CV Pathology 2 Flashcards
troponin - overview
*biomarker of myocardial damage
*normally regulate calcium-mediated contraction of cardiac muscle
*serum elevation = cardiac myocyte death (infarction, myocarditis, trauma)
-serum levels rise in 2-4 hours and peak 24-48 hours after an acute infarct
-levels may be higher and peak earlier with reperfusion = washout from necrotic tissue
ischemic heart disease - overview
*group of related entities resulting from myocardial ischemia
*imbalance between myocardial perfusion and cardiac O2 demand
*chief cause of mortality in US
ischemic heart disease - pathogenesis
*coronary artery disease: decreased blood flow caused by atherosclerosis
ischemic heart disease - clinical variants
- chronic coronary syndromes:
a. stable angina = fixed stenosis
b. prinzmetal = coronary spasm - acute coronary syndromes:
a. unstable angina = fixed stenosis with thrombosis
b. myocardial infarction = obstruction with NECROSIS
myocardial infarction (MI) - overview
*necrosis of heart muscle resulting from ischemia
*increased incidence with age and atherosclerosis risk factors
myocardial infarction (MI) - pathogenesis
*acute thrombotic obstruction of coronary artery due to rupture of atherosclerotic plaque
*disruption typically sudden
*hemorrhage into plaque or additional thrombosis
* > 30 min = irreversible myocyte coagulative necrosis
myocardial infarction (MI) - transmural vs. endocardial
- transmural infarct:
-FULL THICKNESS MYOCARDIAL NECROSIS
-caused by COMPLETE OBSTRUCTION of coronary vessel
-causes STEMI - endocardial infarct:
-only inner portion myocardial necrosis
-obstruction of distal coronary vessels or severe/incomplete obstructions
-causes NSTEMI
normal appearance of myocardium
*viable nuclei
*cross-striations
*intercalated discs
myocardial infarction (MI) - morphology 4-8 hours post-MI
*microscopic coagulative necrosis detectable:
-loss of nuclei (karyolysis)
-beginning loss of cross-striations
wavy CONTRACTION BANDS () extending across the fibers
myocardial infarction (MI) - morphology 12-24 hours post-MI
*gross and microscopically identified hemorrhage
*prominent contraction bands
myocardial infarction (MI) - morphology 1-3 days post-MI
*necrosis elicits NEUTROPHILIC INFILTRATE
myocardial infarction (MI) - morphology 3-7 days post-MI
*influx of MACROPHAGES
*removing necrotic myocytes and neutrophil fragments
myocardial infarction (MI) - morphology 10-14 days post-MI
*granulation tissue
*healing requires ingrowth of new vessels from the infarct margins
*large infarcts take longer to heal than smaller ones
myocardial infarction (MI) - morphology 2-8 weeks post-MI
*healing well underway
*EXTENSIVE COLLAGEN DEPOSITION (scar)
*MI size determines clinical sequelae
myocardial infarction - complication: arrhythmia
*90% develop some rhythm disturbance
*ex: ventricular fibrillation (causes the majority of deaths occurring prior to hospitalizations)
myocardial infarction - complication: contractile dysfunction
*impaired function proportional to size of damage
*ex. transmural infarct causes severe pump failure (cardiogenic shock)
myocardial infarction - complication: mural thrombus
*stasis due to diminished myocardial contractility
*endocardial damage fosters mural thrombosis with risk for left-sided thromboembolism
myocardial infarction - complication: papillary muscle dysfunction/rupture
*leads to post-infarct regurgitation
*mechanical complications most prevalent 3-14 days after MI
myocardial infarction - complication: ventricular dilation/aneurysm
*weakened necrotic muscle → stretching, thinning, and dilation of infarcted region
*large transmural infarctions → ventricular aneurysms
*prone to mural thrombosis
*mechanical complications most prevalent 3-14 days after MI
myocardial infarction - complication: myocardial rupture
*usually occurs < 5 days
*left ventricular rupture → rapidly fatal cardiac tamponade
*ventricular septal rupture → left-to-right shunt
*mechanical complications most prevalent 3-14 days after MI
myocardial infarction - complication: pericarditis
*transmural infarction → painful fibrinohemorrhagic pericarditis
*typically appears 2-3 days after infarction
*resolves after a few days
valvular heart disease - overview
*cardiac dysfunction caused by valvular disease
*usually acquired; more common on left side of heart
*abnormal flow = murmurs (auscultated), thrills (palpated)
valvular stenosis - overview
*failure to open completely
*forward flow obstruction
*due to chronic process (calcification or scarring)
valvular insufficiency - overview
*failure to close completely
*regurgitation of blood (backflow)
*disease of valve cusps or tendinous cords or papillary muscles, e.g. endocarditis
degenerative valve disease - overview
*degenerative changes in valvular extracellular matrix causing valve dysfunction
*related to repetitive mechanical stresses
degenerative valve disease due to calcifications
*age-associated “wear and tear”
