respiratory system embryology - ju medicine · 2020. 12. 19. · embryology. development of the...
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RespiratorySystemEmbryology
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DevelopmentofthenoseandPalate
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Developmentofthenose
• Attheendofthefourthweek,facialprominencesconsistingprimarilyofneuralcrest-derivedmesenchymeandformedmainlybythefirstpairofpharyngealarchesappear
• Thefrontonasalprominence,formedbyproliferationofmesenchymeventraltothebrainvesicles,constitutestheupperborderofthestomodeum
• Onbothsidesofthefrontonasalprominence,localthickeningsofthesurfaceectoderm,thenasal(olfactory)placodes,originateunderinductiveinfluenceoftheventralportionoftheforebrain
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Developmentofthenose
• Duringthefifthweek,thenasalplacodesinvaginatetoformnasalpits(nostril).
• Insodoing,theycreatearidgeoftissuethatsurroundseachpitandformsthenasalprominences.
• Theprominencesontheouteredgeofthepitsarethelateralnasalprominences;thoseontheinneredgearethemedialnasalprominences
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Developmentofthenose
• Duringthefollowing2weeks,themaxillaryprominencescontinuetoincreaseinsize
• Simultaneously,theygrowmedially,compressingthemedialnasalprominencestowardthemidline
• Subsequentlythecleftbetweenthemedialnasalprominenceandthemaxillaryprominenceislost,andthetwofuse
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Developmentofthenose
• Thenoseisformedfromfivefacialprominences
• thefrontalprominencegivesrisetothebridge;andnasalseptum
• themergedmedialnasalprominencesprovidethecrestandtip;
• thelateralnasalprominencesformthesides(alae)
• Olfactorypitformsthenostrilandthenbecomesdeepertoformablindsac(thevestibule)
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Developmentofthenose
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NasalCavities
• 1.Duringthesixthweek,thenasalpitsdeepenconsiderably,partlybecauseofgrowthofthesurroundingnasalprominencesandpartlybecauseoftheirpenetrationintotheunderlyingmesenchyme
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NasalCavities
• 2.Atfirsttheoronasalmembrane(floorofthenose)separatesthepitsfromtheprimitiveoralcavitybywayofthenewlyformedforamina,theprimitivechoanae
• Thesechoanaelieoneachsideofthemidlineandimmediatelybehindtheprimarypalate.
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NasalCavities
• 3.Later,withformationofthesecondarypalateandfurtherdevelopmentoftheprimitivenasalchambers
• thedefinitivechoanaewilllieatthejunctionofthenasalcavityandthepharynx(nasopharynx).
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Paranasalairsinuses
• Paranasalairsinusesdevelopasdiverticulaofthelateralnasalwallandextendintothemaxilla,ethmoid,frontal,andsphenoidbones.
• Theyreachtheirmaximumsizeduringpubertyandcontributetothedefinitiveshapeoftheface.
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Primarypalate• Asaresultofmedialgrowthofthemaxillaryprominences,thetwomedialnasalprominencesmergenotonlyatthesurfacebutalsoatadeeperlevel.
• Thestructureformedbythetwomergedprominencesistheintermaxillarysegment
• Itiscomposedof(a)alabialcomponent,whichformsthephiltrumoftheupperlip;
• (b)anupperjawcomponent,whichcarriesthefourincisorteeth;
• (c)apalatalcomponent,whichformsthetriangularprimarypalate
• Theintermaxillarysegmentiscontinuouswiththerostralportionofthenasalseptum,whichisformedbythefrontalprominence.
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SecondaryPalate
• themainpartofthedefinitivepalateisformedbytwoshelflikeoutgrowthsfromthemaxillaryprominences.
