Channel Your Enthusiasm

ReferencesChapter 19, Part 3 August 30, 2023Biff Palmer’s Ted Talk-Why not? Biff Palmer at TEDxSMU 2013Anna mentioned this issue of lactic acidosis in a panic disorder: The Lactic Acid Response to Alkalosis in Panic Disorder | The Journal of Neuropsychiatry and Clinical NeurosciencesReminder of important clinical lesson: Lactate: panicking doctor or panicking patient? - PMCMelanie regaled the group with an excerpt (page 351) Cohen, J. J., Kassirer, J. P. (1982). Acid-base. United States: Little, Brown.Biff Palmer! Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023Melanie loves this study of chronic respiratory alkalosis on participants to traveled to the High ALpine research station on the Jungfraujoch in the Swiss Alps Chronic Respiratory Alkalosis — The Effect of Sustained Hyperventilation on Renal Regulation of Acid–Base Equilibrium | NEJM (and here’s a great picture: Services: Jungfraujoch Research Station - Climate and Environmental Physics (CEP)JC mentioned that there are cells in the carotid body which are called glomus cells Neurobiology of the carotid body.JC discussed respiratory alkalosis in cirrhosis and here’s a review he had melanie write that addresses this topic: Acid Base Disorders in Cirrhosis - Advances in Kidney Disease and Health and here are some reviews he likes: The hyperventilation of cirrhosis: progesterone and estradiol effects and Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction and Blood-Brain Barrier Permeability Is Exacerbated in Experimental Model of Hepatic Encephalopathy via MMP-9 Activation and Downregulation of Tight Junction ProteinsThe finding of respiratory alkalosis in pregnancy is not a new concept. Here’s a study from 1962: Acid-base balance of arterial blood during pregnancy, at delivery, and in the puerperium - American Journal of Obstetrics & GynecologyMelanie reminded us of the Charlie Brown sad face that occurs after bicarbonate infusion and delay in bicarbonate movement to the CSF! Spinal-Fluid pH and Neurologic Symptoms in Systemic Acidosis | NEJM (part 2 of chapter 11)Josh mentioned this report from Andrew Tarulli (a great neurologist previously at BIDMC who has moved to Overlook Hospital in NJ) Central Neurogenic Hyperventilation: A Case Report and Discussion of Pathophysiology | Allergy and Clinical Immunology | JAMA NeurologyHe also mentioned this important transporters that affect the pH. The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pHRefractory Central Neurogenic Hyperventilation: A Novel Approach Utilizing Mechanical Dead SpaceOutline: Chapter 21Respiratory AlkalosisIncreased pH, low pCO2, variable reduction in HCO3Differentiate from metabolic acidosis where pH is decreased(but pCO2 and HCO3 are likewise decreased)PATHOPHYSIOLOGYPrimary decrease in pCO2 when effective alveolar ventilation is increased beyond that needed to eliminate daily CO2 productionHow does the body respond to hypocapniaMass actionReduction in H+ induced by hypocapnia can be minimized by lowering HCO3One: rapid cell bufferingTwo: later decrease in net renal acid secretion → lower HCO3These two strategies explain the difference between acute and chronic respiratory alkalosisAcute Respiratory AlkalosisWithin 10 minutes, H ions move into extracellular fluidH+ combines with HCO3 → fall in plasma HCO3Converted to CO2 and H2OH+ comes from intracellular buffersProtein, phosphate, hemoglobinH+ may also come from alkalemia-induced increase in cellular lactic acid production (1)⁉️Enough H+ enters ECF to lower HCO3 by 2 mEq for each 10 mmHg decrease in pCO2 (Fig 20-3)Example: pCO2 falls to 20HCO3 falls by 4 → ~20 