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Let's talk about capillaries. There are actually three major different types of capillaries. I'm going to just kind of sketch out all three. I started with the continuous one. I just drew it out to save us a little bit of time. And the continuous capillary is actually the one that you see most commonly throughout the body. So that's why I wanted to start with this one. A couple of things you'll notice. You'll see that there are four nuclei, so four cells here, making up the part of the capillary we're looking at. And there's a red blood cell moving through it, right? And we actually have the cross section on the right side, so you can actually see, if we were to cut along that face that I've cut, this is what you'd actually see. Now there are two specific things I want to point out. One is that there's a little gap here between these two cells. I'm sketching it in yellow just to really point it out. And that gap is called an intercellular, because it's between cells-- intercellular cleft. So the intercellular cleft is that yellow streak that I just drew. And if I was to point it out on this cross section, it would be right there. You can see the little hole between the two where they don't really meet up. Now there are two more spots I want to point out. One right there and one right there in yellow. And they correspond to this spot and this spot. And there, there is actually really nice joining between the two cells, and we call them tight junctions. Kind of a good name for it, I suppose. You can kind of see why they would call it that. And these tight junctions are right there, labeled with my yellow arrows. Now the one thing I haven't drawn-- I'm going to just sketch out right here-- is in green. And this kind of is a layer beneath all these cells. So these cells are making up the wall of my capillary. But behind them, so that the blood actually doesn't see this layer, except for at the intercellular cleft, is a layer called the basement membrane. So this green stuff that I'm drawing for you, this is our basement membrane. And this basement membrane is basically like a foundation for a house. It's going to keep our cells kind of grounded and keep them in place. And that layer is largely made of protein. Let me now show you a second drawing that I did. This is our second type of capillary. This is a fenestrated capillary. You can see the major difference between this one and the first one is that the second one has little holes, or we call them fenestrations. So this is a fenestrated capillary. And these pores-- I'm going to just label them, and you can also call them pores or holes-- these pores are all over the capillary, right? So we still have, just as before, four cells, four nuclei, and one little red blood cell poking his way through. And you still have the intercellular cleft. So just to show you where it is on this one, it's right there where the two cells really don't meet up so nicely. There's a little gap there. And as before, there's going to be a basement membrane, so let me just kind of sketch out the basement membrane all the way around. And on this cross section, you can see now how I've tried to draw it as best I can to show you the pores, but you have to now get a little creative and see where that intercellular cleft is versus where the pores are. So whenever you're looking at the cross section, it's a little tricky, because you have to almost imagine it in three dimensions. Now the one thing that does help us is the fact that on the inside of these endothelial cells. I'm going to draw in blue a little layer of almost like a slime. And this slime layer is called glycocalyx. And what glycocalyx is is basically sugars that are attached to proteins. And this kind of sugary protein mix is all over the inside layer of these endothelial cells. And so what it does is it actually gets across these pores. So even though there's a pore there, you might get a little bit of glycocalyx spanning the pore. And it'll come across, and it'll look like that. The one place where you won't see it is in the intercellular cleft, because that's actually a real spot between cells. So if you have an intercellular cleft like you do here-- let me just draw the arrow down here, right there-- you won't see any glycocalyx there. So we call that little bit of glycocalyx that's bridging the pore, we call that the diaphragm. So these cells, or these fenestrated capillaries, actually have diaphragms over their pores. But I'm going to put a little star next to that, because sometimes you can find fenestrated capillaries that do not have this glycocalyx that's covering the inside. And they, therefore, do not have diaphragms. So this is something that is generally true, but not always true. So let me show you the third type of capillary then. Let me just show you this last drawing. And this is actually the largest of the capillaries. This one, we call this a discontinuous capillary. And another name for discontinuous capillaries, sometimes they call them sinusoids. So I'm just going to write that up here as well. Sinusoids. So these ones, often found in the liver-- that's kind of the most popular place, or sometimes the spleen as well, or bone marrow-- these ones are actually a few things. They are the largest ones. Let me just make a little list over here. They're very large, and they have a lot more of this intercellular cleft space. Look at all these gaps between the cells, right? And I'm just sketching it in yellow, just to highlight it. But there's a lot of gap here between the cells, meaning that these capillaries end up being very leaky. So in addition to being large, they're very leaky. And a final thing about these guys is that unlike the other two capillaries we just talked about, they have a basement membrane that is often incomplete. So sometimes there are whole areas that are missing basement membrane, just like that. You might have some basement membrane here and here, but you can see whole chunks are missing basement membrane. And maybe there's a bit of basement membrane over here. So let me write that as a third point. Incomplete-- I'm going to write BM for Basement Membrane. Incomplete basement membrane. So if this is the case, it'll be easier for things to kind of escape, even if you have a little glycocalyx here. I'm just drawing a layer of glycocalyx on our discontinuous sinusoid capillary. But even if you have this glycocalyx, because of the fact that you have so much of that intercellular cleft space and you don't have many of the tight junctions, it's going to be easier for things to get out. So moving down these three different types, you're getting more and more leaky as you go down. So just keep that in mind is that the leakiness of the vessel is increasing. In fact, the most leaky is this guy down here, the discontinuous type. So think with me for a second. Let's say you're a molecule in here, in the capillary, and you want to get out here into the tissue. What are the ways you can get there? One way would be if you actually just diffused across, right? So one way could be diffusion. And that would work really well if you're a molecule of oxygen or carbon dioxide. Diffusion works well for those molecules. But let's say you're not one of those molecules. Let's say you're a larger molecule, or a charged molecule, how would you get across? So a second way then to get across could be through a vesicle. Maybe you could get into a vesicle here in this cell, and the vesicle could transport you from being on the inside, which is where this X is, to where it can actually get deposited on the other side. And then, of course, it would still have to make its way through the basement membrane. But that's at least a way of getting past the cell. And so this is a second approach, maybe a vesicle could carry the molecule through. A third way could be through this intercellular cleft. Again, you still have to get across that basement membrane, but at least you can get across the cell by simply going around the cell. So maybe that intercellular cleft could be another ticket to freedom. So if you want to get around, you can go that way. That's a third way. So what's a fourth way? Well, now we have to kind of go down to our second drawing, the fenestrated one. And here. I would suggest maybe just going through-- that little x-- maybe just going through that pore. And you have to plow your way through the glycocalyx, if there is some there. But maybe that's another way is going through the fenestration. That could be another way across, right? So these are four ways for things on the inside to get to the outside. And as you look at this list that we made, these four options, you can see then that our idea around leakiness makes sense, because now, especially when you get down to the discontinuous vessels at the bottom, you've got large gaps between the cells, lots of intercellular clefts. You've got vesicles that can apply anywhere. Diffusion can apply anywhere. And you've got the fenestration. So really, every opportunity for things to get out of the capillaries is available in those discontinuous or sinusoid capillaries.