OfficialreprintfromUpToDate

www.uptodate.com2017UpToDate

Simpleandmixedacidbasedisorders

Authors: MichaelEmmett,MD,BiffFPalmer,MD
SectionEditor: RichardHSterns,MD
DeputyEditor: JohnPForman,MD,MSc

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jun2017.|Thistopiclastupdated:Oct18,2016.

INTRODUCTIONEachday,adultsgeneratelargeamountsofacidsthatmustbeexpired,excreted,
metabolizedtononchargedneutralmolecules,and/orbufferedtoavoidfatalacidemia.Theseacidsareofthree
majorclasses:

Approximately15,000mmol(considerablymorewithexercise)ofcarbondioxide(CO2)isproducedeach
day,whichcombineswithwatertoformcarbonicacid(H2CO3).

Metabolicreactionsgenerateseveralthousandmmolperdayoforganicacids,suchaslacticacidandcitric
acid.Theseacidsaremetabolizedtoneutralproducts(suchasglucose)andtoCO2andwater.Normally,
thegenerationandutilizationratesoftheseorganicacidsareequalsothattheirsteadystateconcentration
intheextracellularfluidisrelativelylowandstable.

Approximately50to100meqofnonvolatileacidisproducedeachday(mostlysulfuricacidderivedfromthe
metabolismofsulfurcontainingaminoacidsinthediet).

Acidbasebalanceismaintainedbynormalpulmonaryexcretionofcarbondioxide,metabolicutilizationof
organicacids,andrenalexcretionofnonvolatileacids.

Renalexcretionofacidisachievedbycombininghydrogenionswitheitherurinarybufferstoformtitratableacid,
suchasphosphate(HPO4+H+H2PO4),urate,andcreatinine,orwithammoniatoformammonium(NH3
+H+NH4+)[1].Whenincreasedquantitiesofacidmustbeexcretedbythekidney,themajoradaptive
responseisanincreaseinammoniaproduction(derivedfromthemetabolismofglutamine)witharesultant
increaseinammoniumexcretionintotheurine.

Acidbasestatusisusuallyassessedbymeasuringthecomponentsofthebicarbonatecarbondioxidebuffer
systeminblood:

DissolvedCO2+H2OH2CO3HCO3+H+

Whenbloodgasanalysisiscarriedout,thepartialpressureofCO2(PCO2)andthepHareeachmeasuredusing
analyticalelectrodes.Theserumbicarbonate(HCO3)concentrationisthencalculatedwiththeHenderson
Hasselbalchequation.Generally,thePCO2isreportedinmmHg,andHCO3inmeq/L:

pH=6.10+log([HCO3][0.03xPCO2])

wherethepHisequalto(log[H+])6.10isthenegativelogofKa(logKa),whichisthedissociationconstantfor
thisreaction0.03isthesolubilitycoefficientforCO2inbloodandthePCO2isthepartialpressureofcarbon
dioxideinblood[2].
WhentheHCO3ismeasuredinvenousblood,itisusuallymeasureddirectlyas"totalCO2"withanionselective
electrode.Thedirectlymeasuredvenous"totalCO2"isgenerallyabout2meq/Lgreaterthanthesimultaneously
calculatedarterialHCO3.

NORMALVALUESACCORDINGTOSITEOFSAMPLINGTherangeofnormalvaluesforacidbase
parametersisdifferentforarterialandvenoussamplesandalsovariesamonglaboratories.Theseissuesare
discussedindetailelsewherebutwillbebrieflysummarizedhere.(See"Arterialbloodgases"and"Venousblood
gasesandotheralternativestoarterialbloodgases".)

ArterialbloodgassampleForanarterialbloodgassample,thenormalrangeforpHis7.36to7.44for
bicarbonate(HCO3)concentration,21to27meq/LandforPCO2,36to44mmHg(4.8to5.9kPa).

PeripheralvenousbloodgassampleNormalvaluesforperipheralvenousbloodgasesdifferfromthoseof
arterialbloodduetotheuptakeandbufferingofmetabolicallyproducedCO2inthecapillarycirculationandthe
additionoforganicacidsproducedbythetissuebeddrainedbythevein.Ifatourniquetisusedtofacilitate
phlebotomy,itshouldbereleasedaboutoneminutebeforethesampleisdrawntoavoidchangesinducedby
ischemia[3].

Indifferentstudies,therangeforperipheralvenouspHisapproximately0.02to0.04pHunitslowerthanin
arterialblood,theHCO3concentrationisapproximately1to2meq/Lhigher,andthePCO2isapproximately3to
8mmHg(0.4to1.1kPa)higher[46].Ifvenousmeasurementsareusedforserialmonitoring,periodiccorrelation
witharterialmeasurementsshouldbeperformed.(See"Arterialbloodgases".)

CentralvenoussampleCentralvenoussamplesmaybeanalyzedinpatientswithcentralvenouscatheters.
ThecentralvenouspHisusually0.03to0.05pHunitslowerthaninarterialbloodandthePCO2is4to5mmHg
(0.5to0.7kPa)higher,withlittleornoincreaseinserumHCO3[7,8].

