Regulation of breathing and chemoreceptors

Overview

We breathe automatically, but breathing is constantly adjusted so that arterial PCO2, PO2 and pH stay almost constant, even during exercise.

Control has three parts:

• Respiratory centres in the brainstem that create the rhythm.
• Chemoreceptors that sense CO2, H+ and O2.
• Other receptors and higher centres that modify breathing.

The respiratory centres

The dorsal group sends a ramp signal to the inspiratory muscles: it starts weak and builds up steadily for about 2 seconds, then stops, giving smooth inspiration.

Central chemoreceptors

Location: a chemosensitive area on the ventral surface of the medulla, just beneath the surface.

What they sense: H+ concentration in the cerebrospinal fluid and brain interstitial fluid.

How CO2 stimulates them:

1. A rise in arterial CO2 crosses the blood-brain barrier easily.
2. In the CSF, CO2 + H2O → H2CO3 → H+ + HCO3−.
3. H+ stimulates the chemosensitive neurons.
4. Breathing increases and blows off CO2.

Blood H+ itself crosses the barrier poorly, so changes in blood pH act much less on the central receptors than changes in CO2. CSF also has little protein to buffer H+, so CO2 changes give large pH changes there.

Adaptation

If CO2 stays high for a day or two, the kidneys raise bicarbonate and the CSF bicarbonate also rises. The CSF pH returns towards normal, and the drive to breathe from CO2 falls. This happens in chronic CO2 retention.

Peripheral chemoreceptors

Location:

• Carotid bodies: at the bifurcation of each common carotid artery. Afferents in the glossopharyngeal nerve (IX).
• Aortic bodies: along the arch of the aorta. Afferents in the vagus (X).

The carotid bodies are the more important. They have an extremely high blood flow for their size, so they sense arterial gases, not venous.

What they sense:

• Low PO2: the main stimulus. Response is small until PO2 falls below about 100 mmHg and becomes strong when it falls below about 60 mmHg.
• High PCO2 and high H+: a faster but smaller share of the total CO2 response.

The sensing cells are the glomus (type I) cells. Low O2 closes K+ channels in these cells, they depolarise, Ca2+ enters and they release transmitter onto the nerve endings.

Other receptors and reflexes

• Hering-Breuer inflation reflex: stretch receptors in the bronchial walls send signals through the vagus when the lungs inflate; this stops inspiration. In adults it switches on only at large tidal volumes (above about 1.5 L), protecting against over-inflation.
• Irritant receptors in the airway epithelium: trigger coughing, sneezing and bronchoconstriction.
• J (juxtacapillary) receptors in the alveolar walls: stimulated by fluid in the interstitium (pulmonary oedema), causing rapid, shallow breathing and breathlessness.
• Proprioceptors in joints and muscles: help raise breathing at the start of exercise.
• Higher centres: the cortex allows voluntary control (breath-holding, speaking); emotions and pain change breathing through the limbic system.

Breathing in exercise

Ventilation rises almost at once at the start of exercise, before blood gases change. This is due to signals from the motor cortex and from proprioceptors in moving limbs. Arterial PCO2, PO2 and pH stay nearly normal in moderate exercise.

Clinical relevance

Chronic CO2 retention (some COPD patients)

How it happens: long-standing high CO2 leads to renal and CSF compensation, so the central response to CO2 is blunted. These patients rely more on hypoxic drive from the peripheral chemoreceptors.

What you see: giving uncontrolled high-flow oxygen can raise PO2, reduce breathing and worsen V/Q matching, so CO2 rises further (CO2 narcosis). Oxygen is given in controlled amounts with a target saturation, typically around 88–92%, and blood gases are checked. Follow local guidance.

Cheyne-Stokes breathing

How it happens: in heart failure (slow circulation from lungs to brain) or brain damage, the feedback loop is delayed or over-sensitive.

What you see: breathing slowly increases in depth, then decreases to a pause (apnoea), in repeating cycles.

Opioid overdose

How it happens: opioids depress the respiratory centres and their response to CO2.

What you see: slow, shallow breathing, small pupils, drowsiness; reversed by naloxone.

Hyperventilation

How it happens: anxiety or a voluntary increase in breathing lowers PCO2.

What you see: respiratory alkalosis, tingling and muscle spasm (lower ionised calcium), light-headedness from cerebral vasoconstriction.

Quick revision

• Rhythm: dorsal respiratory group (medulla); pneumotaxic centre limits inspiration.
• Central chemoreceptors: ventral medulla; respond to CSF H+ from CO2; not to O2.
• Peripheral chemoreceptors: carotid (IX) and aortic (X) bodies; respond mainly to PO2 below about 60 mmHg.
• CO2 is the main minute-to-minute driver.
• Hering-Breuer: lung stretch stops inspiration (vagus).
• J receptors: pulmonary oedema, rapid shallow breathing.
• Controlled oxygen in chronic CO2 retainers.

Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).

FAQ