EP1 - Control of Ventilation | Anaesthetic Primary Topic | Respiratory Physiology | CT10

Hi, I'm Arnie and this is Counterten. Counterten is a primary exam podcast lecture series hosted on the Sweet Dreams Anesthesia podcast network. It's focused on the anesthetic exam based in Australia and New Zealand. Today is our first episode and we'll be starting with the topic control or ventilation. We'll go through the learning objectives, luckily there's only one, and then some of the past essay queues and examiner reports. So let's dive straight in. Within control or respiration or ventilation, there's one LO that's listed and that is describe the neural and chemical control or ventilation via central and peripheral chemo receptors and indicate how this is altered by anesthesia and of normal clinical states. Usually this is the first LO that people will go through when they're going through Mach 95 and the thing to recognize is that this is actually two LOs in one. There's a control of ventilation and then there's the alteration by anesthesia. Whenever the word control is used or regulation is used, this usually refers to the basic elements of a sensor, controller and effector. That's something that you have to just imprint in your brain whenever you recognize these two words. When we think about the sensors that are important within controlling ventilation, they can be divided into the chemical factors and mechanical factors. Within chemical factors, these are things that are going to recognize changes with oxygen, carbon dioxide and pH and they can be further classified into the central chemo receptors and the peripheral chemo receptors. Now by far and away, the central chemo receptors are the most important. The unique thing here is they don't respond to changes in oxygen but they only respond to changes in carbon dioxide. They're the most important for the minute to minute ventilation or changes in minute to minute control of your ventilation. They're located in the ventral surface of the medulla and they're actually in the extracellular spinal fluid, not in the central spinal fluid. What happens is that the blood vessels are impermeable to hydrogen but carbon dioxide can diffuse quite easily. When carbon dioxide diffuses, it then reacts with water to form carbonic acid. Carbonic acid then becomes bicarb and a hydrogen ion and it's actually the hydrogen ion in this reaction that stimulates the central chemo receptors. It causes a change in pH and that change in pH is the main regulator of ventilation. There's a lovely diagram in west that depicts this and this is a very key point that as you get closer to the viva examiners love to pick up on. The other thing to mention is that this reaction is fast because of the presence of carbonic anhydrase. Carbonic anhydrase facilitates the reaction of CO2 and water being converted into carbonic acid and without this the reaction is normally slow. However, the cerebrospinal fluid has a high amount of this and therefore this reaction can occur quickly. The important thing to recognize is that the cerebrospinal fluid and the extracellular fluid within this space has a very low buffering capacity. The normal pH is actually less than the normal blood pH so it's 7.32 here compared to the blood which is 7.4. So when bicarb diffuses across the blood brain barrier, we have a very slow ability to compensate because we have low proteins and low bicarbonate. So the change in ventilation actually lasts longer than expected as compared to if you had the normal amount of proteins within your plasma and your blood that would be able to easily buffer the response and change the pH quite quickly. So because this takes a bit longer to achieve, the ventilation response is slightly longer as well. Then we move on to the peripheral chemoreceptors. There's two types. They're the carotid bodies and the aortic bodies. The carotid bodies are located in the bifurcation of the common carotids and the aortic bodies are located above and below the aortic arch. They send their sensory information via different nerves. The carotid bodies are supplied by the cranial nerve 9 which is your glossopharyngeal and more specifically by the herring nerve while the aortic bodies are supplied by your vagus nerve. The impulses travel up high and within these bodies are types of cells called glomus cells. You don't need to know much about glomus cells apart from the fact that they exist and those are the cells that are thought to be actually the chemoreceptive cells. However, there are two types. There's type one and type two. Type one is thought to be rich in dopamine and type two is thought to be more of your capillary and blood supply. The reason why the peripheral chemoreceptors are located within the carotid bodies and aortic bodies in that particular location is because you have a very small arterial to venous O2 difference here. They're actually only responding to the arterial O2 not the venous O2 and their sensitivity is very unique. So the sensitivity to change actually begins at a partial pressure of O2 of up to 500 millimeters of mercury. However, the max response starts to occur at 50 millimeters of mercury and so you'll see this graph in west but it can be a common question as to where does the actual sensitivity begin and it's actually quite high so it recognizes