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1、Laboratory Examination of Liver Laboratory Examination of Liver gallbladderpancreas Diseasesgallbladderpancreas DiseasesPart I2Hepatic arteryPortal veinHepatic veinbiliary tract double blood supplyAnatomic structure characteristicAnatomic structure characteristicdouble output passageways3What is the
2、 function of the normal liver?The liver is very complex and has hundreds of functionsInteracts with all other systems / organsIn summaryProcessing of digested food from the intestineProcessing of digested food from the intestineControl levels of proteins, fats and glucoseControl levels of proteins,
3、fats and glucoseCombat infectionCombat infectionManufacture and excretion of bileManufacture and excretion of bileStore iron and vitaminsStore iron and vitaminsExcretion of drugs and toxinsExcretion of drugs and toxinsRegulation of hormonesRegulation of hormonesRegulation of blood clottingRegulation
4、 of blood clotting4GallbladderGallbladderPancreasPancreasconcentrated bileconcentrated biledigestion of fatdigestion of fatobstruction of biliary tractobstruction of biliary tract enzymes and bilirubinenzymes and bilirubinInvolved in the synthesis of amylase Involved in the synthesis of amylase (pan
5、creatic amylase)(pancreatic amylase)Blood and urine amylaseBlood and urine amylase5Protein Metabolism Tests Bilirubin Metabolism TestsLaboratory TestThe markers of virus hepatitisEnzyme and Iosenzyme Protein Metabolism Tests 7Protein synthesis: hepatic cell : albumin, glucoprotein, lipoprotein, coag
6、ulation factors mononuclear phagocyte system : -Globulin Albumin: edema, ascitic fluid, Coagulation factor: hemorrage Ammonia metabolism： NH3,hepatic encephalopathy Protein Metabolism Tests8The determination of serum total protein the The determination of serum total protein the ratio of albumin and
7、 globulinratio of albumin and globulinserum total protein Biuret reactionAlbumin Dye Bromcresol green Protein Metabolism TestsBiuret methodNH3heat+ +Pink, violet complexPrinciple:Cu2+OH-spectrophotometric analysis540nmTotal protein = Albumin + Globulin+Blue-green productspH4.2principle：A+BCG-spectro
8、photometric analysis ( hemolysis, chylemia ,medicine)630nm11Serum TP 6585g/L A 40 55g/L G 20 40g/L A/G (1.22.4:1) Protein Metabolism TestsAssociated with ageHas nothing to do with the genderReference range 12Common factorsIntension exercise: TP 12%position: TP 35g/L(lying- erect position) A 510% (er
9、ect 15min)hemolysis:TP 3% (Hb 1g/L) tourniquet :TP 10% (3min) chylemia :QueitEmptyLying13Clinical Significance TP and Adehydrationshockloss of waterblood concentrationAddisons disease14 Hypoproteinmia (TP60 or A25 g/L) Decrease productionDecrease production Loss : Malnutrition, absorption Kidney Nep
10、hrotic Syndrome GI tract Protein-losing enteropathy Skin Severe burnComsumption : TB. HyperthyroidismBlood dilution: water retention Increased Losscirrhosis of liver, hepatoma accompany with -globulin ,Chronic Inflammation Protein Metabolism TestsTP and A15Cirrhosis ascitic fluid“大头娃娃大头娃娃”17TP 80g/L
11、 or G35g/L : Hyperproteinemia Chronic hepatic disease: alcoholic liver disease， cirrhosis of liver chronic active hepatitis Protein Metabolism TestsTP and G M proteinemia: multiple myeloma, lymphoma, macroglobulin Chronic infection diseases: sepsis, syphilis, leprosy, malaria Autoimmune hepatitis ,
12、SLE, RF18 3y infant immunodepressant Inborn hypoglobulinemia Protein Metabolism TestsSevere liver impair, M proteinemiaGA/G Serum Protein electrophoretic Serum Protein electrophoretic analysisanalysis20principle : Protein Metabolism Testsisoelectric pointLow pHHigh pHP+PP-Anode (+) cathode（-）Molecul
13、ar mass21A： 5768%1 ：1.05.7 % 2 ：4.911.2%： 7.013%： 9.818.2%Reference range Protein Metabolism Tests22(1)Liver Disease: common feature A ,1 2 , Clinical Significance: Protein Metabolism Tests23Chronic hepatitis , Cirrhosis of liver , hepatomaCirrhosis of liver : -bridgeHepatoma: AFP between A and 1 Ac
