PATHOLOGY OF THE HEART

DR. HENNY SULASTRY, SpPA

Central Diagnostic of Pathology Anatomic M. Hoesin Central General Hospital/ Medicine Faculty of Sriwijaya University 2008

Ischemic Heart Disease

Terminology : episodic chest pain caused by inadequate oxygenation. Causes include partial or complete interruption of arterial blood flow to the myocardium. In most cases the cause is atherosclerotic narrowing of the coronary arteries.

Clinically silent or manifest as angina pectoris, myocardial infarction, chronic IHD. Risk factors Life-style smooking, alkohol Determined genetic factors hyperlipidemia, DM

Physiological Factor Influence the Expression of Ischemia

Energy requirments
Cardiac muscle has high energy requirmnet, demand high energy phosphates to maintain membrane integrity and the consentration gradients of sodium, potassium & calcium

Feature of cardiac muscle

Poor endogenous fuel reserves Well vascularized Aerobic metabolism

Pattern of myocardial blood flow

Perfussion of the myocardial occurs in diastole, systole vessels are compressed by contraction The pattern of flow learned from Physiology and Internal Medicine

General Pathology of Ischaemic Myocardial Injury

The time-related functional, biochemical and ultrastructural changes after coronary artery occlussion from animal studies in dogs and pigs. Following have been observed: Within minutes : cessation of contraction of ischemic area Coagulative necrosis over next 12 hours Necrosis may be inhibited if blood flow is reestablisted within 20-40min

Biochemical Changes

Fall in oxygen tension Loss of mitochondrial (aerobic) respiration Anaerobic glycolysis of glycogen is sole sourse energy rise in lactate Marked fall in intracellular ATP to zero in 4060 min Creatine posphate falls to zero within 15 min of ischemia Inhibition myosin ATPase activity by H+

STRUCTURAL CHANGES OCCURING IN ISCHAEMIC MYOCARDIUM

Ultrastructural changes Mitochondrial and membrane damage (1540 min) More severe upon reperfusion with swollen muscle cells, accumulation of hydrated calcium phosphate in mitochondria and sarcomere disturbance

Ischaemic Heart Disease (IHD)

There are 4 overlapping ischemic syndromes: 1. Angina Pectoris 2. Myocardial Infarction 3. Chronic Ischemic Heart diseases (in elderly patients w/ moderate severe coronary atherosclerosis who insidiously develop CHF 4. Sudden cardiac death is defined as unexpected cardiac death within 1 hour of symptom onset

Angina Pectoris
1.

Stable angina The most common form. Pain that is precipitated by exertion, relieved by rest or by vasodilators. Result from severe narrowing of atherosclerotic coronary vessels

Causative lessions are a fixed stenosis of the lumen of one or more epicardial coronary artery by more than 50% Stenosis morphology 70% lessions are concentric contain of fibrous plaques with small basal lipid 24% lessions are excentric contain of large lipid-pools and fibrous

Unstable Angina 2. Unstable angina ( Unstable Angina Type 1) Is prolonged or recurrent pain at rest Indicated myocardial infarction Caused by disruption of an atherosclerotic plaque. Splitting and fissuring of the fibrous cap with thrombus disposition 3. Prinzmetal angina ( Unstable Angina Type 2) Intermittent chest pain at rest Caused 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 Infarction
The most important cause of morbidity from IHD is one of causes of death. Myocardial coagulative necrosis caused by coronary artery occlusion is characteristic. A series of progressive changes involving gross and microscopic appearance of the heart. Release of myocardial enzymes and other proteins into bloodstream

A process caused by altered membrane permeability of necrotic myocardial cells. The cells involved neuthrophills, macrophages and fibroblasts.

1. 2.

There are 2 interrelated types of myocardial ischemic necrosis :

Transmural Infarction Subendocardial Infarction

1.

