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Human Physiology · Respiratory system

Control of Breathing

You breathe about 20,000 times a day without thinking, yet you can hold your breath, speak and sing at will. This page explains how the brainstem sets the rhythm, how chemical and reflex signals adjust it, what breathlessness really is, and how breathing retraining and oxygen fit in.

12Sections
5Figures
4Tables
10Questions

Part 4 · Respiratory System · Chapter 19 of 47

Learning objectives

By the end of this page you should be able to:

  • Describe the brainstem centres that generate breathing.
  • Explain the roles of central and peripheral chemoreceptors.
  • Describe ventilatory responses to carbon dioxide and oxygen.
  • List reflex and voluntary influences on breathing, including in exercise.
  • Explain the mechanisms and assessment of breathlessness.
  • Apply this to oxygen therapy in COPD and to breathing retraining.

Why it matters

Breathlessness is the symptom that brings most respiratory patients to physiotherapy. Many of our treatments, such as breathing control, pacing and positioning, act on how breathing is controlled and how breathlessness is perceived.

Understanding control also explains why opioids and sedation can be dangerous, why oxygen must be titrated in some patients, and why some people breathe too much rather than too little.

The respiratory centres

Figure 1 · Who controls breathing

Inputs to and outputs from the brainstem respiratory centres Four input boxes on the left: the cortex, central chemoreceptors sensing carbon dioxide, peripheral chemoreceptors sensing low oxygen, and lung and muscle receptors. They all feed the brainstem centres, which send output through the phrenic, intercostal and accessory nerves to the breathing muscles. Brainstem centrespons and medulla: set rhythmCortexvoluntary control, speechCentral chemoreceptorsmedulla: CO2 / acidPeripheral chemoreceptorscarotid, aortic: low O2Lung and muscle receptorsstretch, irritants, movementPhrenic nervesC3–C5 → diaphragmIntercostal nervesthoracic → rib musclesAccessory and abdominalforced breathing, cough
Automatic, but overridable. The brainstem keeps breathing going in sleep; the cortex can override it for speech, breath-holding and breathing exercises.

Groups of neurons in the medulla generate the basic rhythm. A small region called the preBötzinger complex acts as the main pacemaker for inspiration. Centres in the pons smooth the transition between inspiration and expiration.

Output travels down the spinal cord to the phrenic nerves (C3–C5) and the intercostal nerves. Damage high in the cervical cord therefore stops spontaneous breathing.

Chemical control

ReceptorLocationSensesSpeed and strength
Central chemoreceptorsSurface of the medullapH of cerebrospinal fluid, driven by arterial CO2Slower; about two thirds of the CO2 response
Peripheral chemoreceptorsCarotid bodies (and aortic bodies)Low PO2, high CO2, acidFast; the only receptors for low oxygen

Carbon dioxide crosses the blood–brain barrier easily and forms acid in the cerebrospinal fluid. The central chemoreceptors respond, and breathing increases. This is the main moment-to-moment control of breathing.

Figure 2 · Breathing responds strongly to carbon dioxide

Ventilation plotted against arterial carbon dioxide under different conditions Three straight lines of ventilation against arterial carbon dioxide. The normal line rises steeply above about 40 millimetres of mercury. With low oxygen the line is steeper. During sleep, with opioids or in chronic carbon dioxide retention it is flatter. NormalWith low oxygen: steeperSleep, opioids, chronic CO2 retention: flatter3540455055600306090Arterial PCO2 (mmHg)Ventilation (L/min)
CO2 is the main moment-to-moment driver. A rise of a few mmHg can double ventilation. Drugs and sleep blunt the response. Schematic slopes.

The response to oxygen is quite different. Ventilation hardly changes until arterial PO2 falls to about 60 mmHg, then rises steeply. This matches the dissociation curve: above 60 mmHg, saturation stays high anyway.

Figure 3 · Breathing responds weakly to oxygen until it is low

Ventilation plotted against arterial oxygen A curve that is almost flat from 120 down to about 60 millimetres of mercury of arterial oxygen, then rises steeply as oxygen falls further. little response above about 60 mmHgsteep rise whenPO2 falls further3045607590105120Arterial PO2 (mmHg), carbon dioxide held constantVentilation (L/min)
A safety net, not the main driver. The peripheral chemoreceptors raise breathing sharply only once arterial PO2 falls to around 60 mmHg, where saturation starts to drop quickly. Schematic.

