Lecture 9
Regulation of RespirationThe nervous system normally adjusts the rate of alveolar ventilation exactly to the requirement of the body so that the PO2 and PCO2 in the arterial blood are hardly altered even during heavy exercise and most other types of respiratory stress.
Respiratory Center
The respiratory center is composed of several groups of neurons located bilaterally in the medulla oblongata and pons of the brain stem (Fig. 20). It is divided into three major collections of neurons:A dorsal respiratory group (inspiration).
A ventral respiratory group (inspiration & expiration).
The pneumotaxic center (controls rate and depth of breathing).
Dorsal respiratory group of neurons its control of inspiration and of respiratory rhythm
Dorsal respiratory group of neurons extends most of the length of the dorsal portion of the medulla. Most of its neurons are located within the nucleus of the tractus solitaries. The nucleus of the tractus solitarius is the sensory termination of both the vagal and the glossopharyngeal nerves, which transmit sensory signals into the respiratory center from (1) peripheral chemoreceptors, (2) baroreceptors, and (3) several types of receptors in the lungs.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 transected both above and below the medulla, this group of neurons still produces repetitive bursts of inspiratory neuronal action potentials. The basic cause of these repetitive discharges is unknown. This nervous signal is transmitted to the inspiratory muscles, mainly the diaphragm. Normally; the signal begins weakly and increases gradually in a ramp manner for about 2 seconds. Then it 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. Thus, the inspiratory signal is a ramp signal which is important to causes a steady increase in the volume of the lungs during inspiration, rather than inspiratory gasps. There are two qualities of the inspiratory ramp that 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. This shortens the duration of inspiration and expiration. Thus, the frequency of respiration is increased.
A Pneumotaxic center: located in the upper pons, transmits signals to the inspiratory area to control the switch-off point of the inspiratory ramp, thus controlling the duration of the filling phase of the lung cycle. This has a secondary effect of increasing the rate of breathing, due to shorten inspiration, 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.
Lung inflation signals limit inspirationthe hering-breuer inflation reflex
It is stretch receptors located in the muscular portions of the walls of the bronchi and bronchioles throughout the lungs that transmit signals through the vagi into the dorsal respiratory group of neurons when the lungs become overstretched. These signals switch off the inspiratory ramp and stops further inspiration and increases the rate of respiration as signals from the pneumotaxic center. In human beings, this reflex is not activated until the tidal volume increases to more than three times normal (greater than about 1.5 L per breath), so it is a protective mechanism.Ventral respiratory group of neurons: Located in each side of the medulla, about 5ml anterior and lateral to the dorsal respiratory group of neurons. 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 and it does not participate in the basic rhythmical oscillation that controls respiration.
The ventral respiratory area contributes in extra respiratory drive (eg. Heavy exercise). This is due to signals received from the basic oscillating mechanism of dorsal group during increased respiratory drive for increased pulmonary ventilation.
Electrical stimulation of a few of the neurons in the ventral group causes inspiration, whereas stimulation of others causes expiration. They are especially important in providing the powerful expiratory signals to the abdominal muscles during very heavy expiration during heavy exercise.
●The mechanism in controlling basic respiration is discussed, now we will discuss the control of ventilation according the respiratory needs of the body.
Chemical control of respiration
Chemosensitive area of the respiratory center: a chemosensitive area is a neuronal area located bilaterally, lying only 0.2 ml 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: the hydrogen ions may be the only important direct stimulus for these chemosensitive neurons. However, hydrogen ions do not easily cross the blood-brain barrier, so changes in hydrogen ion concentration in the blood have less effect in stimulating the chemosensitive neurons than do changes in blood carbon dioxide.
