Chemical Regulation and Chemoreceptors
The primary stimulus for the respiratory center is carbon dioxide ($CO_2$). Fredericq's classic cross-circulation experiment in dogs proved that if one animal experiences asphyxia, the second develops hyperpnea due to changes in the gas composition of shared blood. The mechanism by which $CO_2$ acts on the brain is specific: hydrogen ions ($H^+$) cross the blood-brain barrier with difficulty, whereas carbon dioxide readily diffuses across it. In the brainstem interstitial fluid, $CO_2$ locally generates hydrogen ions, which serve as the actual trigger.
Chemoreceptors are specialized and divided into two groups:
- Central chemoreceptors: Located on the ventral surface of the medulla oblongata (medulla oblongata) at a depth of about 0.2 mm, as well as in the reticular formation. They respond primarily to changes in pH and $pCO_2$ in the cerebrospinal fluid (CSF).
- Peripheral chemoreceptors: Located in the aortic arch and the carotid sinus region (at the bifurcation of the common carotid artery). The carotid bodies are highly vascularized and innervated by the sinus nerve (a branch of the glossopharyngeal nerve — n. glossopharyngeus). These receptors respond primarily to a decrease in oxygen levels. When $pO_2$ falls below 60–70 mmHg, their firing rate increases sharply.
Airway and Pulmonary Receptors
Neurons of the respiratory center receive continuous afferent input from mechanoreceptors, which are categorized into three main types:
- Slowly adapting stretch receptors: Located in the smooth muscle of the trachea and bronchi; activated during inspiration.
- Irritant (rapidly adapting) receptors: Located in the airway epithelium; stimulated by rapid changes in lung volume or chemical irritants.
- Juxtacapillary (J) receptors: Located in the pulmonary interstitium near capillaries; activated by increased pulmonary capillary pressure or congestion.
Neuronal Organization and Phase Switching
The mechanism of respiratory phase switching relies on a complex interaction among four pools of brainstem neurons:
- Pool I ('early' inspiratory neurons): Receive signals from chemoreceptors, initiate inspiration, activate respiratory muscles, and excite Pool II.
- Pool II ('late' inspiratory neurons): Activated by Pool I, integrate afferent input from pulmonary mechanoreceptors, and transmit excitation to the third pool.
- Pool III: Exerts an inhibitory effect on Pool I, providing the mechanism for terminating inspiration.
- Pool IV (pneumotaxic center): Located in the pons (pons), receives signals from the cerebral cortex, and modulates the activity of all respiratory neurons.
Termination of Inspiration and Reflex Arc
As the lungs fill with air, alveolar stretch receptors are stimulated. Signals travel along afferent fibers of the vagus nerve (n. vagus). This forms the basis of the Hering–Breuer inflation reflex: lung expansion causes reflex inhibition of inspiration.
This process depends on firing frequency. When the firing rate in a single fiber reaches 80–100 impulses/s, it exerts a maximal inhibitory effect on inspiratory neurons. Inhibition develops, inspiration terminates, and passive expiration follows. During forced respiration, active expiration is recruited via expiratory neurons in the ventral respiratory group of the medulla.
Overall, the effector arm of this system includes the phrenic nerve (n. phrenicus), controlling the diaphragm (diaphragma), and intercostal nerves (nn. intercostales), innervating the intercostal muscles (mm. intercostales).