Control of Respiration Neural Mechanisms Chemical Mechanisms 6-May-19 Control of Respiration

Control of Respiration Introduction Function of respiration include Regulation of alveolar ventilation Maintain constant supply of O2 to tissues Normal 250 ml O2 /min This can increase to 20 times during exercise To eliminate CO2 from the tissues Thus PO2, PCO2, pH Maintained at constant values or nearly constant values 6-May-19 Control of Respiration

Control of Respiration Introduction Other functions of respiration include Phonation, singing, laughing, whistling etc In all these Extremely complicated respiratory movements are performed Require coordinated control 6-May-19 Control of Respiration

Neural Control of Respiration Two neural control mechanisms regulate respiration One responsible for voluntary control The other one for automatic control 6-May-19 Control of Respiration

Neural Control of Respiration Voluntary control system Located in cerebral cortex Send impulses to respiratory muscles via Corticospinal tracts (CST) 6-May-19 Control of Respiration

Neural Control of Respiration Automatic system Located in pons and medulla oblongata Efferent output from this system to respiratory muscles Located in spinal cord close to CST 6-May-19 Control of Respiration

Control Systems for Respiration Nerves serving inspiration converge in ventral horns C3,4,5 (phrenic nerve) External intercostal motor neurons Fibres concerned with expiration Converge on internal intercostals motor neurons Cerebral cortex Corticospinal tract Pons & medulla Reticulospinal tract Spinal cord Respiratory muscles 6-May-19 Control of Respiration

Control Systems for Respiration Reciprocal activity Motor neurons to expiratory muscles Inhibited when those to inspiratory muscles are activated & vice versa Cerebral cortex Corticospinal tract Pons & medulla Reticulospinal tract Spinal cord Respiratory muscles 6-May-19 Control of Respiration

Control of Respiration Breathing Pattern During quite breathing Inspiration is brought about by Progressive increase in activation of inspiratory muscles End of inspiration associated with Rapid decrease in excitation Electrical activity (diaphragm) 2 sec 3 sec Inspiration Expiration 6-May-19 Control of Respiration

Control of Respiration Breathing Pattern The progressive activation of inspiratory muscle cause Lungs to fill at constant rate until tidal vol reached End of inspiration associated Rapid decrease in excitation of inspiratory muscles Expiration occurs Electrical activity (diaphragm) 2 sec 3 sec Inspiration Expiration 6-May-19 Control of Respiration

Control of Respiration Respiratory Neurons Two types of brainstem respiratory neurons Inspiratory neurons (I-neurons) Discharge during inspiration Expiratory neurons(E-neurons) Discharge during expiration During quite breathing Remain silent Become active only when ventilation is increased 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers Pneumotaxic center Apneustic center Vagus, glosopharyngeal DRG IX D R G X VRG XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers Composed of several groups of neurons Located bilaterally in Medulla oblongata Pons Three major collection of neurons Dorsal respiratory group (DRG) Ventral respiratory group (DRG) Pneumotaxic center ? Apneustic center IX D R G X XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers Dorsal respiratory group (DRG) Located on the dorsal portion of medulla In or near the Nucleus of Tractus Solitarius(NTS) IX D R G X XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers NTS Sensory terminal of vagus & glossopharyngeal Transmit sensory signals from Peripheral chemoreceptors Baroreceptors Receptors in the lungs IX D R G X XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers DRG made up Of I – neurons Some project monsynaptically to phrenic nerve motor neurons (MN) Cause inspiration IX D R G X XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers VRG Long column extends through Nucleus ambiguus Nucleus retroambiguus in the ventral medulla IX D R G X XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Respiratory Centers VRG has both I & E neurons E – neurons at its rostral end I-neurons at the mid portion E-neurons at its caudal end Some of these neurons project to Respiratory motor neurons IX D R G X XI V R G XII 6-May-19 Control of Respiration

Generation of Breathing Pattern Rhythmic respiratory pattern Appear to be initiated by the Rhythmic discharges of neurons in the medulla and pons A IX D R G X XI V R G XII D 6-May-19 Control of Respiration

Generation of Breathing Pattern Trans-section of brain Below medulla Stops respiration Above the pons Automatic breathing is still present Neurons in medulla & pons Responsible for generating the rhythmic respiratory movements A IX D R G X XI V R G XII D 6-May-19 Control of Respiration

Generation of Breathing Pattern The actual mechanism responsible for Rhythmic respiratory discharge not known However, Group of pacemaker neurons have been identified Pre-Böttzinger Complex Area between nucleus ambiguus & lateral reticular nucleus A IX D R G X XI V R G XII D 6-May-19 Control of Respiration

Pontine & vagal Influence The spontaneous rhythmic discharges of medullary neurons is modified by Neurons in the pons Afferents in the vagus from receptors in the airways and lungs IX D R G X XI V R G XII 6-May-19 Control of Respiration

Pontine & vagal Influence Pneumotaxic center located in Nucleus parabrachialis in dorsal lateral pons Contain both I-neurons & E-neurons Also contain neurons that are active in both phases of respiration Pneumotaxic center IX D R G X XI V R G XII 6-May-19 Control of Respiration

