acid-base-disturbance(酸碱平衡紊乱)

Acid-basedisturbance

Section1.Acid-BaseBalanceSection2.

Simpletypesofacid-basedisturbanceSection3.MixedAcid-baseDisturbanceSection1.Acid-BaseBalance(1)Sourcesofacidandbase(2)Regulationofacid-basebalance(3)Laboratoryparametersofacid-basebalance

Homeostasisisveryimportantforlife.Acid-basebalanceisoneofthemajorrequirements(volume,osmolarityofthebodyfluid,etc.).Thebasicmeaningofacid-basebalanceisthestable[H+]inthebodyfluid.(1)Sourcesofacidandbase

Themainoriginofacidandbaseistheintracellularmetabolism(catabolismofprotein,carbohydrateandfat).

Twokindsofacidsareformedfrommetabolism:1)volatileacid,2)nonvolatileacid.Thevolatileacidistheacid,whichcanbeeliminatedfromlung(respiration).Thenonvolatileacidhastobeeliminatedfromkidneyswithinurine.1)Volatileacid

TheCO2istheend-productofoxidativemetabolismofprotein,carbohydrateandfat.ThedailyproductionofH+(H2CO3)is13~15(20)Mol.H2CO3canbedissociatedtoformhydration(H2O)andCO2.CA(carbonicanhydrase)

H2CO3←--→H2O+CO2TheCO2canbeeliminatedfrompulmonaryexpiration,soH2CO3isvolatileacid.2)unvolatileacid(fixedacid)

Uricacid,phosphoricacid(H3PO4)andsulfuricacid(H2SO4)aretheproductsinthemetabolicprocessofproteinsandnuclearacids.Lacticacidandketonicbodies(β-hydroxybutyricacidβ-羟丁酸andacetoaceticacid乙酰乙酸)canbeformedfromthemetabolicprocessofcarbohydrateandfatasintermediateproducts,whentheoxygensupplyisnotsufficiency.

([H+]=70~100mmol/perday)3)BaseTheproductionofacid(H2CO3,organicacids)ismuchmorethantheproductionofbase(deaminationofAA―>NH3)fromthemetabolisminnormaldiet.Thevegetables,andfruitsalsocontainssomebase(suchascitrate(柠檬酸盐)oxalate(草酸盐)theH+acceptor).Citrate+H+=citricacid(2)Regulationofacid-basebalance1)Chemicalbuffers2)Respiratoryregulation3)Renalregulation4)Cellularregulation1)ChemicalbuffersBufferpair(buffersystem)consistsofaweakacidandits’conjugatebase,suchas

NaHCO3Na2HPO4

Hb-Pr-

HbO-2-------------------------------------------

H2CO3NaH2PO4

HHbHPrHHbO2

H2SO4+NaHCO3=Na2SO4+H2CO3Toconvertstrongacid(H2SO4,HCl)orstrongbaseintoaweakacidorbase.

Tominimizechangesof

[H+

].

Immediatelyavailable(firstdefenseline)

Note,H2CO3/HCO3-systemcannotbuffervolatileacid.(Hb/HbO2system)

buffersystem

the%account

-----------------------------------------------------------------------------------HCO-3/H2CO3

53%Hb-/HHbHbO-2/HHbO2

35%Pr-/HPr7%Phosphate5%--------------------------------------------------------NaHCO3canbeeffectivelyeliminatedbykidneysand(H2CO3←→H2O+CO2)CO2canbeeffectivelyeliminatedbythelung.----“openbuffersystem”HCO-3/H2CO3isthemostimportantbufferpair.

CO2

Cl-

CO2+H2O

C.A.H2CO3

HCO-3

H+--Hb-

RBCHb-/HHbandHbO-2/HHbO2buffersystem2)Respiratoryregulation

Alveolarventilationiscontrolledbymedullaryrespiratorycenter,withCO2,pH,O2asitsmainstimuli.peripheralchemoreceptors(carotid/aorticbody)AlthoughthecentralchemoreceptorissensitivetothechangesofH+,H+isdifficulttodiffuseacrosstheblood-brainbarrier.

