Regulation Of Respiration (Ozansoy) PDF

Mehmet OZANSOY, Ph.D. Dept. of Physiology Respiratory Center  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, lo...

Mehmet OZANSOY, Ph.D. Dept. of Physiology Respiratory Center  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 ventrolateral 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.  The dorsal respiratory group of neurons plays the most fundamental role in the control of respiration Dorsal Respiratory Group of Neurons  Most of its neurons are located within the nucleus of the tractus solitarius (NTS)  NTS is the sensory termination of both the vagal and the glossopharyngeal nerves, which transmit sensory signals into the respiratory center from  peripheral chemoreceptors  baroreceptors  several types of receptors in the lungs  The basic rhythm of respiration is generated mainly in the dorsal respiratory group of neurons.  The nervous signal that is transmitted to the inspiratory muscles, mainly the diaphragm, is not an instantaneous burst of action potentials.  Instead, in normal respiration, it begins weakly and increases steadily 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  The inspiratory signal begins as a 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  There are two qualities of the inspiratory ramp that are controlled:  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 is the usual method for controlling the rate of respiration  The earlier the ramp ceases, the shorter the duration of inspiration.  This also shortens the duration of expiration.  Thus, the frequency of respiration is increased. Pneumotaxic Center  A pneumotaxic center, located dorsally in the nucleus parabrachialis 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. Ventral Respiratory Group of Neurons  The ventral respiratory group of neurons, found in the  nucleus ambiguus rostrally and  the nucleus retroambiguus caudally  The neurons of the ventral respiratory group remain almost totally inactive during normal quiet 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 (Pre-Bötzinger Complex)  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 The Hering-Breuer Inflation Reflex  In addition to the central nervous system respiratory control mechanisms operating within the brain stem,  Sensory nerve signals from  the lungs  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 overstretched  These signals affect inspiration in much the same way as signals from the pneumotaxic center  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 is called the Hering- Breuer inflation reflex.  This reflex also increases the rate of respiration, as is true for signals from the pneumotaxic center. Chemical Control of Respiration  Excess carbon dioxide or excess hydrogen ions in the blood mainly act directly on the respiratory center itself, 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  These in turn transmit appropriate nervous signals to the respiratory center for control of respiration Chemosensitive Area of the Respiratory Center  Chemosensitive area, 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  It in turn excites the other portions of the respiratory center.  The sensory neurons in the chemosensitive area are especially excited by hydrogen ions  In fact, hydrogen ions may be the only important direct stimulus for these neurons.  However, hydrogen ions do not easily cross the blood- brain barrier.  Although carbon dioxide has little direct effect in stimulating the neurons in the chemosensitive area, it does have a potent indirect effect.  It does this 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  Whenever the blood Pco2 increases, so does the Pco2 of both the interstitial fluid of the medulla and the cerebrospinal fluid.  In both these fluids, the carbon dioxide immediately reacts with the water to form new hydrogen ions  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,  Excitation of the respiratory center by carbon dioxide is great the first few hours after the blood carbon dioxide first increases, but then it gradually declines over the next 1 to 2 days, decreasing to about one fifth the initial effect  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 adjacent to the respiratory neurons as well, thus reducing the hydrogen ions back to near normal  A change in blood carbon dioxide concentration has a potent acute effect on controlling respiratory drive but only a weak chronic effect after a few days’ adaptation. Unimportance of Oxygen Changes in oxygen concentration have virtually no direct effect on the respiratory center itself to alter respiratory drive Peripheral Chemoreceptor System  Special nervous chemical receptors, called chemoreceptors, 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.  Most of the chemoreceptors are in the carotid bodies  However, a few are also in the aortic bodies  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.  When the oxygen concentration in the arterial blood falls below normal, the chemoreceptors become strongly stimulated The Phenomenon of “Acclimatization”  Chronic breathing of low oxygen stimulates respiration  Mountain climbers have found that when they ascend a mountain slowly, over a period of days rather than a period of hours, they breathe much more deeply and therefore can withstand far lower atmospheric oxygen concentrations than when they ascend rapidly.  This is called acclimatization.  Within 2 to 3 days, the respiratory center in the brain stem loses about four fifths of its sensitivity to changes in Pco2 and hydrogen ions.  Therefore, the excess ventilatory blow-off of carbon dioxide that normally would inhibit an increase in respiration fails to occur  Low oxygen can drive the respiratory system to a much higher level of alveolar ventilation than under acute conditions.  Instead of the 70 per cent increase in ventilation that might occur after acute exposure to low oxygen, the alveolar ventilation often increases 400 to 500 per cent after 2 to 3 days of low oxygen Other Factors That Affect Respiration  The epithelium of the trachea, bronchi, and bronchioles is supplied with sensory nerve endings called pulmonary irritant receptors that are stimulated by many incidents.  These cause coughing and sneezing.  They may also cause bronchial constriction in such diseases as asthma and emphysema.  Sensory nerve endings have been described in the alveolar walls in juxtaposition to the pulmonary J receptors.  They are stimulated especially when the pulmonary capillaries become engorged with blood or when pulmonary edema occurs in such conditions as congestive heart failure.  Their excitation may give the person a feeling of dyspnea (shortness of breath).  The activity of the respiratory center may be depressed or even inactivated by acute brain edema resulting from brain concussion.  The head might be struck against some solid object, after which the damaged brain tissues swell, compressing the cerebral arteries against the cranial vault and thus partially blocking cerebral blood supply  The most prevalent cause of respiratory depression and respiratory arrest is overdosage with anesthetics or narcotics.  For instance, sodium pentobarbital depresses the respiratory center considerably more than many other anesthetics, such as halothane.  At one time, morphine was used as an anesthetic, but this drug is now used only as an adjunct to anesthetics because it greatly depresses the respiratory center while having less ability to anesthetize the cerebral cortex.