Respiratory Centre

If the brainstem is transected between the mid-brain and the pons (decerebration), respiration in resting animals is not changed significantly. It means that the central mechanisms that control respiration are located in the medulla and the pons. The neurons grouped here are known as the ponttomedullary respiratory centre. A cut that separates the pons from the medulla may not disrupt the respiratory rhythm which will differ from the normal one. Consequently the most essential structures of the respiratory centre are located in the medulla oblongata, this is the medulllary respiratory centre.

Respiratory cycle. The processes in the respiratory system between the beginning of two sequential inspirations are called respiratory cycle. Its duration in resting man is 3-5 sec. The respiratory centre provides a characteristic excitation pattern of the respiratory muscles.

Excitation of motor neurons of phrenic nerves arises at a definite mo­ment (initiation of inspiration). It gradually intensifies (Fig. 153) at the expense of growing frequency of bursts of individual motor neurons and involvement in excitation of new ('late') motor neurons (the phrenic nerve contains about 1000 axons of motor neurons). During quiet breathing in human subjects excitation is intensified within 1-2.5 sec. As a result, the force of diaphragmatic contractions gradually increases. Then excitation of motor neurons of the diaphragm sharply weakens, and inspiration is replaced by expiratory phase. The next inspiration begins 2-3.5 sec later..Inspiration takes less time than expiration, as a rule.

Expiration comprises two stages. The diaphragm remains partially ac­tive in the beginning of expiration, then it goes down (the first or postinspiratory stage). This activity makes expiration more smooth. After cessation of the postinspiratory stage phrenic motor neurons are silent (the second stage).

Excitation of the inspiratory intercostal muscles has nearly the same ex­citation pattern as thai of the diaphragm but it arises a bit later than excita­tion of the diaphragm.

Respiratory neurons. Localization of the respiratory centre can be established by using methods for destruction and stimulation of separate brain areas. But the main information on the arrangement of structures of the respiratory centre has been obtained by means of microelectrodes for recording the membrane and action potentials of individual neurons that are excited in accordance with phases of the respiratory cycle.

There are two principal groups of respiratory neurons—inspiratory and expiratory. Action potentials of typical inspiratory neurons arise 0.1-0.2 Tec before the initiation of inspiration. During inspiration burst frequency gradually increases and reaches 70-100 per second by the end of inspiration (in deep inspiration it may attain 300). When inspiration is switched to ex­piration, bursts either cease or their frequency is sharply reduced.

The frequency of action potentials of expiratory neurons grows during expiration. Termination of bursts or decrease in their frequency takes place before the beginning of the next inspiration (Fig. 154).

Localization of respiratory neurons. The right and left halves of the medulla each contains two accumulations of respiratory neurons, the dor­sal and ventral respiratory nuclei.

The dorsal respiratory nucleus (Fig. 155) is locate near the solitary tract and consists mainly of inspiratory neurons whose axons pass to the phrenic nuclei of the cervical segment of the spinal cord. The axon col­laterals also pass to the ventral respiratory nucleus to form inhibitory synapses on its expiratory neurons. Thus, excitation of neurons of the dor­sal respiratory nucleus inhibits excitation of expiratory neurons of the ven­tral respiratory nucleus. Excitation of the neurons in the dorsal respiratory nucleus is encountered in rare cases (in about 5 per cent).

The ventral respiratory nucleus is rather long; it lies just lateral of the nucleus ambiguus and contains inspiratory and expiratory neurons sending their axons to phrenic, intercostal and laryngeal motor neurons.

The reticular formation of the medulla and pons also has a small number of respiratory neurons.

The third compact accumulation of respiratory neurons was discovered in animals-after transection of the vagus nerves in the anterior part of the pons immediately behind the corpora quadrigemina. The so-called pneumotaxic centre is located here (Fig. 156).

Dependence of Activity of Respiratory Centre on Blood Gas Content

The rate and depth of respiration are determined primarily by the ten­sion of gases dissolved in the blood and by blood concentration of hydrogen ions. The arterial CO₂ tension is of exceptional importance for assessing the value of pulmonary ventilation: it creates the demand to meet the needs of alveolar ventilation, as it were.

