Physiology Lecture Notes on Regulation of Respiration PDF

(002) REGULATION OF RESPIRATION DR. (AUSTRIA ABRAHAM) | 12/08/20 OUTLINE 1. Medullary Respiratory Center I. MAJOR SITES OF VENTILAT...

(002) REGULATION OF RESPIRATION DR. (AUSTRIA ABRAHAM) | 12/08/20 OUTLINE 1. Medullary Respiratory Center I. MAJOR SITES OF VENTILATORY CONTROL - Reticular formation of the medulla A. Respiratory Control Center beneath the floor of the fourth B. Central Controllers ventricle. 1. Medullary Respiratory Center o Dorsal Respiratory group – associated 2. Apneustic Center with inspiration 3. Pneumotaxic Center - Nucleus Tractus Solitarus C. Central Chemoreceptors ▪ at dorsomedial region and D. Peripheral Chemoreceptors receives afferent inputs from E. Lung/Pulmonary Mechanoreceptors/ Sensory CN IX & X which originates Nerves from airways and lungs. 1. Pulmonary Stretch Receptors ▪ Functions as breathing 2. Irritant Receptors pacemaker. 3. J. Receptors (Juxta-Capillary Receptors) o Ventral Respiratory group 4. Bronchial C Fibers F. Other Receptors - Associated with expiration. 1. Nose and Upper Airway Receptors - Inactive in normal respiration 2. Joint Muscle Receptors - Operates when high levels of 3. Somatic Receptors ventilation are required II. INTEGRATED RESPONSES o Pre-Botzinger Complex A. Response to CO2 - Respiratory rhythm, Located in B. Response to PO2 ventrolateral region. C. Response to pH 2. Apneustic center D. Response to Exercise Located in the lower pons III. ABNORMALITIES IN CONTROL OF BREATHING Prolonged inspiratory gasps interrupted A. Sleep Apnea by transient expiratory effort. 1. Obstructive Apnea 2. Central Sleep Apnea Has excitatory effect on the inspiratory B. Cheyne-Stokes Ventilation area of the medulla C. Apneustic Breathing 3. Pneumotaxic Center Located in the upper pons Inhibits inspiration and thus regulate I. MAJOR SITES OF VENTILATORY CONTROL inspiratory volume and respiratory rate (switch off) Cortex - Responsible for voluntary control of breathing Figure 1. (Ventilatory Control System). A. RESPIRATORY CONTROL CENTER Located in the medulla oblongata of the brain stem and is composed of multiple nuclei that generate and modify the basic ventilatory rhythm. o Function - Ventilatory pattern generator, which Figure 2. (The Respiratory Control Center is Located in the sets rhythmic pattern Medulla, the Most Primitive Portion of the Brain). The neurons - An Integrator, which controls are mainly in two areas: the dorsal respiratory group (DRG), which generation of the pattern and controls consists of the nucleus tractus solitarius, and the ventral respiratory the rate and amplitude of the group (VRG), which consists of the rostral nucleus retrofacialis, ventilatory pattern. nucleus paraambiguus, and the caudal nucleus retroambiguus. C1 refers to the first cervical signal segment to the caudal border of the B. CENTRAL CONTROLLERS pons. The fourth ventricle of the brain is located below the Includes the brain, particularly the brainstem cerebellum and above, and between, the pons and the medulla. Page 1 of 5 PREPARED BY: CMED 1C  (002) REGULATION OF RESPIRATION DR. (AUSTRIA ABRAHAM) | 12/08/20 CHEMORECEPTORS D. PERIPHERAL CHEMORECEPTOR Specialized tissues that respond to a change in the chemical composition of the blood or other fluid. Located in the specialized cells in the Aortic Arch (aortic 1. Central Chemoreceptor bodies) and at the bifurcation of the internal and external 2. Peripheral Chemoreceptors carotid arteries (Carotid bodies) in the neck. The carotid and aortic bodies are peripheral chemoreceptors that respond to changes in PaO2 (not the C. CENTRAL CHEMORECEPTOR O2 content), PaCO2, and pH, and they transmit afferent Located in the central nervous system just below the information to the central respiratory control center. Ventrolateral surface of the medulla Sensitive to the PCO2 but not PO2 of blood. Responds to the change in pH of the ECF/CSF when CO2 diffuses out of cerebral capillaries – regulates ventilation. CSF pH has a more important effect in changes in the level of ventilation and the arterial PCO2. Normal CSF pH is 7.32 CO2 and the blood brain