Approach to epigastric pain

Peptic Ulcer Disease (PUD) & functional dyspepsia

Dr. Altun Mahmud Saleh

MBChB, FIBMS (Int. Med.), FKBMS (G & H)
Department of Medicine
College of Medicine
Hawler Medical University
Erbil – Iraq
2022-1-16

36slides
 Onlinemeded

Case 1-

l A 25 year old man presented with epigastric

pain since few days. Pain is moderate in
severity, increases when he is hungry &
relieves with taking food.
l He is smoking 20 cig. per day for last 7 years.
l He has history of same problem since 2 years.

Osmosis-clinic
 Paul bolin

Case 2-

l A 40 years old lady presented with epigastric

pain.
l She had severe back pain recently & she
received diclofenac tablet for her pain.

Kaplan
Case 3-

l A 60 year old man presented with recent onset

epigastric pain, anorexia & weight loss.
l He looks pale.
l Hb 9, ferritin 15.
Case 4-

l A 37 year old lady presented with chronic mild

to moderate epigastric pain. H. pylori test was
–ve. She received a course of oral PPI. Still
she was complaining of same problem. EGD
was done that was normal. CBC, ferritin, FOBT
& abdominal us were normal. The fecal occult blood test (FOBT)
A case of epigastric pain. Which investigation is best for the diagnosis of H.

Pylori?

a. Stool Antigen

b. Rapid Urease Test

Which is the most non-invasive investigation a male with H. Pylori?

a. Urea Breathe Test

Contents of the lecture

l PUD definition
l Pathophysiology/etiology What treatment method do you use for
H.pylori e
l Helicobacter pylori A. 14 days course Of 3 antibiotics and

l Clinical features ppi. B. 7 days course of quadruple

therapy.

l Investigations C. Triple therapy.

l Management
l Complications
l Zollinger–Ellison syndrome
Definition

l Mucosal defect in the

l Lower esophagus, stomach or duodenum
l Jejunum after surgical anastomosis to the
stomach
l Rarely, in the ileum adjacent to a Meckel’s
diverticulum..
Gastric & duodenal ulcer (GU & DU)
 Pathophysiology

HP
H Pylori: in > 50% of general population >90% DU
>70% GU

9O% DU,70% GU.

H Pylori In DU infect D cells leading to
hypergastrinemia & hyperacidity.

30% of GU. Impair mucosal

NSAIDs defense through inhibiting PGs.
NSAIDs Smoking
> Complication & < healing.
Smoking

?Genetics
Rarely ZES
 H.Pylori infection

mu
)

ch
0%

Most patients

sm
1
y (

all
er
it
or

nu
in

mb
m

er
(m
or
e i
n A
Antral-predominant pattern of gastritis

sia
n)
little or no atrophy
Hypergastrinaemia Corpus-predominant pattern of gastritis
a very exaggerated acid production by gastric atrophy and hypochlorhydria
parietal cells, which could lead The hypochlorhydria à allows
to duodenal ulceration. other bacteria to proliferate within the
stomach àbacteria continue to drive the
chronic inflammation and produce mutagenic
nitrites from dietary nitratesà predisposing
to the development of gastric cancer.

Mild pangastritis
little effect on acid secretion
majority develop no significant clinical outcomes
H. Pylori associated diseases
 Clinical features:

40%vomiting In some
Asymptomatic present
Daily vomiting? GOO with complications as
GIB, Perforation.

R/Rs

30% atypical Symptoms

Elderly on NSAIDs: Poor predictors of PUD

Presence.
A case of epigastric pain. Which investigation is best for
nausea, anorexia the diagnosis of H.

Pylori?

a. Stool Antigen

b. Rapid Urease Test

Zollinger-Ellison
syndrome is a rare
digestive disorder
that results in too
much gastric acid.
This excess gastric
acid can cause
peptic ulcers in
your stomach and
intestine. Symptoms
include abdominal
pain, nausea,
vomiting, weight
loss, and diarrhea.
If left untreated,
there can be
serious
complications
 Investigations of PUD

l H. pylori test
- Non invasive (non-endoscopic tests)
- Invasive (endoscopic tests)

l Upper endoscopy
- Taking biopsy in GU
Endoscopic appearance of PU
Gastric Duodenal
Benign gastric ulcer Duodenal ulcer
Treatment of PUD

