PEPTIC ULCER

DISEASE (PUD)

DR EDESIRI IGHORODJE
SNR DERMATOLOGY
UUTH
 OBJECTIVES

To understand the pathogenesis of Peptic ulcer

disease
To identify the role of dyspepsia in the
evaluation of PUD
To identify appropriate treatment strategies for
both H pylori and NSAID associated PUD
 CASE 1

A 53 year old man came for recurrent

epigastric pain.
He has had at least 2 documented PUDs in
the last 5 years.
He was taking intermittent H2RA and
antacids and lately Omeprazole
He would improve whilst on treatment but
relapse within a few weeks of stopping
treatment.
 OUTLINE

INTRODUCTION/DEFINITION
EPIDEMIOLOGY
ETIOLOGY AND RISK FACTORS
PATHOGENESIS
CLINICAL PRESENTATION
INVESTIGATIONS
TREATMENT
PREVENTION
CONCLUSION
REFERENCES
 INTRODUCTION

• A peptic ulcer is a mucosal defect that has a

diameter of at least 0.5 cm that penetrates the
muscularis mucosae; Smaller mucosal defects are
called erosions.
• Dyspeptic symptoms in patients who have no
endoscopic abnormalities, termed nonulcer
dyspepsia.
• Acid peptic diseases can involve the esophagus,
stomach, and duodenum (other examples…)
 DUODENAL ULCER

• Tends to peak at ages 25-75, >M,

• >75% associated with H.pylori.
• Other risks: smoking, NSAIDS, family history.
• Occur most often in D1 ~90% located within 3 cm of the
pylorus; usually <1 cm in diameter, rarely 3 to 6 cm (giant
ulcer).
• Ulcer base often consists of a zone of eosinophilic necrosis
with surrounding fibrosis.
• Malignant DUs are extremely rare.
 GASTRIC ULCER –PROXIMAL AND
DISTAL

• Peaks between 55-65 years.

• H. Pylori and NSAIDS are major risk factors.
Concurrent use of corticosteroids dramatically increase
the risk of ulcer.
• Benign gastric ulcers are normally found on the
lesser curvature, although they can occur anywhere
in the stomach, rare in the gastric fundus
• Treatment more difficult with longer treatment
duration.
 EPIDEMIOLOGY

• Although PUD is strongly related to H. pylori

gastritis and duodenitis, the epidemiology of ulcer
disease has shown secular variations even at times
when H. pylori was ubiquitous.

• The incidence rose in Western countries steeply in

the late 19th and early 20th centuries and has
decreased over the past 30 years, yet peptic
ulceration remains a common disorder.
 • The decline in incidence, associated with a decrease in
hospital admissions and surgery for ulcer disease, is believed
mainly to reflect decreasing prevalence of gastric
colonization with H. pylori; and also widespread application
of eradication therapy, which strongly reduced recurrent
ulcers in H. pylori-positive patients.

• Despite these trends, the incidence of hospital admissions

for complications of ulcers and mortality from ulcer disease
have remained relatively stable over the past decades in both
the United States and other countries
• In Western countries, DU occur more frequently than GU.
• The predominant age at which DU occur is between 20-50
years, whereas GU most commonly occur in patients >40
years old.
• The incidence of gastroduodenal ulcer disease is ≈ 1 to
2/1000 inhabitants/ year.
• Two thirds of patients with ulcers are male, and the disease
is more common in smokers.
• The risk of recurrent disease after initial healing is high;
more than 50% of patients have a recurrent ulcer within 12
months of healing in the absence of treatment.
EPIDEMIOLOGY: NIGERIA
ETIOLOGY AND RISK FACTORS
 1.HELICOBACTER PYLORI
•Most common chronic bacterial infection worldwide
•Found in the stomach of humans in all parts of the world.
•Transmission by fecal-oral, and oral-oral routes, iatrogenic,
•Infection occurs in childhood and persist into middle age.
does not invade the epithelial cell, may adhere tightly
capable of transforming into a coccoid form, which
represents a dormant state that may facilitate survival in
adverse conditions.
 DISEASES CAUSED BY H. PYLORI

GASTRITIS
PUD
GASTRIC ADENOCARCINOMA
LOW GRADE GASTRIC LYMPHOMA
 RISK OF DEVELOPING H.PYLORI
PUD

• The risk for development of an ulcer in the presence of H.

pylori is determined by a combination of host- and bacteria-
related factors.
• Host factors include immune response, smoking, and stress.
• Bacterial factors that increase the risk of ulcer include the
following:
1.a high production of cytotoxin, which reflects the presence of
the s1m1-type of the vacA gene
2.a high level of cytokine induction, owing to the presence of
genes in the cag pathogenicity island
3.enhanced adherence, resulting from babA.
• Thus colonization of HP always results in chronic
inflammation of the gastric mucosa (chronic
gastritis)

• DU and GU results when the consequences of

inflammation allow acid and pepsin in the stomach
to overwhelm the mechanisms that protect the
mucosa against these substances

