This document provides information about peptic ulcers, including their pathogenesis, signs and symptoms, and laboratory findings. Peptic ulcers are caused by an imbalance between aggressive factors like gastric acid and pepsin and defensive mucosal factors. Helicobacter pylori infection is the leading cause of peptic ulcers, causing inflammation and cytokine production. NSAIDs also increase risk by inhibiting prostaglandin synthesis. Common symptoms include epigastric pain, nausea, and vomiting. Endoscopy allows direct visualization of ulcers and biopsy for diagnosis, while tests for H. pylori infection are also important for diagnosis and treatment.

1. ANKIT GILANI
DEPT. OF PHARMACOLOGY & TOXICOLOGY
SEMISTER 01
NIPERD AHMEDABAD

2. CONTENTS :
 INTRODUCTION
 PATHOGENESIS
 SIGNS & SYMPTOMS
 LABORATORY FINDINGS
 COMPLICATIONS

3. INTRODUCTION
 Ulcers are defined as a breach in the mucosa
of the alimentary tract that extends through the
muscularis mucosae into the submucosa or
deeper.
 This is to be contrasted to erosions, in which
there is a breach in the epithelium of the
mucosa only.
 Erosions may heal within days, whereas
healing of ulcers takes much longer.
 Although ulcers may occur anywhere in the
alimentary tract, none are as prevalent as the
peptic ulcers that occur in the duodenum and
stomach.

5. GROSS FEATURES :
 Peptic ulcers are usually single well delineated lesion.
 Shape: Round, oval or linear.
 Size: Usually less than 2cm in diameter.
Lesions less than 0.3 cm are likely to be shallow erosions.
Giant ulcers are usually greater than 3cm in diameter.
May also reach upto 10cm (particularly on lesser curvature ).
Mortality rate is higher in these patients.
Size does not differentiate benign from malignant ulcer.
Some carcinomatous ulcers are less than 4cm and 10%
of benign ulcers are more than 4cm .

7. PATHOGENESIS
AGGRESSIVE
FORCES
DEFENSIVE
FORCES
peptic ulcers are induced by an imbalance between the
gastroduodenal mucosal defenses and the countervailing
aggressive forces that overcome such defenses

8. AGGRESSIVE FORCES
 GASTRIC ACIDITY
 PEPTIC ACTIVITY

9. DEFENSIVE FORCES
 Secretion of mucus by surface epithelial cells
 Secretion of bicarbonate into the surface mucus, to create a
buffered surface microenvironment
 Secretion of acid- and pepsin-containing fluid from the
gastric pits as "jets" through the surface mucus layer,
entering the lumen directly without contacting surface
epithelial cells
 Rapid gastric epithelial regeneration
 Robust mucosal blood flow, to sweep away hydrogen ions
that have back-diffused into the mucosa from the lumen and
to sustain the high cellular metabolic and regenerative
activity
 Mucosal elaboration of prostaglandins, which help maintain
mucosal blood flow

10. CAUSES
INCREASED
IMPAIRED AGGRESSION
DEFENCE
H.Pylori INFECTION,
ISCHAEMIA, NSAIDs (ASPIRIN),
SHOCK, SMOKING,
DELAYED GASRIC ALCOHOL,
EMPTYING,
IMPAIRED REGULATION
GASRO- OF ACID-PEPSIN
OESOPHAGEAL SECRETION,
REFLUX
BILE ACIDS,
GENETIC FACTORS

12. H.pylori infection :
 Helicobacter pylori
previously named
Campylobacter pyloridis,
Gramnegative,microaerophilic bacterium
found in the stomach
 Among the "aggressive forces," H. pylori is
very important, because this infection is
present in 70% to 90% of patients with
duodenal ulcers and in about 70% of those
with gastric ulcers

13. POSSIBLE
MECHANISMS OF
H.pylori INFECTION :
 Although H. pylori does not invade the tissues, it induces an
intense inflammatory and immune response. There is
increased production of proinflammatory cytokines such as
interleukin (IL)-1, IL-6, tumor necrosis factor (TNF), and,
most notably, IL-8
 H. pylori secretes a urease that breaks down urea to form
toxic compounds such as ammonium chloride and
monochloramine.
 elaborate phospholipases that damage surface epithelial
cells.
 Toxin encoding genes : vacuolating toxin (VacA), cytotoxin-
associated gene A (CagA)
 metaplastic foci (colonization)
 Immunogenic proteins of H.pylori.

