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1、临床常用生化检验,(P377-410),检验系实验诊断学教研室 张鹏,临床检验诊断学,1肝功I(ALT AST TBIL DBIL IDIL TP ALB G A/G)2肝功II(LDH ALP GGT TBA AFU CHE PA)3心肌酶谱(AST LDH HBDH CK CK-MB)4肾功(BUN Cr CO2 UA cysC)5血脂(CHO TG HDL LDL VLDL ApoA1 ApoB A1/B Lp(a)6离子六项(K Na Cl Ca P Mg)7 GLU8 胰腺炎两项(AMY LIP)9 脑脊液生化(mic-TP Glu Cl)10 浆膜腔积液生化(TP Glu LDH
2、ADA)11 体液免疫(IgG IgA IgM C3 C4 CH50)12微量元素三项(Fe Cu Zn)13铁代谢(Fe UIBC TIBC TS TRF sTfR Ferr)14铜兰蛋白15 24h尿微量白蛋白16 24h尿肌酐清除率17 24h尿蛋白定量18风湿四项(CRP ASO RF ADNs)19 血清蛋白电泳20 血清免疫固定电泳21 尿蛋白电泳22 尿本周氏蛋白电泳21CSF寡克隆电泳(同时抽血2ml),主要内容,第一节:血糖及其代谢产物的检测第二节:血清脂质和脂蛋白检测第三节:血清电解质检测第四节:血清铁及其代谢产物检测第五节:心脏标志物检测第六节:其他血清酶学检测第七节:内
3、分泌激素检测第八节:治疗药物监测,第一节:血糖及其代谢产物的检测,糖代谢常用检验指标:,空腹血糖口服葡萄糖耐量试验糖化血红蛋白糖化血清蛋白(果糖胺)尿微量白蛋白胰岛素C肽谷氨酸脱羧酶抗体(GAD-Ab)胰岛细胞抗体(ICA),空腹血糖(fasting plasma glucose,FPG),参考范围(reference interval):3.96.1mmol/L,血糖的生理调节肝调节糖代谢,维持血糖的动态平衡。降低血糖的激素:胰岛素升高血糖的激素:胰高血糖素、生长激素、肾上腺素、糖皮质激素,血糖升高的临床意义:糖尿病内分泌疾病应激性高血糖药物影响饱食、高糖饮食剧烈运动或精神紧张,血糖降低的临
4、床意义:血中胰岛素升高或降糖药使用过量缺乏抗胰岛素的激素糖原储存缺乏的疾病急性酒精中毒妊娠期饥饿,口服葡萄糖耐量实验(oral glucose tolerance test,OGTT),OGTT的适用范围:OGTT对无症状、轻型糖尿病的诊断有较大意义,对诊断明确的糖尿病及疗效观察则意义不大。,OGTT的操作步骤:1、试验前8h禁烟,酒,咖啡,禁食 2、空腹抽血3、口服Glucose 75g,计时4、0.5h,1h,1.5h,2h,3h时抽血,马上送检,OGTT的临床意义与结果解释:配合FPG,用于诊断1、糖尿病:diabetes mellitus,DM2、空腹血糖受损:impaired fas
5、ting glucose,IFG3、糖耐量受损:impaired glucose tolerance,IGT,1、任意时刻血糖11.1 mmol/L,或FPG7.0 mmol/L,或OGTT的2 h血糖11.1 mmol/L,并经第二天重复检测(以上三个项目中任意之一)证实,结合临床表现,应考虑糖尿病的诊断。2、FPG在6.1 mmol/L 7.0 mmol/L之间但OGTT的2 h血糖7.8 mmol/L为单纯性IFG。3、FPG6.1 mmol/L但OGTT的2 h血糖在7.8 mmol/L11.1 mmol/L之间为单纯性IGT。,糖化血红蛋白检测,Hb 链末端氨基酸与葡萄糖进行缩合反应
6、形成HbA1c酮氨化合物,反应速度取决于血糖浓度及血糖与Hb的接触时间。临床意义:HbA1c反映抽血前12个月内血糖的平均水平,对鉴别糖尿病性高血糖和应激性高血糖有价值。可作为治疗监测和确定治疗方案的依据。参考范围46%,糖化血清蛋白检测,临床意义同HbA1c,但反映抽血前1个月内的血糖水平。参考范围:1.6-2.1mmol/L,血清胰岛素测定及其释放试验,释放试验:指在OGTT的各个时间点上同时测胰岛素,观察在不同血糖浓度下,胰岛素的释放情况.,血清C肽的测定,C肽:胰岛素产生过程的一种中间产物测C肽的优点:不受外源性insulin的干扰,不受insulin抗体的干扰,临床意义:1、正常人:
7、胰岛素,C肽释放入血量与血糖平行。2、DM病人:由于要经常使用外源性的胰岛素血清C肽的水平往往与血糖不平行。,谷氨酸脱羧酶抗体(GAD-Ab),GAD是自身抗原介导的免疫反应所引起胰岛B-细胞破坏的始动靶抗原,GAD-Ab是糖尿病前期较特异的免疫指标。临床意义:可作为1型糖尿病的预测,普查可发现1型糖尿病的高危人群和个体从2型糖尿病患者中鉴别迟发型1型患者,胰岛细胞抗体(ICA),O型人胰腺切片作抗原,采用IFA检测自身抗体。ICA阳性可预示B-细胞的自身免疫损害,只能作为糖尿病的高危指标,儿童阳性或高水平持续阳性,对1型糖尿病有较高预测率。,必须牢记的三组数值,3.9 6.17.0 11.1
8、6.1 7.8,Clinical Cases,0h 0.5h 1h 1.5h 2h(1)8.8 13.8 17.5 16.8 16.7 male,65yrs,obese(2)6.2 11.7 15.2 16.4 15.0 female,62yrs,presented with“burning mouth”(3)5.2 9.5 10.8 10.1 8.5 male,41yrs(4)5.0 8.6 7.7 7.0 10.2 female,45yrs,第二节 血清脂质和脂蛋白的检测,脂蛋白的结构,脂蛋白的分类,各种脂蛋白的结构与功能,TG:Triglyceride 甘油三脂TCHO:Total Ch
