Chapter Twenty: Respiratory Acidosis

ReferencesBiff Palmer! Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023Josh what is sensed- pCO2 or pH and some exploration suggests that it is not settled! Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes - PMC and this one with catchy title: Out of thin air: Sensory detection of oxygen and carbon dioxide - PMCIf anna does VOG on Haldane- we’ll need references The Response of Extracellular Hydrogen Ion Concentration to Graded Degrees of Chronic Hypercapnia: The Physiologic Limits of the Defense of pH - PMC (this is the correct reference for figure 20-3 reference). JC shared some info from Dr. Adrogue Josh mentioned potential differences between people with respect to oxygen sensors and this study of sherpas: [Association of polymorphisms of 1772 (C-->T) and 1790 (G-->A) in HIF1A gene with hypoxia adaptation in high altitude in Sherpas] and this excellent review: Sensing hypoxia: physiology, genetics and epigenetics - PMCVOG from Amy on renal failure with respiratory acidosis https://pubmed.ncbi.nlm.nih.gov/38936337/Joel and Roger mention these two perspectives on alkali therapy for respiratory acidosis the first from Adrogué and Madias, the second from David Goldfarb: Alkali Therapy for Respiratory Acidosis: A Medical Controversy - American Journal of Kidney DiseasesSodium bicarbonate therapy for acute respiratory acidosisJoel mentioned this paper: https://www.nejm.org/doi/pdf/10.1056/NEJM196607212750301 the “carbon dioxide response curve for chronic hypercapnia in man by Bracket, Wingo et al. NEJM 1969 Josh mentioned a study in female ewes that showed a chloride excretion. Acute renal response to rapid onset respiratory acidosis and followed up with this: No renal dysfunction or salt and water retention in acute mountain sickness at 4,559 m among young resting males after passive ascentThis was also studied by Pitts and Giebisch and others: THE EXTRARENAL RESPONSE TO ACUTE ACID-BASE DISTURBANCES OF RESPIRATORY ORIGIN - PMC giebisch and Pitts (the original paper says “with the technical assistance of mary ellen parks and martha MacLeod but on the JCI website, they remedied this and made Parks and MacLeod authors) Joel mentioned the negative Diablo trial Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical TrialOutline: Chapter 20Respiratory AcidosisClinical disorder characterized byReduced arterial pHElevation of pCO2Variable increase in HCO3Increased pCO2 is also seen in metabolic alkalosisBut here it is appropriateAnd secondaryPATHOPHYSIOLOGY AND ETIOLOGYMetabolism generates 15,000 mmol of CO2 per dayCO2 is not an acid, butCombines with H2O to form H2CO3H2CO3 dissociates to HCO3 and H+Most H+ combines with intracellular buffersHemoglobin in RBCsHCO3 leaves the cell via the chloride exchangerNet resultCO2 generated is primarily carried in blood as HCO3Little change in pHProcess reverses in the alveoliAs H+Hb is oxygenated, H+ is releasedH+ combines with HCO3 to form H2CO3Carbonic anhydrase breaks H2CO3 into H2O and CO2CO2 is exhaledControl of VentilationAlveolar ventilationProvides oxygen for oxidative metabolismEliminates metabolically produced CO2Main stimuli for respirationReduced arterial pO2Increased pCO2Controlled in chemosensitive areas of the medullaRespond to CO2-induced changes in cerebral pHInitial hypoxic stimulation comes from carotid body chemoreceptorsFigure 20-1 is wildpCO2 is maintained within narrow limits despiteLarge daily CO2 loadVariable respiratory quotientVariable metabolic rateMinute ventilation rises 1–4 liters for every 1 mmHg rise in pCO2pO2 does not significantly stimulate ventilation until arterial pO2 <50–60 mmHgActually starts earlierIncreased ventilation lowers pCO2 which inhibits respirationIf pCO2 