Pontine & vagal Influence When this area is damaged Respiration becomes slower Tidal volume greater Pneumotaxic center may play a role Switching between inspiration & expiration Pneumotaxic center IX D R G X XI V R G XII 6-May-19 Control of Respiration

Pontine & vagal Influence Apneustic center Situated in lower pons Send signals to DRG Prevent “switching-off” of respiratory ramp (increase duration of inspiration) Lungs become completely filled with air Pneumotaxic center Apneustic center IX D R G X XI V R G XII 6-May-19 Control of Respiration

Pontine & vagal Influence Apneustic center is inhibited by Vagus & pneumotaxic center Vagotomy & destruction of pneumotaxic center causes Prolonged period of inspiration Apneusis Pneumotaxic center Apneustic center IX D R G X XI V R G XII 6-May-19 Control of Respiration

Control of Respiration Chemical Control Pulmonary ventilation Regulated to meet different levels of metabolic demands Supply O2 Elimination of CO2 Achieved by feed back control of respiratory center activity In response to chemical composition of blood PCO2, H+, PO2 6-May-19 Control of Respiration

Control of Respiration Chemical Control Types of receptors Central chemo-receptors Peripheral receptors Others 6-May-19 Control of Respiration

Central Chemoreceptors Chemosensitive neurons Bilateral beneath the ventral medulla Sensitive to changes in PCO2 & H+ H+ only important direct stimulus Chemosensitive neurons DRG CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+ 6-May-19 Control of Respiration

Central Chemoreceptors H+ crosses the blood-brain –barrier (BBB) very poorly Changes in H+ in blood have less immediate effect on respiration CO2 diffuse easily across BBB It is then hydrated and dissociates to H+ & HCO3- Chemosensitive neurons DRG CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+ 6-May-19 Control of Respiration

Central Chemoreceptors An increase CSF CO2 causes chemoreceptors to stimulate respiration A decrease CSF CO2 causes chemoreceptors to inhibit respiration Chemosensitive neurons DRG CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+ 6-May-19 Control of Respiration

Peripheral Chemoreceptors Located in the carotid & aortic bodies These receptors respond to Lowered arterial O2 tension Rise in arterial CO2 tension Increase in H+ conc in arterial blood 6-May-19 Control of Respiration

Peripheral Chemoreceptors Arterial O2 tension Only site in the body that detect changes in O2 tension of body fluids Peripheral chemoreceptors Receive a lot of blood flow for their size 2000 ml/100 gm/min (cf brain = 54 ml/100 gm/min) 6-May-19 Control of Respiration

Peripheral Chemoreceptors Thus they monitor O2 tension rather than O2 content  O2 cause by anaemia, methaemoglobin, CO poisoning Do not stimulate peripheral chemoreceptors When PO2 falls below 60–80 mm Hg There is an increase in rate of discharge of fibers from the receptors to RC ↑ rate and depth of respiration ↑alveolar ventilation Elimination of CO2 6-May-19 Control of Respiration

Peripheral chemoreceptors Elimination of CO2 Respiratory alkalosis ↓H+ conc CSF Inhibition of respiratory drive Over the course of several days Ionic pumps (pia matter, choroid plexus) Transfer HCO3- from CSF to blood CSF pH returns towards normal Respiratory drive returns 6-May-19 Control of Respiration

Peripheral chemoreceptors Effect of CO2 tension Elevation of CO2 tension also Stimulate peripheral chemoreceptors But most of effect of CO2 is on the central chemoreceptors 6-May-19 Control of Respiration

Peripheral chemoreceptors Effect of H+ concentration ↑in H+ conc Stimulate peripheral chemorecptors Increase in ventilation The increase in alveolar ventilation ↓CO2 tension pH return towards normal Ventilatory drive tends to reduce 6-May-19 Control of Respiration

Control of Respiration Other receptors Pulmonary stretch receptors Lie within the walls of airways They are stimulated by Inflation of the lung Initiate inspiratory inhibition Termination of inspiration Hering – Breuer reflex 6-May-19 Control of Respiration

Control of Respiration Other Receptors Irritant receptors Lie in large airways Between airway epithelial cells Stimulated by Noxious gases, smoke, particulates in inhaled air Initiate reflex that stimulate Coughing, bronchospasm, mucus secretion Breath holding (apnoea) 6-May-19 Control of Respiration

Control of Respiration Other Receptors J-receptors Juxta-capillary Located in the pulmonary interstitium at the level of pulmonary capillaries Stimulated by the distension of pulmonary capillaries Caused by ventricular failure, emboli, chemicals 6-May-19 Control of Respiration

Control of Respiration Other Receptors J-receptors Initiate reflex that cause Rapid, shallow breathing, tachypnoea Nose & upper airway receptors Upper respiratory pathways contain receptors Respond to mechanical, chemical stimuli Reflex initiated Sneezing, coughing, bronchoconstriction 6-May-19 Control of Respiration

Control of Respiration Other Receptors Joint & muscle receptors Impulses from moving limbs Are believed to be part of stimuli for ventilation Early stages of exercises Baroreceptors A rise in BP cause Reflex hypoventilation A fall in BP cause Reflex hyperventilation 6-May-19 Control of Respiration