黃疸、腹瀉課件

Jaundice交通大學(xué)醫(yī)學(xué)院附屬仁濟醫(yī)院上海市消化疾病研究所范竹萍Zhuping_fan@163.comJaundiceDefinition

Accumulationofyellowpigmentintheskinandothertissues(Bilirubin)BilirubinMetabolismBilirubinformationTransportofbilirubininplasmaHepaticbilirubintransportHepaticuptakeConjugationBiliaryexcretionEnterohepaticcirculationBilirubinRBCsSenecentRBCsIronhemoglobinGlobinBilirubinBiliverdinheme

HepaticHemoproteins

nonhemoglobinhemenonhemoglobinhemoproteinPrematuredestructionofnewlyformedRBCs

CMHO

RCBR1-5%Chiefly70+%20%Bilirubinformation120dsTransportofBilirubininPlasmaAlbumin+UBUB~AlbuminComplexMolarRatioBilirubinBilirubinPlasmaproteinAlbuminHaffinitybindingsitesLaffinitybindingsitescanbereplacedbyOtherorganicanionsPHUB2:1>2:1UDPGT:UridineDiphosphateGlucuronylTransferaseUCB:becauseofitstightalbuminbindingandlipidsolubility,itisnotexcretedinurine.CB:islesstightlyboundtoalbuminandiswatersoluble,soitisfilteredattheglomerulusandappearsintheurine.PathophysiologicclassificationofJaundiceHemolyticJaundiceHepaticJaundiceObstructiveJaundice(Cholestasis)CongenitalJaundiceHemolyticJaundicePathogenesisOverproductionHemolysis(intraandextravascular)inheritedorgeneticdisordersacquiredimmunehemolyticanemia(Autoimmunehemolyticanemia)nonimmunehemolyticanemia(paroxysmalnocturna

Hemoglobinruia)IneffectiveerythropoiesisOverproductionmayoverloadtheliverwithUBHemolyticJaundiceSymptoms

weakness,Darkurine,anemia,Icterus,splenomegalyLabUBwithoutbilirubinuriafecalandurineurobilinogenhemolyticanemiahemoglobinuria(inacuteintravascularhemolysis)ReticulocytecountsObstructiveJaundicePathogenesisitisduetointra-andextrahepaticobstructionofbileductsintrahepaticJaundice:Hepatitis,PBC,DrugsExtraHepaticBiliaryObstruction:Stones,Stricture,Inflammation,Tumors,(AmpullaofVater)

Etiologyof

ObstructiveJaundiceIntrahepatic-LivercellDamage/BlockageofBileCanaliculiDrugsorchemicaltoxinsDubin-JohnsonsyndromeEstrogensorPregnancyHepatitis-viral,chemicalInfiltrativetumorsIntrahepaticbiliaryhypoplasiaoratresiaPrimarybiliarycirrhosisEtiologyof

ObstructiveJaundiceExtrahepatic-ObstructiveofbileDuctsCompressionobstructionfromtumorsCongenitalcholedochalcystExtrahepaticbiliaryatresiaIntraluminalgallstonesStenosis-postoperativeorinflammarycholestasis

clinicalfeaturespain,duetogallbladderdisease,malignancy,orstretchingofthelivercapsulefever,duetoascendingcholangitispalpableand/ortendergallbladderenlargedliver,usuallysmoothGeneralsignsofcholestasis

xanthomas:palmarcreases,belowthebreast,ontheneck.Theyindicateraisedserumcholesterolofseveralmonths.Xanthomasonthetendonsheathsareuncommonlyassociatedwithcholestasis.xanthelasmaontheeyelidsscratchmarks:excoriationfingerclubbingloose,pale,bulky,offensivestoolsdarkorangeurineObstructiveJaundice

extrahepatic

urinarychanges

bilirubin:increasedurobilinogen:reducedorabsentfecalchanges

stercobilinogen:reducedorabsentHepaticJaundice

DuetoadiseaseaffectivehepatictissueeithercongenitaloracquireddiffusehepatocellularinjuryGilbert‘ssyndromeAugustinGilbert(1858-1927)Benign,familial,mild,uncojugatedhyperbilirubinaemia(17-85umol/l)NotduetohemolysisNormalliverfunctionandhepatichistologyAffect2-5%populationExcellentprognosisHepaticJaundice