Ø H. pylori eradication
corner stone of treatment
Ø General measures
Stop/avoid smoking, aspirin, NSAID
Alcohol in moderation
No specific dietary advice
Ø Maintenance treatment
Not necessary after successful H. pylori eradication
Minimum effective dose PPI if needed
Ø Surgical treatment
H. Pylori eradication

l 14 days
l First line: 4 drugs (quadruple regimen)
Ø Bismuth containing
(PPI, bismuth, tetracycline, metronidazole)
Ø Non-bismuth containing
(PPI, amoxicillin, metronidazole, clarithromycin)
Eradicate H. pylori whenever +ve
Dumping syndrome is a group of symptoms, such as diarrhea, nausea, and
feeling light-headed or tired after a meal, that are caused by rapid
gastric emptying. Rapid gastric emptying is a condition in which food moves
too quickly from your stomach to your duodenum.
man with no appetite in front of a meal
Symptoms & Causes
Symptoms of early dumping syndrome occur within 30 minutes after a
meal, while symptoms of late dumping syndrome occur 1 to 3 hours after a
meal. The most common cause of rapid gastric emptying and dumping
syndrome is surgery of the stomach or esophagus.
Diagnosis
Doctors typically diagnose dumping syndrome based on symptoms. Your
doctor may also order tests, such as an oral glucose tolerance test or a
gastric emptying scan, to confirm the diagnosis.
Treatment
Doctors treat dumping syndrome by recommending changes to how and
what you eat, medicines, and, in some cases, surgery. Many people with
dumping syndrome have mild symptoms that improve over time with simple
changes in eating and diet.
Eating, Diet, & Nutrition
The first step in treating dumping syndrome is changing h
COMPLICATIONS OF PUD

l Hemorrhage

l Perforation

l Gastric outlet obstruction ( GOO )

 Zollinger Ellison Syndrome (Gastrinoma)
90%: Pancreatic Increase serum
C/F:
head or duodenum gastrin 10-1000 fold
Short history
50% multiple Severe & multiple PU Paradoxical increase
in unusual sites, with secretin.
1/2-2/3 malignant but
D2,Jej,eso.
slow growing Localization by: EUS
Poor response to trt.
& SST Receptor
20-60% part of More complication
scintigraphy.
MEN1 Recurs after surgery.
Diarrhea in 30%.

Diagnosis:
Treatment of ZES

l Surgical resection
Single
No metastasis

l Medical treatment (PPI, octreotide)

Multiple
Metastasis
Q1- A 35-year-old man is evaluated for a 2-month history of
upper abdominal discomfort after eating. He has recently
returned from working in a rural area of a developing country.
He takes no medications.

There is no family history of esophageal or gastric cancer. On

physical examination, vital signs are normal. BM! Is 40.
Centripetal obesity is noted, but abdominal examination findings
are otherwise normal. Laboratory studies reveal a hemoglobin
level of 15 g/dL (150 g/L).
Which of the following is the most appropriate management?

l (A) Barium esophagogram

l (B) Empiric Helicobacter pylori eradication therapy
l (C) H. pylori testing
l (D) Upper endoscopy
Q2- A 58-year-old man is evaluated for a 6-month history of
episodic epigastric abdominal pain. In addition, his wife was
recently diagnosed with Helicobacter pylori infection, and she is
concerned that he may be infected as well.

His epigastric pain occurs on most days and may occur several
times during the day. He characterizes it as a vague discomfort
that does not affect most activities. The discomfort is not
closely related to eating, but he has been eating less. The
discomfort typically resolves spontaneously within 30 to 60
minutes, but it has been occurring more frequently. He has also
noted occasional nausea without vomiting. His weight is 2.3 kg
(5.0 lb) lower than it was 1 year ago at his last appointment.
Family history is negative for gastrointestinal malignancy.
On physical examination, blood pressure is 138/79 mm Hg, and
pulse rate is 80/min. Other vital signs are normal.
BM! is 35. Abdominal examination reveals generalized
tenderness to deep palpation but no palpable mass.

Laboratory studies reveal a hemoglobin level of 12.5 g/dL (125

g/L) and a mean corpuscular volume of 94 fL. Which of the
following is the most appropriate management?

l (A) Empiric treatment of H. pylori

l (B) Empiric trial of omeprazole
l (C) H. pylori serologic testing
l (D) Upper endoscopy
Q3- A 67-year-old woman is evaluated during a
routine examination. She has a history of hip and
knee pain related to degenerative joint disease.

