內(nèi)科學(xué)教學(xué)課件：Pulmonary Tuberculosis

PulmonaryTuberculosis

DefinitionTuberculosisisachronicbacterialinfectioncausedbytuberclebacillusandcharacterizedbytheformationofgranulomasininfectedtissuesandbycell-mediatedhypersensitivity.上葉尖后段下頁背段多灶性多態(tài)性多鈣化少變化

A

contagiousbacterialinfectioncausedbytuberclebacillus.Thelungsareprimarilyinvolved,buttheinfectioncanspreadtootherorgans.Itis

characterizedbythedevelopmentofgranulomaintheinfectedtissues.ThepatientswithTBoftenhavethefollowingsymptoms:toxemiasyptoms,cough,haemoptysisorbloodstreakedsputumEpidemiology

Oneoftheleadinginfectiousdiseasekillers.

Onethirdoftheworld'spopulationiscurrentlyinfectedwithTB.Everysecondanotherpersonisnewlyinfectedwithtuberculosisaroundtheworld.

Eachyearanestimated6-8millionpeopledevelopclinicaldisease.Eachyear

1.2-1.5millionpeopledieofTB.

Theincidenceoftuberculosishasdeclineddramaticallyindevelopedcountriesduetoimprovednutrition,housing,effectivedrugs,vaccines.Itremainsasaprobleminpoorercountries(about80%oftheworld)itsoverallincidenceisincreasingworldwidebecauseoftheenhancedsusceptibilityofAIDSpatientsandtheappearanceofdrugresistantstrains.EtiologyTuberclebacillusisarod-shaped,slow-growing,gram-negative,aerobicbacterium.Thecellwallhashighacidcontent,whichmakesithydrophobic,resistanttooralfluids.TheM.tuberculosiscomplex(MTBC)includesfourTB-causingmycobacteria:M.tuberculosisvar.hominis,M.bovis,M.africanum,andM.microti.M.africanumisnotwidespread,butitisasignificantcauseoftuberculosisinpartsofAfrica.M.boviswasonceacommoncauseoftuberculosis,buttheintroductionofpasteurizedmilkhaslargelyeliminatedthisasapublichealthproblemindevelopedcountries.Becauseofthesurfacelipids,thetuberclebacilluscannotbedecolorizedwithacidalcoholafterstaining.Heatandfuchsineareusuallynecessarytoaccomplishprimarystaining.SinceMTBretainscertainstainsevenafterbeingtreatedwithacidicsolution,itisclassifiedasanacid-fastbacillus(AFB).

Themostcommonacid-faststainingtechniquesaretheZiehl–Neelsenstain,whichdyesAFBsabrightredthatstandsoutclearlyagainstabluebackground.ThisisanacidfaststainofMTB.Thetuberclebacillusdividesevery16to20hours,whichisanextremelyslowratecomparedwithotherbacteria,whichusuallydivideinlessthananhour.M.Tuberculosisistransmittedfrompersontopersonviatherespiratoryroute.ThebacteriaareputintotheairwhenapersonwithTBofthelungscoughsorsneezes.Peoplenearbymaybreatheinthesebacteriaandbecomeinfected.Adequateventilationisthemostimportantmeasuretoreducetheinfectiousnessoftheenvironment.TransmissionPathogenesisInfectiontheinitialentryoftuberclebacilliintothepreviouslyuninfectedlungselicitsanonspecificacuteinflammatoryresponsewhichaccompaniedbyfewornosymptoms.bacilliaretheningestedbymacrophagesandtransportedtotheregionallymphnodes.

numerousacidfastorganismsgrowedwithinmacrophages.Lotsofbrightredrodsareseen,particularlyinmacrophages

Theso-calledKoch'sphenomenonwasdemonstratedbyinoculatinganormalguineapigwithapurecultureoftuberclebacillus.After10–14days,anulcerappearsatthesiteofinjection.Itpersistsuntiltheanimaldies.However,ifthesamecultureoftuberclebacillusisinjectedintoaguineapigpreviouslyinfected3-6weeksprior,ityieldsadifferentresult.itleavesashallowulcerwhichusuallyhealsquickly.三種效應(yīng)T細(xì)胞的產(chǎn)生效應(yīng)分子示意圖CD4+TCD8+TTh0Th1：細(xì)胞免疫IL-12Th2：輔助體液免疫IL-4APC、Th1Tc（CTL）：細(xì)胞毒作用分化：AgAg

