Histology of the small intestine.

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Transcript
00:00Hi, we're back at the microscope. We've been working our way through the gastrointestinal
00:09tract, a tube that runs all the way through us. We've looked at the esophagus and the
00:13stomachs and now we're at the small intestine. The small intestine has got three parts, duodenum,
00:19jejunum, and ileum. And we'll look at all three of those and we'll compare them. So
00:24the small intestine, what we're going to do is we're going to relate the cells and the
00:28structures that we see under the microscope to the different functions. So the small intestine
00:33has got different jobs to do than the stomach had and the esophagus had. And we'll see that
00:37reflected in the anatomy. And I said that the gastrointestinal tract is a tube that
00:44runs all the way through us and it's made up of layers of cells and tissues and that
00:49organisation and those layers are the same all the way through. So we'll look at that
00:53layout first, but parts of those layers change depending upon function. So really today we're
01:01going to focus on the epithelium, the mucosa, how that changes through the small intestine
01:08and why it changes through the small intestine. Remember that this is supposed to be a slow
01:14visual look at these cells. I want to start wide and zoom in. I want to build up a picture
01:22in your mind of how these cells and tissues were arranged so that you can then relate
01:26that to your understanding of the gross anatomy of this tube running through us. And then
01:30you have a better picture, a better understanding of the anatomy and then how all of it works.
01:37All right. That's the aim. Otherwise, you just look at pictures in a textbook, which
01:42would be a lot quicker. All right. What have I got? I've got where the stomach becomes
01:56the duodenum. I've got jejunum and I've got ileum. So we'll start with the duodenum and
02:08we should look at, we'll look at the layers first, the overview, right? I should probably
02:15clean this slide. Okay. So this is on the lowest power. Oh, that is so cool. Straight
02:40away. So there's the inside. So this is the duodenum. Remember the stomach has, it's used
02:50acid to switch on some proteases and it's been churning up the food and then it squirts
02:56a little bit of its contents into the duodenum. So the duodenum then has to, okay, so the
03:02job of the small intestine is to absorb nutrients. The duodenum has a little bit of a special
03:07problem in that, well, at this stage we're still digesting, but also it's getting acidic
03:13contents from the stomach. So acidic stuff can be damaging, right? So what we're seeing
03:18here, here is the inside, the lumen. This is where the food is. So this is the, this
03:23is the epithelium. This is the mucosa here. Oh my, we can see so much in there. That's
03:28beautiful. And look, we've got these little fingery projections. So these are the villi.
03:32So if we go from here, we see the mucosa. So we've got epithelium and laminoprotein
03:37here supporting that. Don't worry, I'm just rushing through briefly now. I'll do this
03:39in more detail in a moment. And then we've got a supporting submucosa and some thin muscle
03:47there. And then we've got two layers of muscle, the muscularis externa. And then on the outside,
03:54we've got the serosa. We've got all the adventitious, the connective tissue that's holding all this
03:59together. In terms of the small intestine, a lot of the small intestine is very mobile.
04:04So it needs to move around. That's what the peritoneum is for. That's what the serosa
04:07is for. With the duodenum, it's mostly retroperitoneal, so it's mostly fixed in place. But hey, look
04:13at me doing way too much detail already. But the layers then, the mucosa, submucosa, muscularis
04:23externa, and serosa, same as we saw in the esophagus, same as we saw in the stomach.
04:31So the two layers of muscularis externa, we have longitudinal and circular muscle there
04:36to do with peristalsis, squeezing the contents along the intestine. The submucosa here, wow,
04:44that looks quite busy, doesn't it? There's a lot going on here. That looks pretty excellent.
