8. Histology of the GI - Part 1 & 2

Describe the appearance of Chief Cells

- Chief Cells are found in the deeper area of glands - They are highly basophilic (purple/blue) due to the high concentration of RER for protein synthesis - They have very round and purple nuclei

Describe the appearance of the G/Enteroendocrine Cells

- Enteroendocrine Cells are found usually at the base of the Gastric Glands (so as to be close to the basolateral membrane and capillary bed) - They are packed with dense neuroendocrine granules near the base - They are small, round, and surrounded by a light rim of cytoplasm (a Halo) - Enteroendocrine hormones come in one of two types: 1. Closed - These cells do not reach the lumenal surface 2. Open - These cells have lumenal microvilli which act as chemoreceptors, triggering hormonal release when the presence of specific compounds are detected by the chemoreceptors

Describe the appearance of Goblet Cells

- Goblet Cells are found interspersed between the Absorptive Enterocytes of the villi's Simple Columnar Epithelium as well as in the crypts - Goblet Cells stain a deeper purple and redish pink than their neighboring cells - The look like sperm with oversized heads - They demonstrate striation within their cytoplasm - Of note, their job is to secrete mucous

Describe the appearance of Colonocytes

- Irregular apical microvilli - Large dilated intercellular spaces indicating active fluid transport - Tall, thin, eosinophilic cells

Describe the appearance of Microfold Cells

- Microfold Cells are found at the Lumen of the Small Intestine overlaying Lymphoid Tissue/Peyer's Patches - Microfold Cells do not demonstrate microvilli - Microfold cells demonstra basally directed invaginations of their cytoplasm that form an, "umbrella," over the underlying tissue

What are Plica Circulares? How do they relate to the histology of the Small Intestine? Where are they in the Small Intestine?

- Much like the Rugae of the Stomach, the Plica Circulares are folds in the wall of the Small Intestine composed of the Mucosa and Submucosa - Unlike Rugae, these structures are permanent and never flatten - The Plica Circulares are absent in the 1st part of the Duodenum but pick up afterwards and become denser and numerous into the Jejunum and Ileum before beginning to diminish towards the Terminal Ileum; this reflects the changing roles of the GI, as macronutrient processing and absorption of derivatives is replaced by water and electrolyte resorption

Describe the appearance of the Enteroendocrine Cells

- Neuroendocrine Cells are marked by their conic/open appearance - They contain dark Dense Core Granule in aggregate near the basolateral membrane

Describe the appearance of Paneth Cells

- Paneth Cells are found in the most basal (deepest) portion of the Intestinal Crypts - They demonstrate large eosinophilic (pink-red) secretory granules

Describe the histological appearance of the Ileum

- Poorly formed but present mucosal villi and crypts - No Plica Circulares are present - Aggregates of Lymphoid Cells, known as Peyer's Patches, are present in the Lamina Propria of the Mucosa and the Submucosa - Peyer's Patches are overlain by M Cells

Describe the histological appearance of the Jejunum

- Prominent Plica Circulares (Submucosa projects lumenally with the Mucosa) - The Mucosa demonstrates long and well formed villi - No Brunner's Glands or Peyer's Patches are present in the Submucosa - The Muscularis Externa is normal - The Serosa/Adventitia are normal

What are Rugae?

- Rugae, or Gastric Folds, are transient corrugations of both the mucosa and the submucosa of the Stomach that run along its length from the Body to the Pylorus. These corrugations are formed by the MM and when a large quantity of food is consumed the MM relax, allowing the Rugae to flatten out in order to accommodate the need for greater volume.

Describe the Epithelium of the Small Intestine Mucosa. List the Cell Types found within it.

- The Epithelium of the Mucosa varies in composition depending on location: 1. Villi - The Epithelium coating the villi is Simple Columnar Epithelium, composed of Absorptive Enterocytes & Goblet Cells* 2. Intestinal Crypts - Found between the Villi, the crypts are coated by Simple Columnar Epithelium composed of Paneth Cells, Enteroendocrine Cells, and Microfold (M) Cells (Also a few Goblet Cells) *- The # of Goblet Cells increases as you move down the Small Intestine

What is, "the basic plan," of the GI Tract?

