Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam Pathology notes prepared by Agam Divide and Rule
2020 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pathology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Vignesh M, who took the responsibility of leading the
team. The following are the name list of the team who worked together, to bring out the material in
good form.

• Kritika Malik
• Amrutha Priya Devi B
• Lavanya E
• Manivasagam R
• Sweta Laxmi S
• Aakash R
• Varsha L
• Keerthana Muthuraman
• Joy Christy A
• Sneha Yakkali
• Sowrathi L K
• Vignesh. M
 THE HEART
ESSAY:
1. Infective / bacterial endocarditis
2. Define Rheumatic fever, details about RHD
3. MI

SHORT NOTES:
1. Heart vegetations
2. Myocarditis
3. Hypertensive Heart Disease
4. Dilated cardiomyopathy
5. Tetralogy of Fallot

SHORT ANSWERS:
1. Superior Vena Cava Syndrome
2. Morphology of cardiac myxoma
3. Types of cardiomyopathy

UPDATES

PATHOLOGY AGAM
ESSAY
1. INFECTIVE ENDOCARDITIS:
 Infective endocarditis is a microbial infection of the heart valves or mural endocardium-
leads to vegetations formation
 Site : Heart valves , mural endocardium , aorta , aneurysm sacs etc.,
 Vegetations :– composed of Thrombolytic debris and organisms – associated with
destruction of underlying cardiac tissues

TYPES OF INFECTIVE ENDOCARDITIS:

FEATURES ACUTE SUBACUTE
Duration < 6 weeks >6 weeks
Organisms Staphyl aureus, Streptococci Streptococcus viridians
Virulence of organisms Highly virulent Less virulent
Previous condition of valves Previously normal Previously damaged
Lesion on valves Invasive , destructive , Usually not invasive or
suppurative suppurative
Clinical Features Features of acute systemic Splenomegaly , clubbing of
infection fingers , petechiae
Complications Acute heart failure/ Infectious complications
overwhelming sepsis are uncommon

ETIOLOGY - INFECTIVE AGENTS:

 Staphylococcus aureus –found on skin, can infect healthy or deformed valves.It is the
major organism responsible for infective endocarditis.
 Streptococcus viridians – normal flora of oral cavity, most commonly causes endocarditis
of damaged/infected valves.
 Other bacteria – HACEK group (Haemophillus, Actinobacillus, Cardiobacterium, Eikinella
and Kingella)
 Coagulase negative staphylococci ( eg- S.epidermitis )-Prosthetic Valve endocarditis
 Other agents : gram –ve bacilli , fungi

AGAM PATHOLOGY
 Pre-disposing Factors

Conditions with Bacteremia Underlying Heat Disease Impaired Host Defence

 Obvious infection  Chronic rheumatic  Leukemia ,

elsewhere. valvular disease. lymphomas
 Previous dental/surgical  Mitral valve prolapse  Cytotoxic therapy-
procedures.  Congenital heart cancer & transplant
 Contaminated needles disease  Neutropenia
by IV drug abusers.
 Obstretic procedures.
 Urinary Catherization

PATHOGENESIS:

PATHOLOGY AGAM
 Endocardial damage and denudation-
Damaged valve or a congenital defect creates an abnormal high velocity blood flow at the
centre and turbulent at the periphery → Cause endocardial damage and denudation of
endothelial surfaces.
 Formation of sterile thrombus:
Damaged endothelial surface → Attracts focal depostition of platelets/fibrin → Aggregation
of platelets and fibrin → Formation of small sterile vegetations (i.e. small thrombi)
 Adherence of microorganisms:
Development of transient bacteremia → Microorganisms enter the circulation → Adhere to
the small sterile vegetation → Infection of sterile thrombi.
 Proliferation of microorganisms within vegetations:
On the deposited microorganisms inside the affected valve, platelets and fibrin are also
deposited which separate them from the bloodstream. The microorganisms proliferate within
vegetations and form colonies.
 Formation of emboli:
The vegetation may get detached form the infective emboli→ Cause spread of infections
into the visceral organs and the brain.
MORPHOLOGY:
 Gross
 Aortic and Mitral valves are most commonly affected and in case of intravenous drug
abusers, the valves of the right heart are the most commonly affected.
 Vegetations-
They are the hallmark or pathognomic of Infective Endocarditis.
 Appearance- Friable, bulky and potentially destructive vegetations.
 Number- May be single or multiple; may involve one or more than one valve.
 Size- Variable, from superficial deposits to bulky exuberant vegetations.
 Changes in the valve: Inflammation and edema.
 Sites: Vegetations are formed on the atrial side of the atrioventricular valves,
ventricular side of the semilunar valves and at the points of closures of leaflets or
cusps.
 Microscopy
 Vegetations are composed of platelets, fibrin, inflammatory cells and masses
 Vegetations of subacute IE may show granulation tissue at the bottom which indicates
healing.
 Later calcification, fibrosis and inflammatory infiltrate can be seen.
AGAM PATHOLOGY
CLINICAL FEATURES:
Fever, chills, weakness, lassitude

