Greetings. Okay, so this is the last lecture of our course. What we want to talk about is the acid-based disturbances and how you analyze these disturbances. So the learning objective then is first, we want to explain how new bicarbonate is generated from from ammonium ions, and are eliminated then by the body. And secondly we want to explain how new bicarbonate is generated by the kidney when fixed acids or titratable acids are eliminated from the body . And third, we want to explain the classifications of four acid-base disorders. You've already heard about these from the respiratory system lectures. But we're going to revisit them. And then fourth, we want to describe how metabolic acidosis is differentiated from respiratory acidosis. We will consider a specific case. Okay, so there's a lot of things to do. So again, why are we worrying about mass balance and pH? As we said in the last lecture, there's a net intake of acids from the diet, and the body generates acids from metabolism. The body's responds to buffer these protons immediately. We buffer them by binding the protion to proteins. The specific protein that we're going to use is hemoglobin. That's one of the major proteins in the blood. As soon as the protons are generated, they move into the cells where they bind to proteins within the cells. This is an immediate protection. The second response that occurs is there's going to be a change in ventilation. This will occur within minutes. That is, we have a change in our minute ventilation. If the lung needs to remove an acid, then it increases the ventilation rate. They'll blow off the CO2 and by blowing off the CO2, we lose acid from the body. The last response is to change the amount of bicarbonate and protons that are lost into the urine. This last response is going to be a job for the kidney. This can take hours. The kidney is our slow responder. The last time we were in here, we talked about how the kidney was moving all of the filtered bicarbonate, or the majority of it, back into the body through the proximal convoluted tubule. But that in the distal collecting duct and in the distal convoluted tubule, that last 10% of the filtered bicarbonate is used to adjust the pH of the blood. As you go through your day and you're ventilating, your breathing, you're blowing off CO2, you are losing bicarbonate from the body. The job of the kidney then is to replenish this lost bicarbonate. It has to replace the lost bicarbonate Reabsorption is simply not sufficient. How does it make new bicarbonate? It does so in two different places and does it by two different mechanisms. So let's consider the first. The first mechanism makes the ammonium ion. It does that in a proximal convoluted tubule. Here in the proximal convoluted tubule, the very first region of the renal tubule, glutamine, is freely filtered. This is an amino acid. It's freely filtered and it enters into the filtrate of the PCT. We also can have glutamine enter into these cells from the blood. This of course from the peritubular capillary. Glutamine, the amino acid, can enter into the cells by facilitated diffusion coming in from the blood. It does so using a co-transporter, a symporter with sodium. Once the glutamine is within the cells, these proximal convoluted cells, the amine group is removed to form NH4+, the ammonium ion. And the ammonium ion is extruded from the cells using an antiporter in exchange for sodium whch enters the cell. In addition to making the ammonium ion this process also makes bicarbonate. That bicarbonate is new bicarbonate. That new bicarbonate then is extruded from the cells using the chloride bicarbonate antiporter. That's what shown here. The ammonia ion that has been generated by these cells, now enters into the renal tubule. That ammonium ion is not able to go across the epithelium of the renal tubules. The ammonium ion is delivered to the thin descending loop, and then the thick ascending loop of Henle. When it gets into this region, it can in fact move across these cells, and enter into the interstitial space. Once it enters into the interstitial space, it's converted from NH4 plus to NH3, to ammonium. Ammonium can move across the collecting duct epithelial cells. It can enter the lumen of the collecting duct. Once it's within the lumen of the collecting duct, that NH3 combines with a proton, a free proton that's present within the filtrate, within this region It then reforms NH4 plus. It has trapped that proton. That proton is no longer free, It is no longer able to decrease the pH in this region. The ammonium ion is excreted into the urine. This is one of the ways that we can lose a proton from the body, and at the same time, we generate a new bicarbabonate ion. Okay, so why have I tortured you with this? This is actually an interesting situation because if the kidney is not working correctly, if for some reason the collecting duct is not working, then what happens is that this NH4 plus ion present in the thick ascending loop of Henle enters the IS and becomes