Transcribed by Chris Bedoya

April 25, 2014

Organ Systems Lectures 42 Renal System Integration by Dr. Wishe and Dr. Schiff Slide 1 Fig 19-1 Kidney Wishe: Ok, you had anatomy, it covered the kidney. Then I came back in this course, did some minor anatomy and some histology, then Dr. Schiff came in with the physiological approach. You just listened to Dr. Curry, and at this point in time you should realize that a lot of organs in the body work together, theyre not separate entities. And the kidney is a super duper important organ. Yes it does get rid of waste products and metabolism, but it also maintains the fluid and electrolyte balance in the body. Id like to think of the kidney as a bank, cause people refer to it as having a conservative function, a saving function. And so the kidney is going to take out of the fluid whatever the body could use, get rid of whatever it doesnt need. If theres too much fluid, too much sodium, it can eliminate that as well. So the organization of the kidney essentially is in 3 parts. Outer portion, the cortex. Most of the kidney is occupied by the medulla. And as you look at the medulla, it seems to be organized into little triangular portions called pyramids. In fact a pyramid is equivalent to a renal lobe. The kidney is referred to a gland, it has an absorbing, a secreting portion, and a duct system, and thats what your typical gland has. As you look at the apex of the renal pyramid youre gonna have your largest ducts, your papillary ducts, opening up into what is referred to as your minor calyces, there are 8-10 of those, then they feed into a major calyces, which are approximately 2-3, then the urine finally passes into this triangular shaped opening of the ureter, and this is referred to as your renal pelvis. As you look at the kidney, it has a real tough CT capsule, and youll find CT in the renal sinus area, which is this region, but you dont find very much CT in the kidney proper. The kidney functions are movement of electrolytes, fluids, from one point to another, and if you put in CT this will just interfere with the functioning of the kidney. People who have had kidney disease, kidney failure, if you look at their kidneys you will find extra CT within the body proper. And thats the reason why it just cant function appropriately. So the human kidney is multi-pyramidal, multi-lobed if you like, whereas something like a monkey has a uni-pyramidal kidney. The kidneys evolutionarily developed in proportion to what the animal does or doesnt do. If you look at the kidneys of desert animals, they release a urine, but its not fluid-like, its gel-like. Desert animals have to conserve water, so they cant just literally pee away the water. They need to save it so they dont dehydrate. So depending on where you live, or where you develop, etc, it all plays a role in how the kidney is set up and functions. Slide 2 Fig 19-1C Uriniferous Tubule Wishe: Here we have a section, a little wedge through the kidney, and what we see in the kidney is the functional unit, which is called the nephron. The nephron in essence is equivalent to the alveolus, or acinus, of a gland. And heres the starting point, a blood vessel enters, thats the afferent arteriole, it passes through the circulatory network, thats the glomerulus, its a capillary network, and then it passes out into the efferent arteriole, which then goes around the entire nephron. This particular part of the nephron is called the renal corpuscle, and it includes two 1