MODIFIED DUKE CRITERIA :

MAJOR CRITERIA MINOR CRITERIA
 Blood culture  Predisposing heart lesions or Intravenous drug use
 Echocardiographic  Fever
identification of a valve  Vascular lesions
involvement  Immunological phenomena – glomerulonephritis; Osler node
 New valvular  Microbiological evidence
regurgitation  Echocardiographic findings

COMPLICATIONS:
 Cardiac : -
 Valvular stenosis or insufficiency
 Ring abscess in the valve
 Perforation , rupture and aneurysm
 Myocardial abscess
 Suppurative pericarditis

 Extracardiac :-
 Embolic complications (due to septic emboli)
 Osler nodes (They are small ,tender subcutaneous nodules that develop in the pulp of
digits or occasionally in fingers and persist for hours)
 Roth spots (retinal hemorrhages with white or pale centres composed of fibrin)
 Focal segmental glomerulonephritis (due to deposition of immune complexes in the
glomeruli)

PATHOLOGY AGAM
2. RHEUMATIC FEVER:
 It is an acute, post-streptococcal immunologically mediated,multisystem inflammatory
disease.
 Occurs few weeks after an episode of group A streptococcal pharyngitis.
 Most common in children between age of 5 to 15 years.
 Both sexes are equally affected.
 2 phases: Acute Rheumatic fever/ Carditis and Chronic Rheumatic heart disease.
 Acute rheumatic carditis is a common manifestation of active RF and progresses to Chronic
rheumatoid heart disease.

PATHOGENESIS

MORPHOLOGY:
 Cardiac lesions : Pancarditis: inflammation of three layers of heart
 Aschoff nodules :
 Hallmark of acute rheumatic fever : Aschoff bodies in heart
 Aschoff bodies consists of
 Foci of T-lymphocytes
 Plasma cells
 Antischkow cells (Pathognomonic)
 Macrophages with abundant cytoplasm and central round to ovoid nuclei
 Chromatin condenses into a central wavy ribbon hence “caterpillar cells” are
found in any layer of the heart resulting in pancarditis.
 Rarely seen in patients with chronic RHD.
 Extracardiac lesions :
 Polyarthritis  Rheumatic arteritis
 Subcutaneous nodules  Chorea minor
 Erythema marginatum  Rheumatic pneumonitis and pleuritis
AGAM PATHOLOGY
 ACUTE RHEUMATIC HEART DISEASE CHRONIC RHEUMATIC HEART DISEASE
ENDOCARDITIS
 Inflammation of endocardium  Vasculitis induced damage is cumulative and
(valvular \ mural ) with each attack it progress
 Rheumatic valvulitis – thickening and  Mitral valve most common and severely
loss of translucency of the valve affected ; Thickening of valve leaflet ; Fusion
leaflets or cusps; left sided valve more of commissures ( fish- mouth appearance );
infected; fibrin deposits along the Shortening , thickening and fusion of Chordae
closure of valves ; Verrucae-nodular tendineae; consequences are chronic venous
or warty vegetations congestion in lungs , pulmonary hypertension
 Rheumatic mural endocarditis –Mac  Aortic valve – 2nd most affected ; aortic
Callum’s stenosis present
 Tricuspid and pulmonary valve rarely affected
RHEUMATIC MYOCARDITIS
 Inflammation of myocardium;  Usually resolve
 Presence of Aschoff bodies;
 Frequent in interventricular septum,
left ventricle and left atrium.
RHEUMATIC PERICARDITIS
 Inflammation of pericardium;  Usually resolve
 fibrinous pericarditis – bread and
butter appearance
CLINICAL FEATURES:
 Manifests as migratory polyarthritis and fever
 Clinical findings of acute carditis – pericardial friction ribs , arrhythmia , cardiac murmurs
REVISED WHO DIAGNOSTIC CRITERIA – REVISED JONES CRITERIA
MAJOR CRITERIA MINOR CRITERIA
 Carditis  Fever
 Polyarthritis  Polyarthralgia
 Chorea (Sydenham’s chorea)  Previous history of RF
 Erythema marginatum  Laboratory findings – ↑ ESR; ↑ CRP; leukocytosis
 Subcutaneous nodules  ECG finding – prolonged PR interval
SUPPORTIVE EVIDENCE OF GROUP A STREPTOCOCCAL INFECTION IN PRECEEDING 45 DAYS
 Positive throat culture for group A streptococci
 Rapid antigen test for group A streptococcus
PATHOLOGY AGAM
3. MYOCARDIAL INFARCTION
Myocardial infarction is a coagulative necrosis of the cardiac muscle and is due to
prolonged severe ischemia.
RISK FACTORS:
 Age:
 Its frequency rises progressively with age and peak is between 40 - 60 years of age.
 It can develop in younger patients with major risks of Atherosclerosis (hyperlipidemia,
hypertension, diabetes and cigarette smoking)
 Sex:
 Males have significantly highter risk than females, mainly during the reproductive period
 After menopause, the risk is similar to that of males.
 The protective factor may be estrogen.
PATHOGENESIS:
 Acute plaque change: They are the sudden morphological changes occurring in an
atheromatous plaque. These include:
 Rupture and fissuring of the plaque: Rupture and fissuring of the plaque → Exposure of
highly thrombogenic plaque constituents → Sudden thrombus formation → Sudden
occlusion of the lumen.
 Erosion/ulceration of plaque: Exposes highly thrombogenous subendothelial basement
membrane → Sudden thrombus formation → Sudden occlusion of the lumen.
 Hemorrhage into the central core of the plaque: Hemorrhage into the central core of the
plaque → Increases plaque size → Sudden occlusion of the lumen.
 Factors triggering acute plaque change are:
 Intrinsic: Plaque composition and structure
 Extrinsic: Blood pressure and platelet reactivity.
 Formation of microthrombi: Exposure of subendothelial collagen after acute plaque
changes → Platelets adhere to the site → Platelet activation and aggregation → Formation
of microthrombi on the atheromatous plaque → Partial/ complete occlusion of the
coronary artery.
 Vasospasm: Activated platelets, endothelial cells and inflammatory cells release mediators
→ Cause vasospasm at the sites of atheroma → Further narrowing of the lumen.
 Activation of the coagulation pathway: Tissue factor released at the place of plaque
change → activates coagulation system → Increase in the size of the thrombus.
 Complete occlusion of the vessel: Within minutes, the thrombus may completely occlude
the lumen of the vessels.
AGAM PATHOLOGY
 Myocardial occlusion: Complete occlusion → Results in ischemic coagulative necrosis of
the area supplied by the particular coronary artery. The anatomic area supplied by that
artery is called “area at risk”.