is fixed, pO2 of 70–80 mmHg will stimulate respirationFigure 20-2Development of HypercapniaBecause CO2 is such a potent respiratory stimulantRespiratory acidosis is usually due to decreased minute ventilationNot increased CO2 productionTable 20-1 lists causesCO2 retention in intrinsic pulmonary diseaseDue to ventilation/perfusion mismatchHypercapnia is beneficialAllows excretion of produced CO2 at lower minute ventilationConsequencesIncreased pCO2 decreases pHIncreased bone and cellular bufferingIncreased renal H secretionRaises serum HCO3Relationship Between Hypercapnia and HypoxemiaAll hypercapnic patients breathing room air have lower alveolar and arterial pO2Total alveolar partial pressures must equal atmospheric pressureHypoxemia generally occurs earlier and is more severe than hypercapniaCO2 diffuses 20× faster than O2Compensation by increasing ventilation in normal lung segmentsImproves CO2 eliminationCannot substantially increase O2 because Hb already saturatedAcute asthma exampleMucus plugging and bronchoconstriction cause hypoxemiaHypoxemia and mechanoreceptors stimulate ventilationProduces respiratory alkalosisRespiratory acidosis is a late findingRespiratory resistance risesMaximal minute ventilation fallspCO2 risesFirst normalizesThen becomes elevatedThereforeNormal pCO2 in acute asthma indicates severe diseaseGeneralization to other lung diseasesEven small increases in pCO2 indicate severe respiratory diseaseHypoxemia-induced hyperventilation delays hypercapniaBut there is 16-fold variability in sensitivity to hypoxemiaLess sensitive individuals develop respiratory acidosis more readilyRegulation of Ventilation in Chronic Respiratory AcidosisTwo common statementsRespiratory centers become less sensitive to CO2 over timeHypoxia becomes the primary respiratory stimulusInsensitivity to CO2Chemoreceptors primarily respond to pHChronic respiratory acidosis increases HCO3Therefore less pH change despite elevated pCO2Less respiratory stimulationWorsening hypercapnia and hypoxiaSimilarlyDiuretic-induced metabolic alkalosis suppresses ventilationDependence on hypoxemiaPatients with chronic respiratory acidosis rely on hypoxia to drive breathingLoss of CO2 stimulation due toRenal compensation raising HCO3Diuretics raising HCO3Making pH less dependent on pCO2Hypoxia drives ventilation when pO2 falls below ~80Makes oxygen administration potentially dangerousCan suppress respiratory driveOxygen also reverses hypoxic vasoconstrictionIncreases V/Q mismatchAcute Respiratory AcidosisBody poorly adapted to acute elevations in pCO2HCO3 cannot buffer H2CO3See Eq 20-4Must use hemoglobin and proteins as buffersSee Eq 20-5HCO3 rises 1 mEq/L for every 10 mmHg increase in pCO2ExamplepCO2 rises to 80HCO3 rises to 28pH falls to 7.17Without bufferingpH would be 7.10Not dramatically differentEtiologyAcute exacerbations of lung diseaseSevere asthmaPulmonary edemaDrug overdoseSleep apnea syndromesCentralObstructiveMixedChronic hypercapnia uncommon in isolated OSACO2 cleared during wakefulnessOSA + structural lung disease + obesityReduced daily alveolar ventilationPersistent CO2 retentionObesity hypoventilation syndromeMechanical ventilationInadequate respiratory rate can cause respiratory acidosisFixed ventilation means increased CO2 production can cause respiratory acidosisCardiac arrestSuggests sodium bicarbonateArterial ABG may miss severity due to poor pulmonary blood flowMixed venous blood may be better guideEnteral or parenteral overfeedingChronic Respiratory AcidosisAfter 3–5 daysHCO3 rises 3.5 mEq/L for every 10 mmHg rise in pCO2ExamplepCO2 = 804 × 3.5 = 14HCO3 should be 38pH ~7.30Allows tolerance of pCO2 values of 90–110Exogenous alkaliUnnecessaryUselessEasily excretedEtiologyCOPDGenetic variation