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Page 1: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial
Page 2: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.1

Page 3: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial structural and functional integrity is fundamental to the maintenance of vessel wall homeostasis and normal circulatory function.

Page 4: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.3

Page 5: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

SMCs are predominant cellular element of the vascular media

SMCs are responsible for vasoconstriction and dilation in response to normal or pharmacologic stimuli.

They also synthesize collagen, elastin, and proteoglycans; and elaborate growth factors and cytokines. They migrate to the intima and proliferate following vascular injury.

Thus, SMCs are important elements of both normal vascular repair and pathologic processes such as atherosclerosis.

Page 6: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Vascular injury ( endothelial injury/dysfunction) stimulates SMC growth. Reconstitution of the damaged vascular wall is a physiologic healing response that includes the formation of a neointima, in which SMCs (1) migrate from the media to the intima, (2) multiply as intimal SMCs, and (3) synthesize and deposit ECM

Page 7: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

During the healing response, SMCs undergo changes that resemble dedifferentiation. In the intima they lose the capacity to contract and gain the capacity to divide.

Intimal SMCs may return to a nonproliferative state when either the overlying endothelial layer is re-established following acute injury or the chronic stimulation ceases.

Page 8: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Arteriosclerosis (literally, "hardening of the arteries") is a generic term for thickening and loss of elasticity of arterial walls. Three patterns of arteriosclerosis are recognized; they vary in pathophysiology and clinical and pathological consequences.

1)Atherosclerosis, the most frequent and important pattern

Page 9: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

2)Mönckeberg medial calcific sclerosis is characterized by calcific deposits in muscular arteries in persons older than age 50. They do not encroach on the vessel lumen.

3)Arteriolosclerosis affects small arteries and arterioles. There are two anatomic variants, hyaline and hyperplastic, both associated with thickening of vessel walls with luminal narrowing that may cause ischemic injury. Most often associated with hypertension and diabetes mellitus.

Page 10: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Atherosclerosis is characterized by intimal lesions called atheromas, or atheromatous or fibrofatty plaques, which protrude into and obstruct vascular lumens and weaken the underlying media. They may lead to serious complications

Page 11: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Fatty streaks are the earliest lesion of atherosclerosis. They are composed of lipid-filled foam cells. They are not significantly raised and thus do not cause any disturbance in blood flow. Fatty streaks begin as multiple yellow, flat spots less than 1 mm in diameter that coalesce into elongated streaks, 1 cm long or longer. They contain T lymphocytes and extracellular lipid in smaller amounts than in plaques.

Page 12: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.9

Fatty streak—a collection of foam cells in the intima.

A. Aorta with fatty streaks ( arrows), associated largely with the ostia of branch vessels.

B. Close-up photograph of fatty streaks from the aorta of an experimental hypercholesterolemic rabbit shown after staining with Sudan red, a lipid-soluble dye, again illustrating the relationship of the lesions to the two-branch vessel ostia.

C. Photomicrograph of fatty streak in an experimental hypercholesterolemic rabbit, demonstrating intimal macrophage-derived foam cells ( arrow).

Page 13: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

The key processes in atherosclerosis are intimal thickening and lipid accumulation. An atheroma or atheromatous plaque consists of a raised focal lesion initiating within the intima, having a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esters), covered by a firm, white fibrous cap.

Page 14: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

The atheromatous plaques appear white to whitish yellow and impinge on the lumen of the artery. They vary in size from approximately 0.3 to 1.5 cm in diameter but sometimes coalesce to form larger masses. Atherosclerotic lesions usually involve only a partial circumference of the arterial wall ("eccentric" lesions) and are patchy and variable along the vessel length.

Page 15: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

The most heavily involved vessels are the abdominal aorta then coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis.

Page 16: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Atherosclerotic plaques have three principal components:

(1) cells, including SMCs, macrophages, and other leukocytes

(2) ECM, including collagen, elastic fibers, and proteoglycans

(3) intracellular and extracellular lipid . These components occur in varying proportions.

Page 17: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Typically, the superficial fibrous cap is composed of SMCs and relatively dense ECM. Beneath and to the side of the cap (the "shoulder") is a cellular area consisting of macrophages, SMCs, and T lymphocytes.

Deep to the fibrous cap is a necrotic core, containing a disorganized mass of lipid (primarily cholesterol and cholesterol esters), cholesterol clefts, debris from dead cells, foam cells, fibrin, variably organized thrombus, and other plasma proteins.

