呼吸系统中英文

呼吸系统中英文第1页/共251页

Anatomy鼻咽喉环状软骨气管支气管肺上呼吸道下呼吸道第2页/共251页RapidgasexchangeVentilationPerfusionDiffusionCleaningtheairAlveoli(300millionalveoliintwoadultlungs,provideasurfaceareaofsome160meterssquare

)

SurportingstructureElasticrecoilStructureandfunctionGeneralConsiderations

第3页/共251页(1)theconductingairways

(deadairspace)第4页/共251页(2)thegasexchangeportions第5页/共251页气管粘膜层粘膜下层外膜上皮(纤毛柱状)固有膜CiliatedcellMucouscellsIgA纤毛粘液排送系统Mucous,serousandmixed

glandsCartilaginous第6页/共251页肺导气部：呼吸部：肺内支气管BronchioleTerminalbronchiole(软骨消失)Respiratorybronchiole（纤毛消失）AlveolarductAlveolarsacAlveoli(SMC消失)6~815~18AlveoliI型（90%）II型Surfactant,repairI肺间质、肺泡间隔：cap.,f,MφCohn孔相互沟通第7页/共251页HistologyoftheAirwaysMucosaSubmucosaCartilageMuscles

ComponentsFunctionsBronchi

aredistinguishedfrombronchiolesprimarilybythepresenceofcartilageintheirwalls.

Bronchiolesalsolacksubmucosalglands.第8页/共251页Epithelium

PseudostratifiedciliatedcolumnarcellsMucous(goblet)cells第9页/共251页BronchialSubmucosalGlands第10页/共251页HistologyoftheAlveolarwallsAlveoliCapillariesPoresofKohn第11页/共251页SimplesquamousStretchyPermeabletoO2andCO2EasilyinjuredDonotdivideReservecellsCuboidalProduceandprocesssurfactantDivideanddifferentiatetotypeIpneumocytes第12页/共251页Section1Chronicobstructivepulmonarydisease第13页/共251页ChronicObstructivePulmonaryDisease(COPD)不可逆气道阻塞Irreversibleairflowobstruction慢支和肺气肿ChronicBronchitisandEmphysema

常常伴发Frequentlyoccurtogether与空气污染和吸烟有关Stronglycorrelatedwithairpollutionandsmoking男多于女Morecommoninmenthaninwomen社会经济影响Socioeconomicimpact第14页/共251页COPDrepresentsagrowingglobalpublichealthproblem.Inonepopulationbasedstudyconductedatmultipleinternationalsites,approximately10%ofparticipants40yearsofageorolderwerefoundtohaveairflowobstructionofatleastmoderateseverityaccordingtospirometriccriteria.(

BuistAS,McBurnieMA,VollmerWM,etal.InternationalvariationintheprevalenceofCOPD(theBOLDStudy):apopulation-basedprevalencestudy.Lancet2007;370:741-50.)第15页/共251页我国国家“十五”课题最新统计数据（2005年公布）显示40岁以上人口COPD患病率为8%。估计全国有2500万人罹患此病，每年因COPD死亡的人数达100万，致残人数达500～1000万，COPD居我国疾病负担的首位。第16页/共251页一、慢支ChronicbronchitisClinicaldiagnosticcriteria慢性咳嗽、咳痰每年３个月连续２年第17页/共251页Chronicbronchitis

