PATHOLOGY OF THE PATHOLOGY OF THE HEARTHEART

DR. HENNY SULASTRY, SpPADR. HENNY SULASTRY, SpPA

Central Diagnostic of Pathology Anatomic Central Diagnostic of Pathology Anatomic M. Hoesin Central General Hospital/ Medicine M. Hoesin Central General Hospital/ Medicine

Faculty of Sriwijaya UniversityFaculty of Sriwijaya University20082008

TerminologyTerminology : : episodic chest painepisodic chest pain caused caused by inadequate oxygenation.by inadequate oxygenation.

Causes include partial or complete Causes include partial or complete interruption of arterial blood flow to the interruption of arterial blood flow to the myocardium.myocardium.

In most cases the cause is In most cases the cause is atherosclerotic atherosclerotic narrowing of the coronary arteries.narrowing of the coronary arteries.

Ischemic Heart DiseaseIschemic Heart Disease

Clinically silent or manifest as angina Clinically silent or manifest as angina pectoris, myocardial infarction, chronic pectoris, myocardial infarction, chronic IHD.IHD.

Risk factorsRisk factors

Life-style Life-style smooking, alkohol smooking, alkohol

Determined genetic factors Determined genetic factors hyperlipidemia, DMhyperlipidemia, DM

Physiological Factor Influence the Expression of Physiological Factor Influence the Expression of IschemiaIschemia

Energy requirmentsEnergy requirments Cardiac muscle has high energy requirmnet, demand high Cardiac muscle has high energy requirmnet, demand high

energy phosphates to maintain membrane integrity and the energy phosphates to maintain membrane integrity and the consentration gradients of sodium, potassium & calciumconsentration gradients of sodium, potassium & calcium

Feature of cardiac muscleFeature of cardiac muscle Poor endogenous fuel reservesPoor endogenous fuel reserves Well vascularizedWell vascularized Aerobic metabolismAerobic metabolism Pattern of myocardial blood flowPattern of myocardial blood flowPerfussion of the myocardial occurs in diastole, systole vessels Perfussion of the myocardial occurs in diastole, systole vessels

are compressed by contractionare compressed by contraction The pattern of flow The pattern of flow learned from Physiology and Internal learned from Physiology and Internal

MedicineMedicine

General Pathology of Ischaemic Myocardial General Pathology of Ischaemic Myocardial InjuryInjury

The time-related functional, biochemical and The time-related functional, biochemical and ultrastructural changes after coronary artery ultrastructural changes after coronary artery occlussion occlussion from animal studies in dogs and from animal studies in dogs and pigs.pigs.

Following have been observed:Following have been observed: Within minutes : cessation of contraction of Within minutes : cessation of contraction of

ischemic areaischemic area Coagulative necrosis over next 12 hoursCoagulative necrosis over next 12 hours Necrosis may be inhibited if blood flow is re-Necrosis may be inhibited if blood flow is re-

establisted within 20-40minestablisted within 20-40min

Biochemical ChangesBiochemical Changes

Fall in oxygen tensionFall in oxygen tension Loss of mitochondrial (aerobic) respirationLoss of mitochondrial (aerobic) respiration Anaerobic glycolysis of glycogen is sole Anaerobic glycolysis of glycogen is sole

sourse energy sourse energy rise in lactate rise in lactate Marked fall in intracellular ATP to zero in 40-Marked fall in intracellular ATP to zero in 40-

60 min60 min Creatine posphate falls to zero within 15 min Creatine posphate falls to zero within 15 min

of ischemiaof ischemia Inhibition myosin ATPase activity by H+Inhibition myosin ATPase activity by H+

STRUCTURAL CHANGES OCCURING IN STRUCTURAL CHANGES OCCURING IN ISCHAEMIC MYOCARDIUMISCHAEMIC MYOCARDIUM

Ultrastructural changesUltrastructural changesMitochondrial and membrane damage (15-Mitochondrial and membrane damage (15-

40 min)40 min)More severe upon reperfusion with More severe upon reperfusion with

swollen muscle cells, accumulation of swollen muscle cells, accumulation of hydrated calcium phosphate in hydrated calcium phosphate in mitochondria and sarcomere disturbance mitochondria and sarcomere disturbance

Ischaemic Heart DiseaseIschaemic Heart Disease(IHD)(IHD)

There are 4 overlapping ischemic There are 4 overlapping ischemic syndromes:syndromes:

