ControlOfBreathingPreClass_Eiting2023.pptx

Control of Breathing Thomas P Eiting, PhD RESP I—Fall 2023 Image credit: Menuet et al., 2020, eLife 9:e57288 Learning Objectives Guyton Ch. 42 • Identify and anatomically locate the three components of the respiratory control system • Describe and localize the brain stem integrating centers re...

Control of Breathing Thomas P Eiting, PhD RESP I—Fall 2023 Image credit: Menuet et al., 2020, eLife 9:e57288 Learning Objectives Guyton Ch. 42 • Identify and anatomically locate the three components of the respiratory control system • Describe and localize the brain stem integrating centers responsible for producing the spontaneous rhythmicity of breathing. • Describe the functional interactions between the brain stem centers in generating signals to initiate respiratory muscle activity. • Identify and describe how sensors detect and send information into the brain stem centers to alter breathing rate. • Identify and locate chemoreceptors that monitor extracellular fluid pH, carbon dioxide, and oxygen tension. • Describe how alterations in pH, carbon dioxide, and oxygen interact to influence or alter ventilation. All images from Guyton text unless noted The Control of Breathing is Complicated Three phases of motor control Breathing functions to control blood levels of oxygen, carbon dioxide, and hydrogen ions (pH). Muscle activity includes diaphragm and assorted accessory muscles such as intercostals, pharyngeal muscles, tongue and facial muscles Sensory inputs from peripheral chemoreceptors, barorecepters, GI and lung receptors, etc Dutschmann and Dick, 2012 Direct and indirect control Rhythmic Breathing is Generated in the Medulla Respiratory Center—Medulla and Pons of the Brain Stem Dorsal Respiratory Group • Inspiration, rhythm Ventral Respiratory Group • Inspiration, expiration Pontine Respiratory Group (Pneumotaxic center and Apneustic center) • Duration, rate Another View of the Respiratory Center Appenzeller et al., 2022 Dorsal Respiratory Group Most DRG neurons are part of the nucleus of the solitary tract (NTS), with additional neurons in the reticular substance of the medulla Receive sensory input from stretch receptors in lungs and peripheral chemoreceptors in carotid and aortic bodies Have intrinsically-firing neurons that fire at specific phases of respiratory cycle; inspiratory ramp signal Contribute to reflex actions, including Ventral Respiratory Group VRG is a column of neurons in and around the nucleus ambiguus Plays a major role in coordinating motor output, through the vagus nerve and premotor neurons the innervate the phrenic motor nucleus Emerging evidence points to the preBötzinger complex as a major CPG of respiratory rhythm Also mediates autonomic regulation and cardiorespiratory coupling, including forced exhalation when, for example, Pontine Respiratory Group PRG (“Pneumotaxic Center” in Guyton) contains neurons in parabrachial nucleus, Kölliker-Fuse (KF) nucleus, and others Limits duration of inspiration, by switching off the inspiratory ramp of the DRG—a stronger signal from this region causes inspiration to be shortened KF drives active exhalation in the “late-E” phase (last 1/3 of expiration) CO2 and H+ Act Directly on Respiratory Center Central chemoreceptors in brainstem are sensitive to pH and CO2 changes. Most sensitive area is the ventral surface of medulla, lateral to pyramidal tract Retrotrapezoid nucleus has glutamatergic neurons that are sensitive to CO2 Serotonergic neurons lie along penetrating arteries of ventrolateral medulla that respond in acidosis CO2 and H+ Act Directly on Respiratory Center Normal Range of PCO2 is about 35-75 mm Hg. Note the huge effect changes in this normal range have on ventilation pH Changes in pH (inverse log of H+) have less than 10% as great of an effect Remember: Blood-brain barrier is much more permeable to carbon dioxide than to hydrogen ions CO2 and H+ Act Directly on Respiratory Center At normal oxygen levels, ventilation is dependent on CO2; at low oxygen partial pressure, breathing is directly stimulated and also more sensitive to CO2 Firing rate of serotonergic neurons in raphe nucleus of medulla increases with pH decreases (caused by elevated CO2) Serotonergic neurons are closely associated with large arteries in ventral medulla where they can Peripheral Chemoreceptor System Responds to changes in O2 in the blood (respond to changes in CO2 and H+ to a lesser extent) Pass via CN IX (carotid bodies) and CN X (aortic bodies) to DRG—sense arterial oxygen pressure Mechanism of Stimulation by Oxygen Deficiency Regulation of Respiration During Exercise Oxygen consumption (and carbon dioxide production) and ventilation rate increase by as much as 20-fold during strenuous exercise Despite this, the concentrations of arterial blood gases remain almost exactly normal. How? Regulation of Respiration During Exercise Example of Abnormal Respiration—CheyneStokes Breathing Overbreathing results in a delay where the brain can sense that too much CO2 has been released or O2 has increased Normally this mechanism is highly damped Cheyne-Stokes breathing is seen in 2 major types of conditions: • Severe cardiac failure • Damage to respiratory control centers