Histology of the Digestive System I Oral cavity, and

N. Swailes, Ph.D. Department of Anatomy and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected]

Required reading

Mescher AL, Junqueira’s Basic Histology Text and Atlas, 12th Edition, Chapter 15: pp249-259 Ross MH and Pawlina W, Histology: A text and Atlas, 6th Edition, Chapter 16: pp526-567

Learning objectives

1) Recognize and name the major layers and components of the generalized gut tube.

2) Examine oral mucosa and determine how it is structurally different from both skin and the generalized gut tube.

3) Determine that different regions of the oral cavity have different types of oral mucosa and these are reflective of the function of each region.

4) Identify the histological features of the esophagus and explain the functional role of each in the process of digestion.

5) Identify the histological features of the stomach and explain the functional role of each in the process of digestion.

Key terms

mucosa esophageal cardiac gland parietal (oxyntic) cell esophageal gland intrinsic factor Meissner’s plexus stomach chief (zymogenic) cell muscularis externa cardia pepsinogen Auerbach’s (myenteric) fundus pepsin plexus body rennin/chymosin somatostatin serosa gastric pit ghrelin oral cavity gastric gland gastrin masticatory mucosa cardiac gland D-cell specialized mucosa principal gland G-cell lining mucosa pyloric gland Ghr-cell lingual papilla surface mucous cell esophagus neck mucous cell cardio-esophageal junction

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Introduction During this lecture you will discover the general structure of the digestive tract and examine the first part of the digestive tract where the primary role is mastication.

A1: General structure of the digestive tract

A. Mucosa The mucosa is composed of an epithelium and its basement membrane, the underlying and a muscularis mucosa.

1. Epithelium - is either stratified squamous (protective) or simple columnar (absorptive). - may contain specialized cells that impart specific functional properties to a region. - often invaginates to form glands for secretion. - often evaginates to form ‘villi’ to maximize surface area for absorption.

2. Lamina propria - composed of loose irregular connective tissue - contains blood vessels, lymphatic vessels and glands - has Mucosa Associated Lymphoid Tissues (MALT) in the form of lymphoid nodules.

3. - is a layer of that moves independently of the muscularis externa. - it is absent from the oral cavity and .

1

A 2 3

B 4

5

C 6

7

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D 8

B. Submucosa A region of dense irregular connective tissue which contains the blood vessels and lymphatic vessels that supply and drain the lamina propria. In addition to glands and MALT it contains:

4. Meissner’s (submucosal) plexus - contains sympathetic fibers and post-ganglionic parasympathetic neurons (ganglion cells) - innervates muscularis mucosa, secretory and sensory cells of the epithelium.

C. Muscularis externa

5. Inner circular - typically a layer of smooth muscle - oral cavity and esophagus are completely or partially composed of skeletal muscle instead.

6. Auerbach’s (myenteric) plexus - located between the two layers of m. externa and innervates them. - it has the same components as Meissner’s plexus.

Clinical Correlation: Hirschprung disease Hirschprung disease is a congenital disease (the ganglia are derived from the neural crest) of the bowel where Meissner’s plexus and Auerbach’s plexus are absent from a length of the distal colon As a result there is an imbalance of smooth muscle contractility in the affected region of bowel and it is unable to relax. The result is extreme constipation and dilation of the region proximal to the affected bowel (e.g. megacolon). Treatment involves surgical resection of the affected area.

7. Outer longitudinal - typically a layer of smooth muscle. - oral cavity and esophagus are completely or partially composed of skeletal muscle instead. - forms a thickened region of skeletal muscle in anal canal called the .

Note: The stomach has an additional oblique layer of smooth muscle in its externa.

D. Serosa or Adventitia The outer region of the gut tube consists of loose irregular connective tissue.

- if the region of the tube is covered in peritoneum, the peritoneal mesothelium can be seen adhered to this connective tissue and it is termed a ‘serosa’. - if the region of the tube is retroperitoneal the mesothelium will be absent and the layer is termed an ‘adventitia’.

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A2: Oral cavity

The oral cavity is the site of mastication, mixing of food with saliva and commencement of the breakdown of carbohydrate. It is composed of the following areas:

1. Hard palate 2. Soft palate 3. Tongue 4. Teeth 1 5. Gingiva (gums) 6. Lip 2

A. Oral mucosa There are three regions of oral mucosa (stratified squamous epithelium + lamina propria) found in the oral cavity: 3 1. Masticatory - keratinized or parakeratinized - withstand the forces of chewing 4 - hard palate and gingiva