Pathology of H pylori 11/28/2023 17

THE EVIDENCE SHOWS THAT HP INFECTION IS UBIQUITOUS IN THE
POPULATION IN BOTH SUBJECTS WITH OR WITHOUT DYSPEPSIA
 RISK FACTORS

HOST FACTORS
Immune response eg pleomorphism of inflammatory cytokines
like IL1-B
Genetic susceptibility: cox 2 polymorphisms (765G>C cox2),
sTREM (soluble triggering receptor expressed on myeloid cells
in peptic ulcer disease etc
BACTERIAL FACTORS (HP strain)
GASTRIC SURGERY
BARRETS OESOPHAGUS
LARGE HIATAL HERNIA (Cameron’s ulcer)
 NSAIDS
• decreases epithelial cell proliferation, growth factors,
angiogenesis,
Environmental factors:
a) smoking
1.decreased proximal duodenal bicarbonate production, ↑gastric
acid and cigarette-induced generation of noxious mucosal free
radicals.
2.Decreases healing rates, impair response to therapy, and
increase ulcer-related complications
 PATHOGENESIS

• In the early 20th century, the pathogenesis of the disorder

was believed to be related to stress and dietary factors.

• In 1971, Sir James Black identified a subtype of the

histamine receptor (H2receptor) that appeared to be the
principal mediator (control )of gastric acid secretion.

• The underlying pathogenesis was found to be related to the

traditional theory of imbalance between acid pepsin and
mucosal resistance. (mucus, bicarbonate, prostaglandins)
 MULTIFACTORIAL PATHOGENESIS

Corrosive effect of HCL, proteolytic effect of pepsin

vs mucosal resistance
 THE MUCOSAL DEFENCE SYSTEM

Mucus-bicarbonate layer
physicochemical barrier
Surface epithelial cells
mucus and HCO3 production,
maintain intracellular pH,
restitution modulated by epidermal growth factor (EGF),
transforming growth factor (TGF) a, and basic fibroblast growth
factor (FGF), prostaglandins
Microvascular circulatory system
provides HCO3-, micronutrients, oxygen and
removes toxic metabolic by-products
 GASTRIC ACID

Is PUD due to gastric acid hypersecretion?

Most patients with gastric ulcers have normal –to-low

acid secretion
Most patients with DU are not hypersecretors
Small proportions are hyper secretors
Gastric acid is required but is not commonly cause of
ulcer
PATHOGENESIS (H.PYLORI)
 PATHOGENESIS-MUCOSAL
INSULTS

Most common mucosal insults are H. pylori and NSAIDS

Uncommon causes
HYPERSECRETION OF GASTRIC ACID
ZOLLINGER ELLISON SYNDROME
SYSTEMIC MASTOCYTOSIS
ANTRAL G CELL HYPERPLASIA
RETAINED ANTRUM SYNDROME
VIRAL INFECTIONS eg CMV. HSV-1
2.NSAIDS
If oral NSAIDs are taken for at least 2 months, the risk
of an
endoscopic ulcer is 1 in 5,
of a symptomatic ulcer is about 1 in 70,
of a bleeding ulcer is about 1 in 150,
and of a death from a bleeding ulcer about 1 in 1300.
 CLINICAL PRESENTATION
CHRONIC RECURRENT DYSPEPSIA ? CAUSE

• Non-ulcer dyspepsia (Functional

dyspepsia ) >50%

• Peptic ulcer disease < 20%

• Gastritis (NSAID, steroids, antibiotics)

 DYSPEPTIC SYMPTOMS

Upper Abdominal pain

Nausea
Abdominal fullness
Belching
Bloating
Easy satiety
 ALARM SYMPTOMS

Recent onset symptoms in patients >45yrs

Anaemia
Significant Weight loss
Recurrent vomiting
Melaena, haematemesis
Dysphagia
 PHYSICAL EXAMINATION

Epigastric tenderness (+/-)

RUQ tenderness may suggest a biliary etiologic
In the presence of GAO, abdominal distension and
succussion splash may be found.
A palpable mass should raise the suggestion of a
gastric malignancy.
Involuntary guarding is indicative of peritonitis
secondary to gastric perforation
 DIFFERENTIALS

GERD

ACUTE ABDOMEN

ABDOMINAL MALIGNANCY
INVESTIGATONS
Fecal antigen test (FAT): detection of antigen shed
in stools.
Culture: Gold standard. Slow and laborious.
(Lacks sensitivity)
DNA probes /PCR on gastric tissue/ gastric juice
Urinary excretion of 15N ammonia
 FIBRE-OPTIC ENDOSCOPY

Diagnosis of HP
Visualization and biopsy of ulcer
In gastric ulcers “do it right first time”
4 good biopsy from ulcer margin, 1 from base
Prognosis
Treatment of ulcer
 BARIUM STUDIES OF UPPER GI

DU appears as a well-demarcated crater, most often seen

in the bulb.
[single-contrast barium meals and double-contrast study(sensitivity
80% vs 90% )