9、olesterol 总胆固醇HDL:High Density Lipoprotein 高密度脂蛋白LDL:Low Density Lipoprotein 低密度脂蛋白VLDL:Very Low Density Lipoprotein 极低密度脂蛋白ApoA1:载脂蛋白A1ApoB:载脂蛋白BLp(a):脂蛋白a,血脂分析的分析前准备,1.测TG、脂蛋白、Apo时要在禁食7-12小时后抽血。TCHO测定不一定要空腹血。2.妊娠后期各项血脂都增高,应在产后查血。3.停用影响血脂的药物数天或数周。4.采血前24小时内不作剧烈运动。5.坐位采血。6.止血带使用不可超过1分钟。,血清TCHO,参考范围:
10、5.17mmol/L 胆固醇的生理功能:(1)是合成肾上腺皮质激素、性激素及维生素D等生理活性物质的重要原料(2)是构成细胞膜的主要成分,临床意义血清TCHO增高见于:冠心病 DM 肾病综合征、类脂性肾病 胆总管阻塞 长期高脂饮食,血清TCHO降低见于:严重肝病 严重贫血 甲亢,血清TG,参考值:0.561.70mmol/LTG是机体储存能量的形式。高TG血症分为原发和继发两类,但不易分辨。,临床意义TG升高见于:冠心病 肥胖症、高脂饮食;糖尿病;肾病综合征;阻塞性黄疸。血清TG降低见于:甲亢、肝衰竭、肾上腺功能减低。,HDL-C 和 LDL-C,HDL C 与冠心病发病呈负相关LDL C水平
11、升高与冠心病发病呈正相关 每升高1mg使冠心病危险性增加1-2%。多见于II型高脂蛋白血症。对诊断冠心病有重要价值。,Lp(a),Lp(a)具有促进动脉粥样硬化和血栓形成的作用,它是冠心病重要的独立危险因子之一。增高也见于炎症、手术、创伤等。,血清载脂蛋白检测,Apo-A1是诊断冠心病的一种较敏感的指标,其血清水平与冠心病发病率呈负相关。ApoB水平升高与动脉粥样硬化、冠心病发病呈正相关。ApoA1/ApoB比值反映了HDL-C与LDL-C的相对水平。,第三节 血清电解质的检测,血清K,参考值:3.5-5.5mmol/L临床意义:1.肾脏方面2.内分泌方面3.利尿剂的影响4.K在细胞内外转移的
12、影响*向细胞内转移*向细胞外转移,血清Na,血清钠参考值:135-145 mmol/L血清Na临床意义:临床较少见。主要见于肾上腺皮质激素增多的情况。血清Na临床意义:1.消化道丢失.2.肾脏丢失3.其他体液丢失4.长期限制钠盐摄入的病人,注意:血清钠浓度与体内钠总量不一定平行 1、体内Na总量时几乎都同时伴有水潴留,血钠被稀释,血钠浓度不一定升高。2、体内钠总量减少时,垂体后叶激素(ADH)分泌减少,肾小管对水重吸收减少,大量水从肾脏排出,血清钠仍可保持正常。,血清CL,参考值:96-106 mmol/L临床意义:1.肾脏的排泄 2.摄入的多少3.体液丢失4.某些利尿剂5.AG正常的代酸,血
13、清Ca,参考范围:2.25-2.75 mmol/L钙的生理作用1.降低神经,肌肉的兴奋性2.参予凝血过程3.在心肌收缩中Ca2+与K+相拮抗4.第二信使,钙的代谢调节1.甲状旁腺素PTH(Parathyroid Hormone)2.1,25-二羟维生素D3(1,25-Dihydroxycholecalciferol)3.降钙素(Calcitonin),血清Ca的存在方式:1.结合钙与离子Ca2.非扩散型Ca与离子Ca保持动态平衡3.血液PH的影响,临床意义:高Ca血症较少见。低Ca血症主要见于以下因素:1.甲状旁腺功能低下2.维生素D缺乏 3.肾脏疾病 4.急性坏死性胰腺炎,血清无机磷,参考范
14、围:0.97-1.61mmol/L临床意义:1.甲状旁腺的影响2.佝偻病,骨质软化症3.骨髓骨折愈合期4.糖尿病5.肾衰,血清Mg,参考范围:0.8-1.2mmol/L临床意义:高镁血症不常见,偶见于肾功能衰竭者。低镁血症主要见于以下情况:1.摄入减少2.渗透性利尿3.长时间使用利尿剂4.细胞毒性药物5.免疫抑制剂,第四节 血清Fe及其代谢物检测,一、血清铁(Fe)二、总铁结合力(TIBC)三、不饱和铁结合力(UIBC)四、转铁蛋白饱和度检测(TS)五、转铁蛋白(TRF)六、血清铁蛋白(Ferr)七、可溶性转铁蛋白受体(sTfR),临床常见的几种情况:1.缺铁 血清铁铁蛋白转铁蛋白 TIBCT
15、S stfR 例:缺铁性贫血2.血红蛋白合成障碍 血清铁转铁蛋白TIBC 例:溶贫,再障,巨幼贫,铅中毒3.肾综 TRF从尿中排出血清铁 TIBC,第五节 心脏标志物,biochemical markers of cardiac injurybiochemical markers of cardiac functionbiochemistry markers of cardiovascular risk,biochemical markers of cardiac injury,Acute Coronary Syndrome,Acute coronary syndrome(ACS)is a s
16、eries of clinical syndromes caused by breaking off or decreasing of coronary blood flow.The syndromes include unstable angina pectoris(UAP),acute myocardial infarction(AMI),and sudden-death ischemic heart disease(SDIHD).,Diagnosis of AMI,diagnostic criteria of ESC/ACC,2000 Typical rise and gradual f
17、all(troponin)or more rapid rise and fall(CK-MB)of biochemical markers of myocardial necrosis with at least one of the following:(a)ischemic symptoms;(b)development of pathologic Q waves on the ECG;(c)ECG changes indicative of ischemia(ST segment elevation or depression);(d)coronary artery interventi