NH3. The NH3 then can enter into the blood and is delivered to the liver. Once it's delivered to the liver, it's converted to urea. by the liver. The liver then generates what's called bun or blood urea nitrogen. The ammonium enters into the cells of the liver. The liver forms urea and then the urea is moved back into the blood. What you find then is a hallmark of a sick kidney, or a kidneys whose collecting duct doesn't work correctly, is a rise in BUN within the blood. The second way, that the kidney can make new bicarbarbonate ion is in the distal convoluted tubule and collecting duct itself. Here it uses the fixed acids. The fixed acids are excreted. These are sulfates, phosphates, and so forth, that came in from the diet, that we couldn't blow off, through through the respiratory system. These cells have luminal surface, here, and the blood surface is here. The peritubular capillary surrounds these cells as well. In this particular case, we are going to deliver to these cells CO2 from the blood. The CO2 from blood can diffuse into the epthelial cells. In the presence of carbonic anhydrase, we generate bicarbonate and a proton. This is new bicarbonate. The new bicarbonate is then delivered to the blood using our chloride bicarbonate antiporter on the basal surfaces of these cells. The generated proton is extruded into the lumen of the tubule in this region. That proton, that free proton can now bind to fixed acids, the phosphate or the sulfate and so forth. Once the proton is bound of course then it's no longer contributing to pH. It is no longer a free proton. We trap then this proton. It is extruded into the urine. There is one other way that we can remove the free proton that we've generated from these cells. That is by using that proton potassium ATPase in these cells. That is what is shown here. The proton can leave the cells, move into the lumen, and get trapped by the fixed acid. In exchange we have the potassium ion that can move into the cells. So for mass balance then,[COUGH] what we want to do is to balance the amount of acid input to the amount of acid output. And as we said the last time we were in here that the acid input for a 70 kilogram individual is about 70 milli-equivalents per day. This is from diet and from metabolism. Our acid output, however, free protons has a pH of about 7.4 so it's 40 nano-equivalents per day. So, we're putting out very, very, very small amounts of free protons. What we are putting out in addition to that protn, is fixed acids, up to the amount of 34 mEq per day, and the amount of ammonium ions, and that's about 35 mEq per day. And as you notice, this adds to approximately 70 milliequivalents per day. So, 69 milliequivalents per day. So the free protons then within, within the urine is almost negligible. The pH of the urine, then is close to neutral. For those of you who want to calculate this, the calculation is here at the bottom. The net acid excretion is the concentration of the ammonium ion within the urine, in the volume of the urine. This is a time sample. And then we have the concentration of the titratable acid, in a volume of the urine. And the amount of bicarbonate that was lost from the body. This is usually, under normal conditions, is usually about zero. Okay, that's in a normal person, and that's in normal conditions. But we can have conditions where there's acid-base disturbances. Such as, you've been vomiting. If you're vomiting, what happens? You're losing acid from the body. If you're vomiting for several days, then, it can affect the pH of the body. You are losing protons, and so the blood then becomes, more and more alkaline. We will have higher and higher amounts base so there is a higher pH with circulation. If we look then at these acid-based disturbances, we can categorize them on the basis of the primary disorder. So in the case where we have a acidosis, specifically metabolic acidosis, we're retaining protons. If we're retain protons for some reason within the body, then we decrease the blood pH. As we decrease the blood pH, it leads to an inadequate amount of bicarbonate. In compensation, the lung tries to blow off CO2. This results in a decrease in PaCO2. This is in contrast to respiratory acidosis. In respiratory acidosis, again, the blood pH decreases because we have an acid condition. But under this condition it's due to holding the CO2 within the blood. Now the arterial blood has a higher CO2. And that, by increasing CO2 in the blood the body becomes acidic. Here the cause is a decrease in ventilation. It is the cause, it is not the compensation. So you can differentiate between a respiratory acidosis and a metabolic acidosis by considering the amount of PaCO2 which is within the body. If the PaCO2 is higher than normal, then it's a respiratory acidosis. We are holding the CO2; ventilation is inadequate. If the PaCO2 is low, lower than normal, then we're trying to blow off the CO2. We'are trying to balance the pH, to compensate for a metabolic acidosis. Things to remember