respiratory system embryology - ju medicine€¦ · embryology. development of the nose and palate....

RespiratorySystemEmbryology

DevelopmentofthenoseandPalate

Developmentofthenose

• Attheendofthefourthweek,facialprominencesconsistingprimarilyofneuralcrest-derivedmesenchymeandformedmainlybythefirstpairofpharyngealarchesappear

• Thefrontonasalprominence,formedbyproliferationofmesenchymeventraltothebrainvesicles,constitutestheupperborderofthestomodeum

• Onbothsidesofthefrontonasalprominence,localthickeningsofthesurfaceectoderm,thenasal(olfactory)placodes,originateunderinductiveinfluenceoftheventralportionoftheforebrain


• Duringthefifthweek,thenasalplacodesinvaginatetoformnasalpits(nostril).

• Insodoing,theycreatearidgeoftissuethatsurroundseachpitandformsthenasalprominences.

• Theprominencesontheouteredgeofthepitsarethelateralnasalprominences;thoseontheinneredgearethemedialnasalprominences


• Duringthefollowing2weeks,themaxillaryprominencescontinuetoincreaseinsize

• Simultaneously,theygrowmedially,compressingthemedialnasalprominencestowardthemidline

• Subsequentlythecleftbetweenthemedialnasalprominenceandthemaxillaryprominenceislost,andthetwofuse


• Thenoseisformedfromfivefacialprominences

• thefrontalprominencegivesrisetothebridge;andnasalseptum

• themergedmedialnasalprominencesprovidethecrestandtip;

• thelateralnasalprominencesformthesides(alae)

• Olfactorypitformsthenostrilandthenbecomesdeepertoformablindsac(thevestibule)

NasalCavities

• 1.Duringthesixthweek,thenasalpitsdeepenconsiderably,partlybecauseofgrowthofthesurroundingnasalprominencesandpartlybecauseoftheirpenetrationintotheunderlyingmesenchyme

NasalCavities

• 2.Atfirsttheoronasalmembrane(floorofthenose)separatesthepitsfromtheprimitiveoralcavitybywayofthenewlyformedforamina,theprimitivechoanae

• Thesechoanaelieoneachsideofthemidlineandimmediatelybehindtheprimarypalate.

NasalCavities

• 3.Later,withformationofthesecondarypalateandfurtherdevelopmentoftheprimitivenasalchambers

• thedefinitivechoanaewilllieatthejunctionofthenasalcavityandthepharynx(nasopharynx).

Paranasalairsinuses

• Paranasalairsinusesdevelopasdiverticulaofthelateralnasalwallandextendintothemaxilla,ethmoid,frontal,andsphenoidbones.

• Theyreachtheirmaximumsizeduringpubertyandcontributetothedefinitiveshapeoftheface.

Primarypalate• Asaresultofmedialgrowthofthemaxillaryprominences,thetwomedialnasalprominencesmergenotonlyatthesurfacebutalsoatadeeperlevel.

• Thestructureformedbythetwomergedprominencesistheintermaxillarysegment

• Itiscomposedof(a)alabialcomponent,whichformsthephiltrumoftheupperlip;

• (b)anupperjawcomponent,whichcarriesthefourincisorteeth;

• (c)apalatalcomponent,whichformsthetriangularprimarypalate

• Theintermaxillarysegmentiscontinuouswiththerostralportionofthenasalseptum,whichisformedbythefrontalprominence.

SecondaryPalate

• themainpartofthedefinitivepalateisformedbytwoshelflikeoutgrowthsfromthemaxillaryprominences.

• Theseoutgrowths,thepalatineshelves,appearinthesixthweekofdevelopmentandaredirectedobliquelydownwardoneachsideofthetongue

SecondaryPalate

• Intheseventhweek,however,thepalatineshelvesascendtoattainahorizontalpositionabovethetongueandfuse,formingthesecondarypalate

SecondaryPalate

• Anteriorly,theshelvesfusewiththetriangularprimarypalate,andtheincisiveforamenisthemidlinelandmarkbetweentheprimaryandsecondarypalates

• Atthesametimeasthepalatineshelvesfuse,thenasalseptumgrowsdownandjoinswiththecephalicaspectofthenewlyformedpalate

SecondaryPalate

• 2foldsgrowposteriorlyfromtheedgeofthepalatineprocesstoformthesoftpalateandtheuvula.

• Theunionofthe2foldsofthesoftpalateoccursduringthe8th week

• The2partsoftheuvulafuseinthemidlineduringthe11th week

• Unilateralcleftlipcanextendtothenose

RespiratorySystem

Primitivegut• Developmentoftheprimitivegutanditsderivativesisinfoursections:

• (a)Thepharyngealgut,orpharynx,extendsfromthebuccopharyngealmembranetothetracheobronchialdiverticulum

• (b)Theforegutliescaudaltothepharyngealtubeandextendsasfarcaudallyastheliveroutgrowth.

