Lecture 22: Control of Respiration (PDF)

Lecture 22: Control of Respiration Dr. Ann Revill [email protected] Office: Dr. Arthur G. Dobbelaere Science Hall 380E Review: Top Hat Question Join code: 437994 2  Lecture Outline By the en...

Lecture 22: Control of Respiration Dr. Ann Revill [email protected] Office: Dr. Arthur G. Dobbelaere Science Hall 380E Review: Top Hat Question Join code: 437994 2  Lecture Outline By the end of this lecture, you will be able to: 1. List the four main components of the control of breathing 2. Describe the role of the preBötzinger Complex, ventral respiratory group, dorsal respiratory group, pneumotaxic center and apneustic center in the control of breathing 3. Summarize how central chemoreceptors detect changes in the partial pressure of carbon dioxide 4. Describe how peripheral chemoreceptors detect changes in the partial pressure of oxygen, carbon dioxide, and hydrogen ions 5. Summarize the stimuli for activation of mechanoreceptors (pulmonary stretch receptors, irritant receptors, joint receptors) and the subsequent effect on breathing pattern 6. Summarize the effects of obstructive sleep apnea on breathing behavior 3  Control of breathing Breathing behavior continues from birth until death (and even fetal breathing movements): Robust Breathing: – involves highly coordinated motor behavior – must continue to be effective despite systemic perturbations: Exercise Sleep-wake cycling Locomotion Postural changes Adaptable Speaking Swallowing Pulmonary disease – Serves homeostatic control of blood gases: PCO2 and PO2 are tightly monitored and regulated 4  Control of breathing There are 4 main components: 1. Control centers in the brainstem 2. Respiratory muscles, controlled by the brainstem main inspiratory muscle? diaphragm 3. Mechanoreceptors in lungs & joints 4. Chemoreceptors Which substances? O2 CO2 pH In addition, voluntary control from the cortex can temporarily override the brainstem – When? breath holding hyperventilation 5 6 Central Respiratory Networks Central pattern generator Motor nuclei Respiratory apparatus Del Negro et al 2018 7  Pons Pons Pneumotaxic center respiratory Apneustic center Respiratory centers control preBötzinger centers in complex brain stem Dorsal respiratory Medullary group (DRG) respiratory center Ventral respiratory Medulla group (VRG) 8 Sherwood 13-29  Inspiratory rhythm generation Inspiratory center Located in the ventrolateral medulla: preBötzinger Complex – Controls basic rhythm for breathing by setting frequency of inspiration Sends inspiratory drive to: – diaphragm (via phrenic nerve) – muscles of the tongue and upper airway Activity pattern: – Volley of action potentials that increase in frequency over a few seconds – Period of quiescence Muscle activity follows the same pattern: – Phrenic nerve activity causes diaphragm contraction – Quiescence leads to diaphragm relaxation 9 Other medullary breathing regions Ventral respiratory group: primarily involved in expiration – Inactive during eupnea – Why? expiration normally passive – When might these neurons be recruited? Exercise Dorsal respiratory group: primarily active during inspiration 10  Pontine breathing centers Pneumotaxic center: – Limits inspiration – Limits tidal volume Apneustic center: – Abnormal breathing pattern – Prolonged inspiration, brief expiration – When might this breathing pattern be seen? Traumatic brain injury 11  Clinical Connection: preBötC & anesthetics & opioids Activity of preBötC neurons is robust and persists through life Activity of preBötC neurons may be depressed by several drugs, for example anesthetics (propofol) and painkillers (opioids) Depression of preBötC neurons activity leads to respiratory depression and ultimately death by respiratory arrest 12  Higher centers and breathing Voluntary control for: speech, sighs (not always voluntary), breath holding Limbic system: emotionally induced changes in ventilation (fear and hyperventilation) 13 How does changing breathing pattern affect blood gases? Breath holding (hypoventilation) will: ↑ PaCO2, ______ ___ ↓ PaO2 Rapid breathing (hyperventilation) will: ↓ PaCO2, _____ ___ ↑ PO2 Small changes in PCO2, H+ and bigger changes in PO2 are potent stimuli to breath! 