Southwestern University-Matias H. Aznar Memorial, Inc.

College of Medicine

Case 1
Submitted by:
II-A Group 1
Abdulatiffh, Sittie Alia
Abecia, Evalaine
Aboy, Jose Lorenz
Acabo, Gideon Rey
Alarcon, Maelisa Grace
Alawi, Juhara
Arellano, Jemer Grace
Arendain, Gerald Ian
Ardosa, Rondy
Atuel, Kristhy
6/25/2014

Case 1
A 50-year old security guard presents with a long-standing history of retrosternal burning and belching
which he commonly gets after meals. He has been smoking since the age of 13 and he consumes five
bottles of beer every night. A month ago he was treated for gastroesophageal reflux dyspepsia. Upper
gastrointestinal endoscopy reveals streaks of red to velvety mucosa at the gastroesophageal junction.
Biopsy from this site shows the presence of gastric and intestinal-type columnar cells.
1. Review the anatomy and histology of the organ involved.

Esophagus:
-

Anatomy
o

Muscular tube (25cm long) -average diameter of 2cm

Extends from the pharynx to the stomach

Function: to convey food from the pharynx to the stomach

Passes through the esophageal hiatus in the muscular right crus of the diaphragm just to the
left of the median plane at the level of T10 vertebra.

Terminates by enetering the stomach at the cardial orifice of the stomach to the left of the
midline at the level of the 7th left costal cartilage and T11 vertebra.

Esophagogastric junction: lies to the left of T11 vertebra; where the mucosa abruptly changes
from esophageal to gastric mucosa

Histology
o

Mucosa

Composed of 3 layers: epithelium, lamina propria, and muscularis externa

Lumen is lined by 0.5 mm thick stratified squamous non-keratinized epithelium

Lamina propria houses the esophageal cardiac glands and occasionally lymphoid
nodules

Muscularis externa consists of single layer of longitudinal smooth muscle fibers

Submucosa

Denses, fibroelastic connective tissue that houses the mucous glands known as
esophageal glands proper

Muscularis externa

Composed of 2 layers: inner circular and outer longitudinal

Upper 1/3 of esophagus has mostly skeletal muscle

Middle 1/3 contains both skeletal and smooth muscles

Lower 1/3 contains only smooth muscles

Has 2 physiologic sphincters: the pharyngoesophageal sphincter and the gastroesophageal

sphincter which prevent reflux into the pharynx from the esophagus and into the esophagus
from the stomach

2. Given the endoscopy and biopsy findings, what is the type of cell adaptation involved in this
case? And discuss its mechanism of cellular adaptation.

METAPLASIA - Barrett's esophagus (sometimes called Barrett esophagus, or columnar epithelium

lined lower oesophagus (CELLO), Barrett syndrome) refers to an abnormal change (metaplasia) in
the cells of the lower portion of the esophagus. It is characterized by the replacement of the normal
stratified squamous epithelium lining of the esophagus by simple columnar epithelium with goblet
cells (which are usually found lower in the gastrointestinal tract) due to cell adaptation.

The concept of Barret's esophagus is simple. The normal squamous mucosa of the esophagus is
replaced by glandular mucosa as an adaptive process usually because there is a reflux of the gastric
(highly acidic) materials from the stomach into the esophagus and therefore, the esophagus responds
by becoming more gastric-like and less squamous-like since gastric mucosa (simple columnar) has
tall columnar epithelial cells which secretes a layer of thick mucus that protects from gastric materials
which the former squamous cells do not have.
Columnar metaplasia of the distal esophagus represents a squamous to columnar metaplastic
reaction that develops from an esophageal stem cell and may pass through an intermediate phase
characterized by the presence of a type of epithelium that possesses a mixture of squamous and
columnar features, termed multilayered epithelium.