AsCO2canfreelydiffuseacrosstheblood-brainbarrier,therespiratorycenterresponsesrapidlytotheperipheralchangesofPaCO2andslowlytothatofH+.

IncreasedPaCO2(>60mmHg,8kPa)andthe

decreasedpHofESFcanstimulatetherespiratorycenterviacentralorperipheralchemoreceptors

andincreasethedepthofrespiration

(hyperventilation,tidalvolumeincreased).MoreCO2canbeeliminatedfromlung,sothatthe[H2CO3]inbloodwillfalltonormalrange,thepHwillincreasetonormalbyregulatetheratioof[HCO3-]and

[H2CO3].Characteristics(a)Timeliness.

Therespiratoryresponsebeginswithinseveralminutes.Therespiratoryresponseoftentakes30minutes

fortherespiratorycompensation.12~24hourstogetmaximalcompensation.(b)PaCO2>60mmHg:stimulatesrespiratorycenter.

>80mmHg:inhibitsrespiratorycenter.

(CO2narcosis)

3)RenalregulationRenalcompensationbeginsfromseveralhoursaftertheadditionofacidload,anditmaytake3~5daystoreachthemaximumofthiscompensatorycapacity.KidneysplayamajorroleintheregulationofpHinthebody.Therenalregulationconsistsoftwoprocesses.(a)Excretionofacids1)SecretionofH+,NH4+2)Excreteallthenonvolatileacid(70~100mmol/perday)producedfromcatabolismoffood.(b)Reabsorbproperlythebicarbonatefilteredfromglomerulus.

WhenthepHisdecreased,morebicarbonateneedstobereabsorbed.

IfthepHisincreased,morebicarbonatewillbeeliminated.MechanismsofH+excretionandHCO3–

reabsorption:

①inproximaltubule:ViaNa+-H+

antiportor(NHE反向转运体)ViasecretionofNH3/NH4+

②indistaltubule+collectingductViaH+-ATPase

ViasecretionofNH3/NH4+

ViaCl--HCO3-exchanger

①inproximaltubule:

Na+-H+antiportor（NHE）Atend,1molH+excretesintothelumenfromtubularepithelialcells,and1molHCO3-isincreasedintheblood.CO2＋H2OH2CO3HCO3-

H＋Na＋TubularepithelialcellTubularlumenCANa＋K＋Na-K-ATPNa＋HCO3-

＋H＋H2CO3CO2＋H2OCAWhenacidosisoccur,theactivityofcarbonicanhydrase。Capillarytube

Na＋CO2ViasecretionofNH3/NH4+H2CO3HCO3-

H＋Na＋Na＋K＋Na-K-ATPNa＋NH4＋GlutamineGlutamate

ketoglutarate酶glutamine

NH3＋glutamate(glutaminase)glutamate

NH3＋-ketoglutarate(glutamatedehydrogenase)

-ketoglutarate＋2e2HCO3-

NH4＋TubularlumenTubularepithelialcellCapillarytube

②indistaltubule+collectingduct

CO2＋H2OH2CO3HCO3-

H＋H-ATPCl

-HPO42

-H2PO4-

pHCAalkalineacidicAcidificationofurineDistalacidificationTubularlumenH-ATPaseCl-HCO3exchangerTubularepithelialcellCapillarytube

CO2＋H2OH2CO3HCO3-

H＋H-ATPCl

-CANH4＋NH3NH3NH3TubularlumenTubularepithelialcellCapillarytube

4)Cellularregulation(a)H+-K+exchange(b)Cl¯-HCO3¯exchange(c)Utilizingofbonesalt(d)SynthesisofureafromNH3(a)H+-K+exchange

When[H+]inECF(serum)isincreased,theH+willmoveintothecells,asaexchangeforelectricalneutrality,K+willshiftfromICFtotheECF.SothepHofECF(serum)willincreasetonormal,buthyperkalemiamayoccur.(b)Cl¯-HCO3¯exchangeWhenCO2inECF(serum)isincreased,CO2willmoveintothecells,CO2combinesH2Otoformcarbonicacid,thenH2CO3dissociatestoformH+andHCO3¯,theHCO3¯movesoutoftheRBC,forneutrality,Cl

¯movesintothecells.(c)Utilizingofbonesalt

Inchronicmetabolicacidosis,bonesalt,Ca3(PO4),isalsoutilizedasabufferbase,buttheexpenseisdecalcificationofboneandosteoporosis(looseandsoftbone).

