Pathology Ch 12 The Heart

Front 1

Cardiac Hypertrophy miRNA

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Cardiac hypertrophy is associated with down-regulation of miR-208 and upregulation of miR-195

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First Heart Field

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first heart field expresses the transcription factors TBX5 and Hand1

Cells derived from the first heart field mainly give rise to the left ventricle

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Second Heart Field

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second heart field expresses the transcription factor Hand2 and fibroblast growth factor-10

cells derived from the second heart field give rise to the outflow tract, right ventricle, and most of the atria

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Gene mutations that lead to atrial and ventricular septal defects

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GATA4, TBX5, and NKX2-5, three transcription factors that are mutated in some patients with atrial and ventricular septal defects, all bind to one another and co-regulate the expression of target genes that are required for the proper development of the heart

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Gene for bicuspid aortic valve

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NOTCH1

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Genes for Tetralogy of Fallot

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JAGGED1 and NOTCH2

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DiGeorge syndrome

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deletion of chromosome 22q11.2
In this syndrome the fourth branchial arch and the derivatives of the third and fourth pharyngeal pouches, which contribute to the formation of the thymus, parathyroids, and heart, develop abnormally. One candidate gene in the deleted region is TBX1, which encodes a transcription factor that regulates the expansion of cardiac progenitors in the second heart field.

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cyanotic congenital heart disease

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When blood from the right side of the circulation flows directly into the left side (right-to-left shunt), hypoxemia and cyanosis (a dusky blueness of the skin and mucous membranes) result because of the admixture of poorly oxygenated venous blood with systemic arterial blood

The most important congenital causes of right-to-left shunts are tetralogy of Fallot, transposition of the great arteries, persistent truncus arteriosus, tricuspid atresia, and total anomalous pulmonary venous connection

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paradoxical embolism

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with right-to-left shunts, emboli arising in peripheral veins can bypass the lungs and directly enter the systemic circulation; brain infarction and abscess are potential consequence

Front 10

Severe, long-standing cyanosis causes?

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causes clubbing of the tips of the fingers and toes (called hypertrophic osteoarthropathy) and polycythemia

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left-to-right shunts

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ASD, VSD, and patent ductus arteriosus increase pulmonary blood flow and are not initially associated with cyanosis. However, left- to-right shunts raise both flow volumes and pressures in the normally low-pressure, low-resistance pulmonary circulation, which can lead to right ventricular hypertrophy and atherosclerosis of the pulmonary vasculature

Eventually, pulmonary vascular resistance approaches systemic levels, thereby producing a new right-to-left shunt that introduces unoxygenated blood into the systemic circulation (late cyanotic congenital heart disease, or Eisenmenger syndrome)

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The four cardinal features of the tetralogy of Fallot (TOF)

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(1) VSD, (2) obstruction of the right ventricular outflow tract (subpulmonary stenosis), (3) an aorta that overrides the VSD, and (4) right ventricular hypertrophy

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Persistent truncus arteriosus (PTA)

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arises from a developmental failure of separation of the embryologic truncus arteriosus into the aorta and pulmonary artery. This results in a single great artery that receives blood from both ventricles and gives rise to the systemic, pulmonary, and coronary circulations. Because there is an associated VSD and mixing of blood from the right and left ventricles, PTA produces systemic cyanosis as well as increased pulmonary blood flow, with the danger of irreversible pulmonary hypertension.

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tricuspid atresia

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results embryologically from unequal division of the AV canal; thus, the mitral valve is larger than normal, and there is almost always underdevelopment (hypoplasia) of the right ventricle. The circulation is maintained to some degree by a right-to-left shunt through an interatrial communication (ASD or patent foramen ovale) and a VSD, which affords communication between the left ventricle and the pulmonary artery that arises from the hypoplastic right ventricle. Cyanosis is present virtually from birth, and there is a high mortality in the first weeks or months of life.