14  Chemoreceptors Chemical control of ventilation: Hypoxia (low PO2), hypercapnia (high PCO2), and acidosis (low pH in blood) all cause an increase in ventilation, which tends to – raise PO2 – lower PCO2 – raise pH Chemoreceptors are specialized structures that sense changes in PO2,PCO2 and pH Peripheral and central chemoreceptors have a KEY role in chemical control of ventilation 15  Central Chemoreceptors Contribute 70% of response to ΔPaCO2 Brainstem chemoreceptors sensitive to changes in CSF pH ↓ pH ↑ pH ↑ breathing rate ↓ breathing rate Medullary chemoreceptors respond: directly to changes in pH indirectly to changes in PaCO2 16 CO2 levels are high preBötC 1. CO2 combines with H2O, producing H+ & 4. Central chemoreceptors are adjacent to HCO3- The BBB is impermeable to both. the CSF & detect the ↓ pH. CO2 is permeable across the BBB – it enters the brain extracellular fluid 5. The ↓ pH signals preBötzinger Comples to increase breathing rate 2. CO2 is permeable across the brain CSF 3. In the CSF: CO2 is converted to H+ & What does ↑ breathing rate do? HCO3-. Increases in PaCO2 will increase CSF ↑ CO2 expired & ↓ PaCO2 & ↑pH (returns PCO2, resulting in increased H+ in CSF (↓ back to normal) 17 pH) Costanzo 5-32  To medullary Peripheral respiratory control center chemoreceptors: Sensory nerve fiber Sensory nerve fiber carotid bodies Carotid sinus Carotid bodies and aortic bodies Carotid artery Aortic bodies Aortic arch Primarily respond to PO2 but also sensitive to pH, and PCO2 Heart 18 Sherwood 13-30 Carotid bodies Ventilation is stable over 60-120mmHg range of PaO2 Strong stimulation of peripheral chemoreceptors occurs at PaO2 values below 60mmHg Important during 500 severely low levels of O2 19 West 8-3  Carotid bodies Peripheral chemoreceptors also produce an ↑ breathing rate after detecting: – An ↑ in PaCO2 Detection of ∆ PCO2 by the peripheral chemoreceptors is less important than its detection by the central chemoreceptors – A ↓ in arterial pH Peripheral chemoreceptors sense an ↑ H+ Stimulated in metabolic acidosis, i.e. there is a ↓ arterial pH West 8-3 20 Mechanoreceptors Pulmonary stretch receptors: RHYTHM GENERATOR – Located in airway smooth muscle – Respond to? stretch – Active in adults >1 L tidal PATTERN GENERATOR volume PREMOTOR NETWORKS When does this happen? exercise AFFERENTS – Signal travels via vagus (mechanosensitive) AFFERENTS (chemosensitive) (X) nerve to terminate MOTONEURONS inspiration – Know as the Breuer- Hering reflex – Effect? Decreased tidal RESPIRATORY MUSCLES volume, increased breathing rate 21  Mechanoreceptors Irritant receptors: – Respond to noxious stimuli Such as? Smoke, pollen, “food going down the wrong pipe” – Afferent input to CNS via vagus nerve – Effect? Bronchiole constriction, coughing, increased breathing rate Joint and muscle receptors – Respond to joint and muscle movement (e.g. chest wall) – Afferent input used for reflexes to adjust for posture – Afferent input also sent to CNS for conscious awareness of breathing movements 22 Clinical Connection: Obstructive Sleep Apnea Characterized by repeated apneas (pauses in breathing) during sleep, followed by arousals – What causes arousals? ↑ in PaCO2 Estimated to affects 5-15% of the American population – Under-diagnosed – More prevalent in obese people, in men, in the elderly, and in conjunction with other diseases such as diabetes Leads to – excessive daytime sleepiness, increased risk of accidents, decreased quality of life – Cardiovascular disease 23 Clinical Connection: Obstructive Sleep Apnea Awake Asleep Tongue and other airway muscles lose tone during sleep Leads to partial or complete closure of the airways 24  Current OSA treatments CPAP (continuous positive airway pressure) Mandibular advancement device No pharmaceutical therapy (yet) 25 26