Electrolyte Abnormalities in the Hospital: Diagnosis and ......Initial evaluation of Hyponatremia • True (hypotonic) hyponatremia vs non-hypotonic hyponatremia (including pseudohyponatremia)?

ElectrolyteAbnormalitiesintheHospital:Diagnosisand

Management

MatthewRivara,MD,FASNAssistantProfessorofMedicine

DivisionofNephrologyUniversityofWashington

Objectives

Useacase-basedapproachtodiscussworkupandmanagementof…

1.  Sodiumandwaterdisordersinhospitalizedpatients▫  Focusonhyponatremia

2.  Potassiumdisordersinhospitalizedpatients▫  Focusonhypokalemia

HypokalemiaCase6–Ayoungwomanwithheartfailure

Case1:bodyfluid

compartments

Hyponatremia/HypernatremiaCase2:RavereviewsCase3:Acaseofiatrogenesis?Case4:Howmuchcanyoudrink?Case5:The“un-watered”patient

Summary & Take home points

Outline

Case1:BodyfluidcompartmentsA20yearoldmanpresentstothehospitalafterexperiencingagrandmalseizure.Examandvitalsondayofadmissionarenormal(PNawas140mEq/L).•  Experiencesarecurrentwitnessedseizurex3minutes•  Blooddrawnimmediatelyà+aniongapmetabolicacidosis,returnedtonormalinlessthan1hour.•  PNawas154mEq/L,butfellbackdownto140mEq/Loverashortperiodoftime.•  Noincreaseinurineoutput,orfreewateradministrationduringthistime

Question:WhatisthebasisoftheacuteriseinPNa?

Bodyfluidcompartments•  Totalbodywater≈50-60%oftotalbodymass▫  2/3inICFand1/3inECF▫  ECF:75%interstitial,25%plasmavolume

TBW = 40L (60% body weight of 70 kg person)

Intracellular fluid volume =

25L, 40% body weight

Extracellular fluid volume =

15L, 20% body weight

Inte

rsti

tia

l fl

uid

vo

lum

e =

12L

(80

% o

f E

CF

)

Pla

sma

vo

lum

e =

3L

(20

% o

f E

CF

)

2/3 1/3

Determinantsofvolumeofcells•  ContentofNaintheECFisthemajordeterminantofitsvolume.

•  ConcentrationofNaintheECFcompartmentisthemostimportantfactorinICFvolume(exceptwhencellshaveothereffectiveosmoles).

• MajorintracellularfactorresponsibleforaccumulationofwaterincellsisretentionofK

K+

K+ K+

K+

K+ K+

Na+

Na+

Na+

ICF ECF

ChangesinvolumesofbodyfluidswithIVfluids

K+

K+

K+

K+

Na+

Na+

ICF ECF Gain of pure water

K+ K+

K+ K+

Na+

Na+

ICF ECF ICF ECF

Na+

Na+

Gain of Isotonic Saline

K+

K+

K+

K+

Na+

Na+

BacktoCase1…

•  Case:A20yearoldmanpresentstothehospitalafterexperiencingagrandmalseizure.Examandvitalsondayofadmissionarenormal(SNawas140mEq/L).Severalhourslaterheexperiencesawitnessedgrandmalseizure.SurprisinglyhoweverhisSNawas154mEq/L,butfellbackdownto140mEq/Loverashortperiodoftime

•  Question:WhatisthebasisoftheacuteriseinhisSNa?

Answer

•  Transienttranscellularshiftinwaterduetosuddenandmassiveincreaseineffectiveosmolesinskeletalmusclecells(pullsH2Oin)

Muscle Cell

H2O

Glycogen + ADP + Pi à ATP + 2H+ +

Na+/H2O

Na+/H2O

2 Lactate-

Case2:Ravereviews•  A19y/omanwithhistoryofanorexianervosapresentstotheERwithcomplaintofweaknessandlethargy.PriortoadmissionwasataravewherehetookMDMA(Ecstasy/Molly)anddrankalargeamountofwatertoavoiddehydrationfromsweating.

•  IntheED,hehadagrandmalseizurex3minutes.BloodwasdrawnimmediatelyaftertheseizureandSNawas130mEq/L.Uosm700mOsm/kg.

