CARDIOVASCULAR PATHOLOGY

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CARDIOVASCULAR PATHOLOGY

• Tutorial II
• William H. Luer M.D.

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TOPICS

• Endocarditis
• Myocarditis
• Pericardial disease

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ENDOCARDITISCAUSES

• Rheumatic fever (covered in lecture)
• Infection
• Non-infective
• Nonbacterial thrombotic endocarditis
• Endocarditis of systemic lupus
• erythematosis (SLE)
• Carcinoid heart disease

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INFECTIVE ENDOCARDITIS

• Definition the infection of the endocardium
  (esp. heart valves) by a microbiological agent,
  with the formation of thrombotic debris and
  organisms known as vegetations.

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INFECTIVE ENDOCARDITIS CAUSES

• Bacteria, most common
• Fungi
• Rickettsiae (Q fever)
• Chlamydiae

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CAUSES OF BACTERIAL ENDOCARDITIS

• Alpha-hemolytic streptococci esp. with damaged
  or otherwise abnormal native valves
• Staphylococcus aureus healthy or deformed
  valves, esp. in intravenous drug abusers
• Coagulase-negative staphylococci esp. with
  prosthetic valves
• HACEK group Haemophilus, Actinobacillus,
  Cardiobacterium, Eikenella, Kingella
  (commensals of oral cavity)
• Gram-negative bacilli

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PREDISPOSING FACTORS FOR INFECTIVE ENDOCARDITIS

• Rheumatic heart disease
• Myxomatous mitral valve
• Calcific valvular stenosis
• Bicuspid aortic valve
• Artificial (prosthetic) valve (but may develop on
  previously normal valve)

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PREDISPOSING FACTORS (CONT.)

• Neutropenia
• Immunodeficiency
• Therapeutic immunosuppression
• Diabetes mellitus
• Alcohol or IV drug abuse
• Sepsis
• Invasive procedures

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PATHOLOGY OF INFECTIVE ENDOCARDITIS

• Vegetations of fibrin, inflammatory cells,
  bacteria or other organisms
• Vegetations located most commonly on heart
  valves, esp. aortic mitral
• Vegetations may erode perforate valve, may
  erode into underlying myocardium to produce an
  abscess (ring abscess)
• Vegetation may produce emboli that produce septic
  infarcts in brain, kidney, myocardium, other
  organs

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Vegetation
Stick in Perforation
Mitral Valve
Infective endocarditis with perforation of
mitral valve leaflet
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Microscopic View of Vegetation of Endocarditis,
Fibrin Inflammatory Cells
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CLINICAL FEATURES OF INFECTIVE ENDOCARDITIS

• Fever, chills
• Fatigue, weight loss, flu-like syndrome
• Murmur (may change as vegetation and/or damage to
  valve changes)
• Petechiae

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COMPLICATIONS OF INFECTIVE ENDOCARDITIS

• Valvular insufficiency or stenosis with resulting
  congestive heart failure
• Myocardial ring abscess
• Suppurative pericarditis
• Septic infarcts abscesses
• Focal diffuse glomerulonephritis

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NONBACTERIAL THROMBOTIC ENDOCARDITIS (NBTE)

• Definition The deposition of sterile
  vegetations on the leaflets of cardiac valves,
  also called MARANTIC ENDOCARDITIS

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NBTE PATHOLOGY

• Vegetations of fibrin, platelets, other blood
  elements (i.e.. a thrombus)
• Vegetations are sterile, nondestructive,
  noninflammatory small (1-5mm)
• Vegetations occur singly or multiply along the
  lines of closure of heart valves

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NBTE PATHOGENESIS

• Probably occurs as a consequence of a
  hypercoagulable state
• Seem with concomitant venous thrombosis /or
  pulmonary embolism
• May be seen with hyperestrogenic state, extensive
  burns, or endocardial trauma from indwelling
  catheters

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NBTE CLINICAL

• Local effect on valve unimportant
• May produce emboli with resultant infarcts
• May eventually organize leaving delicate strands
  of fibrous tissue