Transcribed by Chris Bedoya

April 25, 2014

layers of Bowmans capsule, separated by Bowmans space, it includes the glomerular capillary network, the afferent arteriole that brings blood in, and the efferent arteriole that caries blood out of the system. This is where step 1 occurs, alias filtration. So the renal corpuscle plays an important role in filtration. And then a fluid is produced which you find in Bowmans space which you call the glomerular filtrate, then the glomerular filtrate then passes into the tubular system. The first part is your proximal convoluted tubule, lets call it PCT. The PCT is responsible for your main resorption of the good stuff from the glomerular filtrate. It does resorb all the glucose in the fluid, it resorbs amino acids, fatty acids, fluid itself, and then the remaining fluid passes through your Loop of Henle, which Dr. Schiff will talk about a little. And the way I put it in lecture, it helps maintain the equilibrium of the environment, so that the kidney, the distal convoluted tubule, can do what its supposed to. Then the fluid then passes into the distal convoluted tubule, and here it joins up with the duct system. So all the little branches you see going down represent the duct system of this gland. We start off with collecting tubules, collecting ducts, and finally the largest collecting ducts are down towards the apex of the area, and this particular region is called the area of cribosa, and you can see these little openings here. Thats the openings from the papillary ducts, and when the urine flows out, it goes into the minor calyx. Calyces, then eventually into the major calyces. Slide 3 N Plate 318 Kidney Circulation Wishe: Nice picture depicting circulation through the kidney. Schiff: Youll notice that the capillaries that dip down into the medulla are very straight, very long, and compared to other capillariesmost capillary beds are like nets, a lot of cross-branching and cross-linking. Theres no real direction of flow. Here, in the vasa recta, you have a very definitewell they distinguish it by making some red and some blue depending on whether you have oxygenated or used blood, but you can sort of follow the flow. It goes all the way down in a straight line into the deepest part of the medulla, then up again. There are some cross branches, but not nearly as many as youd find in normal capillaries. The reason for this is that you want, as it goes down, for the blood in the descending part of the vasa recta to equilibrate with the hypertonic medium that its surrounded by in the medulla, the tissue, then as it goes up it keeps equilibrating by taking in more water, because its going into a more dilute environment, and giving off some solute. And the net result of all of this is that as blood passes down and then up these vasa recta loops, it leaves with about 4X as much water as it came in with, or 5X as much water as it came in with. So this is a way of removing water while it still of course takes away some solute, but minimally. You have to remember that were jumping from subject to subject in this, in the descending part of the Loop of Henle, the volume of filtrate drops from about 60 L/day down to about 36 L/day. Obviously its different for different people, but on average, your typical person down to about 36. So 24L/day are reabsorbed. Then remember that in the collecting duct, assuming that ADH is present, the volume of filtrate which arrives from the distal convoluted tubule, and collecting tubule, is about 18 L/day and that drops to about 2, because thats the 2

Transcribed by Chris Bedoya

April 25, 2014

amount of urine you put out, about 2L a day. 1, 3, somewhere in that range, so lets call it 2. Which means that another 16 L/day of water are reabsorbed. So the 16 there, and the 24 in the descending Loop of Henle, youre adding 40 liters/day of water to the medullary tissue. Now, two things are happening. 1 is that theres no room for that. Youve got a volume this big, and youre trying to put 40 liters into it. And theres just no room. And second of course, as this water is dumped in, its diluting the hypertonic medium, the hypertonic tissue, in the medulla. So what youve got to do is remove all this water, and thats what the vasa recta do. Each one takes about 4X as much water as it came in with. In a small capillary thats very thinwalled, small, narrow capillary, thats going all the way down and all the way up, how much water can it take away? But, theres millions of them. So it adds up, or multiplies up. And eventually you can take away a significant amount of water. So, the main role of the vasa recta is to remove the 40 L/day of water that was filtered, or reabsorbed rather, from the filtrate into the tissue of the medulla. After all, where else could it go? Theres no other exit pathway, except the ascending part of the vasa recta. The only other thing that goes out of there is the ascending limb of the Loop of Henle, and does that take away any water? No. Because its not permeable to water. So it cant take away any water. You start off with 36 at the hairpin turn, at the deepest part of the medulla, 36 L/day, and you end up with 36 L/day because no water is transported. So thats not a way to get rid of water. Its only the vasa recta, its the only pathway for getting rid of water. And thats what they do. But if you just sort of flushed it through, you would take away all the solute as well. So you have this gradual equilibration and re-equilibration on the way down and on the way up, which leaves a lot of the solute behind. Even so, for this reabsorption to take place on the way down in the descending Loop of Henle and in the collecting ducts, you need this medulla tissue to be hypertonic, so that osmotically it can draw water out of these parts of the nephron and collecting duct to maintain these high solute concentrations in the medulla. Remember what Dr. Wishe said early on today, and of course he said it before, and I said it before as well, theres no boundary separating cortex from medulla. Theres very little, if any, CT inside the kidney. There are no barriers keeping solute there. So even if you didnt have all this moving up and down in the Loop of Henle, you would still be losing solute up to the cortex just by free diffusion. So what you have to do is keep adding solute to the medulla to maintain the high concentration of the interstitial tissue. And wheres that work done? Its done in the ascending limb of the Loop of Henle because in the ascending limb of the Loop of Henle you reabsorbed lots of solute to bring the osmolality from 1200 at the hairpin turn down to about 285 when youre finally back in the cortex. So youre doing a lot of work just to keep the concentration of solute high in the medulla. Thats homeostasis. You want to keep things the way they are, and you do a lot of work just to stay where you are. Running up the down escalator. This is what life is all about. You sometimes feel like this whole college is running up the down escalator. You put in a lot of work just to stay where you are. Youre making progress, believe me. Wishe: So it has been estimated that there are 1-3 million nephrons per kidney. Thats a tremendous increase in surface area for filtration, resorption, and secretion 3

