---start physio 1.5.97--- we're going to discuss control of ventilation this hour. that's not as well worked out for respiratory system as control of other organ systems eg circulatory. the respiratory equiv of the heart is the chest wall musculature, which isn't one individual unit, it's diaphragm, intercostals, abs...all skeletal muscles...it's difficult to quantify all the muscles - all are skeletal muscles, though, so control of ventilation involves control of skeletal muscle. so think about dr sweeney's lecs about sk musc. there are many parallels between control of resp musc and control of locomotion. in addition to this we know what controls ventilation in abnormal situations, eg dz, and we know what drives it at high altitude, or if you're breathing CO2. but we don't know what drives it at rest, at exercise, under normal conditions. despite these unknowns, we're forging on. FUNCTION OF VENTILATION: maintain proper gas exchange and pH. if you want to do this, you need vent to be proportional to metabolic rate (O2 consumption and/or CO2 production) when you exercise, ventilation rises in proportion to met rate, hyperpnea, but CO2 and O2 levels stay relatively constant. this maintains adequate gas exchange. in animals - variation in O2 consumption can be 50fold, but ventilation can compensate by staying proportional you need vent to stay proportional to metabolic rate, despite changes in mechanical properties of system imposed by clothes, pulmonary dz, sitting, standing, high altitude, cardiac dz, anemia...etc. now in looking at FUNCTIONAL LEVELS OF CONTROL 1. genesis of respiratory cycle: eg genesis of inspiration, expiration, etc goes on for entire life. involves some knowledge of brain, neuroscience 2. control of automatic functions: 3. control of integrated activities: eg, resp must be integrated w/talking, vocalizing, walking, eg. so. GENESIS OF RESP CYCLE: controlled by: networks of neurons in medulla and pons, specific neural arrangements are not known. *brain* controls ventilation. there is no automaticity in resp muscles, no endogenous activity, unlike in heart. if you cut nerves to resp muscles, they won't work anymore. some folks think brain has pacemaker activity like heart, others think that due to network properties in brain, specific neural nets, there is the constant in out of air. just know that BRAIN CONTROLS GENESIS OF CYCLE. CONTROL OF INTEGRATED ACTIVITIES: ventilation integrated w/other activities, voluntary motor activities, speech, temperature regulation...eg, racehorses breathe once per stride - resp integrated w/locomotion. most of this is "beyond scope of this course" which means RO doesn't understand it. CONTROL OF AUTOMATIC FUNCTIONS: deals with several things. one, level of ventilation eg volume/min, which is adjusted to meet metabolic demands - see oxygen uptake graph. ventilation rises in proportion to metabolic rate. this adjustment comes about because brain uses info from peripheral and central chemoreceptors, information that comes over somatic afferents, and motor centers of brain send signals to respiratory area through motor collaterals (movement signals). two, can adjust tidal volume and frequency - minimizes efforst to produce the level of ventilation that's required. you get what you need with minimal effort expended. three: controls operate on rate of firing of neurons, and timing: duration of inspiration and duration of expiration. we're talking sensory and motor neurons, here. slide: arterial pCO2 is increasing, and as it increases, more neurons are firing, and they are firing more frequently, so the rate of firing is being changed. SO WHAT HAPPENS WHEN YOU BREATHE? it is initiated in the brain, and over time, activity in brain increases (during one breath) - brain activity increases and drives inspiration, then drops off, and drives expiration. brain drives motor neuron to diaphragm, so as brain activity increases, phrenic motor neuron activity increases, and as diaphragm contracts, lung volume increases. so all three of these lines are parallel on a chart. / \ / / so tidal volume increases with increased brain activity driving increased phrenic firing driving diaphragm contraction driving increased thoracic volume. how long this lasts is a function of chemical drive, CO2 and movement signals from brain. note that as CO2 increases, there is a faster rate of rise of activity of the phrenic nerve. the peak is always proportional to the tidal volume. as drive to breathe increases, rate of rise increases and end tidal volume increases. but...phrenic nerve activity increases until it suddenly stops abruptly. what turns off inspiration? two things. one, there's activity in the pons, and cells in this area increase their activity the same way the cells in respiratory center do...they gradually increase throughout inspiration,-during which time they signal the offswitch... then decrease. in the brain this happens, and so it's an INTRINSIC mechanism. there are EXTRINSIC mechanism...something outside the brain...derives from receptors in large intrathoracic airways..large bronchi, etc.these airway stretch receptors are sensitive to stretch of airway therefore sensitive to lung volume. so the firing of these receptors is proportional to lung volume/airway stretch. these are called PSR pulmonary stretch receptors, and they activate other cells in brain called "relay", and the relay and the pons together activate the "offswitch" which