Endoscopicimage第18页/共251页Pathogenesis感染吸烟＼气候＼空气污染等第19页/共251页大气道病变Largeairwaydisease咳嗽、咳痰CoughandsputumproductionHistologicalchanges杯状细胞数量增加increasednumbersofgobletcellsintheepithelium粘液腺数量增加increasedvolumeofthesubmucosalmucusglands慢性炎症acomponentofchronicinflammation第20页/共251页Reidindexinnerperichondriumbasallamina第21页/共251页鳞化Squamousmetaplasia第22页/共251页ChronicinflammationHyperemia第23页/共251页小气道病变Smallairwaydisease呼气性呼吸困难DecreaseinmaximumforcedexpiratoryflowHistologicalchanges杯状细胞数量增加presenceofgobletcellsintheliningepithelium慢性炎症acomponentofchronicinflammation第24页/共251页luminalandmucuschronicinflammation第25页/共251页Pathologicchanges起始于大支气管累及小、细支气管①粘膜上皮的损伤和修复纤毛倒伏、脱失上皮细胞变性、坏死脱落，可鳞化上皮再生，杯状细胞大量增生（4~5：12：1）慢性非特异性炎第26页/共251页②腺体变化粘液腺肥大、增生浆液腺化生为粘液腺第27页/共251页③管壁病变充血、水肿，炎细胞浸润平滑肌束断裂，软骨变性萎缩第28页/共251页小细支气管炎晚期病变向小支气管和细支气管及管壁周围组织扩展，形成细支气管周围炎；管壁增厚管腔闭塞第29页/共251页Clinicalfeatures支气管粘膜炎症、粘液分泌旺盛咳痰支气管痉挛，渗出物阻塞喘第30页/共251页晚期表现Latestagemenifestation血氧饱和度低insufficientoxygenationofblood(hypoxemia)呼吸困难laboredbreathing(hypoventilation)右心衰right-sidedheartfailure(corpulmonale)Treatment不能根治Nocure控制症状relievingsymptoms防止并发症preventingcomplications

第31页/共251页二、肺气肿Pulmonaryemphysema

呼吸性细支气管至肺泡的末梢肺组织因持续性含气量增加而呈过度膨胀，伴有肺泡壁弹力组织破坏，间隔断裂致肺泡互相融合，肺容积胀大的病理状态。

Abnormalpermanentenlargementofairspacesdistaltotheterminalbronchiole,accompaniedbythedestructionoftheirwalls.(morphologicallydefined)第32页/共251页

InadequateventilationLessperfusionNarrowedbronchiole第33页/共251页第34页/共251页Pathogenesis蛋白酶和抗蛋白酶水平失衡Imbalancebetweenproteasesand

anti-proteases(alpha-1antitrypsin)inthelungCigarettesmoking

募集粒细胞和巨噬细胞Recruitsneutrophilsandmacrophages氧自由基抑制抗胰蛋白酶Oxidantsandfreeradicalsinhibitthealpha-1-antitrypsincirculatinginthelung慢支和反复感染Chronicbronchitisandrepeatedinfections缺乏Alpha-1antitrypsindeficiency(1%)Whodestroythealveoliwall?第35页/共251页肺气肿类型Typesofemphysema中央性肺气肿Centriacinar(centrilobular)emphysema常见主要累及部位respiratorybronchiole

上叶更常见见于吸烟者第36页/共251页全小叶性肺气肿Penacinar(panlobular)emphysema累及整个腺泡下叶常见1/20ascommonascentriacinaremphysema.Seeninalpha-1-antitrypsindeficiency

肺气肿类型Typesofemphysema第37页/共251页隔旁肺气肿Distalacinar(paraseptal)emphysema或小叶周围性肺气肿远端Thedistalrespiratoryacinusisexpanded主要部位：上叶近胸膜或隔旁肺气肿类型Typesofemphysema第38页/共251页Centriacinar(centrilobular)emphysema第39页/共251页

Centrilobularemphysemainwhichthereare"dirtyholes"thatappearfocallywherethecentralportionsoflungacinihavelostlungparenchymawhilecollectinganthracoticpigmentatthesametime.Thispatternistypicalforsmokers第40页/共251页Centriacinar(centrilobular)emphysema第41页/共251页Emphysemalossofalveolarwalls第42页/共251页镜下：肺泡壁、肺泡间隔萎缩、消失、破坏，互相融合第43页/共251页其它瘢痕旁肺气肿Emphysemawithirregulardistributionrelatedtoscars(obstruction/traction)代偿性肺气肿CompensatoryemphysemaCausedbyremovalorcollapseofadjacentpulmonaryparenchyma肺大泡肺尖、胸膜下局灶性肺泡间隔破坏，形成>2cm(D)囊泡间质性肺气肿儿童多见，肺泡壁、细支气管壁急性破裂，空气进入肺间质第44页/共251页第45页/共251页Numerouslargebullaeapparentonthesurfaceofthelungsinapatientdyingwithemphysema.第46页/共251页临床病理联系Latestagemanifestation气短Shortofbreath,wheezling咳嗽Coughwithorwithoutmucous疲劳FatigueWeightloss下肢水肿Anklefeetlegswelling肺感染lunginfectionsComplications

