8-Gastroenterology and Hepatology

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MEDICAL MASTERCLASS
EDITOR-IN-CHIEF
JOHN D FIRTH
DM FRCP
Consultant Physician and Nephrologist

Addenbrookes Hospital
Cambridge
GASTROENTEROLOGY AND
HEPATOLOGY
EDITOR
SATISH C KESHAV
MBBC h DP hil FRCP

Consultant Physician and Gastroenterologist
John Radcliffe Hospital
Oxford
Second Edition
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Disclaimer
Although every effort has been made to ensure that drug doses
and other information are presented accurately in this publication, the
ultimate responsibility rests with the prescribing physician. Neither the
publishers nor the authors can be held responsible for any consequences
arising from the use of information contained herein. Any product
mentioned in this publication should be used in accordance with the
prescribing information prepared by the manufacturers.
The information presented in this publication reflects the opinions of its
contributors and should not be taken to represent the policy and views of the
Royal College of Physicians of London, unless this is specifically stated.
Every effort has been made by the contributors to contact holders of
copyright to obtain permission to reproduce copyrighted material. However,
if any have been inadvertently overlooked, the publisher will be pleased to
make the necessary arrangements at the first opportunity.
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LIST OF CONTRIBUTORS
Dr RJ Atkinson
MRCP(UK)

Calderdale and Huddersfield NHS Foundation Trust
Huddersfield
Dr GM Hirschfield MA MB BChir PhD MRCP(UK)

Clinical Lecturer in Hepatology
Addenbrookes Hospital
Cambridge
Dr SC Keshav MBBCh DPhil FRCP

Department of Gastroenterology
John Radcliffe Hospital
Oxford
Dr JS Leeds
MBChB MRCP(UK)
Honorary Clinical Lecturer in Gastroenterology

Gastroenterology and Liver Unit
Royal Hallamshire Hospital
Sheffield
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2008, 2010 Royal College of Physicians of London

Published by:
Royal College of Physicians of London
11 St. Andrews Place
Regents Park
London NW1 4LE
United Kingdom
Set and printed by Graphicraft Limited, Hong Kong
All rights reserved. No part of this publication may be reproduced, stored
in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording or otherwise, except as
permitted by the UK Copyright, Designs and Patents Act 1988, without the
prior permission of the copyright owner.
First edition published 2001
Reprinted 2004
Second edition published 2008
This module updated and reprinted 2010
ISBN: 978-1-86016-271-8 (this book)
ISBN: 978-1-86016-260-2 (set)
Distribution Information:
Jerwood Medical Education Resource Centre
Royal College of Physicians of London
11 St. Andrews Place
Regents Park
London NW1 4LE
United Kingdom
Tel: +44 (0)207 935 1174 ext 422/490
Fax: +44 (0)207 486 6653
Email: [email protected]
Web: http://www.rcplondon.ac.uk/
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CONTENTS
List of contributors iii

Foreword vii
Preface viii
Acknowledgements x
Key features xi
1.4.3 Haematemesis and

melaena 39
1.4.4 Acute abdominal pain 46
1.4.5 Jaundice 50
1.4.6 Acute liver failure 54
Diseases and Treatments 60
GASTROENTEROLOGY
AND HEPATOLOGY
2.1
PACES Stations and Acute

Scenarios 3
1.1 History-taking 3
1.1.1 Heartburn and dyspepsia
3
1.1.2 Dysphagia and feeding
difficulties 5
1.1.3 Chronic diarrhoea 8
1.1.4 Rectal bleeding 10
1.1.5 Weight loss 14
1.1.6 Chronic abdominal pain
16
1.1.7 Abnormal liver function
tests 18
1.1.8 Abdominal swelling 21
1.2 Clinical examination 24
1.2.1 Inflammatory bowel
disease 24
1.2.2 Chronic liver disease 24
1.2.3 Splenomegaly 25
1.3 Communication skills and
ethics 27
1.3.1 A decision about feeding
27
1.3.2 Limitation of
management 29
1.3.3 Limitation of
investigation 30
1.3.4 A patient who does not
want to give a history 31
1.4 Acute scenarios 32
1.4.1 Nausea and vomiting 32
1.4.2 Acute diarrhoea 36
2.2
2.3
2.4
2.5
Oesophageal disease 60
2.1.1 Gastro-oesophageal
reflux disease 60
2.1.2 Achalasia and
oesophageal
dysmotility 62
2.1.3 Oesophageal cancer
and Barretts
oesophagus 63
Gastric disease 66
2.2.1 Peptic ulceration and
Helicobacter pylori 66
2.2.2 Gastric carcinoma 68
2.2.3 Rare gastric tumours
69
2.2.4 Rare causes of
gastrointestinal
haemorrhage 70
Small bowel disease 71
2.3.1 Malabsorption 71
2.3.1.1 Bacterial
overgrowth 71
2.3.1.2 Other causes of
malabsorption
72
2.3.2 Coeliac disease 73
Pancreatic disease 75
2.4.1 Acute pancreatitis 75
2.4.2 Chronic pancreatitis
78
2.4.3 Pancreatic cancer 80
2.4.4 Neuroendocrine
tumours 82
Biliary disease 83
2.5.1 Choledocholithiasis 83
2.5.2 Primary biliary
cirrhosis 85
2.5.3 Primary sclerosing
cholangitis 87
2.5.4 Intrahepatic cholestasis

89
2.5.5 Cholangiocarcinoma
89
2.6 Infectious diseases 92
2.6.1 Food poisoning and
gastroenteritis 92
2.6.2 Bacterial dysentery 93
2.6.3 Antibiotic-associated
diarrhoea 94
2.6.4 Parasitic infestations of
the intestine 94
2.6.5 Intestinal and liver
amoebiasis 95
2.6.6 Intestinal features of
HIV infection 95
2.7 Inflammatory bowel disease
95
2.7.1 Crohns disease 95
2.7.2 Ulcerative colitis 98
2.7.3 Microscopic colitis 101
2.8 Functional bowel disorders
101
2.9 Large bowel disorders 103
2.9.1 Adenomatous polyps of
the colon 103
2.9.2 Colorectal carcinoma
104
2.9.3 Diverticular disease
107
2.9.4 Intestinal ischaemia
108
2.9.5 Anorectal diseases 109
2.10 Liver disease 109
2.10.1 Acute viral hepatitis
109
2.10.1.1 Hepatitis A
109
2.10.1.2 Other acute
viral hepatitis
112
2.10.2 Chronic viral hepatitis
113
2.10.2.1 Hepatitis B
113
2.10.2.2 Hepatitis C
114
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CONTENTS
2.10.3 Acute liver failure

115
2.10.4 Alcohol-related liver
disease 116
2.10.5 Drugs and the liver
118
2.10.5.1 Hepatic drug
toxicity 118
2.10.5.2 Drugs and
chronic liver
disease 120
2.10.6 Chronic liver disease
and cirrhosis 120
2.10.7 Focal liver lesion 124
2.10.8 Liver transplantation
127
vi
2.11 Nutrition 129

2.11.1 Defining nutrition
129
2.11.2 Proteincalorie
malnutrition 133
2.11.3 Obesity 133
2.11.4 Enteral and parenteral
nutrition and special
diets 134
3.3 Diagnostic and therapeutic

endoscopy 138
radiology 139
3.5 Rigid sigmoidoscopy and
rectal biopsy 140
3.6 Paracentesis 143
3.7 Liver biopsy 144
Self-assessment 147
Investigations and Practical
Procedures 136
3.1 General investigations 136
3.2 Tests of gastrointestinal and
liver function 137
4.1 Self-assessment questions 147

