Module 5: Gastric Disorders

• Introduction,
• Gastric secretions,
• Peptic ulcer,
• Duodenal ulcer
• Zollinger-Ellison Syndrome
A gastrointestinal disease is one that affects the gastrointestinal (GI) tract, the passage that runs from the mouth to the anus.
Common GI disorders include irritable bowel syndrome (IBS), acid reflux, indigestion, colon cancer, and hemorrhoids and can be
classified into two category Functional and structural Diseases. The GI tract is responsible for digestion—breaking down food so
the body can absorb and direct nutrients to keep you healthy. Many GI diseases disrupt the healthy digestion of the food you
consume. The GI tract includes the:
•Mouth
•Throat
•Esophagus (food tube)
•Stomach
•Small intestine
•Large intestine (colon)
•Rectum
•Anus
Functional Diseases
Functional GI diseases are characterized by chronic (long-term) GI symptoms that arise due to the function or dysfunction of
the digestive system. The most common functional GI diseases are reviewed below.
• Irritable Bowel Syndrome
• Acid Reflux
• Functional Dyspepsia

Structural Diseases
Structural GI diseases occur because there is a change or problem within the structure of the GI tract. These structural issues
can occur anywhere in the GI tract.
• Hemorrhoids
• Diverticulosis
• Colitis
• Anal Fissures
• Anal Fissures
• Colon Polyps or Cancer
Figure 23.4.1
–
Stomach: The
stomach has
four major
regions: the
cardia,
fundus, body,
and pylorus.
The addition
of an inner
oblique
smooth
muscle layer
gives the
muscularis
the ability to
vigorously
churn and
mix food.
Figure 23.4.2 – Histology of the Stomach: The stomach wall is adapted for the functions of the stomach. In the
epithelium, gastric pits lead to gastric glands that secrete gastric juice. The gastric glands (one gland is shown
enlarged on the right) contain different types of cells that secrete a variety of enzymes, including hydrochloride
acid, which activates the protein-digesting enzyme pepsin.
Gastric Secretion
The secretion of gastric juice is controlled by both nerves and hormones. Stimuli in the brain, stomach, and small intestine
activate or inhibit gastric juice production. This is why the three phases of gastric secretion are called the cephalic, gastric, and
intestinal phases (Figure 23.4.3). However, once gastric secretion begins, all three phases can occur simultaneously.

Cephalic phase
The cephalic phase (reflex phase) of gastric secretion, which is relatively brief, takes place before food enters the stomach. The
smell, taste, sight, or thought of food triggers this phase. For example, when you bring a piece of sweet to your lips, impulses
from receptors in your taste buds or the nose are relayed to your brain, which returns signals that increase gastric secretion to
prepare your stomach for digestion. This enhanced secretion is a conditioned reflex, meaning it occurs only if you like or want a
particular food. Depression and loss of appetite can suppress the cephalic reflex.

Gastric phase
The gastric phase of secretion lasts 3 to 4 hours, and is set in motion by local neural and hormonal mechanisms triggered by the
entry of food into the stomach. For example, when your food reaches the stomach, it creates distention that activates the stretch
receptors. This stimulates parasympathetic neurons to release acetylcholine, which then provokes increased secretion of
gastric juice. Partially digested proteins, caffeine, and rising pH stimulate the release of gastrin from enteroendocrine G cells,
which in turn induces parietal cells to increase their production of HCl, which is needed to create an acidic environment for the
conversion of pepsinogen to pepsin, and protein digestion. Additionally, the release of gastrin activates vigorous smooth muscle
contractions.
However, it should be noted that the stomach does have a natural means of avoiding excessive acid secretion and potential
heartburn. Whenever pH levels drop too low, cells in the stomach react by suspending HCl secretion and increasing
mucous secretions.