The joint pain is now well controlled with diclofenac,

which was started 3 months ago. A previous trial of
high-dose acetaminophen was not effective. She
does not have any gastrointestinal symptoms, and
she takes the diclofenac with food most of the time.
Her medical history is otherwise notable for type 2
diabetes mellitus, hyperlipidemia, and hypertension.
Her parents both had coronary artery disease. Her
medications are low dose aspirin, metformin,
chlorthalidone, simvastatin, and diclofenac.

On physical examination, vital signs are normal.

Abdominal examination is unremarkable.
Which of the following is the most appropriate
management?

l (A) Change to enteric-coated aspirin

l (B) Continue the current medication regimen
l (C) Initiate omeprazole, 20 mg once daily
l (D) Initiate omeprazole, 40 mg once daily
Q1- Answer: C

Before pursuing Helicobacter pylori

eradication therapy, noninvasive testing for
H. pylori should be performed to confirm
infection.
Q2- Answer: D

Upper endoscopy is recommended for the

exclusion of upper gastrointestinal structural
causes of dyspepsia; it should be performed
in patients who have alarm features.
Q3- Answer: C

Standard-dose daily proton pump inhibitor

therapy significantly reduces the risk of
NSAID-induced gastric injury.
798 • GASTROENTEROLOGY

Flagella

Urea H2O
Urease

NH3 2CO2
Ammonia
'cloud'
Type IV secretion
system

Other factors
• Vacuolating cytotoxin (vacA)
• Cytotoxin-associated gene (cagA)
• Adhesins (babA)
• Outer inflammatory protein A (oipA)
Fig. 21.35 Factors that influence the virulence of Helicobacter
pylori.

in the UK approximately 50% of people over the age of 50 years

are infected. In the developing world infection is more common,
affecting up to 90% of adults. These infections are probably
acquired in childhood by person-to-person contact. The vast
majority of colonised people remain healthy and asymptomatic,
and only a minority develop clinical disease. Around 90% of
duodenal ulcer patients and 70% of gastric ulcer patients are
infected with H. pylori. The remaining 30% of gastric ulcers are
caused by NSAIDs and this proportion is increasing in Western
Peptic ulcer disease countries as a result of H. pylori eradication strategies.
H. pylori is Gram-negative and spiral, and has multiple flagella
The term ‘peptic ulcer’ refers to an ulcer in the lower oesophagus, at one end, which make it motile, allowing it to burrow and live
stomach or duodenum, in the jejunum after surgical anastomosis beneath the mucus layer adherent to the epithelial surface.
to the stomach or, rarely, in the ileum adjacent to a Meckel’s It uses an adhesin molecule (BabA) to bind to the Lewis b
diverticulum. Ulcers in the stomach or duodenum may be acute antigen on epithelial cells. Here the surface pH is close to neutral
or chronic; both penetrate the muscularis mucosae but the acute and any acidity is buffered by the organism’s production of
ulcer shows no evidence of fibrosis. Erosions do not penetrate the enzyme urease. This produces ammonia from urea and
the muscularis mucosae. raises the pH around the bacterium and between its two cell
membrane layers. H. pylori exclusively colonises gastric-type
Gastric and duodenal ulcer epithelium and is found in the duodenum only in association
with patches of gastric metaplasia. It causes chronic gastritis
The prevalence of peptic ulcer (0.1–0.2%) is decreasing in
by provoking a local inflammatory response in the underlying
many Western communities as a result of widespread use of
epithelium (Fig. 21.35). This depends on numerous factors,
Helicobacter pylori eradication therapy but it remains high in
notably expression of bacterial cagA and vacA genes. The CagA
developing countries. The male-to-female ratio for duodenal
gene product is injected into epithelial cells, interacting with
ulcer varies from 5 : 1 to 2 : 1, while that for gastric ulcer is 2 : 1
numerous cell-signalling pathways involved in cell replication and
or less. Chronic gastric ulcer is usually single; 90% are situated
apoptosis. H. pylori strains expressing CagA (CagA+) are more
on the lesser curve within the antrum or at the junction between
often associated with disease than CagA− strains. Most strains
body and antral mucosa. Chronic duodenal ulcer usually occurs
also secrete a large pore-forming protein called VacA, which
in the first part of the duodenum and 50% are on the anterior
causes increased cell permeability, efflux of micronutrients from
wall. Gastric and duodenal ulcers coexist in 10% of patients
the epithelium, induction of apoptosis and suppression of local
and more than one peptic ulcer is found in 10–15% of patients.
immune cell activity. Several forms of VacA exist and pathology
Pathophysiology is most strongly associated with the s1/ml form of the toxin.
The distribution and severity of H. pylori–induced gastritis
H. pylori
determine the clinical outcome. In most people, H. pylori causes
Peptic ulceration is strongly associated with H. pylori infection. The a mild pangastritis with little effect on acid secretion and the
prevalence of the infection in developed nations rises with age and majority develop no significant clinical outcomes. In a minority (up
 Diseases of the stomach and duodenum • 799

