A Seventh-day Adventist Organization

Gastrointestinal Tract Syllabus

Histology Mentor


I. ESOPHAGUS AND THE GENERAL PLAN OF ORGANIZATION OF THE ALIMENTARY TUBE. The wall of the alimentary tract is described in 4 layers: the mucosa, submucosa, muscularis, and adventitia. Glands that empty their secretions into the lumen may be found in the mucosa, submucosa, or even outside the organ (for example, the pancreas). Features that distinguish one part of the tract from another are largely confined to the mucosa and submucosa.

1. Epithelium

2. Lamina propria (c.t.)

3. Muscularis mucose (smooth muscle)

4. Mucosa

5. Submucosa

6. Muscularis externa (inner circular, outer longitudinal)

7. Myenteric (Auerbach) nerve plexus

A. Esophagus - a flat muscular tube that carries the food from the pharynx to the stomach. Learn to identify the esophagus and look for the following features:

1. Mucosa - as in most other parts of the GI tract consists of 3 layers.

a. Epithelium - in the esophagus it is stratified squamous non-keratinized. Like stratified squamous epithelia elsewhere (skin, oral mucosa and vagina) Langerhans cells reside here. These cells process antigens and present their epitopes complexed with MHC II on their surface. They migrate to regional lymph nodes to present these antigen-MHC II complexes to lymphocytes.

b. Lamina propria - a layer of loose irregular c.t. underlying the epithelium of all mucous membranes. It frequently contains diffuse lymphoid tissue and an occasional lymph nodule. In the upper and lower ends of the esophagus, small mucous glands (cardiac glands) are found in this layer and are more appropriately called mucosal glands.

c. Muscularis mucosae - a thin layer of smooth muscle capable of moving the mucosa relative to the other layers.

2. Submucosa - loose irregular c.t. containing blood and lymph vessels, a submucosal nerve plexus (Meissner's) and submucosal mucous glands (esophageal). Ganglion cells of the parasympathetic and post ganglion fibers of the sympathetic systems compose the nerve plexus. In the lower part of the esophagus veins of the submucosa communicate with both the portal and general venous systems. In portal hypertension they enlarge and sometimes rupture.

3. Muscularis externa - follows the general plan of organization: an inner circular and outer longitudinal layer of muscle with the autonomic myenteric nerve plexus (Auerbach's) in between the layers. The upper 1/4 of the esophagus is skeletal, middle 1/4 is mixed, and the lower 1/2 is smooth muscle.

4. Adventitia - a connective sheath. Where it is covered by mesothelium it is called a serosa; otherwise, it is called a fibrosa or simply adventitia. Little, if any, serosa is associated with the esophagus.

5. Enteric Nervous System - the submucosal and myenteric nerve plexuses together are sometimes called the visceral brain. They consist of a network of sympathetic and parasympathetic elements including clusters of nerve cells. These are motor systems that control muscle contractions and glandular secretions. The parasympathetic system is said to be anabolic stimulating peristalsis and glandular secretions but inhibiting sphincters. The sympathetic system inhibits peristalsis and activates sphincters. While sensory fibers (visceral afferents) are present in these plexuses they are not included in the sympathetic and parasympathetic motor systems even though they play an important role in the reflexes of the visceral brain. However, it should be noted that many of the reflex loops occur within the wall of the viscera and do not involve the spinal cord.

II. STOMACH - Functions include: 1) primary site of protein digestion (pepsin and HCI); hormone secretion (the fundic stomach secretes glucagon and somatostatin; the pyloric stomach secretes gastrin, secretin, and somatostatin); 3) produce intrinsic factor; 4) add fluid and mix contents, and 5) the pyloric stomach produces a protective mucus.

1. Gastric area (mammillated area)

2. Simple columnar mucus-secreting epithelium

3. Tubular glands

4. Lamina Propria surrounding glands

5. Muscularis mucosae (smooth muscle)

6. Mucosa

7. Submucosa

8. Muscularis externa

9. Mesothelial outer surface

A. Mucosa - in the empty stomach it is thrown into many irregular longitudinal folds (rugae), that are flattened out as the stomach is filled. Irregularly shaped mounds of mucosa result from a variation in its thickness. They are called mammilated or gastric areas. Throughout the stomach the surface epithelium consists of tall columnar, mucus-secreting, PAS-positive cells. This is a thick mucus that sticks to the surface cells protecting them from the digestive juices. These mucous lining cells also line the gastric pits or foveolae (irregularly shaped invaginations) into which the mucosal gastric glands empty. The lamina propria contains diffuse lymphoid tissue and occasional nodules. Mast cells are abundant. The muscularis mucosae is typical.