CONSEQUENCES OF MYOCARDIAL INFARCTION:

 Reversible injury: These changes are potentially reversible and they include:
 Biochemical changes: Cessation of aerobic glycolysis occurs within seconds of
myocardial ischemia → Decreased production of ATP→ accumulation of potentially toxic
metabolites (such as lactic acid).
 Functional disturbances: Loss of contractility within 60 seconds →can precipitate acute
heart failure.
 Morphological changes: They are seen at ultrastructural level such as mitochondrial
swelling, glycogen depletion and myofibrillar relaxation. They also develop within a few
minutes.
 Irreversible injury: It develops only after prolonged, severe myocardial ischemia of more
than 20–40 minutes.
 Biochemical changes:
 They cause leakage of cytoplasmic proteins into the blood.
 In the early phases of myocardial cell necrosis, there is breakdown of the
sarcolemmal membrane → leakage of intracellular proteins (such as myoglobin,
LDH, CK, and troponins I and T) into the blood.
 The levels of these leaked myocardial proteins in the blood is used for the diagnosis
as well as management of MI.
 Functional changes: Arrhythmias.
 Morphological changes: Coagulative necrosis of cardiac muscle fibres.
 Pattern of infarctions :
 Transmural infarction – ST Elevation Myocardial Infarct(STEMI)
 By occlusion of Epicardial vessels.
 Caused by combination of Coronary atherosclerosis, acute plaque change &
Superimposed thrombus.
 Subendocardial (Non transmural) Infarction (Non STEMI)
 Seen in severe reduction in BP as in Shock , Chronic Coronary Stenosis.
 Multifocal Microinfarction
 In Microembolization of small intramural vessels.
 Vasculitis
 Endogenous elevated levels of Catechols.
PATHOLOGY AGAM
GROSS:.
 Within first 12 hours:
 No identifiable/apparent gross changes are seen.
 Triphenyl tetrazolium chloride (a histochemical stain) can grossly identify infarct within
 2–3 hours after onset.
 Non-infarcted myocardium appears brick-red (LDH activity is preserved)
 Infarcted area remains unstained pale (loss of dehydrogenases).
 Old infarcts appear white and glistening.
 By 12–24 hours:
 Grossly identifiable.
 Appears pale reddish-blue area (due to stagnated, trapped blood)
 Progressively becomes sharply defined, yellow-tan, and soft.
 After 3–5 days: Mottled with a central pale, yellowish,necrotic region with well-demarcated
border of hyperemic zone (due to granulation tissue).
 By 10 days to 2 weeks: Appears soft and rimmed by a hyperemic zone of highly vascularized
granulation tissue.
 After 2 weeks: Older, healed infarcts appear firm,pale gray and contracted develops into a
fibrous scar.

