General Pathology 601 for Dental Students

Rheumatic Fever and Rheumatic Heart Disease, Valvular Disease,
and Congenital Heart Disease

 

Dr. Grimes Margaret M Grimes, MD
Surgical Pathology
Sanger Hall, 5th Floor
(804) 828-9739
mmgrimes@vcu.edu

 

 

Rheumatic Fever and Rheumatic Heart Disease

Objectives
Upon completion of this section of the lecture you will be able to:

  1. Define rheumatic fever.
  2. Briefly describe the incidence, etiology, pathogenesis, and clinical manifestations of rheumatic fever.
  3. Recognize the most important long-term sequelae of rheumatic fever and the clinicopathologic correlations.

Important Terms in Rheumatic Heart Disease
Group A beta-hemolytic streptococcal infection
Pharyngitis
Pancarditis
Aschoff body/cells
Anitschkow's cells
Mitral Stenosis

Rheumatic fever is a post-streptococcal nonsuppurative inflammatory disease with cardiac and extracardiac manifestations.

Incidence
Although once common worldwide, the incidence has been decreasing for many years especially in the U.S. This may be due to the effect of antibiotics, improved socioeconomic conditions and possibly a change in the virulence of the streptococcus. Although acute rheumatic fever has decreased in incidence, the long-term effects on the valves still constitute a cause of chronic valve disease today.

Etiology
Rheumatic fever follows a Group A beta-hemolytic streptococcal infection, usually pharyngitis. The evidence for this association, even though blood cultures of patients with rheumatic fever are sterile, include:

  • epidemiology: outbreaks of streptococcal pharyngitis are followed by cases of rheumatic fever.
  • patient history: recurrent attacks and exacerbations of rheumatic fever follow streptococcal infections.
  • serology: patients typically have elevated levels of anti-streptococcal antibodies.

Pathogenesis
Presumed due to cross-reaction of antibodies to streptococcal antigens with host cardiac and extracardiac antigens, leading to tissue damage. Alternatively it has been proposed that there is induction of hypersensitivity or autoimmunity by Streptococcal products.

Clinical manifestations
Extracardiac: fever, arthritis, arthralgia, skin lesions, chorea
Cardiac: pancarditis (inflammation of endocardium, myocardium and pericardium)

Cardiac Pathology
The characteristic lesion of acute rheumatic fever is the Aschoff body, consisting of a focus of necrosis (representing the site of antibody-antigen reaction) surrounded by activated histiocytes and lymphocytes. The histiocytes may be mononuclear or multinuclear, and are referred to as Anitschkow's or Aschoff cells. These foci may be found in the pericardium, the myocardium, or in the valves. They ultimately "heal" by fibrosis. Valvular involvement in acute rheumatic fever includes aggregation of fibrin and platelets forming small (1-3 mm) vegetations sometimes called "verrucae" along the lines of closure of the valve leaflets.

Clinically, involvement of the heart in acute rheumatic fever may result in chamber dilatation and conduction abnormalities.

Chronic cardiac manifestations include fibrocalcific valvulitis (scarring and calcification of the leaflets) with shortening and fusion of the chordae tendineae. Chronic scarring of the valves constitutes the most important long-term sequela of rheumatic fever, and usually becomes clinically manifest decades after the acute process.

The scarring of the valve leaflets converts a translucent, pliable valve into a stiff, thickened structure. The orifice becomes stenotic (narrowed). The distortion and fixation of the valve orifice has been likened to a "fishmouth" or "buttonhole". Occasionally shrinkage of valve leaflets causes mitral insufficiency.

The distribution of valve involvement is variable:

  • mitral alone: about 50% of cases
  • combined mitral/aortic: about 45%
  • combined tricuspid and mitral or aortic: about 5-10%
  • pulmonic: very rare

Clinical correlations
Mitral stenosis may result in left atrial enlargement, elevated pulmonary vascular pressure, atrial fibrillation and atrial thrombosis with the danger of embolization. Aortic stenosis leads to left ventricular hypertrophy.

The consequences of mitral insufficiency vary depending on the severity of the regurgitation. In some cases it leads to dilatation and hypertrophy of the left ventricle, and dilatation of the left atrium. Aortic insufficiency leads to left ventricular dilatation.

Patients with chronic rheumatic valvular disease may have severe valvular compromise, and are predisposed to the complications of infectious endocarditis and thromboemboli. They may require long-term antibiotic therapy or valve surgery.

