The document summarizes the regulation of respiration through respiratory centers located in the brainstem and pons. It discusses the dual control of automatic and voluntary respiration, and describes the roles of various centers including the pneumotaxic, apneustic, dorsal respiratory group (DRG), and ventral respiratory group (VRG). Peripheral chemoreceptors like the carotid and aortic bodies that sense blood gases, and pulmonary stretch receptors are also involved in regulating breathing. Higher brain centers and various factors influence respiration.

1. REGULATION OF RESPIRATION

2. REGULATION OF RESPIRATION The mechanism of regulation of respiration is an effective and sensitive mechanism. Our need for O 2 changes from time to time, so also the CO 2 production, but the body O 2 - and CO 2 -status remain more or less constant. I t has a dual control , i.e., as such respiration is automatic but if we want, we can also make it voluntary. Normal respiration is a rhythmic phenomenon, i.e., inspiration - expiration cycle occurs in a regular manner. This is effected by the respiratory centres which receive inputs from peripheral receptors as well as from other centres and then achieve the desired ventilation through the effectors (respiratory muscles) .

4. THE RESPIRATORY CENTRES Respiratory centres are groups of neurons. These are present in the brainstem and are paired (each centre is two in number and situated on either side of the midline). These are interconnected .

5. Pneumotaxic centre (PN) It is situated in the upper pons in the nucleus parabrachialis medialis (NPBM) and in the Kolliker-Fuse nucleus. Its absence causes apneustic type of breathing, i.e., breathing characterised by prolonged inspiration. When the vagi are intact respiration becomes slow and deep after damage of this centre. The pneumotaxic centres relay information from higher centres. They normally cut down the activity of inspiration, so that there is quick initiation of expiration, thus they may help to increase the rate of respiration.

6. APNEUSTIC CENTRE It is situated in the lower pons and stimulates the inspiratory centre to increase inspiratory activity. It gets feedback from vagal afferents and also from other respiratory centres.

7. Medullary respiratory centres: dorsal respiratory group (DRG) The centres have two types of activities - inspiratory and expiratory and are as follows DRG. It is a group of inspiratory neurones, which is diffusely situated on the dorsal aspect of medulla in and around the nucleus of tractus solitarius. It is responsible for generation of the inspiratory ramps (the type of electrical activity which gradually increases and then stops suddenly). This activity of the DRG is rhythmic, which is then transmitted to the respiratory motor neurones in the anterior horn of spinal cord and ultimately leads to contraction of the inspiratory muscles to cause inspiration.

8. Medullary respiratory centres: dorsal respiratory group (DRG) The DRG is autorhythmic and can maintain somewhat rhythmic respiration in absence of all other inputs. For normal rhythmic respiration it is helped by feedback information from peripheral chemoreceptors, vagal inputs, central chemoreceptors and inputs from other centres.

9. Medullary respiratory centres: ventral respiratory group (VRG) It is situated in the ventral aspect of medulla and contains both inspiratory and expiratory neurones. Its cranial part is in the nucleus ambiguus which supplies the accessory muscles of respiration. The caudal part is situated in the nucleus retroambiguus which supplies both the inspiratory and the expiratory muscles (i.e., external and internal intercostals). This ventral group in driven by the dorsal group. Both the medullary centres (DRG and VRG) are interconnected and are equally important for rhythmic respiration.

11. HIGHER CENTRES Cerebral cortex, cingulate gyrus, limbic system and hypothalamus also have influence. They do so via the other centres or can directly influence the respiratory motor neurons. Therefore the DRG is responsible for normal rhythmic inspiration. Expiration occurs automatically when there is no inspiratory activity (the VRG acts in case of voluntary or increased respiratory activity). Other centres and influences from the periphery act to influence this inspiratory activity of DRG.

14. ORGANISATION OF THE RESPIRATORY CENTRES (the classical concept) There is continuous discharge of impulse from the continuously active apneustic centres to the inspiratory centres and also to the pneumotaxic centres. Due to stimulation of the inspiratory centres, inspiration occurs. In the mean time, the pneumotaxic centres are also stimulated. The stimulated pneumotaxic centres now inhibit the apneustic centres, so inspiration is stopped and expiration automatically follows. Now, as apneustic centres are inhibited, pneumotaxic centres are no longer stimulated. So the latter is not inhibiting the former and apneustic centre gets automatically stimulated to start another inspiration.