RespiratoryinfectionsRespiratoryfailureCorpulmanale第47页/共251页第48页/共251页患者，女性，60岁。因反复咳嗽、咳痰11年，伴气促、心悸3年，下肢水肿2年，腹胀3月入院。11年前感冒后发热、咳嗽、咳脓痰。以后每逢冬春季常咳嗽、咳白色泡沫痰，有时为脓痰，反复加重。3年来，在劳动或爬坡后常感心悸、呼吸困难。2年前开始反复下肢凹陷性水肿。3月前受凉后发热、咳嗽加重，咳脓痰，心悸气促加剧并出现腹胀，不能平卧，急诊入院。病例分析第49页/共251页体格检查：体温37.4℃，脉搏98次/min，呼吸28次/min，血压102/79mmHg。慢性病容，端坐呼吸，嗜睡，唇及皮肤明显发绀，颈静脉怒张，吸气时胸骨及锁骨上窝明显凹陷，桶状胸，呼吸动度降低，叩诊呈过清音，双肺散在干湿啰音。心率98次/min，心律齐，心浊音界缩小。腹部膨隆，大量腹水征，肝在肋下7.5cm，较硬，双下肢凹陷性水肿。第50页/共251页实验室检查：血常规：血红蛋白98g/L，白细胞6.7×109/L，其中嗜中性粒细胞占0.89，淋巴细胞0.11。入院后病人突然抽搐，极度烦躁不安，继之神志不清，心率增到156次/min，抢救无效死亡。1．根据主要临床表现作出诊断，并说明诊断依据。第51页/共251页尸检摘要左右胸腔积液各200m1，腹腔积液2000ml呈淡黄色，透明，比重1.012。双肺各重750g，体积增大，极度充气膨胀，切面见双肺散在灶性实变，呈灰白色，部分呈灰白与暗红相间，且以双肺下叶为甚。镜下见双肺末稍肺组织过度充气、扩张，肺泡壁变薄、部分壁断裂；灶性实变区见充血，肺泡内及细支气管腔内有浆液、嗜中性粒细胞充填，部分上皮细胞坏死脱落；第52页/共251页支气管黏膜上皮内杯状细胞增多，部分鳞状上皮化生，个别管腔内见黏液或渗出物形成的栓子，管壁黏液腺增多并肥大，管壁软骨灶性钙化及纤维化，纤维组织增生，淋巴细胞和少量嗜中性粒细胞浸润。心脏重300g，右心室壁厚0.35cm，右心腔明显扩张，肉柱及乳头肌增粗变扁，肺动脉圆锥膨隆，左心及各瓣膜未见明显病变。心源性肝硬化。其他脏器变性、淤血。

第53页/共251页2．说明该患者的疾病的发生发展过程。

3．请用尸检发现解释患者的症状和体征。

咳嗽、咳痰，脓痰，劳动后心悸呼吸困难，下肢凹陷性水肿，腹胀端坐呼吸，嗜睡，唇及皮肤发绀，颈静脉怒张，吸气时胸骨及锁骨上窝凹陷，桶状胸，双肺散在干湿啰音，大量腹水征，肝大、较硬第54页/共251页A67-year-oldmanpresentswithahistoryofdyspnea,whichhasprogressedforthepastseveralyears.Hebegansmokingcigarettesat15yearsofageandcontinuestosmokeonepackperday.Worseningbreathlessnessforcedhimtoretireasalaborer,andhehassoughtemergencycareforwhathecallsbronchitistwiceinthepastyear.Hisphysicalexaminationisnotablefordiminishedbreathsoundsonauscultation,withaprolongedexpiratoryphase.Spirometryrevealssevereairflowobstruction第55页/共251页Thesentinelclinicalfeatureofseverechronicobstructivepulmonarydisease(COPD)isdyspneaonexertion.Itsonsetisusuallyinsidious,anditmayprogresstoseveredisabilityoveraperiodofyearsordecades.Othercommonsymptomsincludecough,sputumproduction,wheezing,andchestcongestion.第56页/共251页Theprincipalpathophysiological

