Exercises-in-AcidBase-Disorders在酸堿紊亂練習(xí)課件

DisclosuresNoneObjectivePhysiologyofrenalacidhandlingDiagnosticapproachtoMetabolicAcidosiswithnormalaniongap.Case-baseddiagnosticworkupoftheRTA’sChemistry:CarbonicAcidCarbonicAcid.[H+

]x[HCO3-

]=k1xH2CO3

=k2x[CO2

]x[H2O]SimplifiedH2CO3

isnotofclinicalinterest[H2O]isconstantin-vivoPCO2

ismorefamiliarthan[CO2]:[H+

]x[HCO3-

]=kxPCO2[

ModifiedHendersonEquation.

]HasselbalchModification3MetabolicAcidosis:The“AnionGap”

Na+Cl-HCO3-Alb-[Na+]-([Cl-]+[HCO3-])Na+Cl-HCO3-Alb-NlAniongapMacidosis~10-12mM/L1.GIbicarbonateloss(typicallyalsowithlowK): diarrhea villousadenoma pancreatic,biliary,smallbowelfistulae uretero-sigmoidostomy obstructeduretero-ileostomyEtiologyof“normalaniongap”(A.K.A.“hyperchloremic”)metabolicacidosisPancreasIleumColonPancreasIleumColonGILossofHCO3-HCO3-HCO3-Cl-HCO3-Cl-K+HCO3-NormalDiarrheaCl-FloodingthecolonwithHCO3-insteadofCl-drivesK+secretionNa+Na+K+K+Cl-HCO3-K+Uretero-ileostomyCausesaNormalAnionGapAcidosis

ilealloopHCO3-SkinCl-2.Ingestions&infusions ammoniumchloride hyperalimentation(arginine/lysine-rich)3.Renalbicarbonate(orequivalent)loss proximalRTA distalRTA typeIVRTA earlyrenalfailure acetazolamide hydratedDKACausesofa“normalaniongap”(A.K.A.“hyperchloremic”)metabolicacidosisProximalRTA(“TypeII”)HCO3-(1)Na+(3)HCO3-H+CO2H2O+H+Na+Na+HCO3-glucoseaminoacidsuratephosphateDefectiveNa+-dependentresorption=Fanconi’sSyndromeDistalRTANa+K+Na+K+PrincipalcellaICcellbICcellHCO3-Cl-HCO3-Cl-Cl-H+ATPADP+PiH+ATPADP+PiCl-AldosteroneNetacidexcretion= urinaryNH4+

+ urinary“titratableacid”(H2PO4-) - urinaryHCO3-

H+NH4+NH3+HCO3-+H2CO3HPO4--+H2PO4-Nottitratable;needtomeasurePresentinProxRTATitratableacidHyperkalemicdistal

RTA:

Na+K+Na+K+PrincipalcellaICcellbICcellHCO3-Cl-HCO3-Cl-Cl-H+ATPADP+PiH+ATPADP+PiCl-AldosteroneACIDOSISINHYPORENINEMICHYPOALDOSTERONISM2.Totalbody K+excessK+3.K+entry intoproximal tubulecellsHCO3-(1)Na+(3)HCO3-H+CO2H2O+H+Na+H+4.Alkalinizationof proxtubulecell byK+/H+exchangeFailedCCD K+secretion5.TotalBodyK+ExcessDecreasesProximalTubuleAcidificationandAmmoniagenesisviaIntracellularAlkalosisDIAGNOSTICAPPROACHMinimumUrinepHUrinaryAnionGapPlasmapotassium

RenalstonesorNephrocalcinosisProx.TubulardysfunctionFEHCO3DailybicarbonatereplacementneedsUrinepHPlasma[HCO3-]mMNormalProximalRTADistalRTA(OxfordTextbookofNephrology-Sorianoetal,1967)UrinepHvs.PlasmabicarbonateinRTAUrinaryAnionGapUrine(Na+K)–ClProtonispartiallyexcretedasNH4(unmeasuredcation)ThegapisusuallyZeroorNegativeIndRTAtheaniongapwillremainzeroorpositiveInotheracidoses,thegapwillbecomemorenegative.Unmeasuredanions-unmeasuredcations18Apositiveurineaniongap~noNH4+Clexcretion (i.e.lowrenaltubuleacidification)Normalacidotic:closedcirclesDiarrhea:closedtrianglesType1orIVRTA:opencirclesBattleetal,NEJM1988FloodingthedistaltubulewithHCO3-insteadofCl-inProximalRTAdrivesK+secretionNa+Na+K+K+Cl-HCO3-K+ProximalRTA:HypokalemiaH+nolongershuntsNa+currentsoK+mustdosoNa+K+Na+K+PrincipalcellaICcellbICcellHCO3-Cl-HCO3-Cl-Cl-H+ATPADP+PiH+ATPADP+PiCl-AldosteroneDistalRTA:

HypokalemiaHyperkalemic

DistalRTANa+K+Na+K+PrincipalcellaICcellbICcellHCO3-Cl-HCO3-Cl-Cl-H+ATPADP+PiH+ATPADP+PiCl-AldosteroneLowAldosteroneVoltagedefectNephrocalcinosis/KidneyStonesDistalRTA(HighIncidence)Alkalineurine:CalciumphosphateprecipitationAcidosis:IncreasedcitratereabsorptionbyproximalnephronProximalRTA(NotSeen):UrinepHnothighCitratenotabsorbedFANCONI’SSYNDROMEonlyin

ProximalRTAHCO3-(1)Na+(3)HCO3-H+CO2H2O+H+Na+Na+HCO3-glucoseaminoacidsuratephosphateDefectiveNa+-dependentresorption=Fanconi’sSyndromeFractionalexcretionofHCO3-FractionalexcretionofHCO3-DailyHCO3RequirementsProximal>4meq/kgDistal1-2meq/kgHyperkalemic1-2meq/kgJAmSocNephrol13:2160-2170,2019PositiveUrinaryaniongapUrinepH&plasma[K+]UrinepH<5.5&high[K+]Hypo-aldosteronismRTA(typeIV)UrinepH>5.5&low/nl[K+]DistalRTA(“TypeI”):secretoryorgradientdefectCase1A55-year-oldwomanpresentswithcomplaintsoflethargy,thirst,muscleweaknessandgeneralizedbodypains.PreviousEDvisitswithhypokalemia.Herserumpotassiumlevelwas2.6mmol/l.OtherElectrolytes:sodium138mmol/lchloride116mmol/lHCO317mmol/lBUN/CreatininenormalGlucose75mg/dLUrineanalysis:pH5.4,2+glucoseUrineaniongap:-20ProximalRTAABG:pH7.25pCO228pO2100totalbicarbonate15.1mmol/lbaseexcess–13.7mmol/lCase1:ProximalRTAMinimumUrinepH<5.5Plasmapotassium

Low-normalRenalstones/NCNoProx.TubulardysfunctionGlycosuria,Phosphate,AA,UrateFEHCO315-20%Dailybicarbonatereplacementneeds>4mmol/kgFEHCO3Intravenousinfusionofsodiumbicarbonateatarateof0.5to1.0meq/kgperhour

UHCO3

x

PCr

FEHCO3

=

———————————

x

100

PHCO3

x

UCrProximalRTA:FEHCO3>15-20%

ClinicalFeaturesofProximalRTAUrinepHdependsonplasma[HCO3-]FractionalHCO3-excretionhigh(15-20%)atnlplasma[HCO3-]Plasma[K+]reduced,worsenswithHCO3-therapyDoseofdailyHCO3-required:10-15mEq/kg/dNon-renal:ricketsorosteomalaciaCausesofProximalRTAPrimaryisolatedproximalRTAhereditary(persistent)

a.autosomaldominant

b.autosomalrecessiveassociatedwithmentalretardationandocularabnormalities

Sporadic(transientininfancy)SecondaryproximalRTA

inthecontextofFanconisyndrome(cystinosis,galactosemia,fructoseintolerance,tyrosinemia,Wilsondisease,Lowesyndrome,metachromaticleukodystrophy,multiplemyeloma,lightchaindisease)

drugsandtoxins(acetazolamide,outdatedtetracycline,aminoglycosideantibiotics,valproate,6-mercaptopurine,streptozotocin,iphosphamide,lead,cadmium,mercury)

otherclinicalentities(vitaminDdeficiency,hyperparathyroidism,chronichypocapnia,Leighsyndrome,cyanoticcongenitalheartdisease,medullarycysticdisease,Alportsyndrome,corticoresistantnephroticsyndrome,renaltransplantation,amyloidosis,recurrentnephrolithiasis)JAmSocNephrol13:2160-2170,2019Case2A38-year-oldwomanwasadmittedwithsevereweakness(3rdepisode)PMH:artificialtearsfordryeyesLaboratoryUrinepH7.1sodium141mEq/Lpotassium3.0mEq/Lcarbondioxide14mEq/Lchloride114mEq/LScreatinine0.8mg/dL(70.7μmol/L)Albumin4.3Urinaryaniongap+4ArchInternMed.

2019;164:905-909DistalRTACase2:DistalRTAArchInternMed.

2019;164:905-909MinimumUrinepH

>5.5Plasmapotassium

Low-normalRenalstones/NCYESProx.TubulardysfunctionNoFEHCO3<3%Dailybicarbonatereplacementneeds<4mmol/kgNephrocalcinosis/RecurrentStones

ConsiderDistalRTAFurosemide/FludrocortisoneTestBaselineurinesampleOraladministrationoffurosemide(40

mg)andfludrocortisone(1

mg).Fluidintakeadlibitum.

Urineq1hx6

hafterthebaselinesample.FailedtoacidifytheirurinetopH<5.3KidneyInternational(2019)71,1310–1316Schirmer’stestpositiveantibodiestotheRo/SSAandLa/SSB+Cryocrit+CausesofdistalRTAJAmSocNephrol13:2160-2170,2019Case350yearoldmalewithNIDDMhasbeenprescribedalowNadietforHTN.HepresentstotheERwithmarkedweakness.Labs: 130|98|18280 8.0|20|1.3