The nervous system normally adjusts the rate of alveolar ventilation almost exactly to the demands of the body so that the oxygen partial pressure (pO₂) and carbon dioxide partial pressure (pCO₂) in the arterial blood are hardly altered, even during heavy exercise and most other types of respiratory stress.
The respiratory center is composed of several groups of neurons located bilaterally in the medulla oblongata and pons of the brain stem. It is divided into three major collections of neurons:
- A dorsal respiratory group, located in the dorsal portion of the medulla, which mainly causes inspiration
- A ventral respiratory group, located in the ventro-lateral part of the medulla, which mainly causes expiration
- The pneumotaxic center, located dorsally in the superior portion of the pons, which mainly controls rate and depth of breathing
Dorsal Respiratory Group
The dorsal respiratory group of neurons plays a fundamental role in the control of respiration and extends most of the length of the medulla. Most of its neurons are located within the nucleus of the tractus solitarius (NTS), although additional neurons in the adjacent reticular substance of the medulla also play important roles in respiratory control.
The NTS is the sensory termination of both the vagal and the glosso-pharyngeal nerves, which transmit sensory signals into the respiratory center from:
- Peripheral chemoreceptors
- Baroreceptors, and
- Several types of receptors in the lungs
Rhythmical Inspiratory discharges from the Dorsal Respiratory Group
The basic rhythm of respiration is generated mainly in the dorsal respiratory group of neurons. Even when all the peripheral nerves entering the medulla have been sectioned and the brain stem has been transected both above and below the medulla, this group of neurons still emits repetitive bursts of inspiratory neuronal action potentials.
The basic cause of these repetitive discharges is unknown. In primitive animals, neural networks have been found in which activity of one set of neurons excites a second set, which in turn inhibits the first. Then, after a period, the mechanism repeats itself, continuing throughout the life of the animal.
Inspiratory ‘Ramp’ Signal
The nervous signal that is transmitted to the inspiratory muscles, mainly the diaphragm, is not an instantaneous burst of action potentials. Instead, it begins weakly and increases steadily in a ramp manner for about 2 seconds in normal respiration.
It then ceases abruptly for approximately the next 3 seconds, which turns off the excitation of the diaphragm and allows elastic recoil of the lungs and the chest wall to cause expiration.
Next, the inspiratory signal begins again for another cycle; this cycle repeats again and again, with expiration occurring in between. Thus, the inspiratory signal is a ramp signal. The obvious advantage of the ramp is that it causes a steady increase in the volume of the lungs during inspiration, rather than inspiratory gasps.
Two qualities of the inspiratory ramp are controlled, as follows:
- Control of the rate of increase of the ramp signal so that during heavy respiration, the ramp increases rapidly and therefore fills the lungs rapidly.
- Control of the limiting point at which the ramp suddenly ceases, which is the usual method for controlling the rate of respiration; that is, the earlier the ramp ceases, the shorter the duration of inspiration. This method also shortens the duration of expiration. Thus, the frequency of respiration is increased.
Pneumotaxic Centre limits duration of Inspiration and Increases Respiration Rate
A pneumotaxic center, located dorsally in the nucleus para-brachialis of the upper pons, transmits signals to the inspiratory area. The primary effect of this center is to control the “switch-off” point of the inspiratory ramp, thus controlling the duration of the filling phase of the lung cycle.
When the pneumotaxic signal is strong, inspiration might last for as little as 0.5 second, thus filling the lungs only slightly; when the pneumotaxic signal is weak, inspiration might continue for 5 or more seconds, thus filling the lungs with a great excess of air.
The function of the pneumotaxic center is primarily to limit inspiration, which has a secondary effect of increasing the rate of breathing, because limitation of inspiration also shortens expiration and the entire period of each respiration. A strong pneumotaxic signal can increase the rate of breathing to 30 to 40 breaths per minute, whereas a weak pneumotaxic signal may reduce the rate to only 3 to 5 breaths per minute.
Ventral Respiratory Group of Neurons influence Inspiration as well as Expiration
Located in each side of the medulla, about 5 millimeters anterior and lateral to the dorsal respiratory group of neurons, is the ventral respiratory group of neurons, found in the nucleus ambiguus rostrally and the nucleus retroambiguus caudally.
The function of this neuronal group differs from that of the dorsal respiratory group in several important ways:
- The neurons of the ventral respiratory group remain almost totally inactive during normal quiet respiration. Therefore, normal quiet breathing is caused only by repetitive inspiratory signals from the dorsal respiratory group transmitted mainly to the diaphragm, and expiration results from elastic recoil of the lungs and thoracic cage.
- The ventral respiratory neurons do not appear to participate in the basic rhythmical oscillation that controls respiration.
- When the respiratory drive for increased pulmonary ventilation becomes greater than normal, respiratory signals spill over into the ventral respiratory neurons from the basic oscillating mechanism of the dorsal respiratory area. As a consequence, the ventral respiratory area contributes extra respiratory drive as well.
- Electrical stimulation of a few of the neurons in the ventral group causes inspiration, whereas stimulation of others causes expiration. Therefore, these neurons contribute to both inspiration and expiration. They are especially important in providing the powerful expiratory signals to the abdominal muscles during very heavy expiration. Thus, this area operates more or less as an overdrive mechanism when high-levels of pulmonary ventilation are required, especially during heavy exercise
Hering-Breuer Inspiration Reflex
In addition to the central nervous system respiratory control mechanisms operating entirely within the brain stem, sensory nerve signals from the lungs also help control respiration.
