From mountain to bedside understanding the clinical
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From mountain to bedside understanding the clinical
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Review
Frommountaintobedside:understandingtheclinicalrelevanceofhumanacclimatisationtohigh-altitudehypoxia
DMartin,JWindsor
CentreforAltitude,SpaceandABSTRACT
ExtremeEnvironmentMedicine(CASEMedicine),UniversityForcenturiesmanhasstrivedtoreachthegreatestCollegeLondon,Instituteofheightsonearth.InordertoexplainthephysiologicalHumanHealthandPerformance,changesthatareneededtoachievethis,physiologistsLondonN195LW,UKhavetendedtofocusontheimprovementsmadeinCorrespondenceto:
oxygendeliverytothebody’stissues.AlthoughthisDrDMartin,CentreforAltitude,explainsmuchoftheacclimatisationprocess,ithasnotSpaceandExtremeEnvironmentbeenabletoaddressthelargeinterindividualvariationsMedicine(CASEMedicine),seeninhumanperformanceataltitude.Inrecentyears,UniversityCollegeLondon,InstituteofHumanHealthandattentionhasshiftedandnowfocusesonmicrovascularPerformance,FirstFloor,
andcellularresponsesinanattempttoexplaintheseCharterhouseBuilding,Archwaydifferences.InvestigatingtheseprocessesnotonlyhelpsCampus,HighgateHill,LondonN195LW,UK;dan.s.martin@tounraveltheprocessofacclimatisingtoaltitude,http://wendang.chazidian.com
mayalsoimproveourunderstandingofthebody’sresponsetohypoxiainthosewithcriticalillness.
Received8July2008
Accepted26September2008
Lackofoxygendullsthemindandjudgement,slowsthereflexes,weakensthemuscles,andtakesawayourhigherfaculties.Thehigheronegoes,themoreseriousaretheseeffects.Toomanypeopleforgetthisexactlyatatimewhentheyshouldbemostresponsivetothedanger.1
TheWorldHealthOrganizationestimatesthatapproximately
内容需要下载文档才能查看35millionpeopletraveltoaltitudesabove3000m
内容需要下载文档才能查看eachyear.2Althoughthispresentsavarietyofphysicalhardships,thesinglegreatestchallengefacedisthefallinbarometricpressureandtheresultingdeclineinthepartialpressureofoxygen.Withtime,humanscanadapttothisharshenvironmentviaaprocessknownasacclimatisa-tion.Thisreviewaimstosummariseourunder-standingoftheacclimatisationprocesstodatebyfocusingonwell-recognisedmechanismsbeforegoingontodiscussnewconceptsinthisfield.Bystudyingthewaythehumanbodyrespondstohighaltitude,wemayalsoimproveourunder-standingofthewayhypoxiaaffectspatients.
ACCLIMATISATIONTOALTITUDE
Hypobarichypoxialeadstoafallintheinspiredpartialpressureofoxygen(PIO2),which,intheabsenceofadaptivemechanisms,lowersalveolarpartialpressureofoxygen(PAO2),andresultsinareductioninthedrivingpressureneededforthediffusionofoxygenacrossthealveolar–capillarybarrier.Theresultofthesechangesisafallinboththearterialpartialpressureofoxygen(PaO2)andthearterialoxygensaturation(SaO2),leadingtoareductioninoxygendeliveredtothetissuesandthepotentialforcellularhypoxiaandorgandysfunction.Asuccessfulperiodofacclimatisationathighaltitudeensuresthathumansareabletofunction
622
inasimilarwaytothatseenatsealevel.Historically,wehaveunderstoodthistoinvolverestoringsea-levelvaluesofoxygendeliveredtothebody’stissues.Oxygendelivery(DO2)isdefinedastheproductofcardiacoutput(Q)andarterialoxygencontent(CaO2)(table1).Here,QistheproductofheartrateandstrokevolumeandCaO2isthesumoftheoxygenboundtohaemoglobinandthatdissolvedintheplasma.Onascenttoaltitude,CaO2fallsandDO2isthereforereduced.Inordertocounteractthis,threeprincipalphysiolo-gicalchangesoccuraspartoftheacclimatisationprocess:(1)Qisincreased;(2)SaO2isrestored;(3)haemoglobinconcentrationisincreased.