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ENDOCARDITIS OF SLE

• Also known as Libman-Sacks endocarditis
• Small sterile vegetations on mitral tricuspid
  valves or fibrous thickenings occurring with the
  antiphospholipid syndrome
• Circulating antiphospholipid antibodies also
  associated with venous or arterial thrombosis,
  recurrent pregnancy loss, and thrombocytopenia

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PATHOLOGY OF SLE ENDOCARDITIS

• Vegetations are small (1-4 mm), single or
  multiple, sterile, granular, and pink
• Frequently located on the undersurfaces of AV
  valves, but may be elsewhere on valves or even on
  mural endocardium of atria or ventricles
• Vegetations consist of finely granular fibrinous
  eosinophilic material
• May have valvulitis, characterized by fibrinous
  necrosis, contiguous with vegetation
• Can result in fibrosis and valve deformity that
  can resemble chronic rheumatic heart disease

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CARCINOID HEART DISEASE (CarHD)

• Seen in one half of patients with carcinoid
  syndrome (episodic skin flushing, cramps, nausea,
  vomiting, and diarrhea)
• Involves endocardium and valves of the right side
  of the heart

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CarHD PATHOLOGY

• Intimal thickenings on the inside surfaces of the
  cardiac chambers valvular leaflets, mainly on
  the right side of the heart
• Thickenings consist of smooth muscle cells
  sparse collagen fibers embedded in an acid
  mucopolysaccharide rich matrix that expands the
  endocardium
• Underlying structure of the heart intact

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CarHD PATHOPHYSIOLOGY

• Carcinoid tumors produce a variety of bioactive
  products including serotonin, kallikrein,
  bradykinin, histamine, prostaglandins,
  tachykinins
• Serotonin appears to induce the cardiac lesions

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CarHD LOCATION

• Lesions are usually right sided since serotonin
  inactivated by pulmonary vascular endothelial
  monoamine oxidase
• Can see left sided lesions if have high levels of
  serotonin not completely inactivated by lungs,
  pulmonary carcinoid, or right to left cardiac
  shunts

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CARCINOID-LIKE HEART LESIONS

• Left sided lesions can be seen with methysergide
  or ergotamine treatment for migraine headache
  since these serotonin analogs are metabolized to
  serotonin by lungs
• Left sided lesions can be seen with fenfluramine
  phemtermine (fen-phen) appetite suppressants
  since they affect serotonin metabolism

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MYOCARDITIS

• Definition inflammatory processes of the
  myocardium that result in injury to the cardiac
  myocytes.

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CAUSES OF MYOCARDITIS INFECTIONS

• Viruses (e.g., coxsackie, ECHO, HIV)
• Chlamydia (e.g., C. psittaci)
• Rickettsiae (e.g., R. typhi)
• Bacteria (e.g., C. diphtheria)
• Fungi (e.g., Candida)
• Protozoa (e.g., toxoplasmosis)
• Helminths (e.g., trichinosis)

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CAUSES OF MYOCARDITIS IMMUNE-MEDIATED

• Postviral
• Poststreptococcal (rheumatic fever)
• Systemic lupus erythematosus
• Drug hypersensitivity (e.g., methyldopa,
  sulfonamides)
• Transplant rejection

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CAUSES OF MYOCARDITIS OTHER

• Sarcoidosis
• Giant cell myocarditis

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MYOCARDITIS GROSS PATHOLOGY

• Heart may appear normal or dilated, some
  hypertrophy may be present
• Ventricular myocardium may be flabby and mottled
  by pale foci and/or minute hemorrhage foci
• May have mural thrombi

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MYOCARDITIS MICROSCOPIC PATHOLOGY

• Interstitial inflammatory infiltrate, may be
  patchy, most commonly have mononuclear cell
  infiltrate, predominantly lymphocytes
• Focal necrosis
• Hypersensitivity myocarditis has lymphocytes,
  macrophages, eosinophils
• Giant cell myocarditis has multinucleated giant
  cells with lymphocytes, eosinophils, plasma
  cells, macrophages with necrosis

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MYOCARDITIS MICROSCOPIC PATHOLOGY (cont.)

