATH: arrhythmia, cardiogenic shock, tamponade, papillary muscle rupture Ineffective pumping: mural thrombus and embolism Healing: pericarditis, ventricular dilation and aneurysm, progressive HF)

Answer 5

Restoration of blood flow to ischaemic myocardium by coronary interventions e.g. thrombolysis, angiplasty, stent placement, CABG Myocardial injury is potentially reversible for 30 minutes after onset --> need rapid diagnosis to permit early intervention and salvage as much "at risk" myocardium as possible - greater chance if within 3 hrs Restoration of flow can prevent some necrosis and retain some function but return of function to the myocardium may be delayed for hours to days (post-ischaemic ventricular dysfunction/ stunning with persisting biochemical abnormalities) and reperfusion injury may occur

Answer 6

- haemorrhage due to leakage through damaged vessels (accounts for >50% of ultimate infarct size) - endothelial swelling and leukocyte aggregation occluding capillaries and limiting reperfusion of critically injured myocardium ("no-reflow") - *oxidative stress -- free radicals from leukocytes and endothelial cells accumulate (cellular antioxidant mechanism compromised by ischaemia) - *Ca overload -- impaired Ca cycling and depletion of ATP - mitochondrial dysfunction -- increase permeability to proteins leading to swelling and rupture --> release mitochondrial components that promote apoptosis - local activation of complement by IgM Ab deposited in ischaemic tissues (increase inflammation and injury) Pathology: - Grossly -- haemorrhagic infarcts due to injured vasculature - Histology -- CONTRACTION BANDS (intensely eosinophilic intracellular stripes) from myocyte sarcomere hyper contraction when exposed to Ca from plasma (and absence of ATP to initiate relaxation) --> altered morphology

Answer 7

Progressive congestive heart failure secondary to long term ischaemic myocardial injury - a/w history of angina (stable) +/- MI - insidious development as compensatory mechanisms of heart begin to fail Morphology: - LV dilation and hypertrophy - evidence of scarring from previous infarcts - patchy fibrous thickening of endothelium - histology: myocardial hypertrophy, diffuse subendocardial myocyte vacuolisation (sublethal ischemic injury), fibrosis Causes of death; - arrhythmia - congestive HF - AMI

Answer 8

Unexpected death within 1 hour of onset of cardiac symptoms or from cardiac causes without symptoms IHD most common cause Other causes: myocardial disease (myocarditis, cardiomyopathy causing LHF and cardiogenic shock), valvular disease (MV prolapse and papillary muscle rupture), conduction system abnormalities (VT/VF cause ischemia), thromboembolism from MI Most common mechanism of death = VF e.g. triggered by myocardial ischaemia induced irritability

Answer 9

Non-ischaemic myocardial inflammation resulting in injury to myocardial fibres Aetiology: - Infections -- **viral most common e.g. Coxsackie virus, influenza; chlamydia, corynebacterium, candida etc - Immune -- post-infectious e.g. post-viral, post-streptococcal acute rheumatic fever; SLE, drug HSR e.g. methyldopa, transplant rejection - Unknown -- sarcoidosis, giant cell arteritis

Answer 10

Pathology: Acute Phase -- - grossly: dilated heart; flabby, pale myocardium with small areas of haemorrhages - mononuclear infiltrates (LYMPHOCYTES) and histiocytes, congestion - direct destruction of cardiomyocytes by virus-mediated lysis --> OEDEMATOUS myocardium, myocardial fibre necrosis Subacute Phase -- - immune dysregulation with molecular mimicry between viral and cardiac Ag Chronic Phase -- - development of dilated cardiomyopathy with marked ventricular dilatation due to extensive myocardial injury - diffuse pericellular myocardial fibrosis (Other variant: hypersensitivity myocarditis, giant cell myocarditis, chagas myocarditis)

Answer 11

Typically young, hx of flu/ viral infection Dyspnea (most common), chest pain, fever, persistent tachycardia and palpitations, congestive heart failure Outcomes: - self-limiting with complete resolution - progressive deterioration to dilated cardiomyopathy - death or cardiac transplantation (in cases of intractable heart failure, arrhythmias)

Answer 12

Heart diseases resulting from a primary abnormality in myocardium Excluding heart disease due to CAD, IHD, HT, myocarditis, valvular disease etc. (all secondary)