4.2 Self-assessment answers 152
The Medical Masterclass Series 158
Index 174
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FOREWORD
Since its initial publication in 2001, Medical Masterclass has been regarded
as a key learning and teaching resource for physicians around the world.
The resource was produced in part to meet the vision of the Royal College of
Physicians: Doctors of the highest quality, serving patients well. This vision
continues and, along with advances in clinical practice and changes in
the format of the MRCP(UK) exam, has justified the publication of this
second edition.
The MRCP(UK) is an international examination that seeks to advance the
learning of and enhance the training process for physicians worldwide. On
passing the exam physicians are recognised as having attained the required
knowledge, skills and manner appropriate for training at a specialist level.
However, passing the exam is a challenge. The pass rate at each sitting of
the written papers is about 40%. Even the most prominent consultants
have had to sit each part of the exam more than once in order to pass.
With this challenge in mind, the College has produced Medical Masterclass,
a comprehensive learning resource to help candidates with the preparation
that is key to making the grade.
Medical Masterclass has been produced by the Education Department of
the College. A work of this size represents a formidable amount of effort
by the Editor-in-Chief Dr John Firth and his team of editors and authors.
I would like to thank our colleagues for this wonderful educational product
and wholeheartedly recommend it as an invaluable learning resource for all
physicians preparing for their MRCP(UK) examination.
Professor Ian Gilmore MD PRCP
President of the Royal College of Physicians
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PREFACE
The second edition of Medical Masterclass is produced and published by

the Education Department of the Royal College of Physicians of London.
It comprises 12 textbooks, a companion interactive website and two
CD-ROMs. Its aim is to help doctors in their first few years of training to
improve their medical knowledge and skills; and in particular to (a) learn
how to deal with patients who are acutely ill, and (b) pass postgraduate
examinations, such as the MRCP(UK) or European Diploma in Internal
Medicine.
The 12 textbooks are divided as follows: two cover the scientific background
to medicine, one is devoted to general clinical skills [including specific
guidance on exam technique for PACES, the practical assessment of clinical
examination skills that is the final part of the MRCP(UK) exam], one deals
with acute medicine and the other eight cover the range of medical
specialties.
The core material of each of the medical specialties is dealt with in seven
sections:
Case histories you are presented with letters of referral commonly
received in each specialty and led through the ways in which the patients
histories should be explored, and what should then follow in the way of
investigation and/or treatment.
Physical examination scenarios these emphasise the logical analysis of
physical signs and sensible clinical reasoning: having found this, what
would you do?
Communication and ethical scenarios what are the difficult issues that
commonly arise in each specialty? What do you actually say to the
frequently asked (but still very difficult) questions?
Acute presentations what are the priorities if you are the doctor seeing
the patient in the Emergency Department or the Medical Admissions
Unit?
Diseases and treatments structured concise notes.
Investigations and practical procedures more short and to-the-point notes.
Self assessment questions in the form used in the MRCP(UK) Part 1 and
Part 2 exams.
The companion website which is continually updated enables you to
take mock MRCP(UK) Part 1 or Part 2 exams, or to be selective in the
questions you tackle (if you want to do ten questions on cardiology, or any
other specialty, you can do). For every question you complete you can see
how your score compares with that of others who have logged onto the site
and attempted it. The two CD-ROMs each contain 30 interactive cases
requiring diagnosis and treatment.
viii
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PREFACE
I hope that you enjoy using Medical Masterclass to learn more about
medicine, which whatever is happening politically to primary care,
hospitals and medical career structures remains a wonderful occupation.
It is sometimes intellectually and/or emotionally very challenging, and also
sometimes extremely rewarding, particularly when reduced to the essential
of a doctor trying to provide best care for a patient.
John Firth DM FRCP
Editor-in-Chief
ix
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ACKNOWLEDGEMENTS
Medical Masterclass has been produced by a team. The names of those who
have written or edited material are clearly indicated elsewhere, but without
the support of many other people it would not exist. Naming names is risky,
but those worthy of particular note include: Sir Richard Thompson (College
Treasurer) and Mrs Winnie Wade (Director of Education), who steered the
project through committees that are traditionally described as labyrinthine,
and which certainly seem so to me; and also Arthur Wadsworth (Project
Co-ordinator) and Don Liu in the College Education Department office. Don
is a veteran of the first edition of Medical Masterclass, and it would be fair to
say that without his great efforts a second edition might not have seen the
light of day.
John Firth DM FRCP
Editor-in-Chief
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KEY FEATURES
We have created a range of icon boxes that sit among the text of the
various Medical Masterclass modules. They are there to help you identify key
information and to make learning easier and more enjoyable. Here is a brief
explanation:
Iron-deficiency anaemia with

a change in bowel habit in a
middle-aged or older patient means
colonic malignancy until proved
otherwise.
This icon is used to highlight points of particular importance.
Dietary deficiency is very

rarely, if ever, the sole cause of
iron-deficiency anaemia.
This icon is used to indicate common or important drug interactions, pitfalls

of practical procedures, or when to take symptoms or signs particularly
seriously.
xi
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GASTROENTEROLOGY AND
HEPATOLOGY
Authors:
RJ Atkinson, GM Hirschfield, SC Keshav and JS Leeds

Editor:
SC Keshav
Editor-in-Chief:
JD Firth
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GASTROENTEROLOGY AND HEPATOLOGY: SECTION 1
PACES STATIONS AND ACUTE

SCENARIOS
1.1 History-taking
TABLE 1 DIFFERENTIAL
DIAGNOSIS OF DYSPEPSIA
Common
Less common
Rare
Letter of referral to general

medical outpatient clinic
Gastric ulceration/gastritis1
Duodenal ulceration/duodenitis1
Gastric carcinoma
Functional dyspepsia
Cholecystitis/gallstones
Chronic pancreatitis
Pancreatic carcinoma
Atypical cardiac pain

Intestinal ischaemia
Dear Doctor,
1. Testing for and treating Helicobacter pylori is of value in these groups.
Re: Mr Ben Harrison, aged

