Chapter Eighteen: Metabolic Alkalosis, part 2 | ReferencesPart 2, March 1, 2023The alkaline tide phenomenon in studies that measured both the alkaline tide and acid secretion, the bicarbonate accumulation increased in linear fashion with the acid secretion. Melanie thought this was first recognized in the 60’s but later found this manuscript from 1939 in JCI! ALKALINE TIDES - PMCMelanie mentioned this old study that explores the respiratory response of metabolic acidosis and finds it “incomplete” compared to expected. EVALUATION OF RESPIRATORY COMPENSATION IN METABOLIC ALKALOSIS and there’s another image in a review by Michael Emmett Figure 1. Metabolic Alkalosis: A Brief Pathophysiologic Review - PMC(here’s the image from JCI) The effect of changes in blood pH on the plasma total ammonia level - SurgeryThis is an interesting case that Melanie mentioned with the help of Stew Lecker Trust the Patient: An Unusual Case of Metabolic Alkalosis - PMCGot Calcium? Welcome to the Calcium-Alkali Syndrome : Journal of the American Society of Nephrology a favorite review of the “calcium alkali” syndrome- previously called milk alkali syndrome but now milk is not commonly part of the syndrome (as with Dr. Sippie). Lety mentioned this issue with a new contaminant of street drugs: Tranq Dope: Animal Sedative Mixed With Fentanyl Brings Fresh Horror to U.S. Drug ZonesHere are two references that illustrate how the urine pH changes over the course of the day. Circadian variation in urine pH and uric acid nephrolithiasis risk The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers - PMCNotes for Melanie’s VOG on reference 47: Maladaptive renal response to secondary hypercapnia in chronic metabolic alkalosisFrom Biff Palmer Figure 4- Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023 - American Journal of Kidney DiseasesAnna’s VOG-  GI composition of cats or somethingOutline: Chapter 18Metabolic AlkalosisElevation of arterial pH, increased plasma HCO3, and compensatory hypoventilationHigh HCO3 may be compensatory for respiratory acidosisHCO3 > 40 indicates metabolic alkalosisPathophysiology: Two Key QuestionsHow do patients become alkalotic?Why do they remain alkalotic?Generation of Metabolic AlkalosisLoss of H+ ionsGI loss: vomiting, GI suction, antacidsRenal loss: diuretics, mineralocorticoid excess, hypercalcemia, post-hypercapniaAdministration of bicarbonateTranscellular shiftK+ loss → H+ shifts intracellularlyIntracellular acidosisRefeeding syndromeContraction alkalosisSame HCO3, smaller extracellular volume → increased [HCO3]Seen in CF (sweating), illustrated in Fig 18-1Common theme: hypochloremia is essential for maintenanceMaintenance of Metabolic AlkalosisKidneys normally excrete excess HCO3Example: Normal subjects excrete 1000 mEq NaHCO3/day with minor pH changeImpaired HCO3 excretion required for maintenanceTable 18-2Mechanisms of MaintenanceDecreased GFR (less important)Increased tubular reabsorptionProximal tubule (PT): reabsorbs 90% of filtered HCO3TALH and distal nephron manage the restContributing factors:Effective circulating volume depletionEnhances HCO3 reabsorptionAng II increases Na-H exchangeIncreased tubular [HCO3] enables more H+ secretionDistal nephron HCO3 reabsorptionStimulated by aldosterone (↑ H-ATPase, ↑ Na reabsorption)Negative luminal charge impedes H+ back-diffusionChloride depletionReduces NaK2Cl activity → ↑ renin → ↑ aldosteroneLuminal H-ATPase co-secretes Cl → low Cl increases H+ secretionCl-HCO3 exchanger needs Cl gradient → low Cl impairs HCO3 secretionKey conclusion: Cl depletion > volume depletion in perpetuating alkalosisAlbumin corrects volume but not alkalosisNon-N Cl salts correct alkalosis without fixing volumeHypokalemiaStimulates H+ secretion and HCO3 reabsorptionTranscellular shift (H/K exchange) → intracellular acidosisH-K ATPase reabsorbs K and secretes