Valvular Disease--Endocarditis, Degenerative Calcific Aortic Valve Stenosis, 
and Mitral Valve Prolapse ("Floppy Mitral Valve")

Objectives
Upon completion of this lecture you will be able to:

  1. Define infective endocarditis.
  2. Contrast the pathology and prognosis of acute and subacute forms of infective endocarditis.
  3. Identify 8 important risk factors of infective endocarditis.
  4. Recognize clinical manifestations and complications of infective endocarditis.

Important Terms in Valvular Disease
Endocarditis
Transient bacteremia

Endocarditis: Infective and Nonbacterial Thrombotic

Infective Endocarditis (Bacterial Endocarditis)
This is an acute or subacute inflammatory disease leading to the accumulation of infected thrombotic material ("vegetations") on valves or adjacent endocardium.

The acute form is usually a rapidly progressive process (days to weeks), due to a highly virulent organism, affecting a previously normal valve, and carrying a poor prognosis.

The subacute form is more indolent (weeks to months), is caused by an organism of low virulence, and usually affects an abnormal valve.

Etiology:

Acute: Staph. aureus 50%
  Streptococci 35%
  other, including fungi 15%
   
Subacute: Strep. viridans 50%
  other Streptococci 15%
  Gram negative bacilli 10%
  other, including fungi 25%

Predisposing factors
Damaged or congenitally abnormal valves, or valve prostheses. Normal valves can also be affected (especially in the acute form).

Important predisposing conditions include:

  1. valves damaged by rheumatic carditis
  2. mitral valve prolapse
  3. congenital cardiac abnormalities
  4. atherosclerotic valve disease
  5. previous cardiac surgery
  6. prosthetic valves
  7. intravenous drug addiction
  8. immunosuppression or immunodeficiency.

Pathogenesis
The classic initiating event is transient bacteremia of S. viridans following dental or oral procedures. Abnormal valves may be prone to the development of sterile thrombi on the endocardial surface. With bacteremia, the thrombus may be colonized, and a fibrinous, bacteria-laden vegetation accumulates on the valve because of altered dynamics of blood flow (less commonly on the endocardium at a congenital septal defect). Any situation in which bacteremia or fungemia occurs may be complicated by the development of endocarditis (e.g. intravenous drug abuse, indwelling catheters, systemic infections, etc.).

Any valve may be affected, but mitral and/or aortic lesions comprise 75% of the cases. In intravenous drug addicts, the incidence of right-sided lesions is increased.

Clinical Manifestations

  • fever
  • petechiae, splinter hemorrhages
  • cardiac murmur (may vary with enlargement or disintegration of the vegetation, or with cusp perforation)
  • positive blood culture

Pathology
Large, friable, infected vegetations composed of fibrin, platelets, and the infecting organisms. In general, the vegetations of acute endocarditis are bulkier than those of the subacute form.

The gross vegetations may break off to form emboli which, being infected, cause septic infarcts. Erosion or perforation of valve cusps or chordae may cause rapid cardiac decompensation.

Complications

  • embolization (and infarcts)
  • perforation of valve cusps
  • rupture of chordae
  • sepsis
  • arrhythmia
  • dehiscence of prosthetic valve
  • valve ring or myocardial abscess
  • deposition of circulating immune complexes in the kidney may result in diffuse glomerulonephritis.

Degenerative Calcific Aortic Valve Stenosis

This pathologic change is generally considered to be a "wear and tear" lesion affecting previously normal aortic valves in elderly individuals, or congenitally abnormal (unicuspid or bicuspid) valves.

Pathology
Nodular dystrophic calcific deposits are present, usually most pronounced at the bases of the cusps, and extending into the sinuses of Valsalva. The free edges of the cusps are usually not affected. The calcification prevents normal opening of the cusps.

Clinical Correlation
Symptomatology varies with the severity of narrowing. Severe cases may include syncope, chest pain, heart failure, and increased mortality. As with other valve abnormalities, there is risk of superimposed infective endocarditis.

Mitral Valve Prolapse ("Floppy Mitral Valve")

This is a congenital condition involving myxomatous degeneration of the mitral valve leaflets. Although most prolapsing valves still function effectively, some individuals (10-15% of cases) develop progressive regurgitation. 

Pathology
Characteristically there is "hooding" or ballooning of the valve leaflets on gross examination. The chordae are typically elongated, and may have abnormal insertions into the leaflets. The valve annulus is often dilated.

On microscopic examination, there is expansion of the spongiosa (the inner zone of the leaflet) by an accumulation of proteoglycans. Duplication of elastic fibers may be noted.

Complications
In some cases, patients develop ventricular or supraventricular arrhythmias. Sudden death occurs rarely, due to undetermined mechanisms. Rupture of chordae may result in "flail" leaflet. Calcification of the leaflet is observed in some cases. There is an increased risk for the development of infective endocarditis. Mitral prolapse is sometimes associated with aortic valve or tricuspid valve prolapse.

