Regulation of Respiration (2024) PDF

PAGE 1 UNIVERSITÄTSMEDIZIN NEUMARKT A. M. https://edu.umch.de www.umfst.ro CAMPUS HAMBURG Associate Professor dr. Adina Stoian 2024 May REGULATION OF RESPIRATION. RESPIRATORY INSUFFICIENCY Respiratory...

PAGE 1 UNIVERSITÄTSMEDIZIN NEUMARKT A. M. https://edu.umch.de www.umfst.ro CAMPUS HAMBURG Associate Professor dr. Adina Stoian 2024 May REGULATION OF RESPIRATION. RESPIRATORY INSUFFICIENCY Respiratory Center PAGE 2 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: (1) a dorsal respiratory group, located in the dorsal portion of the medulla, which mainly causes inspiration; (2) a ventral respiratory group, located in the ventrolateral part of the medulla, which mainly causes expiration; (3) the pneumotaxic center, located dorsally in the superior portion of the pons, which mainly controls rate Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, and depth of breathing. Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 3 Dorsal Respiratory Group of Neurons Controls Inspiration and Respiratory Rhythm 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 in 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 glossopharyngeal nerves, which transmit sensory signals into the respiratory center from the following: (1) peripheral chemoreceptors; (2) baroreceptors; (3) receptors in the liver, pancreas, and multiple parts of the gastrointestinal tract; and (4) several types of receptors in the lungs.  PAGE 4 Nervous control of breathing Thomas, Caroline, BSc, MBChB, FRCA, The Respiratory System, Chapter 9, 121- 135 Brainstem respiratory ‘centres’. These are not discrete anatomical centres, rather they are areas of the brainstem which have a large percentage of neurons with a common function relating to the automatic control of breathing. PRG, pontine respira... Copyright © 2023 Copyright © 2023 by Elsevier, Inc. All rights reserved.  PAGE 5 Dorsal Respiratory Group of Neurons Controls Inspiration and Respiratory Rhythm 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 above and below the medulla, this group of neurons still emits repetitive bursts of inspiratory neuronal action potentials. 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 of time, the mechanism repeats itself, continuing throughout the life of the animal. Similar networks of neurons are present in the human being, located entirely within the medulla; it probably involves not only the dorsal respiratory group but adjacent areas of the medulla as well and is responsible for the basic rhythm of respiration.  PAGE 6 Dorsal Respiratory Group of Neurons Controls Inspiration and Respiratory Rhythm 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 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.  PAGE 7 Dorsal Respiratory Group of Neurons Controls Inspiration and Respiratory Rhythm Inspiratory “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: 1. 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. 2. 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.  PAGE 8 Pneumotaxic Center Limits Duration of Inspiration and Increases Respiratory Rate 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, thereby 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 much greater amounts 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/min, whereas a weak pneumotaxic signal may reduce the rate to only 3 to 5 breaths/min.  PAGE 9 Ventral Respiratory Group of Neurons—Functions in Both Inspiration and 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: 1. 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. 2. The ventral respiratory neurons do not appear to participate in the basic rhythmical oscillation that controls respiration.  PAGE 10 Ventral Respiratory Group of Neurons—Functions in Both Inspiration and 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: 3. 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 also contributes extra respiratory drive. 4. 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.  PAGE 11 Nervous control of breathing Thomas, Caroline, BSc, MBChB, FRCA, The Respiratory System, Chapter 9, 121-135 Afferent impulses to respiratory centres. There are a number of different receptors involved in sensing change in the respiratory system. These feed information via afferent impulses to the respiratory centre, which integrates the information and... Copyright © 2023 Copyright © 2023 by Elsevier, Inc. All rights reserved.  