Intestinal phase
The intestinal phase of gastric secretion has both excitatory and inhibitory elements. The duodenum has a major role in
regulating the stomach and its emptying. When partially digested food fills the duodenum, intestinal mucosal cells release
a hormone called intestinal (enteric) gastrin, which further excites gastric juice secretion. This stimulatory activity is brief,
however, because when the intestine distends with chyme, the enterogastric reflex inhibits secretion. One of the effects of
this reflex is to close the pyloric sphincter, which blocks additional chyme from entering the duodenum. In addition to the
enterogastric reflex, several hormones such as cholecystokinin (CCK) and secretin are released by the enteroendocrine
cells of the duodenum when fatty, acidic, or carbohydrate rich chyme enters the duodenum. CCK and secretin enter the
blood and travel to the stomach inhibiting the production of HCl and pepsin as well as inhibiting gastric motility allowing
time for the duodenum to break down the chyme.
Hormones Secreted by the Stomach
Hormone Production site Production stimulus Target organ Action
Increases secretion by gastric
Stomach mucosa, mainly G Presence of peptides and
Gastrin Stomach glands; promotes gastric
cells of the pyloric antrum amino acids in stomach
emptying
Stomach mucosa, mainly G Presence of peptides and Promotes intestinal muscle
Gastrin Small intestine
cells of the pyloric antrum amino acids in stomach contraction
Stomach mucosa, mainly G Presence of peptides and
Gastrin Ileocecal valve Relaxes valve
cells of the pyloric antrum amino acids in stomach
Stomach mucosa, mainly G Presence of peptides and
Gastrin Large intestine Triggers mass movements
cells of the pyloric antrum amino acids in stomach
Regulates food intake,
Stomach mucosa, mainly Fasting state (levels increase
Ghrelin Hypothalamus primarily by stimulating
fundus just prior to meals)
hunger and satiety
Presence of food in the Stimulates parietal cells to
Histamine Stomach mucosa Stomach
stomach release HCl
Presence of food in the
Serotonin Stomach mucosa Stomach Contracts stomach muscle
stomach
Mucosa of stomach, Presence of food in the Restricts all gastric
Somatostatin especially pyloric antrum; stomach; sympathetic axon Stomach secretions, gastric motility,
also duodenum stimulation and emptying
Mucosa of stomach, Presence of food in the
Restricts pancreatic
Somatostatin especially pyloric antrum; stomach; sympathetic axon Pancreas
secretions
also duodenum stimulation
Mucosa of stomach, Presence of food in the
Reduces intestinal absorption
Somatostatin especially pyloric antrum; stomach; sympathetic axon Small intestine
by reducing blood flow
also duodenum stimulation
Figure 23.4.3 – The Three Phases of Gastric Secretion: Gastric secretion occurs in three phases: cephalic,
gastric, and intestinal. During each phase, the secretion of gastric juice can be stimulated or inhibited. Each
place where figure says “Stimulates stomach secretory activity,” describe what that activity is and how much it
is activated. In the section on the cephalic phase it could say something like: secretion of HCl and pepsin. In the
section on the gastric phase it could say something like: increased secretion of HCl and pepsin and increased
gastric motility. Etc.
The Mucosal Barrier
The mucosa of the stomach is exposed to the highly corrosive acidity of gastric juice. Gastric enzymes that can digest
protein can also digest the stomach itself. The stomach is protected from self-digestion by the mucosal barrier. This barrier
has several components. First, the stomach wall is covered by a thick coating of bicarbonate-rich mucus. This mucus forms
a physical barrier, and its bicarbonate ions neutralize acid. Second, the epithelial cells of the stomach’s mucosa meet at
tight junctions, which block gastric juice from penetrating the underlying tissue layers. Finally, stem cells located where
gastric glands join the gastric pits quickly replace damaged epithelial mucosal cells, when the epithelial cells are shed. In
fact, the surface epithelium of the stomach is completely replaced every 3 to 6 days.