DEFINITIONSOFACIDBASEDISORDERSThefollowingdefinitionsofacidbasedisordersarebasedupon
principlesoftheHendersonHasselbalchequation:

AcidemiaAnarterialpHbelowthenormalrange(lessthan7.36).

AlkalemiaAnarterialpHabovethenormalrange(greaterthan7.44).

AcidosisAprocessthattendstolowertheextracellularfluidpH(hydrogenionconcentrationincreases).
Thiscanbecausedbyafallintheserumbicarbonate(HCO3)concentrationand/oranelevationinPCO2.

AlkalosisAprocessthattendstoraisetheextracellularfluidpH(hydrogenionconcentrationdecreases).
ThiscanbecausedbyanelevationintheserumHCO3concentrationand/orafallinPCO2.

MetabolicacidosisAdisorderthatreducestheserumHCO3concentrationandpH.(See"Approachtothe
adultwithmetabolicacidosis".)

MetabolicalkalosisAdisorderthatelevatestheserumHCO3concentrationandpH.(See"Pathogenesisof
metabolicalkalosis"and"Causesofmetabolicalkalosis".)

RespiratoryacidosisAdisorderthatelevatesthearterialPCO2andreducesthepH.

RespiratoryalkalosisAdisorderthatreducesthearterialPCO2andelevatesthepH.

SimpleacidbasedisorderThepresenceofoneoftheabovedisorderswiththeappropriaterespiratoryor
renalcompensationforthatdisorder.(See'Compensatoryrespiratoryandrenalresponses'below.)
 MixedacidbasedisorderThesimultaneouspresenceofmorethanoneacidbasedisorder.Mixedacid
basedisorderscanbesuspectedfromthepatient'shistory,fromalesserorgreaterthanexpected
compensatoryrespiratoryorrenalresponse,andfromanalysisoftheserumelectrolytesandaniongap.As
anexample,apatientwithseverevomitingwouldbeexpectedtodevelopametabolicalkalosisduetothe
lossofacidicgastricfluid.If,however,thepatientalsodevelopedhypovolemicshockfromthefluidloss,the
ensuinglacticacidosiswouldlowertheelevatedserumHCO3possiblytobelownormalvalues,resultingin
acidemia.(See'Mixedacidbasedisorders'below.)

COMPENSATORYRESPIRATORYANDRENALRESPONSES

GeneralprinciplesTheHendersonHasselbalchequationdescribedaboveshowsthatthepHisdetermined
bytheratiooftheserumbicarbonate(HCO3)concentrationandthePCO2,notbythevalueofeitheronealone.
Eachofthesimpleacidbasedisordersisassociatedwithacompensatoryrespiratoryorrenalresponsethat
limitsthechangeinratioandthereforeinpH(figure1)[9].

WhenametabolicacidbasedisorderreducestheserumHCO3(metabolicacidosis)orincreasestheHCO3
(metabolicalkalosis),thereshouldbeanappropriatedegreeofrespiratorycompensationmovingthePCO2
inthesamedirectionastheserumHCO3(fallinginmetabolicacidosisandrisinginmetabolicalkalosis).
TherespiratorycompensationmitigatesthechangeintheratiooftheserumHCO3toPCO2andthereforein
thepH.Respiratorycompensationinmetabolicacidosisoralkalosisisarapidresponse.Withmetabolic
acidosis,forexample,theresponsebeginswithin30minutes[10]andiscompletewithin12to24hours[11].

WhenarespiratoryacidbasedisordercausesthePCO2toincrease(respiratoryacidosis)ordecrease
(respiratoryalkalosis),compensationoccursintwophases.Thereisanimmediate,smallchangeinserum
HCO3(inthesamedirectionasthePCO2change),whichisduetowholebodybufferingmechanisms.Ifthe
respiratorydisorderpersistsformorethanminutestohours,thekidneysrespondbyproducinglarger
changesinserumHCO3(again,inthesamedirectionasthePCO2).TheseHCO3changesmitigatethe
changeinpH.Renalcompensationsaremediatedbyincreasedhydrogenionsecretion(whichraisesthe
serumHCO3concentration)inrespiratoryacidosisanddecreasedhydrogenionsecretionandurinaryHCO3
lossinrespiratoryalkalosis.Therenalcompensationtakesthreetofivedaysforcompletion.Asaresult,the
expectedfindingsareverydifferentinacute(wholebodybufferingwithoutsignificantrenalcompensation)
andchronic(fullrenalcompensation)respiratoryacidbasedisorders.(See'Respiratoryacidbasedisorders'
below.)

Thecompensatoryrenalandrespiratoryresponsesarethoughttobemediated,atleastinpart,byparallelpH
changeswithinsensoryandregulatorycellsincludingrenaltubulecellsandcellsintherespiratorycenter[12].
Themagnitudeofthecompensatoryresponseisproportionaltotheseverityoftheprimaryacidbase
disturbance.

