Heart Pathology - Part III PDF

# Heart Pathology - Part III ## Introduction * 8 weeks of gestation - heart and vasculature are the first fully functional organ system * Cardiovascular disease - #1 cause of worldwide mortality ## Cardiac Structure and Specializations * **Heart Weight**: 0.4-0.5% of body weight * **Increased He...

# Heart Pathology - Part III ## Introduction * 8 weeks of gestation - heart and vasculature are the first fully functional organ system * Cardiovascular disease - #1 cause of worldwide mortality ## Cardiac Structure and Specializations * **Heart Weight**: 0.4-0.5% of body weight * **Increased Heart Weight or Ventricular Thickness**: Hypertrophy * **Enlarged Chamber Size**: Dilation * **Cardiomegaly**: Increased cardiac weight or size (or both) - resulting from hypertrophy and/or dilation - **Normal Weight:** - 250-320 g (F) - 300-360 g (M) - **Normal Thickness:** - RV - 0.3-0.5 cm - LV - 1.3-1.5 cm ## Myocardium * **Pumping Function**: Occurs through coordinated contraction (during systole) and relaxation (during diastole) of cardiac myocytes (the myocardium). * **Left Ventricular Myocytes**: Arranged in a spiral circumferential orientation to generate vigorous coordinated waves of contraction spreading from the cardiac apex to the base of the heart. * **Right Ventricular Myocytes**: Less structured organization, generating overall less robust contractile forces. * **Endocrine Functions of the Heart**: * **Atrial Cardiomyocytes**: Contain Atrial Natriuretic Peptide * **Ventricular Myocytes**: Contain B-Type Natriuretic Peptide * **Both promote arterial vasodilation and stimulate renal salt and water elimination (natriuresis and diuresis)**. ## Valves * **Atrioventricular Valves**: Tricuspid and Mitral * **Semilunar Valves**: Aortic and Pulmonary * **Lined by Endothelium** * **Trilayered Architecture**: * Fibrosa Layer * Spongiosa Layer * Ventricularis or Atrialis Layer ## Conduction System **Components:** * Sinoatrial (SA) Node Pacemaker * Atrioventricular (AV) Node * Bundle of His (AV Bundle) * Right and Left Bundle Branch Divisions * Purkinje Network ## Effects of Aging on the Heart * Size of the left ventricular cavity is reduced. * Basal ventricular septum protrudes into the left ventricular outflow tract (so-called sigmoid septum). * Fewer myocytes. * Increased connective tissue. * Deposition of extracellular amyloid (most often poorly catabolized transthyretin). * Valvular aging changes. * Progressive Atherosclerosis. | **Category** | **Changes** | |---|---| | **Chambers** | Increased left atrial cavity size, Decreased left ventricular cavity size, Sigmoid-shaped ventricular septum | | **Valves** | Aortic valve calcific deposits, Mitral valve annular calcific deposits, Fibrous thickening of leaflets, Buckling of mitral leaflets toward the left atrium, Lambl Excrescences | | **Epicardial Coronary Arteries** | Tortuosity, Diminished compliance, Calcific deposits, Atherosclerotic plaque | | **Myocardium**| Decreased mass, Increased subepicardial fat, Brown atrophy, Lipofuscin deposition, Basophilic degeneration, Amyloid deposits | | **Aorta** | Dilated ascending aorta with rightward shift, Elongated (tortuous) thoracic aorta, Sinotubular junction calcific deposits, Elastic fragmentation and collagen accumulation, Atherosclerotic plaque | ## Six Principal Mechanisms of Heart Failure * **Failure of the Pump**: Systolic dysfunction; diastolic dysfunction * **Obstruction to Flow**: e.g calcific aortic valve stenosis or systemic hypertension or aortic coarctation * **Regurgitant Flow**: Backward flow of blood that results in increased volume workload and may overwhelm the pumping capacity of the affected chambers. ## Heart Failure * Often called Congestive Heart Failure (CHF). * Condition in which a heart cannot pump blood to adequately meet the metabolic demands of peripheral tissues, or can do so only at elevated filling pressures. * Common end stage of many forms of chronic heart disease. * Acute hemodynamic stresses, such as fluid overload, abrupt valvular dysfunction, or myocardial infarction, can all precipitate sudden CHF. **Physiologic mechanisms maintain arterial pressure and perfusion of vital