Raynaud’s Phenomenon雷诺氏现象

Raynaud’s Phenomenon雷诺氏现象 RN-KKU Raynaud 1 Raynaud’s Phenomenon Rheum Clin North Am 22 (4); 1996 ??????????? UK Scleroderma Study Group (Br J rhem 32:375-61, 1993) 1. Definite = repeat episode ?? biphasic color changes ?????????????????????? 2. Possible = uniphasic color change + numbness / paresthesia 3. No = no color change on cold exposure ???,???????????,?? lab ?????,? gold standard ????????????? Raynaud’s phenomenon ??,?,?????,??????? finger systolic BP, ?????? flowmetry ?????, lasor doppler ????????????? digital pulse wave patterns ???????????????????????????????,??????,? clinical assessment ??????????, ????????? 3-4% (???????????,?) ???????????????,????????????,?? Raynaud’s phenomenon ?? scleroderma RN-KKU Raynaud 2 ???????,????? primary Raynausd’s phenomenon ????????,?????? 2 ??,???,???????? structural changes + vasospastic arterial disease Scleroderma vasculopathy: 1. ?????????????????,??? endothelial cells ?? fibrotic proliferation ??? intima 2. ??,?? component ??? vasculitis 3. ?? failure ????????? neovascularization (?? capillary enlargement ?,??????? atrophy) ????????????????? EM ??? endothelial cells 1. ?:????????????? pinocytic vesicles ???? 2. ???? surface blebs ??????? 3. ?? perinuclear aggregate ?????,? microfilaments ???????????? 4. suggest ?,???,? degenerative response ?,? noxious stimuli Markers ????????,? endothelium ???,?? activated state 1. von Willebrand factor ????????? 2. tissue plasminogen activator ????????? 3. ?? evidence ??? activated platelets 4. ?????????? E-selectin, P-selectin, VCAM-I, ICAM-1 ??????? 5. ????? plasma endothelin RN-KKU Raynaud 3 ????????? histology ??? digital arteries = severe intimal hyperplasia, fibrosis ??? ?? minimal muscular hypertrophy ??? structural change , , resting systolic BP , blood flow to digits , , skin thickening cutaneous hypoxia vasculopathy ???cut. Vessels cold , vasoconstriction + stress drugs slow postocclusive reactive hyperemia ???????,??:???,???? recovery ???,????????????,???? recruitment ??? deep vessels ???????????????????? primary Raynaud’s phenomenon ????,?,?? SSc ???? 1. more dramatic response ?,????????? 2. lower baseline ??? blood flow 3. prolong recovery after rewarming ?? CREST ???? more severe peripheral vascular occlusive disease ??? Raynaud’s phenomenon RN-KKU Raynaud 4 ??? limited scleroderma + anti-centromere +ve ?????????,? peripheral (occulsive) vascular disease ?:???,???? digital gangrene ??,?,????,??????,???????,??? anticardiolipin Ab ?????? hypercoagulable state ??,??,???? Large vessel disease ?? scleroderma ??,??,?:???,???? digital gangrene ??,???????????? gangrene ?????????????,??????, (Br J Rheum 1988, 27:403-6, Ann Rheum Dis 1993, 52:464-66 Systemic Raynaud’s ?? scleroderma ???????????????????????? ????? ??? ??? GI tract ?????????????? cold induced vasospasm ??????,?????,???? ???,??:???, DLCo ??????,??,??,????????????,??,?,? peripheral vasoconstriction ?????????,??????????????????? pulmonary circulation ?,????????, ?,?????,???????:??????????,??,?????????,?? vasodilator ???????????????,??????,???????????? pulmonary HT ??, Detection of CNTD ????,?,????????,?? Raynaud’s phenomenon ??,??????,???,????????,????? CNTD ?,???,?? 1. later age of onset (>35 ?,) RN-KKU Raynaud 5 2. severe Raynaud’s with digital ulceration 3. presence of autoAb (anti-centromere, anti-Scl 70) 4. nailfold capillary loop abnormality (Rheum Clin North Am 1990; 16:75-91) ?,? loop pattern ???????????????? predict ??,?,? localized form ?:????????????,? systemic form Vascular Biology Control of blood vessel reactivity ???????,??? 1. neural signal 2. circulating hormone 3. mediators ??? release ??? circulating cells 4. ??? blood vessels ??? ???,? contractile activity ??? vascular smooth muscles ?????????????,????,???????,????? ?,?????,??,??????????????????,? circulating hormone ??? environmental stimuli ????????? modified ???,??????,????? neurogenic mechanism ??? endothelial cells ????:????,????? circulating hormones = epinephrine, vasopressin autacoids ?? vessel wall = bradykinin, histamine, leukotrienes RN-KKU Raynaud 6 neurotransmitter ??????????? nerves = NE, Ach, substance P mediators ??? circulating cells = serotonin, ADP/ATP mediators ??? endothelium = prostacyclin, endothelin + + physical chemical releasing mediators ??? stim. EC ++, , Ca ?? cells shear stress ?????????? ,O2 EDNO (EC derived nitric oxide) + + + PGI2 adenyl cyclase EDHF (Endothelial derived hyperpolarizin g factor) Ecs ??,?? contractile mediator s ??,???? ??????,???,? endothelial contractile factors (EDCFs) RN-KKU Raynaud 7 ** Endothelin-1 potent ?????? (??,???,? endothelin 1, 2, 3) + activate ??? ETA receptor ?? vascular smooth muscle vasoactive stimuli transform growth factor-, thrombin angiotensin-II vasopressin (TGF-,) ** TXA, PGH ??????????? receptor ???????? 22 ?????? superoxide anion (ECs ????????????????,?????????????????, radical oxigen ?,????? xanthine oxidase ??? nitric oxide synthetase) Neurogenic stimuli Note : 1. ??? heart NE ??,?????,? , adrenergic receptor ??????? sympathetic tone ????,??????? vasodilate effect 2. ??? human digital artery ??,?? , receptor ??? smooth muscle , adrenergic receptor ??,???,? ,1 (,1A, ,1B, ,1D) ??? ,2 (,2A, ,2B, ,2C) RN-KKU Raynaud 8 ???????? small arteries ???????? cutaneous arteries &vein autonomic + parasympathetic (NO, VIP, Ach) + - activate endothelium vascular beds : skin, cerebral, coronary, pulmonary, mesentaric + sympathetic + sensory nervous system (capsaicin sensitive nerve endings release vasodilator peptides ???????? cutaneous vv.) - calcitonin gene-related peptide (CGRP) - substance P - + NO 23 cold exposure ,sympathetic tone ???????? ,myogenic contractile activity (direct effect) ??? inhibit EDNO