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This is Sal here and I'm at Stanford Medical School with Dr. Andy Connelly. Hi there Sal, I'm here to discuss with you histology today. Histology! And, and forgive me, for what is probably a simple question, but what is histology? So it will be the -ology, the study of, in this case the histo-, means tissues. We're going to be looking up the cellular components of organs. Cool... yeah. So what we're going to be looking at today is the histology of the colon. And so for the colon we often have colon specimens coming in from pathology. And so the colon, like you were saying before, is the large intestine. So if you have this piece of large intestine, and its removed from the patient because there is an area of cancer. It might be cancer, they're actually pretty good now about doing colonoscopy. Looking from the inside-- They'll often have looked inside think it looks like cancer take a little piece and send it to us before hand, and then they remove it. And the reason why they want to send it to you is even if they know its cancer how severe is this cancer? How severe is the cancer? They also want to get a really good tissue diagnosis to make sure if they're going to go remove a piece of your colon, that they really know that its cancer rather than it just looks like cancer. So its the definitive proof before they remove it. So then if this is the cancer that's removed they clearly want to be able to check the margins to make sure its removed in its entirety. But often inside of there, they'll find other pieces of tissues, like here's a polyp And when we say check the margins, this is literally, just making sure you've covered enough material so that you've gotten all the cancer in it that you're not kind of cutting through the cancer and that you've missed something. That's right, because this is actually one of the traditional surgical cures of cut it out to cure. Colon cancer, that tends to still be the case. Because you cut it out to make sure you cure it. There are many other kinds of cancers that which spread so widely early on that you don't usually cut out. So then the polyp can be found in a piece of colon removed a polyp is something that just sticks up. Any tissue that sticks up. It's not necessarily cancer. No, so for instance another common place you hear about is some people in the sinuses might have sinus trouble and they'll have a sinus polyp those are almost always just inflamed. And then we'll find areas in which it's just the lining that's been roughened, and we'll take sections of those. And that can happen from just someone being allergic to food Yeah, irritations of such. Yes, irritations of certain sites. So we're going to have the areas where its kind of irritated some in which there's a polyp sticking out and we'll look at it under a microscope and then that's the thing that we're mainly worried about So that's what we're going to cover in the slides that we look at today. So this first one we're looking at is an example of a normal margin And so it's from a little piece from the edge So they actually call the tissue margin? Yeah, tissue margin Normal tissue. So this is the edge of the specimen, and [the surgeons will] say, "Is the margin clear?" Dr: In this case this is an example where the margin IS clear. This is normal-looking colon. S: This is a cross-section, crossing the boundary of the colon, this area at the top right here, would be the inside of the colon, where the poop is... Dr: Doctors say stool. That's the stool in the middle, and the supportive tissue is underneath. S: Part of the structural tissue of the tube? Dr: Right. Now let's drive around the slide. This is a virtual slide where we took the typical glass microscope slide, and put it in a special machine which took lots and lots of photographs at high power, then stitched them all together as one massive image. So that allows you to zoom in and look around. S: To let me get my own bearings, this polyp... Dr: No, this is just regular tissue--a little bit of a fold, not a polyp. S: So how large is this, about a centimeter? Dr: About like that. If I had to guess, about 5-6mm. So, now to drive around, these are the controls for zooming in and out. So I can look at something more closely, and this is the mucosa. S: Mucosa. Sounds very similar to mucus. Dr: Right. The mucosa is the lining that makes the mucus, it's the slimy part. S: This white stuff up here? Dr: This suff is the slimy mucus. So, it keeps the insides from drying out-- because it's a very hydrated gel. It also means that things can glide along without abrading the surface. When you look at it, it has architecture in which these glands, they're like test-tubes sticking down, and the purpose is to increase the surface area. S: And the term gland, is any structure containing fluid and releases the fluid? Dr: A gland is an epithelial structure, so it's made of cells that are packed tightly, and the cells have a top and a bottom, and they're formed into some sort of enfolding or structure, so that there is a middle and an outside. S: When we say something is epithelial, it's the stuff facing the outside world? Dr: Yes. The epithelium is a special class of cells in which they are facing the outside world, again, tightly packed, and there's a top and a bottom. S: And even though to a layperson this area right here does not seem like the outside world, it seems like it's inside of you, we're kind of like big donuts. Dr: That's right. And the colonoscopist proves that it's connected to the outside world. S: MUAHAHA!! I guess they do prove that! XD Dr: So that's still the outside world. This is the architecture where you have enfoldings to increase the surface area. And it's creating this mucus. Let me look at the highest power. Look at these cells! When we look at these cells, there are two main types of cells. There's this one here, which is the goblet cell. S: Goblet cell. It's not just this white part, it goes all the way down there? Dr: Yeah...let me have that pen! It has a top like that, and you see this wine glass? S: It's literally shaped like a goblet! I was circling the wrong handle. Dr: That nucleus belonged to some other cell. What's next to it is these thin cells here, which do not have all the mucus inside of them. These guys are the tall ones. S: Where you see only the nucleus? The white part is just the mucus inside the cell. Dr: Yes. Mucus is the term for either the overall structure or the material that is elaborated up here, chemically it is called mucin, and mucin is almost like that goo runners eat, it is just a lot of sugar holding a lot of water. S: I see. I guess it would be bad branding to call it Mucus-In-A-Bag. MUAHAHA!! >:-} Dr: Exactly! So they stick with "goo". But this one has a lot of sugar, takes in lots of water, that is released and it forms this surface here. S: To let stuff flow by. Dr: What the other cell does is the other main thing in addition to letting things flow through, is to absorb water. So the idea is you do not want to release the 2L of fluid you have around every one of your meals. You want to get a lot of that back. S: That's one of the main functions of the large intestine? Dr: It is. It is a consolidation process to the stool. So you're going to absorb a lot of water and doing it through these cells. S: The mucin comes out here, and the water absorbed by parts without mucin, so right there. Dr: Yupperz. That's right. The two main functions of the colon are right there with those two cells. S: To get a perspective of where we are, the whole thing is about .5cm, what's our scale here? Dr: Our favorite scale-bar here is to look for blood vessels, for red blood cells, One right there, is 7micro- m in diameter. S: 7micro-m. A micrometer is a millionth of a meter, or 1/1000th of 1mm. Dr: That's right. Let's round off to 1/100th of 1mm. S: You put 100 of these next to each other you get 1mm. So 1mm would be bigger than our entire screen. Dr: Right. You see with these glands, 1mm would be this span, which we're saying is about like that, That's why from here to here it might be about 7mm. Dr: RBCs are found in just about every microscopic field, and they're always 7micro-m. When looking here, this is very well formed. You can see these tubular glands, just a hint over here, because they are like test-tubes, sometimes they're not going straight up and down, sometimes they look a little on an angle... S: They actually are reaching the surface, we just don't see it based on the way it's cut? So this one right here, it was cut at an angle, so it looks embedded there in 2D, but in 3D we would see a full tube. Dr: Just to go back to the microscopy, we're seeing this because it's only 4microns thick, and we're sending light through this tissue. So that's why you can get a cross-section that doesn't show you 3D. Very much 2D. S: Cool! So this is what a healthy margin tissue would look like? Dr: Yes, this is a healthy colon, so you would thankfully say on the proximal margin, which is up more towards the mouth, that's clear. You take another section like this from the distal margin, more towards the end, and you say that's clear, so that means they removed the cancer. S: When you say proximal margin is close to the mouth, you're saying the mouth of that cut of the tube, not mouth of the person. Dr: That's right. So the proximal and distal margins are clear, if they look like this.