PAGE 12 Control of Overall Respiratory Center Activity It is important to know how the intensity of the respiratory control signals is increased or decreased to match the ventilatory needs of the body. For example, during heavy exercise, the rates of oxygen (O2) usage and carbon dioxide (CO2) formation are often increased to as much as 20 times normal, requiring commensurate increases in pulmonary ventilation.  PAGE 13 Chemical Control of Respiration The ultimate goal of respiration is to maintain proper concentrations of O2 , CO2 , and H+ in the tissues. Excess CO2 or excess H+ 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 major 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.  PAGE 14 Direct Control of Respiratory Center Activity by Co2 and H+ Chemosensitive Area of the Respiratory Center Beneath the Medulla’s Ventral Surface 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 or H+ concentration. An additional neuronal area, a 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 H+ concentration, and it in turn Regulation of Respiration excites the other portions of the respiratory center. Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 15 Excitation of the Chemosensitive Neurons by H + Is Likely the Primary Stimulus The sensory neurons in the chemosensitive area are especially excited by H+; in fact, it is believed that H+ may be the only important direct stimulus for these neurons. However, H+ ions do not easily cross the blood–brain barrier. For this reason, changes in H+ concentration in the blood have considerably less effect in stimulating the chemosensitive neurons than changes in blood CO2, even though CO2 is believed to stimulate these neurons secondarily by changing the H+ concentration.  PAGE 16 CO2 Indirectly Stimulates the Chemosensitive Neurons 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 H+ and HCO3−; the H+ then have a potent direct stimulatory effect on respiration. Why does blood CO2 have a more potent effect in stimulating the chemosensitive neurons than blood H+? The answer is that the blood–brain barrier is not very permeable to H+, but CO2 passes through this barrier almost as if the barrier did not exist. 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 CO2 immediately reacts with the water to form new H+. More H+ is released into the respiratory chemosensitive sensory area of the medulla when the blood CO2 concentration increases than when the blood H+ concentration increases. For this reason, respiratory center activity is increased very strongly by changes in blood CO2, a fact that we subsequently discuss quantitatively.  PAGE 17 Chemical control of breathing Thomas, Caroline, BSc, MBChB, FRCA, The Respiratory System, Chapter 10, 137-145 Central chemoreceptive areas of the brain. (A) These are not the traditional ‘respiratory centres’ dealt with in Chapter 9. (B) Their environment is closely controlled by the blood–brain barrier which is permeable to the passive diffusion of carbo... Copyright © 2023 Copyright © 2023 by Elsevier, Inc. All rights reserved.  PAGE 18 CO2 Indirectly Stimulates the Chemosensitive Neurons Attenuated Stimulatory Effect of CO2 After the First 1 to 2 Days Excitation of the respiratory center by CO2 is great the first few hours after the blood CO2 first increases, but then it gradually declines over the next 1 to 2 days, decreasing to about one-fifth the initial effect. Part of this decline results from renal readjustment of the H+ concentration in the circulating blood back toward normal after the CO2 first increases the H+ concentration. The kidneys achieve this readjustment by increasing the blood HCO3−, which binds with H+ in the blood and cerebrospinal fluid to reduce their concentrations. But, even more importantly, over a period of hours, the HCO3− also slowly diffuses through the blood– brain and blood–cerebrospinal fluid barriers and combine directly with H+ adjacent to the respiratory neurons as well, thus reducing the H+ back to near normal. A change in blood CO2 concentration therefore has a potent acute effect on controlling respiratory drive but only a weak chronic effect after a few days’ adaptation.  PAGE 19 Quantitative Effects of Blood P co 2 and H + Concentration on Alveolar Ventilation The figure shows quantitatively the approximate effects of blood Pco2 and blood pH (which is an inverse logarithmic measure of H + concentration) on alveolar ventilation. Note especially 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. By contrast, the change in respiration in the normal blood pH range, which is between 7.3 and 7.5, is less than 10% as great. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 20 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. 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 System— PAGE 21 Role of Oxygen in Respiratory Control In addition to control of respiratory activity by the respiratory center itself, still another mechanism is available for controlling respiration – the 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 O2 in the blood, although they also respond to a lesser extent to changes in CO2 and H+ concentrations. The chemoreceptors transmit nervous signals to the respiratory center in the brain to help regulate respiratory activity. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 22 Control of Ventilation Richerson, George B., Boron and Boulapaep Concise Medical Physiology, Chapter 32, 374-383 Anatomy of the peripheral chemoreceptors. (B, Data from Williams PL, Warwick R [eds]: Splanchnology. In Gray’s Anatomy. Philadelphia, WB Saunders, 1980.) Copyright © 2022 Copyright © 2021 by Elsevier, Inc. All rights reserved. Peripheral Chemoreceptor System— PAGE 23 Role of Oxygen in Respiratory Control 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. Peripheral Chemoreceptor System— PAGE 24 Role of Oxygen in Respiratory Control Each of the chemoreceptor bodies receives its own special blood supply through a minute artery directly from the adjacent arterial trunk. 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. Peripheral Chemoreceptor System— PAGE 25 Role of Oxygen in Respiratory Control 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 the figure, 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 mm Hg down to 30 mm Hg, a range in which hemoglobin Regulation of Respiration saturation with oxygen decreases rapidly. Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Peripheral Chemoreceptor System— PAGE 26 Role of Oxygen in Respiratory Control Basic Mechanism of Stimulation of the Chemoreceptors by O2 Deficiency The exact means whereby low Po2 excites the nerve endings in the carotid and aortic bodies are still not completely understood. These bodies have multiple, highly characteristic glandular- like cells, called glomus cells, that synapse directly or indirectly with the nerve endings. Current evidence suggests that these glomus cells function as the chemoreceptors and then stimulate the nerve endings. Glomus cells have O2 -sensitive potassium channels that are Regulation of Respiration inactivated when blood Po2 decreases markedly. Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Peripheral Chemoreceptor System— PAGE 27 Role of Oxygen in Respiratory Control Basic Mechanism of Stimulation of the Chemoreceptors by O2 Deficiency This inactivation causes the cell to depolarize, which in turn opens voltage-gated calcium channels and increases intracellular calcium ion concentration. The increased number of calcium ions stimulates release of a neurotransmitter that activates afferent neurons that send signals to the central nervous system and stimulate respiration. Although early studies suggested that dopamine or acetylcholine might be the main neurotransmitters, more recent studies suggest that during hypoxia, adenosine triphosphate (ATP) may be the key excitatory neurotransmitter released by carotid body glomus cells. Peripheral Chemoreceptor System— PAGE 28 Role of Oxygen in Respiratory Control Basic Mechanism of Stimulation of the Chemoreceptors by O2 Deficiency When the Po2 decreases below around 60 mm Hg, potassium channels close, causing cell depolarization, opening of calcium channels, and increased cytosolic calcium ion concentration. This stimulates transmitter release (adenosine triphosphate [ATP] is likely the most important), which activates afferent fibers that send signals to the central nervous system (CNS) and stimulate respiration. The mechanisms whereby low Po2 influences potassium channel activity are still unclear. Peripheral Chemoreceptor System— PAGE 29 Role of Oxygen in Respiratory Control Increased CO 2 and H+ Concentration Stimulates the Chemoreceptors An increase in CO2 or H+ concentration also excites the chemoreceptors and, in this way, indirectly increases respiratory activity. The direct effects of both these factors in the respiratory center are much more powerful than their effects mediated through the chemoreceptors (about seven times as powerful). Yet, there is one difference between the peripheral and central effects of CO2 — the stimulation via the peripheral chemoreceptors occurs as much as five times as rapidly as central stimulation, so the peripheral chemoreceptors might be especially important in increasing the rapidity of response to CO2 at the onset of exercise.  