to 10% in the West), the infection causes an antral-predominant NSAIDs

pattern of gastritis characterised by hypergastrinaemia and a very Treatment with NSAIDs is associated with peptic ulcers due to
exaggerated acid production by parietal cells, which could lead impairment of mucosal defences, as discussed on page 1002.
to duodenal ulceration (Fig. 21.36). In a much smaller number of
infected people, H. pylori causes a corpus-predominant pattern Smoking
of gastritis leading to gastric atrophy and hypochlorhydria. Smoking confers an increased risk of gastric ulcer and, to a
This phenotype is much more common in Asian countries, lesser extent, duodenal ulcer. Once the ulcer has formed, it is
particularly Japan, China and Korea. The hypochlorhydria allows more likely to cause complications and less likely to heal if the
other bacteria to proliferate within the stomach; these other patient continues to smoke.
bacteria continue to drive the chronic inflammation and produce
mutagenic nitrites from dietary nitrates, predisposing to the Clinical features
development of gastric cancer (Fig. 21.37). The effects of H. Peptic ulcer disease is a chronic condition with spontaneous
pylori are more complex in gastric ulcer patients compared to relapses and remissions lasting for decades, if not for life. The
those with duodenal ulcers. The ulcer probably arises because most common presentation is with recurrent abdominal pain that
of impaired mucosal defence resulting from a combination of H. has three notable characteristics: localisation to the epigastrium,
pylori infection, NSAIDs and smoking, rather than excess acid. relationship to food and episodic occurrence. Occasional vomiting
occurs in about 40% of ulcer subjects; persistent daily vomiting
suggests gastric outlet obstruction. In one-third, the history is
less characteristic, especially in elderly people or those taking
Increased acid
load in duodenum NSAIDs. In this situation, pain may be absent or so slight that
leads to gastric it is experienced only as a vague sense of epigastric unease.
metaplasia Increased
acid Occasionally, the only symptoms are anorexia and nausea, or
4 secretion early satiety after meals. In some patients, the ulcer is completely
HCl 3 ‘silent’, presenting for the first time with anaemia from chronic
undetected blood loss, as abrupt haematemesis or as acute
perforation; in others, there is recurrent acute bleeding without
ulcer pain. The diagnostic value of individual symptoms for peptic
G ulcer disease is poor; the history is therefore a poor predictor
D
2 of the presence of an ulcer.
1 Increased
gastrin release Investigations
5 Depletion of
antral D-cell from G cells Endoscopy is the preferred investigation (Fig. 21.38). Gastric
Further
inflammation somatostatin ulcers may occasionally be malignant and therefore must always
and eventual be biopsied and followed up to ensure healing. Patients should
ulceration be tested for H. pylori infection. The current options available are
Fig. 21.36 Sequence of events in the pathophysiology of duodenal listed in Box 21.34. Some are invasive and require endoscopy;
ulceration. others are non-invasive. They vary in sensitivity and specificity.
Breath tests or faecal antigen tests are best because of accuracy,
simplicity and non-invasiveness. 21
Helicobacter Host factors
pylori factors (IL-1β
(VacA, CagA) and TNF-α
polymorphisms)

Other
environmental
factors
(NSAIDs, smoking)

Antral gastritis Pangastritis

Duodenal Gastric Gastric

ulcer ulcer cancer
Fig. 21.37 Consequences of Helicobacter pylori infection. (CagA =
cytotoxin-associated gene; IL-1β = interleukin-1 beta; NSAIDs =
non-steroidal anti-inflammatory drugs; TNF-α = tumour necrosis factor Fig. 21.38 Endoscopic identification of a duodenal ulcer. The ulcer
alpha; VacA = vacuolating cytotoxin) has a clean base and there are no stigmata of recent haemorrhage.
800 • GASTROENTEROLOGY

