Welcome back. We've talked about how the pressure of oxygen and CO2 is going to change in the lung, depending on breathing and then how that is also going to be reflected in changes in the blood. So, now we're going to talk about how those changes of oxygen and CO2 in the blood are going to regulate how much and how deeply we breathe. So we're going to have two different types of receptors. Central receptors, meaning that their in the brain stem. And then peripheral receptors, which are going to be in the vasculature, and we'll talk more about those in a minute. They're going to be feeding into a respiratory center in the medulla of the brain that is going to integrate that information. So this is just going to be a reflex loop like we've talked about when we were in the nervous system that is then going to control breathing. So remember that the diaphragm, and then the intercostal muscles as well, between the ribs, those are gonna be skeletal muscles. So every time we breathe there's going to be action potential that's sent to those muscles to cause them to contract. It will be through the use of a central pattern generator because it's gonna be the same contractions and relaxations over and over again. And that will be able to be modified so that you can breathe more deeply or more quickly, but still every time breathe, there will be a signal sent to those muscles to cause that to happen. And then that will hopefully fix, the stimulus so that now we will be within the desired range and then the reflex loop will continue to monitor what's going on. So our two types of chemoreceptors, the peripheral ones tTat are going to be found in the carotid arteries and in the aorta, that are going to be sensing three different things. One is that they're going to respond to a decrease in the pressure of oxygen in the arterial blood. So again, they're not measuring how much hemoglobin is present and how saturated it is. It's only measuring the pressure of that small amount of oxygen that's dissolved in the blood and assuming that if that's fine, then hemoglobin and the amount of oxygen in the blood should be fine. It's also responding to an increase in PaCO2. So if there's an increase in the pressure of CO2 in the blood then we need to breathe more as well. And then these receptors are going to respond to a decrease in pH which means that if we have too many protons around, and then if we breathe more, we'll release more CO2, which will decrease the number of protons. And we'll be talking more about all three of these substances that are detected in just a minute. The central system is a little different because it's going to be within the blood brain barrier. And so, protons are not gonna be able to cross the blood brain barrier. But, what will cross the blood brain barrier and be detected is PaCO2. So these central receptors, if we have in increase in arterial PCO2, then CO2 will increase in the brain, and that increase in CO2 in the brain will cause increase in protons and that's actually what sensed as the increase in protons but it's really only reflective of the increase in CO2 in the rest of the body. There are other receptors that are also influence our respiratory rate, and these are actually in the respiratory system itself, where it's we have pulmonary stretch receptors in the smooth muscle of the airways that are going to fire the more the lung that is inflated. So that they can stop inspiration if it's getting, if the volume is getting too large, if there’s too much stretch. So this is called the Hering-Breuer reflex, and it’s going to be present in babies and in adults. But in adults, it’s going to be important mostly just in extremely vigorous exercise, when we're filling our lungs as much as we can, and it's really going to be to say okay, the lung's full enough now, you need to stop inspiring before you do some damage. There are also J receptors, which are in the capillaries of the lung, and are going to respond to lots of pathological situations like vascular congestion, edema, and air in the blood, as well as low lung volumes. It's not clear exactly their role, except that these are going to often cause rapid breathing and or labor breathing which is going to be obviously a symptom of a lot of these issues. So it's, in a way, alerting that there's an issue because of this labored or rapid breathing. Then there are pulmonary irritant receptors which are gonna be in the epithelium so that linings of the airways. These are going to respond to mechanical or chemical irritation and cause you to cough. You feel a tickle and then you cough trying to get that particle or pathogen out. The smart thing about it is it also causes bronchoconstriction so that if you're in some sort of dust cloud and you elicit this response then it's smart to bronchoconstrict so you can try to reduce the amount of other particles that you bring into your lungs. Before we're gonna we've talked now how CO2 and O2 and protons are going to affect how our breathing, our breathing rate and how