3.3 Control of Breathing, Hypoxia, Altitude and Hyperbaric Physiology

3.3 Control of Breathing, Hypoxia, Altitude and Hyperbaric Physiology

The Respiratory Control System

Breathing is controlled by a feedback loop with three parts:

SENSORS                       CONTROLLER                    EFFECTORS
Central chemoreceptors   -->  Medullary respiratory   -->  Diaphragm (phrenic C3-C5)
Peripheral chemoreceptors     centres (dorsal and          Intercostal muscles
Lung stretch / J receptors    ventral respiratory          Accessory muscles
Cortex (voluntary), pain      groups, pre-Botzinger        Upper airway dilators
                              complex); pons modulates

• The pre-Botzinger complex in the ventral medulla generates the basic respiratory rhythm.
• The dorsal respiratory group (nucleus tractus solitarius) integrates afferent input from the glossopharyngeal and vagus nerves.
• The pontine respiratory group fine-tunes the transition between inspiration and expiration.
• Cortical control allows voluntary breath-holding and hyperventilation, and is lost during sleep and anaesthesia, when chemical control dominates.

Central Chemoreceptors and the Carbon Dioxide Response

The central chemoreceptors lie near the ventral surface of the medulla. They respond to the hydrogen ion concentration of the surrounding cerebrospinal fluid (CSF). Carbon dioxide crosses the blood-brain barrier freely, but hydrogen and bicarbonate ions cross slowly, so CSF pH tracks arterial $P_a\text{CO}_2$ closely. Because CSF contains little protein, its buffering capacity is low, which makes it a sensitive detector.

• In awake adults, minute ventilation rises roughly linearly by about 2-3 L/min for each 1 mmHg (about 15-20 L/min per kPa) increase in $P_a\text{CO}_2$ above the resting value.
• The central chemoreceptors provide about 70-80% of the response to carbon dioxide.
• In chronic hypercapnia, CSF bicarbonate rises over days and resets the receptors, so the drive to breathe from carbon dioxide is reduced.

Effects of Drugs on the Carbon Dioxide Response

Peripheral Chemoreceptors and the Hypoxic Response

The carotid bodies at the carotid bifurcation, supplied by the glossopharyngeal nerve (carotid sinus nerve), are the most important peripheral chemoreceptors; the aortic bodies (vagus nerve) contribute mainly to circulatory reflexes. Carotid body type I (glomus) cells have an extremely high blood flow relative to their metabolism, so they sense arterial partial pressure of oxygen, not oxygen content. Anaemia and carbon monoxide poisoning therefore do not stimulate them strongly.

• The hypoxic ventilatory response is hyperbolic: ventilation changes little until $P_a\text{O}_2$ falls below about 8 kPa (60 mmHg), then rises steeply.
• The carotid bodies respond within seconds and also respond to acidaemia and hypercapnia, contributing about 20-30% of the carbon dioxide response.
• Volatile anaesthetics depress the acute hypoxic ventilatory response even at about 0.1 MAC, so residual anaesthetic in recovery can blunt the reaction to hypoxaemia.
• Bilateral carotid endarterectomy can abolish the hypoxic drive.

Types of Hypoxia

Remember oxygen delivery: $\dot{D}\text{O}_2 = CO \times C_a\text{O}_2$, where $C_a\text{O}_2 = (1.34 \times \text{Hb} \times S_a\text{O}_2) + (0.023 \times P_a\text{O}_2)$ with haemoglobin in g/dL and $P_a\text{O}_2$ in kPa.

High-Altitude Physiology

Barometric pressure falls roughly exponentially with altitude, halving at about 5,500 m. The fraction of oxygen remains 0.21, but the inspired partial pressure falls:

$P_I\text{O}_2 = 0.21 \times (P_B - 6.3\text{ kPa})$

At sea level ($P_B$ 101.3 kPa), $P_I\text{O}_2$ is about 19.9 kPa. On the summit of Everest ($P_B$ about 33.7 kPa) it is only about 5.8 kPa.

Acute and Chronic Responses

1. Hyperventilation from carotid body stimulation lowers $P_A\text{CO}_2$ and raises $P_A\text{O}_2$, but causes respiratory alkalosis that initially limits the response.
2. Renal compensation over 2-3 days excretes bicarbonate and lets ventilation rise further. Acetazolamide speeds this process.
3. Erythropoietin rises within hours; haemoglobin increases over weeks.
4. 2,3-Diphosphoglycerate increases, shifting the oxygen dissociation curve to the right, although the respiratory alkalosis shifts it to the left.
5. Hypoxic pulmonary vasoconstriction raises pulmonary artery pressure.

Altitude Illnesses

• Acute mountain sickness: headache, nausea and fatigue after ascent above about 2,500 m.
• High-altitude cerebral oedema: ataxia and confusion; requires descent, oxygen and dexamethasone.
• High-altitude pulmonary oedema: non-cardiogenic oedema from uneven hypoxic pulmonary vasoconstriction; treat with descent, oxygen and nifedipine.

Vaporizers at altitude: a variable-bypass vaporizer delivers an almost constant partial pressure of agent, so its clinical effect is largely unchanged, whereas the heated desflurane vaporizer delivers a constant volume percentage, so the partial pressure falls and the dial setting must be increased.

Hyperbaric Physiology

Pressure increases by about 1 atmosphere (101.3 kPa) for every 10 m of seawater. Under hyperbaric conditions:

• Boyle's law governs gas-filled spaces: volume halves at 2 atmospheres absolute (ATA), causing barotrauma to ears, sinuses and lungs during pressure changes.
• Dissolved oxygen rises with partial pressure (Henry's law). Breathing 100% oxygen at 3 ATA gives a $P_a\text{O}_2$ of about 250-280 kPa and about 6 mL/dL of dissolved oxygen, which is enough to meet resting tissue needs without haemoglobin.
• Nitrogen narcosis occurs when breathing air at depth, typically below about 30 m.
• Oxygen toxicity: central nervous system toxicity (seizures) at high partial pressures, and pulmonary toxicity with prolonged exposure.

Indications for Hyperbaric Oxygen

Anaesthetic implications in a chamber: untreated pneumothorax is an absolute contraindication (a chest drain must be placed); air in endotracheal tube cuffs and infusion devices contracts during compression, so cuffs are filled with saline; defibrillation and electrical equipment carry a fire risk in an oxygen-enriched atmosphere.