21.34 Methods for the diagnosis of Helicobacter

pylori infection 21.36 Indications for Helicobacter pylori eradication
Test Advantages Disadvantages Definite
Non-invasive • Peptic ulcer
Serology Rapid office kits Lacks specificity • Extranodal marginal-zone lymphomas of MALT type
available Cannot differentiate • Family history of gastric cancer
Good for population current from past • Previous resection for gastric cancer
studies infection • H. pylori-positive dyspepsia
13
C-urea breath test High sensitivity and Requires expensive • Long-term NSAID or low-dose aspirin users
specificity mass spectrometer • Chronic (> 1 year) PPI users
Faecal antigen test Cheap, specific (> 95%) Acceptability • Extragastric disorders:
Invasive (antral biopsy) Unexplained vitamin B12 deficiency*
Histology Specificity False negatives Idiopathic thrombocytopenic purpura*
Takes several days Iron deficiency anaemia* (see text)
to process Not indicated
Rapid urease test Cheap, quick, specific Sensitivity 85%
• Gastro-oesophageal reflux disease
(> 95%)
• Asymptomatic people without gastric cancer risk factors
Microbiological ‘Gold standard’ Slow and laborious
culture Defines antibiotic Lacks sensitivity *If H. pylori-positive on testing.
sensitivity (MALT = mucosa-associated lymphoid tissue; NSAID = non-steroidal
anti-inflammatory drug; PPI = proton pump inhibitor)

21.35 Common side-effects of Helicobacter pylori

eradication therapy
21.37 Indications for surgery in peptic ulcer
• Diarrhoea: 30–50% of patients; usually mild but Clostridium
difficile-associated diarrhoea can occur Emergency
• Flushing and vomiting when taken with alcohol (metronidazole) • Perforation
• Nausea, vomiting • Haemorrhage
• Abdominal cramps
• Headache Elective
• Rash • Gastric outflow obstruction
• Persistent ulceration despite adequate medical therapy
• Recurrent ulcer following gastric surgery
Management
The aims of management are to relieve symptoms, induce first undergo eradication therapy to reduce ulcer risk. Subsequent
healing and prevent recurrence. H. pylori eradication is the co-prescription of a PPI along with the NSAID is advised but is
cornerstone of therapy for peptic ulcers, as this will successfully not always necessary for patients being given low-dose aspirin,
prevent relapse and eliminate the need for long-term therapy in in whom the risk of ulcer complications is lower.
the majority of patients. Other indications for H. pylori eradication are shown in Box
21.36. Eradication of the infection has proven benefits in several
H. pylori eradication
extragastric disorders, including unexplained B12 deficiency and
All patients with proven ulcers who are H. pylori-positive should iron deficiency anaemia, once sources of gastrointestinal bleeding
be offered eradication as primary therapy. Treatment is based on have been looked for and excluded. Platelet counts improve
a PPI taken simultaneously with two antibiotics (from amoxicillin, and may normalise after eradication therapy in patients with
clarithromycin and metronidazole) for at least 7 days. High-dose, idiopathic thrombocytopenic purpura (p. 979); the mechanism
twice-daily PPI therapy increases efficacy of treatment, as does for this is unclear.
extending treatment to 10–14 days. Success is achieved in
80–90% of patients, although adherence, side-effects (Box General measures
21.35) and antibiotic resistance influence this. Resistance to Cigarette smoking, aspirin and NSAIDs should be avoided.
amoxicillin is rare but rates of metronidazole resistance reach Alcohol in moderation is not harmful and no special dietary
more than 50% in some countries and rates of clarithromycin advice is required.
resistance of 20–40% have recently become common. Where
the latter exceed 15%, a quadruple therapy regimen, consisting Maintenance treatment
of omeprazole (or another PPI), bismuth subcitrate, metronidazole Continuous maintenance treatment should not be necessary after
and tetracycline (OBMT) for 10–14 days, is recommended. In successful H. pylori eradication. For the minority who do require
areas of low clarithromycin resistance, this regimen should also it, the lowest effective dose of PPI should be used.
be offered as second-line therapy to those who remain infected
after initial therapy, once adherence has been checked. For Surgical treatment
those who are still colonised after two treatments, the choice Surgery is now rarely required for peptic ulcer disease but it is
lies between a third attempt guided by antimicrobial sensitivity needed in some cases (Box 21.37).
testing, rescue therapy (levofloxacin, PPI and clarithromycin) or The operation of choice for a chronic non-healing gastric ulcer
long-term acid suppression. is partial gastrectomy, preferably with a Billroth I anastomosis, in
H. pylori and NSAIDs are independent risk factors for ulcer which the ulcer itself and the ulcer-bearing area of the stomach
disease and patients requiring long-term NSAID therapy should are resected. The reason for this is to exclude an underlying
 Diseases of the stomach and duodenum • 801

