Histology Laboratories

Molecules to Systems
2003
Compiled by
James D. Jamieson, MD/PhD
Thomas L. Lentz, MD

No part of this image collection may be distributed outside of the
Yale University Intranet.
Alberts, B. et al. Molecular Biology of the Cell. 4th Edition, Garland Science, New
York, 2002.
Gartner, L. P. and Hiatt, J. L. Color Atlas of Histology, Williams & Wilkins,
Baltimore, 1994.
Kerr, J. B. Atlas of Functional Histology. Mosby, London, 1999.
Kessel, R. G. and Kardon, R. H. Tissues and Organs: a text-atlas of scanning
electron microscopy. W. H. Freeman, San Francisco, 1979.
Lentz, T. L. Cell Fine Structure. W. B. Saunders, Philadelphia, 1971.
Lodish, H. et al. Molecular Cell Biology. W. H. Freeman, New York, 2000.
Mizoguti, H. Color Slide Atlas of Histology. Nihon Shashin Shinbunsha, Tokyo.
Young, B. and Heath, J. W. Wheaters Functional Histology. Churchill
Livingstone, Edinburgh, 2000.
Micrographs taken by George Palade, Marilyn Farquhar, James D. Jamieson,
Nicolai Simionescu, Maya Simionescu, David Castle, Thomas L. Lentz.

Web Resources
http://info.med.yale.edu/webpath/webpath.htm
Cushing Library Educational Software/Cell Biology/Several Histology Resources
Acknowledgements
Sources of Micrographs, Diagrams and Figures
GI Tract I Laboratory
Esophagus, Stomach and Small Intestine
I .GENERAL FUNCTI ONS OF THE GASTROI NTESTI NAL SYSTEM
The main function of the gastrointestinal system is to provide the
appropriate conditions for processing foodstuffs into molecular species for
absorption into the circulation as follows:
A. Digestion and Absorption: digestion in bulk in the lumen of the gut
(stomach/gastric gland secretions and small intestine/pancreatic
secretions) and local hydrolysis at the microvil lar surface fol lowed
by selective absorpt ion across enterocytes into the circulation vi a the
portal vein and liver or into lymphatics (lipids).
B. Transit: the ordered series movement of material through the tract
carried out by its smooth muscle layers. a by endogenous nerves and
the gut endocrine system.
C. Homeostasis: production of factors maintaining homeostasis of the
gut lumen e.g., mucus; antibacterial agents/Paneth cells; secretory
IgA (Gu t Associated Lymphatic Tissue).
(Stomach and large intestine pattern)
(Small intestine pattern)
II . GENERAL STRUCTURAL FEATURES OF THE GI TRACT
Follows a general plan in entire gastroi ntestinal tract with four concentric
layers:
1. Mucosa (a) lining epithelium
(b) lamina propria
(c) muscularis mucosa
2. Submucosa
3. Muscularis externa
4. Serosa (except where viscus is retroperitoneal; external layer
termed adventitia).
LANDMARKS IN THE GASTROINTESTINAL TRACT
Gut Segment Mucosa Submucosa Muscularis
Esophagus Stratified squamous Striated m. in
epith. (non- keratinized) upper third;
smooth m. in
lower third;
mixe d in mid.
Stomach Abse nce of villi and Triple-laye red
goblet cells; gastric
pits and glands
Duode num Villi; mucosal glands Brunner's
Goblet ce lls + glands
Jejunum Villi; mucosal glands Plicae
Goblet ce lls ++ circulares
Ileum Villi; mucosal glands
Peyer's patches
Goblet ce lls +++
Colon No villi; mucosal glands; Outer coat
Goblet ce lls ++++ arrange d in thre e
longitudinal bundle s
(taeniae coli)
Laboratory on the Gastrointestinal Tract I:
Oral Cavity Through Small Intestine
Basic Histological Organization and Abbreviations:

Four layers

1. Mucosa (M): epithelium (E) + lamina propria (LP) +
muscularis mucosa (MM)

2. Submucosa (SM): thick connective tissue layer with blood
vessels, lymphatics, nerves

3. Muscularis externa (ME): striated in upper part of
esophagus; inner circular (IC), outer longitudinal (OL)

4. Serosa (S) :squamous epithelium (where absent =
adventitia)
LANDMARKS IN THE GASTROINTESTINAL TRACT
Gut Segment Mucosa Submucosa Muscularis
Esophagus Stratified squamous Striated m. in
epith. (non-keratinized) upper third;
smooth m. in
lower third;
mixed in mid.
Stomach Absence of villi and Triple-layered
goblet cells; gastric
pits and glands
Duodenum Villi; mucosal glands Brunner's
Goblet cells + glands
Jejunum Villi; mucosal glands Plicae
Goblet cells ++ circulares
Ileum Villi; mucosal glands
Peyer's patches
Goblet cells +++
Colon No villi; mucosal glands; Outer coat
Goblet cells ++++ arranged in three
longitudinal bundles
(taeniae coli)
Diagnostic characteristics of the gastrointestinal tract
The following are some of the prominent differences between regions
of the gastrointestinal tract. If you can observe these differences you should
be able to distinguish all regions.
Esophagus: Stratified squamous epithelium; muc ous glands in the submucosa.
Striated muscle in the upper portions of the muscularis externa ; smooth
muscle in the lower portion.
Stomach : Simple columnar epithelium arranged to form gastric pits and three
types of glands. Thick, three-layered muscularis externa . No Villi.
Cardia: Cardiac Glands tend to be convoluted and are lined exclusively by
pale staining mucous secreting cells.
Body: Glands of the body are rather straight with limited branching and are
lined by a smaller population of parietal and chief cells.
Pyloru s: Glands of the pylorus posess deeper pits and their basal portions are
more highly coiled and branched than elsewhere in the stomac h. The
basal portion of the glands consist mainly of muc ous secreting cells and
numerous endocrine c ells.
Small Intestine : Simple columnar epithelial c ells with brush borders and goblet
cells ; villi and crypts of Lieberkhn.
Du oden u m: Brunners glands in submucosa. Long villi
Jeju n u m: Thin walled, plicae circulares most prominent. Contains a few
goblet cells.
Ileu m: Peyers patches in submucosa; more goblet cells.
Large Intestine : (Colon ) No villi. Goblet cells are found neither in the gastric pits
nor glands, but are found regularly in the colic c rypts.
Appendix : Resembles c olon but its crypts are not so regularly spaced and
are often missing all together. Numerous lymphatic nodules are
sc attered throughout the lamina propria and reach into the submucosa.
Gall Bladder : Tall columnar c ells with many irregularly shaped villi.
Esophagus to Stomach
E
MM
SM
ME
IC
OL
M
Esophagus: stratified squamous non-keratinized epithelium; striated muscle in upper 1/3.
LP
Adventitia
E (stratified squamous
non-kearatinized)
MM
SM
Submucosal glands
Esophagus
LP
Esophageal - Gastric Junction
Examples of Regional Variations
Esophagus: Stratified Squamous Epithelium
E
MM
SM
ME
IC
OL
M
Stomach: Glands Invaginate into Lamina Propria; No Villi; No
Goblet Cells
E
MM
SM
ME
M
Folds - rugae Simple glands extending to MM
Jejunum: Outoldings of Mucosa on SM; Villi; Goblet Cells Present
E
SM
ME
MM
Folds of submucosa = plicae circulares
Villi projecting from plicae
M
M
Ileum: Villi; Fewer Plicae; More Goblet Cells; Peyers
Patches Prevalent
MM
SM
ME
M
Peyers patches
Villi
Crypts in LP
Mesentery
Serosa
Large Intestine: No Villi; Many Goblet Cells;
Simple Glands Extending to MM
Crypts/colonic glands
MM
SM
ME
M
Lymphoid follice
Tongue
Skeletal (striated) muscle fascicles
Stratified squamous epithelium Vallate papilla
Vallate Papilla
Taste buds
Taste Buds on Papilla
Lingual Tonsil
Germinal centers in lymphoid follicles
Sublingual glands
Parotid Gland
Serous exocrine secretory units (amylase)
Myoepihtelial cells/contractile
Mucous
Serous demilune
Submandibular Gland
(mixed mucous/serous
Stomach and Gastric Glands
Function of Stomach in Lumenal Digestion

1. Secretion of acid by parietal cells: provides pH of ~1.4 for
autoactivation of pepsinogen. Glands in body of stomach.

2. Provides correct pH for action of pepsinogen on proteins.

3. Secretion of pepsinogen by chief cells in glands in body.

4. Secretion of gastrin into circulation from base of glands in
pyloric glands in response to stomach contents (alkaline pH;
peptides). Gastrin stimulates release of histamine from ECL
cells that in turn stimulates acid secretion from parietal cells.

5. Secretion of mucous to protect gastric epithelium.

6. Secretion of intrinsic factor by partietal cells.

(Stomach pattern)
Muscularis Externa of Stomach
Stomach: Glands Invaginate into Lamina Propria; No Villi; No Goblet Cells
E
MM
SM
ME
M
Folds - rugae Simple glands extending to MM
Cardiac Mucosa: Mucous secreting cells only
Gastric pits
MM
LP
Surface mucous cells
Glands
Body (corpus) Mucosa:
Surface mucous cells, chief, parietal,
and ECL cells.
Gastric pits
MM
Glands
Pyloric (antral) Mucosa: Mucous cells and Gastrin endocrine
Gastric pits
SM
Glands
Lymphoid tissue
Surface Mucous Cells: Common to All Regions
Gastric Pit
Gastric Gland
Body of Stomach
Body of Gastric Mucosa
Pit
Isthmus
Neck
Base
LP
Parietal cells
Chief cells
Parietal Cells H&E
LP
Parietal cells
Chief Cells H&E
Secretory granules containing pepsinogen
Lumen of gastric gland
Parietal Cells
(thin epoxy section)
LP
Parietal cells
Intracellular canaliculus
Lumen of gastric gland
Chief cell
LP
Blood vessel
Parietal Cells
(EM)
Mitochondria
Intracellular canaliculus
Pyloric Antral Glands
Pits
MM
Glands
LP
Pyloric Antral Glands: Immunostained for Gastrin *
*
*
*
Lumen of pyloric gland
Gastin Cell in Base of Pyloric Antral Gland
Secretory granules in endocrine G cell containing gastrin
Regulation of Acid Secretion from Parietal Cells
Function of Salivary, Biliary, and Pancreatic Secretions in
Lumenal Digestion

