Gastrointestinal Histology

Part A

  • Duodenum- first part up to the ligament of Treitz;
  • Juodenum- upper 2/5 beyond duodenum
  • Ileum- distal 3/5
  • On the most part they look the same

I.                 Structure/Function overview

A.     S.I. function: absorption of most ingested material – nutrients, electrolytes, and water

B.     Diabolically designed to absorb every molecule

C.    Understand that there is only a single cell layer separating the luminal contents from the underlying C.T.; must protect from a vast variety of material and organisms such as Enteric organisms (bacteria in the S.I.)

D.    Mucous and villus

E.     Plicae circulares (PC)- folds in the S.I. caused by the submucosa

F.     All layers of the GI

G.    Villi- finger-like projections of the lamina propria which thicken the mucosa

II.               Tunica Mucosa

A.     General Archetecture

1.     typical GI tract pattern of epithelium, propria, and muscularis mucosa

2.     Mucosal layer is further characterized by presence of finger-like projections called villi and crypts of Lieberkuhn  that go into the lamina propria

3.     Be sure and look at diagram on p. 264 when studying mucosa

4.     Simple columnar epithelium overlying a basal lamina

5.     Central Lacteal (LA)- drains into the lymphatic vessels; important for draining chylomicronsthat are absorbed by the epithelium

6.     Capillary plexus- immediately underneath the epithelium; drain into the central venules that flow into the submucosal veins;

B.     Cell Types

A.     Epithelium- always simple columnar

1.     Enterocytes (Intestinal Absorptive Cells)-

a.     vast majority covering the villi and upper crypts

b.     columnar cells with their underlying basement membrane operate as a barrier function between the luminal contents and the lamina propria

c.      Single layer of cells with tight and shallow apical junctions against which small molecules and water can readily pass

d.     6-10 L of gastric contents enter duodenum ® 1-2L only go to the colon

e.     UNDER NORMAL CONDITIONS the tight junctions keep out bacteria and their toxins

f.       To increase surface absorptive area each enterocyte has about 3000 microvilli.; with L.M. seen as a striated border; covering these microvilli is a glycocalyx where enzymes for terminal digestion are located.

g.     There is also a LIMITED ability to absorb MACROmolecules via pinocytotic vesicles (very useful in infants)

2.     Goblet Cells

a.     mucous-producing cells among the enterocytes covering the villi

b.     provide lubrication throughout the S.I.

3.     Enteroendocrine cells

a.     found up and down the crypts of the S.I.

b.     See previous lecture

4.     Paneth Cells

a.     orangey-red with H&E; due to numerous cytoplasmic granules filled with lysozyme, an antibacterial substance.

b.     ALWAYS at the base of the crypts

c.      Increase in number down the S.I. (where bacteria conc increases also)

5.     Undifferentiated Stem Cells

a.     undifferentiated columnar cellsin a mid-crypt  position; give rise to 1-4 above

b.     migrate up or down the crypt depending on designation

c.      extrusion zone- tip of villus

B.     Lamina Propria

1.     vast numbers of white blood cells in the c.t.

2.     endigenous fibroblasts, lymphocytes, eosinophils, macrophages, and plasma cells

3.     Plasma cells- imp. For production of sIgA (secretory Immunoglobulin) an Ab which links with the enterocytes and is transported to the apex of the cell for release.

4.     SIgA- prevents bacterial attachment; Mucosal surface defense weapon (MSD baby!)

5.     Intra-epithelial lymphocytes- lymphocytes migrating through the epithelium

C.    Muscularis Mucosa

1.     Inner circular, outer longitudinal

2.     Slips of the inner circular go into the core of the villi, causing them to be partially contractile

III.              Tunica Submucosa

A.     Plicae circulares- amplifications of submucosa;

B.     Composed of loosely, mostly acellular c.t. ,

C.    Meisner’s Plexus common

IV.             Tunica Muscularis

A. LOTS OF AUERBACH’S PLEXUS GANGLIA VISIBLE!!!!!

V.               Tunica Adventitia/Serosa

A.     retroperitoneal duodenum lacks a mesentery—–outer adventitia

B.     jejunum and ileum- well-developed mesenteries—Serosa

Special Features of the Small Intestine

Brunner’s Glands
  • found only in the initial part of the duodenum adjacent to the stomach
  • merge imperceptibly into the pyloric glands of the stomach
  • secrete an alkaline mucous to help neutralize the contents of the stomach via ducts that empty into the base of the crypts

