Chapter1
Fluids,Electrolytes,andAcid–BaseDisorders
1.A36-year-oldwomanisadmittedfordizziness,weakness,poorappetite,fatigue,andsalt-cravingfor4weeks.Shehas historyofasthma,andnotonanymedications.Shehasafamilyhistoryoftype1diabetesandhypothyroidism.On admission,herbloodpressure(BP)is100/60mmHgwithapulserateof100(sitting),and80/48mmHgwithapulserate of120beats/min(standing).Hertemperatureis99.6 F.Laboratoryvaluesareasfollows:
Naþ ¼ 124mEq=LCreatinine ¼ 1 8mg=dL
Kþ ¼ 6 1mEq=LGlucose ¼ 50mg=dL
Cl ¼ 114mEq=LHemoglobin ¼ 13g=dL
HCO3 ¼ 20mEq=LHematocrit ¼ 40 %
BUN ¼ 42mg=dLUrinaryNaþ ¼ 60mEq=L
Basedontheabovehistoryandlaboratoryvalues,whichoneofthefollowingfluidsisAPPROPRIATEinaddition topertinenthormoneadministration?
A.5%Dextroseinwater(D5W)
B.5%Albumin
C.Ringer’slactate(lactatedRingersolution)
D.Normal(0.9%)saline
E.0.45%(Half-normal)saline
TheanswerisD
TheorthostaticBPandpulsechangessuggestvolumedepletion.Hyponatremia,hyperkalemia,elevatedBUNand creatinine,hypoglycemia,andhighurinaryNa+ excretionsuggestadrenalinsufficiency(Addison’sdisease),which isduetoglucocorticoidandmineralocorticoiddeficiency.Hersignsandsymptomsarerelatedtovolumedepletion andelectrolyteabnormalities.HypotensionisrelatedtolossofbothNa+ andwatercausedbydeficiencyofthe abovehormones.
Inadditiontoadministrationofhydrocortisoneandfludrocortisones,thepatientneedsnormalsalineadministrationtoimprovetotalbodyvolume(Discorrect).BothvolumerepletionandhormonetreatmentimproveBP andelectrolytes.
D5Wmayimprovehyperkalemiaandglucose,butnotadequatetoimprovevolume(Aisincorrect).5% albuminmayexpandvolume,butisnotindicatedinthispatient(Bisincorrect).Ringer’slactatemayexacerbate hyperkalemiaandhypercalcemia(about10%ofpatientswithAddison’sdiseasehavehypercalcemia)withlittle effectonhyponatremia.Thus,Cisincorrect.Half-normalsalineisnotadequatetorepletetheentirefluidinthis patient(Eisincorrect).
SuggestedReading
TenS,NewM,MaclarenN.Addison’sdisease2001.JClinEndocrinolMetab86:2909–2922,2001. SarkarSB,SarkarS,GhoshS,etal.Addison’sdisease.ContempClinDent3:484–486,2012.
# SpringerInternationalPublishingSwitzerland2016
A.S.Reddi, AbsoluteNephrologyReview, DOI10.1007/978-3-319-22948-5_1
2.Itisalwaysimportanttoknowhowmuchinfusedcrystalloidorcolloidwillremainintheintravascularcompartmentto improvevolumestatusandhemodynamicstatus. WhichoneofthefollowingfluidscontributesMOSTtothe intravascularcompartment?
A.D5W
B.Half-normalsaline
C.Normalsaline
D.Ringer’slactate
E.CandD
TheanswerisE
Inordertoanswerthequestion,itisimportanttorememberthepercentageoftotalbodywateranditsdistribution invariousfluidcompartments.Ina70kgmanwithleanbodymass,thetotalbodywateraccountsfor60%ofbody weight(42L),andtwo-thirdsofthiswater(i.e.,28L)isintheintracellularfluid(ICF)andone-third(i.e.,14L)isin theextracellularfluid(ECF)compartment(Fig. 1.1).Ofthese14LofECFwater,3.5L(25%)ispresentinthe intravascularand11.5L(75%)intheinterstitialcompartments.Accordingly,if1LofD5Wisinfused, approximately664mLwillmoveintotheICFand336mLwillremainintheECFcompartment.Ofthese 336mL,only84mL(25%)willremainintheintravascularcompartment(Fig. 1.2).
Fig.1.1 Distributionoftotal bodywater(TBW)ina70kg man.ECFextracellularfluid volume,ICFintracellularfluid volume
Intravacular (25%) Interstitial (75%)
42 L
28 L
14 L
3.5 L
11.5 L
Fig.1.2 Distributionof5% dextroseinwater(D5W)in thebody.ECFextracellular fluidvolume,ICFintracellular fluidvolume
(1L or 1,000 mL)
333 mL
Intravascular= 83 mL Interstitium= 250 mL
Ontheotherhand,morefluidisretainedintheintravascularspacewithisotonicfluids.If1Lofnormalsalineis infused,allofthefluidwillremainintheintravascularcompartment,andthenapproximately750mLwillmove intotheinterstitialcompartment,leaving250mLintheintravascularcompartment(Fig. 1.4).Themovementof salineintotheinterstitialcompartmentoccursapproximately30minafterinfusion.Duringthisperiodof intravascularstayofsaline,volumestatusandBPimprove.Urineoutputmayormaynotimproveuntiladditional volumeisinfused.SimilarvolumechangesoccurwithRinger’slactate.Thus,Eiscorrect. Total body water (60%)
Theretentionofhypotonicsolutionssuchas0.45%NaCl(half-normal)isdifferent.0.45%NaClisconsideredto bea50:50mixtureofnormalsalineandfreewater.If1Lof0.45%NaClisinfused,thefreewater(500mL)is distributedbetweenICF(333mL)andECF(167mL)compartments.Of167mL,only42mL(25%)willremainin theintravascularcompartment.Consideringtheother500mL,whichbehaveslike0.9%saline,375mL(75%) willmoveintotheinterstitialspace,and125mLstaysintheintravascularcompartment(Fig. 1.3).Thus,thetotal volumeremainingintravascularlyafter1Lofinfusionwouldbeonly167mL(42+125 ¼ 167mL).
D5W
Fig.1.3 Distributionofhalfnormalsalineinthebody. ECFextracellularfluid volume,ICFintracellularfluid volume
Fig.1.4 Distributionof normalsalineinthebody. ECFextracellularfluid volume,ICFintracellularfluid volume
saline (1,000 mL)
= 167 mL
Normal saline (1L or 1,000 mL)
ECF = 1,000 mL ICF = 0 mL
Intravascular = 250 mL Interstitium = 750 mL
Infusionofcolloidsresultsinevenmuchmoreretentionoffluidsintheintravascularcompartment.If1Lof 5%albuminisinfused,900mLwillstayintheintravascularcompartmentand100mLintheinterstitial compartment.Albuminstaysintheintravascularcompartmentfor >16h.
When1Lof25%albuminisinfused,theintravascularvolumewillbe4Lbecauseapproximately3Loffluid willmovefromtheinterstitiumintotheintravascularcompartment.
Approximatedistributionofvariouscrystalloidsandcolloids(albumin)inbodycompartmentsintheabsenceof shockorsepsisissummarizedinthefollowingtable(Table 1.1).
Table1.1 Approximatedistributionof1LofIVfluidsinbodycompartments
FluidIntracellular(mL)Interstitial(mL)Intravascular(mL) D5W66425283
Normalsaline(0.9%)0752248
Ringer’slactate0752248
Albumin(5%)0100900
Albumin(25%)a 0 30004000 aFluidmovementfrominterstitialtointravascular(plasma)compartment
SuggestedReading
NuevoFR,VennariM,Agro ` FE.Howtomaintainandrestorefluidbalance:Crystalloids.InAgro ` FE(ed).BodyFluid Management.FromPhysiologytoTherapy,Milan,Springer,2013,pp.37–46. ReddiAS.Intravenousfluids:Compositionandindications.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.33–44.
3.A24-year-oldwomanisadmittedforfeverwithchillsandweakness.Sheisfoundtobehypotensiveandtachycardic. Bloodculturesarepositivefor Staphylococcusaureus,andthediagnosisofsepticshockismade.Thereisnoperipheral edema.Basedonthesensitivity,thepatientisstartedonvancomycin.Pertinentlabs:
Na+ ¼ 144mEq/LGlucose ¼ 80mg/dL
K+ ¼ 5.1mEq/LTotalprotein ¼ 5.8g/dL
Cl ¼ 88mEq/LAlbumin ¼ 2.0g/dL
HCO3 ¼ 20mEq/LHemoglobin ¼ 10g/dL
BUN ¼ 30mg/dLHematocrit ¼ 30% Creatinine ¼ 1.7mg/dLUrinaryNa+ ¼ 10mEq/L
WhichoneofthefollowingfluidsisAPPROPRIATEforinitialresuscitation?