mEq/LpH ~7.63Not very efficient at protecting pHWithout compensation pH would be ~7.70Chronic Respiratory AlkalosisCompensatory ↓ renal H secretionBegins within 2 hoursNot complete for 2–3 daysDue to parallel rise in tubular cell pHManifested byHCO3 lossDecreased NH4 in urine4 mEq drop in HCO3 for each 10 mmHg decrease in pCO2Example: pCO2 20 → HCO3 16 → pH ~7.53ETIOLOGYRespiration governed by two sets of chemoreceptorsCentral (respiratory center in brainstem)Peripheral (carotid bodies at bifurcation, aortic bodies at arch)Central chemoreceptorsStimulated by ↑ pCO2 or metabolic acidosisPeripheral chemoreceptorsStimulated by hypoxia (and acidosis)Thus hyperventilation can be produced byHypoxemiaAnemiaReduction in arterial pHOther stimuliPainAnxietyMechanoreceptorsDirect stimulation of respiratory centerTable 21-1HypoxemiaRespiratory response occurs in stagesStage 1Peripheral chemoreceptor activationHyperventilation → respiratory alkalosisIncreased cerebral pH inhibits central respiratory centerLimits hyperventilationNo significant hyperventilation until pO2 < 50–60 mmHgIf lung disease prevents pCO2 reductionHypoxia stimulates ventilation at PaO2 < 70–80 mmHgStage 2⁉️Persistent hypoxemia → ↓ HCO3Lowers pH toward normalRemoves alkalosis inhibitionAllows greater ventilatory responsePulmonary DiseaseCommon in pneumonia, PE, interstitial fibrosisAlso pulmonary edema (though acidosis more common)Hyperventilation may be due to hypoxemiaOften not corrected by oxygenOther contributorsMechanoreceptors in airways, lungs, chest wallSignals via vagus nerveJuxtacapillary receptors (interstitium)Irritant receptors (epithelium)Activated by inflammation or inhaled irritants(asthma, pneumonia)These contribute to dyspnea even without hypoxiaDirect Stimulation of Medullary Respiratory CenterCortical input (psychogenic hyperventilation)Retained amines in hepatic failure (not prostaglandins⁉️)Bacterial toxins (gram-negative sepsis)SalicylatesProgesterone (pregnancy, luteal phase)Persistent acid CSF after rapid correction of metabolic acidosisNaHCO3 raises extracellular pHPeripheral chemoreceptors reduce ventilation → ↑ pCO2CO2 crosses BBB rapidly, HCO3 does notBrain senses ↑ pCO2 → ↓ CSF pHParadoxical prolongation of hyperventilationNeurologic disordersPontine tumors → local acidosis → ↓ CSF pH → ↑ ventilationHypocapnia in acute cerebral accidentsMechanical VentilationOverventilation can cause respiratory alkalosisCorrect byIncreasing dead space (no explanation given 🤷🏻‍♂️)Decreasing tidal volumeDecreasing respiratory rateSYMPTOMSDue to increased CNS and peripheral nerve excitabilityLightheadednessAltered consciousnessParesthesias (extremities, circumoral)CrampsCarpopedal spasmSyncopeCardiacSupraventricular and ventricular arrhythmiasMechanismsImpaired cerebral functionIncreased membrane excitability↓ cerebral blood flow35–40% reduction if pCO2 drops by 20 mmHgPsychogenic hyperventilation symptomsDyspneaHeadacheChest painSymptoms more prominent in acute disease (rapid pH change)Electrolytes↓ phosphate (as low as 0.5–1.5 mg/dL)Due to intracellular shiftIncreased glycolysis → ↑ phosphorylated compoundsDIAGNOSISTachypneaBut could be acidosis or alkalosisConsider sepsisCompensation equations can be ambiguousExample: 7.48 / 20 / XX / 16Could be chronic respiratory alkalosisOr acute respiratory alkalosis + metabolic acidosis 😖Case 21-15-year-old with AMS, playing with aspirinTREATMENTUsually not necessaryDo NOT giveRespiratory depressantsHClPaper bag rebreathing↑ inspired CO2Can correct acute respiratory alkalosisIf chronic → may leave patient with metabolic acidosisCan treat with NaHCO3“Give a mouse a cookie” 😉