Transcribed by Chris Bedoya

April 25, 2014

to take place. Then as weve been looking over the vascularity, theres a tremendous vascular bed supplying this whole area. Dont forget that resorption is occurring, and whats resorbed by the cells of the PCT or DCT, doesnt stay in the cells. It has to go someplace. So it has to go back into the circulation to be re-distributed throughout the body. This is really an active-type of system. Active transport, sodium pump, and of course you need a lot of energy supplied by the mitochondria to make this work efficiently. Slide 4 Fig 19-1 Kidney Organization Wishe: So here we have a nice picture showing you the afferent arteriole entering the glomerulus, the efferent arteriole exiting it. How come I know thats an afferent? Because as you look at the tube, its about twice the diameter of the efferent. And why is it larger than the efferent? Well you have a lot of miscellaneous tissue disappearing, CT, elastic fibers, etc., but theyre replaced by special cells known as your juxtaglomerular, or JG cells. The JG cells play an important role in controlling your blood pressure. Where these two vessels enter and leave, is right over here, is referred to as your vascular pole. A couple other things happen at the vascular pole. This outer layer here is known as Bowmans capsule. Specifically, its the parietal, somatic, outer, external layer of Bowmans capsule. Then you can see a space here, thats Bowmans space. Although we cant see in this particular picture, sitting on top of this glomerular, capillary network, is a second layer of Bowmans capsule. So in essence, Bowmans space exists between the two layers of Bowmans capsule. And this whole apparatus in this region is really your filtering mechanism, the first step in the process. Opposite the vascular pole is the urinary pole, thats where Bowmans space feeds into, becomes continuous with the proximal convoluted tubule. And as your glomerular filtrate, which is produced as a result of filtration, passes through this PCT, the process of resorption takes place. Whatever is then left passes eventually into your Loop of Henle, and then into the distal convoluted tubule. The PCT and DCT are similar, theyre both convoluted. Although the PCT tends to be longer and more convoluted. Doesnt quite look that way in the picture but it is. The DCT then completes the process of resorption, but while absorption is taking place excretion is also occurring. Excretion leads to the elimination of the waste products of metabolism. As a result of protein breakdown in the gut, you get a lot of ammonia released which will poison you, then the ammonia goes to the liver where its de-toxified to urea, then goes back to the kidney for elimination. Urea will poison you as well, but over a longer period of time. But it still has to be eliminated. So certain amount of fluid, nitrogenous waste products, then pass into the duct system. And at this point no longer dealing with glomerular filtrate, but good old urine. And whatever is passing out is going to be eliminated. Slide 5 Plate 16-1 Kidney Cortex & Medulla Wishe: This just shows us under low power, part of the kidney, the upper part being the cortex, and I know Dr. S would prefer me not to draw my red line across over here, so Ill draw it on the outside. Everything above is the cortex, everything below is the medulla.