ItfollowsfromtheabovediscussionthatahighHCO3concentrationmaybeduetometabolicalkalosisor
compensationforchronicrespiratoryacidosis.Conversely,alowHCO3maybeduetometabolicacidosisor
compensationforchronicrespiratoryalkalosis.AnalogousissuesapplytoahighorlowPCO2.Atleasttwoofthe
threevariablesintheHendersonHasselbalchequation(pH,HCO3,PCO2)mustbemeasuredtoassessanacid
basedisorder(andiftwoaremeasured,thethirdcanbededuced).

Theexpecteddegreeofcompensationforeachacidbasedisorderhasbeendeterminedempiricallyby
observationsinhumanswitheitherspontaneousorexperimentallyinducedsimpleacidbasedisorders(figure1).
ThedegreeofcompensationisusuallydefinedbythedecreaseorincreaseinarterialPCO2fromitsnormal
range(inmetabolicacidbasedisorders)orthedecreaseorincreaseinserumHCO3fromitsnormalrange(in
respiratoryacidbasedisorders).Thisapproachpresumesthatthepatienthadnormalvaluespriortotheonsetof
theacidbasedisorder.Thus,intheabsenceofknownbaselinevalues,thereisthepotentialforerrorifthe
patient'sacidbasestatuswasnotnormalattheonsetofthedisorder.

Metabolicacidbasedisorders

MetabolicacidosisRespiratorycompensationformetabolicacidosiscausesthearterialPCO2tofall
approximately1.2mmHg(0.16kPa)forevery1meq/LreductionintheserumHCO3concentration[9,13].The
respiratoryresponsetometabolicacidosisbeginswithin30minutes[10]andiscompletewithin12to24hours
[11].Thereisnolaginrespiratorycompensationwhenmetabolicacidosisdevelopsslowly(eg,4meq/Lfallin
serumHCO3over15hours)[11].Aninabilitytogeneratetheexpectedrespiratoryresponseisusuallyindicative
ofsignificantunderlyingrespiratoryorneurologicdisease,butcanalsooccurattheonsetofacutemetabolic
acidosisbeforetherehasbeenadequatetimeforrespiratorycompensationtofullydevelop[14].

Severalotherpredictiverelationshipshavebeenproposedtodeterminetheappropriaterespiratorycompensation
tometabolicacidosis.Theseinclude:

ArterialPCO2=1.5xserumHCO3+82(Winters'equation)[15]

ArterialPCO2=SerumHCO3+15

ArterialPCO2shouldbesimilartothedecimaldigitsofthearterialpH(eg,25mmHgwhenthearterialpHis
7.25,asettinginwhichtheserumHCO3concentrationwouldbeapproximately11meq/L)[16]

Theseformulasandrulesgenerallygivesimilarresults.Becausetherearenodataoncomparativeaccuracy(see
'Case2'below),thereadermayusetherelationshipruleheorshefindseasiesttorememberandimplement.

Thereisalimittothemaximumrespiratorycompensationthatcanbeattained.Withseveremetabolicacidosis
(eg,serumHCO3concentrationlessthan6meq/L),thePCO2canfallnolowerthan8to12mmHg(1.1to1.6
kPa).Inaddition,thedurationthatsuchcompensationcanbemaintainedislimitedduetorespiratorymuscle
fatigue.

Inadditiontoassessingtherespiratorycompensation,anothercomponentintheevaluationofpatientswith
metabolicacidosisiscalculationoftheserumaniongaptodeterminewhetheritisnormalorelevated.Metabolic
acidosismaybeofthehighaniongaptype,normalaniongaptype(hyperchloremic),orcombinednormaland
elevatedaniongapacidosis.Asanexample,withseverediarrhea,lossofbicarbonateinthestooltypically
generatesanormalaniongapmetabolicacidosis,buttheresultinghypovolemiacanalsoleadtolacticacidosis
andrenaldysfunctionwithahighaniongapacidosis.Withhighaniongapmetabolicacidosis,comparingthe
changeinaniongap(orthedeltaaniongap)withthechangeinbicarbonate(orthedeltabicarbonate)maybe
helpful.Theseissuesarediscussedindetailelsewhere.(See"Approachtotheadultwithmetabolicacidosis",
sectionon'Physiologicinterpretationoftheserumaniongap'and"Thedeltaaniongap/deltaHCO3ratioin
patientswithahighaniongapmetabolicacidosis".)

MetabolicalkalosisTherespiratorycompensationtometabolicalkalosisshouldraisethePCO2byabout
0.7mmHg(0.09kPa)forevery1meq/LelevationintheserumHCO3concentration[9,17,18].Insevere
metabolicalkalosis,thearterialPCO2usuallydoesnotincreaseabove55mmHg(7.3kPa)[17].

RespiratoryacidbasedisordersThecompensatoryresponsetorespiratoryacidbasedisordersoccursin
twostages:

TheinitialacuteresponseisgeneratedbyavarietyofpHbufferingmoleculespresentinallofthefluid
compartmentsofthebody(ie,totalbodybuffering).ReactionswiththesemoleculescausetheserumHCO3
toincrease(inrespiratoryacidosis)ordecrease(inrespiratoryalkalosis)withinminutes.Theacuteresponse
isrelativelymodest.
 Alargerresponsegeneratedbythekidneyiscalledchroniccompensation.Thisresponsebeginssoonafter
theonsetoftheprimaryrespiratorydisorderbutrequiresthreetofivedaystobecomecomplete.Because
ofthisvariationwithtime,differentcompensatoryresponsesareexpectedwithacuteandchronicrespiratory
disorders:

Withchronicrespiratoryacidosis,thekidneyincreasesacidexcretionintheformoftitratableacidand
ammoniumthatgeneratesadditionalHCO3renaltubuleHCO3reabsorptionisalsoincreased,which
maintainsthehigherHCO3concentration(figure2)[19,20].

