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Discuss The Physiological Mechanisms That Contribute To The Regulation of Plasma Osmolarity (NOTES)
Discuss The Physiological Mechanisms That Contribute To The Regulation of Plasma Osmolarity (NOTES)
Myocytefunction,signalingpathways,cellmembraneintegrity,andneuronaldepolarization
arejustafewexamplesofcrucialaspectsofourphysiologythatdependontheconstancyof
theambientosmolarity
Asthesinglemostimportantdeterminantofextracellularosmolarity,theconcentrationof
sodiumintheserummustbetightlyregulatedalongsidewatercontentforthesemyriad
cellularprocessestobedischargednormally.
Thestabilityoftheserumsodiumconcentrationwithinanarrowrangedespitewidevariations
inwaterintake,soluteingestion,andnonurinarywaterlossesistheresultofastrictbalance
betweenwaterintakeandwateroutput.
WaterBalance
Waterbalanceisachievedbyensuringthattheamountofwaterconsumed=waterexcreted.
Thisbalanceismaintainedthroughtheregulationofthetwovariables:
Urinarywaterloss:
Whenanyamountoffluidinexcessofthe650mLisingested(whichiscommondueto
normaldrinkinghabitsdictatedbysocialnorms),theadditionalfreewaterisexcretedthrough
dilutionoftheurine.Conversely,whenanindividualdrinkingtheaverage2Loffluidperday
developsincreasedwaterlossesabovenormal(fromdiarrhea,sweating,increasedrespiratory
losses,etc.),balanceismaintainedthroughconcentrationoftheurine.Thisisachieved
throughthesecretionofADH.
ControlofADHrelease
ADHissynthesisedinthehypothalamusandstoredinposteriorpituitarysecretoryhranules
untilitsreleaseispromptedbyeitherosmoticornonosmoticstimuli(decreasedblood
pressureorintravasculartone).
Osmoticstimuli
TheosmotictriggerforADHreleaseismediatedbyosmoreceptorcellsinthe
circumventricularorgans(whichhavealeakyBBB,exposingneuronstoosmoticflux)OVLT
andtheSFO,whichsenseECFosmolaritythroughcellularswellinginhypotonicconditions
andshrinkageinhypertonicconditions;openingandclosingstretchsensitiveTRV1or4
channels.
ExEvTRPV1KOmiceshowpronouncedserumhyperosmolarityundernormalconditions,
andseverelycompromisedADHresponsestoosmoticstimulationinvivo.Thiswasquantified
usingrutheniumreddyetomonitorchangesinmembraneconductanceanddepolarising
potentialsinresponsetohyperosmolarity.(Naeinietal,2006).
TheosmoreceptorsoftheOVLTandtheSFOpossessprojectionstothesupraopticand
paraventricularnucleioftheanteriorhypothalamus,allowingthemtocommunicatewithADH
stores.
ExEvMcKinleyetAlin2004retrogradetracingstudiesusinganeurotropicvirususedto
identifytheseprojections.
ClinRelDestructionoftheSONandPVNcausesdiabetesinsipiduspresentswithexcessive
urinationandthirstduetolackofADH.
ResponseoccurstoanincreaseinECFosmolarityofaslittleas1%,witha1%decrease
resultingincompletesuppression.Thissensitivityispossiblyduetoimportanceofwaterasa
substrate,yetalsoitspotentialthreattocellularintegrity.
NonOsmoticstimuli
Lowpressuerbaroreceptorsintheatriaandhighpressurebarorecptorsinthecarotidarteries
andaortadetectbloodvolumeandpressure.Inconcert,theserecpetorswillpromptADH
releasewhentheyperceiveadropinbloodvolumeorpressure,sendingafferentsignalstothe
brainviavagusandglossopharyngealnerves.
ThisADHreleaseislesssensitivethanADHreleaseinresponsetoosmoticstimuli,
generatingreleaseata7%change.However,theADHreleaseissignificantlystrongerthan
wheninducedbyosmoticstimuli(duetoitsinvolvementindefenceagainstcirculatory
collapseasopposedtodehydration),andwillprevailoveranycontradictoryosmoticsignals.
ADHincreaseswateruptakeinthekidneys,decreasingosmolarity:
ADHstimulates4actionswhichpromoteantidiuresis:
1. CollectingductADHbindstotheV2receptorsonthebasolateralmembraneofcollecting
ductprincipalcells,resultingintranslocationofaquaporin2(AQP2)waterchannelsintothe
luminalmembranesthroughacyclicAMPsignalingpathway.Thismakestheusually
impermeablecollectingductextremelypermeable,causingpassivewaterreabsorptiondown
itsconcentrationgradientintothehypertonicmedullaryinterstitium.Thisoccurswithin
minutes,allowingrapidandshorttermregulationofwaterloss.Itisnotablethatwhen
elevationsinplasmaADHlevelsaresustainedforlongerthan24h,theexpressionofAQP2is
increased,andthegreaternumberofAQP2channelsavailablefortranslocationintothe
luminalmembraneallowforevengreatermaximalwaterpermeabilityinthecollectingduct.
ExEvFreezefractureofbrattelbororatswhomsufferneurogenicdiabetesinsipidus,and
presentwithoutindentationsintheapicalmembrane.WhenADHisinfused,pimpleclusters
appear,indicatingAQP2hasinsertedinthemembrane.
2. IncreasesureapermeabilityWhenADHbindstoV2,italsostimulatesincreasesurea
permeabilitythroughphosphorylationandupregulationofureatransporterA1(apical)and
A3(basolateral).Thisleadstoalargeeffluxofurea,whichcontributesroughlyhalfofthe
soluteresponsibleforproducingthenecessaryhypertonicmedullaryinterstitium.
