Video: Stomach histology

Have you ever considered how much digestive juices your stomach produces every day? If I told you it was two to three liters, would you believe me? That's quite a lot, isn't it? These juices contain a potent and powerful cocktail of specialized biochemicals which help the body break down and digest food. They contain lots of hydrochloric acid, which is used to kill pesky foreign microorganisms and creates a cozy battery acid-like internal environment which happens to be perfectly suited to the specialized meat-eating enzymes which work to break down food into smaller molecules that can be absorbed in the intestines.

But where does all this gastric juice come from? Well, today, we're going to find out. Let's have a look at the cells and tissues that make up the wall of the stomach. It's time to explore the histology of the stomach.

In this tutorial, we'll be putting the stomach wall under the microscope and find out everything you need to know about the histology of this important digestive organ. We're going to begin our tutorial today by first reminding ourselves about the gross anatomy of the stomach, specifically, its different regions and parts. We're then going to look at the typical microanatomy of the different layers which comprise the wall of the stomach and learn about where exactly all our gastric juices are produced. After that, we'll be looking at some regional differences in the histology of the stomach before finally wrapping it all up with some clinical notes for this topic.

I don't know about you, but I'm hungry to know more. So, let's get started and begin by first reminding ourselves of the gross anatomy of the stomach.

So, we know that the stomach is effectively a distended pouch of the gastrointestinal tract, which is located distal to the esophagus and proximal to the duodenum of the small intestine. The actual stomach itself can be divided into four parts. The cardia is located here around the esophagogastric junction and is defined by the presence of specialized cardiac glands, which we'll learn more about in just a few moments. This next area is called the fundus. It's the area above the esophageal opening and makes up the upper curvature which is in contact with the diaphragm.

The largest division of the stomach is the corpus, meaning the body of the stomach. This, of course, is where most of the mixing and churning occurs. And, finally, we have the pylorus, which is composed of two parts – the pyloric antrum which is followed by the narrower pyloric canal. It terminates here at the pyloric sphincter, which opens to move food into the duodenum.

It's important for us to know the different parts of the stomach as we'll soon see that each region varies histologically. Of course, in anatomy, we always have to keep in mind that form follows function. So, let's just take a second to remind ourselves of the specific roles of the stomach in the digestive process. These include the continuation of mechanical digestion of the ingested food by blending its contents with a highly acidic mixture which is churned by the muscular layers of the stomach to form chyme. The stomach is also involved in chemical digestion of the bolus, firstly, in regards to initiating the digestion of triglycerides or fat macromolecules by secreting lipase enzymes, and the stomach also facilitates the first stages of protein digestion with pepsin enzymes.

Okay, so, we're going to take things down to the microscopic level now and start exploring the nitty-gritty cellular detail of the stomach. And, of course, what will the histology tutorial be without a quick mention of staining, which brings color to the wonderful world of microanatomy.

You probably already know that most body tissues are colorless when viewed under a microscope, which requires us to use stains to make structures appear distinct from one another. Many of these images which we'll explore in this tutorial have been stained using hematoxylin and eosin, more commonly known as H&E staining. This is the most common method of staining in research in clinical settings and works by attaching pink-colored molecules to acidophilic structures such as cytoplasmic proteins, which are basic in nature, and a bluish-purple color to basophilic structures such as DNA or RNA. This is why the nucleus and parts of the cytoplasm which contain RNA appear purple.

Did you know that despite some specializations and modifications along its length, the gastrointestinal tract has a relatively consistent makeup along most of its length? Yep, it's true. This means that regardless of which part of the GIT we're talking about, we can usually define the same for primary layers in the gut wall. These include an outermost covering of connective tissue known as the serosa or adventitia, a well-defined muscular layer known as the muscularis externa which is responsible for peristalsis ensuring that your food keeps moving along nicely through the gut. This usually has two layers – an outer longitudinal layer and an inner circular layer. Deep to that is the submucosa, which is another layer containing blood vessels and nervous tissue. And, finally, the innermost mucosa, which lines the internal environment of the gut known as the lumen.

As I mentioned, this is the general histological makeup of the gastrointestinal tract. What's interesting, however, is that each part of the gastrointestinal tract is highly adapted or specialized for its particular role in the digestive process. And the stomach, of course, is no different. So, let's get to it and check out the histology of this organ out.

So, it's finally time to take a look specifically at the structure of the walls of the stomach. We're going to be using this micrograph for the next little while which has been taken from the corpus or the body of the stomach. We can see the different layers in this section stained with H&E as we mentioned before. Let's take a closer look now at each layer.