68 years
This man has had retrosternal
burning pain for many years,
usually helped by over-thecounter antacids. However, in the
last 6 months his pain has been
more troublesome and sometimes
unresponsive to the antacids,
and he has also developed upper
abdominal discomfort. Has he
abdomen can come from

many sources (eg gallbladder
and pancreas) and therefore a
careful history is essential. Upper
abdominal symptoms may also be
referred from above the diaphragm,
although this is unusual. Young
patients (<45 years) are unlikely to
have malignant disease and can
therefore be investigated noninvasively.
developed a peptic ulcer, or is

something else responsible for
History of the presenting problem
his dyspepsia?
Pain
Yours sincerely,
Introduction
Dyspepsia is an unpleasant sensation
in the upper abdomen. If new, it is
an alarm symptom in patients over
the age of 45 years and requires
rapid investigation because of the
obvious concern that it is due
to a carcinoma of the stomach.
The most common cause is
inflammation or ulceration of the
upper gastrointestinal tract; other
causes are listed in Table 1.
It is important to remember that
pain or discomfort in the upper
Dyspepsia pain is most frequently

felt in the epigastric region. Ask
about the following.
Duration: dyspepsia lasting for
longer than 6 months is likely to
be of benign origin.
Radiation: pain going through
to the back is suggestive of a
duodenal ulcer or a pancreatic
cause; pain radiating to the right
upper quadrant or shoulder tip
may indicate a biliary cause.
Relieving or precipitating factors:
gastric ulcer pain is typically
worst on eating whereas duodenal
ulceration is worst between meals
and relieved by food; biliary pain

may be stimulated by fatty foods;
ischaemic intestinal pain usually
occurs as food passes down the
small bowel and arises some time
after a meal. Does the pain come
on during activity? It seems
unlikely in this case, but angina
can sometimes present as upper
abdominal pain.
Nocturnal pain: functional
disorders very rarely cause
disruption of sleep.
Other symptoms
Key issues to ask about include the
following.
Vomiting: may indicate
obstruction. The nature of the
vomitus is important: gastric
outlet obstruction leads to
regurgitation of undigested food,
sometimes many hours after
it was ingested; haematemesis
clearly suggests peptic ulceration.
Reflux of an acid taste into the
mouth: suggests hiatus hernia.
Smoking and alcohol history
along with caffeine intake are
important in those with reflux
symptoms as they represent
Station 2: History Taking
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GASTROENTEROLOGY AND HEPATOLOGY: PACES STATIONS AND ACUTE SCENARIOS
potentially beneficial lifestyle

modifications.
Early satiety: a significant
symptom associated with gastric
cancer and therefore needs
investigation, but can occur
in benign as well as malignant
disease. Some patients with peptic
ulceration get pain or discomfort
on eating, which leads them to
stop, and early satiety can also be
a feature of functional dyspepsia.
Abdominal distension or bloating:
may suggest a functional cause.
Change in bowel habit: melaena
would indicate the possibility
of peptic ulceration, but also
neoplasia. Diarrhoea may suggest
malabsorption such as found in
chronic pancreatitis, which
commonly causes pale stools
that float (difficult to flush away)
or are fatty/oily (steatorrhoea) in
addition to epigastric pain.
Weight loss: how much and over
how long? Significant loss of
weight increases the likelihood
of significant pathology but can
also occur with benign disease,
in particular if eating causes
pain and induces the patient to
reduce intake.
Dyspepsia with weight

loss necessitates urgent
investigation to rule out gastric cancer.
Episodes of jaundice, dark urine

and pale stools: consider biliary
disease.
and steroids can cause peptic ulcer

disease. Warfarin and drugs that
inhibit platelet function clearly
increase the risk of haemorrhage.
A high alcohol intake predisposes
to gastritis as it is directly irritant
to the stomach. Alcohol excess is
also the leading cause of chronic
pancreatitis in the UK and a risk
factor for cancers of the stomach and
pancreas, hence a detailed alcohol
history is required in this patient.
Past medical and surgical history

Is there a history of peptic ulcer
disease or of gastric surgery? In the
past, partial gastrectomy with or
without gastroenterostomy used to
be performed for bleeding gastric
or duodenal ulcers, and there is
an increased incidence of stomal
ulceration and carcinoma of the
stoma following partial gastrectomy.
Does the patient have a history of
cardiovascular, cerebrovascular
or peripheral vascular disease?
Arteriopaths may have ischaemic
intestinal pain.
Are there any other serious
medical comorbidities? Any major
comorbidities may limit the choice
of investigation for a patient,
eg endoscopy is more risky in
the presence of significant
cardiorespiratory disease.
Plan for investigation and

management
After explaining to the patient that
under normal clinical circumstances
you would examine him you would
plan as follows.
Other relevant history

Medications and alcohol
What remedies have been tried
already and how effective were they?
The lack of symptom relief with
antacids in this case may indicate
that acid is not the cause. NSAIDs
Key investigations for dyspepsia

Ascertain H. pylori status by
serology unless previously treated.
Endoscopy: allows biopsy and
testing for H. pylori if indicated.
Abdominal ultrasound scan.
Routine blood tests

Check FBC for evidence of
Liver function tests: to aid
detection of biliary disease.
H. pylori serology, as long as the
patient has not had previous
eradication therapy.
Consider measuring serum
amylase for pancreatitis if the
patient has suffered recent pain.
Endoscopy
Any structural abnormalities
can be visualised and biopsied;
biopsy of the stomach near the
antrum can also be used to help
detect the presence of H. pylori by
commercially available urease tests.
No matter how likely the

diagnosis of a benign cause,
a patient over the age of 45 years
with new-onset dyspepsia requires
investigation with endoscopy to rule
out malignancy.
Imaging
Upper abdominal ultrasound
scanning allows imaging of the liver,
pancreas and biliary tree and is the
radiological investigation of choice.
It is best used for imaging solid
organs (Fig. 1) and gives little
information on the stomach and
small intestine unless there is
marked pathology, eg gastric cancer
causing thickening of the stomach
wall. Remember that it is not
infallible and can miss distal
common bile duct stones and
minimal changes in the pancreas.
Other tests
If a biliary or pancreatic cause is
likely, then CT or MRI scanning
may be appropriate. If endoscopy is
contraindicated, then a barium meal
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in the mouth, pharynx or

oesophagus, with the history
usually identifying oral problems.
Causes are listed in Table 2, but
the obvious concern is that it
might be due to a carcinoma of the
oesophagus or gastric cardia, which
should be the working diagnosis
until proven otherwise.
Pain on swallowing is known as
odynophagia, but although patients
may describe this together with
dysphagia, it is the latter that is
the most concerning.
Fig. 1 Normal ultrasound appearance of the liver and bile ducts.
may be performed, but this can miss

small lesions and does not allow
tissue sampling.
in swallowing over the last

6 weeks. She has a long history
Although the patient will

often indicate the apparent
level of obstruction on the sternum,
this correlates poorly with the actual
site of blockage.
of reflux symptoms and uses
Management
ranitidine for this. She has also
Specific management will depend

on the cause. For patients with
functional dyspepsia aim for
symptom control, which often
requires a combination of acid
suppression and antispasmodics.
Therapies that have been tried
include proton pump inhibitors,
antispasmodics (such as
mebeverine) and antidepressants
(particularly low-dose amitriptyline).
had a stroke in the past. She

difficulties
Letter of referral to
gastroenterology
outpatient clinic
any weight but is unsure about

this. I am concerned about her
symptoms and would value your
opinion as to whether they are
related to dysmotility or some
other problem.
Yours sincerely,
Introduction
Dysphagia means difficulty
swallowing and is an alarm
symptom that should be investigated
rapidly. It may be due to dysfunction
Dear Doctor,
Re: Mrs Deborah Finch, aged
67 years
I would be grateful for your
assessment of this woman who
has noticed increasing difficulty
does not think she has lost
Related to difficulty in swallowing

Speed of onset: rapidly progressive
dysphagia is suggestive of a
malignant stricture, whereas
gradual onset of symptoms
stretching back over 6 months
or more is typical of a benign
stricture.
Problems with solids and/or
fluids? Strictures (benign or
malignant) usually cause
dysphagia first for food
(particularly bread and meat)
and later for liquids. Dysphagia
for liquids (more so than solids)
DIAGNOSIS OF DYSPHAGIA
Common
Less common
Rare
Benign oesophageal stricture

