Transcript CVS_Part3
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%).
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.
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), progress slowly, induce
local inflammatory reaction.
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.
Cardiac abnormalities: chronic valvular
diseases, high pressure shunts within the
heart (small ventricular septal defects).
Prosthetic heart valves.
Intravenous drug abusers.
Most common of non prosthetic valves (5060%):
-Hemolytic (viridans) streptococci, which
attack previously damaged valves.
Staphylococcus attack healthy or deformed
valves (10-20%).
Prosthetic valve endocarditis is caused
commonly by coagulase-negative
staphylococci (e.g., S. epidermidis).
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.
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.
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.
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).
Endocarditis of the mitral valve (subacute, caused by Streptococcus viridens). The irregular, large friable vegetations are denoted by arrows.
Slide 13.40
B. Acute endocarditis of a congenitally bicuspid aortic valve (caused by Staphylococcus aureus) with severe cuspal destruction and ring abscess (arrow).
Slide 13.41
C. Histologic appearance of vegetation of endocarditis with extensive acute inflammatory cells and fibrin. Bacterial organisms were
demonstrated by tissue Gram stain.
Slide 13.42
D. Gross photograph illustrating healed endocarditis with perforations on bicuspid aortic valve
Slide 13.43
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.
Slide 13.44
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).
Slide 13.45
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).
Cause immediate hemodynamic
complications, if significant effusion is
present.
Resolve without significant sequelae.
Progress to chronic fibrosing process.
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.
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.
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.
Acute suppurative pericarditis
as an extension from
pneumonia. Extensive
purulent exudate is evident in
this in situ photograph.
Slide 13.56
•
•
•
•
Arises most often in the deep veins of the
legs therefore also called deep vein
thrombosis.
Is predisposed by venous circulatory stasis or
partially obstructed venous return e.g. in
cardiac failure, pregnancy and prolonged bed
rest, or varicose veins.
May give rise to pulmonary embolism with
resultant pulmonary infarct.
Often associated with inflammation and then
termed thrombophlebitis
Are abnormally dilated and tortuous veins,
most often superficial veins of lower
extremities.
Are predisposedby increased venous pressure
such as occurs with pregnancy, obesity, or
thrombophlebitis, and in persons whose
occupations require prolonged standing.
An aneurysm is a localized abnormal
dilation of a blood vessel or the wall of the
heart .
It can erode adjacent structures or rupture.
When an aneurysm is bounded by arterial
wall components or the attenuated wall of
the heart, it is called a true aneurysm.
Atherosclerotic, syphilitic, and congenital
vascular aneurysms and the left ventricular
aneurysm that can follow a myocardial
infarction are of this type.
In contrast, a false aneurysm (also called
pseudoaneurysm) is a breach in the vascular
wall leading to an extravascular hematoma
that freely communicates with the
intravascular space ("pulsating hematoma").
The most common false aneurysm is a
post-myocardial infarction rupture that has
been contained by a pericardial adhesion.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 13 February 2006 09:14 PM)
© 2005 Elsevier
Classified by macroscopic shape and size.
Saccular aneurysms are essentially spherical
(involving only a portion of the vessel wall)
and vary in size from 5 to 20 cm in
diameter, often partially or completely filled
by thrombus.
Fusiform aneurysm (involving a long
segment). Fusiform aneurysms vary in
diameter and in length.
Aneurysms and dissections are most
important when they involve the aorta. Both
true and false aneurysms, as well as
dissections, can rupture.
The two most important causes of aortic
aneurysms are atherosclerosis and cystic medial
degeneration of the arterial media.
Other causes also include a wide variety of
disorders that weaken the wall, including
trauma, congenital defects such as berry
aneurysms, syphilis, trauma or dissecting
aneurysm.
Infection of a major artery that weakens its
wall gives rise to mycotic aneurysm.
Thrombosis and rupture are possible
complications.
Atherosclerosis, the most frequent etiology of
aneurysms.
Atherosclerotic aneurysms occur most
frequently in the abdominal aorta: abdominal
aortic aneurysm (AAA).
AAAs are saccular or fusiform
Rupture into the peritoneal cavity or
retroperitoneal tissues with massive,
potentially fatal, hemorrhage
Obstruction of a vessel, particularly of the
iliac, renal, mesenteric, or vertebral
branches that supply the spinal cord
leading to ischemic tissue injury
Embolism from atheroma or mural
thrombus
Impingement on an adjacent structure, such
as compression of a ureter or erosion of
vertebrae
Presentation as an abdominal mass (often
palpably pulsating) that simulates a tumor.
Gross photographs of an
abdominal aortic
aneurysm that ruptured.
A. External view of the
large aneurysm; the
rupture site is indicated
by the arrow.
B. Opened view with the
location of the rupture
tract indicated by a probe.
The wall of the aneurysm
is exceedingly thin and
the lumen is filled by a
large quantity of layered
but largely unorganized
thrombus.
