Welcome back, everybody. I'm out in my backyard again. It's really nice out here and getting ready to kind of continue our discussion here associated with the renal system. We've spent a great deal of time already talking about, well, mainly the anatomy of the kidney, gross and microscopic, and bringing into your forebrain this concept of the nephron, the functional unit of the kidney. And in talking about the nephron, while I've briefly described the different parts of the nephron, we've been focusing mainly on the glomerulus, that capillary bed, that is surrounded by the beginning parts of the nephron proper, the Bowman's capsule.
Going along with those two concepts, we've been playing with this idea of what is called glomerular filtration rate. Glomerular filtration rate. Excuse me.
Glomerular filtration rate refers to the amount of material that is able to leave the glomerulus and move into Bowman's capsule and into the nephron itself per some unit of time. And I'm hoping you remember the number, 125 milliliters per minute is what is kind of our normal glomerular filtration rate. That can be altered depending on pressures within the cardiovascular system. That's what we were doing when we were talking about glomerular filtration rate.
Well, we're going to put glomerular filtration kind of back a little bit. We'll come back to it and talk about some other regulatory mechanisms associated with it. But before I can do that, we need to talk more about the rest of the nephron, the actual tubule. extending away from that Bowman's capsule and what its job is. So to do so, we have to make sure we remember some things from prior lectures.
We're going to do a little bit of reviewing a primary and secondary act of transport in this mini video. And to go along with that, if we have active transport, we probably have passive diffusion also taking place. and some of the molecules that are associated with that passive diffusion. And before we finish this little video, we're going to put it into an example, hopefully something that kind of relates to all of you.
We're going to look at how the nephron is working with active transport and passive diffusion, and how that relates to us reabsorbing molecules like glucose or amino acids. Ready to do this, folks? Let's jump into this.
I'm hoping you remember this image. We've used it prior to kind of give you a visual of what the nephron looks like. We have been spending a lot of time talking about the glomerulus and Bowman's capsule and material moving into Bowman's capsule.
Again, bringing up glomerular filtration rate. So, utilizing principles that we have talked about before with the cardiovascular system to try to understand the forces moving materials into that Bowman's capsule. Now, I'm hoping you also remember that the pressure forcing this material out, well, those materials, literally everything is getting pushed out, or I can't say everything, but a huge amount of material is being pushed from that glomerulus into Bowman's capsule.
Anything smaller than 70,000 molecular weight, which is just about every ion, molecules like glucose, again, amino acids that we've talked about, are getting pushed from inside of that glomerulus into Bowman's capsule. And I have to bring up this second item here, that you need to remember that everything inside of that cardiovascular system is part of the internal components of the body. It's...
inside, as far as we're concerned. But when we move materials from the glomerulus into Bowman's capsule, literally the inside of the nephron is considered outside of the body. Outside of the body. So that means if we're pushing materials from that glomerulus into Bowman's capsule, we have this incredible potential to lose those solutes that we've pushed out, and the fluids that are following that high concentration of solutes. This is potentially very, very dangerous to us.
So why does the body do it? Well, in the development or the understanding of the development of the nephron and the renal system itself, remember some of the jobs that it has. Its job is to manage solutes.
And by managing solutes, we are able to manage fluid volume in the body. So the nephron itself, and especially the tubule network of the nephron, its job is to... Decide what solutes we're going to keep from all of these solutes that we have just thrown out. Now, you may think that's a fairly inefficient way of doing things, but actually not so inefficient.
I know many of you are way too young to remember many, many, many years ago, kind of at the beginning of many of the streaming channels that we have at our disposal at the moment. There was a home improvement show that it would take requests from particular families who were looking to renovate a particular part of their home. Two or three individuals, each with a particular specialty in home renovation, would come to the home and they would discuss the renovation. And then once they've decided on what they wanted to renovate and how they were going to do it, One of these specialists would come to the individuals in the house and say, okay, we need to clean out that area so that we can start renovating it. Well, usually that spot was a highly cluttered, highly packed part of the home.
And so in cleaning out that room, this person would tell the family, you need to pull. everything that's in that room out of there and put it outside on this tarp that the person had outside in the yard. So the family was requested to do so, and so they would.