Oesophageal carcinoma
Oesophageal dysmotility
Stroke
Pharyngeal pouch
Achalasia
External compression from
lung lesion
Scleroderma
Motor neuron disease
Myasthenia gravis
Parkinsons disease
Multiple sclerosis
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often indicates a pharyngeal

problem, eg stroke, motor neuron
disease. Dysphagia for solids and
liquids from the outset is typical
of achalasia.
Is there regurgitation? This may
suggest hold up of food in the
oesophagus. Nasal regurgitation
is associated with neurological
causes of dysphagia.
Pain on swallowing: this occurs
in reflux oesophagitis, achalasia,
oesophageal candidiasis and
herpetic oesophagitis, and also
with benign and malignant
strictures.
Other symptoms
Any mechanical blockage to the
passage of food into the stomach
will restrict calorie intake and result
in weight loss. Severe and rapid
weight loss tends to point to a
malignant process.
Is there a history of reflux acidity
with an acid taste coming up into
the mouth? Chronic acid reflux can
lead to oesophagitis with subsequent
stricture formation, and patients with
gastro-oesophageal reflux disease
(GORD) can also develop dysmotility
due to chronic acid damage.
Epigastric pain may suggest
peptic ulcer disease and reflux.
Patients with some neurological
diseases can develop dysphagia due
to involvement of the upper third of
the oesophagus (striated muscle).
Stroke with pseudobulbar palsy is
the most common, but dysphagia
can also be seen in motor neuron
disease, multiple sclerosis,
Parkinsons disease and
myasthenia gravis.

Drugs
NSAIDs, potassium salts,
bisphosphonates and tetracyclines
have all been implicated as

causes of oesophagitis and
oesophageal stricture formation.
Immunosuppressive medications,
diabetes mellitus, chemotherapy
or HIV infection predispose to
oesophageal candidiasis, which may
be asymptomatic or cause symptoms
of heartburn and dysphagia.
Past medical history

Radiation-induced oesophagitis
may occur weeks or months
after irradiation treatment for
malignancies (eg bronchial
carcinoma). Are there any other
serious medical comorbidities?
These may limit the choice of
investigation for a patient, eg
endoscopy is more risky in the
presence of significant
Social history
Alcohol excess and smoking are both
risk factors for the development
of oesophageal cancer as well as
being aspects of lifestyle that could
be usefully modified in patients
with GORD.

management
you would examine her you would
plan as follows.
Routine blood and radiological

tests
Check FBC for evidence of
iron-deficiency or other anaemia.
Electrolytes.
Renal function (may be impaired
due to dehydration).
Liver and bone function tests
(albumin a marker of nutrition).
Inflammatory markers.
Haematinics.
Plain CXR (may show hiatus

hernia or carcinoma of the lung
leading to dysphagia by external
compression).
Investigation of the oesophagus
Investigation of dysphagia
Barium swallow (urgent).
Endoscopy: biopsy and brushings to
exclude malignancy if any stricture
is identified.
Manometry: consider if endoscopy or
barium study negative to exclude
achalasia.
No matter how likely the

diagnosis of a benign stricture,
a patient with dysphagia requires
investigation with a barium swallow
and endoscopy to rule out malignancy.
Barium swallow This is the most

appropriate initial investigation
when a patient describes high
dysphagia. It allows the site of
pathology to be identified and
forewarns of pitfalls such as a
pharyngeal pouch (Fig. 2), which if
unidentified increases the risk of
perforation at endoscopy if vision
becomes obscured as the endoscope
passes through the cricopharyngeus
muscle.
If dysphagia is not severe or if
a stricture has been previously
diagnosed and located (Fig. 3),
then endoscopy may be the initial
investigation.
Endoscopy Endoscopy allows
characterisation of the type and
length of a stricture. Any stricture
must be brushed and biopsied to
exclude malignancy. Dilatation
and/or stenting may be performed
if a stricture is impassable and
dysphagia severe.
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Manometry and pH studies

Oesophageal manometry may be
useful in diagnosing a motility
disorder (eg oesophageal spasm) if
barium swallow and/or endoscopy
are normal. It may also provide
additional confirmatory evidence
of achalasia (hypertensive lower
oesophageal sphincter that fails
to relax on swallowing) following
a suggestive barium study. pH
studies can direct therapy in
patients with reflux symptoms
and can also identify patients
with silent reflux.
Dysphagia without
oesophageal narrowing should
lead to consideration of dysmotility,
which can be identified and classified
by manometry.
Other tests
Fig. 2 Barium swallow demonstrating a large pharyngeal pouch.
Other investigations may be

required in some cases, eg
serological tests in suspected
scleroderma, electromyography
(EMG) in suspected motor neuron
disease.
Management
on the cause identified (Table 2).
Patients with neurological causes
may require artificial feeding,
particularly if the condition is
non-reversible and likely to
deteriorate over time. Nasogastric
tube feeding may be necessary in
the short term, but for extended
feeding programmes the best
option is percutaneous endoscopic
gastrostomy.
Fig. 3 Barium swallow showing a benign midoesophageal stricture.
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1.1.3 Chronic diarrhoea

gastroenterology clinic
Type of condition
Diseases/comments
Intestinal inflammation
Idiopathic IBD: ulcerative colitis, Crohns disease1

Microscopic/lymphocytic/collagenous colitis
NSAID enteropathy
Intestinal tuberculosis, which may be clinically
indistinguishable from Crohns disease
Radiation enteritis, colitis and proctitis
Chronic infectious diarrhoea
In HIV infection and other immunocompromised individuals:

organisms frequently encountered are microsporidia and
Cryptosporidium; cytomegalovirus and atypical
mycobacterial infections may occur. It is debatable whether
a specific HIV enteropathy exists as a separate entity
Some enteric infections such as giardiasis and amoebiasis
may produce prolonged symptoms even in
immunocompetent individuals1
Tropical sprue
Whipples disease
Clostridium difficile-related diarrhoea is usually acute, but
may be chronic and relapsing1
Intestinal neoplasia
Intestinal lymphoma may complicate coeliac disease and

chronic immunosuppressive therapy
Adenomas, particularly secretory villous adenomas of the
colon, can produce a secretory diarrhoea
Obstructing neoplastic lesions may produce chronic
constipation and paradoxical overflow diarrhoea1
Malabsorption
Pancreatic insufficiency, eg chronic pancreatitis

Coeliac disease1
Bacterial overgrowth1
Bile salt diarrhoea due to ileal disease and reduced
absorption of bile salts
Systemic disorders and

drug-related diarrhoea
Thyrotoxicosis
Secretory neuroendocrine tumours, such as carcinoid,
phaeochromocytoma, VIPoma
Diarrhoea is a frequent side effect of some drugs, such as
olsalazine, mycophenolate mofetil, misoprostol, colchicine
and antibiotics1
Factitious/fictitious
Laxative abuse
Dear Doctor,
Re: Mr Darren Weaver, aged
24 years
Thank you for seeing this
married man with no significant
past medical history who
complains of a 6-month history
of diarrhoea with blood mixed in
with the stool. Problems started
after he ate a dodgy meal and
he assumed that they were
infective, but matters have not
improved. He has lost some
weight and also complains of
arthralgia. What do you think is
responsible for these problems?
Yours sincerely,
Introduction
This man is most likely to have
idiopathic inflammatory bowel
disease (IBD), but it is important
to exclude chronic infection and to
consider other causes of chronic
diarrhoea (Table 3). In older patients
intestinal neoplasia and paradoxical
overflow diarrhoea caused by
chronic constipation must not be
forgotten, and always check that the
patient does actually have diarrhoea,
ie increased daily stool volume.
DIAGNOSIS OF CHRONIC DIARRHOEA
1. Relatively common conditions.