featuresofCOPD第57页/共251页PatientswithsevereCOPDoftenhaveexacerbationsthatresultinmedicalvisitsandhospitalizations.Chronichypoxemiaandhypercapniamaycausepulmonaryhypertensionandcorpulmonale.PatientswithsevereCOPDarealsoatincreasedriskforothersystemicdiseases,includingcardiovasculardisease,osteoporosis,lungcancer,anddepression.(AgustíAG,NogueraA,SauledaJ,Sall

aE,PonsJ,BusquetsX.Systemiceffectsofchronicobstructivepulmonarydisease.EurRespirJ2003;21:347-60.)第58页/共251页Alpha1-AntitrypsinDeficiencyA60-year-oldwhitemanpresentsforevaluationofprogressivedyspnea.Heisaformersmokerwitha20-pack-yearsmokinghistoryanda10-yearhistoryofdiagnosedchronicobstructivepulmonarydisease(COPD).ThereisnofamilyhistoryofCOPD.Severeairflowobstructionisseenonspirometry肺量测定法,withaforcedexpiratoryvolumein1second(FEV1)thatis40%ofthepredictedvalue.Shouldthepatientbeevaluatedforalpha1-antitrypsin(AAT)deficiency?IfAATdeficiencyisdocumented,howshouldhiscasebemanaged?第59页/共251页TheClinicalProblemAATdeficiencyincreasestheriskofCOPD,liverdisease,andseveralotherconditions.Althoughvariousdefinitionshavebeenused,wedefineAATdeficiencyastheinheritanceoftwoseveredeficiencyallelesatthelocusencodingAAT.AATdeficiencyisrelativelycommoninpopulationsofEuropeanancestry始祖,withanestimatedprevalenceof1caseper3000to5000personsintheUnitedStates.TheincidenceofAATdeficiencyinwhitenewbornsissimilartothatofcysticfibrosis.AATisaserineproteaseinhibitorencodedbySERPINA1(alsoknownasPI).AATisahighlyeffectiveinhibitorofneutrophilelastase;animbalancebetweenlevelsofAATandthiselastaseincreasestheriskofemphysema(Fig.1A).第60页/共251页Figure1.PathogenesisofAlpha1-Antitrypsin(AAT)Deficiency.PanelAshowsasimplifiedrepresentationofthemechanismforthedevelopmentofemphysemainpatientswithAATdeficiency.Grosspathologicalexaminationoftenrevealsbasilarpanacinaremphysema,withalveolarseptaldestructionandairspaceenlargementseenonlightmicroscopy.PanelBprovidesanoverviewofliverdiseaseinpatientswithAATdeficiency.Theliverhashepatocytescontainingcytoplasmicglobules,whicharemadeupofpolymerizedAATmolecules.Theaccumulationofthesemoleculesappearstodamagetheliver,butthereisnoconsensusregardingthespecificmechanismsofthisinjury.第61页/共251页MostpersonswithAATdeficiencyinherittwocopiesofthePI*Zallele(Table1).PersonswhoinheritoneoftheheterogeneousgroupofPI*Nullalleles,whichresultintheabsenceofAATproduction,andonePI*Zallele(i.e.,PIZNull)arenotreadilydistinguishedfromthosewhoarehomozygousforthePI*ZalleleonthebasisofserumAATlevelsorproteinphenotyping.Therefore,patientswiththePIZZandPIZNullgenotypesareoftenclusteredtogetherashavingtheZproteinphenotype.TheZproteincanformpolymersthattrapAATwithintheroughendoplasmicreticulumofhepatocytes,theprimarysourceofAATsynthesis,leadingtoreducedlevelsofcirculatingAATinthebloodstream.PatientswiththeZproteinphenotypehaveapproximately15%ofnormalAATlevels.TheaccumulatedAATproteininhepatocytesappearstounderlietheliverdiseaseassociatedwithAATdeficiency(Fig.1B).Thegenetic,biochemical,andpathogeneticfeaturesofAATdeficiencyhavebeenreviewedpreviously.第62页/共251页第63页/共251页ThenaturalhistoryofAATdeficiencyinadulthoodremainspoorlyunderstood.AATdeficiencyisrecognizedinlessthan10%ofpersonsinwhomadiagnosiswouldbeexpectedonthebasisofscreeningstudiesinthegeneralpopulation.ThediagnosisofAATdeficiencyisgenerallymadeaftertheidentificationofCOPDorliverdiseaseorafterthedeficiencyhasbeendiagnosedinafamilymember.ThehealthstatusofpatientswithundiagnosedAATdeficiencyisuncertain,butmanypatientsmaynotbesubstantiallyimpaired.CigarettesmokinggreatlyincreasestheriskofCOPDinpatientswiththeZproteinphenotype.OtherriskfactorsforCOPDinsuchpatientsaremalesexandasthma.Geneticmodifiersoflungandliverdiseaseprobablyexist,althoughtheyremainlargelyundefined.