A.Packedredbloodcells(pRBCs)
B.Half-normalsaline
C.Normalsaline
D.Ringer’slactate
E.Albumin
TheanswerisC
Relativeintravascularvolumedepletionisusualinsepticshock.Thispatienthasevidenceofintravascularvolume depletion.Therefore,thechoiceoffluidisnormalsaline(Ciscorrect).Rapidinfusionofatleast1Lofsalineis neededwithinanhourandthenatleast150–200mL/huntilBP,tissueperfusion,andoxygendeliveryare acceptable.Notethatthepatientswithsepticshockcandeveloppulmonaryedemaatpulmonarycapillary wedgepressures <18mmHg.RaisingHb >10g/dLisnotbeneficial;therefore,transfusionofpRBCsisnot required(Aisincorrect).However,thepatientneedstransfusionofpRBCsonceherHbdropsbelow7g/dL.
Ringer’slactatemaybeconsideredintheabsenceoflacticacidosisandhyperkalemia.BecauseoflowCl ,the patientislesspronetodevelopacutekidneyinjury,ascomparedwithnormalsaline.However,Ringer’slactate andhalf-normalsalinemaynotbeappropriate(BandDareincorrect).
AlbuminmayhelprestoreBPandtissueperfusion,ifBPdoesnotimprovewithsubstantialamountofnormal salineandthepatienthastraceedema.However,peripheraledemamaybepresentinpatientswithsepticshock withoutadequatevolumereplacementbecauseofextravasationoffluidintotheinterstitiumduetoincreased vascularpermeability.Vasopressors,inadditiontoalbumin,mayberequiredtoimproveBP,tissueperfusion,and gasexchange.However,albuminisnottheinitialchoiceoffluidresuscitation.Thus,Eisincorrect.
SuggestedReading
TommasinoC.Volumeandelectrolytemanagement.BestPractResClinAnaesthelol21:497–516,2007.
ReddiAS.Intravenousfluids:Compositionandindications.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.33–44.
4.A30-year-oldmanisadmittedtothetraumaservicewithmultipleabdominalwoundsthatrequiredsplenectomyand repairofseveralorgans.Hehasmultiplesurgicaldrainages.Hisbloodpressureis120/80mmHgwithapulserateof80. Hislabs:
Na+ ¼ 134mEq/LCa2+ ¼ 7.4mg/dL
K+ ¼ 3.1mEq/LPhosphate ¼ 3.5mg/dL
Cl ¼ 88mEq/LAlbumin ¼ 4.1g/dL
HCO3 ¼ 18mEq/LHemoglobin ¼ 11g/dL
BUN ¼ 10mg/dLHematocrit ¼ 34%
Creatinine ¼ 1.1mg/dL
Glucose ¼ 80mg/dL
UrinaryNa+ ¼ 12mEq/L
UrinaryK+ ¼ 10mEq/L
WhichoneofthefollowingfluidscontributesMOSTtotheintravascularcompartment?
A.D5W
B.Half-normalsaline
C.Normalsaline
D.Ringer’slactate
TheanswerisD
Thispatienthasmultipleelectrolyteproblemsbecauseofnonrenallosses.Therefore,theappropriatefluidfor initialtherapyisRinger’slactate,whichcontainsNa+,Cl ,K+,Ca2+,andlactate.Thisfluidshouldbecontinued untilallelectrolyteabnormalitiesarecorrected(Discorrect).
D5Wisnotanappropriatefluidforthispatient,ashehashypokalemia,anddextrosewouldfurtherlower serum[K+].Thismaycauseweaknessandarrhythmia.Also,normalsalinealoneisnotappropriatebecauseitmay lower[K+]evenfurtherbyurinaryexcretion.AlthoughnormalsalinewithK+ administrationwouldminimizeloss ofK+,itmaynotimproveotherelectrolyteabnormalities.
SuggestedReading
TommasinoC.Volumeandelectrolytemanagement.BestPractResClinAnaesthelol21:497–516,2007. ReddiAS.Intravenousfluids:Compositionandindications.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.33–44.
5.A72-year-oldmanwithhistoryofhypertension,type2diabetes,coronaryarterydiseasewithstentplacement,andCHF isadmittedfordyspneaatrest.Henoticedswellingofhislegsfor4weeksdespitesaltrestrictionanddiuretics.HisLV ejectionfraction(EF)is40%.Medicationsincludehumalog(75/25)20unitsQD,furosemide40mgBID,metolazone 2.5mgQD,spironolactone12.5mgQD,carvedilol12.5mgBID,ramipril10mgQD,atorvastatin40mgQD,clopidogrel 75mgQD,andaspirin81mgQD.BP100/60mmHg,pulse102beats/min,markedJVD,crackles,anS3,positive hepatojugularreflex,andpittingedemauptoknees.Labs:Na+ 134mEq/L,K+ 3.8mEq/L,Cl 90mEq/L,HCO3 28mEq/L,BUN46mg/dL,creatinine1.8mg/dL,eGFR <60mL/min,andglucose100mg/dL.HgbA1c7%.Urinalysis issignificantfor2+proteinuria.EKGshowstachycardia.Heweighs98kg. Basedontheabovehistoryandlabvalues, whichoneofthefollowingistheMOSTappropriateinitialmanagementinthispatient?
A.Intravenous(IV)administrationoffurosemide
B.Nesiritide
C.Nitroglycerine
D.Alloftheabove
E.Increasemetalazone
TheanswerisD
Thepatientneedssymptomaticreliefimmediatelyfromvolumeoverload.ContinuousIVfurosemide(5mg/h)is probablybetterthanIVbolusbecauseofestablishedsafetyprofile,greaterurineoutput,andlessrenal impairment.Ifdiuresisispooronfurosemide,nesiritideshouldbetrieduntilurineoutputisimproved.The recommendeddoseofnesiritideis2 μg/kgbolusfollowedby0.01 μg/kg/min.Nesiritidecausesvasodilationinthe venousandarterial,includingcoronaryvasculature.Italsodecreasesvenousandventricularpressureswithslight increaseincardiacoutput.Asaresult,dyspneamayimprove.Withtheuseofnesiritide,therequirementfor furosemidedecreases.Ifurineoutputisnotadequate,nitroglycerineat20 μg/minshouldbeconsidered.Since nitroglycerinecauseshypotension,monitoringofBPisextremelyimportant,andthedrugshouldbediscontinued oncesystolicBPis <90mmHg.Increasingmetolazonedoseisinappropriate.
SuggestedReading
JessupM,BrozenaS.Heartfailure.NEnglJMed348:2007–20018,2003. KrumH,TeerlinkR.Medicaltherapyforheartfailure.Lancet378:713–721,2011. AmerM,AdomaityteJ,QawumR.ContinuedinfusionversusintermittentbolusfurosemideinADHF:anupdatedmetaanalysisofrandomizedcontrolstudies.JHospMed7:270–275,2012.
6.Thepatientimprovedsymptomaticallyovera48hperiod;however,hisurineoutputandedemadidnotimprove substantially.Hisweightdecreasedfrom98to96kg.Repeatlabsshowcreatinineof2.1mg/dL.HisBPismaintained at100/56mmHg. Whatwouldbethenextappropriatestep?
A.Increasethedoseoffurosemide
B.Increasethedoseofnesiritide
C.Startdobutamine
D.Addmetolazonetofurosemide
E.Observepatientforanother24hforurineoutput
TheanswerisC
AdrenergicagonistssuchasdobutamineshouldbeconsideredinviewoflowEF.Dobutamineimprovescardiac outputbydecreasingafterloadandincreasinginotropy.Renalperfusionalsoimprovesatdosesof1–2 μg/kg/min (Ciscorrect).Othertreatmentoptionsdonotimprovethepatient’sclinicalstatus,andmaybeharmful.
SuggestedReading
JessupM,BrozenaS.Heartfailure.NEnglJMed348:2007–20018,2003. KrumH,TeerlinkR.Medicaltherapyforheartfailure.Lancet378:713–721,2011.
7.Despitedobutamine,theurineoutputdidnotimprovesignificantlyin24h.Milrinone,whichisaphosphodiesterase inhibitorwasstartedwithabolusdoseof25 μg/kgfollowedby0.1 μg/kg/mintoimproveinotropy.BP,urineoutput,and edemadidnotimprove.BPis90/70mmHg.Serumchemistryshowscreatininelevelof3.2mg/dL. Whichoneofthe followingtreatmentstrategiesisAPPROPRIATEtoimprovehiscondition?
A.Startperitonealdialysis(PD)
B.Starthemodialysis
C.Startcontinuousvenovenoushemodiafiltration(CVVHDF)
D.Starttolvaptan
E.Startaquapheresis
TheanswerisC
Thepatientdevelopedtype2cardiorenalsyndrome.Diuretics,nesiritide,andnitroglycerineshouldbe discontinued.Ofalltheavailableoptions,CVVHDFisthesuitableoptionbecauseitcanimprovebothfluidstatus andcreatinine(C).PDisaslowprocess,andHDmaynotbehelpfulinviewoflowBP.Tolvaptanmaynotwork thatwellinthispatientwithlowEFanddecreasedurineoutput.AquapheresisisindicatedinpatientswithCHF, butitincreasescreatinineevenfurther.Thus,startingthepatientonCVVHDFisabetteroptionthanother interventions.
