Chapter 12: The heart
Average physiology:
Cardiac hypertrophy describes increases in the heart wall thickness and weight. Dilation describes enlarged chamber size. The two typically represent pathological blood pressure and volume, respectively. Cardiomegaly is used to describe an enlarged heart due to either increased size or weight.
The myocardium is the primary functional unit of systole and diastole, or contraction and relaxation, respectfully. The myocytes of the left ventricle are highly organized spiral orientation to facilitate generation of contractile force. The magnitude of the force generated in contract is a function of the distance of sarcomere contraction hence increased dilation allows for more force generated during contraction. However, excessive dilation there is less overlap of actin and myosin filaments resulting in a smaller magnitude of force: the etiology of heart failure. Being less organized, atrial myocytes generate less force but some contain atrial natriuretic peptide, which induces
Intercalated discs are specialized intracellular junction that allow for rhythmic cardiac contractions. A central component are gap junctions that allow easy flow of ions causing intercellular mechanical and electrical conduction. Pathology of these discs can cause arrhythmia—electromechanical dysfunction—or heart failure.
The leaflets of the atrioventricular: tricuspid and mitral—and the cusps of the semilunar: aortic and pulmonary—valves have a similar structure and both function to insure unidirectional flow. The valves are so thin nutrient supply can be accomplished without dedicated vascular supply. The valves consist of three layers:
Fibrosa: a dense collagenous core at the out-flowing surface, which is also connected to supporting structures
Spongiosa: the central core of lose connective tissue
Venricularis or atrialis: elastin layer on the in-flowing surface
These structures are lined by a layer of endothelial cells as well. The fibrsoa is responsible for the mechanical integrity of the valves while the elastin layer facilitates rapid recoil during closure. The spongiosa layer facilitates interaction between the two layers and is the layer of resident interstitial cells that: synthesize ECM components, metalloproteniases (which degrade ECM), and collagen remodeling proteins—they are essential for valve function.
Dilation of the aortic root can hinder coaptation during cusp closure causing regurgitation while ventral dilation and ruptured tendinous cords of the papillary muscles can lead to dysfunction in valve closure.
Pathology of the valves takes three form largely:
The conduction system responsible for the regular rate and rhythm receives neural (e.g. vagal stimulus), extrinsic adrenergic signalling, PO2and extracellular ion concentrations. There are 4 major components and path of the conduction system are as follows:
Each component has it’s own intrinsic pacemaker rate—the time to complete a cycle of action potential propagation. The fastest functioning pacemaker generally sets the rate of contraction, which is the SA node. The pacemaker rates of each component of the conduction are also listed in decreasing order.
Delayed conduction of the action potential by the AV node is essential to insure that the atria have finished contracting before the ventricles begin to contract.
Blood and serum to the heart is carried by the epicaridal coronary arteries:
Most individuals have a right dominant heart with a balanced distribution (the network of arteries listed above). The posterior interventricular artery comes of the left coronary in individuals with a left dominant heart, which then gives them a left dominant distribution of blood. In individuals with a right distribution, the circumflex comes off the right coronary.
Blood flow to the heart occurs primarily during diastole as the aortic valve partially covers the orifices of the coronary arteries when open. Moreover, contraction of the myocardium reduces perfusion of the intramural arteries.
The myocardium is typically considered a permanent cell population without replicative potential tough there is evidence of some stem cell populations. While present in larger numbers in response to hypertrophy or tissue damage, they do not recover any significant myocardial function of areas of necrosis.
The heart accumulates epicardial fat with age, the left ventricle becomes smaller, a sigmoid septum (bulging of basal septum into left ventricular outflow tract) forms, and gray-blue byproducts of glycogen metabolism increase termed basophilic degeneration. Calcium deposits begin develop on the aortic valve and mitral annulus potentially leading to stenosis. Valves may become fibrotic, mitral leaflets may start buckling back into the left atrium, and filiform processes—lambl exerescences—form along the closure lines of the aorit and mitral valves.
Stenosis and prolapse lead to pressure and volume overloads, which lead to hypertrophy, dilation, and subsequently arrhythmias. The aorta may be come increasingly stenotic impairing its ability to modulate pressure spikes from systole. Progressive stenosis and atherosclerosis can weaken the vessel wall, which can lead to an aortic dissection.
There are 6 major etiologies of heart pathology:
Pump failure: insufficient relaxation or contraction of the myocardium
Flow obstruction: lesions that prevent blood flow through the coronary arteries or through the valves—leading to infarcts and pressure overload
Refurgitant flow: reentry of the ejected blood though an insufficient valve, causing volume overload
Shunted flow: Diversion of blood though septal or vascular defects: either congenital or acquired
Conduction dysfunction: uncoordinated generation of transmission of electrical signaling necessary for contraction and relaxation
Rupture of heart or vessel: trauma or necrosis leading to damaged vessels or septa causing catastrophic exsanguination
As with any pathology, diseases may be due to single pathogenic variants of a gene, several genes, environmental exposure, or idiopathic in nature.
Mechanisms such as increased contractility with increased stress, and activation of neurohumoral systems—norepinephrine release, activation of renin-angiotensin-aldosterone system, or release of atrial natriuretic peptide—are useful acute responses to maintain arterial pressure and organ perfusion but can be the etiology for heart failure after chronic exposure. Along with may other causes, pathological changes can result in dysfunction of myocardial contractile function: systolic dysfunction—and a decreased ejection fraction or insufficient filling: diastolic dysfuntion. Diagnoses put forward by the American College of Cardiology are described in terms of the clinical syndrome of heart failure along with ejection fraction.