第64页/共251页TheclassicpulmonarypresentationofAATdeficiencyissevere,early-onsetpanacinaremphysemawithabasilarpredominanceinadults(Fig.1AandFig.2).However,emphysemamayalsooccurinadiffusedistributionorpredominantlyintheupperlobes.Bronchiectasis,withorwithoutconcomitant伴发的emphysema,islesscommon.Dyspneaisgenerallytheprominentsymptom,butchroniccoughorwheezingmayalsooccur.ThemajorityofchildrenwithAATdeficiencywiththeZproteinphenotypewhoareidentifiedthroughnewbornscreeninghaveabnormalliverfunctiontestsatsomepointduringtheirfirstyearoflife.Approximately10%ofinfantswiththeZproteinphenotypehaveprolongedobstructivejaundice,andabout2%presentinchildhoodwithliverfailurerequiringtransplantation.Asthesechildrenage,thereisanincreasingriskofliverdisease,includingcirrhosisandhepatocellularcarcinoma.ApostmortemstudyinSwedensuggestedthatadultswiththeZproteinphenotypewhodiedfromcausesunrelatedtoAATdeficiencyoftenhadasymptomaticcirrhosis,andthisriskincreasedwithage第65页/共251页Figure2.VariabilityofRadiographicFindingsinPatientswithAlpha1-Antitrypsin(AAT)Deficiency.ComputedtomographyofthechestinpatientswithAATdeficiencyshowsabroadrangeofmanifestations.AATdeficiencyhasclassicallybeenassociatedwiththedevelopmentofbasilar-predominantpanacinaremphysema(PanelA).However,upper-lobe-predominantemphysema(PanelB)andbronchiectasis(PanelC)canalsobeobserved,andsometimesthelungsarenormal(PanelD).第66页/共251页MostpersonsinherittwocopiesofthePI*Mallele,whichisassociatedwithnormalAATlevels.ThePI*SalleleisslightlymorecommonthanthePI*ZalleleinmostEuropeanpopulationsandisassociatedwithmildlyreducedAATlevels.AvailableevidencesuggeststhatpatientswiththePIMZgenotypemaybeatslightlyincreasedriskforCOPDandliverdisease,butthisassociationhasnotbeenproved.PatientswiththePISZgenotypeareatincreasedriskforCOPD,especiallyiftheysmoke,ascomparedwiththosewiththePIMMgenotype,buttheyhavealowerriskthanthosewiththeZproteinphenotype.第67页/共251页StrategiesandEvidenceDiagnosisAATdeficiencyremainsundiagnosedinmanypatients,andthereareoftenlongdelaysbetweentheonsetofrespiratorysymptomsanddiagnosis.Approximately1%ofpatientswithCOPDhaveAATdeficiency,andtheconditionisfrequentlynotdiagnosed.Insomecases,theunderdiagnosis诊断不足ofAATdeficiencymayrelatetoperceived认知risksassociatedwithtestingforageneticcondition.ItisrecommendedthatpatientsbeinformedaboutrisksoftestingforAATdeficiency,includingpotentialgeneticdiscrimination,beforetestingisperformed.ThelackofstudiesdemonstratingthatincreasedAATdetectionleadstoimprovedhealthoutcomeshasledtovaryingapproachestoAATtesting,buttestinghasbeenrecommendedforallpatientswithCOPD,asthmawithirreversibleairflowobstruction,unexplainedliverdisease,ornecrotizingpanniculitis脂膜炎第68页/共251页ThreestrategiesarecommonlyusedtodiagnoseAATdeficiency:measurementoftheserumorplasmaproteinlevel,AATproteinphenotypingofserumorplasma,andAATgenotyping(Table1).ThemeasurementofAATlevelsisaccuratelyperformedinmanylaboratoriesandisareasonableinitialtest,butithaslimitations.WhenanevaluationisperformedonthebasisofafamilyhistoryofAATdeficiency,suchtestingmaynotdetectpersonswhoareheterozygousforadeficiencyallele,whooftenhavelevelsatornearthenormalrange.SinceAATisanacute-phasereactant,levelsmayrisesubstantiallyduringillnessorothertypesofinflammatorystress,althoughtheytypicallyremainwellbelowthenormalrangeinAATdeficientpersons.AsourceofconfusioninevaluatingAATlevelsisthevarietyofmeasurementunitsusedtoexpresstheresults.IftheAATproteinlevelisbelowthenormalrange,furtherassessmentwithproteinphenotypingorgenotypingisrecommended.