partialpressureofoxygeninambientairisreduced. Hypobaria:HighAltitude
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Athighaltitude,thebarometricpressureofambientairisreduced,thusthe PO2=FiO2*PB GasExchange:interfaceoflungsandblood Occursbypassivediffusion Ifpartialpressurefallsinthealveoli,thepartialpressurefallsinthearterial blood o Aspartialpressurefalls,sowillsaturationofhemoglobinwithoxygen. o Thedrivingforcedecreases,sosaturationdecreasesatthatgivenpartial pressure,andtheamountofoxygenboundtohemoglobinisreducedeven further. Barometricpressurefallswithincreasingaltitude Resultsinfeweroxygenmoleculespervolumeofair IdealGasLaw Gasesarecomposedofindividualmoleculesthatcanbecompressedor expanded. Thelowpressure(lowdensity)ofaltitudeallowsthegasestoexpand, resultinginfewermoleculesperunitvolume. o Volume=nRT/P OxygenTransportCascade Athighaltitudesthereisadiminisheddrivingforceforoxygenexchange betweentheambientair,lungs,blood,andtissues. Althoughventilationincreases,itbecomeslimitingasitcannotkeepupwith thedeclineinpO2. Aswemoveupinaltitude,wefacenotonlyadecreaseinthepartialpressure ofoxygen,butadecreaseinthesaturationofhemoglobin. Thetransittimeistoolongtoallowfor100%saturationofhemoglobinwith oxygen. TheabilitytomoveO2fromambientairtotissuedependson: Ventilation:movementofairintothelungs
Diffusion:fromalveolitocapillaries o Diffusionisseverelyaffectedduringexerciseathighaltitudes. o Transittimeinthepulmonarycapillariesremainsrelativelythesameas sealevel(.25seconds),butthedrivingforcefordiffusionismuchless. o Atrestatsealevelbloodisinthecapillarieslongenoughtoachieve approximateequilibriumwithalveolarO2. However,duringexerciseathighaltitude,thetransittimeistoorapidto allowequilibrium,resultinginadiminishedarterialPO2(PaO2).This resultsindiminishedHbsaturationduringexercisethatproducesa decreaseinVO2max. BloodFlow OxygenHemoglobinDissociationCurve Highaltitudedramaticallyreducestheoxyhemoglobindissociationcurve. o ResultsinreducedHboxygenationandO2transport,whichinturn reducesperformanceduringexercise. OxygenUptakeatSeaLevelandHighAltitude Submaximaloxygenuptakeissimilarataltitudeandsealevel VO2maxisdiminishedataltitude o Startstofallatrelativelylowaltitudes Therelativeeffort(%VO2max)isgreaterforanygivensubmaximaleffort. o Perceivedeffortismuchgreaterataltitude EffectsofAltitudeonVO2max AsaltitudeincreasesVO2maxdecreases. o Agivenlevelofworkrepresentsahigherpercentageofmaximumat altitudethanatsealevelandexercisebecomesmoredifficult. ThereislessdifferenceamongindividualsinVO2maxatveryhighaltitudes >6000mor19,685ft. o Duetoextremelylowdrivingpressureofoxygen. VO2maxbeginstodecreaseat~1524m(~3%per300mor1000ft).
