Control of Breathing

Breathing is controlled by a complex network of brainstem centres and chemoreceptors that maintain arterial blood gas homeostasis. Understanding this control system is essential for interpreting ABG results and managing patients with ventilatory failure.

The brainstem respiratory centres consist of the pre-Bötzinger complex in the medulla, which generates the basic respiratory rhythm, and the Bötzinger complex, which modulates expiration. The pontine respiratory group (pneumotaxic centre) refines the rhythm and influences the transition between inspiration and expiration. Damage to these centres (e.g. stroke, opioid overdose) causes respiratory depression.

Ventilation is primarily regulated by arterial PCO2 through central chemoreceptors located on the ventral surface of the medulla oblongata. These receptors respond to changes in the pH of cerebrospinal fluid (CSF), which rapidly reflects changes in arterial PCO2 (CO2 diffuses freely across the blood-brain barrier and reacts with water to form H⁺). An increase in PaCO2 stimulates the central chemoreceptors and drives an increase in ventilation, which restores PaCO2 to normal. This is the dominant and most sensitive chemical stimulus for ventilation.

Peripheral chemoreceptors are located in the carotid bodies (at the bifurcation of the common carotid arteries) and aortic bodies. They respond primarily to low PaO2 (hypoxic drive), and to a lesser extent to high PaCO2 and low pH. The peripheral chemoreceptors are activated only when PaO2 falls below approximately 8 kPa (60 mmHg) — above this threshold, changes in PaO2 have little effect on ventilation.

In chronic hypercapnia (as in severe COPD), the central chemoreceptors adapt to persistently elevated PaCO2, becoming insensitive to it. In these CO2 retainers, the hypoxic drive via peripheral chemoreceptors becomes the dominant stimulus for ventilation. This is the basis of concerns about administering high-flow oxygen to CO2 retainers — abolishing hypoxic drive can cause further hypoventilation and worsen hypercapnia. In practice, target SaO2 of 88–92% in known CO2 retainers.

Acid-base disturbances alter breathing. Metabolic acidosis stimulates ventilation (Kussmaul breathing), reducing PaCO2 as respiratory compensation. Metabolic alkalosis suppresses ventilation, raising PaCO2. Respiratory acidosis (hypercapnia) is compensated metabolically by renal retention of bicarbonate; respiratory alkalosis (hypocapnia) by renal excretion of bicarbonate.