ReferencesChapter 19, Part 3 August 30, 2023Joel and Roger mentioned the most common cause seems to be Sjögren’s syndrome for an acquired distal RTA. We mentioned this in an earlier episode and referenced this example of an absence of the H+ ATPase, presumably from autoantibodies to this transporter. Here’s a case report: Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosis Joel mentioned this paper in the New England Journal of Medicine in which there were patients who had hyperkalemia with a distal RTA: Hyperkalemic Distal Renal Tubular Acidosis Associated with Obstructive Uropathy | NEJM in this setting, some patients  Anna mentioned this article on “ampho-terrible:” It’s the holes!!!    Yano T, Itoh Y, Kawamura E, Maeda A, Egashira N, Nishida M, Kurose H, Oishi R. Amphotericin B-induced renal tubular cell injury is mediated by Na+ Influx through ion-permeable pores and subsequent activation of mitogen-activated protein kinases and elevation of intracellular Ca2+ concentration. Antimicrob Agents Chemother. 2009 Apr;53(4):1420-6Josh mentioned this study on furosemide’s effect on the TAL: Furosemide-induced urinary acidification is caused by pronounced H+ secretion in the thick ascending limb Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride - Kidney InternationalMelanie mentioned treatment of patients with cystinosis Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients | Clinical Kidney Journal | Oxford AcademicAmy shared her observations regarding base supplements including Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis - PubMed and Dosage of potassium citrate in the correction of urinary abnormalities in pediatric distal renal tubular acidosis patients - PubMedRoger mentioned that he has had good luck with Moonstone Nutrition drinks alkali citrates for kidney healthWe referred to David Goldfarb’s teaching on kidney stones in patients with acidification defects:  A Woman with Recurrent Calcium Phosphate Kidney Stones (we also referenced this in an earlier episode but this one is a fan favorite). Joel mentioned the concern of bone loss in distal RTA: Incomplete renal tubular acidosis in 'primary' osteoporosis and Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatmentJC mentioned Ehlers-Danlos syndrome with renal tubular acidosis and medullary sponge kidneys. A report of a case and studies of renal acidification in other patients with the Ehlers-Danlos syndromeLety mentioned concerns of encrustation of stents in stone forming individuals Potassium Citrate as a Preventive Treatment for Double-J Stent Encrustation: A Randomized Clinical TrialJoel schooled us in toluene and the presentation which appears to be an RTA- https://journals.lww.com/JASN/Abstract/1991/02000/Glue_sniffing_and_distal_renal_tubular_acidosis_.3.aspxMelanie mentioned this work by Alan Yu’s lab on a mechanism of hypercalciuria Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers and an accompanying editorial by Goldfarb Refining Diagnostic Approaches in Nephrolithiasis: Incomplete Distal Renal Tubular AcidosisHere’s a nice piece on ifosfamide and phosphate from Josh New clues for nephrotoxicity induced by ifosfamide: preferential renal uptake via the human organic cation transporter 2Here’s this crazy piece on excessive bicarbonate - Gas production after reaction of sodium bicarbonate and hydrochloric acidJosh points out that the pH can be important for inotropy:  An effect of pH upon epinephrine inotropic receptors in the turtle heartMel’s favorite from Halperin because of the pun: Renal tubular acidosis (RTA): recognize the ammonium defect and pHorget the urine pHAmy’s VOG on RTA and OsteoporosisKI Review on acidosis and bone health: Effects of acid on boneGuideline on congenital RTA: Distal renal tubular acidosis: ERKNet/ESPN clinical practice pointsAJKD article on acidosis and bone health: Serum Bicarbonate and Bone Mineral Density in US AdultsCitrate reversing CsA induced acidosis effects: Citrate reverses cyclosporin A-induced metabolic acidosis and bone resorption in ratsOutline: Chapter 19 Metabolic Acidosis part 3Renal Tubular AcidosisAcidosis from diminished net tubular acid secretionThree typesType 1 (Distal)Type 2 (Proximal)Type 4 (…)The acidosis of renal failure could be added to this groupBut NH4+ per nephron is normalThis is a problem of too few nephrons, not tubular acidosisNephrons able to maximally acidify the urineType 1 Distal RTADecrease in net H secretion in the collecting ductMinimal urine pH rises from 4.5 to 5.3HCO3 can fall below 10Three mechanismsDefect in H-ATPase found in cortex and medullaSjögren syndromeCan be genetic chloride bicarbonate exchangerThis pumps bicarbonate out basolateral membrane after it is generated in the splitting of water to form HDefect in cortical Na reabsorptionVoltage-dependent defectConcurrent K secretion defectFound in urinary obstruction and sickle cellVolume deficiency can decrease Na delivery to distal nephronDecreased amount of Na reabsorption can cause a reversible type 1 RTA of this typeIncreased membrane permeabilityAmphotericinpH of 5.0 is 250× plasmaTable 19-7Fractional excretion of bicarbonate in distal RTANormally negligible since bicarbonate can’t exist with pH down around 5In distal RTA it may be as high as 6.5; FEHCO3 is 3%If pH goes up over 7 this can rise to 5–10%Usually in infantsAs they age their urine pH falls a bitThis is called type 3Plasma KH-ATPase defects have low KPatients also have downregulation of H-K-ATPaseDownregulation of NaCl reabsorption in proximal tubuleDecreased filtered bicarbonate means less bicarbonate to