Slide 12.33
Are the most frequent aneurysms of the
aortic root.
Are small saccular lesions most often seen in
the small arteries of the brain, especially in
the circle of Willis.
Are not present at birth but develop at sites
of congenital medial weakness at bifurcations
of cerebral arteries.
Are unrelated to atherosclerosis.
Are often an association of adult polycystic
kidney disease.
Are the most frequent cause of subarachnoid
hemorrhage.
Is a manifestation of tertiary syphilis.
Fortunately, better control and treatment of
syphilis in its early stages have decreased the
frequency of this complication
It is caused by syphilitic aortitis.
It involves the ascending aorta.
Is a longitudinal intraluminal tear usually in
the wall of the ascending aorta, forming a
second arterial lumen within the media.
Aortic dissection is a catastrophic illness
characterized by dissection of blood between
and along the laminar planes of the media,
with the formation of a blood-filled channel
within the aortic wall , which often ruptures
outward, causing massive hemorrhage.
The dissection can extend along the aorta
proximally toward the heart as well as
distally, sometimes all the way into the iliac
and femoral arteries. It often ruptures out,
causing massive hemorrhage.
In some instances, the blood reruptures
into the lumen of the aorta, producing a
second or distal intimal tear and a new
vascular channel within the media of the
aortic wall (to produce a "double-barreled
aorta" with a "false channel").
Clinically presents with severe chest pain.
Can be confused with a heart attack.
Can result in the aortic rupture with bleeding
into the pericardial sac, causing
hemopericardium and fatal cardiac
tamponade.
It is typically associated with hypertension or
with cystic medial necrosis ( esp. in Marfan
syndrome)
It has no relation to atherosclerosis.
Mostly immune reaction related:
◦ Immune complexes.
◦ Antineutrophil cytoplasmic antibodies (ANCAs).
P-ANCAs (perinuclear myeloperoxidase)
C-ANCAs (cytoplasmicproteinase 3)
ANCAs are a heterogeneous group of
autoantibodies directed against enzymes
mainly found within the azurophil or primary
granules in neutrophils, in the lysosomes of
monocytes, and in endothelial cerlls.
The description of these autoantibodies is
based on the immunofluorescent patterns
of staining of ethanol-fixed neutrophils.
Two main patterns are recognized:
one shows cytoplasmic localization of the
staining (c-ANCA).
The second shows perinuclear staining (pANCA) and is usually specific for
myeloperoxidase (MPO).
c-ANCA is typically found in Wegener
granulomatosis and
p-ANCA is found in most cases of
microscopic polyangiitis and Churg-Strauss
syndrome.
The disorders characterized by circulating
ANCAs are called the ANCA-associated
vasculitide
ANCAs serve as useful quantitative diagnostic
markers for these conditions, and their levels
may reflect the degree of inflammatory
activity.
ANCAs rise in episodes of recurrence, and
thus are useful in management..
Slide 12.23
is a necrotizing vasculitis characterized by the
triad of
(1) acute necrotizing granulomas of the upper
respiratory tract (ear, nose, sinuses, throat), the
lower respiratory tract (lung), or both;
(2) necrotizing or granulomatous vasculitis
affecting small to medium-sized vessels (e.g.,
capillaries, venules, arterioles, and arteries), most
prominent in the lungs and upper airways but
affecting other sites as well;
(3) renal disease in the form of focal necrotizing,
often crescentic, glomerulitis.
Limited forms, or more widespread WG.
C-ANCAs in present in serum of more than
95% of patients.
May lead to death within 2 years in more
than 90% if not treated.
The upper respiratory tract lesions range
from inflammatory sinusitis resulting from
mucosal granulomas to ulcerative lesions of
the nose, palate, or pharynx, rimmed by
necrotizing granulomas and accompanying
vasculitis.
Microscopically:
granulomas with necrosis surrounded by
lymphocytes, plasma cells, macrophages,
and variable numbers of giant cells.
In association with such lesions there is a
necrotizing or granulomatous vasculitis of
small and sometimes larger arteries and
veins .
Lesions may ultimately undergo progressive
fibrosis and organization.
The renal lesions are of two types .
In milder or early forms: focal necrotizing
glomerulonephritis.
More advanced glomerular lesions are
characterized by diffuse necrosis,
proliferation, and crescent formation
(crescentic glomerulonephritis).
Males are affected more often than females,
at an average age of about 40 years.
Persistent pneumonitis , chronic sinusitis ,
mucosal ulcerations of the nasopharynx , and
evidence of renal disease.
Untreated, the course of the disease is
malignant; 80% of patients die within 1 year.
Wegener granulomatosis. There is inflammation (vasculitis) of a small artery along with adjacent
granulomatous inflammation, in which epithelioid cells and giant cells ( arrows) can be seen.
Necrotizing vasculitis.
Arterioles, capillaries, venules.
All lesions tend to be of the same age.