(1)IncreasedQ
Withinminutesofascendingtoaltitude,Qincreasesduringbothrestandsubmaximalexer-cise.ThiswasfirstobservedinrestingvolunteersbythephysiologistsCGDouglasandJSHaldaneduringtheirground-breakingexperimentsonPike’sPeak(4300m)in1911.3Onthesamemountain,some60yearslater,http://wendang.chazidian.comingthreedifferentworksettingsonacycleergometer,theteamshoweda10–15%increaseinQduringexerciseinthefirst4daysataltitude.4However,subsequentstudieshaveshownthatthisincreaseisshortlived,andQduringrestandsubmaximalexercisereturnstosea-levelvalueswithinafewweeks.5Interestingly,thecontributionsmadebytheheartrateandstrokevolumedifferdramaticallyduringthistime.Inareviewof11studieslookingattheeffectofaltitudeonthecardiovascularsystem,WolfelandLevine6identifieda14–25%increaseinheartrateandan8–32%fallinstrokevolumeduringthefirst4weeksat3800morhigher.Althoughanincreaseinsympatheticactivitycanlargelyexplainthepersis-tentriseinheartrate,thereasonsforadeclineinstrokevolumearepoorlyunderstood.Thisisparticularlyconfusingbecausestrokevolumedoesnotreturntonormalvalueswhenthecirculatingvolumeisartificiallyrestoredtonormalsea-levelvalues.7However,aswewillseelater,theprocessofacclimatisationisadynamicone,andthecontributionmadebythecardiovascularsystemmayonlyberequiredduringinitialexposuretoaltitude.
(2)RestorationofSaO2
Onceoxygenmoleculesenterthebody,theyencounteranumberofobstaclesbeforetheyfinallyreachthemitochondriaforwhichtheyaredestined.
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Ateachoftheseobstacles,thereisastep-likereductioninthepartialpressureoftheoxygen.Thisiscommonlyreferredtoasthe‘‘oxygencascade’’andwasfirstdescribedataltitudebythepioneeringphysiologistJosephBarcroftmorethan80years
内容需要下载文档才能查看ago.8
内容需要下载文档才能查看Theprofoundeffect
内容需要下载文档才能查看thataltitudehasontheoxygencascadecanbeseenin
内容需要下载文档才能查看fig1usingdata
内容需要下载文档才能查看fromasimulatedhigh-altitudeascentofMountEverest.9Althoughmostofthestepsintheoxygencascadearebeyondhumancontrol,thebodycanlimitthefallinPO2inonekeyarea.Asoxygenentersthealveoli,thePO2fallsasaresultoftheadditionoftheuptakeofoxygenbytheincomingmixedvenousblood.PAO2canbecalculatedfromthealveolargasequation:PAO2=PIO2–(PACO2/R)
whereRistherespiratoryexchangeratio(theratioofthevolumeofcarbondioxideproducedbythetissuestothevolumeofoxygenconsumedperunittime,whichvarieswiththesubstratebeingused,eg,0.7forfatand1.0forglucose).Accordingtothisequation,ifRremainsunchanged,anyreductioninPACO2leadstoanincreaseinPAO2.AsventilationandPACO2areinverselyproportional,anyincreaseintherateordepthofbreathingwillthereforeresultinafallinPACO2andanincreaseinPAO2.