Sphincter of Oddi

  • smooth muscle encircling the intramural portion of the pancreatic and common bile ducts
  • Papilla of Vater- raised opening of the common duct of the pancreas and common bile in the wall of the duodenum
  • Cholecystokinin which is released from enteroendocrine cells of the S.I., in the presence of fatty foods, causes gallbladder contraction with simultaneous relaxation of this sphincter, so that stored bile can be secreted into the duodenum

Peyer’s Patches

  • specialized collection of lymph nodules
  • aggregates of 5-90 nodules arranged in an oval shape; NOT encapsulated
  • 300 patches maybe at puberty
  • 30 in elderly
  • occupy the antimesenteric lamina propria with their apices pushing out into the mucosa causing the mucosal surface to have a bubbly appearance
  • bases break through the muscularis mucosa into the underlying submucosa
  • Germinal centers, mantles and peripheral T zone
  • M cells (Membraneous epithelial cells)- epithelium covering the dome of each follicle

1.     have a few microvilli

2.     network of microfolds covering their apical surfaces

3.     flattened and curved to cover intraepithelial lymphocytes which cross the basal lamina

4.     Seem capable of selectively taking up

a.     certain macromolecules

b.     antigens

c.      specific species of bacteria

  • Due to Peyer’s patches the ileum becomes a powerful immunologic organ for sampling and detecting foreign material in the environment and alerting the immune system
  • Negative- M cells may also be a portal entry for select pathogens

Final Overview

  • proximal-distal modifications in function occur in the small intestine; reflected in structure
  • Proximally- wall is thicker due to a thicker mucosa and taller villi with large absorptive capability
  • Distally- mucosal mass and villus height decrease
  • Brunner’s glands: initially can neutralize stomach acid in the duodenum
  • As intestinal contents move more aborally, becoming more concentrated, goblet cells increase for lubrication purpuses
  • At the distal end of the S.I.- Peyer’s patches— for immunological surveillance
  • Papilla of Vater- Hepato-pancreatic secretions are dumped into the duodenum (most proximal) to aid in digestion
  • BILE SALTS AND COMPLEXES OF INTRINSIC FACTOR-B12 ARE UNIQUE IN THAT THEY CAN ONLY BE ABSORBED AT THE ILEUM to enter the splanchnic circulation
  • Extrahepatic circulation: upon passing through the liver the blood is cleared of bile salts which then return via bile to the duodenum
The Large Intestine

Cecum, appendix, colon, rectum, anal canal

Cecum/Colon

  • absorb about 4/5 of the water from the fluid presented to it from the ileum.
  • No villi; smooth surface; mucous

A.     Tunica Mucosa

  • mostly flat, no villi or prominent folds
  • Digestion is complete at this point and only water and electrolytes need to be absorbed
  1. Epithelium

a.     numerous columnar absorptive cells and scattered goblet cells

b.     crypts still present and these are lined with more goblet cells than absorptive cells

c.      enteroendocrine cells (special stains req.)

d.     Paneth cells are rarely found

e.     Undifferentiated stem cells found in the bases of the crypts and migrate upward to form the other four cell types

f.       Function: absorbs water from the stools to solidify them; mucous lubrication; enhancement of barrier function

  1. Lamina Propria

a.     also controls inflammation as in the S.I.

b.     highly cellular loose c.t.

c.      scattered solitary lymph nodules extending into the underlying submucosa

  1. Muscularis Mucosa

a.     Inner circular, outer longitudinal AGAIN

B.     Tunica Submucosa

  1. Loose c.t. with Meissner’s plexus present

C.    Tunica Muscularis

  1. inner circular, outer longitudinal
  2. unique feature-taenia coli—concentrations of the outer layer into 3 thick bands of muscle equidistant from each other around the wall. Visible grossly and externally.
  3. Auerbach’s plexus

D.    Tunica Adventitia/Serosa

  1. both types present

Appendix

  • vermiform- similar to intestine

A.     Tunica Mucosa

  1. Epithelium

a.     simple columnar cells w/ striated border

b.     crypts filled mostly with goblet cells

c.      some enteroendocrine

d.     rarely Paneth

  1. Lamina Propria

a.     loose, cellular c.t.

b.     solitary and confluent lymph nodes push into the submucosa

c.      NOT PEYER’S PATCHES OR M CELLS

  1. Muscularis Mucosa

a.     NONE; broken up by lymph nodules

B.     Tunica Submucosa

  1. lots of lymph nodules
  2. unique here- unilocular fat

C.    Tunica Muscularis

  1. inner circular, outer longitudinal  AGAIN

D.    Tunica Serosa

  1. must be here?

