Control of breathing

The control system

• Respiratory centres are in the brainstem. The medulla generates the basic rhythm: the dorsal respiratory group drives inspiration, the ventral group is used in active (forced) expiration, and the pre-Bötzinger complex is the rhythm generator. The pons modifies rate and depth: the pneumotaxic centre (upper pons) switches off inspiration earlier and raises the rate; the apneustic centre (lower pons) prolongs inspiration.
• Cortex: voluntary control (breath holding, speech, singing) can override the brainstem until the CO₂ drive wins (breaking point).
• Lung receptors (vagal afferents): slowly adapting stretch receptors in airway smooth muscle end inspiration when the lung is inflated (Hering–Breuer inflation reflex), weak in adults at quiet breathing but important in infants; irritant receptors cause cough, bronchoconstriction and hyperpnoea; J (juxtacapillary) receptors respond to pulmonary congestion and oedema, giving rapid shallow breathing and breathlessness.

Chemoreceptors

• Central chemoreceptors do not respond to hypoxia, and barely to arterial H⁺ (which crosses the blood–brain barrier poorly). CO₂ crosses easily, is hydrated by carbonic anhydrase and lowers CSF pH. CSF has little protein buffer, so small CO₂ changes give large pH changes.
• The carotid body (glomus type I cells) has a huge blood flow for its size and senses the partial pressure of dissolved O₂, not oxygen content. It is therefore not stimulated in anaemia, CO poisoning or methaemoglobinaemia, where PaO₂ is normal. Low O₂ closes K⁺ channels in glomus cells, depolarising them; Ca²⁺ entry releases transmitter onto sinus nerve endings.

Types of hypoxia

In every type, cell injury starts when ATP falls: the Na⁺/K⁺-ATPase fails, Na⁺ and water enter and the cell swells, the earliest reversible change. Tissue hypoxia is the common end-point of all forms of shock.

Cyanosis

Cyanosis appears when deoxygenated haemoglobin in capillary blood reaches about 5 g/dL (50 g/L); the absolute amount matters, not the percentage.

• A severely anaemic patient (Hb 6 g/dL) with SaO₂ 78% has under 2 g/dL deoxyhaemoglobin, so no cyanosis; judge oxygenation by oximetry or gas, not colour. Polycythaemia produces cyanosis easily.
• Central cyanosis (tongue, lips): low arterial saturation, from lung disease or right-to-left shunt (including Eisenmenger reversal once pulmonary hypertension develops).
• Peripheral cyanosis (fingers, toes): slow flow with high O₂ extraction and normal arterial saturation (cold, low cardiac output, Raynaud, or polycythaemia from prolonged altitude, as in a soldier returning from the Siachen glacier with headache and blue fingers).
• Methaemoglobinaemia (ferric iron) gives slate-grey cyanosis with normal PaO₂, chocolate-brown blood and an unreliable pulse oximeter; the local anaesthetics prilocaine and benzocaine can cause it. Treat with methylene blue.

Chronic CO₂ retention and oxygen therapy

• In long-standing hypercapnia (some severe COPD), the kidneys retain bicarbonate and CSF bicarbonate rises, restoring CSF pH, so the central response to CO₂ is blunted and the carotid body response to hypoxia matters more.
• High-flow oxygen (for example 15 L/min by reservoir mask) raises PaCO₂ in these patients mainly because it abolishes hypoxic pulmonary vasoconstriction, sending blood to poorly ventilated alveoli and worsening V/Q matching; the Haldane effect (oxygenated Hb releases CO₂) adds to it. Loss of hypoxic drive is a minor part, so the breathing rate may barely fall.
• Give controlled oxygen to a target SpO₂ of 88–92%. A Venturi mask delivers a fixed, known FiO₂ (24% or 28%) whatever the patient's breathing pattern, unlike a simple face mask or nasal cannula. Never withhold oxygen from a hypoxic patient.
• In acute asthma, the patient normally hyperventilates and PaCO₂ is low. A "normal" or rising PaCO₂ (above about 4.6 kPa, 35 mmHg) with a quiet chest means exhaustion and failing ventilation: life-threatening. A blood gas of pH 7.23 with a normal bicarbonate (26 mmol/L) is acute respiratory acidosis with no time for renal compensation.
• Oxygen toxicity: prolonged high FiO₂ causes free-radical lung injury, absorption atelectasis (nitrogen washed out of poorly ventilated alveoli) and, in premature infants, retinopathy of prematurity.

High altitude

• Inspired PO₂ = FiO₂ × (barometric pressure − 47 mmHg). At one-third of an atmosphere (about 253 mmHg), inspired PO₂ is only about 43 mmHg, too low for useful saturation without supplementary oxygen.
• Acetazolamide inhibits carbonic anhydrase, causing a bicarbonate diuresis and mild metabolic acidosis, speeding acclimatisation and preventing acute mountain sickness. High-altitude pulmonary oedema: descent, oxygen, nifedipine. High-altitude cerebral oedema: descent, oxygen, dexamethasone.

Diving

Abnormal breathing patterns

• Cheyne–Stokes: breathing waxes and wanes with central apnoeas (no effort). In heart failure the slow circulation delays the CO₂ signal reaching the chemoreceptors, so the controller overshoots and undershoots; it also occurs with brain damage, at altitude during sleep and with opioids.
• Kussmaul: deep, regular, sighing breaths with no pauses in metabolic acidosis (diabetic ketoacidosis), driven by peripheral chemoreceptors.
• Apneustic breathing (pontine lesion) and ataxic breathing (medullary lesion).
• Obstructive sleep apnoea: the pharynx collapses during sleep despite continued effort; snoring, witnessed apnoeas and daytime sleepiness. First-line treatment for severe disease is nightly CPAP; sleepy drivers must stop driving until treated.
• An open (sucking) chest wound equalises pleural and atmospheric pressure so the lung collapses; cover with a three-sided occlusive dressing, then insert a chest drain away from the wound.

Remember CO₂ works through CSF H⁺ on the medulla; only the carotid bodies feel a low PaO₂, and they feel pressure, not content.

Exam trap Central chemoreceptors sense CSF H⁺ from CO₂, not hypoxia; carotid bodies are not stimulated in anaemia or CO poisoning.

Exam trap The first response to altitude is respiratory alkalosis; ventilation keeps rising over days as the kidney removes bicarbonate.

How FCPS asks about this

• What central chemoreceptors respond to: H⁺ in CSF produced from arterial CO₂.
• Receptors that sense hypoxia: carotid bodies (nerve IX) and aortic bodies; they detect PaO₂, so anaemic hypoxia does not raise ventilation.
• Acclimatisation at altitude: hyperventilation and respiratory alkalosis, renal HCO₃⁻ loss, rising 2,3-BPG and EPO; acetazolamide speeds it.
• Diver with joint pain and dyspnoea after rapid ascent: nitrogen bubbles (decompression sickness); confusion at depth is nitrogen narcosis.
• No cyanosis despite SaO₂ 78% with Hb 6 g/dL: under 5 g/dL deoxyhaemoglobin.
• COPD PaCO₂ rising on high-flow oxygen: loss of hypoxic pulmonary vasoconstriction worsens V/Q; use a Venturi mask, target 88–92%.
• Cheyne–Stokes in heart failure: delayed chemoreceptor feedback from slow circulation.