Withchronicrespiratoryalkalosis,thekidneybothreducesacidexcretion(whichresultsinapositive
acidbalancethatreducestheserumHCO3concentration)andexcretessomeHCO3(whichfurther
reducestheserumHCO3concentration).

Theserenalresponsesarecarefullyregulated.Asanexample,administeringexogenousHCO3inthe
settingofchronicrespiratoryacidosisandrelativelynormalrenalfunctionresultsintheurinaryexcretion
oftheexcessalkaliwithoutafurtherelevationintheserumHCO3concentration[21].

RespiratoryacidosisThecompensatoryresponsetoacuterespiratoryacidosisincreasestheserum
HCO3concentrationbyabout1meq/Lforevery10mmHg(1.3kPa)elevationinthePCO2(figure3)[9,22].Ifthe
elevatedPCO2persists,theserumHCO3willcontinuetograduallyincreaseand,afterthreetofivedays,the
disorderisconsideredchronic.StudiesmostlyperformedinhospitalizedpatientsfoundthattheserumHCO3
increasesby3.5to4meq/Lforevery10mmHgelevationinPCO2inpatientswithchronicrespiratoryacidosis
[9,19,20,23].However,alaterstudyinstableoutpatientswithchronicrespiratoryacidosisfoundagreater
compensatoryriseinserumHCO3ofabout5meq/Lper10mmHg(1.3kPa)elevationinPCO2[24].

Thecompensatoryresponsetomildtomoderatechronicrespiratoryacidosis(PCO2lessthan70mmHg[9.3
kPa])resultsinanarterialpHthatisusuallymodestlyreduced[9,19,20,23]orinthelownormalrange(figure2)
[24].Thus,moderatetosevereacidemiainapatientwithmildtomoderatechronicrespiratoryacidosisisusually
indicativeofconcurrentmetabolicacidosisorsuperimposedacuterespiratoryacidosis.Conversely,anarterialpH
of7.40orhighersuggestsaconcurrentmetabolicalkalosisoracuterespiratoryalkalosis.

RespiratoryalkalosisThecompensatoryresponsetoacuterespiratoryalkalosisreducestheserum
HCO3concentrationby2meq/Lforevery10mmHg(1.3kPa)declineinthePCO2(figure3)[9,22].Ifthe
reducedPCO2persistsformorethanthreetofivedays,thenthedisorderisconsideredchronicandtheserum
HCO3concentrationshouldfallbyabout4to5meq/Lforevery10mmHg(1.3kPa)reductioninthePCO2(figure
4)[9,25].

DIAGNOSISTherearefourprimaryacidbasedisorders:metabolicacidosis,metabolicalkalosis,respiratory
acidosis,andrespiratoryalkalosis.Becausetherenalcompensationtorespiratorydisorderstakesthreetofive
daystocomplete,theprimaryrespiratorydisorderscanbefurtherdividedintoacuteandchronicrespiratory
acidosisandrespiratoryalkalosis.

InitialevaluationAccuratediagnosisofanacidbasedisorderrequiresmeasurementofserumelectrolytesto
determinetheserumHCO3concentration,theserumpotassium(lookingforhypokalemiaorhyperkalemiawhich
canaccompanymanymetabolicacidbasedisorders),andtheserumsodiumandchlorideconcentrationsto
detectpossiblehyponatremiaorhypernatremiaandcalculationoftheserumaniongap.Inaddition,inpatients
withahighaniongapmetabolicacidosis,analysisoftheincreaseoftheaniongapfromitsbaselinedividedby
thereductioninbicarbonatefromnormal(ie,thedeltaaniongapdividedbythedeltabicarbonate,or
"delta/delta")maybehelpful.Theseissuesarediscussedindetailelsewhere.(See"Approachtotheadultwith
metabolicacidosis",sectionon'Physiologicinterpretationoftheserumaniongap'and"Thedeltaaniongap/delta
HCO3ratioinpatientswithahighaniongapmetabolicacidosis".)
AdefinitivediagnosisofacidbasedisordersrequiresmeasurementofthearterialpHandPCO2aswellasthe
serumchemistriestoidentifytheunderlyingdisorderandtodeterminewhetheramixedacidbasedisorderexists.
However,measurementofarterialpHisnotalwaysrequired.Whenthehistoryandserumelectrolytesclearly
pointtowardaparticulardiagnosis,apresumptivediagnosiscanbemade.Asanexample,arterialbloodgas
analysismightnotberequiredinapreviouslyhealthypatientwitharecenthistoryofseverediarrheawhohasa
lowserumbicarbonate,hypokalemia,andanormalaniongap.Thispatientcanbeassumedtohaveanonanion
gapmetabolicacidosisbecausethereisnoreasontosuspectchronicrespiratoryalkalosis(adisorderinwhicha
lowserumbicarbonatedevelopsasacompensatoryresponse).

