The volume of air inspired and expired per unit time is tightly controlled, both with respect to frequency of breaths and to tidal volume. Breathing is regulated so that the lungs can maintain the and within the normal range, even under widely varying conditions such as exercise.
Breathing is controlled by centers in the brain stem. There are four components to this control system: (1) chemoreceptors for O2 or CO2; (2) mechanoreceptors in the lungs and joints; (3) control centers for breathing in the brain stem (medulla and pons); (4) respiratory muscles, whose activity is directed by the brain stem centers (Fig. 5-32). Voluntary control can also be exerted by commands from the cerebral cortex (e.g., breath-holding or voluntary hyperventilation), which can temporarily override the brain stem.
Figure 5–32 Brain stem control of breathing. Afferent (sensory) information reaches the medullary inspiratory center via central and peripheral chemoreceptors and mechanoreceptors. Efferent (motor) information is sent from the inspiratory center to the phrenic nerve, which innervates the diaphragm. CN, Cranial nerve; DRG, dorsal respiratory group.
Brain Stem Control of Breathing
Breathing is an involuntary process that is controlled by the medulla and pons of the brain stem. The frequency of normal, involuntary breathing is controlled by three groups of neurons or brain stem centers:the medullary respiratory center, the apneustic center, and the pneumotaxic center.
Medullary Respiratory Center
The medullary respiratory center is located in the reticular formation and is composed of two groups of neurons that are distinguished by their anatomic location: the inspiratory center (dorsal respiratory group) and the expiratory center (ventral respiratory group).
Inspiratory center. The inspiratory center is located in the dorsal respiratory group (DRG) of neurons and controls the basic rhythm for breathing by setting the frequency of inspiration. This group of neurons receives sensory input from peripheral chemoreceptors via the glossopharyngeal (CN IX) and vagus (CN X) nerves and from mechanoreceptors in the lung via the vagus nerve. The inspiratory center sends its motor output to the diaphragm via the phrenic nerve. The pattern of activity in the phrenic nerve includes a period of quiescence, followed by a burst of action potentials that increase in frequency for a few seconds, and then a return to quiescence. Activity in the diaphragm follows this same pattern: quiescence, action potentials rising to a peak frequency (leading to contraction of the diaphragm), and quiescence. Inspiration can be shortened by inhibition of the inspiratory center via the pneumotaxic center (see subsequent discussion).
Expiratory center. The expiratory center (not shown in Fig. 5-32) is located in the ventral respiratory neurons and is responsible primarily for expiration. Because expiration is normally a passive process, these neurons are inactive during quiet breathing. However, during exercise when expiration becomes active, this center is activated.
Apneusis is an abnormal breathing pattern with prolonged inspiratory gasps, followed by brief expiratory movement. Stimulation of the apneustic center in the lower pons produces this breathing pattern in experimental subjects. Stimulation of these neurons apparently excites the inspiratory center in the medulla, prolonging the period of action potentials in the phrenic nerve, and thereby prolonging the contraction of the diaphragm.
The pneumotaxic center turns off inspiration, limiting the burst of action potentials in the phrenic nerve. In effect, the pneumotaxic center, located in the upper pons, limits the size of the tidal volume, and secondarily, it regulates the respiratory rate. A normal breathing rhythm persists in the absence of this center.
Commands from the cerebral cortex can temporarily override the automatic brain stem centers. For example, a person can voluntarily hyperventilate (i.e., increase breathing frequency and volume). The consequence of hyperventilation is a decrease in , which causes arterial pH to increase. Hyperventilation is self-limiting, however, because the decrease in will produce unconsciousness and the person will revert to a normal breathing pattern. Although more difficult, a person may voluntarily hypoventilate (i.e., breath-holding). Hypoventilation causes a decrease in and an increase in , both of which are strong drives for ventilation. A period of prior hyperventilation can prolong the duration of breath-holding.
The brain stem controls breathing by processing sensory (afferent) information and sending motor (efferent) information to the diaphragm. Of the sensory information arriving at the brain stem, the most important is that concerning , , and arterial pH.
The central chemoreceptors, located in the brain stem, are the most important for the minute-to-minute control of breathing. These chemoreceptors are located on the ventral surface of the medulla, near the point of exit of the glossopharyngeal (CN IX) and vagus (CN X) nerves and only a short distance from the DRG in the medulla. Thus, central chemoreceptors communicate directly with the inspiratory center.
The brain stem chemoreceptors are exquisitely sensitive to changes in the pH of cerebrospinal fluid (CSF). Decreases in the pH of CSF produce increases in breathing rate (hyperventilation), and increases in the pH of CSF produce decreases in breathing rate (hypoventilation).