So, the serosa is the outermost layer of the stomach and is also sometimes referred to as the adventitia. It consists of simple squamous epithelial cells on the surface known as mesothelium and an inner layer of loose connective tissue that attaches it to the muscle layer below. The word serosa refers to a structure which produces serum, ands true to its name, the epithelial cells of the serous layer produce a lubricating fluid that allows the stomach to move and distend smoothly within the abdomen.

Interesting to note in this image is that we can also see a large artery here. We know this is an artery because it has a thick muscular wall and there are also some red blood cells visible here, too. If you’re up to speed on the vascular supply of the stomach, you'll know that this is probably a branch of some of the gastric or gastroomental arteries which supply the stomach with arterial blood.

We're going to continue now onto the next layer of the stomach wall which is the muscularis externa. This is the primary muscle layer of the stomach, which controls the mass movement of contents within the stomach. As I mentioned earlier, there generally are two muscular layers within the muscularis externa – an outer longitudinal and an inner circular layer. The stomach, however, is the one exception to this and has an additional third oblique muscular layer.

Now it's important to note that all three layers are not uniformly found across the stomach wall, which means that their presence histologically will depend on where the section was procured. So, looking again at our histological section, we're now looking at the outer longitudinal layer, and as you can see in the illustration, these fibers run from superior to inferior along the length of the stomach.

Histologically, muscle cells stain pink because they're acidophilic. We can see them here, and their cell nuclei are basophilic, so they're a little more purple. It's important to note that the longitudinal muscular coat is effectively absent from the anterior and posterior walls of the stomach, should you find yourself with a section taken from either of these regions.

Next up is a middle circular layer. The muscle fibers in this layer traverse or run along the stomach, and if we look closely at our micrograph, we can see that the fibers are orientated in a very different direction compared to the longitudinal ones. Make note, this layer is poorly developed in the cardia of the stomach.

And, finally, we've reached the innermost oblique layer. This is an incomplete layer of muscle fibers which run at an angle to the previous two layers. As I mentioned previously, this muscle layer is unique to the stomach as you won't find it in the rest of the gastrointestinal tract. It's one of these functional variations that we talked about earlier. The oblique fibers are concentrated more towards the cardia of the stomach and extend over both the anterior and posterior walls of the stomach.

We now know that the stomach is involved in mechanical as well as chemical digestion so this robust muscular layer helps to ensure proper churning of the ingested food and gastric juices. It also helps to prevent overdistension of the stomach.

The layers of the muscularis externa are innervated by nerve bundles which form a myenteric plexus, also known as Auerbach’s plexus. It contains both parasympathetic fibers from the vagus nerve and sympathetic fibers originating from the celiac plexus. We can see a couple of those nerve bundles in this section embedded between the muscle layers.

Let's pause for a moment and talk about the autonomic nervous system because I know I always struggle to remember the difference between the sympathetic and parasympathetic functions. Remember, the sympathetic and parasympathetic nervous systems are divisions of the autonomic nervous system, which regulates the internal environment of the body by regulating bodily functions. It acts mostly on a subconscious level, which makes sense since we obviously have no conscious control of what's happening in our stomach.

The sympathetic division is responsible for our response to stress, also called the fight-and-flight response, so it slows down or inhibits the digestive process because digesting your lunch is not a huge priority when, let's say, you're being chased through the woods by a demented cow. The parasympathetic division does the opposite. It up regulates the digestion of food during what's called the rest-and-digest response. When we're relaxed, our body spends time digesting food and banking up energy for our next burst.

We're moving on now with our journey through the wall of the stomach where the next structure we'll meet is the submucosa. This is a layer primarily composed of connective tissue deep to the primary muscular coat of the stomach. It's home to the smallest branch of the vessels and nerves that supply the stomach wall. This is the second connective tissue structure that we've come across, but wait a minute. What exactly is connective tissue?

Well, connective tissue can be many things from blood to tendons and ligaments, but in the stomach, we're talking about what's known as connective tissue proper, which is comprised primarily of collagen fibers. These fibers give the stomach structure and strength, but also flexibility and cushioning allowing it to be durable, but also flexible and mobile.

In the submucosa, blood vessels are distributed widely within the connective tissue matrix; for example, as you can see here, with this submucosal vein. The blood vessels found on the submucosa supply the surrounding tissues with oxygenated blood via arterioles and drain deoxygenated blood away from the venules. They are numerous around the stomach to ensure the stomach has a sufficient blood supply to carry out its digestive functions. There are also lots of lymphatic vessels in the submucosa, which drain cell waste and debris, proteins, and excess interstitial fluid in the form of lymph from the stomach.