IBD, inflammatory bowel disease; VIPoma, vasoactive intestinal peptide-secreting tumour.
what they mean by diarrhoea,

constipation, runs, accident, etc.
Relating to the diarrhoea

Coeliac disease is common and
may present subtly with chronic
diarrhoea and vague malaise.

Patients assign their own meaning
to technical terms, so always check
Stool frequency and volume:

how often, how much and for
how long? Be precise: How many
times have you opened your
bowels since you woke up this
morning? How many times did
you get up last night? Is it a little
or a lot on each occasion? Other
markers of severity would be if

the patient feels faint or unwell
when passing stool, or if there is
undigested food in the stool.
Associated symptoms: ask about
urgency, pain on defecation,
tenesmus, passage of mucus
or pus, bleeding.
If there is rectal bleeding, is the
blood passed freely, sometimes
without any stool? Is it mixed
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with the stool? Is it only present

on the toilet paper when the anus
is wiped (suggesting piles)?
Exclude steatorrhoea: ask if the
stool is bulky and light-coloured,
floats on the water in the toilet,
and/or has an offensive odour.
Other symptoms
Systemic: in any patient
presenting with chronic
diarrhoea ask specific questions
to determine if there has been
weight loss or a systemic response
revealed by fevers and sweats.
Non-specific malaise, with or
without weight loss, is frequently
present in uncomplicated
ulcerative colitis and coeliac
disease. Weight loss, fever, night
sweats and malaise are usually
prominent in patients with
Crohns disease and intestinal
tuberculosis.
Pain: cramping abdominal pain
often accompanies diarrhoea of
any cause. Deep-seated abdominal
pain should alert to the possibility
of Crohns disease, intestinal
tuberculosis and neoplasia.
Pain suggesting pancreatitis or
cholelithiasis may provide a clue
to the cause of steatorrhoea.

Age is important in that neoplasia
is very unlikely in a young patient
such as this man. IBD and coeliac
disease, on the other hand, can
present at any age. Tuberculosis
is particularly common in Asia
and Africa. The rare condition of
Whipples disease occurs almost
exclusively in older men, and
microscopic colitis occurs typically
in older women.
Apart from a positive family history,
there are no known risk factors for
IBD, although in some patients it
appears to be triggered by an
episode of infectious colitis. The

main risks for chronic pancreatitis
are excess alcohol use and
cholelithiasis, although patients
heterozygous for the cystic
fibrosis mutation may be at
increased risk of idiopathic
chronic pancreatitis.
Direct questions are usually needed
to address possible endocrine
disorders, carcinoid syndrome, HIV
disease, travel (When did you last go
abroad? How long were you there?
What were you doing? And the time
before that?), diet, and laxative and
other drug use. Arthralgia, arthritis,
skin rashes and visual symptoms
can be associated with IBD.

management
Examination of the stool
All patients should have stool
examined for bacterial pathogens
and for the ova, cysts and adult
forms of various parasites. Amoebae
may be difficult to detect if a fresh
(hot) stool sample is not examined.
If the test is available, estimation
of faecal leucocytes is invaluable
in distinguishing inflammatory
disease from other causes of
diarrhoea. In some cases it is
necessary to measure the stool
volume over a 24-hour period
or to estimate faecal fat excretion
over a 72-hour period.
Infective causes must be

excluded in all cases of chronic
diarrhoea.
Endoscopy and imaging

Rigid sigmoidoscopy: rectal
involvement is almost universal
in ulcerative colitis, while the
rectum may be spared completely
in Crohns disease. Bleeding,
ulceration and a mucopurulent

exudate may be seen, although in
less severe inflammation there
may simply be loss of vascular
patterns and a granular friable
mucosa. Biopsies should be taken
for histological examination.
Colonoscopy: allows direct
visualisation of the entire colonic
mucosa and in many cases allows
examination and biopsy of the
terminal ileum. It should be
performed in all patients with
suspected colitis or Crohns
disease and may be the most
direct way of establishing a
diagnosis in other patients
(Fig. 4).
Plain abdominal radiograph:
visible dilatation of the large
intestine may presage perforation
and is an emergency, although
this is most unlikely to be seen
in an outpatient setting (see
Section 1.4.2); pancreatic
calcification may help establish a
diagnosis of chronic pancreatitis.
Blood tests
Routine blood tests include
FBC (anaemia, leucocytosis),
electrolytes (hypokalaemia),
renal/liver (hypoalbuminaemia)/
bone profile, inflammatory markers,
iron/ferritin/folic acid/vitamin
B12; clotting screen; anti-tissue
transglutaminase antibodies
(virtually diagnostic of coeliac
disease, although the test may be
falsely negative in patients with
IgA deficiency).
Raised systemic inflammatory

markers are unusual in
ulcerative colitis unless the disease
is severe, but Crohns disease can
produce a marked systemic response
with few clinical signs.
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Intercurrent infectious
diarrhoea should always be
considered, even in patients with
known IBD, particularly before starting
immunosuppression.
The management of patients

with IBD requires a long-term
multidisciplinary approach, including
dietitians, specialist nurses, physicians
and surgeons.
1.1.4 Rectal bleeding

gastroenterology
outpatient clinic
Dear Doctor,
Re: Mr Richard Venner, aged
56 years
Thank you for seeing this man
who has noticed blood in his
stools. Over the last 8 weeks
he has also developed lower
Fig. 4 Ulcerative colitis: (a) normal colonic mucosa; (b) inflamed colonic mucosa at endoscopy.
abdominal discomfort and feels

that he has lost weight. On
examination I thought there
Assessment and management

of nutrition is a key feature of
looking after patients with chronic
diarrhoea, particularly those
with IBD with small intestinal
involvement. Iron, folate and B12
are absorbed preferentially in
different parts of the small intestine
and abnormalities may provide clues
to localisation of disease processes.
In malabsorption due to pancreatic
and biliary disease, fat and fatsoluble vitamin absorption are most
affected: serum calcium, vitamin D
and prothrombin time, which is
prolonged by vitamin K deficiency,
are informative in these cases.
10
In rare cases it may be necessary

to proceed to test fasting gut
hormone profiles to look for
abnormal concentrations of
gastrin, glucagon and vasoactive
intestinal peptide (VIP). The
carcinoid syndrome may be
diagnosed by increased urinary
excretion of 5-hydroxyindoleacetic
acid.
might be a mass in the right

iliac fossa. He is understandably
worried as his mother died of
bowel cancer aged 70 years.
I would be grateful for your
assessment as to the cause
of his bleeding and for further
evaluation of his abdominal
findings.
Yours sincerely,
Management
Specific management will
depend on precise diagnosis.
Attention to nutrition is required
in all cases of chronic diarrhoeal
illness.
Introduction
Rectal bleeding is a common
problem and has a wide differential:
the most common causes are
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DIAGNOSIS OF RECTAL BLEEDING
Common
Less common
Rare
Haemorrhoids
Diverticular disease
Colorectal carcinoma
Anal fissure
Colitis (ulcerative colitis

or Crohns disease)
Colitis (infective)
Angiodysplasia
Arteriovenous malformations
Mesenteric ischaemia
Intussusception
Volvulus
Radiation colitis/proctitis
Trauma
Bleeding disorder
Portal hypertension with
rectal varices
DIAGNOSIS OF A RIGHT ILIAC FOSSA MASS
Common
Uncommon
Rare
Ileal Crohns disease: younger

patients with clinical features
of inflammatory disease
Caecal carcinoma: older
patients with anaemia and
subacute bowel obstruction
Appendix mass:
abscess, mucocele
Ovarian carcinoma1
Tuberculosis (TB): although