Formation of the carbon dioxide in tissues is proportional to the inten­sity of oxidation processes. The CO; content governs the acid-base balance of blood to a considerable degree, hence, the expediency to keep the arterial CO₂ tension at a constant level.

The body of a healthy adult has an adequate (and not the minimal) oxy­gen supply under normal conditions, except for the strenuous physical ex­ertion. For instance, of the alveolar air can be reduced to 80 mm Hg without causing any noticeable disturbances in the body. On the other hand, increase in the oxygen content in inspired air to 40 per cent ( of 304 mm Hg) also does not bring harm.

The organism of terrestrial animals and of man has been adjusted dur­ing evolution to breathing atmospheric air in normal (at sea level) or slight­ly lowered (at low altitude) atmospheric pressure. At the same time, the CO₂ tension is maintained at a relatively constant level, which is sufficient for ensuring the body with the needed amount of oxygen.

The terms 'hypercapnia', 'normocaonia' and 'hyposaonia' are used to designate the high, normal and low CO₂ tension in the blood, respectively.

The normal blood O₂ content is known as normoxia, while oxygen ciency in the body and tissues as hypoxia, and oxygen deficiency in blood as hypoxasmia. Increased oxygen tension is known as hyperoxia. condition in which hypercapnia is coupled with hypoxia is asphyxia.

The normal comfortable respiration at rest is called eupnoea. Hyper capnia and reduction of blood pH (acidosis) are accompanied crease in pulmonary ventilation or hyperpnoea aimed at f the body of excess carbon dioxide. Ventilation increases mainly at pense of increase in the depth of breathing (increase in tidal together with increase in the frequency of breathing. Hypercapnia can induced by breathing gas mixtures with increased (to.6 per cent) CO₂ con­tent.

Hypocapnia and increase in blood pH lead to reduction of ventilation and cessation of breathing or apnoea.

The development of hypoxia first causes moderate hyperpnoea (mainly due to increase in the frequency of breathing) which, with increase in degree of hypoxia, is followed by waning and cessation of breathing. Apnoea due to hypoxia is life-threatening. It is caused by diminution ofoxidation processes in the brain, including that in the respiratory centre neurons. Hypoxic apnoea is preceded by loss of consciousness.

Activity of the respiratory centre in man is under the voluntary control. Holding breath at will for 30-60 sec causes asphyxia-associated changes in blood gas content. After the onset of breathing hyperpnoea develops. Hypocapnia can be easily provoked by deep voluntary breathing and ex­cessive artificial pulmonary ventilation (hyperventilation). Even significant hyperventilation in a wakeful man is not followed by cessation of breathing because respiration is controlled by the forebrain. Hypocapnia is gradually compensated during several minutes.

Hypoxia develops when atmospheric pressure decreases in ascent to high altitude, in strenuous physical work and when respiration, circulation and blood composition are disturbed.

In heavy asphyxia breathing is characterized by the maximal depth to which accessory respiratory muscles contribute. Such respiration accom­panied by breathlessness is called dyspnoea.

Maintenance of normal blood gas content is mainly based on the negative feedback principle. Thus, hypercapnia causes hyperventilation and hypocapnia hypoventilation of the lungs.

Role of Chemoreceptors in Regulation of Respiration

It was established long ago that activity of the respiratory centre depends on the composition of blood supplied to the brain.

Fredericq (1890) has demonstrated this fact in experiments with cross-circulation. The carotid arteries of anaesthetized dogs were cut and then connected cross-wise and the jugular veins were connected separately (Fig. 157). After the vertebral arteries were ligated the head of each dog was sup­plied not with its own blood but with that of the other. If occlusion of the trachea of the first dog, for example, caused asphyxia, then hyperpnoea developed in the second dog. The first dog experienced apnoea some time later, despite increase in the arterial CO; and decrease in 0; tension. This is explained by the fact that the carotid artery of the first dog received blood of the second dog in which hyperventilation caused decrease in the arterial CO; tension.

