Chapter Nineteen: Metabolic Acidosis, The Show, part 1
ReferencesChapter 19, Part 1 Metabolic acidosis June 14, 2023American Society of Nephrology | Medical Students - Kidney TREKS this is the program that Josh mentioned at Mount Desert Island! Effects of pH on Potassium: New Explanations for Old Observations - PMC here’s the review melanie from Peter Aronson that clarifies the fact that there are no H+-K+ antiporters outside the kidney but rather coupled transport-We discussed whether we like “Winter’s formula” Quantitative Displacement of Acid-Base Equilibrium in Metabolic Acidosis | Annals of Internal Medicine Dr. R. W. Winters was charged with larceny https://www.nytimes.com/1982/05/16/nyregion/ex-columbia-u-doctor-charged-with-larceny.htmlJCI - The Maladaptive Renal Response to Secondary Hypocapnia during Chronic HCl Acidosis in the Dog this was a classic experiment exploring the respiratory response to an infusion of HCl but the animals were maintained in a high pCO2 milieu (not generalizable to humans!)Here’s the thoughtful Pulmcrit post (by Josh Farkas) that Josh mentioned regarding correction of anion gap for hypoalbuminemia: Mythbusting: Correcting the anion gap for albumin is not helpfulJC mentioned that the anion gap does change in cirrhosis when the albumin is very low but using the correction factor may not change the clinical findings Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunctionDiagnostic Importance of an Increased Serum Anion Gap | NEJM Melanie mentioned the work of Patricia Gabow on the anion gap. In this review, she refers to work that she had done to try to identify all the organic anions in the anion gap but it falls short. Also, check out this critical look at the delta/delta: The Δ Anion Gap/Δ Bicarbonate Ratio in Lactic Acidosis: Time for a New Baseline?Roger mentioned near drowning in the Dead Sea and the unusual electrolytes in that instance. Near-Drowning in the Dead Sea: A Retrospective Observational Analysis of 69 PatientsWe discussed this classic NEJM article by Daniel Batlle The Use of the Urinary Anion Gap in the Diagnosis of Hyperchloremic Metabolic AcidosisAmy mentioned this review from Uribarri and Oh in JASN on the urine anion gap: The Urine Anion Gap: Common MisconceptionsJoel has a great blog post on the urine osmolar gap. urine osmolar gap – Precious Bodily Fluids Anna’s VoG on the bicarb deficit: Kurtz, I Acid-Base Case Studies, 2nd Edition. Trafford Publishing 2004. And the Fernandez paper that derived a better equationReference for Josh’s VoG: Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney diseaseSevere anion gap acidosis associated with intravenous sodium thiosulfate administrationUnexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathySodium Thiosulfate Induced Severe Anion Gap Metabolic AcidosisSodium Thiosulfate and the Anion Gap in Patients Treated by HemodialysisOutline: Chapter 19 Metabolic AcidosisOverviewLow arterial pHReduced HCO3Compensatory hyperventilation (↓ pCO2)Bicarb < 10 strongly suggests metabolic acidosis (renal compensation for respiratory alkalosis does not go that low)PathophysiologyH+ + HCO3- <=> H2CO3 <=> CO2 + H2OAcidosis results from H+ addition or HCO3 lossResponse to Acid LoadExtracellular bufferingExample: Add 12 mmol H+/L → HCO3 falls from 24 → 12 → pH drops to 7.1 (40 to 80 nmol/L)Intracellular and bone buffering55–60% buffered intracellularly and in bone12 mEq/L acid load only reduces serum HCO3 by ~5 mEq/LH+ into cells → K+ out (hyperkalemia)Notably in diarrhea or renal failureLess effect with organic acidosis (e.g., DKA, lactic acidosis)Respiratory compensationStimulates chemoreceptors → ↑ tidal volume (more than RR)Decreases pCO2, increases pHBegins within 1–2 hours; peaks at 12–24 hoursWinters formula alternative: for every 1 mEq ↓ HCO3, pCO2 ↓ by 1.2Chronic: respiratory compensation is blunted by renal adaptationRenal hydrogen excretion50–100 mEq/day acid generated from diet90% filtered HCO3 reabsorbed in PTAcid secreted:10–40 mEq via titratable acid (TA)30–60 mEq via NH3/NH4 (can ↑ to 250 mEq in acidosis)TA: phosphate (DKA → ketones act as TA)Max excretion up to 500 mEq/day in severe acidosisGeneration of Metabolic