Transmural Infarction
Involving the full thickness of the ventricular wall Caused by severe coronary atherosclerosis with acute plaque rupture and superimposed occlusive thrombosis

Pathogenesis Significant plaques tipically occur in the proximal 2cm of the left anterior descending and left circumflex coronary arteries In few cases vasospasm and platelet aggregation without atherosclerotic stenoses

event erosion, ulceration, fissuring, rupture, hemorrhagic expansion of atherosclerosis plaque Plaques involved in coronary events vulnerable Transient changes in blood pressure and platelet reactivity
Initial

High levels of serum markers of inflammation (CRP) and hypercoagulability ( protein C or S defficiency, factor V Leiden) Thrombosis follow the acute plaque and occludes flow the distal tissues The time interval onset of complete myocardial ischemia and the initiation of irreversible injury 20-40 minutes

If the patient survives thrombi lyse spontaneously Reflow to precariously injured cells may restore viability but leave the cells poorly contractile (stunned) for 1 or 2 days Nearly all transmural MIs affect in left ventricle; 15% involved the right ventricle particularly in posterior-inferior left ventricle infarcts

2. Subendocardial Infarction

Limited to the interior one third of the wall of the left ventricle and often multifocal. Caused by increased cardiac demand in the setting of limiting supply, vasospasm,due to diffuse atherosclerosis disease Plaque disruption with overlying thrombus that 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.

Morphology
Electron Microscope

Reversible phase - Glycogen depletion - mitochondrial swelling - relaxation of myofibrils Irreversible phase - Sarcolemmal disruption - Mitochondrial amorphous densities

Gross changes
Before 6-12 hours usually inapparent 3-6 hours changes occuring By 18-24 hours infarcted tissue is generally readily apparent as discrete pale to cyanotic areas 1st week progressively, yellow, softened 7-10 days hyperemic granulation tissue 6 weeks white fibrous scar

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

Microscopically
Within 1 hour intercellular edema, myocytes become wavy and buckled 4 hour appearance of neutrophyl in interstitium 12 72 hours after MI death myocyte become hypereosinophilic, loss nuclei, coagulative necrosis From 3-7 days after injury appearance of macrophages in ischemic area, dead myocytes are digested by invading macrophages After 7-10 days laying down collagen fibers, granulation tissue progressively replaces necrotic tissue fibrous scar Repair complete at 6 weeks

Potongan histologis dari infark myocardial akut

Clinical Feature

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

dyspnea) Electrocardiographic changes Elevation of serum of cardiomyocyte-specific proteins release from death cells Angiography

Complications
Arrhytmias CHF Cardiogenic shock Ventricular rupture Papillary muscle infarction Fibrinous pericarditis Mural thrombosis Repetitive infarction

Chronic Ischemic Heart Disease

Is seen typically in elderly patients woth moderate to severe multivessels coronary atherosclerosis who insidiously develop CHF Its may result from postinfarction cardiac decompensation or slow ischemic myocyte degeneration

Microscopically

Myocardium

has variable myocyte atrophy with perinuclear deposition of lipofuscin Myocytolisis of single cells or clusters, diffuse perivascular and interstitial fibrosis Patchy to confluent replacement fibrosis (scarring)

Myocardial Hypertrophy and Heart Failure

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

Hypertrophy is a compensatory state of the heart to maintain cardiac out put Overtime hypertrophy can lead to ventricular dilatation. A variety of disorders may cause heart failure including ischemic heart disease (80%), cardiomyopathies, congenital heart disease. The majority of patients with CHF have ventricular hypertrophy In most cases followed by dilation of the ventricles

Multiple factors are involved in the development of cardiac hypertrophy including the following :
Angiotensin II Endothelin-1 Insulin-like Extracellular matrix adrenergic desensitization Calcium homeostasis Protooncogene expression Fetal gen expression

1. 2. 3. 4. 5. 6.

7.
8.