- The GI Tract is a hollow tube with 4 common layers which run the entirety of its length. Those four layers are, inside out: 1. Mucosa 2. Submucosa 3. Muscularis Externa 4. Adventitia/Serosa

Describe the histology of the Gastroesophageal Junction

- The Gastroesophageal Junction is the physiologic sphincter that separates the two structures from each other. - Marked by the, "Z-Line," The Junction is the site of abrupt epithelial change from Stratified Squamous Epithelium (Esophagus) to Simple Columnar Epithelium (Stomach). Also, Gastric Pits begin inferior to this site as well - Of note, Mucous Producing glands present in the submucosa of the Esophagus continue on in the Submucosa of the Stomach until the end of the Cardiac region

Describe the histological appearance of the Duodenum

- The Mucosa are arranged into Villi and Crypts - The Submucosa in the 1st part of the Duodenum is rich with mucoid glands known as Brunner's Glands. Brunner's Glands secrete an alkaline mucous to counteract the acidity of the incoming Chyme - No Plica Circulares are visible - The Muscularis Externa is Normal - The Serosa/Adventitia are normal

How is the Mucosa organized?

- The Mucosa is organized into three different layers itself, from inside out: 1. Epithelium - The Epithelium is a protective lining whose composition will change with respect to the GI Region in which it is found. Cells which often compose it, either singly or in combination, are Stratified Squamous (strictly protective), Columnar (secretory), and Columnar w/t Brush Border (absorptive), among others 2. Lamina Propria - The Lamina Propria is a thin loose connective tissue beneath the Epithelium that contains the vasculature (capillaries), lymphatics (lacteals), nerves, and glands. This layer provides structural and nutritive support to the Epithelium 3. Muscularis Mucosa - The Muscularis Mucosa is a thin layer of smooth muscle which lies at the base of the Mucosa and serves to maintain the Mucosa's characteristic folding, an arrangement which increases surfaces area and so maximizes efficiency

Describe the Mucosa

- The Mucosa is the innermost layer and is responsible for executing the majority of the specialized function particular to each section of the gut (protective, acid production, mucous production, absorption, etc). As a result of its function, this layer demonstrates the clearest and widest variation from region to region along the GI Tract

Describe the Histology of the Gastric Pits & Glands

- The Mucosa of the Stomach is lined by invaginations of the Epithelium that are sectioned, from the surface to the depths as: 1. Gastric Pits 2. Gastric Necks/Isthmuses 3. Gastric Glands - While the epithelium of the Gastric Pits is composed primarily of Surface Mucous Cells which secrete a basic mucin containing substance, as one progresses downwards the composition of the wall changes, coming to include many specialized cells that are responsible for the specialized function of the Stomach - Of note, these glands can delve as deeply as the Muscularis Mucosa, but no further.

Describe the Muscularis Externa

- The Muscularis is the 3rd innermost layer of the GI Tract and is constitutively* composed of an inner circular smooth muscle layer, an outer longitudinal smooth muscle layer, and an autonomic plexus in between known as the Myenteric Plexus or the Auerbach Plexus - Of note, the Myenteric (myo = muscle, enteric = of the gut) Plexus is responsible for controlling the peristalsis of the gut and does so by combination of its own activity, input via synapses from preganglionic parasympathetic fibers, and the passage of postganglionic sympathetic fibers through it * - Except for the upper region of the Esophagus where skeletal muscle is present, in the stomach where an oblique layer is present, and in the Colon where the longitudinal layer is arranged into the classic Taenia Coli

Describe the Serosa/Adventitia

- The Serosa/Adventitia are the outermost layer of any region of the GI Tract. The application of the term Serosa or Adventitia depends on whether the section discussed is intra- or retro- peritoneal. - Adventitia is seen when organs are retroperitoneal and it is a thin connective tissue layer which blends with the character of the surrounding tissue - Serosa is seen when organs are intraperitoneal and is another name for the visceral peritoneum which ultimately reflects to become a mesentery or omenta.* * - Of note, Serosa is composed of Simple Squamous Epithelium, also known as mesothelium

Describe the Submucosa

- The Submucosa is the 2nd innermost layer of the GI Tract and is constitutively composed of a dense and irregular connective tissue that supports the larger blood vessels and lymphatic vessels from which the mucosal branches derive, as well as a collection of autonomic fibers and ganglia known as Meissner's Plexus* - In specific regions of the gut one can also find specialized glands and lymph nodules within the Submucosa * - Meissner's Plexus controls the perfusion of the GI Tract and does so by combination of its own activity, input via synapses from preganglionic parasympathetic fibers, and the passage of postganglionic sympathetic fibers through it

Does the morphology of the Pits, Necks, & Glands change across the Stomach? If so, how? If not, why not?