PulmonaryVentilationvs.OxygenConsumption Oneofthefirstcompensatorymechanismsistoincreaseventilation o Bringsalveolaroxygencontentclosertothatoftheambientair o Altitudehyperventilation Aorticarchandcarotidarteriescontainperipheralchemoreceptorsthat aresensitivetodecreasedpO2. DecreasedpO2sensitizeschemoreceptorstochangeinpCO2 increasedalveolarventilationincreasedalveolarpO2with hyperventilationincreasedoxygenloading Downside:decreasesPCO2 Bicarbonatebuffersystem:H2O+CO2H2CO2H++ HCO3 DrivesthebicarbonatereactiontowardsCO2whichresultsina decreaseinH+ Alkalosis IncreasestheaffinityofHbforoxygen AsarterialPCO2decreases o EffectivelybringsthealveolarpO2somewhat,butcannotcompensate enoughtobringittosealevelvalues. CardiovascularResponsetoAcuteAltitudeExposure IncreasedHR Increasedcardiacoutput Slightdecreaseinstrokevolume Increasedbloodflowduringsubmaximalexercise o Compensatesforarterialdesaturation,soiflessO2isavailable,increases inQ,HR,andbloodflowincreasetomaintainoxygendelivery. IncreasedrestingsystemicBP Meanarterialpressure(MAP)increases
Increaseincatecholamineatrestandexercise o Increaseinsympathoadrenalresponseleadstoincreased vasoconstriction,HR,andcardiacoutput. RERandOxygenIntake RERrisesabove1.0becauseofthebicarbonatebuffersystem o MoreCO2isblownoffbecausethereactionisdriventowardsCO2as moreorganicacidsarebeingproducedthatneedtobebufferedduring exercise. AtaltitudeRERstartsatahigherlevelbutalsoincreases,andreachespeak, earlier. o Partiallyduetodrivetohyperventilate. BloodLactateResponse:AcuteExposuretoAltitude Atrest,lactatelevelsarehigher Atlowworkloads(100watts)thelactatelevelsaremuchhigherthanthesame workloadatsealevel. o Increaseinsympatheticoutputhelpstomobilizemorecarbohydrate increasesamountofATPderivedfromthesubstratesbecauseoflow oxygensaturation. SensoryFunctions Withfallinarterialoxygensaturationanumberofsensoryfunctionsarealso impaired(thebrainisnotanaerobicorgan!) Decreasedlightsensitivity Visualacuityandattentionspanfallasarterialoxygensaturationfallbelow 90% Cognitiveabilitiesandposturalstabilitydecreaseasoxygensaturationfalls below80% PhysicalPerformance Highaltitudedoesnotimpairtheshortterm(<2minutes)anaerobicenergy system. Highaltitudemayimproveperformanceinsingleboutpowerevents(suchas shotput,javelin,longjump,etc.)duetodecreasedairresistance. Highaltitudedecreasestheoxygentransportcapacityofhemoglobinand negativelyaffectsaerobicactivities. SummaryoftheEffectofAcuteExposuretoAltitude(seeslide)
VftAcclimatization:adaptationproducedbyachangeinthenaturalenvironment.
AcclimatizationtoHighAltitude19:04
AcclimatizationtoHighAltitude19:04
Acclimation:adaptationproducedinacontrolledlaboratoryenvironment. Generalmechanismsofacclimatization Regulationofacidbaseoffluidsalteredbyhyperventilation Hbsynthesis o Resultsinhigheroxygencarryingcapacity Changesinsympatheticneurohormonalactivity Acidbasereadjustment:hyperventilationandlactate Asaltitudeincrease,PO2decreases,leadingtoanincreaseinventilation whichincreasesalveolarPO2. Hyperventilationresultsindilutionof[PCO2]=washout o DecreaseinalveolarPCO2 o IncreasegradientofCO2betweenbloodandlungs. o ReductioninarterialPCO2. o Decreaseventilationrate. o At3000malveolarPCO2=2410mmHg o AtsealevelalveolarPCO2=40mmHg Kidneysbegintoexcretebicarbonateionsviarenaltubules(urine),thus reducingthebicarbonatepool.Becausethebicarbonatepoolisnow decreasedthereisanassociatedincreaseinrespiratorycenters responsiveness.Sustainhyperventilationathigheraltitude,increasing PO2. LactateParadox