04:48And we'll talk about that in a moment. But then as we go towards the epithelium again,
04:55so these are villi. These finger-like projections are villi. Oh, this is actually not the lowest
05:03power. There's the lowest power. That's better, isn't it? You can tell how well I prepare
05:10for these. You can see these villi, these finger-like projections. And depending upon
05:16the plane of section, they might look a little bit different. Now, these villi are going
05:21to look a little bit different as we go through the small intestine. And that submucosa is
05:25going to look a little bit different as well. So villi are, what we're looking at here is
05:31we're looking at folds in the epithelium, aren't we? So the epithelium, or folds in
05:37the mucosa, the epithelium is a single layer of cells. And we'll see when we look closer
05:43that it's a single layer of columnar epithelial cells. And these cells are going to be called
05:48enterocytes or absorptive cells. That's their job. They're absorbing nutrients. They're
05:53actually also producing digestive enzymes and tools to help with digestion. But these
06:00villi will be about half a millimetre long or a millimetre long or a millimetre and a
06:05half long, depending upon exactly where you are in the small intestine. Okay, this is
06:10going to sound a little bit gross, but as an anatomist, when you open up the small intestine
06:15and you put your gloved finger on the internal surface of the small intestine, it feels
06:20like velvet. It's very, very soft because you're feeling millions, billions of these
06:28little villi projecting into the lumen. So it feels super soft. So those are the villi.
06:33Okay, so let's zoom back in again. So this magnification, I'm looking at my four times
06:41objective. I've got 10 times magnification here, so 40 times magnification to my eyes.
06:45The magnification is going to be a little bit different to you depending upon what size
06:48screen you've got. If I jump up to the 10 times objective, which we were looking at
06:52just now, you can see what I was talking about. So that's the epithelium there. So the epithelium
07:04is following the surface there. What we're looking at here with the villi is maximising
07:11surface area. So for absorption of nutrients, for absorption of molecules to occur from
07:17inside the small intestine to the blood vessels or, spoiler, some lymphatic vessels, those
07:27molecules just need to pass through as thin a layer as possible. So that's why we have
07:33this simple column epithelium. If I jump up to my 20 times objective and give you a little
07:39bit more light, can you see that those cells on the surface are tall cells, so they are
07:58columnar. There is a single layer of cells, so it's a simple columnar epithelium. And
08:03can you see the fringing, the edging on the surfaces of those cells? So those enterocytes
08:10are responsible for helping with digestion and then taking digestive molecules across
08:15them and into the layer deep to them, which is the lamina propria, the connective tissue.
08:20And inside that lamina propria, we can see some long streaky things. We get a hint of
08:26some vessels in there. So there are capillaries in there, small arterioles, small venules,
08:32and a lacteal. Inside the villus is maybe one or two lymphatic vessels. So the enterocytes are
08:43passing the molecules that have been digested, broken down as small as possible across themselves
08:48and then into the blood vessels and the lymphatic vessel inside the villus. So that, can you see how
08:55that villus is giving more surface area? So if we didn't have that villus, you wouldn't have very
09:01many enterocytes, right? But because we've got lots of villi, we've got lots more enterocytes,
09:06we've got lots more surface area, digestion becomes a lot more efficient. This is really
09:10important. So in some diseases then, where you lose the villi, where you lose these cells,
09:15thinking about celiac disease, how are you going to digest and absorb your nutrients? You're not
09:22going to get your nutrients, are you? And we can see some pink blobs in there. Those are goblet
09:31cells. Goblet cells are making mucus. So the mucus is important here. We see mucus all the way
09:36through this tube of the gastrointestinal tract. It's a bit of a lubricant, keeps everything moving,
09:41also protects the epithelium a little bit. But there's more to the mucus story here,
09:48which we'll get to in a moment. But like I say, nutrients get absorbed across the enterocytes and
09:56passed into the capillaries inside the villus. Now, the thing about the lacteal, so the lymphatic
10:05system is draining fluid from the tissues of the body. Your tissues of your body need to be wet,
10:11right? They need to have the right amount of fluid, the right amount of salts, all that stuff for
10:14your cells to function. So the lymphatic system is draining fluid from the tissues of the body
10:20and returning it to the cardiovascular system. Now, here in the small intestine, they have a
10:24very special job. So some digested fats pass across the enterocytes and into the lacteal.