•  AdmittedtoMedicineànextAM,SNawas120meq/L

Questions

•  Is thisacutehyponatremia?• WhydidhehaveaseizureiftheSNawas130mEq/L?AndwhywasSNathenextmorninglower?

• Whatrolemayanorexianervosaplayintheclinicalpicture?

•  Howdoyoumanage?

InitialevaluationofHyponatremia•  True(hypotonic)hyponatremiavsnon-hypotonichyponatremia(includingpseudohyponatremia)?▫  Isthistruehypotonichyponatremia?

•  Acuity/Severity▫  Isthisacute(<48hr)orchronic?▫  Isthepatientsymptomatic?

•  Etiology▫  IsADHactingornot?Why?▫  Whatisthevolumestatusofthepatient?▫  Wheredidtheexcessfreewatercomefrom?▫  Whycanthekidneysnotexcreteexcesswater?

Non-hypotonichyponatremia•  Hypertonicorisotonichyponatremia▫  Hyperglycemia�  Dilutionalhyponatremia,noriskofcerebraledema�  Cancalculate“corrected”serumsodium(predictedserumsodiumw/correctionofhyperglycemia)�  2mEq/Lforeach100mg/dLincreaseinglucose

▫  Rareothercauses�  IVIGorsurgicalirrigantsolutions(glycineorsorbitol)

•  Pseudohyponatremia(laboratoryartifact)▫  Hypertriglyceridemia(lessrelevantinmodernera)▫ Monoclonalgammopathy

InitialevaluationofHyponatremia•  True(hypotonic)hyponatremiavsnon-hypotonichyponatremia(includingpseudohyponatremia)?▫  Notnecessarytotestforineverycase,buttor/o,checkserumosm

•  Acuity/Severity▫  Isthisacute(<48hr)orchronic?▫  Isthepatientsymptomatic?

•  Etiology▫  IsADHactingornot?Why?▫  Whatisthevolumestatusofthepatient?▫  Wheredidtheexcessfreewatercomefrom?▫  Whycanthekidneysnotexcreteexcesswater?

SymptomsofHyponatremiaIncreasing severity of

hyponatremia and rate of

[Na+] decline

Verbalis JG et al. Am J Physiol. 1986;250(3 pt 2):R444-R451. Slide credit: M. Rosner

Hyponatremic brain

Normalbrain

(normalosmolality)

Watergain(low

osmolality)

Lossofsodium,K+andCl–

(lowosmolality)

Lossoforganic

osmolytes(low

osmolality)

RateofHyponatremia:EffectsonCellularVolume

16

AdrogueHJetal.NEnglJMed.2000;342:1581-589.

Immediateeffectofhypotonicstate

RapidadaptationSlowadaptation

Propertherapy

Water

Understandingthecellularadaptationsiscriticalinthepropertreatmentofacutev.chronichyponatremia

Slide credit: M. Rosner

InitialevaluationofHyponatremia•  True(hypotonic)hyponatremiavsnon-hypotonichyponatremia(includingpseudohyponatremia)?▫  Notnecessarytotestforineverycase,buttor/o,checkserumosm

•  Acuity/Severity▫  Isthisacute(<48hr)orchronic?▫  Isthepatientsymptomatic?

•  Etiology▫  IsADHactingornot?Why?▫  Whatisthevolumestatusofthepatient?▫  Wheredidtheexcessfreewatercomefrom?▫  Whycanthekidneysnotexcreteexcesswater?

Low EABV Edematous states (CHF, cirrhosis, nephrotic syndrome) Adrenal insufficiency (high CRH)

Stress, pain, nausea, drugs, carcinomas, pulmonary disorders, CNS disorders

Bhardwaj, Ann Neurol. 2006

Vasopressin(ADH)

InterpretingUrineOsmolarity

•  ADH“on”or“off”?▫  [TestserumADHlevels]▫  Urineosmolarity?�  ADH“on”àUosms>300�  ADHappropriately“off”àUosms50-150

Collectingductepithelialcell

ADH

V2 receptor

H2O

Urinary space

H2O

H2O

Aquaporin 2

Causesofhypotonichyponatremia?Hypotonic

Hyponatremia

ADH“active”

Volumedepletion

ADH“inactive”

SIADH CHF

CirrhosisIdiopathic

Intracranialprocess

Intrapulmonaryprocess

Hypothyroidism

Adrenalinsufficiency

Lowsoluteintake

PrimarypolydipsiaRenal

dysfunction

Drugs

Othermalignancy

Hypovolemic HypervolemicEuvolemic

Renalfailure

SIADHversuslowEABV?