The vessels drain into nodes that are located around the major vessels of the greater and lesser curvatures and posterior to the stomach, but if you want to know more about this why not check our video on the lymphatics of the stomach and liver to learn all about it.

Finally, autonomic nerve fibers and ganglion cells are also found scattered throughout this layer to form the submucosal plexus, also known as Meissner’s nerve plexuses. A plexus is a bundle of intersecting nerve fibers, and in this case, their parasympathetic nerves. These nerves increase the activity of the stomach tissues, in particular, in regards to glandular secretions and movements of the luminal surface of the stomach.

We're now moving onto the gastric mucosa, which is the innermost layer of the wall of the stomach and that closest to the lumen. It is certainly the most complex of the stomach layers and is comprised of three parts – the muscularis mucosae, the lamina propria, and the epithelial layer. Let's check each of them out now and find out more.

So, let's first look at the muscularis mucosae, which is found immediately adjacent to the submucosa border. It is composed of two thin layers of smooth muscle – an inner circular and outer longitudinal layer which can be difficult to differentiate from one another in section. The muscularis mucosae extends thin smooth fibers into the lamina propria which help move the outflow of gastric gland secretions. The muscularis mucosae is innervated by the submucosal nerve plexus, which we saw earlier.

Let's now have a look at the lamina propria. This is a thin and somewhat irregular layer of connective tissue composed largely of reticular fibers that lies beneath the epithelium providing it with nutrients and support. It is rich in immune cells and is an important contributor to the inflammatory response in the stomach and throughout the GI tract. We can see here that the lamina propria is rather irregular in section and follows the contours of the overlying epithelium. It also stains lighter than the epithelium due to the fact that it is not as densely packed with cells.

Let's now turn our attention to the innermost part of the mucosa, which is the epithelial layer. So, as you can see, there's a lot going on here, but trust me, it's nothing you can't handle. On face view, the surface of the stomach is dotted with millions of tubular infoldings or invaginations which are known as gastric pits. But to get a better idea of what these pits really look like, I'm going to now show you what they look like in longitudinal section.

So, as you can see here, the luminal surface of the stomach is lined with simple columnar epithelium which means it has a single layer of rectangular or column-like cells which extends across the internal surface of the stomach. Based on their location and function, we generally refer to these cells as surface mucous cells. They can also be referred to as foveolar epithelium due to the fact that this epithelial layer extends down into the gastric pits. These cells secrete a thick, insoluble layer of mucous which contains bicarbonate ions, which protects the stomach wall from gastric acid found in the lumen of the stomach. As you can imagine, this is pretty important as without it, our stomachs would basically digest themselves which we all know wouldn't end very well.

The gastric pits are continuous with long-branched tubular structures which are known as gastric glands. These reach deep into the mucosa even as far as the muscularis mucosae, and as the term gland suggests, these are primarily responsible for the production of most of the digestive juices of the stomach.

Each gastric gland can be divided up into three main regions, each of which can be distinguished by the cell types found there. These are the isthmus, the neck, and the base. The isthmus is a short area where the gastric pit and the gland meet. It, too, also contains some surface mucous cells just like those seen in the gastric pit. This region of the gastric gland is also described as a stem cell niche, which means it's where stem cells of the epithelial layer reside. This is extremely important in the regeneration of the stomach epithelial layer.

The stomach epithelium is in contact with a lot of powerful chemicals. As gastric juices are strong enough to digest food, they're definitely strong enough to break down the epithelial and secretory cells found there. These stem cells replace any cells that become damaged as often as every four to six days. Without them, the stomach would have as many holes as a piece of Swiss cheese. That's for sure!

A little deeper into the isthmus is a long neck, which contains mucous neck cells. These are less columnar and present around a nucleus when compared to the surface mucous cells. They also produce a soluble mucus secretion which is less alkaline than that of the surface mucous cells. This secretion is released by sympathetic stimulation, meaning when digesting is not actively occurring in the stomach.

Another cell type found in the neck region as well as in the deeper glands are parietal cells. Also known as oxyntic cells, they produce hydrochloric acid – a strong acid that breaks down food, and importantly, kills microorganisms. These cells also produce a substance called intrinsic factor, which is involved in the absorption of vitamin B12 in the small intestine. Parietal cells are easy to spot when viewed histologically as they have this pinky-orange colored cytoplasm due to their acidophilic nature and kind of look like a fried egg with a round centrally-located nucleus.