14、ute hepatitis: A , G normalLiver Disease: Protein Metabolism Tests24(2) M proteiemia: Multiple Myeloma, Macroglobulinemia Protein Metabolism TestsA , (2, )25(3) Nephropathy A, ; 2, Protein Metabolism TestsNephrotic SyndromeDiabetic nephropathySeveral common pathological electrophoresis patternSevera
15、l common pathological electrophoresis patternSerum Prealbumin Determination28Serum Prealbumin DeterminationReference Value Adult 250400mg/LClinical SignificancePA: hyperthyroidism, nephrotic syndrome collagenosis, Hodgkin Protein Metabolism Tests29PA : Malnutrition,chronic infection, Malignant tumor
16、 Hepatic disease cirrhosis of liver hepatoma chronic active hepatitis obstructive jaundice Protein Metabolism Tests30Key Points-liver cells have strong ability of compensation Acute or focal hepatitis: protein -normal Chronic hepatitis, cirrhosis, cancer : A/G inversion Protein Metabolism TestsProte
17、in electrophoresis :serum not plasmaThe half time of prealbumin is about 2 days, more sensitive than albumin in reflecting early liver damageThe detection of protein are only use to test the reserve protein function of liver cells 31The review of significance albuminThe review of significance albumi
18、n The level of albumin was positively correlated with the number of liver cellsThe half time of albumin in vivo is 1921 days, albumin has no significant change in acute hepatitis.Low albumin due to liver dysfunction implies chronic liver damageAlbumin 25g /L, ascites production, a positive correlati
19、on between the albumin and ascitesAlbumin serve as the indications for recovery after treatmentAlbumin decrease gradually or continued to decreased suggest poor prognosis Protein Metabolism TestsPlasma Coagulation Factor Determination33Plasma Coagulation Factor DeterminationVitamin K dependent facto
20、r (, , )PT: , cirrhosis of liver feature (decompensation stage) prognosis : acute, chronic hepatocellular diseaseAPTT: , liver disease (,), Vitamin K ( ,) TT: fibrinogen，FDP , , , cirrhosis of liver ，hepatoma (affiliate DIC)AT-III： severe liver disease Protein Metabolism Tests34Key pointsMost clotti
21、ng factors are synthesized in the liver shorter than AlbuminProthrombin Time (PT) is a good functional test but usually use INR to correct for lab variabilityPT/INR prolonged in liver diseaseINR: international normalized ratio Protein Metabolism TestsPlasma Ammonia Determination36Plasma Ammonia Dete
22、rminationPrinciple internal kidney NH3 UREA muscles Liver disease NH3 hepatic encephalopathyClinical Significance NH3 : hepatic encephalopathy ,uremia,shock， fulminant hepatitis, extrahepatic portal system shunt ,upper gastrointestinal hemorrhage NH3 :hypoprotein diet ,anemia Protein Metabolism Test
23、s Protein Metabolism Testsornithin cycleliverThe bilirubin metabolism Determination38NORMAL BILIRUBIN METABOLISMUnconjugated = Fat solubleConjugated = Water solubleenterohepatic circulationbacterial enzymestercobilinogen39Bilirubin (85%)Shunt Bilirubin(15-20%)Bilirubin Metabolism TestsPrehepaticHepa
24、ticPosthepaticenterohepatic circulationstercobilinogen40JaundicePrehepatic(Hemolysis)HepaticGenetic defects, primary liver diseasePosthepaticBile Duct ObstructionPancreatic Head CAUnconjugated BilirubinMixedConjugated BilirubinHyperbilirubinemia (Jaundice)Bilirubin Metabolism Tests41Jaundice42excess
25、 production of bilirubin (beyond the livers ability to conjugate it) following hemolysisautoimmune disease; hemolytic disease of the newborn (Rh- or ABO- incompatibility); Sickle cell disease High plasma concentrations of unconjugated* bilirubin*Fat solublePrehepatic (hemolytic) jaundice43Intrahepat
26、ic jaundice Impaired uptake, conjugation, or secretion of bilirubinReflects a generalized liver (hepatocyte) dysfunction hyperbilirubinemia is usually accompanied by other abnormalities in biochemical markers of liver functionPosthepatic jaundiceCaused by an obstruction of the biliary treePlasma bil
27、irubin is conjugated.bile acids increased Characterized by pale colored stools (absence of fecal bilirubin or urobilin), and dark urine (increased conjugated bilirubin)In a complete obstruction, urobilin is absent from the urineSerum Total Bilirubin Determination (STB)46Serum Total Bilirubin Determi
