The peripheral chemoreceptors enhance the responsiveness to low levels of oxygen due to the separate mechanisms involved in sensing arterial oxygen (PaO2) and arterial carbon dioxide (PaCO2) levels. When both hypercapnia (elevated CO2) and hypoxemia (low O2) are present, they have an additive effect on the output of the chemoreceptors and the resulting stimulation of ventilation, often referred to as asphyxia.

The medulla, specifically the dorsal respiratory group (DRG) and ventral respiratory group (VRG), plays a crucial role in generating the rhythmic pattern of breathing. Experimental transection of the brain between the medulla and the pons confirms that periodic breathing is maintained, indicating that the medulla is responsible for the inherent rhythmicity. While there isn't a single pacemaker for breathing identified in the medulla, two distinct nuclei within it contribute to the generation of the respiratory pattern.

The first nucleus is the dorsal respiratory group (DRG), composed of cells in the nucleus tractus solitarius, located in the dorsomedial region of the medulla. These cells receive afferent input from cranial nerves IX and X, originating from the airways and lungs, serving as the initial intracranial processing station for this input.

The second group of medullary cells is the ventral respiratory group (VRG), situated in the ventrolateral region of the medulla. The VRG consists of three cell groups: the rostral nucleus retrofacialis, the caudal nucleus retroambiguus, and the nucleus para-ambiguus. Both inspiratory and expiratory neurons are present in the VRG. The nucleus retrofacialis and the caudally located cells of the nucleus retroambiguus are active during exhalation, while the rostrally located cells of the nucleus retroambiguus are active during inspiration. The nucleus para-ambiguus contains inspiratory and expiratory neurons that travel in the vagus nerve to the laryngeal and pharyngeal muscles.

Overall, the medulla, located in the most primitive portion of the brain, serves as the respiratory control center. The dorsal respiratory group (DRG) in the nucleus tractus solitarius and the ventral respiratory group (VRG) consisting of the rostral nucleus retrofacialis, caudal nucleus retroambiguus, and nucleus para-ambiguus are the main areas where the respiratory control neurons are found.
Fig. 25.2, B ). The responsiveness to low O2 is enhanced because different mechanisms are responsible for sensing PaO2 and PaCO2 in the peripheral chemoreceptors. Thus the presence of both hypercapnia-elevated CO2 and hypoxemia-low O2 (often called asphyxia when both changes are present) has an additive effect on chemoreceptor output and on the resulting ventilatory stimulation.
Control of Ventilation: The Details
The Respiratory Control Center
When the brain is transected experimentally between the medulla and the pons, periodic breathing is maintained, thus demonstrating that the inherent rhythmicity of breathing originates in the medulla. Although no single group of neurons in the medulla has been found to be the breathing “pacemaker,” two distinct nuclei within the medulla are involved in generation of the respiratory pattern (
Fig. 25.3 ). One nucleus is the dorsal respiratory group (DRG), which is composed of cells in the nucleus tractus solitarius and is located in the dorsomedial region of the medulla. Cells in the DRG receive afferent input from cranial nerves IX •Fig. 25.2 The Effects of Hypoxia and Hypercapnia on Ventilation as the Other Respiratory Gas Partial Pressures Are Varied. A, Atagivenpartialpressureofarterialcarbondioxide(PaCO2),ventilationincreasesmoreandmoreaspartialpressureofarterialoxygen(PaO2)decreases.WhenPaCO2isallowedtodecrease(thenormalcondition)duringhypoxia,thereislittlestimulationofbreathinguntilPaO2fallsbelow60mmHg.Thehypoxicresponseismediatedthroughthecarotidbodychemoreceptors.B, ThesensitivityoftheventilatoryresponsetoCO2isenhancedbyhypoxia.
and X, which originate from airways and the lungs and constitute the initial intracranial processing station for this afferent input. The second group of medullary cells is the ventral respiratory group (VRG), located in the ventrolateral region of the medulla. The VRG is composed of three cell groups: the rostral nucleus retrofacialis, the caudal nucleus retroambiguus, and the nucleus para-ambiguus. The VRG contains both inspiratory and expiratory neurons. The nucleus retrofacialis and the caudally located cells of the nucleus retroambiguus are active during exhalation, whereas the rostrally located cells of the nucleus retroambiguus are active during inspiration. The nucleus para-ambiguus has inspiratory and expiratory neurons that travel in the vagus nerve to the laryngeal and pharyngeal muscles. Discharges •Fig. 25.3 The Respiratory Control Center is Located in the Medulla, the Most Primitive Portion of the Brain. Theneuronsaremainlyintwoareas:thedorsalrespiratorygroup(DRG),whichconsistsofthenucleustractussolitarius,andtheventralrespiratorygroup(VRG),whichconsistsoftherostralnucleusretrofacialis,nucleusparaambiguus,andthecaudalnucleusretroambiguus.C1referstothefirstcervicalsignalsegmenttothecaudalborderofthepons.Thefourthventricleofthebrainislocatedbelowthecerebellumandabove,andbetween,theponsandthemedulla.