Edited by Nayan Arora

References

Chapter 19, Part 3 August 30, 2023Biff Palmer’s Ted Talk-Why not? Biff Palmer at TEDxSMU 2013
Anna 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 Neurosciences
Reminder of important clinical lesson: Lactate: panicking doctor or panicking patient? - PMC
Melanie 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 2023
Melanie 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 Proteins
The 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 & Gynecology
Melanie 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 Neurology
He also mentioned this important transporters that affect the pH. The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pH
Refractory Central Neurogenic Hyperventilation: A Novel Approach Utilizing Mechanical Dead Space

Outline: Chapter 21

Respiratory Alkalosis

Increased pH, low pCO2, variable reduction in HCO3
Differentiate from metabolic acidosis where pH is decreased
- (but pCO2 and HCO3 are likewise decreased)
PATHOPHYSIOLOGY
- Primary decrease in pCO2 when effective alveolar ventilation is increased beyond that needed to eliminate daily CO2 production
- How does the body respond to hypocapnia
  - Mass action
    - Reduction in H+ induced by hypocapnia can be minimized by lowering HCO3
      - One: rapid cell buffering
      - Two: later decrease in net renal acid secretion → lower HCO3
    - These two strategies explain the difference between acute and chronic respiratory alkalosis
- Acute Respiratory Alkalosis
  - Within 10 minutes, H ions move into extracellular fluid
    - H+ combines with HCO3 → fall in plasma HCO3
    - Converted to CO2 and H2O
    - H+ comes from intracellular buffers
      - Protein, phosphate, hemoglobin
    - H+ 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 20
      - HCO3 falls by 4 → ~20 mEq/L
      - pH ~7.63
    - Not very efficient at protecting pH
      - Without compensation pH would be ~7.70
- Chronic Respiratory Alkalosis
  - Compensatory ↓ renal H secretion
    - Begins within 2 hours
    - Not complete for 2–3 days
  - Due to parallel rise in tubular cell pH
  - Manifested by
    - HCO3 loss
    - Decreased NH4 in urine
  - 4 mEq drop in HCO3 for each 10 mmHg decrease in pCO2
  - Example: pCO2 20 → HCO3 16 → pH ~7.53
ETIOLOGY
- Respiration governed by two sets of chemoreceptors
  - Central (respiratory center in brainstem)
  - Peripheral (carotid bodies at bifurcation, aortic bodies at arch)
- Central chemoreceptors
  - Stimulated by ↑ pCO2 or metabolic acidosis
- Peripheral chemoreceptors
  - Stimulated by hypoxia (and acidosis)
- Thus hyperventilation can be produced by
  - Hypoxemia
  - Anemia
  - Reduction in arterial pH
  - Other stimuli
    - Pain
    - Anxiety
    - Mechanoreceptors
    - Direct stimulation of respiratory center
    - Table 21-1
- Hypoxemia
  - Respiratory response occurs in stages
  - Stage 1
    - Peripheral chemoreceptor activation
    - Hyperventilation → respiratory alkalosis
    - Increased cerebral pH inhibits central respiratory center
      - Limits hyperventilation
    - No significant hyperventilation until pO2 < 50–60 mmHg
    - If lung disease prevents pCO2 reduction
      - Hypoxia stimulates ventilation at PaO2 < 70–80 mmHg
  - Stage 2⁉️
    - Persistent hypoxemia → ↓ HCO3
    - Lowers pH toward normal
    - Removes alkalosis inhibition
    - Allows greater ventilatory response
- Pulmonary Disease
  - Common in pneumonia, PE, interstitial fibrosis
  - Also pulmonary edema (though acidosis more common)
  - Hyperventilation may be due to hypoxemia
    - Often not corrected by oxygen
  - Other contributors
    - Mechanoreceptors in airways, lungs, chest wall
      - Signals via vagus nerve
    - Juxtacapillary receptors (interstitium)
    - Irritant receptors (epithelium)
      - Activated by inflammation or inhaled irritants
      - (asthma, pneumonia)
    - These contribute to dyspnea even without hypoxia
- Direct Stimulation of Medullary Respiratory Center
  - Cortical input (psychogenic hyperventilation)
  - Retained amines in hepatic failure (not prostaglandins⁉️)
  - Bacterial toxins (gram-negative sepsis)
  - Salicylates
  - Progesterone (pregnancy, luteal phase)
  - Persistent acid CSF after rapid correction of metabolic acidosis
    - NaHCO3 raises extracellular pH
    - Peripheral chemoreceptors reduce ventilation → ↑ pCO2
    - CO2 crosses BBB rapidly, HCO3 does not
    - Brain senses ↑ pCO2 → ↓ CSF pH
    - Paradoxical prolongation of hyperventilation
  - Neurologic disorders
    - Pontine tumors → local acidosis → ↓ CSF pH → ↑ ventilation
    - Hypocapnia in acute cerebral accidents
- Mechanical Ventilation
  - Overventilation can cause respiratory alkalosis
    - Correct by
      - Increasing dead space (no explanation given 🤷🏻‍♂️)
      - Decreasing tidal volume
      - Decreasing respiratory rate
SYMPTOMS
- Due to increased CNS and peripheral nerve excitability
  - Lightheadedness
  - Altered consciousness
  - Paresthesias (extremities, circumoral)
  - Cramps
  - Carpopedal spasm
  - Syncope
- Cardiac
  - Supraventricular and ventricular arrhythmias
- Mechanisms
  - Impaired cerebral function
  - Increased membrane excitability
  - ↓ cerebral blood flow
    - 35–40% reduction if pCO2 drops by 20 mmHg
- Psychogenic hyperventilation symptoms
  - Dyspnea
  - Headache
  - Chest pain
- Symptoms more prominent in acute disease (rapid pH change)
- Electrolytes
  - ↓ phosphate (as low as 0.5–1.5 mg/dL)
    - Due to intracellular shift
    - Increased glycolysis → ↑ phosphorylated compounds
DIAGNOSIS
- Tachypnea
  - But could be acidosis or alkalosis
- Consider sepsis
- Compensation equations can be ambiguous
  - Example: 7.48 / 20 / XX / 16
    - Could be chronic respiratory alkalosis
    - Or acute respiratory alkalosis + metabolic acidosis 😖
- Case 21-1
  - 5-year-old with AMS, playing with aspirin
TREATMENT
- Usually not necessary
- Do NOT give
  - Respiratory depressants
  - HCl
- Paper bag rebreathing
  - ↑ inspired CO2
  - Can correct acute respiratory alkalosis
  - If chronic → may leave patient with metabolic acidosis
    - Can treat with NaHCO3
- “Give a mouse a cookie” 😉