1.

3 PEPTIC ULCER DISEASE

Peptic ulcer disease (PUD) refers to a group of ulcerative disorders of the

gastrointestinal tract characterized by mucosal damage secondary to pepsin and
gastric acid secretion.
It usually occurs in the stomach and proximal duodenum; less commonly, it occurs in
the lower esophagus, the distal duodenum, or the jejunum, as in unopposed
hypersecretory states such as Zollinger-Ellison syndrome.
TYPES OF PEPTIC ULCER
The two most common types of peptic ulcer are called “gastric ulcers” and
“duodenal ulcers”. These names refer to the location where the ulcer is found. Gastric
ulcers are located in the stomach Duodenal ulcers are found at the beginning of the small
intestine known as the duodenum. A person may have both gastric and duodenal ulcers
at the same time. (Feldman Mark.2005)
ETIOLOGY
Most peptic ulcers occur in the presence of acid and pepsin when HP, NSAIDs, or
other factors that disrupts normal mucosal defense and healing mechanisms.
(Feldman Mark.2005)
Table 1.3a : CAUSES OF GASTRO DUODENAL ULCERS
COMMON RARE
• Helicobacter pylori Infection • Acid-hypersecretory states
Gram-negative, motile spiral rod found in 48 percent of (e.g. Zollinger-Ellison
patients with peptic ulcer disease syndrome)
Multiple gastro duodenal, jejunal, or
oesophageal Ulcers
• NSAIDs • Malignancy
5 to 20 percent of patients who use NSAIDs over long Gastric cancer, lymphomas, lung
periods develop peptic ulcer disease.NSAID-induced cancers
ulcers and complications are more common in older • Stress
patients, patients with a history of ulcer or After acute illness, multiorgan failure,
gastrointestinal bleeding, those who use steroids or ventilator support, extensive burns
anticoagulants, and those with major organ impairment (Curling’s ulcer), or head injury
• Other medications (Cushing’s ulcer)
Steroids, bisphosphonates, potassium chloride,
chemotherapeutic agents (e.g., intravenous fluorouracil

PATHOPHYSIOLOGY
The normal stomach maintains a balance between protective factors, such as mucus
and bicarbonate secretion, and aggressive factors, such as acid secretion and pepsin.
Gastric ulcers develop when aggressive factors overcome protective mechanisms.
The two major etiological factors for PUD are Helicobacter pylori infection and
nonsteroidal anti-inflammatory drug (NSAID) consumption. Currently, 70% of all
gastric ulcers occurring in the United States can be attributed to H pylori infection.
In addition to an increase in acid secretion, H pylori infection also predisposes
patients to ulcer disease by disrupting mucosal integrity. The bacterium's spiral shape
and flagella facilitate its penetration into the mucous layer and its attachment to the

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 epithelial layer. Subsequently, it releases phospholipase and proteases, which cause
further mucosal damage.

Helicobacter NSAID
pylori
Gastrinoma
↑Serum
Chronic Blocks Gastrin
Active COX-1
Gastritis
ECL Cell Histamine
↓PGs Release
Peptic Ulcer
Disease HCl, Pepsin Hyper
(More Duodenal Peptic Ulcer secretion
than Gastric) Disease
(More Gastric
than Duodenal) Peptic Ulcer Disease
(Much More Duodenal than
Gastric
(a) (b) (c)
(a) Helicobacter pylori induces a diffuse, chronic, active superficial gastritis,
usually throughout the stomach (b) Nonselective nonsteroidal anti-inflammatory
drugs (NSAIDs) (c) Gastrinoma cells
figure 1.3a: pathogenesis of peptic ulcer