In people with long-standing carbon dioxide retention, the kidneys retain bicarbonate and the cerebrospinal fluid adapts. The central response to CO2 becomes blunted, and low oxygen becomes a relatively larger part of the drive.

Reflex and voluntary influences

InputStimulusEffect
Lung stretch receptors (Hering–Breuer)Large lung inflationShortens inspiration; important in infants and during large breaths
Irritant receptorsDust, smoke, cold airCough, bronchoconstriction, rapid breathing
J receptorsLung congestion, oedemaRapid shallow breathing and breathlessness
Muscle and joint receptorsLimb movementIncrease breathing at the start of exercise
CortexWill, speech, emotion, anxietyOverride automatic rhythm; breath-holding, breathing exercises
SleepLoss of wakefulness driveLower ventilation and CO2 response

Breathing in exercise

Ventilation rises abruptly at the very start of exercise, before blood gases change. This comes from central command and from limb receptors. A slower rise follows, matched to carbon dioxide production.

In moderate exercise, arterial PO2 and PCO2 stay nearly normal. In heavy exercise, lactic acid drives extra ventilation and PCO2 falls.

Breathlessness

Breathlessness (dyspnoea) is a subjective experience of breathing discomfort. The American Thoracic Society statement describes several distinct sensations: air hunger, a sense of increased work or effort, and chest tightness [1].

Brain imaging links breathlessness to cortico-limbic areas also involved in pain and in sensing the body’s internal state [1]. Opioids, both natural and drug, can modify the perception [1].

Sensation [1]Likely mechanismTypical setting
Air hungerDrive to breathe exceeds what ventilation achievesCOPD on exertion, high CO2
Work or effortIncreased muscle load or weaknessNeuromuscular disease, stiff lungs
Chest tightnessAirway receptor stimulationAsthma, bronchoconstriction

Because breathlessness is a perception, emotion, attention and expectation alter it. That is part of why breathing control, relaxation, positioning, a hand-held fan and exercise training reduce it even when lung function does not change. Measurement tools vary in quality, so choose a validated scale [1].

Practical skill · measuring breathlessness

Use the modified Borg scale or a numerical rating during exercise, and a scale such as the MRC dyspnoea scale for usual activity limitation. Record the sensation in the patient’s own words; the quality matters as well as the intensity [1].

Oxygen and carbon dioxide in COPD

Figure 4 · Why too much oxygen can raise carbon dioxide

Mechanisms of oxygen-induced hypercapnia in COPD Excess oxygen in COPD leads to rising arterial carbon dioxide through three routes: worse ventilation-perfusion matching, the Haldane effect, and a smaller reduction in breathing drive. High-flow oxygen in COPDwithout a targetWorse V/Q matchingoxygen releases constriction inpoorly ventilated areasHaldane effectoxygenated haemoglobinholds less CO2Reduced drivea smaller part thantraditionally taughtRising arterial CO2drowsiness, acidosis
Not simply ‘loss of hypoxic drive’. Mismatch and the Haldane effect explain much of the rise; the answer is titrated oxygen, not withholding it [2].

Students are often taught that oxygen is dangerous in COPD because it removes the ‘hypoxic drive’. Abdo and Heunks argue that this fear is not supported by evidence and leads to under-treatment of low oxygen [2].

Worsening ventilation–perfusion matching and the Haldane effect explain much of the rise in carbon dioxide. The safe approach is titrated oxygen to a target range, not withholding it [2].

Breathing too much: dysfunctional breathing

Some people breathe more than their metabolism needs, often with fast upper-chest breathing and frequent sighs. Arterial CO2 falls, and symptoms include light-headedness, tingling, chest tightness and air hunger. This pattern is common alongside asthma and anxiety.