10:32So fats are not, not all the fats are passing into the blood. Most of the fat, I think most of the
10:38fats is the right way of putting that, are passing into the lacteal, passing into the lymphatic vessel
10:45inside the villus. And then that, so lymphatic fluid is normally very watery with some protein
10:55in there. So around the area, around the level of the small intestine, the lymph becomes cloudy
11:01because it has fat in it. This was actually how the lymphatic system was first discovered,
11:07noticed, identified, because up in the abdomen, there's a, there's like a larger dilation of
11:15lymphatic vessels called the cisterna chyli. And you can imagine if you've got tiny little
11:20lymphatic vessels with a clear fluid running through them, they're almost impossible to see.
11:25But after fat from the small intestine has passed into the lymphatic system, you've now got lymphatic
11:33vessels with a cloudy liquid inside them. And the cisterna chyli is a bigger structure. So the
11:38fats pass into the cisterna chyli up the thoracic duct. And then up here in the left venous angle,
11:45where the subclavian vein and the internal jugular vein meet, somewhere up there, that's where the
11:51thoracic duct drains the lymph from most of the body back to the cardiovascular system. That's
11:56where these absorbed fats then go back into the blood. And then they're going around the blood
12:01and the liver and other tissues can deal with them. So that's very special, I think.
12:06When we look at the, so this is a villus, plural villi. So a villus is made up of lots of cells,
12:18right? If I go to a higher power, so now we're using the 40 times objective,
12:26how bright do we want it? Each cell has microvilli. Okay, we can see that quite nicely
12:40there, I think. So the enterocytes, they have a cell membrane and the surface of the cell membrane,
12:47where the nutrients are, is folded. And those tiny, tiny, tiny folds are microvilli. So a
12:56cell has microvilli, lots of cells make up a villus. And what we're seeing with the microvilli
13:04is again, an increase in surface area, more surface area. Because remember, we're actually
13:09looking at quite a big scale here. We're looking at cells, molecules are much, much smaller. So
13:15the tiny folds that we can't really see here, we can just kind of see a border, we can just see an
13:19edge there, right? That microvilli. So the microvilli increase the surface area of the cell
13:24membrane of the enterocyte, helping put digestive molecules into the lumen and helping take
13:33digested, broken down molecules into the cell, across the cell, and into the capillaries and
13:42the lacteals. Okay, so that's two of the cells of the mucosa covered. The epithelial cells,
13:56simple columnar, and the goblet cells. Now, can we see, okay, well, maybe we need to zoom out a
14:02little bit and talk about the structure a bit more. What we're actually seeing with villi,
14:06because we're going to go a little bit deeper and see if we can find at least one of the other
14:11two cell types. What you've got to imagine with the villi is you've kind of got to imagine a plane,
14:16as in like a surface to the small intestine. And then villi are extending up into that. And then
14:24from that plane, there are holes going into the plane. And down there, there are crypts,
14:30intestinal crypts, or the crypts of Lieberkuhn. When we looked at the stomach, we saw gastric
14:36pits. So again, we had a flat surface, holes in the surface, and so millions and millions of holes,
14:41and then little crypts, or little pits as they were in the stomach, crypts in the small intestine.
14:48That's something people commonly mix up. Gastric pits, intestinal crypts. So we've got villi
14:57sticking up and intestinal crypts going down. So what's in those intestinal crypts? That's the 3D
15:03shape you kind of need to imagine, and it's almost impossible to demonstrate.
15:07Maybe we can see, we get a sense there maybe? A bit more light. It's difficult to imagine the
15:22plane of section, but we can kind of see we've got some villi sticking up, and then we've got,
15:28can you see, we've got these intestinal crypts down here. So these deeper parts, and over here.
15:39So we've got the villi up there, sticking up, and then we've got the intestinal crypts going down.