NSAID-induced ulcers account for approximately 26% of gastric ulcers, and they
are believed to be secondary to a decrease in prostaglandin production resulting from
the inhibition of cyclooxygenase. COX-2 selective NSAIDs produce a lesser
reduction in prostaglandins and are associated with fewer peptic ulcers than non
selective COX-1. The greatest risk of developing an ulcer occurs during the first 3
months of NSAID use; thereafter, the risk decreases but continues to be present.
Whether concurrent H pylori infection and NSAID use are synergistic in producing
gastric ulcers remains unclear. Recent accumulating evidence indicates that patients
with H pylori infection may be twice as likely to get a bleeding peptic ulcer.
A rare cause of PUD is Zollinger-Ellison syndrome (ie, Gastrinoma). The hallmark
of Zollinger-Ellison syndrome is the profound hyper secretion of gastric acid.
Gastrinoma cells in the pancreas or duodenum secrete large amounts of gastrin into
the circulation. Elevated serum gastrin levels promote the release of histamine by
acting on receptors for cholecystokininB (CCKB) and for gastrin, which are located
on gastric enterochromaffin-like (ECL) cells. Histamine acts on H2 receptors on
parietal and chief cells to augment hydrochloric acid (HCl) and pepsin secretion.
Significant disruption of the mucosal integrity often results in multiple duodenal and
gastric ulcers. (Feldman Mark.2005)
DIAGONOSIS
Tests used in the diagnosis of peptic ulcer are
• EGD • Hypotonic
(esophagogastroduodenoscopy duodenography
) • Urea breath test
• Diatrizoate sodium • Serologic ELISA

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 • Urine-based ELISA and rapid urine test
• Endoscopic biopsy
• Stool antigen test
(Ramakrishnan K. 2007)
CLINICAL FEATURE
Table 1.3b: SYMPTOMS OF PEPTIC ULCER DISEASE
Duodenal Ulcer 1.Pain that awakens patients from sleep
symptoms: 2. Burning or gnawing sensation in the upper abdomen
3. Pain in the back, lower abdomen or chest area may
occasionally occur
4. Pain that occurs when the stomach is empty (about
two hours
After a mean or during the night). Relief frequently
occurs after eating
Gastric Ulcer symptoms 1. Gastric ulcer pain may be less severe than duodenal
ulcer pain and is noticeably higher in the abdomen
2. Eating may increase pain rather than relieve pain
3. Pain is described as aching, nagging, cramping or
dull
4. Other symptoms may include nausea, vomiting and
weight loss
Some ulcers may produce no symptoms at all. However, occasional painless bleeding,
anaemia or the passage of black, tarry stool may be the first sign of peptic ulcer
disease.
(Berardi RR, Welage LS. 2005)

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 Table 1.3c: RISK FACTORS FOR PEPTIC ULCER
Established Risk Factors Possible Risk Factors Questionable Risk
Factors
• Age over 60 years • NSAIDs-related • Cigarette
• previous peptic ulcer dyspepsia smoking
disease • Duration of • Alcohol
• Previous upper GI NSAIDs use consumption
bleeding • Helicobacter
• Concomitant pylori infection
corticosteroid therapy • Rheumatoid
• high-dose and multiple arthritis
NSAIDs use
• Concomitant
anticoagulant use or
coagulopathy
• Chronic major organ
impairment (e.g.,
cardiovascular disease)
MANAGEMENT

DESIRED OUTCOME

The goals of treatment are relieving ulcer pain, healing the ulcer, preventing ulcer
recurrence, and reducing ulcer-related complications. In HP positive patients with an
active ulcer, a previously documented ulcer, or a history of an ulcer-related
complication, the goals are to eradicate the organism, heal the ulcer, and cure the
disease with a cost-effective drug regimen.

NONPHARMACOLOGIC TREATMENT

• Patients with PUD should eliminate or reduce psychological stress, cigarette

smoking, and the use of Nonselective NSAIDs (including aspirin). If
possible, alternative agents such as acetaminophen, a nonacetylated
salicylate (e.g., salsalate), or a COX-2 selective inhibitor should be used for
pain relief.
• Although there is no need for a special diet, patients should avoid foods and
beverages that cause dyspepsia or exacerbate ulcer symptoms (e.g. spicy
foods, caffeine, and alcohol).

PHARMACOLOGIC TREATMENT

• ERADICATION OF HELICOBACTER PYLORI

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Treatment duration is 10 to 14 days (although courses lasting one to seven days have
been reported to have Comparable effectiveness. eradication rates 80 to 90 percent or
higher.

• PROTON PUMP INHIBITORS

Treatment duration is four weeks for duodenal ulcer and eight weeks for gastric
ulcer 80 to 100 percent healing.

• HISTAMINE H2 BLOCKERS
70 to 80 percent healing in duodenal ulcer after four weeks, 87 to 94 percent after eight
weeks.

• SUCRALFATE (CARAFATE)
Treatment duration is four weeks effectiveness.