Overthecourseofseveraldaysataltitude,ventilationincreasesinvoluntarilyandresultsinareductioninPACO2.Thisislargelyduetothecombinedeffectsoftwophysiologicalresponses:thehypoxicventilatoryresponseandthehypercapnicventilatoryresponse.10AsPAO2falls,peripheralchemoreceptorsinthecarotidandaorticbodiesarestimulated,causingventilationtoincrease.Thisisknownasthehypoxicventilatoryresponse,andthemagnitudeoftheresponsevarieswidelybetweenindividuals.11Atsealevel,anyriseinventilationlowersPACO2andresultsintheslowingofbreathingandanincreaseinPACO2.However,ataltitude,theresponsefromthecentralmedullarychemoreceptorsincreases,triggeringhighlevelsofventilationandariseinPAO2.12Thisresponse,commonlyreferredtoasthehypercapnicventilatoryresponse,isthoughttobeduelargelytothereductioninbicarbonateions(HCO32)thatiscommonlyseeninthecerebrospinalfluidonascenttoaltitude.13ThefallinHCO32istheresultofrenaltubularcellsfailingtoreabsorbHCO32andresultsinacidiccerebrospinalfluid,whichencourageshigherlevelsofventilation.14
ThesechangesresultinanincreaseinPaO2andasubstantialriseinSaO2duetothesteepslopeoftheoxygen–haemoglobindissociationcurveovertherangeofPaO2valuesseenataltitude.Therapidnatureofventilatoryacclimatisationallowstimeforslowerchangesinthehaematologicalsystemtooccur.
(3)Increasedhaemoglobinconcentration
AlongsidethechangesseeninQandSaO2,theacclimatisationprocessalsoresultsinanincreaseintheconcentrationofcirculatinghaemoglobin.Thisisaresultoftwoprocesses.Table1Formulaeforthecalculationofsystemicoxygendelivery
Calculationofoxygendelivery(DO2)
Exampleina70kgman
DO2=Q6CaO2
DO2=4.96194=950.6ml/minQ=HR6SVQ=70670=4.9l/min
CaO2=([Hb]6SaO26H)+(PaO26S)CaO2=(14.06.9861.39)+(13.360.0225)
=19.1+0.3
=19.4mlO2/100mlblood=194mlO2/lCaO2,arterialoxygencontent;H,Hufnersconstant(1.39);[Hb],haemoglobinconcentration;HR,heartrate;PaO2,arterialpartialpressureofoxygen;Q,cardiacoutput;S,solubilitycoefficientofoxygen(0.0225);SaO2,arterialoxygensaturationofhaemoglobin;SV,strokevolume.
PostgradMedJ2008;84:622–627.doi:10.1136/pgmj.2008.068296
Review
a.
Arrivalataltitudecoincideswitharapidfallinplasmavolume.Overseveraldays,healthyindividualsexperienceafallbyupto20%intheirplasmavolumebecausewaterisexcretedasurineorinsteadshiftsintoeithertheinter-stitiumorcells.ThisresultsinarapidincreaseintheconcentrationofcirculatinghaemoglobinandsubsequentrisesinCaO2andDO2.15Althoughthisprocesscanpersistforseveralweeks,overaprolongedstayataltitude,plasmavolumeslowlyreturnstonormal.After18weeksabove4000m,Pugh16foundthatplasmavolumehadfallenby21%;however,3monthslaterthedifferencewasonly10%.b.Withinminutesofarrivalataltitude,increasedcellular
concentrationsoftheprotein,hypoxiainduciblefactor1a(HIF1a),stimulatethereleaseoferythropoietinfromtheliverandkidney.17Erythropoietinsubsequentlybindstoerythroidcelllinesinthebonemarrow,triggeringthereleaseofimmaturenucleatedredbloodcells(reticulocytes)intothecirculation.Insomecases,thiscanleadtoadoublinginthenumberofcirculatingreticulocyteswithin7daysofarrivalataltitude.18Althoughtheplasmaconcen-trationoferythropoietintendstofalloverthecourseof3weeksataltitude,redcellproductionremainsraisedforupto8monthsinthosenewtoaltitudeandcanresultina50%increaseinredcellmass.19
Changesincapillarydensityandmitochondrialvolumeandfunctionataltitude
Therewasarevelationinourunderstandingofhumanadaptationtohypoxiawhentheacceptedhypothesesofchangesinskeletalmusclecapillaryandmitochondrialdensityafterchronicexposuretohypoxiawerequestioned.