PAGE 30 Pulmonary Gas Exchange : The Basics Hennessey, Iain AM, MBChB (Hons) BSc (Hons) MMIS FRCS, Arterial Blood Gases Made Easy, 1.2, 4-17 Control of ventilation. Copyright © 2016 © 2016 Elsevier Ltd. All rights reserved.  PAGE 31 Oxygen and Carbon Dioxide Transport and Control of Respiration Mulroney, Susan E., PhD, Netter's Essential Physiology, Chapter 16, 189-204 Control of Respiration Central and peripheral chemoreceptors regulate respiration by responding to arterial blood gas levels. Central chemoreceptors respond primarily to changes in arterial P co2, which diffuses into the cerebrospinal fluid (CSF)... Copyright © 2025 Copyright © 2025 by Elsevier Inc. All rights reserved, including those for text and data mining, AI training, and similar technologies. Effect of Low Arterial Po2 to Stimulate Alveolar Ventilation When Arterial CO2 and PAGE 32 H+ Concentrations Remain Normal The figure presents the effect of low arterial Po2 on alveolar ventilation when the Pco2 and H+ concentrations are kept constant and shows almost no effect on ventilation as long as the arterial Po2 remains greater than 100 mm Hg. However, at pressures lower than 100 mm Hg, ventilation approximately doubles when the arterial Po2 falls to 60 mm Hg and can increase as much as fivefold at very low Po2 values. Under these conditions, low arterial Po2 obviously drives the ventilatory process quite strongly. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Effect of Low Arterial Po2 to Stimulate Alveolar Ventilation When Arterial CO2 and PAGE 33 H+ Concentrations Remain Normal The lower red curve demonstrates the effect of different levels of arterial Po2 on alveolar ventilation, showing a 6-fold increase in ventilation as the Po2 decreases from the normal level of 100 mm Hg to 20 mm Hg. The upper green line shows that the arterial Pco2 was kept at a constant level during the measurements of this study; pH also was kept constant. Because the effect of hypoxia on ventilation is modest for Po2 values greater than 60 to 80 mm Hg, the Pco2 and H+ responses are mainly responsible for regulating ventilation in healthy humans at sea level. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Chronic Breathing of Low O2 Stimulates Respiration Even More—The Phenomenon of PAGE 34 “Acclimatization” 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 O2 concentrations than when they ascend rapidly, this phenomenon is called acclimatization. The reason for acclimatization is that within 2 to 3 days, the respiratory center in the brain stem loses about 80% of its sensitivity to changes in Pco2 and H+. Therefore, the excess ventilatory blow-off of CO2 that normally would inhibit an increase in respiration fails to occur, and low O2 can drive the respiratory system to a much higher level of alveolar ventilation than under acute conditions. Instead of the 70% increase in ventilation that might occur after acute exposure to low O2, the alveolar ventilation often increases by 400% to 500% after 2 to 3 days of low O2, which helps immensely in supplying additional O2 to the mountain climber.  PAGE 35 Regulation of Respiration During Exercise During strenuous exercise, O2 consumption and CO2 formation can increase as much as 20-fold. Yet, in the healthy athlete, alveolar ventilation ordinarily increases almost exactly in step with the increased level of oxygen metabolism. The arterial Po2, Pco2, and pH remain almost exactly normal. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 36 Regulation of Respiration During Exercise Measurements of arterial Pco2, pH, and Po2 show that none of these values changes significantly during exercise, so none of them becomes abnormal enough to stimulate respiration as vigorously as observed during strenuous exercise. Therefore, what causes intense ventilation during exercise? At least one effect seems to be predominant. The brain, on transmitting motor impulses to the exercising muscles, is believed to transmit collateral impulses into the brain stem at the same time to excite the respiratory center. This action is analogous to the stimulation of the vasomotor center of the brain stem during exercise that causes a simultaneous increase in arterial pressure.  