Duringthe2-8weeksafterprimaryinfection,lymphocytesenterareasofinfection,wheretheyelaboratechemotacticfactors,interleukins,andlymphokies.Monocytesentertheareaandtransformintomacrophages.tuberculosisgranulomaiscomposedofepithelioidcellLanghanstypegiantcells

caseousnecrosis,andsurroundedbylyphocyte.pathology1.infiltration2.caseousnecrosis3.hyperplasia

granulomasareseenhere.Theyhaveroundedoutlines.TheonetowardthecenterofthephotographcontainsseveralLanghansgiantcells.Granulomasarecomposedoftransformedmacrophagescalledepithelioidcellsalongwithlymphocytes.Thelocalized,smallappearanceofthesegranulomassuggeststhattheimmuneresponseisfairlygood.

caseousnecrosis(characterizedbycompletelossoftissuestructureandatextureresemblingsoftcheese)canbeseeninthecenter.

Thisisanexampleoftuberculosis,youcanseegranulomas

ofthelung.Thepatternofsmallernoduleswhichhaveapropensityforupperlobe.

Oncloserinspection,thegranulomashaveareasofcaseousnecrosis.Thispatternofmultiplecaseatinggranulomasprimarilyintheupperlobesismostcharacteristicofsecondarytuberculosis.Thetransformationof

thepathologicalchanges

1.tohealabsorptionanddissipationFibrosisandcalcification2.TodeteriorateInfiltrationDissolutionanddisseminationSymptomsConstitutionalsymptomsFatigueweightlosslowfevernightsweatsPulmonarysymptomsCoughHaemotysisChestpainDyspnea

Chroniccoughisprincipalrespiratorysymptom.sputumisusuallyscantandnonpurulent.Haemoptysisisfrequentandisusuallylimitedtobloodstreaking.sputum.massive,life-threateninghaemoptysisisrare.

PhysicalexaminationFindingsonphysicalexaminationofthelunginpatientswithpulmonarytuberculosisaretypicallyfewandgenerallycanbeappreciatedonlyinthepresenceofextensivedisease.Radiographicfeatures

Radiographicexaminationofthechestiscommonlythefirstdiagnosticstudyundertaken,afterthehistoryandphysicalexamination.Themostfrequentsitesaretheapicalandposteriorsegmentsoftheupperlobeandthedorsalsegmentofthelowerlobe.However,inpatientswithHIVinfection,achestradiographmaybenormalinupto11%ofpatientswithpositivesputumcultures.LaboratoryFindings

1.Sputumsmearmicroscopy:ThefirststepinthediagnosticsequenceisnearlyalwaysstainingandexaminingreadilyavailablespecimensforAFB.However,thesensitivityofmicroscopicexaminationisrelativelylow.

Ziehl–NeelsenstainandKinyoun-stainedsmearsofsputum

Auraminefluorochromestainofsputumsmear

MycobacteriumtuberculosisWhenthelungisinvolved,sputumistheinitialspecimenofchoice.ifexpectoratedsputumisnotreadilyavailableforexamination,expectorationmaybeinducedorsamplesobtainedbyinduction2.MycobacterialCulture：Cultureinliquidmediaisconsideredthecurrentdiagnosticgoldstandard.Cultureisanessentialstepfordiagnosisandisnecessaryforphenotypicdrugsusceptibilitytesting.3.

SerologicTests：Severalantigens,includinghighlypurifiedandrecombinantantigensspecificforM.tuberculosiscomplex,havebeenusedinserologicantibodytestswithvariableresults.

4.Fiberopticbronchoscop:Bronchoscopyhasahighyieldinthediagnosisoftuberculosis.BronchoscopicprocedureshavebeenespeciallyhelpfulinthediagnosticevaluationsofpatientswithHIVinfectionwithnegativesputumsmearmicroscopy5.

Pleuralfluidcultures:Mtuberculosisarepositiveinlessthan25%.6.

Needlebiopsyofthepleura:patientswithpleuraleffusionscausedbyMtuberculosis.7.Susceptibilitytesting:thefirstisolateofMtuberculosis(whenatreatmentisfailing).8.

ELLISAANDPCRhasbeenusedtodianosis,buttheyarerareappliedsuccessfullyinroutineclinicaltreatment.SpecialexaminationTuberculinskintest

PPDtest:0.1mLofstandardpurifiedprotein(5TU)isinjectedintradermallyonthevolarsurfaceoftheforearm.Thetransversewidth(inmillimeters)oftheinduration(redspot)attheskintestsiteshouldberecordedafter48-72hours.