Respiration is intensified under the influence of CO₂, H⁺ and moderate hypoxia which exert an indirect influence on the respiratory centre neurons. Excitability of respiratory neurons and of other nerve cells is reduced under the action of these factors. Consequently, they intensify ac­tivity of the respiratory centre by influencing special chemoreceptors.

There are two groups of chemoreceptors that regulate respiration: peripheral (arterial) and intracranial (medullary).

Arterial chemoreceptors are stimulated by the increased CO₂ and decreased O₂ tension and are located in the carotid sinuses and aortic arch. They reside in specialized small bodies abundantly supplied with arterial blood. The carotid chemoreceptors are of importance for the regulation of respiration. The aortic chemoreceptors have a weak influence on respira­tion but contribute to the control of blood circulation.

The carotid bodies are located in the bifurcation of the common carotid artery into the internal and external carotids. The mass of each carotid body is about 2 mg. The body contains rather large epithelioid type 1 cells surrounded by small interstitial type II cells. Type I cells make contacts with the endings of the afferent fibres of the carotid sinus nerve (Hering nerve), which is the branch of the glossopharyngeal nerve. It is still uncer­tain what: structures of the carotid body, either type I or type II cells or nerve fibres, are the receptors proper.

Chemoreceptors of the carotid and aortic bodies are the unique recep­tor formations which are stimulated by hypoxia. The afferent signals in the fibres branching out of the carotid bodies can be registered also at a normal (100 mm Hg) arterial 0; tension. With its decrease from 80 to 20 mm Hg the rise in the frequency of impulses is especially pronounced.

In addition, afferent impulses oflhe carotid bodies are intensified with increase in the arterial CO₂ tension and H⁺ concentration. A stimulating action of hypoxia and hypercapnia on these chemoreceptors is mutually in­tensified. On the contrary, under hyperoxia sensitivity of the chemorecep­tors to CO₂ is sharply reduced.

The carotid body chemoreceptors are highly sensitive to variations in the blood gas content. The degree of their activation rises with variations in the arterial CO₂ and O₂ tension, and is dependent even on inspiratory and expiratory phases in deep and slow breathing.

Sensitivity of the chemor-eceptors is under neural control: it is decreased upon stimulation of the vagus nerve efferents and rises when the sympathet­ic fibres are stimulated.

The chemoreceptors, especially those of the carotid bodies, rather quickly inform the respiratory centre about the O₂ and CO₂tension in the blood flowing to the brain.

Intracranial chemoreceptors. Denervation of the carotid and aortic bodies eliminates the effect under which respiration is intensified in response to hypoxia. In this case hypoxia is only responsible for decreased ventilation but activity of the respiratory centre still depends on the CO₂ tension and is conditioned by the function of intracranial chemoreceptors.

Intracranial chemoreceptors are located in the ventral surface of the medulla laterally of the pyramids (Fig. 158). Perfysion of this brain area by solution with low pH sharply intensifies breathing. Under the increase in pH, breathing becomes weaker (in animals with denervated carotid bodies breathing is arrested on'expiration). The same effect is achieved when this surface of the medulla is either cooled or treated with local anaesthetics.

Intracranial chemoreceptors are located in the medulla at the depth of not more than 0.5 mm. Two receptor areas have been discovered designated by the letters M and L with small area S lying between them. It is insensitive to the concentration of H⁺ ions but on its destruction all the effects produced by excitation of areas M and L disappear. It might be that the afferent pathways from the intracranial chemoreceptors to the respiratory nuclei of the medulla pass here.

Under normal conditions, the medullary chemoreceptors are con­tinuously stimulated by H⁺ ions of medullary interstitial fluid. Its H⁺ con­centration depends on the arterial CO; tension and is increased in hyper­capnia.

The influence of the intracranial chemoreceptors on the activity of the respiratory centre is stronger than that of the peripheral ones. They markedly change pulmonary ventilation. Thus, the pH decrease in the cerebrospinal fluid by 0.01 causes the increase in ventilation by 41/min.

