Pathology 104

Dental Histology

Fall 2003

G. Meyer

THE DIGESTIVE SYSTEM

The digestive system consists of the oral cavity, mouth, esophagus, stomach, small intestine, large intestine, rectum and anus, and its associated glands--salivary glands, liver and pancreas. Its function is to obtain from the ingested food the metabolites necessary for growth and energy needs of the body. Food is digested and transformed into small molecules that can be easily adsorbed through the lining of the gastrointestinal tract.

The first step in the complex process known as digestion occurs in the mouth, where food is ground into smaller pieces and moistened by saliva, which also initiates the digestion of carbohydrates. Digestion is continued in the stomach and small intestine, where the food, (which has been transformed into amino acids, sugars, fatty acids, etc.) is absorbed. Water absorption occurs in the large intestine, causing the undigested contents to become semisolid.

The Oral Cavity

The oral cavity contains the tongue, the teeth and the pharynx. This part of the digestive system will be studied next week.

The Esophagus

The esophagus is a muscular tube whose function is to transport food from the mouth to the stomach. It is covered by a non-keratinized stratified squamous epithelium. The upper and lower thirds contain mucus-secreting esophageal glands. Also in the upper third, striated muscle is found, which serves to allow us to actively swallow the bolus of food; the middle third contains mixed striated and smooth muscle, while the lower third of the tube contains only smooth muscle.

This simplified Flow diagram shows how the various sections of the GI tract lead into one another.

Oral Cavity Esophagus Stomach Cardia Fundus(body) Pylorus

Small Intestine Duodenum Jejunum Ileum

Large Intestine Colon Rectum Anal canal Anus

Remember from what was said above that the esophagus is a tube which delivers food to the stomach where digestion begins. The partly digested meal is delivered to the small intestine where digestion continues and absorption of nutrients occurs. The residue then passes into the large intestine where water is absorbed along with residual nutrients left after p passage through the small intestine. The passage of the relatively dehydrated fecal mass is facilitated by the secretions of large numbers of goblet cells in this area of the GI tract. Finally the feces are voided through the anus.

From the esophagus to the rectum, the wall of the alimentary canal, or digestive tube, is comprised of 4 layers designated as:

1. Mucosa

epithelium

lamina propria

muscularis mucosa

2. Submucosa

3. Muscularis externa

inner circular layer of smooth muscle

outer longitudinal layer of smooth muscle

4. Serosa (or Adventitia)

Blood vessels, nerves and lymphatics reach the GI tract through the mesentery, run through the serous coat and then branch and penetrate the gut wall. These 4 layers are nicely demonstrated on this diagram of the esophagus, and on this H & E of the fundic stomach.

Functions of the layers of the GI tract

1. Epithelium: To provide a selectively permeable barrier between the contents of the tract, and the tissues of the body.

To facilitate the transport and digestion of food

To promote the absorption of the products of digestion

2. Lamina Propria and Submucosa

Protection. These layers are rich in diffuse lymphoid tissue and lymph nodules. Plasma cells in the lamina propria produce IgA which is transported into the gut lumen after complexing with a receptor on the basal surface of the epithelial cells.

Blood vessels, nerves and lymphatics course through these layers.

3. Muscularis mucosa:

Promotes limited movement of the mucosa and thus increases it's contact with food.

4. Muscularis externa

The contractions of the muscularis externa propel and mix the food in the digestive tract, and this contraction is co-ordinated by the parasympathetic ganglia of Meissner's and Auerbach plexuses.

5. Serosa

Provides a smooth surface on the gut to allow easy movement during digestive contractions.

6. Adventitia

Some parts of the gut are attached directly to other organs. In such cases the connection is via connective tissues, and is called an adventitia

Finally, the gut contains many intramural and extramural glands which provide the tube with lubricating mucous, enzymes, water and other substances. The intramural glands are in the mucosa, and/or submucosa and differ considerably along the length of the tract. The extramural glands are the liver, pancreas and gall-bladder. They empty their secretions into the duodenum.

The esophagus: is a tube which conducts food from the mouth to the stomach. It is lined with a non-keratinized stratified squamous epithelium. Mucous secreting glands occur in the mucosa or submucosa; their secretions lubricate the tube. The upper third of the muscularis externa consists of skeletal muscle, the middle third of mixed skeletal and smooth muscle, and the lower third of smooth muscle. Why? Between the esophagus and the entrance to the stomach, there is an abrupt change from a stratified squamous epithelium to a simple columnar epithelium, which is found through the rest of the canal, until reaching the anus. The cardiac sphincter controls the entrance of food into the stomach--it is an unimpressive structure.

