NARRATOR: Metabolic processes generate various acids. If these acids were not removed, they would accumulate, causing acidosis. The lungs can rid the body of carbonic acid, a volatile acid, by blowing off carbon dioxide. However, only the kidneys can rid the body of all other acids. The kidneys are also responsible for maintaining levels of the crucial base bicarbonate. So the kidneys must accomplish two things-- excrete hydrogen ions, or H plus, and conserve or generate new bicarbonate, HCO3 minus, as needed. Let's look inside the kidneys to see how they secrete hydrogen ions into the filtrate and conserve bicarbonate by reabsorbing it. As usual, most of the reabsorption occurs in the proximal convoluted tubule, or PCT. The kidneys reabsorb filtered bicarbonate, which is part of the crucial bicarbonate buffer system, the main extracellular fluid buffer system. Recall how the bicarbonate buffer system works. Carbon dioxide combines with water to form carbonic acid. This step is catalyzed by the enzyme carbonic anhydrase. Carbonic acid dissociates to form hydrogen and bicarbonate ions. These same reactions occur in the PCT cell. Carbon dioxide combines with water to form carbonic acid, which then splits to form hydrogen and bicarbonate ions. For now, let's follow the hydrogen ion. The hydrogen ion is transported across the apical membrane out of the cell and into the filtrate against its gradient. This requires either primary active transport or secondary active transport in exchange for sodium. At this point, the PCT cell has successfully eliminated a hydrogen ion. The second task for this PCT cell is to reabsorb bicarbonate. This means that it must move bicarbonate from the filtrate into the blood. What you need to know is that the major route bicarbonate takes from the filtrate to the blood does not involve transport proteins in the apical membrane. So how do you suppose bicarbonate is reabsorbed from the filtrate? Is it (a) by passing through tight junctions between cells; (b) by passing through the apical membrane by simple diffusion; or (c) by being converted to carbon dioxide, which can cross the apical membrane by simple diffusion? The correct answer is C. Bicarbonate is converted to carbon dioxide. Bicarbonate is charged so it cannot pass through plasma membranes by simple diffusion. And tight junctions usually keep molecules from passing between cells. So how does this work? Basically, the reaction that we saw inside the cell simply runs in reverse in the filtrate. Bicarbonate in the filtrate combines with our newly secreted hydrogen ion to form carbonic acid, which is split by carbonic anhydrase, forming water and carbon dioxide. Because it is a lipid soluble gas, carbon dioxide moves easily into the cell by simple diffusion. And the reactions we described before begin again. This may seem to be a roundabout way of doing things, but it effectively brings bicarbonate from the filtrate into the PCT cell. The last step in reabsorbing bicarbonate is to move it from the cell into the blood. Fortunately, the basolateral membrane has transport proteins that move bicarbonate out of the cell. This is secondary active transport coupled with either chloride or sodium. The exported bicarbonate then moves into the blood of the peritubular capillary, completing its reabsorption. We've now gone through all the steps that a PCT cell uses to secrete hydrogen ions and reabsorb bicarbonate. These steps may seem overwhelmingly complicated, so let's simplify them down to the essential reactions. These are the things you really need to keep in mind. For each hydrogen ions secreted into the filtrate, a bicarbonate in the filtrate is consumed only to be regenerated inside the cell and exported to the blood. While we have shown these basic reactions occurring in the PCT, they can also occur in most of the rest of the nephron. Notice that this process depends on the presence of bicarbonate in the filtrate. What do you think happens to the export of hydrogen ions once there is no more bicarbonate in the filtrate? Does it (a) stop because there is no more bicarbonate to buffer the hydrogen ions so the cycle can't go around anymore; (b) continue until the urine is so acidic that the hydrogen ion transporters cannot overcome the pH gradient; or (c) continue because other substances in the filtrate buffer the hydrogen ions? The correct answer is C. It continues because other substances in the filtrate buffer the hydrogen ions. One such substance is phosphate. Notice that this allows the body to continue exporting hydrogen ions to the filtrate while generating new bicarbonate. This bicarbonate is new because it comes from carbon dioxide generated by metabolism inside PCT and other cells. It does not come from carbon dioxide generated from bicarbonate in the filtrate. In reality, phosphate and bicarbonate compete for secreted hydrogen ions, and so both of the processes we have looked at occur simultaneously in many parts of the nephron. There is one other way PCT cells generate new bicarbonate. It involves ammonium excretion and is described in your textbook.