•  History?•  Physicalexamination?▫  Vitals,orthostatics,JVP,etc▫  Advancedexam:IVCcollapsibility,bedsideTTE•  LabTests?▫  Urinesodium�  Low(<20meq/L)àvolumedepletion�  Notlow(>40meq/L)àSIADH▫  Serumuricacid�  <4mg/dlàconsistentwithSIADH

Iliternormalsaline(350mosm/L)

SIADH w/ urine osm 400 mosm/L

875mlurine125mlfreewater

SIADH w/ urine osm 900 mosm/L

390mlurine

610mlfreewater

Iliternormalsaline(350mosm/L)

+

+

OtherdiagnosticmaneuversforSIADHversuslowEABV?

What about just giving IV fluids?

Case2again•  A19y/omanwithhistoryofanorexianervosapresentswithweakness,lethargy,andinabilitytoconcentrate.PriortoadmissionwasataravewherehetookMDMAanddranklotsofwater.

•  IntheED,hehadagrandmalseizure.Afterward,SNawas130mEq/LandUosmwas700mOsm/kg.

•  Vitals:Ht5’7”andwt105Lbs(45kg).Afebrile.HR80BP110/70

•  Exam:Post-ictal,diaphoretic.Ralesonchestexam

Answerstocase2•  Isthisacutehyponatremia?▫  YES!Why?▫  Ingestionoflargevolumeofwater▫  IngestionofEcstasy,adrugthatleadstosecretion/releaseofvasopressin,andthusSIADH

• WhydidhehaveSz?▫  Acutehyponatremia▫  SNafromvenoussampleafterSzoverestimatespriorSNa.NumberofosmolesincreasedinmusclecellduringSz

• What’stheroleofanorexianervosa?▫  Lowmusclemass(50%ofTBW).▫  SmallerpositivewaterbalancecausesgreaterfallinhisSNa.

Case2,continued•  Treatment?▫  Symptomaticandacute:DrawoutwaterfromskullbyraisingtheSNaacutely/ASAP

▫  Givehypertonicsalinerapidly:1-2cc/kgbolusof3%NSover10min(maximumof100cc).Mayrepeat1-2moretimesasneededuntilsymptomsimprove.

▫  Goalis4-6mEq/LincreaseinSNaover1-2hr.

▫  CloselyfollowSNaandandwatchforreabsorptionofwaterfromreservoirinintestineormusclecells.

▫  Donotexceed15mEq/Linfirst48hrs.

Case3–Acaseofiatrogenesis?

•  80yearoldwomenishospitalizedfor1wkhistoryofprogressiveweakness,nauseaandanorexia.Hasbecomebedriddenandconfusedduringpast3days.Shehashypertensionmanagedwithenalaprilandchlorthalidoneinitiated3weeksago.OnadmissionSNawas110mEq/L,Kof3

•  PhysicalExam:T37.3C,BP110/65,HR95andRR14.Wt47kg.BMI20.Cardiacandpulmonaryexamsnormal.Nofocaldeficitsonneuroexam.Noedema,ascites.

LabstudiesParameter Admission

PlasmaAdmissionUrine

Na(mEq/L) 110 30

K(mEq/L) 3

Cl(mEq/L) 72 30

HCO3(mEq/L) 30

Cr 1

BUN 9

Glucose 90

Osmolality 231 500

Whatisthecauseofthispatient’s

hyponatremia?