The stomach: Within the stomach, the food is mixed with digestive juices and churned into a viscous pulp called chyme. Digestion continues until ingredients are broken down enough to be passed into the intestine for further digestion and absorption.

The stomach is divided into 3 histological regions: the cardia, the body (fundus) and the pylorus. Since these differ only in the type of glands present, we'll look at the body, since this comprises the largest part of the gut. As with the remainder of the digestive tract, it consists of a mucosa, a submucosa, a muscularis externa and a serosa.

The mucosa and submucosa are thrown into a number of large folds called rugae --these allow the stomach to expand considerably when filled with food. Upon and between these rugae, the mucosa is thrown into ridges called mucosal ridges and between the mucosal ridges are small channels called gastric pits. Extending from the bottom of these pits, and opening into the pits, are the gastric glands.

The glands of the body of the stomach contains three major types of secretory cells:

1. Chief (Peptic) Cells. These are found in the lower portion of the gland and show basophilic staining. These cells secrete zymogen granules which contain the enzyme pepsinogen, which is the inactive precursor of pepsin . Pepsin is formed when pepsinogen is exposed to the acid environment of the stomach, by the splitting off of a peptide. Once some pepsin is formed, it can catalyze the conversion of pepsinogen to pepsin.

2. Parietal (Oxyntic) Cells. The acid medium in which pepsin works best is provided by the parietal cells. The cytoplasm of these cells shows intense eosinophilic staining, due to the presence of large numbers of mitochondria. Parietal cells secrete 0.16 M HCl. they do this by actively secreting H+ ions derived form the action of carbonic anhydrase on carbonic acid. Cl- is actively transported across the cell membrane where it combines with H+ to form HCl. These cells also synthesize and secrete intrinsic factor, which is required for the absorption of vitamin B 12 in the small intestine. Lack of intrinsic factor leads to B 12 deficiency and pernicious anemia.

3. Mucous Neck Cells. Are located near the opening of the glands into the gastric pits. These cells secrete a chemically different variety of mucus which protects the gastric epithelium from the harsh acid of the stomach.

The exit from the stomach to the first segment of small intestine, the duodenum, is controlled by the pyloric sphincter, which is formed by a thickening of the circular muscle of the stomach wall. The muscles of the pyloric antrum are responsible for most of the mixing that occurs in the stomach. With the pyloric sphincter closed, vigorous contraction of the antrum propels food into the body of the stomach. Relaxation of the antrum, aided by contraction of the muscles in the body, allows food to funnel back into the antrum. This continues until mixing and breakdown of solid particles occurs. When this occurs, hormones released from the duodenal mucosa, as well as nervous reflex control, result in relaxation of the sphincter, and the chyme is smoothly passed into the duodenum.

The small Intestine. In the small intestine (SI), the processes of digestion are completed and the products of digestion are absorbed. The length of the small intestine (6 m) permits prolonged contact between the food and digestive enzymes, as well as between digested products and the absorptive cells of the epithelial lining. The small intestine consists of 3 segments, the duodenum, jejunum and ileum. These 3 segments have many characteristics in common, and so will be discussed as one unit.

The SI contains the 4 layers characteristic of the GI tract - mucosa, submucosa, muscularis externa and serosa.

In order to increase the surface area available for digestion and absorption, the inner surface of the SI shows a number of gross and microscopic specialization's:

Plicae circulares: are permanent folds of the intestinal lining including both the mucosa and submucosa. They increase the surface area about 3 fold

Villi: cover the entire surface of the SI and increase the surface area a further 10 fold.

Microvilli: cover the apical surfaces of the absorptive cells which line the villi. They increase the surface area about 20 fold.

Taken together, all of these surface specialization's increase the surface area available for digestion and absorption about 600 fold for a total effective area of 200 m2.

So the plicae are the large folds which consist of mucosa and submucosa. Extending from each plica, are numerous smaller leaflike projections, the villi, which are evaginations of the mucosa. Each villus consists of a core of lamina propria with an epithelial cell coating. Each villus contains capillaries, lacteal vessels (lymph vessels), nerves and some smooth muscle fibers. These are concerned with the absorption of digested foods and with movement of the villi, which aids in adsorption. Numerous lymphocytes, lymph nodules and other cells of the immune system are found in the lamina propria of the villi.

The villi are lined with columnar absorptive cells (enterocytes) and mucous secreting (goblet) cells. Microvilli on the surface of the enterocytes increase the surface area available for digestion and absorption, while the secretions of the goblet cells protect and lubricate the intestinal lining.