Rectum

  • 5-7″ long
  • similar to colon, nut lacks taenia coli
  • anal columns or rectal columns of Morgagni- longitudinal folds in the lower 1-2″ which terminate about .5″ from the anal orafice
  • Anal valves- bases of the columns are connected here
  • Mucosal lining epithelium is simple columnar with crypts occupied by numerous goblet cells

Anal Canal

  • terminal few cm of the alimentary canal

A.     Mucosa

  1. epithelium is stratified squamous and the muscularis mucosa disappears
  2. at oriface there is skin characterized by typical keratinizing stratified squamous epithelium with hairs

B.     Submucosa

  1. contains tortuous veins that dilate to form hemorrhoids
  2. also contains sebaceous glands
  3. APOCRINE sweat glands

C.    Tunica Muscularis

  1. inner circular layer forms the internal anal sphincter
  2. outer longitudinal- first smooth—then becomes external anal sphincter

D.    Tunica Adventitia/Serosa

Part B

I.                 Organ structural design

A.     Inside out

1.     Mucosa

a. delicate c.t. with a luminal epithelium

2.     Submucosa

b. underlying layer of c.t.

3.     Muscularis

a. 2-3 layers of muscle

4.     Adventitia/serosa

a.     outermost, c.t.  (with c.t. plus mesothelium = serosa)

B.     More detail

1.     Mucosa

a.     varies greatly

b.     reflects the diversity of functions of the alimentary canal

c.      always three layers

1.     Epithelium + baseement membrane

a.     type of epithelium varies according to need

2.     Lamina propria

a.     loose c.t. with abundance of immunological cells

b.     also, capillaries, lymph, and glands

3.     Muscularis mucosa

a.     Very thin layer of smooth muscle

2.     Tunica Submucosa

a.     loose c.t., less cellular

b.     Meissner’s plexus- network of nerves and ganglia

c.       Large blood vessels, lymphatics, maybe glands, and Meissner’s plexus found here

d.     Acts as a padding for the Mucosa

3.     Tunica Muscularis  (Muscularis Externa)

a.     main body of muscle for the alimentary canal

b.     smooth muscle, inner circular, outer longitudinal

c.      Network of nerves and ganglia- Auerbach’s plexus

d.     Muscularis is responsible for peristalsis of the alimentary canal

4.     Tunica Adventitia or Serosa

a.     C.T. always around the muscularis; provides padding and protection

b.     When the alimentary canal faces the peritoneal cavity- the C.T. is wrapped in  a layer of simple squamous epi. Called the mesothelium.  (Derived from somatic and splanchnic mesoderm lining and facing the coelomic cavity)

c.      C.T. + mesothelium = Serosa

d.     Examples of Serosa lined are distal esophagus, stomach, jejunum, ileum, parts of the large intestine

e.     In areas devoid of mesothelium, (thoracic esophagus, duodenum, and ascending and descending colon, only adventitia

II.               The Enteric Nervous System (ENS)

Consists of nerve cell bodies and their processes found in the wall of the gut.

Submucosal or Meissner’s plexus

1.     mainly in the large and small intestines

Myenteric or Auerbach’s plexus

1.     found between the inner circular and outer longitudinal layers of the tunica muscularis

2.     Hirsprung’s Disease- lack of ganglia in rectocolon

See Fig on p. 251.

Function of ENS

1.     Controls peristaltic movement by contracting and relaxing the muscularis mucosa and externa.

2.     Part of the autonomic nervous system, separate but modulated by the sympathetic and parasympathetic nervous systems

3.     “brain of the gut”- there are as many neuron cell bodies here as in the spinal cord

4.     Peristalsis is maintained even with out CNS connections in vitro

III.              Enteroendocrine System

A.     Variety of small cells lining the GI tract in a distribution pattern seen on p. 252 (no need to memorize)

B.     Include APUD, chromaffin, argentaffin, and neuroendocrine cells

C.    Not seen in H&E; must use EM or spec stains.

D.    Contain electron dense secretory granules

E.     Endocrine cellsthat secrete their products across the basement membrane into the underlying capillaries where their hormonal products are enter circulation.

F.     Placement in columnar epithelium allows them to respond to certain stimuli in the lumenal solutions; produce amines and peptides which have profound effects on GI function (more in Pathology)

The Esophagus

I.                 Info

A.     mostly intrathoracic, muscular organ designed to pipe food into the stomach

B.     Reverse movement

C.    When empty, collapsed and situated into longitudinal folds

D.    Layers

1.     Tunica Mucosa

A.     Epithelium

1.     stratified, squamous, Non-Keratinizing epithelium

2.     occasional mucous-secreting glands

B.     Lamina Propria

1.     loose c.t.; clusters of lymphocytes

2.     not very cellular because there is not much need for immunological surveillance because of the thick epithelium and secretory products.