AGAM PATHOLOGY
MORPHOLOGY:
 Most of transmural infarcts (>50%) involve at least a portion of the left ventricle and/or
interventricular septum.
 Isolated infarction of the right ventricle and infarction of the atria are rare.
 Pattern of left ventricular infarcts:
 Left anterior descending (LAD) coronary
artery occlusion (40–50%): Infarcts involve:
 Anterior wall of left ventricle near the
apex
 Anterior portion of ventricular septum
 Apex circumferentially.
 Right coronary artery occlusion (30–40%):
Infarcts involves:
 Region of the inferior/posterior wall of
left ventricle
 Posterior portion of interventricular septum (inferior infarct)
 Inferior/posterior right ventricular free wall (in some).

COMPLICATIONS OF MI:
 Contractile dysfunction: Left ventricular failure with hypotension, Pulmonary vascular
congestion and Interstitial pulmonary transudates→ Pulmonary edema and Respiratory
impairment → Pump failure (Cardiogenic shock)
 Arrhythmias: Due to myocardial irritability/Conductance disturbance there is Sinus
Bradycardia, Atrial fibrillation, Heart block, Tachycardia, Ventricular premature contraction,
Ventricular Tachycardia & ventricular Fibrillation.
 Myocardial Rupture :
 Rupture of ventricular free wall with Hemopericardium and Cardiac tamponade.
 Rupture of Ventricular septum- Acute VSD & Lt to Rt Shunting.
 Papillary muscle rupture – Mitral regurgitation.
 Ventricular aneurysm: True Aneurysm → Due to ventricular wall weakened by coagulative
necrosis, Neutrophilic infiltration and Lysis of Myocardial connective tissues.
 Pericarditis: Fibrinous or Fibrohomarrhagic pericarditis due to myocardial inflammation
(Dressler Syndrome).
 Infarct Expansion: Due to weakening of necrotic muscle there is stretching, thinning and
dilation of infarct region.

PATHOLOGY AGAM
 Mural thrombus: Local abnormality in contractibility and endocardial damage leads to
mural thrombus and thromboembolism.
 Papillary muscle dysfunction: Mitral/Tricuspid incompetence due to ischemic dysfunction
of papillary muscles.
 Progressive late heart failure.

LAB DIAGNOSIS OF MI :
 Based on blood levels of protein that leak out of irreversibly damaged myocytes.
 Ratte of appearance depends on intra cellular location , Molecular weight, Blood flow,
lymphatic drainage and rate of elimination from blood.
 Most sensitive and specific biomarker: cTnT and cTnI
 Enzymes in MI (Mnemonic: My Time To CALL)
 Myoglobin
 Troponin T
 Troponin I
 Creative kinase
 AST
 LDH
 Cardiac Troponin T (cTnT)
 Begins to rise at 3-12 hrs
 Peak at 12- 48 hrs
 Cardiac Troponin I (cTnI)
 Begins to rise at 3-12 hrs
 Peak at 24 hrs
 Creatine kinase MB (CK-MB)
 Sensitive
 Not specific (elevated after
skeletal muscle injury)
 Begins to rise at 3-12 hrs
 Peak at 24 hours
 Returns to normal in 48-72 hrs

AGAM PATHOLOGY
SHORT NOTES:
1. HEART VEGETATIONS:
INFECTIVE ENDOCARDITIS
 Microbial infection of heart valve or mural endocardium results in formation of vegetation
(thrombotic debris + organisms)
 Friable, bulky, potentially destructive lesions containing fibrin, inflammatory cells and
bacteria
 Single or multiple and may involve more than one valve
 Prone to embolization and lead to septic infarcts and mycotic aneurysm
Aortic and mitral affected > right heart valve (IV Drug abuser)
 Acute infective endocarditis :
 Staph aureus infection of a previously normal heart
 Necrotising and destructive lesions
 Subacute infective endocarditis :
 Infection of deformed valve by lower virulent organism
 Overall less destruction
 Exhibit granulation tissue at their bases → fibrosis → calcification → chronic
inflammatory infiltrate.

NON INFECTIVE VEGETATIONS

 Nonbacterial thrombotic endocarditis (NBTE)
 Deposition of small sterile thrombi on the leaflets of the cardiac valves
 Single or multiple
 Location : Along the line of closure of the leaflets/ cusps
 Histologically :
 Bland thrombi loosely attached to the underlying valve
 Non invasive
 Do not elicit inflammatory reactions
 Source of systemic emboli leading to infarcts in brain, heart
 Common in cancer and sepsis patient (debilitated patients) and hence name marantic
endocarditis & endocardial trauma
 Strong association with mucinous adenocarcinoma

PATHOLOGY AGAM
 Endocarditis of SLE (Libman-sacks disease)
 Mitral and tricuspid valvulitis with sterile vegetations
 Morphology : single or multiple, oink vegetations with a warty appearance
 Location : Under surfaces of atrioventricular valves, valvular endocardium, chords,
mural endocardium of atria and ventricles (Mitral valve >> aortic valve)
 Histologically : finely granular, fibrinous eosinophilic material containing cellular
debris including nuclear remnants