At the same time, intracranial chemoreceptors respond to changes in the arterial CO₂; tension later (in 20-30 sec) than the peripheral ones (in 3-5 sec). This can be explained by the fact that certain time is needed for the stimulating factors to diffuse from the blood into the interstitial fluid.

Signals arriving from intracranial and peripheral chemoreceptors are necessary for rhythmicity of the respiratory centre and correspondence be­tween pulmonary ventilation and blood gas content. Impulses from in­tracranial chemoreceptors augment excitation of both inspiratory and ex­piratory neurons.

Role of Mechdnoreceptors in Regulation of Respiration

Hering-Breuer reflex. Signals arriving from the mechanoreceptors located in the lungs along the vagal afferents facilitate the sequence of respiratory phases, i.e. rhythmicity of the respiratory centre. After the vagus nerves that transmit these impulses have been cut breathing in animals becomes slower and deeper. On inspiration the inspiratory activity is growing at the same rate until a new higher level has been achieved (Fig. 159). It means that the afferent signals passing from the lungs act faster to ensure the inspiration-expiration sequence than the respiratory centre! devoid of feedback with the lungs. Following vagotomy, the expiratory phase becomes longer. Hence, impulses from the pulmonary receptors also facilitate the inspiration-expiration sequence and -make the expiratory phase shorter.

Strong and constant respiratory reflexes that accompany changes in the lung volume were described by Hering and Breuer in 1868. Increase in the, lung volume induces three reflex effects. First, lung inflation in inspiration may cause premature inhibition of inspiration (the inspiratory-inhibitory reflex). Second, lung inflation in expiration causes delay of the onset of the next inspiration, and expiratory phase becomes longer (\^e expiratory-facilitating reflex). Third, rather forceful inflation of the lungs induces augmented inspiration or sigh.

Decrease in the lung.volume determines deeper inspiration and short expiration, i.e. facilitales initiation of the next inspiration (lung deflation reflex).

Thus, activity of the respiratory centre depends on changes in the lung volume. The Hering-Breuer reflexes ensure the so-called volume feedback of the respiratory centre with the executive apparatus of the respiratory system.

The importance of the Hering-Breuer reflexes consists in the regulation of respiratory depth and rate, depending on condition of the lungs. When the vagus nerves are intact, hyperpnoeic respiration caused by hypercapnia or hypoxia is manifested by intensification of both respiratory depth and rate.

Following vagal blockade, breathing frequency is not increased, pulmonary ventilation is gradually augmented only due to deeper breathing.As a result, the maximal value of pulmonary ventilation is reduced by nearly 50 per cent. Thus, signals passing from the pulmonary 'receptors ensure increased respiratory rate in hyperpnoea caused by hyper­capnia and hypoxia.

The importance of the Hering-Breuer reflexes in the regulation of quiet breathing in adult men, as distinct from animals, is not great. At rest tem­porary blockade of the vagus nerves by local anaesthetics does not cause any significant changes in the respiratory depth and rate. A higher frequen­cy of respiration in hyperpnoea in man and animals is ensured by the Hering-Breuer reflexes.

These reflexes are well pronounced in newborn babies and of impor­tance in shortening respiratory phases, particularly those of expiration. Their intensity decreases in the first days and weeks after birth.

The lungs contain numerous endings of the afferent nerve fibres. Three groups of pulmonary receptors are known, namely, pulmonary stretch receptors, lung-irritant receptors and receptors with C-fibres. No special­ized chemoreceptors for CO₂ and O₂ were found in the lungs of mammals.