turns off inspiration. when pons and relay signals reach appropriate point, boom. inspiration is turned off. a cell is attached to pulmonary stretch receptor and rate of firing of cell is charted...you can see that when lung volume increases, the cell fires. if you hold lung at large volume, firing continues - it's proportional to lung volume. PSR firing frequency increases as lung volume increases. extrinsic mechanism. pons firing increases as inspiration continues....intrinsic mechanism. when firing of both reaches threshold, offswitch is triggered and inspiration ends. [so far, so good, i think :)] so we have then: Hering-Breuer mechanism: vagal reflex Pons | \/ PSR---(via vagus nerve)---------->relay----->offswitch------->OFF what happens? brain fires, phrenic fires, muscles contract, lung volume increases, intrinsic/extrinsic firing, switch off. so, how much lung volume do you need to reach offswitch? early in breath, you need LARGE volume, because ponsian contribution is small (recall pons activity increases w/time of inspiration). later in inspiration, required volume component is very small. why do we need to know this? well, we need to know how you change TV and frequency when we change drive to breathe. drive to breathe: chemical: high CO2, low O2, or movement signals: increases phrenic activity. so if we have high rate of rise of activity, lung volume (high drive, high CO2, movement) will increase very rapidly, and therefore it will continue to increase a lot because the offswitch volume threshold is high early on, so you get a large tidal volume and a shorter time. so you have more breaths/min. so high drive give high tidal volume and high frequency. a low drive yields a low rate of rise, plenty of time for pons to generate increased firing, so need only small tv to reach threshold. so then you get low TV and low frequency. once you reach offswitch threshold, expiration occurs. can be entirely passive: relaxation of resp muscles and lung recoil wiill do it. usually, it's not passive. at rest, expiration is usually braked - eg, it is SLOWER than passive would be. this is 'cause inspiratory muscles REDUCE but do not STOP their contraction during expiratory phase. so they RETARD the expiratory phase, like a parachute retards the rate of fall. or you can have active expiration, forcing breath out, recruiting expiratory muscles to get gas out (eg in exercise). now, look at optimization that brain can do of TV and frequency, so that whatever ventilatory effort you need is done w/minimal amt of work. so lets do an experiment: say you need a certain alveolar Ventlation V*a, and you want to know how much power P is needed to acheive it? you can do this at various frequencies, from low to high. suppose you want V*a = 5 L/min you can do that at low frequency f = one 5 L breath/min, or one 10 L breath/2 min but as frequency f gets lower, stretch of lung INCREASES...lung gets noncompliant. as f increases, stretch decreases. to breathe we need to stretch lung and overcome airway resistance. at low frequency, airway resistance is low, and effort to overcome it is low. as f increases, you get increased resistance, faster air movement, more dead space ventilation..so you have INCREASED effort to overcome resistance. total effort = work to over come stretch + work to overcome resistance... this tells you when total work of breathing is at a minimum, and that will be the normal frequency for that animal. horse's is low, cat's is higher. but you need to see what's normal for that animal. now, if you change mechanical properties of the system...if you make th lungs stiffer, it's HARDER to stretch them. so at every point on the curve, you need more effort. this will cause the sum to shift to right...so the frequency will increase. so if you have stiff lungs, it's better to breathe at high frequency, low tidal volume. if you increase resistance, sum moves to lower frequency. you want to breathe at low frequency, with increased tidal volume. eg, if you breathe through straw, or have asthma, you save energy by breathing at low frequency & high tidal volume. so that's the observation: what's the mechanism??? alveolar volume represents stretch airway represents resistance thorax = container there's the receptor in the airway - PSR - which signals the RELAY which signals the offswitch. as volume increases, more firing of receptor remember the enclosure acts on everything inside of it. airways and lung. lets make lungs stiff. (edema, congestion, collagen, etc). take a breath - thorax expands. lungs are hard to stretch, airways are easier to stretch. so effort of chest wall is exerted more on airways than on lung. airways expand relatively more. so the PSR fires more. this shuts off inspiration early. this increases frequency and lowers tidal volume. to increase airway resistance: make stiffer through edema, contract smooth muscle to constrict, whatever. then when volume of thorax increases, lung expands more readily than airway. so PSR fire at lower frequency, it takes longer to turn off inspiration, so you get a lower frequency and a higher tidal volume, because lung is stretching more. so this Hering-breuer reflex determines size of inspiration and frequency of inspiration and you can optimize TV and frequency for conditions, so that minimal effort is expended, given level of ventilation and particular mechanical state. reminder: this is a vagally mediated reflex. ---end---