• (c)Themidgutbeginscaudaltotheliverbudandextendstothejunctionoftherighttwo-thirdsandleftthirdofthetransversecolonintheadult.

• (d)Thehindgutextendsfromtheleftthirdofthetransversecolontothecloacalmembrane

Respiratorydiverticulum

• Whentheembryoisapproximately4weeksold,therespiratorydiverticulum(lungbud)appearsasanoutgrowthfromtheventralwalloftheforegut

• Thelocationofthebudalongtheguttubeisdeterminedbysignalsfromthesurroundingmesenchyme,includingfibroblastgrowthfactors(FGFs)thatinstructtheendoderm


• Theepitheliumoftheinternalliningofthelarynx,trachea,andbronchi,aswellasthatofthelungs,isentirelyofendodermalorigin.

• Thecartilaginous,muscular,andconnectivetissuecomponentsofthetracheaandlungsarederivedfromsplanchnicmesodermsurroundingtheforegut.

• Initiallythelungbudisinopencommunicationwiththeforegut


• Whenthediverticulumexpandscaudally,twolongitudinalridges,thetracheoesophagealridges,separateitfromtheforegut

• Subsequently,whentheseridgesfusetoformthetracheoesophagealseptum,theforegutisdividedintoadorsalportion,theesophagus,andaventralportion,thetracheaandlungbuds


• Therespiratoryprimordiummaintainsitscommunicationwiththepharynxthroughthelaryngealorifice

Esophagus

• Atfirsttheesophagusisshort

• butwithdescentoftheheartandlungsitlengthensrapidly

• Themuscularcoat,whichisformedbysurroundingsplanchnicmesenchyme,isstriatedinitsuppertwo-thirdsandinnervatedbythevagusthemusclecoatissmoothinthelowerthirdandisinnervatedbythesplanchnicplexus.

Anomaliesofthetracheaandesophagus

Tracheoesaphagealfistula(TEF)

• Abnormalitiesinpartitioningoftheesophagusandtracheabythetracheoesaphagealseptumresultinesophagealatresiawithorwithouttracheoesaphagealfistulas

• Thesedefectsoccurinapproximatelyin1/3000births,and90%resultintheupperportionoftheesophagusendinginablindpouchandthelowersegmentformingafistulawiththetrachea

• Predominantlyaffectmaleinfants


• IsolatedesophagealatresiaandH-typeTEFwithoutesophagealAtresiaeachaccountfor4%ofthesedefects.

• Othervariationseachaccountforapproximately1%ofthesedefects.

Tracheoesaphagealfistula(TEF)• TEFisthemostcommonanomalyinthelower

respiratorytract

• InfantswithcommontypeTEFandesophagealatesiacoughandchokebecauseofexcessiveamountsofsalivainthemouth

• Whentheinfanttrytoswallowmilkitrapidlyfillstheesophagealpouchandisregurgitated

• AcomplicationofsomeTEFsispolyhydramnios,sinceinsometypesofTEFamnioticfluiddoesnotpasstothestomachandintestines

• Also,gastriccontentsand/oramnioticfluidmayenterthetracheathroughafistula,causingpneumonitisandpneumonia.


• Theseabnormalitiesareassociatedwithotherbirthdefects,includingcardiacabnormalities,whichoccurin33%ofthesecases.

• InthisregardTEFsareacomponentoftheVACTERLassociation(Vertebralanomalies,Analatresia,Cardiacdefects,Tracheoesophagealfistula,Esophagealatresia,Renalanomalies,andLimbdefects)

• acollectionofdefectsofunknowncausation,butoccurringmorefrequentlythanpredictedbychancealone.

Trachealatresiaandstenosis

• AreuncommonanomaliesandusuallyassociatedwithoneoftheveritiesofTEF

• Insomecaseawebtissuemayobstructstheairflow(incompletetrachealatresia)

Larynx

Larynx

• Theinternalliningofthelarynxoriginatesfromendoderm,butthecartilagesandmusclesoriginatefrommesenchymeofthefourthandsixthpharyngealarches

• Asaresultofrapidproliferationofthismesenchyme,thelaryngealorificechangesinappearancefromasagittalslittoaT-shapedopening

• Subsequently,whenmesenchymeofthetwoarchestransformsintothethyroid,cricoid,andarytenoidcartilages,thecharacteristicadultshapeofthelaryngealorificecanberecognized

• Ataboutthetimethatthecartilagesareformed,thelaryngealepitheliumalsoproliferatesrapidlyresultinginatemporaryocclusionofthelumen.

• Subsequently,vacuolizationandrecanalizationproduceapairoflateralrecesses,thelaryngealventricles

• Theserecessesareboundedbyfoldsoftissuethatdifferentiateintothefalseandtruevocalcords.