o Initialexposuretoaltitudecausesanincreasein[lactate],thisisoriginally attributedtoareductioninPO2andincreasedanaerobicglycolysis. However,afterfewweeksofacclimatization,[lactate]decreasesatsame relativeworkloadanddespitelackofincreaseinVO2maxoranincreasein tissueoxygenation. o Lactateparadoxisnotreallyaparadoxatall Increasedsympatheticandadrenaloutput(epinephrine)stimulates glycogenolysis(breakdownofglycogen). Increasedglycogenolysisleadstoanincreaseinglycolysisand resultingelevationinallglycolyticintermediates(includingpyruvate). LactateDehydrogenase(LDH)hasaveryhighrateofactivity comparedtootherreactionscompetingforpyruvateasasubstrate. RatioofPyruvate:Lactate=1:10to1:20(dependingonLDH isoform). Therefore,anyelevationinPyruvatewillleadtoanincreaseinLactate regardlessoftheavailabilityofoxygen. o Acclimatization=decreasedepinephrine=decreasedglycogenolysis= decreasedglycolysis=decreasedpyruvate=decreasedlactate HematologicalandCellularChanges ReadjustmentoftherelationshipbetweenPO2andHbO2:shiftstothecurve downandtotheright. o Shiftsresultsfromtheformationof2,3Diphosphoglycerate Redbloodcellsarespecializedfornonoxidativemetabolism 2,3DPGisabyproductofglycolysis 2,3DPGbindslooselywithhomeoglobin,reducingitsaffinityfor oxygen. Levelsareelevatedduringadaptationtoaltitude. Increasedlevelsof2,3DPGcausearightwardshiftinthedissociation curve. Improvesdeliverytothetissuesbutdecreasesamountofbindingat lungs. HematologicalChanges o Increaseintheoxygencarryingcapacity
AcclimatizationtoHighAltitude19:04
Aninitialdecreaseinplasmavolumeleadstoanincreaseinthe hematocritofarterialblood(anapparentincreaseinCaO2) Shiftinvolume:intravascularfluidtointerstitialandintracellular spaces Diuresis:increasedfluidlosswhichmayleadtodehydration Ambientairisdryandcool Increasedevaporationofbodywaterininspiredair Inphysicallyactiveindividuals,fluidlossismorepronounceddueto increasedwaterlossfromsweat. Increasedsynthesisoferythrocytesandhemoglobin IncreaseinthetotalnumberofRBCs Increasedsynthesisandreleaseoferythropoietin(EPO) HypoxiaInducibleFactor(HIF1) o AnimalsrespondtolowPO2byincreasingthetranscriptionofanumberof genesinvolvedinoxygendelivery. o HypoxiaInducibleFactor(HIF1_isthemasterintracellularregulatory factorresponsibleforinductionofthesegenes. o HIF1isaheterodimerictranscriptionfactorconsistingofbetaandalpha subunits. o HIF1isexpressedinalltissuesinresponsetohypoxia. Over40targetgenes,whichfallinto3groups: Oxygendelivery EPO,NitricOxideSynthase,VascularEndothelialGrowthFactor EnergyMetabolism GLUT1,Hexokinase,LDH,PFK,PyruvateKinase CellViability IGF2,IGFbindingproteins o RegulationofHIFbyOxygen
AcclimatizationtoHighAltitude19:04
WhenPO2ishighHIF1alphaissubjectofprolylhydroxylation HydroxylationallowsforinteractionwithVHL VHLrecruitselonginsBandC,Cullin2,RBX1,formingaubiquitin proteinligasecomplex. UpiquitinationtargetstheHIF1alphafordegradationby26S Proteasome WhenPO2islow,HIF1alphaescapesprolylhydroxylationand ubiquitnation ThisallowsHIF1alphatodimerizewithHIF1beta TheHIFdimmercanthenbindwithhypoxiaresponseelementsand combinewithvariouscofactors. Thisleadstoanincreaseintranscriptioninitiationcomplexand mRNAsynthesis Erythropoietin(EPO) o Erythropoietin(EPO)isahormoneproducedbythekidneysthatisa growthfactorforerythrocytes. o EPObindstoreceptorsonhemocytoblastsfoundinbonemarrow. Thesewillbecomeerythrocytes. o EPOcanbeproducedbyDNArecombinanttechniques. MuscleAdaptations Increasedcapillarydiameterandlength Increasedincapillarysize/numberperfiber o Maybeduetodecreaseinfibersize(inabilitytoperformadequately lossinmusclemass) HIFinducesvascularendothelialgrowthfactor(VEGF) Increaseinmitochondrialnumberandconcentration NegativeAspectsofAltitudeAcclimatization BodyMassandComposition o Significantdecreaseinleadbodymassandfatmass
