The organization of breathing is described by Whipp BJ in his study on the physiological mechanisms dissociating pulmonary CO2 and O2 exchange dynamics during exercise in humans. The chapter aims to equip students with the knowledge to answer various questions related to the central organization of breathing, the role of central and peripheral chemoreceptors in regulating respiration, the comparison between chemoreceptors and pulmonary mechanoreceptors in regulating respiration, ventilatory control during special circumstances like exercise and high altitude, and the effects of abnormalities in ventilatory control.

Breathing is an automatic process that people do without consciously thinking about it. However, they can voluntarily modify their breathing pattern and even hold their breath. The control of ventilation involves the generation and regulation of rhythmic breathing by the respiratory center located in the brainstem. This rhythm is influenced by input from higher brain centers and systemic receptors. The main goals of breathing are to minimize work from a mechanical perspective and to maintain and regulate positive pressures of arterial blood O2 (PaO2) and CO2 (PaCO2) from a physiological perspective. Additionally, breathing helps maintain acid-base balance in the brain by regulating PaCO2. Automatic respiration begins at birth, as the placenta is responsible for gas exchange in the fetus while in utero. Once born, the lung takes over this function, and oxygen and carbon dioxide are exchanged through passive diffusion across the maternal circulation.

There are four major sites involved in ventilatory control: the respiratory control center, central chemoreceptors, peripheral chemoreceptors, and pulmonary mechanoreceptors/sensory nerves. The respiratory control center, located in the medulla oblongata of the brainstem, consists of multiple nuclei responsible for generating and modifying the basic ventilatory rhythm. It includes a ventilatory pattern generator that sets the rhythmic pattern and an integrator that controls the generation of the pattern, processes input from higher brain centers and chemoreceptors, and regulates the rate and amplitude of the ventilatory pattern. The integrator receives input from various higher brain centers such as the cerebral cortex, hypothalamus, limbic system (including the amygdalae), and cerebellum.

Central chemoreceptors, located just below the ventrolateral surface of the medulla in the central nervous system, detect changes in the interstitial fluid's PaCO2 and pH within the brainstem. These chemoreceptors play a role in modulating ventilation. On the other hand, peripheral chemoreceptors are found in specialized cells in the aortic arch (aortic bodies) and at the bifurcation of the internal and external carotid arteries (carotid bodies) in the neck. They are responsible for sensing the arterial blood's PaO2, PaCO2, and pH. The information gathered by the peripheral chemoreceptors is then relayed back to the integrator nuclei in the medulla through the vagus nerves and carotid sinus nerves, which are branches of the glossopharyngeal nerves. Pulmonary mechanoreceptors and sensory nerve stimulation respond to lung inflation, irritation, or the release of local mediators in the airways. They also contribute to modifying the ventilatory pattern.

The respiratory control center's collective output to the motor neurons located in the anterior horn of the spinal column controls the muscles involved in respiration. This output determines the automatic rhythmic pattern of respiration. Specifically, the diaphragm's activity is controlled by motor neurons in the cervical region of the spinal column through the phrenic nerves. The intercostal muscles and accessory muscles of respiration are controlled by motor neurons in the thoracic region of the spine.
Whipp BJ. Physiological mechanisms dissociating pulmonary CO2 and O2 exchange dynamics during exercise in humans. Exp Physiol. 2007;92:347-355.
Upon completion of this chapter, the student should be able to answer the following questions: 1.
Describe the central organization of breathing.
2.
Explain the role of central and peripheral chemoreceptors in regulating respiration.
3.
Compare and contrast the roles of chemoreceptors and pulmonary mechanoreceptors in regulating respiration.
4.
Describe ventilatory control during special circumstances (e.g., exercise and high altitude).
5.
Describe the effects of abnormalities in ventilatory control.
eople breathe without thinking, and they can willingly modify their breathing pattern and even hold their breath. Control of ventilation includes the generation and regulation of rhythmic breathing by the respiratory center in the brainstem and its modification by the input of information from higher brain centers and from systemic receptors. The goals of breathing are, from a mechanical perspective, to minimize work and, from a physiological perspective, to maintain and regulate positive pressures of arterial blood O2 (PaO2) and CO2 (PaCO2). Another goal of breathing is to maintain acid-base balance in the brain by regulating PaCO2. Automatic respiration begins at birth. In utero, the placenta, not the lung, is the organ of gas exchange in the fetus. Its microvilli interdigitate with the maternal uterine circulation, and PaO2 transport and PaCO2 removal from the fetus occur by passive diffusion across the maternal circulation.
Ventilatory Control: An Overview
There are four major sites of ventilatory control: (1) the respiratory control center, (2) central chemoreceptors, (3) peripheral chemoreceptors, and (4) pulmonary mechanoreceptors/sensory nerves. The respiratory control center is located in the medulla oblongata of the brainstem and is composed of multiple nuclei that generate and modify the basic ventilatory rhythm. This center consists of two main parts: (1) a ventilatory pattern generator, which sets the rhythmic pattern, and (2) an integrator, which controls generation of the pattern, processes input from higher brain centers and chemoreceptors, and controls the rate and amplitude of the ventilatory pattern. Input to the integrator arises from higher brain centers, including the cerebral cortex, hypothalamus, limbic system including the amygdalae, and cerebellum.
Central chemoreceptors are located in the central nervous system just below the ventrolateral surface of the medulla. These central chemoreceptors detect changes in the PaCO2 and pH of interstitial fluid in the brainstem, and they modulate ventilation. Peripheral chemoreceptors are located on specialized cells in the aortic arch (aortic bodies) and at the bifurcation of the internal and external carotid arteries (carotid bodies) in the neck. These peripheral chemoreceptors sense the PaO2, PaCO2, and pH of arterial blood, and they feed information back to the integrator nuclei in the medulla through the vagus nerves and carotid sinus nerves, which are branches of the glossopharyngeal nerves. Pulmonary mechanoreceptors and sensory nerve stimulation, in response to lung inflation or to stimulation by irritants or release of local mediators in the airways, modify the ventilatory pattern.
The collective output of the respiratory control center to motor neurons located in the anterior horn of the spinal column controls the muscles of respiration, and this output determines the automatic rhythmic pattern of respiration. Motor neurons located in the cervical region of the spinal column control the activity of the diaphragm through the phrenic nerves, whereas other motor neurons located in the thoracic region of the spine control the intercostal muscles and the accessory muscles of respiration.