a partial pressure O2 change up to 500 millimeters of mercury and usually by the 50 percent at a partial pressure of O2 at 50 millimeters of mercury there's already been anywhere between 25 to 75 percent change in your ventilation that's occurred. Because of the location of these peripheral chemoreceptors they respond much quickly to changes in your chemical stimulus than your central chemoreceptors. However, the overall change that they create in your ventilation is much more proportionally smaller so they're responsible for less than 20 percent of your total response change to ventilation while your central chemoreceptors are responsible for 80 percent. Now the unique thing between the carotid bodies and aortic bodies apart from their sensory nerve innovation is also what they respond to. So we said that the central chemoreceptors don't respond to oxygen partial pressure changes they technically respond to hydrogen changes through partial pressure of CO2 or CO2 diffusing across the blood-brain barrier. While the carotid bodies and the aortic bodies they both respond to oxygen so the importance is that they respond to hypoxic conditions or hypoxemia conditions. The carotid body also responds to changes in pH while the aortic body does not respond to changes in pH and all these changes when they occur together are synergistic at changing the ventilation even more pronounced compared to just an isolated change. So those are the chemical factors and there we go into the mechanical factors. So mechanical factors in terms of sensors can be broken down into your lung receptors. So here we have your pulmonary stretch receptors or aka your slow adapting receptors and these lie within the airway smooth muscle. They're activated when the lung stretches and typically these are kind of the sensory innovations via the vagus nerve but they're activated when the tidal volumes are greater than a litre usually as we get older we we go away from these reflexes but when we're young or neonates this is what leads to that classic herring brewing reflex which is that when your tidal volume is greater than a litre then it activates the inspiration or decreases the respiratory rate overall. Additionally we have the uratin receptors so these lie within the airway epithelial cells again they're carried by the cranial nerve 10. Their stimulus can be anything such as noxious gas smoke or dust and they can cause anything like bronchoconstrictions or hypoxia which is the increase in respite and they're thought to play a role in asthma. Then you have J receptors these are located within the alveolar walls themselves and they're closer to capillaries. They respond to chemicals injected into the pulmonary circulations themselves so a clinical example would be the engorgement of capillaries maybe associated with something like heart failure or congestive cardiac failure which leads to an activation of that increased respite shallow breathing and that dyspnea that you might see in patients that are having acute pulmonary edema. You have the bronchial C fibres which are within the bronchial circulation so J fibres are within your pulmonary circulation while your bronchial fibres are in your bronchial circulation and their stimulus can be also chemicals and they can lead to an increase in respite shallow breathing bronchoconstrictions and increasing your mucous secretions. Then you have a multitude of other receptors they're within your nose your upper airways they respond to irritants and especially in the upper airways you can get their classical laryngeal spasm when these are activated. You have your joint and muscle receptors which are thought to be activated when there's limb movement and a potential hypothesis for why we can increase in respite with exercise. There's your gamus system which is associated with that within the muscle spindles and these also are thought to be sensing muscle elongation and then reflexively causing a increase rate in your respiration. We have your arterial baroreceptors as well so your baroreceptors are in your carotid sinus and your aortic arch and this makes sense that the fact that if you have an increase in your blood pressure you decrease your ventilation and if you have a decrease in blood pressure you increase your ventilation and we'll get back we'll get into that when we get into cardiac physiology but an increase in ventilation is helping to increase your your venous return and so it's improving blood flow back so when you have low blood pressure you want to increase your ventilation to try to increase your blood flow back to your heart to increase your preload and then therefore increase your cardiac output and then other senses are linked with things like pain and temperature so when you have a painful stimuli you'll typically have an initial period of apnea and then hyperventilation and that period of apnea can be very small you can also have a heating to the skin that can cause hyperventilation as well so there's a multitude of mechanical receptors or mechanical stimuli you don't have to remember all of them and what they do individually but you just have to be able to list them out especially in a vivisetting when people tell you or ask you a broad question of what are the senses of control of ventilation and you can break it down to chemical and