Disorders of Cardiovascular System – Pathophysiology and Pathogenesis

Ischemic Heart Disease (Disorders of Cardiovascular System)

A. General considerations

  • In Disorders of Cardiovascular System, Causes of Ischemic Heart Disease include partial or complete interruption of arterial blood flow to the myocardium. In most cases, the cause is atherosclerotic narrowing of the coronary arteries, sometimes acutely aggravated by superimposed thrombosis or vasospasm.
  • The ischemia may be clinically silent or manifest as angina pectoris, myocardial infarction, or chronic IHD.
  • Frequency is increased in patients who manifest the metabolic syndrome, a group of risk factors including central obesity, atherogenic lipid patterns, hypertension, insulin resistance (sometimes overt diabetes), and evidence of a proinflammatory state, such as elevated C-reactive protein. Obesity and physical inactivity, and probably genetic factors, predispose to the metabolic syndrome.

B. Angina pectoris

Angina pectoris is episodic chest pain caused by inadequate oxygenation of the myocardium.

1. Stable angina is the most common form of angina.

  • It is pain that is precipitated by exertion and is relieved by rest or by vasodilators, such as nitroglycerin.
  • It results from severe narrowing of atherosclerotic coronary vessels, which are thus unable to supply sufficient oxygenated blood to support the increased myocardial demands of exertion.

2. Unstable angina is prolonged or recurrent pain at rest.

  • It is often indicative of imminent myocardial infarction.
  • It is generally caused by disruption of an atherosclerotic plaque with superimposed thrombosis. It can also be caused by embolization or vasospasm.

3. Prinzmetal angina is intermittent chest pain at rest. It is generally considered to be caused by vasospasm.

 

C. Myocardial infarction

  • Myocardial infarction is the most important cause of morbidity from IHD and is one of the leading causes of death in the Western world.
  • Myocardial coagulative necrosis caused by coronary artery occlusion is characteristic.
  • Myocardial infarction is marked by a series of progressive changes involving the gross and microscopic appearances of the heart (Table 10-1). It is also marked by release of myocardial enzymes and other proteins into the bloodstream, a process caused by altered membrane permeability of necrotic myocardial cells.
  • The cells involved in the evolution of a myocardial infarct include neutrophils, macrophages, and fibroblasts. (Lymphocytes and plasma cells are not involved.)
  • There are two distinct patterns of myocardial ischemic necrosis.
  1. Transmural infarction traverses the entire ventricular wall from the endocardium to the epicardium.
  2. Subendocardial infarction is limited to the interior one-third of the wall of the left ventricle.

Complications

  • Arrhythmia is the most common cause of death in the first several hours following infarction.
  • Myocardial (pump) failure can lead to congestive heart failure and/or shock. The likelihood and severity are determined by the size and location of the lesion.
  • M yocardial rupture is a catastrophic complication that usually occurs within the first 4 to 7 days and may result in death from cardiac tamponade, compression of the heart by hemorrhage into the pericardial space.
  • R uptured papillary muscle
  • Mural thrombosis is thrombus formation on the endocardium overlying the infarct; may lead to left-sided embolism.
  • Ventricular aneurysm

 

Rheumatic Fever (Disorders of Cardiovascular System)

Rheumatic fever is a multisystem inflammatory disorder with major cardiac manifestations and sequelae, most often affecting children between 5 and 15 years of age.
1. It is also characterized by transient mild migratory polyarthritis.
2. It usually occurs 1 to 4 weeks after an episode of pharyngitis caused by group A β-hemolytic streptococci. Group A streptococcal infections of other parts of the body rarely lead to rheumatic fever. An elevated titer of antistreptolysin O (ASO) is evidence of a recent streptococcal infection.

Etiology

Rheumatic fever is apparently of immunologic origin rather than a result of direct bacterial involvement; however, the precise nature of the immune mechanisms of injury remains unclear. It is postulated to occur as a result of streptococcal antigens that elicit an antibody response reactive to streptococcal organisms, as well as to human antigens in the heart and other tissues. The incidence has been remarkably reduced in the Western world in recent years.

Aschoff body

  • This is the classic lesion of rheumatic fever.
  • This is an area of focal interstitial myocardial inflammation that is characterized by fragmented collagen and fibrinoid material, by large cells (Anitschkow myocytes), and by occasional multinucleated giant cells (Aschoff cells).