- The morphology of these structures does in fact change and does so in the following way: 1. Cardia - Short pits, coiled glands, and mucous is the primary secretion 2. Fundus & Body - Short Pits, long branched glands (3-7 per pit), and HCL, Pepsinogen, mucous, and neuroendocrine compounds are the primary secretions 3. Pylorus - Deep pits, shorter coiled glands, and mucous, gastrin, and somatostatin are the primary secretions - In essence, where acid might leave the stomach, the pits focus on producing protective compounds. In the middle of the Stomach the digestive compounds are produced

Describe the appearance of NMC's

- These cells line the Necks of the Gastric Glands - They are less columnar than their surface counterparts - They are found in clusters between Parietal Cells - They are NOT Parietal Cells

Describe the appearance of the Absorptive Enterocytes

- They form Simple Columnar Epithelium - They demonstrate a basal membrane nucleus - They demonstrate prominent apical villi and glycocalyx - They stain eosinophilic-ally (pink)

Describe the appearance of Parietal Cells

- They reside primarily in the neck between NMC's but can also be found in the deeper parts of glands - They are bright pink and look like, "proud fried pink eggs" - They are pyramidal, very eosinophilic (pink) and have round central nuclei - They are often studded with Canaliculi, microvillated invaginations of the membrane to increase surface area for H+ transport

What is the general function of the Large Intestine?

- To absorb water, to absorb ions, to concentrate feces, and to produce large quantities of mucus to facilitate its movement out

What is the general function of the Stomach?

- To begin the breakdown of proteins and fats by acidification, to begin the digestive process by release of enzymes, and to release substances which permit the uptake of key vitamins and minerals downstream

What is the general function of the Small Intestine?

- To neutralize the acidity of incoming chyme, to continue processing of macronutrients, and to absorb the derivatives of said process.

What is the general function of the Esophagus?

- To permit the passage of food from the mouth to the Stomach and rest of the GI Tract

Does the GI Tract change along its length? If so, in what way?

- While the tract maintains the same 4 layers throughout, each section of the gut will have special cell types within certain layers or unique arrangements of those layers which will reflect the special function characteristic of the given region

Describe the functions of each of the cells of the Mucosa

1. Absorptive Enterocytes - These cells are the majority cell of the Villi of the Small Intestine and use their Microvilli to aid in the process of nutrient absorption 2. Goblet Cells - These cells live across the entirety of the Small Intestine's Epithelial lining and are responsible for the release of Mucin and other mucid substances used to protect the Gut Wall from the damaging chemical components of the lumen and to lubricate the passage of food and waste through the GI Tract 3. Paneth Cells - These cells are secretory in nature and release granules filled with Lysozyme, Phospholipase A2, and Defensins, all of which are compounds of the Innate Immune System that break down bacterial cell walls 4. Enteroendocrine Cells - These cells are found in the Intestinal Crypts and use chemoceptors to detect nutrient and release hormones in response to their presence. For example, populations of EC's in the Duodenum release CCK in response to Lipids 5. Microfold (M) Cells - These cells overlie Peyer's Patches in the Small Intestine and serve to accept antigens from the lumen and deliver them to nearby Dendritic Cells which in turn facilitate T Helper Cell activation, which in turn trigger the appropriate B Cells to become Plasma Cells that secrete IgA for release into the Lumen

Describe the histology of the Stomach

1. Mucosa - Lined primarily by Simple Columnar Epithelium* and arranged into "Gastric Pits," which lead to, "Gastric Glands," which are all surrounded by Lamina Propria. Depending on the area of the region of the Stomach, the pits and glands take on different proportions 2. Submucosa - Small mucous secreting glands can be found in the cardia but otherwise it is composed, as usual, of vasculature and nerves (lymphatics mostly come in the lower GI) 3. Muscularis Externa - 3 layers of smooth muscle are present, the Inner Oblique, Middle Circular, and Outer Longitudinal 4. Adventitia/Serosa - The Stomach is intraperitoneal ; thus, the Stomach has Serosa *- Depending on the region of the Stomach, the Epithelium will be studded with specialized cells amongst the Simple Columnar Epithelial cells

Describe the histology of the Esophagus

1. Mucosa - Stratified squamous non-keratinized epithelium 2. Submucosa - Small mucus secreting glands present, otherwise normal. These glands are responsible for allowing food to slide down the tube 3. Muscularis Externa - Upper 1/3 is entirely skeletal, middle 1/3 is mixed, and lower 1/3 is entirely smooth 4. Adventitia/Serosa - The Esophagus is Retroperitoneal with the exception of the last 3/4 of an inch; thus, the Esophagus has adventitia for its length except for the distal 3/4 of an inch, which is Serosa