mechanical chemical you'll always remember by your chemoreceptors but the mechanical ones you just have to be able to rattle off and you don't have to know too much but just the basic and if you ever stark you just say that the sensory nerve is typically your cranial nerve 10 which is your vagus nerve so going into the control of ventilation so the control of ventilation is within the brainstem and we have your neurons here in your pons in your medulla when we look at your medulla we have the medullary medullary respiratory center and this is thought to be in the reticular formation beneath the floor of your fourth ventricle you have your ventral lateral region and here we will find our pre-botsynga complex and the pre-botsynga complex is commonly brought up when we talk about control of ventilation and that's thought to be important in the respiratory rhythm and pattern that we generate then we have your dorsal respiratory group and your ventral respiratory group and the way I remember that is this simple acronym DIVE so the dorsal respiratory group DI is thought to be important with inspiration or associated with inspiration while your ventral respiratory group VE is thought to be associated with expiration so if you imagine a picture where the stimulus from your crowded bodies and aortic bodies is traveling via your glossopharyngeal your hering nerve and your vagus nerve these are going up to your nucleus tractor solitaris then there's a few interneurons that are then connected to your central region within your medulla and your pons and then you have your effectors down your nucleus ambiguous and your dorsal motor nucleus of your cranial nerve 10 as well so when we go and have actually a further look at how inspiration and expiration works we have a pretty typical inspiratory pattern so nuns divide nuns describes this classically in three phases we have the inspiratory phase with that ramp like increase in neuron activity the post-inspiratory phase or the expiratory phase one where there's a decline in the discharge of the motor neurons and there's a passive expiration and there's an expiratory phase two which is your third phase or your third part which is the inspiratory muscles are now silent and then there's a recruitment of expiratory muscles that can occur that doesn't normally occur in normal quiet breathing so these were all the main central controllers in the medulla so just to recap we have the medullary respiratory center we have the ventral lateral region with the pre-botsing complex and you'll read different texts that say where the pre-botsing complex are located in different regions but the important ones to remember are always your dorsal respiratory group and your ventral respiratory group with that acronym dive then when we look at the ponds the ponds have two distinct areas the ponds have the pneumotaxic center and the aponeuristic center the pneumotaxic center is in the upper ponds and this can turn off the inspiratory ramp and it's thought to be having a role in fine-tuning the respiratory rhythm because normal rhythm can exist without it so it's not essential for having a rhythm but it's thought to fine-tune the rhythm remember the respiratory rhythm is mainly controlled by the pre-botsing complex then you have the aponeuristic center which is in the lower ponds and this is thought to be important in prolonging that ramp-like inspiratory phase and typically you see those classic patients at the dors death that have those inspiratory gasps that occur so they have the prolonged inspiratory gasps with the gasps with the weird breathing pattern afterwards and this is thought to be attributed to the aponeuristic center now these aren't the only controllers in the body so we've talked about the medulla and the ponds within the brain system but we know we can control respiration by ourselves so we can control it with the cortex control because we can do it while we're talking right now so we can override our automated breathing and actually actively think about it with our cortex and therefore we can hyperventilate and hyperventilate and there's other parts of the brain that are linked to the controller so we have the limbic system which is important because when we get anxious or have changes in our emotion we change our respiration depending on what type of emotion that we're feeling and we also have the hypothalamus linked in with the limbic system the last part of this control sensor control and effector model is the effectors themselves and these are the muscles for respiration which we'll get into further when we talk about other topics in particular when we talk about mechanics of breathing as our next topic but as a brief overview what you must understand is that the chief muscle of expiration is the diaphragm expiration is a passive process majority of the time and is active within disease state or if we actively do it and then we can recruit other muscles such as your intercostal muscles your psoriasis muscles your abdominal muscles to help with the expiration process as well it's a coordinated maneuver that occurs to expire and when it becomes uncoordinated especially in children that are developing or neonates that's when we have associations or hypotheses of children having sudden infant death syndrome so that's the first part of the LO which