Video: Esophagus histology

This is your esophagus. Yes, that seemingly simple twenty-five centimeter tube which provides our swallowed food with a pathway allowing it to reach the stomach. Well, believe it or not, the esophagus is not just a simple piece of tube or a length of plain old garden hose connecting one organ to another. Behind its somewhat ordinary facade, it's actually got quite a complex makeup. You see, when we swallow food, it doesn't just simply fall down into our stomach. Our esophagus actually pushes it down. Even if we were to eat upside down, our esophagus always ensures our lunch makes it to where it needs to go.

How can this be? Well, I'm glad you asked. If you're up for a non-spidey adventure, we'll find our answer by looking at this simple organ at the microscopic level. Yep, that's right! It's time to explore the histology of the esophagus.

So to begin this tutorial, we're going to start by our reminding ourselves what is the esophagus anyway. Well, to answer this question, we'll first refresh our memories about the gross anatomy of the esophagus. Following this, we'll whiz through a quick recap on the basics of histology and correlate this with the tissue layers found within the esophagus at a histological level.

Finally, to conclude, we'll discuss some of the relevant pathologies or clinical conditions which may manifest in the esophagus taking a look at how these problems may be visualized at a microscopic level. And when you've completed all of that with a good level of understanding, you'll be a true master of this sometimes overlooked region. So, what are we waiting for? Let's go.

To begin, let's remind ourselves about the basics of esophageal anatomy and its position within the body.

As a whole, the esophagus is basically a long fibromuscular tube measuring around about twenty to thirty centimeters in length. It extends from the bottom of the pharynx at the level of the cricoid cartilage to the cardiac opening of the stomach shown here. It forms the third part of the alimentary canal and is also divided up into three divisions - the cervical part, which runs from the laryngopharynx to the thoracic inlet formed by the first ribs; the thoracic part, which extends from the thoracic inlet to the esophageal hiatus of the respiratory diaphragm; and finally, the abdominal part, which is only one to two centimeters long and connects with the cardia of the stomach.

With that covered, let's quickly move on to discuss the general histology of the gastrointestinal tract, which provides the template for the structure of the esophagus.

Although regional-specific specializations exist along the length of the gastrointestinal or digestive tract, the basic layers of its wall remain relatively uniform throughout the majority of its length. The first layer in direct contact with the lumen is the mucosa. This is further divided into the surface epithelium, the lamina propria, and the lamina muscularis mucosae, and carries a pivotal role in providing a barrier to infection, amongst other functions including digestion within the stomach and absorption in the intestines.

The second layer is the submucosa - sub implying that this is deep to the mucosa. The submucosa acts as an interface between the mucosa and the layers of the smooth muscle which control peristalsis.

The third layer is the tunica muscularis, which can be a double layer of either smooth or skeletal muscle depending on the region we're analyzing. This layer is very important to the process of peristalsis, which is the involuntary propulsion of food contents through the gastrointestinal tract.

The fourth and final layer is the tunica externa. Throughout the majority of the GI tract, this is also known as the serosa, but in the esophagus, is for the most part known as the adventitia.

If at this point you feel bewildered and fear for the future of your histological career, don't be alarmed. We'll now break this down and visualize how each layer appears under a microscope.

So I can tell the anticipation has been rising, but now it's finally time for us to look at the histology of the esophagus.

So today we'll be examining the histology of the esophagus using this micrograph which shows a transverse section of the esophagus stained with the very commonly used hematoxylin and eosin or H&E. We'll begin with the layers closest to the lumen found at the center of the esophagus where our food passes through and then continue outwards from here working through each layer until we reach the outermost aspect of the esophagus.

Are you ready? Let's do it!

In direct contact with the lumen is the mucosa. This is the innermost part of the esophageal wall, and if you remember, it is made up of three separate parts. These are the surface epithelium, the lamina propria, and the lamina muscularis mucosae. When analyzing micrographs in general, the appearance of the mucosa - in particular, its surface epithelium - often provides a good indication of where in the body the tissue has originated. Let's consider this in the next few slides.

So this micrograph demonstrates a typical section of esophageal surface epithelium. It also happens that within our GI tract, this particular type of surface epithelium is relatively unique and is known as stratified squamous non-keratinized epithelium. Let's dissect this long and complicated-looking phrase into its component parts.

So, stratified epithelium - what could this mean? Well, stratified refers to the fact that we observe many, many cell layers stacked on top of one another, like this brick wall, for example. Layers on top of layers on top of other layers - can you think why? Well, this stratified or layered arrangement of epithelial cells within the esophagus is required to withstand the abrasive force from a masticated or chewed up lump of food known as a bolus as it passes through the lumen, and as a consequence, there is a high cell turnover within this region.

