 Hello everyone welcome to Physiology Open. In this video we are going to deal with one of the most difficult topics in physiology that is acid based pallets. So let's begin. Any substance which adds a hydrogen ion into a solution is known as acid while any substance which binds with hydrogen ion is known as a base. The concentration of hydrogen ions in our body is very less it's approximately 50 nano equivalents per liter. Because the concentration of hydrogen ions is so less it is expressed as negative logarithm of the concentration of ions. This is known as pH and since it's negative log it's inversely related to concentration of hydrogen ions. More hydrogen ions means less pH and vice versa. Normal pH of extra cellular fluids ranges from 7.38 to 7.42. Decrease in pH is known as acidosis that is more hydrogen ions are there while increase in pH is known as alcoholosis. Now on a day to day basis lot of acids are being added to our body clothes. Due to metabolism carbon dioxide is being produced. This carbon dioxide after its reaction with water produces H2O3 which then dissociates into hydrogen ions and bicarbonate. So carbon dioxide you see can add hydrogen ions into the solution. But since carbon dioxide can be excreted out by respiratory system as a gas it's known as volatile acid. But there is direct addition of other acids as well like galactic acid. These acids are known as non volatile acids. In total approximately 50 milli equivalents of acids are added into our body clothes per day. So concentration of hydrogen ions is in nano equivalents while acids added per day is in milli equivalents. So with the values you might have understood that with this much addition of acids pH will change drastically. And since body enzymes work best in a narrow range of pH it is critically important that the added acids need to be handled well. That means the amount of acids added should equal the amount of acids excreted from the body. But you see if we wait for acid excretion the amount of acid added will drastically change the pH and affect the functioning of the enzymes. So it's required that within the body there should be something which prevents the changes in pH due to addition of the acids while our body excretes the acids. So there are two things happening. One there are buffers which act as first line of defense and bind with the acid produced to prevent immediate change in pH. And second lungs and kidneys take part in excretion of acid. Lungs basically excrete carbon dioxide and kidneys excrete the non volatile acids. And kidneys also restore the buffers used up in buffering the acid which we will see in a short while. So we will see each option one by one. Just one thing before we proceed. Here mostly we will speak from the perspective of handling acids since body has to handle the daily production of acids. However in the end we will see actually these actions can proceed both ways and the same things can handle bases as well. Okay so first let's see buffers. Buffers can bind with hydrogen ions reversibly. So depending on the concentration of the reactants the equation can proceed either way. This is the general feature of all buffers. In this video we will not deal with dissociation constant of buffers for that there will be another video. Here we will focus on the overall big picture concept of acid base balance. Okay so most important buffer present in bodies bicarbonate which can combine with H plus ions and form a weak acid carbonic acid. So this is what we discussed with the buffer equation isn't it? But H2CO3 has one very important feature. This carbonic acid can dissociate into H plus ions and bicarbonate ions as already discussed with buffer equation but this is a weak dissociation. Instead it can dissociate into carbon dioxide and water in presence of enzyme carbonic and hydrates. So when hydrogen ions increase bicarbonate combines with hydrogen ions and reaction proceeds towards this side but it does not allow H2CO3 to accumulate. Instead it breaks down to carbon dioxide and water and this carbon dioxide is in turn excreted out by respiratory system. So what is happening is that bicarbonate is preventing pH change but in the process it is getting used up. Plus also see that it's due to this reaction that if more carbon dioxide is produced or respiratory system is depressed this reaction will start proceeding in opposite direction. Since reactant this side will be more. So H plus ions will be produced this will cause acidosis. In short acidosis is of two types. First one where bicarbonate is being used up due to addition of normal ethyl acids and excretion of carbon dioxide is occurring. So this type is decreasing bicarbonate ions and the other type is due to increase of carbon dioxide because ultimately carbon dioxide will add hydrogen ions. So now you can very well guess what we call these acidosis. Causes which decrease bicarbonate ions are known as causing metabolic acidosis while that which increase carbon dioxide are known as causing respiratory acidosis. Okay apart from bicarbonate there are other buffers too that is proteins act as buffers and phosphate ions act as buffers but to understand the big picture we'll keep them aside and discuss in the video on buffers. So anyways whatever the cause of addition of acids our kidneys and lungs come into action. Obviously here we are talking when their functions are normal. So first let's talk about lungs. Well our body has chemoreceptors which detect the partial pressure of carbon dioxide. This stimulates respiration and hence causes more excretion of carbon dioxide. Also these chemoreceptors are stimulated even by pH itself that is hydrogen ion concentration. Don't you think it's logical? It's kind of feed-forward action. Since hydrogen ions and combining with bicarbonate ultimately will form carbon dioxide so stimulation of chemoreceptors with hydrogen ions makes sense isn't it? Okay now let's see what our kidneys do. Kidneys do three things. One they reabsorb the filtered bicarbonate that is prevent the loss of bicarbonate. See bicarbonate is freely filtered through the glomerulus. With the plasma concentration of bicarbonate being 25 mili equivalents per liter and total glomerular filtration per day being 180 liters per day, total amount of filtered bicarbonate will be 4500 mili equivalents per day. This should be reabsorbed isn't it? So kidneys absorb this filtered bicarbonate mostly in proximal tabule and thick ascending limb or plump of Henle. Some amount which is left is absorbed in distal tabule and collecting duct. Second the kidneys regenerate bicarbonate. We have said before that bicarbonate is being