They would pull everything out, put it on this tarp that's out on the outside, and then the expert would come out and say, okay, while they're renovating what's going on in that room, I have a second tarp and the second tarp was about a tenth of the size of the first tarp. And he would tell the individuals, okay, you can keep whatever you can fit on that small tarp. This of course panicked the individuals in the home because they had to make a decision on what they actually really needed and what they were going to keep in the house, everything else was going to be given away, taken away, and they would do it. And of course it helped the home reorganize, helped the room become what it was that they wanted it to be, and so there were multiple facets to this.
The nephron does exactly that by having the glomerulus throw everything out, put it out on that tarp outside, It will be the job of the rest of the nephron to literally decide what we're going to keep, what's important for the body. We'll pull it back into the body. We'll reabsorb it. Hopefully, when we reabsorb those solutes, water will follow. And whatever we don't reabsorb, we let it go in the tubule, and eventually it will be thrown out.
So the rest of the nephron, the tubule component, is the deciding factor here in what we are going to keep. Everybody got that? Well, I'm hoping you do. So, it's about keeping solutes.
Water will follow those solutes then back into the body. The particular solutes that we're looking to keep, well, remember, all ions are really small. So, they were pushed out of that glomerulus as the pressures are pushing them into Bowman's capsule.
So, we're inside of the nephron. We have sodium, potassium, chloride, calcium, very important to us, magnesium. And you'll see as we talk about the nephron's tubule that there are particular active transporters, passive transporters that are allowing us to pull back the amount of sodium, the amount of potassium, chloride, these ions back into the body.
And again, by using that solute concentration, We're going to pull back water as well. Glucose. Glucose.
is getting pushed into the nephron. And as you know, we need glucose in the body for energy. So it's a huge component of this nephron to be able to pull glucose back into the body. Glucose is a solute. And if we pull that back in, pull it back out of the nephron, guess what's going to follow it?
Water is going to follow it as well. We're also going to be managing particular levels of other solutes like CO2, hydrogen ion, very, very important, and bicarb, all right, and bicarb. So all of these, the nephron has to manage.
Now, in talking about all of this, I didn't really talk about dealing with waste products or other materials that didn't get filtered. So the secretion of materials from the vascular network that is sitting around the nephron, pushing it into the nephron. There's still a possibility of that.
And, of course, letting go of particular materials that we don't need, at least at this point in time, like urea. Everybody got that? Okay, let's review really quickly here then. All right, we're going to review active transport. Ready?
Let's do this. So in this image, let's make sure you understand what we're looking at here. Over to your right.
It says the filtration or the lumen. This is inside of the distal, or excuse me, inside of the nephron tubule. It doesn't matter where, but this is inside of the nephron tubule.
These structures that you see here, it says tubular cells. These are the cells that make up the wall of the nephron or the nephron tubule. Back over here in this area, this is the interstitial space, the space outside of the cells. next to and outside of the nephron, next to the blood vessels that are going to be sitting along the outside of the nephron itself. The idea?
Well, solutes. And let's talk about one of the solutes. We'll say sodium.
You remember way back at the beginning of this semester? Sodium, higher concentration outside of the cell than inside. Because of that, the And here, this, well, let me give you some names to remember here. The basolateral and apical surfaces of these cells. The apical surface is the top pointing into the lumen of the tube.
The apical surface of these cells has multiple sodium channels, and the doors are open. So that means as sodium comes through in the fluid of the nephron, concentration of sodium inside the cell is far less than in the lumen. Sodium passively moves in by way of diffusion.
By way of diffusion. Does that make sense, folks? As sodium moves into the cell, on the basolateral surface, baso meaning bottom, lateral, this is the lateral side of these cells, you're going to find sodium potassium pumps. Sodium potassium ATPases. What is this supposed to be doing?
pushing sodium out of the cell, pulling potassium in. As sodium comes into the cell, it gets pumped out and into the interstitial area on the backside of these cells. That means the concentration in this area is going to become fairly high with sodium because it's being physically actively transported into that area. So we have sodium moving from inside of the lumen of the tube into the cells, actively pushed.
into the interstitial area. And because the concentration of sodium is so high here, in comparison to what's inside of the blood vessel, it moves into the blood vessel. We have reabsorbed sodium.