As pressure and volume increase the cardiac myocytes undergo hypertrophy mediated by trophic signals such as those mediated by β-adrenergic receptors. Hypertrophic myoctyes have enlarged nuclei and increased ploidy to meet the increased demand of protein synthesis and reflects a pressure-overload hypertrophy due to aortic stenosis, for example. New sarcomeres are assembled in parallel to increase contractile force causing concentric thickening of the ventricular wall.
This is the most common valvular disorders and effects about 2% of the population. Because the etiology is due to “wear and tear,” individuals begin to present in the seventh decade of life. Those with congenital bicuspid valves begin to present 1-2 decades earlier as bicuspid valves endure more mechanical stress. Chronic injury due to the contributing factors of atherosclerosis (i.e. hyperlipidememia, hypertension, inflammation, etc.) appear to accelerate calcification. However, they differ significantly in etiology as diseased valves contain cells that resemble osteoblasts—treatments of atherosclerosis are not effect in preventing calcium degeneration.
Clincal features. Stiffening and narrowing of the aortic orifice results in increased pressure differential across the valve, increased left ventricular pressure, and subsequently concentric left ventricular hypertrophy. Hypertrophied myocardium is often ischemic, usually complicated by atherosclerosis, and angina pectoris my occur. Systolic and diastolic dysfunction may be impaired leading to cardiac decompensation and congestive heart failure. Development of angina and syncope are indicators of extremely poor prognosis.
Approximately 1% of the population has a bicuspid aortic valve from birth and is associated with pathogenic variants on 18q, 5q, and 13q. Dysfunction in NOTCH1 has been identified as one possible etiology.
The raphe or line of incomplete separation between two cusps is frequently a sight of significant calcium deposition. Bicuspid aortic valves tend to become stenotic or insufficient, are prone to infective endocarditis, and associated with aortic dilation or dissection. 50% of all cases of aortic stenosis are of bicuspid valves.
Deposition of calcium on the mitral valve develops in an annulus, or ring, at the base of the leaflets. While usually asymptomatic it can cause:
Regurgitation
Stenosis
Arrhythmias that can occasionally lead to sudden death if the calcifications impinge on conduction system
Embolic stoke due to formation of thrombogenic surface
Infective endocarditis
Mitral valve annular calcifications are most common in females older than 60 and among individuals with mitral valve prolapse.
Degeneration of the fibrous layer cause hooding of the valve leaflets and prolapse back in to the left atrium during systole.
Pathogenesis. Most cases are idiopathic but is uncommonly associated with with the pathogenic variant of FBN-1 implicated in Marfan syndrome as well as loci involved in remodeling of valvular extracellular matrix and intercellular adhesion. Mouse models have shown TGF-β inhibitors prevent development of prolapse.
Clinical Features. The snapping of the valve and chordae tendineae during systole produces a characteristic mid-systolic click sometimes followed by a mid systolic murmur. A minority of patients develop angina-like symptoms and dyspnea likely related to mitral valve insufficiency. Roughly 3% of individuals will develop at least one of the following:
Infective endocarditis
Mitral insufficiency with or without chordal rupture
Systemic infarct due to embolism of leaflet thrombi
Ventricular or atrial arrhythmias
It is diagnosed by echocardiography and symptomatic patients may be treated with with installation of a mechanical valve.
Rheumatic fever is a multisystem inflammatory disease typically occurring within a few weeks after infection of group A streptococcal pharyngitis. Acute rheumatic carditis is often a manifestation of rheumatic fever and can progress to rheumatic heart disease. Rheumatic heart disease is characterized by fibrotic valvular changes is virtually the only case of mitral valve stenosis. Today rheumatic heart disease mostly effects individuals living in economically repressive nations.
Pathogensis. Acute rheumatic fever is a consequence of immune system mediated biomimicry: anti-bodies and CD4+ T-cells directed against streptococcal M proteins also recognize cardiac self-antigens. This causes a classical immune response: complement activation, recruitment of Fc-receptor cells, macrophage activation. Aschoff bodies—a large cluster of T lymphocytes, macrophages, and plasma cells—can be in a layer of the heart, termed pancarditis (peri-, myo-, and endo-carditis). Injury causes:
Leaflet thickening
Commissural fusion and shortening
Chordae tendineae thickening and shortening
Chronic stenosis can cause dilation of the left atria, which is associated with formation of mural thrombi. Mitral valve stenosis can also cause pulmonary vascular and parenchymal changes (e.g. <+eg+>) and subsequently hypertrophy of the right ventricle. Occasionally mitral stenosis is associated with aortic valve stenosis.
Clincial features. Diagnosis of rheumatic fever is made on evidence of a group A streptococcal infection and positive findings of at least one of the following:
Migratory polyarthritis of large joints
Pancarditis
Subcutaneous nodules
Erythema marginatum of the skin
Involuntary, rapid, purposeless movements (termed sydenham chorea)
Or one of the preceding with two minor signs/symptoms i.e. fever, arthralgia, elevated blood levels of acute phase reactants.