16. Vascular pathology II. VASCULITIS • Vessel wall inflammation is termed vasculitis • Can affect several organs (systemic vasculitis) or a single organ (e.g., skin, CNS) • Pathogenesis: divided into infectious vasculitis (e.g., angioinvasive Aspergillosis) and noninfectious vasculitis Noninfectious systemic vasculitides • Rare • Significant number of cases are diagnosed during autopsy because the symptoms of diseased organs are not considered as consequences of vasculitis • Lethal if untreated Classification according to vessel size Large vessel vasculitis - affects the aorta and its major branches Medium vessel vasculitis - affects the main visceral arteries and their branches Small vessel vasculitis - affects intraparenchymal arteries, arterioles, capillaries, and veins LARGE VESSEL VASCULITIDES TAKAYASU ARTERITIS General features • In females; age less than 40 years • Pathomechanism: T-cell-mediated immune response to vessel wall antigen(s) Morphology • Granulomatous inflammation in the aorta and its proximal branches fibrous thickening of the aortic arch with obliteration of the mouths of the great vessels • Other arteries can also be affected Clinical features • Slowly progressive course • Diminished upper extremity pulses (pulseless disease) ischemic symptoms in the arms • Ocular and neurologic disturbances are common GIANT CELL ARTERITIS General features • In individuals above 50 years of age • Pathomechanism: T-cell-mediated immune response to vessel wall antigen(s) Morphology • Segmental transmural granulomatous inflammation of head arteries, most often involving temporal arteries, but also ophtalmic or vertebral arteries Consequence: stenosis or complete obliteration of the vessel Clinical features • Fever, fatigue, weight loss; sedimentation rate >50 mm/h • Palpable nodularity of the tortuous temporal artery • Headaches, facial pain, jaw claudication during chewing • Visual symptoms + sudden unilateral visual loss blindness • Diagnosis: histological examination of biopsy specimen of the temporal artery MEDIUM VESSEL VASCULITIDES POLYARTERITIS NODOSA General features • In middle aged adults who may had previous HBV or other viral infection; seems mediated by immune complex deposition (eg., HBsAg-HBsAB) in arteries • Necrotizing arteritis involving most often renal arteries > heart >liver > GI > muscles > other • Negatives: does not involve pulmonary arteries and glomerular capillaries; negative for ANCA autoantibodies Morphology Simultaneous presence of early and healed lesions Early lesions: segmental fibrinoid necrosis of arterial wall with transmural and periadventitial inflammatory infiltrates; consequences: 1) vessel wall weakening: microaneurysm formation, rupture, hemorrhage in the adjacent tissues; 2) endothelial necrosis: thrombosis and distal infarcts Healed lesions: fibrous thickening of the arterial wall, scars at sites of infarction Clinical features • Fever, malaise, weight loss, eosinophilia in peripheral blood + presentation related to the tissues involved • Multiple small infarcts in the kidneys: increased se-creatinine, hypertension, hematuria, proteinuria • Multiple small infarcts in the heart progressive heart failure (ECG changes, serum elevation of creatine kinase MB, coronarography: significant stenosis is not present at the orifices) • Etc., KAWASAKI DISEASE General features • Pathomechanism: mediated by anti-endothelial cell antibodies? • Usually self-limited illness in infants and children Morphology • Affects medium and small arteries; coronary arteries are often involved • Necrotizing arteritis with thrombosis and aneurysm formation + rupture Clinical features • Acute febrile illness, oral/conjunctival erythema, skin rash, and lymphadenomegaly 1 16. Vascular pathology II. • Myocardial infarction SMALL VESSEL VASCULITIDES Glomerular capillary involvement (glomerulonephritis; GN) is present Classification according to pathogenesis • Antibody-mediated (ANCA-associated, anti-GBM disease) • Immune complex-mediated (IgA vasculitis) ANCA-ASSOCIATED VASCULITIDES Pathogenesis II hypersensitivity Target antigens: lysosomal proteins, such as proteinase 3 (PR3) or myeloperoxidase (MPO) released from activated neutrophils formation of autoantibodies termed anti-neutrophilic cytoplasmic antibodies (ANCAs) ANCAs induce neutrophil degranulation and necrotizing inflammatory injury to endothelial cells of small vessels GRANULOMATOSIS WITH POLYANGIITIS (GPA, formerly Wegener’s granulomatosis) General features • Usually in the 5th decade; more common in men • Serology: positive for PR3-ANCA • Triad: involvement of kidneys, lungs and upper airways (nose, sinuses, pharynx) Morphology • Kidneys: necrotizing GN crescents • Upper airways and lungs: necrotizing-granulomatous