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Lecture 27

PHYSIOL 201 Lecture 27: Lecture 27

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Elizabeth Rust

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Lecture 27: Renal Regulation of pH and Ca+2 Slide 2 When pH starts to change, proteins change their shape -If the shape changes, the function will be affected Normal pH is 7.4 (same as arterial blood) Eliminating H+ from the kidney is normal to maintain normal pH Lungs control CO2 which is an acid and this is how they control pH -When there is more CO2, it drives the reaction to the right and vice versa -Responds faster compared to the kidney -The changes can be instantaneous because it is neural inputs Kidneys take longer Slide 3 Our system has buffers -The CO2-bicarbonate is one of our buffer system -We also have proteins which hydrogen ion can bind to and change its conformation but also serves to maintain pH -The major extracellular buffer is CO2-Bicarbonate -The major intracellular buffer are the proteins inside the cell and the phosphate If hydrogen ion concentration is increasing a lot, then even with buffers pH is changing (just changes less compared to if you had no buffers at all) Slide 4 Lungs handle CO2 Kidneys handle the bicarbonate -This is what we’ll go through today The kidneys eliminate or replenish H concentration by how much bicarbonate is present -Lung maintains the left side of the equation while kidney maintains the right side Slide 5 If the equation makes sense, you do not have to worry about this slide The normal bicarbonate/CO2 level is 20 -If the ratio is increasing than 20, this could be due to bicarbonate increasing or CO2 decreasing. This will lead to an alkalosis -If the ratio is decreasing, it can lead to acidosis Slide 6 The respiratory system can be a cause in hydrogen ion concentration change -Referred to as respiratory acidosis or alkalosis -Indicates that the problem is with the lungs Breakdown of proteins generates acid -Most individuals are always battling an acid load GI issues can lead to acid-base imbalances -Just know that this is happening and the why will be discussed later When someone had diarrhea, we have high flow rate through the large intestine -We are not absorbing as much fluid -One of the things that is lost through the intestine is bicarbonate -The amount of bicarbonate being lost increases when we have diarrhea -This will lead to an increase in H concentration Vomiting does the opposite -Stomach contents are acidic -This releases H and decreases the H concentration in the body If the kidneys are not functioning, this will cause an acid-base imbalance -They maintain acid-base balance Slide 7 If bicarbonate is excreted by the kidney, H is gained by the ECF -This would lower the pH of the plasma compartment If addition bicarbonate is added to the ECF compartment, then H is secreted and excreted Slide 9 14.33.jpg With Na, in the apical membrane, there are Na cotransporters and on the basolateral side there is the Na-K pump -Same with glucose and water; they go through the membrane using transporters Bicarbonate is not as simple -There are no bicarbonate transporter in the apical membrane -No way to recover the bicarbonate unless there is a creative way (which there is) What we have is if we assume we are under normal conditions, then if the bicarbonate that was filtered was not recovered you would become more and more acidic overtime and having a net loss of bicarbonate The way that reabsorption occurs of bicarbonate is (lot of the reabsorption is occurring in the proximal tubule) have carbonic anhydrase within the cells that are lining the tubules -There is also carbonic anhydrase in the tubular lumen of the proximal tubule on the apical membrane -There is a bicarbonate transporter on the basolateral side -There is a transporter for H on the apical side but not a bicarbonate transporter What the cell does is that it takes CO2 and H2O (both readily available) and converts it to carbonic acid which breaks down to bicarbonate and H ion using carbonic anhydrase within the cell -So you’re increasing the amount of bicarbonate within the cell using this process There is active transporters for H that are secreting the H -An example is the Na-H antiporter that is absorbing Na and secreting H -There’s also a H-ATPase in some regions where the transporter uses ATP to secrete H So if this active transporter transports H into the lumen and when H goes out into the lumen, bicarbonate goes the other way Since bicarbonate is being made within the cell, this allows for a gradient to be formed which allows bicarbonate to diffuse into the extracellular fluid and be absorbed The hydrogen that is secreted is not excreted -It’s job is to react with the bicarbonate that is present in the lumen -As the H is secreted and increasing the concentration of H in the lumen, there is carbonic anhydrase here as well so the reaction goes the other way and produces CO2 and H2O -CO2 and H2O can diffuse through the membrane So this is not net secretion and excretion of hydrogen -There is secretion of hydrogen but then it comes back in as water so it is not lost -So we are not doing a net gain of bicarbonate -So the bicarbonate that was filtered is not excreted -Is essentially reabsorption This is assuming we are under acidic conditions -The first step is to reabsorb the bicarbonate Slide 11 Typically we have an acid load -We are generating the acid load through metabolism -The kidney has to have an requirement to add more bicarbonate to buffer the hydrogen ions that are being made by metabolism There are two mechanisms by which the kidney can do this (next slide) Slide 12 One is to continue to secrete hydrogen -Basically, after all the bicarbonate has been reabsorbed, the kidneys begin to excrete the hydrogen -This causes a net gain of bicarbonate in the ECF compartment Two is they can break down amino acid glutamine and how much glutamine is broken do
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