Greetings, so today we're going to talk about acid-base balance in the body, in particular, the role of the kidney in maintaining acid-base balance. why are we even interested in acid-base? The thing that you should remember is that if we have a pH, that is too many free hydrogen ions within the body, then the body becomes too acidic. That can cause denaturation of proteins. If we have a situation where the blood becomes too basic, we can also have denaturation of proteins. The proteins that we could lose, their activity that we could lose include enzymes, channels, and transporters. The body essentially would not be able to maintain metabolism. It comes to a rip roaring halt. So we need to maintain the body pH then within a very narrow bracket. We talked about this a little bit already in the respiratory lectures, but today we want to look at how the kidney is involved. Our learning objectives then are, number one, we're going to describe how the body buffers the free proton that enters either from the diet or is generated by metabolism by each day. Secondly, we want to explain the role of the lung and of the bicarbonate - CO2 buffer pair in maintain the stability of the pH within the body. And third, we want to talk about the role of the kidney in reabsorbing the filtered bicarbonate to maintain the plasma pH, so this is just simply what's filtered from the plasma. And four, we'll talk about the role of the kidney in reabsorbing the filtered proton to maintain the plasma pH. Okay, so let's get started. So the first thing we need to remember is, what are acids and bases? Acids are substances that donate protons, and bases are substances that accept protons. In our biological systems, the fluid systems have such very, very low free amounts of protons that we use a logarithmic scale to describe how much we have within the biological system. This is called the pH. The pH is measured, on a scale from 14 to 7 to 0. A pH of 0 is very acidic. A pH of 7 is neutral, and a pH of 14 is very basic. And as you recall, within the stomach we had a pH of 2, so we have very, very acidic pH within the stomach. But for the most part the body's pH is between a pH of 7.35 and 7.45. We usually refer to it as a pH of 7.4. All right, so why do we have a change in pH as we go through our daily lives? It is because of two things. One is that coming in from the diet, we have fatty acids, we have amino acids, we have sulfates, and we have phosphoric acids. These are components of the food material that we're bringing in. This is from the diet. The second acid input that's occurring is that we are generating it through metabolism, aerobic metabolism. We generate CO2 and water. Technically CO2 is not an acid, but physiologists view CO2 as a volatile acid. We'll talk a bit about that in just a few minutes. In anaerobic metabolism, we can generate lactic acids and ketotic acids. So there are conditions then where we can through metabolism generate a lot of acids, and through our diet we bring in a lot of acids. The body is challenged to deal with this, because on a daily input, the amount of the acids that come in is usually about 1 milliequivalent per kilogram of body weight. So if we have an individual who is 70 kilograms, there could be as much as 70 milliequivalents of acids being delivered to the body on the daily basis. The first thing that the body has to do is to buffer this material. It does so by binding the protons, the free protons to intracellular proteins in particularly to hemoglobin. The second thing is that it buffers protons with the extracellular buffering system, which is bicarbonate. It immediately buffers the free protons. But the body still has to get rid of the acids, and the way that it does so, is then through ventilation. It simply uses the lung to blow off CO2. As you blow off CO2, then you are releasing a proton from the body. Ventilation occurs within a few minutes, whereas our buffering system occurs instantaneously, essentially within seconds. The kidney, as we all know, is a little slow. So the kidney is going to regulate the acids by its urine output. The kidney excretes fixed acids. Fixed acids are the things like sulfuric acid, and phosphoric acid. These are acids which can not be released by breathing through the lung. The kidney also is going to generate an ammonium ion. The ammonium ion and the fixed acids effectively trap the free proton. Once the proton is bound to either a phosphate group or sulfate group or to ammonia, then what happens is that it no longer adds to the pH. It is removed then from the body. This material will be excreted into the urine. But the kidney takes a few hours in order for it to reach a balance. Our end result is that the plasma will have a pH of about 7.4, and that the urine a variable pH. But that the urine pH also stays fairly neutral. So there