TB may cause an ileitis and
regional lymphadenopathy, it
rarely causes a palpable mass
Lymphoma
1. Not in this patient!
haemorrhoids, colorectal cancer

and diverticular disease; other
causes are shown in Table 4. The
patients age is an important factor:
younger patients are more likely to
have an inflammatory diagnosis,
whereas those over 55 years have
an increased risk of colorectal
cancer.
The suggestion of a right iliac fossa
mass raises other diagnostic
possibilities (Table 5).
The two main questions to ask

about an abdominal mass are
as follows.
Is it related to the gut (including
liver and pancreas) or another intraabdominal organ (eg ovary, kidney)?
Is it part of a more generalised
disease process?
Blood seen on wiping only is

typical of a perianal cause,
whereas blood mixed in with
the stool suggests colonic disease.
Although haemorrhoids may

occasionally bleed briskly, such
symptoms should not be attributed to
haemorrhoids without investigation.
How much? Small amounts of

bleeding may be caused by anal
fissures; large volumes of blood
loss require investigation, but
even benign causes may lead to
substantial haemorrhage.
Patients often overestimate

blood loss because small
amounts can discolour the water in the
toilet giving the false impression of a
large haemorrhage.

Regarding the rectal bleeding
Duration: a long history
(>6 months) means that the
diagnosis is unlikely to be
carcinoma.
When does it occur? Bleeding
from haemorrhoids usually
coincides with bowel opening,
whereas bleeding from other
causes may lead to passage of
blood at other times.
What is it like? Bright red blood is
commonly seen in distal lesions,
whereas dark-red blood may be
transported from the proximal
colon. Is it malaena, which
indicates an upper gastrointestinal
tract source or occasionally a
caecal lesion?
Is it seen in the pan, mixed in
with the stools or on wiping?
Other symptoms
Perianal: discomfort or itch may
indicate haemorrhoids. Anal
fissures may be exquisitely
painful: haemorrhoids are not
usually painful unless they have
thrombosed.
Abdominal pain: that caused by
diverticular disease is typically felt
in the left iliac fossa. Cramping
pain may occur in colitis. Pain is
generally a late sign in neoplasia.
Severe pain accompanying
bleeding in an ill patient is
highly suggestive of mesenteric
ischaemia.
Alteration in bowel habit:
any change, particularly to
diarrhoea/looseness, is highly
significant, especially in the
presence of rectal bleeding. This
would probably indicate colorectal
11
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cancer but is also seen in

inflammatory conditions (eg
Crohns disease). A history of
chronic constipation is commonly
obtained in patients with
diverticular disease or anal
fissures.
Nausea or vomiting: these
may indicate partial intestinal
obstruction, particularly if
associated with colicky
abdominal pain.
hypercholesterolaemia, because
they are relevant to treatment
options that might be considered
(eg assessment of surgical risk)
and because the presence of
vascular disease would increase
the likelihood of symptoms being
due to mesenteric ischaemia.
Angiodysplastic bleeding from the
colon is said to be more common in
patients with aortic valve stenosis.
Drugs
Anorexia and (particularly)
weight loss: these are worrying
symptoms, again possibly
indicating a neoplasm but also
seen in inflammatory bowel
disease and intestinal TB, and
can considerably pre-date bleeding
and the development of an
abdominal mass.
Systemic symptoms: fever may be
vague and at best non-specific, but
reports of mouth ulcers, arthralgia
and gritty eyes are common in
patients with Crohns disease.
Symptoms of pelvic disease: ask
explicitly about urethral discharge
and pneumaturia (which means
that there must be a fistula
between bladder and bowel),
and in women also enquire about
vaginal symptoms such as
discharge.

Past medical and surgical history
Enquire about the previous
diagnosis or possibility of
chronic liver disease with portal
hypertension, which might result
in rectal varices, and also about
bleeding diathesis or radiotherapy
to the abdomen or pelvis, either of
which could lead to rectal bleeding.
Take note of previous cardiovascular,
cerebrovascular or peripheral vascular
disease, diabetes, hypertension or
12
Ask particularly about the use of

aspirin, NSAIDs and warfarin.
Family history
The scenario states that this patients
mother had bowel cancer: try to
elicit exactly what the problem
was. A family history of colorectal
carcinoma or colonic polyps
strengthens the argument for
thorough investigation, particularly
in a younger patient, although in
this mans case there is no debate:
he has caecal carcinoma until
proved otherwise. A family history
of inflammatory bowel disease might
also be relevant, and remember that
the rare condition of hereditary
haemorrhagic telangiectasia is an
autosomal dominant disorder.
Common causes of rectal

bleeding
Haemorrhoids: may have perianal
symptoms; do not cause change in
bowel habit.
Colorectal carcinoma: may have
change in bowel habit and weight
loss; family history is important.
Diverticular disease: history of
chronic constipation and left iliac
fossa pain.

management
you would examine him you would

plan as follows.

tests
FBC: microcytic anaemia suggests
chronic blood loss, a raised
platelet count inflammation or
brisk bleeding.
Electrolytes, renal and liver
function tests: abnormality may
be an early indicator of metastatic
colorectal neoplasia or suggestive
of significant liver disease and
therefore of rectal varices;
hypoalbuminaemia may be
due to protein loss from the gut
and/or chronic inflammation.
Coagulation studies (bleeding
diathesis).
Inflammatory markers: may
be substantially raised in
diverticulitis and intestinal
inflammation.
Group and save or cross-match
blood (if the patient is very
anaemic or as a prelude to
surgery).
CXR: look in particular for
features of metastatic disease.
Locating the source and cause of

rectal bleeding
Frank rectal bleeding can originate
anywhere in the gastrointestinal
tract, including the upper tract
(oesophagus, stomach or duodenum)
if haemorrhage is brisk enough.
Depending on the circumstances
it may therefore be necessary to
examine both upper and lower
ends of the bowel, but usually
only the lower tract needs to
be examined. Tests should be
selected in the light of the clinical
picture, potential benefit, local
availability and acceptability to
the patient.
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as angiodysplasia, and it does not

allow the possibility of intervention.
It is now rarely used in centres
where colonoscopy is readily
available.
Mesenteric angiography and red
cell scanning Brisk bleeding from
a source that cannot be found
by other tests can sometimes be
identified if the patient can be
investigated during the bleeding
episode. Angiography has a low yield
if employed when the patient is not
actively bleeding, but if a source of
active bleeding can be identified at
angiography then embolisation of
the bleeding vessel can often be
performed.
Fig. 5 Two sigmoid diverticula seen at colonoscopy.
Investigation of an abdominal mass