AcclimatizationtoHighAltitude19:04
Timerequiredforacclimatization o Dependentonelevation Onaverage,acclimatizationrequiresatleast2weeks. o Circulatoryfactors:reducedcirculatorycapacity SubmaximalExercise o Oxygenconsumptionremainsstableduetodecreasedcardiacoutput,but enhanced(av)O2difference MaximalExercise o Decreasedbloodflow o DecreaseinmaximalHRandSV
AcclimatizationtoHighAltitude19:04
o Enhancedparasympathetictone AerobicCapacityFollowingAltitude Sealevelperformancedoesnotimproveafterlivingortrainingataltitudedue to: o Lossofmusclemass o ReducedmaximumHR o DecreasedSV CombinationTraining LiveHigh/TrainLow Livingathighaltitudeandtrainingatlealevelshowedthegreatestincreasein VO2max Thestrategycombinesaltitudeacclimatizationandmaintenanceofsealevel training. Researchsuggestthattobenefit: o ThealtitudemustbelocatedatanelevationhighenoughtoraiseEPO.
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
Naturalcaves:gaseoushyperbaricenvironment
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
Deepestcaveexploredtodate:KruberaVoronjaCave(7188ft.deep) Mining Deepestminetodate:TauTonaGoldMine,SouthAfrica(3900m) Partialpressureofoxygenrises,sothegaseousenvironmentdoesnotposea problem.Thebiggestissueinminesandcavesisactuallyventilationbecausethe shaftsandworkspacesaresosmall.Thetemperatureisalsoanissuemine shaftsmustbeairconditionedtomaketheareaworkablebecausetheair temperaturecanbeashighas55degreesC(>135degreeF). Challenges Primary o Largeincreaseinambientpressure(Pb) o Rapidchangesnpressureperunitdistance o Aqueousenvironment Cantbreathehere! Closedventilatorysystemofhumansdoesnotallowforventilation forceswouldrupturealveoli Secondary o Hypothermia(heatloss) o Inefficientmovement o Restrictiveequipment HyperbariaUnderwater Pressureagainstadiversbodyincreasesdirectlywiththedepthofthedive Hyperbariaisproducedvia2forces
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
o Weightofthecolumnofwaterdirectlyabovethediver(hydrostatic pressure) o Weightoftheatmosphereatthewaterssurface Pressurechangesaremuchmorerapidinaqueousenvironmentvs.gaseous environments BoylesLaw Ataconstanttemperaturethevolumeofagivenmassofgasvariesinversely withitspressure. o Whenthepressuredoubles,thevolumeisreducedbyonehalf o Decreasingthepressurebyonehalfexpandsthevolumeofanygasto2x itsprevioussize. EffectofDivingDepthonChangeinAtmosphericPressureandGasVolume Atsealevel(1atm)lungvolumeisapproximately6L.Bythetime10mis reached,theatmosphericpressurehaddoubled. Forevery10metersdescended,1atmisaddedtothepressure BreathHoldDiving Thedurationofabreathholddiveisdependenton o Durationofthebreathholduntilcarbondioxidereachesthebreathhold breakpoint o Relationshipbetweenthediverstotallungcapacityandresiduallung volume ArterialPO2candecreaseto60mmHgwhilePCO2increasesto50mmHg HyperventilationandBreathHolding o Hyperventilationextendsthebreathholdperiodbydecreasingarterial PCO2from40mmHgto15mmHg o BlackoutcanoccurfromacriticalreductioninarterialPO2 o BloodpHwillshiftinthedirectionofincreasedalkalinityduetodecreased [H+] o Reductionincerebralbloodflow ThoracicSqueeze
