Gi Histology Lectures I & Ii Final Version

The gastrointestinal tract (GI) can be considered as a hollow tube extending from one end of the body to the other.

The GI tract starts with the oral cavity (discussed in separate lecture) and continues with the esophagus, the stomach, the small intestine, and the large intestine (Figure 1).

Although these organs have different functions, they have the same general histological plan (Figure 2).

Mucosa:
-All the regions of the GI Tract possess a lining epithelium that lines the lumen of each region.

-This lining epithelium may be protective (esophagus), secretory (stomach), and/or absorptive (small intestine) in function.

-Under the lining epithelium is a region of connective tissue that is called the lamina propria (a general term given to any connective tissue under a lining epithelium).

-Under the lamina propria, there is a region of muscle called the muscularis mucosa.

-Together, these three regions - the lining epithelium, the lamina propria and the muscularis mucosa - make up the lining mucus membrane.

The esophagus is a tube (approximately 25 cm long) running from the pharynx to the stomach. Food is propelled along the esophagus (at a rate of about 5 cm/sec) by voluntary muscular action in the oral cavity followed by involuntary waves of muscle contraction (i.e., peristalsis) in the walls of the esophagus

-needs to put up with roughage from oral cavity --> stomach, so it's lined by a protective epithelium (yellow arrow). This is a nonkeratinized stratified squameous epithelium that protects the esophagus from ABRASIVE damage.
-Outside the body, have protective epithelium but it's keratinized. Inside in wet body cavities usually nonkeratinized

-This is a cross section through the esophagus

-What is the dark stuff? This is part of the lining of the epithelium. It is dark because they're mitotic because the cells lining the lumen constantly need to be replaced
-The GI Tract is actively replaces all the time, which is why it's so sensitive to chemotherapy (kills mitotic cells)
-Have a lymphatic nodule on left
-Then have mucosal glands

Under the non-keratinized squamous epithelium one finds the lamina propria. Under the lamina propria are the muscularis mucosa, the submucosa, and the muscularis externa. Most of the esophagus is surrounded by an adventitia.

-Lining epithelium
-All the dots are the nuclei/lining cells
-Basophilic cells
-Muscularis externa

-Lining epithelium
-Nuclei coming to surface
-Basophilic / dividing cells underneath that
-Lamina propria
-Muscularis mucosa
-Lining mucosa = Submucosa the lining epithelium, the lamina propria and the muscularis mucosa - make up the lining mucus membrane
-Muscularis externa.
-Yellow arrows pointing to the mitotic cells

-microplicae on the surface
-surface of esophagus

-TEM of surface lining of esophagus
-cross sections are microplicae
-they are thin sections through the cell
-the B is pointing to bacteria
-the arrows point to microplicae
-there is a mitochondria that can be seen
-nonstratified squameous epithelium
-has organelles in it all the way to the surface

-basal cells
-these are mitotic cells that are producing new cells and displacing others to the surface
-very active cells

Meissner’s plexus
-arrow points to ganglionic cell body in the submucosa

-Note the two layers of muscle and the large ganglionic cell bodies of Auerbach’s plexus that stimulate the two layers of muscle to undergo peristaltic waves to move things down the esophagus

Junction of esophagus with stomach

Glands of the Esophagus:
There are two types of glands in the esophagus.
1. The first type, termed the Submucosal Glands, is found in the submucosa throughout the length of the esophagus. These glands lubricate the esophagus by secreting a protective mucin.
2. The second populations of glands of the esophagus are called Cardiac Glands. These are located in the lamina propria of the lining mucosa at two different sites: at the junction of the esophagus and the stomach (these glands are similar to glands found in the cardiac portion of the stomach, hence, the name) and between the cricoid cartilage and the fifth tracheal ring. The cardiac glands also secrete a protective mucin.

When food enters the stomach, it is churned and mixed with the digestive enzymes and after 3-4 hours it is transformed into a semi-fluid known as chyme. Very little absorption occurs in the stomach; some water, alcohol and drugs are absorbed in the stomach, but mainly the function of the stomach is digestion (breaking down of the food products).

Anatomically, the stomach is divided into four regions: the cardiac portion, the fundus, the body, and the pyloric portion. If one were to cut into the stomach and observe the lining, it will appear grayish-pink. One would also see very large folds along the surface of the stomach that run in a longitudinal direction. These large folds, which involve both the lining mucosa and the submucosa, are known as Rugae.

Glands are different in the different regions of the stomach. In the cardiac region, they are called cardiac glands.
In the fundus and in the body, the glands are essentially the same and are simply called gastric glands (or fundic glands).
In the pyloric region, they are called pyloric glands.