Transcribed by Chris Bedoya

April 25, 2014

Schiff: The reason is in this mornings section Dr. Wishe drew the orange line right across the middle of the section, and my comment was, and remember theres no barrier separating the medulla and the cortex, except for the orange line that Dr. Wishe drew. So, this time he avoided it. But the point is, if you look at this micrograph, there is no barrier, and so the solute ions, sodium, whatever, in the medulla that keep this hypertonic can drift freely out and have to be replaced on a constant basis. So even though in addition to the water, theres also diffusion that you have to overcome, so therefore you have to work even harder to walk up your down escalator. You keep pumping those ions into the medulla interstitial tissue. Wishe: So there is a gradual mixing of the medullary with the cortical tissue. We started off by mentioning renal pyramid, and I think I mentioned each renal pyramid is equivalent to a renal lobe, so if you have 8 pyramids, you have a kidney that has 8 lobes. It turns out that part of this medulla sends whats referred to as medullary rays up into the cortex. Just for arguments sake Ill put another medullary ray over here, so now the cortex is divided into smaller units known as renal lobules. So you have the cortex covering the base of the pyramid, as well as that part extending down a short distance along the sides. Thats the renal lobule. Slide 6 Fig 19-12 Kidney Cortex Wishe: Nice clear cut sharp picture on the cortex. Basically you see cross and oblong sections through tubules, and of course the glomeruli are really very sharp. If we look in this area, this seems to be a lumen, and that lumen seems to be entering the glomerulus. So this is really the vascular pole, whether this is the afferent arteriole entering, or the efferent arteriole exiting, one cant really tell by looking at this particular picture. In a similar fashion, at the opposite end is your urinary pole. Theyre never on the same sides, theyre always at opposite ends. Like the north and south poles. And this is Bowmans space, and it seems to be making a junction with this tubule, so Bowmans space feeds into, leads into the PCT. And the glomerular filtrate which is produced as a result of filtration is passed into your proximal tubule. A lot of the tubules you see in the picture are kind of fuzzy, and theres a reason for that. Because the PCT has your ruffled border. Microvilli. And this increases the surface area tremendously so that the process of resorption can occur as efficiently as possible. Some of these smaller tubules with shorter cells, this sort of simple cuboidal type of epithelium, represents sections through your distal tubule. And this nice cross section, and the lumens look clear. As you look at this particular area you can just about see some nuclei at the base, the cells look small compared to the cells on top, which are larger cells. And those cells on top are part of the macula densa, which plays a role in blood pressure control. Its a sensor for changes. And once it detects these changes, then different messages are sent out, leading to the production of various hormones and changes in blood pressure. Slide 7 Fig 19-3 Renal Corpuscle Wishe: High powered. Similar thing. And here you can see the macula densa, but better. Its a little big larger mag. And you know somehow that this clump of cell sin here is going to represent the arterioles, afferent and efferent. The other thing that 5

Transcribed by Chris Bedoya

April 25, 2014

happens at the vascular pole, this outer layer of Bowmans capsule sort of becomes continuous with the inner layer, or visceral layer, of Bowmans capsule. And that inner layer of Bowmans capsule sits on top of the glomerulus. Theyre both simple squamous epithelial layers. The outer layers looks more like your typical simple squamous cell. The inner layer is sort of modified and the cells are called podocytes. Podo means foot, cyte means cell. So these cells specifically sit on top of the glomerular capillary network. Slide 8 Fig 19-4 Renal Corpuscle Wishe: This is really a good diagram to use when youre studying about the kidney. This is showing you the whole filtration process very nicely. This whole region in here is actually your vascular pole. Heres the afferent arteriole entering, the efferent arteriole exiting. As you look at the cells around the lumen, these cells are larger, increasing the overall diameter. And the blood coming in is a certain amount. But as the blood circulates through the glomerulus, some of the fluid is being removed. So the blood that exits the efferent arteriole doesnt have to be as large as the afferent. In addition, the presents of JG cells doesnt really exist in this part of the system. As you look at the glomerular capillary network, its broken up into little pieces or sections, which we could technically call lobules if youd like. Its like when I did the lecture, I held up the wire, this is one lobule, thats another lobule, thats just the arrangement. And all these yellow thing-a-majigs sitting on top of the capillary happens to represent the inner layer of Bowmans capsule. And you can look at them even in this diagramatic representation, they look a little weird. These are the podocytes. Heres your urinary pole, where Bowmans capsule feeds directly into the proximal convoluted tubule. And as you look at the cells in the PCT, you can see these little lines representing the little border, microvilli, the brush border. There all modifications of microvilli. Striated border, ruffled border, unlike an osteoclast, theyre all the same thing. And over here we have a section through the distal tubule. Heres your normal cells, they should be a bit shorter, they should be more simple cuboidal in nature. And these cells right in here represent the components of the macula densa. Theyre larger, more columnar in nature-type of cell. Slide 9 Fig 19-5 Podocytes Diagram Wishe: Heres another picture showing you the podocyte. Heres your bulging nucleus. And it sort of looks like an octopus if you will. Coming off the podocyte you have these major, or primary processes, and they give rise to smaller, minor, secondary processes. And each one of those minor processes ends in a foot-like structure called the pedicle. Slide 10 Fig 19-8 Podocytes EM Wishe: And this picture shows you the interrelationship of the various components. So heres your glomerular capillary network, endothelial cells, then youll notice a space between, a fenestration, a pore, a gap, which isnt that large. Maybe 700-900 Angstroms in diameter. Once you have gaps, wherever you have them, you know something is gonna leak from one place to another place. Youll definitely have fluid 6

