Lecture 23 - Gastrointestinal Tract - Part 2 - Clinical Correlates

HISTOLOGY COURSE
LECTURE XIX – DIGESTIVE TRACT – CLINICAL

CORRELATES
MD I
ALL SAINTS UNIVERSITY SCHOOL OF MEDICINE
Dr. Marie Affana

Lecture Objectives
● Describe the changes in the autonomic nerve plexus in the wall of the GIT that may lead to
Hirschsprung Disease (congenital mega colon).
● Describe the change in the epithelium of the lower esophagus resulting from chronic acid reflux
(Barrett’s Esophagus).
● Explain the consequences of varicosities of the esophagus and the rectum.
● Describe the changes that occur in the wall of the gastro intestinal tract after surgical procedures like
appendectomy, which may lead to adhesions.
● Describe the changes in the villi in mal absorption syndrome.
● Describe the changes to the wall of the stomach in the development of ulcers.
● Describe the histological appearance of a adenomatous polyp of the large intestine.

● Describe the main complications of chronic peptic ulceration.
Achalasia
Motor disorder of the distal esophagus secondary to progressive degeneration of the Auerbach plexus
(ganglion cells in the myenteric plexus)
Etiology
The etiology of primary/idiopathic achalasia is unknown
Secondary achalasia occurs due to diseases that cause esophageal motor abnormalities
- Chagas disease: protozoan parasite Trypanosoma cruzi destroys intramural ganglion cells other diseases
include amyloidosis, sarcoidosis, scleroderma, neurofibromatosis, Fabry disease, and eosinophilic esophagitis.
Pathogenesis
Inflammation and degeneration of neurons of the Auerbach’s plexus
The cause of the degeneration is unknown but may be autoimmune as suggested by the association with
variants in the HLA-DQ regions in affected patients and the presence of antibodies to enteric neurons
primarily leads to loss of nitric oxide-producing, inhibitory neurons that affect the relaxation of esophageal
smooth muscle results in loss of normal relaxation of the lower esophageal sphincter (LES) and rise in
basal sphincter pressure.
Results in aperistalsis
Prognosis
Disease is progressive without treatment that ultimately leads to end-stage achalasia characterized by
esophageal tortuosity, angulation, and megaesophagus (diameter >6 cm)
Symptoms
Dysphagia for solids
and liquids
Regurgitation
Difficulty belching
Vomiting
Heartburn/substernal
chest pain
Weight loss
Radiography
may demonstrate mediastinal widening
Barium esophagram
not a sensitive test for achalasia, as it may be interpreted as normal in up to 1/3 of
patients
positive findings include 1) dilation of the proximal esophagus 2) “bird-beak” appearance
at the esophageal sphincter 3) aperistalsis 4) delayed emptying of barium
Upper endoscopy
may reveal dilated esophagus that contains residual material
esophageal mucosa usually appears normal
often performed after esophageal manometry to rule out malignancy
Esophageal manometry
Gold standard - required to establish diagnosis
Findings include increased LES pressure, inability of the LES to relax, decreased
peristalsis, and diffuse esophageal spasm
“bird-beak”
appearance
Barrett Esophagus
● Metaplastic transformation of esophageal lining : normal squamous epithelium → columnar
epithelium → intestinal metaplasia (with globlet cells)
● Result of chronic gastroesophageal reflux disease (GERD)
● Pathogenesis
○ mucosal injury causes acute and chronic inflammatory change
○ esophageal stem cells develop columnar intestinal metaplasia

● Risk factors
○ GERD > 5-10 years
○ age > 50 years
○ male > female
○ obesity
● Associated conditions: Risk of progression to adenocarcinoma
Barrett Esophagus
Presentation Evaluation
● Diagnosis with upper endoscopy with biopsy

● Symptoms
showing both
○ heartburn ● Histology
○ Metaplastic columnar epithelium with

