Understand the causes of hypokalaemia and hyperkalaemia.docx

Understand the causes of hypokalaemia and hyperkalaemia.docx

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Understandthecausesofhypokalaemiaandhyperkalaemia

Understandthecausesofhypokalaemiaandhyperkalaemiaandhowtotreatpatientspresentedwiththedisorders.

Potassiumdisordersincontext:

normalpotassiumphysiologyWhereispotassiumnormallyfound?

Foranaverageadult（70kg）thereis（roughly）3500mmolofpotassiuminthebody.Ofthis:

3150mmol（90%）isintheintracellularfluid

350mmol（10%）isintheextracellularfluid.

Somostpotassiumisintracellularandismainlyfoundinmuscle.

Potassiumisthemainintracellularcation:

itsconcentrationisaround100-120mmol/linsidecells.

Theconcentrationofextracellularpotassiumismuchlower,around4mmol/l（therangeis3.5-5.2）.Inadditionthereisasignificantamountofextracellularpotassiuminbone（outsideofcells）.

Onlyabout15mmol（0.4%ofthetotal）isfoundintheplasma.Consequently,theconcentrationofpotassiumintheplasmaissignificantlyinfluencedbytranscellularshiftsofpotassiumacrosscellmembranes.

Whatcontrolsshiftsofpotassium?

TheNa/KATPasepumpspotassiumintocellsinexchangeforsodium.Severalfactorsaffecttherateofmovementofpotassiumintocells.ThesearelistedinTable1.

备注：

Betaadrenoceptoragonists

Alkalosis

Alphaadrenoceptorantagonists

Glucagon（高血糖）

Betablockers

Raisedosmolality（发酵的，无氧代谢，乳酸酸中毒）

Exercise（运动后）

Howdoesthebodyhandletheoverallbalanceofpotassium?

AnormalWesterndietcontainsabout100mmolofpotassiumperday.

Excretionofpotassiumoccursviathefollowingroutes:

Kidneys（90%）

Colon（10%）

Skin（negligibleinnormalcircumstances）.

Howdoesthebodycontrolexcretionofpotassiumbythekidneys?

Potassiumisreabsorbedandsecretedatvariouspointsalongthenephron.Controlofpotassiumexcretionisachievedmostlythroughcontrollingactivesecretioninthecollectingduct.Intheprincipalcellsofthecollectingtubule,potassiumisactivelytransportedacrossthebasolateralmembraneviatheNa/KATPasepump.Thisgeneratesahighintracellularconcentration,whichthendrivessecretionintothetubularlumen.

Aldosterone,anadrenalsteroidhormone,activatestheintracellularmineralocorticoidreceptorwhichthroughseveralpathwaysupregulatestheactivityoftheepithelialsodiumchannelandthebasolateralNa/KATPase.Thisincreasesuptakeofsodiumviatheepithelialsodiumchannelandallowspotassiumtobeexchangedforsodium.

Cortisolcannotactivateintracellularmineralocorticoidreceptorsbecauseitisbrokendownbytheenzyme11beta-hydroxysteroiddehydrogenase,whichisfoundinthebrushborder.Ifthisenzymeisdeficientthencortisoldoeshavealdosterone-likeactivity.

FactorsthataffectexcretionofpotassiumbythekidneysarelistedinTable2.

Howcanwemeasureexcretionofpotassiumbythekidneys?

Thekidneyisthemainorganresponsibleforhomeostasisofpotassium.Insomecircumstancesitcanbehelpfultomeasurerenalpotassiumexcretiontohelpdeterminethecauseofpotassiumdisturbances.Thereareseveralwaysofexaminingexcretionofpotassiumbythekidneys.

Spoturinarypotassiumconcentration

Thisisthesimplestandmostusefulmethodforexaminingexcretionofpotassiumbythekidneys,butitmayvaryduringthedayaccordingtourinaryconcentration.Youcanreducethiserrorbysimultaneouslymeasuringtheurinarycreatininetoestimatethedegreeofurinaryconcentrationandexpressingthisasaratio.

24hoururinarypotassiummeasurement

Thisgivesamoreaccuratepicture,butitisinconvenientandcollectionsmaybeincomplete.

Interpretingurinarypotassiumresults

Urinaryelectrolyteresultsareoftendifficulttointerpretandlaboratory“normal”valueswillincludeabroadrangeasthekidneyshavethecapacitytoincreaseanddecreasepotassiumexcretiontomaintainpotassiumhomoeostasis.Urinaryexcretionofpotassiumissignificantlyaffectedbydiuretictherapy,makinginterpretationverydifficult.Wheninterpretingurinarypotassiumitisusefultoconsiderwhetherurinarypotassiumexcretionishighorlow.

备注：

描述尿液中钾浓度的正常范围。

Hypokalaemia

Whatcauseshypokalaemia?

Therearethreemainmechanisms:

Pseudo-hypokalaemia（

Transcellularredistribution

Depletionofpotassium.

Pseudo-hypokalaemia

Thisoccurswhensamplesfrompatientswithveryhighwhitecellcounts（especiallyrelatedtoacutemyeloidleukaemia）arestoredatroomtemperaturebeforebeinganalysed.

Inthesecircumstanceslargeamountsofpotassiummaybetakenupbythewhitecellscausinganinvitrohypokalaemia.