Glands of the SI. Between the villi are small openings of simple tubular glands called Crypts of Lieberkuhn. they are located in the mucosa, and do not extend into the submucosa These glands contain a variety of different cells, depending upon their location in the SI. Those in the duodenum contain Paneth cells and enteroendocrine cells, in addition to enterocytes and goblet cells. Additionally they contain cells which are capable of division, to replace cells which are constantly being shed into the lumen (cells of the villi have a life span of about 5 days). Paneth cells secrete lysozyme, and perhaps other enzymes. Enteroendocrine cells secrete a variety of hormones, which control the many and varied functions of the intestinal tract.

A couple of important regional differences and specialized functions should be noted:

Upper duodenum: Brunner's glands are found in the submucosa of the duodenum adjacent to the pyloric sphincter. These glands contain mucous cells which produce an alkaline, glycoprotein-rich secretion. The pH of this secretion is between 8-9 and it serves the dual function of neutralizing the acid pH of the chyme, and of protecting the duodenal mucous epithelium against the low pH of the gastric contents. Pancreatic enzymes work best at alkaline pH. Additionally the Brunner's glands release a hormone called urogastrone, which inhibits HCl secretion by the parietal cells.

Ileum: Peyer's patches are permanent lymphatic nodules which are found in the mucosa and submucosa of the ileum. These nodules show the characteristic germinal centers and cortical areas of lymph nodes.

Gastrointestinal hormones: The mucosa of the GI tract contains numerous cells producing a variety of peptide hormones. These cells are part of a larger endocrine cell system called the gastroenteropancreatic (GEP) system. These cells produce not only hormones, but paracrine substances, which diffuse locally to their target cells. Some of these are gastrin, cholecystokinin (CCK), secretin and gastric inhibitory peptide. The GI hormones are all polypeptides, and the endocrine cells which secrete them are of neural crest origin. this neuronal relationship is reflected by the fact that most GI hormones are also present in the CNS, with neurotransmitter-like propertied. Thus CCK is also found in the brain. Recent studies suggest that it may act on an appetite center in the hypothalamus, to reduce the appetite.

At the end of the SI lies the ileocolic sphincter, a projection of ileum into the colon, created by a thickening of the circular muscle. This sphincter reflexively contracts when the proximal colon fills up, thereby controlling the rate of release of the ileal contents.

The Large Intestine. The LI consists of the colon (ascending, transverse, descending), the appendix, the rectum and the anal canal. The 4 layers characteristic of the GI tract are present throughout, However, there are no plicae and no villi. Temporary folds are present. The luminal surface is smooth. Crypts of Lieberkuhn extend into the mucosa. These are lined with columnar absorptive cells and contain large numbers of goblet cells; in fact the further down the LI you go, the more goblet cells are present. Enteroendocrine cells are also present in the crypts. This organ is well suited to its main functions, which are the absorption of water, the formation of the fecal mass, and the secretion of mucus to lubricate the mucosal surface. In the colon, the outer longitudinal layer of the muscularis externa is arranged in 3 pronounced bands, the taenia coli, which can be seen at the gross level. The contraction of these, and of the circular muscle layer helps to move the fecal mass towards the rectum.

The appendix is a blind, fingerlike projection connected to the cecum of the LI. The lamina propria is filled with large masses of lymphoid nodules, which frequently extend into the submucosa. Since it is a blind pouch, it is prone to the accumulation of fecal material and is s common source of infection. In acute appendicitis, there is a neutrophilic exudation involving the wall of the appendix. Later there may be abscesses along with ulceration into the peritoneal cavity--peritonitis.

The rectum extends from the sigmoid colon to the beginning of the anal canal, and is similar in appearance to the colon, with an even greater number of goblet cells.

Anal canal. At the junction between the rectum and anal canal, the epithelium changes from simple columnar to stratified squamous (non-keratinized), indicative of the increased abrasion and stress put on this part of the GI tract during defecation. The inner circular muscle layer at the upper end of the anal canal is thickened to form the internal anal sphincter comprised of smooth muscle and under autonomic control. Farther down the anal canal, there is a change in the outer longitudinal muscle from smooth to skeletal muscle to form the external anal sphincter, which is (fortunately) under voluntary control. Finally, the lower portion of the anal canal joins with the external skin, covered with keratinized stratified squamous epithelium.

When food reaches the stomach after a period of some hours of fasting, gastric activity begins. At the same time, the lower bowel is advised to make room for materials which will soon arrive there. This occurs by means of the gastrocolic reflex, which initiates a mass movement of the colonic contents. That is why the urge to defecate usually comes after a meal, especially after the morning meal, when the bowels are very reactive after a rest.