Symptomsweakness,lossappetite,hepatomegaly,palmarerythema,spiderLabFindingsliverfunctiontestsareabnormalbothCBandUCBBilirubinuria

Hepatic

Jaundiceurinarychanges

bilirubin:normalorincreasedurobilinogen:normalorreducedfecalchanges

stercobilinogen:normalorreduced黃疸鑒別血清膽紅素尿膽紅素CBUCBCB/STB尿膽紅素尿膽原（umol/L)正常人0-6.81.7-10.20.2-0.4-0.84-4.2梗阻性黃疸明顯增加輕度增加>0.5+++減少或卻失溶血性黃疸輕度增加明顯增加<0.2-明顯增加肝細(xì)胞性黃疸中度增加中度增加>0.2;<0.5+正常/輕度增加Jaundice

diagnosis(1)historyandexaminationurine,stoolsserumbiochemistrybilirubin

transaminases-AST,ALTalbuminalkalinephosphataseJaundice

diagnosis(2)hematologyhemoglobinWBCplateletsprothrombintime+/-parenteralvitaminKabdominalultrasoundandchestX-rayfurtherinvestigations-determinedbythebasisofthejaundice,e.g.pre-hepatic,hepatic,extra-hepaticDiagnosis—

conjugatedhyperbilirubinemia

theliverisabletoconjugatebilirubin,buttheexcretionisimpaired.failureofbilirubinexcretionbyhepatocytes:Dubin-JohnsonsyndromeRotor'ssyndromeobstructiontobiliaryflowi.e.cholestasis,bothintra-hepaticandextra-hepaticDiagnosis—

unconjugatedhyperbilirubinemia

increasedbilirubinformationfailureofbilirubinuptakefailureofbilirubinconjugation(Gilbert'sdisease)unconjugatedhyperbilirubinemia

increasedbilirubinformationhemolysis

ineffectiveerythropoiesis:megaloblastic

anaemia

irondeficiencyhemoglobinopathiesunconjugatedhyperbilirubinaemia

failureofbilirubinconjugationneonataljaundiceCriglerNajjarsyndromedruginhibitione.g.chloramphenicolextensivehepatocellulardiseasee.g.hepatitis,cirrhosisIdentificationofcause

dilatedductsonultrasound-percutaneoustranshepaticcholangiograpyundilatedductsonultrasound-endoscopicretrogradecholangio-pancreatographyneedlebiopsyoftheliverAccompaniedSymptomsFeverPain,CharcotsyndromeHepatomegalySpleenmegalyAscitesGIbleedingitchJaundice-

Differentialdiagnosis1.

OnceJaundiceisrecognized,itisimportanttodeterminewhetherhyperbilirubinemiaispredominantlyCBorUCB?2.DifferentiationofhemoliticfromothertypeofJaundiceisusuallynotdifficult.3.Thelaboratoryfindingsareinconstantinpartialbiliaryobstructionanddifferentiationfromintrahepaticcholestesisisparticularlydifficult.Jaundice-

DifferentialdiagnosisDifferentialDiagnosisUCBorCBExcludeUCB(e.g.hemolysisorGilbertSynd.)DistinguishhepatocellularfromobstructiveDistinguishintrahepaticfromextrahepaticcholestasisSUMMARYHavethepatienthadanisolatedelevationofserumbilirubin?Isthebilirubinelevationduetoanincreasedunconjucatedorconjucatedfraction?Isthehyperbilirubinemiahepatocellularorcholestatic?Ifcholestatic,isitintra-orextrahepatic?TrueorfalseJaundiceistheyellowpigmentationofskinyellowpigmentationofskinisalwayscausedbyjaundiceJaundiceindicateabnormalLFTThedepthofjaunticeshowstheseverityofliverdiseasesifhepaticSometimesthereisoverlapbetweenhepaticandposthepaticjaundiceIt’seasytorecognicethedeferencebetweenprehepaticandhepaticjaundiceCaseStudy1History:68-year-old,jaundice,stomachpain,“darkurine”,itchingoftheskin,rapidweightlossof21lbLabdataCBCwithinnormallimitsTotalbilirubin:238μmol/lGGT:300U/lALP:360U/lAST:80u/lALT:75u/lUrinalysis:positivebilirubin,normal

