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52 Cards in this Set
- Front
- Back
Flowchart of Physiologic and Pathologic hypertrophy:
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pre-natal: hyperplasia
post-natal: hypertrophy Note 3 kinds of increased workload. |
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MYOCARDIAL ADAPTATION:
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Temporary changes may be physiologic (e.g. heart rate, resistance, output) without associated structural changes.
ADAPTATION involving structural changes (hypertrophy) may be physiologic or pathologic. |
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Top: normal
Bottom: LVH |
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PHYSIOLOGIC HYPERTROPHY:
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*Increased cardiac size in response to chronic endurance exercise, pregnancy, etc
*Preservation of cardiac structure and function *MILD increase in thickness of wall of LV (1.3 cm vs 1.1 cm) *MILD increase in volume of LV *L:W ratio of myocardial cells increased *CAPABLE of REGRESSION (by apoptosis) |
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CARDIAC ADAPTATION (FRANK STARLING):
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*Increased end diastolic volumes cause increased myocyte stretching.
*Stretched fibers contract more forcibly resulting in increased cardiac output. *If stretched fibers can maintain adequate cardiac output, heart failure is compensated. *Stretched fibers increase myocardial oxygen requirements. *Ultimately, cardiac muscle cannot produce adequate output, resulting in decompensated heart failure. |
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What characterizes PATHOLOGIC HYPERTROPHY:
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*Growth of heart is associated with changes in patterns of gene expression, cardiac architecture, and cardiac physiology.
*Afterload/Pressure OVERLOAD (Load against which heart contracts to eject blood; maximum tension of muscle mass at end of systole). *Preload/Volume OVERLOAD (Maximum volume of blood at end of diastole). |
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AFTERLOAD- PRELOAD/ TIME FACTOR: HOW ARE CONSEQUENCES INFLUENCED BY AMOUNT OF TIME?
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*Consequences are influenced greatly by the time of development of volume overload or pressure overload.
-Preload/Volume Overload: Mitral regurgitation (MR) due to ruptured papillary muscle vs MR due to chronic rheumatic valvular disease. -Afterload/Pressure Overload: Massive pulmonary embolus vs slowly developing pulmonary hypertension. |
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PATHOLOGIC HYPERTROPHY--What do we see in Afterload (pressure overload) states?
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*Increased cardiac mass.
*Hypertension, valvular stenosis. *Sarcomere width is greater than length (W>L). *Concentric hypertrophy. *Little or no change in chamber volume. |
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PATHOLOGIC HYPERTROPHY--What do we see in Preload (volume overload) states?
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*Valvular regurgitation, regional dysfunction after MI, dilated cardiomyopathy
*Increased cardiac mass with increased chamber volume *Sarcomere length is greater than width (L>W) *Eccentric hypertrophy |
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Middle is normal.
Left: Pressure overload Right: Volume overload |
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Diagram: How does the normal heart end up going to:
atrophy? physiologic hypertrophy? concentric hypertrophy? eccentric hypertrophy? |
Again, note difference b/t pressure and volume overload.
Big pathologic differences b/t the two as well. Huge fibrosis and arrythmia risk in volume overload hearts. |
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MASSIVE CARDIOMEGALY/COR BOVINUM
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LEFT VENTRICULAR HYPERTROPHY
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PATHOLOGIC HYPERTROPHY--what do we see from a microscopic point of view?
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*Increased size of myocardial cells (Increased numbers of sarcomeres).
*Increased nuclear size with BOXCAR appearance. *No significant increase in capillaries, resulting in relative ischemia. *Interstitial fibrosis. |
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L: normal
R: myocardial hypertrophy *Huge nuclei, huge amounts of DNA. |
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Cardiac Myocyte on EM
A=Nucleus B=Z-line C=A-band D= Mitochondria |
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HEART/ INTERSTITIAL FIBROSIS
C=Collagen |
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Interstitial Fibrosis/ Myocardium on trichrome stain.
Blue=Fibrosis |
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L: Concentric Hypertrophy of Left ventricle
Middle: Normal R: Eccentric Hypertrophy of Both ventricles |
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MYOCARDIAL HYPERTROPHY--what happens at the nuclear level?
what 3 genes are implicated? |
*Increased mRNA
*Increased protein synthesis *Induction of immediate early genes: c-fos egr-1 c-jun |
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PATHOLOGIC HYPERTROPHY--discuss molecular changes:
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*Reexpression of fetal gene program (ANP, fetal myosin, etc).
*Recapitulation of fetal metabolic program (glycolysis). *Reorganization of sarcomeres. *Altered calcium homeostasis. *Changes in myocyte contractility/relaxation. *Death of myocytes by apoptosis --> fibrosis. *Electrical remodeling (alterations in expression/function of ion transporting proteins). |
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CARDIAC HYPERTROPHY--what initiates the molecular changes?
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*Mechanical stimuli (e.g. stretching or mechanotransduction via integrins)--> Activation of receptor mediated signaling pathways--> hypertrophy.