Historically,itwasbelievedthatasustainedreductioninoxygenavailabilitywouldleadtoincreasesincapillarydensityandaerobicmetabolicactivityinordertorestorecellularenergyrequirements.20However,earlystudiesofcapillarydensity,onwhichtheseideasweregrounded,failedtotakeintoaccountthedramaticdecreaseinmusclefibrecross-sectionalareaandskeletalmusclemass.2122Althoughoverallcapillarydensityappearedtoincrease,thecapillarytofibreratioremainedunchanged.Thustheapparentriseincapillarydensitysimplyrepresentedthereductioninmusclecross-sectionalarea.23
TraditionalideaswerequestionedfurtherwhenskeletalmusclebiopsyspecimenstakenfromclimbersreturningfromtheHimalayasrevealeda30%reductioninmitochondrialvolumedensity.21Inthesamegroupofsubjects,theactivityofcitratesynthaseandcytochromeoxidaseenzymeslocatedwithinthemitochondriawerereducedby,20%.24Asthesetwoenzymesareinvolvedinthecitricacidcycleandoxidativephosphorylation,respectively,thiswouldresultinreducedoxidativecapacityafterprolongedexposuretohypoxia,whichhasbeenfurtherconfirmedinotherstudies.2225Thiscombinedbodyofevidenceopposesprecedingtheoriesandsuggeststhatmusclecapillarityisincreased,whereascellularaerobiccapacityandmitochondrialvolumedensityarebothreducedataltitude.
SHORTCOMINGSOFTHECLASSICALACCLIMATISATIONEXPLANATION
Theclassicalexplanationofacclimatisationtomoderatealtitudehasevolvedovermanyyearsthroughdescriptionofphysiologicalprocessesoperatingsynergisticallytoincreaseoxygenfluxtocellswhenfacedwithenvironmentalhypobarichypoxia.SoeffectiveisthisadaptationthatCaO2tendstosurpasssea-levelvaluesinmostlowlandpeopleafteranadequateperiodofacclimatisation(fig2).2627However,ithas
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Review
Figure1Theoxygencascadeduringrestatsealevelandatanaltitudeof8100m.DatatakenfromasimulatedascentofMountEverest,OperationEverestII.9
becomeclearthat,despitethisremarkableadaptivephenom-enon,exerciseperformanceataltitudeandsusceptibilitytoaltitude-relatedillnesses,suchasacutemountainsickness,highaltitudepulmonaryoedema,andhighaltitudecerebraloedema,differsmarkedlybetweenindividuals.Ourpreviousunder-standingofacclimatisationfailstoexplainthesesignificant
内容需要下载文档才能查看 内容需要下载文档才能查看 内容需要下载文档才能查看interindividualdifferences.
High-altitudeheroesarerarelyathletesatsealevel
Interindividualvariabilityinexerciseperformanceataltitudeisconsiderable.Accomplishedhigh-altitudemountaineersareanexampleofthosewhoadaptwelltoextremedegreesofhypoxia.ShortlyafterthefirstsuccessfulsummitofMountEverestbyReinholdMessnerandPeterHabelerwithouttheaidofsupplementaloxygen,aninvestigationwasperformedwiththeaimofelucidatingthetraitsthatpermithumansurvivalatsuchheights.28Atsealevel,Messner,Habelerandanumberoftheirclimbingcolleagueswerestudiedalongsideagroupofsedentarycontrolsubjects.Measuresofaerobicperformance,includingstaticanddynamiclungvolumes,echocardiography,skeletalmusclemitochondrialvolumedensityandmaximaloxygenconsumption,wereperformed.Withnosignificantdifferencesnotedbetweenthetwogroupsofsubjects,theauthorswereforcedtoconcludethatatsealevel‘‘elitehigh-altitudeclimbersdonothavephysiologicaladaptationstohighaltitudethatjustifytheiruniqueperformance’’.28
Sea-levelperformancefailstopredictaltitudeperformance
Exceptionalhigh-altitudeathletesfailtodisplayanyremarkablephysiologicalfeaturesatsealevel,butthosewhocopepoorlywithhypobarichypoxiaareequallydifficulttoidentify.29Nosingletesthastheabilitytodifferentiatethosewhofarewellataltitudefromthosewhodonot.Earlyhypobaricchamberstudiessuggestedanassociationbetweenabluntedhypoxicventilatoryresponseandthedevelopmentofacutemountainsickness.3031However,thesefindingshavenotbeenconfirmedinthefield.3233
Despitemanydecadesofinvestigation,theonlyreliableindicatorofwell-beingataltitudeisaprevioushistoryofsuccessfulascenttoasimilarelevation.Thisdifficultyinpredictingindividualsuccessorfailureonexposuretohypoxia
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Figure2Changeinarterialoxygencontentafteracclimatisationto5260m.ArterialoxygencontentataltitudecalculatedwithfigurestakenfromCalbetetal.26
isseeninclinicalpracticewhenmanaginghypoxicpatients,particularlythosecategorisedascriticallyill.Despiteadvance-mentsinmedicaltechnologyandaclearerunderstandingofthepathophysiologicalprocessesunderlyingcriticalillness,clin-iciansstillstruggletoaccuratelydifferentiatesurvivorsfromnon-survivorsamongapopulationofprofoundlyhypoxicpatients.
