Regulation of Respiration — Medullary and Pontine Centres, Chemoreceptors, Reflexes and Abnormal Breathing

Breathing is matched to metabolic demand by a control system with three parts: a central neural respiratory generator in the brainstem, a sensory input system (chemoreceptors and lung mechanoreceptors) and the muscular effectors (diaphragm, intercostals and accessory muscles). The generator sets rhythm and depth; sensory input modifies them; the muscles carry out the command.

Inspiration is active — the diaphragm and external intercostals contract, intrapleural and alveolar pressures fall, and air flows in. Quiet expiration is passive, driven by the elastic recoil of the lungs. The combined input produces a resting rate of about 12 breaths per minute in an average adult.

The respiratory centre has three neuronal groups: the dorsal respiratory group (DRG) in the nucleus tractus solitarius, the ventral respiratory group (VRG) in the medulla, and the pontine respiratory group in the pons, which is subdivided into the pneumotaxic and apneustic centres.

Central chemoreceptors lie on the ventral surface of the medulla and in the retrotrapezoid nucleus. They respond to H+ in the cerebrospinal fluid. CO2 is lipid-soluble and crosses the blood-brain barrier freely, forming H+ in the CSF. So the central receptors effectively track arterial PCO2, which is the chief determinant of respiratory drive under normal conditions.

Peripheral chemoreceptors are the carotid bodies at the bifurcation of the common carotid artery (afferents in the glossopharyngeal nerve, CN IX) and the aortic bodies in the aortic arch (afferents in the vagus, CN X). They are most sensitive to a fall in PaO2, with some response to H+ and CO2. The carotid bodies provide only about 15% of the total resting drive, but during hypoxia the carotid body response dominates.

For how the different causes of low oxygen affect PaO2 — and therefore whether the carotid bodies are stimulated at all — see types of hypoxia.

The CO2 response curve plots minute ventilation against PaCO2. A rise in PaCO2 increases ventilation steeply through both sets of chemoreceptors. The curve is shifted by other stimuli and by drugs — a frequent question in physiology and anaesthesia.

The pattern of breathing also differs. Hypoxia produces rapid, shallow breaths (rate rises more than tidal volume), which lowers the oxygen cost of breathing. Hypercapnia produces deep, slow breaths (tidal volume rises more than rate), which limits dead-space ventilation and clears CO2 efficiently.

During sleep, especially REM sleep, breathing becomes irregular with hypopnoeas and apnoeas, accessory muscles are paralysed, and the respiratory centre responds less to changes in PaO2 and PaCO2.

Mechanoreceptors in the airways, lungs and pulmonary vessels send information through the vagus nerve (CN X) to the respiratory centre.

Cheyne-Stokes respiration (CSR) is periodic breathing: a crescendo-decrescendo waxing and waning of tidal volume that alternates with central apnoea or hypopnoea. It is most strongly associated with heart failure and stroke, and in heart failure it predicts a worse outcome (arrhythmias, admissions, sudden death). A prolonged circulation time between lungs and chemoreceptors is one of its risk factors. Classic CSR has a cycle length of about 45–75 seconds.

Cushing's triad — irregular respiration, hypertension and bradycardia — signals raised intracranial pressure and impending herniation.

On polysomnography, a central apnoea is cessation of airflow for 10 seconds or longer with no respiratory effort (no chest or abdominal movement) — unlike obstructive apnoea, where effort continues against a closed airway. Cheyne-Stokes breathing is scored when both criteria below are met.

1. Three or more consecutive central apnoeas or hypopnoeas separated by a crescendo-decrescendo change in breathing amplitude, with a cycle length of 40 seconds or longer.
2. Five or more such events per hour, recorded over at least 2 hours of monitoring.

Hypercapnia causes flushed skin, headache, lethargy, inability to concentrate and disorientation; with worsening CO2 retention come confusion, somnolence, seizures and, in severe cases, coma — the state called CO2 narcosis. Raised PaCO2 also lowers alveolar PO2 (alveolar gas equation).

In an acute exacerbation of COPD, giving high-flow oxygen can raise PaCO2. The old explanation was loss of a 'hypoxic drive' in patients whose central chemoreceptors had become insensitive to CO2. That theory is no longer widely accepted: the fall in minute ventilation is transient and does not match the rise in PaCO2.

• Loss of hypoxic pulmonary vasoconstriction: oxygen releases vasoconstriction in poorly ventilated alveoli, increasing V/Q mismatch and dead-space ventilation — the main mechanism.
• Haldane effect: oxygenated haemoglobin carries less CO2, releasing it into the blood.
• Limited reserve: these patients cannot raise minute ventilation enough to blow off the extra CO2.