Transcript Pathology of Non-Atherosclerotic Vascular Diseases II

Pathology of
Non-Atherosclerotic
Vascular Diseases II
Prof. Dr. Gamze MOCAN KUZEY
NEU
Department of Pathology
Vascular Lesions
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Atherosclerosis
Arteriolosclerosis
Varicose veins
Trombophlebitis
Lymphedema
Aneurysms
Dissection
Vasculitis
Vasculitis
Vasculitis
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Inflammation of the walls of vessels
The two most common mechanisms of
vasculitis are
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the direct invasion of vascular walls by infectious
pathogens and
immune-mediated mechanisms
Physical and chemical injury, such as
irradiation, mechanical trauma, and toxins
can also cause vascular damage.
Pathogenesis of Noninfectious
Vasculitis
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immune complex deposition,
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antineutrophil cytoplasmic antibodies,
(ANCAs),
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anti-endothelial cell antibodies.
Immune Complex Deposition
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DNA-anti-DNA complexes are
present in the vascular lesions of
systemic lupus erythematosusassociated vasculitis
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IgG, IgM, and complement in
cryoglobulinemic vasculitis
Antineutrophil cytoplasmic
Antibodies, (ANCAs)
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ANCAs are a heterogeneous group of
autoantibodies directed against enzymes
mainly found
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within the azurophil or primary granules in
neutrophils,
in the lysosomes of monocytes,
and in endothelial cells (EC)
Antineutrophil cytoplasmic
antibodies (ANCAs)
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Two main patterns are recognized by
immunofluorescent staining:
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one shows cytoplasmic localization of the staining
(c-ANCA), and the most common target antigen is
proteinase-3 (PR3), a neutrophil granule
constituent.
The second shows perinuclear staining (p-ANCA)
and is usually specific for myeloperoxidase
(MPO).
Antineutrophil cytoplasmic
antibodies (ANCAs)
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c-ANCA is typically found in Wegener
granulomatosis
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p-ANCA is found in most cases of
microscopic polyangiitis and Churg-Strauss
syndrome
ANCAs
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The disorders characterized by circulating
ANCAs are called the ANCA-associated
vasculitides.
ANCAs serve as useful quantitative
diagnostic markers and their levels may
reflect the degree of inflammatory activity
Anti-endothelial Cell Antibodies
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Antibodies to ECs, perhaps induced by
defects in immune regulation, may
predispose to certain vasculitides, such as
those associated with SLE and Kawasaki
disease
Classification of Vasculitis
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The systemic vasculitides are classified on
the basis of
the size and anatomic site of the involved blood
vessels
 histologic characteristics of the lesion,
 and clinical manifestations.
There is considerable clinical and pathologic
overlap among them
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Giant cell (temporal) arteritis
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Rare in persons younger than age 50,
extraordinary trophism for a single arterial site
remains unexplained
high incidence in populations of Nordic origins.
The diagnosis depends on biopsy and histologic
confirmation,
Because of the segmental nature of the
involvement, adequate biopsy requires at least a 2to 3-cm length of artery, and negative or atypical
findings on biopsy do not rule out the condition.
Giant cell (temporal) arteritis
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the most common form of systemic vasculitis
in adults,
acute and chronic, often granulomatous,
inflammation of arteries of large to small size
affects principally the arteries in the headespecially the temporal arteries,
but also the vertebral and ophthalmic arteries
and the aorta, where it may cause thoracic
aortic aneurysm.
Giant cell (temporal) arteritis
Pathogenesis
The morphologic alterations suggest an
immunologic reaction against a
component of the arterial wall, such as
elastin
 The granulomatous nature of the
inflammation, association with certain
human leukocyte antigens (HLA-DR),
and the response to corticosteroid
therapy, are consistent with T cellmediated and antigen-driven injury
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TAKAYASU ARTERITIS
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granulomatous vasculitis of medium and larger
arteries, described in 1908 by Takayasu,
characterized by ocular disturbances
and marked weakening of the pulses in the
upper extremities (pulseless disease).
The pathologic findings are vasculitis and
subsequent fibrous thickening of the aorta,
particularly the aortic arch and its branches,
with narrowing or virtual obliteration of the
origins or more distal portions
TAKAYASU ARTERITIS- MORPHOLOGY
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Classically involves the aortic arch,
but in one third of cases it also affects the remainder
of the aorta and its branches,
in half the cases, it affects the pulmonary arteries.
When the aortic arch is involved, the orifices of the
major arteries to the upper portion of the body may
be markedly narrowed or even obliterated by intimal
thickening
The coronary and renal arteries may be affected
TAKAYASU ARTERITIS- MORPHOLOGY
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The changes range from an adventitial mononuclear infiltrate
with perivascular cuffing of the vasa vasorum to intense
mononuclear inflammation in the media.
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Granulomatous inflammation in some cases may be
indistinguishable from those in giant cell (temporal) arteritis.
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Thus, distinctions among active giant cell lesions of the
aorta are based largely on the age of the patient, and most
giant cell lesions of the aorta in young patients are
designated Takayasu arteritis.
POLYARTERITIS NODOSA (PAN)
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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.
POLYARTERITIS NODOSA (PAN)MORPHOLOGY
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Classic PAN occurs as segmental transmural
necrotizing inflammation of arteries of medium to
small size, in any organ
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with the possible exception of the lung, and most
frequently kidneys, heart, liver, and gastrointestinal
tract
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Individual lesions may involve only a portion of the
vessel circumference and have a predilection for
branching points and bifurcations
POLYARTERITIS NODOSA (PAN)MORPHOLOGY
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Particularly characteristic of PAN is that
all stages of activity may coexist in
different vessels or even within the same
vessel.