Figure 5 · Breathing exercises in asthma

Pooled effects of breathing exercises in adults with asthma Four results. Quality of life improved by 0.42 points at three months. Hyperventilation symptoms fell by 3.22 points. FEV1 per cent predicted rose by 6.88 per cent. Effects on asthma control were inconclusive. Asthma quality of life (3 months)+0.42 pointsHyperventilation symptoms (Nijmegen)−3.22 pointsFEV1 % predicted+6.88%Asthma control (ACQ)inconclusiveBreathing exercises versus inactive control; 22 trials, 2,880 adults [3]
Retraining the breathing pattern helps how people feel. Evidence certainty ranged from moderate to very low [3].

Santino and colleagues reviewed 22 trials of breathing exercises in adults with asthma, including yoga, Buteyko and Papworth methods [3]. Breathing exercises improved quality of life and reduced hyperventilation symptoms. Effects on asthma control were inconclusive, and certainty ranged from moderate to very low [3].

Clinical relevance for the physiotherapist

  • Breathlessness management. Combine positioning, breathing control, pacing and exercise; measure with validated scales [1].
  • COPD exacerbations. Do not withhold oxygen; follow the prescribed target and watch for drowsiness [2].
  • Asthma and dysfunctional breathing. Breathing retraining improves quality of life and symptoms [3].
  • Post-operative patients on opioids. Blunted CO2 response; monitor rate, depth and alertness.
  • Spinal cord injury. Injuries at or above C3–C5 affect phrenic output and spontaneous breathing.

Assessment and application

ObservationPossible control problemResponse
Slow, shallow breathing and drowsiness after opioidsDepressed central driveUrgent medical review
Fast upper-chest breathing, sighing, tingling, normal oxygenDysfunctional breathingBreathing retraining [3]
Breathlessness out of proportion to testsPerception amplified by fear or attention [1]Education, breathing control, graded exercise
Drowsy COPD patient on high-flow oxygenRising CO2 [2]Inform team; check target and blood gas

Common mistakes

  • Thinking oxygen is the main everyday driver of breathing; it is carbon dioxide.
  • Equating breathlessness with low saturation [1].
  • Withholding oxygen from hypoxaemic COPD patients for fear of hypoxic drive [2].
  • Dismissing breathing retraining as relaxation only [3].
  • Ignoring the effect of sedatives and sleep on breathing.

Exam preparation

Long answer

Describe the chemical regulation of respiration.

  • Respiratory centres (Figure 1).
  • Central and peripheral chemoreceptors (table).
  • CO2 response and its modifiers (Figure 2).
  • O2 response (Figure 3).
  • Clinical: chronic CO2 retention and oxygen therapy [2].

Short notes

  • Hering–Breuer reflex.
  • Peripheral chemoreceptors.
  • Dyspnoea [1].
  • Breathing exercises in asthma [3].

Viva and practical

  • “What drives breathing at rest?” — mainly arterial CO2 via central chemoreceptors.
  • “Is oxygen dangerous in COPD?” — titrate it; do not withhold it [2].
  • “What is air hunger?” — one distinct quality of breathlessness [1].
  • OSCE: teach breathing control to a breathless patient.

Current evidence

Exam and traditional teaching

Oxygen in COPD abolishes hypoxic drive; breathlessness is a single sensation reflecting lung damage.

What the evidence adds

Breathlessness has distinct qualities processed in cortico-limbic brain areas [1].

Oxygen-induced hypercapnia is mainly due to V/Q and Haldane effects; titrate rather than withhold [2]. Breathing exercises help quality of life in asthma [3].

What the student should understand

Breathing is controlled chemically, reflexly and voluntarily, and breathlessness is perceived in the brain. Physiotherapy works on all three.

Check yourself

10 questions on this page. Tap one to see the answer and the reasoning.

Q1. Brain imaging shows that the sensation of breathlessness activates:
  1. (A) Only the spinal cord
  2. (B) Cortico-limbic areas also involved in pain and body awareness
  3. (C) Only the cerebellum
  4. (D) No brain areas

Answer: (B) Dyspnoea stimuli activate cortico-limbic areas involved with interoception and nociception [1].

Q2. Breathlessness is best described as:
  1. (A) A single sensation
  2. (B) Several distinct sensations such as air hunger, effort and chest tightness
  3. (C) A sign, not a symptom
  4. (D) Always the same as low oxygen

Answer: (B) Mechanistically distinct breathing sensations have been identified [1].

