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Respiratory Control and Acidosis

Jun 28, 2025

Overview

This lecture covers the mechanisms controlling alveolar ventilation and details the differential diagnosis and pathophysiology of respiratory acidosis.

Control of Ventilation

  • Ventilation is regulated by the medullary respiratory center integrating brain and peripheral chemoreceptor input.
  • Central chemoreceptors (mainly in the medulla) detect pH changes and adjust ventilation to regulate arterial pH.
  • The cerebral cortex can increase ventilatory drive (pain, anxiety) and provides tonic inhibition.
  • Pontine respiratory centers help fine-tune respiratory rate and tidal volume.
  • Progesterone receptors in the CNS, when stimulated, increase ventilation.
  • Peripheral chemoreceptors (carotid and aortic bodies) respond to changes in pCO₂, pH, and significant drops in pO₂.
  • Other receptors (J receptors, stretch receptors, irritant receptors) further modulate respiratory drive.

Alveolar Ventilation Equation

  • Alveolar ventilation is calculated as respiratory rate × (tidal volume − dead space).
  • Partial pressure of arterial CO₂ (pCO₂) = (CO₂ production rate × inspired air pressure) ÷ alveolar ventilation.
  • Main causes of increased pCO₂: low respiratory rate and low tidal volume; less commonly, high dead space or increased CO₂ production.

Causes of Respiratory Acidosis

  • Obstructive lung diseases: COPD (most common), asthma (only in severe attacks).
  • Central hypoventilation: drug overdose (alcohol, narcotics, benzodiazepines, others), brainstem lesions, obesity hypoventilation syndrome, central hypoventilation syndrome (Ondine's curse).
  • Neuromuscular disorders: diseases affecting spinal cord, peripheral nerves, neuromuscular junction, or muscles.
  • Poor compliance of the respiratory system: interstitial lung disease, ARDS, pulmonary edema, chest wall deformities (e.g., kyphoscoliosis).
  • Hypermetabolic states: rare conditions like extreme fever, seizures, or overfeeding.

Common Clinical Entities

  • COPD: airway inflammation and parenchymal destruction cause airway obstruction, air trapping, hyperinflation, and decreased alveolar ventilation.
  • Drug overdose: respiratory depressants first lower respiratory rate; risk increases dramatically when multiple drug classes are combined.
  • Obesity hypoventilation syndrome (OHS): characterized by obesity and awake hypoventilation; distinct from but often overlapping with obstructive sleep apnea; complications include hypoxia and right heart failure.

Rare Conditions

  • Central hypoventilation syndrome (Ondine's curse): failure of autonomic ventilation control, typically normal voluntary breathing, may be congenital or acquired.

Key Terms & Definitions

  • Respiratory acidosis — acid-base disorder caused by insufficient ventilation leading to CO₂ retention.
  • Alveolar ventilation — volume of air reaching perfused alveoli per minute.
  • Tidal volume — air volume inhaled or exhaled in a normal breath.
  • Dead space — lung regions where gas exchange does not occur.
  • Obesity hypoventilation syndrome (OHS) — chronic hypoventilation during wakefulness in obesity without other causes.
  • Central hypoventilation syndrome (Ondine's curse) — impaired automatic respiratory drive, especially during sleep.

Action Items / Next Steps

  • Review the causes of respiratory alkalosis in the next lecture.
  • Be familiar with key causes and clinical features of respiratory acidosis for exams.