What is the change that does not occur during acclimatization to high altitude: increased pulmonary (lung) ventilation, increased sensitivity of central chemoreceptor mechanisms to hypoxia (low oxygen levels) and carbon dioxide, increased 2,3-bisphosphoglycerate (2,3-DPG) concentration in red blood cells (RBCs), or metabolic alkalosis?

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High Altitude Acclimatization: The Exception

Metabolic alkalosis does not occur during acclimatization to high altitude; instead, respiratory alkalosis develops initially, which is then partially compensated by renal mechanisms that create a compensatory metabolic acidosis, not alkalosis.

Physiological Changes During High Altitude Acclimatization

The body undergoes several well-characterized adaptations when exposed to hypobaric hypoxia at high altitude:

Respiratory Adaptations (Options 1 & 2 - These DO Occur)

  • Increased pulmonary ventilation is a fundamental response to high altitude, driven by hypoxic stimulation of peripheral chemoreceptors in the carotid and aortic bodies 1, 2
  • This hyperventilation increases both respiratory rate and tidal volume to compensate for reduced oxygen availability 1
  • Increased sensitivity of peripheral chemoreceptors to hypoxia develops during acclimatization, allowing sustained hyperventilation even as pH changes 3
  • Notably, the peripheral chemoreceptors (not central chemoreceptors as stated in the question) become more sensitive to hypoxia during acclimatization, which continues to drive ventilation even when pH becomes alkaline 3

Hematologic Adaptations (Option 3 - This DOES Occur)

  • 2,3-DPG concentration in red blood cells increases during high altitude acclimatization 3
  • This rightward shift of the oxygen-hemoglobin dissociation curve facilitates oxygen unloading to tissues despite lower arterial oxygen tensions

Acid-Base Changes (Option 4 - This Does NOT Occur)

The key distinction: High altitude exposure causes respiratory alkalosis, not metabolic alkalosis 1, 2

  • Hyperventilation at altitude blows off CO₂, reducing PaCO₂ and creating respiratory alkalosis 1, 3
  • The kidneys respond by excreting bicarbonate to partially compensate for the respiratory alkalosis 3
  • This renal compensation creates a metabolic acidosis (decreased bicarbonate), not metabolic alkalosis 3
  • During acclimatization, the internal milieu becomes alkaline initially, but the kidney works to restore acidity by eliminating bicarbonate 3

Clinical Pitfall to Avoid

The confusion likely stems from misunderstanding the compensatory mechanisms. While the initial response to altitude is respiratory alkalosis, the body does not develop metabolic alkalosis as an adaptive response. Instead, metabolic alkalosis is typically seen in clinical conditions involving acid loss (vomiting, diuretic use) or alkali accumulation 4, 5, 6, none of which are part of normal high altitude acclimatization.

Answer: Option 4 (metabolic alkalosis) is the change that does NOT occur during high altitude acclimatization.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

High Altitude Travel Considerations for Amlodipine Users

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

CO2/H(+) sensing: peripheral and central chemoreception.

The international journal of biochemistry & cell biology, 2003

Research

Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2022

Research

Treatment of severe metabolic alkalosis in a patient with congestive heart failure.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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