Acid-Base Disorders - UCSF CME

1 Acid-Base DisordersSharon Anderson, of Nephrology and HypertensionOregon Health & Science UniversityPortland VA Medical CenterOctober 2012 UCSF 2012 General Acid-Base RelationshipsHenderson Hasselbach equation:pH = pK + log HCO3_/pCO2H+= 24 x pCO2/HCO3_ pH unit = 10 nm/L H+Approach to Acid-Base Disorders1. Consider the clinical setting!2. Is the patient acidemic or alkalemic?3. Is the primary process metabolic or respiratory?4. If metabolic acidosis, gap or non-gap?5. Is compensation appropriate?6. Is more than one disorder present?Simple Acid-Base DisordersConditionpHPrimary DisorderCompensationMetabolic acidosis pH HCO3 pCO2 Metabolic alkalosis pH HCO3 pCO2 Respiratory acidosis pH pCO2 HCO3 Respiratory alkalosis pH pCO2 HCO3 Expected Compensatory ResponsesMetabolic Acidosis Etiology: Inability of the kidney to excrete the dietary H+load, or increase in the generation of H+(due to addition of H+ or loss of HCO3 )Metabolic Acidosis: Elevated Anion GapAG = Na+ (Cl + HCO3 ) = 12 2[Note.]

2 Diagnostic utility is best when AG > 25]Causes of AG Metabolic Acidosis [Classic]CAT MUDPILERSC cyanide, carbon monoxide, CPK (rhabdo)A alcoholic ketoacidosisT tolueneM methanolU uremiaD DKA/alcoholic KAP paraldehyde, phenforminI INH, ironL lactic acidosisE ethylene glycolR rhabdo, renal failureS salicylatesCauses of AG Metabolic Acidosis [Updated]Mehta AN, et al. Lancet 272:892, 2008 GOLDMARKG glycols (ethylene, propylene, diethylene)O oxoproline L L lactateD D lactateM methanolA aspirinR renal failureK ketoacidosisIntoxications Causing High AG Acidosis Aspirin - [high salicylate level; also primary respiratory alkalosis] Methanol - [optic papillitis] Ethylene Glycol - [calcium oxalate crystals] ParaldehydeAnion Gap in Hypoalbuminemia The true anion gap is underestimated in hypoalbuminemia (= fall in unmeasured anions).

3 AG must be adjusted Formulas for adjusted AG: For every fall in albumin, AG by Consider the patient s normal AG to be (2 x alb) + ( x phosphate) Adjusted AG = Observed AG + ( x [normal alb - adjusted alb]The Delta/Delta: AG/ HC03 Rationale: For each unit INCREASE in AG (above normal), HC03should DECREASE one unit (below normal) Normal values: AG = 12, HC03= 24 Use of the Delta/Delta: ExamplesAG HCO3 Diagnosis18 ( 6)18 ( 6)Appropriate; pure AG acidosis18 ( 6) 22 ( 2)HCO3has less thanpredicted, so HCO3is too high;mixed AG acidosis AND met alk18 ( 6) 12 ( 12) HCO3 has more thanpredicted, so HCO3is too low;mixed AG AND non AG acidosisCauses of Low Anion GapEtiology: Fall in unmeasured anionsor rise in unmeasured cationsHyperkalemiaLithium intoxicationHypercalcemiaHypermagnesemia Bromide (dextromethorphan, ipratropium, pyridostigmine)Monoclonal gammopathies [esp.)]

4 IgG]Osmolar GapMeasured serum osmolality >calculated serum osmolality by > 10 mOsmCalc Sosm = (2 x Na) + + Glu/18 Causes of High Osmolar GapIsotonic hyponatremiaHyperlipidemiaHyperproteinem iaMannitolGlycine infusionChronic kidney diseaseIngestionsEthanol, isopropyl alcohol, ethylene glycol, mannitolContrast MediaRelationship between AG and Osmolar GapAG Osm gap CommentsEthylene glycol++ *Double gapMethanol+ + *Double gapRenal failure+ + *Double gapIsopropyl alcohol +Ethanol +Lipids, proteins +Causes of Normal AG (Hyperchloremic)

5 Metabolic AcidosisHigh K+Low K+Adrenal insufficiencyDiarrheaInterstitial nephritisRTANH4Cl, Arg HClUreteral diversionCauses of Normal AG (Hyperchloremic) Metabolic AcidosisHARDUPSH yperalimentationAcetazolamide, amphotericinRTAD iarrhea; overcorrected or early DKAU reteral diversionPancreatic fistula, posthypocapniaSpironolactone/saline resuscitationUse of the Urine Anion Gap (UAG) in Normal AG AcidosisBatlle DC, et al. NEJM 318:594, 1988 Urine AG = (Na + K) ClNegative UAG = Normal, or GI loss of HCO3 Positive UAG = Altered distal renal acidificationCaveats: Less accurate in patients with volume depletion (low urinary Na); and in patients with increased excretion of unmeasured anions ( ketoacidosis), where there is increased excretion of Na and K to maintain electroneutrality)Use of the Urinary AG in Normal Gap AcidosisBatlle DC, et al.

