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1、肝脏疾病的实验室检查LABORATORY EXAMINATION OF LIVER DISEASEEmphasisTo understand:The function of the liver The classification of jaundice The laboratory assessment of liver diseaseThe function of the liverCarbohydrate metabolism:Synthesis and storage of glycogenGlycogenolysis and gluconeogenesisProtein metabo
2、lism:Synthesis and degradation of proteins(not immunoglobulins)Amino acid metabolism and urea formationLipid metabolism:Synthesis of lipoproteins,phospholipids,cholesterolFatty acid metabolismBile acid synthesisExcretion and detoxification:Bilirubin and bile acid excretionDrug detoxification and exc
3、retionSteroid hormone inactivation and excretionMiscellaneous:Iron storageVitamin A,D,E,B12 storage and metabolism肝脏病常用的实验室检查肝脏的基本功能一.碳水化合物的代谢 1.糖原的合成和储存 2.糖原的分解和糖异生二.蛋白质的代谢 1.蛋白质的合成和降解 2.氨基酸的代谢和尿素的生成三.脂类代谢 1.脂蛋白,磷脂和胆固醇的合成 2.脂肪酸的代谢 3.胆汁酸的代谢四.生物转化,分泌和排泄 1.胆红素和胆汁酸的排泌 2.药物的解毒和排泌 3.激素的灭活和排泌五.其他 1.铁储存 2.
4、维生素A,D,E,B12的储存和代谢 Laboratory investigation of liver diseasesLaboratory investigation:Routine liver function testsTrue liver function testsSpecial testsRoutineliver function testsBilirubinsTotal proteinAlbuminTransaminases Alkaline phosphatase-glutamyltransferaseBile acid levelsTrue liver function t
5、ests:BilirubinAlbuminBile acid levelsBromosulfophthalein(四溴酚酞磺酸钠)excretion testCoagulation studiesblood ammoniaSpecial tests:1-antitrypsin-fetoproteinHepatitis markersSpecific autoantibodiesImmunoglobulinsCaeruloplasmin(铜蓝蛋白)ferritin肝脏病常用的实验室检查一.常规肝功能实验 1.胆红素 2.总蛋白 3.白蛋白 4.转氨酶 5.碱性磷酸酶 6.r-谷氨酰转移酶二.“真
6、正的”肝功能实验 1.四溴酚酞磺酸钠或靛氰绿排泌实验 2.血浆胆汁酸浓度 3.凝血研究 4.血氨 5.胆红素 6.白蛋白 三.特殊实验 1.抗胰蛋白酶 2.甲胎蛋白 3.肝炎标志物 4.特异性自身抗体 5.免疫球蛋白 6.铜蓝蛋白 7.铁蛋白肝脏病常用的实验室检查目的:1.了解肝细胞有无损伤以及损伤程度 2.对肝胆系统疾病进行病原、病种、病型的诊断 3.对肝脏功能状态作动态比较,观察疗效及估计预后 4.手术前的准备和用药监护,评价肝脏的储备功能 5.健康普查 BILIRUBIN METABOLISM 1.Production2.Transport to the liver3.Hepatocyt
7、e uptake4.Conjugation5.Biliary secretion6.Gut degradation and excretion胆红素的代谢过程Classification of bilirubin(HPLC)1.(Alpha)fraction bilirubin:unconjugated bilirubin+albumin free bilirubin-kernicterus2.(Beta)fraction bilirubin:monoconjugated bilirubin3.(Gamma)fraction bilirubin:biconjugated bilirubin4.