3. What is the most likely cause?

We need to take special considerations on such morphological change in the patients epithelial
lining. Basing on the case, the patient has been smoking since 13 years of age and has been
consuming 5 bottles of beer every night.
Smoking weakens the lower esophageal sphincter, the muscle between the esophagus and stomach
that keeps contents from flowing back into the esophagus. The stomach is naturally protected from
the acids it makes to help break down food. However, the esophagus is not protected from the acids.
When the LES weakens, stomach contents may reflux into the esophagus possibly damaging the
lining of the esophagus. Furthermore tobacco smoke has chemical that may cause mucosal irritation
to cells.
Alcohols effect on the body on the other hand is that it may cause direct damage to esophageal and
gastric mucosae. In addition, toxic acetaldehyde metalize from alcohol could affect the function of the
esophagus and stomach. It is also a depressant and relaxant which may contribute to its effect on the
LES thereby initiating reflux of the gastric acids into the esophagus thereby eliciting changes in cell
structure just like tobacco. In addition alcohol potentiates the depressant effect of nicotine in the CNS
thereby affecting the muscle tone of the LES.

Alcohol and tobacco paves the way for acid reflux into the esophagus through its effect on the LES.
Presence of acid in the esophagus initiates compensatory mechanisms in the cells to adapt to this
new environment hence the metaplasia observed in the esophageal lining.
4. Is this physiologic or pathologic? Reversible or irreversible?

This is a pathologic form of metaplasia, since the change is caused by chronic irritation of the lower
esophagus by the reflux of hydrochloric acid from the stomach and carries with it undesirable effects
such as the ones experience by the patient. However, the change in the epithelium is reversible if the
patient undergoes a combination of anti-reflux therapy and endoscopic thermal injury.

5. What other types of cellular adaptation? Discuss and differentiate each type as to its causes, mechanism, microscopic findings, and
give examples.
Cellular Adaptation

Causes

Mechanism
Mechanical stretch/agonists/growth factors
|
Signal transduction pathways
|

- Increased functional demand

Hypertrophy

Transcription factors
- Stimulation by hormones and growth factors
|
Increased synthesis of contractile proteins
Increased induction of embryonic/fetal genes
Increased production of growth factors
Physiologic
- Hormonal

Hyperplasia

- Compensatory
Pathologic
-

Atrophy

- Growth factor-driven proliferation of mature cells

- Increased output of new cells from tissue stem cells

Excess hormones or growth factors acting on

target cells

Physiologic

- Decreased protein synthesis

Normal development

Pathologic
-

Decreased workload (atrophy of disuse)

Loss of innervation (denervation atrophy)

- Increased protein degradation in cells

Diminished blood supply

- Increased autophagy

Inadequate nutrition

Loss of endocrine stimulation

Pressure

Cellular Adaptation
Hypertrophy
-

Microscopic Findings
Increase in the size of the
cells, resulting to increase
size of the organ
No new cells, just larger cells

Examples
The
for

most common stimulus for hypertrophy of muscle is increase workload

example, the bulging muscles of bodybuilders engaged in
pumping iron result from an increase in size of the
individual muscle fibers in response to increased
demand.

In the heart, the stimulus for hypertrophy is usually chronic hemodynamic overload, results
from either hypertension or faulty vales

Physiologic hypertrophy of the uterus during pregnancy. A, Gross appearance of a normal

uterus (right) and a gravid uterus (removed for postpartum bleeding) (left). B, Small spindle-

shaped uterine smooth muscle cells from a normal uterus, compared with C, large plump cells
from the gravid uterus, at the same magnification.
Hyperplasia
-

Increase in the number of

cells in an organ or tissue
Takes place if the cell
population is capable of
dividing

Hormonal hyperplasia is well illustrated by the proliferation of the glandular epithelium of the
female breast at puberty and during pregnancy. Usually accompanied by enlargement
(hypertrophy) of the glandular epithelial cells.