Ca3(PO4)2+4H+←→3Ca2++2H2PO4¯

(d)SynthesisofureafromNH3inlivercells.(3)Laboratoryparametersofacid-basebalance

1)pH2)PaCO23)Standardbicarbonate(SB)Actualbicarbonate(AB)4)Bufferbase(BB)5)Baseexcess(BE)6)Aniongap(AG)1)pH

pHisthenegativelogarithm(-log)of[H+]inasolution.[H+]=40nmol/L(pH=7.4)Thenormalrangeinarteryblood=7.35~7.45(7.41)ThesurvivalrangeofpH=6.8~7.8AccordingtotheHenderson-Hasselbalchequation:ThepKaisthedissociationconstantofcarbonicacid(=6.1)

24[HCO3¯]metabolicfactorpH=6.1+log---------------------------------------1.2[H2CO3]respiratoryfactors

20=6.1+log----------=6.1+1.3=7.4

1ThepHisdeterminedbytheratioof[HCO3¯]20--------------=---------[H2CO3]1

Note:NomatterhowtheabsoluteamountsofHCO3¯andH2CO3change,oncetheratioremains20/1,thepHwouldbe7.4(normal).

Clinicalsignificance

(anticoagulantarteryblood,insulationofair)AnormalrangeofpHmayrepresentthreedifferentsituations:①acid-basebalance;②compensatoryacidosisoralkalosis;③amixeddecompensatoryacidosisand

decompensatoryalkalosis.pH<7.35decompensatoryacidosispH>7.45decompensatoryalkalosis

2)PaCO2

PaCO2isthetensionofCO2dissolvedinarterialplasma.Thenormalrange=33~46(40)mmHg(mercury)(4.39~6.25kPa).Generallyspeaking,thePaCO2isdeterminedmainlybytherespiration,sothePaCO2iscalledthe“respiratoryfactor”.

Hyperventilation--------PaCO2

Hypoventilation--------PaCO2

SignificancePaCO2>46mmHgPrimaryincrease:respiratoryacidosisSecondaryincrease:metabolicalkalosis(compensatedbylung)PaCO2<33mmHgPrimarydecrease:respiratoryalkalosis

Secodarydecrease:metabolicacidosis(compensatedbylung)3)Actualbicarbonate(AB)

Standardbicarbonate(SB),

SBismeasuredunder“standardcondition”(temperature37~38℃,fulloxygenationofhemoglobin,PaCO2=40mmHg).

Standardconditionmeansthattherespiratoryfactoriseliminated,thenthe[HCO3¯]isonlyaffectedbymetabolicfactor.Thenormal[HCO3¯]is22~27(24)mmol/L.

HigherSBmeansmetabolicalkalosisorrespiratoryacidosiscompensatedbykidneys.LowSBmeansmetabolicacidosisorrespiratoryalkalosiscompensatedbykidneys.ABismeasuredunder“actualcondition”.becausethebloodsampleissealedofffromairafteritstaking,thePaCO2ismaintainedatitsoriginallevel.So,ABisinfluencedbybothrespiratoryfactorandmetabolicfactor.

NormallytheAB=SB.IfAB>SB(CO2retention),thereasonmustbetheeffectofrespiratoryfactor,whichindicatesrespiratoryacidosisormetabolicalkalosiscompensatedbylung.IfAB<SB(CO2depletion),thereasonmustbetherespiratoryfactor,whichmeansrespiratoryalkalosisorthemetabolicacidosiscompensatedbylung.4)Bufferbase(BB)

