Path 12: Heart go brrrrrrrrr Flashcards
Layers of tri-layer architecture of cardiac valves
Endothelium
Fibrosa
Ventricularis/Atrialis Layer
Cardiac myocytes rely on ________ for energy
oxidative phosphorylation
Diastole comprises ____ [fraction] of the cardiac cycle
2/3
With tachycardia, the relative duration of ____ decreases
diastole
Frank-Starling mechanism
1) Increased filling volumes dilate the heart
2) Actin-myosin crossbridge formation increases
3) Contractility increases
Normal EF
45-65%
Causes of hypertrophy
Pressure overload
Volume overload
Trophic signals (aka ß activation)
Hypertrophic myocyte cellular characteristics
1) increased protein synthesis
2) Increased mitochindira
3) Multiple/enlarge nuclei
4) DNA ploidy
Patterns of hypertrophy
Pressure overload: sarcomeres are PARALLEL to long axes of cells. Wall thickness increases
Volume overload: sarcomeres assembled in series with existing ones. Heart weight increases, but wall thickness does not. Dilation of ventricle
Why does hypertrophy make heart vulnerable to ischemia
1) Increased oxygen demand
2) Hypetrophic growth not accompanied by capillary growth
3) Fibrous tissue resists diastolic filling
Genes expressed in hypertrophic myocytes
FOS
JUN
MYC
EGR1
Most common left HF causes
1) Ischemia
2) HTN
3) Aortic/mitral dx
4) Primary myocardial dx
Pulmonary changes from pulmonary edema
1) Perivascular and interstitial edema
2) Progressive widening of alveolar septa
3) Accumulation of fluid in alveolar spaces
Histologic changes pointing to previous episodes of pulmonary edema
Hemosiderin laden macrophages
AKA Heart Failure Cells
Mechanism of hemosiderin laden macrophages
Extravasated red cells phagocytosed and accumulated iron is hemosiderin
CHF auscultation findings
1) Fine rales in bases (inspiratory)
2) S3 (volume overload)
3) S4 (increased myocardial stiffness
Mitral regurgitation in HF caused by
Dilation of heart outwardly displaces papillary muscle
Most common cause of right HF
Left HF
Isolated right HF caused by
Usually pulmonary pathologies
Marker used to quantitatively assess CHF progression
BNP
Cardiac cell embryologic origin
Mesoderm
First wave of cardiac folding in embryo produces
Left ventricle
Second wave of cardiac folding in embryo produces
Right ventricle, outflow tract, atria
Most common genetic cause of congenital heart dx
Down syndrome
Left-to-right shunts types
ASD
VSD
PDA
Atrial Septal Defect presentation
Usually silent till adulthood
Pulmonary valve murmur
Patent foramen ovale
Persistent foramen can open when right sided pressures are elavated, sometimes creating a right-left shunt or paradoxial embolism
90% of VSDs happen in
Membranous interventricular septum
VSD below pulmonary valve
Infundibular VSD
VSD presentation age
Manifest in children
VSD clinical features (morphology changes)
Irreversible pulmonary vascular disease
Right hypertrophy
Pulmonary hypertension
VSD treatment
Most close spontaneously so surgery is delayed
Surgery if no closure
PDA structure
PA joins aorta just distal to left subclavian
PDA auscultation
Persistent machinery like murmur
Mechanisms that close Ductus arteriosus
Increased atrial oxygenation
Decreased pulmonary vascular resistance
Declining prostaglandin E2 levels
Causes of PDA
Hypoxia in infant
Other defects increase pulmonary vascular resistance
Treatments to close PDA
Prostaglandin inhibitors
Percutaneous/surgical
When should a PDA be preserved
Co-occurring defects that obstruct pulmonary outflow tracts
Done by admin of Prostaglandin E1
Four features of Tetralogy of Fallot
1) VSD
2) Obstruction of the right ventricular outflow tract
3) Overriding aorta
4) Right ventricular hypertrophy (secondary to to pressure overload)
Tetralogy of Fallot classic presentation
Cyanotic at birth
Loud murmur
Transposition of great vessels types
L- uncommon, often well tolerated (corrected)
D- most common, leads to death without shunting
Cause of tricuspid atresia
unequal canal division makes tricuspid smaller and mitral larger
Tricuspid atresia symptom
Cyanosis
How is circulation maintained in tricuspid atresia?