The muscularis externa is unique in that in addition to the inner circular layer and the outer longitudinal layer there is an inner oblique layer of muscle. This additional layer makes the muscularis externa very thick and facilitates the churning action of the stomach. Finally, the stomach is surrounded by a serosa.

NOTE: NO GLANDS IN THE SUBMUCOSA. THEY'RE ALL CONFINED TO THE LAMINA PROPRIA

-This shows the surface of the stomach via SEM

• If you look closely at the surface of stomach also have thousands of little pits all over the surface of the stomach – these are gastric pits

-at the black arrows you can see the gastric pits

-you can also see the outlines of the surface cells that pucker up into the lumen

-the gastric pits are continuous with the underlying glands. 3-7 gastric glands empty into gastric pits that let out digestive enzymes out into the stomach to mix with foodstuff

-white is protective mucin

-Gastric Glands: About 3-7 glands empty into each gastric pit. Lining the surface of the stomach one finds tall columnar surface mucus cells. These lining mucus cells extend into the gastric pit. The surface mucus cells have mucin granules in their apical cytoplasm that is released to provide a protective coat over the surface of the stomach. The lining cells are continuously being sloughed off and are replaced by the division of cells deep in the gastric pits about every 3-4 days.

The glands themselves are divided into three different regions - the mouth (the opening), the neck (the constricted region), and the base (the rest of the gland).

-simple columnar epithelium with mucin
-have muscularis mucosa
-submucosa – NO GLAND
-note sections through the glands
-arrows show gastric pits

-note the neck and base of the gland
-the main cell type is the chief cell type (pepsinogen, intrinsic factor) all the blue cells! Filled with secretory granules, but they have a tendency to be leeched out so you get foamy appearance
-lumen of stomach at the top
-other cells are parietal cells making HCL and intrinsic factor

In the CARDIAC REGION OF THE STOMACH:
o In base have the chief cells – synthesizing and producing pepsinogen
o The 2nd major cell type is an UNUSUAL CELL – look pink in H&E .. round with deep invaginations lined w microvili and have mitochondria. These cells are synthesizing and secreting HCL – called parietal cells also make INTRINSIC FACTOR – helps with vitamin B12
o A third cell type usually confined to neck, make mucus – the MUCUS NECK CeLLS
o Have enteroendocrine cells – these cells do not show up well in H&E prep but show up well with silver stains. Also been called argentivin cells (bc of affinity for silver stain). Need to know both names. – GREEN circles

He loves this pic

1. Chief Cells: The major cell type found in the gastric glands is called the Chief Cell. These pyramidal shaped chief cells are found mainly in the base of the gland. They are filled with RER and Golgi and are active zymogenic cells. They actively secrete the proteolytic enzyme pepsinogen that is exocytosed into the lumen of the gland. When pepsinogen reaches the acidic environment of the stomach (pH of 2-3), it is cleaved into its active form, pepsin. Pepsin is important in breaking peptide bonds.

2. Parietal Cell (PINK CELLS -- filled w/ membrane -- tubular vesicular elements; mitochondria): The Parietal Cell is a unique cell. It is a roundish cell that is filled with mitochondria and tubular vesicular elements (similar to SER). It has deep invaginations termed canaliculi. The canaliculi are lined with microvilli. Because this cell is filled with membrane it is very eosinophilic (i.e., stains pink with H & E stain). The parietal cell is responsible for secreting HCL. In addition to HCL, the parietal cell secretes the intrinsic factor which binds to vitamin B12 and facilitates the absorption of this particular vitamin (which can lead to pernicious anemia if not absorbed).

3. Mucus Neck Cell: This third type of cell found in the gastric gland is sometimes difficult to find on histological slides. These cells are confined to the neck region of the gastric gland, are frequently squeezed between parietal cells, and secrete an acetic mucin (as compared with the neutral mucin of the lining mucus cells).

4. Enteroendocrine Cells: These represent a diverse population of endocrine cells found along the sides of the gastric glands. Their product is not secreted into the lumen of the gastric gland, but into the surrounding blood vessels of the lamina propria. These enteroendocrine cells ("entero" referring to the fact that they are found in the gut) produce a wide variety of hormones that are released into the circulation. These cells are found throughout the length of the small intestine as well as in the stomach. Because these cells have a unique affinity for silver salts, they have also been referred to as argentaffin cells.