Decreased sensitivity (small ulcers (<0.5 cm), presence of previous

scarring, or in postoperative patients.]
GU may represent benign or malignant disease.,
discrete crater with radiating mucosal folds originating from the
ulcer margin.
Ulcers >3 cm in size or those associated with a mass are more often
malignant. up to 8% of GUs that appear to be benign by Xray are
malignant by endoscopy or surgery..
 OTHER INVESTIGATION IN
DYSPEPTIC PATIENTS

Abdominal USS
Haematological/Biochemical tests
Stool tests- occult blood
Others as needed
 TREATMENT GOALS AND THERAPEUTIC OPTIONS

GOALS
Subjective improvement
Healing of ulcer crater
Treatment of HP infection
Preventing complications
THERAPEUTIC OPTIONS
Choice of therapy will depend on a drug availability (bismuth), cost,
antibiotic resistance pattern, side effect, dosing and compliance and
prevalence of gastric cancer.
PPI are important adjunct to RX as the increase the bioavailability
and stability of the antibiotics.
 OTHER TX OPTIONS

Sequential therapy (2x5, 3x5)

A PPI + amoxicillin 1 g twice dly x 5/7 followed by the
PPI + clarithromycin 500 mg + tinidazole or metronidazole 500
mg bd for 5 days
Concomitant therapy
PPI + amoxicillin 1 g, clarithromycin 500 mg + tinidazole or
metronidazole 500 mg twice daily for 7-14 days

Others: Mucosal protective agents used in place of PPI in

some programmes. Octreotide, a somatostatin analogue used as
part of quadriple therapy
 FOLLOW UP OF PATIENTS AFTER
ERADICATION OF INFECTION

Breath tests:
Recent treatment with PPI/ antibacterials may
suppress H.pylori and cause a false negative
breath test. Thus, delay for at least 4 weeks after
treatment is completed.

Fecal antigen tests

Endoscopy
Serological tests: not useful as antibody titers
decline over 6-12 months
 DIET AND PUD

Drink a lot of milk!

Don’t eat spices!
Don’t eat fried foods!
Don’t eat pepper!
Current evidence suggest that
Stress, spicy food, alcohol are insignificant risks.
frequent ingestion of milk is associated with increased acid
secretion.
 TREATMENT OF ULCERS NOT ASSOCIATED
WITH HP

(usually associated with NSAIDS)

Discontinue drug if possible, concurrent use of
PPI, H2RA,or cytoprotective agents (misoprostol)
Use of selective cyclooxygenase 2 (COX 2)
inhibitors
 PREVENTIVE STRATEGIES-
GENERAL RULES

 Targeting modifiable risk factors

1. Use the lowest effective dose for the shortest period of
time
2. Avoid concomitant therapy with corticosteroids, triple
AAA
3. Use safer NSAIDS (coxibs, diclofenac, aceclofenac and
ibuprufen)
4. Less use of NSAIDS with the highest GI toxicity
5. Eradicate H-pylori infection in patients with prior ulcer
history
 ENTERIC COATED OR BUFFERED
ASA FORMULATIONS

Will this reduce the risk of UGIE?

Yes will reduce dyspepsia and improve tolerability

No, will not reduce the risk of ulceration and GI
bleeding which is caused by a systemic effect on
prostaglandin reduction
 PARENTERAL OR RECTAL
ADMINISTRATION OF NSAIDS

Will this reduce the risk of UGIE?

No, will not reduce the risk of Gastroduodenal

ulceration or GI bleeding which is caused by a
systemic effect on prostaglandin reduction
 COMPLICATIONS OF PUD

BLEEDING
Risk factors for bleeding include
1. multimorbid patients,
2. associated NSAID intake
3. no previous history of ulcer disease
(DUSUK study group-Scand J gastroenterol, 1997)

PENETRATION
PERFORATION
GASTRIC OUTLET OBSTRUCTION
 REFRACTORY ULCERS

—
• Ulcers are considered refractory if healing is not evident
after 8-12 weeks of therapy; the latter time frame is
most appropriate for larger gastric ulcers (GU)

• Persistent HP infection,NSAID, Heavy smoking, Carcinoma,

hypergastrinoma

• REFRACTORY SYMPTOMS VS REFRACTORY

ULCERATION: Persistent symptoms in the absence
of an active ulcer on endoscopy suggest that other
etiologies for the pain should be sought
 CASE 1

A 53 year old man came for recurrent

epigastric pain.
He has had at least 2 documented PUDs in
the last 5 years.
He was taking intermittent H2RA and
antacids and lately Omeprazole
He would improve whilst on treatment but
relapse within a few weeks of stopping
treatment.
 CONSIDER THESE

• ALARM SYMPTOMS

• MALIGNANCY

• R/O PERFORATION

• RULE OUT OTHER DDX

• USE OF NSAIDS
 REFERENCES

• Pathogenesis and management of Peptic ulcer

disease; NPMCN Revision course 2014. Dr
Funmilayo Lesi FMCP, FWACP Associate
Professor/ Consultant Physician Gastroenterology/
Hepatology Unit, Department of Medicine
CMUL/LUTH

• Cecil Medicine 23rd Ed