8、(Delta)fraction bilirubin:conjugated bilirubin+albuminClassification of jaundicePre-hepatic:liver diseases not presentHepatic:hepatocellular disease Posthepatic:cholestasis(obstruction)溶血性黄疸时的胆红素代谢肝细胞性黄疸时的胆红素代谢梗阻性黄疸时的胆红素代谢Laboratory findings in different types jaundicesSerum total bilirubin(mol/L)Ex
9、amination of urinedirectindirecturobilinogenbilirubinNormal subjectsHemolytic jaundiceHepatocellular jaundiceObstruct jaundice06.8High HighHigh 1.713.7High HighHighNormalHigh HighdownNegativeNegativepositiveStrongly positiveCase exampleSpherocytosis in a female aged 16 years,patient was jaundiced,wi
10、th enlargment of the spleen,bilirubin was not in the urine.Total Bili54mol/L(20)Direct Bili 10mol/L(10)Alb40g/L(3050)ALT14U/L(35)ALP106U/L(30120)Pre-hepatic：liver diseases not presentWhen the liver is presented with bilirubin in an amount that exceeds the conjugating mechanism 1.increased bilirubin
11、production Haemolysis 2.congenital hyperbilirubinaemia Ineffective erythropoiesis Gilberts syndromeCase exampleAn 11-year-old boy was jaundiced and generally unwell.his urine,which become dark the day before the onset of jaundice,was positive for bilirubin.Total Bili85mol/L(20)Direct Bili 25mol/L(10
12、)TP78g/L(6080)Alb41g/L(3050)ALT3140U/L(35)ALP144U/L(30120)Hepatic：hepatocellular disease When the causal abnormality is in the liver 1.hepatitis acute:viral hepatotoxins chronic:chronic active chronic persistent 2.Intra-hepatic cholestasis Cirrhosis space occupying lesions 3.congenital hyperbilirubi
13、naemia Dubin-Johnson syndrome Rotor syndromeCase exampleA 45-year-old female with a past history of cholelithiasis,now presenting with right upper abdominal pain.At operation several stones were removed from the common bile duct.Total Bili139mol/L(20)Direct Bili 75mol/L(10)TP77g/L(6080)Alb41g/L(3050
14、)ALT35U/L(35)ALP550U/L(30120)Posthepatic:cholestasis(obstruction)When there is obstruction to the biliary system 1.extrahepatic cholelithiasis胆石症 tumours stricture狭窄 biliary atresia闭锁 cholangitis胆管炎 2.intrahepatic viral hepatitis drugs infiltrations浸润 cirrhosis cholangitis biliary atresiaLaboratory
15、findings in different types jaundicesSerum total Serum total bilirubin(bilirubin(mol/L)mol/L)Examination of urineExamination of urinedirectdirectindirectindirecturobilinogenurobilinogen bilirubinbilirubinNormal subjectsNormal subjectsHemolytic jaundiceHemolytic jaundiceHepatocellular jaundiceHepatoc
16、ellular jaundiceObstruct jaundiceObstruct jaundice0 06.86.8HighHigh HighHighHighHigh 1.71.713.713.7HighHigh HighHighHighHigh NormalNormalHighHigh HighHighdowndownNegativeNegativeNegativeNegativepositivepositiveStrongly positiveStrongly positiveENZYMES 血清酶及同功酶检查 肝细胞内酶的定位 血清酶及同功酶检查 肝脏酶的器官定位酶存在浓度较高的器官肝
17、细胞与血浆相对比值ASTALTLDHALPGGT心脏,肝脏,肌肉,肾肝脏,肾肝脏,红细胞,心脏,肌肉,白细胞,肿瘤肝脏,骨,肠道,胎盘肝脏,胰腺,肾脏,前列腺78002850150正常/异常正常/异常Alkaline phosphatase(ALP)Alkaline phosphatase1.Tissue non-specific protein2.Intestinal protein3.Placental protein4.placental-like proteinAlkaline phosphataseTypical RIs for ALP activityNew born1 month
