- The esophagus is the first true gut-tube organ.

Its circular shape and four

histologic layers will serve as a model for the remainder of the GI tract.

- Anatomy of the Esophagus

- The esophagus is long. It starts in the neck and upper
mediastinum (upper third of the esophagus), courses
through the posterior mediastinum (middle third of
esophagus), and then penetrates the diaphragm into
the abdomen, where it connects with the stomach
(lower third of the esophagus). This division into
thirds is an oversimplification—the esophagus is a
continuous organ with a continuous network of
blood vessels, lymphatics, and nerves—but for the
sake of keeping track of the anatomy and pathology
relative to our position in the esophagus, we speak as
if it is literally divided into thirds.
- The esophagus is the most posterior organ, posterior
to the trachea, in the neck and upper mediastinum.
The aorta begins anterior to the trachea and
esophagus but loops around back to be the most
posterior organ of the inferior posterior
mediastinum. The esophagus crosses the diaphragm
at T10—the gastroesophageal junction—the
stomach separated from the esophagus by the lower
esophageal sphincter (LES). We talk about
sphincters at the end of the lesson. But here in
anatomy, the LES serves to mark the end of the
esophagus and the beginning of the stomach.
-
Figure 1: Anatomy of the Esophagus
In the neck, the esophagus is posterior to the trachea, separated by a small gap, filled in by
adventitia. In the superior mediastinum, the aorta originates anteriorly to the trachea and
arches to become the most posterior structure within the mediastinum. The esophagus
penetrates the diaphragm into the stomach. Several branches from the aorta provide the
vascular supply down the length of the esophagus. Most importantly, the veins that drain
the distal esophagus connect to the portal veins and caval veins. In times of increased portal
pressure, blood can exit the portal system to the caval system as esophageal varices.

The arterial supply to the esophagus comes from multiple

arteries, which form more of a web than a direct arterial
supply. The web is redundant—there are no watershed
areas in the esophagus. The lower third of the
esophagus is supplied by a branch of the left gastric artery,
which is itself a branch of the celiac trunk. The middle
third is supplied by branches of the aorta and bronchial
arteries. The upper third is fed by branches of the thyroid
artery. The arterial supply is not very high-yield, but it
establishes the concept of the thirds, and that the vascular
supply is going to come from different sources. This sets up
the discussion about the veins, which become clinically
significant.

The venous drainage follows the concept of the arterial

supply. The lower thirdof the esophagus is drained by
branches of the left gastric vein. This is particularly high-
yield because drainage for the gut is usually to the liver
through the portal vein. The venous drainage in the
mediastinum uses the hemiazygos and azygous veins, as
well as branches of the intercostal veins. There is a
connection between the azygos and hemiazygos veins and
the left gastric vein. The gut is arranged so that the
structures of digestion and absorption send their blood to
the liver via the portal vein, through which the liver does its
thing (Hepatobiliary Course) before returning blood to the
systemic circulation via the hepatic vein and inferior vena
cava. The rest of the body sends blood directly back to the
vena cavae. All veins are interconnected, and blood follows
the path of least resistance. When there is portal
hypertension (GI: Hepatobiliary: Cirrhosis), the flow from
the gut to the liver may reverse, flowing through the
esophageal veins into the azygous veins, causing
esophageal varices. The upper third of the esophagus is
drained by the inferior thyroid veins.

Histology of the Esophagus

We first describe the histological arrangement of the gut in
the esophagus lesson because it is the first of our lessons
that coves a true gut-tube organ. This arrangement is
consistent throughout the gut—from the esophagus to the
top of the pectinate line, the structure of these four layers is
consistent. We will spend a long time on it here, and only
summarize it in future lessons. Because each layer has
sublayers (we did not decide to classify them this way,
medical science did), it tends to really confuse learners.

There are four histological layers, starting from within the

gut lumen and working outward: 1) mucosa, 2) submucosa,
3) muscularis externa, and 4) serosa/adventitia. Follow
along with Figure 2 and Figure 3.
Figure 2: Histology of the Esophagus
The histological layers of the esophagus and their sublayers. This illustration has accentuated
the esophagus’s length below the diaphragm in order to elongate and, therefore, visually
separate the layers (and sublayers of the mucosa and muscularis externa).

In a cross-section of the gut tube, viewing these structures

as concentric rings, it is most appropriate to refer to them
as being more inward to or outward from the lumen and
relative to each other. But if the gut tube is sliced
longitudinally and laid flat, the lumen will be on top and
the adventitia on the bottom, and the structures can be said
to be above or below each other. We use the latter method
to describe them. First, we describe the three layers and
identify the sublayers of each layer, and then we go into the
details of each layer. 