2. MYOCARDITIS
 Inflammation of myocardium muscle due to infection / primary inflammatory response.
FEATURES:
 Ventricular myocardium is
flabby and often mottled by
either pale foci or minute
hemorrhagic lesions.
 Active myocarditis is
characterized by an interstitial
inflammatory infiltrate
associated with focal myocyte
necrosis
 A diffuse, mononuclear,
predominantly lymphocytic
infiltrate is most common
 Hypersensitivity myocarditis
has interstitial infiltrates,
principally perivascular, composed of lymphocytes, macrophages, and a high proportion of
eosinophils
 A morphologically distinctive form of myocarditis, called giant-cell myocarditis, is
characterized by a widespread inflammatory cellular infiltrate containing multinucleate
giant cells (fused macrophages) interspersed with lymphocytes, eosinophils, plasma cells,
and macrophages. Focal to frequently extensive necrosis is present.
 The myocarditis of Chagas disease is distinctive by virtue of the parasitization of scattered
myofibers by trypanosomes accompanied by a mixed inflammatory infiltrate of neutrophils,
lymphocytes, macrophages, and occasional eosinophil

AGAM PATHOLOGY
3. HYPERTENSIVE HEART DISEASE
 Causes pressure overload and ventricular hypertrophy.
 Although most commonly seen in the left heart as the result of systemic hypertension
 Pulmonary hypertension can cause right-sided HHD, or cor pulmonale.

PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE (COR -PULMONALE)

 Due to right ventricular pressure overload.
 Chronic cor pulmonale is characterized by
 Right ventricular hypertrophy
 Dilation
 Right-sided failure.
 Right ventricular wall thickness ≥ 1.0 cm
 Acute cor pulmonale can follow massive pulmonary
embolism.
 Marked dilation of the right ventricle without
hypertrophy
 Cross-section: the normal crescent shape of the right ventricle is transformed to a dilated
ovoid.
 Pulmonary hypertension most commonly occurs as a complication of left-sided heart
disease

SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE

Pathologic criteria for the diagnosis of systemic HHD
 Left ventricular hypertrophy (usually concentric) in the absence of other cardiovascular
pathology.
 Clinical history or pathologic evidence of hypertension in other organs (e.g., kidney).
 Weight of heart ≥500 gm
 Thickness ≥2.0 cm
Hypertension

Left ventricular pressure overload hypertrophy (initially without ventricular dilation)

Left ventricular wall thickening increases the weight and increase in overall cardiac size

PATHOLOGY AGAM
Features:
 Associated with increased interstitial connective tissue with consequent left atrial
enlargement.
 Compensated systemic HHD may be asymptomatic, producing only electrocardiographic or
echocardiographic evidence of left ventricular enlargement.
 In many patients, systemic HHD comes to attention due to new atrial fibrillation induced by
left atrial enlargement, or by progressive CHF.
Microscopically
 Earliest change of systemic HHD is an increase in the transverse diameter of myocytes,
 At a more advanced stage accompanied by interstitial fibrosis.

4. DILATED CARDIOMYOPATHY
Characterized morphologically and functionally by progressive cardiac dilation and
contractile (systolic) dysfunction, usually with concomitant hypertrophy.
PATHOGENESIS
 Genetic Influences
 Mutations in TTN , gene that encodes titin(20%)
 In genetic forms of DCM, autosomal dominant
inheritance is the predominant pattern.
 Mitochondrial genes that result in defects in
oxidative phosphorylation.
 Mitochondrial defects typically manifest in the
pediatric population, while X-linked DCM
typically presents after puberty and into early
adulthood.
 Mutations in genes encoding enzymes involved
in β-oxidation of fatty acids.
 X-linked cardiomyopathy can also be associated
with mutations affecting the membrane-associated dystrophin protein (Duchenne and
Becker muscular dystrophies)
 Alcohol and other toxins
 Alcohol or its metabolites (especially acetaldehyde)
 myocardial injury caused by certain chemotherapeutic agents, including doxorubicin (
 Targeted cancer therapeutics (e.g., tyrosine kinase inhibitors).
 Cobalt is an example of a heavy metal with cardiotoxicity and has caused DCM
AGAM PATHOLOGY
 Childbirth: A special form of DCM, termed peripartum cardiomyopathy, can occur late in
pregnancy or up to months postpartum
 Iron overload in the heart: Hereditary hemochromatosis or from multiple transfusions.
 Supraphysiologic stress
 Persistent tachycardia, hyperthyroidism, or even during development.
 Excess catecholamines: secondary to intracranial lesions or emotional duress. i.e
Takotsubo cardiomyopathy :
 Left ventricular contractile dysfunction following extreme psychological stress
 Affected myocardium may be stunned or show multifocal contraction band necrosis.
 “Apical ballooning” that resembles a “takotsubo,” Japanese for “fishing pot for
trapping octopus”
HISTOLOGY
 The histologic abnormalities in DCM are nonspecific and usually don’t point to an etiology.
 Myocyte hypertrophy and interstitial fibrosis