Exercisecapacityremainslimitedafteracclimatisationtohighaltitude
Anyonewhohastravelledtohighaltitudewillreportthatexerciseisseverelylimited,andthishasbeenwelldocumentedinreportsovermanycenturies.34Asacclimatisationresultsinareturntosea-levelvaluesforsystemicDO2,itisunclearwhyexercisecapacity,measuredbyareductioninmaximumoxygenuptake(VO2max),remainssignificantlylimitedataltitudeafteradequateacclimatisation.93536AcuteexposuretohypoxialeadstoapredictablereductioninVO2max,whichisproportionaltothereductioninCaO2.37ThisdirectrelationshipbetweenCaO2andVO2maxislostafteracclimatisation,suggestingthatotherprocessesarecontributingtotheexercisedecrement.Debateovertheunderlyingmechanismofthisphenomenonhasbeenongoingforanumberofdecades.Ithasbeensuggestedthattheperipheral‘‘microcirculation’’mayplayanimportantroleinthepersistentlimitationofexercisecapacityataltitude.35However,thisdistalcomponentoftheoxygen-transportationsystemhasnotbeendirectlystudiedinlowlandsubjectsascendingtoaltitude.
Arecentstudyhascomparedtherestingforearmbloodflowofhigh-altitude-dwelling(4200m)Tibetansandagroupoflowlandcontrolsubjectsatsealevel(206m).38TheforearmbloodflowoftheTibetanswasdoublethatoftheAmerican
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comparisongroupandwasassociatedwitha.10-foldincreaseincirculatingconcentrationsofbioactivenitricoxideproducts.38DespitehavinglowersystemicCaO2thantheAmericanlowlanders,theTibetanshadhigherregionallevelsofforearmDO2,perhapsbecauseofincreasedperipheralgenerationofnitricoxide.Thisfindingisbeginningtodrawattentionawayfromcentralcardiorespiratoryprocesses,andinvestigatorsarenowstartingtostudytheperipheralcirculationtogainabetterunderstandingofhypoxicadaptation.
PROPOSEDHYPOXIASURVIVALSTRATEGIES
Facedwithareducedavailabilityofoxygen,humansmustredressthesupply-and-demandbalancetoavoidcellulardysfunctionanddeath.Theclassicdescriptionofacclimatisa-tiondependsonastrategyofimprovingsystemicDO2;othermethodsofrestoringoxygenbalanceincludereducedcellularoxygenconsumptionandimprovedefficiencyofenergygenera-tion.
Reducedcellularoxygenconsumption
Inmammalianspecies,itispossibletoreduceglobaloxygenconsumptionbyloweringmetabolicactivity,asiscommonlyseeninhibernatinganimalsandthedevelopingfetus.Atthecellularlevel,cellsfromanoxia-tolerantanimalssuchasturtlesshowareductioninmetabolicrateof,25%afterexposureto30minofanoxia.3940Afterthereintroductionofoxygen,thisprocessisrapidlyreversed.Thisanoxia-inducedhypometabolicstateismainlybroughtaboutbydownregulationofATP-consumingmembraneionchannels41andpermitsneutralcellularenergybalanceduringoxygendeprivation.