VSD/ASD providing shunting
Coarctation of aorta patient population
Males and Turner syndrome
Infantile form of coarctation of aorta features
Tubular hypoplasia in aortic arch proximal to a PDA
Adult coarctation of aorta features
Discrete, ridgelike folding of aorta opposite to closed ductus arteriosus
4 step sequence in MIs
1) Plaque is disrupted exposing subedothelial collagen
2) Platelets adhere and realease TXA2 and ADP increasing aggregation and vasospasm
3) Tissue factor coagulation grows thrombus
4) Artery is occluded
What are ultrastructural changes
Changes in heart that set in within a few minutes of ischemia
Glycogen depletion, myofibrillar relaxation, mitochondrial swelling
How long to get irriversible MI damage
20-30 min
Earliest detectable feature of myocyte necrosis
Disruption of sarcolemmal membrane. Macromolecules leak into blood (troponin)
How long for infarct to reach full extent
3-6 hours
Apex of heart supplied by
LAD
Dominant coronary artery
RCA vs LCX
depends of on who supplies posterior 1/3 of septum
Transmural infarction occurs when a ______ vessel is occulded
Epicardial
Subendocardial infarcts occur
When there is lysis of plaque prior to transmural necrosis
MI gross autopsy buzzword timeline
Less than 12 hours: Not many changes, can see necrosis with stain
12-24 hours: Reddish blue discoloration, extravasated blood
1-3 Days: acute inflammation
3-7 Days: Macrophages
7-10 Granulation tissue
Myocyte vacuolization
Intracecullar accumulations of salt/water
Seen in infarct periphery
How long to fully heal MI
6-8 weeks
Factors contributing to reperfusion injury
1) mitochondrial dysfunction
2) Myocyte hypercontracture
3) Free radicals
4) Leukocyte aggregation
Top marker for MI in past
CK-MB
Clinically useful biomarkers of myocardial damage
CTnT and cTnI (troponin T and I)
Troponins begin to rise in ______ and peak _____ after MI
2-4 hours
24-48 hours
Intense pericarditis a week after MI name and MOA
Dressler syndrome
Due to a formation of antibodies agaisnt damaged myocardium
Patients with greatest risk of free-wall rupture, expansion, mural thrombi
Anterior transmural
Chronic IHD presentation
LVH, cardiomegaly, dilation
Long QT genetics
K+ channel loss of function or NA+ gain of function
Brugada genetics
NA+ loss of function SCNL genes
hypertensive heart disease features
Pressure overload, ventricular hypertrophy
Cor pulmonale aka
Right sided hypertensive heard disease
Acute cor pulmonale ventricle morphology
Marked dilation w/o hypertrophy
Most common valvular abnormality
Calcific Aortic Stenosis
Calcific aortic stenosis caused by
Chronic injury from hyperlipidemia, htn , inflamation
Morphological hallmark of calcific aortic stenosis
Mounded calfified masses on outflow surfaces that prevent cuspal opening
Aortic stenosis sx
Narrow valve increases ventricular pressure. LVH goes on to CHF
bicuspid aortic valve significance
Malformed valve gets stressed and calficies. cc: Aortic stenosis
Bicuspid aortic valve course of symptoms
Assymptomatic early in life
Big risk for calcific stenosis, aortic regurg
Where do mitral valve calcifications happen
Fibrous annulus
Done usually affect function… importantly can be thrombus formatio. site
Mitral valve prolapse population
Old women
Mitral valve prolapse in marfan cause
FBN1 fibrillin gene alter TGF-B signaling
Histology of Mitral valve prolapse
myxomatous degeneration of spongiosa layer
MVP heart sound
Mid systolic click
Rheumatic fever cause
2-3 weeks after strep
Type 2 hypersensitivity. Cross reactivity
M proteins resemble cardiac antigens
Rheumatic fever histo
Aschoff bodies: t lymphocyte foci (acute only)
Anitschkow cells: plump large macrophages
Subendocardial lesions can can induce irregular thickenings called _______ plaques, usually in the ____
MacCallum
Left atrium
Rheumatic fever anatomic changes
Mitral valve thickening, commisural fusion/shortening and thickening of the tendinous cords
Rheumatic fever sx
Migratory polyarthritis
Pancarditis
Subcutaneous nodules
Erythema Marginatum
Sydenham Chorea
MPSES
Most common endocarditis bug
S Viridans (cavities)
S. Areus (drugs)
Morphology of Infectious endocarditis
Vegetations on heart valves
Nonbacterial Thrombotic Endocarditis characterized by
Sterile thrombi on valve leaflets
Nonbacterial Thrombotic Endocarditis happens in
Cancer/sepsis patients with hypercoagulable states
Carcinoid syndrome sx
Flushing , diarrhea, dermatitis, bronchoconstriction
Carcinoid heart disease happens after
Massive hepatic metastatic burden, bc liver normall metabolizes circulating mediators.
Carcinoid syndrome heart lesion morphology
Glistening white intimal plaquelike thickenings of endocarcial surfaces
Tricuspid insuficiency and pulmonary stenosis
Dilated Cardiomyopathy (DCM) is characterized morphologically and functionally by _______
progressive cardiac dilation and contractile (systolic) dysfunction, usually with concomitant hypertrophy.
Arrhythmogenic right ventricular cardiomyopathy sx
Right sided HF and rhythm disturbances
Can cause sudden cardiac death
Arrhythmogenic cardiomyopathy+hyperkeratosis =
Naxos syndrome
Hypetrophic cardiomyopathy caused by (genetic)
Mutations to sarcomeric protein genes
Restrictice cardiomyopathy characterized by
Impaired ventricular diastolic filling due to ventricular compliance decrease
Amyloidosis cardiomyopathy features
Restrictive
β-pleate sheet accumulation
Either on congo red stain H&E
Most common cause of myocarditis
Viruses
esp coxsackie A/B
Chagas disease sx and histo
Myocarditis
scattered myofibers by trypanosomes accompanied by a mixed inflammatory infiltrate of neutrophils, lymphocytes, macrophages, and occasional eosinophils
Chemotoxic agents for heart
Doxorubicin
Danorubicin
Chemo
Serous pericarditis associated with
Inflammatory diseases
Constricitve pericarditis
Happens when pericardium scars limiting diastolic expansion. No ability to increase output
Most common primary heart tumor
Myxoma
Mixoma pathogenesis
Benign
Primitive multipotent mesenchyme
myxoma histo
stellate or globular myxoma cells with abundant ground substance
Sea-anemone shape tumor in heart
Papillary fibroelastoma
most common peds tumor in heart
Rhabdomyoma
Rhabdomyoma disease course
Regresses sponatneously
Prinzmetal angina due to
Smooth muscle hyperreactivity in coronary artery call
What happens 1-3 days after MI
Coagulation necrosis, neutrophils, early pericarditis
Concentric vs eccentric hypertrophy
Concentric: Sarcomeres add in parallel in response to increased afterload/pressure
Eccentric: adds sacomeres in series in response to volume overload
Squating in TOF helps how
Increases SVR to force blood into pulmonary circulation
PE in lung periphery causes
Wedge shape necrosis (infarction)