2. Specialized 5 - keratinized with papillae - dorsal surface of the tongue

3. Lining 6 - non-keratinized - robust and flexible - cheeks, inner lip, soft palate etc.

** Note that oral mucosa DOES NOT have a Clinical Correlation: Aphthous stomatitis muscularis mucosa! Aphthous stomatitis (also known as canker sores) occur only in lining mucosa (non-keratinized). The cause of these ulcers is unknown but citrus fruits, physical trauma and stress have been implicated in Clinical Correlation: Oral squamous cell carcinoma their development. Oral squamous cell carcinoma affects around 30,000 Americans each year. It can occur anywhere in the oral cavity, but it is most common in certain areas of Clinical Correlation: Cold sores the lining mucosa: floor of the mouth, ventral and Cold sores are a result of herpes simplex virus-1 lateral surfaces of the tongue and the soft palate. The infection which only occurs in keratinized chief risk factors for this cancer are smoking and epithelium. It presents as visible sores or ulceration. alcohol use. Surgery and radiation therapy are the A cure for the condition has not been developed. treatments of choice. Once infected the virus remains in the body for life

and recurrent outbreaks may occur.

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B. Tongue The tongue is composed mostly of intrinsic skeletal muscle fibers arranged in longitudinal, transverse and vertical bundles. Its dorsum is covered in 1 specialized mucosa and the remainder is covered in lining mucosa.

Lingual papillae

1. Filiform - most numerous 2 - no taste buds - very thick keratin layer

2. Fungiform - less numerous and irregularly arranged - contain taste buds - lightly keratinized

3. Circumvallate - 7-12 papillae in front of terminal sulcus 3 - contain taste buds - serous glands of von Ebner cleanse taste buds

4. Foliate - poorly developed in humans - contain taste buds - located in postero-lateral surface of tongue

Taste buds Specialized regions of the oral mucosa that contain: 4

5. Taste pore - molecules dissolved in saliva enter the taste pore

6. Gustatory microvilli - bind to receptors on the gustatory microvilli

7. Gustatory cell 7 - depolarizes the gustatory cell 6 9 8. CN VII (chordae tympani) or CNIX - transmit signals to the brain 5

9. Basal cell - stem cell population that replaces old/damaged gustatory cells 8 10. Serous glands of von Ebner (not shown) - secretions from these submucosal glands wash away food particles around the taste buds so that they can process new uncontaminated tastes 5 | Page: Digestive Histology Part 1 Swailes

A3: Esophagus

The esophagus is a muscular tube through which food is carried from the to the stomach.

i. Mucosa

1. Non-keratinized stratified squamous epithelium 1 - resists abrasive forces of bolus during swallowing.

2. Lamina propria 2 Loose irregular connective tissue containing:

Cardiac esophageal glands (not shown) - mucous secreting glands located in distal region of the esophagus near stomach.

Lymphoid aggregates (not shown) - MALT (Mucosa Associated Lymphoid Tissue

3. Muscularis mucosae - typical layer of circumscribing smooth muscle. 3

ii. Submucosa Dense irregular connective tissue containing:

4. Esophageal glands - small mucous-secreting glands - lubricates epithelium and assists in the 4 passage of the bolus.

iii. Muscularis externa

5. Inner circular muscle 6. Outer longitudinal muscle 5 Note the type of muscle in the esophagus varies: rd - upper 1/3 is skeletal only. 6 - middle 1/3rd is mixed smooth and skeletal. - lower 1/3rd is smooth only.

This organization reflects the fact that swallowing begins with a controlled motion (skeletal) and progresses to involuntary peristalsis (smooth).

iv. Adventitia/Serosa

7. Mesothelium (or not) At the esophageal hiatus (T10) the esophagus becomes covered in peritoneum (mesothelium) this is a serosa. Above this, there is no mesothelium just 7 connective tissue, this is an adventitia.

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B A4: The Stomach

The stomach is responsible for both mechanical and chemical digestion. It continues the digestion of carbohydrates, initiates the digestion of proteins and A produces the viscous chyme. D There are four distinct regions of the stomach: A. Cardia B. Fundus C. Body C D. Pylorus

Organization of the stomach wall

i. Mucosa

1. Simple columnar epithelium - produce neutral pH mucous - protects cells from enzymes/acid

2. and - tubular infoldings of the epithelium (pits) that receive acid and enzyme secretions from branched tubular glands (see later).

3. Lamina propria - contains the gastric pits and glands 1

4. Muscularis mucosae - thin circumscribing smooth muscle.

2 ii. Submucosa - typical dense irregular CT layer 3 - thrown into folds called rugae that allow distension of the stomach 4 iii. Muscularis externa 5. Inner oblique smooth muscle 5 6. Middle circular smooth muscle - thickens distally to form pyloric sphincter. 6

7. Outer longitudinal smooth muscle 7 The additional layer of oblique smooth muscle perhaps reflects the extent of churning and mixing the stomach performs during digestion. 8 iv. Serosa 8. Mesothelium - the stomach is peritonized and therefore has a thin CT layer covered with mesothelium. 7 | Page: Digestive Histology Part 1 Swailes

Structure of a principal gastric gland The principal gland is the most common gland in the stomach. (Note: the other types of gland pyloric and cardiac are discussed later).

i. Gastric pit The gastric ‘pit’ portion is the initial straight infolding of the epithelium. It is lined by: i. pit 1. Surface mucous cells - are columnar epithelial cells specialized 1 for secretion. - protect mucosa from self-digestion. 2

ii. Gastric glands Branched tubular glands with a neck and base 3 located in the lamina propria of the mucosa. neck The cells in this region can be identified as:

2. Neck mucous cells - secrete mucus to protect mucosa from ii. gland self-digestion.

3. Parietal (oxyntic) cells 4 - found in the upper portion of the gland. base - are large round cells with central nucleus - stain intensely eosinophilic due to the 5 concentration of mitochondria. - secrete HCl and intrinsic factor.

