Lesson 18

Systemic Deseases of Connective Tissue

Key points:
1. Rheumatic fever: classification and morphogenesis, morphological characteristics.
2. Rheumatoid arthritis. Morphogenesis, morphology of joint manifestations (stages of progression of rheumatoid polyarthritis, complications and consequences).
3. Bekhterev's disease: pathological anatomy.
4. Systemic lupus erythematosus: pathological anatomy, immunomorphological changes inthe skin, blood vessels, heart, kidneys. Complications, causes of death.
5. Systemic scleroderma (sclerosis): pathological anatomy, visceral manifestations of systemic scleroderma. Complications, causes of death.
6. Dermatomyositis: pathological anatomy, clinical and anatomical forms. Complications,causes of death.
7. Endocarditis. Parietal fibroplastic (Löffler's) endocarditis. Causes, development, morphological changes, consequences.
8. Myocarditis. Idiopathic myocarditis. Causes, mechanism of development. Morphology,consequences.
9. Heart defects: congenital and acquired. Causes of acquired heart defects, pathogenesis, morpho-logical characteristics.
10. Cardiomyopathy: dilatory, hypertrophic, restrictive. Causes, pathogenesis, morphologicalchanges in the heart and other organs.
11. Vasculitis. Causes, mechanism of development, morphological changes in vessels andorgans; consequences. Nonspecific aortoarteritis (Takayasu disease). Giant cell arteritis(Horton's disease); nodular periarteritis; Wegener's granulomatosis. Obliterativethrombangiitis (Burger disease). Primary and secondary vasculitis.
Sources:
1. Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015. P.7-64.
2. Kumar, Vinay, Abul K Abbas, Jon C Aster, and Stanley L. 1915-2003 Robbins. Robbins Basic Pathology. 10th ed. Philadelphia, PA: Elsevier/Saunders, 2018. P.1-33, 51.
3. Klatt, Edward C. Robbins and Cotran Atlas of Pathology. Third edition. Philadelphia, PA: Elsevier Saunders, 2015.
4. Klatt, Edward C., and Vinay Kumar. Robbins and Cotran Review of Pathology. Fourth edition. Philadelphia, PA: Elsevier Saunders, 2015. P.3-17
.
5. Harsh Mohan. Essential Pathology for Dental Students.Fourth edition. Jaypee Brothers,Medical Publishers Pvt. Limited, 2011. P.1-77
.

Normal aortic valve, gross

The aortic valve, similar to the other semilunar valve—the pulmonic valve—has three thin, deli-cate cusps. The coronary artery orifices () can be seen just above the aortic valve cusps. The endocardium is smooth; beneath it can be seen the red-brown myocardium. The aorta above this valve displays a smooth intimal surface with no atherosclerosis.

Normal tricuspid valve, gross

The leaflets of the atrioventricular valves (mitral and tricuspid) are thin and delicate. Similar to the mitral valve, the leaflets shown here have thin chordae tendineae () that tether the leaflet margins to the papillary muscles of the ventricu-lar wall below the valve. The right atrium can be seen above the valve.

Fibrinous pericarditis, gross

A window of adherent pericardium is reflected to reveal thin strands () of fibrinous exudate extending from the epicardial surface to the pericardium, typical for fibrinous pericarditis. A clinical finding is a friction rub (heard by the student on the night of the patient’s admission to the hospital, but inaudible with increasing serous fluid collection when the attending physician examines the patient on morning rounds, and the term serofibrinous pericarditis is more appropriate). Diffuse fibrinous pericarditis is more typical of sys-temic conditions, such as uremia or systemic lupus erythematosus, whereas focal pericarditis may overlie a transmural MI (Dressler syndrome).

Fibrinous pericarditis, microscopic

The pericardial surface shows strands of pink fibrin () extending outward to the left. There is minimal underlying inflammation. Even-tually the fibrin can be organized and cleared, although sometimes adhesions may remain. Fibrinous pericarditis results from inflam-mation or vascular injury that leads to exudation of fibrin, typically with some accompanying fluid. Causes include an underlying MI, uremia, rheumatic carditis, autoimmune diseases (although these are most often mostly serous), radiation to the chest, and trauma.

Rheumatic heart disease, gross

Acute rheumatic fever (ARF) can produce pancarditis, but shown here are the characteristic small verrucous vegetations () of rheumatic endocarditis located over areas of fibrinoid degeneration on the valve cusp margins. These vegetations, composed of platelets and fibrin and located at the valve closure line, are usually no more than 2mm in size but may produce an audible murmur. These lesions are not likely to embolize and do not produce significant valvular deformity at this early stage of rheumatic valvulitis.

Rheumatic heart disease, gross

This mitral valve is shown from above the inflow from a dilated left atrium and shows the typical fish-mouth shape following chronic rheumatic valvulitis with scarring and narrow valve opening (). There can be both stenosis and insufficiency, with the former predominating. The mitral valve is most often affected with rheumatic heart disease (RHD); followed by mitral and aortic valves to-gether; then aortic alone; then mitral, aortic, and tricuspid valves together.