15. EXPERIMENTAL PROOF If a section (A) is made above the pons, normal respiration continues. A section (B) below the medulla oblongata stops all respiratory activities; that means the respiratory centres are in between these two levels. A section (C) through the upper part of pons results in apneustic type (prolonged inspiration) of breathing; that means, above this level there is a centre which inhibits inspiration. If the vagus nerves are intact this effect is not seen well but if both the vagi are cut the apneustic type of breathing develops in proper form. A section (D) above medulla oblongata with intact vagi maintain rhythmic respiration even after cutting the vagi. It means the medullary centres are the ramp generators.

16. ORGANISATION OF THE RESPIRATORY CENTRES (the modern concept) The respiratory centres are composed of an extensive and complex network of neurones, extending through the brainstem (“ bulbopontine respiratory neuronal complex ”). In this complex there is one inspiratory ramp generator which drives the inspiratory muscle. Another group of neurone is stimulated which also compute the vagal inputs and suddenly stimulates a third group called the inspiratory off switch (IOS). IOS, once stimulated, depresses the ramp generation, so inspiration stops and expiration follows. IOS is finely tuned by the pneumotaxic centres and also by the chemoreceptor drive. The rhythmic respiration is the function of the medullary respiratory centres and other agents just help it. The inspiratory ramp generator is the DRG but at present another group of neurone in the medulla.

18. THE PERIPHERAL MECHANISM INFLUENCING RESPIRATION These are various receptors situated in different parts of the body. These are connected to the respiratory centres by means of nerves. One group of them sense the chemical composition of the blood in respect to O 2 , CO 2 , H + , and help the respiratory centres to determine the amount of ventilation needed. Another group detects the amount of ventilation actually achieved and inform the centres which then adjust the respiration accordingly.

19. RECEPTORS PRESENT IN THE LUNGS: PULMONARY STRETCH RECEPTORS These are situated among the smooth muscles of the small airways and are stimulated due to alteration of the shape (e.g., stretching) of these airways. These receptors influence the centre via vagi by Hering-Breuer reflexes and lead to changes in respiration.

20. Hering-Breuer reflex (HB reflex) It is a volume reflex and operates due to inflation and deflation of the lungs. Accordingly it is of two types: HB inflation and HB deflation reflex. Receptors for both the varieties are situated in between the smooth muscles of the small airways. The receptors are unmyelinated nerve endings which are stimulated due to change of shape of the airways .

22. HB inflation reflex When air enters inside the lungs during inspiration the airways are stretched and stretch receptors are stimulated. The impulse is then rapidly conducted to the respiratory centres by myelinated vagal afferents, which cut down inspiratory activity. So, inspiration stops and expiration starts. In man the effect of HB inflation reflex is to increase the rate of breathing when the tidal volume is high (1.0 L or more) as in case of physical exercise. Expiration follows and the next inspiration starts very quickly as the respiratory demand is very high. This way respiration becomes quicker. This HB inflation reflex cuts down inspiration before the lung volume increases very much and thus helps the lungs to operate at lower volume.

23. HB deflation reflex HB reflex does not operate during normal condition. It operates when the lungs are deflated very much and stimulates inspiration. The receptors are stimulated due to change of shape of the small airways in a collapsed area. This reflex also prevents collapse of the lungs (atelectasis) and helps to open up a collapsed portion.

24. RECEPTORS PRESENT IN THE LUNGS: LUNG IRRITANT RECEPTORS These are nerve endings and are situated in between the epithelia lining the respiratory tract. They respond to irritant materials in the inspired air (like cigarette smoke) and reflexly cause cough or bronchospasm via vagi (myelinated fibres).

25. RECEPTORS PRESENT IN THE LUNGS: J - RECEPTORS J - receptors are situated in the alveoli near the pulmonary capillaries and are connected to the centres by the vagi (nonmyelinated fibres). They are stimulated by: 1) engorgement of pulmonary capillaries, 2) pulmonary oedema, 3) microembolism in lungs. Stimulation of these receptors leads to inhibition of the skeletal muscles (which was his observation in Bhopal gas tragedy).