Thiazide-inducedhyponatremia•  Increasedincidenceinwomenandelderlypatients

•  Pathogenesisunclear,butpotentialcauses:▫  VolumelossàADH-inducedwaterretention▫  ?Increasedthirstduetoxerostomia▫  ?IncreasedADHrelease

Returningtothelabs…

Parameter AdmissionPlasma

AdmissionUrine

10hrPlasma

10hrUrine

Na(mEq/L) 110 30 121 25K(mEq/L) 3 2.7Cl(mEq/L) 72 30HCO3(mEq/L) 30Cr 1BUN 9Osmolality 231 500 252 180UrineOutput 400cc/hr

InEDgiven80ccof3%salineandmentationrapidlyimproves.Afteradmission,someadditionalisotonicfluidisgiven.10hourslater…

Sonowwhat?

• Whichofthefollowingisthemostappropriatetreatmentforthispatient?

(A) 0.9%Saline

(B)  5%Dextroseinwater+KCl

(C)  Fluidrestriction+KCl

(D) Tolvaptan

Answer

•  5%Dextroseinwater+KCltodropSNabacktogoalrateofrise

• Whatisthegoalratetoavoidavoidosmoticdemyelination(ODS)?▫  Chronic(>48hr):0.5mEq/Lperhour,≤10mEqinfirst24hr(6-8inthosewithRFforODS)and≤18infirst48hr.

▫  Acute(<48hr)symptomatic:1-2mEq/Lperhour,correctingby4-6mEq/Land/orcorrectionofsymptoms.

OsmoticDemyelinationSyndrome(ODS)

Symptoms seen 2-6 days after correction: •  Dysarthria (CPM) •  Dysphagia (CPM) •  Ataxia, dystonia •  “Locked in” state •  Acute flaccid paralysis •  Coma

Case4:Howmuchcanyoudrink?•  45yearoldmanwithschizophrenia,wellmanagedonanti-psychotics,intermittentlyunhoused,alsowithalcoholusedisorder,presentstotheHMCemergencydepartmentwithrightlegswelling,erythema,pain.Diagnosedclinicallywithcellulitis.

•  Onarrival,vitalsignsarestable.Notorthostatic.

Parameter ValuePlasmavaluesNa(mEq/L) 116K(mEq/L) 3.5Cl(mEq/L) 88Bicarb(mEq/L) 26Creatinine(mEq/dL) 0.8BUN(mEq/dL) 9Glucose(mEq/dL) 119Osmolality(mOsm/kg) 246Bloodalcohol UndetectableUrineOsmolality(mOsm/kg) 75Na(mEq/L) 7

Questions

•  Is thisacutehyponatremia?• Whatarethepossibleetiologiesforhishyponatremia?

•  Howdoyoumanage?

InitialevaluationofHyponatremia•  Truehyponatremiavsnon-hypotonichyponatremia?▫  Truehyponatremia(lowserumosms)

•  Severity/chronicity?▫  Moderatetosevere,likelychronicgivenasymptomatic

•  Etiology▫  IsADHactingornot?

�  No!(Howdoyouknow)▫  Whatisthevolumestatusofthepatient?

�  Euvolemic▫  Wheredidtheexcessfreewatercomefrom?

�  Beer+water▫  Whycanthekidneysnotexcretetheexcesswater?

�  Lowsoluteintakew/highwaterintakelikely

Primarypolydipsiavs.Lowsoluteintake•  Key:Hyponatremiaensueswhenwaterintakeexceedsmaximumurineoutput

•  NormalAmericandiet(perday):

÷=8to12litersurine/day

•  Lowsoluteintake(“tea-and-toast”or“beerpotomania”)

÷=2.6litersurine/day

600-900mosms

75mOsmsperliter

200mosms

75mOsmsperliter

Case5:The“un-watered”patient•  61y/ofemalewithh/obipolardisorderandpasth/olithiumusetransferredfromAlaskawithintractableseizures.WorkupdemonstratedneuronalK+channelAb.PatientadmittedtoICU,startedonpulsesteroids,wasNPOduetoAMS.Alsoonkeppraanddepakote.

•  Vitals:T36.1HR65BP110/68RR1296%RA.Wt50kg

•  Exam:▫  GEN:Somnolent.▫  Neuro:Followingsimplecommands.Intactgag.Facesymmetric.▫  Ext:Noedema

First36hoursofadmission…135

4.2

103

26

15

0.78 88

Ca 9.8

SNa156(36hrsafteradmit)Outs:IncontinentIns:NS75cc/hrTFat45cc/hr

HypernatremiaQuestion:Whatarethemajorcausesofhypernatremiainhospitalizedpatients?