cancer. In an emergency, ‘under-running’ the ulcer for bleeding independent risk factor for late development of malignancy in the
or ‘oversewing’ (patch repair) for perforation is all that is required, gastric remnant but the risk is higher in those with hypochlorhydria,
in addition to taking a biopsy. For giant duodenal ulcers, partial duodenogastric reflux of bile, smoking and H. pylori infection.
gastrectomy using a ‘Polya’ or Billroth II reconstruction may Although the relative risk is increased, the absolute risk of cancer
be required. remains low and endoscopic surveillance is not indicated following
gastric surgery.
Complications of gastric resection or vagotomy
Up to 50% of patients who undergo gastric surgery for peptic Complications of peptic ulcer disease
ulcer surgery experience long-term adverse effects. In most cases Perforation
these are minor but in 10% they significantly impair quality of life. When perforation occurs, the contents of the stomach escape into
Dumping Rapid gastric emptying leads to distension of the the peritoneal cavity, leading to peritonitis. This is more common
proximal small intestine as the hypertonic contents draw fluid in duodenal than in gastric ulcers and is usually found with ulcers
into the lumen. This leads to abdominal discomfort and diarrhoea on the anterior wall. About one-quarter of all perforations occur
after eating. Autonomic reflexes release a range of gastrointestinal in acute ulcers and NSAIDs are often incriminated. Perforation
hormones that provoke vasomotor features, such as flushing, can be the first sign of ulcer and a history of recurrent epigastric
palpitations, sweating, tachycardia and hypotension. Patients pain is uncommon. The most striking symptom is sudden, severe
should therefore avoid large meals with high carbohydrate content. pain; its distribution follows the spread of the gastric contents
over the peritoneum. The pain initially develops in the upper
Chemical (bile reflux) gastropathy Duodenogastric bile reflux leads abdomen and rapidly becomes generalised; shoulder tip pain is
to chronic gastropathy. Treatment with aluminium-containing caused by irritation of the diaphragm. The pain is accompanied by
antacids or sucralfate may be effective. A few patients require shallow respiration, due to limitation of diaphragmatic movements,
revisional surgery with creation of a Roux en Y loop to prevent and by shock. The abdomen is held immobile and there is
bile reflux. generalised ‘board-like’ rigidity. Bowel sounds are absent and
liver dullness to percussion decreases due to the presence of
Diarrhoea and maldigestion Diarrhoea may develop after any peptic
gas under the diaphragm. After some hours, symptoms may
ulcer operation and usually occurs 1–2 hours after eating. Poor
improve, although abdominal rigidity remains. Later, the patient’s
mixing of food in the stomach, with rapid emptying, inadequate
condition deteriorates as general peritonitis develops. In at least
mixing with pancreaticobiliary secretions, rapid transit and bacterial
50% of cases, an erect chest X-ray shows free air beneath the
overgrowth, may lead to malabsorption. Diarrhoea often responds
diaphragm (see Fig. 21.11B, p. 773). If not, a water-soluble contrast
to small, dry meals with a reduced intake of refined carbohydrates.
swallow will confirm leakage of gastroduodenal contents. After
Antidiarrhoeal drugs, such as codeine phosphate (15–30 mg
resuscitation, the acute perforation should be treated surgically,
4–6 times daily) or loperamide (2 mg after each loose stool),
either by simple closure or by conversion of the perforation into
are helpful.
a pyloroplasty if it is large. On rare occasions, a ‘Polya’ partial
Weight loss Most patients lose weight shortly after surgery and gastrectomy is required. Following surgery, H. pylori should be
30–40% are unable to regain all the weight that is lost. The usual treated (if present) and NSAIDs avoided. Perforation carries a
cause is reduced intake because of a small gastric remnant but mortality of 25%, reflecting the advanced age and significant
diarrhoea and mild steatorrhoea also contribute. comorbidity of the population that are affected.

