Chapter Twenty One: Respiratory Alkalosis

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” 😉