Allthepeoplesusceptibleto

tuberculousisshouldhavePPDtest:

1.Peoplewhohavehadcloseday-to-daycontact

withsomeonewhohasactiveTBdisease.(afamilymember,friend,orco-worker)·

2.

PeoplewhohassymptomsofTB,suchas:

acoughthathangson,

fever,

weightloss,nightsweats,constanttiredness,lossofappetite.

3.

PeoplewhohaveloweredimmunitysuchasHIVinfectionorcertainmedicalconditions.

4.PeoplewhoneedtogiveBCG

vaccine.PPDtest(induration)Thestandardofjudgement

48-72hskinnodediameter：PPDNegative-Positive+≧5mmpositive++≧10

mmPositive+++≧20

mm(orbleb)1.Negativereactiondoesnotruleoutthediagnosisoftuberculosis.2.False-negativereactionsoccur:①malnutrition；

②oldage；③immunologicorlymphoreticulardisorders（HIVinfection、Lymphoreticularmalignancies）；④corticosteroidorimmunosuppressivetherapy；chronicrenalfailure；⑤virusvaccinationsorinfections；⑥fulminanttuberculosis；⑦impropertestingtechnique；⑧problemswiththeantigen3.False-positivereactions:①inoculationwithBCGSpecialexaminationIFN-γreleaseassays(IGRAs)

IFN-γreleaseassays(IGRAs)areusedforthediagnosisoflatenttuberculousinfection(LTBI)，TwoIGRAsarecurrentlyapprovedintheUnitedStates,theQuantiFERON-TBtestandtheT-SPOT.TBtest

TheIGRAshaveseveraladvantages:Thetestscanbeperformedinonepatientvisit,theyaremorespecificinthepresenceofBCGvaccinationorinfectionwithnontuberculousmycobacteria,theyarenotsubjecttoreadervariability,andtheydonotstimulatewanedimmunity(theboosterreaction,describedearlier).1.TheQuantiFERON-TBtests：measuretheamountofIFN-γreleasedfromsensitizedlymphocytesinwholebloodincubatedovernightwithmixturesofM.tuberculosisantigens,ESAT-6andCFP-10.2.TheT-SPOT-TBtests：utilizesanELISPOTformattoquantifythenumberofcellsinperipheralbloodthatsecreteIFN-γwhenstimulatedwithESAT-6andCFP-10Clinicalclassification1.Primarytuberculosis2.hematogenouspulmonarytuberculosis

3.secondarypulmonarytuberculosisinfiltrativeTBcavitaryTBtuberculomacaseouspneumoniafibrocavitaryTB4.tuberculouspleurisy5.extrapulmonarytuberculosis肺結(jié)核病自然過程示意圖

thecombinationofperipherallunglesion,lymphangitisandhilarlymphnode.Thereisasmalltan-yellowsubpleuralgranulomainthemid-lungfieldontheright.Inthehilumisasmallyellowtangranulomainahilarlymphnode.Primarytuberculosis

TheGhoncomplexisseenhereatcloserrange.Primarytuberculosisisthepatternseenwithinitialinfectionwithtuberculosisinchildren.Reactivation,orsecondarytuberculosis,ismoretypicallyseeninadults.Usuallyasymptomatic.AnonspecificpneumoniaHilarlymphnodeenlargementBronchialobstruction(Segmentalatelectasis)Pleuraleffusionmaybepresent

Smallhomogeneousinfiltrates(usuallyintheupperlobe)HilarandparatracheallymphnodeenlargementhematogenouspulmonarytuberculosisInthepast,hematogenousTBoccurredchieflyininfantsandadolescentespeciallyinthepeoplewithlowimmunefunction.Currently,however,exceptamongHIV-infectedpersons,itismorecommonamongolderpersons,asaresultofendogenousreactivationandbloodstreaminvasion.SeveretoxemiasymptomsDyspneaisrare

Uniformsize,densitydistributionthebilateral,diffusesmallgranulomasoftencontainnumerousmycobacteriumInfiltrativetuberculosisTheusuallocation:apicalorposteriorsegmentsoftheupperlobes;dorsalsegmentsofthelowerlobes.Variousradiographicmanifestations:

fibrocavity-nodules-infiltratesTheTBlesionoftenlocatesatposteriororapicalsegmentoftheupperlobeorthesuperiorsegmentofthelowerlobe,especiallyattheapexoflungjustasthepicturepointsout.