Stomach Ulcers vs. GERD

Stomach ulcers and gastrointestinal reflux disease (GERD) are acid-related conditions and are often confused due to
similar symptom presentation and treatment. Stomach ulcers can be caused by bacteria, certain medications, or
substances, whereas GERD results from an issue with the muscle between the esophagus and stomach
Peptic ulcers
Peptic ulcers are open sores that develop on the inside lining of your stomach and the upper portion of your small intestine.
Normally, a thick layer of mucus protects the stomach lining from the effect of its digestive juices. But many things can
reduce this protective layer, allowing stomach acid to damage the tissue. The most common symptom of a peptic ulcer is
stomach pain.
Peptic ulcers include:
•Gastric ulcers that occur on the inside of the stomach
•Duodenal ulcers that occur on the inside of the upper portion of your small intestine (duodenum)

Causes of ulcers?
People used to think that stress or certain foods could cause ulcers. But researchers haven’t found any evidence to support
those theories. Instead, studies have revealed two main causes of ulcers:
•Helicobacter pylori (H. pylori) bacteria.
•Pain-relieving NSAID medications.

H. pylori bacteria
H. pylori commonly infects the stomach. About 50% of the world’s population has an H. pylori infection, often without any
symptoms. The H. pylori bacteria stick to the layer of mucus in the digestive tract and cause inflammation (irritation), which
can cause this protective lining to break down. This breakdown is a problem because your stomach contains strong acid
intended to digest food. Without the mucus layer to protect it, the acid can eat into stomach tissue.
However, for most people the presence of H. pylori doesn’t have a negative impact. Only 10% to 15% of people with H.
pylori end up developing ulcers .
Pain relievers
Another major cause of peptic ulcer disease is the use of NSAIDs, a group of medications used to relieve pain. NSAIDS can
wear away at the mucus layer in the digestive tract. These medications have the potential to cause peptic ulcers to form:
•Aspirin (even those with a special coating).
•Naproxen (Aleve®, Anaprox®, Naprosyn® and others).
•Ibuprofen (Motrin®, Advil®, Midol® and others).
•Prescription NSAIDs (Celebrex®, Cambia® and others).
Acetaminophen (Tylenol®) is not an NSAID and won’t cause damage to your stomach. People who can’t take NSAIDs are
often directed to take acetaminophen.
Not everyone who takes NSAIDs will develop ulcers. NSAID use coupled with an H. pylori infection is potentially the most
dangerous. People who have H. pylori and who frequently use NSAIDs are more likely to have damage to the mucus layer, and
their damage can be more severe. Developing an ulcer from NSAID use also increases if you:
•Take high doses of NSAIDs.
•Are 70 years or older.
•Are female.
•Use corticosteroids (drugs your doctor might prescribe for asthma, arthritis or lupus) at the same time as taking NSAIDs.
•Use NSAIDS continuously for a long time.
•Have a history of ulcer disease.
Rare causes
Infrequently, other situations cause peptic ulcer disease. People may develop ulcers after:
•Being seriously ill from various infections or diseases.
•Having surgery.
•Taking other medications, such as steroids.
Peptic ulcer disease can also occur if you have a rare condition called Zollinger-Ellison syndrome (gastrinoma). This condition
forms a tumor of acid-producing cells in the digestive tract. These tumors can be cancerous or noncancerous. The cells
produce excessive amounts of acid that damages stomach tissue.