3.     Mucosal or Cardiac Glands- at the distal junction of the esophagus and stomach these mucous-secreting glands ore found.   Adjacent to “cardiac” portion of the stomach.

C.    Muscularis Mucosa

1.     longitudinally- oriented smooth muscle bundles

2.Submucosa

A.     Mucous-secreting glands called Submucosal glands or esophageal glands proper, which serve to lubricate the esophagus, distributed throughout.

B.     Clinical significance- submucosal veins in the distal 8 cm of the esophagus.  These anastomose with the portal vein and can become extremely dilated when cirrhosis of the liver occurs.  The thinned, dilated vessels form varices which protrude into the lumen of the esophagus and can rupture, causing a dramatic death.

3.Muscularis

A.     proximal ¼- purely striated but transitions into smooth muscle

B.     distal half- usually purely smooth

C.    No anatomic correlatle to the lower esophageal sphincter

4.Adventitia/Serosa

A.     outermost layer of the thoracic esophagus- adventitia (c.t. that connects to the surrounding structures/tissues

B.     After passing through the diaphragm, into coelomic cavity—mesothelium—Serosa

Stomach
  • Food storagee, mixing, acidic breakdown for absorption in the s.i.
  • 4 zones- Cardia, fundus, body, pylorus
Tunica Mucosa
  • the mucosa is complex, with histological diversity in the different zones
  • Remember the functions of the zones
  • Rugae- folds, even when distended, due to an increase in the thickness of the underlying submucosa
  • Pits and Ph

1.     Epithelium

A.Surface Mucous cells- columnar cells with abundant mucous granules and small apical microvilli; covers entire surface; secrete alkaline mucous( for acidity )

Homogeneous and Mucous-secreting
SMCs line pits which lead from the surface to the deeper glands
Pits branch into 5-8 tubular glands.
The nature of the glands is what accounts for the heterogeneity of the stomach mucosa
Renewed by undifferentiated stem cells in the neck of each gland

2.     Lamina Propria

limited; “wisps”of cells and c.t.; crowded

3.     Muscularis Mucosa

A. Bottom of the glands

Tunica Submucosa
  1. coarse, loose collagen
  2. Amplification of this layer sends the overlying mucosa into rugae(folds)
Tunica Muscularis
  1. The stomach has THREE layers instead of two
  2. Inner oblique, middle circumferential, outer longitudinal

Glandular composition of the Stomach

  • No clear-cut division in the location or distribution of the gland types
  • Central- source of acid, digestive enzyme
  • Proximal and distal- abundance of mucous to protect the esophagus and duodenum
  • Cardiac glands- only mucous
  • Pyloric glands- only mucous
  • Gastric glands (fundus and body)- sites of enzyme and acid secretion
  • REMEMBER THE PITS OF EACH ARE STILL LINED BY SMCs
  • Histo crap- coiled or straight; not important
  • There are biochemical differences in the mucous elaborated by the neck cells vs. the gland cells.
  • Remember: there are Cardiac glands in the mucosa of both the gastric region of the stomach and the distal esophagus

Gastric gland Histology

1.     Neck region

  1. the neck of the gland is the junction of the top portion of every gland into a gastric pit
  2. Beginning of the gland
  3. Mixed pop. Of columnar mucous-secreting cells and STEM cells
  4. Mucous Neck cells

1.     more acidic, less viscous than the SMCs

2.     contained in granules in cytoplasm

3.     can’t distinguish from SMCs w/o spec. stains

  1. Stem Cells

1.     undifferentiated cells that will give rise to other cell types in the glands and pits

2.     Can become mucous neck cells, SMCs (which have turnover rate of 4-7 days)

3.     Difficult to identify

  1. See fig p. 258

2.     Body and Base

  1. Parietal (Oxyntic cells)

1.     large, eosinophiloic cells, easily identifiable

2.     Function: secrete HCl; Produce intrinsic factor

3.     Predominate in the body of glands, but can be found elsewhere

4.     Acidophilia due to MITO

5.     When resting- filled with tubules and vesicles when stimulated merge to form an intracellular canalicular system

6.     Intrinsic factor- combines with Vit B12 in the s.i. for absorption

  1. Chief Cell

1.     Basophilic

2.     Grestest abundance at the base and body of gastric glands

3.     Produce pepsinogen which in stomach becomes pepsin which is a proteolytic enzyme which initiates protein digestion

  1. Enteroendocrine cells

1.     APUD system cells; found at the base

2.     Secretes a serotonin (not a TQ?)

3.     See fig p. 259

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