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DevelopmentoftheUrinarySystemObjectives:

• Describethedevelopmentandfateofthepronephricduct• Describethedevelopmentandfateofthemesonephrickidney• Describethedevelopmentandfateofthemetanephrickidneyandureter• Understandtheascentofthemetanephrickidneyanditschangingblood

supply• Describethedevelopmentoftheurinarybladderandthetissuesthat

contributetoitsdevelopment.Introduction;Theurinarysystemdevelopsfromtheintermediatemesoderm(kidneysandureters)andthecloaca(bladderandurethra).KidneyDevelopment;Theintermediatemesodermformsbilateralstripsoftissuethatextendthroughthelengthoftheembryolyingoneachsidebetweentheparaxialmesodermandthelaterallatemesoderm.Foldingmovementsoftheembryoinweek4leavetheintermediatemesodermpositionedontheposteriorwallofthebodycavity.

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Thekidneygoesthrough3phasesofdevelopment;pronephric,mesonephric,andmetanephric.Eachphasetakesplaceinadifferentpartoftheintermediatemesodermalongthelengthoftheembryo,andeachofthephasesoverlaptosomeextentintime.Duringthepronephricphase(approximatelyweeks3to5),aductbeginstoappearintheintermediatemesodermadjacenttothecervicalsegmentsoneachsideoftheembryo.Thetipsoftheseductsextendcaudallyandconnecttothecloaca.Followingtheseparationofthecloacaintotherectoanalcanalandurogenitalsinusbytheurorectalseptum,theopeningsoftheductarefoundenteringtheurogenitalsinus.

Theintermediatemesoderminthecervicalsegmentsoftheembryo,alongwiththeadjacentpartoftheducttowhichtheygaverise,soondegenerate.However,therestoftheductintheintermediatemesodermofthethoracic,lumbarandsacralsegmentsoftheembryoremains.Theductisnowproperlycalledthemesonephricductalthoughtheformername‘Wolffianduct’isstillsometimesused.Themesonephricphasefollowsthepronephricphaseandoccursintheintermediatemesodermofthethoracicandlumbarsegments.Beginninginthefourthweek,mesonephrictubulesresemblingnephronsappearintheintermediatemesodermintheseregions.Thesetubulesopenintothemesonephricduct.Foratimethesemesonephrictubulessecreteurineintothemesonephricductwhichconveysittotheurogenitalsinus.Muchoftheintermediatemesoderminthisregionthenbeginstodegenerateandhasmostlydisappearedbythebeginningoffourthmonthofdevelopment.Someofthetubulesandpartoftheduct,however,areretainedinmaleembryosandincorporatedintostructuresinthereproductivesystemastheefferentductulesofthetesticleandthevasdeferens.

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Theintermediatemesodermthatliesadjacenttothesacralsegmentsoftheembryo(i.e.inthedevelopingpelvis)isreferredtoasthemetanephricblastema.Beginningaround5weeksafterfertilization,themetanephricblastemabeginstoreleasemolecularsignals,whichstimulatethemesonephricducttoextendabranchtubeintoit.Thebranchtubeiscalledtheuretericbudanditextendsfromthemesonephricductatapointveryclosetowheretheductentersthecloaca.Throughaseriesofreciprocalinductiveinteractions,themetanephricblastemaandtheuretericbudgiverisetotheadultkidneyandureter.Failureoftheuretericbudandmetanephricblastematointeractleadstorenalagenesis.Whenrenalagenesisisunilateral,theremainingkidneywillundergocompensatoryhypertrophyandfulfilltheroleof2kidneysforthenewborn.Whenrenalagenesisisbilateralthefetuscansurvivetotermbecausetheplacentaremoveswastesfromfetalblood.However,theconditionistypicallyfatalforthenewborn.Theintermediatemesodermthroughoutthecervical,thoracic,andlumbarsegmentsoftheembryoisdestinedtoregress,andthesamefatewouldhaveaffectedthemetanephricblastema,exceptthattheuretericbudsecretesfactorsthatrescueandpromoteitsfurtherdevelopment.Themetanephricblastemawillformtheurine-producingstructuresofthekidney,includingtheglomeruliandnephrons;the