is the control of ventilation the second part is the alteration with anesthesia and other states and the first state to think about is the response to exercise so with exercise we know that ventilation increases promptly so as soon as we start exercising we increase the ventilation however there's no clear reason why we increase this ventilation because there's no actual changes that have occurred in our body in terms of oxygen levels carbon dioxide levels and our pH levels when we initially start exercising so there's lots of theories out there but we know that ventilation can increase by around about 15 times from resting levels when we do start exercising and our increase in ventilation closely matches our oxygen and carbon dioxide output the important thing is that arterial partial pressure of CO2 doesn't actually increase when we're exercising until we're actually at the end of exercise we're reaching our anaerobic threshold arterial partial pressure of O2 actually doesn't decrease much it actually increases slightly and our pH levels are pretty constant again until we reach that anaerobic threshold where now we're increasing our lactate production so why if we're not having chemical changes are we increasing our ventilation the theory that we said previously was thought to be with the mechanical receptors and being the joint receptors and so the movements of the joints are thought to be or muscles are thought to be a possible reason for increasing ventilation in the first few seconds of exercise there's also thought to be other theories such as the possible oscillations of the arterial partial pressure of O2 and the partial pressure of CO2 which can be stimulating the stimulating the peripheral chemo receptors but overall if you ask this question you you can just say that it's not clearly known but there's thought to be joint receptors and other theories out there as possible instigators for increasing ventilation with the initiation of exercise then thinking about changes in ventilation in other altered states so we have the typical one of response to ventilation with an increase in altitude so altitude typically causes a three phase response and this is pretty easy to understand when we go through it step by step so as you're climbing a mountain for example your atmospheric pressure is decreasing and at altitude you have hypoxemia the hypoxemia will stimulate your peripheral chemo receptors remember they're the ones that respond to partial pressure of O2 changes not your central chemo receptors this stimulates an increase in minute ventilation when we get the increase in minute ventilation we then drive off our CO2 so our partial pressure of CO2 decreases so now we have counteracting stimulus the partial pressure of CO2 decreasing will then cause my central chemo receptors to stop any further increase in my minute ventilation then over the next two to three days as my pH equilibrates within that CSF extracellular fluid remember it's the hydrogen concentration in extracellular fluid which is important as that normalizes this allows the hypoxic respiratory drive to then be reinstigated and then we get that increase in minute ventilation again so initially we have an increase in minute ventilation then leveling out or a plateau being our phase two and then a restart of the increase in ventilation and the important thing there is that partial pressure of CO2 is the main driver in controlling minute ventilation on a respite basis and in some disease states like the chronic CO2 retainers which type 2 respiratory failure oxygen then becomes a main driver but in everyday condition in healthy individuals partial pressure of CO2 is the main controller other altered states where we have changes in ventilation pregnancy so with pregnancy we have a typical increase in minute ventilation and tidal volume so overall by the end of the first trimester majority of changes have already cared with our respiratory system in terms of ventilation increases and this is mainly because of the increased progesterone shifting our sensitivity of partial pressure of CO2 to the left so therefore at lower partial pressures of carbon dioxide we then have an increase in ventilation occurring overall ventilation is increased by 50 percent 40 percent of that is an increase in tidal volume and 10 percent of that is an increase in respite and this is there for a couple of reasons one due to the due to the progesterone but secondly also due to the increase in basal metabolic rate which is increased by around about 1.2 times normal as well and then finally we have the changes in our control of ventilation via anesthetic agents so you can say a broad overarching statement in saying that almost all general anesthetic drugs will reduce ventilation in a dose dependent fashion the important thing to understand is that are these drugs changing the apnea threshold which is the partial pressure of CO2 which spontaneous breathing returns or are they changing the gain of response to a change of ventilation so what I mean by gain is that the amount of change in our ventilation that it cares due to changes in chemical or mechanical factors and remember an example is we have a gain of 15 times on normal ventilation when we start exercising so it's anesthesia decreasing this gain or anesthetic agents affecting