Upper GI tract disorders

Learning outcomes
• Discuss common causes of reflux
• Define oesophagitis, hiatus hernia and ulcers
(gastrointestinal and duodenal)
• Discuss the epidemiology of ulcers
• Describe the aetiology (include any primary
causes, predisposing and precipitating causes)
of ulcers
• Understand the pathophysiology of ulcers
• List the signs and symptoms of ulcers
• Appreciate the drugs used e.g. antacids, H2
receptor antagonists, proton pump inhibitors,
antibiotics for H.Pylori in terms of
pathophysiology
The digestive system
Gastro-oesophageal reflux disease
(GORD)
Commonest cause of indigestion (affects
30% of population)
Caused by retrograde flow of gastric
acid into the lower oesophagus due to
an incompetent cardiac sphincter
Cardiac sphincter
Aetiology
 intra-abdominal pressure (e.g.
distension, pregnancy)
 acid production (from certain foods
or drugs)
Delayed gastric emptying
(e.g. pyloric stenosis)

Pyloric stenosis
Presence of hiatus hernia
Alcohol & smoking can worsen the
problem

Sliding hiatus hernia (80%) Rolling or Para-Oesophageal hernia (20%)

https://www.youtube.com/watch?v=imgDFUjQ4Vc
Pathophysiology
 sphincter tone allows regurgitation of
stomach contents
Oesophageal mucosa exposed to
stomach acid leading to inflammation
and ulceration
Severity depends
on gastric contents
Acid usually cleared by peristalsis in 1-3
minutes
Delayed gastric emptying increases
acidity chyme
Weak peristalsis increases exposure
time
Clinical Features
Regurgitation and epigastric heartburn
within 1-2 hours of eating
Acidbrash: regurgitation of stomach acid
into the mouth

Waterbrash: increased salivation

Dysphagia due to occlusion of
oesophagus
 oesophageal peristalsis
Intolerance of acidic foods and alcohol

A persistent cough, particularly at night,

may develop as a result of refluxed acid
irritating the trachea
Complications
Long-standing inflammation can cause
scarring and narrowing (a stricture) of
the lower oesophagus

Barrett's oesophagus: the cells that line

the lower oesophagus are changed and
are more likely to become cancerous
Diagnosis
Barium swallow
Endoscopy
Treatment
Weight loss
Sleep with head higher than stomach
Avoid gastric irritants (e.g. smoking,
fatty foods, alcohol)
H2 receptor agonists
Proton pump inhibitors
Metochlopromide: anti emetic which
promotes gastric emptying
Endoscopic treatment of Barrett's Oes.
Endoscopic ablation (also now as the Halo® system)
uses heat energy (radiofrequency ablation/RFA) to
destroy abnormal tissue in the oesophagus (it shouldn’t
damage healthy tissue)

After the endoscopic oesophageal landmarks are defined,

the oesophageal wall is sprayed with acetylcysteine 1%
and then flushed with water to remove excess mucous for
the Halo® 360 ablation procedure

Ablation is repeated until the entire Barrett's oesophagus

has been treated with RF energy
Peptic Ulcer
A peptic ulcer is a break or ulceration in
the protective mucosal lining of lower
oesophagus, stomach or duodenum
Ulcers occur when the sub-mucosa is
exposed to Hydrochloric acid (HCl) &
pepsin
oesophageal ulcer

gastric ulcer

duodenal ulcer
The gastric mucosa contains numerous
gastric glands which contain several different
cell types
Microscopic anatomy of the stomach
Causative factors
Bacterial infection: helicobacter pylori
responsible for 90% of DU & 70% of GU
Habitual use of NSAIDS accounts for
30% of GU
 number of acid secreting cells
 gastrin levels or failure of gastrin
inhibition
Rapid gastric emptying
(?)Stress
Smoking (especially GU)
Genetic (higher risk in first degree
relatives)
Helicobacter pylori: pathophysiology
Ulcers occur when acid and pepsin
concentrations penetrate mucosal lining

Helicobacter pylori burrow under mucus

barrier & trigger inflammation through
the release exotoxins & enzymes
H-pylori move by means of tiny flagella at
the end of the cell
Breaks in mucosal lining
expose underlying tissue
to gastric secretions

Pepsin digests tissue in the gut wall

ulcer
duodenum
gastric ulcer
Damaged area becomes raw and
inflamed
Blood vessels are eroded causing
bleeding
External gut wall may perforate leading
to spillage of gut contents
Clinical features
Chronic condition with relapses and
remissions
Dyspepsia due to excess acid production
Nausea and anorexia