• Theseoutgrowths,thepalatineshelves,appearinthesixthweekofdevelopmentandaredirectedobliquelydownwardoneachsideofthetongue
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SecondaryPalate
• Intheseventhweek,however,thepalatineshelvesascendtoattainahorizontalpositionabovethetongueandfuse,formingthesecondarypalate
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SecondaryPalate
• Anteriorly,theshelvesfusewiththetriangularprimarypalate,andtheincisiveforamenisthemidlinelandmarkbetweentheprimaryandsecondarypalates
• Atthesametimeasthepalatineshelvesfuse,thenasalseptumgrowsdownandjoinswiththecephalicaspectofthenewlyformedpalate
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SecondaryPalate
• 2foldsgrowposteriorlyfromtheedgeofthepalatineprocesstoformthesoftpalateandtheuvula.
• Theunionofthe2foldsofthesoftpalateoccursduringthe8th week
• The2partsoftheuvulafuseinthemidlineduringthe11th week
• Unilateralcleftlipcanextendtothenose
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RespiratorySystem
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Primitivegut• Developmentoftheprimitivegutanditsderivativesisinfoursections:
• (a)Thepharyngealgut,orpharynx,extendsfromthebuccopharyngealmembranetothetracheobronchialdiverticulum
• (b)Theforegutliescaudaltothepharyngealtubeandextendsasfarcaudallyastheliveroutgrowth.
• (c)Themidgutbeginscaudaltotheliverbudandextendstothejunctionoftherighttwo-thirdsandleftthirdofthetransversecolonintheadult.
• (d)Thehindgutextendsfromtheleftthirdofthetransversecolontothecloacalmembrane
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Respiratorydiverticulum
• Whentheembryoisapproximately4weeksold,therespiratorydiverticulum(lungbud)appearsasanoutgrowthfromtheventralwalloftheforegut
• Thelocationofthebudalongtheguttubeisdeterminedbysignalsfromthesurroundingmesenchyme,includingfibroblastgrowthfactors(FGFs)thatinstructtheendoderm
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Respiratorydiverticulum
• Theepitheliumoftheinternalliningofthelarynx,trachea,andbronchi,aswellasthatofthelungs,isentirelyofendodermalorigin.
• Thecartilaginous,muscular,andconnectivetissuecomponentsofthetracheaandlungsarederivedfromsplanchnicmesodermsurroundingtheforegut.
• Initiallythelungbudisinopencommunicationwiththeforegut
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Respiratorydiverticulum
• Whenthediverticulumexpandscaudally,twolongitudinalridges,thetracheoesophagealridges,separateitfromtheforegut
• Subsequently,whentheseridgesfusetoformthetracheoesophagealseptum,theforegutisdividedintoadorsalportion,theesophagus,andaventralportion,thetracheaandlungbuds
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Respiratorydiverticulum
• Therespiratoryprimordiummaintainsitscommunicationwiththepharynxthroughthelaryngealorifice
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Esophagus
• Atfirsttheesophagusisshort
• butwithdescentoftheheartandlungsitlengthensrapidly
• Themuscularcoat,whichisformedbysurroundingsplanchnicmesenchyme,isstriatedinitsuppertwo-thirdsandinnervatedbythevagusthemusclecoatissmoothinthelowerthirdandisinnervatedbythesplanchnicplexus.
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Anomaliesofthetracheaandesophagus
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Tracheoesaphagealfistula(TEF)
• Abnormalitiesinpartitioningoftheesophagusandtracheabythetracheoesaphagealseptumresultinesophagealatresiawithorwithouttracheoesaphagealfistulas
• Thesedefectsoccurinapproximatelyin1/3000births,and90%resultintheupperportionoftheesophagusendinginablindpouchandthelowersegmentformingafistulawiththetrachea
• Predominantlyaffectmaleinfants
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Tracheoesaphagealfistula(TEF)
• IsolatedesophagealatresiaandH-typeTEFwithoutesophagealAtresiaeachaccountfor4%ofthesedefects.
• Othervariationseachaccountforapproximately1%ofthesedefects.