Describe the histology of the Small Intestine

1. Mucosa - The Mucosa is marked by two prominent microstructures; projections of the Lamina Propria outwards into Villi and invaginations deep into the deep Lamina Propria near to the MM forming Intestinal Crypts. Both the projections and the invaginations are covered with Epithelium whose composition varies by location in the Mucosa* 2. Submucosa - Mucous secreting glands can be found in certain regions of the Small Intestine, as well as lymphoid cells**, but otherwise it is composed, as usual, of vasculature, nerves, and lymphatics which serve the overlying Mucosa* 3. Muscularis Externa - 2 layers of smooth muscle are present, the Inner Circular and the Outer Longitudinal 4. Adventitia/Serosa - The first part of the Duodenum, the Jejunum, and the Ileum are intraperitoneal while the 2nd, 3rd, and 4th sections of the Duodenum are retroperitoneal; thus, the 2nd, 3rd, and 4th parts are surrounded by Adventitia while the remainder is surrounded by Serosa * - See Plica Circulares ** - These lymphoid cells are known as Peyer's Patches, they run from the Submucosa to the Mucosa, and they only begin to appear in the Ileum

Describe the histology of the Large Intestine

1. Mucosa - The mucosa is marked by a flat and absorptive surface pocked with a multitude of epithelial invaginations deep into the Lamina Propria. Simple Columnar Epithelium lines the surface and the crypts and is composed of Colonocytes (absorptive), Goblet Cells*', and Enteroendocrine Cells'. At the bases of the Crypts lie stem cells for all other epithelial cell types. Also within the Mucosa lie Lymphoid Nodules which are located in the Lamina Propria 2. Submucosa - The Submucosa does not participate in any folding and is a flat layer deep to the Mucosa providing structural support and passage for the Meissner's Plexus, Arterioles, and Venules which supply the capillary beds and Muscularis Mucosa above 3. Muscularis Externa - The Muscularis Externa is almost identical to that of the Small Intestine with one exception; while the layers are the same, the Outer Longitudinal Layer is banded in a characteristic pattern known as Tenia Coli 4. Serosa/Adventitia - The Large Intestine begins as Intraperitoneal with the Cecum, but after that alternates by section; thus, the outermost layer varies with the gross anatomy * - Goblet Cells become more and more numerous the closer to the Rectum you go '- Of note, these cells are identical in appearance to those found in the Small Intestine

List the cell types of the Pits, Necks, and Glands and describe their functions (Cells of the Epithelium)

1. Surface Mucous Cell (SCE) - These line the Pit primarily (but also the Neck somewhat) and secrete an alkaline-mucin fluid which protects the cells of the glands from being digested by the acid and enzymes they secrete 2. Mucous Neck Cells - These line the Neck primarily and secrete an acidic-mucin fluid 3. Parietal Cells - These reside in the Neck and Gland and secrete HCL, Bicarbonate*, & Intrinsic Factor. Of note, exposure of PC's to Gastrin triggers the production of its secretory products 4. Stem Cells - These cells reside in the Neck and differentiate, growing up or down, into all the cells of the Neck, Pit, and Gland 5. Chief Cells - These reside primarily in the Gland and secrete Pepsinogen & Gastric Lipase 6. G Cells - These are interspersed among the cells of the Gland and are enteroendocrine cells which secrete Gastrin and a variety of hormones (each subtype of G Cell secretes a particular hormone) which can affect nearby cells, nearby neurons, or adjacent sections of the gut via the capillary beds. These cells regulate peristalsis, motility, enzyme, water, and ion secretion, and hormones which trigger satiety * - Bicarbonate is released from the basolateral membrane where it is taken up by the Submucosal Capillary network and delivered to SMC's which add it to the mucous layer, thus increasing its protective capacity

From what region of the GI was the this slide obtained?

1st part of the Duodenum: Brunner's in SM, Villi at top

From what region of the GI was the following slide obtained?

Descending Colon: Lymph Tissue (only found in the Ileum and Colon, lots of Goblet Cells

To what does the black arrow point?

LP in Villus. Notice the deep MM

Is the following cell type a Goblet Cell, Paneth Cell, Neuroendocrine Cell, Colonocyte, or Mucous Neck Cell?

Paneth Cell: Eosinophilic Granules, near the base

What is the function of the cell indicated by the arrow?

The cell is Enteroendocrine: Halo in the cytoplasm, closed appearance, aggregation at the base