[box type=”download”] Understanding of the principles of control — Pontine — Pneumotaxic centre — Medullary receptor groups — Lung receptors — Voluntary control — Voluntary control being via cortical motor neurones in pyramidal tract [/box]
The brain stem and central pattern generator
The brain stem (pons and medulla) acts as the central pattern generator.
These neurons exhibit reciprocal inhibition, i.e. inspiration inhibits expiration and vice versa.
These dorsal and ventral respiratory groups in medulla receive input from the chemoreceptors and lung receptors and drive the respiratory muscle motor neurones (intercostals, phrenic [diaphragm], abdominal).
The medullary respiratory groups are connected with pneumotaxic centre in the pons, which is critical for normal breathing.
The pneumotaxic centre receives input from the hypothalamus and higher centres, coordinates medullary homeostatic functions with factors such as emotion and temperature, and affects the pattern of breathing.
Voluntary control is mediated by cortical motor neurones in the pyramidal tract bypassing brainstem neurons.
[box type=”download”] — Effects of rising CO2 upon ventilation rate. Influence of metabolic acidosis or alkalosis — Synergistic relationship between falls in PO2 and rises in PCO2 — Central chemoreceptors as the major determinants of CO2 response — Effect of blood PCO2 upon CSF acidity hence upon central chemoreceptors — Peripheral [carotid + aortic] chemoreceptors as minor determinants of response [/box]
Chemoreceptors detect arterial PCO2, PO2 and pH – PCO2 is the most important.
Alveolar PCO2 (PACO2) is normally ∼5.3 kPa (40 mmHg), and PAO2 normally 13 kPa (100 mmHg).
An increase in PACO2 causes ventilation to rise in an almost linear fashion.
Increased acidity of the blood (e.g. lactic acidosis in severe exercise) causes the relationship between PCO2 and ventilation to shift to the left, and decreased acidity causes a shift to the right.
Conversely, PO2 normally stimulates ventilation only when it falls below ∼8 kPa (∼60 mmHg).
However, when both factors act, (a fall in PO2 and a rise in PCO2) the resultant increase in ventilation is synergistic (more than additive).
The central chemoreceptors are located over the ventrolateral surface of the medulla, close to the exit of the cranial nerves IX and X.
It responds indirectly to blood PCO2, but does not respond to changes in PO2.
As a result, the pH of the CSF around the chemoreceptor is determined by the arterial PCO2 and CSF [HCO3−], according to the Henderson–Hasselbalch equation.
A rise in blood PCO2 therefore makes the CSF more acid.
The central chemoreceptor is responsible for ∼80% of the response to CO2 in humans.
Its response is delayed because CO2 has to diffuse across the blood–brain barrier.
As the blood–brain barrier is impermeable to H+, the central chemoreceptor is not affected by blood pH.
The peripheral chemoreceptors are located in the carotid and aortic bodies.
The carotid bodies are small distinct structures located at the bifurcation of the common carotid arteries, and are innervated by the carotid sinus nerve and thence the glossopharyngeal nerve.
The carotid body is formed from glomus (type I) and sheath (type II) cells.
Glomus cells are chemoreceptive, and contact carotid sinus nerve axons.
The aortic bodies are located on the aortic arch and are innervated by the vagus.
They are similar to carotid bodies.
Peripheral chemoreceptors respond to changes in PCO2, H+ and, importantly, PO2.
They are responsible for ∼20% of the response to increased PCO2.
[box type=”download”] Stretch receptors — Vagally-innervated bronchial wall receptors — Irritant receptors — Role in irritant cough and airway constriction J receptors — Role in generation of tachypnoea due to odema, emboli or inflammation[/box]
These are located in the bronchial walls.
Stimulation (by stretch) causes short, shallow breaths, and delay of the next inspiratory cycle.
They provide negative feedback to turn off inspiration.
They are innervated by the vagus.
They are largely responsible for the Hering–Breuer inspiratory reflex, in which lung inflation inhibits inspiration to prevent overinflation.
Juxtapulmonary (J) receptors.
These are located on the alveolar and bronchial walls close to the capillaries.
They cause depression of somatic and visceral activity by producing rapid shallow breathing or apnoea, a fall in heart rate and blood pressure, laryngeal constriction and relaxation of the skeletal muscles via spinal neurones.
They are stimulated by increased alveolar wall fluid, oedema, microembolisms and inflammation.
The afferent nerves are small unmyelinated (C-fibre) or myelinated nerves in the vagus.
These are located throughout the airways.
In the trachea they cause cough, and in the lower airways hyperpnoea (rapid breathing); stimulation also causes bronchial and laryngeal constriction.
They are also responsible for the deep augmented breaths every 5–20 min at rest, reversing the slow collapse of the lungs that occurs in quiet breathing.
They are stimulated by irritant gases, smoke and dust, rapid large inflations and deflations, airway deformation, pulmonary congestion and inflammation.
The afferent nerves are rapidly adapting myelinated fibres in the vagus.
Proprioceptors (position/length sensors).
These are located in the Golgi tendon organs, muscle spindles and joints.
They are important for matching increased load.
They are stimulated by shortening and load in the respiratory muscles (but not diaphragm).
Afferents run to the spinal cord via the dorsal roots.
It should be noted that input from non-respiratory muscles and joints can also stimulate breathing.