6 NEJM 318:594, 1988 Plasma KUAGU pHDiagnosisNormal < +< deficiencyElevated+> RTAN ormal low +> RTAN ormal low > HCO3lossUse of the Urine Osmolal Gap When UAG is positive, and it is unclear if increased cation excretion is responsible, urine NH4concentration can be estimated from urine osmolal gap Calc Uosm = (2 x [Na+K]) + urea + glu/18 The gap between the calculated and measured Uosm = mostly ammonium In patients with metabolic acidosis, urine ammonium should be > 20 mEq/L. Lower value = impaired renal acidificationCalculation of Bicarbonate Deficit The bicarbonate space differs according to the clinical setting look it up!

7 If metabolic acidosis warrants Rx, bicarb deficit may be hundreds of mEq; need continuous infusion, not random amps In metabolic acidosisBicarb deficit = HCO3 space x HCO3 deficit/literHCO3 space = lean body wt (kg)HCO3 deficit/liter = [desired HCO3 ] [measured HCO3 ]Osmolar GapAnionGapGI Fluid Loss?UremiaLactateKetoacidsSalicylateEth yleneglycolMethanolNormalIncreasedDiarrh eaIleostomyEnteric fistulaUrine pHDistal RTA (Type 1)Serum KProximal RTA (Type 2)Type 4 RTAHighNormalNoYes> < to Metabolic AcidosisDo UAGM etabolic AlkalosisEtiology: Requires both generation of metabolic alkalosis (loss of H+through GI tract or kidneys) and maintenance of alkalosis (impairment in renal HCO3excretion)Causes of metabolic alkalosisLoss of hydrogenRetention of bicarbonateContraction alkalosisMaintenance factors.

8 In GFR, in HCO3reabsorptionMetabolic AlkalosisCLEVER PD Contraction Licorice Endo: Conn s, Cushing s, Bartter s Vomiting Excess Alkali Refeeding alkalosis Post-hypercapnia DiureticsUse of Urine Cl in Metabolic AlkalosisChloride responsiveChloride resistant(UCl< 15 mEq/L)UCl> 20 mEq/L)GI lossWith urine K < 15 Renal lossLaxative abuse, K depletionLow Cl intakeWith urine K > 20 Exogenous alkaliHypotensive: Bartter sHypertensive: hyperaldo,Cushing s, Liddles, otherUse of Spot Urine Cl and KUrine ChlorideVery Low(< 10 mEq/L)Vomiting, NG suctionPostdiuretic, posthypercapneicVillous adenoma, congenitalchloridorrhea, post- alkali> 20 mEq/LUrine Potassium> 30 mEq/LDiuretic phase of diuretic Rx, Bartter s, Gitelman s, primary aldo, Cushings, Liddle s, secondary aldosteronismLow (< 20 mEq/L)Laxative abuseOther profound K depletionTreatment of Metabolic Alkalosis1.

9 Remove offending Chloride (saline) responsive alkalosis: Replete volume with Chloride non responsive (saline resistant) alkalosis:Acetazolamide (CA inhibitor)Hydrochloric acid infusionCorrect hypokalemia if presentCalculation of Bicarbonate ExcessBicarb excess = HCO3 space x HCO3 excess/literHCO3 space = lean body wt (kg)HCO3 excess/liter = [measured HCO3 ] [desired HCO3 ]Respiratory Disorders Result from abnormal hypoventilation (acidosis) or hyper ventilation (alkalosis) Can be due to either CNS, pulmonary, or thoraco abdominal disordersRespiratory AcidosisCauses of Respiratory AcidosisInhibition of medullary respiratory center ( drugs)

10 Disorders of respiratory muscles and chest wallUpper airway obstructionDisorders affecting gas exchange across pulmonary capillariesMechanical ventilationTreatment of Respiratory AcidosisRx the primary disorder; mechanical ventilationRespiratory AlkalosisCauses of Respiratory AlkalosisHypoxemiaPulmonary diseaseStimulation of medullary respiratory centerMechanical ventilationCHAMPSCNS DiseaseAnxietyProgesteroneHypoxiaMech ventSalicylates/sepsisTreatment of Respiratory AlkalosisRx the primary disorder; mechanical ventilation; paper bagMixed Acid-Base Disorders : Clues Degree of compensation for primary disorder is inappropriate Delta AG/delta HCO3_= too high or too low Clinical historyCommon Clinical States and Associated Acid-Base DisturbancesClinical StateAcid base DisorderPulmonary EmbolusRespiratory AlkalosisHypotensionMetabolic AcidosisVomiting Metabolic AlkalosisSevere DiarrheaMetabolic AcidosisCirrhosisRespiratory AlkalosisRenal FailureMetabolic AcidosisSepsisRespiratory Alkalosis/Metabolic AcidosisPregnancyRespiratory AlkalosisDiuretic UseMetabolic AlkalosisCOPDR espiratory AcidosisAcid- base Disorders in GI DiseaseGennari JF.