5. TETRALOGY OF FALLOT
 VSD
 Obstruction of the right ventricular outflow
tract (subpulmonary stenosis)
 an aorta that overrides the VSD and
 right ventricular hypertrophy
 Heart is typically enlarged and is classically “boot-
shaped” due to marked right ventricular
hypertrophy.
 VSD is usually large with the aortic valve at the
superior border, thereby overriding the defect and
both ventricular chambers.
 The obstruction to right ventricular outflow is most often due to narrowing of the
infundibulum (subpulmonic stenosis) but can be accompanied by pulmonary valvular
stenosis.
 Sometimes there is complete atresia of the pulmonary valve and variable portions of the
pulmonary arteries, such that blood flow through a PDA, dilated bronchial arteries, or both,
is necessary for survival. Aortic valve insufficiency or an ASD may also be present; a right
aortic arch is present in about 25% of cases.

PATHOLOGY AGAM
SHORT ANSWERS:
1. SUPERIOR VENA CAVA SYNDROME
 Compression or invasion of the SVC due to bronchogenic carcinoma or mediastinal lymph
node or lesions from mediastinum like aortic aneurysm.
 Leads to marked dilation of veins of the head, neck and arm with cyanosis.
 Pulmonary vessel compression leads to respiratory distress.
 Clinical Features:
 Cerebral Edema
 Headache
 Swollen Face
 Cyanosis
 Dyspnoea
 Collateral Circulation
 Right Arm swelling

2. CARDIAC MYXOMA
These tumors are usually single sometimes multiple.
 Fossa ovalis in the atrial septum favored.
 Size ranges from small (<1cm) to large (>=10cm) and can be sessile or pedunclated.
 Pedunculated form is mobile and moves to the atrioventricular valve during systole leading
to intermittent obstruction.
 Sometimes exert wrecking ball effort damaging valve leaflets.
 Associated with Carney Syndrome.
 Histology:
 Myxomas are stellate or globular myxoma cells embedded within acid
mucopolysaccharide (Lepidic cells).
 Peculiar vessels or gland like structures are characteristic.
 Hemorrhage and mononuclear inflammation is present.

3. TYPES OF CARDIOMYOPATHY
 Dilated cardiomyopathy – Enlarged ventricle
 Hypertrophic cardiomyopathy – Enlarged stiff septum
 Restrictive cardiomyopathy – Walls of ventricle become stiff

AGAM PATHOLOGY
UPDATES
1. CARDIAC REGENERATION:
 There is considerable interest in replacing damaged myocardium by inducing cardiac
regeneration in vivo or implanting stem cell–derived cardiac cells.
 Implanted cells may show some cardio myocyte differentiation, but the durability of this
benefit has been limited, and they do not contribute significantly to the restoration of
contractile force; moreover, failure to successfully integrate these cells into the conduction
pathways of the host heart carries the very real risk of autonomous arrhythmic foci.
.
2. RIGHT SIDED HEART FAILURE:
 In many cases of chronic cardiac decompensation, patients with biventricular CHF have
symptoms reflecting both right-sided and left-sided heart failure.
 Besides a careful history and physical examination, serum levels of B-type (or brain)
natriuretic factor (BNP) have become a tool to quantitatively assess the extent of CHF.
 BNP is released by ventricular cardio myocytes during increased wall stress; a low value has
a high negative predictive value for CHF.
 Echocardiography provides a measure of ejection fraction, wall motion, valvular function,
and possible mural thrombosis.

3. TRANSPOSITION OF GREAT ARTERIES:

 In the less common levo -TGA (l-TGA, also commonly referred to as “congenitally
corrected” TGA), the right atrium connects to a ventricle with the internal morphology of a
left ventricle (atrio ventricular discordance), which in turn empties into the pulmonary
arteries (ventriculo arterial discordance)
 At the same time, the left atrium connects to a morphologic right ventricle, which empties
into the aorta l-TGA does not lead to cyanosis and indeed can be entirely asymptomatic,
being diagnosed in adulthood only during a workup for other cardiac issues.
 Nevertheless, l-TGA will result in hypertrophy of the morphologic right ventricle and
eventually can cause heart failure; it is also often associated with other CHD such as VSD,
ASD, and patent foramen ovale.

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4. “ADULT” POSTDUCTAL COARCTATION:
 In the more common “adult” postductal coarctation, theaorta is sharply constricted by a
tissue ridge adjacent to the non-patent ligamentum arteriosum.
 The constricted segment is made up of smooth muscle and elastic fibers derived from the
aortic media. Proximal to the coarctation, the aortic arch and its branch vessels are dilated
and the left ventricle is hypertrophied.

5. PREDUCTAL COARCTATION:
 Preductal coarctation is characterized by circumferential narrowing of the aortic segment
between the left subclavian artery and the ductus arteriosus;
 The ductus typically is patent and is the main source of (unoxygenated) blood delivered to
the distal aorta.
 The pulmonary trunk is dilated to accommodate the increased blood flow; because the
right side of the heart now perfuses the body distal to the narrowed segment (“coarct”),
the right ventricle typically is hypertrophied.