Other anatomic changes

Characteristics include pancarditis, inflammation of the pericardium, myocardium, and endocardium. Pericarditis may result in pericardial, pleural, or other serous effusions. Myocarditis may lead to cardiac failure and is the cause of most deaths occurring during the early stages of acute rheumatic fever. Endocarditis leads to valvular damage.

Rheumatic endocarditis usually occurs in areas subject to the greatest hemodynamic stress, such as the points of valve closure and the posterior wall of the left atrium, resulting in the formation of the so-called MacCallum plaque. The mitral and aortic valves, which are subjected to much greater pressure and turbulence, are more likely to be affected than are the tricuspid and pulmonary valves. In the early stage, the valve leaflets are red and swollen, and tiny, warty, bead-like, rubbery vegetations (verrucae) form along the lines of closure of the valve leaflet. The small, firm verrucae of acute rheumatic fever are nonfriable and are not a source of peripheral emboli

As a consequence of fibrotic healing, the valves become thickened, fibrotic, and deformed, often with fusion of valve cusps, as well as thickening of the chordae tendineae. Calcification is often prominent. These late sequelae, which often occur many years after the episode of rheumatic fever, are grouped under the term rheumatic heart disease:

  • The mitral valve is the valve that is most frequently involved in rheumatic heart disease.
    • It is the only valve affected in almost 50% of cases.
    • It can be affected by stenosis with fish-mouth buttonhole deformity, insufficiency, or a combination of both.
    • Mitral stenosis is marked by diastolic pressure higher in the left atrium than in the left ventricle.
  • The aortic valve is affected most often along with the mitral valve. It can be affected by stenosis or insufficiency.
  • The tricuspid valve is affected along with the mitral valve and aortic valves (trivalvular involvement) in approximately 5% of cases of rheumatic heart disease.
  • The pulmonary valve is rarely involved.

Noncardiac manifestations of acute rheumatic fever

  • Fever, malaise, and increased erythrocyte sedimentation rate
  • Joint involvement
    • Arthralgia—joint pain without clinically evident inflammation
    • Arthritis—overt joint inflammation presenting as painful, red, swollen, hot joints, usually involving larger joints, especially the knees, ankles, wrists, and elbows
    • Migratory polyarthritis—sequential involvement of multiple joints
  • Skin lesions, including subcutaneous nodules, small painless swellings usually over bony prominences, and erythema marginatum, a distinctive skin rash characteristic of rheumatic fever, often involving the trunk and extremities
  • C entral nervous system involvement, including Sydenham chorea, characterized by involuntary, purposeless muscular movements, and bizarre grimaces, as well as emotional lability

 

Endocarditis (Disorders of Cardiovascular System)

A. Infective endocarditis

This bacterial, or sometimes fungal, infection of the endocardium is marked by prominent involvement of the valvular surfaces.

  • Characteristics include large, soft, friable, easily detached vegetations consisting of fibrin and intermeshed inflammatory cells and bacteria.
  • Complications may include ulceration, often with perforation, of the valve cusps or rupture of one of the chordae tendineae.

Classification

  1. A cute endocarditis is caused by pathogens, such as Staphylococcus aureus (50% of cases). This type of endocarditis is often secondary to infection occurring elsewhere in the body.
  2. Subacute (bacterial) endocarditis is caused by less virulent organisms, such as Streptococcus viridans (more than 50% of cases). This type of endocarditis tends to occur in patients with congenital heart disease or preexisting valvular heart disease, often of rheumatic origin.

Clinical features

a. Valvular involvement

  • The mitral valve is most frequently involved.
  • The mitral valve along with the aortic valve is involved in about 40% of cases.
  • The tricuspid valve is involved in more than 50% of cases of endocarditis of intravenous drug users, in whom endocarditis is most often caused by staphylococcal infection.

b. Complications

  • Distal embolization occurs when vegetations fragment.
  • Embolization can occur almost anywhere in the body and can result in septic infarcts in the brain or in other organs.
  • The renal glomeruli may be the site of focal glomerulonephritis (focal necrotizing glomerulitis) caused by immune complex disease or by septic emboli.