Figure 3: Histological Layers of the Esophagus

These low-magnification histological samples clearly demonstrate the histological layers. We
are only showing low-magnification views to concentrate on the full thickness of the
esophagus without getting bogged down with the details. The mucosa (with its epithelium),
lamina propria, and muscularis mucosae sit atop the submucosa, and the muscularis externa
lies beneath the submucosa. The first panel does not show the lower margin of the
esophagus, where the serosa (the lining of the peritoneal cavity) or adventitia would be. In
the second panel, the lumen is at the top, and the serosal edge is at the bottom. 

The mucosa is made of three sublayers: epithelium, lamina

propria, and muscularis mucosae. The epithelium varies by
location in the GI tract. In the esophagus, it is pharyngeal
epithelium— nonkeratinized stratified squamous
epithelium. Like any epithelium, it has a basement
membrane that separates it from connective tissue. That
connective tissue is the lamina propria. In the lamina
propria are the very small blood vessels, nerves, and
lymphatics that serve the epithelium. Separating the lamina
propria from the submucosa is a very thin muscular band
called the muscularis mucosae. This is not a muscle of
motility. It is not a muscle that changes the diameter of the
lumen. This is also certainly not the muscularis externa
(because their names are similar, readers get them confused
—you will not).

Figure 4: Histological Layers of the Esophageal Mucosa 

The mucosa consists of the epithelium (shown here as nonkeratinized stratified squamous
epithelium), the lamina propria and its blood vessels, and the muscularis mucosae. The
successive increases in magnification reveal more detail about the epithelium, its relationship
to the lamina propria, and the stratum basale and stratum spinosum. The stratum spinosum
resembles that of skin, but there is no granulosum or corneum layer. Instead, the cells are
engorged with the glycogen. 

The submucosa is a band of connective tissue that spans

the distance below the mucosa and above the muscularis
externa. Technically, it is below the muscularis mucosae of
the mucosa, and above the circular smooth muscle of the
muscularis externa. The submucosa contains submucosal
glands (structures that usually secrete into the lumen) and
the submucosal plexus (Meissner’s plexus), which
influences the production of those glands. The submucosa
is also the conduit for the blood vessels, lymphatics, and
nerves destined for the lamina propria of the mucosa.
Figure 5: Submucosa of the Esophagus 
The submucosa lies between the muscularis mucosae and the inner layer of the muscularis
externa. The esophagus can be identified by its nonkeratinizing stratified squamous
epithelium in the mucosa and the presence of mucinous submucosal glands (pale staining
cytoplasm) in the submucosa. The submucosa contains small- to medium-sized arteries. 

The muscularis externa has three sublayers—the inner,

circular smooth muscle; the outer, longitudinal smooth
muscle; and the myenteric (Auerbach’s) plexus between the
two muscle sublayers that innervates the muscles and
serves motility. We detail the muscles and how they cause
motility later in this lesson.

The adventitia/serosa is the connective tissue below the

muscularis externa. In it are the large blood vessels,
lymphatics, and nerves that penetrate through the circular
smooth muscle of the muscularis externa to the myenteric
plexus of the muscularis externa—the blood vessels and
nerves that become the submucosal vessels and submucosal
plexus and the blood vessels and nerves of the lamina
propria. 

As we move from the adventitia/serosa to the lumen, the

vessels get smaller and smaller until they become the
capillaries that feed the most distal epithelial cells.
Adventitia is connective tissue. Serosa is when that
adventitia is separated from another organ’s adventitia by
the lining of the peritoneal cavity—the mesothelium. We
get into this concept in GI: Abdominal Wall: Embryology
of the Peritoneal Cavity. So if this doesn’t jive yet, don’t
worry, it will.
Esophageal Physiology of Swallowing
We covered the initial phases of swallowing in the lesson
on the mouth, GI: Digestion and Absorption: Start to
Finish: The Mouth. There, we covered the oral phase and
the pharyngeal phase. Food was directed to the oropharynx.
The food bolus passed by the palatine arches and struck the
mucosa of the oropharynx. The pharyngeal phase is
involuntary: the trachea closes and the esophagus opens.
The food bolus is now ready to be moved into the stomach
through the esophagus. Here, we continue with the
esophageal phase.

Figure 6: The Phases of Swallowing

You saw this in this last lesson. It’s just here to reorient you.