1. Region of fundus and body - gastric glands in this region are called fundic (but more appropriately peptic) glands. They are relatively straight tubular glands slightly coiled at their blind end. They empty into the pits.

The glands consist of:

a. Mucous neck cells - small cells interspersed with parietal cells may be precursors of surface cells and arise by mitosis of undifferentiated cells in the neck region. They produce a soluble mucus that lubricates the chyme as it is processed.

b. Chief cells - typical zymogen cells (basal rough endoplasmic reticulum, apical secretion granules and Golgi apparatus apical to the nucleus) concentrated at the base of the glands. They produce pepsinogen, rennin and gastric lipase.

c. Parietal cells - concentrated in isthmus and interspersed with mucous neck and chief cells. They are large round cells with eosinophilic cytoplasm due to a high concentration of cytoplasmic membranes. These consist of mitochondria, SER, and intracytoplasmic canaliculi with many microvilli. When activated the number of smooth vesicles is reduced and the width of the canaliculi and number of microvilli in the canliculi increase. Parietal cells produce hydrochloric acid and intrinsic factor. One stimulus for acid secretion is by histamine released from mucosal mast cells. Parietal cells have special histamine receptors (H2) that differ from those involved in allergic responses (H1) on their surface. See Science 258:1662-1665, 1992. Secretion is also stimulated by the vagus nerve (acetyl choline). Hormones produced by the DNES also contribute to regulation of gastric function.

d. Endocrine cells - single cells that are dispersed among the principal cells and that bind (argyrophilic) or reduce (argentaffin) silver salts. They usually contain membrane limited granules that accumulate near the basal membrane. The granules store a polypeptide hormone and may also contain a monoamine such as serotonin. These cells are part of the diffuse neuroendocrine system (DNES) and similar cells may be found in the epithelia of the intestines and respiratory tract. In the stomach they produce the peptide hormone gastrin to lacally (paracrine secretion) stimulate acid secretion. Gastrin is also produced by similar cells in the small intestine. Other hormones that come from these gastric cells are: somatostatin, prostaglandin, and gastric inhibitory peptide all of which inhibit acid secretion as does urogastrone (epidermal growth factor) from Brunner's glands. In addition the stomach is one of the sources of glucagon, and vasoactive intestinal polypeptide.

2. Pyloric region - the pyloric (mucous) glands occupy the outer half of the mucosa; pits occupy the inner half. The mucous secretory glands are coiled tubes. The cells are similar to the mucous neck cells. They produce a protective mucus that includes the enzyme lysozyme.

3. Cardiac region (or junction) - transition from esophagus (stratified squamous non keratinized epithelium) to stomach (simple columnar mucus-secreting epithelium). A very narrow region in the stomach contains mucosal, mucous-secreting cardiac glands.

4. Pyloric junction - transition from pyloric stomach to duodenum with the appearance of submucosal, pure mucous, Brunner's glands, and intestinal villi covered with a simple columnar epithelium containing goblet cells.

B. Submucosa, muscularis externa, and serosa follow the general plan of organization, except that in some regions an outer circular layer of smooth muscle is added and at the pyloric junction special arrangements of smooth muscle forms the pyloric sphincter.

III. SMALL INTESTINE - mostly covered by a serosa, the small bowel's muscularis externa, submucosa, and mucosa follow the general plan of organization. The features of the mucosa, and to some extent, the submucosa, differentiate different regions of the small bowel from each other and from other parts of the GI tract.

1. Muscularis externa

2. Submucosa

3. Muscularis mucosae

4. Lamina propria

5. Simple columnar epithelium covering villi and lining glands (crypts)

6. Mucosa

Learn to recognize the duodenum by the presence of Brunner's glands or pancreas or bile duct as a distinctive segment of small bowel, and to identify ileum with Peyer's patches.