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Tracheoesaphagealfistula(TEF)• TEFisthemostcommonanomalyinthelower
respiratorytract
• InfantswithcommontypeTEFandesophagealatesiacoughandchokebecauseofexcessiveamountsofsalivainthemouth
• Whentheinfanttrytoswallowmilkitrapidlyfillstheesophagealpouchandisregurgitated
• AcomplicationofsomeTEFsispolyhydramnios,sinceinsometypesofTEFamnioticfluiddoesnotpasstothestomachandintestines
• Also,gastriccontentsand/oramnioticfluidmayenterthetracheathroughafistula,causingpneumonitisandpneumonia.
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Tracheoesaphagealfistula(TEF)
• Theseabnormalitiesareassociatedwithotherbirthdefects,includingcardiacabnormalities,whichoccurin33%ofthesecases.
• InthisregardTEFsareacomponentoftheVACTERLassociation(Vertebralanomalies,Analatresia,Cardiacdefects,Tracheoesophagealfistula,Esophagealatresia,Renalanomalies,andLimbdefects)
• acollectionofdefectsofunknowncausation,butoccurringmorefrequentlythanpredictedbychancealone.
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Trachealatresiaandstenosis
• AreuncommonanomaliesandusuallyassociatedwithoneoftheveritiesofTEF
• Insomecaseawebtissuemayobstructstheairflow(incompletetrachealatresia)
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Larynx
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Larynx
• Theinternalliningofthelarynxoriginatesfromendoderm,butthecartilagesandmusclesoriginatefrommesenchymeofthefourthandsixthpharyngealarches
• Asaresultofrapidproliferationofthismesenchyme,thelaryngealorificechangesinappearancefromasagittalslittoaT-shapedopening
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• Subsequently,whenmesenchymeofthetwoarchestransformsintothethyroid,cricoid,andarytenoidcartilages,thecharacteristicadultshapeofthelaryngealorificecanberecognized
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• Ataboutthetimethatthecartilagesareformed,thelaryngealepitheliumalsoproliferatesrapidlyresultinginatemporaryocclusionofthelumen.
• Subsequently,vacuolizationandrecanalizationproduceapairoflateralrecesses,thelaryngealventricles
• Theserecessesareboundedbyfoldsoftissuethatdifferentiateintothefalseandtruevocalcords.
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• Sincemusculatureofthelarynxisderivedfrommesenchymeofthefourthandsixthpharyngealarches,alllaryngealmusclesareinnervatedbybranchesofthetenthcranialnerve,thevagusnerve
• Thesuperiorlaryngealnerveinnervatesderivativesofthefourthpharyngealarch,andtherecurrentlaryngealnerveinnervatesderivativesofthesixthpharyngealarch
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Anomaliesofthelarynx
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Laryngealatresia
• Laryngealatresiaisarareanomalyandcauseobstructionoftheupperfetalairway
• Alsoknownascongenitalhighairwayobstructionsyndrome(chaos)
• Distaltotheatresiaorstenosisthelungareenlargedandcapableofproducingechoes(echogenic)
• Alsothediaphragmisflattenedorinvertedandfetalascitesandhydrops(accumulationofserousfluid)ispresent
• Prenatalultra-sonograpghypermitsdiagnosis.
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LungsandBronchialtreedevelopment
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Trachea,Bronchi,andLungs
• Duringitsseparationfromtheforegut,thelungbudformsthetracheaandtwolateraloutpocketings,thebronchialbuds
• Atthebeginningofthefifthweek,eachofthesebudsenlargestoformrightandleftmainbronchi
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Trachea,Bronchi,andLungs
• Therightthenformsthreesecondarybronchi,andtheleft,two
• thusforeshadowingthethreelobesontherightsideandtwoontheleft
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Trachea,Bronchi,andLungs
• Withsubsequentgrowthincaudalandlateraldirections,thelungbudsexpandintothebodycavity
• Thespacesforthelungs,thepericardioperitonealcanals,arenarrow.