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uretericbudsformthecollectingsystem,includingcollectingtubules,collectingducts,calyces,pelvisandureter.Underthemolecularinfluenceofthemetanephricblastema,theuretericbudbeginstobranchrepeatedly,firstformingthemajor,thenminorcalyces,thenthecollectingductsandtubules.Sometimestheuretericbudwilldivideoneormoretimesbeforeenteringintothemetanephricblastema.Thisresultsinbranchingduplicationsoftheureter.Thisistypicallyanasymptomaticcondition,butacommonobservationinthedissectingroom.

Occasionallythemetanephricblastemainducesthemesonephricducttosprout2uretericbudsresultingintwouretersthatentertheurogenitalsinusseparately.

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Signalsfromthecellsatthetipsofthecollectingtubulesattheendsoftheuretericbudbranchescausecondensationsofmesodermcellscalledmetanephrictissuecapstoorganizeadjacenttothem.Thetissuecapsdevelopcavitieswithinthem,formingnephricvesicles.Thevesicleselongateformingnephrons.Oneendofthedevelopingnephronconnectswiththeendofthecollectingtubule.Theother(blind)endisinvaginatedbycapillaries,whichformaglomerulus.About1millionofthesenephronswilldevelopineachkidney.

Nephronformationistypicallyfinishedbythetimeofbirthandthekidneyinitiallyhasalobulatedappearance.Afterbirth,thekidneygrowsinsizeandthelobulationofthesurfacedisappearsasthetubuleselongateandthekidneyaccumulatesinterstitialconnectivetissue.AscentoftheKidneyThemetanephricblastemaandtheuretericbudsarelocateddeepwithinthepelvisoftheembryoandsomustchangepositiontoreachtheirnormallocationintheupperabdomen.Thisisaccomplishedasaresultofthestraighteningofthecurvatureoftheearlyembryonicbody,andthroughtheelongationofthepelvis,whichvirtuallygrowsoutfromunderneaththekidneys.Asthekidneysfirstdevelopinthepelvis,thekidneyhilus(wheretherenalpelvisentersthekidney)facesanteriorly,andbloodsupplycomesfromthelocalvesselsinthepelvis.Asthekidneysascend,theypassbetweenumbilicalarteries(latertobecomethecommoniliacs),theybegintorotatemedially,theirureterslengthen,andbloodsupplychangestosuccessivelymoresuperiorbranchesoftheaorta.

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Sequenceofkidneyascent,passingbetweentheumbilical(commoniliac)arteries.Notethelobulatedappearanceofthefetalkidneyandthemedialrotationofthehilusasthekidneyascends.

Sequenceofkidneyascentshowingthechangingbloodsupplyfromarterialbranchesoftheaortaatsuccessivelyhigherlevels.Whenoneofthevesselsfromwhichthekidneyformerlyreceiveditsbloodsupplyisretained,itformsanaccessoryrenalartery,arisingfromtheaorta,inferiortothenormalrenalartery.Kidneysthathavefailedtoascendcompletely(ectopickidneys)willhaveectopicvascularsupply,willnothavecompletedtheirfullrotationmedially,andwillhaveaureterthatisanappropriatelengthfortheirectopicposition.Thishelpsindistinguishingacongenitallyectopickidneyfromonethathasreached,butthenslippedoutfromitsnormalposition(renalptosis/droppedkidney).Occasionally,thekidneysmaybecomefusedintoasingleorganwhilestillinthepelvis.Themostcommonformisthehorseshoekidney,examplesofwhichcanbeseenintheJCBGrantAnatomyMuseum.Fusedkidneysaretypicallyectopicbecausetheinferiormesentericarterywillpreventtheirnormalascent.