○ regurgitation
goblet cells (normally in stomach and
● Physical exam intestines) in esophageal mucosa
● Visualization of abnormal distal esophageal
○ typically normal
mucosa
Goblet Cells,
Staining Blue
in Esophagus
with Alian
Blue Stain
Barrett Esophagus
A common cause for

inflammation is a so-called
"Barrett esophagus" with
epithelial metaplasia to gastric-
type mucosa above the
gastroesophageal junction.
The metaplasia results from

chronic gastroesophageal
reflux disease (GERD).
Note the columnar epithelium

to the left and the squamous
epithelium at the right. This is
"typical" Barrett mucosa,
because there is intestinal
metaplasia as well (note the
goblet cells in the columnar
mucosa).
Acute gastritis
This is a more typical acute
gastritis with a diffusely
hyperemic gastric mucosa.
There are many causes for
acute gastritis: alcoholism,
drugs, infections, etc.
On microscopic examination at high power, this gastric

mucosa shows infiltration by neutrophils. This is
acute gastritis.
Gastric Ulcer
Seen below is a gastric ulcers of large size on upper
endoscopy. All gastric ulcers are biopsied, since
gross inspection alone cannot determine whether a
malignancy is present. Smaller, more sharply
demarcated ulcers are more likely to be benign.
Microscopically, the ulcer here is sharply demarcated,

with normal gastric mucosa on the left falling away into
a deep ulcer whose base contains inflamed, necrotic
debris. An arterial branch at the ulcer base is eroded
and bleeding.
CAUSES
Peptic Ulcer Disease
•Peptic ulcer: a defect in the gastric •H. pylori
or duodenal mucosa with a diameter of at
least 0.5 cm and a depth that penetrates •NSAIDs
through the muscularis mucosae • Inhibit COX-1 and COX-2 → decrease
in prostaglandin production
•Gastric ulcer: a peptic ulcer of the → erosion of the gastric mucosa
gastric mucosa, typically located along • Decrease mucosal blood flow
the lesser curvature in the transitional • Inhibit mucosal cell proliferation
portion between the corpus and antrum
•Acid hypersecretion: acid hypersecretion
•Duodenal ulcer: a peptic ulcer of (e.g., Zollinger-Ellison syndrome) and
the duodenal mucosa, usually located on increased gastrin production → ↑
the anterior or posterior wall of H+ secretion and parietal cell mass → delivery
the duodenal bulb of excessive acid to the duodenum
Gastric adenocarcinoma
A moderately
differentiated gastric
adenocarcinoma is
infiltrating up and into
the submucosa below
the squamous mucosa
of the esophagus.
The neoplastic glands

are variably sized.
CELIAC DISEASE
● A chronic hereditary intestinal malabsorption disorder caused by intolerance to gluten (a cereal
protein found in wheat and rye and less so in barley and oats)
● Pathogenesis
○ gluten (specifically gliadin) becomes an antigen by acting as a substrate for tissue transglutaminase
■ tissue transglutaminase deaminates dietary gluten forming negatively-charged gluten fragments
○ fragments are phagocytosed by antigen presenting cells (APCs) and presented to T-helper cells
■ cytokines released promote aggregation of killer lymphocytes
○ lymphocytes cause mucosal damage with loss of villi and proliferation of crypt cells
○ damage primarily occurs in the proximal small bowel
○ timing and dose of gluten when introduced into the diet has importance
PRESENTATION
● Many may be asymptomatic (absent in children until they eat food

containing gluten)
● Diarrhea
● Failure to thrive
● Growth retardation
● Weight loss
● Weakness and pallor
● Secondary to iron-deficiency anemia
PRESENTATION
● Physical exam
● Classic dermatitis
herpetiformis
● pruritic, red,
papulovesicular lesions
on shoulders, elbows,
knees
● Inflammatory cutaneous
disease with chronic
relapsing course
CELIAC SPRUE/DISEASE
NORMAL
HISTOLOGY
Biopsy shows
a pathognomonic
blunting of
intestinal villi and
flat mucosa with
hyperplastic glands
and diffuse
lymphocytic
infiltration
The small intestinal
mucosa at high
magnification shows
marked chronic
inflammation in a
case of celiac disease
(sprue).
The enteropathy
shown here has loss
of crypts, increased
mitotic activity, loss
of brush border, and
infiltration with
lymphocytes and
plasma cells (B-cells
sensitized to
gliaden).
Acute Appendicitis
Microscopically,
acute appendicitis
is marked by
mucosal
inflammation and
necrosis.
Acute Appendicitis
•Migrating abdominal pain: most common and specific symptom
• Typically constant and rapidly worsens
• Most patients present within 48 hours of symptom onset.
• Initial diffuse periumbilical pain: caused by the irritation of the visceral peritoneum (pain is
referred to T8–T10 dermatomes) [6]
• Localizes to the RLQ within ∼ 12–24 hours: caused by the irritation of the parietal
peritoneum
•Associated nonspecific symptoms