Radiological imaging: a plain
abdominal radiograph may show
inflamed loops of bowel appearing
as soft-tissue shadowing
containing gas. Abdominal
ultrasound may reveal thickened
bowel loops or an associated
abscess. CT scanning is usually
the preferred test: it is best able
to determine the origin of a mass,
and is essential in the full staging
of colorectal cancer and
lymphoma.
Fig. 6 Colonoscopy showing a colonic carcinoma.
Colonoscopy After proctoscopy/

sigmoidoscopy, this is the preferred
investigation in most cases, offering
direct visualisation of the entire
colon (Figs 5 and 6) and of the
terminal ileum, with the ability
to take tissue samples and, in some
cases, provide therapy, including
polypectomy, sclerotherapy,
electrocautery, endoclip placement
and removal of lesions by
endomucosal resection. The
procedure is not without risk:
there is a small chance of intestinal

perforation (about 1 in 750) and
bleeding, which is increased in
cases of florid inflammation,
obstructing tumours and severe
diverticulosis, or when interventions
are undertaken.
Laparoscopy/laparotomy: in some
patients it may not be possible
to fully characterise a mass with
non-invasive imaging techniques,
in which case direct visualisation
and biopsy may be necessary.
Surgery may also be needed if
there are symptoms suggestive
of intestinal obstruction such as
nausea or vomiting.
Management
Barium enema This is generally
less reliable than colonoscopy in
detecting colonic neoplasia and
diverticular disease, cannot
diagnose vascular lesions such

on the precise diagnosis. Treatment
of anaemia by blood transfusion
and/or iron supplementation may
be required.
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TABLE 6 CAUSES
OF WEIGHT LOSS IN A YOUNG WOMAN
Type of condition
Cause
Gastrointestinal
Coeliac disease1
Crohns disease
Pancreatic insufficiency
Endocrine
Diabetes mellitus1
Thyrotoxicosis1
Addisons disease
Eating disorder
Deliberate dieting1
Anorexia nervosa1
Chronic infection
Tuberculosis2
Malignancy
Haematological
1. Common conditions.
2. Common in high-risk groups.
1.1.5 Weight loss

gastroenterology clinic
malignancy is an obvious concern,

particularly in older patients, in a
young woman the diagnoses of
malabsorption, thyrotoxicosis,
diabetes mellitus and intentional
weight loss are more likely (Table 6).
Dear Doctor,
Re: Mrs Sarah Jones, aged
24 years
This young woman has noticed
that her clothes are becoming
Diabetes and thyrotoxicosis

are very common: diabetes
affects 12% of the population and
thyrotoxicosis affects 1 2% of women
at some time in their lives.
looser-fitting, despite her eating

normally, and she is sure that
she has lost at least 5 kg in
weight, even though she is not
Weight loss: it is vitally important

to actually document this (on the
same scales if at all possible).
Patient perceptions are sometimes
misleading and to embark on a
protracted series of investigations
for a problem that does not exist
is clearly not sensible! If patients
have not weighed themselves, ask
if clothes/trousers have become
looser. Rapid weight loss,
particularly in middle-aged
or elderly patients, is often
associated with malignancy. Ask
patients directly if they are trying
to lose weight: how does their
weight now compare with that 5
and 10 years ago? Have they been
on a special diet and has a

generally healthy lifestyle. On
closer questioning, she has also
noticed some diarrhoea recently
and feels tired most of the time.
I would be most grateful for your
assessment.
Yours sincerely,
Introduction
Tiredness is a common and nonspecific symptom. Weight is usually
fairly constant and loss of 5% or
more of the usual body weight must
be taken seriously. Although
14
on a diet recently, or at any

other time?
Make sure that the patient

has actually lost weight before
embarking on a hunt for a cause of
weight loss.
Appetite: decreased appetite

invariably leads to weight loss
and is a feature of many diseases.
Weight loss in the context of a
good or increased appetite is
suggestive of thyrotoxicosis or
diabetes mellitus.
Diarrhoea/steatorrhoea: the latter
is a sign of malabsorption and is
characterised by loose, oily, bulky,
offensive stools that are difficult
to flush away. It can be caused
by mucosal disease (eg coeliac
disease, Crohns disease) or
by pancreatic insufficiency
(eg chronic pancreatitis, cystic
fibrosis). Remember, however, that
diarrhoea does not necessarily
imply a primarily gastrointestinal
cause of weight loss: it may be a
feature of thyrotoxicosis.
Abdominal pain: should alert to
the possibility of Crohns disease,
particularly if located in the right
iliac fossa and associated with
weight loss. Repeated attacks of
central/epigastric pain, especially
in the context of high alcohol
intake, should raise the possibility
of chronic pancreatitis. Pain does
not occur in coeliac disease.

In this young woman it will clearly
be very important to enquire if she
has had problems with anorexia
nervosa or bulimia in the past, also
about features that suggest diabetes
mellitus (polyuria, polydipsia) or
thyrotoxicosis (tremor, agitation,
etc.). Family history may be
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relevant: there is a 10% risk of

coeliac disease in the offspring of an
affected parent, and diabetes and
thyroid disease also have a genetic
component.
Unlikely in this woman, but much
commoner in an older patient,
would be a past history of
malignancy. If there is, then onset
of weight loss is very suspicious of
recurrence or metastatic disease.

management
A wide range of conditions can
cause tiredness and weight loss,
but often the cause is evident after
the history and examination such
that only a few investigations are
necessary. In the absence of an
obvious clinical diagnosis the
following would be appropriate.
Urine and blood tests

Check urine with dipsticks for
glucose, blood and protein. Check
FBC, electrolytes, renal/liver/bone
function tests, inflammatory
markers (erythrocyte sedimentation
rate and/or C-reactive protein),
glucose, thyroid function tests,
malabsorption markers (ferritin,
folate, B12), and anti-tissue
transglutaminase antibodies (coeliac

disease often presents insidiously).
Consider short Synacthen test.
A raised platelet count

may be found with chronic
gastrointestinal blood loss, but it is
also an inflammatory marker that is
often raised in active inflammatory
bowel disease, especially Crohns
disease.
Imaging
CXR: look for tuberculosis,
mediastinal lymphadenopathy,
or (very unlikely in this woman,
but common in older smokers)
bronchial neoplasm or metastatic
disease.
Abdominal ultrasound or (better)
CT scanning are non-invasive and
may detect inflammatory masses
or thickened oedematous loops
of small bowel in Crohns disease,
intra-abdominal collections,
lymphadenopathy or renal
carcinoma.
test results, eg lymph node biopsy,

but if there are no clear clinical
diagnostic leads and nothing has
emerged from the blood tests
described, CXR and abdominal
imaging, then further investigation
is almost certainly not warranted
and it is likely that attention can
most fruitfully be directed towards
psychological causes of tiredness
and weight loss, eg eating disorder
or depression.
If iron-deficiency anaemia is
present, both the upper and lower
gastrointestinal tract should be
investigated. Barium follow-through
or small bowel enema may reveal
Crohns disease. Coeliac disease
is confirmed by total or subtotal
villous atrophy on duodenal
biopsies (Fig. 7).
Do not forget that the

radiological appearances of
intestinal tuberculosis may look
identical to Crohns disease, so keep a
high index of suspicion, particularly in
Asian patients.
Other tests
Management
Other investigations may be directed

by clinical suspicion or preliminary
Management will be dictated by the

specific diagnosis made.
Fig. 7 Coeliac disease: (a) histologically normal small bowel with normal villi contrasts with (b) total villous atrophy of coeliac disease.
15
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gastroenterology
outpatient clinic
assuming that these have not been

missed by the referring doctor,
makes this diagnosis less likely.