• SURGERY
Rarely needed similar to H2 blockers.
Berardi RR, Welage LS.2005)

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 Table 1.3d: Drug Regimens to Eradicate Helicobacter Pylori
Drug #1 Drug #2 Drug #3 Drug #4
Proton pump inhibitor–based three-drug regimens
Omeprazole 20 mg twice daily Clarithromycin 500 Amoxicillin 1 g twice
or Lansoprazole 30 mg twice mg twice Daily daily
daily or Metronidazole
or Pantoprazole 40 mg twice 500mg twice daily
daily
or Esomeprazole 40 mg daily
or Rabeprazole 20 mg daily

Bismuth-based four-drug Bismuth Metronidazole 250– Tetracycline

regimens subsalicylate 525 mg 500 mg 500 mg four
Omeprazole 40 mg twice four times daily four times daily times daily
daily or Amoxicillin
or Lansoprazole 30 mg twice 500 mg four
daily times
or Pantoprazole 40 mg twice daily, or,
daily Clarithromycin
or Esomeprazole 40 mg daily 250–500 mg
or Rabeprazole 20 mg daily four times
or Standard ulcer-healing daily
dosages of an H2-receptor
antagonist taken for 4–6 weeks
Although treatment is minimally effective if used for 7 days, 10–14 days of treatment is recommended. The antisecretory drug may be
continued beyond antimicrobial treatment in the presence of an active ulcer. In an active ulcer, acid suppression is added to hasten
pain relief
Oral Drug Regimens Used to Heal Peptic Ulcers or Maintain Ulcer Healing
Table 1.3e:Oral Drug Regimens Used to Heal Peptic Ulcers or Maintain Ulcer Healing
Drug Duodenal or Gastric Maintenance of Duodenal or
Ulcer Healing (mg/dose) Gastric Ulcer Healing
(mg/dose)
Proton pump inhibitors
Omeprazole 20–40 daily 20–40 daily
Lansoprazole 15–30 daily 15–30 daily
Rabeprazole 20 daily 20 daily
Pantoprazole 40 daily 40 daily
Esomeprazole 20–40 daily 20–40 daily
H2-receptor antagonists
Cimetidine 300 four times daily 400–800 at bedtime
400 twice daily
800 at bedtime
Famotidine 20 twice daily 20–40 at bedtime
40 at bedtime
Nizatidine 150 twice daily 150–300 at bedtime
300 at bedtime
Ranitidine 150 twice daily 150–300 at bedtime
300 at bedtime
Promote mucosal defense
Sucralfate (g/dose) 1 four times daily 1–2 twice daily
2 twice daily 1 four times daily
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COMPARISON OF COMMON FORMS OF PEPTIC ULCER
Table 1.3f: COMPARISON OF COMMON FORMS OF PEPTIC ULCER
CHARACTERISTIC H. PYLORI– NSAID-INDUCED SRMD
INDUCED
CONDITION Chronic Chronic Acute
SITE OF DAMAGE Duodenum > stomach Stomach > duodenum Stomach >
duodenum
INTRAGASTRIC PH More dependent Less dependent Less dependent
SYMPTOMS Usually epigastric pain Often asymptomatic Asymptomatic
ULCER DEPTH Superficial Deep Most
superficial
GI BLEEDING Less severe, single More severe, single More severe,
vessel vessel superficial
mucosal
capillaries
H. pylori, Helicobacter pylori; NSAID, nonsteroidal anti-inflammatory drug; SRMD, stress-related mucosal
damage.

COMPLICATIONS

If ulcers remain untreated they may lead to:

• Bleeding
• Perforation (an actual puncture through the stomach)
• Obstruction (repeated attacks may cause scar tissue that can block the
digestive tract)

FOLLOW-UP

• Patients should be re evaluated in 6-8 weeks with a repeat endoscopy to

document complete healing of the gastric ulcer.
• Maintenance therapy with antisecretory medications (e.g., H2 blockers, PPIs)
for 1 year is indicated in high-risk patient
• Patients with recurrent gastric ulcers should be questioned in detail about
NSAID use (particularly over-the-counter varieties), and endoscopy with
biopsies should be repeated to help rule out malignancy and to check for the
persistence of H pylori.
• Instruct patients to avoid NSAIDs.
• Discourage alcohol consumption and cigarette smoking because these
activities impair gastric mucosal protection.

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