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
o Compressedlungvolumebelow1.5to1.0Lleadstopulmonarytissue damage o Aslongastotallungvolume>residualvolume,sufficientairremainsin thelungs BelowRVstructuresstarttocollapsebarotraumas o Similarproblemsoccurinotherclosedspaces Middleear Sinuses Teeth FreeDivingHazards:InabilitytoEqualizeInternalandExternalGasPressure o MaskSqueeze:airinthefacemaskorgogglescancreateavacuumwithin themaskonceunderwaterwhichleadstocapillaryrupture o Aerotitis:inabilitytoequalizeearpressureduringdescentduetoupper respiratoryinfection Theeardrumstretchesandmovesinwardwhichcancause hemorrhages o Aerosinusitits:inflamedsinusescancausesinusmembranebleeding duringdescent Snorkeling Snorkelingallowstheswimmertobreathecontinuallywiththefaceimmersed inwater Snorkeldepth/lengthislimitedby2factors o Increasedhydrostaticpressureonthechestcavitywithincreaseddepth Notenoughdifferencecreatedbetweenpulmonaryandenvironment pressurestodrawairin o Increasedpulmonarydeadspacewithincreasingsnorkelvolume Limitsforsnorkeling o Limitedtoadepthof~1meter o Airatsurfacepressure(760mmHg)
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
o Thoraxatambientpressure Ambientpressureincreases1atmforevery10meterdepth At1meterambientpressure=760+76mmHg o Maximalinspirationachievedat80mmHg At1meterdifferenceequalsonly4mmHg Notenoughventilationtoovercomeincreaseddeadspacefromsnorkel +anatomicaldeadspace ScubaDiving Supplyingairunderpressuretopermitcompleteindependencefromthe surface Twoscubadesigns o Opencircuit Tankscontain2000Lofcompressedairfora1hourdivetomoderate depths Compressedairflowsthroughatwostageregulatorthat: Reducestankpressuretoabreathablepressureataparticular depth Releasesairondemandatapressureequaltoambient Problems Airisexhaledintothewaterandthus75%oftheoxygeninthetank iswasted Increasedmass(density)ofairrequiredatincreaseddepthleadsto increasedpulmonaryventilationwhichwilldepletethetankof oxygenveryquickly Significantheatandmoisturelossasinspiredairwarmsand humidifies o Closedcircuit:generallyreservedforpeoplespendingextendedperiodsat depth Operatesinthesamemannerasclosedcircuitspirometry Smallcylinderdeliversoxygentoabag(pressureregulator)from whichthediverbreathes
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
Valvesdirecttheflowofgases Noexpiredairisreleasedintothewaterandthusthedivercanbe submergedfor3hours Problems Potentialforcarbondioxideoutputtoexceeditsrateofabsorption whichwillleadtoarterialcarbondioxidebuildup Highconcentrationsofexpiredoxygencancauseadverse physiologicaloutcomes RiskFactors o Increasedresistancetobreathingwithincreaseddensityofcompressed gasmixtureatdepth o Toxicityofoxygenathighpressures o Anestheticeffectsofnitrogenathighpressure o Excessheatlossfromenvironmentstressandinhaledgasmixture o Freegasdevelopmentingassupersaturatedbodytissues AscentBarotrauma Scubadivingairisadjustedtoambientpressure o Ambientpressuredecreases1ATM/10mascent Failuretoexhale=closedvolume Volumewilldoubleforevery10mascent Overinflatethealveolirupture AirEmbolism Thevolumeofairinhaledunderwaterwillexpandindirectproportiontothe reductioninexternalpressureasthediverascendstothesurface Ifthediverfailstoexhalewhenascendingtothesurfacetheexpandinggas willeventuallyrupturethelungs(lungburst) Airbubblesthatenterthepulmonarysystemasaresultofbreathholdingcan leadtoairembolism.