MeasurementofperipheralvenouspHandPCO2isanalternativediagnosticprocedurethatisalessinvasive
andmoreconvenientapproachthanarterialmeasurements.However,venousmeasurementshavesome
importantlimitations.Asaresult,arterialmeasurementsarepreferred.Ifvenousmeasurementsareusedfor
serialmonitoring,periodiccorrelationwitharterialmeasurementsshouldbeperformed.Theseissuesare
discussedindetailelsewhere.(See'Normalvaluesaccordingtositeofsampling'above.)

Wesuggestthefollowingthreestepapproachinmostpatients:

Step1:Establishtheprimarydiagnosis:

MetabolicacidosisischaracterizedbyalowserumHCO3andalowarterialpHtheserumaniongap
maybeincreasedornormal.

MetabolicalkalosisischaracterizedbyanelevatedserumHCO3andanelevatedarterialpH.

RespiratoryacidosisischaracterizedbyanelevatedarterialPCO2andalowarterialpH.

RespiratoryalkalosisischaracterizedbylowarterialPCO2andanelevatedarterialpH.

Withtheexceptionofchronicrespiratoryalkalosisandmildtomoderaterespiratoryacidosis(see'Mixed
acidbasedisorders'below),compensatoryresponsesdonotusuallyreturnthearterialpHtonormal.

Thus,anormalarterialpHinthepresenceofsubstantialchangesinbothserumHCO3andarterial
PCO2isusuallyindicativeofamixedacidbasedisorder(whichcouldincludeaniatrogenicacute
respiratoryalkalosisifdiscomfortfromthearterialpuncturecausesthepatienttohyperventilate).

Step2:Assessthedegreeofcompensationasdefinedabovefortheindividualdisorders.Asubstantially
reducedorexcessivelevelofcompensationisindicativeofamixedacidbasedisorder.(See'Compensatory
respiratoryandrenalresponses'above.)

Thecompensatoryresponsemustbecorrelatedwiththehistory.Thisisparticularlytrueinrespiratoryacid
basedisorderssincetherenalcompensationoccursoverthreetofivedays.Thus,theexpectedlevelof
compensationissmallerwithacuterespiratorydisorderscomparedwithchronicrespiratorydisorders.As
notedabove,thenormalcompensatoryresponsetorespiratoryacidosisisanincreaseintheserumHCO3
concentrationbyabout1meq/Lforevery10mmHg(1.3kPa)elevationinthePCO2acutelyandabout3.5to
5meq/Lforevery10mmHg(1.3kPa)elevationinthePCO2iftheunderlyingrespiratoryproblempersistsfor
threetofivedaysormore.(See'Respiratoryacidosis'above.)

Step3:Determinewhetherornottheaniongapiselevated.Thisisespeciallyimportantforpatientswith
metabolicacidosis.Iftheaniongapisincreased,thenanalyzetheratiooftheincreaseinaniongaptothe
decreaseintheHCO3concentration.Thisiscalledthedeltaaniongap/deltaHCO3ratio.Interpretationof
theaniongapandthedeltaaniongap/deltaHCO3ratioarediscussedelsewhere.(See"Approachtothe
adultwithmetabolicacidosis",sectionon'Physiologicinterpretationoftheserumaniongap'and"Thedelta
aniongap/deltaHCO3ratioinpatientswithahighaniongapmetabolicacidosis".)
Thefinalstepistoestablishtheclinicaldiagnosis.Oncetheacidbasedisorder,ordisorders,isidentified,the
underlyingcauseorcausesofeachdisordershouldbedeterminedandaddressed.

Case1Apatientwithanunknownpasthistorypresentswithrespiratorydistress.ArterialbloodshowsapH
of7.32,PCO2of70mmHg(9.3kPa),andHCO3of35meq/L.TheHCO3isapproximately11meq/Labovethe
normalrange,andthePCO2isapproximately30mmHgabovethenormalrange.Thesevaluesarecompatible
withadiagnosisofasimple(fullycompensated)chronicrespiratoryacidosis.However,theresultsarealso
compatiblewithamixedacidbasedisorder.Asanexample,anacuterespiratoryacidosiscausingariseinPCO2
to70mmHg(9.3kPa)shouldincreasetheserumHCO3byabout3meq/Ltoabout27meq/L.If,beforetheonset
ofrespiratoryacidosis,vomiting(ametabolicalkalosis)hadincreasedtheserumbicarbonateby8meq/L,the
combinedeffectsofacuterespiratoryacidosisandmetabolicalkalosis(amixedacidbasedisorder)wouldresult
inidenticallaboratoryfindings.Thehistoryusuallyhelpstodistinguishamongthesepossibilities.

