Gastrointestinal Tract Reading

Learning Objectives

  • Describe the histological characteristics of the layers comprising each segment of the gastrointestinal tract and describe how they relate to their function.
  • Name and describe four transitional junctions in the GI tract
  • Describe the topography of the gastric gland, its component cells, and architectural differences between glands in the three regions of the stomach
  • Describe the structure of the small intestine, how its surface area is maximized, and the cells that comprise its epithelium
  • Contrast the histological appearance of the large intestine from that of the small intestine


The digestive system is responsible for the ingestion and digestion of dietary substances, the absorption of nutrients, and the elimination of waste products. The secretions of the associated glandular organs, such as the salivary glands, pancreas, liver, and gall bladder, aid the GI tract in accomplishing these functions. This laboratory will focus on the sequential segments of the gastrointestinal tract; a subsequent laboratory will focus on the glandular organs.

Basic Organization of the Gastrointestinal Tract


The GI tract is a muscular tube with a histological organization that is similar across all of its segments. Several distinct, concentric layers line each segment of the tract.

  • The mucosa surrounds the lumen of the GI tract and consists of an epithelial cell layer supported by a thin layer of connective tissue known as the lamina propria. The muscularis mucosa is a thin layer of smooth muscle that supports the mucosa and provides it with the ability to move and fold.
  • The submucosa is a thick connective tissue layer that contains arteries, veins, lymphatics, and nerves.
  • The muscularis externa surrounds the submucosa and is composed of two muscle layers, the inner circular layer and outer longitudinal layer. These two layers move perpendicularly to one another and form the basis of peristalsis.
  • The adventitia consists of connective tissue containing blood vessels, nerves, and fat. In the portions of the tract within the peritoneal cavity, it is lined by the mesothelium.

These four layers can be identified in most gastrointestinal segments, although different segments demonstrate important structural variations that can provide clues to their functions. The greatest structural variations occur in the mucosal layers. There are four distinct types of mucosal variations:

  • Protective mucosa is characterized by a stratified squamous epithelium. It is found in the oral cavity, pharynx, esophagus, and anal canal.
  • Secretory mucosa contains cells that are responsible for the secretion of digestive enzymes. It is found exclusively in the stomach.
  • Absorptive mucosa contains two key structures, crypts and villi, and is responsible primarily for absorbing digested nutrients. It is found along the entirety of the small intestine.
  • Absorptive mucosa specializes in water absorption and mucous secretion. It is found in the large intestine.

There are four junctions in the GI tract that are characterized by abrupt changes in the mucosal lining: the gastro-esophageal junction, the gastro-duodenal junction, the ileo-cecal junction, and the recto-anal junction.


The esophagus (image above) is a muscular tube that transports food from the pharynx to the stomach. It is lined by a stratified squamous epithelium and has a prominent muscularis mucosa and thick muscularis externa. The muscularis externa of the esophagus is unique in that it transitions from striated to smooth muscle over the length of the tube. The esophagus ends in the gastro-esophageal junction.

The gastro-esophageal junction is notable because the epithelium transitions from stratified squamous in the esophagus to simple columnar epithelium in the stomach. Damage to the esophageal epithelium caused by acid reflux from the stomach can induce metaplasia in the esophageal epithelium, a process known as Barrett's Esophagus.



This slide shows the structure of the stomach lining under the light microscope. The stomach is the site where food is mixed with gastric juice and reduced to a fluid mass called chyme. The layers of the stomach wall follow the basic plan described above. The epithelium of the mucosal layer forms gastric glands that produce acid and enzymes that help digest food. The submucosa is composed of loose connective tissue with some blood vessels. In a non-distended state, the stomach mucosa is found in prominent folds called rugae. Rugae allow for dissension of the stomach after a large meal. The stomach is distinct from other segments of the GI tract in having three layers of smooth muscle in the muscularis externa. In addition to the inner circular and outer longitudinal layers, there is an oblique layer that sits between the submucosa and inner smooth muscle layer. The three layers of muscle generate powerful churning of the stomach contents to facilitate digestion.