18、1 month3 years3 16years16 60yearsPregnancy(3rd trimester)30 100U/L70 250U/L70 220U/L70 350U/L30 120U/L50 250U/LAlkaline phosphataseSerum ALP activity is raised in:1.physiological:children/teenagers,pregnancy2.Liver disease:cholestasis3.Bone disease:Pagets disease,Hyperparathyroidism,osteomalasia(骨软化
19、）,malignancy4.malignancy:bronchus,gut,testes5.other:transient hyperphosphatasaemia of infancy碱性磷酸酶 原理 碱性磷酸酶存在于细胞表面，梗阻和药物直接引起的反应损害胆小管，引起细胞膜破裂溶解，导致碱性磷酸酶在到达高峰前几天逐渐上升，升高程度与梗阻期限正相关。参考值 连续监测法：成人40-100U/L，儿童250U/L 临床意义 1、肝胆系统疾病 2、黄疸的鉴别诊断 3、骨骼疾病 4、生长中儿童、妊娠中晚期血清ALP生理性升高。5、其他 6、碱性磷酸酶的活性需要阳离子（锌、镁等），输血和EDTA抗凝可引
20、起假性碱性磷酸酶降低。Case exampleA 26-year-old woman with jaundice,and a dark urine.ALT 1495U/L(50)ALP242U/L(30120)Total bili89mol/L(20)TP75g/L(6080)Alb42g/L(3050)Glob33g/L(2535)Case exampleA 61-year-old woman with advanced carcinoma of the breast,and radiological evidence of metastatic liver disease.ALT 30U/
21、L(50)ALP637U/L(30120)-GT599U/L(30)Ca2.27mmol/L(2.152.55)Total bili13mol/L(20)TP70g/L(6080)Alb37g/L(3050)Glob33g/L(2535)Case exampleA 51-year-old woman presenting with deep jaundice,biliary colic and a history of cholelithiasis.ALT 181U/L(50)ALP1075U/L(30120)Total bili340mol/L(20)TP69g/L(6080)Alb36g/
22、L(3050)Glob33g/L(2535)-glutamyl transpeptidase（-glutamyltransferase）原理在肝脏，GGT存在于胆小管的表面和微粒体内，胆小管损伤和暴露于微粒体酶诱导剂（如乙醇，甲氰咪胍，巴比妥酸盐等）后，GGT升高。参考值 连续监测法：50U/L临床意义1、胆道阻塞性疾病 2、急、慢性病毒性肝炎、肝硬化3、急慢性酒精性肝炎、药物性肝炎4、其他Case exampleA 78-year-old woman with advanced carcinoma that has metastasized to the liver.ALT 134U/L(5
23、0)ALP806U/L(30120)-GT3130U/L(30)Ca2.47mmol/L(2.152.55)Total bili42mol/L(20)TP65g/L(6080)Alb32g/L(3050)Glob33g/L(2535)Case exampleAcute infectious hepatitis in a 25-year-old man.ALT 1050U/L(50)ALP150U/L(30120)-GT65U/L(30)Total bili200mol/L(20)Case exampleThe following results were obtained from three
24、 male heavy drinkers aged in their early thirties.ABCALT 3311331U/L(50)AST243340U/L(25)-GT86148342U/L(30)Transaminasesaspartate aminotransferase alanine aminotransferaseDetermination of serum enzymes and isoenzymesrelative activity of ALT and AST in human tissueorgan or tissueALTASTheartliverskeleta
25、l musclekidneypancreasspleenlungserythrocytesserum4502850300120013080457178007100500045001400700500151血清氨基转移酶及同功酶检查包括丙氨酸氨基丙氨酸氨基转移移酶及天天门冬氨酸氨基冬氨酸氨基转移移酶 谷丙谷丙转氨氨酶（ALT，GPT）谷草谷草转氨氨酶（AST，GOT）参考值 比色法（Karmen法）连续监测法 ALT 5-25卡门氏单位 10-40U/L AST 8-28卡门氏单位 10-40U/L 血清氨基转移酶及同功酶检查临床意义（1）急性病毒性肝炎，二者均显著升高。（2）慢性病毒性肝炎，转
26、氨酶轻度上升或正常。（3）酒精性肝病、药物性肝炎、脂肪肝、肝癌等非病毒性肝 炎,转氨酶轻度上升或正常。（4）肝硬化，转氨酶活性取决于肝细胞进行性坏死程度。（5）肝内外胆汁淤积，转氨酶轻度上升或正常。（6）急性心肌梗塞后6-8小时，AST增高,18-24小时达高峰。Case exampleAnicteric hepatitisA 15-year-old girl complaining of an influenza-like illness.She attended a boarding school where an outbreak of hepatitis had recently oc