Left-sided heart failure

most common form of heart failure Often occurs secondary to ischemic heart disease and hypertension Right-sided heart failure may occur with intrinsic pulmonary disease or pulmonary hypertension or secondary to left-sided heart failure

Microscopically

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

Hypertensive Heart Disease Systemic (left-sided) Hypertensive Heart Disease

Diagnosis criteria :

Left ventricular hypertrophy typically concentric Absence of other lesions that induce cardiac hypertrophy ( e.g. aortic valve stenosis aortic coarctaction)

Pathogenesis

Myocyte hypertrophic enlargement occurs in response to increased work. Myocytes cannot devide the only way that cells can augment contractile proteins. Thickened myocardium reduces left ventricle compliance impairing diastolic filling while increasing oxygen demand. Myocyte hypertrophy increases the distance for oxygen and nutrient diffusion from adjacent capillaries Coronary atherosclerosis + hypertension add element of ischemia

Morphology

The left ventricular wall is thickened (>2cm) Heart weight is increased ((>500gm) Myocyte and muclei are enlarged Long-term diffuse interstitial fibrosis, focal myocyte atrophy, degeneration Resulting left ventricle chamber dilatation and wall thinning

Hypertensive Heart Disease Pulmonary (Right-Sided) Heart Disease (Cor Pulmonale)

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

Basically causes right ventricular hypertrophy ventricular pathology excluded Acute CP refers to right ventricular dilatation after massive pulmonary embolization Chronic CP result from chronic right ventricular pressure overload

Hypoxemia and acidosis vasoconstriction in pulmonary vasculature exacerbates pulmonary hypertension

Morphology Often 1 cm, dilatation or both are present. Can cause tricuspid regurgitation The left side of the heart normal Pulmonary arteriolar wall thickening and artherosclerosis occur.

Acquired Valvular and Endocardial Disease

Rheumatic Heart Disease Collagen Vascular Diseases Bacterial Endocarditis Nonbacterial Thrombotic Endocarditis Mitral Valve Prolapse

Rheumatic fever

Definitoin multisystem inflammatory disorder with major cardiac manifestations and sequelae, in children between 5 and 15 years of age. 1-4 weeks after an episode of tonsilitis or other infection caused by group A -hemolytic streptococci. Etiology Immunologic origin. The postulate result of streptococcal antigens that elicit an antibody response reactive to streptococcal organism as well as to human antigens in the heart and others tissues.

Rheumatic Fever

1. 2.

Acute Rheumatic Fever Chronic Rheumatic Fever

Acute Rheumatic Fever

ARF is a multisystem disease of childhood that occurs following an acute streptococcal infection usually pharyngitis (sore throat) Diagnosis is based in clinical hystory and 2 of 5 major (Jones) criteria, minor criteria (include fever, arthralgia, leukocytosis ). Strephococcus pyogenes from group A -hemolytic streptococci. ARF affects the pericardium, myocardium,

endocardium and valves pancarditis Clinical feature learned in Pediatric Medicine

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

The

 The

antibodies produced are directed against streptococcal cell wall components (fibrillary M protein) and cross-react with the following target tissues : Heart muscle Heart valve connective tissue Thymic cells Human glomerular basement membrane Neuronal cytoplasm in sub-thalamic and caudate nuclei in the brain Skin Lymphocytes

Characteristic features in the acute phase:

bodies pathognomonic Transient fibrinous pericarditis contain Aschoff bodies Inflammatory valvulitis beady fibrinous vegetation (verrucae)
Aschoff


1.

Microscopically:
Myocadial changes, 2 histological pattern :

Non specific myocarditis : edema, inflammatory cells and rarely a small-vessel arteritis Specific granulomatous myocarditis : present throughout the heart but most commonly in the interventricular septum Focus granulomatous called Aschoff Nodule Aschoff nodules contain : necrosis fibrinoid, aschoff giant cells (multinucleated macrophages), Anitschkow myocytes ( cell with a characteristic bar of chromatin and owl eye nucleus

Aschoff body Classic lession (patognomonic) of rheumatic fever an area of focal interstitial myocardial inflammation that is characterized by fragmented collagen and fibrinoid necrosis materials in the central surounded by large cells (Anitschkow myocites) and multinucleated giant cell macrophages (Aschoff cells) and lymphocytes mostly T helper cells. With time the the Aschoff nodule regresses to a small scar Other anatomic changes Pancarditis