SumofallbufferbasesinbloodInplasma:HCO3¯=24Protein¯=17InRBC:Hb¯

HbO2¯=6.3HPO42¯=1.0BB=45~52mmol/L(48)Determinedbymetabolicfactors5)Baseexcess(BE)Under“standardcondition”(temperature37~38℃,fulloxygenationofhemoglobin,PaCO2=40mmHg),

titratethewholebloodtopH7.4withhowmuchacidorbase(mmol/L).Ifwithacid,thereismustmorebase(excess)intheblood,BEisexpressedwithpositivevalueIfwithbase,thereismustmoreacid(deficit)intheblood,BEisexpressedwithnegativevalueNormalBE=-3.0~+3.0OnlymetabolicfactordeterminestheBE.InmetabolicalkalosisthepositiveBEincreases.InmetabolicacidosisthenegativeBEincreases.6)Aniongap(AG)UCUANa+

Cl

－HCO3

－DeterminedcationundeterminedanionsundeterminedcationsAGisthedifferencebetweenunmeasuredanion(UA)andunmeasuredcation(UC).AG=UA-UCDeterminedanionUCNa+

Cl－HCO3

－AGUAAccordingtotheprincipleoftheelectroneutrality:UA+HCO3¯+Cl¯=UC+Na+TheAGcanbecalculatedby:AG=UA-UCandUA-UC=Na+-(Cl¯+HCO3¯)SoAG=Na+-(Cl¯+HCO3¯)Thenormalrangeis10~14mmol/L.AGindicatesthoseanions,otherthanHCO3¯andCl¯.ActuallytheAGrepresentstheproteinswithnegativecharge,phosphate,sulfateandorganicanions(lacticacid,keto-acid,etc.).AnincreasedAGisthesamemeaningastheaccumulationofnonvolatileacidsinthebodyandmustbethemetabolicacidosis.Significance(a)Fortheclassificationofmetabolicacidosis1)metabolicacidosiswithnormalAG(withincreasedCl

¯)2)metabolicacidosiswithhighAG(withnormalCl

¯).(b)Diagnosisofmixedacid-baseimbalancesSection2.

Simpletypesofacid-basedisturbanceAcidosis(acidemia)occurswhenpHdropsbelow7.35

Alkalosis(alkalemia)occurswhenthepHrisesabove7.45AprimaryrespiratoryproblemisdeterminedifthePaC02islessthan33mmHg(alkalosis)orgreaterthan46mmHg(acidosis).

AprimarymetabolicproblemiswhentheHC03islessthan22mEq/L(acidosis)orgreaterthan27mEq/L(alkalosis).

1.

metabolicacidosis

concept:theprimarydisturbanceisadecreaseof[HCO-3]inthearterialplasma

1)causeandpathogenesis--Excessiveproductionoffixedacidslacticacidosis:ischemia,hypoxiaglycolysis

heartfailure/shock/respirotoryfailure

ketoacidosis:diabetes,starvationlipolysis

--Disordersintheexcretionofacidicmetabolitesrenalfailure:GFR,eliminationoffixedacids

typeIrenaltubularacidosis(RAT-I):excretionofNH4

1)causeandpathogenesis--ExcessivelossofHCO3-lossfromintestinaljuice:diarrhea,tubedrainage(引流),intestinalfistulas(瘘)type-IIrenaltubularacidosis(RAT-II):CA,excretionofHand

reabsorptionofHCO3--Excessiveintakeofexogenousacids:NH4Cl,aspirin--Blooddilution--Hyperkalemia:H-Kexchange

2)classification--NormalAGmetabolicacidosislossofHCO3fromintestinalorrenalroutes,ordepletionofHCO3bybufferingfixedacids

tomaintainelectroneutrality,Cl

--HighAGmetabolicacidosisfixedacids----H++unmeasuredanion

buffering,HCO3

replacethenegativechargesofdecreasedHCO3thus,

Clisnormal

Na＋AGHCO3-Cl

-AGHCO3-Na＋AGHCO3-Cl

-Cl－HCO3-

3)

compensatoryregulation

①buffer:firstlineofdefense②respiratorycompensationKussmaul/hypocapnia

③cellularcompensationhyperkalemia

④renalcompensationrenaldysfunction×[H+]:C.A.H+,NH3secretion

reabsorptionofHCO3

4)

changesofacid-baseparameters

pH<7.35;SB;AB;AB<SBBB;negativevalueofBE;