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About 30% of patients with PAN have
hepatitis B antigen in their serum. There is no
association with ANCA.
KAWASAKI DISEASE (MUCOCUTANEOUS
LYMPH NODE SYNDROME)
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arteritis that often involves the coronary
arteries,
usually in young children and infants (80% of
cases are <4 years old), and
is the leading cause of acquired heart
disease in children in North America and
Japan.
It is associated with the Mucocutaneous
Lymph Node Syndrome
Mucocutaneous Lymph Node Syndrome
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Epidemic in Japan,
also been reported in Hawaii & increasingly in
the continental United States.
20% of patients develop cardiovascular
sequelae,
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ranging in severity from asymptomatic vasculitis of the
coronary arteries, coronary artery ectasia, or aneurysm
formation
to giant coronary artery aneurysms (7 to 8 mm) with rupture
or thrombosis, myocardial infarction, or sudden death.
Mucocutaneous Lymph Node Syndrome
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an acute but usually self-limited illness
manifested by
 fever,
 conjunctival and oral erythema and
erosion,
 edema of the hands and feet,
 erythema of the palms and soles,
 a skin rash often with desquamation,
 enlargement of cervical lymph nodes
KAWASAKI DISEASE
MORPHOLOGY
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The vasculitis is PAN-like, with necrosis
and pronounced inflammation affecting the
entire thickness of the vessel wall, but
fibrinoid necrosis is usually less prominent
KAWASAKI DISEASE
Pathogenesis
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vasculitis results from an immune reaction
characterized by T-cell and macrophage
activation to an unknown antigen, secretion
of cytokines, polyclonal B-cell hyperactivity,
and the formation of autoantibodies to
endothelial cells and smooth muscle cells,
leading to acute vasculitis
MICROSCOPIC POLYANGIITIS
(MICROSCOPIC POLYARTERITIS,
HYPERSENSITIVITY ANGIITIS,
LEUKOCYTOCLASTIC VASCULITIS)
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This type of necrotizing vasculitis generally
affects arterioles, capillaries, and venulesvessels smaller than those involved in PAN.
In contrast to PAN, all lesions tend to be of
the same age.
MICROSCOPIC POLYANGIITIS
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It typically presents as:
"palpable purpura" involving the skin,
involvement of the mucous membranes,
lungs,
brain,
heart,
gastrointestinal tract,
kidneys,
muscle.
Skin biopsy is often diagnostic
MICROSCOPIC POLYANGIITIS
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In contrast to PAN, necrotizing
glomerulonephritis (90% of patients) and
pulmonary capillaritis are particularly
common
The major clinical features are hemoptysis,
arthralgia, abdominal pain, hematuria,
proteinuria, hemorrhage, and muscle pain or
weakness.
MICROSCOPIC POLYANGIITIS
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In many cases, an immunologic reaction to
an antigen such as
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drugs (e.g., penicillin),
microorganisms (e.g., streptococci), heterologous
proteins,
tumor antigens are the precipitating cause
In 70% of patients, p-ANCAs are present.
MICROSCOPIC POLYANGIITIS-MORPHOLOGY
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histologically similar to PAN
In contrast to PAN, muscular and large
arteries are usually spared;macroscopic
infarcts similar to those seen in PAN are
uncommon.
It has the same spectrum of manifestations
as Wegener granulomatosis, granulomatous
inflammation is absent.
MICROSCOPIC POLYANGIITIS-MORPHOLOGY
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Histologically, segmental fibrinoid necrosis of
the media may be present, but in some
lesions the change is limited to infiltration with
neutrophils, which become fragmented as
they follow the vessel wall (leukocytoclasia).
The term leukocytoclastic angiitis (LCA) is
given to such lesions, most commonly found
in postcapillary venules
Disseminated vascular lesions
of hypersensitivity angiitis
may also appear in;
 Henoch-Schönlein purpura,
 essential mixed cryoglobulinemia,
 vasculitis associated with some of the
connective tissue disorders,
 vasculitis associated with malignancy.
Churg-Strauss syndrome
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In allergic granulomatosis and angiitis
(Churg-Strauss syndrome), necrotizing
vasculitis accompanied by granulomas with
eosinophilic necrosis.
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p-ANCAs are present in approximately 50%
of patients.
Churg-Strauss syndrome
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There is a strong association with allergic
rhinitis, bronchial asthma, and eosinophilia
Vessels in the lung, heart, spleen, peripheral
nerves, and skin are frequently involved by
intravascular and extravascular granulomas,
infiltration of vessels and perivascular
tissues by eosinophils is striking.
WEGENER GRANULOMATOSIS
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Wegener granulomatosis is a characterized by the
triad of necrotizing vasculitis
acute necrotizing granulomas of the upper
respiratory tract (ear, nose, sinuses, throat), the
lower respiratory tract (lung), or both;
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;
renal disease in the form of focal necrotizing, often
crescentic, glomerulitis.
WEGENER GRANULOMATOSIS
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In some patients the disease is restricted to
the respiratory tract "limited" Wegener
granulomatosis
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Widespread Wegener granulomatosis affects
the eye, skin, and (rarely) other organs,
notably the heart, the clinical syndromes may
be very similar to PAN with the addition of
respiratory involvement.
WEGENER GRANULOMATOSIS
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Upper respiratory tract lesions range from
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inflammatory sinusitis resulting from mucosal
granulomas to
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ulcerative lesions of the nose, palate, or
pharynx, rimmed by necrotizing
granulomas and accompanying vasculitis.