18、on(e.g.coronary angioplasty).,Acute chest pain,Circulation,2000,102:118-122,Test negative,serum enzyme markers of cardiac injury,aspartate aminotransferase(AST),creatine kinase(CK),isoenzyme of creatine kinase(CK-MB),lactate dehydrogenase(LDH),-hydroxybutyrate dehydrogenase(HBDH),Evolution of serum
19、enzyme markers after AMI,item lag period peak time sustain period multiple of rise CK-MB 38h 1624h 14d 20 CK 410h 2448h 36d 10 AST 410h 2448h 36d 10 LDH 810h 4836h 714d 6 HBDH 1224h 4836h 714d 10,serum protein markers of cardiac injury cardiac troponin(cTn),features:high specificity,long half-time p
20、eriod,“golden standard”classifications:cTnI and cTnT,Recommendations for the Use of Cardiac Markersin Coronary Artery Diseases-NACB,1998,Recommendation:Cardiac troponin(T or I)is the new standard for diagnosis of myocardial infarction and detection of myocardial cell damage,replacing CK-MB.Strength/
21、consensus of recommendation:Class II.Recommendation:There is no longer a role for lactate dehydrogenase(LDH)and its isoenzymes(HBDH)in the diagnosis of cardiac diseases.Strength/consensus of recommendation:Class I.,serum protein markers of cardiac injury CK-MBmass,The detection CK-MBmass by monoclon
22、al antibodies is the recommended assay method for CK-MB.It can avoid the interference of CK-BB and shows a higher sensitivity and specificity comparing with the detection of CK-MB activity by immunodepression method.,detection of CK-MB activity,detection of CK-MBmass,We can use CK-MBmass as the defi
23、nive marker at the absence of cTn.,serum protein markers of cardiac injury myoglobin(Myo),Features:low MW(17000-18000)serum quantification rises early high sensitivity low specificityMainly to role out AMI at the ocassion of negative result.,Combination of biochemical markers in diagnosing AMI,Recom
24、mendation:Two biochemical markers should be used for routine AMI diagnosis:an early marker(reliably increased in blood within 6 h after onset of symptoms)and a definitive marker(increased in blood after 69 h,but has high sensitivity and specificity for myocardial injury,remaining abnormal for severa
25、l days after onset).Strength/consensus of recommendation:Class II.,Recommendation:For detection of AMI by enzyme or protein markers,in the absence of definitive ECGs,the following sampling frequency is recommended:Marker Admission 24 h 69 h 1224 hEarly(6 h)x x x x(x)indicates optional determinations
26、.Strength/consensus of recommendation:Class II.,biochemical markers of cardiac function,B-type natriuretic peptide(BNP)N-terminal pronatriuretic peptide(NT-proBNP)As for patients presented with dyspnea,the detection of BNP or NT-proBNP can help to differentially diagnose the cardiogenic dyspnea from