• Sincemusculatureofthelarynxisderivedfrommesenchymeofthefourthandsixthpharyngealarches,alllaryngealmusclesareinnervatedbybranchesofthetenthcranialnerve,thevagusnerve

• Thesuperiorlaryngealnerveinnervatesderivativesofthefourthpharyngealarch,andtherecurrentlaryngealnerveinnervatesderivativesofthesixthpharyngealarch

Anomaliesofthelarynx

Laryngealatresia

• Laryngealatresiaisarareanomalyandcauseobstructionoftheupperfetalairway

• Alsoknownascongenitalhighairwayobstructionsyndrome(chaos)

• Distaltotheatresiaorstenosisthelungareenlargedandcapableofproducingechoes(echogenic)

• Alsothediaphragmisflattenedorinvertedandfetalascitesandhydrops(accumulationofserousfluid)ispresent

• Prenatalultra-sonograpghypermitsdiagnosis.

LungsandBronchialtreedevelopment

Trachea,Bronchi,andLungs

• Duringitsseparationfromtheforegut,thelungbudformsthetracheaandtwolateraloutpocketings,thebronchialbuds

• Atthebeginningofthefifthweek,eachofthesebudsenlargestoformrightandleftmainbronchi


• Therightthenformsthreesecondarybronchi,andtheleft,two

• thusforeshadowingthethreelobesontherightsideandtwoontheleft


• Withsubsequentgrowthincaudalandlateraldirections,thelungbudsexpandintothebodycavity

• Thespacesforthelungs,thepericardioperitonealcanals,arenarrow.

• Theylieoneachsideoftheforegut

Trachea,Bronchi,andLungs• Ultimatelythepleuroperitonealandpleuropericardialfoldsseparatethepericardioperitonealcanalsfromtheperitonealandpericardialcavities

• andtheremainingspacesformtheprimitivepleuralcavities


• Themesoderm,whichcoverstheoutsideofthelung,developsintothevisceralpleura.

• Thesomaticmesodermlayer,coveringthebodywallfromtheinside,becomestheparietalpleura

• Thespacebetweentheparietalandvisceralpleuraisthepleuralcavity

Trachea,Bronchi,andLungs• Duringfurtherdevelopment,secondarybronchidividerepeatedlyinadichotomousfashion,forming10tertiary(segmental)bronchiintherightlungand8intheleft,creatingthebronchopulmonarysegmentsoftheadultlung.

• Bytheendofthesixthmonth,approximately17generationsofsubdivisionshaveformed

• Beforethebronchialtreereachesitsfinalshape,however,anadditional6divisionsformduringpostnatallife.

• Branchingisregulatedbyepithelial-mesenchymalinteractionsbetweentheendodermofthelungbudsandsplanchnicmesodermthatsurroundsthem

• Signalsforbranching,whichemitfromthemesoderm,involvemembersofthefibroblastgrowthfactor(FGF)family.

• Whileallofthesenewsubdivisionsareoccurringandthebronchialtreeisdeveloping,thelungsassumeamorecaudalposition,sothatbythetimeofbirththebifurcationofthetracheaisoppositethefourththoracicvertebra.

MaturationoftheLungs


• Uptotheseventhprenatalmonth,thebronchiolesdividecontinuouslyintomoreandsmallercanals(canalicularphase)

• thevascularsupplyincreasessteadily.

• Respirationbecomespossiblewhensomeofthecellsofthecuboidalrespiratorybronchioleschangeintothin,flatcells


• Thesecellsareintimatelyassociatedwithnumerousbloodandlymphcapillaries,andthesurroundingspacesarenowknownasterminalsacsorprimitivealveoli

• Duringtheseventhmonth,sufficientnumbersofcapillariesarepresenttoguaranteeadequategasexchange,andtheprematureinfantisabletosurvive.


• Duringthelast2monthsofprenatallifeandforseveralyearsthereafter,thenumberofterminalsacsincreasessteadily

• Inaddition,cellsliningthesacs,knownastypeIalveolarepithelialcells,becomethinner,sothatsurroundingcapillariesprotrudeintothealveolarsacs

• Thisintimatecontactbetweenepithelialandendothelialcellsmakesuptheblood-airbarrier.

• Maturealveoliarenotpresentbeforebirth


• Inadditiontoendothelialcellsandflatalveolarepithelialcells,anothercelltypedevelopsattheendofthesixthmonth.Thesecells,typeIIalveolarepithelialcells,producesurfactant,

• Beforebirththelungsarefulloffluidthatcontainsahighchlorideconcentration,littleprotein,somemucusfromthebronchialglands,andsurfactantfromthealveolarepithelialcells(typeII)

• Theamountofsurfactantinthefluidincreases,particularlyduringthelast2weeksbeforebirth.