deeply we breath and we haven't really addressed proton transport in the blood, so we're gonna do that right now. Where in the tissues we know that oxygen is going to be released from hemoglobin so that now we're gonna have deoxyhemoglobin and deoxyhemoglobin has a greater affinity for CO2 as well as protons. So, just like CO2, protons can bind hemoglobin and so that hemoglobin will bind protons and this is convenient because this is happening in the tissues where you're dumping oxygen and now we want to pickup CO2. And we've got extra protons from metabolism, and so those will be picked up by the hemoglobin. So this is a major buffer in the blood, is hemoglobin. And normally, we do have a shift in pH of the blood where our arterial blood is gonna be 7.4 and venous blood 7.36. If we didn't have hemoglobin, that difference would be much bigger. The venous blood would have a much lower pH, so it's a major effect. It doesn't completely erase the change in PH, but it makes the difference much less. Once we get then to the lung, oxygen is gonna be there in hot large amounts and it's going to bind to hemoglobin and cause a release of the protons. Then the protons will, as we've said before, they're gonna cause this reaction to go this way. Which causes CO2 to be produced. But that's fine, we're in the lung, the spot where the CO2 is gonna be removed and diffused into the alveolus. So that's gonna emove the protons that we picked up and correct the pH. So we can have a 0.08 unit change in pH for every 10 mm mercury change in PaCO2. So, keep in mind, that if we increase CO2, we're gonna also increase protons and lower PH. That means, that if we have a problem with the respiratory system, we can cause a problem in acid-base balance. So this gets back to the very first slide of this series of lectures, where we said the role of the respiratory system is not only to get oxygen to the tissues and pick CO2 up from the tissues. But it 's also to regulate acid-based balance. So that means, that if we have a problem with the respiratory system, very often that's gonna be accompanied by problems with pH. And so, if we have ventilation decreases for some reason, then we already said, that means we're hypoventilating which means that our CO2 is gonna increase. We're not removing it as efficiently as we should be. If CO2 increases, proton concentration increases which means pH decreases. So that means we can, we'll have a condition called acidosis where we have too much acid. It's called respiratory acidosis, because the whole reason why we got into this problem was that ventilation fail. We stop breathing as much as we should. We can have the converse situation where for some reason, ventilation increases. We're hyperventilating for some reason. We said hyperventilation means that the pressure of CO2 decreases below 40. We're breathing more, bringing in more fresh air, which means the CO2 gets removed from the body more quickly and it goes below 40 mm of mercury. If CO2 decreases, that means proton concentration decreases. Which means the pH increases and we have alkalosis. And again, since the whole source of this alkalosis is an increase in ventilation, then it's respiratory alkalosis. So this is just a picture of what we've talked about already where, when we're in the tissues, they're gonna have a low oxygen concentration. So oxygen is gonna diffuse out of the red blood cells. That's going to mean that we now have deoxyhemoglobin. And at the same time, we're getting CO2 to diffuse into the red blood cell, which means that a lot of it will be, 60% of it will be converted to bicarbonate. And that means we will also be producing protons which will then combine to hemoglobin. We're gonna now switch gears a little bit, because we've already said that oxygen and CO2 and proton concentration or pH can all affect how often we breath our ventilatory rate. And now we're gonna look more specifically at the graphs for that data. Where we see, with oxygen as the arterial oxygen changes, then the minute ventilation will change. At 100 mm of mercury, are normal arterial oxygen pressure, we have a certain amount of ventilation. Then if the oxygen starts to decrease, then we will increase ventilation. That makes sense. The interesting thing about this, is the slope of this curve near and around this 100 mm mark is basically flat. Even when were out at a 80 mm of mercury, we really have not increased ventilation. It's when we get closer to 60 mm of mercury when we start to increase ventilation because of a low oxygen pressure. So that seems kind of counter intuitive. But it shows that really the body is not overly concerned about changes in oxygen pressure. Not until they get really low. And one reason for this is, because when you're out at 80 mm of mercury, your hemoglobin is still basically saturated. So the content of oxygen in your blood has basically not changed, and so there really is no reason to be concerned at that point. This is gonna be in contrast to CO2, where as soon as CO2 increases at