27、 the others.The detection of BNP or NT-proBNP can not replace echocardiogram(ECHO)or left ventricular ejection fraction(LVEF)in the evaluation of cadiac function.,biochemistry markers of cardiovascular risk,Contributors to cardiovascular risk,TC/HDLblood coagulation factor(Fbg,Factor,PAI1)homocystei
28、ne(HCY)High sensitivity C reactive protein(hs-CRP),Risk evaluation and precaution of cardiovascular disease,hs-CRP for primary risk evaluation and precaution,MRFIT(Multiple Risk Factors Intervention Trial),LH Kuller,Am J Epidemiol 1996,3.2 mg/L CRP,Adjusted relative risks for hs-CRP quintiles in app
29、arently healthy men and women,Ridker PM,Circulation 2001,Interactive effects of hs-CRP and lipid profile,Ridker PM,Circulation 2001,Conclusion,Who should take the hs-CRP assay for primary risk evaluation and precaution?everybody undergoing a cardiovascular check-up or a lipid screen for cardiovascul
30、ar risk assessment is a candidate for hs-CRP testing.what other parameters in combination with hs-CRP?Together with TC:HDLwhere increased risk starts?low risk 3 mg/L Results and the meaning?For a reliable result to avoid out-liers due to short term acute phase responses every result 3 mg/L should be
31、 confirmed by a second sample(also cholesterol determination is based on two repeated measurements.)CRP results 10 mg/l should be discarded as they are indicative of an acute disease.,hs-CRPfor secondary risk evaluation and precaution,CRP in UAP predicts event free survival,One year event free survi
32、val:,CRP 3,CRP 3,Odds Ratio=8.6,LM Biasucci,Circulation 1999,CRP&Troponin I in risk prediction,RJ de Winter,Cadiovasc Res 1999,Conclusion,Who should take the hs-CRP assay for secondary risk evaluation and precaution and when?Patients with stable ungina-anytime patients with UAP-at the time of chest
33、pain start or overpatients of post MI(3 weeks)patients undergoing PTCA pre-proceduralwhat other parameters in combination with hs-CRP?Together with Troponin I or TResults and the meaning?CRP 3mg/L predicts increased risk for a combined end point of cardiac death,myocardial infarction,recurrent insta
34、bility or restenosis after PTCACRP 10mg/L predicts increased risk of death,第六节:其他血清酶的检查,ACPT,ACPNPAMYLIPCHE,第七节:内分泌激素检测,T3,T4,TSH,fT3,fT4PTHcortisol,aldosterone,17-OH,17-KS,ACTHcatecholamines(E,NE,DA),VMA,HMAE2,E3,LH,FSH,PRL,progesterone/testesteronGH,ADH,第八节 治疗药物监测,TDM:Theraputic drug monitoring给药方案个体化,提高治疗效果及时诊断和处理药物过量,避免中毒进行临床药代动力学和药效学研究,探讨新的给药方案节省药物和经费,重点,Glu,OGTT,糖化血红蛋白测定的意义几种脂蛋白测定的临床意义肌钙蛋白在急性心肌梗死诊断中的地位,thanks,