28、nation (STB)Principle: Connect bilirubin diazo bilirubin Unconnect bilirubin STB=UCB +CBBilirubin Metabolism Testsdiazo reagentdirect reactionsurface active agent + diazo reagent indirect reaction47Reference Value Adult 3.417 .1mol/LClinical Significance17.134.2Latent jaundic171Mild342ModerateSevere
29、normalnormalBilirubin Metabolism TestsReflect the intensity of the jaundice48 Hemolytic jaundice STB 85.5 mol/L Hepatocellular jaundice 17.1171mol/L Obstructive jaundice complete: 342 mol/L uncomplete:171 265mol/LBilirubin Metabolism TestsJudge the causes of jaundice 49 To distinguish the type of ja
30、undiceTPYE STB UCB CBHemolytic+slightlyObstructive+slightly+Hepatocellular+Bilirubin Metabolism TestsBilirubin Metabolism TestsJudge the type of jaundice together with UCB and CBSerum Conjugated and Unconjugated BilirubinPrinciple Serum+diazo reagent CB Reference Value Conjugated Bilirubin 06.8mol/L
31、 Unconjugated Bilirubin 1.710.2 mol/LSTB-CB=UCB1minBilirubin Metabolism Tests52Clinical Significance(1)Differential Diagnosis of Jaundice 20% Hemolytic Jaundice 2050% Hepatocellular 50% Obstructive(2)Hepatic Damage: CB but STB (-) 30 50% patientsBilirubin Metabolism TestsCB/STB53 Bilirubin -unconjug
32、ated bilirubin -single glucose hyaluronic acid bilirubin -double glucose hyaluronic acid bilirubin -bilirubin proteinHigh performance liquid chromatographic methodCombined with albumin is StrongBig molecular Cant be filtrated by glomerularLong half-lifeSTB, CBUrine CB(-)Bilirubin Metabolism TestsBil
33、irubin Metabolism TestsUrobilirubin and Urobilinogen55Urine: Urobilirubin(-) UCB glomerular membran CB trace determination CB renal threshold 34mol/L Urobilinogen（ trace） slight enterohepatic circulation kidney urobilinogenReference Value Urobilirubin (- ) Urobilinogen (-)or() 0.844.2mol/L56Clinical
34、 Significance Obstruction of biliary tract (stone, pancreatic carcinoma) Liver cell damage hepatitis ,cirrhosis of liver AlkalosisCongenital Jaundice Dubin-Johnson, Rotor Syndrome (+) Gilbert and Crigler-Najjar Syndrome（-）Bilirubin Metabolism TestsUrobilirubinHemolytic Jaundice Urobilirubin(-)57Dubi
35、n-Johnson syndrome肝细胞对某些阴离子排泄障碍肝细胞对结合胆红素排泄障碍 Roter Roter syndromesyndrome肝细胞摄取非结合胆红素障碍肝细胞排泄结合胆红素障碍非结合、结合胆红素非结合、结合胆红素均增高均增高结合胆红素结合胆红素增高增高返58Gilbert syndrome肝细胞摄取非结合胆红素功能障碍肝细胞摄取非结合胆红素功能障碍葡萄糖醛酸转移酶不足葡萄糖醛酸转移酶不足非结合胆红素非结合胆红素 增高增高Crigler-Najjar syndrome新生儿核黄疸新生儿核黄疸肝细胞肝细胞缺乏葡萄糖醛酸转移酶缺乏葡萄糖醛酸转移酶59 Liver cell dam
36、age Hemolytic anemia Hemorrhage Ileus Alkaline urine Obstruction biliary tract New born infant Aciduria Bilirubin Metabolism TestsUrobilinogen Urobilinogen Urobilinogen Urobilinogen 60Bilirubin Fractions Present in Blood and UrineBilirubin Metabolism TestsYes, serum Conjugated bilirubin 34 mol/LDire
37、ct-reacting bilirubinUnboundConjugated Never Indirect-reacting bilirubin Albumin-boundUnconjugated(90%)UrineMeasured Serum61Differential Diagnosis of JaundiceFeaturesPrehepatic(Heamolytic)Intrahepatic(Hepatocellular)Posthepatic(Obstructive)STB Unconjugated NormalConjugatedNormal CB/STB 20%2050%50%Ur
38、ine bilirubinAbsentPresentIncreasedUrobilinogenIncreasedPresentAbsent Bile acid（BA）Determination63Bile acid（BA）determination primarybile acidsprimarybile acidscholesterolIntestinal tractbacterareabsorptionportal veinEnterohepaticEnterohepatic circulation circulationLiver synthesisliver secreteLiver
39、second bile acidconjugated bile acid bileFree bile cidIntestinal tractBile ductsbileGlycine or taurine 64Clinical significanceLiver cell damage:Acute hepatitis: 20 ULN rise The disease ease, BA decreased faster than bilirubin Continue to rise may have serious liver damage Cirrhosis Chronic active he
40、patitis and liver cancer, alcoholic liver diseasethe active sensitive indexhelp to estimate the prognosis and disease recurrenceBile acid（BA）determination 65Biliary obstruction Gallstones, biliary tumor ,intrahepatic bile extrahepatic bile duct obstructionPortal shuntPhysiologic increaseafter meals Clinical significanceFast animal 12 hours, take preprandial sample, feed animal moderately fatty meal, then take postprandial blood sample 2 hours later.Bile acid（BA）determination Thanke you !
