vasculitis blood vessel pathology imp pdf

medically important condition

1. Vasculitis - Vasculitis refers to a broad and heterogeneous disease spectrum characterized by inflammation and damage of the blood vessel. Vessels of any type in virtually any organ can be affected , but most vasculitis affect small vessels ranging in size from arterioles to capillaries to venules. The two common pathogenic mechanisms of vasculitis are immune-mediated inflammation and direct invasion of vascular walls by infectious pathogens .

2. Vasculitis: Definition - Pathologist Rheumatologist A clinicopathologic process characterized by inflammatory dest r uction of blood vessels that results in occlusion or destruction of the vessel and ischemia of the tissues supplied by that vessel. "Systemic vasculilides " Inflammatory destruction of blood vessels​ Infiltration of vessel wall with inflammatory cells​ Leukocytoclasis ​ Elastic membrane disruption​ Fibrinoid necrosis of the vessel walls​ chemia , occlusion, thrombosisAneurysm formation Rupture, hemorrhage

3. Pathogenesis IgAV is a leukocytoclastic vasculitis with an IgA-dominant immune complex deposited within or around the small vessels. IgAVN manifests similarly to IgAN , both characterized by hematuria , proteinuria and glomerular mesangial immune complex deposition, and its pathogenesis can be explained by a similar “four-hit” theory (25), that is, increased production of circulating galactose-deficient IgA1 (hit1) binds to specific IgA1 autoantibodies (hit2), forming pathogenic circulating immune complexes (CICs) (hit3), which then deposits in the glomerulus and triggers inflammatory responses (hit4). -

4. This hypothesis highlights the critical role of Gd-IgA1 in renal injury. First hit is provided by elevated AECA levels of IgA1 isotype (30), followed by the binding of IgA1-AECA complexes to specific b2 glycoprotein I receptors on vascular endothelial cells (hit2), inducing excessive production of proinflammatory factors such as interleukin-8 (IL-8), which in turn stimulates neutrophil recruitment (hit3), and then neutrophils are activated by the interaction of IgA1 and IgA1 Fc alpha receptor I ( FcaRI , also called CD89), causing extensive damage to the vascular endothelium wall via antibody-dependent cellular cytotoxicity (ADCC), complement-mediated cytotoxicity (CDC), and reactive oxygen species (ROS), ultimately leading to systemic vascular inflammation and permeation (hit4).

5. Vasculitis: Classification - Large-vessel vasculitis 1.Aorta and the great vessels (subclavian, carotid) 2.Claudication, blindness, stroke Medium-vessel vasculitis 1.Arteries with muscular wall 2.Mononeuritis multiplex (wrist/foot drop), mesenteric ischemia, cutaneous ulcers Small-vessel vasculitis 1.Capillaries, arterioles, venules 2.Palpable purpura, glomerulonephritis, pulmonary hemorrhage

6. Giant Cell (Temporal) Arteritis - It is a chronic inflammatory disorder of large to small- sized arteries that principally affects arteries in the head- especially the temporal arteries- but also the vertebral and ophthalmic arteries. Ophthalmic arterial involvement can lead abruptly to permanent blindness; consequently, giant cell arteritis is a medical emergency requiring prompt recognition and treatment.

7. - T-cell-mediated immune response against one of handful of vessel wall antigens that drives subsequent proinflammatory cytokine production (particularly TNF). Anti-endothelial cell and anti-smooth muscle cell antibodies can also be demonstrated in roughly two thirds of patients, although it is unclear whether these are causal or a consequence of other immune injury.

8. - A cellular immune etiology is supported by the characteristic granulomatous response, a correlation with certain MHC class II haplotypes, and a prompt therapeutic response to steroids.

9. MORPHOLOGY - Intimal thickening (with occasional thromboses) that reduces the luminal diameter. Classic lesions exhibit medial granulomatous inflammation centered on the internal elastic lamina that produce elastic lamina fragmentation There is an infiltrate of T cells (CD4+ CDS+) and macrophages. Although multinucleated giant cells are seen in approximately 75% of adequately biopsied specimens Granulomas and giant cells can be rare or absent.

10. - Inflammatory lesions are only focally distributed along the vessel and long segments of relatively normal artery may be interposed. The healed stage is marked by medial attenuation and scarring with intimal thickening, typically with residual elastic tissue fragmentation and adventitial fibrosis.

11. Clinical Features. - Rare before age 50 Symptoms may be only vague and constitutional- fever,fatigue , weight loss-or there may be facial pain or headache, most intense along the course of the superficial temporal artery, which can be painful to palpation. Ocular symptoms (associated with involvement of the ophthalmic artery) appear abruptly in about 50% of patients.

