ENDOCARDIUM

1. ENDOCARDIUM DISEASES OF THE HEART Dr Eman MS Muhammad

2. RHEUMATIC FEVER • Definition: • An auto-immune collagen disease characterized by inflammatory changes in the fibrous tissue of different body structures specially the heart, joints, subcutaneous tissue, blood vessels, and CNS.

3. General consideration: It accounts for 40 % of all heart diseases and 90 % of heart diseases in children. It is a febrile illness follows an attack of streptococcal pharyngitis. Its incidence has fallen in developed countries as a result of improved living conditions and use of antibiotics. Heart failure (HF) due to diffuse myocardial injury may occur during acute illness and is occasionally fatal. In large majority of cases the myocardial function usually recovers completely.

4. Subsequent disability is due to injury to the myocardial valves, resulting in permanent distortion, and chronic cardiac failure. • Rheumatic fever (RF) tends to recur after subsequent attacks of streptococcal pharyngitis and each recurrence ↑the risk of serious valvular diseases.

5. Etiology: • RF may follow upper respiratory tract infections as tonsillitis and pharyngitis caused by group A of ß- hemolytic streptococci after a latent period of 2-4 weeks. • Only a small number of patients with streptococcal infection develop an attack of RF. • The bacteria are neither found in the lesions nor in the blood stream. • Streptococci antigens are not found in the heart in fatal cases of RF nor in acute carditis caused directly by streptococci toxins.

6. It is clear that streptococci pyogenes and myocardium shares common antigens. Two mechanisms are involved: an autoimmune reaction triggered by streptococci infection, and hypersinsitivity reaction producing antibodies cross react with cardiac antigens. Similar antibodies occur after uncomplicated streptococci infections and in patients who develop poststreptococcalglomerulonephritis but not RF. RF develops after recovery from infection. High ASO titer is used as a diagnostic aid. Recurrent attacks are common.

7. Treatment of streptococcal pharyngitis with antibiotics does not abolish the risk of subsequent RF. Long term administration of penicillin prevents further attacks of streptococcal pharyngitis and of subsequent RF.

8. Age: Common in children and young adults, between 5-20 years, rare before the age of 3 years. Girls are affected more than boys. There is strong individual predisposition. Predisposing factors: Overcrowding, damp weather, poor housing and low socioeconomic conditions. These factors predispose to upper respiratory tract infections.

9. Pathogenesis: Rheumatic fever is a systemic disease affecting the connective tissue around arterioles, and can occur after an untreated strepococcal throat infection, specifically due to group A ß- hemolytic streptococcus (GAS), Streptococcus pyogenes. It is believed to be caused by antibody cross-reactivity. This cross-reactivity is a type II hypersensitivity reaction and is termed molecular mimicry.

10. Usually, self reactive B cells remain anergicin the periphery without T cell co-stimulation. During a streptococcal infection, mature antigen-presenting cells such as B cells present the bacterial antigen to CD4+T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints,[producing the symptoms of rheumatic fever.

11. S. pyogenes is a species of an aerobic gram-positive, cocci that are non-motile, non-spore forming, and forms chains and large colonies. S. pyogenes has a cell wall composed of branched polymers which sometimes contain M protein, a virulence factor that is highly antigenic. The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin,[heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction.

12. However, the only proven cross-reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement, and also through Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells.

13. Rheumatic valvular lesions may also involve a cell-mediated immunereaction as these lesions predominantly contain T-helper cells and macrophages. In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis (pancarditis). The inflammation may cause a serofibrinous pericardial exudate described as "bread-and-butter" pericarditis, which usually resolves without sequelae.

14. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Warty projections arise from the deposition, while subendocardial lesions may induce irregular thickenings called MacCallum’s patches or MacCallum’s plaques.

15. Acute rheumatic fever • Changes in the heart: • Although all the three layers of the heart are affected in acute RF (pancarditis)the severity of their individual involvement varies greatly.

16. Pericarditis: It is an exudative inflammation with effusion of serous fluidand deposition of fibrin on both pericardial surfaces. Sometimes a thick layer of fibrin is formed giving them a rough shaggy appearance which has been compared with that observed when two generously buttered pieces of bread are pressed together and then pulled apart (bread and butter appearance).

17. Myocarditis: • In acute fatal cases the myocardium is flabby and the ventricles especially the left, are dilated. • Sometimes tinny pale foci may be just visible; the Aschoff bodies which are pathgnomonicof RF. • They are scattered throughout the myocardium being numerous in the left atrium and ventricle. • The Aschoff bodies develop in the connective tissue septa of the myocardium.