ExEvimportanceofureainplasmaosmolarityregulationshowninratsonlowproteindiets,
whomcannotconcentratetheirurine.
3. LoopofHenleAmplificationofcountercurrentmultipliersystemADHstimulatesthe
activityoftheNKCCpumplocatedintheTALH,drawingmoreionsfromthelumenintothe
4.
interstitium.AstheTALHisimpermeabletowater,watercannotfollowtheseions,making
theinterstitiummorehypertonic.Thisdrawsmorewateroutofthefiltratepassingthroughthe
waterpermeableDLH,concentratingthefiltrateasitsnotNaClpermeable.Thisfacilitates
increaseddiffusionofNa+outofthethinALHpassively,increasingmedullaryinterstitial
osmolarity(drawingmorewateroutoftheDLH)andenablingtheNKCCtopumpmore
sodiumintotheinterstitiumastheconcentrationgradientisreduced.Thisestablishesa
corticopapillarygradient,withincreasedinterstitialconcentrationdrawingwateroutofthe
nowpermeableCDandconcentratingtheurine.
VasarectaThiscorticopapillarygradientismaintainedbythevasarecta,whichprevents
washoutofthegradientduetoitsUshape.Thisisfacilitatedbytheslowbloodflowinthe
vasarecta,allowingtimefortheplasmawithinittoequilibratewiththesurrounding
interstitialfluid.
ADHbindstoV1,PLClinkedreceptors,triggeringcontractionofvascularsmoothmuscle
throughraisedcalciumlevels.Thisvasoconstrictionslowsbloodflowinvasarectaevenmore,
furtherminimisingdepletionofmedullarysolutes.
ClinRelDiuretuicsareusedtherapeuticallytoreducewaterreabsorption,inducingpolyuriato
easeeffectsofhighBPorOedema.LoopdiureticssuchasfurosemideinhibittheNKCCand
haveavasodilatoryeffectonthevasarecta,actingantagonisticallytoADH.
Electivewaterintake:
Thisiscontrolledthroughstimulationofthirstandsaltcravings.
Thirstcontrolisundoubtedlysensitivetoplasmaosmolarity.Forexample,anincreaseofonly
2%plasmaosmolarityproducesastrongdesiretodrink,comparedtoa15%decreaseinblood
volumetostimulatethesameeffect.
Thismechanismiscontrolledbythemedianpreopticnucleus,activatedbyosmosensitive
neuronsintheorganumvasculosumofthelaminaterminals(OVLT)andthesubfornical
organ(SFO).
ExEvDestructionofthisregionofthehypothalamusinhumansresultsinpartialortotalloss
ofdesiretodrink,evenwithextremelyhighsaltconcentrationintheextracellularfluid.
However,thirstcontrolislesssensitivethanADHregulation,andiscomplicatedbyavariety
ofotherinfluences.
Thirststimulationoccursataplasmatonicityapproximately10mOsmhigherthandoes
osmoticstimulationofADHrelease;thus,a23%increaseinplasmaosmolarityisrequired
tostimulatethirst,incontrasttothe1%increaserequiredtostimulateADHrelease.Infact,
theosmoticsetpointforthirststimulationroughlycorrelateswiththepointatwhichurineis
maximallyconcentratedthroughADHsaction,soincreasedwaterintakeispromptedonly
whenthekidneysabilitytoconservewaterisnearlyatitscapacity,therebyservingasa
secondlineofdefenseagainstseverehypernatremia.
UnlikeAVPsminutetominutecontroloverurinarywaterexcretion,thesethirstcontrol
mechanismsdonotreflectregulationofplasmaosmolaritypersebutinsteadexisttoprevent
overcorrectionofhyperosmolarity,asgastrointestinalabsorptionofingestedwatercantakeup
toanhour.Thedefenseagainstovercorrectionisfurtherbolsteredbythefactthatfluidintake
rapidlycausesatransientsuppressionofboththirstandAVPlevels,significantlybeforeany
resultantdropinplasmaosmolarity.
Thirstcontrolisalsoinfluencedbyotherfactorsthanosmolarity,suchasdrymouthand
hypotension.
Sodiumbalance
Regulationofosmolaritycannotbeachievedwithoutbalancingtheintakeandexcretionof
sodiumwiththatofwater.
ADHplaysaroleinloweringosmolarity,byincreasingwaterreabsorptioninthekidneys,
thusdilutingthebodilyfluids.Thisisimportantinsituationssuchasdehydration,whereyou
loseproportionatelymorewaterthansolute(sodium),sotheosmolarityofyourbodilyfluids
increases.Inthissituation,thebodymustconservewaterbutnotsodium,stemmingtherisein
osmolarity.
Topreventosmolarityfromdecreasingtobelownormal,thekidneysalsohavearegulated
mechanismforreabsorbingsodiuminthedistalnephron.Thismechanismiscontrolledby
aldosterone
However,ifinasituationwhereyourlosesofsodiumandwaterandproportionatetothe
compositionofbodilyfluids,suchassignificantbleedingfromtraumaorsurgery,thebody
needstoconservebothwaterandsodium.
http://mediwikis.com/wiki/index.php/Regulation_of_Plasma_Osmolarity_(water)_and_Volume_(sodiu
m)
https://www.ncbi.nlm.nih.gov/pubmed/7766344
https://www.scribd.com/presentation/249343118/RegulationofBodyFluidVolumeandPlasma
Osmolarity
file:///Users/totunla/Downloads/Surmacz%20Regulation%20of%20Fluid%20and%20Electrolyte
%20Balance1.pdf
https://mcb.berkeley.edu/courses/mcb135e/kidneyfluid.html