27、curred.There was no bilirubin in her urine.ALT 325U/L(50)ALP118U/L(30120)Total bili17mol/L(20)TP65g/L(6080)Alb39g/L(3050)Glob26g/L(2535)Case exampleCholestatic acute hepatitisA 35-year-old male,recently returned from south-east Asia,presented with 5 days of increasing jaundice.ALT 1640U/L(50)ALP500U
28、/L(30120)Total bili220mol/L(20)TP66g/L(6080)Alb37g/L(3050)Glob29g/L(2535)Case exampleChronic active hepatitisA 36-year-old woman who had hepatitis 9 months before.The condition had not settled and she was admitted for further investigation.ALT 350U/L(50)ALP400U/L(30120)Total bili45mol/L(20)TP113g/L(
29、6080)Alb30g/L(3050)Glob83g/L(2535)Chronic active hepatitisChronic persistent hepatitisALTGlobAlb210 times normalIncreasedHypoalbuminaemia 2 times normalNormalNormal PROTEIN METABOLISMHyperproteinaemia1.Haemoconcentration Dehydration Venous stasis2.Hypergammaglobulinaemia polyclonal Chronic infection
30、 Chronic liver disease Autoimmune disease Sarcoidosis(肉状瘤病)monoclonal Myelomatosis(骨髓瘤病)Waldenstrms macroglobulinaemia Benign蛋白质代谢功能检查参考值：成人血清总蛋白60-80g/L，白蛋白40-55 g/L，球蛋白20-30 g/L，A/G为1.5-2.5:1临床意义:1、血清总蛋白及白蛋白增高：急性失水、肾上腺皮质功能减退。2、血清总蛋白及球蛋白增高 （1）慢性肝脏疾病 （2）M蛋白血症 （3）自身免疫性疾病 （4）慢性炎症与慢性感染 3、A/G倒置：严重肝功能损伤C
31、ase exampleA 23-year-old woman admitted unconscious with diabetic ketoacidosis.examination found poor skin turgor,dry mouth.Na 136mmol/L(132144)tCO28mmol/L(2333)TP96g/L(6080)Alb55g/L(3050)Glob41g/L(2535)Glu 23.0mmol/L(3.05.5)Crea 310mol/L(60120)Case exampleA 42-year-old woman diagnosed as having chr
32、onic active hepatitis.Total Bili12mol/L(20)Direct Bili 3.6mol/L(10)TP93g/L(6080)Alb36g/L(3050)Glob57g/L(2535)ALT248U/L(130mmol/L(96110)TP39g/L(6080)Alb11g/L(3050)Glob28g/L(2535)Case exampleA 44-year-old man with advanced liver disease.ALT 61U/L(50)ALP555U/L(30120)Total bili128mol/L(20)TP54g/L(6080)A
33、lb19g/L(3050)Glob35g/L(2535)胆汁酸代谢检查 原理：胆固醇 胆酸 脱氧胆酸 鹅脱氧胆酸 石胆酸 熊脱氧胆酸 初级胆酸 次级胆酸 生理作用：1.对胆汁分泌的影响：促进水和溶质排出，维持胆固醇和卵磷脂排泌 2.对胆固醇代谢的影响：1/3胆固醇分解代谢，保持胆固醇的溶解性，调节 肝肠对胆固醇的合成。3.在脂肪的吸收，转运，分解代谢方面起重要作用：提高脂类的溶解度，促 进脂肪乳化，增强胰腺脂解作用，促进脂类吸收。胆汁-回肠-门静脉-肝脏8090%一次性清除，一次进餐后胆汁酸经历24次肠肝循环，一般12小时血清水平是空腹的2倍左右，参考值：总胆汁酸（酶法）0-10 umol/L
34、 临床意义：1、肝细胞功能损害 2、胆道梗阻 3、门脉分流 4、进食后血清胆汁酸可一过性增高肝脏纤维化的检查发生：1.肝细胞分泌，型胶原，蛋白多糖2.储脂细胞分泌，型胶原，蛋白多糖，层连蛋白3.血窦内皮细胞分泌型胶原，纤维连结蛋白4.枯否细胞分泌胶原酶指标：1.透明质酸（hyaluronic acid)2.型前胶原氨基端肽（procollagen N terminal peptide)3.型胶原(collagen)4.层粘连蛋白(laminin)DISORDERS OF THE LIVERCongenital Gilberts disease Crigler-Najjar syndrome D
35、ubin-Johnson syndrome Rotor syndromeHepatitis Acute ChronicCholestasis Extrahepatic IntrahepaticCirrhosisAnoxia缺氧症InfiltrationDrug toxicity 项目英文名结果单位参考值标志1.谷草转氨酶2.谷丙转氨酶3.谷草/谷丙4.谷氨酰转移酶5.碱性磷酸酶6.总蛋白7.白蛋白8.球蛋白9.白/球蛋白10.总胆红素11.直接胆红素12.间接胆红素13.总胆汁酸ASTALTAST/ALTGGTALPTPALBGLOA/GTBILDBILIBILTBA85731.1617815062.331.930.41.0522.87.315.526.2U/LU/LU/LU/Lg/Lg/Lg/Lmol/Lmol/Lmol/Lmol/L10-4210-608-5837-14060-8335-5516-351-2.51.71-20.500.1-3.421.61-20.40.0-20