In the CARDIAC REGION OF THE STOMACH:
o In base have the chief cells – synthesizing and producing pepsinogen
o The 2nd major cell type is an UNUSUAL CELL – look pink in H&E .. round with deep invaginations lined w microvili and have mitochondria. These cells are synthesizing and secreting HCL – called parietal cells also make INTRINSIC FACTOR – helps with vitamin B12
o A third cell type usually confined to neck, make mucus – the MUCUS NECK CeLLS
o Have enteroendocrine cells – these cells do not show up well in H&E prep but show up well with silver stains. Also been called argentivin cells (bc of affinity for silver stain). Need to know both names. – GREEN circles

Transmission EM

Higher magnification of a parietal cell
these cells are unique, make HCl

Diagram of a parietal cell, showing the main steps in the synthesis of hydrochloric acid. Blood CO2 under the action of carbonic anhydrase produces carbonic acid. This dissociates into a bicarbonate ion and a proton, H+, which reacts with the chloride ion to produce hydrochloric acid. The bicarbonate ion returns to the blood and is responsible for a measurable increase in blood pH during digestion.

-The two extreme ends of the stomach (cardiac and pyloric) are lined w cells like the neck cells, find very few other cell types BUT the two sections look different
cardiac pits are more shallow and straighter than in the pyloric region
note in pyloric region you cant get straight sections through them because they’re all convoluted

In the CARDIAC REGION OF THE STOMACH:
o In base have the chief cells – synthesizing and producing pepsinogen
o The 2nd major cell type is an UNUSUAL CELL – look pink in H&E .. round with deep invaginations lined w microvili and have mitochondria. These cells are synthesizing and secreting HCL – called parietal cells also make INTRINSIC FACTOR – helps with vitamin B12
o A third cell type usually confined to neck, make mucus – the MUCUS NECK CeLLS
o Have enteroendocrine cells – these cells do not show up well in H&E prep but show up well with silver stains. Also been called argentivin cells (bc of affinity for silver stain). Need to know both names. – GREEN circles

• The glands in the pyloric and cardiac region are similar, more simplex
o Find few parietal or chief cells, but find lots of cells like the mucus neck cells at the two extreme ends of the stomach

No glands found in submucosa of stomach
now we’re talking about the intestines
foodstuff stays 3-4 hours in stomach + digestive enzymes = chyme
chyme goes to small intestines
this is where we get most of biproducts of digestions and further digestion

-3 sections of intestine: duodenum, jejunum, and ileum
-the first part is 10 inches, jejunum is 2/5 and ileum is 3/5
-in the first portion of the intestines is where you get the rest of the digestive enzymes from the pancreas as well as bile being released into the duodenum
-get these proteolytic lipolitic and carb splitting enzymes
-in order to facilitate absorption, the small intestine tries to increase the surface area. It does this in a couple ways. It’s LONG about 20 feet long.
-It also has very large folds involving lining and submucosa that run ina circular pattern around the intestines
-begins in the duodenum and goes down the length of the ileum
– this are called the plicae circularis
– large macroscopic folds
-then you find this little villus like progestions .5 mm in projection just mucosa
- these are intestinal villi
-most of products of digestion are absorbed in the small intestine

Transition from stomach to duodenum

Duodenum jejunum and ileum have both subtle and major differences
-intestinal villi can take on different shapes and densities: in the duodenum the intestinal villi are broad and leaf shaped (like his hand?) and they are very numerous. A lot are found here back to back
-as you move to jejunum and ileum they become more slender and finger shaped and less numerous
__
A. The intestinal villi are more prominent in the first portion of the small intestine; they are broad and leaf shaped. As one moves down the length of the small intestine, through the jejunum and most of the ileum, they become more slender and less numerous. This is a subtle change.

B. There is an increase in the relative number of goblet cells to the intestinal absorptive cells as one passes through the length of the small intestine. This, too, is a subtle change.

C. There are, however, some characteristics that enable one to distinguish duodenum from ileum. In the first portion of the duodenum there is a prominent population of branched mucus glands, located in the submucosa. Among other things, these glands secrete an alkali mucin that neutralizes the acidic chyme from the stomach. These glands, known as Brunner's Glands, are an identifying feature of the duodenum.

D. With respect to the ileum, there is a very prominent population of lymphatic nodules known as Peyer's Patches. They are an identifying histological feature of the ileum.

The small intestine increases the surface area available for absorption in a number of ways. First, is the formation of large folds called the plicae circularis. The plicae circularis involve both the lining mucosa and the submucosa and run in a circular pattern around the lumen of the small intestine. The plicae begin towards the end of the duodenum and are most prominent in the jejunum; they disappear about half way through the ileum. Second, there are little folds or projections, involving only the lining mucosa, that are termed intestinal villi. The intestinal villi are about a half to a millimeter and a half in height.