Involves skin, mucous membranes, lungs
, brain, heart, GI , kidneys and muscle.
Precipitating cause~~ immunologic
reaction to an antigen (drug: penicillin),
(microorganisms: strept.), heterlogous
proteins and tumor antigens.
P-ANCAs in 70% of patients.
Skin biopsy is often diagnostic.
Histologically there is infiltration of vessel
wall with neutrophils, which become
fragmented(leukocytoclasia).
Leukocytoclastic vasculitis in a skin biopsy showing fragmentation of neutrophil
nuclei in and around vessel walls.
Slide 12.29
PAN is a systemic vasculitis of small or
medium-sized muscular arteries (but not
arterioles, capillaries, or venules), typically
involving renal and visceral vessels but
sparing the pulmonary circulation.
Clinical manifestations result from ischemia
and infarction of affected tissues and organs
Classic PAN occurs as segmental transmural
necrotizing inflammation of arteries of medium to
small size, in any organ with the possible
exception of the lung
Most frequently kidneys, heart, liver, and
gastrointestinal tract.
Individual lesions may involve only a portion of the
vessel circumference .
Weakening of the arterial wall due to the
inflammatory process may cause aneurysmal
dilation or localized rupture.
Impairment of perfusion, causes
ulcerations, infarcts, ischemic atrophy, or
hemorrhages in the area supplied by these
vessels.
The histologic picture during the acute
phase is characterized by transmural
inflammation of the arterial wall with
neutrophils, eosinophils, and mononuclear
cells, frequently accompanied by fibrinoid
necrosis. The lumen may become
thrombosed.
.
Later, the acute inflammatory infiltrate
disappears and is replaced by fibrous
thickening of the vessel wall that may extend
into the adventitia.
Particularly characteristic of PAN is that all
stages of activity may coexist in different
vessels or even within the same vessel.
Disease of young adults. The course may be
acute, subacute, or chronic and is
frequently remittent and episodic, with long
symptom-free intervals.
The most common manifestations are
malaise, fever and weight loss;
hypertension; abdominal pain and melena
(bloody stool); diffuse muscular aches and
pains; and peripheral neuritis. Renal arterial
involvement is often prominent and is a
major cause of death.
Polyarteritis nodosa. Polyarteritis nodosa with segmental fibrinoid necrosis and thrombotic occlusion
of the lumen of this small artery. Note that part of the vessel wall at the upper right ( arrow) is
uninvolved.
Slide 12.28
Segmental acute and chronic (most often
granulomatous) vasculitis involving
predominantly the larger arteries in the
head, particularly the branches of the
carotid artery (temporal a.branches of the
ophthalmic a.
Over age of 50, F:M = 2:1.
Characteristically, segments of affected
arteries develop nodular thickenings with
reduction of the lumen and may become
thrombosed.
There is granulomatous inflammation of the
inner half of the media ,with lymphocytes
and, multinucleate giant cells and
fragmentation of the internal elastic lamina.
The healed stage reveals collagenous
thickening of the vessel wall; sometimes the
artery is transformed into a fibrous cord.
Temporal arteritis is most common in older
individuals and rare before age 50.
fever, fatigue, weight loss
facial pain or headache, often most intense along
the course of the superficial temporal artery, which
may be painful to palpation.
More serious are ocular symptoms (associated with
involvement of the ophthalmic artery)range from
diplopia to transient or complete vision loss.
The diagnosis depends on biopsy and histologic
confirmation.
Temporal (giant cell) arteritis.
A. H&E stain of giant cells at the degenerated internal elastic membrane in active
arteritis.
B. Elastic tissue stain demonstrating focal destruction of internal elastic
membrane ( arrow) and intimal thickening (IT) characteristic of long-standing or
healed arteritis.
Slide 12.24
Is characterized by segmental,
thrombosing, acute and chronic
inflammation of medium-sized and small
arteries, principally the tibial and radial
arteries and sometimes secondarily
extending to veins and nerves of the
extremities.
Previously a condition that occurred almost
exclusively among heavy cigarette-smoking
men, Buerger disease has been increasingly
reported in women, probably reflecting
smoking increases.
The disease begins before age 35 in most
cases.
The relationship to cigarette smoking is one
of the most consistent aspects of this
disorder.
Later complications are chronic ulcerations of
the toes, feet, or fingers and frank gangrene
in some patients.
Characterized by segmental acute and chronic
vasculitis of medium-sized and small arteries,
mostly of the extremities.
Microscopically, acute and chronic inflammation
permeates the arterial walls, accompanied by
thrombosis of the lumen, which may undergo
organization and recanalization.
The inflammatory process extends into contiguous
veins and nerves, and in time all three structures
become encased in fibrous tissue.
Thromboangiitis obliterans (Buerger disease). The lumen is occluded by a
thrombus containing two abscesses ( arrows). The vessel wall is infiltrated with
leukocytes.
Slide 12.31