1.1. Angina PectorisAngina Pectoris2.2. Myocardial InfarctionMyocardial Infarction3.3. Chronic Ischemic Heart diseasesChronic Ischemic Heart diseases (in (in

elderly patients w/ moderate – severe elderly patients w/ moderate – severe coronary atherosclerosis who insidiously coronary atherosclerosis who insidiously develop CHFdevelop CHF

4.4. Sudden cardiac deathSudden cardiac death is defined as is defined as unexpected cardiac death within 1 hour unexpected cardiac death within 1 hour of symptom onsetof symptom onset

1.1. Stable angina Stable angina The most common form.The most common form. Pain that is precipitated by exertion, Pain that is precipitated by exertion,

relieved by rest or by vasodilators.relieved by rest or by vasodilators. Result from severe narrowing of Result from severe narrowing of

atherosclerotic coronary vesselsatherosclerotic coronary vessels

Angina PectorisAngina Pectoris

Causative lessions are a fixed stenosis of Causative lessions are a fixed stenosis of the lumen of one or more epicardial the lumen of one or more epicardial coronary artery by more than 50%coronary artery by more than 50%

Stenosis morphologyStenosis morphology70% lessions are concentric contain of 70% lessions are concentric contain of

fibrous plaques with small basal lipidfibrous plaques with small basal lipid24% lessions are excentric contain of 24% lessions are excentric contain of

large lipid-pools and fibrouslarge lipid-pools and fibrous

Unstable AnginaUnstable Angina

2. Unstable angina ( Unstable Angina Type 1)2. Unstable angina ( Unstable Angina Type 1) Is prolonged or recurrent pain at restIs prolonged or recurrent pain at rest Indicated myocardial infarctionIndicated myocardial infarction Caused by disruption of an atherosclerotic Caused by disruption of an atherosclerotic

plaque.plaque. Splitting and fissuring of the fibrous cap with Splitting and fissuring of the fibrous cap with

thrombus dispositionthrombus disposition

3. Prinzmetal angina3. Prinzmetal angina ( Unstable Angina Type 2)( Unstable Angina Type 2) Intermittent chest pain at restIntermittent chest pain at rest Caused by vasospasmCaused by vasospasm

Sequential progression of coronary artery lesion morphology, beginning with stable chronic plaque, responsible for typical angina, and leading to the various acute coronary syndromes

Myocardial InfarctionMyocardial InfarctionThe most important cause of morbidity from The most important cause of morbidity from

IHD is one of causes of death.IHD is one of causes of death.Myocardial coagulative necrosis caused by Myocardial coagulative necrosis caused by

coronary artery occlusioncoronary artery occlusion is characteristic. is characteristic.A series of A series of progressive changesprogressive changes involving involving

gross and microscopic appearance of the gross and microscopic appearance of the heart.heart.

Release of myocardial enzymes and other Release of myocardial enzymes and other proteins into bloodstream proteins into bloodstream

A process caused by altered membrane A process caused by altered membrane permeability of necrotic myocardial cells.permeability of necrotic myocardial cells.

The cells involved The cells involved neuthrophills, neuthrophills, macrophages and fibroblasts.macrophages and fibroblasts.

There are There are 2 interrelated types2 interrelated types of of myocardial ischemic necrosis :myocardial ischemic necrosis :

1.1. Transmural InfarctionTransmural Infarction

2.2. Subendocardial InfarctionSubendocardial Infarction

1.1. Transmural InfarctionTransmural Infarction Involving the full thickness of the ventricular Involving the full thickness of the ventricular

wallwall Caused by severe coronary atherosclerosis Caused by severe coronary atherosclerosis

with acute plaque rupture and superimposed with acute plaque rupture and superimposed occlusive thrombosisocclusive thrombosis

PathogenesisPathogenesisSignificant plaques tipically occur in the Significant plaques tipically occur in the

proximal 2cm of the left anterior proximal 2cm of the left anterior descending and left circumflex coronary descending and left circumflex coronary arteriesarteries

In few cases vasospasm and platelet In few cases vasospasm and platelet aggregation without atherosclerotic aggregation without atherosclerotic stenosesstenoses

Initial event Initial event erosion, ulceration, erosion, ulceration, fissuring, rupture, hemorrhagic expansion fissuring, rupture, hemorrhagic expansion of atherosclerosis plaqueof atherosclerosis plaque

Plaques involved in coronary events Plaques involved in coronary events vulnerablevulnerable

Transient changes in blood pressure and Transient changes in blood pressure and platelet reactivityplatelet reactivity