PAGE 37 Regulation of Respiration During Exercise Interrelationship Between Chemical and Nervous Factors in Controlling Respiration During Exercise When a person exercises, direct nervous signals presumably stimulate the respiratory center by almost the proper amount to supply the extra O2 required for exercise and to blow off extra CO2. Occasionally, however, the nervous respiratory control signals are too strong or too weak. Chemical factors then play a significant role in bringing about the final adjustment of respiration required to keep the O2, CO2 and H+ concentrations of the body fluids as nearly normal as possible.  PAGE 38 Regulation of Respiration During Exercise Interrelationship Between Chemical and Nervous Factors in Controlling Respiration During Exercise The lower curve shows changes in alveolar ventilation during 1 minute of exercise, and the upper curve shows changes in arterial Pco2. At the onset of exercise, the alveolar ventilation increases instantaneously, without an increase in arterial Pco2. This increase in ventilation is usually great enough so that at first it actually decreases arterial Pco2 below normal. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 39 Regulation of Respiration During Exercise Interrelationship Between Chemical and Nervous Factors in Controlling Respiration During Exercise The presumed reason why the ventilation forges ahead of the build-up of blood CO2 is that the brain provides an “anticipatory” stimulation of respiration at the onset of exercise, causing extra alveolar ventilation even before it is necessary. After 30 to 40 seconds, the amount of CO2 released into the blood from the active muscles approximately matches the increased rate of ventilation. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 40 Regulation of Respiration During Exercise Interrelationship Between Chemical and Nervous Factors in Controlling Respiration During Exercise The figure summarizes the control of respiration during exercise in another way, this time more quantitatively. The lower curve of this figure shows the effect of different levels of arterial Pco2 on alveolar ventilation when the body is at rest—that is, not exercising. The upper curve shows the approximate shift of this ventilatory curve caused by neurogenic drive from the respiratory center that occurs during heavy exercise. The points indicated on the two curves show the arterial Pco2 first in the resting state and then in the exercising state. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 41 Regulation of Respiration During Exercise Interrelationship Between Chemical and Nervous Factors in Controlling Respiration During Exercise Note in both cases that the Pco2 is at the normal level of 40 mm Hg. In other words, the neurogenic factor shifts the curve about 20-fold in the upward direction, so ventilation almost matches the rate of CO2 release, thus keeping arterial Pco2 near its normal value. The upper curve also shows that if during exercise the arterial Pco2 does change from its normal value of 40 mm Hg, it has an extra stimulatory effect on ventilation at a Pco2 value greater than 40 mm Hg and a depressant effect at a Pco2 value less than 40 mm Hg. Regulation of Respiration Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 42, 531-540 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 42 Other Factors That Affect Respiration Effect of Irritant Receptors in the Airways The epithelium of the trachea, bronchi, and bronchioles is supplied with sensory nerve endings called pulmonary irritant receptors that are stimulated by many factors. They may also cause bronchial constriction in persons with diseases such as asthma and emphysema. Function of Lung J Receptors A few sensory nerve endings have been described in the alveolar walls in juxtaposition to the pulmonary capillaries—hence, the name J receptors. They are stimulated especially when the pulmonary capillaries become engorged with blood or when pulmonary edema occurs in conditions such as congestive heart failure. Although the functional role of the J receptors is not clear, their excitation may give the person a feeling of dyspnea.  PAGE 43 Other Factors That Affect Respiration Brain Edema Depresses the Respiratory Center The activity of the respiratory center may be depressed or even inactivated by acute brain edema resulting from a brain concussion. For example, 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 the cerebral blood supply. Occasionally, respiratory depression resulting from brain edema can be relieved temporarily by intravenous injection of a hypertonic solution, such as a highly concentrated mannitol solution. These solutions osmotically remove some of the fluids of the brain, thus relieving intracranial pressure and sometimes re-establishing respiration within a few minutes.  