the apnea threshold and commonly they'll do a bit of both typically you'll see drugs like opioids will increase our apnea threshold so therefore the partial pressure of CO2 that you need to reach for you to now stimulate breathing is typically increased by around about five to ten millimeters of mercury with drugs like inhalation agents this this is also increased and then you also have a change in the gain of response occurring so typically with opioids you have a classic type of breathing you have a high tidal volume low respite type of breathing and with inhalation anesthetics you get a typical high respite low tidal volume type of breathing this covers the first LO and the only LO in control of ventilation and takes us nicely into talking about the previous SAQs now for SAQs I do recommend using mac95 they divide the SAQs up nicely into topics and within control of ventilation/respiration there's around about seven previous SAQs that have been asked so luckily not too many and but there are a few repeats the most recent question that was asked was describe the respiratory responses to hypoxemia in both the awake and anaesthetized patient it had a pretty good pass rate of 60% asked recently in 2021 and the examiner report was very helpful it pretty much laid out what was expected for a candidate to get a pass mark and it's pretty straightforward they'd expect you to define hypoxemia outline the components of the associated physiological control system so this is again going back to the sensor controller integrate effector model that we've spoken about appreciate the difference between the respiratory drive and the partial pressure of O2 outline hypoxic pulmonary vasoconstriction and then address some of the effects of anesthesia upon these responses I do think that the ketamine nightmare's answers probably the best one to look at in terms of guiding you on how to structure it because it follows this kind of stepwise approach and so when you go about answering it you can start by defining what hypoxemia is which is universally agreed upon as less than a partial pressure of arterial oxygen of less than 60 millimeters of mercury go into those sensor control integrator models and then be more specific obviously you're looking for the sensors in terms of peripheral chemoreceptors because you know the central chemoreceptors do not respond to the changes in oxygen and these are predominantly done with the peripheral chemoreceptors so how these are relayed via the aortic and carotid bodies how these are attenuated with anesthesia so effects of inhalation anesthetics induction agents attenuating this response as well as opioids inhibiting this response and then essentially doing the same talking about the medullary dive area in terms of the dorsal respiratory group and the ventral respiratory group and how they individually control inspiration and expiration and then talking about how these are affected by drugs such as opioids and other receptors that are within this area that will affect the GABA receptors the mu receptors and depress the ability of the controller to effectively give commands to the effector subsequently the effector will then have a decrease in the ability to increase its minute ventilation in an enthetized patient compared to an awake patient and you should draw a typical diagram that you see you need to kind of imprint in your brain which is shows the entire partial pressure of oxygen or partial pressure of oxygen on the x-axis and the minute ventilation response on the y-axis and here you get this typically blunted response even at a mac of 0.1 which is a key thing to write down in your answer that there's significant depression of the response to hypoxemia with a mac level of 0.1 then additionally you want to add on things such as what hypoxic pulmonary vasoconstriction entails so the normal role of HPV is to increase the VQ matching and HPV has a typical biphasic response where the phase phase one is the immediate response that plateaus within five minutes the exact reason why it occurs is not thought to be truly elicited but it's thought to be involving potassium channels or calcium channels and it relates to the partial pressure of oxygen within the alveola itself as well as a minor effect from the oxygen concentration within mixed venous blood the second response in the biphasic phase occurs later on around about the 40 minute mark in a plateaus and so you need to be able to kind of write down in a succinct manner this biphasic response and how anesthetic agents can attenuate this so in particular we have the effect with volatile anesthetics inhibiting your L-type calcium channels and this leads to a decrease in hypoxic pulmonary vasoconstriction while prepofol is thought to be less potent on the its attenuating effects and therefore is preferred in specific types of surgery the next SAQ was from 2015 and it asked outline the role of carbon dioxide in the maintenance of ventilation and I think this question can be answered well if you understand that carbon dioxide is a product of metabolism and you relate everything back to this typical equation which is or this essential equation which is that the partial pressure of arterial CO2 is equal to the CO2 production divided by the alveolar ventilation times a constant k and this equation essentially