High levels of serum markers of High levels of serum markers of inflammation (CRP) and hypercoagulability inflammation (CRP) and hypercoagulability ( protein C or S defficiency, factor V ( protein C or S defficiency, factor V Leiden)Leiden)

Thrombosis follow the acute plaque and Thrombosis follow the acute plaque and occludes flow the distal tissues occludes flow the distal tissues

The time interval onset of complete The time interval onset of complete myocardial ischemia and the initiation of myocardial ischemia and the initiation of irreversible injury 20-40 minutesirreversible injury 20-40 minutes

If the patient survives If the patient survives thrombi lyse thrombi lyse spontaneouslyspontaneously

Reflow to precariously injured cells may Reflow to precariously injured cells may restore viability but leave the cells poorly restore viability but leave the cells poorly contractile (stunned) for 1 or 2 dayscontractile (stunned) for 1 or 2 days

Nearly all transmural MIs Nearly all transmural MIs affect in left affect in left ventricle; 15% involved the right ventricle ventricle; 15% involved the right ventricle particularly in posterior-inferior left particularly in posterior-inferior left ventricle infarctsventricle infarcts

2. 2. Subendocardial InfarctionSubendocardial Infarction

Limited to the interior one third of the wall of Limited to the interior one third of the wall of the left ventricle and often multifocal.the left ventricle and often multifocal.

Caused by increased cardiac demand in Caused by increased cardiac demand in the setting of limiting supply, the setting of limiting supply, vasospasm,due to diffuse atherosclerosis vasospasm,due to diffuse atherosclerosis diseasedisease

Plaque disruption with overlying thrombus Plaque disruption with overlying thrombus that spontaneously lysesthat spontaneously lyses

Progression of myocardial necrosis after coronary artery occlusion. Necrosis begins in a small zone of the myocardium beneath the endo cardial surface in the center of the ischemic zone.

MorphologyMorphology

Electron MicroscopeElectron Microscope

Reversible phaseReversible phase

- - Glycogen depletionGlycogen depletion

- mitochondrial swelling- mitochondrial swelling

- relaxation of myofibrils- relaxation of myofibrils Irreversible phaseIrreversible phase

- Sarcolemmal disruption- Sarcolemmal disruption

- Mitochondrial amorphous densities- Mitochondrial amorphous densities

Gross changesGross changes

Before 6-12 hoursBefore 6-12 hours usually inapparent usually inapparent 3-6 hours3-6 hours changes occuring changes occuring By 18-24 hoursBy 18-24 hours infarcted tissue is generally infarcted tissue is generally

readily apparent as discrete pale to cyanotic readily apparent as discrete pale to cyanotic areasareas

11stst week week progressively, yellow, softened progressively, yellow, softened 7-10 days7-10 days hyperemic granulation tissue hyperemic granulation tissue 6 weeks6 weeks white fibrous scar white fibrous scar

lnfark myocard, atherosclerosis ruptur, myocardium diganti dengan Jaringan parut berwarna putih keabuan pada ventricel

MicroscopicallyMicroscopically

Within 1 hourWithin 1 hour intercellular edema, myocytes intercellular edema, myocytes become wavy and buckledbecome wavy and buckled

4 hour appearance of neutrophyl in interstitium4 hour appearance of neutrophyl in interstitium 12 – 72 hours after MI12 – 72 hours after MI death myocyte become death myocyte become

hypereosinophilic, loss nuclei, coagulative hypereosinophilic, loss nuclei, coagulative necrosisnecrosis

From 3-7 days after injuryFrom 3-7 days after injury appearance of appearance of macrophages in ischemic area, dead myocytes macrophages in ischemic area, dead myocytes are digested by invading macrophagesare digested by invading macrophages

After 7-10 daysAfter 7-10 days laying down collagen fibers, laying down collagen fibers, granulation tissue progressively replaces necrotic granulation tissue progressively replaces necrotic tissue tissue fibrous scarfibrous scar

Repair complete at 6 weeksRepair complete at 6 weeks

Potongan histologis dari infark myocardial akut

Clinical FeatureClinical Feature

Based mainly inBased mainly in symptoms (chest pain, nausea, diaphories, symptoms (chest pain, nausea, diaphories,

dyspnea)dyspnea) Electrocardiographic changesElectrocardiographic changes Elevation of serum of cardiomyocyte-specific Elevation of serum of cardiomyocyte-specific

proteins release from death cellsproteins release from death cells AngiographyAngiography