SuggestedReading
HouseAA,HaapioM,LassusJ,etal.Therapeuticstrategiesforheartfailureincardiorenalsyndromes.AmJKidneyDis 56:759–773,2010.
DeVecchisR,BaldoC.Cardiorenalsyndrometype2:fromdiagnosistooptimalmanagement.TherapeutClinManagm 10:949–961,2014.
8.A50-year-oldwomanwithalcoholabusepresentstotheEmergencyDepartmentforthefirsttimewithdyspnea, worseningabdominaldistention,andswollenlegsforthelast4weeks.Pastmedicalhistoryincludes1pintofalcohol adayfor20years.Sheisnotonanymedications.Sheeatsregulardiet.BPis124/68mmHgwithpulserateof80beats/ min.Shehascrackles,anS3,tenseascites,andpittingedemauptotheknees.Pertinentlabs:serum[Na+]128mEq/L; [K+]3.6mEq/L;creatinine0.8mg/dL.ChestX-rayshowspulmonarycongestion. Whichoneofthefollowingchoices regardinghermanagementisCORRECT?
A.Restrictfluids
B.Furosemide40mgorally
C.Furosemide40mgIV
D.Furosemideandmetolazone
E.Hemodialysis
TheanswerisC
SincehermajorproblemisNa+ andwaterretention,restrictionofbothwillhelploseweight.Sincethepatienthas crackleswithpulmonarycongestion,shewouldbenefitfromIVinfusionofaloopdiureticsuchasfurosemide (40mgBID;someprefertogive80mg).Thus,Ciscorrect.Oncepatientisstable,spironolactoneat100mgshould bestartedinitiallywithup-titrationevery2–3daysby100mgupto400mg/day.If,urineoutputisnotadequate, furosemideupto160mg(80mgBID)shouldbetried.BedrestisadvisabletoimprovecardiacoutputandGFR. HerascitesandCHFshouldimprove.Ifherascitesdoesnotimprovedespitetheabovetreatmentmodality,large volumeparacentesiswith5%albumin(8g/L)replacementisrecommended.Dailyweight,BP,andintake/output (I/O)shouldberecorded.Otheroptionsarenotappropriate.
SuggestedReading
RunyonBA.Managementofadultpatientswithascitesduetocirrhosis:Anupdate.Hepatology49:2087–2107,2009. EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenal syndromeincirrhosis.JHepatol53:397–417,2010.
9.Withtheabovemanagement,shelost14kgin7days.Herserum[Na+]is134mEq/L,andcreatinineremainsat 0.8mg/dL.ShereceivededucationaboutrestrictedNa+ dietandabstinencefromalcohol,anddischargedon spironolactone400mgQDandfurosemide80mgBID.Sheisgivenclinicappointmentin2weeks.Intheclinic,she wasfoundtohaveseverevolumedepletion,andweightlossofanother4kg.Herascitesdidnotincreaseduringthis 2-weeksperiod. Whatwouldyoudonext?
A.Decreasespironolactoneandfurosemidedoseandgiveclinicappointmentin1week
B.Discontinuediureticsandadvisetodrinkwater,andseeherintheclinicin1week
C.AdmitherandhydrateherwithD5W
D.Admitherandhydrateherwith0.45%NaCl
E.Admither,discontinuediuretics,andstartinitiallywith5%albumin,andifnecessarynormalsaline
TheanswerisE
Sheshouldbehospitalizedforvolumereplacementandstabilization.Diureticsshouldbestopped,and5% albuminshouldbegiven(100g/day).Aliterofnormalsalinecanbeconsideredwith50gof5%albuminthe nextday.DailyweightwithBPandI/Osshouldbefollowed.Ondischarge,furosemidedoseshouldbedecreasedto 40mgBIDwithreducingdoseofspironolactone,asindicated.Follow-upin1–2weeksisneeded.ChoicesAtoD areinappropriate.
SuggestedReading
RunyonBA.Managementofadultpatientswithascitesduetocirrhosis:Anupdate.Hepatology49:2087–2107,2009. EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenal syndromeincirrhosis.JHepatol53:397–417,2010.
10.A46-year-oldmanisreferredtoyoubyaprimarycarephysicianforevaluationofproteinuriaandlegedemafor 3months.Thepatientishealthyotherwise.Heisnotonanymedications;however,hehasalonghistoryofsmoking. Thepatientnoticededemaoflowerextremities2monthsago.Hehasmildshortnessofbreathonwalking.BPis 132/80mmHgwithapulserateof74beats/min.Physicalexaminationisnormalotherthanpittingedemainlower extremities.Serumchemistryandcompletebloodcountarenormal(creatinine0.8mg/dL).Serumalbuminis3.2g/dL. Urinalysisreveals4+proteinuriaandfattycasts.Urineproteintocreatinineratiois7.2,and24hproteinis7.1g.His urinaryNa+ is142mEq/L.Heweighs94kg.Thepatientagreestorenalbiopsy,whichshowsmembranousnephropathy. Workupforsecondarycausesofmembranousnephropathyisnegative.Hehasnoinsurance. Whichoneofthe followingchoicesregardingtheinitialmanagementofhisedemaisCORRECT?
A.Limitfluidrestrictionto750mL/day
B.RestrictdietaryNa+ to88mEq(2g)perday
C.Startfurosemide40mgorally
D.StartanACE-I
E.B,C,andD
TheanswerisE
RestrictionofNa+ (88mEq)inthedietisthefirststepinthemanagement.Furosemide40mgQDandlisinopril (anACE-I)20mgQDshouldbestartedtoimproveedemaandproteinuria.Limitingwateratthistimeisnot appropriate.Thepatient’sweight,edema,BP,proteinuria,creatinine,K+,andurinaryNa+ forcomplianceofdiet shouldbefollowedfrequently.Addingamilorideseemstolowerproteinuria,ifnoorpartialresponsetolisinopril isobserved.
SuggestedReading
SchrierRW.Renalsodiumexcretion,edematousdisorders,anddiureticuse.In:SchrierRW(ed).RenalandElectrolyte Disorders,7thed,WoltersKluwer/LippincottWilliams&Wilkins,Philadelphia,2010,pp.45–85. Rondon-BerriosH.Newinsightsintothepathophysiologyofoedemainnephroticsyndrome.Nefrologia 31:148–154,2011.
11.A48-year-oldwomanwithsmallcelllungcancerisbroughttotheemergencydepartmentwithalteredmentalstatusof 4daysdurationandquestionableseizuredisorder.Herhusbandsaysthatthepatientissippingwaterfrequentlybecause ofdrymouth.HerBPis130/80mmHgwithpulseof74beats/min.Following2Lof0.45%salinein24h,thefollowing labdataareobtained:
SerumNaþ ¼ 114mEq=L
Serumosmolality ¼ 238mOsm=kgH2 O
UrineNaþ ¼ 140mEq=L
UrineKþ ¼ 34mEq=L
Urineosmolality284mOsm=kgH2 O
24hurinevolume ¼ 1L
Regardingelectrolyte-freewaterclearance(Te CH2 O ),whichoneofthefollowingisCORRECT?
A. 0.75L
B. 0.52L
C.+0.52L
D.+0.75L
E. 0.82L
TheanswerisB
Theconceptof Te CH2 O isusedtocalculatethekidneys’abilitytoconserveorexcretethedailyintakeoffluidsto maintainnormalserum[Na+].Wheneverwaterbalanceisdisturbed,eitherhypo-orhypernatremiadevelops.In suchasituation,calculationof Te CH2 O ishelpfulinevaluatingserum[Na+]byusingthefollowingformula:
CH2 O ¼ V1 UNa þ Uk =PNa ðÞ
whereVisurinevolume/24h,UNa,UK,andPNa areurineNa+,K+,andplasmaNa+ concentrationsin mEq/L.Substitutingthedatafromthepatient,weobtain
Wheneverthevalueisnegative,thekidneyisaddingwatertothebody,resultinginhyponatremia.Ontheother hand,whenthe Te CH2 O ispositive,thekidneyisremovingwaterfromthebodywiththeresultanthypernatremia. Thepatientreceivedhypotonicsolutionwithfurtherreductioninserum[Na+].Thus,optionBiscorrect.
SuggestedReading
ThurmanJM,BerlT.Disordersofwatermetabolism.In:MountDB,SayeghMH,SinghAJ(eds).CoreConceptsinthe DisordersofFluid,ElectrolytesandAcid-BaseBalance.NewYork,Springer,2013,pp.29–48. ReddiAS.Disordersofwaterbalance:Physiology.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders.Clinical EvaluationandManagement.NewYork,Springer,2014,pp.91–100.