Transcribed by Chris Bedoya

April 25, 2014

passing through here. Youll have molecules passing through here, but you will not have cells passing through this fenestration, theyre too large. And if youre dealing with a very large molecule, that wont pass through the gap either. The pores represent the first step in filtration. Endothelial cells, the podocytes, theyre both simple squamous epithelium resting on a basement membrane. Thats what youre seeing in this particular area. The question is there one basement membrane, or two? Because both cells should technically have their own basement membrane. The way this picture appears it looks like theres one basement membrane consisting of three components. And the central, darker component is called lamina densa, then we had an external and an internal component as well. Lets just assume theres one component, so this represents the whole basement membrane. And this basement membrane will hold back molecules that weigh more than 150,000 MW. Im not a biochemist. Neither are you, and neither of us can envision molecular weight. I mean we can envision a of a pound, or an 1/8 of a pound, but not something this small. So this basement membrane is the second step in filtration. And then we notice these little foot-like structures implanting on the basement membrane. These are called pedicles. And theyre actually the termination of the secondary, or minor, processes. As a result there are little gaps created between the pedicles. And theyre called slits. And the slits are covered by slit membranes. And then the cells also release a secretion known as podocalyxin. So your third step of filtration, these molecules must get through the slit or gap, covered by the slit membrane, covered by the podocalyxin. And this trio of things holds back anything that weighs more than 70,000 MW. Anything under that will now pass into this space (top, lighter colored section), which is Bowmans space, and thats where it becomes known as your glomerular filtrate. Some people call it capsullar urine, but glomerular filtrate has more of a meaning, as Dr. Schiff speaks about the glomerular filtrate rate and stuff like that. Capsullar urine tells you that somehow it has somewhat association with the capsule, but thats about it. Slide 11 Fig 19-10 Mesangial Cells Wishe: Now when you look at the capillary network, again with me holding up this wire, and you make a cross sectional cut. So here we have cross sections through 4 different areas of the capillary. All this little fuzzy stuff on the outside represents, this is called the podocyte process, we could just as well call it the pedicles as well. And its the pedicles that sit on the basement membrane. So somewhere buried in this dark layer will be your basement membrane. Thats the way its labeled. But as you get between these capillary sections, call it intercapillary regions, this membrane from the podocyte continues to go around. But what about the membrane thats surrounding the endothelial cells of the capillary network itself, the glomerulus. That seems to somehow disappear. That then becomes a weakened area. So you find the presence of another cell type, called a Mesangial cell, and that provides additional support to the area where youre missing one membrane, or part of a membrane. But the Mesangial cell also acts as a macrophage, and anything that might leak into this intercapillary space will be phagocytized by these cells. Theyre sort of stellate in shape, but you cant see that looking at this particular picture. In addition, the Mesangial cell, plus the podocyte, helps regenerate the 7

