Download Rheumatic Fever and Heart Disease

Pathology of Cardiovascular
System
Lectures 1 - 2
Valvular Diseases; Rheumatic Heart
Disease, Endocarditis & Myocarditis
Dr. Samir Al Bashir, MD.
Valve Diseases
• Manifested by:
- Stenosis:- failure of the valve to open
completely, obstructing forward blood flow.
- Insufficiency:- failure of the valve to
close completely so allowing Regurgitation
(reverse flow).
• The disorder can be: a. pure b. mixed
• The disorder can be: a. isolated b.
combined.
• Valve abnormalities produce abnormal heart
sounds called murmers.
• Valve abnormalities can be :•
- Congenital or – acquired.
• The most common abnormalities are acquired
stenosis of the mitral and aortic valves.
• The stenosis is almost always due to primary cusp
abnormality and is always a chronic process.
• The regurgitation is either due to cusp
abnormality or disease of the supporting
structures like papillary muscles or the chordae
tendinae and can be acute or chronic.
Acute Rheumatic Fever
• Definition: Rheumatic fever is an acute,
immunologically
mediated,
multi-system
inflammatory disease - follows an episode of
group A beta-hemolytic streptococcal pharyngitis
after an interval of a few weeks.
– Epidemiological studies and patient history
– Serological studies: elevated levels of
antibodies
to
streptococcal
enzymes
(streptolysin O and DNAse B).
Acute Rheumatic Fever
• Occurs in only 3% of patients with group A
streptococcal pharyngitis.
• Peak incidence: ages of 5-15 years.
• Incidence declined over the past 30 years
• Heart during acute phase  acute rheumatic
carditis  after many years may cause chronic
valvular deformities.
• It also affects large joints causing Arthritis.
Rheumatic Fever Diagnosis
–
–
–
–
–
–
–
Evidence of recent infection + 2 or more Jones criteria:
Migratory large joint polyarthritis
Pancarditis
Subcutaneous nodules
Erythema marginatum of skin
Sydenham’s chorea
Fever, arthralgias, ECG changes, raised CRP etc…
6
Acute Rheumatic Fever
Pathogenesis
• It is a hypersensitivity reaction induced by group A
streptococci.
• Antibodies directed against the M proteins of group A
streptococci cross-react with normal proteins in the
tissues, leading to tissue damage.
• Alternatively, rheumatic fever may result from an
immune response against the offending bacteria.
Acute Rheumatic Fever
Pathology
• Inflam. infiltrates in many tissues: synovium, joints,
skin, and heart.
• Focal fibrinoid necrosis provokes inflam. response
• Fibrosis is common especially in cardiac tissues.
• Blood cultures are sterile.
Acute Rheumatic Carditis (Pancarditis)
inflam. changes in all layers of the heart
Myocardium
• Scattered multiple foci of inflammation “Aschoff
Bodies” lie proximate to small vessels.
– Consisting of central fibrinoid necrosis surrounded by
lymphocytes, and large macrophages (basophilic
cytoplasm and vesicular nuclei) known as Anitschkow
cells, which may become multinucleated forming
Aschoff giant cells (cardiac histiocytes).
• Diffuse interstitial inflammatory infiltrates
• Acute changes may resolve completely or progress to
scarring and chronic valvular deformities.
Acute Rheumatic Carditis (Pancarditis)
Endocardium
• Common, may affect any valve, mostly mitral and aortic
valves.
• Valves are edematous and thickened with foci of
fibrinoid necrosis. (Aschoff nodules uncommon).
• Formation of small vegetations “fibrinous clots” along
the lines of valve closure (Verrucous Endocarditis).
Pericardium
• Fibrinous pericarditis, sometime associated with serous
or serosanguinous pericardial effusion.
Acute Rheumatic Carditis (Pancarditis):
Clinical Manifestations
• Symptoms:
– Pericardial friction rubs,
– Weak heart sounds,
– Tachycardia (rapid beating) and
– Arrhythmias.
• In severe cases: myocarditis  cardiac dilation 
functional mitral valve insufficiency or even
congestive heart failure.
Acute Rheumatic Heart Disease
Pathogenesis and Key Morphologic Changes
Small vegetations (verrucae) are visible along the line of
closure of the mitral valve leaflet.
Verrucous Endocarditis
in Acute Rheumatic Fever
Aschoff Body in Acute Rheumatic Carditis
Aschoff Body with “Caterpillar” Nuclei
Fibrinous Pericarditis
in Acute Rheumatic Fever
Chronic Rheumatic Heart Disease
• Characterized by irreversible deformity of one or more
cardiac valves. Usually mitral valve is abnormal (alone
in 70% of cases).
• Combined aortic and mitral valve disease is present in
another 25% of cases. Aortic valve alone is rarely
affected.
• Tricuspid and Pulmonic valves are extremely rare to be
affected.
Pathological changes:
• Chronic scarring and calcification of the valve leaflets,
→ stiff and thickened structure → stenotic valve orifice
and improper closure (regurgitation).
• Shortening, thickening and fusion of the chordae
tendineae.