Case2Apatientpresentswithdiarrhea.ArterialbloodshowsapHof7.24,PCO2of24mmHg(3.2kPa),
andHCO3or10meq/L.ThelowpHindicatesacidemia,andthelowserumHCO3concentrationindicates
metabolicacidosis.TheserumHCO3concentrationof10meq/Lisapproximately14meq/Lbelownormal.This
shouldstimulaterespiratorycompensationanda17mmHg(2.3kPa)fallinthePCO2(14x1.2=17)from40
to23mmHg(5.3to3.1kPa).Theseresultsareconsistentwithasimplemetabolicacidosis.Theotherestimation
equationsforthedegreeofcompensationcitedabovegivesimilarresults.Winters'equationpredictsaPCO2of
23mmHg(1.5x10+82)the"HCO3+15"rulepredictsaPCO2of25mmHg(3.3kPa).Inaddition,thePCO2
isthesameasthedecimaldigitsofthearterialpH.(See'Metabolicacidosis'above.)

APCO2significantlyhigherthantheexpectedvaluewouldbeconsistentwithaconcurrentrespiratoryacidosis,
asmightoccur,forexample,ifthepatientwereobtundedandhadrespiratorycenterdepression.If,ontheother
hand,thePCO2werelowerthan20mmHg(2.7kPa),thenaconcurrentrespiratoryalkalosiswouldbepresent.
Thecombinationofmetabolicacidosisandrespiratoryalkalosisisoftenseenwithsalicylateintoxicationorseptic
shock.(See"Salicylate(aspirin)poisoninginadults",sectionon'Acidbaseabnormalities'.)

MixedacidbasedisordersSomepatientshavetwo,three,ormorerelativelyindependentacidbase
disorders.Thesemixeddisordersincludecombinationsofmetabolicdisorders(eg,vomitinginducedmetabolic
alkalosisplushypovolemiainducedlacticacidosis),mixedmetabolicandrespiratorydisorders(eg,metabolic
acidosisandrespiratoryalkalosisinsalicylateintoxication),andmorecomplexcombinations.

Asdiscussedintheprecedingsection,theevaluationofpatientswithacidbasedisordersinitiallyrequires
identificationofthemajordisorder,andthendeterminationofwhetherornotthedegreeofcompensationis
appropriate.Ifthecompensationisnotappropriate,thenthisisindicativeofasecondacidbasedisorder(ie,a
mixedacidbasedisorderispresent).Thefollowingexamplesareillustrative:

Ifmetabolicacidosisistheprimarydisorder,anarterialPCO2substantiallyhigherthantheexpected
compensatoryresponsedefinesthemixeddisorderofmetabolicacidosisandrespiratoryacidosis,whilean
arterialPCO2substantiallylowerthanexpecteddefinesthemixeddisorderofmetabolicacidosisand
respiratoryalkalosis(whichcouldbeproducedbyacutehyperventilationduetothediscomfortofobtaining
thebloodsample).

Ifrespiratoryacidosisisthemajordisorder,thentheserumHCO3shouldbeappropriatelyincreased.Ifthe
serumHCO3isnotashighasexpected,thenmetabolicacidosisalsoexistsandthearterialpHmaybe
substantiallyreduced.Bycontrast,iftheserumHCO3ishigherthanexpected,thenmetabolicalkalosis
complicatestherespiratoryacidosisandthearterialpHmaybeinappropriately"normal."

Inpatientswithahighaniongapmetabolicacidosis,adiagnosisofamixedmetabolicacidosisandametabolic
alkalosisisgenerallysuggestedbycalculationandinterpretationofthedeltaaniongapandthedeltaHCO3.
(See"Thedeltaaniongap/deltaHCO3ratioinpatientswithahighaniongapmetabolicacidosis".)

Case3Determiningtheappropriatecompensatoryresponsemaybemoredifficultwithrespiratoryacid
basedisordersbecausecompensatoryresponsesdifferinacuteandchronicdisturbances.Considerthefollowing
arterialbloodvalues:pH7.27,PCO270mmHg(9.3kPa),andHCO331meq/L.ThelowpHandhypercapnia
indicatethatthepatienthasrespiratoryacidosis.Ifthisisacutehypercapnia,thenthe30mmHg(4kPa)risein
PCO2shouldincreasetheserumHCO3concentrationbyabout3meq/L(toabout27meq/L).Ifthisischronic
hypercapnia,theserumHCO3shouldincreasebyabout11meq/L(toabout35meq/L).Theobservedvalueof31
meq/Lisbetweentheseexpectedlevelsandcouldhavemultipleexplanations,including:

ChronicrespiratoryacidosiswithasuperimposedmetabolicacidosisthathasreducedtheserumHCO3from
35to31meq/L.Thismightoccurinapatientwithchronicobstructivepulmonarydiseasewhodeveloped
diarrheaduetoviralgastroenteritisorlacticacidosisfromsepsis.

AcuterespiratoryacidosiswithasuperimposedmetabolicalkalosisthathasincreasedtheHCO3from27to
31meq/L.Thiscouldoccurinapatientwithrespiratorydepressionduetoasedatingdrugwhoalso
developedvomitingorwastakingdiuretics.