*clinical: usually asymptomatic
*pathogenesis: repeated valve injury → exacerbated blood flow → endothelial injury → Ca2+ deposition
*heaped-up calcified masses on cusp outflow side:
-protrude/impede valve opening (stenosis)
-cusps show thickened fibrosis
degenerative valve disease due to alterations in the extracellular matrix
*idiopathic
*ballooning/hooding of leaflets:
-enlarged, redundant, thick, rubbery, floppy leaflets
*deposition of myxomatous (mucoid) material:
-increased proteoglycan and decreased fibrillar collagen/elastin
-fibrosis with scarring
rheumatic heart disease - overview
*cardiac manifestation of rheumatic fever
*acute immunologically-mediated, multisystem inflammatory disease that occurs after group-A beta-hemolytic streptococcal infections
rheumatic heart disease - clinical features
*evidence of preceding group A streptococcal infection (10 days to 6 weeks)
*acute rheumatic fever
*signs of carditis: pericardial friction rubs, cardiac dilation, mitral insufficiency, CHF
rheumatic heart disease - pathogenesis
*tissue damage caused by combination of anti-M protein antibodies and T cell-mediated reactions
*CD4+ T cells recognize streptococcal peptides AND host antigens elicit cytokine-mediated inflammation
rheumatic heart disease - pathology
*pancarditis = all layers of heart affected
1. pericarditis → fibrinous exudate
2. myocarditis: ASCHOFF BODIES
-collections of T-lymphocytes, scattered plasma cells, and plump, activated macrophages with necrosis (see image)
-scattered in interstitial tissue
3. valvulitis:
-FIBRINOID NECROSIS (fibrin deposition along closure lines)
-vegetations (small thrombotic verrucae)
infective endocarditis - overview
*microbial infection of heart valves or mural endocardium with underlying tissue damage
*marked by presence of vegetations = infected thrombus with organisms
infective endocarditis - pathogenesis
*microorganism seeds the bloodstream (bacteremia usually)
*acute = destructive infections by highly virulent organisms in NORMAL valves (STAPH AUREUS)
*chronic = infections by low virulence organisms in previously abnormal valves (Strep viridans)
infective endocarditis - clinical presentation
*rapid onset of fever, chills, weakness
*murmurs in majority of patients
infective endocarditis - gross pathology
*vegetations are friable, bulky, destructive:
-fibrin and inflammatory cells
-bacteria or other organisms
*vegetations are prone to embolization:
-often contain virulent organisms
-abscesses, septal infarcts, or mycotic aneurysms
infective myocarditis - overview
*infectious agents or inflammatory processes targeting the myocardium
*usually VIRAL
infective myocarditis - pathogenesis
*viral infection (classically, Coxsackie viruses)
*injury stems from direct cytopathic effects or by secondary immune response damage
infective myocarditis - pathology
*myocardial inflammation and edema
*may resolve without significant sequelae
*heal by progressive fibrosis
dilated cardiomyopathy - mechanism of failure
*impairment of contractility (systolic dysfunction)
dilated cardiomyopathy - causes
*genetic (~50%)
*alcohol, peripartum, myocarditis, etc
dilated cardiomyopathy - gross morphology
*four-chamber dilation & hypertrophy
*ischemic appearance
dilated cardiomyopathy - microscopic morphology
*non-specific, with myocyte hypertrophy and interstitial fibrosis
hypertrophic cardiomyopathy - mechanism of failure
*impairment of compliance (diastolic dysfunction)
hypertrophic cardiomyopathy - causes
GENETIC
hypertrophic cardiomyopathy - gross morphology
*thick-walled without ventricular dilation
*disproportionate septal thickening
hypertrophic cardiomyopathy - microscopic morphology
*marked myocyte hypertrophy & disarray
*interstitial fibrosis
restrictive cardiomyopathy - mechanism of failure
*impairment of compliance (diastolic dysfunction)
restrictive cardiomyopathy - causes
*systemic disorders affecting myocardium
*amyloidosis
*radiation-induced fibrosis
*Loeffler syndrome
*endomyocarditis
restrictive cardiomyopathy - gross morphology
*ventricles normal size
*atria dilated
restrictive cardiomyopathy - microscopic morphology
*interstitial deposition/fibrosis (amyloid, eosinophilia, endomyocardial fibrosis)
atrial myxoma - overview
*benign neoplasm arising from primitive multipotent mesenchyme
*most common primary tumor of the heart
*familial syndromes associated with myxomas
atrial myxoma - clinical symptoms
*elaboration of IL6 causes fever & malaise
*valvular obstruction
*embolization of fragments
atrial myxoma - pathology
*left atrium:
-pedunculated with stalk (usually 2-6 cm; ball valve obstruction of mitral or tricuspid valve)
-gelatinous amorphous extracellular matrix (scattered myxoma cells, abnormal vessel-like formations)
papillary fibroelastoma
*benign tumor of valvular endocardium
*hair-like projections
rhabdomyoma
*benign tumor of myocytes
*bizarre, markedly enlarged myocytes (Spider cells)
*usually associated with tuberous sclerosis
