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1、痛风,四川大学华西医院,石桂秀,The GOUT,Gout has the unique distinction of being one of the most frequently recorded medical illnesses thru-out history. It was once incorrectly thought to be a disease of the wealthy. Caused by eating too much rich food and drinking fine wines.,What Is Gout (痛风的概念）,Gout a form of a
2、rthritis also known as metabolic arthritis or gouty arthritis . It is the sudden, severe attacks of pain, tenderness, warmth, and swelling in some joints. Gout usually affects one joint at a time, the big toe. It also can affect other joints such as the ankle, heel, instep, knee, wrist, elbow, finge
3、rs, and spine.,痛风的流行病学,高尿酸血症 痛风 西方国家 5%20% 0.5-1% 中 国 10.1% 0.34% 近年来患病率呈上升趋势！,痛风是高等动物特有的疾病,Why our body produce urate? Why nonprimates and most mammals with much lower serum urate（10 times lower）? How does hyperuricemia lead to an inflammatory response to urate crystals?,尿酸的生理功能,Urate may serve as
4、primary antioxidant in human blood, remove singlet oxygen and radicals as effectively as vitamin C. Level of plasma uric acid (300 mM) are approximately 6 times those of vitamin C in humans May play a role in immunity as an adjuvant. Only crystalline uric acid can serve as an adjuvant (shi et al. 20
5、03) Low levels of uric acid led to delayed tumor rejection and treating the tumor mice with uric acid enhanced the rate rejection,Absence of Uricase in humans,Humans the only mammals gout develop spontaneously In most fish, amphibians and nonprimate mammals, UA generated from purine metabolism under
6、goes oxidative degradation through uricase enzyme, producing more soluble compound allantoin. In humans, uricase gene is crippled by 2 mutations that introduce premature stop codons Absence of uricase, combined extensive reabsorption of filtered urate, resulting urate levels in human plasma approxim
7、ately 10 times than other mammals (30-59 mmol/L) Hyperuricemia has detrimental in humans-pathogenetic roles in gout and nephrolithiasis and putative roles in hypertension and other CV disorders.,- the fact that loss of uricase occurred in the same era suggests that it may have conferred a survival a
8、dvantage during that period - our ancestors in the Miocene era were mainly limited to a diet of fruits and grasses (low in sodium); this low sodium diet may have led to a hypotensive “crisis” - loss of uricase and accumulation of uric acid might have compensated for Hypotension - biped more dependen