Acuterespiratoryacidosissuperimposedonmildchronicrespiratoryacidosis.Suppose,forexample,thata
patienthaschronicrespiratoryacidosiswithaPCO2of55mmHg(7.3kPa)andanappropriateserumHCO3
of30meq/L.Thepatientthendevelopspneumonia,whichacutelyincreasesthePCO2to70mmHg(9.3
kPa).TheserumHCO3wouldrisefurthertoabout31meq/L.

Acuterespiratoryacidosisthatisevolvingintoachronicdisorder(betweenoneandthreedays).

Thus,thecorrectdiagnosisinaprimaryrespiratoryacidbasedisordercanbeestablishedonlywhencorrelated
withtheclinicalhistoryandphysicalexamination.Thisistrueevenwhenthearterialbloodvaluesappearto
representasimpledisorder.IftheserumHCO3concentrationhadbeen35meq/Linthisexample,thefindings
wouldhavebeencompatiblewithanuncomplicatedchronicrespiratoryacidosis.However,similarfindingscould
havebeeninducedbyacuterespiratoryacidosisplusmetabolicalkalosis.Thehistoryusuallyhelpstodistinguish
amongthepossibilities.(See'Respiratoryacidbasedisorders'above.)

SUMMARY

Acidbasestatusisusuallyassessedbymeasuringthecomponentsofthebicarbonatecarbondioxidebuffer
systeminblood.Whenbloodgasanalysisiscarriedout,thepartialpressureofCO2(PCO2)andthepHare
eachmeasuredusingelectrodes,andthebicarbonate(HCO3)concentrationiscalculatedwiththe
HendersonHasselbalchequation.WhentheHCO3ismeasuredinvenousblood,itisusuallymeasured
directlyas"totalCO2"withanionselectiveelectrode.Thedirectlymeasuredvenous"totalCO2"isgenerally
about2meq/LgreaterthanthesimultaneouslycalculatedarterialHCO3.(See'Introduction'above.)

Therangeofnormalvaluesforacidbaseparametersisdifferentforarterialandvenoussamplesandalso
variesamonglaboratories(see'Normalvaluesaccordingtositeofsampling'above):

Foranarterialsample,thenormalrangeforpHis7.36to7.44forbicarbonate(HCO3)concentration,
21to27meq/LandforPCO2,36to44mmHg(4.9to5.9kPa).

Foraperipheralvenoussample,therangeforpHisapproximately0.02to0.04pHunitslowerthanin
arterialbloodforHCO3concentration,approximately1to2meq/LhigherandforPCO2,approximately
3to8mmHg(0.4to1.1kPa)higher.

Foracentralvenoussample,therangeforpHisusually0.03to0.05pHunitslowerthaninarterial
blood,andthePCO2is4to5mmHg(0.5to0.7kPa)higher,withlittleornoincreaseinserumHCO3.
 Eachsimpleacidbasedisorderisnormallyassociatedwithacompensatoryresponsethatreducesthe
changeintheHCO3/PCO2ratioandthereforeinpH(figure1).(See'Metabolicacidbasedisorders'above
and'Respiratoryacidbasedisorders'above.)

Asimpleacidbasedisorderincludestheinitialdisturbanceofacidbasestatusandtheappropriatedegreeof
compensationforthatdisturbance.(See'Definitionsofacidbasedisorders'above.)

Thesimultaneouspresenceofmorethanoneacidbasedisturbanceiscalledamixedacidbasedisorder.
Mixedacidbasedisorderscanbesuspectedfromthepatient'shistory,fromalesserorgreaterthan
expectedcompensatoryresponse,andfromanalysisofthedeltaaniongapanddeltaHCO3.(See
'Definitionsofacidbasedisorders'above.)

Wesuggestthefollowingthreestepapproachfortheevaluationofmostpatientswithacidbasedisorders
(see'Initialevaluation'above):

Establishtheprimarydiagnosis.MetabolicacidosisischaracterizedbyalowserumHCO3andalow
arterialpHtheserumaniongapmaybeincreasedornormal.Metabolicalkalosisischaracterizedbyan
elevatedserumHCO3andanelevatedarterialpH.Respiratoryacidosisischaracterizedbyanelevated
arterialPCO2andalowarterialpH.RespiratoryalkalosisischaracterizedbylowarterialPCO2andan
elevatedarterialpH.(See'Initialevaluation'above.)

Assessthedegreeofcompensationasdefinedabovefortheindividualdisorders.Ifcompensationis
inadequateorexcessive,thisisindicativeofamixedacidbasedisorder.(See'Initialevaluation'above
and'Compensatoryrespiratoryandrenalresponses'above.)