ComplicationsComplications

ArrhytmiasArrhytmias CHFCHF Cardiogenic shockCardiogenic shock Ventricular ruptureVentricular rupture Papillary muscle infarctionPapillary muscle infarction Fibrinous pericarditisFibrinous pericarditis Mural thrombosisMural thrombosis Repetitive infarctionRepetitive infarction

Chronic Ischemic Heart DiseaseChronic Ischemic Heart Disease

Is seen typically in elderly patients woth Is seen typically in elderly patients woth moderate to severe multivessels coronary moderate to severe multivessels coronary atherosclerosis who insidiously develop atherosclerosis who insidiously develop CHFCHF

It’s may result from postinfarction cardiac It’s may result from postinfarction cardiac decompensation or slow ischemic myocyte decompensation or slow ischemic myocyte degenerationdegeneration

MicroscopicallyMicroscopically

Myocardium has variable myocyte atrophy Myocardium has variable myocyte atrophy with perinuclear deposition of lipofuscinwith perinuclear deposition of lipofuscin

Myocytolisis of single cells or clusters, Myocytolisis of single cells or clusters, diffuse perivascular and interstitial fibrosisdiffuse perivascular and interstitial fibrosis

Patchy to confluent replacement fibrosis Patchy to confluent replacement fibrosis (scarring)(scarring)

Myocardial Hypertrophy and Heart Myocardial Hypertrophy and Heart FailureFailure

Myocardial hypertrophy is an Myocardial hypertrophy is an adaptive responseadaptive response that increases the contractile strength of the that increases the contractile strength of the myocyte and increase amounts of sarcometric myocyte and increase amounts of sarcometric protein without increase myocyte number under protein without increase myocyte number under condition of hemodynamic overload ( chronic condition of hemodynamic overload ( chronic hypertension, valvular stenosis, valvular hypertension, valvular stenosis, valvular insufficiency, myocardial injury)insufficiency, myocardial injury)

Hypertrophy is a compensatory state of the Hypertrophy is a compensatory state of the heart to maintain cardiac out putheart to maintain cardiac out put

Overtime hypertrophy can lead to Overtime hypertrophy can lead to ventricular dilatation.ventricular dilatation.

A variety of disorders may cause heart A variety of disorders may cause heart failure including ischemic heart disease failure including ischemic heart disease (80%), cardiomyopathies, congenital heart (80%), cardiomyopathies, congenital heart disease.disease.

The majority of patients with CHF have The majority of patients with CHF have ventricular hypertrophyventricular hypertrophy

In most cases In most cases followed by dilation of the followed by dilation of the ventriclesventricles

Multiple factors are involved in the Multiple factors are involved in the development of cardiac hypertrophy development of cardiac hypertrophy including the following :including the following :

1.1. Angiotensin IIAngiotensin II

2.2. Endothelin-1Endothelin-1

3.3. Insulin-likeInsulin-like

4.4. Extracellular matrixExtracellular matrix

5.5. ββ – adrenergic desensitization – adrenergic desensitization

6.6. Calcium homeostasisCalcium homeostasis

7.7. Protooncogene expressionProtooncogene expression

8.8. Fetal gen expressionFetal gen expression

Left-sided heart failure Left-sided heart failure

most common form of heart failuremost common form of heart failure Often occurs secondary to ischemic heart disease Often occurs secondary to ischemic heart disease

and hypertensionand hypertension

● ● Right-sided heart failureRight-sided heart failure

may occur with intrinsic pulmonary disease or may occur with intrinsic pulmonary disease or pulmonary hypertension or secondary to left-sided pulmonary hypertension or secondary to left-sided heart failureheart failure

MicroscopicallyMicroscopically

the damaged myocytes contain a vacuolated the damaged myocytes contain a vacuolated appearance of the cytoplasm due to increased appearance of the cytoplasm due to increased amaunts of glycogen and degenerative changes amaunts of glycogen and degenerative changes due to loss of myofibrilsdue to loss of myofibrils

Hypertensive Heart DiseaseHypertensive Heart DiseaseSystemic (left-sided) Hypertensive Heart Systemic (left-sided) Hypertensive Heart

DiseaseDisease

Diagnosis criteriaDiagnosis criteria : :

Left ventricular hypertrophy typically concentricLeft ventricular hypertrophy typically concentric Absence of other lesions that induce cardiac Absence of other lesions that induce cardiac

hypertrophy ( e.g. aortic valve stenosis aortic hypertrophy ( e.g. aortic valve stenosis aortic coarctaction)coarctaction)

PathogenesisPathogenesis

Myocyte hypertrophic enlargement occurs in Myocyte hypertrophic enlargement occurs in response to increased work.response to increased work.