urobilinogenSerumamylase:elevatedCaseStudy1Question:Whatisthemostprobablediagnosisforthispatient?Whichlabtorytestsprovidedthemostinformation,andwhichprovidedtheleast?CaseStudy2History:38-year-oldwhitefemale,jaundice,rightupperquadrantabdominalpain,nausea,vomiting,itchingskin.Shehasahistoryofintravenousdruguseandalcoholabuse.CaseStudy2Labdataelevatedtotalbilirubin(136μmol/l)elevatedconjugatedbilirubin(102μmol/l)Urine:orange-brown,3+bilirubin,normalurobilinogenelevatedALP(1.5ULT),GGT(3ULT),ALT,AST(5ULT)Modestincrease:SerumcholesterolandtriglycerideCaseStudy2QuestionWhatistheprobablediagnosisforthispatient?Why?Whatotherlaboratorytestwouldrecommendtoconfirmthisdiagnosis?Whichlaboratorytestsorderedprovidedthemostinformation?Why?DiarrheaDefinitionincreaseinthe

frequencyofbowelmovementsincreasein

stoolliquidityinsomecasesincreaseindaily

stoolweight(>200g/d)DiarrheaPathophysiologicalmechanismsDiagnosisEtiologyClinicalmanifestationAccompaniedSymptomsDifferentialdiagnosisofdiarrheaPathophysiologicalmechanismssecretorydiarrhea(increasedintestinalsecretion)OsmoticdiarrheaDecreasedintestinalsurfaceareaand/orintestinalabsorptionInflammatarydiarrheaRapidtransitofintestinalcontents(shortenedtransittime)Pathophysiologicalmechanismssecretorydiarrhea(increasedintestinalsecretion)

infections(choleratoxin,E-col,salmonella,staphylococcal)Hormonal(GutHormones,ZES,VIP),cancer(calcitonin,Prostaglandins)miscellaneous(laxativesabuse,villousadenomaoftherectum)agentsAdenylatecyclasecAMPsystemsecretorydiarrheaactivateNaClsecretorydiarrhoeainfectioncholerahormonalVerner-Morrisonsyndrome(VIPassociated)carcinoidsyndromegastrinoma

medullarythyroidcancerphenolphthaleinabusebilesaltmalabsorptionCholera:thesimplifiedversion

PathophysiologicalmechanismsOsmoticdiarrheaItcausedbyaccumulationofthefollowingsinthegutlumen

watersaltspoorlyabsorblesolutesmaldigestionofingestedfoodfailuretotransportanosmoticallyactivedietarynonelectrolyte(E:glucose)intestinalLumenbeingosmoticallyactivediarrheaosmoticdiarrhoeadisaccharidasedeficiencyprimarilylactasedeficiencylaxativeabuse(about20%ofpatientsCalculationofosmoticgap

PathophysiologicalmechanismsDecreasedintestinalsurfaceareaand/orintestinalabsorptionE:surgicalremoval;malabsorptionsyndromePathophysiologicalmechanismsRapidtransitofintestinalcontents(shortenedtransittime)