15:45It's quite a difficult thing to imagine. And remember that these intestinal crypts are kind
15:49of tubes, really. So of course, because they're wiggly tubes, depending upon the plane of section,
15:54they might look like, they might look like a nice long tube like that one there, or they might look
16:03like a whole bunch of circles and ovals like they do here. All right, let's go down. What's in the
16:13intestinal crypts? That looks like quite a good one, right? And can you see how, as we go down
16:21the intestinal crypts, we're getting closer to the next layer, the submucosa? Let's zoom in again.
16:32What I'm looking for are paneth cells, really. So the other two cell types are paneth cells and
16:39enteroendocrine cells. Now the enteroendocrine cells, I'm not really going to point out,
16:46but they're involved in signaling and controlling what the cells are doing,
16:49what the small intestine is doing by signaling locally. The paneth cells, now they tend to be
16:55down in the crypts and they're very granular. What about that one? So that's my 20 times,
17:09this is my 40 times objective. Look down here, can you see, so we're at the bottom of the crypts
17:19here, and we've got some cells with lots of granules in them. So down here we've got paneth
17:25cells, which have a role in dealing with pathogens, because of course we're taking external things and
17:31passing them through the body. So the immune system needs to be pretty careful here. And we've
17:36got enteroendocrine cells down here, which are managing the functions of the cells in different
17:42regions of the GI tract, keeping it all organized and controlled. We've still got some goblet cells
17:46down here. Also down here we have stem cells. Now, so you see what the cells here look like,
17:55down in the bottom of the intestinal crypts? Well, let's go back up to the surface
18:02and look how the epithelial cells, the enterocytes, the absorptive cells,
18:13that's all the same cell type, three different names, sorry. They look quite different, right?
18:20But these cells on the surface here, they're lost, I think these are lost, they last like three to
18:26five days. So they're constantly being replenished by stem cells down in the crypts. So the stem
18:33cells in the crypts keep producing new epithelial cells, which grow up to the surface and are lost,
18:38just like we see on the skin, right? The surface of the skin is lost, new cells from below come up
18:43to replace them. Which means that if you have something like celiac disease, if you have a
18:50disease where the cells here are injured, destroyed, you lose your enterocytes, you lose
18:57your villi, you still have a population of cells down in the crypts which will rebuild all of this,
19:11which is incredibly important because the small intestine is vital for life,
19:15you cannot live without your small intestine. So that's what's going on here.
19:21Right, much of what I have said, looking at the duodenum, will apply to the other parts of the
19:28small intestine. But I said that each region is a little bit special, so we have to think about
19:35the different functions. So the small intestine is about digestion and absorption of nutrients.
19:42But the duodenum is receiving stuff from the stomach, so acidic contents. Now what we see here
19:50so up here we've got the epithelium, we have the supporting lamina propria,
19:58and there will be a little bit of smooth muscle in there, that muscularis mucosa layer. But deep
20:03to that here we're looking at the submucosa. And this is quite special, looks quite different in
20:09the duodenum. Here we are looking at Brunner's glands. Brunner's glands produce mucus, they
20:16produce a slightly alkaline mucus. So we see the glands down in the submucosa but they duct up
20:23into the, onto the surface of the epithelium. So the epithelium up here then is covered by
20:30the alkaline mucus secreted by the Brunner's glands down here, which buffers the acidic
20:38pH of the contents coming from the stomach, protecting the cells of the duodenum.
20:44And then as you pass along the small intestine away from the duodenum, you don't have this acid
20:49problem to deal with anymore, so we don't find Brunner's glands, and they're in the submucosa
20:53there. And can you see the muscle surrounding all that as well? Okay, so we've looked at the
21:02duodenum. That's what the villi look like here. You know, they're cool, they exist. Villi,
21:08intestinal crypts, submucosa,
21:14muscle, cirrhosa. Okay, so how does the duodenum compare to the jejunum?