Myocytes cannot devide Myocytes cannot devide the only way that the only way that cells can augment contractile proteins.cells can augment contractile proteins.

Thickened myocardium reduces left ventricle Thickened myocardium reduces left ventricle compliance compliance impairing diastolic filling while impairing diastolic filling while increasing oxygen demand.increasing oxygen demand.

Myocyte hypertrophy increases the distance for Myocyte hypertrophy increases the distance for oxygen and nutrient diffusion from adjacent oxygen and nutrient diffusion from adjacent capillariescapillaries

Coronary atherosclerosis + hypertension Coronary atherosclerosis + hypertension add add element of ischemiaelement of ischemia

MorphologyMorphology

The left ventricular wall is thickened (>2cm)The left ventricular wall is thickened (>2cm) Heart weight is increased ((>500gm)Heart weight is increased ((>500gm) Myocyte and muclei are enlargedMyocyte and muclei are enlarged Long-term Long-term diffuse interstitial fibrosis, focal diffuse interstitial fibrosis, focal

myocyte atrophy, degeneration myocyte atrophy, degeneration Resulting left ventricle chamber dilatation and Resulting left ventricle chamber dilatation and

wall thinningwall thinning

Hypertensive Heart DiseaseHypertensive Heart DiseasePulmonary (Right-Sided) Heart DiseasePulmonary (Right-Sided) Heart Disease

(Cor Pulmonale)(Cor Pulmonale)

Cor Pulmonale (CP) is the right-sided counterpart Cor Pulmonale (CP) is the right-sided counterpart to systemic hypertensive heart diseaseto systemic hypertensive heart disease

BasicallyBasically causes right ventricular causes right ventricular hypertrophy ventricular pathology hypertrophy ventricular pathology excludedexcluded

Acute CPAcute CP refers to right ventricular dilatation refers to right ventricular dilatation after massive pulmonary embolizationafter massive pulmonary embolization

Chronic CPChronic CP result from chronic right result from chronic right ventricular pressure overloadventricular pressure overload

Hypoxemia and acidosisHypoxemia and acidosis vasoconstriction in pulmonary vasoconstriction in pulmonary vasculaturevasculature exacerbates exacerbates pulmonary pulmonary hypertensionhypertension

MorphologyMorphologyOften Often ≥ 1 cm, dilatation or both are present.≥ 1 cm, dilatation or both are present.Can cause tricuspid regurgitationCan cause tricuspid regurgitationThe left side of the heart The left side of the heart normal normalPulmonary arteriolar wall thickening and Pulmonary arteriolar wall thickening and

artherosclerosis occur.artherosclerosis occur.

Rheumatic Heart DiseaseRheumatic Heart DiseaseCollagen Vascular DiseasesCollagen Vascular DiseasesBacterial EndocarditisBacterial EndocarditisNonbacterial Thrombotic EndocarditisNonbacterial Thrombotic EndocarditisMitral Valve ProlapseMitral Valve Prolapse

Acquired Valvular and Endocardial Acquired Valvular and Endocardial DiseaseDisease

Rheumatic feverRheumatic fever

DefinitoinDefinitoin multisystem inflammatory disorder multisystem inflammatory disorder with major cardiac manifestations and sequelae, with major cardiac manifestations and sequelae, in children between 5 and 15 years of age.in children between 5 and 15 years of age.

1-4 weeks after an episode of tonsilitis or other 1-4 weeks after an episode of tonsilitis or other infection caused by group infection caused by group A A ß-hemolytic ß-hemolytic streptococci.streptococci.

Etiology Etiology Immunologic origin. Immunologic origin. The postulate The postulate result of streptococcal antigens result of streptococcal antigens

that elicit an antibody response reactive to that elicit an antibody response reactive to streptococcal organism as well as to human streptococcal organism as well as to human antigens in the heart and others tissues.antigens in the heart and others tissues.

Rheumatic FeverRheumatic Fever

1.1. Acute Rheumatic FeverAcute Rheumatic Fever

2.2. Chronic Rheumatic FeverChronic Rheumatic Fever

Acute Rheumatic FeverAcute Rheumatic Fever ARF is a multisystem disease of childhood that ARF is a multisystem disease of childhood that

occurs following an acute streptococcal infection occurs following an acute streptococcal infection usually pharyngitis (“sore throat”)usually pharyngitis (“sore throat”)

Diagnosis is based in clinical hystory and 2 of 5 major Diagnosis is based in clinical hystory and 2 of 5 major (Jones) criteria, minor criteria (include fever, (Jones) criteria, minor criteria (include fever, arthralgia, leukocytosis ).arthralgia, leukocytosis ).