• Nausea
• Anorexia
• In up to 80% of cases
• Hamburger sign: If there is no loss of appetite, appendicitis is unlikely. [7]
• Vomiting
• Low-grade fever
• Diarrhea
• Constipation
Acute Appendicitis
Here, the mucosa shows ulceration
and undermining by an extensive
neutrophilic exudate.
Adenomatous Polyp
A small adenomatous polyp

(tubular adenoma) is seen
here.
This lesion is called a

"tubular adenoma" because
of the rounded nature of
the neoplastic glands that
form it.
It has smooth surfaces and

is discrete. Such lesions
are common in adults.
Adenomatous Polyp
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.
However, it is still well-

differentiated and
circumscribed, without invasion
of the stalk, and is benign. Two
colonoscopic views of a small
polyp that proved to be a
tubular adenoma are seen in
the next slide.
Adenomatous Polyp
Hirschsprung Disease
Congenital megacolon: functional (vs mechanical) intestinal obstruction
Pathogenesis: Absence of ganglion cells/enteric nervous plexus in intestine due to failure of neural crest
cell migration
Lack of nerves causes constant contraction
Symptoms
- Bilious vomiting
- Failure to pass meconium in first 48 hours of life
- Chronic constipation due to large bowel obstruction
Physical exam
- Abdominal distention
- Extremely tight anal sphincter
- No stool in rectal vault
•Hirschsprung disease is caused by defective caudal migration
of parasympathetic neuroblasts (precursors of ganglion cells) from the neural crest to
the distal colon. This process takes place between the 4th and 7th week of development.
•Affected segments are histologically characterized by the absence of the Meissner

plexus and Auerbach plexus (submucosal and myenteric plexus ganglion) beginning at
the anorectal line, leading to: [3]
• Inability of the myenteric plexus to control the intestinal wall muscles
→ uncoordinated peristalsis and slowed motility
• Spastic contraction of intestinal muscles → stenosis and functional obstruction
• Expansion of the colon segment proximal to the aganglionic section
(possible megacolon)
Evaluation
Gold standard diagnosis

- Rectal suction biopsy: Lack of
ganglionic cells in submucosa
Imaging
- Abdominal radiography: distended
bowel loops and lack of air in rectum
This Histological image with
staining of
Acetylcholinesterase
(AchE) positive fibers (in
brown) shows
aganglionosis in the
mucosa.

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HISTOLOGY COURSE

LECTURE XIX – DIGESTIVE TRACT – CLINICAL

Dr. Marie Affana

● Describe the histological appearance of a adenomatous polyp of the large intestine.

○ mucosal injury causes acute and chronic inflammatory change

○ esophageal stem cells develop columnar intestinal metaplasia

○ GERD > 5-10 years

○ age > 50 years

○ male > female

● Diagnosis with upper endoscopy with biopsy

○ Metaplastic columnar epithelium with

A common cause for

The metaplasia results from

Note the columnar epithelium

On microscopic examination at high power, this gastric

Microscopically, the ulcer here is sharply demarcated,

The neoplastic glands

■ tissue transglutaminase deaminates dietary gluten forming negatively-charged gluten fragments

■ cytokines released promote aggregation of killer lymphocytes

○ damage primarily occurs in the proximal small bowel

● Many may be asymptomatic (absent in children until they eat food

•Associated nonspecific symptoms

A small adenomatous polyp

This lesion is called a

It has smooth surfaces and

Goblet cells are less numerous

However, it is still well-

•Affected segments are histologically characterized by the absence of the Meissner

Gold standard diagnosis

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