pathology

• Rheumatic fever


  An auto-immune collagen disease characterized by inflammatory changes affecting the fibrous tissue of different body organs specially the heart and joints
• Rheumatic fever


  • Age: 5-15 years
• Predisposing factors for rheumatic fever

  • Upper respiratory tract infections
  • Low socioeconomic conditions such as damp weather, overcrowding and poor housing
• Pathogenesis of rheumatic fever

  1. Group A beta hemolytic streptococcal infection causes an upper respiratory tract infection (tonsillitis and pharyngitis) after a latent period of 2-4 weeks

  2. Antigenic similarity (Cross Reactivity): antibodies against streptococcal antigens (M protein) as ant streptolysin O (ASO) and anti-hyaluronidase reacts with human tissue antigens, since both are immunologically identical

  3. Altered Antigenicity: Binding of streptococcal antigen to human tissue antigens rendering them antigenic, producing antibody against self-antigens (autoantibody)
• Organs affected by rheumatic lesions

  • Heart
  • Joints
  • Ligaments and tendons
  • Skin
  • Brain
  • Serous membranes
  • Lung
• Stages of rheumatic fever

  1. Acute stage - occur in all organs and characterized by production of specific lesion (Aschoff nodule)

  2. Chronic stage - affecting mainly the heart and characterized by fibrosis which is responsible for the complication of rheumatic fever
• Cardiac lesions in rheumatic fever

  • All layers of the heart are affected (pancarditis) including pericarditis, myocarditis and endocarditis
  • Usually the left side is more affected than the right one
• Aschoff's nodules


  Grayish in color, 1-2 mm in diameter, collagen fibers undergo fibrinoid degeneration or necrosis surrounded by inflammatory reaction, Aschoff's cells (modified cardiac histiocytes) and Aschoff's giant cells present, cardiac muscles near show edema, necrosis and infiltration
• Fibrinous pericarditis


  Formed of scanty serous exudate and excess fibrin deposition on both visceral and parietal layers of pericardium giving the appearance of bread and butter appearance
• Pericardial lesions


  • Milk patches or milk spots (white patch of fibrosis on the surface of the heart)
  • Adhesive mediastino pericarditis (adhesions between visceral and parietal pericardium and between parietal pericardium and surrounding mediastinal structures)
• Mural endocardial lesion


  Aschoff's nodules mainly on the posterior wall of the left atrium, healing by fibrosis giving white fibrous patch (MacCallum's Patch)
• Valvular endocardial lesion


  • Acute rheumatic valvulitis (swollen cusps with marked edema, infiltration by histiocytes, lymphocytes and plasma cells, adherence of cusps leading to stenosis)
  • Rheumatic vegetations (degeneration and necrosis of endothelium at line of contact of inflamed cusps, firm, adherent, 1-3 mm in size, on atrial surface of mitral and tricuspid valves and over the chordae tendineae)
• Chronic rheumatic valvulitis


  Fibrotic, thick, irregular with calcified patches, chordae tendineae fibrosed, thick and short, abnormal vascularization, fibrosis, hyalinosis and sometimes calcification, retraction of cusps causing incompetence
• Joint lesions in rheumatic fever

  • Affect large joints of extremities, characterized by fleeting arthritis (one joint affected after the other), joint enlarged, swollen, red, hot and painful, joint cavity shows turbid serous exudate, synovial membrane, capsular and pericapsular tissues show congestion, edema and infiltration, articular cartilage not affected, resolution with complete restoration of joint function
• Subcutaneous nodules


  Few in number, up to 2 cm in size, in relation to spine, elbow, wrist and superior occipital protuberance, same structure as Aschoff's nodules
• Brain lesions (chorea)


  Involuntary, purposeless movements particularly of the extremities, edema, thrombosis, hemorrhage and perivascular round cell infiltration in basal ganglia and cerebral cortex
• Other lesions in rheumatic fever

  • Pleura and peritoneum show serofibrinous inflammation
  • Aschoff's nodules form in media and adventitia of large arteries
• Complications of rheumatic fever