Strephococcus pyogenes from group Strephococcus pyogenes from group A A ß-hemolytic ß-hemolytic streptococci.streptococci.

ARF affects the pericardium, myocardium,ARF affects the pericardium, myocardium, endocardium and valves endocardium and valves pancarditispancarditis

Clinical feature Clinical feature learned in Pediatric learned in Pediatric MedicineMedicine

PathogenesisPathogenesis

The immune reaction to streptococcal The immune reaction to streptococcal antigen is idiosyncratic, seen in 3% antigen is idiosyncratic, seen in 3% patiensts with a streptococcal sore throat.patiensts with a streptococcal sore throat.

The antibodies produced are directed The antibodies produced are directed against streptococcal cell wall components against streptococcal cell wall components (fibrillary M protein) and cross-react with the (fibrillary M protein) and cross-react with the following target tissues :following target tissues :

• Heart muscleHeart muscle• Heart valve connective tissueHeart valve connective tissue• Thymic cellsThymic cells• Human glomerular basement membraneHuman glomerular basement membrane• Neuronal cytoplasm in sub-thalamic and Neuronal cytoplasm in sub-thalamic and

caudate nuclei in the braincaudate nuclei in the brain• SkinSkin• LymphocytesLymphocytes

Characteristic features in the acute Characteristic features in the acute phase:phase:

Aschoff bodies Aschoff bodies pathognomonic pathognomonicTransient fibrinous pericarditis contain Transient fibrinous pericarditis contain

Aschoff bodiesAschoff bodies Inflammatory valvulitis Inflammatory valvulitis beady fibrinous beady fibrinous

vegetation (verrucae)vegetation (verrucae)

Microscopically:Microscopically:

1.1. MyocadialMyocadial changeschanges, 2 histological pattern :, 2 histological pattern : Non specific myocarditisNon specific myocarditis : edema, inflammatory : edema, inflammatory

cells and rarely a small-vessel arteritiscells and rarely a small-vessel arteritis Specific granulomatous myocarditisSpecific granulomatous myocarditis : present : present

throughout the heart but most commonly in throughout the heart but most commonly in the interventricular septum the interventricular septum

Focus granulomatous called Focus granulomatous called Aschoff NoduleAschoff Nodule Aschoff nodules contain : necrosis fibrinoid, Aschoff nodules contain : necrosis fibrinoid,

aschoff giant cells (multinucleated aschoff giant cells (multinucleated macrophages), Anitschkow myocytes ( cell macrophages), Anitschkow myocytes ( cell with a characteristic bar of chromatin and owl with a characteristic bar of chromatin and owl eye nucleuseye nucleus

Aschoff bodyAschoff body

Classic lession (patognomonic) of rheumatic Classic lession (patognomonic) of rheumatic fever fever

an area of focal interstitial myocardial an area of focal interstitial myocardial inflammation inflammation

that is characterized by fragmented collagen that is characterized by fragmented collagen and fibrinoid necrosis materials in the central and fibrinoid necrosis materials in the central surounded by large cells (surounded by large cells (Anitschkow myocitesAnitschkow myocites) ) and multinucleated giant cell macrophages and multinucleated giant cell macrophages ((Aschoff cellsAschoff cells) and lymphocytes mostly T ) and lymphocytes mostly T helper cells.helper cells.

With time the the Aschoff nodule regresses to a With time the the Aschoff nodule regresses to a small scarsmall scar

Other anatomic changes Other anatomic changes PancarditisPancarditis

1. Pericarditis 1. Pericarditis inflammation of the pericardium may inflammation of the pericardium may

result in pericardial,pleural or others result in pericardial,pleural or others serous effusions.serous effusions.

2. Myocarditis 2. Myocarditis inflammation of the inflammation of the myocardium may lead to cardiac failure, myocardium may lead to cardiac failure, the cause of most deaths occuring during the cause of most deaths occuring during the early stages of acute rheumatic the early stages of acute rheumatic fever.fever.