•  Primarywaterdeficit▫  Reducedwaterintakeordefectivethirstmechanism▫  Increasedwaterloss

�  Renalloss:Central/nephrogenicDI,osmoticdiuresis�  GIloss:Vomiting,Nasogastricsuction,osmoticdiarrhea�  Insensiblelosses:Respiratory,skin▫  Shiftofwaterintocells:Seizures

•  PrimarygainofNa+▫  Infusionofhypertonicfluidinoliguricpatients

Factorstoassessthepatientwithhypernatremia•  Thirst(History):Whyispatientnotcompensating?

• Whatissourceofwaterloss?(urinevolume?)�  HighinsensiblewaterlossorGIloss(NGTsuction,diarrhea)

�  Polyuria?Urineflowrateandeffectiveosmolality:�  Osmoticdiuresis:Uosm400-500mOsm/kg� Waterdiuresis:Uosm<150mOsm/kg(LowADH)

Uosm >400-500mOsm/kg

>3L/day

Tumors (pituitary)Post-surgery, TBIInfiltration (sarcoid)

Renal interstitial dz & Drugs (Li mostly)

Case5-Subsequentmanagement

•  FoleycatheterplacedwithUOP175cc/hr

•  SNa=156

• Urineosm:140mosm/kg

•  Totalbodyfreewaterdeficit:TBWx([SNa/140]–1)▫  25Lx([156/140]–1)=2.9L

•  Treatment:D5Wat250cc/hrandFWB300Q6hr.

ChangesinSNaandUNa

SNa

UNa

Mentation improve, but UOP now increased to 250-300cc/hr

UK

Questions

•  IsthispartialorcompletenephrogenicDI?Whatdoyoudo?

• WhataretreatmentsforLithiuminducedNephrogenicDI?A.  Stoplithium(ifpossible,butwithcaution)B.  AmilorideC.  NSAIDs

Response to DDAVP? 4mcg IV DDAVP: Uosm 100->125 2hr after DDAVP.

•  Started on indomethacin with drop in urine output from 250-350cc/hr to 60-125cc/hr

Case6:Ayoungwomanwithheartfailure•  A32yearoldwomanwithnoPMHpresentstourgentcarewithabdominalpainx4months,foundtohaveBPof240/180.•  Deniesheadaches,visualchanges,chestpain• OnROS,endorses2weeksoflegswelling

•  PhysicalExam:T37.3C,BP240/183,HR87.Cardiacexamwith+S3,displacedPMIlaterally,1+LEedema,lungswithcracklesatbases

Case6,continued

•  InitiallabsintheEDàK2.4,HCO336,Cr1.2,andBNP3000.EKGconcerningforLVH.

•  ShewasgivenIVLabetolol30mg,POAmlodipine10mg,andPOLisinopril10mgwithimprovementinherBPsto188/140.

•  TTE:NormalLVsize,withconcentricLVHandmoderatelyreducedsystolicfunctionandglobalhypokinesis(LVEF30%).

Case6questions

Whatisthedifferentialdiagnosisforthispatient’shypokalemiawithmetabolicalkalosisinthesettingofseverehypertension?1.  Primaryhyperaldosteronism2.  Renalarterystenosisleadingtosecondary

hyperaldosteronism3.  Otherrareconditionsa)  Inheritedmonogenicdisordersb)  Apparentmineralocorticoidexcess

Hyperaldosteronism•  Estimatedtoberesponsiblefor20%ofsevere/resistantHTNinadults•  Includesboth▫  Bilateraladrenalhyperplasia(60%)▫  Aldo-producingadenomas(40%)

•  Clinicalfeatures▫  HTN▫  Hypokalemia(only~30%)▫  Metabolicalkalosis(only10-35%)

ScreeningforHyperaldosteronism•  Labtest:Serumaldosteroneandplasmareninactivity(PRA)▫  Ideally8am,OFFMRAs,Oktobeonotherdrugs�  ThoughACEI/ARBcanraisePRA,B-blockersdecreasePRA▫  Definition:�  Aldosterone/PRA>20,AND�  Serumaldosterone>15ng/dL

•  IscreeneveryonewithresistantHTNorwithHTN+spontaneous(orminimallyprovoked)hypokalemiaormetabolicalkalosis

“CaseConfirmation”forhyperaldo• Neededinmostcases▫  Exception:HTN,spontaneoushypokalemia,undetectablePRA,PAC>20ng/dL

•  Bestchoiceforinpatients:▫  Salineinfusiontest:2LNSover4hours,thencheckserumaldosteroneà+testis>12ng/dL

• NeedtocontrolserumpotassiumandBPprior

Hyperaldosteronismconfirmed–Nextstep?