Moving deeper into the gastric gland, we next come to the base of the gland. Down here, we can see another type of cell known as chief cells, also known as peptic or zymogenic cells. These cells secrete a zymogen called pepsinogen, which when exposed to the hydrochloric acid from the parietal cells, becomes pepsin – an enzyme that breaks down proteins. They also secrete a weak lipase enzyme which begins the process of lipid digestion.

If we look closer at our micrograph, we can get a better view of what a chief cell looks like histologically. They're more purple in color especially at their basal aspect as they contain large volumes of RNA needed to produce the protein-based enzymes. You'll also notice that they often tend to have a somewhat triangular appearance in section. We can also see the zymogen granules within the cell cytoplasm of the chief cells which is, of course, the precursor or inactive enzyme material which is to be secreted by these cells.

Another cell type I want to briefly mention are the neuroendocrine cells, also known as enteroendocrine cells, which release hormones into the local tissues to initiate digestive actions and protective responses. Unless specifically stained for, these cells are very difficult to see in tissue, but are normally located at the base of the gland. These hormones act as local messengers, and one example of this is gastrin, which is produced in response to protein in the lumen amongst other stimuli. Gastrin then initiates the production of HCl and pepsinogen from parietal and chief cells.

Just before we move on, remember the muscularis mucosae, the layer of muscle at the bottom of the mucosa? Well, its constant movement means that the secretions don't just fall to the bottom of the gastric gland. Instead, they're pushed into the lumen of the stomach where they can act on the digested food.

We mentioned a lot of different cell types and secretions just now, so I want to take a quick look over these gastric juices again.

Starting at the top of the gastric pit, the surface or foveolar mucous epithelium produces mucus to protect the luminal wall from the powerful digestive substances. The protective secretions are alkaline or basic to neutralize the acid close to the cells. Then scattered throughout the gastric glands our parietal cells that produce hydrochloric acid to break down food and kill microorganisms – an intrinsic factor to aids the absorption of B12.

Next, we saw some chief cells also called peptic or zymogenic cells and they produce pepsinogen to break down proteins. Neuroendocrine cells secrete hormones which act as chemical signals to initiate specific functions in the surrounding tissues, and finally, stem cells don't secrete anything, but replace damaged cells in the gastric gland.

Okay, so, that's all we need to know about the gastric glands. It's a lot, I know, but don't worry, you can run through this video as many times as you like to make sure you've got the hang of it.

So, so far, we've been looking at the typical histology of the body of the stomach, let's take a look now at some regional differences in the histology of the stomach.

The first area we're going to look at is the esophagogastric junction which, as its name suggests, is the region where the distal end of the esophagus meets the cardia of the stomach. Histologically, this region is pretty interesting because we can see clearly there's an almost instant transition from the stratified squamous epithelium of the esophagus seen here to the simple columnar epithelium of the stomach here.

In this slide, we can also see the other histological layers that we know – the mucosa, the submucosa, and a well-defined muscularis externa. This thickened muscularis externa is contracted most of the time to keep the sphincter closed, and when it relaxes, it allows swallowed food to pass from the esophagus to the stomach. Failure of this sphincter results in regurgitation of stomach acid into the esophagus often referred to as gastric reflux. This results in what many of us would call heartburn, which our esophagus is not so fond of as chronic gastric reflux can be related to the development of esophageal cancer.

Another specialization in the region of the esophagogastric junction are cardiac glands, which are modified versions of the gastric glands which we looked at a few moments ago. These glands mainly produce mucus, which helps protect the esophageal epithelium from the highly acidic gastric juices. These glands are shallower than those seen in other parts of the stomach and are primarily composed of pale-staining tall columnar epithelial cells which secrete the mucous layer. They generally do not contain parietal or chief cells as found in typical gastric glands.

The next region we are going to examine for regional differences is the fundus which you can see in this micrograph. In this part of the stomach, the composition of the gastric pits and glands is much the same as those seen in the body of the stomach. The major giveaway here, however, is seen in the muscularis externa, which is not well developed compared to other parts of the stomach. Functionally, this, of course, makes sense since the amount of churning is much less here compared to the body of the stomach.

We can also identify small ridges or folds in this micrograph, known as rugae. These are visible to the naked eye and are characteristic anatomical feature of the internal stomach wall. Rugae are formed by folds of the mucosa and submucosa of the stomach wall only with the muscularis externa and serosa remaining unfolded as seen in the image. Rugae function to direct chyme towards the pylorus while also allowing for expansion or filling of the stomach.