barrier o Arterial CO2 crosses the blood-brain barrier and rapidly equilibrates with CSF CO2. o H+ and HCO3− ions cross the barrier slowly. o Arterial CO2 combines with metabolic CO2 to dilate the smooth muscle. o When compared with arterial blood, the pH of CSF is lower and the PCO2 is higher, with little protein buffering. Figure 4. (Respiratory control by peripheral chemoreceptors in the carotid and aortic bodies). Contain Type I cells (Glomus) - Rich in mitochondria, Cytoplasmic Table 1. Normal Values for the Composition of Cerebrospinal Fluid reticulum cytoplasmic granules and Arterial Blood - Primarily responsible for sensing the level of PaO2, PaCO2 and pH in the blood - they feed information back to the integrator nuclei in the medulla through the vagus nerves and carotid sinus nerves, which are branches of the glossopharyngeal nerves. The only Chemoreceptor that responds to changes of PaO2 Responsible for 40% of the ventilator response to PaCO2 E. LUNG/PULMONARY MECHANORECEPTOR/ SENSORY NERVES 1. Pulmonary Stretch Receptors Also called slowly-adapting pulmonary stretch receptors Responsible for the Hering Breuer reflex Inspiratory-Inhibitory reflex - arises from afferent stretch Figure 3. (Carbon Dioxide and the Blood-Brain Barrier). PaCO2 receptors. crosses the blood-brain barrier and rapidly equilibrates with CO2 in Activated by increasing lung inflation. cerebrospinal fluid (CSF). H+ and HCO3− ions cross the barrier Prevents hyperinflation, prevents lungs from slowly. The partial pressure of arterial carbon dioxide (PaCO2) exploding combines with CO2 generated by metabolism to dilate the smooth This stretch reflex is mediated by vagal fibers muscle. In comparison with arterial blood, the pH of CSF is lower and the PCO2 is higher, with little protein buffering. Page 2 of 5 PREPARED BY: CMED 1C  (002) REGULATION OF RESPIRATION DR. (AUSTRIA ABRAHAM) | 12/08/20 2. Irritant Receptors B. RESPONSE TO PO2 Also called rapidly-adapting pulmonary stretch Only the peripheral chemoreceptors are involved receptors. Increased response if the PCO2 is raised Located between airway epithelial cells. There is negligible control during normoxic conditions Contains myelinated fibers from vagus nerve The control becomes important at High altitude and in (CN X) long-term hypoxemia caused by chronic lung disease. Stimulated by noxious gases, smoke, dust and cold air Parasympathetic –bronchoconstriction C. RESPONSE TO pH Sympathetic –bronchodilation Reduction in arterial blood pH stimulates ventilation. 3. J Receptors (Juxta-Capillary Receptors) Sensed by peripheral chemoreceptors. Located in the alveolar walls. If the reduction is severe, central chemoreceptors may be Consists of slow-adapting unmyelinated vagal stimulated. C fibers. Plays a role in rapid, shallow breathing and D. RESPONSE TO EXERCISE dyspnea. Ventilation increases immediately when exercise 4. Bronchial C Fibers begins, and this increase in minute ventilation closely Supplied by bronchial circulation matches increases in O2 consumption and CO2 Responds quickly to chemicals injected in production that accompany exercise. bronchial circulation. In moderate exercise no changes on blood gases & pH. Responses includes rapid shallow breathing In severe/heavy exercise, PO2 increases slightly, PCO2 bronchoconstriction and mucous secretion. decreases slightly, pH decreases due to lactic acid from anaerobic metabolism. F. OTHER RECEPTORS During maximal exercise, a physically fit individual can 1. Nose and Upper Airway Receptors achieve an O2 consumption of 4L/min. with a minute irritant receptors that cause sneezing, coughing ventilation volume of 120L/min., which is almost 15 times and bronchoconstriction the resting level. 