Pancreatic secretions:

Centroacinar/small duct cells:
Watery secretion rich in HCO
3
pH 7.4; neutralizes acid
gastric content in duodenum.

Provides correct pH for activation of trypsinogen by
microvillar protease = enterokinase > cascade activation of
pancreatic proenzymes. Stimulated by secretin released from
gut wall in response to low luminal pH


Function of Salivary, Biliary, and Pancreatic Secretions in
Lumenal Digestion: continued

Pancreatic secretions:
Acinar cells: exocytosis into pancreatic duct of enzymes and
proenzymes for digestion; stimulated by CCK which is released
from gut wall in response to L amino acids and fatty acids in
duodenum.

Proteins: trypsinogen, chymotrypsinogen, proelastase,
procollagenase (all activated by trypsin in gut lumen after
activation of tyrpsinogen by enterokinase; inactive as secreted).

Carbohydrates: amylase.

Lipids: Prophospholipase, lipase, cholesterolesterase.

Nucleic acids: RNAse, DNAse.

Function of Salivary, Biliary, and Pancreatic Secretions in
Lumenal Digestion: continued

Bile:

Bile salts: detergents for emulsification of lipids into water
soluble forms for digestion by lipases etc. Synthesized from
cholesterol.

Secretory IgA: protection of gut lumen.

Bile pigment: waste from RBC destruction (bilirubin).

Duodenum
Small intestine pattern)
Diagram of Duodenum
Duodenum:
Characteristic Brunners
glands in LP and SM
ME
MM
Villi
SM
Brunners glands
Duodenum
(PAS stain)
Brunners gland
Duct from Brunners gland into gut lumen
Lymphoid follicle
Jejunum
Diagram of Jejunum and Ileum
Jejunum: Prominent plicae circulares; villi on plicae; goblet cells more common
E
SM
ME
MM
Folds of submucosa = plicae circulares
Villi projecting from plicae
M
M
Ileum
Ileum: villi; fewer plicae; more goblet cells; Peyers Patches prevalent
MM
SM
ME
M
Peyers patches
Villi
Crypts in LP
Mesentery
Serosa
Ileum
ME
Peyers patches with lymphoid follicles
Germinal center
LP
Villi
Crypts
SM
Dome with M cells
Ileum
Peyers patch with lymphoid follicles
Germinal center
LP
Villi
Crypt
s
MM
Site of M cells
Transcytosis across intestinal epithelium
The Enterocyte
SEM of Intestinal Villi
Intestinal Villus
LP
Lymphatic vessel
Brush border/microvilli on enterocytes
Goblet cells
Blood vessel
Smooth muscle bundle
Cells of immune system
Villous Core LS
LP
Lymphatic vessel
Brush border/microvilli on enterocytes
Goblet cell
Smooth muscle bundle
Blood vessel
LP
Lymphatic vessel
(lacteal)
Brush border/microvilli on
enterocytes
Goblet cell
Villous Core XS
Capillary
Lymphocytes and plasma cells
EM of Enterocyte
Surface of Enterocyte
Microvilli
Junctional complex
Junctional Complexes Between Enterocytes
Junctional Complexes Between Enterocytes; Freeze Fracture
Brush Border on Enterocyte
Goblet cell
Enterocytes
Brush border
Terminal bar
Microvilli LS
Junctional
complex between
enterocytes
Microvilli XS
Actin cores
Epithelial Renewal and Gut Protection
Cell Renewal in Gut
Villi and Crypts
Villi
Crypts
LP
MM
Mitoses in crypt in jejunum (*)
*
*
*
*
Base of Crypts
Paneth Cells
Lumen of crypt of Lieberkhn
LP
Paneth cells
Some pathology to think about.
Barretts esophagus. Consequence of chronic acid reflux GERD). The stomach would be
to the right of the field. What type of mucosa is Barretts? what does this tell you about stem cells?
Precancerous lesion. What would you do?
Helicobacter pylori. Common cause of gastric ulcers. Where are these bacteria located?
How would you treat the problem?
Celiac sprue. 1:2000 Caucasians; genetic. Note flattened epithelium and shortened villi
compared to normal intestine on left. What symptoms might these changes cause?
Crohns disease (Ulcerative colitis). What layer of the intestinal wall is
affected? What symptoms can you predict based on the histology?
Crohns disease. Higher power. What are the blue staining cells in the lamina propria?
What does this tell you?