3-Mar-16Control of Respiration1 Neural Mechanisms Chemical Mechanisms

3-Mar-16Control of Respiration2 Introduction  Function of respiration include –Regulation of alveolar ventilation Maintain constant supply of O 2 to tissues –Normal 250 ml O 2 /min –This can increase to 20 times during exercise To eliminate CO 2 from the tissues Thus P O2, P CO2, pH –Maintained at constant values or nearly constant values

3-Mar-16Control of Respiration3 Introduction  Other functions of respiration include –Phonation, singing, laughing, whistling etc  In all these –Extremely complicated respiratory movements are performed –Require coordinated control

3-Mar-16Control of Respiration4 Neural Control of Respiration  Two neural control mechanisms regulate respiration –One responsible for voluntary control –The other one for automatic control Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

3-Mar-16Control of Respiration5 Neural Control of Respiration  Voluntary control system –Located in cerebral cortex –Send impulses to respiratory muscles via Corticospinal tracts (CST) Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

3-Mar-16Control of Respiration6 Control Systems for Respiration  Automatic system –Located in pons and medulla oblongata –Efferent output from this system to respiratory muscles Located in spinal cord close to CST Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

3-Mar-16Control of Respiration7 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 Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

3-Mar-16Control of Respiration8 Control Systems for Respiration  Reciprocal activity –Motor neurons to expiratory muscles Inhibited when those to inspiratory muscles are activated &vice versa Cerebral cortex Pons & medulla Spinal cord Respiratory muscles Corticospinal tract Reticulospinal tract

3-Mar-16Control of Respiration9 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 Inspiration Expiration 2 sec3 sec Electrical activity (diaphragm)

3-Mar-16Control of Respiration10 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 Inspiration Expiration 2 sec3 sec Electrical activity (diaphragm)

3-Mar-16Control of Respiration11 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

3-Mar-16Control of Respiration12 Respiratory Centers IX X XI XII D R G V R G Vagus, glosopharyngeal Pneumotaxic center DRG VRG Apneustic center

3-Mar-16Control of Respiration13 Respiratory Centers  Composed of several groups of neurons –Located bilaterally in Medulla oblongata Pons IX X XI XII D R G V R G Pneumotaxic center Apneustic center

3-Mar-16Control of Respiration14 Respiratory Centers  Three major collection of neurons –Dorsal respiratory group (DRG) –Ventral respiratory group (DRG) –Pneumotaxic center –? Apneustic center IX X XI XII D R G V R G Apneustic center Pneumotaxic center

3-Mar-16Control of Respiration15 Respiratory Centers  Dorsal respiratory group (DRG) –Located on the dorsal portion of medulla In or near the Nucleus of Tractus Solitarius(NTS) IX X XI XII D R G V R G

3-Mar-16Control of Respiration16 Respiratory Centers  NTS –Sensory terminal of vagus & glossopharyngeal Transmit sensory signals from –Peripheral chemoreceptors –Baroreceptors –Receptors in the lungs IX X XI XII D R G V R G

3-Mar-16Control of Respiration17 Respiratory Centers  DRG made up –Of I – neurons Some project monosynaptically to phrenic nerve motor neurons (MN) –Cause inspiration IX X XI XII D R G V R G

3-Mar-16Control of Respiration18 Respiratory Centers  VRG  Long column extends through –Nucleus ambiguus –Nucleus retroambiguus in the ventral medulla IX X XI XII D R G V R G

3-Mar-16Control of Respiration19 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 X XI XII D R G V R G

3-Mar-16Control of Respiration20 Generation of Breathing Pattern  Rhythmic respiratory pattern –Appear to be initiated by the Rhythmic discharges of neurons in the medulla and pons IX X XI XII D R G V R G A D

3-Mar-16Control of Respiration21 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 IX X XI XII D R G V R G A D

3-Mar-16Control of Respiration22 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 IX X XI XII D R G V R G A D

3-Mar-16Control of Respiration23 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 X XI XII D R G V R G