Determinewhetherornottheaniongapiselevated.Ifitis,thenanalyzetheratiooftheincreasein
aniongaptothedecreaseintheHCO3concentration.Thisisthedeltaaniongap/deltaHCO3ratio.
Whenananiongapacidosisexists,thesechangesshouldbequantitativelysimilartooneanotherthat
is,thedeltaaniongapshouldbeofsimilarmagnitudeasthedeltaHCO3.(See'Initialevaluation'
above.)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

REFERENCES

1.RoseBD,PostTW.ClinicalPhysiologyofAcidBaseandElectrolyteDisorders,5thed,McGrawHill,New
York2001.p.328.
2.RoseBD,PostTW.ClinicalPhysiologyofAcidBaseandElectrolyteDisorders,5thed,McGrawHill,New
YorkCity2001.p.307.
3.CengizM,UlkerP,MeiselmanHJ,BaskurtOK.Influenceoftourniquetapplicationonvenousblood
samplingforserumchemistry,hematologicalparameters,leukocyteactivationanderythrocytemechanical
properties.ClinChemLabMed200947:769.
4.KellyAM,KyleE,McAlpineR.VenouspCO(2)andpHcanbeusedtoscreenforsignificanthypercarbiain
emergencypatientswithacuterespiratorydisease.JEmergMed200222:15.
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PO2ininitialemergencydepartmentassessment.EmergMedJ200724:569.
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 7.MalinoskiDJ,ToddSR,SloneS,etal.Correlationofcentralvenousandarterialbloodgasmeasurements
inmechanicallyventilatedtraumapatients.ArchSurg2005140:1122.
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9.AdroguHJ,MadiasNE.Secondaryresponsestoalteredacidbasestatus:therulesofengagement.JAm
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10.WiederseinerJM,MuserJ,LutzT,etal.Acutemetabolicacidosis:characterizationanddiagnosisofthe
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11.PierceNF,FedsonDS,BrighamKL,etal.Theventilatoryresponsetoacutebasedeficitinhumans.Time
courseduringdevelopmentandcorrectionofmetabolicacidosis.AnnInternMed197072:633.
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YorkCity2001.p.542.
13.BushinskyDA,CoeFL,KatzenbergC,etal.ArterialPCO2inchronicmetabolicacidosis.KidneyInt1982
22:311.
14.DanielSR,MoritaSY,YuM,DzierbaA.Uncompensatedmetabolicacidosis:anunderrecognizedriskfactor
forsubsequentintubationrequirement.JTrauma200457:993.
15.AlbertMS,DellRB,WintersRW.Quantitativedisplacementofacidbaseequilibriuminmetabolicacidosis.
AnnInternMed196766:312.
16.FulopM.AguideforpredictingarterialCO2tensioninmetabolicacidosis.AmJNephrol199717:421.
17.JavaheriS,ShoreNS,RoseB,KazemiH.Compensatoryhypoventilationinmetabolicalkalosis.Chest
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136:1011.
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Topic2352Version19.0
GRAPHICS

Expectedcompensationrangesforsimpleacidbasedisorders

Reproducedwithpermissionfrom:HarringtonJT,CohenJJ,KassirerJP.Mixedacidbasedisturbances.In:
Acid/Base,CohenJJ,KassirerJP(Eds),Little,Brown,Boston:1982.Copyright1982LippincottWilliams&
Wilkins.www.lww.com.

Graphic79833Version7.0
Compensationtochronicrespiratoryacidosis

NinetyfivepercentsignificancebandsforplasmapHandH+andHCO3
concentrationsinchronichypercapnia.Becauseofthecompensatoryriseinthe
plasmaHCO3concentration,thereismuchlesschangeinH+concentration
andpHthaninacutehypercapnia.

SchwartzWB,BrackettNCJr,CohenJJ.JClinInvest196544:291.Bycopyright
permissionoftheAmericanSocietyforClinicalInvestigation.

Graphic63315Version3.0
Compensationstoacuterespiratoryacidosisand
alkalosis

CombinedsignificancebandsforplasmapHandconcentrationsofH+andHCO3
inacuterespiratoryacidosisandalkalosisinhumans.Inuncomplicatedacute
respiratoryacidbasedisorders,valuesfortheH+andHCO3concentrations
will,withanestimated95percentprobability,fallwithintheband.Valueslying
outsidethebandindicatethepresenceofacomplicatingmetabolicacidbase
disturbance.

ArbusGS,HerbertLA,LevesquePR,etal.NEnglJMed1969280:117.Bypermission
fromtheNewEnglandJournalofMedicine.

Graphic58687Version5.0
Compensatoryresponsetochronicrespiratoryalkalosis

CombinedsignificancebandsforplasmapHandconcentrationsofH+and
HCO3inchronicrespiratoryalkalosisinhumans.Inuncomplicatedchronic
respiratoryalkalosis,valuesfortheH+andHCO3concentrationswill,withan
estimated95percentprobability,fallwithintheband.Valueslyingoutsidethe
bandindicatethepresenceofacomplicatingmetabolicacidbasedisturbance.
NotethatthecompensatoryreductionintheplasmaHCO3concentrationisso
effectivethatthereislittlefallinpH.

GennariJF,GoldsteinMB,SchwartzWB.JClinInvest197251:1722.Bycopyright
permissionoftheAmericanSocietyforClinicalInvestigation.

Graphic75327Version2.0
Contributor Disclosures
Michael Emmett, MD Consultant/Advisory Boards: ZS Pharma [Treatment of hyperkalemia (Potassium binder,
zirconium silicate)]. Bi F Palmer, MD Nothing to disclose Richard H Sterns, MD Nothing to disclose John P
Forman, MD, MSc Nothing to disclose

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