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Total Anomalous Pulmonary Venous Connection

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in which the pulmonary veins fail to directly join the left atrium, results embryologically when the common pulmonary vein fails to develop or becomes atretic

Consequences of TAPVC include volume and pressure hypertrophy and dilation of the right side of the heart, and dilation of the pulmonary trunk. The left atrium is hypoplastic, but the left ventricle is usually normal in size

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coarctation of the aorta

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Typically there is hypertension in the upper extremities; in contrast, there are weak pulses and hypotension in the lower extremities, associated with manifestations of arterial insufficiency (i.e., claudication and coldness)

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hypoplastic left heart syndrome

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In severe congenital aortic stenosis or atresia, obstruction of the left ventricular outflow tract leads to underdevelopment (hypoplasia) of the left ventricle and ascending aorta, sometimes accompanied by dense, porcelain-like left ventricular endocardial fibroelastosis

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Supravalvular aortic stenosis

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is an inherited form of aortic dysplasia in which the ascending aortic wall is greatly thickened, causing luminal constriction. In some cases it is a component of a multiorgan developmental disorder resulting from deletions on chromosome 7 that include the gene for elastin. Other features of the syndrome include hypercalcemia, cognitive abnormalities, and hallmark facial anomalies (Williams-Beuren syndrome)

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Ischemic heart disease (IHD)

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In more than 90% of cases, the cause of myocardial ischemia is reduced blood flow due to obstructive atherosclerotic lesions in the coronary arteries. Thus, IHD is often termed coronary artery disease (CAD) or coronary heart disease

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Stable angina

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results from increases in myocardial oxygen demand that outstrip the ability of stenosed coronary arteries to increase oxygen delivery; it is usually not associated with plaque disruption

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Unstable angina

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caused by plaque rupture complicated by partially occlusive thrombosis and vasoconstriction, which lead to severe but transient reductions in coronary blood flow

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Stable angina

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It is caused by an imbalance in coronary perfusion (due to chronic stenosing coronary atherosclerosis) relative to myocardial demand, such as that produced by physical activity, emotional excitement, or any other cause of increased cardiac workload. Typical angina pectoris is usually relieved by rest (which decreases demand) or administering nitroglycerin, a strong vasodilator (which increases perfusion).

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Prinzmetal variant angina

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uncommon from of episodic myocardial ischemia that is caused by coronary artery spasm. Although individuals with Prinzmetal variant angina may well have significant coronary atherosclerosis, the anginal attacks are unrelated to physical activity, heart rate, or blood pressure. Prinzmetal angina generally responds promptly to vasodilators, such as nitroglycerin and calcium channel blockers.

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Unstable or crescendo angina

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pattern of increasingly frequent pain, often of prolonged duration, that is precipitated by progressively lower levels of physical activity or that even occurs at rest. In most patients, unstable angina is caused by the disruption of an atherosclerotic plaque with superimposed partial (mural) thrombosis and possibly embolization or vasospasm (or both). Unstable angina thus serves as a warning that an acute MI may be imminent; indeed, this syndrome is sometimes referred to as preinfarction angina.

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MI in women

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women are protected against MI and other heart diseases during the reproductive years. However, the decrease of estrogen following menopause is associated with rapid development of CAD, and IHD is the most common cause of death in elderly women

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MI sequence

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The initial event is a sudden change in an atheromatous plaque, which may consist of intraplaque hemorrhage, erosion or ulceration, or rupture or fissuring.
When exposed to subendothelial collagen and necrotic plaque contents, platelets adhere, become activated, release their granule contents, and aggregate to form microthrombi.
Vasospasm is stimulated by mediators released from platelets.
Tissue factor activates the coagulation pathway, adding to the bulk of the thrombus.
Frequently within minutes, the thrombus evolves to completely occlude the lumen of the vessel.

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left anterior descending branch of the left coronary artery (LAD) supplies

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most of the apex of the heart (distal end of the ventricles), the anterior wall of the left ventricle, and the anterior two thirds of the ventricular septum

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triphenyltetrazolium chloride

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If the patient died at least 2 to 3 hours after the infarct, however, it is possible to highlight the area of necrosis by immersion of tissue slices in a solution of triphenyltetrazolium chloride

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The most sensitive and specific biomarkers of myocardial damage are cardiac-specific proteins

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Troponins I and T (proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle). Troponins I and T are not normally detectable in the circulation. Following an MI, levels of both begin to rise at 2 to 4 hours and peak at 48 hours

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long QT syndrome

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The most frequent mutations are in the gene encoding KCNQ1 and result in decreased potassium currents

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The minimal criteria for the diagnosis of systemic HHD