Te
Te CH2 O ¼ 11 140 þ 34=114 ðÞ¼ 0 52L
12.A72-year-oldwoman,wholivesalone,wasadmittedforweakness,inabilitytowalk,andforgetfulnessovera2-week periodoftime.Shecooksherownmeals.Sheisslightlylethargic.PhysicalexaminationshowsBP124/74mmHg;pulse 78/minandnoorthostatichypotension.Lungandheartexaminationisnormal.Labsare:
SerumUrine
Na+ ¼ 120mEq/LVolume ¼ 1L/day K+ ¼ 3.6mEq/LNa+ ¼ 20mEq/L
Cl ¼ 88mEq/LK+ ¼ 12mEq/day
BUN ¼ 6mg/dLUreanitrogen ¼ 246mg
Creatinine ¼ 0.5mg/dLOsmolality ¼ 110mOsm/kgH2O
Glucose ¼ 90mg/dL
Uricacid ¼ 5.2mg/dL
Osmolality ¼ 250mOsm/kgH2O
Totalprotein ¼ 6.8g/dL
WhichoneofthefollowingistheMOSTlikelycauseforherhyponatremia?
A.Pseudohyponatremia
B.Hypertonichyponatremia
C.Hyponatremiaduetoteaandtoastdiet
D.Hyponatremiaduetohydrochlorothiazide(HCTZ)
E.Syndromeofinappropriateantidiuresis(SIADH)
TheanswerisC
Thepatientdoesnothavepseudohyponatremia,asserumglucoseandtotalproteinarenormal.Also,shedoesnot havehypertonichyponatremiabecauseherserumglucoseisnormalandshehasnoosmolalgap,suggestiveofthe presenceofeithermannitolorglycerol(AandBareincorrect).
Basedonphysicalexamination,thepatienthaseuvolemichyponatremia.Generally,thetypicalAmericandiet generatesaminimumof600mOsmperday(assuming60gproteinintake).AllofthesemOsmareexcretedeither in12Lofurine,ifurineosmolalityis50mOsm/kgH2Oor0.5Lofurineifurineosmolalityis1200mOsm/kgH2O (TotalmOsm/Urineosmolalityor600/50 ¼ 12Lor600/1200 ¼ 0.5L).Thus,anormalindividualwithintact dilutingandconcentratingabilitycanexcreteurinefrom0.5to12Lwithoutanychangeinwaterbalance (orplasmaosmolality).
Thepatienthasurineosmolalityof110mOsm/kgH2O;therefore,shecanexcreteallhermOsmin2.2Lof urine(110/50 ¼ 2.2L).However,hertotalmOsmwereonly110,suggestingpoorsoluteintake.Ifthispatient drinks >2.7L(2.2+0.5Linsensibleloss)offluidsdailyandhersoluteexcretionisonly110mOsm,shewillbein apositivewaterbalancewithsubsequentdevelopmentofhyponatremia.
Lackofsoluteintakeimpairsthekidney’sabilitytodilutetheurineto <100mOsm/kgH2O,asreducedsolute excretionlimitswaterexcretion.Herhyponatremiawillimprovewithdietthatcontainsatleast60gprotein,salt (100mEqNa+),and40–60mEqK+.Thus,thepatientcarriesthediagnosisofhyponatremiaduetoteaandtoast (Ciscorrect).
ShedoesnothaveeitherHCTZ-inducedhyponatremiaorSIADH,asotherlabssuchasuricacid(usuallylow inbothconditions)isnormalforherage(DandEareincorrect).
SuggestedReading
JamisonRL,OliverRE.Disordersofurinaryconcentrationanddilution.AmJMed72:308–322,1982.
BerlT.Impactofsoluteintakeonurineflowandwaterexcretion.JAmSocNephrol19:1076–1078,2008. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
13.A44-year-oldmenstruatingwomanhadabdominalsurgerylastingfor4h.Perioperatively,shereceivednormalsalineto maintainBPandurineoutput.Postoperatively,shereceived0.45%salineat120mL/h,andmorphineforpain.Herurine outputwas110mL/h.24hlater,shewasawakeandcomplainedofnauseaandheadache.Thefollowinglabswere availableatthetimeofconsultation:
SerumNa½þ¼ 130mEq=L
UrineNa½þ¼ 100mEq=L
UrineK½þ¼ 30mEq=L
Urineosmolality ¼ 440mOsm=kgH2 O
Urineoutput ¼ 100ml=h
Pre‐opNa½þ¼ 139mEq=L
Weight ¼ 64kg
WhichoneofthefollowingregardingtheamountofwaterdeficitisCORRECT?
A.4.2L
B.1.6L
C.3.2L
D.2.1L
E.3.6L
TheanswerisD
Thefollowingtwoformulascanbeusedtocalculatewaterexcess:
1.Waterexcess ¼ Totalbodywater(TBW)xactual[Na+] ¼ Pre-op[Na+] NewTBW
Weight ¼ 64kg
TBW ¼ 64 0 5 ¼ 32L
ActualNa½þ¼ 130mEq=L
Pre‐opNa½þ¼ 139mEq=L
NewTBW ¼ 32 130=139 ¼ 29 92L
Waterexcess ¼ PreviousTBW NewTBW or32 29:92 ¼ 2:1L
2.Alternativecalculation:
Pre‐optotalbodyNaþ ¼ TBW serumNa½þ or32 139 ¼ 4448mEq
Positivewaterbalance ¼ TotalbodyNaþ =ActualNa½þ or4448=130 ¼ 34 2L
Waterexcess ¼ 34 2 32 ¼ 2 2L
Thus,choiceDiscorrect.
SuggestedReading
ThurmanJM,BerlT.Disordersofwatermetabolism.In:MountDB,SayeghMH,SinghAJ(eds).CoreConceptsinthe DisordersofFluid,ElectrolytesandAcid-BaseBalance.NewYork,Springer,2013,pp.29–48.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
14.A27-year-oldmanwithresectionofpinealglandtumordevelopedpersistenthyponatremia.Hecomplainsofweakness andmilddizziness.PhysicalexaminationrevealsaBPof114/70mmHgandapulserateof100beats/min(supine), 100/60mmHgandapulserateof120beats/min(standing),respiratoryrateof16/min,andatemperatureof99.1 F. Cardiacexamisnormal.Lungsarecleartoauscultation.Thereisnoperipheraledema.Hereceives2.5Lofnormal salinedaily.
Labstudies:
Naþ ¼ 122mEq=L
Kþ ¼ 4 2mEq=L
Cl ¼ 96mEq=L
HCO3 ¼ 27mEq=L
BUN ¼ 22mg=dL
Creatinine ¼ 1 4mg=dL
Glucose ¼ 80mg=dL
Totalprotein ¼ 7:69g=dL
Uricacid ¼ 3:5mg=dL
Urineosmolality ¼ 700mOsm=kgH2 O
UrineNaþ ¼ 350mEq=L
UrineKþ ¼ 24mEq=L
Urinevolume ¼ 4L=24h
WhichoneofthefollowingistheMOSTlikelycauseofthispatient’shyponatremia?
A.Pseudohyponatremia
B.Latevomiting
C.Adrenalinsufficiency
D.Cerebralsaltwasting
E.SIADH
TheanswerisD
Pseudohyponatremiaisrelatedtoextremelyhighlevelsofproteinsandtriglycerides.Althoughtriglycerides werenotmeasured,histotalproteinconcentrationwasnormal.Therefore,thispatientdoesnothave pseudohyponatremia.
Vomitingisaconsideration;however,serum[Cl ]andurinary[K+]arenotconsistentwithvomiting.In general,patientswithlatevomitingconserveNa+,andexcretelowNa+ becauseofvolumedepletion.Also,K+ excretionisenhancedinbothearlyandlatevomiting.Therefore,optionBisincorrect.
AdrenalinsufficiencyisalsoaconsiderationinviewofnormaltolowBPandincreasedpulserateaswellas increasedurinaryNa+ excretion.However,normalCl ,HCO3 andglucoselevelsexcludethediagnosisof adrenalinsufficiency.
Hypotonichyponatremia,lowserumuricacidlevel,relativelynormalBP,highurineNa+ andosmolality suggestthediagnosisofSIADH.However,highpulserateandslightlyelevatedHCO3 andBUNlevelsare unusualinpatientswithSIADH.PatientswithSIADHareeuvolemicandlowertheirserumNa+ levelswith normalsaline.Theclinicalpresentationofthispatientissuggestiveofvolumedepletion,ratherthaneuvolemia. Therefore,SIADHisunlikelyinthispatient.
Cerebralsaltwasting(CSW)isthemostlikelycauseofthispatient’shyponatremia.Hypovolemiaandserum aswellasurinestudiesareconsistentwithCSW.Thus,optionDiscorrect.
SuggestedReading
MaesakaJK,ImbrianoLJ,AliNM,etal.Isitcerebralorrenalsaltwasting.KidneyInt76:934–938,2009. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
15.A42-year-oldmanwasadmittedforsubarchnoidhemorrhage.Followingclippingoftheaneurysm,hedevelops hyponatremia(Na+ droppedfrom136to124mEq/L).Atentativediagnosisofcerebralsaltwasting(CSW)was made. WhichoneofthefollowingdistinguishesCSWfromSIADH?