We're moving onto our final region now which is the pylorus where we can also see some regional differences in the mucosa of the stomach wall.

So, I have two sections from this region to share with you – one from the pyloric antrum and the other from the pyloric canal. In general, the gastric pits of the pyloric region tend to be deeper than those found in the body of the stomach. The pyloric glands, which are continuous with the gastric pits, often present as more branched or coiled compared to other regions.

Like cardiac glands, those found in the pylorus are comprised of tall columnar mucus-secreting epithelial cells. Remember, this type of epithelium stains pale due to the mucinogen content contained within. Enteroendocrine cells are also present here while chief and parietal cells are once again absent in this region. The pylorus also has a well-developed muscularis externa which propels the churned stomach contents, now known as chyme, into the duodenum.

And just as we've reached the end of the stomach, we’ve reached the end of our tutorial today. Before we finish, let's quickly look at some of the information we learn today from a more clinical perspective.

For most of us, we tend to only think about what we're enjoying on our taste buds, but at this stage, our gastrointestinal tract is only getting started with its work. Once we've enjoyed the moment, we don't really give our food a second thought, unless we're feeling unwell. Then, it's pretty difficult to think of anything else. Let's take a quick look at what happens when the stomach doesn't function as it should.

The internal environment of the stomach is a bit of a balancing act between being acidic enough to break down foods and microorganisms and not digesting the walls of the stomach itself. The mucus that lines the walls does a pretty good job of protecting the stomach tissue, but sometimes, something throws off this balance, like bacteria, diet, or the use of non-steroidal anti-inflammatories. This can result in a condition known as gastritis. It is caused by inflammation and erosion of the gastric mucosa by gastric acid and can lead to nausea, vomiting, and upper abdominal pain.

Gastritis can be treated with various medications which reduce the amount of acid produced, such as proton pump inhibitors, those which neutralize excess stomach acid, as well as antibiotics, used to kill off bacterial infection. The mucosal lining of the stomach regenerates pretty quickly, every four to six days in fact, which means the stomach can usually repair itself pretty quickly when treated properly. However, without treatment, the wall of the stomach will become continually eroded leading to the development of a gastric or peptic ulcer. In extreme cases, this can lead to a perforation leading to further infection of the abdominal cavity in the form of peritonitis.

So, that's it! Everything you need to know about the histology of the stomach. Before we go though, let's summarize what we talked about today.

So, we're going to go back to this histological image of the body of the stomach and here we can see the serosa – the outermost layer of the stomach wall which was composed of simple squamous epithelial cells known as mesothelium. The layer immediately adjacent to the serosa is the muscularis externa, and unlike the rest of the gastrointestinal tube, we learned that there are three distinct muscle layers here – the outer longitudinal layer, the middle circular layer, and the one that is unique to the stomach, the innermost oblique layer.

Remember, we also talked about the myenteric plexus found between the muscle layers. It carries both sympathetic and parasympathetic nerve fibers to control the gross movements of the stomach. Below the muscularis externa is the submucosa – another connective tissue layer where blood vessels, lymphatic, and nerves are found. It was here that we saw the submucosal or Meissner's plexus of parasympathetic nerves which provides secretomotor innervation to the mucous membrane.

And, finally, the deepest layer, the mucosa. We saw three distinct tissues here. First, we saw the muscularis mucosa – the thin muscle layer that keeps the mucosa in a constant state of motion and forms the rugae. Next was the lamina propria which is connective tissue surrounding the gastric pits, and the surface epithelium, simple columnar cells lining the internal or luminal wall and gastric pits. Within the gastric pits, we saw a number of different cells each producing different substances important to the digestive process.

Very quickly, we talked about the foveolar epithelial cells and mucous neck cells and how they produce a viscous mucus to protect the internal wall of the stomach and dilute the contents, parietal cells which produce hydrochloric acid and intrinsic factor, and chief or zymogenic cells which produce pepsin. Finally, we looked at the regional differences in the tissues of the stomach comparing the cardia, the fundus, and the pylorus of the stomach.

So that's it! Everything you need to know about the histology of the stomach all broken down into very digestible chunks. Thanks for sticking with me throughout this tutorial. I really hope it was helpful, and don't forget to check out all these images on our atlas and test your knowledge on our quiz on the histology of the stomach.

Good luck and happy studying!