• Theylieoneachsideoftheforegut
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Trachea,Bronchi,andLungs• Ultimatelythepleuroperitonealandpleuropericardialfoldsseparatethepericardioperitonealcanalsfromtheperitonealandpericardialcavities
• andtheremainingspacesformtheprimitivepleuralcavities
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Trachea,Bronchi,andLungs
• Themesoderm,whichcoverstheoutsideofthelung,developsintothevisceralpleura.
• Thesomaticmesodermlayer,coveringthebodywallfromtheinside,becomestheparietalpleura
• Thespacebetweentheparietalandvisceralpleuraisthepleuralcavity
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Trachea,Bronchi,andLungs• Duringfurtherdevelopment,secondarybronchidividerepeatedlyinadichotomousfashion,forming10tertiary(segmental)bronchiintherightlungand8intheleft,creatingthebronchopulmonarysegmentsoftheadultlung.
• Bytheendofthesixthmonth,approximately17generationsofsubdivisionshaveformed
• Beforethebronchialtreereachesitsfinalshape,however,anadditional6divisionsformduringpostnatallife.
• Branchingisregulatedbyepithelial-mesenchymalinteractionsbetweentheendodermofthelungbudsandsplanchnicmesodermthatsurroundsthem
• Signalsforbranching,whichemitfromthemesoderm,involvemembersofthefibroblastgrowthfactor(FGF)family.
• Whileallofthesenewsubdivisionsareoccurringandthebronchialtreeisdeveloping,thelungsassumeamorecaudalposition,sothatbythetimeofbirththebifurcationofthetracheaisoppositethefourththoracicvertebra.
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MaturationoftheLungs
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MaturationoftheLungs
• Uptotheseventhprenatalmonth,thebronchiolesdividecontinuouslyintomoreandsmallercanals(canalicularphase)
• thevascularsupplyincreasessteadily.
• Respirationbecomespossiblewhensomeofthecellsofthecuboidalrespiratorybronchioleschangeintothin,flatcells
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MaturationoftheLungs
• Thesecellsareintimatelyassociatedwithnumerousbloodandlymphcapillaries,andthesurroundingspacesarenowknownasterminalsacsorprimitivealveoli
• Duringtheseventhmonth,sufficientnumbersofcapillariesarepresenttoguaranteeadequategasexchange,andtheprematureinfantisabletosurvive.
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MaturationoftheLungs
• Duringthelast2monthsofprenatallifeandforseveralyearsthereafter,thenumberofterminalsacsincreasessteadily
• Inaddition,cellsliningthesacs,knownastypeIalveolarepithelialcells,becomethinner,sothatsurroundingcapillariesprotrudeintothealveolarsacs
• Thisintimatecontactbetweenepithelialandendothelialcellsmakesuptheblood-airbarrier.
• Maturealveoliarenotpresentbeforebirth
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MaturationoftheLungs
• Inadditiontoendothelialcellsandflatalveolarepithelialcells,anothercelltypedevelopsattheendofthesixthmonth.Thesecells,typeIIalveolarepithelialcells,producesurfactant,
• Beforebirththelungsarefulloffluidthatcontainsahighchlorideconcentration,littleprotein,somemucusfromthebronchialglands,andsurfactantfromthealveolarepithelialcells(typeII)
• Theamountofsurfactantinthefluidincreases,particularlyduringthelast2weeksbeforebirth.
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MaturationoftheLungs• Fetalbreathingmovementsbeginbeforebirthandcauseaspirationofamnioticfluid
• Thesemovementsareimportantforstimulatinglungdevelopmentandconditioningrespiratorymuscles
• Whenrespirationbeginsatbirth,mostofthelungfluidisrapidlyresorbedbythebloodandlymphcapillaries,andasmallamountisprobablyexpelledviathetracheaandbronchiduringdelivery.
• Whenthefluidisresorbedfromalveolarsacs,surfactantremainsdepositedasathinphospholipidcoatonalveolarcellmembranes.
• Withairenteringalveoliduringthefirstbreath,thesurfactantcoatpreventsdevelopmentofanair-water(blood)interfacewithhighsurfacetension
• Withoutthefattysurfactantlayer,thealveoliwouldcollapseduringexpiration(atelectasis).