Gastric Glands

Gastic Gland

The gastric gland is the basic secretory unit of the stomach and contains a variety of component cells located in characteristic locations. The gland begins at the gastric pit, the opening to the lumen of the stomach. The pit itself contains mostly mucous-secreting cells, visible because of their pale-staining mucous droplets. The isthmus and neck of the gland lead down to the lowest portion, its base. Parietal cells, which secrete HCl and intrinsic factor, are located primarily in the isthmus and neck regions and appear highly eosinophilic, while the chief cells responsible for pepsinogen secretion are located closer to the base of the gland and appear granulated and basophilic. The muscularis mucosa is also visible here.

Cells of Gastric Glands

There are several types of cells that are important in producing stomach secretions.

Mucous-secreting cells produce mucous and bicarbonate ions, which protect the stomach epithelium from the damaging effects of stomach acid. They appear pale and contain obvious mucous droplets. These cells are located in all layers of the gastric gland, but are particularly prominent in the gastric pit and in the neck of the glands.

Parietal cells secrete hydrochloric acid and intrinsic factor, which is important for the absorption of vitamin B12 in the terminal ileum. They have a characteristic pyramidal shape and are usually found in the isthmus of the gastric gland. Parietal cells have a characteristic tubulovesicular system that fuses with their membrane canaliculi when they become activated. Parietal cells have a characteristic "fried-egg" appearance, with a basophilic, centrally located nucleus and a rather eosinophilic cytoplasm. These cells secrete HCl and intrinsic factor which aids in the absorption of vitamin B<sub>12</sub>.

Parietal Cells
Parietal Cells

Chief cells are found in the base of the gastric glands and produce pepsinogen, which is stored in large apical secretory granules. After pepsinogen is secreted, it is converted by the acidic environment of the stomach to pepsin which is an active protease. Chief cells have a basally located nuclei and a basophilic cytoplasm with abundant rough endoplasmic reticulum and many secretory granules that contain pepsinogen. These are secreted into the lumen of the gastric gland.

Chief Cells
Chief Cells

Enterochromaffin-like (ECL) cells produce histamine, which is important in the release of stomach acid. They are typically found in the base of the gastric glands.

G-cells secrete the peptide hormone gastrin into the blood stream.

Stem cells divide to replace the other cells in the gastric glands. They are located primarily in the neck of the glands.

Regions of the Stomach

The three different regions of the stomach are distinguished on the basis of the histological characteristics of the mucosal glands.


Stomach Cardia

The cardia is a circumferential ring about 3 centimeters deep distal to the gastro-esophageal junction. Its glands tend to be convoluted and are lined primarily by mucous-secreting cells that lubricate the incoming food and protect the lining of the stomach near the gastro-esophageal junction. Below the glands of the mucosal layer are the lamina propria and muscularis mucosa, which are responsible for support and folding, respectively.


Stomach Body

The body is the main part of the stomach and is bounded by the greater and lesser curvatures. Its glands are straight with limited branching and are lined by a smaller population of mucous-secreting cells than those of the cardia. The mucosa of the body of the stomach has much deeper and less coiled gastric glands than that of the cardia. These are deep invaginations that begin as gastric pits. The glands contain mucous cells, chief cells, parietal cells, and enterochromaffin-like (ECL) cells. The muscularis mucosa and submucosa are also visible.


Stomach Pylorus

The pylorus is the distal third of the stomach and terminates at the beginning of the duodenum. It possesses glands with deeper pits and large amounts of coiling and branching. These glands contain many mucous-secreting cells, ECL cells, and G-cells. The mucosa of the pyloric antrum possesses deep gastric pits and gastric glands.

Small Intestine

The small intestine is responsible for the continued digestion and absorption of the GI tract contents. Reflecting its absorptive function, the surface area of the small intestine is amplified significantly at three levels.

  • Microvilli make up a brush border on the surface of the columnar cells of the mucosal epithelium.
  • Villi are finger-like projections of the epithelium and lamina propria that project into the lumen.
  • Plicae circulares are folds of the mucosal epithelium, lamina propria, muscularis mucosa and submucosa that project into the lumen. Plicae circularis are most prominent in the jejunum.