• Healing myocarditis results in fibrosis
• Chagas disease has parasitization of myofibers by
  Trypanosomes with neutrophils, lymphocytes,
  macrophages, and eosinophils

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MYOCARDITIS CLINICAL

• Fatigue, dyspnea, palpitations, precordial chest
  pain, fever
• Can be asymptomatic
• Heart failure, dilated cardiomyopathy
• Arrhythmias
• Mitral regurgitation
• Can result in sudden death

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PERICARDIAL DISEASE

• Pericardial effusion
• Pericardial hemorrhage
• Pericarditis

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PERICARDIAL EFFUSION

• Distention of pericardial sac by transudate
• Causes include infection, autoimmune disease,
  congestive heart failure, renal failure,
  malignancy, myocardial infarction, drugs, and
  radiation
• Clinically may see low blood pressure, dyspnea,
  dizziness, and chest pain
• If fluid compresses heart get cardiac tamponade
  with severe decrease in cardiac output

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PERICARDIAL HEMORRHAGE

• Bleeding into the pericardial sac
• Causes include cardiac rupture from myocardial
  infarction or perforating trauma and ruptured
  aortic dissection
• May produce compression of the heart with
  resulting cardiac tamponade

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PERICARDITIS TYPES

• Serous pericarditis
• Fibrinous serofibrinous pericarditis
• Purulent or suppurative pericarditis
• Hemorrhagic pericarditis
• Caseous pericarditis
• Adhesive mediastinopericarditis
• Constrictive pericarditis

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PERICARDITIS CAUSES

• Infections
• Rheumatic fever
• Autoimmune disease
• Drug reaction
• Myocardial infarction
• Uremia
• Malignancy
• Radiation

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SEROUS PERICARDITIS

• Characteristically produced by noninfectious
  inflammations (e.g. rheumatic fever, SLE,
  scleroderma, tumors, uremia)
• May be produced by adjacent infection (e.g.
  bacterial pleuritis)
• Microscopically see inflammatory reaction in
  epicardium and pericardium with PMNs,
  lymphocytes, and histiocytes
• Slow leakage of fluid of high specific gravity
  rich protein content into pericardial sac, (about
  50-200 ml)

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FIBRINOUS SEROFIBRINOUS PERICARDITIS

• Most frequent types of pericarditis
• Composed of serous fluid mixed with a fibrinous
  exudate
• Common causes include acute myocardial
  infarction, uremia, radiation, rheumatic fever,
  SLE, trauma, postinfarction syndrome

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FIBRINOUS SEROFIBRINOUS PERICARDITIS (CONT)

• In fibrinous pericarditis, have finely granular
  pericardial surface may produce a pericardial
  friction rub
• In serofibrinous pericarditis, inflammation leads
  to leakage of fluid inflammatory cells into
  pericardial sac in addition to fibrin
• Fibrin may be digested or organize

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Granular Visceral Pericardial
Surface of Fibrinous Pericarditis
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PURULENT OR SUPPURATIVE PERICARDITIS

• Pus in pericardial sac usually from infective
  organisms
• Acute inflammatory reaction involving pericardium
  with purulent exudate
• If survive usually organizes, may produce
  constrictive pericarditis

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HEMORRHAGIC PERICARDITIS

• Blood mixed with fibrin or pus
• Can be seen with tuberculosis and other bacterial
  infections, malignancy, and following cardiac
  surgery

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CASEOUS PERICARDITIS

• Usually due to tuberculosis
• Caseous granulomatosis inflammation involves the
  pericardium
• May lead to fibrocalcific chronic constrictive
  pericarditis

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ADHESIVE MEDIASTINOPERICARDITIS

• May follow suppurative or caseous pericarditis,
  cardiac surgery, or mediastinal radiation
• Pericardial sac obliterated adherence of the
  outer portion of the parietal pericardium to
  surrounding structures produces great stain on
  cardiac function
• Increased work on heart leads to cardiac
  hypertrophy and dilatation

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CONSTRICTIVE PERICARDITIS

• May follow suppurative, hemorrhagic, or caseous
  pericarditis
• Pericardial sac obliterated heart surrounded by
  dense adherent layer of scar tissue with or
  without calcification (if extreme encasement
  called concretio cordis)
• Encasing scar limits diastolic expansion of heart
  leading to decreased cardiac output