21:23All right, okay, what is, what's the job of the jejunum, or jejunum, if you prefer? Well,
21:31remember that the duodenum is also receiving secretions from larger glands. The pancreas
21:37puts exocrine secretions into the duodenum to help with digestion. We have the liver putting
21:43things into the duodenum from the bile duct, right? So the duodenum, there is some absorption
21:51going on, still a lot of digestion. As we move into the jejunum, still some digestion, lots of
21:57absorption. Here we're going to try and absorb as many of these digested molecules as possible,
22:02right? All right, what does this look like? It looks, it's upside down. That's probably not
22:08helpful, right? Let me turn it around so it's in the same orientation as the last one. Oh yeah,
22:15beautiful, perfect. Right,
22:24we can see, we can see, I don't know, so we can see villi, they're looking pretty fat now. So
22:31we've got the villi, we've got the intestinal crypts, but that looks like a villus as well,
22:38right? This shape here, it's not. This is one of the, we always call them plicae circularis
22:47because that's the plural, plica circularis, I guess. So this is another surface area adaptation.
22:54Inside the small intestine, particularly inside the jejunum, it's folded up. So we've got big
23:02folds covered in, those are the plicae circularis, and then we have little villi projections,
23:09and then from the cells we have little micro villi projections. We have surface anatomy, sorry,
23:13we have surface area, surface area, surface area adaptations to maximise the surface area.
23:20So that there is a plicae circularis, and we are, oh look, see, no sign of the Brunner's glands in
23:28the submucosa. So can you see that folded shape? And these are called plicae circularis because
23:37this fold will run in a ring around the small intestine. It's one of the ways you can identify
23:42the small intestine on x-ray radiographs is by looking for these lines. So plicae circularis,
23:52these villi are sideways, but
23:59villi, same epithelium. We're looking at simple, single layer, simple columnar epithelium, again,
24:09some more enterocytes. They're still helping with digestion. They're really busy with absorption.
24:14The goblet cells on this particular stain are red, which is nice. So we see lots of goblet cells.
24:19We see lots of goblet cells. And then you can see the crypts over here. And in the crypts,
24:24we have the same cells we saw before, the stem cells, paneth cells, enteroendocrine cells.
24:29And then the mucosa then is made up of those epithelial cells.
24:36And there's other cells being supported by the lamina propria. And that's the connected tissue
24:42that we're seeing making this shape here. And we can see some larger blood vessels in there as well.
24:48So mucosa, big villi, short crypts, not much of the submucosa. We can see, probably,
25:02we can see the muscularis mucosa there. And then we have the two muscle layers of the muscularis
25:07externa and a little bit of cirrhosis there, maybe. Maybe imagine there's a bit of cirrhosis
25:13there. So again, same organisations we saw elsewhere. The main difference, then, is look
25:23how the epithelium is different. Again, we're thinking about a function,
25:27really, really maximising surface area now to maximise absorption. So that's the jejunum.
25:32OK, so we see what the jejunum looks like. The last part of the small intestine is the
25:46ileum. OK, what's happening in the ileum then? Well, hopefully, the jejunum has done most of
25:52the absorption. It has absorbed most of the nutrients, the fats, the carbohydrates, the
25:57proteins. The ileum, so good. This is the right way around. What are we seeing here? Well, this
26:09hardly looks the same at all. I think we can see the villi, but the villi are less prominent.
26:17Then we've got these big purpley patches here. What on earth are those? Well, those are Peyer's
26:22patches. Then we've got the muscle there and the cirrhosis. Let's jump in. Let's have a look.
26:33Let's jump into a slightly higher power. Looks good. Well, there's a nice clean villus there.
26:40Let's jump into that villus. So again, we've still got villi. They're not as amazing looking
26:52as we saw in the jejunum. So there are fewer villi. We haven't got the plicae circularis anymore,
26:59have we? All right, this is just a ring. So we haven't got the plicae circularis like we saw
27:08in the jejunum. So there are fewer surface area adaptations, fewer villi. The villi are less
27:15impressive. But the villus itself, it looks pretty similar to the previous
27:22ones we looked at in the duodenum and jejunum in that, again, we've got a single layer of tall
27:30cells with simple columnar epithelium. So these are enterocytes still helping with digestion,
27:38still absorbing nutrients, but they have slightly more specific absorption functions. For example,
27:44these guys are absorbing vitamin B12 at this point. They're absorbing bile salts to be reused.