B. Non-bacterial thrombotic endocarditis

  • This form of endocarditis is associated with debilitating disorders, such as metastatic cancer and other wasting conditions.
  • Characteristics include small, sterile fibrin deposits randomly arranged along the line of closure of the valve leaflets.
  • The disease can result in peripheral embolization but, unlike infective endocarditis, the emboli are sterile.

C. Libman-Sacks endocarditis

  • Libman-Sacks endocarditis occurs in systemic lupus erythematosus (SLE). It is characterized by small vegetations on either or both surfaces of the valve leaflets.

D. Endocarditis of the carcinoid syndrome

  • The cause is secretory products of carcinoid tumors (vasoactive peptides and amines, especially serotonin [5-hydroxytryptamine]).
  • The valves on the left side of the heart are rarely involved, because serotonin and other carcinoid secretory products are detoxified in the lung.
  • This form of endocarditis results in thickened endocardial plaques characteristically involving the mural endocardium or the valvular cusps of the right side of the heart.

Valvular Heart Disease (Disorders of Cardiovascular System)

  • Valvular heart disease occurs often as a late result of rheumatic fever. It may be secondary to various other inflammatory processes.
  • This disease may be congenital.
  • In addition, valvular heart disease can occur even with prosthetic cardiac valves, which are subject to physical deterioration or can be the site of thrombus formation or infectious endocarditis. They can also cause mechanical disruption of red blood cells, resulting in hemolytic anemia with schistocyte formation.

a. Mitral valve (Disorders of Cardiovascular System)

  • Prolapse is the most frequent valvular lesion and is common in young women (Figure 10-3). It is also common in patients with Marfan syndrome.
    • Characteristics include myxoid degeneration of the ground substance of the valve.
    • Results include stretching of the posterior mitral valve leaflet, producing a “floppy” cusp (parachute deformity) with prolapse into the atrium during systole. These changes produce a characteristic systolic murmur with a midsystolic click.
    • The lesion is usually benign and asymptomatic but can result in mitral insufficiency. It is often associated with a variety of arrhythmias and predisposes to infective endocarditis.
  • Stenosis is almost always due to rheumatic heart disease.
  • Insufficiency is usually a result of rheumatic heart disease. It can also result from mitral valve prolapse, infective endocarditis, or damage to a papillary muscle from myocardial infarction. It can be secondary to left ventricular dilation, with stretching of the mitral valve ring.

b. Aortic valve (Disorders of Cardiovascular System)

This valve, along with the mitral valve, is frequently involved in rheumatic heart disease and in infective endocarditis.

  • Stenosis often presents as calcific aortic stenosis caused by calcification of:
    • An otherwise normal aortic valve as an age-related degenerative change. This condition, called degenerative calcific aortic stenosis, is the most common cause of calcific aortic stenosis in persons older than 60 years of age. This designation is used when the stenotic valve has three cusps.
    • A congenital bicuspid aortic valve. These patients present with calcific stenosis one to two decades before patients with anatomically normal valves.
    • A valve affected by rheumatic heart disease. In this case, scarring may be evidenced by fusion of the valve commissures.
  • Insufficiency can be caused by:
    • Nondissecting aortic aneurysm resulting from cystic medial necrosis
    • Rheumatic heart disease, usually in association with mitral valve disease
    • Syphilitic (luetic) aortitis (now rare) with dilation of the aortic valve ring

c. Tricuspid valve (Disorders of Cardiovascular System)

  • This valve is rarely involved alone in rheumatic heart disease but may be involved together with the mitral and aortic valves. This trivalvular involvement accounts for approximately 5% of cases of rheumatic heart disease. The tricuspid valve may be involved in the carcinoid syndrome.

d. Pulmonary valve (Disorders of Cardiovascular System)

  • This valve is most commonly affected by congenital malformations, occurring either alone or along with other congenital defects, such as in the tetralogy of Fallot. It is rarely involved in rheumatic heart disease, although it may be involved in the carcinoid syndrome.