The medullary chemoreceptors respond directly to changes in the pH of CSF and indirectly to changes in arterial PCO2 (Fig. 5-33). The circled numbers in the figure correspond with the following steps:
Figure 5–33 Response of central chemoreceptors to pH. The circled numbers correspond to the numbered steps discussed in the text. CSF, Cerebrospinal fluid; DRG, dorsal respiratory group.
1. In the blood, CO2 combines reversibly with H2O to form H+ and HCO3− by the familiar reactions. Because the blood-brain barrier is relatively impermeable to H+ and HCO3−, these ions are trapped in the vascular compartment and do not enter the brain. CO2, however, is quite permeable across the blood-brain barrier and enters the extracellular fluid of the brain.
2. CO2 also is permeable across the brain-CSF barrier and enters the CSF.
3. In the CSF, CO2 is converted to H+ and HCO3−. Thus, increases in arterial PCO2 produce increases in the PCO2 of CSF, which results in an increase in H+ concentration of CSF (decrease in pH).
4. and 5. The central chemoreceptors are in close proximity to CSF and detect the decrease in pH. A decrease in pH then signals the inspiratory center to increase the breathing rate (hyperventilation).
In summary, the goal of central chemoreceptors is to keep arterial PCO2 within the normal range, if possible. Thus, increases in arterial PCO2 produce increases in PCO2 in the brain and the CSF, which decreases the pH of the CSF. A decrease in CSF pH is detected by central chemoreceptors for H+, which instruct the DRG to increase the breathing rate. When the breathing rate increases, more CO2 will be expired and the arterial PCO2 will decrease toward normal.
There are peripheral chemoreceptors for O2, CO2, and H+ in the carotid bodies located at the bifurcation of the common carotid arteries and in the aortic bodies above and below the aortic arch (see Fig. 5-32). Information about arterial PO2, PCO2, and pH is relayed to the DRG via CN IX and CN X, which orchestrates an appropriate change in breathing rate.
Each of the following changes in arterial blood composition is detected by peripheral chemoreceptors and produces an increase in breathing rate:
Decreases in arterial PO2. The most important responsibility of the peripheral chemoreceptors is to detect changes in arterial PO2. Surprisingly, however, the peripheral chemoreceptors are relatively insensitive to changes in PO2: They respond when PO2 decreases to less than 60 mm Hg. Thus, if arterial PO2 is between 100 mm Hg and 60 mm Hg, the breathing rate is virtually constant. However, if arterial PO2 is less than 60 mm Hg, the breathing rate increases in a steep and linear fashion. In this range of PO2, chemoreceptors are exquisitely sensitive to O2; in fact, they respond so rapidly that the firing rate of the sensory neurons may change during a single breathing cycle.
Increases in arterial PCO2. The peripheral chemoreceptors also detect increases in PCO2, but the effect is less important than their response to decreases in PO2. Detection of changes in PCO2 by the peripheral chemoreceptors also is less important than detection of changes in PCO2 by the central chemoreceptors.
Decreases in arterial pH. Decreases in arterial pH cause an increase in ventilation, mediated by peripheral chemoreceptors for H+. This effect is independent of changes in the arterial PCO2 and is mediatedonly by chemoreceptors in the carotid bodies (not by those in the aortic bodies). Thus, in metabolic acidosis, in which there is decreased arterial pH, the peripheral chemoreceptors are stimulated directly to increase the ventilation rate (the respiratory compensation for metabolic acidosis; see Chapter 7).
In addition to chemoreceptors, several other types of receptors are involved in the control of breathing including lung stretch receptors, joint and muscle receptors, irritant receptors, and juxtacapillary (J) receptors.
Lung stretch receptors. Mechanoreceptors are present in the smooth muscle of the airways. When stimulated by distention of the lungs and airways, mechanoreceptors initiate a reflex decrease in breathing rate called the Hering-Breuer reflex. The reflex decreases breathing rate by prolonging expiratory time.
Joint and muscle receptors. Mechanoreceptors located in the joints and muscles detect the movement of limbs and instruct the inspiratory center to increase the breathing rate. Information from the joints and muscles is important in the early (anticipatory) ventilatory response to exercise.
Irritant receptors. Irritant receptors for noxious chemicals and particles are located between epithelial cells lining the airways. Information from these receptors travels to the medulla via CN X and causes a reflex constriction of bronchial smooth muscle and an increase in breathing rate.
J receptors. Juxtacapillary (J) receptors are located in the alveolar walls and, therefore, are near the capillaries. Engorgement of pulmonary capillaries with blood and increases in interstitial fluid volume may activate these receptors and produce an increase in the breathing rate. For example, in left-sided heart failure, blood “backs up” in the pulmonary circulation and J receptors mediate a change in breathing pattern, including rapid shallow breathing and dyspnea (difficulty in breathing).