Next, let us consider the term squamous, which refers to the shape of the epithelial cells here. In our esophagus facing the lumen, we have squamous epithelia, which essentially means the cells are flattened in appearance. But some of you eagle-eyed anatomists may have spotted that this isn't the only type of epithelium that can be seen here. Yep, in the deeper basal regions of the surface epithelium, you may notice cells which are more square-shaped in appearance. These are known as cuboidal cells. Can you guess why this may be?

Well, these cuboidal cells sit directly on the basement membrane of the surface epithelium and are actively proliferating or multiplying stem cells. When old cells are lost from the luminal surface, they're replaced by new cells which are generated by mitotic divisions of the cuboidal cells in the basal region. These cuboidal cells are not only distinguishable by their shape, but also by their color. Because these are mitotically active cells - meaning that they are dividing and multiplying to make more cells - they're synthesizing a lot of nucleic acids such as DNA and RNA, which are basophilic and stain bluish-purple when using our H&E stain.

Now compare this with cells in the apical region closest to the lumen and you'll observe these look pinker with an H&E stain. These cells are not stem cells, and therefore, have smaller, flattened nuclei relative to those found deeper in the surface epithelium.

So this leaves only one mystery - what do we mean by non-keratinized? Well, keratinization is a process whereby cells migrating to the apical surface lose their nuclei and undergo apoptosis, or in other words, they die. In general, the main function of keratin is to provide additional protection to the epithelium it covers. For example, we find cells that have undergone keratinization in regions such as the skin or parts of the oral cavity that are prone to dehydration. It's also found in areas which experience particularly heavy abrasion or environmental stress like your hands and your feet.

Compare a micrograph of the esophagus with the micrograph of the skin, and this should become clear. In the esophageal micrograph, we see most of the cells retaining their nuclei. On our example of the skin, however, we can clearly see the layer of dead anucleate keratinized cells covering the surface epithelium. I should also mention that the esophageal surface epithelium may become keratinized when under consistent environmental stress, such as smoking or chronic consumption of alcohol.

So there you have it - our stratified squamous non-keratinized surface epithelium of the esophagus.

The next layer of the mucosa is known as the lamina propria mucosae, which lies deep to the surface epithelium of the esophagus that we just looked at. It's composed of loose areolar connective tissue and is home to a host of different cell types, such as fibroblasts, lymphocytes, macrophages, and mast cells, and even some smooth muscle cells.

As a whole, the lamina propria is highly elastic which allows it to undergo expansion and contraction as food passes through the esophagus. It's also highly vascular - meaning, it contains a relatively dense network of minute arteries, veins, and lymphatic vessels. This is important as the surface epithelium is entirely avascular - meaning, no blood vessels traverse this area. Oxygen and other nutrients diffuse through the capillary wall through the lamina propria mucosa and into the surface epithelium so that they may become nourished. Similarly, carbon dioxide and other cellular wastes are removed from the surface epithelium via the veins and lymphatic vessels found in the lamina propria.

Protrusions or indentations of the lamina propria into the surface epithelium like those seen here are common and are known as the connective tissue papillae. These allow for greater area of contact between the lamina propria and surface epithelium which allows for better nourishment to the surface epithelium. When a papilla is cut in section, we may not be able to see it in its entirety and that's why they sometimes appear as islands within the overlying surface epithelium just like you see here. In reality, however, they are always continuous with the lamina propria below.

The lamina propria mucosae also act as a reservoir for many immune or lymphoid cells whose purpose involves surveying the area for the invasion of any foreign unwanted microorganisms.

The last layer of the mucosa is the lamina muscularis mucosae, which lies immediately deep to the lamina propria forming an interface between the mucosa and the submucosa. It is a thin layer of smooth muscle oriented in a generally longitudinal arrangement and allows the mucosa to fold and change shape as the food bolus is propelled along its surface. Histologically speaking, the lamina muscularis mucosae can be relatively easy to identify as it appears a slightly darker shade of pink relative to the overlying lamina propria and underlying submucosa.

Moving away from the mucosa, we progress into the submucosa and this layer is composed of dense, irregular connective tissue which means that the collagen fibers are highly abundant and are thrown into a sporadic arrangement within the tissue. But how do we go identifying this? Much the same as the lamina propria mucosae, there's more to the submucosa than just connective tissue. It also contains larger arteries and veins and lymphatic vessels and esophageal glands can often be found here.