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Themetanephrickidneybeginstofunctionataround9weeksoffetaldevelopment.Fetalurineisexcretedintotheamnioticcavitywhereismakesamajorcontributiontothevolumeofamnioticfluid.Fetalswallowingisessentialforcontrollingthevolumeoffluidintheamnioticcavity,andtheamnioticfluidalsocontainsgrowthfactorsthatareimportantinstimulatingthedevelopmentofthefetaldigestivesystem.Theamnioticfluidthatthefetusswallowsisabsorbedbytheintestineintothefetalcirculation.Theplacentathenremovestoxinsandexcessvolumeintothematernalcirculation.DevelopmentoftheBladderThebladderdevelopsfromtheendodermoftheurogenitalsinus(theanteriorofthe2chamberscreatedwhentheurorectalseptumdividesthecloaca),andthesplanchnicmesodermsurroundingit.Openingintothecloacaarethetwomesonephricductsandtheallantois.Theallantoisisablind-endeddiverticulumthatextendsfromthesuperiorsurfaceoftheurogenitalsinusuptotheconnectingstalk(andlatertheumbilicalcordwhichorganizesaroundtheconnectingstalk). TheurogenitalsinusviewedfrombehindTheupperpartoftheurogenitalsinusbeginstodilateasitfillswithurine.Partofthisexpansionisthroughincorporationofthecaudalendsofthemesonephricductsandtheinferiorpartoftheallantois.

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Asaresultofthisexpansion,theuretersandthemesonephricductscometoopenseparatelyintotheurogenitalsinus.Theascentofthekidneysdrawstheuretericbudscraniallyintothedilatingpartoftheurogenitalsinus,whichbecomesthebladder.Theopeningsofthemesonephricductsremaininthelowerpartoftheurogenitalsinus,whichdoesnotexpandasmuch.Thelowerpartoftheurogenitalsinusdevelopsintotheurethra.Eachmesonephricductwilldevelopintoavasdeferensinthemale.Theywilldegenerateinfemales.Theupperpartoftheallantoisnarrowsformingatubularstructurecalledtheurachus,whichtheninvolutestobecomeafibrouscord-likestructurecalledthemedianumbilicalligament,whichcanbefoundpassingfromthefundusofthebladdertotheumbilicus.Failureoftheurachustoinvolutecompletelycanresultinpatentremnantssuchasthoseshowninthefollowingdiagrams.

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References Carlson, B.M. Human Embryology and Developmental Biology. 5th edition. Elsevier Saunders. 2014. Moore, K.L and T.V.N. Persaud. The Developing Human. Clinically Oriented Embryology. 8th edition. Saunders Elsevier. 2015. Sadler, T.W. Langman’s Medical Embryology. 10th edition. Lippincott Williams & Wilkins. 2012. Schoenwolf, G., S. Bleyl, P. Brauer and P. Francis-West. Larsen’s Human Embryology. Elsevier Churchill Livingston. 2014. Tuchmann-Duplessis, H., David, G. and P. Hagel. Illustrated Embryology. Volume 1: Embryogenesis. Springer-Verlag. 1972 Tuchmann-Duplessis, H., David, G. and P. Hagel. Illustrated Embryology. Volume 2: Organogenesis. 1072

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Summary

• The kidneys and ureters develop from the intermediate mesoderm.

• Three successive types of kidney develop in the embryo. The pronephric kidney develops first, located in the cervical region. It is transient and non-functional. Before it degenerates, it gives rise to the pronephric duct, which enters the part of the cloaca that will become the urogenital sinus. The mesonephric kidney follows next and develops in the thoracic and lumbar regions. It takes over the remains of the pronephric duct as the mesonephric duct. Excretory tubules form in the mesonephric kidney and empty into the mesonephric duct. The mesonephric kidney functions transiently but has degenerated by the fourth month. The final kidney that develops is the metanephric kidney. It develops in the pelvis from intermediate mesoderm called the metanephric blastema, and from an outgrowth of the mesonephric duct called the ureteric bud.

• Through a series of reciprocal interactions between the metanephric blastema and

the ureteric bud, the ureteric bud forms the collecting system, including the ureter, renal pelvis, major and minor calyces, collecting ducts and collecting tubules. The metanephric blastema forms the nephrons.

• The metanephric kidneys are initially located in the pelvis and must gradually

shift position, ascending into the abdomen.

• The urinary bladder and urethra develop from the urogenital sinus, which was created by division of the cloaca.