14.  . The possible mechanisms are as follows: Although H. pylori does not invade the
tissues, it induces an intense inflammatory and immune response. There is increased
production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis
factor (TNF), and, most notably, IL-8. This cytokine is produced by the mucosal epithelial
cells, and it recruits and activates neutrophils.
 Several bacterial gene products are involved in causing epithelial cell injury and induction
of inflammation. H. pylori secretes a urease that breaks down urea to form toxic
compounds such as ammonium chloride and monochloramine. The organisms also
elaborate phospholipases that damage surface epithelial cells. Bacterial proteases and
phospholipases break down the glycoprotein-lipid complexes in the gastric mucus, thus
weakening the first line of mucosal defense. Epithelial injury is also caused by a
vacuolating toxin (VacA). Another toxin, encoded by the cytotoxin-associated gene A
(CagA), is a powerful stimulus for the production of IL-8 by the epithelial cells.
 H. pylori enhances gastric acid secretion and impairs duodenal bicarbonate production,
thus reducing luminal pH in the duodenum. This altered milieu seems to favor gastric
metaplasia (the presence of gastric epithelium) in the first part of the duodenum. Such
metaplastic foci provide areas for H. pylori colonization.
 Several H. pylori proteins are immunogenic, and they evoke a robust immune response
in the mucosa. Both activated T cells and B cells can be seen in chronic gastritis caused
by H. pylori. The B lymphocytes aggregate to form follicles. The role of T and B cells in
causing epithelial injury is not established, but T-cell-driven activation of B cells may be
involved in the pathogenesis of gastric lymphomas.

15. NSAIDs
(aspirin, ibuprofen, naproxen):
 Suppression of mucosal prostaglandin synthesis is
the key to NSAID-induced peptic ulceration.
 Inhibition of prostaglandin synthesis increases
secretion of hydrochloric acid and reduces
bicarbonate and mucin production. Loss of mucin
degrades the mucosal barrier that normally prevents
acid from reaching the epithelium.
 Synthesis of glutathione, a free radical scavenger, is
also reduced.
 Some NSAIDs can penetrate the gut mucosal cells
as well.
 By mechanisms not clear, some NSAIDs also impair
angiogenesis, thus impeding the healing of ulcers.

16. SOME OTHER CAUSES OF
ULCERS :
 Cigarette smoking impairs mucosal
blood flow and healing.
 Alcohol has not been proved to directly
cause peptic ulceration, but alcoholic
cirrhosis is associated with an increased
incidence of peptic ulcers.
 Corticosteroids in high dose and with
repeated use promote ulcer formation.

17. ACUTE GASTRIC
ULCERATION
 Focal, acutely developing gastric mucosal defects may appear after severe
stress and are designated stress ulcers. Generally, there are multiple lesions
located mainly in the stomach and occasionally in the duodenum.
Stress ulcers are most commonly encountered in the following conditions:
 Severe trauma, including major surgical procedures, sepsis, or grave illness
of any type
 Extensive burns (the ulcers are then referred to as Curling ulcers )
 Traumatic or surgical injury to the central nervous system or an intracerebral
hemorrhage (the ulcers are then called Cushing ulcers)
 Chronic exposure to gastric irritant drugs, particularly NSAIDs and
corticosteroids

18. SIGNS AND SYMPTOMS
 Epigastric pain : The pain tends to be worse at night and occurs
usually 1 to 3 hours after meals during the day. Classically, the pain
is relieved by alkalis or food, but there are many exceptions.
(duodenal ulcers are relieved by food, while gastric ulcers are
exacerbated by it)
 waterbrash (rush of saliva after an episode of regurgitation to dilute
the acid in oesophagus - although this is more associated
with GERD)
 nausea, and copious vomiting
 loss of appetite and weight loss
 hematemesis (vomiting of blood) this can occur due to bleeding
directly from a gastric ulcer, or from damage to the oesophagus
from severe/continued vomiting.