Page 18: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Foam cells are large, lipid-laden cells that derive predominantly from blood monocytes (tissue macrophages), but SMCs can also imbibe lipid to become foam cells.

Around the periphery of the lesions, there is usually evidence of neovascularization (proliferating small blood vessels). Typical atheromas contain relatively abundant lipid.

Atheromas often undergo calcification.

Page 19: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.6

Major components of well-developed atheromatous plaque:

fibrous cap composed of proliferating smooth muscle cells, macrophages,

lymphocytes, foam cells, and extracellular matrix. The necrotic core consists

of cellular debris, extracellular lipid with cholesterol crystals, and foamy

macrophages.

Page 20: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.7

Gross views of atherosclerosis in the aorta.

A. Mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow.

B. Severe disease with diffuse and complicated lesions.

Page 21: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.8

Histologic features of atheromatous plaque in the coronary artery.

A. Overall architecture demonstrating a fibrous cap (F) and a central lipid core (C) with typical cholesterol clefts. The lumen (L) has been moderately narrowed. Note the plaque-free segment of the wall ( arrow). In this section, collagen has been stained blue (Masson trichrome stain).

B. Higher-power photograph of a section of the plaque shown in A, stained for elastin ( black) demonstrating that the internal and external elastic membranes are destroyed and the media of the artery is thinned under the most advanced plaque ( arrow).

C. Higher-magnification photomicrograph at the junction of the fibrous cap and core showing scattered inflammatory cells, calcification ( broad arrow), and neovascularization ( small arrows).

Page 22: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.11

American Heart Association classification of human atherosclerotic lesions from the fatty dot (type I) to the complicated type VI lesion. The diagram also includes growth mechanisms and clinical correlations.

Page 23: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

The advanced lesion of atherosclerosis is at risk for the following pathological changes that have clinical significance:

1) Focal rupture, ulceration, or erosion of the luminal surface of atheromatous plaques may result in exposure of highly thrombogenic substances that induce thrombus formation or discharge of debris into the bloodstream, producing microemboli composed of lesion contents (cholesterol emboli or atheroemboli).

Page 24: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

2) Hemorrhage into a plaque, especially in the coronary arteries, may be initiated by rupture of either the overlying fibrous cap or the thin-walled capillaries that vascularize the plaque. A contained hematoma may expand the plaque or induce plaque rupture.

Page 25: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

3)Superimposed thrombosis, the most feared complication, usually occurs on disrupted lesions (those with rupture, ulceration, erosion, or hemorrhage) and may partially or completely occlude the lumen. Thrombi may heal and become incorporated into and thereby enlarge the intimal plaque.

Page 26: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

4)Aneurysmal dilation may result from ATH-induced atrophy of the underlying media, with loss of elastic tissue, causing weakness and potential rupture

5) Calcifications.

Page 27: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.5

Natural history of atherosclerosis

Page 28: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Major Nonmodifiable Increasing age Male gender Family history Genetic abnormalitiesPotentiallyControllable Hyperlipidemia Hypertension Cigarette smoking Diabetes

Page 29: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Lesser, Uncertain, or Nonquantitated Obesity Physical inactivity Stress ("type A" personality) Postmenopausal estrogen deficiency  High carbohydrate intake Alcohol Lipoprotein Lp(a) Hardened (trans)unsaturated fat intake Chlamydia pneumoniae

Page 30: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Low-density lipoproteins (LDLs): When too much LDL (bad) cholesterol

circulates in the blood, it promotes atheroma formation in the arteries.LDLs contribute to heart disease because they carry large amounts of cholesterol.

Very-low-density lipoproteins (VLDLs): is also considered to be a type of bad cholesterol because it helps cholesterol build up on the walls of arteries

Chylomicrons also promote atherosclerosis.

Page 31: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

High-density lipoproteins (HDLs): is known as “good” cholesterol, because high levels of HDL seem to protect against heart attack. Low levels of HDL (less than 40 mg/dL) also increase the risk of heart disease. HDLs help to reverse the effects of high cholesterol by collecting cholesterol from other lipoproteins and transporting it to places where it can be utilized by the cells

Page 32: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

This concept, called the response to injury hypothesis, considers atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by injury to the endothelium. Moreover, lesion progression is sustained by interaction between modified lipoproteins, monocyte-derived macrophages, T lymphocytes, and the normal cellular constituents of the arterial wall.