Answer 13

Dilated/ Congestive Cardiomyopathy (most common - 90%) - progressive cardiac dilation and contractile dysfunction - LVEF <40% - causes: genetic (20-50%), alcohol (direct toxicity and decrease thiamine), haemochromatosis, drug doxorubicin - histology (non-specific): interstitial thrombosis, intracardiac mural thrombi, myocyte hypertrophy * Hypertrophic Cardiomyopathy - MC cause of death in young athletes - asymmetric (eccentric) marked hypertrophy of IVS relative to LV/RV (IVS>LV/RV) and diastolic dysfunction - left ventricular outflow tract obstruction in 1/3 due to systolic anterior motion of mitral valve (HOCM) - LVEF 50-80% - histology: characteristic myocardial fibre DISARRAY (causing myocyte hypercontractilty --> unable to relax); interstitial fibrosis, LV outflow tract plaque (anterior MV leaflet contacts septum during systole), thickened septal vessels - causes: genetic (100%) Genetic defect in dilated cardiomyopathy involving proteins of cytoskeleton pre-dominantly vs. genetic defects in hypertrophic cardiomyopathy encode proteins of sarcomere Clinical complications: - progressive heart failure - sudden death - AF, arrhythmias - stroke

Answer 14

Restrictive Cardiomyopathy (least common) - primary diastolic dysfunction due to reduced compliance (with decreased filling of ventricles and dilation of atria) - LVEF 45-90% - causes: amyloidosis (most common), radiation-induced interstitial fibrosis, idiopathic Arrhythmogenic RV Cardiomyopathy - progressive fibroadipose replacement of ventricular myocardium causing severely thinned RV wall - inherited AD, with variable penetrance - primarily in young - RVF and various arrhythmias, especially V-tach and VF

Answer 15

Systemic - left sided - due to chronic pressure overload - concentric LVH --> can decrease diastolic filling with time --> LA dilation - dilation if CHF develops with volume overload in late stage - pathology: transverse diameter of myocytes is increased, prominent nuclear enlargement and hyperchromasia (boxcar nuclei), intercellular fibrosis Cor pulmonale - right sided - due to pulmonary HT - acute: RV dilation (develops faster than hypertrophy) - chronic: RV hypertrophy + dilation (if ventricular failure develops) - atheromatous plaques in pulmonary arteries Morphology of Hypertension: Concentric ventricular hypertrophy, coronary atherosclerosis, CHF

Answer 16

Concentric - sarcomeres duplicate in parallel to long axis - mechanism = increase afterload - causes: HT, AS, (10% HCM c.f. asymmetric) Eccentric - sarcomeres duplicate in series - mechanism = increase preload - causes: - LVH -- MR, AR, left-to-right shunt e.g. VSD - RVH -- TR, PR

Answer 17

Inflammation of pericardium Aetiology: - idiopathic (most common) - infection -- similar to pathogens that cause myocarditis - drugs -- similar to myocarditis e.g. methyldopa - uraemia - malignancy -- lung most common, breast Pathology: - fibrinous inflammation with pericardial effusion - dense scar tissue with dystrophic calcification --> constrictive pericarditis (most commonly due to TB, previous open-heart surgery) Presentation: - fever, tachycardia - chest pain, relieved on leaning forward - pericardial friction rub - pericardial effusion (muffled heart sound, Kussmaul sign, pulsus paradoxus) Treatment: - underlying cause - pericardiocentesis (if there is effusion)

Answer 18

Function: unidirectional blood flow (open with appropriate caliber, competent) AV valves - leaflets with attachment to ventricle via tendinous cords and papillary muscles - mechanism: papillary muscle contraction during systole; total area of leaflets > orifice with overlap during systole Semilunar valves - 3 leaflets attaching to ventricle-arterial junction (in an arc) - mechanism: semilunar cusps with arc shape attachment --> act as hanging basket to hold blood and allow time for blood to flow into coronary arteries; total area of leaflets > orifice

Answer 19

Stenosis (causing hypertrophy) and regurgitation (causing dilatation - congestive - and hypertrophy) Mechanisms of stenosis: - fusion of commissure - thickening of leaflets (fibrosis/calcification) Mechanisms of regurgitation: - abnormality of annulus -- dilation - abnormality of leaflet e.g. cusp retraction (fibrosis) or expansion (myxoid change), cusp perforation/ destruction (IE) - abnormality of tendinous cord e.g. chordal shortening/ lengthening/ rupture - abnormality of papillary muscle -- dysfunction (ischaemia/ infarction)

Answer 20

MS and AS - fusion of commissure due to post-inflammatory scarring: RF - degenerative calcification of AS MR - leaflet abnormalities: RF, IE, MV prolapse - tensor apparatus abnormalities: papillary muscle or tendinous cord rupture - LV/annulus abnormalities: myocarditis, DCM, mitral ring calcification AR - leaflet abnormalities: RF, bicuspid AV - tensor apparatus abnormalities: degenerative aortic root dilation - aortic diseases: Marfan, RA, ankylosing spondylitis 4 main aetiologies of heart valve diseases: - congenital - degenerative - post-inflammatory - post-infective