Ulcer symptoms?
Some people with ulcers don’t experience any symptoms. But signs of an ulcer can include:
•Gnawing or burning pain in your middle or upper stomach between meals or at night.
•Pain that temporarily disappears if you eat something or take an antacid.
•Bloating.
•Heartburn.
•Nausea or vomiting.
In severe cases, symptoms can include:
•Dark or black stool (due to bleeding).
•Vomiting.
•Weight loss.
•Severe pain in your mid- to upper abdomen.
Ulcers diagnosis
Endoscopy
If you have severe symptoms, your provider may recommend an upper endoscopy to determine if you have an ulcer. In this
procedure, the doctor inserts an endoscope (a small, lighted tube with a tiny camera) through your throat and into your
stomach to look for abnormalities.
H. Pylori tests
Tests for H. pylori are now widely used and your provider will tailor treatment to reduce your symptoms and kill the bacteria. A
breath test is the easiest way to discover H. pylori. Your provider can also look for it with a blood or stool test, or by taking a
sample during an upper endoscopy.
Imaging tests
Less frequently, imaging tests such as X-rays and CT scans are used to detect ulcers. You have to drink a specific liquid that
coats the digestive tract and makes ulcers more visible to the imaging machines.
You may also have the following lab tests to see if you have an H. pylori infection:
•Blood tests. These check for infection-fighting cells (antibodies) that mean you have H. pylori.
•Stool culture. A small sample of your stool is collected and sent to a lab. In 2 or 3 days, the test will show if you have H.
pylori.
•Urea breath test. This checks to see how much carbon dioxide is in your breath when you exhale. You will swallow a urea pill
that has carbon molecules. If you have H. pylori, the urea will break down and become carbon dioxide. You will have a sample
taken of your breath by breathing into a bag. It will be sent to a lab. If your sample shows higher than normal amounts of
carbon dioxide, you have H. pylori.
Zollinger-Ellison syndrome (ZES) is a group of symptoms comprised of severe peptic ulcer disease, gastroesophageal reflux
disease (GERD), and chronic diarrhea caused by a gastrin-secreting tumor of the duodenum or pancreas (gastrinoma triangle) or
both that results in increased stimulation of acid-secreting cells of the stomach. Gastrinoma is a functional neuroendocrine
tumor that secretes gastrin, which causes ZES.The earlier misconception was that the location of gastrinoma was in
the pancreas. However, gastrinomas occur in the duodenum more than the pancreas by three times, especially in the
first portion of the duodenum. There are other non-neuroendocrine tumors secreting gastrin, but not at a level to cause
significant symptoms.

These tumors, called gastrinomas, release the hormone gastrin. This causes the stomach to release too much acid. Stomach
acid is needed to break down cause painful peptic ulcers inside the lining of your stomach and intestine. While gastrinoma
tumors do cause health problems, they are typically not cancerous tumors.

The symptoms of ZES are similar to those of other ulcers. They include:
•Nausea
•Vomiting
•Weight loss
•Diarrhea
•Abdominal pain, sometimes burning in nature
•Severe heartburn (GERD or gastroesophageal reflux disease)
•Intestinal bleeding (such as black or tarry stool, or blood in the stool)
Pathophysiology
Gastrin works on the parietal cells of the gastric glands, causing them to secrete more hydrogen ions into the stomach lumen. In
addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Normally, hydrogen ion secretion is
controlled by a negative feedback loop by gastric cells to maintain a suitable pH, however, the neuroendocrine tumor that is
present in individuals with Zollinger–Ellison Syndrome has no regulation, resulting in excessively large amounts of secretion.
Thus, there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The
increase in acidity contributes to the development of peptic ulcers in the stomach, duodenum (first portion of the small bowel)
and occasionally the jejunum (second portion of the small bowel), the last of which is an 'atypical' ulcer.

Besides causing excess acid production, the tumors are often cancerous. Although the tumors tend to grow slowly, the cancer
can spread elsewhere — most commonly to nearby lymph nodes or your liver.

Association with MEN 1

Zollinger-Ellison syndrome may be caused by an inherited condition called multiple endocrine neoplasia, type 1 (MEN 1). People
with MEN 1 also have tumors in the parathyroid glands. They may have tumors in their pituitary glands as well.

About 25% of people who have gastrinomas have them as part of MEN 1. They also may have tumors in the pancreas and other
organs.
Diagnosis
Zollinger–Ellison syndrome may be suspected when the above symptoms prove resistant to treatment when the symptoms
are especially suggestive of the syndrome, or when endoscopy is suggestive. The diagnosis is made through several laboratory
tests and imaging studies:

•Secretin stimulation test, which measures evoked gastrin levels. Note that the mechanism underlying this test is in contrast
to the normal physiologic mechanism whereby secretin inhibits gastrin release from G cells. Gastrinoma cells release gastrin
in response to secretin stimulation, thereby providing a sensitive means of differentiation.

•Fasting gastrin levels on at least three occasions

•Gastric acid secretion and pH (normal basal gastric acid secretion is less than 10 mEq/hour; in Zollinger–Ellison patients, it is
usually more than 15 mEq/hour)

•An increased level of chromogranin A is a common marker of neuroendocrine tumors.

In addition, the source of the increased gastrin production must be determined using MRI or somatostatin receptor
scintigraphy.