PAGE 44 Other Factors That Affect Respiration Overdosage of Anesthetics and Narcotics Perhaps the most prevalent cause of respiratory depression and respiratory arrest is overdosage with anesthetics or narcotics. For example, 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. Because of their capacity to cause respiratory depression, opioids are responsible for a high proportion of fatal drug overdoses around the world. In the United States, approximately 70,000 people died from drug overdose in 2017, largely due to respiratory arrest.  PAGE 45 Other Factors That Affect Respiration Periodic Breathing An abnormality of respiration called periodic breathing occurs in several disease conditions. The person breathes deeply for a short interval and then breathes slightly or not at all for an additional interval, with the cycle repeating itself over and over. One type of periodic breathing, Cheyne-Stokes breathing, is characterized by slowly waxing and waning respiration occurring about every 40 to 60 seconds, as illustrated in the figure. Regulation of Respiration Cheyne-Stokes breathing, showing changing Pco2 in Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter the pulmonary blood (red line) and delayed changes 42, 531-540 in the Pco2 of the fluids of the respiratory Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. center (blue line).  PAGE 46 Other Factors That Affect Respiration Periodic Breathing Disorders of Ventilatory Control Principles of PulmonaryMedicine Weinberger, Steven E., MD, MACP, FRCP;Cockrill, Barbara A., MD; Mandel, Jess, MD, FACP.© 2019.  PAGE 47 Other Factors That Affect Respiration Basic Mechanism of Cheyne-Stokes Breathing When a person overbreathes, thus blowing off too much CO2 from the pulmonary blood while at the same time increasing blood O2, it takes several seconds before the changed pulmonary blood can be transported to the brain and inhibit the excess ventilation. By this time, the person has already overventilated for an extra few seconds. Therefore, when the overventilated blood finally reaches the brain respiratory center, the center becomes depressed to an excessive amount, at which point the opposite cycle begins—that is, CO2 increases, and O2 decreases in the alveoli. Again, it takes a few seconds before the brain can respond to these new changes.  PAGE 48 Other Factors That Affect Respiration Basic Mechanism of Cheyne-Stokes Breathing When the brain does respond, the person breathes hard once again and the cycle repeats. The basic cause of Cheyne-Stokes breathing occurs in everyone. However, under normal conditions, this mechanism is highly damped. That is, the fluids of the blood and respiratory center control areas have large amounts of dissolved and chemically bound CO2 and O2. Therefore, normally, the lungs cannot build up enough extra CO2 or depress the O2 sufficiently in a few seconds to cause the next cycle of the periodic breathing.  PAGE 49 Other Factors That Affect Respiration Basic Mechanism of Cheyne-Stokes Breathing However, under two separate conditions, the damping factors can be overridden, and Cheyne-Stokes breathing does occur: 1. When a long delay occurs for transport of blood from the lungs to the brain, changes in CO2 and O2 in the alveoli can continue for many more seconds than usual. Under these conditions, the storage capacities of the alveoli and pulmonary blood for these gases are exceeded; then, after a few more seconds, the periodic respiratory drive becomes extreme and Cheyne-Stokes breathing begins. This type of Cheyne-Stokes breathing often occurs in patients with severe cardiac failure because blood flow is slow, thus delaying the transport of blood gases from the lungs to the brain. In patients with chronic heart failure, Cheyne-Stokes breathing can sometimes occur on and off for months.  PAGE 50 Other Factors That Affect Respiration Basic Mechanism of Cheyne-Stokes Breathing However, under two separate conditions, the damping factors can be overridden, and Cheyne-Stokes breathing does occur: 2. A second cause of Cheyne-Stokes breathing is increased negative feedback gain in the respiratory control areas, which means that a change in blood CO2 or O2 causes a far greater change in ventilation than normally. For example, instead of the normal two- to threefold increase in ventilation that occurs when the Pco2 rises 3 mm Hg, the same 3-mm Hg rise might increase ventilation by 10- to 20-fold. The brain feedback tendency for periodic breathing is now strong enough to cause Cheyne-Stokes breathing without extra blood flow delay between the lungs and brain. This type of Cheyne-Stokes breathing occurs mainly in patients with damage to the respiratory centers of the brain. The brain damage often turns off the respiratory drive entirely for a few seconds, and then an extra-intense increase in blood CO2 turns it back on with great force. Cheyne-Stokes breathing of this type is frequently a prelude to death from brain malfunction.  