MaturationoftheLungs• Fetalbreathingmovementsbeginbeforebirthandcauseaspirationofamnioticfluid

• Thesemovementsareimportantforstimulatinglungdevelopmentandconditioningrespiratorymuscles

• Whenrespirationbeginsatbirth,mostofthelungfluidisrapidlyresorbedbythebloodandlymphcapillaries,andasmallamountisprobablyexpelledviathetracheaandbronchiduringdelivery.

• Whenthefluidisresorbedfromalveolarsacs,surfactantremainsdepositedasathinphospholipidcoatonalveolarcellmembranes.

• Withairenteringalveoliduringthefirstbreath,thesurfactantcoatpreventsdevelopmentofanair-water(blood)interfacewithhighsurfacetension

• Withoutthefattysurfactantlayer,thealveoliwouldcollapseduringexpiration(atelectasis).

MaturationoftheLungs• Respiratorymovementsafterbirthbringairintothelungs,whichexpandandfillthepleuralcavity.

• Althoughthealveoliincreasesomewhatinsize,growthofthelungsafterbirthisdueprimarilytoanincreaseinthenumberofrespiratorybronchiolesandalveoli.

• Itisestimatedthatonlyone-sixthoftheadultnumberofalveoliarepresentatbirth

• Theremainingalveoliareformedduringthefirst10yearsofpostnatallifethroughthecontinuousformationofnewprimitivealveoli.

Anomaliesofthelung

Clinicalnotes(RDS)• Surfactantisparticularlyimportantforsurvivalof

theprematureinfant

• Whensurfactantisinsufficient,theair-water(blood)surfacemembranetensionbecomeshigh,bringinggreatriskthatalveoliwillcollapseduringexpiration.

• Asaresult,respiratorydistresssyndrome(RDS)develops

• Thisisacommoncauseofdeathintheprematureinfant(30%ofallneonataldiseases)

• Inthesecasesthepartiallycollapsedalveolicontainafluidwithahighproteincontent,manyhyalinemembranes,andlamellarbodies,probablyderivedfromthesurfactantlayer

Clinicalnotes(RDS)• RDS,isthereforealsoknownashyaline

membranedisease,accountsforapproximately20%ofdeathsamongnewborns

• IntrauterineAsphyxiamayproduceirreversiblechangesintypeIIcells

• Recentdevelopmentofartificialsurfactantandtreatmentofprematurebabieswithglucocorticoids(betamethasone)tostimulatesurfactantproductionhavereducedthemortalityassociatedwithRDS

• ItAlsoallowedsurvivalofsomebabiesasyoungas5.5monthsofgestation

• Thyroxineisthemostimportantstimulatorforsurfactantsproduction

Clinicalnotes(OtherAnomalies)

• Althoughmanyabnormalitiesofthelungandbronchialtreehavebeenfound(e.g.,blind-endingtracheawithabsenceoflungsandagenesisofonelung)mostofthesegrossabnormalitiesarerare

• Abnormaldivisionsofthebronchialtreearemorecommon;someresultinsupernumerarylobules.

• Thesevariationsofthebronchialtreehavelittlefunctionalsignificance,buttheymaycauseunexpecteddifficultiesduringbronchoscopies.

Clinicalnotes(OtherAnomalies)• ectopiclunglobesarisingfromthetracheaoresophagus

• Itisbelievedthattheselobesareformedfromadditionalrespiratorybudsoftheforegutthatdevelopindependentlyofthemainrespiratorysystem.

Clinicalnotes(OtherAnomalies)• Mostimportantclinicallyarecongenitalcystsofthelung

• whichareformedbydilationofterminalorlargerbronchi

• Thesecystsmaybesmallandmultiple,givingthelungahoneycombappearanceonradiograph

• Ortheymayberestrictedtooneormorelargerones

• Cysticstructuresofthelungusuallydrainpoorlyandfrequentlycausechronicinfections

LungHypoplasia• Ininfantswithcongenitaldiaphragmatichernia(CDH)thelungisunabletodevelopnormally

• Becauseitiscompressedbytheabnormallypositionedabdominalviscera

• Itischaracterizedbyreducedlungvolume

• MostinfantswithCDHdieofpulmonaryinsufficiencyastheirlungsaretoohypoplastictosupportlife

Oligohydroamniosandlungs

• Whenoligohydroamnios(reducedamnioticfluid)isseverelungdevelopmentisretarded

• Severepulmonaryhypoplasiaresults

Lungsofthenewborninfants

• Freshandhealthylungscontainsomeairsopulmonarysamplesfloatinwater

• Thelungsofthestillborninfantsarefirmandsinkinwaterbecausetheycontainfluidsnotair.

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respiratory system embryology - ju medicine€¦ · embryology. development of the nose and palate....

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