  • Myocardial fibrosis
  • Subacute infective endocarditis affecting formed valve
  • Valvular stenosis or incompetence
  • Pericardial adhesions ending in congestive heart failure
• Thrombosis

  Formation of a compact mass composed of the elements of the circulating blood inside a vessel or heart cavity during life
• Causes of thrombosis (Virchow's Triad)

  • Endothelial injury
  • Alteration in normal blood flow
  • Hypercoagulability
• Endothelial injury

  • Can act without combination with other factors
  • Causes: Degenerative, Mechanical, Inflammation
• Alterations in normal blood flow

  • Turbulence caused by endothelial injury or dysfunction, forming countercurrents
  • Local pockets of stasis e.g. aneurysms, varicose veins, atheroma, compression
  • Stasis is a major contributor in the development of venous thrombi
• Causes of hypercoagulability (thrombophilia)

  • Acquired: Platelets, Fibrinogen, RBCs, WBCs, Plasma
  • Inherited: Point mutations in factor V gene and prothrombin gene
• Mechanism of thrombosis

  1. Platelet adhesion

  2. Platelet secretion

  3. Platelet aggregation

  4. Activation of coagulation cascade
• Primary hemostasis (Reversible thrombus)


  • Platelet adhesion to exposed endothelial matrix via vWF
  • Platelet secretion of ADP and TXA2
  • Platelet aggregation
• Secondary hemostasis (Irreversible thrombus)


  • Platelet factor III activates coagulation cascade
  • Tissue factor activates coagulation cascade
  • Thrombin converts fibrinogen to fibrin
• Classification of thrombi


  • By color: pale, red & mixed
  • By size: non-occlusive, occlusive and propagating
  • Septic or aseptic
  • Site: Arterial, Cardiac, Venous
• Morphology of thrombi

  • Lines of Zahn: Laminations representing pale platelet and fibrin deposits alternating with darker red cell-rich layers
  • Arterial thrombi usually begin at sites of turbulence or endothelial injury
  • Venous thrombi characteristically occur at sites of stasis
• Cardiac thrombi


  • Mural thrombi: Occurring in heart chambers or aortic lumen
  • Vegetations: Thrombi on heart valves due to abnormal myocardial contraction or endomyocardial injury
  • Infected vegetations = infective endocarditis
• Capillary thrombi


  • Caused by acute inflammation, severe cold & frostbite
• Fate of thrombi

  1. Propagation

  2. Embolization

  3. Dissolution

  4. Organization and recanalization
• Disseminated Intravascular Coagulation (DIC)


  Widespread fibrin thrombi in the microcirculation causing diffuse circulatory insufficiency, platelet and coagulation protein consumption, and activation of fibrinolytic mechanisms
• Embolism


  Impaction of a detached intravascular solid, liquid, or gaseous mass that circulates in the blood to a site distant from its point of origin
• Pulmonary Embolism

  • Over 95% originate from leg deep vein thromboses
  • Fragmented thrombi from DVTs are carried through the right side of the heart before entering the pulmonary arterial vasculature
  • Saddle embolus can occlude the main pulmonary artery
  • Paradoxical embolism can pass through a cardiac defect to the systemic circulation
  • Small and median size emboli pass out into the smaller, branching pulmonary arteries
• Embolus

  A fragment of a dislodged thrombus or other material that is carried in the bloodstream and can obstruct a blood vessel
• Rare forms of emboli

  • Fat droplets
  • Nitrogen bubbles
  • Tumor fragments
  • Bone marrow
  • Foreign bodies
• Unless otherwise specified, emboli should be considered thrombotic in origin
• Pulmonary embolism (PE)


  An embolus that originates from a deep vein thrombosis (DVT) and lodges in the pulmonary arterial vasculature
• In more than 95% of cases, Pulmonary embolism (PE) originate from leg deep vein thromboses (DVTs)
• DVTs occur roughly two to three times more frequently than PEs