comes from west and if you can rearrange it to then work out what are the factors that affect production of CO2 and maintaining that partial pressure of CO2 at a constant rate in the body which is set to be around about 40 millimeters of mercury plus or minus two to three millimeters of mercury you can then kind of work backwards and figure out all the factors so I think the prepofol dreams answer here is really nice they divide the factors simply into that sensor control effector model again and looking more specifically at the sensors so in this case the chemical factors CO2 is going to affect both the central chemo receptors and the peripheral chemo receptors you're going to talk about which one of these is more important more potent we know that the central chemo receptors attribute to attribute to 80 percent of the change in ventilation while the peripheral only do 20 percent however the peripheral ones are faster we then go back into talking about the controllers and the dorsal ventral dorsal respiratory group and the ventral respiratory group and then you can relate the effect back onto that equation of changing ventilation by increasing your muscles of expiration and inspiration to increase respiratory rate or ventilation you know that alveolar ventilation is a product of both respiratory rate times the tonal volume and so you can then say that these two factors are increased when there is an increase in partial pressure of CO2 to try to equilibrate back to the homeostatic levels of 40 millimeters of mercury and when it decreases we then decrease respite the other sqs that have been asked pre-2013 so the chances of them coming up are less likely but that doesn't mean they can't come up certainly the question where it asks list the physiological factors which increase respiratory rate and include a brief explanation of the mechanisms by which each achieves this increase is a great question that asks pretty much what we went through in terms of the sensors initially talking about the sensor controller effects a model so again if you take this back to basics and you know that the sensors can be divided into sensors of chemical factors and mechanical factors that will then relay information back to the controller we can then break down how we're going to structure this question and so therefore I think about it very simply as in chemical factors being carbon dioxide oxygen and pH mechanical factors being stretch receptors bronchial C fibers the J fibers the irritant receptors additional reflexes such as your blood pressure changing and your baroreceptor reflexes then looking at more peripheral things that can change respite so your cerebral control can override respite and then things that happen with the disease state so things that can change basal metabolic rate whether this is exercise uh infection pregnancy or neonates and then link that back up into how they all change respite finally the last question that we have from 2005 is described the physiological factors influencing the carbon dioxide tension and arterial blood I think again this lends itself back into their equation which I harbor on a lot about but it's back to the basics of that partial pressure of arterial CO2 is equal to the production of CO2 divided by the alveolar ventilation times k which is the constant so again if you think about these three components in terms of the partial pressure of CO2 the production which can then be thought about as things that increase production and decrease production and you can link that into metabolic rate and then you can think about things that increase ventilation and decrease ventilation so they can be normal physiological things that increase ventilation and then nonphysiological things such as the effects of drugs or anesthesia that affect ventilation and how this balance will affect my partial pressure of CO2 when you talk about carbon dioxide tension that's talking about the partial pressure in arterial blood the side note to this is that remembering that CO2 production is in the aerobic phase of metabolism not in the anaerobic phase and for each glucose molecule that gets converted into energy you produce six components of partial pressure of CO2 or six particles of partial pressure of CO2 that are produced two of them within the citric acid cycle and one via the intermediary phase where pyruvate gets converted into acetyl-CoA so this takes us to the end of our control of ventilation topic the quick few things that I want to recap on is that this is usually the first topic that anyone who's starting the curriculum will cover so the importance of understanding this sensor controller effect and model is very key to understanding this topic and then for subsequent topics as well understanding the difference between the central and chemo central chemo receptors and the peripheral chemo receptors in terms of where they're located what they respond to in terms of the chemical factors is also key and finally understanding the concept that anesthesia or the drugs we use at anesthesia can affect both the apnea threshold and the gain of the normal responses to try to change ventilation and drugs can do individual things or they can work on both those factors as well so thanks again for listening and we'll be back next time with our topic on mechanics of breathing