Answer 21

Bicuspid AV - 1-2% normal population at birth - may be familial - aortic root enlargement at commissural and supra-aortic levels - a/w coarctation (narrowing) of aorta, patent ductus arteriosus, ventricular septal defect complicated by predisposition to late degenerative changes: - AR, AS, IE

Answer 22

Senile calcific aortic sclerosis - calcific deposits within aortic cusps and aortic sinuses (not involving free edges) - may extend to anterior mitral leaflet occasionally (usually normal) - pathogenesis: degenerative wear and tear + dystrophic calcification - pathogenesis: chronic injury by hyperlipidemia, HT, inflammation etc. - sequelae and complications: AS

Answer 23

Systolic prolapse of mitral leaflet >2mm into left atrium above the annulus plane -- "floppy" valve +/- resulting MR F>M 7:1 Pathology: - a primary form of myxomatous degeneration (deposition of mucoid onto MV) --> ballooning leaflets enlarged, thick; tendinous cords elongated - histology: thinning of fibrosa layer of valve with expansion of middle spongiosa layer due to mucoid material - concomitant tricuspid lesion in 20-40% Associated conditions: (connective tissue disorders) - Marfan's syndrome, osteogenesis imperfecta, ASD, pulmonary emphysema, cystic medial necrosis of aorta Sequelae and Complications: - MR, IE --> rupture tendinous cord - Lambl's papillary excrescences (small thrombi formed endocardial surfaces at valve contact margins, may embolise) - small platelet thrombi at sites of cusp contact --> retinal embolisation and stroke

Answer 24

Horseshoe shaped calcified ridge on ventricular surface of mitral valve - calcific deposits in angle between leaflets and ventricular wall (incorporating chordal attachments on leaflets) sequelae and complications: - generally does not affect valvular function unless severe --> MR due to immobilisation, MS, conduction disturbance due to impingement of AV node

Answer 25

Acute, *immunologically mediated *multi-system disease *secondary to group A streptococcal pharyngitis - 3% of infections (genetic susceptibility) - most often in children Pathogenesis: - Type II HSR: Ab against M proteins of streptococci cross react with tissue glycoprotein in the heart, joint and other tissues - -> onset of symptoms 2-3 weeks after infection - -> absence of bacteria in lesions Pathology: - exudative and inflammatory response affecting connective tissue and basement membrane - early phase: fibrinoid necrosis, oedema of connective tissue, increase in acid mucopolysaccharide - intermediate phase: ASCHOFF BODIES (fibrinoid necrosis surrounded by T cells, plasma cells and histiocytes) - late phase: organisation and fibrosis Carditis --> Pancarditis - Aschoff bodies in all 3 layers of the heart - myocardium with diffuse interstitial inflammatory infiltrates with scattered Aschoff bodies - Endocardium with fibrinoid necrosis and fibrin deposition along lines of closure --> fibrous thickening (McCallum's Patch) --> form 1-2mm verrucous vegetations with no bacteria (valvulitis) - pericardium with fibrinous pericarditis (exudate) and effusion

Answer 26

Diagnosis -- JONES' CRITERIA - Major: carditis, migratory polyarthritis, chorea, erythema marginatum, subcutaneous nodules - Minor: fever, arthralgia, previous RF, increase acute phase reactants (ESR/CRP/WBC), prolonged PR interval on ECG Dx = 2 major OR 1 major + 2 minor with evidence of preceding streptococcal infection e.g. increase ASOT, +ve throat culture, recent scarlet fever Clinical presentations: as in Jones' Sequelae and Complications: - chronic rheumatic heart disease - --> accumulation of previous inflammation and scarring - replace Aschoff bodies - causing irreversible deformity of valves - --> leaflet thickening, commissural fusion and shortening, thickening and fusion of chordae tendinae - --> stenosis (buttonhole) > regurgitation -- mainly affect mitral valve - --> pressure or volume overload -- increases predisposition to IE - -> LA pressure overload in MS leads to dilation which precipitates AF --> increase formation of large mural thrombi and also eventually leads to CHF - adhesive pericarditis Prognosis and Causes of Death - poor prognosis if significant murmur, cardiomegaly, CHF; previous repeated episodes - main causes of death: cardiac failure, subacute IE, thromboembolism (mural thrombi or septic emboli) Treatment: - Penicillin/Erythromycin x10 days - Prednisone if severe carditis