 

Congenital Heart Disease (Disorders of Cardiovascular System)

Causes and associations

  • The etiology is usually undetermined.
  • Chromosomal abnormalities, such as Down syndrome, some of the other trisomies, and Turner syndrome, are often complicated by congenital heart disease.
    • The association of Turner syndrome with coarctation of the aorta is notable.
    • Endocardial cushion defects, which result in atrial and ventricular septal defects and atrioventricular valve deformities, are frequently associated with Down syndrome (trisomy 21).
  • There is an apparent increase in the incidence of patent ductus arteriosus in patients living at high altitudes, suggesting an association with fetal oxygen deprivation.

Rubella (German measles) infection is a prominent cause of congenital heart disease:

  • There is strong evidence of a link between maternal rubella during the first trimester of pregnancy and a constellation of fetal defects, known as the congenital rubella syndrome, which includes cardiovascular defects, microcephaly with mental retardation, deafness, cataracts, and growth retardation.
  • Cardiac malformations are especially frequent and commonly include patent ductus arteriosus, aortic stenosis, ventricular septal defect, and pulmonary infundibular or valvular stenosis, sometimes occurring as part of the tetralogy of Fallot.
  • Before or during pregnancy, it is often important to determine the mother’s immune status to rubella. Demonstration of antirubella antibodies of the IgM class indicates recent primary infection, whereas demonstration of IgG antibodies indicates either recent primary infection, past infection, or reinfection.

Functional abnormalities of congenital heart disease.

These can be classified according to the presence or absence of cyanosis.

  1. Noncyanotic diseases include those with no shunt (e.g., aortic stenosis, coarctation of the aorta) and those with a left-to-right shunt (e.g., patent ductus arteriosus, atrial or ventricular septal defect). In atrial septal defects, both pressure and oxygen saturation may be equalized between the two atria.
  2. Cyanotic diseases include transposition of the great vessels (survival depends on the presence of a shunt between the left and right ventricles), malformations with a rightto- left shunt (e.g., the tetralogy of Fallot), and disorders in which a left-to-right shunt reverses to right-to-left because of increased pulmonary arterial pressure (e.g., late cyanosis, tardive cyanosis).

 

Diseases of the Myocardium (Disorders of Cardiovascular System)

Cardiomyopathy

This term refers to diseases of the heart muscle that are noninflammatory and are not associated with hypertension, congenital heart disease, valvular disease, or coronary artery disease. Usually, these diseases are characterized by otherwise unexplained ventricular dysfunction (heart failure unresponsive to digitalis, ventricular enlargement, ventricular arrhythmias). It occurs in several forms:

a. Congestive or dilated cardiomyopathy is the most common form of cardiomyopathy.

  • Characteristics include four-chamber hypertrophy and dilation and both rightand left-sided intractable heart failure.
  • Etiology is most often unknown. In some cases, dilated cardiomyopathy is related to alcoholism (alcohol cardiomyopathy), thiamine deficiency (beriberi heart), or prior myocarditis. Some forms are associated with mutant cytoskeletal proteins, such as dystrophin or desmin; mutations of sarcomeric proteins, such as cardiac myosin heavy chain; and other muscle proteins, such as actin. Mutations in mitochondrial genes have also been implicated.
  • A multi-etiologic variant of dilated cardiomyopathy, known as peripartum cardiomyopathy, is associated with the latter stages of pregnancy and the period extending from weeks to months postpartum.

b. Restrictive cardiomyopathy

  • The cause is infiltrative processes within the myocardium that result in stiffening of the heart muscle, which interferes with pumping action.
  • This cardiomyopathy is exemplified by cardiac amyloidosis, which may result in both right- and left-sided heart failure.

c. Hypertrophic cardiomyopathy

It’s often inherited as an autosomal dominant characteristic. Thus far, several genes have been implicated in the genesis of this disorder: genes coding for β-myosin heavy chain (most common mutation, thus far), cardiac troponins T and I, α-tropomyosin, myosin-binding protein C, and myosin light chain .

  • Gross characteristics include hypertrophy of all chamber walls, especially the ventricular septum (asymmetric septal hypertrophy).
  • Microscopic characteristics include disoriented, tangled, and hypertrophied myocardial fibers.
  • The cardiomyopathy may result in left ventricular outflow obstruction, placing the patient in danger of syncope and even sudden death, which often occurs unexpectedly in young athletes.

d. Arrhythmogenic right ventricular cardiomyopathy

It’s a rare disorder characterized by gradual replacement of right ventricular muscle by fat, by arrhythmias, and sometimes by sudden death in athletes.