18. Microscopy reveals a focus of eosinophilic hyaline material which contains fibrin and indicates exudation of plasma proteins from small vessels. • It is surrounded by an aggregates of lymphocytes, macrophages, occasional polymorphs and large cells with two or three nuclei or a single convoluted nucleus. • In time the Aschoff bodies subside and healing occurs, leaving minute scars in the CT of the myocardium.

19. Aschoff’s body

21. Endocarditis: • The endocardium shows diffuse inflammatory edema and light cellular infiltrate. • Aschoff bodies develop and are particularly numerous in the posterior wall of the left atrium just above the insertion of posterior mitral cusp. • Healing may result in thickening and irregularity of the endocardium in this area McCallum’s patch. • In acute RF, the most prominent endocardial lesion consists of thrombotic vegetationsforming a line of multiple, fine, adherent, grey pink, firm, nodular deposits 1-3mm on the surface of the valve cusps.

22. They form mainly on the line of contact between the cusps when the valves close. • Similar vegetations form on the chordaetendinae.

23. Microscopically: Aschoff bodies are seen on the valves. There is also an inflammatory edema, infiltration by polymorph, lymphocytes, macrophages and focal fibrinoid necrosis. Focal ulceration occurs and acute thrombotic vegetation are formed in these areas. There is aningrowth of capillaries from the base of the valves. This is followed by organization of vegetations and diffuse thickening of the cusps.

24. Organization of vegetations on the cusps results in fibrous union between adjacent cusp margins → valve stenosis. • Organization of vegetations on the chordaetendinae leading to their becoming matted together as thick fibrous bands at their valvular ends. • This causes shortening of the chordae and distortion of the cusps → valve incompetence → regurgitation. • With recurrent acute attacks, the injury to the valve becomes more severe and further fibrous thickening and deformity results.

25. When patients die in acute illness, all four valves are commonly inflamed, but residual effects with permanent distortion are usually confined to the mitral and aortic valves, probably because of their greater hemodynamic stresses.

26. Rheumatic vegetations

27. Chronic rheumatic heart diseases: • Following recovery from RF the function of the myocardium usually returns to normal, although minute fibrous scars mark the site of healed Aschoff bodies. • Organization of fibrous peicarditis results in fibrous peicardial adhesions or even obliteration of the sac, but the fibrous tissue is seldom thick enough to impair cardiac function.

28. Injury to the valves commonly causes permanent deformity resulting in stenosis or incompetence or a combination of both defects. • In 30% of RF the valve lesions results in heart failure. • The risk of chronic endocarditis depends upon the age, being higher following RF in early childhood and in patients with repeated attacks. • The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords.

29. Sometimes the valvular lesion progresses rapidly, but more often there is an interval of 5-30 years of apparent good health before the clinical features of valvular disease develops. • In chronic RF both the mitral and aortic valves are affected in 50% of cases, and the mitral valve alone in about 25% of cases. • The mitral, aortic and tricuspid valves are involved in about 15% of cases, while involvement of all 4 valves or of the aortic valve alone is rare. • The valves of the right side of the heart are never affected alone.

30. Strep throat Antibody production Antibody cross-reaction with heart Vegetations Aschoff body Pericarditis

31. Changes in other tissues in RF: • Joints: • Fleeting arthritis (one joint is affected after the other) • It occurs specially in large joints. • The joint cavity shows serous exudate (joint effusion). • Synovial, capsular and pericapsular tissues (tendons and their sheaths) show congestion, edema, cellular infiltrate of histiocytes, lymphocytes, plasma cells and scanty Aschoff bodies.

32. Articular cartilage is not affected, so with resolution of inflammation complete restoration of the joint functions occur.

33. Subcutaneous nodules: • It develops over bony prominences or tendons of the arms and legs, elbow, wrist, spine, occipital protuberance in severe cases. • They are most commonly found on the extensor surfaces of the elbow and overlying the ulna. • The nodules are between 1 and 2 cm in diameter, painless and resemble enlarged Aschoff bodies.

34. SUBCUTANEOUS NODULES

35. Brain: • Edema, thrombosis, hemorrhage and perivascular round cell infiltration occur in the basal ganglia and cerebral cortex. • It causes sudden, involuntary, irregular, purposeless, rapid movements particularly of the extremities called “Sydenham's chorea” with muscularin-coordination and weakness.

36. Skin: Erythematous skin rashes may occur; “erythemamarginatum”. It is a long-lasting reddish rash that begins on the trunk or arms as macules, which spread outward and clear in the middle to form rings, which continue to spread and coalesce with other rings. This rash typically spares the face and is made worse with heat.