all, we're gonna have a large increase in minute ventilation. So you can just see how the slope of these two curves is completely different and how the body is gonna be much more sensitive to the arterial CO2, then it is gonna be to O2. And the reason for this is, because if our PaCO2 is increasing, that means our proton concentration is also increasing. And so that's really a reflection of the fact that the pH of the body is changing and that's not a good thing. That's what the body wants to prevent and really stay on top of. So we also know that those peripheral receptors are gonna also respond to the pH. Where as the pH goes down and the proton concentration increases, we're gonna increases, we're gonna increase minute ventilation. So this is just a change in pH independent of oxygen or CO2. Just a change in pH by itself will change how much we breathe. So that if we have a low pH, meaning we have increased protons, then by breathing more we know, then, we're gonna be hyperventilating, which means our PaCO2 will drop. And if that drops, then that means protons will fall and that will help correct our acid-base disturbance. So we're gonna now talk about a few situations when it's a what we call metabolic source of an acid base disturbance instead of a respiratory source. So we talked about how we could have hyper or hypoventilation, and how that was going to affect the pH of the body. So if we have decreased ventilation, then that means that CO2 is gonna increase, which means that the proton concentration is going to increase and pH is gonna decrease. And since that was a cause of the problem, then that's respiratory acidosis. If we have increased ventilation, then PaCO2 is gonna decrease and then protons will also decrease because of that set of chemical reactions and the flux through those, which means the pH will increase. And we'll have respiratory alkalosis. But what if instead we had just a change in acid base amounts of the body? Let's imagine what we call metabolic acidosis. Let's say that you're exercising a lot and so you're forming a lot of lactic acid. So that's just a metabolic process, you're forming a lot of acid. So these receptors, the peripheral chemoreceptors, are gonna sense, hey, CO2 and O2 are fine, but now we've got this increase in protons from this lactic acid. Just based on that, we're gonna change ventilation. And so the plasma proton concentration is going to increase from the lactic acid. Now we're gonna increase our ventilation. We're gonna basically hyperventilate as a compensation because of all this lactic acid. That means our PaCO2 is going to decrease, because we're hyperventilating to try to blow off the lactic acid. We can also have metabolic alkalosis. So let's say that you have a bad stomach bug and you're just vomiting and vomiting which, remember, means you're gonna be expelling lots of protons. So you're gonna have a decrease in your proton concentration, which means you're going to have an increase in your pH. It has nothing to do with respiration, but that means you're going to move this way along this curve and so you will then decrease your ventilation. Your only concern at this point is just the acid base balance. And so that means if you decrease your ventilation, you’re hypoventilating, and now PaCO2 is going to increase. Since CO2 correlates with protons, you’re trying to hold onto CO2, cuz that's gonna increase your number of protons as a compensation. So this idea and these concepts between metabolic and respiratory acidosis and alkalosis are really important. We're gonna be talking about them more when we get to the renal system, so keep these in mind. So we've talked about, we just talked about respiratory acidosis and alkalosis where we're gonna have increases and decreases in CO2 that is going to then cause a change in pH. Or we can have metabolic acidosis and alkalosis, which are going to change the pH, which is then going to cause a change in our breathing, which will then change PaCO2. And one thing I forgot to mention is, if you look at this chart and you look at these two columns, either the plasma proton concentration or the pH versus the PaCO2, they're different for each case. So that if you know a patient's pH and their arterial CO2, then you can determine whether it's respiratory acidosis versus metabolic acidosis, respiratory alkalosis versus metabolic alkalosis. You'll only need to know those two numbers. We also saw that even though the body is monitoring oxygen pH and CO2 in the blood, CO2's going to be what the body is most sensitive to, and that we do have the central chemoreceptors. They're gonna sense changes in PCO2 that's gonna cross the blood-brain barrier and enter the brain stem, and then that will cause a change of pH, that then is going to be the component that's actually sensed by the central chemoreceptors. And then, the peripheral chemoreceptors are gonna sense PO2, PCO2, and proton concentration. And that we can change ventilation purely by changing the acid-base balance of the body.