Villi are outward folds of mucosa and lamina propria. Villi are lined by epithelial enterocytes that contain a brush border and perform most of the intestinal digestive and absorptive functions. Goblet cells with their clear mucous droplets are interspersed between these enterocytes. The lamina propria supports the epithelial cells and makes up the core of the villus. Within the lamina propria is a central lymphatic vessel known as a lacteal, which is crucial for the absorption of lipids from the intestine. Blood vessels and immune cells are also prominent in the lamina propria. Villi also contain a strand of smooth muscle that cause them to move and mix the contents of the intestinal lumen.

Crypts of Lieberkuhn

Crypts of Lieberkuhn

The intervening depressions between the villi are known as crypts of Lieberkuhn and can be thought of as the intestinal analogs of the gastric glands. The epithelia of the villi extend down into the lamina propria where they form crypts. Many important cells reside in the crypts. Paneth cells, which appear spotted and eosinophilic, support the host defense against microbes. Enteroendocrine cells produce hormones that govern motility and secretion, just as they do in the stomach. Note the pale cytoplasm of the enteroendocrine cells. Stem cells replenish the other cell types and are found at the base of the crypts.

Segments of the Small Intestine

The small intestine begins after the gastro-duodenal junction and is divided into duodenum, jejunum and ileum.



The duodenum contains the same wall layers seen in the previous portions of the GI tract: mucosa, submucosa, and muscularis externa. The mucosa and lamina propria form long villi. The epithelial cells of the mucosa contain enzymes that facilitated digestions of large macromolecules. In addition, the duodenum receives digestive enzymes produced in the pancreas.

The duodenum contains within its submucosa extensive glands called Brunner's glands. The cells in the glands secrete an alkaline mucous that neutralizes the pH of chyme from the stomach and protects the epithelium of the duodenum. These glands are unique to the duodenum.



The jejunum is the site of a great deal of nutrient absorption and creates the greatest surface area of the three segments of the small intestine. This cross section through the jejunum shows prominent plicae circulares lined by numerous villi. Plicae circulares are more extensive in the jejunum compared to the duodenum and ileum. Note that while the submucosa and mucosa extend into the plicae circulares, the muscularis externa does not. Each villus is lined by an epithelium with numerous enterocytes that absorb the small molecules produced through digestion of food.



The ileum has the shortest villi and is characterized by abundant Peyer's patches in the submucosa. Peyer's patches are diffuse lymphoid tissue that play an important immunological role in sampling the contents of the GI tract.

The small intestine ends with the ileo-cecal junction.

Large Intestine


The large intestine absorbs water and concentrates waste material that is formed into feces. It lacks villi and contains a disproportionately large number of goblet cells. The lamina propria has many macrophages, plasma cells, eosinophils, and lymphoid nodules. Note the arrangement of the external muscular layer into an inner circular layer and outer longitudinal layer.

The large intestine feeds into the rectum, which stores the feces and has a columnar epithelium with abundant goblet cells. Feces pass out of the rectum, through the anus, and out of the body. The anus is characterized by a stratified squamous epithelium that undergoes a gradual transition to skin containing sebaceous and apocrine sweat glands.

The recto-anal junction features an important change in epithelial structure. The rectum is characterized by the same columnar epithelium that lines the majority of the gastrointestinal tract's secretory and absorptive areas. The anus, on the other hand, has a stratified squamous epithelium that provides a greater deal of protection to the underlying tissue.

Recto-Anal Junction

Enervation of GI Tract

Throughout the gastrointestinal tract, postganglionic parasympathetic neurons supply the glands and smooth muscle layers. In doing so, they coordinate peristalsis and digestion. In the first portion of the GI tract, from the oral cavity to the upper esophagus, food moves by voluntary muscular action. In the following portion, from the lower esophagus through the large intestine, food moves by peristalsis. The cells of the Auerbach's (myenteric) plexus are located between the inner circular and outer longitudinal layers of the muscularis externa and are responsible for generating peristaltic movements.

Auerbach's Plexus

The submucosal plexus, or Meissner's plexus, is located in the submucosal layer and controls the mucosal glands and the muscularis mucosa

Meissner's Plexus