MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY

DIGESTIVE PATHOLOGY 1 neutral mucus; protection from gastric

contents
GENERAL OVERVIEW:
o Meissner’s plexus (congregation of ganglion and
➢ Proximal part of the esophagus to the distal part of nerve fibers) that innervate the esophagus
the anal canal • Normal non-keratinizing esophageal squamous
➢ Hollow tube of varying diameter mucosa is seen in the photo, and there is
➢ Same basic structural organization underlying submucosa containing mucus
➢ Most of the differentiation will occur in the mucosa glands, with a duct surrounded by lymphoid
(because there are parts that have special structures / tissue. At the right is the muscularis with smooth
specialization since it has different functions muscle as well as outer skeletal muscle.
➢ Functions of mucosa: Protection, absorption,
secretion
➢ Difference in mucosal characteristic architecture will
rely on specific functions that the organ will perform
➢ All parts of alimentary canal follow the same
structure:
o Mucosa
▪ Lamina propria
▪ Muscularis mucosae
o Submucosa
o Muscularis externa • MUSCULARIS EXTERNA
o Serosa o Upper 3rd = striated
o Lower 3rd = smooth muscle
ESOPHAGUS
o Two muscle layers
▪ Inner circular – circumferential constriction
▪ Outer longitudinal – for food to move down
o Aurbach plexus (myenteric plexus) – nerve
control for muscles of esophagus which
allows for peristalsis
o NO SEROSA but adventitia is present

• Fixed muscular tube that delivers food and liquid

from the pharynx to the stomach
• Conduent of food bolus, so after mastication in the
oral cavity, it will be transferred to the esophagus to the
stomach
• Overall length of 25cm
• On cross-section, the lumen is collapsed and has a
branched appearance due to longitudinal folds
o Lumen expands without mucosal injury
o When bolus enters, branched appearance is lost
COMMON PATHOLOGY OF ESOPHAGUS:
• MUCOSA:
o Non-keratinized stratified squamous epithelium 1 ) ACUTE ESOPHAGITIS
(same with that of skin except that skin is
keratinized) • Manifested here by increased neutrophils in the
• SUBMUCOSA: submucosa as well as neutrophils infiltrating into
o Dense irregular connective tissue the squamous mucosa
o Larger blood and lymphatic vessels • Predominant cell = neutrophils
o Glands in the mucosa secrete the mucus that is • The acute inflammation can be caused by
used to lubricate and protect the luminal wall of the infections, ingestion of irritative chemicals, drugs
esophagus such as NSAIDS (aspirin, ibuprofen),
o Mucosal glands: chemotherapy, and radiation
▪ Esophageal mucus glands - scattered • Temporary condition, integrity of mucosa remains
along the length of the esophagus, most intact; no irreversible injury
densely found in the upper portion of the
esophagus; Tubuloalveolar glands = secrete
acidic mucus for continued digestion of food
particles
▪ Esophageal cardiac glands – similar in
structure to the cardiac glands in the
stomach, and so naturally, they are more
numerous at the lower part of the esophagus
where it connects to the stomach; will secrete
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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY
2 ) Barret Esophagus • Divided into 3 histologic regions based on the type of
glands
o Cardia
o Fundus
o Pylorus
• MUCOSA
o Simple columnar
▪ Surface mucous cells with mucinogen granules
(found at the apex; makes up most of the
volume of the cell)
• Columnar metaplasia of esophageal squamous o Rugae
epithelium to simple columnar (you need to have the ▪ Longitudinal folds and ridges
protection of mucus-secreting cells because of the ▪ Prominent in narrower regions
constant introduction of the injury) ▪ Poorly developed in upper surface
• Columnar cells = can produce mucus ▪ Distended → disappear
• Continuous injury → adaptation ▪ Accommodate expansion and filling
• Complication of long-standing GERD (weakened o Foveolae
esophageal sphincter → backflow of gastric contents ▪ Aka gastric pits
to the esophagus) ▪ Openings in the mucosal surface
• Esophagus is not equipped to fight that much gastric ▪ Gastric glands open into the bottom of the
acid within its lumen gastric pits
• Precursor of dysplasia and esophageal carcinoma
• Endoscopically appear salmon-pink (inflamed)
• Epithelial metaplasia to gastric-type mucosa above the
gastroesophageal junction
• The metaplasia results from chronic gastroesophageal
reflux disease (GERD).
• Note the columnar epithelium (left) and the ▪ This is the normal appearance of the gastric
squamous epithelium (right). antrum extending to the pylorus at the
right of center. The first portion of the
duodenum (duodenal bulb) is at the far
right.
o FUNDIC GLANDS
▪ Produce gastric juice of the stomach of the
stomach
▪ Present all throughout except cardia and
pyloric areas
• This is the “typical” Barrett mucosa, because there is ▪ Simple branched tubular glands
intestinal metaplasia as well (note the goblet cells in ▪ Extend from the bottom of gastric pit to
the columnar mucosa) muscularis mucosae
▪ Cell types:
STOMACH
 Mucous neck cells – found in the neck of
fundic glands and produce mucus
 Enteroendocrine cells – secrete
endocrine hormones
 Undifferentiated adult stem cells –
regenerative capacity of mucosal cells
should there be destruction
 Chief cells
• Expanded part of the digestive tube o Deeper part of the fundic gland
• Lies beneath the diaphragm o Protein-secreting cells
• Receives food bolus from esophagus ▪ Pepsinogen = main
• Where food is processed further into chyme product converted to
• Divided into 4 anatomic regions: pepsin
o Cardia – surrounds esophageal orifice
o Fundus – lies above the level of horizontal line
drawn through the esophageal orifice
o Body – lies below the horizontal line drawn on the
fundus
o Pylorus – funnel shaped region up to the distal
narrow sphincteric region