2. Joint and Muscle Receptors During a strenuous exercise: o Arterial pH begins to fall as lactic acid is liberated Responsible for abrupt increase of Ventilation that occurs during the first few second of exercise. from muscles during anaerobic metabolism. This decrease in arterial pH stimulates ventilation that Once activated, there is initial increase in the is out of proportion to the level of exercise. The ventilation level of exercise at which sustained metabolic 3. Somatic Receptors (lactic) acidosis begins is called the anaerobic Located in the Intercostal muscles, Rib Joints, threshold. Accessory Muscles of Respiration and Tendons Respond to changes in the Length and Tension of Respiratory Muscles. C. ABNORMALITIES IN THE CONTROL OF Play a role in Terminating Inspiration BREATHING Augment respiratory muscle force which is Changes in the ventilatory pattern can occur for both important in individuals with increased airway primary and secondary reasons. resistance and decreased pulmonary compliance During sleep, approximately one third of normal individuals have brief episodes of apnea or hypoventilation that have no II. INTEGRATED RESPONSES significant effects on PaO2 or PaCO2. The apnea usually lasts less than 10 sec., and it occurs in the A. RESPONSE TO CO2 lighter stages of slow-wave and rapid eye movement (REM) Primary factor in the control of ventilation under normal sleep. conditions. In a normal awake individual, there is a linear rise in ventilation as PaCO2 reaches and exceeds 40 mm Hg. A. SLEEP APNEA SYNDROMES PaCO2 – reduced by hyperventilation. The duration of apnea is abnormally prolonged, and it changes PaO2 and PaCO2 in the blood Arterial PCO2 is the most important stimulus to ventilation under most conditions and is normally tightly controlled. 1. Obstructive Apnea (OSA) Most of the stimulus comes from the Central o Is the most common of the sleep apnea chemoreceptors, but the peripheral chemoreceptors also syndromes, and it occurs when the upper contribute and their response is faster. airway (generally the Hypopharynx) closes Response is magnified if the arterial PO2 is Lowered. during inspiration obstructing the airway and causes cessation of airflow. Response is reduced by sleep, increasing age, genetic, racial, personality factors, and if the work of breathing is increased Page 3 of 5 PREPARED BY: CMED 1C  (002) REGULATION OF RESPIRATION DR. (AUSTRIA ABRAHAM) | 12/08/20 2. Central Sleep Apnea o Ventilatory drive to the respiratory neurons decreases o Have repeated episodes of apnea, during which time they make no respiratory effort, every night o The degree of hypercapnia and hypoxemia is lesser compared to OSA. The difference between the two apneas is that in obstructive apnea, the patient makes some respiratory effort to overcome the obstruction; while in central sleep Figure 5. (Cheyne-Stokes respiration pattern). apnea, they make no respiratory effort. SUDDEN INFANT DEATH SYNDROME (SIDS) CENTRAL ALVEOLAR HYPOVENTILATION (Ondine’s curse) most common cause of death in infants in the first year of life o A rare disease in which voluntary breathing is intact after the perinatal period. but abnormalities in automaticity exist. Cause of SIDS is not known, abnormalities in ventilatory o most severe of the central sleep apnea syndromes. As control, particularly CO2 responsiveness have been a result, people with central alveolar hypoventilation implicated. can breathe as long as they do not fall asleep. For Placing infants on their backs to sleep (which reduces the these individuals, mechanical ventilation or more potential for CO2 rebreathing) has dramatically decreased recently, bilateral diaphragmatic pacing (like a cardiac (but not eliminated) the rate of death from this syndrome. pacemaker) can be lifesaving. C. APNEUSTIC BREATHING B. CHEYNE-STOKES VENTILATION Characterized by sustained periods of inspiration Characterized by varying tidal volume and ventilatory separated by periods of exhalation. frequency. Loss of Inspiratory-Inhibitory activities that results in augmentation of the inspiratory drive. After a period of apnea, tidal volume, and respiratory frequency increase progressively over several breaths, Occurs in individuals with central nervous system injury. and then they progressively decrease until apnea recurs. Seen in individuals with central nervous system diseases, head trauma, and increased intracranial pressure and also in individuals who suffered stroke Due to slow blood flow in the brain in association with periods of overshooting and