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. 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. We'll talk more about those in a minute. They are going to be feeding into a respiratory center in the medulla of the brain that will integrate that information. So this is a reflex loop like we've talked about when we were in the nervous system. This one will control breathing. Remember that the diaphragm, and then the intercostal muscles between the ribs. Those are skeletal muscles. Every time we breathe there will be an action potential sent to those muscles to cause them to contract. It will be through the use of a central pattern generator because it will have the same contractions and relaxations over and over again. We will be able to modify these rhythms so that you can breathe more deeply or more quickly. Bbut still every time we take a breath, 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 are going to be found in the carotid arteries and in the aorta. These will sense three different things. One is that they're going to respond to a decrease in the pressure of oxygen in the arterial blood. Again, they're not measuring how much hemoglobin is present and how saturated it is. They 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. They also responding to an increase in PaCO2. 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 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. Protons are not able to cross the blood brain barrier. What will cross the blood brain barrier and be detected is CO2. So these central receptors, if we have in increase in arterial PaCO2, then CO2 will increase in the brain, and that increase in CO2 in the brain will cause an increase in protons. That's actually what is sensed, 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 also influence our respiratory rate. These are actually in the respiratory system itself. we have pulmonary stretch receptors in the smooth muscle of the airways that fire the more the lung is inflated. They can stop inspiration If the lung volume is getting too large, if there’s too much stretch. This is called the Hering-Breuer reflex. It is 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. These 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 will be obviously a symptom of a lot of these issues. So it is, in a way, alerting that there's an issue because of this labored or rapid breathing. Then there are pulmonary irritant receptors which are in the epithelium that line the airways. These are respond to mechanical or chemical irritation. They 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. You can try to reduce the amount of other particles that you bring into your lungs. Before we consideer how CO2 and O2 and protons are going to affect how our breathing, our breathing rate and how deeply we breath, we need to addressed proton transport in the blood. We we will do that right now. In the tissues we know that oxygen is going to be released from hemoglobin. That gives us deoxyhemoglobin. Deoxyhemoglobin has a greater affinity for CO2 as well as protons. So, just like CO2, protons can bind hemoglobin. That hemoglobin will bind protons. This is convenient because this is happening in the tissues where you're dumping oxygen and now we want to pickup CO2. We've got extra protons from metabolism, and so those will be picked up by the hemoglobin. This is a major buffer in the blood, is hemoglobin. Normally, we do have a shift in pH of the blood where our arterial blood is going to 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 the blod gets to the lung, oxygen is going to be there in large amounts. 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 going to cause this reaction to go this way. This causes CO2 to be produced. But that's fine, we're in the lung, The spot where the CO2 is going to be removed. CO2 diffuses into the alveolus. So that's going to remove the protons that we picked up and correct the pH. 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 going to also increase protons and lower the pH. That means, that if we have a problem with the respiratory system, we can cause a problem in acid-base balance. 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. It 's also to regulate acid-based balance. That means, that if we have a problem with the respiratory system, very often that's going to be accompanied by problems with pH. If we have ventilation decrease for some reason, then we already said, that means we're hypoventilating. This means that our CO2 is going to 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 failed. 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. Again, since the 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 going to have a low oxygen concentration. So oxygen is going to 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 going to 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. Now we will look more specifically at the graphs for that data. Here we see with oxygen, as the arterial oxygen changes, then the minute ventilation will change. At 100 mm of mercury, our normal arterial oxygen pressure, we have a certain amount of ventilation. Then if the oxygen starts to decrease, 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. 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, There really is no reason to be concerned at that point. This is going to be in contrast to CO2, where as soon as CO2 increases at all, we're going to have a large increase in minute ventilation. You can just see how the slope of these two curves is completely different. The body is going to be much more sensitive to the arterial CO2, then it is going to be to O2. The reason for this is because if our PaCO2 is increasing, that means our proton concentration is also increasing. 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 going to increase, we're going to increase minute ventilation. 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 going to be hyperventilating, which means our PaCO2 will drop. If that drops, then that means protons will fall and that will help correct our acid-base disturbance. So we're going to now talk about a few situations when we have a metabolic source of an acid-base disturbance instead of a respiratory source. We talked about how we could have hyper- or hypoventilation, and how that was going to affect the pH of the body. If we have decreased ventilation, then that means that CO2 is going to increase, which means that the proton concentration is going to increase and pH is going to decrease. Since that was the cause of the problem, it is 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. That's just a metabolic process. You're forming a lot of acid. So these receptors, the peripheral chemoreceptors, are going to 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 going to change ventilation. And so the plasma proton concentration is going to increase from the lactic acid. Now we're going to increase our ventilation. We're going to 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 acid. We can also have metabolic alkalosis. So let's say that you have a bad stomach bug and you're just vomiting. Vomiting means you're going to be expelling lots of protons. So you're going to have a decrease in your proton concentration. This means you're going to have an increase in your pH. It has nothing to do with respiration, but that is a means by which you can move this way along this curve. So you will then decrease your ventilation. Your only concern at this point is just the acid-base balance. If you decrease your ventilation, you’re hypoventilating, now PaCO2 is going to increase. Since CO2 correlates with protons, you’re trying to hold onto CO2, because that's gonna increase the number of protons as a compensation. This idea and these concepts between metabolic and respiratory acidosis and alkalosis are really important. We're going to 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 going to have increases and decreases in CO2 that is going to then cause a change in pH. 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, to alter PaCO2. One thing I forgot to mention is, if you look at this chart, look at these two columns. 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 going to sense changes in PCO2 that's going to cross the blood-brain barrier and enter the brain stem, and then that will cause a change in pH. That then will be the component that's actually sensed by the central chemoreceptors. The peripheral chemoreceptors will sense PO2, PCO2, and proton concentration. And that we can change ventilation purely by changing the acid-base balance of the body.