3-Mar-16Control of Respiration24 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 IX X XI XII D R G V R G Pneumotaxic center

3-Mar-16Control of Respiration25 Pontine & vagal Influence  When this area is damaged –Respiration becomes slower –Tidal volume greater  Pneumotaxic center m ay play a role –Switching between inspiration & expiration IX X XI XII D R G V R G Pneumotaxic center

3-Mar-16Control of Respiration26 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 IX X XI XII D R G V R G Pneumotaxic center Apneustic center

3-Mar-16Control of Respiration27 Pontine & vagal Influence  Apneustic center is inhibited by –Vagus & pneumotaxic center  Vagotomy & destruction of pneumotaxic center causes –Prolonged period of inspiration Apneusis IX X XI XII D R G V R G Pneumotaxic center Apneustic center

3-Mar-16Control of Respiration28 Chemical Control  Pulmonary ventilation –Regulated to meet different levels of metabolic demands Supply O 2 Elimination of CO 2  Achieved by feed back control of respiratory center activity –In response to chemical composition of blood P CO2, H +, P O2

3-Mar-16Control of Respiration29 Chemical Control  Types of receptors –Central chemo-receptors –Peripheral receptors –Others

3-Mar-16Control of Respiration30 Central Chemoreceptors  Chemosensitive neurons –Bilateral beneath the ventral medulla  Sensitive to changes in P CO2 & H +  H + only important direct stimulus DRG CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ HCO H + Chemosensitive neurons

3-Mar-16Control of Respiration31 Central Chemoreceptors  H + crosses the blood- brain –barrier (BBB) very poorly –Changes in H + in blood have less immediate effect on respiration  CO 2 diffuse easily across BBB –It is then hydrated and dissociates to H + & HCO 3 - DRG CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ HCO H + Chemosensitive neurons

3-Mar-16Control of Respiration32 Central Chemoreceptors  An increase CSF CO 2 causes chemoreceptors to stimulate respiration  A decrease CSF CO 2 causes chemoreceptors to inhibit respiration DRG CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ HCO H + Chemosensitive neurons

3-Mar-16Control of Respiration33 Peripheral Chemoreceptors  Located in the carotid & aortic bodies  These receptors respond to –Lowered arterial O 2 tension –Rise in arterial CO 2 tension –Increase in H + conc in arterial blood

3-Mar-16Control of Respiration34 Peripheral Chemoreceptors  Arterial O 2 tension –Only site in the body that detect changes in O 2 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)

3-Mar-16Control of Respiration35 Peripheral Chemoreceptors  Thus they monitor –O 2 tension rather than O 2 content  O 2 cause by anaemia, methaemoglobin, CO poisoning –Do not stimulate peripheral chemoreceptors

3-Mar-16Control of Respiration36 Peripheral Chemoreceptors  When P O2 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 CO 2

3-Mar-16Control of Respiration37 Peripheral chemoreceptors  Elimination of CO 2 –Respiratory alkalosis ↓ H + conc CSF Inhibition of respiratory drive  Over the course of several days –Ionic pumps (pia matter, choroid plexus) Transfer HCO 3 - from CSF to blood CSF pH returns towards normal Respiratory drive returns

3-Mar-16Control of Respiration38 Peripheral chemoreceptors  Effect of CO 2 tension  Elevation of CO 2 tension also –Stimulate peripheral chemoreceptors –But most of effect of CO 2 is on the central chemoreceptors

3-Mar-16Control of Respiration39 Peripheral chemoreceptors  Effect of H + concentration  ↑ in H + conc –Stimulate peripheral chemorecptors –Increase in ventilation  The increase in alveolar ventilation – ↓ CO 2 tension –pH return towards normal –Ventilatory drive tends to reduce

3-Mar-16Control of Respiration40 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

3-Mar-16Control of Respiration41 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)

3-Mar-16Control of Respiration42 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

3-Mar-16Control of Respiration43 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

3-Mar-16Control of Respiration44 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