第69页/共251页ProteinphenotypingisperformedatspecializedlaboratoriesbyevaluatingtheisoformpatternsofAATproteinwiththeuseofanisoelectricfocusinggel.OnelimitationofthisapproachistheinabilitytoidentifyPI*Nullalleles,sincethesevariantsproducenocirculatingprotein.Commerciallyavailablegenotypingkits,whichoftenusedriedbloodspots,aredesignedforthemolecularidentificationofthemostcommonabnormalAATvariants(PI*SandPI*Z).Thisapproachcanmissoneofthemorethan30raregeneticvariantsthatleadtoreducedproteinlevels(e.g.,PI*Mheerlen),absentproteinlevels(assortedPI*Nullalleles),ornormallevelsofadysfunctionalprotein(e.g.,PI*F).32Uncommongeneticvariantscanalsoleadtoconfusionaboutpaternityiftheyarenotproperlyassessed.Toovercometheselimitations,thetestingoflevelsorproteinphenotypingshouldbeperformedwithgenotypetesting.第70页/共251页EvaluationandFollow-upTheevaluationandtreatmentofAAT-deficientpatientsaresummarizedinFigure3.ThetakingofamedicalhistoryandthephysicalexaminationshouldincludeassessmentforCOPDandsignsofchronicliverdisease,aswellaslesscommonmanifestationsofsevereAATdeficiency:necrotizingpanniculitisandvasculitis,primarilyanti–proteinase-3-positivevasculitis(e.g.,Wegener’sgranulomatosis).Adetailedfamilyhistoryandassessmentofenvironmentalandoccupationalexposures(e.g.,tosmokingoroccupationaldust)isimportant.AfterthediagnosisofAATdeficiencyisconfirmed,referraltospecialistsinlungandliverdiseaseswithexperienceinmanagingAATdeficiencyisrecommended.Baselineevaluationshouldincludeassessmentofliverandpulmonaryfunction,includingspirometry(bothbeforeandafterbronchodilation)andtestingoflungvolumesanddiffusingcapacityofthelungsforcarbonmonoxide.第71页/共251页COPDthatisassociatedwithAATdeficiencyrarelydevelopsbeforetheageof30years.TomonitorforthedevelopmentorprogressionofCOPDinpatientswithAATdeficiency,annualpulmonary-functiontesting(spirometryandtestingoflungvolumesanddiffusingcapacityofthelungsforcarbonmonoxide)isrecommendedforpatientsovertheageof30yearsorinyoungerpatientswithrespiratorysymptoms.Chestradiographymayhelptoruleoutotherlungconditionsbutisnotsensitiveforthedetectionofemphysema.Chestcomputedtomography(CT)mayidentifybronchiectasisandprovidedetailsontheseverityofemphysema,buttheassociatedradiationexposurearguesagainstthefrequentuseofCT.EvaluationofoxygenationshouldbeperformedinpatientswithCOPD.第72页/共251页WhenapatientwiththePIZZgenotypepresentswithchronicliverdisease,othercausesshouldbeconsidered.LiverbiopsyisnottypicallyrequiredtodiagnoseAAT-relatedliverdisease,butitmaybehelpfulincertaincasestoruleoutothercausesofliverdiseaseandtoassessseverity.Inadditiontotakingamedicalhistoryandperformingaphysicalexamination,varyingstrategiesareusedtoassessforthedevelopmentofliverdiseaseinAAT-deficientpatients.Thesestrategiesrangefrommeasuringliverfunction(generallyonanannualbasis)toobtainingaliverbiopsyspecimen.Somehepatologistsuseabdominalultrasonographyandtestingofalpha-fetoproteinlevelstomonitorpatientsforhepatocellularcarcinoma,buttheappropriatefrequencyandroleofthesetestsareuncertain.AATtestingofrelativesshouldbediscussedwithpatientswhohaveAATdeficiency.Testingofsiblings同胞isstronglyrecommended.第73页/共251页三、支气管扩张Bronchiectasis肺内小支气管的持久性扩张为特征的慢性呼吸道疾病。管内分泌物潴留继发化脓性炎。---咳嗽、大量脓痰、咯血Bronchiectasisisthepermanentdilationofbronchiandbronchiolescausedbydestructionofthemuscleandelasticsupportingtissue,resultingfromorassociatedwithchronicnecrotizinginfections.Itisnotaprimarydiseasebutratherissecondarytopersistinginfectionorobstructioncausedbyavarietyofconditions.