Rheumatic heart disease, gross

In time, chronic rheumatic valvulitis may develop by organization of acute and recurrent endocardial inflammation along with fibrosis, as shown here affecting the mitral valve, as viewed from the opened LV, with the aortic valve at the top. Note the shortened and thickened chordae tendineae (). This complication can take decades to become slowly symptomatic. Val-vular stenosis can lead to prominent left atrial enlargement, which predis-poses to mural thrombus formation and systemic embolization

Rheumatic heart disease, microscopic

The Aschoff nodule of ARF typically occurs in the myocardial interstitium. It is a nodular perivascular collection of mainly mononuclear inflammatory cells. This manifestation of RHD occurs 10 days to 6 weeks after group A streptococcal pharyn-gitis. This carditis results from molecular mimicry and immunologic cross-reaction with the strep-tococcal capsular M protein. The endocardium, myocardium, and epicardium can be affected, producing a pancarditis. Serologic markers of rheumatic fever may include antistreptolysin O, antihyaluronidase, and anti–DNase B.

Rheumatic heart disease, microscopic

The most characteristic cellular component of this Aschoff nodule is the Aschoff giant cell. These appear here as large cells with two or more nuclei that have prominent nucleoli. Scattered mono-nuclear inflammatory cells accompany them and can be occasional neutrophils. Such inflammation can occur not only in myocardium, but also in endocardium (including valves) and epicardium. Involvement of all three cardiac layers is termed pancarditis. Myocardial involvement leads to death in about 1% of patients with ARF. RHD is now so uncommon that the number of strepto-coccal infections needed to treat to prevent one case of RHD is over 10,000.

Rheumatic heart disease, microscopic

This long, thin cell with an elongated nucleus, which occurs with acute rheumatic carditis, is the Anichkov myocyte. Signs and symptoms of ARF are most likely to appear in children. Extracardiac manifestations may include “major” Jones criteria: subcutaneous nodules, erythema marginatum, fever, and polyarthritis. “Minor” criteria include ar-thralgia, fever, previous RF, leukocytosis, elevated sedimentation rate, and C-reactive protein. There is a propensity for reactivation of RF with subsequent episodes of group A streptococcal pharyngitis. Chronic RHD is usually the result of multiple recurrent episodes of ARF.

Infective enadocarditis, gross

The aortic valve shows a large, irregular, red-dish tan vegetation. Virulent organisms, such as Staphylococcus aureus, produce an acute bacterial endocarditis within days, similar to the lesion shown here, whereas some organisms, such as the viridans group of Streptococcus,produce a more slowly developing subacute bacterial endocarditis. Endocarditis is marked by fever with heart murmur. Predisposing risks for endocarditis include bacteremia and previously damaged or deformed valves, but endocarditis can involve anatomically normal valves.

Infective endocarditis, gross

The more virulent bacteria causing the acute bacterial form of infective endocarditis can lead to serious valvular destruction, as shown here involving the aortic valve. Irregular reddish tan vegetations overlie valve cusps that are being destroyed by the action of the proliferating bacte-ria. Portions of the vegetation can break off and become septic emboli that travel to other organs, leading to foci of infarction or infection.

Infective endocarditis, gross

Healing of infective endocarditis may leave residual valve damage. Shown here is a larger fenestration of an aortic valve cusp as a con-sequence of healed infective endocarditis, with partial destruction of another cusp. The result of this valvular damage is aortic insufficiency and a jet lesion with adjacent focal endocardial fibrosis of the left ventricular myocardium from regurgitant flow. A murmur may be audible. Larger fenestra-tions may cause valvular insufficiency.

Infective endocarditis, micro-scopic

The valve leaflet in the left panel has friable vegetations composed of fibrin and platelets (pink) mixed with inflammatory cells and bacterial colonies (blue). The friability explains how por-tions of the vegetation can break off and embo-lize. In the right panel a septic embolus fills the lumena of a small artery showing inflammation and necrosis. Left-sided endocarditis can be compli-cated by embolization to the systemic circulation, whereas right-sided embolization affects the lungs. Cardiac valves are relatively avascular, so high-dose, prolonged antibiotic therapy is needed to eradicate the infection.

Nonbacterial thrombotic endo-carditis, gross

The small pink vegetation on the leftmost aortic cusp margin represents the typical finding with nonbacterial thrombotic endocarditis (NBTE), or so-called marantic endocarditis. This is one form of noninfective endocarditis. NBTE tends to occur in individuals with a hypercoagulable state (e.g., Trousseau syndrome, a paraneoplastic syn-drome associated with malignancies) and in very ill patients. These vegetations are rarely larger than 0.5cm. They are very prone to embolize, however. Patients with NBTE often have con-comitant venous thromboembolic disease. Note the normal right and left coronary artery orifices above the valve cusps.

Libman-Sacks endocarditis, gross

Flat, pale tan, spreading vegetations are visible over the mitral valve surface. They even spread onto the adjacent chordae tendineae. This patient has systemic lupus erythematosus. These vegetations can occur on any valve or even on endocardial surfaces. These vegetations appear in about 4% of patients with systemic lupus erythematosus and rarely cause problems because they are not large and rarely embolize. Note also the thickened, shortened, and fused chordae tendineae that represent remote RHD.