Brunner’s glands – mucus glandsnote stomach duodenum and muscularis mucosa

SEM looking down surface of duodenum – note broad back to back intestinal villi
-if you look closely at this, can note that at arrows point to cervices. These are NOT static structures. They are moving up and down! Why? Because in the center of each of these villi are a blind ending lymphatic that receives chylomicrons with fats in it
-lymphatics has to move via surrounding muscle
-blind ending lymphatic here gets filled with chylomicron and becomes milk white so they’re called the CENTRAL LACTEALS

-this is higher magnificationat top microvillous brush border
-mucin is leeched out of goblet cells so they appear clear (black arrows)
-in the middle in white is the central lacteal

-this is higher magnificationat top microvillous brush border
-mucin is leeched out of goblet cells so they appear clear (black arrows)
-in the middle in white is the central lacteal

More details
-looking in between two villiin between yellow arrows is the microvillous brush border. Beneath purple hare elongated nuclei of columnar cells
-black arrows to goblet cells 

-what are at red arrows?
Lymphocytes! Underneath is connective tissue of lamina propria

This is a TEM of same thing – black arrow shows microviluos brush border

then have tall coluimnar cells
they are held together very closely

note lots of organelles connective tissue at bottom

Microvilli being supported by actin filaments
cell border between yellow arrows is complex

-This shows at high magnification the surface of the small intestines with SEM

-looks like shag rug – microvillous cell border

-also notice the shape of the cells!

-See that its pentagonal/hexagonal in shape?
This is so they can fit together!

This is a goblet cell full of mucin and then have absorptive cell on either side.

This is looking down into intestinal glands – cryps of liberkuhn
basal part of cells have MM and connective tusse
arrow shows you panneth cells

The intestinal glands (i.e., Crypts of Lieberkuhn) are lined by goblet cells and intestinal absorptive cells. Enteroendocrine cells are also found along their lateral borders. At the bottom of the gland is a prominent population of zymogenic cells. These cells, called Paneth Cells, contain large refractile granules in their apical cytoplasm that stand out as a histological feature. Despite their obvious occurrence, little is known about the Paneth cells except that their granules contain a lot of zinc and an enzyme known as lysozyme which lyses certain kinds of bacteria

Panneth cells
-prominent feature is on base of cells ? 
-Associated with these glands find another cell type! They are not found lining the inside, but they’re on the outside and they are endocine – the enteroendocrine cells are on the periphery here but not showing up bc they have affnity for silverstain
-find enteroendocrine cells and panneth cells in small intestines****

Panneth cells at bottom, enteroendocrine cells , goblet cells, mitotic cells, daughter cells being displaced to top. 

Cells are either sloughed off or undergo apoptosis

PEYERS PATCHES!!!!
Region of small intestines with large lymphatic nodules they pucker into the lumen.
Made of lymphocytes

Large intestine have lieum coming up then cecum, vermiform appendix (filled w debris, can be source of infection) ascending, transverse, descending, sigmoid colon and rectumlarge intestine about 5 feet longmost of reabsorption of foodstuff happens in small intestinein large intestine have solidification of biproduct of small intestine

A. The large intestine is about 5 feet long.

B. Reabsorption of water and solidification of the by-products of digestion occur mainly in the large intestine.

C. The first portion of the large intestine is the cecum which has the vermiform appendix attached. Next, the ascending colon, the transverse colon, descending colon, sigmoid colon, rectum and finally the anal canal. All have the same general histology.

D. Crypts of Lieberkuhn (i.e., the intestinal glands) are also found in the large intestine.

E. The appendix is characteristically full of debris and possesses a large amount of lymphatic tissue.

F. The anal canal possesses large longitudinal folds called rectal columns (not unlike the rugae of the stomach or the plicae circularis of the small intestine in that they involve both the lining mucosa and the submucosa). It is lined by a non-keratinzed stratified squamous epithelium continuous with the keratinized squamous epithelium of the skin

This is a section through the appendixcan be area of chronic infectioncharacterized by a lot of debrisalso find a lot of lymphatic material around it because it can be a source of chronic infectionalso differs from the rest of the large intestine in that THERE ARE NO TENAIE COLI present in the appendix ********

Large intestinethe lining epithelium then muscularis mucosasubmucosa
Muscularis externaDark purple are all goblet cells that help to get biproduct through the large intestine

E. Histologically, the large intestine is different from the small intestine in a number of important respects.

1. There are no villi in the large intestine.

2. The intestinal glands (crypts of Lieberkuhn) are deeper in the large intestine (i.e., .5 to .75 mm versus 0.3 to 0.5 in small intestine).