第74页/共251页Bronchialobstruction.Commoncausesaretumors,foreignbodies,andoccasionallyimpactionofmucus.Undertheseconditions,thebronchiectasisislocalizedtotheobstructedlungsegment.Necrotizing,orsuppurative,pneumonia,particularlywithvirulentorganismssuchasStaphylococcusaureusorKlebsiellaspp.,maypredisposetobronchiectasis.Inthepast,postinfectivebronchiectasiswassometimesasequeltothechildhoodpneumoniasthatcomplicatedmeasles,whoopingcough,andinfluenza,butthishassubstantiallydecreasedwiththeadventofsuccessfulimmunization.Post-tubercularbronchiectasiscontinuestobeasignificantcauseofmorbidityinendemicareas.

第75页/共251页扩张的支气管，支气管壁结构不清楚，发生了坏死性炎症，破坏管壁。第76页/共251页Pathologicalchanges病变支气管圆柱状或囊状扩张左下叶多见管腔内常有脓第77页/共251页第78页/共251页反复炎症导致瘢痕形成，在肺叶之间造成粘连。第79页/共251页第80页/共251页临床病理联系Clinicalsymptoms：咳嗽、大量脓痰由粘膜化脓性炎症刺激2.咯血是支气管炎症破坏血管。3.胸痛炎症累及胸膜4.肺脓肿、脓气胸、脑脓肿5.晚期可引起肺心病。第81页/共251页ClinicalCourseTheclinicalmanifestationsconsistofsevere,persistentcoughwithexpectorationofmucopurulent,sometimesfetid恶臭的,sputum.Thesputummaycontainflecksofblood;frankhemoptysiscanoccur.Symptomsareoftenepisodicandareprecipitatedbyupperrespiratorytractinfectionsortheintroductionofnewpathogenicagents.Clubbingofthefingersmaydevelop.Incasesofsevere,widespreadbronchiectasis,significantobstructiveventilatorydefectsdevelop,withhypoxemia,hypercapnia,pulmonaryhypertension,and(rarely)corpulmonale.第82页/共251页四、支气管哮喘Bronchialasthma肺高敏反应或其他因素引起的一种以发作性、可逆性支气管痉挛为特征的慢性支气管炎性疾病。临床表现：反复发作、伴有哮鸣音的呼气性呼吸困难、咳嗽、胸闷Asthmaisachronicinflammatorydisorderoftheairwaysthatcausesrecurrentepisodesofwheezing,breathlessness,chesttightness,andcough,particularlyatnightand/orearlyinthemorning