Pulmonary'stretch receptors. Excitation of stretch receptors arises and grows when the lung volume is enhanced. The frequency of action poten­tials in stretch receptor afferents is increased in inspiration and decreased in expiration. Deeper inspiration increases the frequency of impulses sent by stretch receptors to the respiratory centre. The threshold for pulmonary stretch receptors is not the same. Nearly half of them are also excited in ex­piration; in some of them rare impulses arise even in complete lung collapse but in inspiration the frequency of impulses in them sharply increases (/ow- ihreshold receptors). Other receptors are excited only during inspiration when the lung volume exceeds functional residual capacity (high-threshold receptors). In prolonged increase in the lung volume taking many seconds the discharge frequency of receptors diminishes very slowly (slow adapting stretch receptors). The discharge frequency of pulmonary stretch receptors is lowered in increase in the CO₂ content in the airway lumen.

Each lung contains about 1000 stretch receptors. They are mostly pre­sent in smooth muscles of the airway wall, from the trachea to small bron­chi. The alveoli and pleura are devoid of them.

Increase in the lung volume stimulates stretch receptors indirectly. Their direct stimulus is the inner tension of the airway wall, which depends on pressure difference on both sides of their wall. Increase in the lung volume causes the elastic recoil force of the lung to increase. The alveoli with a tendency to collapse distend the bronchial walls in the radial direc­tion. Therefore, stimulation of stretch receptors depends not only on the lung volume but also on the elastic properties of pulmonary tissue, on its compliance. Stimulation of receptors of the extrapulmonary airways (the trachea and large bronchi) lying in the thoracic cavity is mainly determined by the negative pressure in the pleural cavity though it also depends on the degree of contraction of smooth muscles of their walls.

Stimulation of pulmonary stretch receptors gives rise to the inspiratory-inhibitory Hering-Breuer reflex. Most of the afferent fibres from pulmonary stretch-receptors pass to the dorsal respiratory nucleus of the medulla in which the activity of inspiratory neurons undergoes different changes. About 60 per cent of them is inhibited under these conditions. They act in accordance with the activity of the inspiratory-inhibitory Hering-Breuer reflex (neurons I_a). In contrast, other inspiratory neurons are excited on stimulation of stretch receptors (neurons I_b). In addition, there are the so-called P-neurons which are stimulated by the impulse? passing from only pulmonary stretch receptors.

Respiratory changes depend on the stimulation frequency of pulmonary stretch receptor afferents. The inspiratory-inhibitory and expiratory-facilitating reflexes arise only at relatively high (over 60 per se­cond) frequencies of electrostimulation. In contrast, in low-frequency elec-trostimulation (20-40 per second) inspiration becomes deeper and expira­tion shorter. It might be supposed that relatively rare discharges of pulmonary stretch receptors in expiration facilitate the onset of the next in­spiration.

Lung-Irritant Receptors and Their Influence on the Respiratory Centre

The lung-irritant receptors arepresent predominantly in the epithelium and subepithelial layer of the airways. Their number is particularly great around the tracheal bifurcation and the roots of the lungs. Part of them possess the properties of both the mechano- and chemoreceptors and are stimulated in rapid variations of the lung volume. The thresholds for their stimulation are higher than those for the majority of pulmonary stretch receptors. Impulses in the lung-irritant receptor afferents arise for only a short time in the form of outbursts when the lung volume is changed (manifestation of rapid adaptation). These receptors are also called the racjjdiy adapting pulmonary, meghanoreceptors. Some of them are excited even during normal Inspiration and expiration. Among the numerous fac­tors that cause their stimulation are dust particles, mucus accumulated in the airways, various irritants like vapours of ammonia, ether, sulphur dioxide, cigarette smoke, and certain biologically active substances that form in the airway walls, especially histamine. Stimulation is also facilitated by decrease in lung compliance. It is particularly strong in bron­chial asthma, lung oedema, pneumothorax, and pulmonary congestion which are responsible for typical shortness of breath (dyspnoea) in stimulation of the irritant receptors human subjects experience the uncomfortable sensation of the type of rasping and burning.

Stimulation ot trie'imTant receptors in the larynx and trachea provokes cough. When the bronchial receptors are stimulated, inspiration becomes deeper and expiration shorter at the expense of the earlier onset of the next inspiration. As a result, the respiratory rate increases. Lung-irritant receptors also contribute to lung collapse and their impulses bring about reflex bronchoconstriction.