26. PROPRIOCEPTORS IN THE CHEST WALL These are mainly the muscle spindles in the muscles of inspiration (mainly intercostals) together with the receptors in tendons, joints and ligaments in the thoracic cage. They are also called “load detecting receptors” as they sense the load of ventilation and accordingly regulate the amount and force of muscle contraction to achieve the desired ventilation. Afferent information from these spindles to the cortex gives rise to the sense of breathlessness when respiratory demand increases.

28. CENTRAL CHEMORECEPTORS It is a specialised area in the brainstem, situated in the ventromedial aspect of the medulla near the origin of 9th and 10th nerves. It is a separate area from the respiratory centres but connected to the respiratory centres. Central chemoreceptors are not stimulated by hypoxia. The neurones here can sense the change in H + in the brain interstitial fluid which is in equilibrium with the H + in cerebrospinal fluid. When H + increases, it causes stimulation of breathing. CO 2 from blood cannot pass the blood brain barrier so easily. Therefore, CO 2 does not influence the activity of these receptors directly but do so by producing hydrogen ions.

29. CENTRAL CHEMORECEPTORS

30. PERIPHERAL CHEMORECEPTORS These are the carotid bodies and the aortic bodies. They sense the PCO 2 , PO 2 and pH of blood. They are connected to the respiratory centres via 9th (carotid bodies) and 10th (aortic bodies) nerves. When there is increased PCO 2 , decreased PO 2 or decreased pH, they are stimulated and lead to stimulation of respiration.

31. THE CAROTID BODIES & THE AORTIC BODIES The carotid bodies are situated on either side at the bifurcation of the common carotid arteries. They are small projections from the wall of the vessels. They are composed of glomus tissue and are also called glomus caroticum. The carotid body is composed of mainly two types of cells called type I and type II cells; of them the type II is a neuroglial cell and type I is the receptor cell. Catecholamines are released from these type I cells (Ca mediated) in response to hypoxia. Catecholamines then stilmulate the afferent nerve endings. The carotid bodies are supplied by the afferent fibres of 9th nerve.

32. THE CAROTID BODIES ARE THE MAIN RECEPTORS FOR HYPOXIA They are richly supplied with blood. Blood flow is 2 L/minute per 100 g of tissue and is the highest of all organs in the body. A slight difference in PO 2 can be detected by this organ, though for a marked change in respiration a sufficient hypoxia is needed. The carotid bodies can be stimulated due to sympathetic stimulation as well. Being situated peripherally the carotid bodies can send information about the changed PCO 2 through the nerves. They also respond to changed pH. A fall in pH leads to stimulation of respiration through the carotid bodies.

33. AORTIC BODIES The aortic bodies are many small masses situated in the arch of aorta. They are supplied by the 10th cranial nerve. Being inaccessible, they have been studied less. It is presumed that, more or less they behave like the carotid bodies. It is also said that, in human, aortic bodies show no response to pH change.

35. ARTERIAL BARORECEPTORS These are stretch receptors situated in different parts of the arterial tree. They are stimulated by rise of BP and lead to reflex inhibition of respiration (apnoea) along with other effects. When BP is low they are not stimulated, so respiration is not inhibited and there is tachypnea (increased rate of respiration).

36. TEMPERATURE RECEPTORS ON SKIN These receptors on their stimulation change the breathing pattern momentarilly. A rise of body temperature leads to rise of ventilation as seen in fever.

37. CORONARY CHEMORECEPTORS Stimulation of coronary chemoreceptors leads to inhibition of respiration (apnoea) and then followed by rapid shallow respiration.

39. ROLE OF HIGHER CENTRES: THE CORTEX Voluntary regulation of respiration is done by cerebral cortex and we can increase, decrease or even stop respiration at our will. There is direct pathway from the cortex to the respiratory motor neurons via the corticospinal tract. Stimulation of premotor area also leads to stimulation of respiration.

40. ROLE OF HIGHER CENTRES: THE LIMBIC SYSTEM Different parts of the limbic system, e.g., the cingulate gyrus and also the hypothalamus show relation with respiration. Emotional activities (the typical example is sobbing) also lead to a change in respiration. That means these structures, being the seat of emotion, can influence respiration.