6. INITIAL THERAPIES FOR ACUTE MI:

 Oxygen supplementation to improve blood oxygen saturation for patients with hypoxia or
respiratory distress
 Nitrates to induce vasodilation and reverse vasospasm
 Antiplatelet agents such as aspirin, ADP receptor inhibitors, and GPIIb /IIIa inhibitors.
 Anticoagulant therapy with unfractionated heparin, low molecular weight heparin, direct
thrombin inhibitors, and/or factor Xa inhibitors to prevent coronary artery thrombus
propagation.
 Beta blockers to decrease myocardial oxygen demand and to reduce the risk of
arrhythmias, unless contraindicated such as in heart failure.
 Prompt reperfusion to salvage myocardium, by either fibrinolytic medications or
transcatheter intervention.
 Improve myocardial oxygen supply versus demand by management of other factors, such
as anxiety, ischemic pain, abnormal hemodynamics, anemia, and respiratory disorders.
 Early arrhythmia monitoring and management.

AGAM PATHOLOGY
7. CLINICAL FEATURES OF MI:
 Owing to the characteristic electrocardiographic changes resulting from myocardial
ischemia or necrosis in various distributions, a transmural infarct is sometimes referred to
as an ST-elevation myocardial infarct (STEMI) and a sub endocardial infarct as a non–ST-
elevation infarct (NSTEMI).
 Depending on the extent and location of the vascular involvement, micro infarctions show
nonspecific changes or can even be electrocardiographically silent.
 Cardiac troponins begin to rise in 2 to 4 hours and peak at 24 to 48 hours after an acute
infarct.
 With reperfusion, troponin levels may be higher and peak earlier owing to more rapid
washout of the marker from the necrotic tissue.
 Significant acute elevation in serum troponin can also be seen in other conditions that
cause death of cardiac myocytes, such as myocarditis and myocardial trauma.
 On the other hand, low-level serum troponin elevation (“troponin leak”) can occur in a host
of other conditions, including congestive heart failure, pulmonary embolus, renal failure,
and sepsis.
 These elevations do not usually follow the same abrupt-injury time course, so serial
measurements may be helpful in distinguishing different etiologies.

8. VALVULAR HEART DISEASE OCCURANCE:

 Stenosis or insufficiency can occur alone or together in the same valve.
 Valvular disease can involve only one valve (the mitral valve being the most common
target) or more than one valve.
 Abnormal flow through diseased valves typically produces abnormal heart sounds called
murmurs; severe lesions can even be externally palpated as thrills.
 Depending on the valve involved, murmurs are best heard at different locations on the
chest wall; moreover, the nature (regurgitation versus stenosis) and severity of the valvular
disease determines the quality and timing of the murmur (e.g., harsh systolic or soft
diastolic murmurs).

9. PATHOGENESIS OF ACUTE RHEUMATIC FEVER:

 In keeping with immunologic basis, streptococci are completely absent from the lesions.
 A genetic susceptibility is likely to influence the development of the cross-reactive immune
responses.
 The chronic fibrotic lesions are the predictable consequence of healing and scarring
associated with the resolution of the acute inflammation.
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10. COMPLICATIONS OF IE:
 Sepsis, arrhythmias (suggesting invasion into underlying myocardium and conduction
system), and systemic embolization bode particularly ill for the patient.
 Left untreated, IE generally is fatal.
 However, with appropriate long-term (6 weeks or more) antibiotic therapy and/or valve
replacement, mortality is reduced.
 For infections involving low-virulence organisms (e.g., S. viridans), the cure rate is 98%, and
for enterococci and S. aureus infections, cure rates range from 60% to 90%; however, with
infections due to gram-negative bacilli or fungi, one-half of the patients ultimately
succumb.
 The cure rate for endocarditis arising on prosthetic valves is uniformly worse, and valve
replacement is commonly required.

11. HISTOLOGIC ABNORMALITIES IN DCM:

 Most muscle cells are hypertrophied with enlarged nuclei, but some are attenuated,
stretched, and irregular.
 In DCM caused by truncating mutations in the titin gene, myocytes may exhibit
hyperchromatic, highly distorted “Ninja star”-like nuclei although these can be a
nonspecific finding, identifying them in greater than or equal to 5% of myocytes is highly
suggestive of a titin-truncation mutation.

12. PRIMARY CARDIAC TUMORS:

 Primary malignant tumors of the heart are exceedingly rare, and usually are either an
angiosarcoma or a sarcoma with poor differentiation and MDM2 oncogene amplification.
 These and other sarcomas of the heart are not clinically or morphologically distinctive from
sarcomas arising in other locations.
 Fibromas and lipomas resemble their counterparts elsewhere; only the myxomas, papillary
fibro elastomas, and rhabdomyomas merit further mention here.