12. ELASTIN STAIN -

13. Doctor, Doctor, my teenage son coughed up blood - 15 y/o male with hx of chronic sinusitis and congestion, here with complaints of hemoptysis and dyspnea but stable now.

14. Previously called Wegeners granulomatosis Differential diagnosis 1. Sarcoid 2. TB 3. Churg Strauss Epidemiology of WGN mostly kidney and lung with granuolomas a du l ts (4th and 5th decades) >>>kids caucasians >>> noncaucasian initially with respiratory symptoms and then rena l insufficiency

15. Diagnosis: Clinical findings of sinusitis and pulm finding, order high resolution CT. Check ANCA: (90% of WGN have the marker) with 70% sensitivity Bx : lung: granulomas with geographic patterns of central necrosis and accompanying vasculitis renal: 10% with granulomas, segmental necrotizing GN RX: rapid therapy needed Steroids cyclophosphamide

16. Showing features characteristic of granulomatosis with polyangiitis - a vasculitis and granulomas with multi-nucleated giant cells. -

17. Churg- Strauss Syndrome Churg-Strauss syndrome is a small- vessel necrotizing vasculitis classically associated with asthma, allergic rhinitis,lung infiltrates, peripheral hypereosinophilia, and extravascular necrotizing granulomata. Multisystem diseases with cutaneous involvement (palpable purpura)gastrointestinal tract bleeding, and renal disease (primarily as focal and segmental glomerulosclerosis). Myocardial involvement may give rise to cardiomyopathy

18. - Lung and extrapulmonary sites (skin, heart, nervous system, GI) have prominent eosinophilic infiltrate, granulomatous reaction around necrotic foc i with radially arranged histiocytes and pallisading giant cells near small arteries or arterioles , eosinophilic vasculitis May have fibrin-rich edema, lymphocytes , sarcoid- like granulomas, focal fibrosis and eosinophilic microabscesses

19. Behcet Disease - Beh c et disease is a small- to medium- vessel neutrophilic vasculitis that classically presents as a clinical triad of recurrent oral aphthous ulcers, genital ulcers, and uveitis.

20. Thromboangiitis obliterans or Buerger's disease is a segmental occlusive inflammatory condition of arteries and veins, characterized by thrombosis and recanalization of the affected vessels. It is a non-atherosclerotic inflammatory disease affecting small and medium sized arteries and veins of upper and lower extremities. The etiology of thromboangiitis obliterans is unknown, but use or exposure to tobacco is central to the initiation and progression of the disease. Thromboangiitis obliterans Buerger's Disease -

21. MORPHOLOGY - focal acute and chronic vasculitis of small­ and medium-sized arteries . predominantly of the extremities. Acute and chronic inflammation , accompanied by luminal thrombosis. The thrombus can contain small microabscesses composed of neutrophils surrounded by granulomatous inflammation

22. Clinical Features - Early manifestations include cold induced Raynaud phenomenon (see later), leg pain induced by exercise that is relieved on rest (intermittent claudication), instep foot pain induced by exercise (instep claudication), and a superficial nodular phlebitis. Chronic extremity ulcerations develop, progressing over time to frank gangrene. Smoking abstinence in the early stages of the disease can often ameliorate further attacks; however, once established, the vascular lesions typically do not respond to smoking abstinence.

23. Infectious Vasculitis - Arteritis can be caused by the direct invasion of infectious agents, usually bacteria (Pseudomonas being the classic example) or fungi, in particular Aspergillus and Mucor species. Vascular invasion can be part of a localized tissue infection (e.g., bacterial pneumonia or adjacent to abscesses).

24. - Vascular infections can weaken arterial walls and culminate in mycotic aneurysms (see earlier), or can induce thrombosis and infarction.

25. Management Spectrum of Disease: Cutaneous vasculitis includes various disease states, ranging from skin-limited to systemic involvement. Therapeutic Approaches: Treatment varies based on severity and systemic involvement, with options including topical steroids, oral glucocorticoids, and steroid-sparing agents like colchicine and dapsone. Management Challenges: Effective management is crucial due to the significant impact on patients’ quality of life, but high-quality data guiding treatment is limited.

26. A nonsteroidal therapeutical agent that has shown promise in treating a wide array of vascular diseases is Pentoxifylline (Trental), a potent hemorheological agent that modifies the plasticity of red blood cells, allowing them to pass through narrowed vascular spaces. Drugs that are targeted specifically at neutrophil function can also be effective in cases of neutrophilic vasculitis . Therapeutical success with the sulfonamide sulfasalazine (Azulfidine), which is split at its azo linkage by colonic bacteria into 5-aminosalicylic acid and sulfapyridine (the latter undergoing significant systemic absorption), has been reported in canine LCCV

27. - Nelson's Pediatrics Harrison's Internal Medicine Google search for pictures AAP Board PREP CMDT 2004 References