Page 33: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.13

Processes in the response to injury hypothesis.

1, Normal.

Page 34: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.14

2, Endothelial injury with adhesion of monocytes and platelets (the

latter to denuded endothelium).

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Slide 12.15

3, Migration of monocytes (from the lumen) and smooth muscle cells (from the media) into the intima.

Page 36: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.16

4, Smooth muscle cell proliferation in the intima.

Page 37: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.17

5, Well-developed plaque.

Page 38: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 12.18

Page 39: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Central to this thesis are the following: Accumulation of lipoproteins, mainly LDL,

with its high cholesterol content, in the vessel wall

Chronic endothelial injury, usually subtle, increased permeability, leukocyte adhesion,

and thrombotic potential.

Page 40: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Adhesion of blood monocytes (and other leukocytes) to the endothelium, followed by their migration into the intima and their transformation into macrophages and foam cells

Adhesion of platelets Release of factors from activated

platelets, macrophages, or vascular cells that cause migration of SMCs from media into the intima

Page 41: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Proliferation of smooth muscle cells in the intima, and elaboration of extracellular matrix, leading to the accumulation of collagen and proteoglycans

Enhanced accumulation of lipids both within cells (macrophages and SMCs) and extracellularly.

Page 42: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

primary prevention programs, aimed at either delaying atheroma formation or causing regression of established lesions in persons who have never suffered a serious complication of atherosclerotic coronary artery disease

secondary prevention programs, intended to prevent recurrence of events such as myocardial infarction in patients with symptomatic disease.

Page 43: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

based on risk factor modification: abstention from or cessation of cigarette smoking, control of hypertension, weight reduction and increased exercise, moderation of alcohol consumption, and, most importantly, lowering total and LDL blood cholesterol levels while increasing HDL. on

Page 44: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial
Page 45: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Definition: rheumatic fever is an acute, immunologically mediated, multi-system inflammatory disease that follows, after a few weeks, an episode of group A beta hemolytic streptococcal pharyngitis (3% of patients).

The incidence and mortality of rheumatic fever has declined over the past 30 years (due to improved socioeconomic condition and rapid diagnosis and treatment of strep. pharyngitis.

Page 46: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Affect the heart during its acute phase acute rheumatic carditis.

Cause chronic valvular deformities (many years after the acute disease.

Page 47: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Hypersensitivity reaction induced by group A strept. (ab. Against protein M

Cross-reaction /

Autoimmune response

Page 48: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Inflammatory infiltrates occur in a wide range of tissues: synovium, joints, skin, heart.

Focal fibrinoid necrosis mixed inflammatory reaction (diffuse or localized) Fibrosis (chronic rheumatic heart disease) .

Page 49: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Pancarditis (endo- myo- pericarditis). Multiple foci of inflammation within the

connective tissue of the heart. (Aschoff bodies: central fibrinoid necrosis, surrounded by chronic mononuclear inflammatory infiltrate and occasional large histiocytes).

Diffuse interstitial inflammatory infiltrates (may lead to generalized dilation of the cardiac chambers).

Page 50: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Pericardial involvement: fibrinous pericarditis, sometime associated with serous or serosanguinous effusion.

Endocardium: ◦ Mostly mitral and aortic valve.◦ Valves are edematous and thickened with

foci of fibrinoid necrosis. (Aschoff nodules uncommon).

◦ Verrucous endocarditis (small vegetations along lines of valve closure).

Acute changes may resolve completely or progress to scarring and chronic valvular deformities.

Page 51: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Arthritis: large joints, self limited, no chronic deformities.

Lung: uncommon, chronic interstitial inflammation and fibrinous pleuritis.

Skin: skin nodules, erythema marginatum.

Page 52: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Irreversible deformity of one or more cardiac valves (previous acute valvulitis).

Left side of heart > right. Reduction of diameter (stenosis), or

improper closure (regurgitation), or both. May lead to cardiac failure (overload) May predispose to infective endocarditis.

Page 53: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Stenosis > regurgitation. Females > males. In stenosis:

◦ Leaflets are thick, rigid, and interadherent.◦ Dilatation and hypertrophy of left atrium.◦ Mural thrombi may be present systemic emboli.◦ Lungs are firm and heavy (chronic passive

congestion).◦ Right heart may be affected later.

In regurgitation:◦ Retracted leaflets.◦ Left ventricular hypertrophy and dilatation.