The esophageal phase is involuntary and mediated by the

parasympathetics. The esophageal phase begins with the
relaxation of the upper esophageal sphincter, which allows
the food bolus to pass into the esophagus. The esophagus
must then move the bolus from the top to the bottom of the
esophagus. This process is facilitated by gravity. The
esophagus can move food up into the stomach if the patient
is inverted, but it isn’t very good at it (try drinking milk
while doing a headstand). But because the esophagus can
direct a food bolus against gravity, the esophagus must do
more than simply act as a tube through which the food
falls. Indeed, the esophagus has muscle all around its
circumference that can contract in a sequential, coordinated
fashion to propel the food bolus in one direction.

The muscularis externa of the upper third of the esophagus

isn’t like we described above. It is skeletal muscle,
reflecting the muscle and mucosa from which it is derived
—the pharynx. In the lower third of the esophagus, the
muscularis externa has the circular and longitudinal
sublayers—smooth muscle. The transition happens closer
to the top than the bottom, but the point is that there is a
change. Primary peristalsis, the coordinated, sequential
contraction and relaxation of esophageal smooth muscle
segments as caused by the food bolus hitting the palatine
arches and the back of the oropharynx, is regulated by the
vagus nerve. Secondary peristalsis, the coordinated,
sequential contraction and relaxation of esophageal smooth
muscle segments as caused by the food bolus being stuck in
the esophagus, is regulated by the stretching of the enteric
plexus. You get one shot at primary peristalsis per food
bolus. If the food bolus gets stuck, the esophagus can take
care of itself. Both forms of peristalsis require smooth
muscle changes.

Peristaltic propulsion occurs as a result of the contraction

of the circular muscle and relaxation of the longitudinal
muscle in the propulsive or upstream segment together with
the relaxation of the circular muscle and contraction of the
longitudinal muscle in the downstream receiving segment.
Now that we’ve said it the way textbooks do, let’s say it
again without the complexity of the longitudinal muscle
business.

The vagus nerve is going to open up the segment receiving

the bolus. At the same time, the vagus nerve is going to
close the segment the bolus is currently in, starting just
behind the food bolus. Like the squeezing of a tube of
toothpaste (aimed at the floor if the person is upright), the
food bolus is moved into the next segment. At which time
the next segment is relaxed, and the segment it is currently
in is contracted. The vagus nerve is in control but acts
through the myenteric plexus. Preganglionic fibers of the
vagus nerve synapse on ganglionic neurons in the
myenteric plexus. Those ganglionic neurons have short
postganglionic projections to the smooth muscle nearby.
The presynaptic fibers always release acetylcholine and
activate ionotropic acetylcholine receptors on ganglionic
neurons. The postganglionic fibers can either release
smooth muscle-contracting acetylcholine (via M -G - 3 q

IP /Ca  second messengers) or smooth muscle-

3
2+

relaxing nitric oxide (via guanylyl cyclase-cGMP dilation).

Vasoactive intestinal peptide also dilates, but we’re trying
to keep this limited in scope.

Figure 7: Primary vs. Secondary Peristalsis

A food bolus contacting the oropharynx initiates primary peristalsis, in which the vagus
nerve coordinates a series of contractions (ACh) and dilations (NO) down the length of the
esophagus. If the food bolus gets stuck, distention of the esophagus results in another
peristaltic wave independent of the vagus nerve.

Most of the GI tract has the usual arrangement of circular

and longitudinal muscles. Most of the GI tract isn’t
contracted at rest. Contraction occurs to move the food
bolus, but every once in a while, there are
sphincters. Sphincters have very developed circular layers
of the muscularis externa. In their default position,
sphincters are tightly contracted. This means, wherever
they exist, they separate two compartments of the gut tube.
The lower esophageal sphincter (LES) separates the
esophagus from the stomach, acting as a two-way valve.
Acidic stomach contents shouldn’t come into the esophagus
(reflux), and a food bolus can’t get into the stomach unless
the sphincter opens. As the vagus conducts peristalsis, it
also coordinates the opening of the LES.

Figure 8: Vagal Innervation of the Esophagus and LES

Preganglionic fibers run down the vagus nerve to the myenteric plexus. There, they will
activate either contraction-stimulating, ACh-releasing postganglionic neurons or
contraction-inhibiting, NO-releasing postganglionic neurons. The peristaltic contraction is
timed with the opening of the LES to allow the food bolus in.

As we will remind you in every organ system, smooth

muscle contracts via calcium and dilates via cGMP. Almost
always, calcium is released from the endoplasmic reticulum
after the activation of the GPCR associated with G . q

Multiple pathways activate cGMP and, therefore, dilation

—the most notable is nitric oxide or the GPCR associated
with G .
s

Citations
Figures 3, 4, 5: Originating from the University of Alabama at
Birmingham, Department of Pathology PEIR Digital Library
at http://peir.net pursuant to a license grant by the UAB Research
Foundation.