37. ERYTHEMA MARGINATUM

38. Pleura and Peritoneum: • They show serofibrinous inflammation. • Blood vessels: • Aschoff’s nodules form in the media and adventitia of the large arteries.

39. Clinical features of acute RF: • RF develops usually 2-4 weeks after streptococcocal sore throat infection. • Symptoms are fever tachycardia, malaise, arthralgia flitting from one joint to another. • The affected joints are sometimes swollen. • The most serious effect on the heart at this stage is rheumatic myocarditis which causes various degrees of acute HF. • Signs of acute pericarditis usually appear later in the acute illness.

40. The valvular lesions are undetectable at this stage. • Evidence of secondary mitral incompetence due to dilatation of the LV or valvular abnormalities from previous attacks. • Chorea may develop during or apart from acute illness due to cerebral irritability. • Skin rashes and subcutaneous nodules may develop during or apart from acute illness too. • There is no specific test for RF. • A raised ESR, elevated C-reactive protein, and high ASOT are usually present. • Anemia and slight leucocytosis.

41. Causes of death: Heart failure: from active carditis or secondary to chronic rheumatic valvulitis. Embolic manifestation: from atrial or vascular thrombosis. It causes death in 20-35% of cases. Bacterial endocarditis: causes death in 10-15% of cases. Pneumonia: in congested lungs.

42. ENDOCARDITIS • Definition: • Inflammation of the valvularendocardium. • Types: • Infective endocarditis (bacterial endocarditis): • Acute infective endocarditis or acute bacterial endocarditis (AIE or ABE). • Subacute infective endocarditis or subacute bacterial endocarditis (SIE or SBE).

43. Non-infective endocarditis: • Rheumatic endocarditis. • Atypical verrucousendocarditis (Libman-Sacks endocarditis). • Non infective thrombotic endocarditis (Terminal endocarditis)

44. Infective endocarditis • When micro-organisms gain entrance to the blood stream, they are usually rapidly eliminated. • In some circumstances, they may settle on the endocardial surface, usually on the valve cusps, with the formation of thrombi known as “vegetation”. • Iinfectiveendocarditis, is characterized by fever, toxemia, embolic phenomena, heart failure and sometimes glomerulonephritis.

45. Traditionally, infective endocarditis is classified into acute and subacute types. • The former affects a normal heart, and is rapidly fatal because it is due to bacteria of high virulence. • Thelatter affects a damaged organ and gives rise to a more prolonged illness because it is due to less virulent organisms. • The distinction is valuable but many patients present features intermediate between these two extremes.

46. Predisposing factors: • The main factors which predispose to infective endocarditis are: • Conditions which cause bacteremia, septicemia, pyemia. • Abnormalities of the heart which favor the lodgment of micro-organism on the endocardial surface, usually of the valves. • Impairment of the host defense mechanism.

47. SUBACUTE INFECTIVE ENDOCARDITIS • Subacute infective endocarditis (SIE), subacute bacterial endocarditis (SBE), orendocarditislenta. • Etiology: • It is caused by bacteria relatively of low virulence. • The most important is “viridans”group of α- hemolytic streptococci. • It forms part of the normal flora of the mouth and pharynx. • It is followed by steptococcusbovis, and staphylococcus epidermis; gut and skin commensal.

48. Pathogenesis: • The organisms enter the blood stream from dental sepsis and throat infections during mastication, dental extraction and tonsillectomy (bacteremia). • They invade valves predisposed to infection by: • Chronic rheumatic valvulitis. • Congenital malformations as bicuspid aortic valve, pulmonary stenosis, septal defects ... etc. • These predisposing factors cause roughness of the cusps upon which minute platelet thrombi form.

49. In the presence of bacteremia, the distorted valves and/or the congenital defect become infected, via adhesion and subsequent colonization of the surface area. The bacteria lodge in the thrombi, multiply and invade the cusps. This causes an inflammatory response, with recruitment of matrix metalloproteinases, and destruction of collagen. Subacute bacterial endocarditis can be considered a form of Type III hypersensitivity reaction.

50. Pathological lesions: • The lesionconsists of friable, soft, bulky, polypoid, and easily detached vegetations (thrombi). • They are shaggy, grey reddish, or brown in color, projecting from the surface of the valve cusps. • They usually develop on the contact surface of a cusp, where they may be patchy or continuous, and also spread to the contact surfaces of the adjacent cusp (s). • Spread from the aortic valve to the anterior mitral cusp, and vice versais common. • The micro-organisms invade the cusp tissue and cause necrosis, which may lead to cusp rupture.