are important terms that we have to remember. You were given these when we were doing the respiratory system, but I want to refresh your memory. The first is acidemia. IN the term acidemia, "emia" always means in the blood. So this would be an acid in the blood. So acidemia is a state in which our blood pH, the arterial blood, is less than 7.35. The second term that we need to remember is alkalemia. Alkalemia, again, in the blood means an alkalosis within the blood. That is it's a basic condition. That basic condition simply means that the pH is greater than 7.45. Again, it's our arterial blood. When we talk about acidosis, this is the process that lowers the blood pH to, if it's an acidosis, to less than 7.35. For alkalosis, it is the process that raises the arterial blood pH to above 7.45. Okay, so then the other thing that we have to remember is the lung. The activity of the lung. That is simply that the ratio bicarbonate to CO2 is what determines pH. And you all know that as you increase the PaCO2, that is the partial pressure for CO2 within the blood, the blood is becoming more acidic. And that obviously, the opposite occurs if we decrease the amount of PaCO2. That is, we blowoff our CO2, then we are making the blood become more basic. And that's just simply what we learned within the respiratory system. We can also change the other part or the other component of the equation, which is the carbonic anhydrase equation, and that is simply bicarbonate. If bicarbonate levels within the blood decrease, the situation becomes more acidic. And if the bicarbonate in the blood is increasing, then our blood is becoming more basic. And the equation that we're referring to is the carbonic anhydrase equation, where we can take CO2 and water, and we can form carbonic acid, and then it will dissociate into a proton and bicarbonate. If we increase the amount of CO2 and drive that off from the lung, we are removing it from the body. This pulls the reaction in this direction. WE lose the proton. This is something, that you all know, is regulated by the respiratory control center within the brain. If we have a rise in pH, a rise in circulating acids, then you will start to ventilate at a faster rate. But what is the role of the kidney in this? The role of the kidney is a little more complicated. The first is that the kidney needs to reclaim all of the filtered bicarbonate that has occurred. So as bicarbonate comes across the filtration barrier within the glomerulus, it is freely filters, and the proton is freely filtered. They will enter into the renal tubule lumen in the same concentrations that they were in the plasma. So the bicarbonate and the proton ions are within the filtrate. On the blood side of the tubule, we want to move the bicarbonate back to the blood. We talked about this a couple of lectures ago when we said that bicarbonate is not able to get across the proximal convoluted tubules. The tubules do not have a transporter for bicarbonate. Instead we convert the bicarbonate and the proton into carbonic acid, which dissociates into water and CO2 in the presence of carbonic anhydrase. This enzyme is present on the luminal surfaces of the PCT epithelial cells. The water and the CO2 entered the cells. and bicarbonate and a proton are produced. The proton leaves the cells to reneter the lumen of the tubule. That's done so with a proton ATPase. It is also done by a cotransporter, an antiporter with sodium. Sodium enters the cell and the proton goes back out into the lumen of the tubule. The bicarbonate which was filtered. is now inside the PCT epithelial cell. This bicarbonate leaves the cell at the basal surface with an anti-porter, where chloride enters the cell, the bicarbonate leaves the cell to enter into the blood. So we have a circuitous route for reabsorption of the bicarbonate where it is first converted to water and CO2. Then we regenerate bicarbonate and a proton once inside the cells. Absorption of filtered bicarbonate in the proximal convoluted tubule takes up the majority of the bicarbonate that's within the filtrate. So this is reabsorption. It accounts for about 70 to 80% of the filtered bicarbonate. Importantly, this process requires the activity of carbonic anhydrase. Later in the tubules, in a separate region, the distal convoluted tubule and in the collecting duct, we have a set of cells, which are called intercalated cells. These cells are interspersed among the principal cells. They are fewer in number than the principal cells in this region. These intercalated cells balance pH. There are two types of intercalated cells: there's the A cell and the B cell. The A cell, the type A cell, secretes the proton into urine. When active we will end up with an acidic urine. The type B cell secretes bicarbonate, and we will end up with a basic urine. So how does this work? What I've