Chronic Rheumatic mitral valvulitis
• The most common cause of mitral stenosis, it causes
stenosis > regurgitation. Females > males.
Mitral Stenosis:
• Leaflets are thick, rigid, and inter-adherent. And the
orifice is narrowed “fish mouth” deformity.
• Dilatation and hypertrophy of left atrium.
• Endocardium is thickened above posterior mitral leaflet .
Mitral Regurgitation:
• Valve leaflets are retracted.
• Left ventricular dilation and hypertrophy (added volume
load)
Mitral valve, rheumatic mitral stenosis - diffuse fibrous
thickening & distortion of valve leaflets, commissural
fusion (arrow) "fish mouth" shape.
Chronic Aortic Valvulitis
Males > females and usually associated with mitral
valvulitis.
May occur in congenital bicuspid aortic valve (2%)
Aortic stenosis:
• Valve cusps are thickened, firm and adherent to each
other  the aortic valve orifice is reduced to a rigid
triangular channel.
• Aortic stenosis increases the pressure load on left
ventricle causing hypertrophy.
• Subsequent left ventricular failure is associated with
dilation of the chamber.
Surgically removed specimen of rheumatic aortic stenosis
demonstrating thickening and distortion of the cusps with
commissural fusion (rigid triangular channel)
Calcific Aortic Stenosis
(degenerative calcific aortic stenosis)
• Degenerative changes in the cardiac valves are part of
normal aging process, but it can develop into pathologic
stenosis.
• Leaflets are rigid and deformed by fibrosis and calcified
masses, leading to valve sclerosis.
• It differs from rheumatic aortic stenosis by:
– The calcium deposits lie behind the valve cusps.
– The free edges of the cusps are usually not affected.
– Calcific stenosis does not fuse the cusps.
• Symptom: severe cases may cause angina, syncope
(fainting), congestive heart failure, L.V. hypertrophy,
and sudden death due to arrhythmia.
Degenerative calcific aortic stenosis of a normal valve
having three cusps. Nodular masses of calcium are heaped
up within the sinuses of Valsalva (arrow). The commissures
are not fused.
Mitral Valve Prolapse
• Primary form of myxomatous degeneration of mitral
valve
• Common cardiac disorder (up to 3% of adult
population).
• It is usually an isolated problem but it may arise as a
complication of certain connective tissue disorders (e.g.
Marfan’s syndrome).
• Most patients are asymptomatic, some have palpitations
and fatigue, or atypical chest pain, and mid-systolic
click with a late systolic murmur.
Mitral Valve Prolapse
• The valve leaflets (posterior cusp) are soft and enlarged
→ balloon intruding into left atrium during systole.
• Chordae tendineae are elongated, fragile and may
rupture in severe cases.
Microscopic examination
• Excessive amounts of loose, edematous, faintly
basophilic tissue within the middle layer of the valve
leaflets (spongiosa) and chordae.
Complications
• Mitral regurgitation and congestive heart failure.
• Sudden death caused by ventricular arrhythmias.
• Infective endocarditis.
Left ventricle demonstrates ballooning with prolapse of the
posterior mitral leaflet into the left atrium.
Infective Endocarditis (IE)
•
•
Infection of the cardiac valves or the endocardium,
which results in the formation of vegetation on valve
(s), mostly aortic and mitral valves.
Infective Endocarditis is divided into two forms:
• Acute Infective Endocarditis
• Subacute Infective Endocarditis
Infective Endocarditis
Organism
Valve
Response
Progression
Resolution
Acute
Subacute
High virulence
(staphylococcus
aureus)
Normal and
deformed
Necrosis and
ulceration
Rapid and
destructive
Death (50%)
Low virulence
(α hemolytic
streptococcus)
Deformed
Local inflammatory
reaction
Slow and less
destructive
Recovery (antibiotic)
Acute infective endocarditis - serious destruction in the
aortic valve.
Irregular reddish tan vegetations overlie valve cusps that
are being destroyed.
Endocarditis of the mitral valve
(subacute, caused by streptococcus viridans)
IE.: Etiology, Pathogenesis
Bacteremia: Causative Organisms
• -Hemolytic streptococci (viridans) attacks deformed
valves (50-60%).
• Staphylococcus aureus attacks healthy or deformed
valves (intravenous drug abusers) (10-20%).
• Coagulase-negative staphylococci
attacks prosthetic valve.
(S.
epidermidis)
IE.: Etiology, Pathogenesis
High risk group
• Obvious hematogenous infection as with:
– Cardiac abnormalities: as chronic valvular diseases
and high pressure shunts within the heart (small
ventricular septal defects).
– Intravenous drug abusers (right side of the heart).
– Prosthetic heart valves.
– Previous dental, surgical or interventional procedure
(e.g. urinary catheterization).
• Occult source of bacteremia
– small injuries to skin or mucosal surfaces such as
brushing the teeth.
IE.: Pathology
Acute Endocarditis
Gross:
• Vegetations may obstruct valve orifice and cause rupture
of the leaflets, cordae tendineae, or papillary muscles.
