9

Pathology of the
Gastrointestinal Tract
LM 202
Dr. Hassan Kofahi
Oral Cavity
Dental caries (Tooth decay)
• Results from focal demineralization of tooth
structure (enamel and dentin).
• Caused by acids generated during the
fermentation of sugars by bacteria.
• Caries is the main cause of tooth loss before
the age of 35.
• Dental caries can be reduced by:
• Proper oral hygiene
• Fluoridation of the drinking water
• Fluoride is incorporated into the crystalline structure
of enamel, forming fluoroapatite, which is resistant to
degradation by bacterial acids.
Gingivitis
• Inflammation of the gingiva.
• Most commonly, occurs in response to a bacterial
biofilm, known as the plaque, on the surface of
teeth.
• Dental plaque is a sticky biofilm composed of bacteria,
salivary proteins, and dead epithelial cells.
• As it accumulates, plaque becomes mineralized to
form calculus (Tartar).
• Symptoms: gingival erythema (redness), edema,
and bleeding.
• Gingivitis can be reversed by good oral hygiene to
reduce plaque and calculus formation.
• If not treated, gingivitis can progress to
periodontitis.
Periodontitis
• Periodontitis is an inflammation that
affects the supporting structures of
the tooth.
• With progression, periodontitis may
result in the destruction of
periodontal ligament and alveolar
bone and, eventually, tooth loss.
• Associated with poor oral hygiene.
Aphthous Ulcers (Canker Sores)
• Common superficial mucosal ulcerations in the
mouth.
• Affect up to 40% of the population.
• More frequent in the first 2 decades of life.
• Extremely painful.
• The cause is unknown.
• Tend to be familial.
• Could associate (in some cases) with other diseases
such as celiac disease, inflammatory bowel disease and
Behçet disease.
• Morphology: shallow ulcer that have a hyperemic
base often covered by a thin exudate (yellow-
white color) and surrounded by a narrow zone of
erythema (redness).
• Usually resolve spontaneously in 7-10 days, but
often recur.
Herpetic stomatitis (cold sore)
• Caused mainly by Herpes simplex virus type-1 (HSV-1). less
commonly by HSV-2.
• Herpes simplex virus causes a self-limited primary infection that
can be reactivated later in life.
• The primary infection usually occurs early in childhood (2-4 years of
age) and it is often asymptomatic.
• Most of the adults harbor latent (inactive) HSV-1 infection, in the facial
sensory nerves, that can reactivate.
• Reactivation of HSV results in recurrent herpetic stomatitis,
known commonly as “cold sore”.
• Symptoms: a burning pain followed by small blisters or sores.
• Appear on the lips (herpes labialis), nasal orifices, buccal (cheek)
mucosa, gingiva, and hard palate.
• Typically resolve within 7 to 10 days
• Reactivation can be triggered by several factors including:
• Stress
• UV light
• Upper respiratory-tract infection
• Immunosuppression
Esophagus
Gastroesophageal Reflux Disease (GERD)
• Reflux of gastric contents into the lower esophagus.
• Very common
• Occurs as a result of abnormal function of the lower esophageal sphincter or as a
result of an increased abdominal pressure.
• Risk factors:
• Alcohol and tobacco use
• Obesity
• Certain types of food
• Certain drugs
• Pregnancy
• Hiatal hernia (will be discussed next)
• Delayed gastric emptying
• Increased gastric volume
GERD: Clinical features
• Occur at any age, but more common in people over 40.
• Symptoms:
• Heartburn
• Dysphagia (difficulty in swallowing)
• Less often, noticeable regurgitation of sour-tasting gastric contents.
• Complications:
• Esophageal ulceration
• Hematemesis (vomiting of blood)
• Melena (blood in stools)
• Stricture development (narrowing or tightening of the esophagus)
• Barrett esophagus
• Treatment: Proton pump inhibitors (relief the symptoms by reducing the
gastric acidity)
Hiatal hernia
• Characterized by the protrusion of the
stomach into the thorax through a gap in
the diaphragm.
• Could be congenital or occurs later in life.
• Occurs when weak muscle allow the
stomach to push through the diaphragm.
• Causes:
• In most of the cases, the cause is unknown.
• Risk factors include obesity, pregnancy and old
age.
• Symptoms: Occur in less than 10% of the
cases.
• Similar to GERD
Barrett Esophagus
• A complication of chronic GERD.
• Characterized by intestinal
metaplasia within the esophageal
squamous mucosa.
• Metaplastic replacement of the
normal esophageal squamous
mucosa by intestinal-type columnar
epithelium with goblet cells in the
lower esophagus.
• Occurs in 10% of individuals with
GERD.
• Increases the risk for development
of esophageal adenocarcinoma.
Stomach
Mechanisms of Protection of the gastric
mucosa
• The stomach environment is extremely harsh
• Low pH (pH≈1).
• Peptic enzymes.
• Normally, the gastric mucosa is protected from the harsh
environment by the following mechanisms:
• The gastric epithelium is covered by a layer of mucus.
• Secretion of bicarbonate ions by surface epithelial cells.
• The rich blood supply of the gastric mucosa efficiently buffers and removes
acids that back-diffuse into the lamina propria.
Injury of the gastric mucosa
• Disruption of any of the protective mechanisms of gastric mucosa
may result in injury.
• The main causes of gastric injury include:
• Heavy use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as Aspirin,
ibuprofen and naproxen.
• Mechanism: NSAIDs inhibit the synthesis of prostaglandins and, as a result, inhibits the
production of mucus and bicarbonate and reduces the mucosal blood flow.
• H. pylori infection
• Uremia (high urea in the blood)
• Smoking
• Alcohol
• Ingestion of harsh chemicals (accidentally or suicidal attempts)
Acute Gastritis
• Acute gastritis: is an acute inflammatory reaction in the gastric mucosa.
• Often transient and self-limited
• Causes:
• Heavy use of NSAID
• Heavy alcohol consumption
• Systemic diseases that predispose to a breakdown of the protective mucous layer.
• Pathogenesis: acute gastritis occurs when gastric acid breaks through the protective
mucous layer, causing injury to gastric epithelial cells and initiating a superficial acute
inflammatory reaction.
• Symptoms:
• Epigastric pain
• Nausea and vomiting.
• In more severe cases, there may be mucosal erosion, ulceration, hemorrhage, hematemesis,
melena, or, rarely, massive blood loss.
• Could be asymptomatic
Chronic gastritis
• Chronic gastritis causes less severe but more persistent symptoms
than acute gastritis.
• Causes:
• Infection with Helicobacter pylori (H. pylori).
• Autoimmune chronic gastritis.
• Chronic NSAID use
Helicobacter pylori (H. pylori) Gastritis