A. Mucosa - permanent folds of mucosa, the plicae circulares, have a core of submucosa. They increase surface area and aid in mixing the contents. Mucosal villi further increase the surface area and only consist of epithelium covering a core of lamina propria. Crypts of Lieberkuhn, or intestinal glands, are epithelially lined tubular depressions in the mucosa surrounded by lamina propria.

1. Epithelium - simple, tall, columnar epithelium consisting of absorptive cells interspersed with goblet cells on the villi and, in the crypts, proliferating and differentiating cells. Absorptive and goblet cells develop in the crypts and migrate to the tip of the villus where they are shed - time: about 5 days. Paneth cells do not migrate but have a life span of about 20 days.

a. Absorptive cells (Enterocytes) - columnar cells with a regular striated border of microvilli. The microfilaments in the microvilli are actin. They anchor in the terminal web consisting of a mixture of intermediate filaments, actin microfilaments and spectrin, so that there is potential for movement in the apical part of the cell. A terminal bar apparatus surrounds the apex of the cells. Digestive enzymes are associated with the microvilli as well as proteins involved with membrane transport of nutrients. Absorption involves diffusion and active transport of small molecules across the plasma membrane. Sodium is pumped across the basolateral cell membrane as it is cotransported with glucose across the apical membrane. Water follows these osmotically. In the case of fat absorption, components of fat are absorbed, reassembled in the cisternae of the SER, coated with protein, and released as chylomicrons between the epithelial cells to be carried away in lymph lacteals or fenestrated capillaries of the blood. The enterocytes also secrete enzymes that aid in digestion as well as secretory immunoglobulins. Over the lymph nodules of Peyer's patches, some of the absorptive cells are replaced by specialized cells designed to present antigens to the lymphoid tissue - these are called M cells.

b. Goblet cells - goblet shaped apical portion of these cells contains mucous granules. The nucleus is small, dense and pressed toward the base of the cell. The Golgi apparatus is prominent.

c. Paneth cells - found at the base of the crypts, they have eosinophilic apical granules and secrete enzymes including lysozyme that digests bacterial cell walls. They do not migrate to the villus.

d. Argentaffin cell - part of the diffuse neuroendocrine system. Their basally-placed secretion granules may or may not contain a biogenic amine such as serotonin. Moreover some are exposed to the intestinal lumen (open) others are not (closed). They produce polypeptide hormones, including

1. Secretin - stimulates enzyme-poor pancreatic secretion

2. Cholecystokinin (pancreozymin) - gall bladder contraction. Stimulates enzyme-rich pancreatic secretion

3. Gastrin - stimulates acid secretion by stomach

4. Many others that influence GI function

2. Lamina propria - especially rich in diffuse lymphoid tissue with frequent solitary nodules.

a. Peyer's patches are aggregates of lymph nodules that occur in the terminal ileum. These extend into the submucosa. In the gut-associated lymphoid tissue (GALT) and in the bronchus-associated lymphoid tissue (BALT) some of the columnar epithelial cells over lymph nodules are replaced by cells that are specialized for antigen processing. Their surface has short irregular microvillous folds and their basal cytoplasmic folds surround many lymphocytes. These "M" cells ("M" stands for microfolds.) present unprocessed antigens to the underlying lymphoid tissue. These cells are especially abundant over nodules of Peyer's patch.

b. During the 5 day trip of epithelial cells from the glands to the villus tips fibrocytes and probably blood vessels and nerves migrate with the epithelium to the villus tip where macrophages remove c.t. elements that undergo apoptosis and the epithelium is exfoliated.

3. Muscularis mucosae - follows general plan

B. Submucosa - follows general plan, except:

1. Brunner's glands - pure mucous submucosal glands are limited to the duodenum. They are most concentrated near the stomach and secrete alkaline mucus. They also produce urogastrone (epidermal growth factor), that inhibits gastric acid secretion and stimulates epithelial proliferation.

C. Muscularis - follows general plan

D. Serosa is incomplete in part of duodenum.

IV. LARGE INTESTINE - the various regions; cecum, ascending, transverse, etc. - are histologically similar. It absorbs some nutrients (vitamin K), water and secretes mucus. Look for the transition between ileum and colon (ileocecal junction)

A. Mucosa - there are no plica circulares or villi. The surface simple columnar epithelium arises from the intestinal crypts. The concentration of goblet cells is greater than in the small bowel, but there are no Paneth cells, their presence is indicative of chronic disease. Abundant diffuse lymphatic tissue is found in the lamina propria. The epithelium of the crypts of the large bowel responds to cylic AMP by secreting fluid and electrolytes. The surface epithelium does not.