3. Endocarditis3. Endocarditis inflammation of inflammation of endocardial, lead to valvular damageendocardial, lead to valvular damage

PancarditisPancarditis

2. Pericardium2. Pericardium changeschanges: :

shaggy fibrinous deposits on the visceral shaggy fibrinous deposits on the visceral and parietal surfaces and parietal surfaces ‘bread-and –butter’‘bread-and –butter’ pericarditispericarditis

3. Endocardium and valves changes3. Endocardium and valves changes : :

valve leaftlets inflammed and valve leaftlets inflammed and edematous edematous deposition of tiny fibrin deposition of tiny fibrin nodules along the leaflets termed verrucous nodules along the leaflets termed verrucous endocarditisendocarditis

Chronic Rheumatic HeartChronic Rheumatic Heart DiseaseDisease

Long term structural damageLong term structural damage Diffuse fibrosis causing Diffuse fibrosis causing thickened, shrunken, thickened, shrunken,

less pliableless pliable The valve leaftlets or cups of the affected The valve leaftlets or cups of the affected

valvesvalves fibrous adhessions fibrous adhessions stenosis stenosis Most common in mitral valves and oartic valveMost common in mitral valves and oartic valve The mitral valve The mitral valve have “ have “fish mouth”fish mouth”

appearanceappearance Complication Complication bacterial endocarditis, mural bacterial endocarditis, mural

thrombi, congestive heart failure, adhesive thrombi, congestive heart failure, adhesive pericarditis.pericarditis.

Characteristic features of the chronic Characteristic features of the chronic (or healed ) valve:(or healed ) valve:

Fibrous thickening of leafletsFibrous thickening of leafletsBridging fibrosis across valve commisuresBridging fibrosis across valve commisures fishmouth/ button hole stenosisfishmouth/ button hole stenosisThickened, fused and shortened chordaeThickened, fused and shortened chordaeCalsification in the fibrous leaftletsCalsification in the fibrous leaftletsSubendocardial collections of Aschoff Subendocardial collections of Aschoff

nodules nodules Mc Callum plaques Mc Callum plaques

Rheumatic endocarditis Rheumatic endocarditis occurs in areas occurs in areas subject to greatest hemodynamic stress, such as subject to greatest hemodynamic stress, such as the points of valve closure and the posterior wall the points of valve closure and the posterior wall of the left atrium of the left atrium MacCallum plaque.MacCallum plaque.

Early stageEarly stage valve leaflets are red and valve leaflets are red and swollen, tiny, warty, bead-like, rubbery swollen, tiny, warty, bead-like, rubbery vegetation (verrucae) form along the line of vegetation (verrucae) form along the line of closure of valve leaflet.closure of valve leaflet.

Late stageLate stage fibrotic healing, the valve become fibrotic healing, the valve become thickened, fibrotic, deformed, fusion of valve thickened, fibrotic, deformed, fusion of valve cups, calsification cups, calsification are grouped under the term are grouped under the term rheumatic heart disease.rheumatic heart disease.

The diseases involve :The diseases involve :

1.1. Mitral valve Mitral valve involved in 65%-70% of involved in 65%-70% of cases.cases.

2.2. Combine aortic and mitral valve Combine aortic and mitral valve 20%- 20%-40% of cases afffected a long the mitral 40% of cases afffected a long the mitral valve.valve.

3.3. Tricuspid and pulmonary valve Tricuspid and pulmonary valve less less frequently affected a long the mitral valve frequently affected a long the mitral valve and the aortic valves in 5% cases.and the aortic valves in 5% cases.

4.4. Pulmonary valve Pulmonary valve rarely. rarely.

Chronic Rheumatic Heart Disease “ fish mouth or Button hole”

. Endokarditis rematik katup mitral. Tonjolan-tonjolan multipel berwarna kelabu, berbentuk mirip kulit (verukosa) tampak pada bagian penutupan katup: dikelilingi oleh deposit-defosit fibrin yang baru terjadi (merah)

EndocarditisEndocarditis

Cardiac disorders are marked mainly by Cardiac disorders are marked mainly by valve vegetationsvalve vegetations

Major examples :Major examples :

1.1. Infective endocarditisInfective endocarditis

2.2. Nonbacterial thrombotic endocarditisNonbacterial thrombotic endocarditis

3.3. Endocarditis associated with SLE Endocarditis associated with SLE ((Libman-Sacks endocarditisLibman-Sacks endocarditis))

Infective Endocarditis Infective Endocarditis

Bacterial, fungal, infection of the Bacterial, fungal, infection of the endocardium endocardium involvement of valvular involvement of valvular surfaces.surfaces.