A.AbilitytoexcreteNa+ load
B.Lowserumuricacidlevel
C.NormalserumK+ level
D.IncreasedFEuricacid andFEPO4
E.FailuretonormalizeFEuricacid oncetheunderlyingcauseiseliminated
TheanswerisD
CSWoccursinpatientswithsubarachnoidhemorrhageandotherCNSdisorders.Itischaracterizedbylowblood andplasmavolumesandnegativesaltbalance.CSWandSIADHarecharacterizedbyhypotonichyponatremia, abilitytoexcreteNa+,lowserumuricacidlevelbecauseofincreasedsecretion,resultinginhighFEuricacid and normalserumK+ levels.However,FEuricacid returnstobaselineoncethecauseofSIADHiscorrectedbutitwill remainhighinpatientswithCSW.Also FEPO4 remainshighinCSWandisnormalinSIADH.
SuggestedReading
MaesakaJK,ImbrianoLJ,AliNM,etal.Isitcerebralorrenalsaltwasting.KidneyInt76:934–938,2009. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
16. WhichoneofthefollowingchoicesregardingtreatmentofhyponatremiaisCORRECTintheabovepatient?
A.Fluidrestriction
B.Hypertonicsalineandfurosemideadministration
C.Useofvasopressinantagonist
D.Saltintakeandfludrocortisone
E.Useofdemeclocyclineandurea
TheanswerisD
PatientswithCSWarehypovolemicwithlowBPandorthostaticchangesbecausetheylosesaltintheurine. Therefore,thetreatmenttoimproveserum[Na+]isvolumeexpansionwithNaClandfludrocortisone.Thus, choiceDiscorrect.Othertreatmentmodalitiesdonotimproveserum[Na+]inpatientswithCSW.ChoicesA, B,C,andEarebeneficialinpatientswithSIADH.
SuggestedReading
MaesakaJK,ImbrianoLJ,AliNM,etal.Isitcerebralorrenalsaltwasting.KidneyInt76:934–938,2009. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
17.A20-year-oldwomancollapsesatawildpartyseveralhoursaftertakingecstasy. Whichoneofthefollowing electrolyteabnormalitiesisMOSTlikelytobefoundinthissubject?
A.Hyperkalemiaduetovigorousdancinganddrugabuse
B.Hypokalemiaduetoexcess β-adrenergicsurge
C.Hypokalemicperiodicparalysisprecipitatedbyecstasy
D.Hyponatremiaduetoaneffectonvasopressinsecretionandfluidintake
E.Hyponatremiaduetovigorousdancingandfluidintake
TheanswerisD
Ecstasyisapopularnameforaring-substitutedformofmethamphetamine.Itgainedthepopularityofa“club drug”amongadolescents,youngadultsandsubjectsattending“rave”parties.Amongothersideeffects,suchas rhabdomyolysis,arrhythmias,andrenalfailure,ecstasycausessymptomatichyponatremiaandsuddendeath. EcstasyinducesvasopressinsecretionandretentionofwaterinthestomachandintestinebydecreasingGI motility.HyponatremiadevelopsasaresultofwaterreabsorptionfromtheGItractandexcessiveoralintakein thepresenceofhighvasopressinlevels.Thus,optionDiscorrect.Otheroptionshaveverylittleroleinthe developmentofhyponatremiainthepresenceofecstasy.
SuggestedReading
HallAP,HenryJA.Acutetoxiceffectsof‘ecstasy’(MDMA)andrelatedcompounds:Overviewofpathophysiologyand clinicalmanagement.BrJAnaesth96:678–685,2006.
Kalantar-ZadehK,NguyenMK,Chang,Retal.Fatalhyponatremiainayoungwomanafterecstasyingestion.NatClin PractNephrol2:283–288,2006.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
18.Amarathonrunnerwasdisorientedanddeliriouspost-race,andwasfoundtohaveaserum[Na+]128mEq/L.Hisweight wasslightlyhigherthanpre-raceweight. WhichoneofthefollowingistheMOSTappropriatefluidadministration?
A.1LofD5W
B.1Lof0.45%saline
C.3%Salineinsmallvolumeboluses
D.1L0.9saline
E.0.5L7.5%saline
TheanswerisC
Therecommendedinitialfluidmanagementinsymptomaticexercise-induced,euvolemichyponatremicpatientis 3%salineinsmallvolumeboluses.Hypotonicfluidssuchas0.45%salineorisotonicD5Wshouldbeavoided becauseoffurtherdecreaseinserum[Na+].Normalsaline(0.9%)isthefluidofchoicetoreplacevolume, althoughastudyreportedgoodresultswithisotonicsalineinathletes.Isotonicsalinemaynotbeasuitable solutiontocorrecthyponatremiainpatientswithelevatedorinappropriatehighlevelsofvasopressin.Although both3and7.5%salinearehypertonic,3%salineisusuallythepreferredfluidforsymptomatichyponatremic patients.Thus,answerCiscorrect.
SuggestedReading
VerbalisJG(ed).Diagnosis,evaluation,andtreatmentofhyponatremia:Expertpanelrecommendations.AmJMed126: A1-S42,2013.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
19.A60-year-oldwomanwithhistoryoflungcancerisadmittedforweaknessandlethargyfor4weeks.Herserum[Na+]is 120mEq/L.Sheweighs60kg.Herserumosmolalityis250mOsm/kgH2Owithurineosmolalityof616mOsm/kg H2O.ThediagnosisofSIADHismade. Whatwouldbeherserum[Na],ifshereceives1Lofisotonicsaline?
A.122mEq/L
B.116mEq/L
C.118mEq/L
D.120mEq/L
E.124mEq/L
TheanswerisC
TheselectionoffluidsinthetreatmentofSIADHdependsonaclear-cutunderstandingofthefluid,serum,and urineosmolalities.Inaddition,thephysicianshouldevaluatethetotalbodywater(TBW)contentaswellasthe totalbodyNa+ (TBNa)content.IwouldliketouseTBNa contentratherthantotalplasmaosmolalitybecauseboth calculationswouldyieldsimilarresults.Asystematicapproachwouldyieldthecorrectanswer.
First,calculateTBWandTBNa ofthepatientasfollows:
TBW ¼ WtkgðÞ % ofwater=kg ¼ 60 0 5 ¼ 30L
TBNa ¼ TBW serumNa ½ ¼ 30 120 ¼ 3600mEq
Second,calculatetheamountofurinevolumethatisrequiredtoexcretetheosmolesofagivenfluidtobe administeredtothepatient.Thiscanbecalculatedbydividingurineosmolalityintofluidosmolality. Intheabovepatient,thenewserum[Na+]canbeobtainedasfollows:
Osmolesosmolality ðÞ of0:9 % NaCl ¼ 308Naþ ¼ 154andCl ¼ 154 ¼ 308 ðÞ
Urineosmolality ¼ 616mOsm
Amountofurinerequiredtoexcrete308osmoles ¼ 308=616 ¼ 0 5L
Thepatientreceived1Lof0.9%saline;however,thepatientexcretedalltheosmolesin0.5Lofurine.Therefore, thepatientretained0.5Loffreewater,whichcausestheTBWtoincreasefrom30to30.5L.AssumingtheTBNa remainsat3600mEq,thenewserum[Na+]wouldbe:
3600=30 5 ¼ 118mEq=L
Thus,inapatientwiththediagnosisofSIADH,administrationof0.9%NaClwouldresultinlowerratherthan increaseinserum[Na+].Thus,optionCiscorrect.
SuggestedReading
RoseBD.Newapproachestodisturbancesintheplasmasodiumconcentration.AmJMed81:1033–1040,1986. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
20.An80-yearoldwomanwasadmittedfornausea,headache,andpsychosisfor2days:Pastmedicalhistoryincludes hypertension,andherphysicianincreasedhydrochlorothiazide(HCTZ),from12.5to25mgdaily.Thepatientwas drinkingwatermorethanusual.HerBPwas120/70mmHgandpulserateof80beats/min.TherewerenoorthostaticBP andpulsechanges.Serumchemistry:Na+ 112mEq/L,K+ 3.2mEq/L,Cl 90mEq/L,andglucose90mg/dL.Theurine osmolalityis220mOsm/kgH2O.Sheweighs70kg. Whichoneofthefollowingstatementsregardingher hyponatremiaisCORRECT?
A.FurosemideratherthanHCTZisafrequentcauseofhyponatremia.
B.HCTZimpairsurineconcentratingcapacity
C.Electrolyte-freeH2OclearancedecreaseswithHCTZ
D.Electrolyte-freeH2OclearanceincreaseswithHCTZ
E.Noneoftheabove
TheanswerisC
Hyponatremiaisawell-documentedcomplicationofdiureticuse.About73%ofcasesofhyponatremiawere relatedtothiazidediureticuse.20%ofcaseswereattributedtoacombinationofthiazidesandK+-sparing diuretics,and8%wererelatedtofurosemideuse.Thus,HCTZratherthanfurosemideisthemostcommon causeofhyponatremiabecausethiazidesimpairmaximumurinarydilutionbutnotconcentratingability.Urine osmolalityisusually >100mOsm/kgH2Oamongthiazideusers.Theexpectedurineosmolalityforthisdegreeof hyponatremia(118mEq/L)withnormaldilutingcapacityshouldbeabout50mOsm/kgH2O.However,this patientisunabletolowerurineosmolality <100mOsm/kgH2ObecauseoftheeffectofHCTZonrenalwater handling.HCTZdecreasesfreeH2Oclearance(i.e.,morewaterreabsorption)andcausesinabilitytolowerurine osmolalityto <100mOsm/kgH2O.
