Control of Breathing PDF

Ventilation: Control of Breathing Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Ventilation: Control of Breathing 1 Learning Outcomes • Describe the location of the primary respiratory centre • Describe the role of t...

Ventilation: Control of Breathing Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Ventilation: Control of Breathing 1 Learning Outcomes • Describe the location of the primary respiratory centre • Describe the role of the VRG in the medulla in the neural control of respiration • Describe the role of the pons in the neural control of respiration • Describe the levels at which the basic pattern of neural activity can be altered • Describe the inputs to the medulla which affect respiration Neural and Chemical Controllers of Ventilation • Alveolar ventilation rate is normally adjusted so that PO2 and PCO2 in the arterial blood are hardly altered even during heavy exercise and other respiratory stresses • Four major sites responsible for this adjustment: – – – – Respiratory control centre (source of central pattern generator) Central chemoreceptors Peripheral chemoreceptors Pulmonary mechanoreceptors Innervation of Muscles in Respiration Muscles Nerve Location of Motor Neuron Diaphragm Phrenic nerve C3-C5 ventral horn External Intercostal muscles Intercostal nerves Thoracic spinal cord ventral horn Larynx & pharynx Vagus (CN X) & glossopharyngeal (CN IX) nerves Nucleus ambiguus Tongue Hypoglossal nerve (CN XII) Hypoglossal motor nucleus Sternocleidomastoids & Trapezius Accessory nerve (CN XI) Spinal accessory nucleus, C1-C5 Nares Facial nerve (CN VII) Facial motor nucleus Internal Intercostal muscles Intercostal nerves Thoracic spinal cord ventral horn Abdominal muscles Spinal nerves Lumbar spinal cord ventral horn Primary Muscles of inspiration Secondary Muscles of inspiration Secondary muscles of expiration Experimental Evidence for Location of Respiratory Neurons • • • Section above the level of the pons, the basic rhythm continues Section the spinal cord below C3-C5, the intercostal muscles are paralysed Section below the medulla, all breathing ceases Respiratory “Centres” • • Term probably incorrect - it implies there are discrete anatomical regions that can be identified macro- or microscopically Better description would be diffuse networks that are active together to bring about the respiratory effect • ‘Centres’ located in medulla oblongata and pons • Collect sensory information about O2 and CO2 levels in blood • Determines signal sent to respiratory muscles which leads to alveolar ventilation Dorsal and Ventral Respiratory Groups Dorsal Respiratory Group • • • • • • Most of these neurons are located within the nucleus tractus solitarius Receives sensory input from organs of thorax and abdomen Neurons in this group emit repetitive bursts of inspiratory neuronal action potentials Cause of repetitive bursts not known Involves respiratory ramp for 2 seconds followed by cessation for 3 seconds Ramp can be altered by – Controlling rate of  of ramp (heavy breathing, ramp increases rapidly so lungs fill rapidly) – Controlling limiting point at which ramp suddenly stops (control rate of respiration) Ventral Respiratory Group Pneumotaxic & Apneustic Centres • • Centres modulate, but are not essential for, normal respiratory output Pneumotaxic centre located dorsally in nucleus parabrachialis medialis of upper pons • 1o effect is to control switch-off point of inspiratory ramp (so controls filling phase of lung cycle) • Strong pneumotaxic signal - inspiration may last for less than 0.5 second while a weak pneumotaxic signal - inspiration may last for 5 or more seconds Chemical Control of Ventilation • Ultimate goal of ventilation is to maintain proper levels of PO2, PCO2 & pH (H+) • Hypercapnia (↑PCO2) and acidosis (↓pH) detected by central respiratory centre • Hypoxia (↓PO2) detected by peripheral chemoreceptors in carotid and aortic bodies, also detects Hypercapnia (PCO2) and acidosis (pH) Location of Central Chemoreceptors • • • • • Exact location of central chemoreceptors is controversial Hans Loeschke, Marianne Schlafke and Robert Mitchell identified candidate regions near ventrolateral medulla Applying acid solutions to these areas ed ventilation Chemosensitive neurons now also identified bilaterally beneath ventral surface of the medulla and in medullary raphe Neurons in these area very sensitive to H+ ions (may be only important direct stimulus) Mechanism of Action of Central Chemoreceptors • Chemosensitive area located bilaterally beneath ventral surface of the medulla • Neurons very sensitive to H+ ions (may be only important direct stimulus) • H+ ions do not cross blood brain barrier very well, however, CO2 crosses easily • es in blood PCO2 causes PCO2 to  in interstitial fluid of medulla and CSF • CO2 combines with H2O to form H+ ions by action of carbonic anhydrase Peripheral Chemoreceptor Control