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1、肝脏疾病的实验室检查,LABORATORY EXAMINATION OF LIVER DISEASE,Emphasis,To understand:The function of the liver The classification of jaundice The laboratory assessment of liver disease,The function of the liver,Carbohydrate metabolism:Synthesis and storage of glycogenGlycogenolysis and gluconeogenesisProtein m
2、etabolism:Synthesis and degradation of proteins(not immunoglobulins)Amino acid metabolism and urea formationLipid metabolism:Synthesis of lipoproteins,phospholipids,cholesterolFatty acid metabolismBile acid synthesis,Excretion and detoxification:Bilirubin and bile acid excretionDrug detoxification a
3、nd excretionSteroid 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
4、1.铁储存 2.维生素A,D,E,B12的储存和代谢,Laboratory investigation of liver diseases,Laboratory investigation:,Routine liver function testsTrue liver function testsSpecial tests,Routineliver function tests,BilirubinsTotal proteinAlbuminTransaminases Alkaline phosphatase-glutamyltransferaseBile acid levels,True liv
5、er function tests:,BilirubinAlbuminBile acid levelsBromosulfophthalein(四溴酚酞磺酸钠)excretion testCoagulation studiesblood ammonia,Special 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
6、磷酸酶 6.r-谷氨酰转移酶二.“真正的”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
7、the liver3.Hepatocyte 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:b
8、iconjugated bilirubin4.(Delta)fraction bilirubin:conjugated bilirubin+albumin,Classification of jaundice,Pre-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 jaundices,
9、Case exampleSpherocytosis in a female aged 16 years,patient was jaundiced,with enlargment of the spleen,bilirubin was not in the urine.,Pre-hepatic：liver diseases not present,When the liver is presented with bilirubin in an amount that exceeds the conjugating mechanism 1.increased bilirubin producti
10、on Haemolysis 2.congenital hyperbilirubinaemia Ineffective erythropoiesis Gilberts syndrome,Case 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.,Hepatic：hepatocellular disease,When the causal ab
11、normality is in the liver 1.hepatitis acute:viral hepatotoxins chronic:chronic active chronic persistent 2.Intra-hepatic cholestasis Cirrhosis space occupying lesions 3.congenital hyperbilirubinaemia Dubin-Johnson syndrome Rotor syndrome,Case exampleA 45-year-old female with a past history of cholel
12、ithiasis,now presenting with right upper abdominal pain.At operation several stones were removed from the common bile duct.,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.int
13、rahepatic viral hepatitis drugs infiltrations浸润 cirrhosis cholangitis biliary atresia,Laboratory findings in different types jaundices,Enzymes,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,Alkaline phosphatase(ALP),Alkaline phosphatase,1.Tissue non-specific protein2.Intestinal protein3.Placental protein4.pl
14、acental-like protein,Alkaline phosphataseTypical RIs for ALP activity,Alkaline phosphatase,Serum ALP activity is raised in:1.physiological:children/teenagers,pregnancy2.Liver disease:cholestasis3.Bone disease:Pagets disease,Hyperparathyroidism,osteomalasia(骨软化）,malignancy4.malignancy:bronchus,gut,te
15、stes5.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抗凝可引起假性碱性磷酸酶降低。,Case exampleA 26-year-old w
16、oman with jaundice,and a dark urine.,Case exampleA 61-year-old woman with advanced carcinoma of the breast,and radiological evidence of metastatic liver disease.,Case exampleA 51-year-old woman presenting with deep jaundice,biliary colic and a history of cholelithiasis.,-glutamyl transpeptidase（-glu
17、tamyltransferase）,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.,Case exampleAcute infectious hepatitis in a 25-year-old man.
18、,Case exampleThe following results were obtained from three male heavy drinkers aged in their early thirties.,Transaminases,aspartate aminotransferase alanine aminotransferase,Determination of serum enzymes and isoenzymesrelative activity of ALT and AST in human tissue,血清氨基转移酶及同功酶检查,包括丙氨酸氨基转移酶及天门冬氨酸
19、氨基转移酶 谷丙转氨酶（ALT，GPT）谷草转氨酶（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 exampleAnic
20、teric hepatitisA 15-year-old girl complaining of an influenza-like illness.She attended a boarding school where an outbreak of hepatitis had recently occurred.There was no bilirubin in her urine.,Case exampleCholestatic acute hepatitisA 35-year-old male,recently returned from south-east Asia,present
21、ed with 5 days of increasing jaundice.,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.,Protein metabolism,Hyperproteinaemia,1.Haemoconcentration Dehydration Venous stasis2.Hypergam
22、maglobulinaemia polyclonal Chronic infection 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
23、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,Case exampleA 23-year-old woman admitted unconscious with diabetic ketoacidosis.examination found poor skin turgor,dry mouth.,Case exampleA 42-year-old woman diagnosed as having chronic active hepatitis.,Hypoproteinaemia,1.Haemodilution Dilutional state iatro
24、genic water overload specimen from IV drip arm2.Decreased synthesis malnutration/malabsorption liver disease analbuminaemia3.Loss skin-burns,exudative lesions renal-nephrotic syndrome gut-protein-losing enteropathy,Hypoproteinaemia,4.Hypogammaglobinaemia transient in neonate/infant primary/secondary
25、 malignancy ureamia diabetes mellitus AIDS5.Other pregnancy malignancy,1、血清总蛋白及白蛋白减低：（1）肝细胞损害影响总蛋白与白蛋白合成（2）营养不良（3）蛋白丢失过多（4）消耗增加（5）血清水分增加2、血清球蛋白降低（1）生理性（2）免疫功能抑制（3）先天性低-球蛋白血症,Case exampleBlood specimen taken for routine postsurgery assessment.,Case exampleA 44-year-old man with advanced liver disease
26、.,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 临床意义：1、肝细胞功能损害 2、胆道梗阻 3、
27、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 liver,Congenital Gilberts disease Crigler-Najjar syndrome Dubin-Johnson syndrome Rotor syndromeHepatitis Acute ChronicCholestasis Extrahepatic IntrahepaticCirrhosisAnoxia缺氧症InfiltrationDrug toxicity,