41. ROLE OF SPINAL CORD Spinal cord provides the pathways to the respiratory motor neurones both for automatic and voluntary respiration. Along with this, for a desired increase or decrease in the activity of these neurones and integration between the neurones controlling the antagonist and protagonists, is helped by the spinal interneurones. These interneurones are influenced by supraspinal influence as well as by afferent inputs through the sensory nerves.

42. INTEGRATED CONTROL Activity of the respiratory centres as such is suficient to maintain rhythmic respiration when the respirartion demand is constant. But in changed situation, feedback information from different receptors in the body are essential to change the respiration according to the need. These information for usual control are of two types. One from the chemoreceptors and the other mainly from the volume receptors in lung. After computing these information, respiratory demand is determined and the same is achieved by the respiratory centres through the muscles of respiration.

43. MAJOR FACTORS IN THE CONTROL OF RESPIRATION

44. MODIFIED RESPIRATIONS: COUGH It is the process where respiration is modified and utilised to expel the unwanted materials from the respiratory passage. It usually results due to stimulation of lung irritant receptors but can also be initiated voluntarily. In the process, there is a deep inspiration followed by a violent expiration against the closed glottis which then suddenly opens. This creates a high postive pressure inside the chest (up to 100 mm of Hg) and high velocity of air outflows through the mouth (up to 900 km/ hour). It helps in keeping the respiratory passage clean.

45. MODIFIED RESPIRATIONS: SNEEZING & HICCUP Sneezing : It is like cough but the air outflow occurs through the nose without any closure of the glottis. Hiccup : It is produced due to sudden closure of the glottis during inspiration caused by a spasmodic contraction of the diaphragm.

46. Effects of CO2 on Respiration Normal respiration is a function of CO 2 . When PCO 2 increases (hypercapnia) respiration is stimulated to get rid of the CO 2 . When PCO 2 decreases (hypocapnia) there is no stimulation, so respiration stops to build up the PCO 2 . If alveolar PCO 2 is increased, CO 2 content of the body increases and respiration is stimulated. If the alveolar PCO 2 is increased by 1%, respiratory minute volume increases by 2 to 3 litres. 80% of this increase is due to central chemoreceptors and 20% is due to peripheral chemoreceptors. This increased ventilation helps to wash out the CO 2 . The response to increased P co 2 is less during sleep, in old age, in divers and in trained athletes.

47. Effects of Hypoxia on Respiration Hypoxia means decreased O 2 in the body, so in hypoxia the aim is to increase O 2 supply to the body. It is done by increasing alveolar ventilation through stimulation of chemoreceptors. The respiratory centers are depressed by hypoxia by direct effect. Though hypoxia by itself is not a good stimulus for respiration but in presence of increased CO 2 it becomes a very much potent stimulus. During hypoxia, the amount of reduced haemoglobin in blood increases which also lowers the H + in blood (Hb is less acidic than HbO 2 ) and inhibits respiration.

48. Effects of pH on Respiration The effect of pH or [H + ] on respiration is also important (in fact CO 2 acts by producing H +) . H + acts via chemoreceptors and leads to stimulation of respiration. H + in blood increases in respiratory and metabolic acidosis. In respiratory acidosis the cause is CO 2 excess. So, here both the central and peripheral chemoreceptors are stimulated easily as CO 2 can pass easily througth the blood brain barrier. It case of metaboilc acidosis the carotid bodies are stimulated immediately but as the H+ from blood cannot enter into the brain so easily it takes time to affect respiration through central chemoreceptors and ultimately respiration is strongly stimulated (Kussmaul breathing). Respiration is inhibited in alkalosis.

49. Effects of physical exercise on respiration Physical exercise leads to increased ventilation (up to 100 litre/ minute). Ventilation is increased even before the start of exercise due to the activity of the higher centres (the motor cortex and also the hypothalamus). Associated sympathetic stimulation may also lead to stimulation of breathing during exercise. Increased temperature of blood stimulates breathing. Movement of joints and contraction of the muscles lead to reflex stimulation of ventilation. In moderate exercise, ventilation though increases, PCO 2 remains remarkably constant and PO 2 may be slightly increased. Lactic acid liberated during severe exercise may stimulate respiration (it can not be buffered and H + concentration increases).