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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY
 Parietal cells
COMMON PATHOLOGIES OF THE STOMACH
1 ) Acute Gastritis
o Aka oxyntic cells
o Neck of the fundic gland
o Most numerous in the upper and middle part
o Appear triangular
o HCl
o Intrinsic factor (complexing of vitamin B12)
o Forms part of gastric juice
o Destruction of mucosa = loss of intrinsic
factor = vitamin B12 deficiency =
pernicious anemia & decrease in HCl
• CARDIAC GLANDS
o Mucus-secreting cells
o Limited to the narrow region > cardia
o Protects esophagus against gastric contents
o Glands are tubular, tortuous, occasionally branched
o Flattened basal nucleus
• PYLORIC GLANDS
o Located in the pyloric antrum
o Branched, coiled, tubular glands
o Wide lumen
o Similar to surface mucous cells
2 ) Chronic Gastritis
• LAMINA PROPRIA
o Scant, restricted to space surrounding the gastric
pits and glands
• MUSCULARIS MUCOSAE
o Two thin layers
(1) Inner Circular
(2) Outer Longitudinal
o Contraction = help outflow of the gastric gland
secretions
• MUSCULARIS EXTERNA (for blending & mixing food
bolus > transport > persitalsis)
o Outer longitudinal – for transport
o Middle circular – for mixing within that area
o Inner Oblique – also for mixing within that area
*Only the stomach has these three layers
• Erosive gastritis
• Inflammatory type of injury of stomach mucosa
• CAUSES
o NSAIDS – inhibit the cyclooxygenase pathway
o Cigarette smoking – may lead to ulceration if it is
heavy / continuing smoking
o Heavy alcohol intake
o Burn injury – curling injuries
o Brain injury – Cushing’s
• Focal damage to the gastric mucosa with acute
inflammation, necrosis and hemorrhage
• Manifest as acute gastric erosions which are often
multiple
• Erosions are less shallow than ulcerations, so there is
damage to the mucosa up until the shallow part of
the mucosa
• Endoscopically, there are reddened stomach lining
but we do not see ulcers / craters
• If the injury does not subside, patient has chronic
gastritis
• On microscopic examination at HPO, this gastric
mucosa shows infiltration by neutrophils.
o Signs of gastritis: reflux, sour taste in the mouth,
chronic cough with white phlegm
• Chronic mucosal inflammation and atrophy of
the mucosal glands
• H. pylori gastritis
o Most common form
o Increased gastric secretion occurs
o Test = Urea Breath Test
o May lead to peptic ulcer disease
o H. pylori has Urea that counteracts with the
acidity of the gastric contents which
allows for the survival of H. pylori
o Also, other enzymes that allow it to penetrate
into the mucosa, neutralizing the
mucosa
o Low socioeconomic class
• Chronic gastritis and peptic ulcer disease are
often accompanied by infection with
Helicobacter pylori.
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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY
• This small curved to spiral rod-shaped bacterium
is found in the surface epithelial mucus of most
patients with active gastritis