Transcribed by Chris Bedoya

April 25, 2014

basement membrane. Remember this is filtration. Take your air conditioner. Every year youre supposed to take out your filter, wash it, or replace it. If you dont youre not gonna get appropriate amount of air coming into the room, etc. Same thing happens here. The filter is gonna get clogged. You have to unclog it. So the old filter is eliminated, and you create a new filtering mechanism. Slide 12 Plate 16-1 Fig 3 Kidney Cortex Wishe: Here again basically were looking at the renal corpuscle. Theres the distal convoluted tubule, and heres the macula densa. And notice all the fuzzy lumens, they definitely belong to the proximal tubules. Slide 13 Fig 19-15 Proximal Convoluted Tubule Cells Wishe: This is kind of cool. It shows you a bunch of cells that line the proximal tubule. This sort of looks like maybe some broccoli or something, but more appropriately it resembles your hair brush. These are all microvilli standing up to increase your surface area. Youll find that particularly heavily in terms of the cells of the PCT, and the distal tubule you dont really see that at all. The other thing, as you look at the base of the cell, youre gonna find a lot of mitochondria, thats where your sodium pump is located. You need energy to be able to transport something from the lumen into the cell, through the cell, and out into the vascularity. Also the lateral cell walls tend to inter-digitate like this. Like theyre almost locked together. If you look at the lateral cell walls of the distal convoluted tubules they tend to be more clear-cut and straight. Slide 14 Fig 19-14 Proximal Convoluted Tubule Wishe: This really shows you the brush border. So Im drawing the borderline between the cell and this lighter staining area on the top. Thats your brush border. Slide 15 Fig 19-19 Distal Convoluted Tubule Wishe: This is just again comparing cells belonging to the proximal versus your distal tubule. Slide 16 Fig 19-21 Macula Densa Wishe: Real nice picture of the macula densa. And these are your capillary networks making up the glomerulus. Notice the cells of the macula densa are much larger. Slide 17 Fig 19-22 Collecting Tubules and Ducts Wishe: When it comes to the collecting tubules, they start off as simple cuboidal cells, you make it into the collecting ducts and the cells are much more columnar. Slide 18 Plate 16-5 Medulla Collecting Tubules Wishe: Just showing you some more collecting ducts. Slide 19 Fig 19-22 Collecting Ducts Wishe: (nothing)

Transcribed by Chris Bedoya

April 25, 2014

Slide 20 Fig 19-14 JG Apparatus Wishe: And as you get to the largest collecting ducts, theyre pretty tall columnar epithelium. Your turn. Schiff: Ok. You notice the macula densa is sensing, remember, is the sensory part of the macula densa is the part facing the lumen of the distal tubule. Because what its looking for is the osmolality of the filtrate thats going through that part, that just came through the ascending part of the Loop of Henle and its leading to the distal convoluted tubule, and in the ascending Loop o Henle is started out at the hairpin turn at around 1200 mOsm/kg, very high osmolality, and as it goes up water stays where its put because you dont have water permeability in the ascending limb of the Loop of Henle but you do have this transport of solute out. If the GFR is normal, then a certain amount of the solute gets removed. If the GFR is slow, lower than normal, then the liquid is going through this ascending limb of the Loop of Henle more slowly, and theres more time available for the transport mechanisms to get rid of the solute, so more solute gets pumped out and you end up with a lower osmolality when you finally reach the area where the macula densa is. On the other hand if your GFR is high, then fluid is flowing through this whole nephron faster than usual, and it zips by. And in the ascending limb of the Loop of Henle theres not enough time to remove enough solute so it ends up with a higher, with more solute left behind, so theres a higher osmolality. So higher osmolality corresponds to a higher GFR. Lower osmolality corresponds to lower GFR. The normal level, it turns out is about 285. Whats the significance of 285 by the way? Well, its lower than 310. Remember you started out with an osmolality up in the cortex of 310, by the time this fluid got back its 285. That means relative to fluid, relative to water, more solute was left behind. Thats where the osmolality build up and maintenance in the medulla is taking place. Thats where the work is done. In any case, the macula densa then senses this surrogate measurement of the GFR, because high osmolality means high GFR, and low osmolality means low GFR. If the GFR is low, then what does it do? The macula densa secretes renin. Renin is secreted into the blood stream, into the afferent arteriole, which is basically the other side of the membrane of the macula densa, and when the renin reaches there theres some angiotensinogen, which is normally present in the circulation, its a small protein, and the renin which is an enzyme, changes the angiotensinogen to angiotensin I. The angiotensin I does two things. Well it doesnt have any power or effect by itself, but there are two things that can happen. It gets converted to angiotensin II by an enzyme, angiotensin converting enzyme (ACE). Most of it travels through the general circulation, the angiotensin I does, until it reaches the lungs where most of the converting enzyme exists. And since all your blood goes through the lungs, then all of this angiotensin I gets converted to angiotensin II. And what angiotensin II does is two effects. One is its a vasoconstrictor. So its spreading through your entire circulatory system and causes your blood vessels to constrict. That will raise blood pressure. Because you have the same amount of liquid in a smaller tube, the pressure goes up. The second thing it does is it acts specifically on the adrenal cortex to tell it to secrete aldosterone. Aldosterone is the steroid hormone that tells cellssteroid hormones generally act as gene initiators, or transcription initiators, 9