Hyperaldo–Nextstep?

•  Adrenalvenoussamplingbyhighvolumeinterventionalradiologistorvascularsurgeon

•  Exception:Patients<35yearsofagewithcompletelysuppressedPRAandPAC>20ng/dL

Hyperaldo–NextStep?

Renalarterystenosis•  Prevalence10%-30%insevereorrefractoryHTN

Renalarterystenosis•  Clinicalclues:▫  Diffusevasculopathy(CAD,CVD,PVD)▫  Youngwomen(FMD)▫  Systolic+diastolicabdominalbruit(specific,notsensitive)▫  Isolatedsystolicbruit(sensitive,lessspecific)▫  Headaches,tinnitus,neckpain(FMD)▫  RiseincreatininewithACEI/ARB(oranyanti-HTNtherapy)

•  Key:knowwhatyouwilldowithresultsoftestingbeforeyouproceed

Renalarterystenosis–cont.

•  Diagnosis:centerdependent▫  Renalarteryduplex–onlyifyouhavegoodvascularlab,butgivesyousomefunctionalresults▫  CTAorMRAoftheabdomen•  Therapy:▫  FMD-renalarteryangioplasty(withoutstenting)�  Diseasecanrecur,buttypically>5-10yearslater�  Recommendedtoscreenothervascularbeds�  AllpatientsneedASA▫  Atherosclerosis–medicalmanagement(CORALandASTRALtrials)

Monogeniccauses•  Rare,butinterestinganddemonstratepathophysiology

•  Diseasesofdistaltubuleorcollectingduct

•  Theseareoftenassociatedwithhypokalemiaandmetabolicalkalosis(mimicprimaryhyperaldo)

•  3mostcommon(stillrare): ▫  Liddlesyndrome▫  Apparentmineralocorticoidexcess(AME)▫  Glucocorticoidremedialhyperaldosteronism

Bloodpressurehigh

Checkplasmaaldosteroneand

reninlevels

HighreninHighaldosterone

LowreninHighaldosterone

LowreninLowaldosterone

Reninoma

Renalarterystenosis

Primaryhyperaldo(Conn’ssyndrome

GlucocorticoidRemedial

Aldosteronism

Licoriceingestion

AME

Liddle’ssyndrome

Evaluationofhypokalemia+metabolicalkalosis…

Backtoourpatient…

•  Aldosteroneandrenintestingshowed:▫  Aldosterone:4ng/dL▫  PRA<0.1ng/mL/hr

•  CTAabdomenshowednorenalarterystenosis

•  StartedonHFtreatmentàcarvedilol,Lisinopril,loopdiuretic

•  PersistentBP>180/100

Liddlesyndrome•  Autosomaldominantmutationoftheepithelilalsodiumchannel(eNAC)

•  Deletionsorsubstitutionscauseaninabilityofthesesubunitstoundergodegredation

•  Diagnosis:▫  AldoandreninareLOW▫  Genetictesting/sequencing

•  Treatment:amiloride,startat5mgdaily,upto15mgdaily

Summary&Takehomepoints1.  Hyponatremiaandhyponatremiaarereallydisorders

ofWATERimbalancebetweenfluidcompartments

2.  CriticalchallengeinevaluationofhyponatremiaisdistinguishinglowEABVversusSIADH

3.  Hypernatremiainahospitalizedpatientisnearlyalwaysduetoinadequatefreewateradministration

4.  Ininpatientswithhypokalemiaandhypertension,thinkaboutaldosterone

•  Acknowledgements:▫  YoshioHall,MD,MS▫  BobRoshanravan,MD,MS

Questions?