(a) Macroscopic aspect of a normally regenerating liver. (b) Pale liver with hemorrhage
resulting from stenosis of the suprahepetic vena cava. (c) H&E staining of a normally

regenerating liver section ( 400 original magnification). Note the number of mitotic figures
present in the section (black arrows). (d) H&E staining of the liver shown in panel (b) ( 200
original magnification). Note the presence of necrotic areas (asterisk).
Atrophy

Reduced in size of an organ

or tissue resulting from a
decrease in cell size and
number

Carpal Tunnel Induced Atrophy: Chronic, severe compression of the median nerve within the
carpal tunnel has led to atrophy of the Thenar muscles (hand on right). A normal appearing
Thenar Eminence is demonstrated on left.

Normal brain of a young adult. B. atrophy of the brain in an 82 years old male with
atherosclerotic cerebrovascular disease, resulting in reduce blood supply. Note that

loss of brain substance narrows the gyri and widens the sulci. The meninges have
been stripped from the right half of each specimen to reveal the suface of the brain

6. Discuss the clinico-pathologic correlations of cell adaptation in this case.

Barrett esophagus is a complication of chronic GERD that is characterized by intestinal metaplasia
within the esophageal squamous mucosa. Barrett esohagus most common in males and it typically
presents between 40 and 60 years of age.
Prolonged exposure of the esophagus to the refluxate can erode the esophageal mucosa, promote
inflammatory infiltrate, and ultimate epithelial necrosis. This chronic damage is believed to promote
the replacement of healthy esophageal epithelium with the metaplastic columnar cells of the Barrett
esophagus, the cellular origin of which remains unknown. This likely is an adaptive response of the
esophagus, which, if not for the increased rate of cancer, would have been beneficial.
Smoking prevents production of bicarbonate ions by reducing synthesis of prostaglandins, which
controls bicarbonate secretion. It also causes alterations in the epithelial barrier leading to changes in
the composition of the underlying immune cell population. One of the components of tobacco is
nicotine, which increases acid and pepsin secretion, as well as,gastric motility.
Alcohol impairs the ability of the lower esophageal sphincter (LES) to contract. Prolonged use
damages the protective mucosa in the esophagus and leads to changes in cells that causes
overproduction of gastric acid.
Barrett esophagus can be recognized as one or several tongues or patches of red, velvety mucosa
extending upward from the gastroesophageal junction. This metaplastic mucosa alternates with
residual smooth, pale squamous (esophageal) mucosa and interfaces with light-brown columnar
(gastric mucosa distally). The secretory columnar epithelium can resist the erosive action of the
gastric secretions, suggesting that they may be an adaptation to the chronic acid exposure. Columnar
epithelium has a reddish color and velvet-like texture from the pale, glossy appearance of squamous
epithelium.
Goblet cells normally line the intestines, not the esophagus. When goblet cells develop in a place
where they are not supposed to be, like the lining of the esophagus, it is called intestinal metaplasia.
Intestinal metaplasia can develop any place where squamous mucosa is normally found. When
intestinal metaplasia occurs in the squamous mucosa it is called Barrett esophagus.
Diagnosis of Barrett esophagus requires both endoscopic evidence of abnormal mucosa above the
gastroesophageal junction and histologically documented intestinal metaplasia. Goblet cells, which
have distinct mucous vacuoles that stain pale blue by H & E and impart the shape of a wine goblet to
the remaining cytoplasm define intestinal metaplasia and are necessary for diagnosis of Barrett
esophagus.

Modifiable

Non-modifiable

Smoking at the age of 13

Consumes 5 bottles of beer/night
History of burning and belching after meals

Age- 50 years old

sex-male

Smoking

Chronic GERD

Prevents HCO3 production

cell injury

dec. LES tone

Inc. gastric acid production

Alteration in the epithelial barrier

Alcohol
direct damage to LES

direct

inc. reflux of gastric juices

Cellular injury
Cellular adaptation
METAPLASIA
Change of squamous epithelium
To columnar type
Red, velvety mucosa on gastroesophageal
Junction upon endoscopy

cellular
adaptation