1. Peripheral Arterial Disease Aortic Aneurysms / Vasculitis Peter B. Baker, MD

2. Objective for Part 1 1. Describe aneurysms of the peripheral vessels by type and morphology 2. Differentiate atherosclerotic aneurysm, syphilitic aneurysm and dissecting hematoma by pathology, clinical presentation and prognosis 3. Describe the life threatening cardiovascular manifestations of Marfan syndrome

3. Types of Aneurysms Handout I.A  True aneurysm Aneurysm wall has all 3 layers  False aneurysm Aneurysm wall is adventitia only

4. Types of Aneurysms

5. Vascular Aneurysms  Etiologies  Atherosclerosis  Syphilis  Vasculitis (ie PAN)  Infection (mycotic)  Trauma  Congenital defect

6. Atherosclerotic Aortic Aneurysm Handout I.C  Men > Women - familial  Abdominal aorta most common site  Pathogenesis involves medial atrophy  Complications emboli (athero- or thrombo-) branch occlusion compression of adjacent structure risk of rupture increases with aneurysm size 4 – 4.9 cm, 1% per year 5 – 5.9 cm, 11% per year > 6 cm, 25% per year

7. Atherosclerotic Aneurysm Atherosclerotic Aneurysm Abdominal Aorta

8. Atherosclerotic Aneurysm - Histology Atherosclerotic Plaque Atherosclerotic Aortic Aneurysm

9. Syphilitic Aortic Aneurysm Handout I.D  Thoracic aorta  Pathology inflammation of vasa vasorum obliterative endarteritis ischemic necrosis of media fibrosis (“tree bark”) of intima  Complications compression of adjacent structures aortic valve regurgitation

10. Syphilitic Aortic Aneurysm

11. Syphilitic Aortitis Vasa Vasorum Syphilitic Aortitis

12. Obliterative Endarteritis Obliterative Endarteritis in Syphilitic Aortitis

13. Dissecting Aortic Hematoma Handout I.E Pathology intimal tear split between middle and outer third of the media media may be normal or show degeneration Complications rupture – hemorrhage branch obstruction Predisposing conditions hypertension connective tissue disorders with medial degeneration

14. Aortic Dissection Classification Based on Extent of Involvement

15. Dissecting Aortic Aneurysm Gross Specimen H Aorta PA

16. Dissecting Hematoma Extending Into Common Iliac Arteries H H

17. Dissecting Hematoma of the Aorta – Histologic Section Lumen Media Dissection Dissecting Hematoma - Aorta

18. Aorta – Normal Media (Elastic Stain) Media of Normal Aorta

19. Aorta with Severe Medial Degeneration Aorta with Medial Degeneration

20. Aorta with Severe Medial Degeneration – Colloidal Iron Stain Aorta with Medial Degeneration – Colloidal Iron Stain

21. Objective for Part 2  Describe the etiology, pathology and selected clinical presentations of vasculitides involving large, medium size and small arteries

22. Causes of Vasculitis Handout II.A  Infection  Immunologic mechanisms  Radiation  Trauma  Caustic substances  Unknown

23. Vasculitis – Pathogenesis Handout II.A - B Immune complexes circulating or form in-situ Antineutrophilic cytoplasmic antibodies (ANCA) perinuclear (pANCA, Myeloperoxidase-ANCA) – microscopic polyangiitis cytoplasmic (cANCA, Proteinase3-ANCA) – Wegener Antiendothelial antibodies Cell-mediated immunity

24. Vasculitis-Classification Large Vessel Giant cell (temporal) Takayasu Medium – sized vessel Polyarteritis nodosa Kawasaki Small – sized vessel Microscopic polyangiitis Wegener granulomatosis

25. Temporal Arteritis Handout II.C.1  Etiology – unknown ?T-cell mediated injury  Clinical – rare before age 50, F > M, headache, visual disturbances, fever, weight loss, swelling over temporal artery  Pathology - Granulomatous or nonspecific chronic inflammation - Intimal proliferation / fibrosis with luminal narrowing - Segmental distribution