B. Submucosa follows general plan.

C. Muscularis externa is altered from the general plan in that the external longitudinal muscle is concentrated in 3 bands - the taeniae coli. These are like drawstrings so that haustra (sacculation) are formed.

D. Serosa or adventitia is present.

V. RECTUM AND ANAL JUNCTION - At the anal canal the simple columnar epithelium of the rectum (like the colon) changes to stratified squamous. At first it is nonkeratinized (anal canal) but soon becomes thin skin. Enlarged hemorrhoidal veins may be seen in the mucosa of both the rectal and anal canals. Circumanal, apocrine sweat glands are associated with the perianal skin.

VI. APPENDIX - it is like the colon, except many lymphoid nodules fill the mucosa and submucosa, so that the crypts occur in scattered groups. Its function must be related to the lymphoid tissue it contains that declines with age. "M" cells are found in the epithelium overlying the lymph nodules.

1. Mesothelium

2. Muscularis externa

3. Submucosa

4. Lymph nodules

5. Muscularis mucosae

6. Tubular glands

7. Lamina Propria

8. Simple columnar epithelium

9. Mucosa

Glands of the Gastrointestinal Tract

I. PANCREAS - two components: exocrine and endocrine

1. Acini

2. Thin c.t. septa

3. Islets of Langerhans

4. Interlobular duct (surrounded by thick layer of dense connective tissue)

A. Exocrine pancreas

1. Histology - a pure serous gland. It secretes enzymes that digest protein, carbohydrate, fat and nucleic acids. Each acinus partly surrounds the terminal portion of an intralobular duct. The duct cells thus surrounded by acinar cells are called centroacinar cells. Intralobular ducts are inconspicuous and open into the conspicuous interlobular ducts. These are conspicuous because they are surrounded by a dense connective tissue sheath. This sheath is the primary support for the pancreas, since there is very little intralobular connective tissue and the capsule is very thin.

2. Control - stimulation by the vagus and cholecystokinin - when acid chyme enters the intestine, cholecystokinin is released from neuroendocrine cells this, along with increased vagal activity, stimulates the release of an enzyme rich secretion. Secretin, another intestinal hormone, stimulates the centroacinar cells and intralobular ducts to release a secretion poor in enzymes and rich in bicarbonate.

B. Endocrine pancreas - islets of Langerhans are nests of light staining cells scattered among the pancreatic acini. As in other endocrine organs the capillaries are fenestrated. There are at least 3 types of cells that contain membrane limited secretion granules.

1. Alpha cells produce glucagon that elevates blood glucose.

2. Beta cells produce insulin that lowers blood glucose. Proinsulin is formed in the RER and is split in the Golgi region to insulin and then packaged for secretion. Secretion of insulin is stimulated by elevated blood glucose and modified by parasympathetic and sympathetic nerves.

3. Delta cells produce somatostatin. The role of somatostatin may be to regulate other secretions.


1. Bile duct

2. Portal vein

3. Hepatic artery

4. Portal area or canal

5. Central vein (blood flows from portal area to central vein through

6. Liver sinusoids

7. Plates of hepatocytes

A. Functions - It is both an endocrine and an exocrine organ, the liver is organized so that its parenchymal cells are intimately associated with both vascular sinusoids and bile canaliculi. The liver produces a large number of blood-borne proteins (albumin, lipoproteins, fibrinogen, clotting factors, complement system proteins, renin substrate, etc.) It buffers blood glucose levels by forming and degrading glycogen under endocrine control, metabolizes hormones and drugs, stores iron, fat, protein, and vitamins; it contains many macrophages in its sinusoids, and produces bile. It concentrates dimeric IgA from the blood and secretes it in the bile. A large share of nutrients absorbed by the intestine enters the liver directly via the portal vein where they are processed or stored.