Answer 27

Microbial invasion and implantation on heart valves - acute = infection of previously normal valve by high virulence org e.g. s. aureus -- high moratity - 50-60% subacute = infection of previously damaged valve by lower virulence org e.g. s. viridans -- insidious, good recovery (s. aureus can attacked damaged valves too) Pathogenesis: - transient bacteraemia --> tooth brushing, dental extraction, IVDA, manipulation of genitourinary tract - underlying heart lesion --> valvular disease, high pressure shunts within heart, valvular replacements (turbulent blood flow damages valve --> fibrin and platelet adhere --> trap circulating micro-organism --> fibrin encases vegetation) Heart valves are avascular so infection is difficult to treat!! Pathology: Acute IE - bulky friable lesions (yellow) containing fibrin, micro-organisms and inflammatory cells - destruction of valves, rupture of chordae tendinae and papillary muscles - erode into myocardium --> ring abscess - shedding of emboli with formation of micro-abscess where they lodge --> septic infarcts Subacute IE - more firm vegetation, less valve destruction and myocardium involvement - chronic inflammation, granulation tissue at base, fibrosis, calcification

Answer 28

Diagnosis: DUKE CRITERIA Pathologic criteria: (either +ve = definite) - +ve micro-organisms in a vegetation or - pathologic lesions (histological confirmation of active infection) Major clinical criteria: (both+ve = definitive) - blood culture positive x2 (for typical pathogens e.g. viridians strep, s. aureus, enterococci) - ECHO +ve for endocardial involvement (oscillating intracardiac mass on valve, abscess, new partial dehiscence of prosthetic valve) or new valvular lesion Minor clinical criteria: - predisposing heart condition or IVDA - fever >38 celsius - vascular: Janeway lesions, conjunctival haemorrhage, major arterial emboli, mycotic aneurysm, septic pulmonary infarcts - immunologic: Osler's nodes, Roth's spot, rheumatoid factor, GN - microbiological: +ve blood culture but not meeting major criteria - ECHO: consistent with IE but not major criteria Definitie IE - either pathologic criteria - 2 major criteria or 1 major + 3 minor or 5 minor Possible IE - 1 major + 1 minor or 3 minor Rejected IE - firm alternate diagnosis for manifestations - resolution of manifestations with antibiotic therapy for <4 days - no pathologic evidence of IE at surgery or autopsy

Answer 29

Constitutional symptoms due to continuos bacteraemia - low grade fever, malaise, weight loss (low virulence) - high fever, chills, septicaemia (acute IE) Cardiac Manifestations - changing murmur, heart failure, heart block, arrhythmias Septic embolisation - systemic e.g. kidney, spleen, blood vessels, brain - pulmonary Circulating Immune complex deposition - cutaneous -- splinter haemorrhage, Janeway lesions (painless, haemorrhagic), petechiae, Osler's nodes (red, raised, tender nodules), Roth spots - renal -- GN Prognosis depends on infecting organisms and complications - s. viridians 98% recovery with antibiotics - s. aureus and enterococci 60-90% Complications with poor prognosis - GN, septicemia, arrhythmias, systemic embolisation

Answer 30

Can be caused by both systolic and diastolic dysfunction Ddx: liver disease, renal failure, thyroid diseases, anaemia Frank starling --> increase EDV --> dilate heart and increase fibre stretching --> contract more forcibly to compensate for dysfunction --> compensated HF Dilation increases wall tension and O2 demand unable to meet body demands --> papillary muscle dysfunction, mitral regurgitation, LA dilation --> decompensation LHF - MC due to IHD/CHD, HT, AV/MV disease, cardiomyopathy - LVH and dilation, myoctype hypertrophy - IHD causes HF by infarction (decrease contractility and CO), longer term hypertrophy (altered interstitial matrix and arrhythmia), ischaemia (hypocontractile myocardium decreasing systolic function) -- vice versa: HF can exacerbate ACS as cardiomegaly increase O2 demand of the heart hence increasing chance of ACS - pulmonary congestion, oedema and pleural effusion -- SOB, orthopnea, PND - reduced peripheral perfusion: confusion, AKI - ---> interstitial (eosinophilic) transudates, alveolar septal edema and edema fluid in alveolar space, congested capillaries RHF - MC due to LHF (pul HT increase burden) - congestive hepatomegaly, portal HT with subsequent congestive splenomegaly - transudative effusion at pleural space but no pulmonary oedema - pedal and sacral oedema - ---> Nutmeg liver (centrilobular zone - zone 3 - necrosis)

CVS Pathology Flashcards

(54 cards)