• Vegetations may erode into myocardium to produce
abscess in perivalvular tissue (ring abscess).
• Friable vegetations may become systemic emboli 
infarcts (brain, kidneys, myocardium) and abscesses.
Micro: vegetations consist of large number of organisms,
fibrin and blood cells.
IE.: Pathology
Subacute Endocarditis:
Gross: vegetations are firmer and less destructive (ring
abscess uncommon).
– Systemic emboli may develop and cause infarcts,
without abscesses.
Micro: granulation tissue is seen at the base of the
vegetations.
– Later:
fibrosis,
calcifications
and
chronic
inflammatory infiltrates.
IE.: Clinical
• Onset: gradual or explosive (organisms).
– Organism of low virulence cause low-grade fever,
malaise, weight loss, and flulike syndrome .
– Organism of high virulence cause high fever, shaking
chills, and weakness.
• Cardiac murmurs.
• Blood culture is important (only minority of cases remain
negative).
IE.: Complications
• Regurgitation leading to congestive heart failure.
• Myocardial abscess (ring abscess).
• Extension of infection to the root of aorta (mycotic
aneurysm).
• Systemic emboli, also pulmonary emboli in right-sided
endocarditis.
• Enlargement of spleen, and clubbing of digits
(particularly in subacute cases).
• Petechiae, nail-bed splinter hemorrhage.
• Renal
complications
(glomerulonephritis
and
Infarction)
Bacterial Endocarditis Remote Embolic Effects
Nonbacterial Thrombotic Endocarditis
(NBTE)
Marantic Endocarditis
• Characterized by small sterile vegetations (less than 5
mm), on the valve leaflets along the line of closure.
• Vegetations contain fibrin, platelets and other blood
components.
• The valve leaflets are normal, no inflammation or
fibrosis
• Mitral valve is the most common site, followed by aortic
valve
• Hypercoagulable state are the usual precursor to NBTE
Chronic DIC, hyperestrogenic states, malignancy
(mucinous adenocarcinoma).
Nonbacterial Thrombotic Endocarditis (NBTE).
Nearly complete row of thrombotic vegetations along the
line of closure of the mitral valve leaflets.
Libman-Sacks Endocarditis (LSE)
• Small sterile vegetations on ventricular or both
surfaces of mitral & tricuspid valves in some patients
with Systemic Lupus Erythematosus.
RHD: row of small vegetations along the lines of closure of
the valve leaflets.
IE: large, irregular masses on the valve cusps that extend
onto the cords.
NBTE: small, bland vegetations, usually attached at the
line of closure.
LSE: has small or medium-sized vegetations on either or
both sides of the valve leaflets.
Myocardial Diseases
A group of diseases intrinsic to myocardial fibers,
including mainly:
• Myocarditis
• Cardiomyopathies: primary non-infectious
abnormalities in the myocardium.
Myocarditis
• A group of Inflammatory conditions of the myocardium
that result in injury to cardiac myocytes.
• The heart is dilated, and the myocardium is flabby and
pale, contains small areas of hemorrhage.
• Clinical features range from an asymptomatic state to
severe congestive heart failure at late stage.
– Lethal ventricular arrhythmias accounts for most
sudden cardiac deaths.
Myocarditis: Major Causes
Infections
• Viruses: the most common cause in USA (e.g.,
coxsackievirus A and B, HIV and echoviruses).
• Chlamydia (e.g., C. psittaci)
• Rickettsia (e.g., R. typhi [typhus fever])
• Bacteria:
– Corynebacterium [diphtheria],
– Neisseria [meningococcus],
– Borrelia [Lyme disease]
• Fungi (e.g., Candida)
• Protozoa (e.g., Trypanosoma cruzi [Chagas disease], the
most common cause in South America)
• Helminths (e.g., trichinosis)
Myocarditis: Major Causes
Immune-Mediated Reactions
• Postviral
• Poststreptococcal (rheumatic fever)
• Systemic lupus erythematosus
• Drug hypersensitivity (e.g., methyldopa, sulfonamides)
• Transplant rejection
Unknown : Sarcoidosis, and Giant cell myocarditis
Myocarditis: Microscopically
• Viruses: edema, inflammatory infiltrate dominated by
lymphocytes, and myocyte degeneration and necrosis.
– Chronic cases: ventricular dilation, inflammation is
less obvious, myocardial fibrosis becomes more
prominent
• Parasites: the organism is demonstrable histologically,
(Chagas disease, trypanosomes directly infect cardiac
muscle fibers).
• Bacteria: neutrophilic infiltrate, and abscess.
• Cardiac transplant rejection: interstitial lymphocytes
and myocyte degeneration.
• Giant cell myocarditis is characterized by an
inflammatory infiltrate in which multinucleated giant
cells are prominent.
Lymphocytic Myocarditis: Dense mononuclear
inflammatory cell infiltrate.
Hypersensitivity Myocarditis
Giant cell myocarditis
Myocarditis caused by Trypanosoma cruzi (Chagas
disease). Intracellular organisms inside a myocyte