AcidosisMechanismsInability to excrete H+ (slow)Addition of H+ or loss of HCO3 (rapid)Anion Gap (AG)Normal: 5–11 (falling due to rising Cl-)Mostly due to negatively charged proteins (albumin)Adjust for albumin: AG ↓ 2.5 per 1 g/dL albumin ↓Revised: AG = unmeasured anions - unmeasured cations↑ AG = addition of unmeasured anions (e.g., lactate, ketones)Hyperchloremic acidosis: ↓ HCO3 replaced by ↑ Cl (normal AG)Delta–Delta AnalysisAdjust AG for albuminNormal ΔAG:ΔHCO3 = 1.6:1 (early 1:1)<1 → high + normal AG acidosisOther causes of AG variationHigh AG without acidosis: hemoconcentration, alkalosisLow AG: hypoalbuminemia, ↑ unmeasured cations (lithium, IgG, lab artifact)Urine Anion Gap (UAG)Normal = ~0; should be very negative (< -20) in acidosisType 1 & 4 RTA → UAG positive or near zeroInvalid in ketoacidosis or volume depletion (Na retention → ↓ distal acidification)Urine Osmolal GapEstimate NH4+ via osmolar gapRequires urine Na, K, glucose, ureaEtiologies and DiagnosisLactic AcidosisPyruvate → lactate (LDH; NADH → NAD+)Normal production: 15–20 mmol/kg/dayMetabolized in liver/kidney → pyruvate → glucose or TCANormal lactate: 0.5–1.5 mmol/L; acidosis if > 4–5 mmol/LCauses:↑ production: hypoxia, redox imbalance, seizures, exercise↓ utilization: shock, hepatic hypoperfusionMalignancy, alcoholism, antiretroviralsD-lactic acidosisShort bowel/jejunal bypassGlucose → D-lactate (not metabolized by LDH)Symptoms: confusion, ataxia, slurred speechSpecial assay neededTx: bicarb, oral antibioticsTreatmentUnderlying causeBicarb controversial: may worsen intracellular acidosis, overshoot alkalosis, ↑ lactateTarget pH > 7.1; prefer mixed venous pH/pCO2Ketoacidosis (Chapter 25 elaborates)FFA → TG, CO2, H2O, ketones (acetoacetate, BHB)Requires:↑ lipolysis (↓ insulin)Hepatic preference for ketogenesisCauses:DKA (glucose > 400)Fasting ketosis (mild)Alcoholic ketoacidosisPoor intake + EtOH → ↓ gluconeogenesis, ↑ lipolysisMixed acid-base (vomiting, hepatic failure, NAGMA)Congenital organic acidemias, salicylatesDiagnosis:AG, osmolar gap (acetone, glycerol)Ketones: nitroprusside only detects acetone/acetoacetateBHB can be 90% of total (false negative)Captopril → false positiveTreatment:Insulin +/- glucoseRenal Failure↓ excretion of daily acid loadGFR < 40–50 → ↓ ammonium/TA excretionBone buffering stabilizes HCO3 at 12–20 mEq/LSecondary hyperparathyroidism helps with phosphate bufferingAlkali therapy controversial in adultsIngestionsSalicylatesSymptoms at >40–50 mg/dLEarly: respiratory alkalosis → Later: metabolic acidosisTreatment: bicarb, dialysis (>80 mg/dL or coma)MethanolMetabolized to formic acid → retinal toxicityOsmolar gap elevatedTx: bicarb, ethanol/fomepizole, dialysisEthylene glycol→ glycolic/oxalic acid → renal failureSame treatment + thiamine/pyridoxineOtherToluene, sulfur, chlorine gas, hyperalimentation (arginine, lysine)GI Bicarbonate LossDiarrhea, bile/pancreatic drainage → loss of alkaline fluidsUreterosigmoidostomy → Cl-/HCO3- exchange in colonCholestyramine → Cl- for HCO3-Renal Tubular Acidosis (RTA)Type 1 (Distal)↓ H+ secretion in collecting duct → urine pH > 5.3Etiologies: Sjögren, RA, amphotericinFeatures: nephrocalcinosis, stones, hypokalemiaDiagnosis: NAGMA, persistent ↑ urine pHTreatment: alkali (1–2 mEq/kg/d adults; 4–14 kids), K+ if neededType 2 (Proximal)↓ HCO3 reabsorptionBicarb threshold reduced → self-limitedCauses: multiple myeloma, Fanconi, ifosfamideFeatures: rickets/osteomalacia, no stones, pH variableDiagnosis: NAGMA, pH < 5.3, high FE HCO3 when HCO3 loadedTreatment: alkali (10–15 mEq/kg/d), thiazidesType 4Aldo deficiency/resistance → hyperkalemia + mild acidosisK+ inhibits NH4 generationTx: correct K+, consider loop diureticsSymptomsHyperventilation (dyspnea)pH < 7.0–7.1 → arrhythmias, ↓ contractilityNeurologic: lethargy → coma (CSF pH driven)Skeletal growth issues in childrenTreatment PrinciplesNo alkali needed for keto/lactic acidosis unless pH < 7.2Bicarbonate DeficitDeficit = HCO3 space * (desired - actual HCO3)HCO3 space: 50–70% of body weightWatch for:K+ shifts: beware hypokalemia when correcting acidosisNa+ load in CHFDialysis if necessary
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