Furosemideimpairsconcentratingabilityofthekidney,andfreewaterclearanceisincreasedratherthan decreased.Therefore,furosemidealonedoesnotcausehyponatremia,butacombinationofHCTZandfurosemidecanresultinhyponatremia.However,somepatientsmaydevelophyponatremiawithorthostaticBPand pulsechangeswithchronicuseoffurosemideduetototalbodyNa+ andwaterloss.Thus,theanswersA,B,D,and Eareincorrect.
SuggestedReading
SpitalA.Diuretic-inducedhyponatremia.AmJNephrol191:447–452,1999.
AstrafN.LoursdeyR,ArialAI.Thiazide-inducedhyponatremiaassociatedwithdeathorneurologicdamagein outpatients.AmJMed70:1163–1168,1981.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
21. WhichoneofthefollowingstrategiesregardingtreatmentofhyponatremiaisCORRECT?
A.Restrictfluidsto1L/day
B.DiscontinueHCTZ
C.Increaseserum[Na+]from112to130mEq/Lin6hby3%saline
D.Increaseserum[Na+]from112to118mEq/Lin3hby3%salinewithagoalto130mEq/Lin48h
E.Increaseserum[Na+]from112to130mEq/Lin24hbynormalsaline
TheanswerisD
Thispatienthasacutesymptomatichyponatremia,whichrequiresimmediatetreatment.Althoughcontroversial, treatmentshouldbepromptinviewofpreventingprogressionofcerebraledemaandhypoxia,whichfarexceed theriskofosmoticdemyelination.Initially,serum[Na+]shouldbecorrectedby2mEq/Lperhourfrom112to 118mEq/Lin3–4huntilsymptomsresolve.Then,correctionshouldnotexceed18mEQin48hto130mEq/L with3%ornormalsaline(Discorrect).Administrationofhypertonicsalineshouldbeadjustedtoachievethe targetserum[Na+]byfrequentdeterminationsofserum[Na+]andurineNa+ andK+ levels.
RestrictionoffluidsanddiscontinuationofHCTZarenotappropriateforacutesymptomatichyponatremia, althoughadequateafterreliefofsymptoms.Administrationofnormalsalineisinadequateandinappropriateto thispatient.Also,rapidconnectionofserum[Na+]to130mEq/Lin6hmaybeariskforosmoticdemyelination. Thus,answersA,B,C,andEareincorrect.
Ithasbeenshownthatslowcorrectionofthiazide-inducedsymptomatichyponatremiain18–56hmaybe associatedwithahighrateofpermanentneurologicdamage.Thus,promptcorrectiontorelievesymptomsis required.
Itshouldbenotedthatapatientwithhyponatremiaandhypokalemiawhoisadmittedforweaknesscanbe successfullytreatedwithKCl.
SuggestedReading
SpitalA.Diuretic-inducedhyponatremia.AmJNephrol191:447–452,1999.
AstrafN.LoursdeyR,ArialAI.Thiazide-inducedhyponatremiaassociatedwithdeathorneurologicdamagein outpatients.AmJMed70:1163–1168,1981.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
22. Whichoneofthefollowingpossiblemechanismregardingthiazide-inducedhyponatremiaisFALSE?
A.Hypovolemia-stimulatedvasopressinreleaseandincreasedH2Oreabsorptioninthecorticalcollectingduct
B.Activationoftubuloglomerularfeedback(TGF)systemwithearlydiuretictherapyplusconsequentdecreaseinGFR
C.Increasedproximaltubulesoluteandwaterreabsorption
D.ImpairedfreeH2Oexcretion,particularlyintheelderlysecondarytoarelativedecreaseinPGE2
E.GreaterurinaryH2OthanNa+ lossduringthiazidetreatment
TheanswerisE
Thiazidescausenotonlymildasymptomaticbutalsoseveresymptomatichyponatremia,asshownintheabove case.Thedisorderisalsolife-threateninginsomesusceptiblepatients.Althoughthemechanismsforthiazideinducedhyponatremiaarenotfullyunderstood,severalpossibleexplanationshavebeensuggested.These include:(1)volumecontraction;(2)earlydiuretic-inducedinactivationofTGFsystem;(3)decreasedGFRdue toabovetwomechanisms;(4)stimulatedreleaseofvasopressinandincreasedH2Oreabsorption;(5)relative decreaseinvasodilatoryPGsynthesisinelderlysubjectswithunopposedvasopressinaction;and(6)decreasein urinarydilution.
Inaddition,diuretic-inducedhypokalemiamayfurtherexacerbatehyponatremiabytranscellularcation exchange(duetoosmolalitychanges),inwhichK+ movesoutofthecelltoimprovehypokalemiaandNa+ movesintothecelltomaintainelectroneutrality.Therefore,optionsAtoDarecorrect.
LossofNa+ andH2OoccurssoonafterHCTZuse;however,chronicallyH2OlossislessthanNa+ loss(Eisfalse).
SuggestedReading
SpitalA.Diuretic-inducedhyponatremia.AmJNephrol191:447–452,1999.
AstrafN.LoursdeyR,ArialAI.Thiazide-inducedhyponatremiaassociatedwithdeathorneurologicdamagein outpatients.AmJMed70:1163–1168,1981.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
23.A49-year-oldmalewasbroughttotheEmergencyDepartmentforevaluationofnausea,fatigue,andweaknessfor24h. Hiswifesaysthathehadbeenhavingbingedrinkingwithoutanyfoodintake.Heisnottakinganymedications.On physicalexamination,hewaseuvolemic.Hisweightis70kg.BPis100/60mmHgwithapulserateof82beats/min. Serum[Na+]is120mEq/L;[K+]3.8mEq/L;BUN8mg/dL;creatinine0.6mg/dL;andosmolality230mOsm/kg H2O.Urinestudiesare:Osmolality75mOsm/kgH2O;Na+ 10mEq/L;andK+ 20mEq/L.Thediagnosisofbeer potomaniawasmade.Assumingnourineoutputin2–3h, whichoneofthefollowingistheMOSTappropriate therapyforthispatient?
A.D5W
B.0.9%NaCl
C.3%NaCl
D.0.45%NaCl
E.FluidrestrictionandNaCltablets
TheanswerisB
Treatmentofacutesymptomatichyponatremiaduetobingedrinkingisatherapeuticchallengetophysicians becauseofwaningandwaxingsymptoms.Areviewoftheliteratureonhyponatremiaduetobeeringestionshows administrationof0.9%NaCl,0.45%NaClwithKClsupplementation,and3%NaClandfluidrestrictiontono treatment.Thus,treatmentofhyponatremiadependsontheseverityanddurationofonsetofsymptoms.
Thispatienthasmildtomoderatesymptomsofhyponatremia.Theappropriatetreatmentappears0.9% salineratherthan3%saline(Biscorrect).RapidcorrectionofserumNa+ from120to126mEq/Lby3%saline isnotnecessaryinthispatient.Furthermore,rapidcorrectionofserumNa+ to >130mEq/Linanalcoholicmay precipitateosmoticdemyelinationsyndrome.Therefore,eitherinfusionof0.9%saline(1Lin24h)orfluid restrictiontoincreaseserumNa+ by <10mEq/Lin24hor <18mEq/Lin48hisadvisable.
D5WisnotthesolutionofinitialchoiceinthispatientbecauseitisconvertedintofreeH2Oandmaylower serum[Na+]evenfurther.D5Wcanbestartedifcaloricintakeisneededafterserum[Na+]reachesapproximately128mEq/L.Also,fluidrestrictionwithsupplementationofNaCltabletsisnottheappropriatechoice.
SuggestedReading
SanghaviSR,KellermanPS,NanovicL.Beerpotomania:anunusualcauseofhyponatremiaathighriskof complicationsfromrapidcorrection.AmJKidneyDis50:673–681,2007.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
24.A28-year-oldwomanwasadmittedfornausea,vomiting,blurredvision,andquestionableseizures.Shewaselectively intubatedforair-wayprotection.Furtherhistorywasobtainedfromthemother,whostatedthatthepatienthad nonbloodydiarrheafor2daysanddrankseverallitersofwater.Thepatientisastrictvegan,andingoodhealth,and doesnottakeanymedications.PhysicalexaminationrevealedathinfemalewithaBPof116/72mmHgwithapulseof 98beats/min.Lungandheartexaminationwerenormal.Therewasnoperipheraledema.Herweightwas64kg.Six weeksagoshedeliveredahealthybabyandherserum[Na+]was140mEq/L.Thelaboratoryresultsshowed:
SerumUrine
Na+ ¼ 114mEq/LNa+ ¼ <20mEq/L K+ ¼ 2.7mEq/LK+ ¼ 6mEq/L
Cl ¼ 78mEq/LOsmolality ¼ 40mOsm/kgH2O
HCO3 ¼ 17mEq/L
Creatinine ¼ 0.5mg/dL
BUN ¼ 4mg/dL
Glucose ¼ 100mg/dL
Uricacid ¼ 2.9mg/dL
Osmolality ¼ 240mOsm/kgH2O
Assuminghertotaloutput(diarrhealfluid,urineoutput,andinsensibleloss)is2L/day,howmuchwatershemay haveconsumedthatloweredherserum[Na+]from140to114mEq/L?