drawn here is an intercalated A cell. The lumen is on this side and this is blood, in our peritubular capillary on this side. What we have is that bicarbonate and the proton are delivered from the filtrate into this distal region the tubules. Here we will generate carbonic acid. The carbonic acid in the presence of carbonic anhydrase, dissociates into water and CO2. The water and the CO2 can enter into these intercalated A cells. These cells are impermeable to bicarbonate directly, but you can move water and CO2 into the cells. Once inside the cells, then we regenerate with carbonic anhydrase activity bicarbonate. This bicarbonate then can leave from the basal surface of the cells, and enter into the blood. In exchange chloride enters into the cell. We use an antiporter to move the bicarbonate out of the cells and into the blood in exactly an analogous manner to what we had done in the proximal convoluted tubule. Where in the proximal convoluted tubule it was 70 to 80% of the bicarbonate in the filtrate, here we're only using the remaining 20 to 30% of filtered bicarbonate. The proton that is generated by these cells has multiple exit sites. One of them is again our proton ATPase, which is a pump. It simply moves protons out of the cell. We also have a proton exchanger by which the proton leaves and sodium enters. Again this is analogous to what we have in the proximal convoluted tubule. But in this region there's also an ATPase, which moves protons out of the cell, and a potassium enters the cell. That means that in a condition where we have an acidic pH, we move protons out of the body. We're going to be losing protons into the urine and move bicarbonate back into the blood Under these conditions then,the kidney changes the proton balance. As we lose protons, we are also gaining potassium. We will move potassium into the cells, and eventually potassium exits the cells and enter into the blood. So under these conditions where we have an acidic urine, or we have an an acid condition within the body, then we will have an increase in the potassium concentration within the plasma. That increase in the potassium concentration then can lead to hyper, hyper, meaning high, kalemia. And again, this is potassium in the blood. Now, that's the type A cell. The type B cell sits right next to the type A cells, and if the situation for the body is that the body has a very high basic pH, it wants to get rid of bicarbonate. It doesn't want to be bringing bicarbonate back into the body, Then the type A cell is not active, but the type B cell in this area is active. This cell is the mirror image of the type A cell. So if you took the type A cell and you simply flipped it over then the bicarbonate-chloride antiporters are on the lumenal surface of these cells. Under these conditions then, we can secrete the bicarbonate into the lumen of the tubule, and move the proton generated inside the the cell eventually into the blood. The type B cell then under basic conditions, do not raise blood potassium. We would actually have a decrease in blood potassium. THis is the converse of the type A cell. This activity would give us a hypokalemia condition. When we have a very basic situation, we have an alkalosis, occurring within the body. Now, the kidneys' job is to get rid of the excess bicarbonate. Okay, so what's are key concepts then? So the first of these is that our daily diet and metabolism generates a net increase in acids. And secondly, that the kidneys along with the lungs are going to maintain the body's pH by regulating the bicarbonate- CO2 buffer system. The lungs will exert an immediate effect. This is within a few minutes by controlling the PaCO2. The kidneys have a slower effect by controlling the bicarbonate and the proton concentration. The kidney is going to move a proton back into the body when there's an alkalosis that's occurring within the blood. And the kidney will excrete the bicarbonate. It does the reverse when we have an acidic condition. If we have too many protons, we excrete the protons into the urine, and move bicarbonate back into the blood. And so the third concept then is the kidneys maintain this acid-base homeostasis. They reabsorb the filtered bicarbonate in the proximal convoluted tubule. That's simply moving all of our buffering system back into the blood, because it would be very expensive for the body to lose all of that bicarbonate. It needs it for immediate neutralization of free protons. And secondly, that the kidney excretes either the bicarbonate or the proton into the urine depending on the body's needs. And again, when you look at these cases, then what you want to to think about is what does the body need? Does the body have a pH that's too high, that is sort of an alkaline condition, or does the body have a pH that's too low? Okay, so see you in the next lecture.
