Presentation on theme: "VASCULAR PATHOLOGY By DR. OLA OMRAN ASSOCIATE PROFESSOR"— Presentation transcript:
1VASCULAR PATHOLOGY By DR. OLA OMRAN ASSOCIATE PROFESSOR PATHOLOGY CONSULTANTPATHOLOGY DEPARTMENT
2VASCULITIS DEFINITION: It means “inflammation of the walls of the vessels” and can be associated to many different clinical conditions20 primary forms of vasculitis are recognizedClassifications according to vessel size, role of immune complexes, presence of specific autoantibodies, granuloma formation, organ tropism, and even population demographics.Several vasculitides tend to affect only vessels of particular caliber or tissue beds
3VASCULITISThe two most common pathogenic mechanisms of vasculitis are:immune-mediated inflammationdirect invasion of vascular walls by infectious pathogens. Predictably, infections can also indirectly induce a noninfectious vasculitis, for example, by generating immune complexes or triggering cross-reactivity.Physical and chemical injury, such as from irradiation, mechanical trauma, and toxins, can also cause vasculitis.
4VASCULAR PATHOLOGY VASCULITIS .CLASSIFICATION OF VASCULITIS BASED ON THE PATHOGENESIS:*Direct Infection Bacterial(Neisseria) Rickettsial(spotted fever) Spirochetal(Syphilis) Fungal(aspergillosis) Viral(herpes zoster)
7Noninfectious Vasculitis (immune-mediated inflammation) Immune complex deposition 1. Vasculitis associated with drug hypersensitivity (e.g., penicillin), antibodies directed against the drug-modified self proteins lead to the formation of immune complexes.Manifestations frequently involving the skin and can be mild and self-limiting or severe and even fatal.Discontinuation of the offending agent is often curative.2. vasculitis associated with viral infections, antibody to viral proteins may form immune complexes detectable in the serum and in the vascular lesions; for example, as many as 30% of patients with polyarteritis nodosa have an underlying hepatitis B infection with vasculitis attributable to complexes of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg.
82. Antineutrophil Cytoplasmic Antibodies (ANCA): Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens, so-called ANCAs.ANCAs are a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and endothelial cells.Two general types of ANCAs based on immunofluorescence staining patterns:Cytoplasmic localization (c-ANCA), wherein the most common target antigen is p roteinase-3 (PR3), a neutrophil granule constituentPerinuclear localization (p-ANCA), wherein most of the autoantibodies are specific for myeloperoxidase (MPO).c-ANCA in Wegener granulomatosis & p-ANCA in microscopic polyangiitis and Churg-Strauss syndrome. ANCAs is useful quantitative diagnostic markers for the ANCA-associated vasculitides, and their levels reflect the degree of inflammatory activity. Although the mechanisms are unknown, ANCAs can directly activate neutrophils and stimulates neutrophils to release reactive oxygen species and proteolytic enzymes.
93. Anti-Endothelial Cell Antibodies Antibodies to ECs may predispose to certain vasculitides, for example Kawasaki disease.Another Classifications according to vessel size:………
10Vasculitis type* Examples Description Giant-cell (temporal) arteritis Large-Vessel Vasculitis (Aorta and Large Branches to Extremities, Head, and Neck)Giant-cell (temporal) arteritisGranulomatous inflammation; also frequently involves the temporal artery. Usually occurs in patients older than age 50 and is associated with polymyalgia rheumatica.Takayasu arteritisGranulomatous inflammation usually occurring in patients younger than age 50Medium-Vessel Vasculitis (Main Visceral Arteries and Their Branches)Polyarteritis nodosaNecrotizing inflammation typically involving renal arteries but sparing pulmonary vesselsKawasaki diseaseArteritis with mucocutaneous lymph node syndrome; usually occurs in children. Coronary arteries can be involved with aneurysm formation and/or thrombosis.Small-Vessel Vasculitis (Arterioles, Venules, Capillaries, and Occasionally Small Arteries)Wegener granulomatosisGranulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels, including glomerulonephritis. Associated with c-ANCAs.Churg-Strauss syndromeEosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels. Associated with asthma and blood eosinophilia. Associated with p-ANCAs.Microscopic polyangiitisNecrotizing small-vessel vasculitis with few or no immune deposits; necrotizing arteritis of small and medium-sized arteries can occur. Necrotizing glomerulonephritis and pulmonary capillaritis are common. Associated with p-ANCAs.
131. GIANT CELL (TEMPORAL) ARTERITIS. MOST common form of systemic vasculitisAdults males over 50ysacute or chroniclarge sized vessels ( affects temporal arteries, ophtalmic(blindness) and aorta (aneurysm)GP: tender, nodular thickening of the artery reduction of the lumenthrombosis.MP: Granulomatous inflammation in inner half of media with giant cells.