Anaemia Anaemia is common many years after subtotal Gastric outlet obstruction 21
gastrectomy. Iron deficiency is the most common cause; folic The causes are shown in Box 21.39. The most common is an
acid and B12 deficiency are much less frequent. Inadequate ulcer in the region of the pylorus. The presentation is with nausea,
dietary intake of iron and folate, lack of acid and intrinsic factor vomiting and abdominal distension. Large quantities of gastric
secretion, mild chronic low-grade blood loss from the gastric content are often vomited and food eaten 24 hours or more
remnant and recurrent ulceration are responsible. previously may be recognised. Physical examination may show
evidence of wasting and dehydration. A succussion splash may
Metabolic bone disease Both osteoporosis and osteomalacia can
be elicited 4 hours or more after the last meal or drink. Visible
occur as a consequence of calcium and vitamin D malabsorption.
gastric peristalsis is diagnostic of gastric outlet obstruction. Loss
Gastric cancer An increased risk of gastric cancer has been of acidic gastric contents leads to alkalosis and dehydration with
reported from several epidemiological studies. Surgery itself is an low serum chloride and potassium and raised serum bicarbonate
and urea concentrations (hypochloraemic metabolic alkalosis).

21.38 Peptic ulcer disease in old age 21.39 Differential diagnosis and management of
gastric outlet obstruction
• Gastroduodenal ulcers: have a greater incidence, admission rate
Cause Management
and mortality.
• Causes: high prevalence of H. pylori, use of non-steroidal Fibrotic stricture from duodenal ulcer Balloon dilatation or surgery
anti-inflammatory drugs and impaired defence mechanisms. (pyloric stenosis)
• Atypical presentations: pain and dyspepsia are frequently absent Oedema from pyloric channel or Proton pump inhibitor therapy
or atypical. Older people often develop complications, such as duodenal ulcer
bleeding or perforation, without a dyspeptic history.
• Bleeding: older patients require more intensive management Carcinoma of antrum Surgery
because they have more limited reserve to withstand hypovolaemia. Adult hypertrophic pyloric stenosis Surgery
802 • GASTROENTEROLOGY