• The rod-shaped bacteria are seen here with a
methylene blue stain.
3 ) Peptic Ulcer Disease
• Often at or near the lesser curvature, in the antral or
prepyloric regions
• Involvement of deeper part of the mucosa up to the
part of the muscularis externae
• Involvement up until the adventitia = perforation
• H. pylori-mediated processes
o Bacterial ureases and proteases breakdown
glycoproteins in gastric mucus
o Increased permeability of the gastric mucosa to
hydrogen ion, resulting in back diffusion
of hydrogen ion
• Dysplasia, neoplasia, carcinoma formation
• Increased permeability = stomach starts to be
susceptible to its own contents or acids leading to
ulcer formation
• Chronic NSAID use = decrease in prostaglandin
formation or production
• Decreased or no prostaglandin = increased
susceptibility of stomach and duodenum to peptic
ulcer
• Common in population with shell fish, raw food,
seafood
• 1cm acute gastric ulcer is shown here in the upper
fundus.
• The ulcer is shallow and sharply demarcated, with
surrounding hyperemia and some small ulcers
• It is probably benign. However, all gastric ulcers
should be biopsied to rule out a malignancy.
(In sequence: small, medium, large ulcers)
→ The larger the ulcer, the higher the chance that
the ulcer may be a malignant precursor
4 ) Gastric Hemorrhage
• Here are some larger areas of gastric hemorrhage
that could best be termed “erosions” because
the superficial mucosa is eroded away.
• If the hemorrhage is chronic, it may lead to anemia;
will manifest tarry stools (blackening) due to
slow transit time from the stomach to the
intestine > rectum > anus. This condition is
called Melena
• Such erosions are typical for the pathologic
process termed gastropathy, which describes
gastric mucosal injury without significant
inflammation.
• The findings here fit with acute erosive
gastropathy, but there are other patterns.
• Etiologies for the various gastropathies can include:
alcohol, drugs such as NSAIDS, stress, uremia,
bile reflux, portal hypertension, radiation, and
chemotherapy.
*Gastric ulcers, peptic ulcer disease, and even erosions
may lead to complications: (1) obstruction (2)
hemorrhage (3) perforation
5 ) Gastric ulcer
• Here is a gastric ulcer. It is shallow and is about 2-
4 cm in size. This ulcer on biopsy proved to be
malignant, so the stomach was resected as
shown here.
• Severe abdominal pain, painful to touch
• Surgical emergency and requires opening of
abdominal cavity and closing of the
perforation
• Perforation = leakage of gastric juices and protease
enzymes to the nearest structure in the lesser
curvature or abdominal aorta
• The ulcer at the right is penetrating through the
muscularis and approaching an artery.
• Erosion of the ulcer into the artery will lead to
another major complication of ulcers—
hemorrhage. This hemorrhage can be life-
threatening.
• Chronic blood loss may lead to an iron deficiency
anemia.
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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY

• Microscopically, the ulcer here is sharply

• Principal site for digestion and absorption
demarcated, with normal gastric mucosa on
• MUCOSA
the left falling away into a deep ulcer whose
• SPECIAL STRUCTURES
base contains inflamed, necrotic debris. An
o Plicae circularis
arterial branch at the ulcer base is eroded
▪Vales of Kerckring
and bleeding.
▪Permanent transverse folds
▪Contain a core of submucosa
▪Numerous in distal part of duodenum
▪and the beginning of jejunum
• Villi
o Fingerlike and leaflike projections
• Microvilli
o Major amplification of the luminal surface
• The mucosa at the upper right merges into the
o Give the apical region a striated appearance
ulcer at the left which is eroding through the
• 5 Cell Types:
mucosa.
o Enterocytes
• Ulcers will penetrate over time if they do not heal.
o Goblet cells
• Penetration leads to pain. If the ulcer penetrates
o Paneth cells
through the muscularis and through
o Enteroendocrine cells
adventitia, then the ulcer is said to “perforate”
o M cells
and lead to an acute abdomen.
• LAMINA PROPRIA
6 ) Duodenal ulcer
o Nodules of Lymphatic tissue
o Large and numerous in the ileum
o Located on the side of the intestine opposite the
mesentery
o PEYER’S PATCHES

• The strongest association with Helicobacter pylori is

with duodenal peptic ulceration—over 85% of
duodenal ulcers but with very low malignant
potential
• Seen here is a penetrating acute ulceration in the
duodenum just beyond the pylorus.
• MUSCULARIS MUCOSAE
SMALL INTESTINE o Inner Circular – segmental movement of bolus
o Outer Longitudinal – bigger transport
• SUBMUCOSA
o Brunner’s glands / submucosal glands
▪ Highly alkaline secretion – contradicts very acidic
gastric juice / secretions
• Longest component of the digestive tract ▪ Branched tubular glands
• 3 anatomic portions • MUSCULARIS EXTERNA
o Duodenum o Inner circular
▪First shortest, widest part o Outer longitudinal
▪Begins at the pylorus *No common pathologies in small intestine
▪Ends at the duodenojejunal junction
o Jejunum LARGE INTESTINE
▪Begins at the duodenojejunal junction
▪Constitutes upper 2/5 of small intestine
o Ileum
▪Lower 3/5 of small intestine
▪Ends at ileocecal junction

• Reabsorption of electrolytes and water

• Elimination of wastes
• Cecum, vermiform appendix
• Colon:
o Ascending

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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY
o Transverse • Since this is an inflammatory reaction, you will have
o Descending the typical signs and symptoms such as vomiting
o Sigmoid • Common: vomiting, nausea, loss of appetite, fever,
• Rectum anorexia
• Anal Canal • Gross changes:
• SPECIAL STRUCTURES: o Congested appendix with a swollen distal half
o Teniae coli covered by purulent exudate
▪ 3 narrowed thickened equally spaced • Histologic appearance
▪ Bands of outer longitudinal muscularis externa o Acute inflammatory infiltrate extending from the
▪ Cecum and colon mucosa through the full thickness of the
o Hausta. Coli appendiceal wall
▪ Sacculations or spaces between teniae coli o Microscopically, acute appendicitis is marked by
o Omental appendices mucosal inflammation and necrosis
▪ Small fatty projections of the serosa
o MUCOSA
▪ No villi, no plicae circulares
▪ Straight tubular intestinal glands
▪ Crypts of Leiberkuhn
o MUSCULARIS EXTERNA
▪ Inner Circular o Here, the mucosa shows ulceration and
▪ Outer longitudinal undermining by an extensive neutrophilic
o Identifying structure: mucosal lining, no exudate
invaginations, uniform glands
o CECUM

o Neutrophils extend into and through the wall of

▪ Blind pouch distal to the ileocecal valve
▪ First entry to the large intestine
▪ (Arrow: appendix), where the T coli will meet
o APPENDIX
the appendix in a case of acute appendix in a
case of acute appendicitis.
o Clinically, the patient often presents with right
lower quadrant abdominal pain.
o Rebound tenderness of the right lower quadrant
is often noted on physical examination, as well
as positive obturator or psoas sign.
o An elevated WBC count is usually present.