organs:** * **Frank-Starling mechanism**: * Increases filling volumes -> dilates the heart. * Enhances contractility. * **Activation of Neurohumoral Systems**: * Augment heart function and/or regulate filling volumes and pressures. * **Release of Norepinephrine**: * Elevates heart rate, augments myocardial contractility and increases vascular resistance. * **Activation of Renin-Angiotensin-Aldosterone System**: * Promotes water and salt retention. * **Release of Atrial Natriuretic Peptide**: * Diuresis and vascular smooth muscle relaxation. * **Myocardial Adaptations**: * Ventricular remodeling - collective molecular, cellular, and structural changes that occur in response to injury or altered ventricular loading. ## Cardiac Hypertrophy * The pattern of hypertrophy reflects the nature of the stimulus. * **Pressure-Overload Hypertrophy**: * New sarcomeres are predominantly assembled in parallel to the long axes of cells. * **Concentric Hypertrophy**: Ex. Due to hypertension or aortic stenosis. * **Volume-Overload Hypertrophy**: * Characterized by new sarcomeres being assembled in series within existing sarcomeres, leading primarily to ventricular dilation. * **Eccentric Hypertrophy**: Ex. Due to valvular regurgitation. * Not accompanied by a proportional increase in capillary numbers. * Associated with heightened metabolic demands. * Accompanied by deposition of fibrous tissue (interstitial fibrosis). * Vulnerable to ischemia-related decompensation, which can evolve to cardiac failure. * **Molecular Changes**: Expression of immediate-early genes (e.g., FOS, JUN, MYC, and EGR1). ## Left Sided Heart Failure **Causes**: * IHD * Hypertension * Aortic and Mitral Valvular Diseases * Primary Myocardial Diseases **Effects**: * Congestion of pulmonary circulation. * Stasis of blood in the left sided chamber. * Hypoperfusion of tissues. **Morphology**: * **Heart**: Vary depending on the disease process. Nonspecific microscopic changes: Hypertrophy and interstitial fibrosis. * **Lung**: Pulmonary congestion and edema. Heart failure cells. **Clinical Manifestations:** * Cough and dyspnea. * Orthopnea or paroxysmal nocturnal dyspnea. * Cardiomegaly, tachycardia, a third heart sound due to volume overload (S3), or a fourth heart sound (S4) due to increased myocardial stiffness. * Reduced ejection fraction. * Azotemia. * Cerebral hypoperfusion - hypoxic encephalopathy. **Types of Left Sided Heart Failure**: * **Systolic Failure**: Insufficient ejection fraction (pump failure). Caused by disorders that damage or derange the contractile function fo the left ventricle. * **Diastolic Failure**: Left ventricle is abnormally stiff and cannot relax during diastole. Hypertension is the most common underlying etiology. May appear in older patients without any known predisposing factors, possibly as an exaggeration of the normal stiffening of the heart with age. ## Right Sided Heart Failure **Morphology**: * **Heart**: Varies with cause. Hypertrophy and dilatation of the right atrium and ventricle. * **Liver**: Congestive hepatomegaly- "nutmeg liver" appearance. Centrilobular necrosis. Cardiac cirrhosis. * **Spleen**: Congestive splenomegaly. * **Bowel Wall**: Chronic congestion and edema. **Clinical Manifestations**: * Hallmark of Right-Sided Heart Failure - Edema of the peripheral and dependent portions of the body, especially foot/ankle (pedal) and pretibial edema. * Anasarca can also occur. * Fatigue. * Increased peripheral venous pressure. * Ascites. * Enlarged liver and spleen. * Distended jugular veins. * Anorexia and complaints of GI distress. * Swelling in the hands and fingers. * Dependent edema. * Kidney and brain are also prominently affected. * Renal congestion is more marked. * **Serum B-type (or brain) natriuretic factor (BNP)**: * Quantitatively assess the extent of CHF. * Released by ventricular cardiomyocytes during increased wall stress. * **Echocardiography**: * Provides a measure of ejection fraction, wall motion, valvular function. ## Heart Failure Treatment * Correct the underlying cause. * Salt restriction. * Pharmacologic agents - diuretics, positive inotropes, ACE inhibitors. * Cardiac resynchronization therapy. * Mechanical ventricular assist devices.