PAGE 51 Other Factors That Affect Respiration Voluntary Control of Respiration The respiration can be controlled voluntarily for short periods, and a person can hyperventilate or hypoventilate to such an extent that serious derangements in Pco2, pH, and Po2 can occur in the blood. In fact, the world record for duration of voluntary breath-holding (apnea) under static resting conditions (and not hyperventilating with pure oxygen before the attempt) is reported to be 11 minutes and 54 seconds. Hyperventilation with pure oxygen and expelling large amounts of CO2 before the apnea attempt has permitted individuals to hold their breath underwater for over 24 minutes. Ultra-elite apnea competitors are able to suppress respiratory urges to the point where oxygen saturations fall to as low as about 50%, and unconsciousness limits the duration of breath-holding.  PAGE 52 Sleep apnea The term apnea means absence of spontaneous breathing. Occasional apneas occur during normal sleep, but in persons with sleep apnea, the frequency and duration are greatly increased, with episodes of apnea lasting for 10 seconds or longer and occurring 300 to 500 times each night. Sleep apneas can be caused by obstruction of the upper airways, especially the pharynx, or by an impaired central nervous system respiratory drive.  PAGE 53 Sleep apnea Obstructive Sleep Apnea Is Caused by Blockage of the Upper Airway The muscles of the pharynx normally keep this passage open to allow air to flow into the lungs during inspiration. During sleep, these muscles usually relax, but the airway passage remains open enough to permit adequate airflow. Some people have an especially narrow passage, and relaxation of these muscles during sleep causes the pharynx to close completely so that air cannot flow into the lungs. In persons with sleep apnea, loud snoring and labored breathing occur soon after falling asleep. The snoring proceeds, often becoming louder, and is then interrupted by a long silent period during which no breathing (apnea) occurs.  PAGE 54 Sleep apnea PAGE 9 Netter's Integrated Review of Medicine Rajagopalan, Kartik N.; Augelli, Dianne M. © 2021. Obstructive Sleep Apnea. ECG,Electrocardiogram; EEG, electroencephalogram.  PAGE 55 Sleep apnea Obstructive Sleep Apnea Is Caused by Blockage of the Upper Airway These periods of apnea result in significant decreases in Po2 and increases in Pco2, which greatly stimulate respiration. This stimulation, in turn, causes sudden attempts to breathe, which result in loud snorts and gasps followed by snoring and repeated episodes of apnea. The periods of apnea and laboured breathing are repeated several hundred times during the night, resulting in fragmented restless sleep. Therefore, patients with sleep apnea usually have excessive daytime drowsiness, as well as other disorders, including increased sympathetic activity, high heart rate, pulmonary and systemic hypertension, and a greatly elevated risk for cardiovascular disease.  PAGE 56 Sleep apnea Obstructive Sleep Apnea Is Caused by Blockage of the Upper Airway Obstructive sleep apnea usually occurs in older obese persons in whom there is increased fat deposition in the soft tissues of the pharynx or compression of the pharynx due to excessive fat masses in the neck. In a few individuals, sleep apnea may be associated with nasal obstruction, a very large tongue, enlarged tonsils, or certain shapes of the palate that greatly increase resistance to the flow of air to the lungs during inspiration. The most common treatments of obstructive sleep apnea include the following: (1) surgery to remove excess fat tissue at the back of the throat (a procedure called uvulopalatopharyngoplasty), remove enlarged tonsils or adenoids, or create an opening in the trachea (tracheostomy) to bypass the obstructed airway during sleep; (2) nasal ventilation with continuous positive airway pressure (CPAP).  