E:irritablebowelsyndrome[Functionaldiarrhea]laxativesabusepostvagotomydiarrheapostgastrectomydumbingsyndromestoolvolumeliquiditycontacttimeincreasesmallbowelmucosacontentsincreaseinintestinalmotility(intestinalhurry)reduceEtiologyAcuteDiarrheainfectionFoodpoisoningSystematicdiseases(influenza,sepsis,etc)MiscellanousEtiologyAcuteDiarrheainfection1.viral2.bacterialcampylobacteriaShigellaE.ColiSalmoneilaetc3.fungal4.parasitic(amebicTrophozoites,Giardia)AcuteDiarrheaFoodpoisoningbacterial,plants,chemicalpoison(arsenic,...)Systematicdiseases(influenza,sepsis,measle,etc)MiscellanousAllergicdiseasesAllergicpurpura,enteropathy..endocronicdiseases(ZES,etc.)Drugs:laxatives,5-Fu,etc.EtiologyChronicDiarrheaIntestinalGastric(chronicgastritis,subtotalgastrectomy)Pancreatic(ChronicPancreatitis,PancreaticCancer,etc.)Hepatobiliary(livercirrhosis,obstructivejaundice)functionalcausesEndocronic(Hyperthyroidscrisis,ZES,Carcinoids)Drugs(Reserpin,Ismelin,Laxatives,etc.)Others(uremia,hypogammaglobulemia,etc.)ChronicDiarrheaIntestinalinfections(T.B.,Chronicbacteriadysentery,etc.)parasitics(Amebiadysentery,Giardiasis,etc.)IBD(ulcerativecolitis,Crohn’s,etc.)Mal-absorptionsynd.(lactasedeficiency,etc.)tumorsSymptomsAcutediarrhea

durationlessthan2weeksonset:Abrupt，frequent,smallfecaldischargeCrampingabdominalpain,tenesmusestool:increasedRoutinexseverecases:dehydration,electrolytedisturbances,metabolicacidosis,collapsehypovolumia,tetany.Acutediarrhea

Symptomsvolumeliquidityflecksofblood,mucusWBC,RBC,pus,destroyedepitheliumSymptoms

Chronicdiarrhea

durationmorethan2monthsChronicdiarrhea

SymptomsOnset:gradual/insidiousDiarrheaofvariableseverityDiarrheaalternatewithconstipationColickyabdominalpain,distentionintestinalcausesinsmallbowelpathology:abdominalpain,whenpresent,isperiumbilicalorrightiliacfossathefrequencyofdefecationisoftenreducedthestoolmaybewellformedbutitisbulky,offensive,andmaybepaleincolortheremaybesignsandsymptomsofmalabsorptionintestinalcausesinlargebowelpathology:thereisoftenadefectinthereabsorptionofwaterfromthefaecesstoolsmaybeprofuseandwateryand/ormixedwithbloodandmucustheremaybelowerabdominalpainwithtenesmusandurgencystoolwatery,bloody,steatorrheacontains:inflammatorycells/mucus/pus,indigestedfoodsevere/long-standingcases:

weightloss,malnutrition,edema,multivitsdeficiency,malabsorption,wasting,edema,bonepainAccompaniedSymptomsseveredehydration

(cholera,pancreaticcholera-WDHA,etc.)fever

(Acutebacillerydysentery,Typhoid,TBenteritis,etc.)tenesmus

(Acutedysentery,proctitis,etc.)markedlyweightloss

(cancerofgut,malabsorption,etc.)Arthralgia/Arthritis

(IBD,connectivetissuediseases,etc.)masses

(malignantcancerofGI,TB,peritonitis,etc.)DiagnosticProceduresInformationP.E.Findings

fever,dehydration,malnutrion,anemia,jaundice,arthralgia,abdominalmasses,Tenesmus,digitalrectalexamination.LabfindingsDiagnosticProceduresinformationinepidemics(Dysentery,v.Cholerae,Typhoid,foodpoisonning,enteritis)foodallergypastillness(antibioticrelateddiarrhea,etc.)medicationtaken(corticosteroids,laxatives,etc.)predisposingconditions(surgicalresection,parasiticinfection,etc.)

BloodUrineStoolMicroscopyTolerancetestsBreathtestsCultureofJejunalaspirates5HIAA(urinaryexcretion)VitB12absorptiontestX-rayBariumEndoscopySuctionbiopsytechnique(JejunalmucosahistologyLabfindingsinvestigationsofdiarrhoeadigitalrectalexamination,toexcludeoverflowdiarrhoeaduetoconstipationandalowrectalcarcinomabloodtestsinclude