50. Other effects of exercise on respiration Increased pulmonary blood flow increases the number of active capillaries and also distension of the capillaries leading to an increased area of the alveolocapillary membrane thus increasing pulmonary gas exchange.

51. SLEEP AND RESPIRATION During sleep, due to loss of general alertness, effect of cortical influence on brain stem centres is absent, hence respiration is left to automatic control through chemical and neural feedback. Effect of CO 2 is also decreased but response to decreased O 2 is normal. Due to decreased muscle tone in the airways there may be obstruction, particularly in the upper respiratory tract resulting in sleep apnoea (increases with age due to decreased activity of the central mechanism).

53. HYPERVENTILATION When both rate and depth of respiration are increased the condition is called hyperventilation . Voluntary hyperventilation is the condition when ventilation is increased voluntarily. So, alveolar ventilation becomes more than is needed. The resultant condition is called hypocapnia . Hypocapnia may lead to alkalosis , and many other consequent complications like tetany . Decreased CO 2 also leads to stoppage of respiration. That s why voluntary hyperventilation is followed by apnoea .

54. Effects of voluntary hyperventilation on the alveolar CO 2 tension (as the ventilation rate (VE) rises, the PCO 2 falls).

55. TYPES OF BREATHING Apnoea: No respiration. Hyperpnoea: Hyperventilation. Eupnoea: Normal respiration. Tachypnoea: Increased rate with decreased tidal volume. Bradypnoea: Very slow respiration .

56. Apnoea Apnoea means arrest of respiration. Apnoea may be due to different reasons. Voluntary apnoea : When one stops respiration voluntarily, it is called voluntary apnoea or breath holding. This results in accumulation of CO 2 in the body, hence respiration is severely stimulated and at one point the subject cannot but is forced to take respiration. This is called breaking point . The duration of breath holding in normal adults is about 50 seconds.

57. Apnoea Deglutition apnoea : During deglutition, as the food bolus passes through the pharynx, the larynx is reflexely closed and respiration stops. This is called deglutition apnoea. Adrenaline apnoea : When adrenaline is injected in high dose (in a cat), apnoea occurs, this is called adrenaline apnoea (adrenaline increases BP —> baroreceptors are stimulated —> inhibitory impulse to centre —> respiration is stopped).

58. DYSPNOEA & ORTHOPNOEA Normal respiration is an effortless automatic phenomenon, when effort is to be given for breathing, it results in an unpleasant sensation called dyspnoea . Physiological dyspnoea may occur in violent muscular exercise when most of the breathing reserve is utilised. Pathological dyspnoea occurs in bronchial asthma, bronchitis, emphysema, heart failure (in asthma is due to increased work of breathing). When dyspnoea occurs only in lying down position but not in erect posture, then it is called orthopnoea . It occurs in congestive cardiac failure.

59. SPECIAL TYPES OF BREATHING When respiration shows alternate waxing and waning of tidal volume, it is called Cheyne-Stokes respiration . The respiratory centres are depressed which do not behave normally and if stimulated they over-react. In such conditions, due to slow rate of perfusion, even normal ventilation lowers the PCO2 and this stops respiration gradually. Then CO2 builds up but it takes again longer time to reach the brain due to slow circulation to repeat the cycle. Cheyne-Stokes respiration is also seen in brain injury, in high altitude during sleep and in normal children during sleep.

60. Biot's Respiration When the respiration is characterised by alternate eupnoea and apnoea then it is called Biot's respiration . It is seen in case of meningitis, severe brain damage, etc. It is also called periodic breathing.

61. Kussmaul Breathing The other names of this condition are air hunger and acidotic breathing . It occurs in case of metabolic acidosis as in diabetic ketoacidosis, renal failure, etc. The respiration is characterised by rapid and deep breathing. This is due to stimulation by increased H + . The main action of H + of blood is via peripheral chemoreceptors. H + ions can also cross the blood brain barrier slowly when the concentration is high and persistent. In that case the central chemoreceptors are also stimulated.

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