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(1) left ventricular hypertrophy (usually concentric) in the absence of other cardiovascular pathology and (2) a history or pathologic evidence of hypertension

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Cor pulmonale

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isolated pulmonary HHD is frequently called, stems from pressure overload of the right ventricle, and is characterized by right ventricular hypertrophy, dilation, and potentially failure secondary to pulmonary hypertension.

most frequent causes are disorders of the lungs, especially chronic respiratory diseases such as emphysema, or primary pulmonary hypertension

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Serious complications of mitral valve prolapse

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(1) infective endocarditis; (2) mitral insufficiency, sometimes with chordal rupture; (3) stroke or other systemic infarct, resulting from embolism of leaflet thrombi; or (4) arrhythmias, both ventricular and atrial.

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Rheumatic fever (RF)

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immunologically mediated, multisystem inflammatory disease that occurs a few weeks after an episode of group A streptococcal pharyngitis

RHD is characterized principally by deforming fibrotic valvular disease, particularly mitral stenosis

Distinctive lesions occur in the heart, called Aschoff bodies, which consist of foci of lymphocytes (primarily T cells), occasional plasma cells, and plump activated macrophages called Anitschkow cells (pathognomonic for RF)

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RF is characterized by a constellation of findings

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(1) migratory polyarthritis of the large joints, (2) pancarditis, (3) subcutaneous nodules, (4) erythema marginatum of the skin, and (5) Sydenham chorea, a neurologic disorder with involuntary rapid, purposeless movements

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Infective endocarditis

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Predisposing diseases rheumatic heart disease was the major antecedent disorder, but more common now are mitral valve prolapse, degenerative calcific valvular stenosis, bicuspid aortic valve (whether calcified or not), artificial (prosthetic) valves, and unrepaired and repaired congenital defects

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major offender in intravenous drug abusers with IE

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S. aureus

The roster of the remaining bacteria includes enterococci and the so-called HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella)

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Carcinoid heart disease

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manifestation of the systemic syndrome caused by carcinoid tumors

characterized by episodic flushing of the skin, cramps, nausea, vomiting, and diarrhea

Plasma levels of serotonin and urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid correlate with the severity of the right heart lesions

most common cardiac manifestation is tricuspid insufficiency, followed by pulmonary valve insufficiency

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COMPLICATIONS OF ARTIFICIAL VALVES

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Thromboembolic complications - necessitates long-term anticoagulation in all individuals with mechanical valves

Infective endocarditis

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dilated cardiomyopathy (DCM)

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progressive cardiac dilation and contractile (systolic) dysfunction, usually with concomitant hypertrophy. It is sometimes called congestive cardiomyopathy

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Hypertrophic cardiomyopathy (HCM)

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characterized by myocardial hypertrophy, poorly compliant left ventricular myocardium leading to abnormal diastolic filling, and in about one third of cases, intermittent ventricular outflow obstruction

HCM is caused by mutations in genes encoding sarcomeric proteins

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Restrictive cardiomyopathy

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characterized by a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole

An important specific subgroup is amyloidosis

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myocarditis

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Coxsackieviruses A and B and other enteroviruses probably account for most of the cases. Other less common etiologic agents include cytomegalovirus, HIV, and a host of other agents

There are also noninfectious causes of myocarditis. Myocarditis can be caused by hypersensitivity reactions (hypersensitivity myocarditis), often to drugs such as antibiotics, diuretics, or antihypertensive agents. Myocarditis can also be associated with systemic diseases of immune origin, such as rheumatic fever, systemic lupus erythematosus, and polymyositis

Front 44

hyperthyroidism

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tachycardia, palpitations, and cardiomegaly are common; supraventricular arrhythmias occasionally appear

Front 45

hypothyroidism

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cardiac output is decreased, due to reductions in stroke volume and heart rate. Increased peripheral vascular resistance and decreased blood volume result in narrowing of the pulse pressure, prolongation of circulation time, and decreased flow to peripheral tissues.

Histologic features of hypothyroidism include myofiber swelling with loss of striations and basophilic degeneration, accompanied by interstitial mucopolysaccharide-rich edema fluid. A similar fluid sometimes accumulates within the pericardial sac. The term myxedema heart has been applied to these changes.