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
Continuedexpansionoftrappedairwhenascendingtothesurfacecollapses therupturelung(pneumothroax) HenrysLaw Thequantityofgasdissolvedinaliquidatagiventemperaturevariesdirectly with: o Thepressuredifferentialbetweenthegasandliquid o Thesolubilityofthegasinaliquid DecompressionSickness Duringascent,excessnitrogeninthetissuesofthebodybegintoform bubbles Decompressionsicknessoccurswhenthedissolvednitrogenmovesoutof solutionwhileascendingtothesurfacetoorapidlyfollowingadeepdive NitrogenElimination o Stagedecompression Divermakesoneormorestopswhenascendingtothesurface Therateofascentenablestheexcessnitrogentodiffusefromthe tissuesintothebloodwithouttheformationofbubbles Nitrogentendstodissolveintoandoutoffatsmoreslowly. Symptomsappearwithin3hoursofdive o Severejointpain:resultsfromairemboliinsmallarterioloesofthejoints o Neurologicaldisorders:rangingfromconfusion/disorientationandmotor impairmenttoparalysis o Skinmottling:patchydiscolorationduetocutaneousischemia Severecomplicationsofinadequatedecompression o BubblesintheCNStissuecancauselesionsinthebrainandspinalcord o Bubblesinthelungsmaycausechokingandleadtoasphyxia o Bubblesinthebrainandarteriesblocktheflowofblood(airemboli),which canleadtocellulardamageanddeath.
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
ComplicationsofRepeatedDecompressionSickness o Dysbaricosteonecrosis Bubblesreducecapillarybloodflowtobone Airembolileadtobonecelldeath Primarilyobservedintheendofthelongbones TreatmentofInadeqauteDecompression o Portable/collapsiblerecompressionchamber NitrogenNarcosis Thepartialpressureofnitrogenincreaseswiththedepthofthedive,thereby increasingnitrogenexchangeacrossthealveolarmembraneintheblood o Allnoblegasescausenarcosis Chemicallyinertbutnarcoticpropertiesdependnsolubilityinfat (includingelementsofthenervoussystemsuchasthemyelinsheath) o Mechanismofnarcosisisunknown:thoughttobeassociatedwith disruptionofcellmembranefunction Nitrogennarcosis:highpartialpressureofnitrogenintheCNSproducesan anestheticeffect Raptureofthedeep:dissolvednitrogeninitiallyinduceschangesinmental statesimilartothoseobservedwithalcohol o MartinisLaw:10mdescent=1martini HighPressureNervousSyndrome(HPNS) Increasingpressurereversestheeffectsofnarcosis o Hyperexcitability o Mechanismisunknown:fluidityofmembranes,NTrelease,postsynaptic effects Occursatpressure>200m o Formsabarriertoverydeepdiving
HyperbaricEnvironment:PhysiologicalChallengesand Response19:04
Symptoms o Rapidtremor,poorcoordination,involuntaryjerkingmovements,micro sleep Noevidenceofadaptationinhumans Additionofnarcoticgasesdecreasestheeffectandincreasesmaximum depth o trimix:helium,nitrogen,oxygen o Heliox:heliumandoxygen o Nitrox:airenrichedwithoxygen OxygenPoisoning Occurswhenbreathing100%oxygenfortoolong o 1ATM>12hours o 7ATM>5minutes Breathinghighpressureofoxygencan: o Irritaterespiratorypassagesandleadtobronchopneumonia o ConstrictcerebralbloodvesselsandalterCNSfunction Canleadtoconvulsions o Bluntcarbondioxideelimination:pHshift HeliumandOxygen Animalsbreathingan80%helium/20%oxygenmixcanbedecompressedin 1/6thedecompressiontimeofananimalbreathingnormalair(80:20,N:O) Humansubjectsbreathing80%helium/20%oxygenhavenoapparent problemswithhelioxdecompressionschedulesthatarethetimerequired fornormalairbreathingdives. Abilityforhumanstofunctionclearheadedatdepthswhereairbreathing diverswereincapacitatedbynitrogennarcosis. Negativeeffectsofbreathinghelium o HPSisnottotallyavoided o Changesinvoicecharacteristics o Considerableheatloss