Characteristics include large, soft, friable, Characteristics include large, soft, friable, easily detacted easily detacted vegetations vegetations consisting of consisting of fibrin intermshed inflammatory cells and fibrin intermshed inflammatory cells and bacteria.bacteria.

Complication Complication ulceration, perforation, ulceration, perforation, rupture of chordae tendineae.rupture of chordae tendineae.

Classification Classification 1.1. Acute endocarditisAcute endocarditis pathogens is highly virulent organism such as pathogens is highly virulent organism such as

Staphylococcus aureus (50% of cases).Staphylococcus aureus (50% of cases). Clinically rapidly developing fever with rigor, Clinically rapidly developing fever with rigor,

malaise weakness.malaise weakness. Death occurs in days to weeks in 50%- 60% of Death occurs in days to weeks in 50%- 60% of

cases.cases.

2. Subacute (bacterial)endocarditis2. Subacute (bacterial)endocarditis by less by less virulent organisms such as Streptococcus virulent organisms such as Streptococcus viridans ( more than 50% cases), occur in viridans ( more than 50% cases), occur in congenital heart disease or preexisting valvular congenital heart disease or preexisting valvular heart disease.heart disease.

PathogenesisPathogenesisBacteriemia are prerequisites that can come Bacteriemia are prerequisites that can come

from infections from elsewhere in the body, from infections from elsewhere in the body, intravenous drug abuse, dental or surgical intravenous drug abuse, dental or surgical procedures, injury to gut, urinary tract, procedures, injury to gut, urinary tract, oropharynx or skin, neutropenia and oropharynx or skin, neutropenia and immunosuppressionimmunosuppression

Endocarditis bacterial can occurs on normal Endocarditis bacterial can occurs on normal valves and in certain valvular and others valves and in certain valvular and others cardiac condition ( CHD, VSD, CRHD )cardiac condition ( CHD, VSD, CRHD )

MorphologyMorphology Friable 0.5-2.0 cm, microba laden vegetationFriable 0.5-2.0 cm, microba laden vegetation Bulky (1-2cm)Bulky (1-2cm) Vegetations are typically on the downstream Vegetations are typically on the downstream

margin of a jet lession margin of a jet lession Acute infective endocarditis has a large Acute infective endocarditis has a large

vegetations can cause embolic complicationvegetations can cause embolic complication Subacute infective endocarditis tend to be small Subacute infective endocarditis tend to be small

vegetationsvegetations Ring abcessRing abcess

Valvular involvementValvular involvement Mitral valveMitral valve Mitral valve along with the aortic valveMitral valve along with the aortic valve Tricuspid valve Tricuspid valve 50% cases, most caused by 50% cases, most caused by

staphylococcal infectionstaphylococcal infection..

• ComplicationsComplications Distal embolizationsDistal embolizations Septic infarctsSeptic infarcts Focal necrotizing glomerulitis Focal necrotizing glomerulitis caused by caused by

immune complex disease or by septic emboliimmune complex disease or by septic emboli

Endokarditis infektif. Suatu massa trombotik polipoid yang baru (“vegetasi) tampak pada garis penutupan katup aorta.

Nonbacterial thrombotic Nonbacterial thrombotic endocarditisendocarditis

Marantic endocarditisMarantic endocarditisOccurs in settings of Occurs in settings of

cancer(adenocarcinomas), prolonged cancer(adenocarcinomas), prolonged debilitating ilness, DICdebilitating ilness, DIC

Morphology:Morphology:Small (1-5mm) sterile, bland fibrin, platelet Small (1-5mm) sterile, bland fibrin, platelet

thrombithrombiVegetations can embolize systemicallyVegetations can embolize systemically

Endocarditis associated with SLE Endocarditis associated with SLE ((Libman-Sacks endocarditis)Libman-Sacks endocarditis)

Pathogenesis uncertainPathogenesis uncertain Affected in mitral and tricuspid valvesAffected in mitral and tricuspid valves Findings : fibrinoid necrosis, mucoid Findings : fibrinoid necrosis, mucoid

degeneration, small, fibrinous, sterile degeneration, small, fibrinous, sterile vegetationsvegetations

Comparison of the lesions in the four major forms of vegetative endocarditis. The acute rheumatic heart disease (RHD) is marked by a flow of small, warty verrucae along the lines of the valve leaflets. Infective endocarditis (lE) typically shows large irregular and destructive masses that can extend onto the chordae. Nonbacterial thrombotic endocarditis (NBTE) typically shows small, bland vegetations, usually attached at the line of closure. One or many may be present. Libman-Sacks endocarditis ( has small or medium-sized