PaCO2secondarily

5)

effectonbody

①cardiovascularsystem

hyperkalemiaarrhythmia[H+]:contractilityperipheralresistance②centralnervoussystem[H+]ATP,γ-aminobutyricacid(somnolence嗜睡,coma)

3)respiratorysystemKussmaul’breathing4)osseoussystembonegrowth,rickets(佝偻病）,osteodystrophy（骨营养不良）

6)principlesoftreatmentMETABOLICACIDOSIS-metabolicbalancebeforeonsetofacidosis-pH7.4

metabolicacidosispH7.1-HCO3-decreasesbecauseofexcesspresenceofketones,chlorideororganicions-body’scompensation-hyperactivebreathingto“blowoff”CO2-kidneysconserveHCO3-andeliminateH+ionsinacidicurine-therapyrequiredtorestoremetabolicbalance-lactatesolutionusedintherapyisconvertedtobicarbonateionsintheliver0.510

2.respiratoryacidosis

concept:Theprimarydisturbanceisanelevationinplasma[H2CO3]

1)causeandpathogenesisBarbital（镇静剂sedative）depressionofCNSheadinjury①CO2breatheparalysisofrespiratorymusclesoutdiseaseofairwayorlungchestinjury

②inhalationofCO2

2)compensation①buffer:H2CO3systemRBCbuffer

②respiratorycompensation③cellularcompensationH+-K+exchange④renalcompensationmain,butslow

acuterespiratoryacidosisisoftendecompensated.

CO2RBCCO2＋H2OH2CO3H＋HCO3-＋Hb(O2)-HHb(O2)Cl-HCO3-Cl-

3)

changesofacid-baseparameters

pH<7.35;PaCO2

＞45mmHgSB;AB;AB＞SB;BB;BE;

4)effectonbody①CNSmoreseriousthanthatofmetabolicacidosisPaCO2brainbloodvesselsdilationheadache

CO2narcosisrespirationmentaldearrangement;coma

“pulmonaryencephalopathy”②cardiovascularsystem,similartometabolicacidosis5)principlesoftreatment

improveventilation

RESPIRATORYACIDOSISmetabolicbalancebeforeonsetofacidosispH=7.4respiratoryacidosispH=7.1breathingissuppressedholdingCO2inbodybody’scompensationkidneysconserveHCO3-ionstorestorethenormal40:2ratiokidneyseliminateH+ioninacidicurine-therapyrequiredtorestoremetabolicbalance-lactatesolutionusedintherapyisconvertedtobicarbonateionsintheliver403.metabolicalkalosis

concept:

theprimarydisturbanceisanincreaseof[HCO-3]inthearterialplasma

1)causesandpathogenesis

--Excessivelossoffixedacidfromstomach:vomiting,gastricsuction,“HCl”

fromkidneys:hyperaldosteroim,H+HCO3-

diuretics(furosemide速尿,etacrynicacid),K+

--Excessiveintakeofalkalinesubstancestoredblood(citrate)1)causesandpathogenesis

--Disturbanceinelectrolytes

hypokalemia,hypochloremia2)Classification

--chloride(orsaline)-responsivealkalosislossofgastricfluid(HCl),etc--chloride(orsaline)-resistantalkalosis

sodium-rataininghormones

forexample,hyperaldosteronism,cushing’ssyndrome3)

compensationofthebody

①buffer:

②respiratorycompensation:incomplete,thesubsequenthypoxiawilloffsettheinhibitingeffectofincreasedpH.③cellularcompensationhypokalemia

④renalcompensationCA

,glutaminase

4)principlesoftreatment

pH＞7.45;PaCO2

＞46mmHgSB;AB;AB＞SB;BB;BE;

5)effectsonbody

①

CNS:excitatoryeffect

②

neuromuscularexcitability

pHfreeCa2+tendonhyperflexia,convulsion

③

hypokalemiaarrhythmiaGlutamicacidGlutamicdecarboxylase-GABAGABAtransaminasesuccinicacidpH(-)(+)Glutamicacid

