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PulmonaryTuberculosis
江德鵬:博士,副教授,副主任醫(yī)師,碩士生導(dǎo)師,留美學(xué)者,重慶市中青年醫(yī)學(xué)高端后備人才。2000年畢業(yè)于上海第二軍醫(yī)大學(xué),本科畢業(yè)后于第三軍醫(yī)大學(xué)西南醫(yī)院中心ICU從事重癥監(jiān)護(hù)工作6年,后調(diào)入重慶醫(yī)科大學(xué)附屬第二醫(yī)院呼吸科工作,已從事臨床工作15年,具有多學(xué)科工作經(jīng)歷,擅長(zhǎng)呼吸危重癥的救治。發(fā)表SCI論著4篇,CSCD核心論著10余篇,主持國(guó)家自然科學(xué)基金1項(xiàng),其他基金2項(xiàng)。聯(lián)系方式depengjiang@163.comDefinitionTuberculosisisachronicbacterialinfectioncausedbytuberclebacillusandcharacterizedbytheformationofgranulomasininfectedtissuesandbycell-mediatedhypersensitivity.
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.TodeteriorateInfiltrationDissolutionanddisseminationClinicalfindingsSymptomsPhysicalexaminationRadiographicfeatures(補(bǔ))LaboratoryFindingsImagingSymptomsConstitutionalsymptomsFatigueweightlosslowfevernightsweatsThesystemicfeaturesoftuberculosisincludefeverinapproximately35%to80%,malaise,andweightloss;theremaybeavarietyofhematologicabnormalities,especiallyleukocytosisandanemia.PulmonarysymptomsCoughHaemotysisChestpainDyspnea
Tuberculosisisaverycomplicateddisease.Theextentofdiseasevariesfromminimalinfiltratesthatproducenoclinicalillnessandthatarebarelydiscernibleonchestradiographstomassiveinvolvementwithextensivecavitationanddebilitatingconstitutionalandrespiratorysymptoms.
Withtheprogressionofpulmonarytuberculosis,thenormalpulmonaryarchitectureislost.fibrosis,volumelossandupwardcontractionaretypical.however,recentlydiseasedareasmayhealwithrealtivelylittledistructionwheneffectivechemotherapyisadminstered.
TheonsetmaynotbeaccompaniedbyanyoftheacutesignsbutmayappearinsidiouslyHowever,itisincorrecttoviewthisonsetasoneofslowprogression.Infact,pulmonarytuberculosisusuallyreachesitsfullextentwithinafewweeks.
Chroniccoughisprincipalrespiratorysymptom.sputumisusuallyscantandnonpurulent.Haemoptysisisfrequentandisusuallylimitedtobloodstreaking.sputum.massive,life-threateninghaemoptysisisrare.
SpecificsymptomAnaphylaxiaanergytuberculosis
PhysicalexaminationFindingsonphysicalexaminationofthelunginpatientswithpulmonarytuberculosisaretypicallyfewandgenerallycanbeappreciatedonlyinthepresenceofextensivedisease.Cracklesmaybeheardintheareaofinvolvement,alongwithbronchialbreathsounds,whenlungconsolidationisclosetothechestwall.Amphoricbreathsoundsmaybeindicativeofacavity.Findingssuchaslymphnodeenlargement,suggestiveofextrapulmonarytuberculosis,mayalsoindicateconcurrentpulmonaryinvolvementRadiographicfeatures
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(guò)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.theycanusuallyberecognizedonchestX-rayfilmsandareoftenhelpfulindistinguishingtuberculosisfrompulmonaryneoplasms.
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.PayattentiontoimprovenutritionHospitalizationnotnecessaryinmostpatients.Hospitalizedpatientswithactivediseaserequireaprivateroomwithappropriateventilationuntiltheybecomesputumsmear-negativeforacid-fastbacilli.(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.Isoniazidisalsotheonlychoicetopreventthetuberculosis.RifampinisoniazidisbactericidalforextracellularandintracellularpoolsTB.ItisalsothemostpowerfuldruginthetreatmentofTB.Sideeffect:drughepatitis,gastroentericreaction
pyrazimidepyrazinamideareagainstintracellularorganisms.Pyrazimidehasbeenfoundtobepaticularlyusefulduringthefirst2monthsoftreatment.Pyrazimidecancrosstheblood-brainbarrierSideeffect:drughepatitis,hyperuricemia(arthralgia)ethambutolEthambutolisonlybacteriostatic.Sideeffect:opticneuritis(monitorvisionandfieldofview)StreptomycinStreptomycinisbactericideagainstextracellularSideeffect:ototoxicity,nephrotoxicity(creatinine
ureanitrogen)
TreatmentforTBusesantibioticstokillthebacteria.Thethreeantibioticsmostcommonlyusedarerifampicin,isoniazidandethambutol.TBrequiresmuchlongerperiodsoftreatment(around6to12months)toentirelyeliminatemycobacteriafromthebody.Therecommendedbasictreatmentregimenforpreviouslyuntreatedpatientswithpulmonarytuberculosisconsistsofaninitial(orintensive)phaseofisoniazid,rifampin,pyrazinamide,andethambutolgivenfor2months,followedbya4-monthcontinuationphaseofisoniazidandrifampin.Theinitialphaserapidlyreducesthebacterialburden,bykillingtheactivelygrowingbacteria,whilethecontinuationphaseisprotractedandintendedtoeliminatethesubpopulationofbacteriathatarereplicatingmoreslowly.Thechoiceofregimenforthecontinuationphasedependson3factors:1)thepresenceorabsenceofcavitationontheinitialchestradiograph2)theculturestatusatthecomp
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