Pancarditis
1. Pericarditis inflammation of the pericardium may result in pericardial,pleural or others serous effusions. 2. Myocarditis inflammation of the myocardium may lead to cardiac failure, the cause of most deaths occuring during the early stages of acute rheumatic fever. 3. Endocarditis inflammation of endocardial, lead to valvular damage

2. Pericardium changes: shaggy fibrinous deposits on the visceral and parietal surfaces bread-and butter pericarditis
3. Endocardium and valves changes :

valve leaftlets inflammed and

edematous deposition of tiny fibrin nodules along the leaflets termed verrucous endocarditis

Chronic Rheumatic Heart Disease

Long term structural damage Diffuse fibrosis causing thickened, shrunken, less pliable The valve leaftlets or cups of the affected valves fibrous adhessions stenosis Most common in mitral valves and oartic valve The mitral valve have fish mouth appearance Complication bacterial endocarditis, mural thrombi, congestive heart failure, adhesive pericarditis.

Characteristic features of the chronic (or healed ) valve: Fibrous thickening of leaflets Bridging fibrosis across valve commisures fishmouth/ button hole stenosis Thickened, fused and shortened chordae Calsification in the fibrous leaftlets Subendocardial collections of Aschoff nodules Mc Callum plaques

Rheumatic endocarditis occurs in areas subject to greatest hemodynamic stress, such as the points of valve closure and the posterior wall of the left atrium MacCallum plaque.
Early stage valve leaflets are red and swollen, tiny, warty, bead-like, rubbery vegetation (verrucae) form along the line of closure of valve leaflet. Late stage fibrotic healing, the valve become thickened, fibrotic, deformed, fusion of valve cups, calsification are grouped under the term rheumatic heart disease.

The diseases involve :

1. 2.

3.

4.

Mitral valve involved in 65%-70% of cases. Combine aortic and mitral valve 20%40% of cases afffected a long the mitral valve. Tricuspid and pulmonary valve less frequently affected a long the mitral valve and the aortic valves in 5% cases. Pulmonary valve 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)

Endocarditis
1.

2.
3.

Cardiac disorders are marked mainly by valve vegetations Major examples : Infective endocarditis Nonbacterial thrombotic endocarditis Endocarditis associated with SLE (Libman-Sacks endocarditis)

Infective Endocarditis
Bacterial, fungal, infection of the endocardium involvement of valvular surfaces. Characteristics include large, soft, friable, easily detacted vegetations consisting of fibrin intermshed inflammatory cells and bacteria. Complication ulceration, perforation, rupture of chordae tendineae.

Classification 1. Acute endocarditis pathogens is highly virulent organism such as Staphylococcus aureus (50% of cases). Clinically rapidly developing fever with rigor, malaise weakness. Death occurs in days to weeks in 50%- 60% of cases.

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

Pathogenesis Bacteriemia are prerequisites that can come from infections from elsewhere in the body, intravenous drug abuse, dental or surgical procedures, injury to gut, urinary tract, oropharynx or skin, neutropenia and immunosuppression Endocarditis bacterial can occurs on normal valves and in certain valvular and others cardiac condition ( CHD, VSD, CRHD )

Morphology Friable 0.5-2.0 cm, microba laden vegetation Bulky (1-2cm) Vegetations are typically on the downstream margin of a jet lession Acute infective endocarditis has a large vegetations can cause embolic complication Subacute infective endocarditis tend to be small vegetations Ring abcess

Valvular involvement
Mitral valve Mitral valve along with the aortic valve Tricuspid valve 50% cases, most caused by staphylococcal infection.

Complications
Distal embolizations Septic infarcts Focal necrotizing glomerulitis caused by immune complex disease or by septic emboli

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

Nonbacterial thrombotic endocarditis

Marantic endocarditis Occurs in settings of cancer(adenocarcinomas), prolonged debilitating ilness, DIC Morphology: Small (1-5mm) sterile, bland fibrin, platelet thrombi Vegetations can embolize systemically

Endocarditis associated with SLE (Libman-Sacks endocarditis)

Pathogenesis uncertain Affected in mitral and tricuspid valves Findings : fibrinoid necrosis, mucoid degeneration, small, fibrinous, sterile vegetations

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