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MaturationoftheLungs• Respiratorymovementsafterbirthbringairintothelungs,whichexpandandfillthepleuralcavity.
• Althoughthealveoliincreasesomewhatinsize,growthofthelungsafterbirthisdueprimarilytoanincreaseinthenumberofrespiratorybronchiolesandalveoli.
• Itisestimatedthatonlyone-sixthoftheadultnumberofalveoliarepresentatbirth
• Theremainingalveoliareformedduringthefirst10yearsofpostnatallifethroughthecontinuousformationofnewprimitivealveoli.
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Anomaliesofthelung
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Clinicalnotes(RDS)• Surfactantisparticularlyimportantforsurvivalof
theprematureinfant
• Whensurfactantisinsufficient,theair-water(blood)surfacemembranetensionbecomeshigh,bringinggreatriskthatalveoliwillcollapseduringexpiration.
• Asaresult,respiratorydistresssyndrome(RDS)develops
• Thisisacommoncauseofdeathintheprematureinfant(30%ofallneonataldiseases)
• Inthesecasesthepartiallycollapsedalveolicontainafluidwithahighproteincontent,manyhyalinemembranes,andlamellarbodies,probablyderivedfromthesurfactantlayer
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Clinicalnotes(RDS)• RDS,isthereforealsoknownashyaline
membranedisease,accountsforapproximately20%ofdeathsamongnewborns
• IntrauterineAsphyxiamayproduceirreversiblechangesintypeIIcells
• Recentdevelopmentofartificialsurfactantandtreatmentofprematurebabieswithglucocorticoids(betamethasone)tostimulatesurfactantproductionhavereducedthemortalityassociatedwithRDS
• ItAlsoallowedsurvivalofsomebabiesasyoungas5.5monthsofgestation
• Thyroxineisthemostimportantstimulatorforsurfactantsproduction
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Clinicalnotes(OtherAnomalies)
• Althoughmanyabnormalitiesofthelungandbronchialtreehavebeenfound(e.g.,blind-endingtracheawithabsenceoflungsandagenesisofonelung)mostofthesegrossabnormalitiesarerare
• Abnormaldivisionsofthebronchialtreearemorecommon;someresultinsupernumerarylobules.
• Thesevariationsofthebronchialtreehavelittlefunctionalsignificance,buttheymaycauseunexpecteddifficultiesduringbronchoscopies.
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Clinicalnotes(OtherAnomalies)• ectopiclunglobesarisingfromthetracheaoresophagus
• Itisbelievedthattheselobesareformedfromadditionalrespiratorybudsoftheforegutthatdevelopindependentlyofthemainrespiratorysystem.
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Clinicalnotes(OtherAnomalies)• Mostimportantclinicallyarecongenitalcystsofthelung
• whichareformedbydilationofterminalorlargerbronchi
• Thesecystsmaybesmallandmultiple,givingthelungahoneycombappearanceonradiograph
• Ortheymayberestrictedtooneormorelargerones
• Cysticstructuresofthelungusuallydrainpoorlyandfrequentlycausechronicinfections
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LungHypoplasia• Ininfantswithcongenitaldiaphragmatichernia(CDH)thelungisunabletodevelopnormally
• Becauseitiscompressedbytheabnormallypositionedabdominalviscera
• Itischaracterizedbyreducedlungvolume
• MostinfantswithCDHdieofpulmonaryinsufficiencyastheirlungsaretoohypoplastictosupportlife
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Oligohydroamniosandlungs
• Whenoligohydroamnios(reducedamnioticfluid)isseverelungdevelopmentisretarded
• Severepulmonaryhypoplasiaresults
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Lungsofthenewborninfants
• Freshandhealthylungscontainsomeairsopulmonarysamplesfloatinwater
• Thelungsofthestillborninfantsarefirmandsinkinwaterbecausetheycontainfluidsnotair.
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Thankyou