*Integrins can signal myocyte to produce various growth factors that serve as ligands (paracrine/ autocrine). *Ligands (e.g. Angiotensin II, ET-1, NE, IGF-I, TGF-B; some stimulate fibroblasts to produce extracellular matrix--> Interstitial fibrosis). *Ligands bind to and activate G-protein coupled receptors and receptor tyrosine kinases (MAPK, PI3K). *Initiation of intracellular signaling cascades. |
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Summary chart of mechanical stress in Myocardial Hypertrophy:
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Summary of events from Robbins of events leading to Cardiac Hypertrophy and eventually dysfunction:
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REGRESSION OF HYPERTROPHY--how does it occur? 3
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*Suppression of pro- growth pathways
*Activation of protein degradative pathways *Ubiquitin proteosome system (Fibrosis can't ever reverse) |
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LEFT SIDED CARDIAC FAILURE: what causes it?
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*Ischemic heart disease (CAD)
*Systemic hypertension *Aortic and mitral valve disease *Primary myocardial disease |
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LEFT SIDED CARDIAC FAILURE: what do you see?
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*Hypertrophy and dilatation of LV
*Myocyte hypertrophy and variable interstitial fibrosis *Dilatation of LA with increased risk of atrial fibrillation *Stasis in atrial appendage--> thrombus--> formation--> embolization |
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LEFT SIDED CARDIAC FAILURE: PULMONARY CONGESTION AND EDEMA--
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*Perivascular and interstitial edema--> Edema of alveolar septa--> Edema fluid in alveolar spaces-->
*Extravasation of RBCs--> Phagocytosis of RBCs with accumulation of iron (hemosiderin) in macrophages (heart failure cells). |
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PULMONARY EDEMA from left side heart failure.
Yellow arrow points to Edema Fluid. |
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PULMONARY EDEMA
E=Edema Fluid/ Low Power |
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PULMONARY EDEMA
Arrows=Congestion E=Edema Fluid/ High Power |
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*LUNG HEART FAILURE CELLS
*Yellow-brown pigment= iron (hemosiderin) containing macrophages |
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LEFT SIDED CARDIAC FAILURE
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*Decreased renal perfusion--> Activation of renin-angiotensin-aldosterone system--> Retention of salt and water.
*Pre-renal azotemia (precursor to kidney disease). *Hypoxic encephalopathy. |
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RIGHT SIDED CARDIAC FAILURE--what causes it?
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*Most commonly caused by left sided failure.
*Associated with lung disorders ("cor pulmonale"): -Parenchymal diseases of lung. -COPD. -Disorders of pulmonary vasculature (Primary pulmonary hypertension, thrombo-emboli, etc). |
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RIGHT SIDED CARDIAC FAILURE--what pathologic changes do you see?
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*Hypertrophy and dilatation of RV
*Myocyte hypertrophy with variable interstitial fibrosis *Dilatation of RA *Pericardial effusions |
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RIGHT VENTRICULAR HYPERTROPHY
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RIGHT VENTRICULAR HYPERTROPHY in xs.
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BILATERAL ECCENTRIC HYPERTROPHY AND DILATATION/ COR BOVINUM. This is late stage.
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RIGHT VENTRICULAR HYPERTROPHY resultant from TRANSPOSITION OF GREAT VESSELS.
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RIGHT SIDED CARDIAC FAILURE--what do you see in the body's other tissues?
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*Passive congestion of liver with variable centrilobular necrosis (Nutmeg liver) with possible progression to cardiac sclerosis.
*Congestive splenomegaly. *Pleural, pericardial, peritoneal (ascites) effusions. *Peripheral edema. |
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NUTMEG LIVER, gross view.
Dark areas= centers of lobules top left--actual nutmeg. |
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NUTMEG LIVER
Central Vein is visible. Periphery is spared. This is passive liver congestion as a result of Right side heart failure. |
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LIVER in CARDIAC SCLEROSIS
Blue= collagen (fibrosis) Later stage than nutmeg liver; a result of right heart failure. |
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HEART FAILURE-- ∆ b/t systolic and diastolic:
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SYSTOLIC: Insufficient cardiac output due to loss of myocardial contractility
DIASTOLIC: Cardiac output is preserved at rest, but LV is abnormally stiff or restricted |
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AGING CHANGES in MYOCARDIUM:
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*Increased mass
*Increased subepicardial fat *Brown atrophy (Lipofucsin) *Basophilic degeneration *Amyloid deposition (transthyretin) |
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AGING CHANGES in the HEART structure:
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*Increased LA cavity size, decreased LV cavity size, sigmoid shaped ventricular septum--> hypertrophy.
*Aortic valve calcification, mitral annulus calcification, fibrous thickening of leaflets, Lambl’s excrescences. *Increased tortuosity and cross sectional diameters of coronary vessels, plaques. *Dilated ascending aorta, fragmentation of elastica and plaque formation. |
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*Lambl’s Excrescences on aortic valve. Fibrin that has become organized. Occurs in aging hearts.
*Small filiform processes near closure lines of valve. Arise from organized thrombi. |
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BROWN ATROPHY
Occurs in aging hearts. Or patients who have prolonged disease. |
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*BROWN ATROPHY (LIPOFUSCIN)
*Arrows=Lipofuscin |
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BASOPHILIC DEGENERATION. A change you can see in the heart; a by-product of glycogen metabolism.
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CARDIAC AMYLOIDOSIS
A=Amyloid Deposits *In aging hearts. |
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CARDIAC AMYLOIDOSIS
A= Congo Red; Red=amyloid B= Congo Red Polarized; Green= Amyloid and White= Collagen |