Cardiovascular system pathology

1. Valvular Hear Disease
Valvular disease may resultin stenosis,insufficiency (regurgitation or incompetence), or both.
• Stenosis is the failureof a valveto open completely, obstructingforward flow.
• Insufficiency results from failureof a valve to close completely, thereby allowingregurgitation
(backflow) of blood.
Degenerative Valvedisease
Term used to describechanges that affect the integrity the valve ECM.
 Calcification- typically theaortic then the mitral valve.
 Alterations in ECM- increaseproteoglycan and diminished fibrillar collagen and elastin
(myxomatosis degeneration).
 Changes in the production of matrix metalloproteinaseor their inhibitors.
 Age
Calcific Aortic Stenosis
 Most common casuseof aortic stenosis
 Asympomatic
Morphology
 Hallmark is heaped-up calcified masses on te outflow sideof the cusps
 These protrude into the sinuses of valsalvaand mechanically impedevalve opening
 Commissural fusion notcommon but secodnary fibrosis and thinkeningo fthe cusp ma y occur

2. Myxomatous Mitral Valve
Morphology
Gross
 Myxomatous degeneration of the mitral valve
 one or both mitral valveleaflets arefloppy and prolapse
 Mitral valves balloon back into the left atriumduringsystole
 Women more than men
 Affected leaflets are enlarged,redundant, thick and rubbery
 The tendinous cords tend to be elongated thinned and occasionally rupture
Histology
 Thinningof the valvelayer know as tge fibrosa layer (structural integrity depends on that layer )
 Middlelayer the spongiosa is increased becauseof the deposition of myoxmatous material.
Rheumatic valve disease
The valvular disease principally takes the form of deforming fibrotic mitral stenosis; indeed
rheumatic heart disease is essentially the only cause of acquired mitral stenosis.
Morphology
Acute rheumatic fever
 characterized by discreteinflammatory foci within a variety of tissue(aschoff bodies)
 Aschoff bodies arepathognomonic for rheumatic fever
 Aschoff bodies composed of:
1. Collections of lymphocytes (primarily T cells),
2. Scattered plasma cells,
3. Plump activated macrophages called Anitschkow cells associated with zones of fibrinoid
necrosis.
 TheAnitschkow cells abundantcytoplasm,nuclei with chromatin that is centrally condensed into
a slender, wavy ribbon (so-called “caterpillar cells”).
 Duringacute rheumatic fever, Aschoff bodies can be found in any of the three layers of the
heart—pericardium,myocardium,or endocardium (includingvalves).
 Rheumatic fever is said to causepancarditis,with the followingsalientfeatures:
1. Pericardium may exhibita fibrinous exudate,which generally resolves without sequelae.
2. Myocardium-myocarditis—takes the form of scattered Aschoff bodies within the interstitial
connective tissue.
3. Valve -fibrinoid necrosisand fibrin deposition alongthelines of closure(Fig.11.19A) forming1-
to 2-mm vegetations—verrucae—that causelittledisturbancein cardiac function.
Chronic rheumatic
Gross
characterizedby
 Organization ofacute inflammation
 Subsequent scarring
 Aschoff bodies arereplaced by fibrous scar
 Valve cusps and leaflets becomes perminently thickened and retracted
 Clasically themitral valves exhitis:

3. 1. Leaflet thickening
2. commissural fusion
3. shortening, and thickeningand fusion of the chordaetendineae (Fig. 11.19C to E).
 Fibrous bridging across thevalvular commissuresand calcification createfish mouth or
buttonhole stenoses
Histology
Neovascularization (visibility evidentin and diffuse fibrosisthatobliterates the normal leaflet
architecture
N. B:The most important functional consequenceof rheumatic heart diseaseis valvularstenosisand
regurgitation.

4. Infective Endocarditis
Infective endocarditis (IE) is a microbial infection of the heart valves or the mural endocardiumthat
leads to the formation of vegetations composed of thrombotic debris and organisms,often associated
with destruction of the underlyingcardiac tissues
Two forms.
• Acute endocarditis refers to tumultuous, destructiveinfections,frequently involvinga highly
virulentorganismattackinga previously normal valve.Itis associated with of substantial morbidity
and mortality, even with appropriateantibiotic therapy and/or surgery.
• Subacute endocarditis refers to infections by organisms of lowvirulenceaffectinga previously
abnormal heart, especially scarred or deformed valves.The diseasetypically appearsinsidiously and—
even if untreated— follows a protracted courseof weeks to months; most patients recover after
appropriateantibiotic therapy.
Morphology
In both forms:
 Friable
 bulky,
 and potentially destructive vegetations containingfibrin,inflammatory cells,and
microorganisms arepresenton the heart valves (Figs.11.20 and 11.21).
N.B:The aortic and mitral valves arethe most common sites of infection, although the tricuspid valve
is a frequent target in the setting of intravenous drugabuse.
N. B: Most consistent sign of infective endocardits is fever.

5. Non infective endocarditis
Non bacterial ThromboticEndocarditis (NBTE)
Nonbacterial thromboticendocarditis(NBTE) is characterized by thedepositionof sterilethrombi on
cardiac valves,typically inthosewith anunderlyinghypercoagulablestate.
The vegetations in NBTEaretypically small (1 to 5 mmin diameter) andvalvular damageisnota
prerequisite.Indeed,theconditionusually occurson previously normal valves.Rather,hypercoagulable
states aretheusual precursorto NBTE; such conditionsincludechronicdisseminated intravascular
coagulation.

