Introduction part 1
The homo sapiens heart pumps over 5 liters of blood per minute to meet the body’s need. However, abnormal changes in their structure may lead to disturbing physiological consequences.
Cardiovascular disease reduces life expectancy and increases health cost, & is the number one cause of worldwide death. The overall weight of the heart averages about 325gm (0.5% of body weight), with much coming from the left ventricle. The left ventricle thickness is about 1.4cm, while the right ventricle thickness is about 0.4cm.
Hypertrophy results from an increase in heart’s weight or thickness, which is the cause of cardiomegaly. However, cardiomegaly may also result from both dilation and hypertrophy or either of them. Dilation is simply, the enlargement of the chamber size.
The myocardium composes of cardiac myocytes responsible for systole & diastole. Ventricular systole depends on the effective overlap of the actin & myosin filament, that causes the shortening of the sarcomere & eventually the myocyte.
In a normal ventricular dilation (diastole), heart filling stretches the cardiac muscle, increasing the degree of sarcomere shortening, & eventually the force of contraction. In excessive dilation, the actin-myosin overlap reduces, resulting in a decrease in the force of contraction and heart failure.
Atrial myocytes produce atrial natriuretic peptide, effective in vasodilation, natriuresis & diuresis, & beneficial in hypertension and congestive heart failure. The intercalated discs link up individual cardiac myocytes and contain specialized intercellular structures including gap junctions, for mechanical, electrical integration.
Gap junctions provide passage of ions across the membranes of adjoining cells. The abnormalities in their spatial distribution & respective proteins result in arrythmias & heart failure from ischemic & myocardial heart disease.
Introduction part 2
The heart valves enable a unidirectional flow of blood through the heart, & include mitral, tricuspid, aortic & pulmonary valves. The architecture of the valves from their outflow to inflow surface include: dense collagenous core> loose connective tissue> elastin layer> endothelial covering.
The function of the semilunar valves depends mainly on their structural integrity and movement. Therefore, in conditions of aortic root dilation, this can affect the semilunar valves, resulting in regurgitation. However, the function of the atrioventricular valves (AVV) depends on chordae tendineae, papillary muscles & the valves’ structural integrity. Conditions due to papillary muscle dysfunction, tendon rupture, & ventricular dilation may affect AVV closure, resulting in regurgitation.
In order to ensure a coordinated contraction of cardiac muscle, specialized excitatory and conducting myocytes- the cardiac conduction system is essential. They include: SA node> AV node> bundle of His> Right & left bundle branch> left anterior & posterior fascicles of the LBB> Purkinje fibers.
The three major coronary arteries include: left anterior descending (septal & diagonal branches); left circumflex artery (marginal branches); right coronary artery.
CARDIAC ORGANOGENESIS AND CAUSES OF CONGENITAL HEART DFECTS
By 15th day, earliest cardiac precursors from lateral mesoderm form 1st & 2nd heart field crescent cells> Progenitor cells of the 1st heart field form the LV, while that of 2nd heart field form the RV, atria, & conotruncus (outflow tract)> By 20th day, a beating tube forms that loops rightward> by 28th day, heart chambers begin to form>
neural crest cells migrate to divide the conotruncus into aortic arch & pulmonary trunk> endocardial cells invade ECM, to proliferate & differentiate into mesenchymal cells> ECM swells to form endocardial cushions that produce the atrioventricular valves (AVV) & outflow tract valves (OTV)> By the 50th day, further separation of ventricles, atria & AVV produce the four heart chambers.
Causes: partial loss of transcription factors following genetic abnormalities; congenital rubella infection; gestational diabetes; teratogenic therapeutic drugs; folate deficiency.
Next, we shall discuss the pathologies of cardiovascular system.
Congestive heart failure (heart failure)
Results from failure of the heart to pump blood sufficiently enough to meet metabolic demands of tissues. The two types are left & right sided heart failure.
Predisposing factors: chronic heart disease from chronic work overload, in valvular disease or hypertension; myocardial infarction; acute hemodynamic stresses from fluid overload or acute valvular dysfunction. These factors may cause systolic dysfunction.
Other predisposing factors: massive left ventricular hypertrophy, myocardial fibrosis, amyloid deposition, & constrictive pericarditis. These factors cause diastolic dysfunction.
How the heart responds: via the Frank-starling mechanism (increased filling volume to dilate the heard in order to enhance heart contraction); ventricular remodeling (hypertrophy); norepinephrine release by sympathetic nerves (increases HR, contraction, & vascular resistance); activation of ANP & renin-angiotensin-aldosterone system (to maintain filling volumes & pressure).
Signs & symptoms: low cardiac output & tissue perfusion; pooling of blood in the venous system; pulmonary edema; peripheral edema.
Decompensated cardiac hypertrophy
This condition results from cumulative changes that occur during cardiac hypertrophy. Clinical manifestations include: cardiomegaly, cardiac failure, & sudden death.
Two forms of hypertrophy: pressure, & volume overload hypertrophy.