Page 54: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Males > females. Associated with mitral valvulitis. Aortic stenosis:

◦ Valve cusps are thickened, firm and interadherent rigid triangular channel.

◦ Left ventricular hypertrophy.◦ Subsequent left ventricular failure and dilation.

Aortic regurgitation: retraction of leaflets.

Page 55: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Occurs 10 days to 6 weeks after pharyngitis. ? Of genetic susceptibility. Peak incidence: 5-15 years. Pharyngeal culture may be negative, but

anti streptolysin O (ASO) titer will be high. Arthritis: large joints, migratory. Acute carditis: pericardial friction rubs, weak

heart sounds, tachycardia and arrhythmias. myocarditis cardiac dilation functional

mitral valve insufficiency or even congestive heart failure.

Page 56: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Manifestation after years or decades after the initial episode of rheumatic fever.

Signs and symptoms depend on which involved valve(s): cardiac murmurs, hypertrophy, dilation, congestive heart failure, arrhythmia, thromboembolic complications and infective endocarditis.

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Slide 13.34

A. Acute rheumatic mitral valvulitis superimposed on chronic rheumatic heart disease. Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet (arrowheads). Previous episodes of rheumatic valvulitis have caused fibrous thickening and fusion of the tendinous cords.

Page 58: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Slide 13.35

B. Microscopic appearance of an Aschoff body in a patient with acute rheumatic carditis. The myocardial interstitium has a circumscribed collection of mononuclear inflammatory cells, including some large histiocytes with prominent nucleoli, a prominent binuclear histiocyte, and central necrosis.

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Slide 13.36

C. & D. Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets, commissural fusion (arrow in C), and thickening and shortening of the tendinous cords. Marked dilation of the left atrium is noted in the left atrial view ( C).

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Slide 13.37

D. Opened valve. Note the neovascularization of the anterior mitral leaflet (arrow).

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Slide 13.38

E. Surgically removed specimen of rheumatic aortic stenosis demonstrating thickening and distortion of the cusps with commissural fusion ( E from Schoen FJ, St. John-Sutton M:

Contemporary issues in the pathology of valvular heart disease. Hum Pathol 18:568, 1967.)

Page 62: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Characterized by the deposition of small masses of fibrin, platelets, and other blood components on the leaflets of the cardiac valves (sterile).

Pathogenesis/ association:◦ Subtle endothelial abnormalities.◦ Hypercoagulability.◦ Association with malignancy (50%).

Page 63: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Gross:groups of small nodules on the lines of valve closure (similar to those of acute rheumatic fever), valve leaflets are normal.

Aortic valve most common site. Micro: fibrin and platelets aggregates, no

inflammation or fibrosis. Clinically asymptomatic, if large: may

embolize, may become infected.

Page 64: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Definition: infection of the cardiac valves or mural surface of the endocardium, resulting in the formation of an adherent mass of thrombotic debris and organisms.

Divided into:◦ Acute: high virulent organisms (staphylococcus

aureus), infect even normal valves, progress rapidly, little local host reaction.

◦ Subacute: infection of previously abnormal valves by organisms of low virulence (-hemolytic streptococci-viridans), progress slowly, induce local inflammatory reaction.

Page 65: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Bacteremia: i.v. drug abusers, elsewhere infection, previous dental, surgical or interventional procedure (catheterization).

In some cases the source of bacteremia is occult.

Infective endocarditis is a particularly difficult infection to eradicate because of the avascular nature of the heart valves.

Page 66: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Cardiac abnormalities: chronic valvular diseases, high pressure shunts within the heart (small ventricular septal defects).

Prosthetic heart valves. Intravenous drug abusers.

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Most common of non prosthetic valves (50-

60%): -Hemolytic (viridans) streptococci, which

attack previously damaged valves and causes subacute IE.

Staphylococcus attack healthy or deformed valves (10-20%).

Prosthetic valve endocarditis is caused commonly by coagulase-negative staphylococci (e.g., S. epidermidis).

Page 68: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Valvular vegetations containing bacteria or other organisms.

Aortic and mitral valves are the most common sites. (right side valves in i.v.users)

Vegetations may be single or multiple, involve one or more valve(s), differ in appearance according to the causative agent.

Page 69: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Vegetations: may obstruct valve orifice, lead to rupture of ( the leaflets, cordae tendineae, or papillary muscles), abscess in perivalvular tissue (ring abscess), friable vegetations may become systemic emboli infarcts + abscesses.