HSevere hypokalemia reduces Cl reabsorption → ↑ H+ secretionImportant with mineralocorticoid excessRespiratory CompensationHypoventilation: 0.7 mmHg PCO2 ↑ per 1 mEq/L HCO3 ↑PCO2 can exceed 60Rise in PCO2 increases acid excretion (limited effect on pH)EpidemiologyGI Hydrogen LossGastric juice: high HCl, low KClStomach H+ generation → blood HCO3Normally recombine in duodenumVomiting/antacids prevent recombination → alkalosisAntacids (e.g., MgOH)Mg binds fats, leaves HCO3 unbound → alkalosisRenal failure impairs excretionCation exchange resins (SPS, MgCO3) → same effectCongenital chloridorrheaHigh fecal Cl-, low pH → metabolic alkalosisPPI may help by reducing gastric Cl loadRenal Hydrogen LossMineralocorticoid excess & hypokalemiaAldosterone → H+ ATPase stimulation, Na+ reabsorption → negative lumen → ↑ H+ secretionDiuretics (loop/thiazide)Volume contractionSecondary hyperaldosteronismIncreased distal flow and H+ lossPosthypercapnic alkalosisChronic respiratory acidosis → ↑ HCO3Rapid correction (ventilation) → unopposed HCO3 → alkalosisGradual CO2 correction neededMaintenance: hypoxemia, Cl lossLow chloride intake (infants)Na+ reabsorption must exchange with H+/K+H+ co-secretion with Cl impaired if Cl is lowHigh dose carbenicillinHigh Na+ load without ClNonresorbable anion → hypokalemia, alkalosisHypercalcemia↑ Renal H+ secretion & HCO3 reabsorptionCan contribute to milk-alkali syndromeRarely causes acidosis via reduced proximal HCO3 reabsorptionIntracellular H+ ShiftHypokalemiaCommon cause and effect of metabolic alkalosisH+/K+ exchange → intracellular acidosis → ↑ H+ excretionRefeeding SyndromeRapid carb reintroduction → cellular shiftNo volume contraction or acid excretion increaseRetention of BicarbonateRequires impaired excretion to become significantOrganic anions (lactate, acetate, citrate, ketoacids)Metabolism → CO2 + H2O + HCO3Citrate in blood transfusion (16.8 mEq/500 mL)8 units → alkalosis riskCRRT + citrate anticoagulantSodium bicarbonate therapyRebound alkalosis possible with acid reversal (e.g., ketoacidosis)Extreme cases: pH up to 7.9, HCO3 up to 70Contraction AlkalosisNaCl and water loss without HCO3Seen in vomiting, diuretics, CF sweatMild losses neutralized by intracellular buffersSymptomsOften asymptomaticFrom volume depletion: dizziness, weakness, crampsFrom hypokalemia: polyuria, polydipsia, weaknessFrom alkalosis (rare): paresthesias, carpopedal spasm, lightheadednessMore common in respiratory alkalosis due to rapid pH shift across BBBPhysical exam not usually helpfulClues: signs of vomitingDiagnosisHistory is keyIf unclear, suspect:Surreptitious vomitingCFSecret diuretic useMineralocorticoid excessUse urine chlorideTable 18-3: urine Na is misleading in alkalosisTable 18-4: urine chemistry changes with complete HCO3 reabsorptionVomiting: low urine Na, K, Cl + acidic urineSufficient NaCl intake prevents this stageExceptions to low urine Cl:Severe hypokalemiaTubular defectsCKDDistinguishing from respiratory acidosisUse pH as guideCaution with typo (duplicate pCO2)A-a gradient might helpTreatmentCorrect K+ and Cl− deficiency → kidneys self-correctUpper GI losses: add H2 blockersSaline-responsive alkalosisTreat with NaClMechanisms:Reverse contraction componentReduce Na+ retention → promote NaHCO3 excretion↑ distal Cl delivery → enable HCO3 secretion via pendrinMonitor urine pH: from 5.5 → 7–8 with therapyGive K+ with Cl, not phosphate, acetate, or bicarbonateSaline-resistant alkalosisSeen in edematous states or K+ depletionEdema (CHF, cirrhosis): use acetazolamide, HCl, dialysisAcetazolamide: may ↑ CO2 via RBC carbonic anhydrase inhibitionMineralocorticoid excess: K+ + K-sparing diuretic (use caution)Severe hypokalemia:eNaC Na+ reabsorption must be countered by H+ if no K+Corrects rapidly with K+ replacementRestores saline responsivenessRenal failure: requires dialysis