Now what could these be? So this micrograph shows an esophageal gland highlighted here in green, and far-fetched as this may sound, but I've always considered these lobular-looking structures to look like tiny blackberries embedded within the tissue. Can you see what I mean?

Within these glandular clusters, mucous secretions are produced, and through their elongated ducts, these secretions are emptied into the lumen of the esophagus. These mucous secretions provide an additional lubrication and protection to the esophageal wall.

Okay, so hang on there, guys. We've almost completed this section, and just to remind you of our progress so far, we've discussed the mucosa and its three subdivisions - the stratified squamous non-keratinized epithelium, the lamina propria mucosae, and the lamina muscularis mucosae, and the submucosa contained immediately deep to this. And we'll now consider the muscular layers responsible for the function of our esophagus known as the tunica muscularis and the outermost layer responsible for the integrity of the esophagus as a whole - the tunica externa.

So, we now arrive at the tunica muscularis - a double layer of muscle deep to the submucosa. So, when trying to identify this layer, the easiest method is to look for a thick, slightly darker staining region external to the submucosa with two distinctive layers. These can be divided by an intermediate region of connective tissue containing blood and lymphatic vessels along with nerves controlling peristalsis, and we'll look at these two layers of the tunica muscularis in just a moment. But, first, let's discuss the specific type of muscle we found within the tunica muscularis.

So, you might be interested to know that it is actually region-dependent - meaning that there are different types of muscle tissue in different parts of the esophagus. So, let's take a look.

For this purpose, we'll divide our esophagus into a superior third, an intermediate third, and an inferior third. The tunica muscularis of the superior third of the esophagus is composed of skeletal muscle. If you recall, these cells are long cylindrical and striated. They're also multinucleate, so they have more than one nucleus per cell given that they form via the fusion of multiple myoblasts. And in the esophagus, these cells play a role in the voluntary phases of swallowing.

The tunica muscularis of the inferior third of the esophagus is composed entirely of smooth muscle. Now if you've watched our video on smooth muscle histology, you might remember that these cells appear as elongated spindles or fusiform-shaped cells which have tapered ends. Unlike skeletal muscle, smooth muscle myocytes contain one single centrally-placed nucleus and this involuntary muscle plays a role in peristalsis.

The tunica muscularis of the intermediate esophageal portion is a mixture of these muscle types - skeletal and smooth muscle - and both muscle types appear as the esophageal innervation transitions from somatic to autonomic and voluntary to involuntary, respectively. Of course, this transition from skeletal to smooth muscle makes perfect sense given that any sensations of overdistension felt after swallowing large chunks of foodstuffs is short-lived and can only be consciously perceived for a couple of seconds. Got that? We can now give this knowledge some wider context with respect to the tunica muscularis.

So let's return to our micrograph. Okay, and here you'll remember that we said that the tunica muscularis is a double-layered region of the muscle in the wall of the esophagus. And this image shows the inner circular layer of muscle passing circumferentially around the outside of the submucosa, and this is the inner circular layer of the tunica muscularis.

Sequential contraction of these rings of smooth muscle will allow for the movement of the food bolus inferiorly to the stomach. In this micrograph, we observe the additional muscle layer, which, unlike the inner muscular layer, contain the longitudinal fiber arrangement. This is the outer longitudinal layer of the tunica muscularis. This means that instead of fibers surrounding the lumen circumferentially, fibers run in the vertical plane along the length of the esophagus.

So here we are - the outermost and final layer of the esophageal wall known as the tunica externa. The tunica externa is a supporting layer formed of loose connective tissue and surrounds all structures forming the gastrointestinal tract including structures such as the duodenum and the large intestine, and there are two types of tunica externa which are the adventitia or the serosa.

The adventitia surrounds the cervical and thoracic segments of the esophagus and it turns out that the adventitia surrounds regions of the GI tract which are relatively fixed in position, and as with all examples of loose connective tissue, the extracellular matrix is composed of both elastin and reticular fibers. However, it is the ground substance forming the bulk of the mass in this tissue.

The serosa by contrast surrounds the abdominal aspect of the esophagus, and passing through the esophageal hiatus and into the peritoneal cavity, this relatively short portion of the esophagus is known as retroperitoneal and is freely movable within this space. Histologically, this is a type of mesothelium or visceral peritoneum surrounding structures such as the stomach and the small intestine.

And there we have it. We've discussed the structure of the four layers of the wall of the esophagus.

Before we look at some clinical correlates about today's topics, let's wrap up our anatomy tour by looking at the innervation of the esophageal wall. So, now we know that the esophageal wall contains several muscular layers which work to move swallowed food from the pharynx to the stomach. Of course, no muscle tissue is an island and need some sort of innervation from our nervous system.