• H. pylori is a bacteria that can survive in the harsh environment of the

stomach.
• Causes the majority of chronic gastritis and peptic ulcer cases
worldwide.
• In most of the cases, H. pylori gastritis is asymptomatic.
• More than 50% of the world population are infected with H. pylori.
• Prevalence of H. pylori in Jordan is high (more than 80% of the
population are infected with H. pylori according to one study).
Helicobacter pylori Gastritis
• Most often presents as an antral gastritis with increased acid production.
• The increased acid production may give rise to peptic ulcer disease of the duodenum
or stomach.
• The organism survive in the mucous layer adherent to gastric mucosa.
• H. pylori infection initiates a chronic immune response in the gastric
mucosa.
• The ongoing inflammation causes injury to the gastric epithelium.
• Over time, infection can result in:
• Metaplasia of the gastric mucosa to small intestinal type mucosa
• Loss of gastric epithelium (atrophy).
• Increases the risk of stomach cancer.
Autoimmune gastritis
• Accounts for less than 10% of cases of chronic gastritis.
• Pathogenesis: Caused by auto-antibodies to parietal cells.
• Parietal cells are epithelial cells that secrete hydrochloric acid (HCl) and
intrinsic factor in the stomach.
 Intrinsic factor is important for the absorption of vitamin B12.
• The auto-antibodies lead to a loss in parietal cells causing reduction in acid
and intrinsic factor secretion.
• Deficient acid secretion induces the production of Gastrin, causing
hypergastrinemia (i.e., high levels of gastrin in the blood) and causes
hyperplasia of the G cells.
 Gastrin is a hormone produced by G cells in the stomach to stimulate the production of
HCl.
• Deficient intrinsic factor production causes B12 deficiency which leads to
pernicious anemia.
 Hyperplasia of G cells
Gastrin Normal
HCl
Intrinsic
Parietal Cells factor
Gastrin