Caseousnecrosis

bilateral

upperinfiltrates

Whenthereisextensivecaseationandthegranulomasinvolvealargerbronchus,itispossibleformuchofthesoft,necroticcentertodrainoutandleavebehindacavity.Cavitationistypicalforlargegranulomaswithtuberculosis.Cavitationismorecommonintheupperlobes.cavitarytuberculosisPulmonarycavitiesmaypersisteventhougheffectivechemotherapyhasresultedinapparentcure.cavities,aspergillomainachronictuberculouscavinandbronchiectasisisthecommonreasonhaemoptysis.Pulmonarycavitiesmaypersisteventhougheffectivechemotherapyhasresultedinapparentcure.

Rightupperlobecavitywithabcessformationtuberculoma

Satellitelisionsdevelopconcomitantly.theycanusuallyberecognizedonCTfilmsandareoftenhelpfulindistinguishingtuberculosisfrompulmonaryneoplasms.

caseouspneumonia

FibrocavitaryTB

Cavitiesmaybesourceofmajorhemoptysis,especiallyinthepresenceofcontinuedactivedisease.persistentterminalpulmonaryarterieswithincavtiesmaybeasourceofprofoundbleeding.Extensivedestruction:widespreadcavitation,fibrosisscarsWiththeprogressionofpulmonaryTB,thenormalpulmonaryarchitectureislost.fibrosis,volumeloss,andupwardcontractionaretypical.pleuraltuberculosisPleuraleffusionoftenappearsinpleuraltuberculosis.presenceoffluidbetweenthevisceralandparietalpleura.Itcanbeseenwhen>300ml

offluidispresentonachest

radiograph.

AstuberculosisbecomesinactiveorHeals,fibroticscarringbecomesapparentonthechestradiograph.

Fibroticlessionsmaydevelopcalcifications.TheactivityoftuberculosismaybejudgedfromCT.ItisneverwisetojudgetuberculosistobeinactiveonlyontheXrayfilm.Diagnosis

1.ThediagnosisoflatentTBinfection(LTBI)LTBIisoneofexclusion,basedonthefindingofdelayed-typehypersensitivity(DTH)andtheabsenceofactiveTB.IFN-γreleaseassays(IGRAs)andtuberculinskintest(TST)areusedforthediagnosisoflatenttuberculousinfection(LTBI)

2.DiagnosisofPulmonary

tuberculosis

Historyand

clinicalsymptoms:fatigue,weightloss,fever,nightsweats,cough,orbloodsputumPulmonaryinfiltratesonchestradiograph,mostoftenapical.Positivetuberculinskintestreaction(mostcases).Acid-fastbacillionsmearofsputumorsputumculturepositiveforMycobactenumtuberculosis.TreatmentAllprovedcasesshouldbereportedtolocalpublichealthdepartments.(CDC)Treatmentofpatientsshouldbeconductedbyskillfulphysicians.Payattentiontoimprovenutrition(一)Drugtherapy

Tuberculosisrequiresearly,regular,long-timetreatmentwithacombinationofspecialandappropriatedrugs.

1.AntituberculosisdrugsFirst-linedrugs

Second-linedrugsIsoniazid(INH)Kanamycin(KM)Rifampin(RFP)Paminosalacylicacid(PAS)Pyrazinamide(PZA)Amikacin(AM)Ethambutol(EMB)Capreomycin(C)Streptomycin(SM)

Tuberculouspatientsexitsinthreepools:ametabolicallyactiveextracellularpoolandrelativelymetabolicallyinactiveintracellularandnecroticcaseumpools.RifapinandisoniazidarebactericideforextracellularandintracellularpoolsTB.Streptomycinisbactericideagainstextracellularandpyrazinamideareagainstintracellularorganisms.

isoniazidIsoniazidhavebeenusedclinicallyfor50years.ItisthemostefficientbactericideforTB,especialintheearlydays.isoniazidisbactericideforextracellularandintracellularpoolsTB.Isoniazidcancrosstheblood-brainbarrier(tubercularmeningitis)

Sideeffect:drughepatitis,peripheralneuritis.VataminB6canbeusedasthetreatmentofperipheralneuritiscausedbyisoniazid,butitwillalsoalleviatetheeffectofisoniazid.sotherearenogoodsolutiontopreventtheperipheralneuritis.Isonia