第83页/共251页About70%ofcasesaresaidtobe"extrinsic"or"atopic"andareduetoIgEandTH2-mediatedimmuneresponsestoenvironmentalantigens.Intheremaining30%ofpatients,asthmaissaidtobe"intrinsic"or"non-atopic"andistriggeredbynon-immunestimulisuchasaspirin;pulmonaryinfections,especiallythosecausedbyviruses;cold;psychologicalstress;exercise;andinhaledirritants.第84页/共251页外源性支气管哮喘(Extrinsicasthma):I型变态反应，吸入过敏原，多见于儿童。内源性支气管哮喘（Intrinsicasthma）:呼吸道感染、寒冷、锻炼、紧张、吸入刺激物、药物等导致哮喘发作，成人多见。第85页/共251页PathogenesisThemajoretiologicfactorsofasthmaaregeneticpredispositiontotypeIhypersensitivity("atopy"),acuteandchronicairwayinflammation,andbronchialhyper-responsivenesstoavarietyofstimuli.Theinflammationinvolvesmanycelltypesandnumerousinflammatorymediators,buttheroleoftype2helperT(TH2)cellsmaybecriticaltothepathogenesisofasthma.

第86页/共251页CytokinesproducedbyTH2cellsaccountformostofthefeaturesofasthma-IL-4stimulatesIgEproduction,IL-5activateseosinophils,andIL-13stimulatesmucusproduction.AllthreeofthesecytokinesareproducedbyTH2cells.Inaddition,epithelialcellsareactivatedtoproducechemokinesthatpromoterecruitmentofmoreTH2cellsandeosinophils,aswellasotherleukocytes,thusamplifyingtheinflammatoryreaction.第87页/共251页Thisclinicalpictureiscausedbyrepeatedimmediatehypersensitivityandlate-phasereactionsinthelungthatgiverisetothetriadofintermittentandreversibleairwayobstruction,chronicbronchialinflammationwitheosinophils,andbronchialsmoothmusclecellhypertrophyandhyperreactivity.

第88页/共251页支气管腔充满粘液，粘膜下层平滑肌肥大、水肿、炎症。(mainlyeosinophils).第89页/共251页大量的嗜酸性粒细胞第90页/共251页ClinicalCourseAnattackofasthmaischaracterizedbyseveredyspneawithwheezing;thechiefdifficultyliesinexpiration呼气.Thevictimlaborstogetairintothelungsandthencannotgetitout,sothatthereisprogressivehyperinflationofthelungswithairtrappeddistaltothebronchi,whichareconstrictedandfilledwithmucusanddebris.Intheusualcase,attackslastfrom1toseveralhoursandsubside消退eitherspontaneouslyorwiththerapy,usuallybronchodilatorsandcorticosteroids.第91页/共251页SUMMARYAsthmaAsthmaischaracterizedbyreversiblebronchoconstrictioncausedbyairwayhyper-responsivenesstoavarietyofstimuli.AtopicasthmaiscausedbyaTH2andIgE-mediatedimmunologicreactiontoenvironmentalallergensandischaracterizedbyacute(immediate)andlate-phasereactions.TheTH2cytokinesIL-4,IL-5,andIL-13areimportantmediators.Triggersfornon-atopicasthmaarelessclearbutincludeviralinfectionsandinhaledairpollutants.Eosinophilsarekeyinflammatorycellsfoundinallsubtypesofasthma;eosinophilproductssuchasmajorbasicproteinareresponsibleforairwaydamage.Airwayremodeling(basementmembranethickeningandhypertrophyofbronchialsmoothmuscle)addstotheelementofobstructivedisease.第92页/共251页Section2PneumoniaPulmonaryinfectionsintheformofpneumoniaareresponsibleforone-sixthofalldeathsintheUnitedStates.Thisisnotsurprisingbecause(1)theepithelialsurfacesofthelungareconstantlyexposedtolitersofvariouslycontaminatedair;(2)nasopharyngealfloraareregularlyaspiratedduringsleep,evenbyhealthypersons;(3)othercommonlungdiseasesrenderthelungparenchymavulnerabletovirulentorganisms.Itisthereforeasmallmiraclethatthenormallungparenchymaremainssterile.