 

Myocarditis

  • This myocardial disease most often presents as biventricular heart failure in young persons who do not have valvular, rheumatic, or congenital heart disease.
  • Morphologic characteristics include diffuse myocardial degeneration and necrosis with an inflammatory infiltrate.
  • Myocarditis is most often viral, and coxsackievirus is frequently the cause.
  • In parts of South America, myocarditis may be a component of Chagas disease, which is caused by the protozoan Trypanosoma cruzi.

Diseases of the Pericardium (Disorders of Cardiovascular System)

a. Noninflammatory conditions

  • Hydropericardium is an accumulation of serous transudate in the pericardial space. It may result from any condition causing systemic edema. It is most often caused by congestive heart failure or by edematous conditions due to hypoproteinemia, such as the nephrotic syndrome or chronic liver disease.
  • Hemopericardium is an accumulation of blood in the pericardial sac. It is usually caused by traumatic perforation of the heart or aorta or by myocardial rupture associated with acute myocardial infarction.

b. Acute pericarditis

  • Serous pericarditis is associated with SLE, rheumatic fever, and a variety of viral infections. It is characterized by production of a clear, straw-colored, protein-rich exudate containing small numbers of inflammatory cells.
  • Fibrinous or serofibrinous pericarditis is characterized by a fibrin-rich exudate. It may be caused by uremia, myocardial infarction, or acute rheumatic fever.
  • Purulent or suppurative pericarditis is characterized by a grossly cloudy or frankly purulent inflammatory exudate. It is almost always caused by bacterial infection.
  • Hemorrhagic pericarditis is characterized by a bloody inflammatory exudate. It usually results from tumor invasion of the pericardium, but can also result from tuberculosis or other bacterial infection.

c. Chronic (constrictive) pericarditis

This disease is usually of tuberculous or pyogenic staphylococcal etiology.

  • Characteristics include thickening and scarring of the pericardium with resultant loss of elasticity. This prevents the pericardium from stretching and thus interferes with cardiac action and venous return, often mimicking the signs and symptoms of right-sided heart failure.
  • Proliferation of fibrous tissue with occasional small foci of calcification is marked.

 

Congestive Heart Failures (Disorders of Cardiovascular System)

Congestive heart failure may be failure of the left ventricle, right ventricle, or both. This condition often presents with dyspnea and/or edema. Assay of B-type natriuretic peptide (BNP), which is elevated in heart failure, can aid in the distinction of heart failure from a number of other conditions such as asthma, acute coronary syndrome, chronic obstructive pulmonary disease, or pulmonary embolism, which can also present with dyspnea or edema.

Left-sided heart failure

Causes

  • Ischemic heart disease, especially myocardial infarction
  • Hypertension
  • Aortic and mitral valvular disease
  • Myocardial diseases, such as cardiomyopathies and myocarditis

Clinical manifestations

  • Dyspnea and orthopnea caused by pulmonary congestion and edema regularly occurs
  • Pleural effusion with hydrothorax often results.
  • Reduction in renal perfusion, causing activation of the renin-angiotensin-aldosterone system and leading to retention of salt and water, is less frequent.
  • Cerebral anoxia is less frequent.

 

Right-sided heart failure

Causes

  • Left-sided heart failure is the most common cause of right-sided heart failure.
  • Left-sided lesions, such as mitral stenosis
  • Pulmonary hypertension often caused by chronic lung disease (cor pulmonale)
  • Various types of cardiomyopathy and diffuse myocarditis
  • Tricuspid or pulmonary valvular disease

Clinical manifestations

  • Renal hypoxia, leading to greater fluid retention and peripheral edema than seen in left-sided failure. Edema occurs first in dependent areas and often manifests early as so-called pitting edema of the ankles. Other manifestations of fluid retention include pleural effusion and sometimes ascites. Hydrothorax can be a manifestation of either left-sided or right-sided heart failure.
  • Enlarged and congested liver and spleen. Chronic passive congestion of the centrilobular veins of the liver surrounded by relatively pale, sometimes fatty, peripheral regions leads to a “nutmeg” pattern.
  • Distention of the neck veins