27:52Bile salts are involved in emulsification of fats and fat digestion. So the ileum is still
27:59absorbing nutrients, but it's absorbing more specific nutrients, right?
28:05The jejunum has done most of the bulk work at this point. And we can still see goblet cells,
28:11loads and loads of goblet cells. And if that's a villus there, we can see,
28:19I think we can see that brush border still, right? So we can see the pinky edge. We can see the
28:27microvilli of these cells. And as we go down, so we don't see a super clear.
28:44So we still have these intestinal crypts, crypts of Lieberkuhn.
28:49But these masses here, and you can see that there's, that they are more stained in the middle
28:57and less stained on the outside. These are Peyer's patches. These are lymphoid nodules. I said that
29:06we're passing external things through the insides of us. So the gut and the gut
29:15So the gut and the epithelium has a really important barrier role. And here we have
29:22Peyer's patches. We have, this is part of the immune system. Here we have cells of the immune
29:27system looking at what's passing through the GI tract and able to mount an immune response to
29:33things that shouldn't be there. Things that you really don't want getting into the true inside of
29:37you. So that's what we mean by Peyer's patches. So we see lots of Peyer's patches in the ileum,
29:44which we didn't see in the jejunum. We didn't see in the duodenum, not like this.
29:49And then actually, if I jump up to a higher power here, look, this is,
29:55these are the muscle layers here, but they look, and this particular specimen, I don't know what
30:01animal this is from, they look, they look pretty weedy. But we do still have two layers of muscle
30:09here. So this is the muscularis externa again. So the same pattern, the same layer, as we've seen
30:14earlier in the GI tract, just thinner, but we have a circular layer of smooth muscle cells,
30:20and we have a longitudinal layer of smooth muscle cells. And on the outside, you're just getting a
30:26hint of the staining of the cirrhosis there. But we're not seeing it too clearly. But again,
30:31and also the submucosa is a bit, it's, it's a bit, it's a bit thin, but in the submucosa,
30:38in other levels, we've said that's where we see blood vessels and nerves. And look,
30:41that's where we're seeing blood vessels and nerves. So again, in the ileum,
30:45mucosa, submucosa, muscularis externa, cirrhosa, the same cells just arranged a little bit more
30:56differently. And that's it. That's the histology of the small intestine. And those are the
31:04differences between duodenum, jejunum, and ileum that everybody talks about. There is no
31:15clear division like, well, we know where the duodenum is, right? It does the curvy thing.
31:22I've done more videos on the gross anatomy of the parts of the small intestines. The duodenum
31:26curves around and we have a point where we say that's where the duodenum becomes the jejunum.
31:31But that's a gross anatomical feature. Boom, we say that's where it changes. But actually,
31:36if you look at the histology, it's a gradual change from across the duodenum to the jejunum.
31:42And there's no clear division between when the jejunum becomes the ileum. But if you look at one
31:47end, as we did here, you can see that the cells and the organisation, the structure is different
31:52in the jejunum to the ileum, but it's a gradual change from jejunum to ileum. There's not a clear
31:58border. Yeah. All right. I hope I didn't go on for too long. Probably did. I hope that was
32:08interesting, though. Classic histology of the small intestine. Like I say, this is an organ
32:12that's absolutely crucial for life. And understanding the histological structure is
32:18crucial to understanding diseases of the small intestine. And these are the cells that are being
32:23affected. And when these cells are destroyed, you can imagine all the knock on effects of
32:28poor digestion of nutrients, poor absorption of nutrients. So you can imagine what happens
32:33in terms of signs and symptoms in the rest of the body. Right. Anywho. See you next week.