9、t on blood pressure to maintain cerebral perfusion,Possible reasons for human and primates loss their uricase,the experiment - rats fed a low-sodium diet then treated with oxonic acid, a uricase inhibitor - this effect can be blocked by allopurinol (reduces uric acid biosynthesis),.,Pathophysiology
10、of gout: How does hyperuricemia lead to an inflammatory response to urate crystals? -presence of crystals stimulates a two-pronged inflammatory signal * activation of complement results in chemoattractant generation which activates and attracts bloodstream neutrophils * vascular endothelial cells mu
11、st first be activated by cytokines generated by macrophages lining the synovium (IL-1, IL-6 and TNF-) - new evidence indicates a role for the inflammasome in the onset of gout,痛风的临床表现,痛风可发生于任何年龄，高峰年龄为40岁左右；男性多见，女性只占5%，且多为绝经后妇女；约50%有遗传史；多见于肥胖和脑力劳动者；在关节炎中，痛风性关节炎占5%。 可分为四个阶段 无症状期 急性期 间歇期 慢性期,一、无症状期 只表现
12、为高尿酸血症而无任何症状 由无症状的高尿酸血症发展至痛风一般经历数年至数十年，但可终生不发生痛风 高尿酸血症进展为痛风的机制不明确，但通常与血尿酸水平和持续时间相关,血尿酸 尿酸盐结晶在关节腔内的沉积 白细胞吞噬尿酸盐结晶 细胞内的溶酶体等破坏 释放蛋白水解酶，激肽组胺和趋化因子 炎症细胞释放IL-1，IL-6，TNF 局部血管扩张，渗透性增高，白细胞聚集 急性关节炎,二、急性关节炎期,关节炎特点： 第一次发作多发生于凌晨突然发生，2448h达到高峰； 多在大足趾的蹠关节，也可发生于足弓，踝，跟，膝，腕，指和肘关节； 多侵犯单个关节，偶可多个关节同时受累，大关节可伴有关节腔积液； 主要表现为关
13、节的红、肿、热、痛； 可有全身症状； 持续1-20天，经治疗缓解或自我缓解； 少数患者可遗留皮肤色素沉着，脱屑。,三、 间歇期 两次发作之间的静止期 大多数患者反复发作，少数只发作一次 间隔时间为0.5-1年，少数长达5-10年 未用抗尿酸药物者，发作次数渐趋频繁,四、慢性期 慢性关节炎。 痛风石：出现于病后3-42年，平均11年，小于5年者少见，多见于耳廓、手、足、肘、膝等。 肾脏病变 痛风性肾病 尿酸性肾石病,痛风诊断,痛风的分类标准,EULAR关于痛风的诊断建议 -2006年,建,议,推荐力度和95% CI,1.关节炎急性发作时,表现为快速发生的严重疼痛、肿胀,和压痛,6-12小时达高峰
14、,尤其是皮肤表面发红,虽对痛 风诊断无特异性,但高度提示晶体性炎症,88(8096),2.有典型的痛风(如复发性痛风足),单纯临床诊断应是准,确的,但未证实晶体的存在不能确诊痛风,95(9198),3.滑液或痛风石吸取物中证实有尿酸盐结晶可确诊痛风,96(93100),4.对不能确诊的炎性关节炎,均推荐在其滑液中常规找尿,酸盐结晶,90(8397),5.无症状性关节内证实有尿酸盐结晶可确诊痛风间歇期,84(7891),Zhang W, et al. Ann Rheum Dis, 2006,65:1301-1311,基于循证医学和Delphi技术,EULAR关于痛风的诊断建议 -2006年,建,
15、议,推荐力度和95%CI,6.痛风与败血症可同时存在,故怀疑化脓性关节炎时,即使,证实有尿酸盐晶体存在,也应行革兰染色和滑液培养,93 (8799),7.作为痛风最重要的危险因素,血尿酸的高低不能证实或,排除痛风,因不少的高尿酸血症者不发展为痛风,而在痛风,急性发作期,血尿酸水平可正常,95(9299),8.某些痛风患者,尤其是有家族史的年轻痛风患者(年龄小,于25岁的发作者)或有肾结石者,应行肾脏尿酸分泌测定,72 (6281),9.虽然放射线有助于鉴别诊断,且可显示慢性痛风的典型,特征,但对早期或急性痛风的确诊无帮助,86(7994),10.应评估痛风和相关并发症包括代谢综合症(肥胖、高脂
16、,血症、高血糖、高血压)的危险因素,93(8898),Zhang W, et al. Ann Rheum Dis, 2006,65:1301-1311,痛风的分类标准1 -1963年罗马标准 如下4项中满足2项, 突然发作的疼痛性关节肿胀, 2周内缓解 血尿酸:男性7mg/dl,女性6mg/dl 有痛风石 滑液或组织中有尿酸盐结晶(金标准),Kellgren JH,et al,editors.The epidemiology of chronic rheumatism.,City, state: Oxford Blackwell,1963,P327.,J clin Rheumatol,2009,15:22-24,临床标准(2/3) 敏感性66.7%, 特异性88.5%, 阳性预测值 76.9%,阳性预测值:符合标准的患者,中,经金标准验证有病病例(真,阳性)所占的比例,敏感性:发现病人能力,特异性:确定非病人能力,痛风的分类标准2 -1968年纽约标准 满足以下2项中任何一