14GIANT CELL (TEMPORAL) ARTERITIS. Thickened, nodular, and tender arteries
15Temporal (giant cell) arteritis thickened, nodular, and tender segmentGiant cells & granuloma at the degenerated internal elastic membrane in active arteritis H&EElastic tissue stain demonstrating focal destruction of internal elastic membrane (arrow) and intimal thickening (IT) characteristic of long-standing or healed arteritis
16Giant cell arteritis Elastic tissue stain demonstrating: focal destruction of internal elastic membrane (arrow) andintimal thickening (IT) characteristic of long-standing or healed arteritis.
17GIANT CELL ARTERITIS...(cont.) CLINICAL FEATURES:Old patients with fever, fatigue, loss of weight, with or w/o facial pain and headache.More severe form ….involvement of ophtalmic artery diplopia or blindness of abrupt onset.
182. TAKAYASU ARTERITIS. Predominant in females below 50´s Propable autoimmune mechanism,characterized by ocular manifestations/weakness of pulses in upper extremities (reduced brachial pulse), due to vasculitis of Aortic Arch + branches narrowing obliteration.
19TAKAYASU ARTERITIS...(cont.) MICROSCOPIC:Mononuclear infiltration of adventecia.Giant-cell granulomatous inflammation NOT distinguishable from giant-cell arteritis.CLINICAL:Reduced brachial pulse, difference in BP between R & L arm>10 mm Hg, coldness+ numbness of fingers,,Visual defects blindness.
20Takayasu arteritisA, Aortic arch angiogram showing narrowing of the brachiocephalic, carotid, and subclavian arteries (arrows).B, Gross photograph of two cross-sections of the right carotid artery demonstrating marked intimal thickening with minimal residual lumen.C, Destruction and fibrosis of the arterial media and an infiltrate of mononuclear inflammation, including giant cells.
213. POLYARTERITIS NODOSA (PAN). Medium sized arteritis affecting multiple organs (skin, peripheral nerves, gut, kidney and heart.Childhood late adulthood (average 40 ys)Associated with Hepatitis B, C or both (most common in injection drug abusers).Probably mediated by immune complexes (Igs + viral Ags) circulating and deposited in inflammed vessels.
23POLYARTERITIS NODOSA..(cont.) Diagnosis:*Elevated BUN or creatinine*Proven hepatitis B/C virus infection*Angiographic signs of aneuryms/vascular occlusion (60% sensitive)*MP: Demonstration of necrotizing inflammation (segmental fibrinoid necrosis) & granulocytes in medium sized vessels (biopsy).
24Polyarteritis nodosaThere is 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 uninvolved24
254. WEGENER´S GRANULOMATOSIS. Granulomatous inflammation & necrotizing vasculitisAverage age is about 40 yrs.Affects upper respiratory tract, lower respiratory tract and kidneys.Other organs affected:Eye (proptosis/diplopia),Skin (ulcers, purpura)It may remain localized to one site for yrs./mos. systemic later (fever, fatigue, loss of weight, anemia, leukocytosis and increased ESRESR
264. WEGENER´S GRANULOMATOSIS….CONT CLINICAL FEATURES:*Chronic sinusitis(90%)*Chronic pneumonitis in about 95% of patients.*Mucosal ulcerations of nasopharynx (75%)*Renal disease (80%)
28Wegener granulomatosis inflammation of a small artery along with adjacent granulomatous inflammation, in which epithelioid cells and giant cells (arrows)
295. BUERGER´S DISEASE (Thromboangiitis obliterans) Characterized by segmental thrombosis acute / chronic inflammation of medium and small arteries MOSTLY tibial and radial ar teries, and secondarily involvement of veins and nerves of limbs.Apparently heavy cigarette-smokers are MOST frequently affected (endoth. cells hypersensitivity?)Moreover increased prevalence of HLA-A9/ HLA-B5 in these patients and in Israel, Japan, India (genetic trait?)
30Buerger disease The lumen is occluded by a thrombus containing two abscesses (arrows). The vessel wall is infiltrated with leukocytes.
31BUERGER´S DISEASE..(cont.) Microscopically:acute + chronic inflammation in arterial walls + thrombosisorganization/recanalization. Also, thrombosis contains microabscesses + granulomatous inflammation extension to veins/nerves.Late complication: chronic ulceration of toes or fingers gangrene.
32BUERGER´S DISEASE...(cont.) CLINICAL FEATURES:Claudication in feet and/or hands sometimes centrally radiated.Numbness and tingling in limbs + Raynaud´s phenomenon.Skin ulcerations + gangrene of digits
33TUMORS OF BLOOD VESSELS Cavernous hemangioma Large blood filled vascular spacesSeparated by mild to moderate amount of CT stromaIntravascular thrombosis may be seen.
34Kaposi sarcoma Coalescent red-purple macules and plaques of the skin sheets of plump, proliferating spindle cells