absorb with Na, hence more Na excretion from proximal tubuleThis increases distal sodium delivery and increases aldosteroneVoltage defect also has decreased renal K clearance → hyperkalemiaDifferentiate from type 4 RTA by looking at urine pHLower in type 4Higher in voltage-dependent distal RTANephrocalcinosisHypercalciuria, hyperphosphatemia, nephrolithiasis, and nephrocalcinosis are frequentComes from bones buffering the acidosisKidney decreases reabsorption of these so they are lost in urineTwo other factorsLow urinary citrateHypokalemia drives thisAcidosis drives thisHigh urine pH (CaPhos stones)All corrected by correcting the metabolic acidosisIncomplete Type 1Defective urinary acidification but not acidemicIncreased proximal NH3 production lowers urinary HLow urinary citrateCan progress to complete type 1Etiology of Type 1Sjögren syndrome, rheumatoid arthritis19-8Clinical manifestationsStonesHypokalemiaGrowth defectsDiagnosisNAGMA and elevated urine pH5.3 in adults5.6 in childrenDifferentiate Type 1 vs Type 2Give bicarbonate drip1 mEq/kg/hrUrine pH remains high with Type 1Does not go up as it does with proximal Type 2Incomplete distal RTAGive acid load0.1 mmol/kgUrine pH remains >5.3 in classicFalls in normal patients (usually below 5)TreatmentTreat metabolic acidosisMinimize potassium lossReduce bone catabolismPrevent stonesAlkali requirementAdults: 1–2 mEq/kg/dayChildren: 4–14 mEq/kg/dayAlkaliSodium bicarbonateSodium citratePotassium citrate if hypokalemia persists despite correcting acidosisOr for calcium stone diseaseTreat hypokalemiaType 2 Proximal RTADecreased HCO3 reabsorption90% of bicarbonate reabsorption happens in proximal tubuleBicarbonate wasting starts normally at 26–28 mmol/L (Tm for bicarbonate)In RTA 2 the Tm falls to a lower level (maybe 17)Serum bicarbonate falls to 17 and stabilizesType 2 RTA is self-limitingTypically HCO3 around 14–20 Distal acidification intactCarbonic anhydrase inhibitor can block 80% of proximal HCO3 reabsorptionOnly 30% of filtered bicarbonate excreted due to distal H secretionTotal absence of proximal reabsorption results in HCO3 11–12Clinical difference in treatmentIn Type 2, giving bicarbonate and raising serum HCO3 above Tm → more wasted in urineFEHCO3 can reach 15% with normal serum HCO3Urine pH >7.5Below Tm, urine pH <5.3In Type 1, curve relating HCO3 excretion to plasma HCO3 similar to normal (with increased obligatory urine HCO3 due to higher urine pH)Defect in HCO3 reabsorptionCan be isolatedOr part of Fanconi syndromePathogenesis (three steps)Na-H exchange (apical membrane)Na-K-ATPase (basolateral membrane)Carbonic anhydraseIntracellularLuminalMultiple myeloma most common adult causeIfosfamideCan also cause phosphate wasting, NDI, and Type 1 RTAK balanceCommon but variableMild hypokalemia at baseline due to increased Na wasting → hyperaldosteronismWorse with bicarbonate therapyDistal delivery of nonreabsorbable anion increases obligate cation lossFigure 19-7Bone diseaseRickets (children), osteomalacia/osteopenia (adults)Up to 20%Phosphate wasting and vitamin D deficiency may contributeImpaired growthNo nephrocalcinosis or nephrolithiasisLower urine pHNonreabsorbable amino acids and organic anions bind calciumEtiology19-9Idiopathic and cystinosis (children)Carbonic anhydrase inhibitorsMultiple myelomaDiagnosisNAGMA and pH <5.3Look for Fanconi syndromeRaise serum HCO3 and watch urine pH riseFEHCO3 15–20%TreatmentCorrect acidosis to allow normal growthDifficult due to rapid urinary lossMay need 10–15 mEq/kg/dayHCO3 or citrateMore than 20 mEq HCO3 can cause stomach rupture from CO2 generationSmall dose thiazide to increase proximal Na reabsorption and HCO3 reabsorptionIdiopathic Type 2 may improve after yearsType 4 RTAAldosterone deficient or resistantNormally stimulates H secretion and K secretionLoss causes hyperkalemia and metabolic acidosisHyperkalemia antagonizes NH4 generationHigh K may outcompete NH4 on Na-K-2Cl in TALHLess ammonium recyclingLess NH3 available in collecting ductCorrecting hyperkalemia can correct acidosisMetabolic acidosis generally mildHCO3 >15Urine pH <5.3 (generally, not always)Mineralocorticoid can treat but causes hypertension and sodium retentionOften responds to loop diureticRhabdomyolysis can cause high anion gap metabolic acidosisSymptomsRespiratory compensation increases 4–8 fold → dyspneapH <7.0–7.1Fatal ventricular arrhythmiasReduced cardiac contractilityDecreased response to inotropesNeurologicalLethargy to comaMore related to CSF pH than plasmaLess neurologic symptoms than respiratory acidosisBBB more permeable to CO2 than HCO3Skeletal problemsDecreased growthKids/infants: anorexia, nausea, listlessnessTreatmentGeneral principlesCorrect with HCO3No alkali required for lactic or ketoacidosisGoal: pH >7.2Equations on page 629 need “log”Example: pH 7.1, pCO2 20, HCO3 6Raise HCO3 to 8 if pCO2 stays 20Raise to 10 if pCO2 risesParagraph “regardless…” highlights risks of bicarbonateBicarbonate deficitDeficit = HCO3 space × HCO3 deficit per literHCO3 space50% body weight (normal)60% (mild–moderate acidosis)70% (severe, HCO3 <8–10)Example: 70 kg, raise HCO3 6→10 using 0.7 space = 196 mEqRough guideline; does not account for ongoing acid productionEarly large bump in bicarbonateDrifts down as bicarbonate moves intracellularlyPlasma potassiumK depletion can cause metabolic acidosisMetabolic acidosis increases K“Normal” K may mask depletion (see DKA)Beware correcting acidosis in hypokalemiaHeart failureBicarbonate comes with sodium loadComment that bicarbonate moves into cellBut Na remains extracellularDialysis can be used