6. Endocarditis in Systemic Lupus Erythematosus: Libman-Sacks Endocarditis
Libman-Sacks endocarditisis characterized by the presence of sterile vegetations on the valves of
patients with systemic lupus erythematosus.
Cardiomyopathies
Cardiac diseases dueto intrinsic myocardial dysfunction aretermed cardiomyopathies (literally,
“heart musclediseases”);these can be primary—that is,principally confined to the myocardium—or
secondary presenting as the cardiacmanifestation of a systemic disorder.

7. However, three timehonored clinical,functional,and pathologic patterns arerecognized (Fig. 11.23
and Table 11.5):
• Dilated cardiomyopathy (DCM) (including arrhythmogenic right ventricular cardiomyopathy)
• Hypertrophic cardiomyopathy (HCM)
• Restrictive cardiomyopathy
Of the three major patterns, DCM is most common (90% of cases),and restrictivecardiomyopathy is
the least frequent.
Dilated Cardiomyopathy
DCM characterized by:
 Progressivecardiac dilation
 Contractile(systolic) dysfunction
 Usually with concurrenthypertrophy
Morphology
Gross
 Enlarged (up to two to three times the normal weight )
 Flabby

8.  With dilation in all chambers
 Because of the wall thinning thataccompanies the dilation ,the ventricular thickness may be
less than,equal or greater than normal .
 Mural thrombi can also be present
Histology
 Most myoctes exhibithypertrophy with enlarged nuclei
 Myoctes may also beattenuated,stretched and irregular.
 Variable interstitial and endocardial fibrosis fibrosis with scattered areas of replacement fibrosis.
 In DCM caused by iron overload itis marked by accumulation of intramyocardial hemosiderin by
prussian bluestain.
Causes
Most cases of Dilated Cardiomyopathy are idiopathic.
Some common causes includes:
 Genetics
 Infections and other toxic exposure
 Alcohol
 Iron overload
 Peripartumcardiomyopathy
DCM(Arrhythmogen Right ventricular cardiopulmonary)
Is an autosomal dominantdisorder classically manifestwith rightsided heart failureand rhythm
disturbances which can causesudden cardiacdeath.
Morphology
 The right ventricular wall is severely thinned owing to myocytes
 Replacement by fatty infiltration and lesser amounts of fibrosis.

9. Hypertrophic cardiomyopathy
HCM characterized by:
 Myochardial hypertrophy
 Defective diastolicfilling
 In 1/3 of the cases ventricular outflowobstruction

Morphology
Gross
 Marked by massivemyocardial hypertrophy without ventricular dilation
 Asymmetric septal hypertrophy - Disproportionatethickeningof the ventricular septumrelate to
the left ventricle free wall
 In 10% of cases concentric hypertrophy is seen
 On longitudinal section the ventricular cavity loses itround - ovoid shapeand acquirea banana
likeconfiguration.
 Mitrialvalveis affected
Histology
 Marked by myocyte hypertrophy, haphazard myocyte(and myofiber ) dissarry
 Interstitial fibrosis
N.B: HCM is an important causeof sudden cardiac death.In almost1/3 of cases of of sudden cardiac
death in athletes younger than 35 years of age the underlyingcauseis HCM

10. RestrictiveCardiomyopathy
RC is characterized by :
Primary decreasein ventricular compliance
Resultingin impaired ventricular fillingduringdiastole(simply putthe wall becomes stiffer).
Morphology
Gross
 The ventricles arenormal approximately normal sizeor slightly enlarged
 The cavities arenot dilated
 The myocrium is firm
 Both atria aretypically dilated as a consequnce of restricted ventricular fillingand pressure
overloads
Histology
 Variabledegrees of interstitial fibrosis
N.B: Although the gross morphology is similarfor restrictivecardiomoptahy of disoarartecauses
endomyocardial biopsy often can reveal a specific etiology.
Types of restrictive cardiomyopathy
This form of cardiomyopathy may be idiopathicor may be associated with systemic diseases that
affect the myocardium, for example, radiation fibrosis,amyloidosis,sarcoidosis,or products of inborn
errors of metabolism.
Three forms of restrictivecardiomyopathy merit brief mention.

11. Amyloidosis is caused by the deposition of extracellular proteins with te dredilection from forming
insoluableBpleted sheets.
Endomyocardial fibrosis-is principally a diseaseof children and young adults in Africa and other
tropical areas.Itis characterized by dense diffusefibrosis of the ventricular endocardiumand
subendocardium,often involvingthe tricuspid and mitral valves.
Loeffler endomyocarditis also exhibits endocardial fibrosis,typically associated with ormation of large
mural thrombi. It has no geographic or population predilec tion.It is characterized by peripheral
hypereosinophilia and eosinophilictissueinfiltrates;releaseof eosinophil granulecontents,
especially major basic protein,prob ably engenders endocardial and myocardial necrosis, followed by
scarring,layeringof the endocardium by thrombus, and finally thrombus organization.