in sensitivity to hypoxemia and CO2Blue bloatersLow response to CO2Hypoxia becomes primary respiratory stimulusPink puffersStrong CO2 responseTachypnea develops earlyCompensation for loss of lung tissuePickwickian syndromeObesity hypoventilation syndromeBook mistakenly says hyperventilationChest wall weight impairs breathingMore complex than thatWeight loss only helps some patientsProgesterone can improve conditionSuggests central respiratory defectMay coexist with OSAUnlike OSA, Pickwickian patients have chronic respiratory acidosisSYMPTOMSNeurologicHeadacheBlurred visionRestlessnessAnxietyCan progress toSomnolence (CO2 narcosis)TremorAsterixisDeliriumIncreased CSF pressurePapilledemaDue to increased cerebral blood flowSymptoms due to CSF acidemiaLess common in metabolic acidosisHCO3 crosses BBB poorlyLess common in chronic respiratory acidosisLess severe acidemiaArrhythmiasPeripheral vasodilationHypotensionParticularly when pH <7.1Cor pulmonalePeripheral edemaCan occur despite normal GFRSuggests relationship between respiratory acidosis and renal sodium handlingOr possibly hypoxiaDIAGNOSISLast full paragraph on page 659 discusses ambiguity of ABGsNicely doneFigure 20-6Two additional examplesBoth instructiveFinal sentence“In summary, the confidence bands are useful guides in the interpretation of acid-base measurements. However, this interpretation cannot proceed in a vacuum and must be correlated with a complete history and physical examination.”Use of the Alveolar-Arterial Oxygen GradientDerivation1 atmosphere = 760 mmHgWater vapor = 47 mmHgNitrogen = 563 mmHgLeaves ~150 mmHg oxygenNo net movement of water or nitrogenTherefore O2 + CO2 must account for remaining pressurePAO2 = PIO2 − PACO2Must multiply CO2 by 1.25 to account for respiratory quotientPAO2 = PIO2 − (1.25 × PACO2)Since CO2 diffuses rapidlyPACO2 ≈ PaCO2Normal valuesPIO2 = 150PaCO2 = 40PAO2 = 150 − (1.25 × 40)PAO2 = 100Normal A-a gradient5–10 mmHg in young adults15–20 mmHg in elderlyA-a gradient = PAO2 − PaO2Combined equationA-a gradient = PIO2 − (1.25 × PaCO2) − PaO2A-a gradient increased in intrinsic pulmonary diseaseOxygen has difficulty entering bloodMay also be increased in some extrapulmonary disordersNo explanation givenNormal A-a gradient argues against pulmonary diseaseSuggestsCentral hypoventilationPrimary metabolic alkalosisChest wall weaknessRespiratory muscle weaknessTREATMENTComplete discussion beyond scope of textAcute Respiratory AcidosisGive oxygen for hypoxiaCorrect underlying cause of hypercapniaOr intubateSodium bicarbonateRole not well definedMay help if pH <7.15Especially severe asthmatics on ventilatorsAvoid inPulmonary edemaCan worsen congestionCNS effectsDoes not protect CNS because HCO3 does not cross BBBIncreased pCO2Must monitor mixed venous pHLate metabolic alkalosisRare according to authorTromethamine (THAM)Binds hydrogenRapidly cleared by kidneys“THAM is of uncertain safety”Chronic Respiratory AcidosisGoalsAdequate oxygenationImprove effective alveolar ventilation if possibleRarely need to treat pH directlyBeware oxygenCan act as respiratory depressantDietary modificationsReduce carbohydratesImproves respiratory drive for unclear reasonsWeight reductionImproves respiratory mechanicsTarget pO2 60–65Reduces pulmonary vasoconstrictionReduces secondary polycythemiaMechanical ventilationLower pCO2 graduallyRapid correction can induce metabolic alkalosisSeizuresComaEffect of superimposed metabolic alkalosisMetabolic alkalosis depresses ventilationDiscontinue diureticsGive salineAcetazolamideAcetazolamide caveatsNeed appropriate bicarbonate target, not normalCan transiently increase pCO2 before diuretic effectMay be due to partial inhibition of carbonic anhydrase in RBCs needed for CO2 carrying capacity