Join Roger Rodby, a nephrologist with a wealth of clinical experience, alongside Josh Waitzman, a nephrologist and scientist, Melanie Honig, a clinical contributor, Anna Gaddy, and JC, as they delve deep into metabolic acidosis. They explore the biochemistry of lactate, the Warburg effect in cancer, and treatment controversies surrounding bicarbonate therapy. The panel also navigates risks related to liver dysfunction, toxic ingestions, and the implications of lactate in various clinical scenarios, all while providing fascinating insights into acid-base disorders.

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

In a fascinating discussion, nephrologists Josh Waitzman, Roger Rodby, Melanie Honig, and Juan Cabral-Villis unpack the complexities of metabolic acidosis. They delve into the mechanisms behind acid-base balance, highlighting the role of extracellular and intracellular buffering. The group discusses the practical limits of bicarbonate replacement, mechanisms affecting potassium levels during acidosis, and asserts the importance of understanding anion gap implications in clinical settings. Their dynamic exchanges make complex concepts accessible and engaging.

Join nephrologists Juan Carlos Villas, Melanie Honig, and Roger Rodby as they humorously navigate the complexities of metabolic alkalosis. They dissect the critical role of chloride in kidney function and share personal anecdotes related to their medical journeys. The experts clarify misconceptions about bicarbonate retention versus chloride loss and discuss the significant impact of diuretics. Insights into standardized terminology for chronic kidney disease and the intricate mechanisms of bicarbonate reabsorption in renal physiology round out this informative conversation.

Dive into the fascinating world of acid-base physiology and renal health! The hosts dissect personal experiences while unraveling the complexities of acid-base disorders and their clinical significance. Discover the role of dietary acid load on urinary pH, revealing surprising insights on the effects of animal versus plant proteins. The discussion unveils the intricacies of blood gas analysis, the bicarbonate buffering system, and the importance of accurate measurements in patient care. History, education, and practical challenges create a rich tapestry of knowledge!

This discussion humorously tackles renal physiology with sci-fi analogies. Celebrating awards, the speakers share their journey together in education while reflecting on their supportive community. They delve into the complexities of heart failure management, emphasizing the significance of clinical exam over imaging. Key connections between proteinuria and heart failure are explored, as well as the intricacies of liver disease treatment. The episode wraps up with insights on managing edema and the multifaceted use of minoxidil in hypertension.

Dive into the fascinating world of renal physiology as experts dissect the intricacies of interstitial spaces and their crucial roles in fluid management. Explore the nuances of edema, from pitting versus non-pitting types, to innovative treatment strategies like compression stockings over diuretics. Insights on nephrotic syndrome reveal the delicate balance between underfilling and overfilling, emphasizing the importance of nephrologist guidance. With humor and expertise, the discussion also illuminates the complexities of managing lymphedema and heart failure.

Melanie, a passionate researcher on diuretics, joins heart failure expert Craig Brater, who has contributed significantly to the field. They dive into the vital role of diuretics in managing conditions like heart failure and the complexities of dosing strategies. Lety shares innovative methods for estimating furosemide doses based on creatinine levels, emphasizing more accurate formulas over traditional ones. The discussion also touches on sodium intake's impact on treatment efficacy and the intriguing link between sleep apnea and nocturnal urination challenges.