Transcellularredistribution

Transcellularredistribution（movementofpotassiumintocells）isusuallyatransientphenomenon.Itcanoccurinseveralconditions:

Alkalosis

Excesslevelsofinsulin

Drugs-betaadrenoceptoragonists（suchassalbutamol）andtheophylline（inoverdoses）

Hypokalaemicperiodicparalysis-thisisararedisordercharacterisedbyacuteepisodesofrapidmovementofpotassiumintocellsresultinginacutemuscleweakness.Itmaybeduetoageneticdisorderormayrarelybeseeninhyperthyroidism.

Depletionofpotassium

Depletionofpotassiumismostoftenduetolossofpotassiumviathekidneys（mostcommonlythroughdiureticuse）,butitcanalsooccurwhenpotassiumislostviathegastrointestinaltractandskin.

Gastrointestinalcausesofhypokalaemiainclude:

Diarrhoea

Abuseoflaxatives

Villousadenomas.

VillousadenomasarethoughttosecretecyclicAMPandprostaglandins,whichdisturbcoloniciontransport.

Highlossesthroughtheskincanoccurwithprofusesweating,forexamplewithprolongedexerciseinhotclimates.

Severalfactorscanincreaseurinaryexcretionofpotassium:

Excessofmineralocorticoids

Increaseddeliveryofsodiumtothedistalnephron

Metabolicalkalosis,orchloridedepletion,orboth

Depletionofmagnesium.

Excessofmineralocorticoidscanbefurtherdividedaccordingtowhetheraldosteronelevelsarehighorlow（Tables4and5）.

Aldosterone

Adrenalhyperplasia

Adenoma

Excessdeliveryofsodiumtothedistalnephroncanbedueto:

HighNaClintake（forexample,inappropriatereplacementoffluidwithtoomuchnormalsaline）

Diuretics

Osmoticdiuresis,forexampleduetohyperglycaemiaormannitol

Renaltubularacidosis,particularlyproximalrenaltubularacidosiswheretreatmentwithhighdosesofbicarbonatehasbeengiven

Barrter'ssyndrome,agroupofrelatedgeneticdisordersinvolvingabnormaliontransportintheloopofHenleleadingtosodiumwasting,metabolicalkalosis,anddepletionofpotassium

Gitelman'ssyndrome,avariantofBarrter'ssyndromewherethedefectisinthedistaltubule.FeaturesaresimilartothoseofBarrter'ssyndromebutwiththeadditionofhypercalciuria.

Patientswithmetabolicalkalosisandchloridedepletionduetorecurrentvomitingalsodevelophypokalaemia.Metabolicalkalosisincreasespotassiumexcretionfromthecorticalcollectingductbyreducingtheexchangeofpotassiumionsforhydrogenions.Lowconcentrationsofchlorideinthedistaltubularfluidmayalsostimulatepotassiumsecretion.UrinarychlorideconcentrationsmayhelpyoutodistinguishwhetherrenalpotassiumwastingisduetovomitingfromtheeffectofdiureticsortoBarrter'sandGitelman'ssyndromes.

Urinarychlorideconcentrationswillbe:

Low（<10mmol/l）inpatientswithrecurrentvomiting

High（>20mmol/l）inpatientswithBarrter'sandGitelman'ssyndromes.

Urinarychloridevariesinpatientstakingdiureticsdependingonwhenthediuretichasbeentaken.Urinarychloridewillbehigherafteradiureticandwillfalltolowlevelswhentheeffecthaswornoff.

Magnesiumdepletionisassociatedwithrenalpotassiumwasting.Inmostcasestheunderlyingcauseofmagnesiumdepletionalsocauseshypokalaemia,however,thereissomeevidencethatreducedintracellularmagnesiumconcentrationincreasespotassiumsecretionbyreleasingmagnesiumdependentinhibitionofROMKchannels.Wherehypomagnesaemiaandhypokalaemiaco-exist,correctionoftheserummagnesiumisnecessarybeforethehypokalaemiacanbecorrected.

Whataretheclinicalconsequencesofhypokalaemia?

Cardiac

Themostseriouseffectsareontheheart.Electrocardiogram（ECG）changesinclude:

Twaveflattening

STdepression

ProminentUwaves.

Hypokalaemiacaninduceventriculararrhythmiasand,inparticular,itincreasestheriskofdigoxintoxicity.

Neuromuscular

Neuromusculareffectsare:

Weakness

Paralysis

Rhabdomyolysisduetolossofmyocyteintegrity.

Gastrointestinal

Gastrointestinaleffectsare:

Constipation

Ileus.

Renal

Renaleffectsare:

Polyuria

Polydipsia

Chronicinterstitialnephritis.

Whatistherelevanceofhypokalaemiainpatientswithacutemyocardialinfarction?

Themanagementofhypokalaemiainacutemyocardialinfarctionremainscontroversial.

Hypokalaemiaisassociatedwithanincreasedriskofventriculararrhythmiasandpreviousguidelineshaveadvisedmaintainingpotassiumlevelsabove4mmol/linpatientswithacutemyocardialinfarction.Arecentlargestudyhasshowna“U”shapedrelationshipbetweenpostadmissionserumpotassiumlevelsandmortalityinpatientswithacutemyocardialinfarction.Increasesinmortalitywereseeninpatientswithhypokalaemia（serumpotassium<3.5mmol/lbutalsoinpatientswithhigherlevelsofpotassium（>4.5mmol/l）.Consequentlywhilsthypokalaemiashouldbecorrectedinpatientswithacutemyocardialinfarction,overcorrectionshouldbeavoided.

Thereisevidencethathypokalaemiaincreasestheriskofcardiaceventsinthelongtermandthathigherdietaryintakeofpotassiumisassociatedwithlowercardiovascularmortality.

Assessmentofhypokalaemia:

Ap