Stimulation of the irritant receptors causes augmented breaths or sighs in response to lung inflation. The importance of this reflex consists in the following. In quiet breathing man regularly takes deep breath, about three times in an hour. By the time of onset of such a sigh the uniformity of ventilation and lung compliance decrease. This gives rise to stimulation of the irritant receptors so that a deep sigh is superimposed on the next in­spiration. The lungs become expanded, and uniformity of their ventilation is recovered.

Receptors with C-fibres. These receptors are located near the lung capillaries in the alveolar interstitial tissue (the so-called J-receptors that were discovered in 1955 by A.S. Paintal in Dehly) and in the airway walls. They are stimulated by a number of biologically active substances such as phenyl diguanide, capsaicine, bradykinin, and prostaglandins. In healthy animals J-receptors have weak tonic activity. The primary stimulus of these receptors is the increase in the volume of interstitial fluid. This takes place in severe exercise and in pathological conditions (pneumonia, pulmonary oedema, microembolism, lung congestion). Stimulation of the receptors with C-fibres evokes apnoea followed by rapid shallow breathing and bronchoconstriction.

Receptors of the pleura. The importance of these receptors in the regulation of normal breathing is not great. Pleura has neither stretch nor chemoreceptors that significantly affect the respiratory centre activity.

When the smooth pattern of the pleural layers is impaired due to in­flammation (pleurisy), respiratory movements are attended by strong pain­ful sensation. Pain arises mainly due to stimulation of the parietal pleura receptors.

Pneumotaxic centre. Separation of the pons from below the guadrigeminal body is accompanied by respiratory changes similar to those that arise after vagotomy. The respiratory rate is decreased due to longer inspirations and expirations. Additional vagotomy makes inspirations ex­tremely prolonged—they take scores of seconds or minutes. Inspiration of the unusually long duration is called apneusis (Fig. 162). The structures of the upper portion of the pons whose destruction after vagotomy leads to the appearance of apneusis are known as the pneumotaxic centre.

It has been established that bilateral connections exist between the respfratory bulbar and pneumotaxic centres. Stimulation of separate zones of the pneumotaxic centre may cause a premature inspiration or expira­tion.

Visual material

1. Oxyhaemoglobin dissociation curve.

2. The scheme of the pump of Setchenov.

3. The scheme of microtonometer by Krog.

4. The scheme of diffusion of gases.

5. Functional system of breath.

6. Transport of gases blood.

7. The scheme of structure and purtial pressure of inhaled, exhaled and alveolar air.

8. Graflogichesky structure «breath Regulation».

9. Breath regulation.

10. Experience by Frederic.

11. Humoral breath regulation.

Rerferences

1. Глебовский В.Д., Шимарева В.Д. Дыхание // Физиология плода у детей. – М.: Медицина, 1988. – С.60-87.

2. Физиология человека: Учебник /В двух томах. Т. I /Под ред. В.М.Покровского, Г.Ф.Коротько. –М.:Медицина, 2003. – С. 98-108.

3. Физиология человека (курс лекций в 2-х книгах). Учебник /Под ред. Н.А.Агаджанян, Л.З.Тель, В.И. Циркин, С.А.Чеснокова. – Алма-Ата: Казахстан, 1992. –С. 58-65.

4. Основы физиологии человека /Под ред. Б.И.Ткаченко. – С.-Петербург, 1994. Т. I. – С. 124-125.

5. Физиология. Основы и функциональные системы: Курс лекций. /Под ред. К.В.Судакова. –М.:Медицина, 2000. – С. 12-27.

6. Теория функциональных систем организма. Под ред. К.В. Судакова. М., 1996. – 95 с.

Control questions (feedback)

1. The mechanism of the first breath of the child.

2. With what it is connected low size elastic draughts of lungs at an exhalation at the newborn?

3. Value of reflexes of Goering and Brayer at newborns.

4. As frequency of breath of the child changes at sucking movements.

5. What is irritant receptors and their value in the breath mechanism?

Дата добавления: 2015-08-10