Micro: large number of organisms + fibrin and blood cells. Neutrophilic inflammatory reaction occurs the infection extends beyond the avascular valves.

Page 70: Slide 12.1  ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial

Vegetations are firmer, less destructive, and ring abscess are uncommon.

Micro: Granulation tissue is seen at the base of the vegetations, later: fibrosis, calcifications and chronic inflammatory infiltrates. Systemic emboli may develop but they don’t undergo suppuration.

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Onset: gradual or explosive (~organisms).◦ Low-grade fever, malaise, weight loss.◦ High fever, shaking chills.

Cardiac murmurs. Enlargement of spleen, clubbing of digits (particularly in subacute

cases). Systemic emboli (neurologic deficits, retinal abnormalities,

necrosis of digits, and infarcts of the myocardium. Pulmonary emboli in right-sided endocarditis. Mycotic aneurysms. Petechiae (due to micro emboli or deposition of immune

complexes. Renal lesions: renal infarcts and glomerulonephritis. Valvular regurgitation and congestive heart failure due to

progressive valvular destruction. Blood culture for aerobic and anaerobic organisms is very

important (only minority of cases remain negative).

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Slide 13.40

Endocarditis of the mitral valve (subacute, caused by Streptococcus viridens). The irregular, large friable vegetations are denoted by arrows.

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Slide 13.41

B. Acute endocarditis of a congenitally bicuspid aortic valve (caused by Staphylococcus aureus) with severe cuspal destruction and ring abscess (arrow).

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Slide 13.42

C. Histologic appearance of vegetation of endocarditis with extensive acute inflammatory cells and fibrin. Bacterial organisms were demonstrated by tissue Gram stain.

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Slide 13.43

D. Gross photograph illustrating healed endocarditis with perforations on bicuspid aortic valve

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Slide 13.44

Diagrammatic comparison of the lesions in the four major forms of vegetative endocarditis. The rheumatic fever phase of RHD (rheumatic heart disease) is marked by a row of warty, small vegetations along the lines of closure of the valve leaflets. IE (infective endocarditis) is characterized by large, irregular masses on the valve cusps that can extend onto the cords (see Fig. 13–18 A). NBTE (nonbacterial thrombotic endocarditis) typically exhibits small, bland vegetations, usually attached at the line of closure. One or many may be present (see Fig. 13–20). LSE (Libman-Sacks endocarditis) has small or medium-sized vegetations on either or both sides of the valve leaflets.

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Slide 13.45

Nonbacterial thrombotic endocarditis (NBTE).

A. Nearly complete row of thrombotic vegetations along the line of closure of the mitral valve leaflets.

B. Photomicrograph of NBTE showing bland thrombus, with virtually no inflammation in the valve cusp (c) or the thrombotic deposit. The thrombus is only loosely attached to the cusp (arrow).

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Primary: mostly viral, sometimes by other microorganisms (pyogenic bacteria, mycobacteria and fungi.

Secondary to: acute myocardial infarction, cardiac surgery, or radiation to the mediastinum.

Associated systemic disorders, mostly with uremia.

Less common 2ndry causes: rheumatic fever, SLE, and metastatic malignancies (bloody effusions).

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Cause immediate hemodynamic complications, if significant effusion is present.

Resolve without significant sequelae. Progress to chronic fibrosing process.

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In uremia, and acute rheumatic fever: the exudate is fibrinous and impart a shaggy irregular pericardial surface (bread and butter pericarditis).

Viral pericarditis fibrinous exudate. Acute bacterial pericarditis fibrinopurulent

pericarditis. Tuberculosis caseous materials. Pericardial metastases: irregular nodules. Exudate usually resolve unless there is excessive

suppuration or caseation, where healing leads to chronic pericarditis.

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Ranges from delicates adhesions to dense fibrotic scars that obliterate the pericardial space.

In extreme cases the heart can’t expand during diastole : constrictive pericarditis.

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Atypical chest pain (worse on reclining). High pitch friction rub. Significant exudate cardiac tamponade

faint distant heart sounds, distended neck veins, declining cardiac output, and shock.

Chronic constrictive pericarditis venous distension and low cardiac output.

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Slide 13.56

Acute suppurative pericarditis as an extension from pneumonia. Extensive purulent exudate is evident in this in situ photograph.