of Respiratory Activity – The Carotid Body • • • • Carotid bodies & aortic bodies should not be confused with the carotid sinus (baroreceptor) and the baroreceptors of the aortic arch How low PO2 excites nerve endings is still largely unknown Bodies have multiple highly characteristic glandular-like cells (Glomus cells) that synapse directly or indirectly with nerve endings Both sympathetic & parasympathetic NS innervate carotid body Chemosensitivity of the Carotid Body • Senses decreased arterial PO2 – Low PO2, but normal PCO2 and pH –  in firing rate of carotid sinus nerve – At normal values of PCO2 and pH a  of PO2 causes progressive  in firing rate • Can sense increases in arterial PCO2 – Results show graded es in PCO2 at a fixed blood pH (7.45) and fixed PO2 (80mmHg), produced graded es in firing rate of carotid sinus • Can sense decreases in arterial pH (e.g. metabolic acidosis) – Blood pH (7.25) and fixed PO2 (80mmHg), firing rate of carotid sinus nerve is greater over all PCO2 values Signal Transduction of Glomus cell Modulation of Respiratory Output Respiratory system receives input from 2 other sources: – Stretch and chemical/irritant receptors – Higher CNS centres that control non-respiratory activity • Slowly adapting pulmonary stretch receptors – Hering-Breuer reflex (1868) – Helps to prevent over-inflation of the lungs – Stretch receptors located in muscular portions of walls of bronchi and bronchioles – Send signals thro’ vagal nerves (CNX) to DRG neurons when lungs overstretched – Feedback response initiated that ‘switches off ‘ inspiratory ramp – In humans reflex not activated until tidal volume es to about 3 times normal (i.e. 1.5L / breath) Modulation of Respiratory Output • Rapidly adapting pulmonary stretch (Irritant) receptors – Epithelium of trachea, bronchi and bronchioles contains sensory nerve endings, pulmonary irritant receptors – Responsible for coughing and sneezing • C-fibre receptors (J Receptors) – Receptors in alveoli and conducting airways close to capillaries – Respond to chemical and mechanical stimuli – Stimulated during conditions like pulmonary oedema, congestion, pneumonia, Also from endogenous chemicals such as histamine – Induces shallow breathing, bronchoconstriction & mucus secretion Cough Reflex • • • Nerve endings of vagus and/or visceral afferent fibres are activated by irritation of trachea or bronchi Action potentials travel to medulla and spinal cord respectively Response has 3 phases: – Preparatory inspiration – Compressive phase • • • Glottis closed by vagal efferent activity Forced expiration against a closed glottis Pressure increases – Expulsive phase • • Glottis suddenly opens and trapped air is expelled at high speed by contraction of internal intercostals and abdominal muscles Result is to dislodge mucous covering airways and carry irritant away to mouth Higher Brain Centre Activity • • • • • • Voluntary Hyperventilation Breath-holding Speaking Singing Whistling Playing musical wind instruments Some cortical neurons send axons to respiratory centres in medulla Some cortical premotor neurons send axons to motor neurons controlling respiratory muscles Summary of Control of Ventilation References • Boron, WF & Boulpaep, EL (2017) Medical Physiology (3rd Edition) – • Guyton & Hall (2016) Textbook of Medical Physiology (13th Edition) – • • • • • • Chapter 24 Respiratory Regulation p298-312 Naish, J & Syndercombe Court, D. (2019). 3rd Edition. Medical Sciences – • Chapter 42 Regulation of Respiration p539-548 Preston RR & Wilson TE (2013) Lippincott’s Illustrated Reviews: Physiology (1st Edition) – • Chapter 32 Control of Ventilation p700-720 Chapter 13 The Respiratory System p603-642 Hadjikoutis, S et al. (1999) Cough in motor neuron disease: a review of mechanisms. Quarterly Journal Medicine 92: 487-494 Kemp, PJ (2006) Detecting acute changes in oxygen: will the real sensor please stand up? Experimental Physiology 91(5): 829-834. Parkes, MJ (2006) Breath-holding and its breakpoint. Experimental Physiology 91: 1-15 Prabhakar, NR (2006) O2 sensing at the mammalian carotid body: why multiple O2 sensors and multiple transmitters? Experimental Physiology 91: 17-23. Ward, JPT (2008) Oxygen sensors in context. BBA 1777: 1-14. Widdicombe, JG (1995) Neurophysiology of the cough reflex. European Respiratory Journal 8: 1193-1202 Normal and Abnormal Respiratory Patterns • • • • • • Eupnea – normal breathing Sigh - larger than normal breath that occurs at regular intervals in normal subjects Inspiratory Apneusis – prolonged inspirations separated by brief expirations Vagal breathing – slow, deep inspirations due to vagal interruption Cheyne-Stokes respiration – benign respiratory pattern. Cycles of gradual  in TV, followed by gradual  in TV, then apnea – bilateral cortical disease, healthy people at high altitude Ataxic breathing – irregular inspirations, separated by long periods of apnea – medullary lesions