Improvedefficiencyofenergyproduction
Analternativestrategyforsurvivingprolongedandextremehypoxiaisamoreefficientuseofoxygenduringtheprocessofaerobicenergyproduction.42Althoughhardtoimagine,thelatterhypothesishasbeendemonstratedinisolatedmitochon-driainwhichoxidativephosphorylationbecamemoreefficientduringexposuretohypoxia.43Thismayexplainthereductioninoxidativecapacitydescribedinclimbersreturningfromaprolongedperiodataltitude.Alterationofuncouplingproteinfunctionmaybeonemechanismthatfacilitatesimprovedefficiencyofoxygenuseduringaerobicmetabolism.Uncouplingproteinsallowprotonstore-enterthemitochondriainthefinalstagesofoxidativephosphorylation,therebybypassingATPsynthaseandeffectivelygeneratinganenergy‘‘leak’’.44Fine-tuningofthisenergyleakinthecell’sfavourmaypermitimprovedmetabolicefficiency.
THERELEVANCEOFHIGH-ALTITUDEPHYSIOLOGYTOCLINICALMEDICINE
Thestudyofhealthyvolunteersascendingtoaltitudemayhelptodefineandimproveourunderstandingofthelimitsofhumantolerancetohypoxia.Hypoxaemiaandcellularhypoxiaarecommonincriticallyillpatients,butitisunclearwhetherthesepatientsareabletoadapttohypoxiainasimilarmannertothosehealthyindividualswhoacclimatisetoaltitude.Underlyingpathology,infectionandthedevelopmentofcriticalillnessinthesepatientsmaypreventacomparableacclimatisa-tionprocess.Cellularmechanismsthatdeterminesystemicresponsetohypoxiaarebeingunravelledatanincrediblerate.PerhapsthemostimportantoftheseinrecentyearshasbeenthediscoveryofHIF1aanditsroleinoxygenhomoeostasisbyregulationofmultiplegeneloci.4546Inthefuture,theroleof
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HIF1ainthepathophysiologyofcancer,mycocardialischaemiaandcerebralhypoxiamaybemanipulatedbeneficially.TheroleofHIF1ainapoptosisandischaemicpreconditioningholdparticularlyexcitingpotential.47–49
High-altitudestudiesmaysuggestnoveladaptivemechan-ismsinpeoplewhodemonstratetolerancetoenvironmentalhypoxia,leadingtotranslationalresearchinhypoxicpatients.Climbersmakingabrieftriptogreataltitudemountanimpressivepolycythaemiainordertoincreasesystemicoxygenflux.Tibetans,whohavelivedataltitudeforcountlessgenerations,donotshowthispossiblycounterproductiveadaptation,butdemonstratemarkedchangesintheperipheralcirculation.38Inthelattersituation,changesinthemicrocircu-latory–mitochondrialunitmayaccountforlong-termhypoxictolerance.Changessuchasthismaybemirroredincriticalillness.50Evidencesuggeststhat,earlyincriticalillness,restorationofnormallevelsofoxygendeliveryisbeneficialtooutcome,51whereasfollowingthesamelineofmanagementinestablishedcriticalillnesscanbeharmfultopatients.5253ThesestudiesreliedonmeasurementsofsystemicDO2,andtheirresultsmaybeexplainedbythefactthatpersistentdisruptionofthemicrocirculationisassociatedwithpooroutcomeinsepticcriticallyillpatients.5455Furthermore,excessiveuseofoxygenmayleadtoinflammatorychangesfollowedbyirreversibledamageinthepulmonarytractthroughthereleaseofoxygenfreeradicals.5657
Commonthemesbetweenhypoxiccriticalillnessandadaptationtothehigh-altitudeenvironmentareinspiringresearchintothisfield.Investigatorsarenowlookingbeyondtheoxygenfluxprocesstoexplorethehypothesisthatrelativechangesinoxygenconsumptionmayexplaindifferencesinaerobicperformanceataltitude.58
CONCLUSIONS
Ourunderstandingofhowhumansadapttohypoxiaathighaltitudecontinuestodevelop.Overthelastcentury,researchhasrevealedchangesinthecardiorespiratoryandhaematologi-calsystemsthatallowexcursionstoaltitudethroughaugmen-tationofsystemicoxygendelivery.Morerecently,focushasturnedtotheperipheralmicrocirculationandtheprocessofATPproductionthatoccurswithinthemitochondria.Althoughdifferentarenas,high-altitudephysiologyandcriticalillnesshaveinterestingparallelswhichcouldbeexploitedinordertobenefithypoxicpatients.Continuingworkinthefieldofhigh-altitudemedicineandphysiologymayhelptounravelthecomplexmechanismsthatunderliethereasonsforsurvivalinahypoxicenvironment.Theassociationofgeneticmarkerswith
Keylearningpoints
c
Theclassicalexplanationofacclimatisationtomoderatealtitudeisrestorationofsystemicoxygendelivery.