Vomiting in 40% of patients

Chronic episodic pain in upper abdomen
Diagnosis of Helicobacter pylori
Rapid urease test (known as the CLO
test - Campylobacter-like organism test)
H. pylori secrete urease enzyme (which
converts urea to ammonia and carbon
dioxide)
The test is performed at the time of
gastroscopy
Complications
Anaemia following haemorrhage
(haematemesis or malaena)
Peritonitis following perforation

Spread of infection in presence of

subphrenic abscess
 risk of gastric cancer
Treatment
Avoid foods that cause symptoms
 Alcohol and smoking
Stress reduction
Surgery
Pharmacological management aims
to:
Neutralise stomach acid
 acid secretion
 vagal stimulation
Aid the protective coating over the
ulcerative site
Histamine (H2) receptor antagonists
Major breakthrough used to heal GU and
DU
Examples include: ranitidine (Zantac),
nizatidine (Axid) and cimetidine
(Tagamet, Dyspamet)
There are two types of histamine
receptors (H1 for allergies and H2 for 
HCl production)
H2 antagonists block histamine receptors
in gastric cells
Blockage leads to a reduction in gastric
acid output
Will heal 80% of DU’s after four weeks
Side effects include: GI disturbances
(diarrhoea), headache, dizziness, rash,
tiredness and altered LFT
Proton pump inhibitors
PPI’s act by blocking the hydrogen -
potassium - adenosine triphosphatase
enzyme system (gastric proton pump) of
the gastric parietal cell
The proton pump is
responsible for
secreting H+ ions
into the gastric
lumen
Examples include: lansoprazole (Zoton),
omeprazole (Losec)
Side effects include gastric disturbance
 stomach acidity may result in an
impaired ability to digest and absorb
certain nutrients, such as iron and the B
vitamins
There may also be an  incidence of
infection since the  pH of the stomach
normally kills ingested bacteria
Antacids
An antacid is an alkaline substance
that counteracts stomach acidity
They buffer gastric acid,  the pH in
order to  acidity in the stomach
They are inexpensive, readily available
and safe
However, they are not curative and
only useful for the treatment of fairly
minor symptoms
Examples include: magnesium
hydroxide, calcium carbonate (Rennie),
sodium bicarbonate (Alka-Selzter,
Bismuth subsalicylate (Pepto-Bismol)
Side effects include bloating and
flatulence
Constipation (calcium)
Diarrhoea (magnesium)
Aluminium may block absorption of
digoxin and tetracycline
Some antacids also contain sodium
alginate (derived from seaweed)
Gaviscon for example, contains sodium
alginate, calcium carbonate and sodium
bicarbinate
The combination of the
three substances create a
foam barrier (raft) on top
of the gastric contents
Mucosal Strengtheners
Form a sticky gel at pH < 4. This gel
adheres to the base of the ulcer to form
a coat that protects against further
erosion and promotes healing

Examples include: Sucralfate (aluminium

hydroxide and sulphated sucrose) &
Bismuth chelates (unpleasant to take)
Antibiotics
Used for H. pylori infection (following
diagnosis)
One-week triple-therapy:
1. Proton pump inhibitor
2. Amoxicillin 1g b.d.
3. Either: Clarithromycin 500mg b.d.
Metronidazole 400mg b.d.
Triple therapy eradicates H. pylori in over
90% of cases
Side effects include:
• Reinfection & antibiotic-induced colitis is
rare but possible
• Diarrhoea in 30-50% of patients
• Nausea & vomiting
• Abdominal cramps
• Headache
• Skin rashes
• Metallic taste in mouth (metronidazole)
 References
• Adams, M.P, Josephson, D.L. and Holland Jr., LN (2005)
Pharmacology for Nurses: A Pathophysiologic approach,
New Jersey: Pearson Education, Inc.
• Garden O.J., Bradbury A.W., Forsythe J., (2004)
Principles and Practice of Surgery, Edinburgh: Churchill
Liningstone
• Heuther, S.E. (2004) “Alterations of digestive function”
In: Heuther, S.E. and McCance, K.L. (eds)
Understanding pathophysiology, 3rd Ed, Missouri:
Mosby, 981 - 1023
• Hillier K, and Naylor, R.J. (2002) “Drugs and the
Gastrointestinal System”. In: Page, C. Curtis, M., Sutter,
M., Walker, M. and Hoffman, B. (eds.), Integrated
Pharmacology, 2nd ed., Edinburgh: Mosby, 455-482