is the CO2 levels within the arterial system. Typically, this PaCO2 is 40 millimolars of mercury. The amount of bicarbonate, will be 24 milliequivalents per milliliter. that is the concentration of the bicarbonate within the blood under normal conditions. Okay, so how should you analyze these acid-base disorders? As I said this is sort of review for you because we have done this already once in the respiratory system, but let's go through it. So the first question you ask is, what is the pH of the arterial blood? This determines the state. Remember we said we could have a normal state, that a pH of 7.4. Acidemia, means that it's going to be less than 7.35. If it's alkalemia, it'll be greater than 7.45. The second is, you want to know is it metabolic or is it respiratory? That, what's the underlying cause? And you want to know, is it an acidosis or an alkalosis? In this class we're not going to deal with mixed acid-base disorders. What is a mixed disorder? For example, an individual is retaining CO2 due to emphysema. He is not ventilating his CO2 adequately. At the same time, he is vomiting. So he is losing protons. This individual could have a neutral pH. But he's got two different different disorders going on. remember, in this particular class we're not going to deal with a mixed disorder, only acidosis or alkalosis, and it's a simple acidosis or alkalosis. So the thing that you want to do then is to examine the amount of bicarbonate to see whether or not it's normal. So it should be 24 mEq per liter and check the PaCO2 see whether or not it's normal. That's 40 millimeters of mercury. The thing to remember is the compensation is never going to bring the body back to an exact pH of 7.4. So the pH is always going to reflect the disorder. It will be brought back towards neutral but it's not going to be exactly neutral. Then, the last thing we want to deal with is, what is the compensation? In metabolic disorders, the compensation will be a change in the PaCO2, the ventilation rate is going to change. We will either blow off CO2, because we have an acid condition, or we will holding CO2 because we have a basic condition. In respiratory disorders, compensation reflects changes in bicarbonate. This occurs in the collecting duct. The intercalated cells, will move bicarbonate, back to the blood in respiratory acidosis. The intercalated A cells move bicarbonate back into the blood. Under these conditions, the type A cell is working. It gneerates acidic urine. It's getting rid of protons. But if we have an alkalosis, or alkaline condition, then we want to secrete bicarbonate into the urine. In this case the protons are moved into the blood. Let's just go over a case together, so you can see what I'm talking about. Mary is dehydrated from two days of severe diarrhea. Her labs show a blood pH of 7.3 and her blood sodium is 143 mM. Her her bicarbonate is 16 millequivalents per liter. Her PaCO2 is 33 millimeters of mercury. What's her acid-base status? So the first thing we look at is pH. The pH is 7.3. That's less than 7.4. Recall that 7.4 is normal. That means that she has acidemia. The second question is what's the underlying process. So, if she has acidemia, we can immediately rule out alkalosis. Whether metabolic or respiratory alkalosis doesn't apply. So, now you have to decide, is it the respiratory problems that caused the acidosis or metabolism is the cause? Look at the PaCO2. It is 33 millimeters of mercury. Normal PaCO2 should be 40 mmHg. We have a low PaCO2. Low PaCO2 means that it cannot be the lung that is the problem. Instead the lung is trying to compensate. The lung is blowing off as much CO2 as it can to try to correct for the pH. So that means that if the lung is compensating, then the underlying cause has to be metabolic acidosis. It's acidosis, because we already determined that it has a low pH. It is metabolic acidosis. This correlates with severe diarrhea. What happens with severe diarrhea? The body loses bicarbonate out the wazoo. By losing bicarbonate from the body then the blood pH is going to become more acidic. Okay, so, see how easy that was? Alright? So, all you have to do is sort of think through these values. Look at your numbers and then decide which values are normal. and, which are abnormal. All right. What's our key concepts? The key concepts, are, one, we have from the daily diet and metabolism a net increase in acids. Two, that the kidney maintains an acid-base homeostasis by reabsorbing filtered bicarbonate, forming titratable fixed acids, and then excreting ammonium ions. Three, there are four types of acid based disturbances that the body can be presented with. Four the acid base disturbances are classified as to the direction of change of the pH. It is acidosis or alkalosis, and by our underlying problem which is ventilation or metabolism. Okay, so that's the last of our lectures. It is the end of the course. We hope that you've enjoyed it. It's been a fun time for us. And so, perhaps you'll join us again next year. Bye bye.