Clinical Correlation: Helicobacter pylori Clinical Correlation: Pernicious anemia H. pylori is a gram-negative bacterium found in the Pernicious anemia is a megaloblastic anemia which stomach of many patients with gastric ulcers. It is is the result of impaired DNA synthesis in remarkable that this bacterium can survive the acid erythrocytes during hematopoiesis. Vitamin B-12 is conditions of the stomach. It does so by using its required during this process but it is not readily helical shape and flagellum to burrow into the absorbed by the gut and must first bind to an mucus on the surface of the stomach. Once in the intermediary glycoprotein called intrinsic factor to mucus it produces large amounts of the enzyme facilitate its absorption. IF is produced by parietal urease which breaks down urea to surround itself in cells in the stomach. a cloud of its alkali byproducts - bicarbonate and In cases of atrophic gastritis (chronic inflammation ammonium. The immune response to H.pylori of the stomach mucosa) parietal cells are destroyed results in inflammation of the stomach lining and and IF production impaired resulting in decreased the area becomes prone to acid and enzyme Vit-B12 uptake and impaired erythrocyte damage resulting in a gastric ulcer. production.

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4. Chief (zymogenic) cells - are located in lower portion of gastric gland - stain intensely basophilic - secrete pepsinogen and rennin/chymosin

Pepsinogen - inactive ‘zymogen’ of the proteolytic enzyme pepsin - constructed inside the cell in this way to avoid digesting the cell's own proteins. HCl - activated once safely outside the cell when HCl cleaves extraneous 44 amino acids to reveal active site.

Rennin/Chymosin - chymosin is produced by chief cells in infant mammals - curdles and coagulates milk to maximize digestion time - rennin (not renin) extracted from stomach of infant calves is the authentic method of producing cheese

5. Enteroendocrine cells - form part of the diffuse neuroendocrine system - are difficult to detect with traditional H&E staining. - release hormones into blood vessels of the lamina propria in the stomach which have varying regulatory effects on the digestive processes.

G-cells - located in the body and pylorus of the stomach. - release gastrin in response to presence of protein in the stomach.

Gastrin: - increases the secretions from parietal cells - increases secretions from chief cells - increases contraction of m. externa (gastric motility).

D-cells - located in the pylorus of the stomach. - release somatostatin in response to increased acid in the stomach.

Somatostatin - targets G-cells to inhibit the release of their hormones.

Ghrelin cells - Located in the body of the stomach. - Release ghrelin in response to fasting conditions when glucose - levels decrease.

Ghrelin - targets the hypothalamus to increase appetite.

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Comparing gastric glands

The appearance of the gastric glands and the cells present can vary depending on the region of the stomach observed (we already saw that different neuroendocrine cells were present in different regions).

1. Cardiac glands - are located in the cardia of the stomach. - have short gastric pits. - have long, coiled gastric glands. - contain primarily mucous secreting cells. - protect the mucosa from acid/enzyme damage and provide lubrication as food enters stomach.

2. Principal glands (see previous) - are located in fundus and body. - have short gastric pits - have long, often branched, gastric glands - contain mucous, chief and oxyntic cells - contain neuroendocrine cells that release gastrin and ghrelin

3. Pyloric glands - are located in the pylorus of the stomach. - have long gastric pits. - have short coiled gastric glands - contain primarily mucous secreting cells. - protect the mucosa from acid/enzyme damage and lubricate en route to the . - contain neuroendocrine cells that release gastrin and somatostatin.

2 3 1

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A5: Mystery Tissue

Using your knowledge of digestive system histology so far, can you identify the precise location from which the section below was taken and explain the reasoning behind your answer.

Clinical Correlation: Barrett’s esophagus Barrett’s esophagus is a metaplasia (change in form) of the epithelium lining the inferior aspect of the esophagus. The normal stratified squamous epithelium is replaced by patches of metaplastic columnar epithelium normally seen in more distal parts of the digestive tract. It is thought to be the result of an adaptive change from the chronic exposure to stomach acids and enzymes during reflux esophagitis. The condition is a premalignant condition. It may appear histologically similar to the gastro-esophageal junction.

METAPLASIA = a (reversible) change in form in response to an abnormal stimulus

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