Carbon dioxide stimulates the chemosensitive area: Although carbon dioxide has little direct effect in stimulating the neurons in the chemosensitive area, it does have a potent indirect effect as follow:
1- By reacting with the water of the tissues to form carbonic acid, which dissociates into hydrogen and bicarbonate ions; the hydrogen ions then have a potent direct stimulatory effect on respiration (Fig. 21). But the blood brain barrier is not very permeable to hydrogen ions, but carbon dioxide passes freely through this barrier.
2-Also when the blood PCO2 increases, carbon dioxide passes freely through blood brain barrier. The PCO2 of both the interstitial fluid of the medulla and the cerebrospinal fluid increases as well. In both these fluids, the carbon dioxide immediately reacts with the water to form new hydrogen ions. Thus more hydrogen ions are released into the respiratory chemosensitive sensory area of the medulla when the blood carbon dioxide concentration increases than when the blood hydrogen ion concentration increases. For this reason, respiratory center activity is increased very strongly by changes in blood carbon dioxide.
An increase in blood carbon dioxide concentration has a potent acute effect (in first few hours of increases) on controlling respiratory drive but only a weak chronic effect after a few days adaptation as carbon dioxide stimulatory effect decreased after the first 1 to 2 days. This decline results from (1) renal readjustment, by increasing the blood bicarbonate, which binds with the hydrogen ions in the blood and cerebrospinal fluid to reduce their concentrations. Also (2)over a period of hours, the bicarbonate ions also slowly diffuse through the blood-brain and blood– cerebrospinal fluid barriers and combine directly with the hydrogen ions nearby the respiratory neurons as well, thus reducing the hydrogen ions back to near normal.
● quantitatively there is a very marked increase in ventilation caused by an increase in PCO2 in the normal range between 35 and 75 mm Hg. By contrast, the change in respiration in the normal blood pH range between 7.3 and 7.5 is less than one tenth as great.
Unimportance of oxygen for control of the respiratory center (fig 22)
The hemoglobin oxygen buffer system delivers almost exactly normal amounts of oxygen 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 except under special conditions in which the tissues get into trouble for lack of oxygen. Changes in oxygen concentration have no direct effect on the respiratory center but it has an indirect effect, acting through the peripheral chemoreceptors.Peripheral chemoreceptor system for control of respiratory activityrole of oxygen in respiratory control
The peripheral chemoreceptors are special nervous chemical receptors, which are located in several areas outside the brain. They are especially important for detecting changes in oxygen in the blood, although they also respond to a lesser extent to changes in carbon dioxide and hydrogen ion concentrations. The chemoreceptors transmit nervous signals to the respiratory center in the brain to help regulate respiratory activity. These chemoreceptors are (1) carotid bodies are located bilaterally in the bifurcations of the common carotid arteries. Their afferent nerve fibers pass through Herings nerves to the glossopharyngeal nerves and then to the dorsal respiratory area of the medulla.
(2) The aortic bodies (fewer) are located along the arch of the aorta; their afferent nerve fibers pass through the vagi, also to the dorsal medullary respiratory area.
(3) And a very few chemoreceptors are located elsewhere in association with other arteries of the thoracic and abdominal regions.
● 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 % of oxygen removed from the flowing blood is virtually zero. So these chemoreceptors are exposed at all times to arterial blood, not venous blood, and their PO2s are arterial PO2s.
●The impulse rate from chemoreceptors (chemoreceptors stimulation) is sensitive to changes (low) in arterial PO2 particularly in the range of 60 down to 30 mm Hg, a range in which hemoglobin saturation with oxygen decreases rapidly.
●Basic mechanism of stimulation of the chemoreceptors by oxygen deficiency is still unknown.
Figure 21 Stimulation of the brain stem inspiratory area by signals from the chemosensitive area located bilaterally in the medulla, lying only a fraction of a ml beneath the ventral medullary surface. Note also that hydrogen ions stimulate the chemosensitive area, but carbon dioxide in the fluid gives rise to most of the hydrogen ions.
Figure 22 decreased blood oxygen concentration stimulates chemorecepters in the carotid and aortic bodies