▪ Thin, fingerlike extension of the cecum

▪ Uniform layer of longitudinal muscle in the
RECTUM
muscularis externa
▪ Large number of lymphatic nodules that extend
into the mucosa
▪ Distensible up to a point
COMMON PATHOLOGIES OF LARGE INTESTINE:
1 ) APPENDICITIS

• Dilated distal portion of the alimentary canal

• Upper part = transverse rectal folds
• X teniae coli (since there is no movement needed)
• ANAL CANAL
o Most distal portion
o Glands extend into submucosa
o Anal columns; Anal sinuses

• Obstruction of the appendiceal lumen resulting in

bacterial proliferation and invasion of the
mucosa
• Presents as right lower quadrant pain, usually it is
vague at first, starts off at the periumbilical area
then as it progresses, you will have stretching of
adventitia of the appendix

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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY
o Colorectal zone
▪ Upper third
▪ Simple columnar epithelium
o Anal transition zone
▪ Middle third
▪ Transition between epithelia
o Squamous zone • True neoplasms
▪ Lower third • Usually asymptomatic
▪ Stratified squamous epithelium o TUBULAR ADENOMA
▪ Most common adenomatous polyps
• RECTUM AND ANAL CANAL ▪ Small pedunculated
▪ Contain malignant foci
o TUBULOVILLOUS
▪ 15% of adenomatous polyps
▪ Surface covered by fingerlike villi
▪ Intermediate malignant potential
o VILLOUS ADENOMAS
▪ 10%
▪ Larger than tubular adenomas
▪ Sessile and velvety
▪ Large number of fingerlike villi
▪ Highest potential for malignancy
o SESSILE SERRATED ADENOMAS
▪ Endoscopically, mucosal folds
▪ Resemble hyperplastic polyps
▪ Predilection for the right colon
• Adenomas can be classified as:
o SUBMUCOSA o Diminutive (1 to 5 mm in diameter)
▪ Terminal ramifications of superior rectal artery; o Small (6 to 9 mm)
▪ and rectal venous plexus o Large (> & = to 10 mm)
o MUSCULARIS EXTERNA • The greater the size = higher chance for it to be
▪ Uniform longitudinal sheet in rectum malignant
▪ Disappears at the ATZ • More villous features = also higher chance for it to
▪ Circular layers form sphincters be malignant
• Advanced adenomas are either >/=10mm or are <1
BENIGN POLYPS cm with at least 25% villous features, high-grade
dysplasia, or carcinoma
• Tubulovillous adenomas have 25 to75% villous
features
• Villous adenomas have >75% villous architecture

• Polyp TUBULAR ADENOMA

o Any elevation of the intestinal surface
o Pedunculated polyp – narrow stem
o Sessile polyp – broad-based attachment
• Hyperplastic polyps
o No clinical significance

• This small adenomatous polyp (tubular adenoma) on

a small stalk is seen microscopically to have
more crowded, disorganized glands than the
normal underlying colonic mucosa.
• Goblet cells are less numerous and the cells lining the
glands of the polyp have hyperchromatic nuclei.
• Inflammatory polyp
o Benign lymphoid polyps
o Inflammatory pseudopolyps
o Granulation tissue and remnants of mucosa,
caused by inflammatory bowel disease
• Hamartomatous polyps
• Microscopically, a villous adenoma is shown at its
o Juvenile polyp
edge on the left, and projecting above the
o Peutz-Jegher polyps
basement membrane at the right.
▪ No malignant potential
• The cauliflower-like appearance is due to the
ADENOMATOUS POLYPS
elongated glandular structures covered by
dysplastic epithelium.
• Though villous adenomas are less common than
adenomatous polyps, they are much more likely

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MEDICAL HISTOLOGY LECTURE – DIGESTIVE PATHOLOGY
to have invasive carcinoma in them (about 40%
of villous carcinoma)

• A microscopic comparison of normal colonic mucosa

on the left and that of an adenomatous polyp
(tubular adenoma) on the right is seen here.
• The neoplastic glands are more irregular with darker
(hyperchromatic) and more crowded nuclei.
• This neoplasm is benign and well-differentiated, as it
still closely resembles the normal colonic
structure.

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