Q3. Which may modulate the perception of breathlessness?
  1. (A) Endogenous and exogenous opioids
  2. (B) Vitamin C
  3. (C) Calcium
  4. (D) Iron

Answer: (A) Opioids may modulate perception of dyspnoea [1].

Q4. The traditional explanation that oxygen causes hypercapnia in COPD only through loss of ‘hypoxic drive’ is:
  1. (A) Fully correct
  2. (B) An oversimplification; V/Q mismatch and the Haldane effect also contribute
  3. (C) Never discussed
  4. (D) Proven wrong in every patient

Answer: (B) The fear of oxygen based on hypoxic drive is not supported by evidence; other mechanisms matter [2].

Q5. The recommended approach to oxygen in an acute COPD exacerbation is:
  1. (A) Withhold oxygen
  2. (B) Titrated oxygen to a target
  3. (C) Maximum flow always
  4. (D) Oxygen only at night

Answer: (B) Titrated oxygen management is recommended [2].

Q6. In adults with asthma, breathing exercises compared with inactive control improved quality of life at three months by about:
  1. (A) 0.04 points
  2. (B) 0.42 points
  3. (C) 4.2 points
  4. (D) No change

Answer: (B) AQLQ improved by a mean of 0.42 [3].

Q7. Breathing exercises in asthma reduced hyperventilation symptoms measured by the:
  1. (A) Borg scale
  2. (B) Nijmegen Questionnaire
  3. (C) MRC scale
  4. (D) Barthel Index

Answer: (B) Nijmegen scores fell by about 3.22 points [3].

Q8. Which breathing exercise type was most common in the asthma trials?
  1. (A) Buteyko only
  2. (B) Yoga
  3. (C) Papworth only
  4. (D) Incentive spirometry

Answer: (B) Fourteen of 22 studies used yoga-based breathing [3].

Q9. Effects of breathing exercises on asthma control (ACQ) were:
  1. (A) Strongly positive
  2. (B) Inconclusive
  3. (C) Harmful
  4. (D) Not measured

Answer: (B) ACQ results were inconclusive [3].

Q10. Which instrument issue did the ATS dyspnoea statement highlight?
  1. (A) Measures are all perfect
  2. (B) Many breathlessness instruments are poorly characterised
  3. (C) Breathlessness cannot be measured
  4. (D) Only oxygen saturation should be used

Answer: (B) The statement proposed a framework because instruments are often poorly characterised [1].

Quick review

Key takeaways

  • Medulla generates rhythm; phrenic C3–C5 drives the diaphragm.
  • CO2 is the main driver via central chemoreceptors.
  • Oxygen drive rises only below about 60 mmHg, via carotid bodies.
  • Breathlessness has distinct qualities and is processed in the brain [1].
  • In COPD, titrate oxygen; hypercapnia is not just loss of drive [2].
  • Breathing exercises improve quality of life in asthma [3].

Further reading

SourceWhy it earns its place
Parshall MB et al. — Am J Respir Crit Care Med, 2012The authoritative statement on breathlessness [1]
Abdo WF, Heunks LMA — Critical Care, 2012Oxygen and CO2 in COPD [2]
Santino TA et al. — Cochrane Review, 2020Breathing exercises in asthma [3]
West JB — Respiratory Physiology: The EssentialsControl of ventilation

References

  1. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. American Journal of Respiratory and Critical Care Medicine. 2012;185(4):435–452. doi:10.1164/rccm.201111-2042ST PMID 22336677 Official statement
  2. Abdo WF, Heunks LMA. Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care. 2012;16(5):323. doi:10.1186/cc11475 PMID 23106947 Review
  3. Santino TA, Chaves GSS, Freitas DA, Fregonezi GAF, Mendonça KMPP. Breathing exercises for adults with asthma. Cochrane Database of Systematic Reviews. 2020;3(3):CD001277. doi:10.1002/14651858.CD001277.pub4 PMID 32212422 Cochrane review

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Reviewed by the Physiotherapist India Team. · Human Physiology contents