vasculitis and necrotizing granulomas • Lungs: cavitation due to necrosis of small vessels and parenchyma; common in lower lobes Clinical features • Kidneys: rapidly progressive GN sy: hematuria, proteinuria, increasing serum creatinine; within 1 year, the patient requires hemodialysis • Lungs: bilateral nodular infiltrates + cavitation on X-ray • Chronic sinusitis; nasopharyngeal ulcers epistaxis MICROSCOPIC POLYANGIITIS (MPA) General features • Necrotizing vasculitis involving arterioles, capillaries, and venules • All lesions are in the same stage of inflammation • Serology: MPO-ANCA positivity Morphology • Kidneys: necrotizing GN crescents • Lungs: alveolar capillaritis pulmonary hemorrhage • Skin: neutrophilic infiltration of dermal vessels + fibrinoid necrosis of vessel walls purpuras • GI, muscles, etc. Clinical features Kidneys: symptoms of rapidly progressive GN Lungs: hemoptysis (spit of blood) Skin: vasculitic purpuras GI: ulcerations abdominal pain, melaena; muscles: weakness, myalgias (CK) ANTI-GBM DISEASE Lectured in the chapter of kidney diseaes IgA VASCULITIS (formerly: Henoch-Schönlein purpura) General features • Type III hypersensitivity: immune complex vasculitis with IgA-deposits in arterioles, capillaries and venules • Mainly in children; most frequent vasculitis in childhood Morphology • Necrotizing vasculitis in the skin, the bowels, the joints, and the kidneys • In the kidneys, immunostaining reveals mesangial deposits of IgA; light microscopy: necrotizing GN crescents Clinical features • Skin: purpuras, principally in the lower extremities • Bowels: abdominal pain, bleeding • Joints: arthritis and arthralgia • Kidneys: hematuria, proteinuria and azotemia. Outcome depends on the extent of crescent formation; overall prognosis is good DISEASES OF VEINS Extremely common; 90% involve varicose veins or thrombophlebitis/phlebothrombosis VARICOSE VEINS Abnormally dilated, tortuous veins due to chronically elevated intraluminal pressure. Common sites • Esophageal varices • Varicosity of superficial veins of the lower extremity • Hemorrhoids (piles) • Varicocele ESOPHAGEAL VARICES • In portal hypertension, the submucosal veins of distal esophagus undergo dilation (portocaval shunt) 2 16. Vascular pathology II. • Spontaneous rupture hemorrhagic shock exsanguination • Autopsy: 2000-3000 ml-s of fresh blood fills the stomach and small bowels Remember three common causes of hemorrhagic shock: rupture of esophageal varices rupture of aortic aneurysm/dissection of aorta arrosion of arteries of pancreas by duodenal peptic ulcer VARICOSITY OF SUPERFICIAL VEINS OF THE LOWER EXTREMITY Dilation of the saphenal veins; frequency: in 10 to 20% of the general population!!! Pathogenesis Chronically intraluminal pressure - pregnancies - previous deep vein thrombosis - prolonged standing (waiter, hair-dresser) Complications • Valve-incompetency, stasis + local thrombosis, persistent anasarca • Stasis dermatitis and trophic ulceration on the medial aspect of the ankle and lower leg varicose ulcers: heal poorly, bacterial superinfection is frequent • Thrombosis is frequently associated with inflammation (thrombophlebitis) however, low risk of pulmonary thromboembolism HEMORRHOIDS • Dilations of the anal and perianal submucosal venous plexuses • Affects 5% of the adult population Pathogenesis • Chronic constipation with straining at stool low-residue Western diet • Venous stasis of pregnancy • Portal hypertension Complications • Anal bleeding • Prolapse through the anal verge • Sec. inflammation, thrombosis and infarction - acute intense pain VARICOCELE • Varicosity of the pampiniform venous plexus within the spermatic cord • Frequent in young men; more common on the left side (the left internal spermatic vein empties into the renal vein, the right internal spermatic vein drains directly the inferior vena cava) • Consequence: the intrascrotal temperature raises a reduction in the rate of spermiogenesis oligospermia in the semen (< 20 M sperms/ml) danger of infertility THROMBOSIS IN DEEP LEG VEINS Most important consequence pulmonary embolism Risk factors • Advanced age (>60 years) • Congestive heart failure (stasis in venous circulation) • Bed rest or immobilization • Tissue injury: fracture of femur neck (frequent event in the elderly), polytraumatisation • After ortopedic or abdominal surgery • Pregnancy, after delivery • Disseminated cancer • In young adults: factor V gene mutation rendering factor V resistant to protein C inactivation; inherited deficiencies of natural anticoagulants: antithrombin III, protein C, or protein S OBSTRUCTION OF CAVAL VEINS Compression or infiltration of superior caval vein by bronchial cc or mediastinal lymphoma dilation of veins of head, neck and arms + venous edema