B. Stroma and Portal Canal

1. Capsule - a fibrous connective tissue layer surrounding the liver and covered by mesothelium except next to the diaphragm. It is thickened in the region of the porta where the vessels and nerves enter and leave the organ. This connective tissue forms an extensive branching system that surrounds the vessels and nerves it accompanies. Together these structures form a tree-like support of the liver. Its branches are called portal canals, but when seen in cross-section, they are named portal areas. Little c.t. is associated with the hepatic veins and especially their terminal branches, the central veins. Two interlacing tree-like patterns are formed by these vessels; the hepatic veins emptying into the inferior vena cava, and the portal vein and its branches that arise from the porta.

2. Portal canals

a. Contents - 1) branches of the portal vein, 2) branches of the hepatic artery, 3) tributaries of the bile duct, 4) tributaries of the lymphatics, and 5) nerves.

b. Distribution - portal canals are usually found where 3 lobules of hepatic tissue meet. Terminal branches of the vessels extend out from the portal canal between the polygonal shaped lobules.

C. Parenchyma

1. Hepatocytes - large polygonal shaped, epithelial cells. They have fine chromatin in their nuclei and a finely granular cytoplasm that may show vacuolation due to glycogen and fat. Ultrastructurally they contain scattered mitochondria with few cristae, RER and SER that respond to functional demands, lysosomes and peroxisomes. Bile canaliculi are formed by the plasma membrane of adjacent hepatocytes and are surrounded by actin filaments. The actin can alter the size and shape of the canaliculi. J. Histo & Cytochem: 41:353, 1993. Tight junctions between these membranes prevent the bile from leaking out of the canaliculi into the perisinusoidal space of Disse' and thus into the blood. Irregular microvilli extend from the hepatocyte surface into the space of Disse' and are bathed by plasma.

2. Organization - the hepatocytes form irregular, branching plates or cords that are usually only a single cell thick. Sinusoids lined by an endothelium with an incomplete basal lamina and having fenestrations of various sizes surround these plates and cords. The endothelial cells are separated from the hepatocytes by the space of Disse' in which a few fibrocytes, lipocytes and reticular fibers may be found. The lipocytes may be the source of fibroblasts especially in cirrhosis. Inside the sinusoids stellate shaped macrophages (Kupffer cells) abound and are a significant component of the mononuclear phagocytic system. The cords and plates are arranged radially around a central vein toward which blood flows in the sinusoids. There are three ways of defining the fundamental unit of liver structure.

a. Classical lobule - the central vein is at the center; portal canals are found around the periphery toward which the bile flows.

b. Portal lobule - the portal canal with its bile duct is at the center of a triangular shaped lobule with central veins at each of the apices. Bile flows from canaliculi through ductules (canals of Herring) into the bile duct.

c. Liver acinus - a more or less cylindrical region surrounding terminal branches of the hepatic artery and portal vein that are located about halfway between two central veins. A gradient of oxygen tension and nutrients occurs so that 3 zones are recognized. Zone 1 - nearest the artery - is richly supplied with oxygen and nutrients; Zone 3 - nearest the central vein - is marginally supplied.

3. Functional considerations

a. Secretion of blood proteins - these first enter the space of Disse' and then the blood. Abundant lymph rich in plasma proteins flows from the liver. Much of this lymph must come from the space of Disse'.

b. Detoxification - hormones, bilirubin, drugs and toxins are metabolized or converted to water soluble conjugates by the SER. There is a tremendous increase in the amount of SER when an animal is given barbiturates. This increases the rate at which these drugs can be metabolized.

c. Regeneration - the liver has a great capacity to regenerate.


A. Mucosa

1. Function - primarily concentrates bile by the active transport of sodium ions across the lateral and basal cell membranes of the epithelial cells, anions and water follows the sodium.

2. Epithelium - a very characteristic simple, tall columnar epithelium with many irregular microvilli on the apex. Junctional complex and scattered desmosomes anchor the cells together, but space between cells is widened during active transport.

3. Lamina propria - when the muscularis contracts, the mucosa is thrown into complex folds so the epithelially lined pockets become surrounded by lamina propria. In the neck region, mucous-secreting glands may be found.

B. Muscularis - an irregular relatively thin layer of smooth muscle that contracts when stimulated by cholecystokinin and the vagus nerve. The sphincters of the bile duct relax when the vagus is stimulated.

C. Serosa covers part of the gall bladder.