Guess what's following that high concentration of sodium? Water. Water is following it. So as sodium is being moved, water is being pulled from the tubule as well.
We call this bulk flow. Bulk flow. Everybody got that? Pretty simple kind of just review. Okay.
Let's take this. Let's do it again. Another image.
Very similar to the one before. Again, tubular lumen over here. So inside of the nephrons. Here's the cells of the nephron. The back end.
The interstitial areas of it. And here's our capillary again. I'm going to put our terms up here again, apical and basolateral surfaces. Sodium, passively moving, or I should say following its concentration gradient into the cells because there's a higher concentration outside versus inside. As it comes in, we pump it out by way of the sodium potassium pumps into the interstitial area.
It gets moved into the actual capillary beds and what's going to follow folks? Water is going to follow the concentration of sodium. We do this process with multiple ions.
Multiple ions. Now I want you to notice how, well, we're pumping sodium out and we're pulling potassium in. So in this process here, remember, potassium has a higher concentration inside the cell than outside. There are actually channels for potassium, so we have the possibility of losing potassium in the urine.
We'll talk about that a little bit later in another mini video. Alright. We've got that down.
Let's do it one more time. I've flipped the image a little bit here. Over here to your left, inside of the nephron, the tubular cells associated with the nephron.
This must be the apical surface. This is the basolateral surface now. Interstitial area and the capillaries, the peritubular capillaries. Sodium going downhill following its concentration gradient.
into the cell, getting pumped out the back end by the sodium-potassium pump into the interstitial area. Osmolarity is getting higher and higher because of the solutes that are sitting in this interstitial area. Water is attracted to that. It follows. It follows.
As sodium moves in, or the sodium concentration moves into the capillaries, water will follow. We have sucked back in the water. that we were losing initially. Does that make sense, folks? That was looking at diffusion and allowing things to happen with some active transport, the sodium-potassium pump.
You hopefully also remember that there are some secondary active transporters out there, and in the kidney, they are plentiful. Just some examples here of these secondary active transporters, and I'm using it to give you... a little closer relationship with glucose and amino acid reabsorption. So as you look at the image over to your right, the co-transport, sodium's coming into the cell.
Remember, higher concentration out versus in, so it wants in bad. We're going to grab a glucose, or this exchanger, or excuse me, this co-transporter says, well, sodium, you can't come in unless glucose comes with you. Grabs the glucose, pull it in.
We are now reabsorbing glucose. The same with amino acids. These co-transporters are going to be really important, and they're using what we've talked about before, this major concentration difference for sodium, as a driving force to kind of pull in other molecules.
We can use sodium as a counter-transporter. Sodium wants in. We need to get rid of hydrogen ion.
We use the concentration gradient associated with sodium to literally get rid of those hydrogen ions so that we can manage pH in the body. This is going to be thrown into the lumen of the nephron so that we can excrete it. And as you probably already know a little bit about, your urine is slightly acidic.
Why? Because we are getting rid of hydrogen ions from the body. Everybody got that? Okay. Enough review.
Filtration. I need to get you to think about what's moving from the glomerulus again into the nephron. Filtration is equal to, up here you can see the term PS, times glomerular filtration rate.
Do you remember the number? 125 milliliters per minute. Well, what does PS stand for?
PS is referring to the plasma concentration of whatever solute. we want to focus on. So we could say sodium, we could say glucose, amino acids, whatever the concentration of that in the plasma, well when we get to the glomerulus and there is this pressure to push things out, the amount of material, the solute that is filtered, is going to depend on its concentration and the glomerular filtration rate. and the glomerular filtration rate. Everybody got that?
Now, this filtration The amount that is moving into the nephron, we call that the filtered load, or in some cases, you'll hear the tubular load. Okay, why? Because this is the load of material for that substance in the nephron tubule.
Everybody got that? And usually the units associated with that is milligrams per minute. That's because, remember, glomerular filtration rate was milliliters per minute. And the actual concentration of the solutes that we're looking at are in milligrams per milliliter.
Factor out our units, it will come to be milligrams per minute filtered into the nephron. Now this is important, and we're going to use this understanding of filtered load and what the nephron can handle. Because its job, if you remember, is to pull back what we need in our body. So let me...