Paradoxical aciduria occurs because of enhanced renal absorption of MEN 1). Some patients present with metastatic disease and,
of Na+ in exchange for H+. Endoscopy should be performed after in these circumstances, surgery is inappropriate. In the majority
the stomach has been emptied using a wide-bore nasogastric of these individuals, continuous therapy with omeprazole or other
tube. Intravenous correction of dehydration is undertaken and, PPIs can be successful in healing ulcers and alleviating diarrhoea,
in severe cases, at least 4 L of isotonic saline and 80 mmol of although double the normal dose is required. The synthetic
potassium may be necessary during the first 24 hours. In some somatostatin analogue, octreotide, given by subcutaneous
patients, PPI drugs heal ulcers, relieve pyloric oedema and injection, reduces gastrin secretion and may be of value. Other
overcome the need for surgery. Endoscopic balloon dilatation of treatment options for pancreatic neuro-endocrine tumours are
benign stenoses may be possible in some patients but in others discussed on page 678. Overall 5-year survival is 60–75% and
partial gastrectomy is necessary; this is best done after a 7-day all patients should undergo genetic screening for MEN 1.
period of nasogastric aspiration, which enables the stomach
to return to normal size. A gastroenterostomy is an alternative
operation but, unless this is accompanied by vagotomy, patients Functional disorders
will require long-term PPI therapy to prevent stomal ulceration.
Functional dyspepsia
Bleeding
This is defined as chronic dyspepsia in the absence of organic
See page 780.
disease. Other commonly reported symptoms include early satiety,
fullness, bloating and nausea. ‘Ulcer-like’ and ‘dysmotility-type’
Zollinger–Ellison syndrome
subgroups are often reported but there is overlap between these
This is a rare disorder characterised by the triad of severe peptic and with irritable bowel syndrome.
ulceration, gastric acid hypersecretion and a neuro-endocrine
tumour (p. 678) of the pancreas or duodenum (‘gastrinoma’). Pathophysiology
It probably accounts for about 0.1% of all cases of duodenal The cause is poorly understood but probably covers a spectrum
ulceration. The syndrome occurs in either sex at any age, although of mucosal, motility and psychiatric disorders.
it is most common between 30 and 50 years of age.
Clinical features
Pathophysiology Patients are usually young (< 40 years) and women are affected
The tumour secretes gastrin, which stimulates acid secretion twice as commonly as men. Abdominal discomfort is associated
to its maximal capacity and increases the parietal cell mass with a combination of other ‘dyspeptic’ symptoms, the most
three- to sixfold. The acid output may be so great that it reaches common being nausea, satiety and bloating after meals. Morning
the upper small intestine, reducing the luminal pH to 2 or less. symptoms are characteristic and pain or nausea may occur on
Pancreatic lipase is inactivated and bile acids are precipitated. waking. Direct enquiry may elicit symptoms suggestive of irritable
Diarrhoea and steatorrhoea result. Around 90% of tumours occur bowel syndrome. Peptic ulcer disease must be considered,
in the pancreatic head or proximal duodenal wall. At least half while in older people intra-abdominal malignancy is a prime
are multiple and tumour size can vary from 1 mm to 20 cm. concern. There are no diagnostic signs, apart from inappropriate
Approximately one-half to two-thirds are malignant but are often tenderness on abdominal palpation, perhaps. Symptoms may
slow-growing. Between 20% and 60% of patients have multiple appear disproportionate to clinical well-being and there is no
endocrine neoplasia (MEN) type 1 (p. 688). weight loss. Patients often appear anxious. A drug history should
be taken and the possibility of a depressive illness should be
Clinical features considered. Pregnancy should be ruled out in young women
The presentation is with severe and often multiple peptic ulcers before radiological studies are undertaken. Alcohol misuse
in unusual sites, such as the post-bulbar duodenum, jejunum or should be suspected when early-morning nausea and retching
oesophagus. There is a poor response to standard ulcer therapy. are prominent.
The history is usually short, and bleeding and perforations are
common. Diarrhoea is seen in one-third or more of patients and Investigations
can be the presenting feature. The history will often suggest the diagnosis. All patients should
be checked for H. pylori infection and patients over the age of
Investigations 55 years should undergo endoscopy to exclude mucosal disease.
Hypersecretion of acid under basal conditions, with little increase While an ultrasound scan may detect gallstones, these are rarely
following pentagastrin, may be confirmed by gastric aspiration. responsible for dyspeptic symptoms.
Serum gastrin levels are grossly elevated (10- to 1000-fold).
Injection of the hormone secretin normally causes no change Management
or a slight decrease in circulating gastrin concentrations, The most important elements are explanation and reassurance.
but in Zollinger–Ellison syndrome it produces a paradoxical Possible psychological factors should be explored and the
and dramatic increase in gastrin. Tumour localisation (and concept of psychological influences on gut function should be
staging) is best achieved by a combination of CT and EUS; explained. Idiosyncratic and restrictive diets are of little benefit
radio-labelled somatostatin receptor scintigraphy and 68gallium but smaller portions and fat restriction may help.
DOTATATE PET scanning may also be used for tumour detection Up to 10% of patients benefit from H. pylori eradication therapy
and staging. and this should be offered to infected individuals. Eradication also
removes a major risk factor for peptic ulcers and gastric cancer
Management but at the cost of a small risk of side-effects and worsening
Some 30% of small and single tumours can be localised and symptoms of underlying gastro-oesophageal reflux disease. Drug
resected but many tumours are multifocal (especially in the context treatment is not especially successful but merits trial. Antacids,
 Diseases of the stomach and duodenum • 803

such as hydrotalcite, are sometimes helpful. Prokinetic drugs,

such as metoclopramide (10 mg 3 times daily) or domperidone
(10–20 mg 3 times daily), may be given before meals if nausea,
vomiting or bloating is prominent. Metoclopramide may induce
extrapyramidal side-effects, including tardive dyskinesia in young
patients. H2-receptor antagonist drugs may be tried if night pain
or heartburn is troublesome. Low-dose tricyclic agents, such as
amitriptyline, are of value in up to two-thirds.
Symptoms that can be associated with an identifiable cause
of stress resolve with appropriate counselling. Some patients
have major psychological disorders that result in persistent
or recurrent symptoms and need behavioural or other formal
psychotherapy (p. 1190).

21
Normal gastric
epithelium

Helicobacter CagA
pylori

Chronic atrophic
gastritis

Achlorhydria

Intestinal
Bacterial metaplasia
colonisation
of stomach Helicobacter
pylori
Diet
Smoking
Dietary Dysplasia
Nitrosamines
nitrates

Carcinoma
Fig. 21.39 Gastric carcinogenesis: a possible mechanism.
(CagA = cytotoxin-associated gene)