26. Temporal Arteritis - Histology L Temporal Arteritis

27. Temporal Arteritis - Histology Temporal Arteritis

28. Takayasu Arteritis Handout II.C.2  Etiology – unknown  Clinical – age < 40 years, visual disturbances, weak arm pulses, neurologic manifestations, hypertension  Pathology - Involves aortic arch and branches - May involve descending aorta and pulmonary artery - Intimal fibrosis - Granulomatous or nonspecific chronic inflammation

29. Takayasu Arteritis with Severe Narrowing of the Carotid Artery

30. Takayasu Arteritis - Histology A Takayasu Arteritis

31. Polyarteritis Nodosa Handout II.D.1  Etiology – unknown  Clinical - most often in young adults, occasionally in pediatric age or older adults - can be acute, relapsing or chronic - manifestations include hypertension, abdominal pain, renal failure, GI hemorrhage, muscle pain, neuritis, fever, weight loss, infarcts - 30% have circulating HBsAg-HBsAb immune complexes

32. Polyarteritis Nodosa Handout II.D.1  Pathology Medium to small muscular arteries involved Vasculitis is haphazard and segmental Frequency: kidney > liver > heart > GI Early findings - fibrinoid necrosis, neutrophils Vasculitis heals by fibrosis May develop thrombosis, aneurysm formation

33. Polyarteritis Nodosa in a Small Muscular Artery Polyarteritis Nodosa

34. Polyarteritis Nodosa in a Small Muscular Artery Polyarteritis Nodosa

35. Polyarteritis Nodosa with Aneurysm and Thrombosis Thrombus Polyarteritis Nodosa with Aneurysm and Thrombus

36. Hemorrhagic Small Bowel Infarction in Polyarteritis Nodosa

37. Polyarteritis Nodosa with Early Healing Intima Lumen Polyarteritis with Early Healing

38. Allergic Granulomatosis (Churg-Strauss) Handout II.D.1.d  Pathology similar to PAN and microscopic polyangiitis  Bronchial asthma / allergic rhinitis / eosinophilia / pANCA in <50%  Granulomas / infiltration of vessels by eosinophils  Involves lung, heart, spleen, peripheral nerves, skin

39. Kawasaki Disease Mucocutaneous Lymph Node Syndrome Handout II.D.2  Etiology – ?T-cell response to an infection  Clinical – Infants and children, fever, oral mucosa erythema, skin rash, lymphadenopathy, erythema of palms and soles  Pathology Coronary artery vasculitis (accounts for fatalities in 1 – 2%)

40. Microscopic Polyangiitis Handout II.E.1  Etiology – reaction to an antigen / pANCA  Clinical – skin rash, other organs  Specific disorders – H-S purpura, cryoglobulinemia, malignancy  Pathology Involves microvasculature Fibrinoid necrosis Karyorrhexis of PMN’s (leukocytoclastic)

41. Skin Biopsy with Microscopic Polyangiitis

42. Microscopic Polyangiitis

43. Wegener Granulomatosis Handout II.E.2  Etiology – cANCA  Clinical – sinusitis, pneumonitis, renal failure, glomerulonephritis  Pathology - Distribution - kidneys / upper and lower respiratory tract - Necrotizing granulomas - Vasculitis with fibrinoid necrosis

44. Wegener’s granulomatosis – Small Artery with Fibrinoid Necrosis Wegener Granulomatosis

46. Thromboangiitis Obliterans Buerger Disease Handout II.E.3  Etiology – unknown / ? genetic influence  Clinical – cigarette smoking, < 35 years, claudication of extremities, ischemic ulcers, gangrene  Pathology Vasculitis with thrombosis PMN collections in thrombi

47. Wegener Granulomatosis

49. Thank you for completing this module  If you have any questions or feedback, please contact me:  Peter.Baker@ChildLab.com

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