A.8L
B.9L
C.11L
D.13L
E.15L
Theanswer:isC
First,calculatehertotalbodywater(TBW)andtotalbodyNa+ priortoadmission,andthencalculatewater excess.
Second, addtotaloutputfor2days(4L)towaterexcessof7.3L.Therefore,thepatientmayhaveconsumed approximately11Lofwater.Thus,answerCiscorrect.
SuggestedReading
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
25.IntheEmergencyDepartment,shereceived100mLof3%NaCl,andherurineoutputwasnotedtobe200mL/h. Repeatserum[Na+]in4hwas119mEq/L.Shewasextubated.ThepatientdidnotreceiveanyIVfluidsorother interventionsforthenext20h.Theurineoutputincreasedto300mL/h.After24h,herserum[Na+]was141mEq/L. WhichoneofthefollowingistheMOSTappropriatenextstepinthemanagementofherhyponatremia?
A.D5Wat100mL/h
B.Freewaterbolusesat200mLQ6HviaN/Gtube
C.0.45%Salineat100mL/h
D.Restrictfluidto1L/day
E.DDAVP1–2 μgIVor4 μgsubcutaneouslywithfreewaterboluses(200mLQ6H)
TheanswerisE.
Althoughserum[Na+]canbecorrectedrapidlyinpolydipsicpatients,theincreaseof27mEqin24histoorapid becauseofincreasedurineoutput.Serum[Na+]mayfurtherincrease,ifurineoutputdoesnotdecrease. Therefore,theappropriatemanagementatthistimeistopreventfurtherincreaseinserum[Na+],anddemyelination,andthesechangescanbereversedbyreadministrationofDDAVPandhypotonicfluids.Studiesin animalsandhumanssuggestthatthistypeofmanagementisappropriatetopreventfurtherincreaseinserum [Na+].DDAVP1–2 μgIVshouldbestartedwithfreewaterbolusesorD5W.Thus,optionEiscorrect.Infusionof hypotonicsolutionsaloneisnotsufficienttoreversedemyelination.
SuggestedReading
SternsRH,HixJK,SilverS.Treatingprofoundhyponatremia:Astrategyforcontrolledcorrection.AmJKidneyDis 56:774–779,2010.
ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
26.A32-year-oldwomanwithAIDSwasreferredtotherenalclinicforevaluationofpersistenthyponatremia.Therewas nohistoryofrecentinfections,butadmitstodailyintakeofbeerandattimesdepression.Thepatientisthinbutnot cachectic.BPis120/80mmHgwithapulseof78beats/min.Therearenoorthostaticchanges.Examinationoflungand heartarenormal.Noperipheraledemaisappreciated.Serumandurinechemistries:
SerumUrine
Na+ ¼ 126mEq/LOsmolality ¼ 578mOsm/kgH2O
K+ ¼ 4.2mEq/LNa+ ¼ 80mEq/L
Cl ¼ 94mEq/LK+ ¼ 40mEq/L
HCO3 ¼ 23mEq/L
BUN ¼ 12mg/dL
Creatinine ¼ 0.5mg/dL
Glucose ¼ 104mg/dL
Albumin ¼ 3.4g/dL
Normalliverfunctiontestsandcortisol
Osmolality ¼ 264mOsm/kgH2O
WhichoneofthefollowingtreatmentsisINAPPROPRIATEinthispatient?
A.Waterrestriction
B.Lithium
C.Demeclocycline
D.Selectiveserotoninreuptakeinhibitor(SSRI)
E.Dilantin
Theanswer: isD
ExceptforSSRI,othertreatmentmodalitieshavebeentriedtoimprovechronicasymptomatichyponatremiain patientswithectopicproductionorstimulationofADH.SSRIssuchassertraline,paroxetine,andduloxetine inhibitthereuptakeofserotonin,thuscausinghyponatremia.SSRIsinduceSIDAHbyseveralmechanismsthat include:(1)stimulationofADHsecretion;(2)augmentationofADHactionintherenalmedulla;(3)resettingthe osmostatthatlowersthethresholdforADHsecretion;and(4)interactionofSSRIswithothermedicationsvia p450enzymes,resultinginenhancedactionofADH.Thus,Discorrect.DilantininhibitsADHsecretion,sothatit willimprovehyponatremia.
SuggestedReading
JacobS,SpinlerSA.Hyponatremiaassociatedwithselectiveserotonin-reuptakeinhibitorsinolderadults.Ann Pharmacother40:1618–1622,2006.
MortJR,AparasuRR,BaerRK.Interactionbetweenselectiveserotoninreuptakeinhibitorsandnonsteroidalantiinflammatorydrugs:Reviewoftheliterature.Pharmacotherapy26:1307–1313,2006.
27.A65-year-oldmanwithsmallcellcancerofleftlungisfoundtohavehyponatremiaduetoSIADH.Heisseenbya nephrologist,whostartedhimonafluidrestrictionof1L/day.Patientrefusedtotakedemeclocyclinebecauseofhis alcoholuseandureaforgastrointestinalupset.Forawhile,hisserum[Na+]wasmaintainedbetween130and135mEq/L. Thepatientwasgivenafollow-upvisitin3months,atwhichtimehepresentedwithweakness,fatigue,andtheinability toconcentrateduringconversation.Healsocomplainedthathehadasenseoffalling.HecheckedhisBPwhichwas 140/78mmHg.Headmittedtodrinking >1Loffluids/daybecauseofincreasedthirst.Hisserum[Na+]is124mEq/L, andeuvolemic.OtherlaboratoryresultsareconsistentwithSIADH. Whatistheappropriatestepinthemanagement ofhishyponatremia?
A.Fluidrestrictionundersupervision
B.Normalsaline
C.Tolvaptan
D.Hypertonicsaline
E.Salttablets
TheanswerisC
Thepatientissymptomaticfromhischronichyponatremia.Impairmentincognitivefunctionandfallswith fracturesarenotuncommoninpatientswithchronichyponatremia.Thepatientshouldbeadmittedtothe hospitalfortworeasons:(1)toimprovesymptomswithanincreaseinserum[Na+]to128–130mEq/Lina24h period,and(2)considerationforanoralvaptan,asthepatientisnoncomplianttofluidrestriction.Tolvaptanis theoralformthatisavailableas15,30,and60mgtablets.
Tolvaptanshouldbestartedinahospitalsettingformonitoringofserum[Na+]duringthedosage-titration phase.Thedrugisstartedat15mgoncedailyandtitratedupto60mgdailywithoutfluidrestriction.Oncethis patient’ssymptomsimprove,hecanbedischarged2–3daysonafixeddoseoftolvaptan.
Tolvaptanisindicatedinpatientswitheuvolemicandhypervolemichyponatremicpatients.Itshouldnotbe usedinpatientswithhypovolemichyponatremia.Clinicalstudieshaveshownbeneficialeffectsoftolvaptan.
TheSALTtrials,whichincludedpatientswithSIADH,CHF,andcirrhosis,showedthattolvaptanincreased serum[Na+]by4.5mEq/Londay4,and7.4mEq/Lovera30-dayperiodcomparedwithfluidrestrictionalone. Thepatientswerealsofollowedupforameanof701days.Meanserum[Na+]increasedfrom131to >135mEq/L.
Thispatientwillbenefitfromtolvaptanusetoincreasehisserum[Na+]andpreventfallsandfractures.Thus, Ciscorrect.Otheroptionsdonothelplong-termhyponatremia
SuggestedReading
ThurmanJM,BerlT.Disordersofwatermetabolism.In:MountDB,SayeghMH,SinghAJ(eds).CoreConceptsinthe DisordersofFluid,ElectrolytesandAcid-BaseBalance.NewYork,Springer,2013,pp.29–48. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
28.A3-month-oldinfantisadmittedforirritability.PhysicalexaminationisunremarkableotherthanaBPof 128/92mmHg.Serum[Na]is123mEq/L,creatinine <0.3mg/dL;BUN5mg/dL,vasopressin <1pg/mL(normal 1–13.3),urineosmolality284,andurineNa+ 35;otherchemistriesarenormal. Whichoneofthefollowingisthe MOSTlikelydiagnosisinthisinfant?