used by buffering. So there should be some way that bicarbonate is regenerated isn't it? And third kidney is excrete hydrogen ions. The second and third options go hand in hand and occur in intercalated cells of collecting duct. So let's see how these three things are happening in kidney. So here is a schematic diagram of proximal tubular cell. This side is tubular fluid and this side is interstitial side. The membrane of the cell towards the tubular fluid is a pical membrane and the other side is basolateral membrane. And this another diagram is showing intercalated cells of collecting duct. Now this proximal tubular cell has carbonic anhydrase enzyme inside the cytoplasm as well as on a pical membrane. While this intercalated cell also has carbonic anhydrase enzyme but only in the cytoplasm. In proximal tubular cell inside the cytoplasm carbon dioxide combines with water in presence of carbonic anhydrase enzyme and forms H2CO3. This H2CO3 dissociates into hydrogen ions and by carbonate ions. Hydrogen ion moves into the tubular fluid by a hydrogen ethypase and sodium hydrogen exchanger. Now in tubular fluid hydrogen combines with a filtered bicarbonate and this reaction which is happening inside the cells moves in reverse direction in presence of the membrane enzyme carbonic anhydrase. So this carbon dioxide moves back into the cell. So basically what is happening? This carbon dioxide again undergoes same cycle. Now see with each cycle one bicarbonate is also forming in the cytoplasm. This bicarbonate moves into the interstitial fluid and is absorbed. So one hydrogen secretion is causing absorption of one bicarbonate but this does not really lead to excretion of more hydrogen ions be clear here. Since it's recycling rather it leads to reabsorption of filtered bicarbonate ions. So this mechanism is preventing loss of bicarbonate ion. Same thing happens in thick ascending limbo-flopof-end-lay for a whatever bicarbonate ion escapes absorption in proximal tubules. But kidneys also regenerate bicarbonate which has been used up in excrete hydrogen ions. This happens in these intercalated cells of distal tubule and collecting tact. Here intracellularly produced carbon dioxide combines with water and forms H plus ions in bicarbonate ions just like we saw in the proximal tubular cells. Hydrogen ion is secreted. However the secreted hydrogen ion does not combine with bicarbonate in tubular fluid because not much bicarbonate is remaining there since most of it has already been absorbed and there is no membrane bound carbonic anhydrase there isn't it? So hydrogen ion moves into the tubular fluid and bicarbonate enters into the interstitial cell. So this is a new bicarbonate which has formed. Now with the secretion of hydrogen ions what happens is tubular fluid becomes acidic. So pH of tubular fluid decreases. However pH cannot exceed more than 4 to 4.5 because as it reaches this pH the concentration gradient for secretion of hydrogen ions becomes too high. So more hydrogen ions cannot be secreted. Now remember pH will change very fast since kidneys have to excrete lot of acids. In mili equivalents remember? So to prevent this urine has buffers, phosphate buffer and ammonia buffer. Phosphate binds to hydrogen ions preventing decrease in pH. This also helps in formation of bicarbonate. Since hydrogen ion secretion can continue causing production of bicarbonate. However the amount of phosphate excreted each day is not sufficient enough to allow adequate regeneration of new bicarbonate. So quickly all the available phosphate in tubular fluid will combine with hydrogen ions and then again the urine will become acidic. So further job is done by the production of ammonium ions. Ammonium ion is formed by the metabolism of glutamine in proximal tubule. With this metabolism even bicarbonate ions are produced. Ammonium enters into the tubular fluid and bicarbonate enters into the interstitial side and then it goes into the blood. Now the ammonium in the tubular fluid is then reabsorbed by the thick ascending limb into the medullary interstitium where it is present in equilibrium with ammonia. This ammonia diffuses via collecting tubular cells and enter into the tubular fluid. So here they combine with the secreted hydrogen ions forming ammonium ion which is then excreted out. Now when secreted hydrogen ions is less this ammonia which is a gas will not retain here it will come back into the interstitium. So what happens that then it is absorbed back into the blood and is converted into urea in presence of bicarbonate. So basically the bicarbonate which was formed during the synthesis of ammonium ions is used up for neutralization of ammonia if it's not excreted. So basically bicarbonate is added only when ammonium ion is excreted. Its only formation won't help much. So what we are suggesting here is that excretion of ammonium ions is very well tied to pH. First of all that when pH decreases formation of ammonium ions increases in proximal tubelesses. Also with increase in H plus secretion ammonia will bind to H plus ions and this ammonium ion will be excreted. So this ammonia buffer is very important for the continued excretion of hydrogen ions in kidney. So this is how our body handles acids in day to day basis just to summarize once bicarbonate ion is the most important buffer in extracellular fluids and it's being used up with the production of acids forming H2CO3 and finally carbon dioxide and water. Carbon dioxide is excreted by lungs. Kidneys excrete hydrogen ions and reabsorb filtered bicarbonate. Hydrogen ion in the tubular fluid is buffered by phosphate and ammonia and by virtue of this there is regeneration of new bicarbonate ion. Before ending let's talk what happens if there is excessive loss of acids from the body or with the addition of base. The puffers which we discussed will start acting in opposite direction. The bases will combine with H2CO3 and bicarbonate ions. Since H2CO3 is decreasing the overall reaction will proceed towards opposite side that is carbon dioxide will combine with water and form carbonic acid. So there will be decreased excretion of carbon dioxide from lungs. Then kidneys will decrease the secretion of hydrogen ions and instead may also start secreting bicarbonate ions. So the secretion also happens in other types of intercalated cells in which bicarbonate ion moves to the tubular fluid and hydrogen ion move to the interstitial side. So body is well equipped to handle changes in pH on either side. Hopefully the video clarified some of your concepts in acid-base balance. Thanks for watching the video. If you liked it do press the share and subscribe button. Thank you.