Causes of pressure overload hypertrophy: systemic hypertension; aortic stenosis; aortic regurgitation; weight lifting exercises. Causes of volume-overload hypertrophy include aerobic exercises (beneficial); mitral regurgitation; aortic regurgitation; & myocardial infarction
Other causes of cardiac hypertrophy include: dilated cardiomyopathy; hypertrophic cardiomyopathy; mitral regurgitation; aortic regurgitation; activation of β-adrenergic receptors; ischemic heart disease.
Pathogenesis: expression of immediate-early genes (c-fos, c-myc, c-jun, EGR1)> genetic expressions of fetal/embryonic forms of β-myosin, collagen, ANP> increase in myocyte size> disproportionate capillary number> low oxygen & nutrient delivery to hypertrophied heart> fibrous tissue deposition> increase in myocardial wall tension, heart rate, & contractility> high oxygen demand & consumption.
Other contributing pathogenetic factors: abnormal myocardial metabolism; alterations in intracellular handlings of calcium ions; myocytes apoptosis; down-regulation of miR-208 (noncoding RNA which inhibits protein expression).
Left-sided heart failure
This is the failure of left ventricular wall contraction, resulting in pulmonary congestion, tissue hypoperfusion, & organ dysfunction. Macroscopically, there is left ventricular hypertrophy & dilation. Two forms: systolic & diastolic failure.
Systolic failure results from factors that damage the contractile function of the left ventricle, leading to insufficient cardiac output. Diastolic failure arises from the abnormal stiffness of left ventricle & restricted ability to relax during diastole. In diastolic failure, cardiac output is preserved at rest, but affected during strenuous exercises due to rises in left ventricular filling pressure.
Common causes include: hypertension; ischemic heart disease; myocardial diseases; aortic and mitral valvular diseases.
Predisposing factors for diastolic failure: age >65; female gender; hypertension (most common); diabetes mellitus; bilateral renal artery stenosis; obesity; myocardial fibrosis in cardiomyopathies & IHD; cardiac amyloidosis; restrictive pericarditis.
Clinical manifestations: left atrial dilation & stasis; atrial fibrillation; thrombosis & thromboembolic stroke; pulmonary congestion, & edema; cough & dyspnea; orthopnea; paroxysmal nocturnal dyspnea; hypoxic encephalopathy; irritability; restlessness.
Other clinical manifestations: reduction in renal perfusion & activation of renin-angiotensin-aldosterone system> salt & water retention> expansion of extracellular fluid volume> exacerbation of pulmonary edema> prerenal azotemia in severe renal hypoperfusion. It is complicated by right-sided heart failure.
Diagnosis: Kerly B-lines on X-ray images, which signifies perivascular and interstitial edema in the interlobular septa.
Cor pulmonale
This is an isolated right-sided heart failure that results from various disorders affecting the lungs. Causes of Cor pulmonale are: hypoxia; chronic sleep apnea; high altitude; parenchymal diseases of the lungs; primary pulmonary hypertension; recurrent lung thromboembolism.
Pathogenesis: increased pulmonary hypertension> hypertrophy & dilation of the right ventricle & atrium.
Clinical manifestations: congestive hepatic central vein & hepatomegaly: portal hypertension, splenomegaly (≥150gm), & bowel edema; pericardial & peritoneal effusions; ascites; ankle & pretibial edema; presacral edema; anasarca; mental deficits.
Other clinical manifestations: congestive kidney, peripheral edema with azotemia; left ventricular dysfunction, lung edema, & pleural effusion; biventricular CHF.
Treatment and management: ACE inhibitors; β-1 adrenergic blockers; diuretics.
Right to left shunt
This arises from abnormal channels between heart chambers or blood vessels, resulting in blood flow from pulmonary to systemic circulation.
Causes include: tetralogy of Fallot; transposition of great arteries; persistent truncus arteriosus; tricuspid atresia; total anomalous pulmonary venous connection.
Clinical manifestations: hypoxemia; cyanosis; paradoxical embolism; brain infarction & abscess; hypertrophic osteoarthropathy (clubbing of the tips of fingers & toes from prolonged cyanosis).
Left to right shunt
This arises from abnormal channels between heart chambers or blood vessels, resulting in blood flow from systemic to pulmonary circulation. The causes are: patent ductus arteriosus; atrial septal defect (ASD); ventricular septal defect (VSD).
Clinical manifestations: increased volume and pressure in pulmonary circulation; right ventricular hypertrophy & pulmonary artery atherosclerosis; pulmonary arterial vasoconstriction; pulmonary vascular resistance & hypertension; right to left shunt; late cyanosis.
Atrial septal defect
This is an abnormal, fixed opening in the atrial septum arising from incomplete tissue formation resulting in left to right shunt. Symptoms are usually evident after age 30.
Clinical manifestations: murmur around the pulmonary valve; right-sided volume overload. Complications are: heart failure; paradoxical embolism; irreversible pulmonary hypertension.
Patent foramen ovale
A small opening created by an unsealed open flap of tissue in the atrial septum at the oval fossa after birth. The unsealed flap may open due to factors that add more pressure on the right side of the heart.
Predisposing factors: sustained pulmonary hypertension; sneezing; bowel movement; coughing.
Clinical manifestations: brief right to left shunt; paradoxical embolism.
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