Congenital Heart Disease

Objectives
Upon completion of this lecture you will be able to:

  1. Discuss congenital heart disease classifications.
  2. Name the most common congenital heart defect in children.

Important Terms in Congenital Heart Disease
Ventricular Septal Defect (VSD)
Atrial Septal Defect (ASD)
Patent Ductus Arteriosus (PDA)
Tetralogy of Fallot 

By definition, congenital heart disease is present at birth. Congenital abnormalities of the heart and great vessels affect about 0.8% of live births. Although some forms result in intrauterine demise, probably most are live births. Some forms present clinically immediately after birth; others may not present until adulthood. Congenital heart disease may consist of a single morphologic abnormality (isolated), or multiple abnormalities (complex).

Etiology
The etiology is often obscure, but both genetic and environmental associations have been observed. Approximately 5% of congenital heart disease cases overall are associated with chromosomal abnormalities. For instance, congenital heart disease is a feature of trisomies 21, 18 and 13, and the incidence of congenital heart disease is increased in children of patients with congenital heart disease. There is an increased incidence of cardiac abnormalities associated with Rubella, thalidomide, alcohol and certain other exposures. Probably the greatest potential for developmental abnormality occurs upon exposure to environmental insults during the first six weeks of gestation.

Classification
Morphologic abnormalities in congenital heart disease are sometimes broadly classified as either shunts or obstructive lesions. Shunts consist of abnormal communications between chambers of the heart and/or great vessels. Obstructive lesions include stenosis or atresia of valves, or abnormal narrowing of a vessel, such as coarctation of the aorta.

Clinically, congenital heart disease may also be classified as cyanotic or acyanotic. In cyanotic disease, the systemic blood contains poorly oxygenated venous blood, either because of a right-to-left shunt across a septal defect or through a patent ductus arteriosus; or because there is inadequate blood flow through the lungs, as in pulmonic stenosis. In acyanotic disease, there is adequate or increased flow through the lungs, as in a left-to-right shunt.

Ventricular Septal Defect (VSD)
This is the most common form of congenital heart abnormality. It may occur as an isolated lesion or in combination with other abnormalities. These defects can range in size from probe-patent to several centimeters. The clinical signs and symptoms depend on the size of the lesion.

Small defects may close spontaneously, or be well-tolerated clinically since the size of the shunt is small. A small VSD is sometimes complicated by the development of infective endocarditis. This is because the jet stream of blood through the small shunt can damage the endothelium on the down-stream side of flow, leading to formation of small fibrin thrombi on the endocardial surface--a good site for colonization by bacteria in transient bacteremia.

Large defects may result in significant left-to-right shunts, increased pulmonary vascular resistance and right ventricular hypertrophy. There may then be reversal of the flow and cyanosis. 

Atrial Septal Defect (ASD)
There are three major types of ASD, classified by location. Size varies from small to large. Some cases are associated with other cardiac abnormalities.

Symptoms depend on the size of the defect. Large lesions may not present until adulthood. Left-to-right shunting leads to an increase in pulmonary blood flow. Some patients may develop inreased pulmonary vascular resistance and reversal of shunt. Paradoxic embolism may occur (embolization from the venous circulation to the systemic circulation across the septal defect).

Patent Ductus Arteriosus (PDA)
Most cases of PDA occur as isolated lesions. Normally the ductus closes functionally within the first 1-2 days of life (due to increased oxygen levels and changes in prostaglandin metabolism). The ductus may remain patent in premature infants with respiratory distress. PDA occurring in a full term infant may result from a structural abnormality. The length and diameter of the patent ductus is variable.

PDA is associated with a left-to-right shunt and therefore is initially acyanotic. The development of increased pulmonary vascular resistance may lead to reversal of flow and cyanosis.

Tetralogy of Fallot
This is an example of a complex form of congenital heart disease. It is characterized by:

  1. ventricular septal defect
  2. obstruction of right ventricular outflow tract ("subpulmonic stenosis")
  3. overriding aorta
  4. right ventricular hypertrophy.

This abnormality accounts for 15% of cases of congenital heart disease and is the most common form of cyanotic congenital heart disease. The direction of blood flow, and hence the severity of clinical symptoms, depends on the severity of the obstruction to right ventricular outflow. This obstruction morphologically may be due to a narrowing of the infundibulum (subpulmonic) or stenosis or atresia of the pulmonic valve. 


Digital Legends for Labs
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Lab 13 | Lab 14 | Lab 15 | Lab 15b | Lab 16 | Lab 16b | Lab 17 | Lab 18

 


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Updated September 5, 2007