and the Kidney硬皮病肾课件.ppt

Must distinguish SRC from other formx of TMA particularly TTP/HUS who characteristically present with thrombocyoopenia, purpura, and prominent microangiopathic hemosysis and have rapidly progressive renal failure * Characteristic histologic finding in kidney in SRC is intimal proliferation and thickening that leads to narrowing and obliteration of vascular lumen with concentric onion skin hypertrophy. 1.Subinitiaml fibrin deposition without inflammation in an interlobular artery Marked narrowing of vascular lumen diminishes distal perfusion, potentially leading to tissue necrosis if there is near total or total occlusion 2. Complete obliteration of vascular lumen * Branches of a muscular renal artery. * Scleroderma and the Kidney David Shure July 14, 2009 DD: Renal Failure ATN Renal Scleroderma Crisis Epidemiology Prevalence: 19-75 cases per 100,000 Susceptibility Age: peak occurrence 35-65 F:M 7-12:1 Environmental Factors: infection Occupational exposure: silica dust Usually occurs w/in 4-5 yrs of SSc onset Local vs Systemic Disease Classification dcSSC: diffuse cutaneous SSc lcSSc: limited cutaneous SSC SSc sine scleroderma – internal organ involvement Environmentally induced scleroderma Overlap syndrome: ie MCTD Calcinosis cutis Raynaud Phenomenon Esophageal dysmotility Sclerodactyly Telangiectasia Pathogenesis Complex and poorly understood Immune activation Inflammatory response Vascular damage Excessive synthesis EC matrix and collagen deposition Hypothesis: interplay between early immunological events and vascular changes leading to generation of a pop of activated fibrogenic fibroblasts believed to be effector cells in disease Vascular and Endothelial Changes Appear to precede other features of SSc Vasoconstriction ET-1: significantly elevated in SSc and assoc with pulm htn, may initiate fibrosis Superoxide anions: released from endothelium neutralize NO Defective vasculogenesis: fewer circulating endothelial ell precursors ie CD34+, CD133+ and VEGF