Let's use an example here. In this graph, we're going to look at glucose and the reabsorption of glucose by way of transporters, all right, the co-transporters that we talked about before. So if you remember, glucose is pretty dependent on sodium concentrations for it to get moved.
Does that make sense? This graph down at the bottom, this is the filtered load of glucose. Now remember, this has to do with the concentration of glucose in blood and the glomerular filtration rate.
All right. Over here to the left is the actual concentration of glucose in your blood. In your blood.
All right. Got that down? Curves that we have here. This curve is the first one I want you to pay attention to. This curve is letting you know how efficient the nephron is at being able to reabsorb, reabsorb glucose.
It is not infinite in its power to reabsorb it. That's something to remember. But it has a fairly strong capacity of being able to reabsorb it.
There's lots of carriers and exchangers inside of the nephron that are allowing this mechanism for reabsorption. But again, it can be overwhelmed. So that's why you see up here the term saturable, meaning there's a lot of capacity, but you can overrun that capacity.
So this curve is trying to tell us what we can actually handle. All right. Well, again, filtered load is equal to the concentration of glucose over here times the glomerular filtration rate.
And if that's the case, that's the case. I can let you know that, well, the usual concentration, okay, of glucose in plasma is sitting at somewhere between 0.9 milligrams per mil. If we multiply that by 125 milliliters per minute, the glomerular filtration rate, we get 112 milligrams per minute. That's what we can handle.
This we can absorb. We can reabsorb glucose at this concentration. This concentration of glucose that we have up here for the plasma is fairly normal for most of us with a balanced diet.
So this curve is telling us, oh, we can reabsorb that no problem. No problem. Everybody got that?
Okay. Well, let's take this to the extreme. If, if you're in a situation where you are not able to manage glucose very well, you guys know about disorders like this. Diabetes. Diabetes is a situation where particular hormones that are secreted are not, not done, it's not being secreted very well.
Insulin. Insulin is very important for the production of particular exchangers so that we can absorb glucose, absorb it into the cells. Not that, folks.
Well, if we do not have those exchangers and carriers to allow glucose to get into the cells. That means glucose in the plasma, in the fluids of our body, increases in concentration. It's not getting into cells. Cells can't burn it. They can't utilize it.
That means, again, the concentration of glucose in our body, in the fluids of our body, goes up. Well, glomerular filtration doesn't necessarily change. So that means if the concentration goes up, multiply that times the glomerular filtration, the filtered load is going to go up. Let's put some numbers to this.
Alright, let's see here. If this filtered load goes up and gets moved along this axis here from where it was before at about 112 and gets pushed, that's going to put pressure on the nephron to decide, do we hang on to glucose? Do we have the ability to reabsorb glucose?
Well, this is a difficult situation. In situations of diabetes, the concentration of glucose in our blood can rise well beyond 3.2 milligrams per milliliter. Multiply that by 125 milliliters per minute, that's 400 milligrams per minute of glucose getting pushed into the nephron. If we follow, okay, that's the new filtered load right there. If we follow that along our axis, here's 400, here's 400 right here.
So at that 400 spot, If we follow that and follow it up to our curve for reabsorption, well, you can see how it bends and flattens out at 300 milligrams per minute. This is our limit. That's the best the nephrons can do.
They cannot, if the concentration is beyond 400 or beyond 300, it can't hang on to that glucose. That means it's going to stay inside the nephron. If it stays inside the nephron, glucose, it's a solute. Guess what stays with it?
Water. Water. I want you to look at this other component.
If we are allowing glucose to stay in the urine or stay in the nephron, it's going to be excreted. So you can see beyond 300 milligrams per minute, we're going to be losing glucose in the urine. Losing glucose in the urine.
So losing that in the urine, you may have heard from other classes or other biology bits of information that in diabetic patients, diabetic mellitus patients, the urine actually has, you'll hear that. urine is sweet? Well, it's because it has a higher concentration of glucose in it.
So we're excreting and the more, or the higher I should say, the glucose load gets, the more we'll be excreting. This is trying to illustrate how important the transport mechanisms within the nephron are for trying to hang on to particular solutes. And once we surpass those capabilities, We're going to get rid of that material. How are we doing, folks? You hanging in there?
We're going to end this mini lecture, and we'll come back and talk more about the actual nephron tubule in our next video. Talk to you soon.