Most important, located in the muscular portions of the walls of the bronchi and bronchioles throughout the lungs are stretch receptors that transmit signals through the vagi into the dorsal respiratory group of neurons when the lungs become over stretched.
These signals affect inspiration in much the same way as signals from the pneumotaxic center; that is, when the lungs become overly inflated, the stretch receptors activate an appropriate feedback response that “switches off” the inspiratory ramp and thus stops further inspiration.
This mechanism is called the Hering-Breuer inflation reflex. This reflex also increases the rate of respiration, as is true for signals from the pneumotaxic center.
In humans, the Hering-Breuer reflex probably is not activated until the tidal volume increases to more than three times normal (>≈1.5 liters per breath). Therefore, this reflex appears to be mainly a protective mechanism for preventing excess lung inflation rather than an important ingredient in normal control of ventilation.
Chemical Control of Respiration
The ultimate goal of respiration is to maintain proper concentrations of O₂, CO₂, and hydrogen ions in the tissues. It is fortunate, therefore, that respiratory activity is highly responsive to changes in each of these substances. Excess CO₂ or excess hydrogen ions in the blood mainly act directly on the respiratory center, causing greatly increased strength of both the inspiratory and the expiratory motor signals to the respiratory muscles.
Oxygen, in contrast, does not have a significant direct effect on the respiratory center of the brain in controlling respiration. Instead, it acts almost entirely on peripheral chemoreceptors located in the carotid and aortic bodies, and these chemoreceptors in turn transmit appropriate nervous signals to the respiratory center for control of respiration.
Chemosensitive Area of the Respiratory Center beneath the Ventral surface of the Medulla
We have mainly discussed three areas of the respiratory center: the dorsal respiratory group of neurons, the ventral respiratory group, and the pneumotaxic center. It is believed that none of these is affected directly by changes in blood CO₂ concentration or hydrogen ion concentration. Instead, an additional neuronal area, a chemosensitive area, shown in Figure 2, is located bilaterally, lying only 0.2 millimeter beneath the ventral surface of the medulla.
This area is highly sensitive to changes in either blood pCO₂ or hydrogen ion concentration, and it in turn excites the other portions of the respiratory center.
Excitation of the chemosensitive neurons by hydrogen ions is likely the primary stimulus. Although CO₂ has little direct effect in stimulating the neurons in the chemosensitive area, it does have a potent indirect effect. It has this effect by reacting with the water of the tissues to form carbonic acid, which dissociates into hydrogen and bicarbonate ions.
Effect of Blood pCO₂ and Hydrogen Ions on Respiratory Rate
The marked increase in ventilation caused by an increase in pCO₂ in the normal range between 35 and 75 mm Hg, which demonstrates the tremendous effect that CO₂ changes have in controlling respiration.
Changes in O₂ Have Little Direct Effect on Control of the Respiratory Center
Changes in O₂ concentration have virtually no direct effect on the respiratory center itself to alter respiratory drive (although O₂ changes do have an indirect effect, acting through the peripheral chemoreceptors.
The hemoglobinoxygen buffer system delivers almost exactly normal amounts of O₂ to the tissues even when the pulmonary PO₂ changes from a value as low as 60 mm Hg up to a value as high as 1000 mm Hg. Therefore, except under special conditions, adequate delivery of O₂ can occur despite changes in lung ventilation ranging from slightly below onehalf normal to as high as 20 or more times normal.
This is not true for CO₂ because both the blood and tissue PCO₂ change inversely with the rate of pulmonary ventilation; thus, the processes of animal evolution have made CO₂ the major controller of respiration, not O₂.
Yet for those special conditions in which the tissues get into trouble for lack of O₂, the body has a special mechanism for respiratory control located in the peripheral chemoreceptors, outside the brain respiratory center; this mechanism responds when the blood O₂ falls too low, mainly below a pO₂ of 70 mm Hg.
Peripheral Chemoreceptor and Role of Oxygen in Regulation of Respiration
In addition to control of respiratory activity by the respiratory center itself, still another mechanism is available for controlling respiration. This mechanism is the peripheral chemoreceptor system, shown in Figure 4. Special nervous chemical receptors, called chemoreceptors, are located in several areas outside the brain.
Most of the chemoreceptors are in the carotid bodies. However, a few are also in the aortic bodies, and a very few are located elsewhere in association with other arteries of the thoracic and abdominal regions.
The carotid bodies are located bilaterally in the bifurcations of the common carotid arteries. Their afferent nerve fibers pass through Hering’s nerves to the glossopharyngeal nerves and then to the dorsal respiratory area of the medulla. The aortic bodies are located along the arch of the aorta; their afferent nerve fibers pass through the vagi, also to the dorsal medullary respiratory area.
Each of the chemoreceptor bodies receives its own special blood supply through a minute artery directly from the adjacent arterial trunk. Further, blood flow through these bodies is extreme, 20 times the weight of the bodies themselves each minute. Therefore, the percentage of O₂ removed from the flowing blood is virtually zero, which means that the chemoreceptors are exposed at all times to arterial blood, not venous blood, and their pO₂ values are arterial pO₂ values.
Decreased Arterial Oxygen stimulates the Chemoreceptors
When the oxygen concentration in the arterial blood falls below normal, the chemoreceptors become strongly stimulated. This effect is demonstrated in Figure 5, which shows the effect of different levels of arterial pO₂ on the rate of nerve impulse transmission from a carotid body.
Note that the impulse rate is particularly sensitive to changes in arterial pO₂ in the range of 60 down to 30 mm Hg, a range in which hemoglobin saturation with oxygen decreases rapidly.