3. There is a significant increase in the number of goblet cells relative to the number of intestinal absorptive cells.

4. There are few, if any, Paneth cells or enteroendocrine cells in the large intestine.

5. In the small intestine, there is the typical arrangement of the muscle in the muscularis externa (i.e., inner circular and outer longitudinal arrangement of layers). Throughout the large intestine (except in the appendix), there is a modified muscularis externa: the outer layer is broken into three discrete bands called the teniae coli. Like the small intestine, the large intestine is surrounded by a serosa.

Higher magnification of lining epithelium. Same cell type as small intestine but no villi

This is importrant clinicallyas you move through rectum to anal canal at end of anal canal get abrupt transition from one type of epithlelium to the otherat green arrow have this which is continuous with skin on outside what do you find between the transition sites? Squameous cell carcinoma!!! CANCER anal canal is closed so you have large folds__rectal columnsall are RELISTEN

This shows hemorrhoidal vessels found along the canal

Adventitia and Serosa:

Outside any region of the GI Tract, one will find one of two things
1. Connective tissue that is continuous with connective tissue of the surrounding organs (adventitia).

2. More commonly, however, a thin slippery membrane known as the serosa surrounds the GI Tract.
-->The serosa consists of a single layer of squamous or cuboidal cells called the mesothelium under which there is a variable amount of connective tissue.
-->The slippery serosa allows organs in the abdominal cavity to slide over one another without damaging each other.
-->The serosa may be connected to the body wall by an extension termed the mesentery.

**ESOPHAGUS HAS AN ADVENTITIA BUT MOST ORGANS OF GI TRACT HAVE SEROSA

Nerves of the GI Tract:

-In addition to the above-mentioned layers, there are two prominent nerve plexuses along the length of the GI tract.

1. The first, Meissner's Plexus, is located in the submucosa.

2, The second, Auerbach's Plexus (also termed the Myenteric Plexus), is found between the layers of muscle making up the muscularis externa (i.e., between the inner circular and the outer longitudinal layers of the muscularis externa).
Among other things, these nerve plexuses coordinate muscular contractions

Main features of the different types of epithelial cells lining the stomach and its glands as seen with an electron microscope.
(A) Mucous surface cell.
(B) Gland neck mucous cell.
(C) Chief or zymogenic cell.
(D) Parietal or axyntic cell.
(E) Argentaffin or enteroendocrine cell.

In the CARDIAC REGION OF THE STOMACH:
o In base have the chief cells – synthesizing and producing pepsinogen
o The 2nd major cell type is an UNUSUAL CELL – look pink in H&E .. round with deep invaginations lined w microvili and have mitochondria. These cells are synthesizing and secreting HCL – called parietal cells also make INTRINSIC FACTOR – helps with vitamin B12
o A third cell type usually confined to neck, make mucus – the MUCUS NECK CeLLS
o Have enteroendocrine cells – these cells do not show up well in H&E prep but show up well with silver stains. Also been called argentivin cells (bc of affinity for silver stain). Need to know both names. – GREEN circles

• The glands in the pyloric and cardiac region are similar, more simplex
o Find few parietal or chief cells, but find lots of cells like the mucus neck cells at the two extreme ends of the stomach

Between the intestinal villi, there are tubular glands that appear as invaginations into the lamina propria. These glands are called the intestinal glands, (also termed the Crypts of Lieberkuhn). Going up the center of each villus is a lymphatic vessel called the central lacteal. After a fatty meal, fat accumulates in the lacteals (referring to milk) that appear milky white. The intestinal villi structures have muscle in them that move the villi up and down. This motion facilitates the movement of the fat from the central lacteal into the lymphatics

The intestinal glands (i.e., Crypts of Lieberkuhn) are lined by goblet cells and intestinal absorptive cells. Enteroendocrine cells are also found along their lateral borders. At the bottom of the gland is a prominent population of zymogenic cells. These cells, called Paneth Cells, contain large refractile granules in their apical cytoplasm that stand out as a histological feature. Despite their obvious occurrence, little is known about the Paneth cells except that their granules contain a lot of zinc and an enzyme known as lysozyme which lyses certain kinds of bacteria

Fig. 8: (A) General structure of the appendix as seen in cross section. (B) Enlarged view of the mucous membrane and submucosa of the appendix as seen in cross section. (C) General structure of the pelvic colon as seen in cross section. (D) Structure of two crypts of Lieberkühn of the colon.

Fig. 9: (A) General structure of the rectum, anal canal, and sphincters of the anal canal. (B) Structure of the junction of the upper and lower halves of the anal canal as seen on longitudinal section.