undershooting ventilator effort in response to changes in PCO2. Figure 6. (Normal breathing pattern compared with Apneustic breathing pattern). Figure 4. (In Cheyne-Stokes Breathing, Tidal Volume and, as a Consequence, Arterial Blood Gas Levels Wax and Wane). In general, Cheyne-Stokes breathing is a sign of vasomotor instability, particularly low cardiac output. PaCO2, partial pressure of arterial carbon dioxide; PaO2, partial pressure of arterial oxygen Figure 7. (Some Patterns of Breathing). A, Normal rate of breathing is in the range of 12 to 20 breaths per minute. B, When sensory input is removed from various lung receptors (mainly stretch), each breathing cycle is lengthened and tidal volume is increased, so that alveolar ventilation is not significantly affected. Page 4 of 5 PREPARED BY: CMED 1C  (002) REGULATION OF RESPIRATION DR. (AUSTRIA ABRAHAM) | 12/08/20 C, When input from the cerebral cortex and thalamus is also B. Cheyne-stokes ventilation. eliminated, together with vagal blockade, the result is prolonged C. Apneustic breathing inspiratory activity broken after several seconds by brief expirations (apneusis). 5. Specialized tissues that respond to a change in the chemical composition of the blood or other fluid: A. Chemoreceptors POINTS TO REMEMBER: B. Somatic Receptors Ventilatory control: composed of C. Joint and muscle receptors o respiratory control center o central chemoreceptors 6. Primary factor in the control of ventilation under normal conditions: o peripheral chemoreceptors A. Response to exercise o pulmonary mechanoreceptors/ sensory nerves B. Response to CO2 PaCO2 is the major factor that influences ventilation C. Response to pH Respiratory control center: composed of o dorsal respiratory group 7. Also called rapidly-adapting pulmonary stretch o ventral respiratory group receptors: Rhythmic breathing depends on a: A. Irritant receptors o continuous (tonic) inspiratory drive from the dorsal B. Pulmonary stretch receptors respiratory group. C. J receptors o intermittent (phasic) expiratory input from the cerebrum, thalamus, cranial nerves, and ascending 8. In central sleep apnea, ventilatory drive to the spinal cord sensory tracts respiratory neurons: The peripheral and central chemoreceptors respond to A. Remains the same changes in PaCO2 and pH. B. Decreases C. Increases The peripheral chemoreceptors (carotid and aortic bodies) are the ONLY chemoreceptors that respond to changes in 9. Characterized by varying tidal volume and ventilatory PaO2. frequency: Acute hypoxia and chronic hypoxia affect breathing A. Sleep apnea differently because the slow adjustments in CSF [H+] in B. Chyne-stokes ventilation. chronic hypoxia alter sensitivity to CO2. C. Apneustic breathing Irritant receptors protect the lower respiratory tract from particles, chemical vapors, and physical factors, primarily by 10. Normal value of PCO2 in arterial blood: inducing cough. C fiber J receptors in the terminal A. 40 respiratory units are stimulated by distortion of the alveolar B. 44 walls (by lung congestion or edema). C. 50. The two most important clinical abnormalities of breathing are obstructive and central sleep apnea. PaO2, PaCO2, and pH remain within normal limits during Answers: C, B, B, C, A, B, A, C, B, A moderate exercise; however, during strenuous exercise, pH falls, which stimulates ventilation, whereas PaO2 and PaCO2 remain relatively normal. REFERENCE 1. Berne, R. M., Koeppen, B. M., & Stanton, B. A. (2010). Berne & Levy Physiology. Philadelphia, PA: TEST YOUR KNOWLEDGE Mosby/Elsevier. 1. Activated by increasing lung inflation: A. J receptors B. Joint and muscle receptors C. Pulmonary stretch receptors 2. Has a more important effect in changes in the level of ventilation and the arterial PCO2. A. CSF O2 B. CSF pH. C. CSF CO2 3. Located in the medulla oblongata of the brain stem and is composed of multiple nuclei that generate and modify the basic ventilatory rhythm: A. Central Controllers B. Respiratory receptor C. Pneumotaxic Center 4. Characterized by sustained periods of inspiration separated by periods of exhalation: A. Sleep apnea Page 5 of 5 PREPARED BY: CMED 1C