So, you're probably familiar with the term peristalsis, which is a process of mostly involuntary propulsion of food contents through the gastrointestinal tract. This is coordinated by bundles of nerves bound together in plexuses within the walls of the gastrointestinal tract, and these are the submucosal and myenteric plexuses, respectively.

So, this is the submucosal plexus, also known as Meissner's plexus, which is the bundle of nerve fibers running in the connective tissue of the submucosa deep to the lamina muscularis mucosae, as we observe here. Its function is to innervate cells of the surface epithelium and the smooth muscle of the muscularis mucosae.

Moving deeper into the esophageal wall, we're now looking at the myenteric plexus sandwiched in between the inner circular layer and the outer longitudinal layer of the tunica muscularis, and it's also sometimes referred to as Auerbach's plexus. The myenteric plexus innervates both muscular layers of the tunica muscularis, and therefore, controls the peristaltic movements of the esophageal wall.

And that concludes our tour of the esophageal wall. Done, fini, finito! You're only a few steps away now from reaching your goal of esophageal mastership, so let's finish up by giving our newfound histological knowledge some clinical perspective.

For this last section, we're going to analyze some useful clinical notes, useful bite-sized chunks of information on relevant medical conditions you may encounter along the way in your scientific or medical journey. First, we'll discuss a condition known as gastroesophageal reflux disease and then move on to Barrett's esophagus.

In normal circumstances, once the esophageal contents have reached the inferior most abdominal portion, they'll pass through the gastroesophageal junction guarded by the lower esophageal sphincter and into the cardia of the stomach. In some individuals, however, the sphincter can become weakened and subsequently contents begin to move in a retrograde fashion - that is, out of the stomach and back into the esophagus. And given that the esophagus and the stomach are not identical at the histological level, the esophagus simply isn't prepared for this. What results is essentially degradation of the esophageal lining.

First, reflux esophagitis can occur where the lining of the esophagus becomes inflamed due to acid reflux from the stomach. Once the lower esophageal sphincter has become incompetent, severe heartburn can manifest in burning sensations around the chest wall, and over time, the mucosal lining of the esophagus begins to break down and gastroesophageal reflux disease, commonly abbreviated to GERD, occurs. During this process, the squamous epithelium lining the esophagus as shown here begins to convert to a columnar epithelium. Recall that columnar means rectangular-shaped which is visible histologically down a microscope, and when metaplasia or abnormal changes to the tissue results, this is known as Barrett's esophagus.

If you look closely, you should be able to see two different types of epithelium, so to the right, we see stratified squamous epithelium which we would usually find within our esophagus, but looking to the left, we see markedly different epithelia. This is columnar epithelium, rectangular, and is usually found in our stomach. The most distinguishing feature, however, is the presence of goblet cells which produce mucus and are normally only found in the small intestine. It is these cells that are the most important indicator in diagnosing Barrett's esophagus.

Okay, so we've finished. Esophageal histology? Easy.

Let's wrap up this tutorial with a quick summary of what we've discovered today.

To summarize, when we began our voyage, we discussed the gross anatomy and topography of the esophagus, and do you recall that role of three that we touched on? The third portion of the alimentary canal, three subdivisions, which are? Great, you totally got it - cervical, thoracic, and abdominal.

We also discussed the histological layers of our esophageal wall from the lumen all of the way through to the tunica adventitia and the various specializations occurring in each of these areas. Take a look at this micrograph demonstrating the histological layers of the esophagus and pause this video to try and have a go at identifying the cellular layers. Working from the lumen outwards, we begin with the mucosa which consists of stratified squamous non-keratinized epithelium which overlies the lamina propria mucosae followed by the lamina muscularis mucosae.

We then moved to the submucosa which we saw contained esophageal glands and the nerve plexus aptly known as the submucosal plexus. Next up was the tunica muscularis with its inner circular layer and outer longitudinal layer separated by a nerve plexus known as the myenteric plexus. And, finally, we examined the tunica externa of the esophagus.

Finally, we considered the significance of gastroesophageal reflux disease and how over time acidic depending modifications occur within our epithelial histology resulting in columnar-appearing cells in a condition known as Barrett's esophagus.

Okay, so, now the curtains come to a close and we all know bundles more information about esophageal histology. The next time your teacher talks about strange-sounding epithelia and mind-boggling mucosas, you'll know exactly what they mean.

Enjoy your studies, guys, and thanks for watching this Kenhub video.