19. SIGNS AND SYMPTOMS
(cont.)
 melena (tarry, foul-smelling feces due
to oxidized iron from hemoglobin)
 rarely, an ulcer can lead to a gastric or
duodenal perforation, which leads to acute
peritonitis. This is extremely painful and requires
immediate surgery.
 Bloating and abdominal fullness
 Bleeding is the chief complication, occurring in up to
one third of patients, and may be life-threatening.
When untreated, the average individual requires 15
years for healing of a peptic ulcer.

20. LABORATORY FINDINGS :
 Endoscopy is a highly sensitive diagnostic method
because it allows accurate assessment of the ulcer,
by recognizing the lesion, by demonstrating it’s
activity and by demonstrating the presence of a
hemorrhage. Moreover, endoscopy allows biopsies
in peptic ulcers which can highlight the benign or
malignant character of the lesion. Evaluation of a
healed peptic ulcer is also done by endoscopy which
can demonstrate the existence of the scar.
 Radiography of peptic ulcer, may be a
complementary method of diagnostic, especially
when is suspected a gastric emptying disorder
(pyloric stenosis).

22.  Determination Helicobacter pylori, the causative agent of
most peptic ulcers, is a compulsory element in the diagnosis of
peptic ulcer. Determination of Helicobacter pylori is made by
direct methods and indirect methods.
 Direct methods require endoscopy with biopsy. The presence
oh Helicobacter pylori is determined by histological
examination.
 Indirect methods do not require endoscopy and are represented
by the determination of Helicobacter pylori antibodies from the
plasma and respiratory tests. Helicobacter pylori antibodies,
also can be detereminated in saliva and eradication of
Helicobacter pylori infection can be demonstrated by
determination of bacteria in the stool (fecal test antigen against
Helicobacter pylori). The most sensitive indirect methods of
diagnosis of infection with Helicobacter pylori are respiratory
tests and fecal antigen anti Helicobater pylori

23. COMPLICATIONS
The possible complications of peptic ulcer
are:
 Upper gastrointestinal bleeding, is the most
common complication, approximately 15%
 Perforation leading to peritonitis
 penetration
 Pyloric stenosis
 Malignancy of the ulcer, the risk of
developing this complication is low.

24.  Complications
 Gastrointestinal bleeding is the most common complication. Sudden
large bleeding can be life-threatening.[5] It occurs when the ulcer erodes
one of the blood vessels, such as the gastroduodenal artery.
 Perforation (a hole in the wall) often leads to catastrophic
consequences. Erosion of the gastro-intestinal wall by the ulcer leads
to spillage of stomach or intestinal content into the abdominal cavity.
Perforation at the anterior surface of the stomach leads to
acute peritonitis, initially chemical and later bacterial peritonitis. The first
sign is often sudden intense abdominal pain. Posterior wall perforation
leads to bleeding due to involvement of gastroduodenal artery that lies
posterior to the 1st part of duodenum.
 Penetration is when the ulcer continues into adjacent organs such as
the liver and pancreas.[6]
 Scarring and swelling due to ulcers causes narrowing in the duodenum
and gastric outlet obstruction. Patient often presents with severe
vomiting.
 Cancer is included in the differential diagnosis (elucidated
by biopsy), Helicobacter pylori as the etiological factor making it 3 to 6
times more likely to develop stomach cancer from the ulcer.[7]

27. Data from Death and DALY estimates for 2004
by cause for WHO Member States
(Persons, all ages)