A.Classicalsyndromeofinappropriateantidiuretichormonesecretion(SIADH)
B.NephrogenicSIADH(NSIADH)
C.Congestiveheartfailure(CHF)
D.Dehydration
E.Drug-inducedhyponatremia
TheanswerisB
NSIADHissimilartoSIADH,butrare.Itwasfirstdescribedin2005ininfantswithhyponatremiaandhighurine osmolality.UnlikeSIADH,patientswithNSIADHhaveundetectableorextremelylowADHlevels.NSIADHisa gain-of-functionmutationinvasopressinV2receptor(Biscorrect).Treatmentisfluidrestriction,urea,and vaptans.NSIADHwasalsodescribedinpatientsolderthan10yearsofage.Otheroptionsareincorrectbecause theseconditionsareassociatedwithhighADHlevels.Itshouldbenotedthatindrug-inducedhyponatremia,the ADHlevelsmaybenormalorhigh.
SuggestedReading
ThurmanJM,BerlT.Disordersofwatermetabolism.In:MountDB,SayeghMH,SinghAJ(eds).CoreConceptsinthe DisordersofFluid,ElectrolytesandAcid-BaseBalance.NewYork,Springer,2013,pp.29–48. ReddiAS.Disordersofwaterbalance:Hyponatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.101–131.
29. WhichoneofthefollowingistheLEASTlikelycauseofnonhypotonichyponatremia?
A.Granulatedsugar(sucrose)
B.Hyperproteinemia
C.Hypercholesterolemia
D.Hypertriglyceridemia
E.Methanol
TheanswerisE
Inacasereport,topicalapplicationofgranulatedsugartoaninfectedwoundresultedinhypertonic hyponatremia.Unlikeoralsucrose,directlyabsorbedsucrosefromawoundintocirculationdoesnotmetabolize intoglucoseandfructose.Thisresultsinhypertonichyponatremia.Elevatedproteinsasinmultiplemyeloma,a differentformofcholesterolfoundinlipoproteinX(2)ortriglyceridescauseisotonichyponatremia.Lipoprotein
Xhasbeendescribedinpatientswithcholestaticliverdiseasesuchasprimarybiliarycirrhosis.Patientswith severetriglyceridemiawillhavealactescentserum.However,methanolcausesosmolalgapbutnotnonhypotonic hyponatremia.
SuggestedReading
TurchinA,SeifterJL,SeelyEW:Mindthegap.NEnglJMed349:1465–1468,2003. ReutersR,BoerW,SimmermacherR,etal.Abagfullofsugarmakesyoursodiumgodown.NephrolDialTransplant 20:2543–2544,2005.
30.A50-year-oldhypertensivemanisadmittedforheadacheandalteredmentalstatus.ACTscanoftheheadshows subarachnoidhemorrhage.Heisreceivinghyperalimentation,andhisurineoutputis4L/day.Also,thenursenotices diarrheaof1-dayduration.HisserumNa+ is149mEq/L,K+ 3.3mEq/L,HCO3 26mEq/L,BUN44mg/dL,creatinine 1.6mg/dL,andglucose200mg/dL.HisurineNa+ is70mEq/L,andurineosmolality380mOsm/kgH2O.Hisvolume statusisadequate. WhichoneofthefollowingistheMOSTlikelycauseofhishypernatremia?
A.Nephrogenicdiabetesinsipidus
B.Partialcentraldiabetesinsipidus
C.Osmoticdiarrhea
D.Osmoticdiuresis
E.7.5%NaCladministrationtoimprovebrainedema
TheanswerisD
Patientswitheithernephrogenicdiabetesinsipidusorpartialcentraldiabetesinsipidushavemostlywater diuresisratherthanhighsolutediuresis.Theosmolalexcretionisnormalindiabetesinsipidus.Patientswith diabetesinsipidushavelowurineosmolalitydespiteahighserumosmolalityorhypernatremia.Thepatientis excretingatotalof1520mOsm/day(380 4 ¼ 1520).Therefore,thepatienthassolutediuresis.Thus,optionsA andBareunlikelyinthispatient.OptionCisalsounlikelybecausetheurinaryNa+ levelis70mEq/L,whichis highinconditionssuchasdiarrhea.Inapatientwithdiarrhea,thekidneyconservesratherthanexcretingNa+. OptionEisalsounlikelybecausethepatientdoesnothaveanyvolumeexpansionduetohypertonicsaline infusion,andthepatientshouldhaveasodiumdiuresis.Thepatienthasosmoticdiuresis,whichisthecauseofhis hypernatremia(Discorrect).Ingeneral,theurineosmolalityinosmoticdiuresisisrelativelyhigherthanserum osmolality.Thefollowingflowdiagram(Fig. 1.5)showsthedifferentialdiagnosisofpolyuria.
Fig.1.5 Diagnosticapproach tothepatientwithpolyuria
Urine osmolality (<300 mOsm)
Polyuria
Central DI
Nephrogenic DI
Gestational DI
Urine osmolality (>300 mOsm)
Electrolytes (NaCl, NaHCO3)
Sugars (glucose, mannitol, glycerol or BUN)
SuggestedReading
OsterJR,SingerI,ThatteL,etal.Thepolyuriaofsolutediuresis.ArchInternMed157:721–729,1997. ThurmanJM,BerlT.Disordersofwatermetabolism.In:MountDB,SayeghMH,SinghAJ(eds).CoreConceptsinthe DisordersofFluid,ElectrolytesandAcid-BaseBalance.NewYork,Springer,2013,pp.29–48. ReddiAS.Disordersofwaterbalance:Hypernatremia.InReddiAS.Fluid,Electrolyte,andAcid-BaseDisorders. ClinicalEvaluationandManagement.NewYork,Springer,2014,pp.133–150.
Water diuresis Solute diuresis
31.A74-year-oldmanisadmittedtothenursinghomeforlethargy,disorientation,andconfusion.Thenurse’srecordshows thatthepatienthadcerebrovascularaccident5yearsago.Thepatientdidnothaveanyfever,diarrhea,orfluidloss. Urineoutputisrecordedas700mL/day.
Onadmission,theBPis100/70mmHgwithapulserateof100beats/min(supine)and80/60mmHgwithapulserate of110beats/min(sitting).Physicalexaminationisnormalexceptfordrymucousmembranes.Heweighs70kg. Laboratoryvaluesare:
SerumUrine
Na+ ¼ 168mEq/LNa+ ¼ 12mEq/L
K+ ¼ 4.6mEq/LOsmolality ¼ 600mOsm/kgH2O
Cl ¼ 114mEq/L
HCO3 ¼ 26mEq/L
Creatinine ¼ 1.9mg/dL
BUN ¼ 64mg/dL
Glucose110mg/dL
Whatwouldhiswaterdeficitbewhencalculatedfordesiredserum[Na+]of140mEq/L?
A.3–4L
B.4.1–5L
C.5.1–6L
D.6.1–7L
E. >8L
TheanswerisE
Anyoneofthefollowingformulascanbeusedtocalculatewaterdeficit:
Formula1
Waterdeficit ¼ PrevioustotalbodywaterTBWðÞ actualNa½þ¼ DesiredNa½þ NewTBW
NewTBW ¼ PreviousTBW ActualNa ½þ
DesiredNa½þ
Example : Weight ¼ 70kg
PreviousTBW ¼ 70 0 6 ¼ 42L
ActualNa½þ¼ 160mEq=L
DesiredNa½þ¼ 140mEq=L
NewTBW ¼ 42 160=140 ¼ 48L
Waterdeficit ¼ NewTBW PreviousTBWor48
Formula2
Waterdeficit ¼ PreviousTBW
Byusingtheaboveexample,weobtain:
Actual Naþ 1
DesiredNa½þ
Formula3(aroughestimate)
AneditorialbySternandSilver(QJM96:549–552,2003)suggeststhatadministrationof3–4mL/kgofelectrolyte-free watercanlowerserum[Na+]by1mEq/Linaleanindividual.Totalwaterdeficitcanbecalculatedasweightin kg mLtobeadministered(3or4mL) thedifferencebetweentheactualanddesired[Na+] Ifweapply4mL/kgtoa70kgindividualtoreduceserum[Na+]from160to140mEq/L,thewaterdeficitwouldbe: 70 4 20or280 20 ¼ 5.6L
Another random document with no related content on Scribd:
*** END OF THE PROJECT GUTENBERG EBOOK PAITA
Updated editions will replace the previous one—the old editions will be renamed.
Creating the works from print editions not protected by U.S. copyright law means that no one owns a United States copyright in these works, so the Foundation (and you!) can copy and distribute it in the United States without permission and without paying copyright royalties. Special rules, set forth in the General Terms of Use part of this license, apply to copying and distributing Project Gutenberg™ electronic works to protect the PROJECT GUTENBERG™ concept and trademark. Project Gutenberg is a registered trademark, and may not be used if you charge for an eBook, except by following the terms of the trademark license, including paying royalties for use of the Project Gutenberg trademark. If you do not charge anything for copies of this eBook, complying with the trademark license is very easy. You may use this eBook for nearly any purpose such as creation of derivative works, reports, performances and research. Project Gutenberg eBooks may be modified and printed and given away—you may do practically ANYTHING in the United States with eBooks not protected by U.S. copyright law. Redistribution is subject to the trademark license, especially commercial redistribution.
START: FULL LICENSE