-aminobutyricacid

6)

principlesoftreatment--salineresponsivealkalosis:0.9%NaCl

hypokalemia:KCl

--salineresistantalkalosis:

hyperaldosteronism:antisterone(安体舒通）

diuretic：diamox(乙酰唑胺)，CAinhibitor

METABOLICALKALOSIS-metabolicbalancebeforeonsetofalkalosis-pH=7.4

metabolicalkalosispH=7.7-HCO3-increasesbecauseoflossofchlorideionsorexcessingestionofNaHCO3-body’scompensation-breathingsuppressedtoholdCO2-kidneysconserveH+ionsandeliminateHCO3-inalkalineurine-therapyrequiredtorestoremetabolicbalance-HCO3-ionsreplacedbyCl-ions1.2525

4.

respiratoryalkalosis

concept:

theprimarydisturbanceisdecreaseof[H2CO3]inplasma

1)

causeandpathogenesis

--hyperventilation

psychogenicfactors:hysteria(癔病)braindiseases:encephalitis(脑炎）

reflectivestimulation:hypoxemia,fever,pain

misoperationofventilator

2)Classificationandcompensation--acuterespiratoryalkalosis①buffer:H2CO3systemRBCbuffer

②respiratorycompensation:③cellularcompensationH+-K+exchange④renalcompensationmain,butslowRBCCO2＋H2OH2CO3H＋HCO3-＋Hb(O2)-HHb(O2)Cl-Cl-HCO3-CO2

--chronicrespiratoryalkalosisapartfromH-K,Cl-HCO3exchanger④renalcompensationCA

,glutaminase

3)changesofacid-baseparameters

pH>7.45;PaCO2

;AB

SBBBBE~;AB＜SB

4)

effectsonbodyItisassameasmetabolicalkalosis,butmoreeasier.--dizziness(头晕)andconvulsion(抽搐)--neuromuscularexcitability

5)principlesoftreatmentinhalationof5%CO2RESPIRATORYALKALOSISmetabolicbalancebeforeonsetofalkalosispH=7.4respiratoryalkalosispH=7.7-hyperactivebreathing“blowsoff”CO2-body’scompensation-kidneysconserveH+ionsandeliminateHCO3-inalkalineurine-therapyrequiredtorestoremetabolicbalance-HCO3-ionsreplacedbyCl-ions

1.

doubleacid-basedisturbance1)metabolicacidosisplusrespiratoryacidosis

heartbeat[HCO-3]respirationstopcharacterPaCO2

pH

2)metabolicalkalosis

plus

respiratoryalkalosishepaticfailure/feverPaCO2

diuretic/vomiting

character

[HCO-3]

pH

3)respiratoryacidosis

plus

metabolicalkalosis

pulmonaryheartdiseasediureticpH±

Section3.MixedAcid-baseDisturbance

4)respiratoryalkalosis

plus

metabolicacidosis

infectiveshock/diabetes/renalfailure

fever

pH±5)metabolicacidosisplusmetabolicalkalosis

ketoacidosis(diabetes)vomiting

pH±

2.

tripleacid-basedisturbance

1)

respiratoryacidosis/metabolicacidosis/alkalosispulmonaryheartdisease;vomiting2)

respiratoryalkalosis/metabolicacidosis/alkalosisfever;vomiting;diarrhea(foodpoisoning)

BasicQuestionsTherearethreecriticalquestionstokeepinmindwhenattemptingtointerpretarterialbloodgases(ABGs).

FirstQuestion:Doesthepatientexhibitacidosisoralkalosis?

SecondQuestion:Whatistheprimaryproblem?Metabolic?orRespiratory?

ThirdQuestion:Isthepatientexhibitingacompensatorystate?

InordertounderstandABGanalysisandrememberwhatisabnormal,youneedtoreviewwhatisnormal.

RememberDefinitionsAcidosis(acidemia)occurswhenpHdropsbelow7.35

Alkalosis(alkalemia)occurswhenthepHrisesabove7.45AprimaryrespiratoryproblemisdeterminedifthePaC02islessthan35mmHg(alkalosis)orgreaterthan45mmHg(acidosis).

AprimarymetabolicproblemiswhentheHC03islessthan22mEq/L(acidosis)orgreaterthan26mEq/L(alkalosis).AssessmentStep1StepOne:Determinetheacid/basestatusofthearteri