AGAM PATHOLOGY
13. CARDIAC TRANSPLANTATION:
 Antibody-mediated rejection is also recognized as a mechanism of injury; donor-specific
antibodies directed against major histocompatibility complex proteins lead to complement
activation and the recruitment of Fc receptor–bearing cells.
 These donor-specific antibodies cause allograft compromise by inducing endothelial cell
injury leading to microvascular damage with thrombosis.
 Antibody mediated rejection shows mild perivascular edema and scattered adherent
intravascular inflammatory cells; it is often confirmed by immune histochemical staining for
complement fragment C4d, a long-lived catabolite that is released during complement
cascade activation.

14. ONE LINERS:

 Atrial cardio myocytes have cytoplasmic storage granules that contain atrial natriuretic
peptide, and ventricular myocytes contain B-type natriuretic peptide.
 Valve endothelium do not express ABO or histocompatibility antigens, so cryopreserved
valvular tissues can be transplanted with relative immunity.
 There is considerable interest in exploring the possibility of replacing damaged myocardium
by inducing cardiac regeneration in vivo or implanting stem cell–derived cardiac cells.
 “Tolerated” forms of Congenital Heart Disease usually produce clinically important
manifestations only after birth—uncovered by the transition from fetal to perinatal
circulation; roughly one-half will be diagnosed in the first year of life, although some milder
forms may not be discovered until adulthood (e.g., ASD).
 Preservation of ductal patency (by administering prostaglandin E1) may be life-saving for
infants with various congenital malformations that obstruct the pulmonary or systemic
outflow tract.
 Genetic factors include specific loci implicated in familial forms of CHD and certain
chromosomal abnormalities (e.g., trisomies 13, 15, 18, and 21, and monosomy X/Turner
syndrome).
 Aortic stenosis and atresia affected patients require surgeries that allow the right ventricle
to become the pump for the systemic circulation, with the lungs perfused from either a
parallel right ventricular conduit or passively from the venae cavae.
 Measurements of coronary flow across the stenosis (flow reserves) provide a better
assessment of the consequences of fixed coronary artery occlusions, when multifocal.
 Most atherosclerotic stenoses can be accessed by coronary catheterization.

PATHOLOGY AGAM
 Acute plaque changes—typically associated with intra lesional inflammation—precipitate
the formation of a superimposed thrombus that partially or completely occludes the artery.
It remains to be seen whether aggressive anti-inflammatory regimens are a means to
reduce such acute coronary events.
 Bicuspid valves incur greater mechanical stress than normal tricuspid valves, which may
explain their accelerated stenosis.
 Turbulence induced by ongoing valvular deformities leads to additional fibrosis. This is a
prime example of a common theme in valvular heart disease in which the consequences of
valve pathology may contribute to progression of that valve pathology in a positive
feedback loop.
 Increasingly—especially in patients who are not good “open” surgical candidates—bio
prosthetic valves are deployed by catheter-based approaches (transcatheter aortic valve
replacement or TAVR) wedging the new valve into the outflow tract without resecting the
original diseased valve.
 In pregnant women with a particular genetic predisposition, elevated antiangiogenic
molecules can potentially lead to a micro vascular angiogenic imbalance (micro vascular
loss in excess of angiogenesis), ultimately resulting in functional ischemic injury.
 Many of the causal mutations involve genes encoding desmosomal junctional proteins at
the intercalated disk (e.g., plakoglobin) as well as proteins that interact with the
desmosome (e.g., the intermediate filament desmin).
 Radiation used to treat breast, lung, or mediastinal neoplasms can cause pericarditis,
pericardial effusion, and chronic pericardial disorders.
 Anthracycline toxicity is dose-dependent, with the cardio toxicity risk increasing when
cumulative lifetime doses exceed 250 mg/m2
 Chamber dilation in MI: Because of the weakening of necrotic muscle, there may be
disproportionate stretching, thinning, and dilation of the infarcted region (especially with
antero septal infarcts).
 Endomyocardial fibrosis is linked to nutritional deficiencies and/or inflammation related to
parasitic infections (e.g., hypereosinophilia); worldwide, it is the most common form of
restrictive cardiomyopathy
 More recently, immune checkpoint inhibitors administered for treatment of cancer have
occasionally led to an (often fatal) lymphocytic myocarditis.
 Infections and malignancies, particularly Epstein-Barr virus–associated B-cell lymphomas
that arise in the setting of chronic T-cell immunosuppression – a post-operative
complication of heart transplantation
AGAM PATHOLOGY
 Radiation causing myocardial disease: Radiation therapy to the thorax can cause free
radical damage that in turn can lead to fibrosis of any of the cardiac structures;
manifestations include accelerated atherosclerosis, valvular stenosis, pericardial
constriction, and/or a restrictive cardiomyopathy due to interstitial fibrosis.

15. NEW TOPICS DISCUSSED:

 Pg 534 – Treatment of CHF
 Pg 551 – Consequences and Complication of MI (updated)
 Pg 580 – Metastatic tumours
 Pg 580 – Cardiac devices
 Pg 581 – Ventricular assist devices

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