PAGE 57 Sleep apnea PAGE 9 Netter's Integrated Review of Medicine Rajagopalan, Kartik N.; Augelli, Dianne M. © 2021. Treatment for Obstructive Sleep Apnea. CPAP, Continuous positive airway  PAGE 58 Issues in School-Going Children Nicholson, Alf, Building Blocks in Paediatrics, 30, 313-321 Example of polysomnograph results showing the two types of sleep apnoea. Sleep apnoea can be detected by reduced air flow and a delayed desaturation following the apnoea. Normally, the thorax and abdomen move in the same direction; however, the mo... Copyright © 2023 © 2023 Elsevier Limited. All rights reserved.  PAGE 59 Kussmaul breathing pattern PAGE 12 It is a compensatory mechanism for metabolic acidosis The rhythm it is normal, regular but the amplitude of the respirations it is increased The most frequent causes: diabetic ketoacidosis and chronic renal failure (uremia)  PAGE 60 Biot breathing pattern PAGE 13 A series of rapid and shallow respiratory cycles, followed by regular or irregular apnea periods of 5-10 seconds The most frequent causes: severe lesions of the respiratory neurons- drugs (opioid type), head trauma,high intracranial pressure, stroke, CNS’ infections  PAGE 61 Respiratory Insufficiency Diagnosis and treatment of most respiratory disorders depend heavily on understanding the basic physiological principles of respiration and gas exchange. Some respiratory diseases result from inadequate ventilation. Others are caused by abnormalities of diffusion through the pulmonary membrane or abnormal blood transport of gases between the lungs and tissues. Therapy is often entirely different for these diseases, so it is not satisfactory simply to make a diagnosis of “respiratory insufficiency.”  PAGE 62 Study of Blood Gases and Blood pH Among the most fundamental of all tests of pulmonary performance are determinations of the blood partial pressure of oxygen (Po2), carbon dioxide (CO2), and pH. It is often important to make these measurements rapidly as an aid in determining appropriate therapy for acute respiratory distress or acute abnormalities of acid–base balance. The following simple and rapid methods have been developed to make these measurements within minutes, using no more than a few drops of blood.  PAGE 63 Study of Blood Gases and Blood pH Determination of Blood pH Blood pH is measured using a glass pH electrode of the type commonly used in chemical laboratories. However, the electrodes used for this purpose are miniaturized. The voltage generated by the glass electrode is a direct measure of pH and is generally read directly from a voltmeter scale, or it is recorded on a chart.  PAGE 64 Study of Blood Gases and Blood pH Determination of Blood CO2 A glass electrode pH meter can also be used to determine blood CO2. When a weak solution of sodium bicarbonate is exposed to CO2 gas, the CO2 dissolves in the solution until an equilibrium state is reached. In this equilibrium state, the pH of the solution is a function of the CO2 and bicarbonate ion (HCO3−) concentrations. When the glass electrode is used to measure CO2 in blood, a miniature glass electrode is surrounded by a thin plastic membrane. A solution of sodium bicarbonate of known concentration is in the space between the electrode and plastic membrane. Blood is then superfused onto the outer surface of the plastic membrane, allowing CO2 to diffuse from the blood into the bicarbonate solution. Only a drop or so of blood is required. Next, the pH is measured by the glass electrode, and the CO2 is calculated using the formula that was previously provided.  PAGE 65 Study of Blood Gases and Blood pH Determination of Blood Po2 The concentration of O2 in a fluid can be measured by a technique called polarography. Electric current is made to flow between a small negative electrode and the solution. If the voltage of the electrode is more than −0.6 volt different from the voltage of the solution, O2 will deposit on the electrode. Furthermore, the rate of current flow through the electrode will be directly proportional to the concentration of O2 (and therefore to PO2 as well). In practice, a negative platinum electrode with a surface area of about 1 square millimeter is used, and this electrode is separated from the blood by a thin plastic membrane that allows diffusion of O2 but not diffusion of proteins or other substances that will “poison” the electrode. Often, all three of the measuring devices for pH, CO2 , and Po2 are built into the same apparatus, and all these measurements can be made within a minute or so using a single droplet-sized sample of blood. Thus, changes in the blood gas levels and pH can be followed almost moment by moment at the bedside.