G cells
Autoimmune gastritis Hypergastrinemia

HCl
Intrinsic Pernicious
B12 deficiency
Loss of factor anemia
Auto-antibodies Parietal Cells
(Anti-parietal cell
antibodies)
Peptic Ulcer Disease (PUD)
• Deep ulcers of the stomach (gastric ulcers) or first
portion of the duodenum (duodenal ulcers).
• Duodenal ulcers are 4 times more common than gastric
ulcers.
• Generally, develops on a background of chronic gastritis.
• Mostly, caused by:
• H. pylori infection (5% to 10% of H. pylori–infected individuals
develop ulcers)
• NSAID use
• Occurs due to an imbalance between mucosal defenses
and damaging forces (described earlier).
PUD: Clinical features
• Symptoms:
• Burning stomach pain
• Gastric ulcer pain increases by meals.
• Duodenal ulcer pain is relieved by meals and increases 2-3 after meals and at night.
• Nausea, vomiting, bloating, and belching may be present.
• Complications:
• Iron deficiency anemia
• Hemorrhage (minimal to massive)
• Perforation (a medical emergency): erosion of the entire wall of stomach, causes peritonitis.
• Treatment:
• proton pump inhibitors to reduce the acidity.
• Antibiotic treatment to eradicate H. pylori infection.
• Surgery (in the severe cases).
Small and Large Intestines
Intestinal Obstruction
• Obstruction occur more frequently in the small
intestines due to its narrow lumen.
• Causes of mechanical obstruction:
• Hernia: occur when the intestines break through a
weakened area in the abdominal wall.
• Intestinal adhesions: formation of fibrous band
between two segments of the intestines.
• Intussusception: occurs when a segment of the
intestine telescopes into the immediately distal
segment.
• Mostly occur in infants and children
• The most affected site is the ileocecal junction.
• Volvulus: occurs when a loop of intestine twists
around itself.
• Tumors
• Infarction
Intestinal obstruction: clinical features
• Symptoms:
• Abdominal pain and distention
• Vomiting
• Constipation
Lactose Intolerance

• Also known as Lactase deficiency or hypolactasia.

• Lactose is:
• A disaccharide that is composed of a glucose molecule and a galactose
molecule.
• Present in milk and dairy products.
• In the small intestines, lactose is digested into glucose and galactose by a
digestive enzyme known as lactase.
• Lactose intolerance is caused by lactase deficiency.
• Lactase deficiency could be congenital (rare) or acquired.
• Acquired lactase deficiency occurs after childhood and results from
the downregulation of lactase gene expression.
Lactose Intolerance:
• Due to lactase deficiency, the majority of lactose
molecules are not digested and absorbed in the
small intestines and pass into the colon.
• In the colon, the bacteria ferment lactose
molecules and generate gases and acids.
• The undigested lactose molecules, as well as
fermentation products, raise the osmotic
pressure in the lumen, causing an increased flow
of water into the lumen (diarrhea).
Symptoms:
• Diarrhea
• Nausea, Abdominal cramps and sometimes, vomiting
• Bloating
The symptoms usually begin 30 minutes after
ingesting milk or dairy products.
Celiac Disease
• Also known as celiac sprue or gluten-sensitive
enteropathy.
• Patients with celiac disease have an abnormal
immune response to components of gluten, a
protein that is present in wheat and wheat by-
products.
• The abnormal immune response induces an
inflammatory process that results in atrophy of
small intestinal villi
• Loss of intestinal villi reduces the surface area and
cause malabsorption.
• Mangement: Removal of gluten from the diet.
Inflammatory Bowel Disease (IBD)
• A chronic inflammatory condition that affects the large or small intestines.
• Caused by an inappropriate activation of immune system in the intestinal
mucosa.
• The inappropriate activation of immune system is the result of complex interactions
between intestinal microbiota (normal bacterial flora in the intestines) and host
immunity in genetically predisposed individuals.
• IBD includes two forms:
• Crohn disease
• Ulcerative colitis
• The distinction between those two forms of IBD is based on the
distribution of affected sites and the morphologic expression of disease at
these sites
Crohn disease
• A systemic disease that predominantly affects the intestines, but also has
extrainestinal manifestations.
• Results in a transmural inflammation (involves the full thickness of the
intestine) of the ileum and the colon
• Clinical features:
• The clinical manifestations of Crohn disease are extremely variable .

• In most patients, disease begins with intermittent attacks.

• Symptoms:
• Diarrhea
• Fever
• Blood in the stool (occurs when the colon is affected)
• Abdominal pain, most commonly in the right lower quadrant.
• Extraintestinal symptoms: including inflammation of the joints, skin, eyes, liver and bile duct.
• Symptomatic periods is often followed by asymptomatic intervals that last for weeks
to many months before disease reactivation.
• Disease reactivation can be associated with a variety of external triggers, including
physical or emotional stress, specific dietary items, NSAID use, and cigarette
smoking.
Ulcerative Colitis
• An inflammatory disease of the colon, limited to the mucosa and
submucosa.
• Clinical features:
• Ulcerative colitis is a relapsing disorder, characterized by attacks of:
• Bloody diarrhea
• Lower abdominal pain and cramps.
• The symptoms may persist for days, weeks or months before they subside.
Both Crohn disease and ulcerative colitis increase the risk of
neoplasia.