c
Thereducedexercisecapacityandmarkedinterindividualvariationinperformanceataltitudearedifficulttoexplaininthefaceofnormalsystemicoxygendelivery.
c
Changesintheperipheralmicrocirculationandmitochondrialenzymaticpathwaysmayprofoundlyalterthebalancebetweenoxygensupplyanddemandatacellularlevelonascenttoaltitude.
c
Lessonslearntfromhealthyvolunteersexposedtothehypobarichypoxiaencounteredataltitudemaybenefitpatientswithhypoxiaresultingfromdisease.
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Currentresearchquestions
c
Dochangesintheperipheralcirculationaffectthediffusionofoxygenintotissuesataltitude?
c
Dohumanspossesscellularstrategiesforcopingwithprolongedhypoxia?
c
Willmechanismsthatidentifyperformanceathighaltitudetranslateintotoolsforpredictingsurvivalofhypoxiaintheclinicalsetting?
beneficialadaptationsinthemicrocirculatory–mitochondrialunitmayonedayprovideclinicianswiththetoolsthattheyrequiretoaccuratelypredicttolerancetohypoxiaandthereforeincreaseapatient’slikelihoodofsurvival.
MULTIPLECHOICEQUESTIONS(TRUE(T)/FALSE(F);ANSWERSAFTERTHEREFERENCES)
1.After1weekataltitude,thefollowingphysiologicalparametershavereturnedtonormal:
(A)Heartrate(B)Strokevolume(C)Cardiacoutput
(D)Amountofbicarbonateexcretedintheurine(E)
Plasmavolume
2.OnreturnfromanexpeditiontotheHimalayas:
(A)Mitochondrialvolumedensityinskeletalmuscleisdecreased
(B)Cellularaerobiccapacityisincreased
(C)Capillarydensityisincreasedinskeletalmuscle
(D)Haemoglobinconcentrationremainsraisedforseveralmonths
(E)
Heartrateandstrokevolumerapidlyreturntonormal
3.Thefollowingincreasewithinhoursofascendingtoaltitude:
(A)Serumconcentrationsofhypoxia-induciblefactoranderythropoietin
(B)Sympatheticoutflow(C)Plasmavolume
(D)Heartrateandcardiacoutput(E)
Redcellproduction
4.Onascenttoaltitude,thefollowingincrease:
(A)Barometricpressure
(B)Fractionofinspiredoxygen
(C)Partialpressureofinspiredoxygen(D)Saturatedvapourpressureofwater
(E)
Partialpressureofalveolarcarbondioxide
5.Thefollowingphysiologicalprocessesincreasethepartialpressureofalveolaroxygen:
(A)Anincreaseinrespiratoryrateandtidalvolume(B)Ahigh-carbohydratediet
(C)Theuseofsupplementaloxygen(D)Adecreaseinplasmavolume
(E)
Anincreaseintheconcentrationofcirculatinghaemoglobin
Competinginterests:None.626
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