Transcribed by Chris Bedoya

April 25, 2014

and it tells various cells to make more Na/K ATP-ases. And so in various parts of the body, particularly in most ducts of glands, or in this case in the distal part of the distal convoluted tubule and collecting tubule, you make more Na/K ATP-ases which help to reabsorb sodium from the filtrate, in exchange for potassium. Now, there are two effects of this. The sodium that is reabsorbed stays in the blood stream, and since sodium is not very permeable, the extra sodium osmotically keeps water in your blood stream so it increases the volume of blood, of plasma. So now youve got two things going on, youre constricting the blood vessels but youre trying to add more water to enlarge the volume of blood. Between them they really raise the blood pressure. How does that fix the low GFR? Well if you have a higher mean arterial pressure, then you have a higher hydrostatic pressure in the capillaries of the glomerulus, and you get more filtration. So it increases your GFR. The other thing that it does by the way, which Dr. Curry mentioned, is while its reabsorbing sodium its replacing it with potassium, because remember its a sodium/potassium antiporter thats power driven by ATP-ase. And you can end up losing a lot of potassium in your urine, and end up hypokalemic, and changes in the potassium levels in your plasma can affect synaptic transmission, muscle contraction, pacemaker activity, cause arrhythmias, things like that, which Im not really gonna go into now. What else? Alright. Were running out of time here. Wishe: Renin and aldosterone, I think you still have to do the aldosterone part. Schiff: Well aldosterone is whats stimulating the formation of sodium pumps which increase the sodium in the plasma, so that osmotically you get a larger plasma volume. If you dont have aldosterone production, your blood pressure drops, and well get into that with endocrinology next week. Wishe: So renin and aldosterone tend to raise your blood pressure, but theres another hormone, ADH, produced by the pituitary, anti-diarrhetic hormone, which also puts its two cents in to raise your blood pressure. Schiff: Right, because you put out less urine. Wishe: And if you have high blood pressure by the way, one of the medications the doctors put you on are diuretics, to make you pee more to get rid of more fluid, more sodium, and the pressure should drop at that point. There are two antihypertensive agents. One happens to be produced by the kidney, and its called medullipin, and its produced as an inactive form, medullipin I, goes to the liver and becomes medullipin II, and that tends to drop your blood pressure. The other thing are your cardiodilantins, produced by your cardiac muscle cells. They also are antihypertensive. Im finished. Hes finished. Schiff: Im finished. Wishe: Were ready to go home, go to sleep.

10

Transcribed by Chris Bedoya Schiff: Have a good weekend.

April 25, 2014

11