Related to the pain
Dear Doctor,
Re: Mr Geoffrey Archer, aged
67 years
This man, who does not readily
seek medical attention, came to
the surgery recently complaining
of a 6-month history of crampy
epigastric pain and one stone
Nature of the pain: is it constant,

intermittent or colicky? Colicky
pain is characteristic of luminal
obstruction (intestinal, biliary or
ureteric). Pain that is ever-present
is unusual, but should raise the
suspicion of malignant disease
with local infiltration into
neighbouring structures.
weight loss. He has no significant

change in bowel habit but has
a history of ischaemic heart
disease, hypertension and
peripheral vascular disease.
Your input into his further
investigation and management
would be greatly appreciated.
Localisation of pain: gastric

pain typically localises to the
epigastrium, small bowel pain to
the umbilicus and large bowel
pain to the iliac fossae; pancreatic
pain typically radiates through to
the back.
Yours sincerely,
Introduction
The differential diagnosis of chronic
abdominal pain is shown in Table 7.
In this man there must clearly
be concern over the possibility
of a malignant cause, but his
cardiovascular risk factors make
mesenteric ischaemia a possibility.
Crohns disease can present with
abdominal pain and weight loss,
but the lack of bowel symptoms,
16
Visceral pain is notoriously

difficult to localise: do not be
misled as to the site of a problem
purely because of the location of
the pain.
Exacerbating or relieving factors:

gastric ulcers, mesenteric
ischaemia, biliary colic and
intestinal obstruction are typically
made worse by eating, with biliary
colic particularly associated with
fatty foods. Duodenal ulcers often
DIAGNOSIS OF CHRONIC ABDOMINAL PAIN
Common
Uncommon
Rare
Peptic ulcer disease

Gastric carcinoma
Biliary colic
Pancreatic carcinoma
Irritable bowel syndrome
Mesenteric ischaemia
Crohns disease
Subacute bowel obstruction
(adhesions, luminal stricture,
herniae)
Addisons disease
C1-esterase deficiency
improve after eating. Chronic

pancreatitis is worsened by
alcohol ingestion.
Pain at night: nocturnal pain
is typically associated with
significant pathology and should
not be attributed to functional
disease (eg irritable bowel
syndrome) without thorough
investigation to exclude other
causes.
Other symptoms
Weight loss: this man has lost
a stone in weight and, as with
nocturnal pain, weight loss
should raise thoughts of
significant pathology and
must not be dismissed lightly.
Weight loss does not

necessarily indicate malignant
disease: it may feature in any condition
where eating provokes pain.
Vomiting: many causes of chronic

abdominal pain may be associated
with vomiting, but particular
thought should be given to
peptic ulcer disease and gastric
malignancy causing gastric
outlet obstruction and intestinal
obstruction.
Change in bowel habit: may be
seen in Crohns disease, irritable
bowel syndrome, diverticular
disease and colonic malignancy.
Chronic pancreatitis may be
associated with diarrhoea due to
exocrine pancreatic insufficiency.
Changes suggesting biliary
disease: dark urine and/or pale
stools.

A history of previous surgery may
suggest adhesions and obstruction.
Have there been any previous
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episodes of pain, or of problems

that might support a diagnosis of
Crohns, eg mouth ulcers, perianal
lesions?
Like all arterial diseases, mesenteric
ischaemia is associated with
hypertension, other atherosclerotic
diseases (eg ischaemic heart disease,
peripheral vascular disease both
suffered by this man and stroke),
smoking, diabetes and
hypercholesterolaemia.
A history of alcohol abuse would
raise the possibility of chronic
pancreatitis, and a careful drug
history is essential: is the patient
taking aspirin, NSAIDs or other
ulcerogenic drugs?

management
tests
FBC: iron-deficiency anaemia
would raise the possibility of
upper gastrointestinal blood loss,
which in this man with epigastric
pain would be most likely due to
peptic ulcer disease or gastric
malignancy; a raised platelet
count can be seen with
gastrointestinal blood loss but is
also an indicator of inflammation
(eg Crohns disease).
Electrolytes and renal function
tests: in the absence of vomiting
or unrelated disease these
are likely to be normal; the
combination of hyperkalaemia,
hyponatraemia and mildly
raised urea would raise the very
remote possibility of Addisons
disease.
Deranged liver function tests
(particularly bilirubin, alkaline
phosphatase and -glutamyl
transaminase) might suggest
biliary pathology.
CXR: particularly for features of

metastatic disease.
Amylase is usually normal in

chronic pancreatitis.
Endoscopy
In this man, where the epigastric
location of pain and presence of
weight loss indicates that peptic
ulceration or gastric malignancy
are the most likely diagnoses, upper
gastrointestinal endoscopy is the
investigation of choice. In contrast,
alteration in bowel habit associated
with abdominal pain and weight loss
should prompt you to consider
colonoscopy.
Radiological tests
Plain abdominal radiograph
and ultrasound scan: there is a
limited role for plain radiographs
unless you suspect an acute
obstructive or ischaemic
episode. Pancreatic calcification
may be seen in chronic
pancreatitis. Ultrasonography
may demonstrate gallstones,
biliary dilatation, liver metastases
or a pancreatic mass.
Gallstones are a common

finding, and unless there is
corroborative evidence that they might
be causing problems (eg abnormal
liver function tests, thick-walled
gallbladder) they may well be an
incidental finding.
Barium studies: small bowel

studies may show strictures in
Crohns disease that are difficult
to diagnose in any other way.
CT and MRI: abdominal CT

may show pancreatic masses,
pancreatic duct irregularity or
calcification (chronic pancreatitis)
and can be used to stage gastric
or other malignancies and (with
newer machines) mesenteric
vessel disease. MRI can be
used to investigate biliary
dilatation (magnetic resonance
cholangiopancreatography) or
suspected mesenteric ischaemia
(magnetic resonance
angiography).
CT and MRI are not first-line

techniques for the investigation
of abdominal pain and will usually
be indicated to clarify or stage
abnormalities found on ultrasound
or endoscopy or, if these have been
normal, to further investigate a patient
where the index of suspicion is high
that there is still an underlying
significant pathology.
Angiography: this remains

the investigation of choice for
confirming mesenteric ischaemia
and also offers the possibility
of therapeutic intervention
(angioplasty).
Significant mesenteric
ischaemia is unlikely unless
at least two of the major intestinal
arteries are involved, eg coeliac
plexus and superior mesenteric
artery.
Management
17
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tests
hepatology outpatient
clinic
TABLE 8 LIVER
Blood test
Significance of elevated level
Transaminases
Raised serum ALT and AST usually signify hepatocellular damage,

but consider other source of AST (heart and skeletal muscle, kidney,
red cells)
Extreme elevations of AST and ALT occur mainly with drug toxicity,
acute viral hepatitis and ischaemic damage to the liver
Moderate elevations of AST and ALT are seen in alcohol-related,
autoimmune, chronic viral, and other acute and chronic liver disease
Dear Doctor,
Re: Mrs Kate Beaumont, aged
FUNCTION TESTS AND THEIR SIGNIFICANCE
cholesterol (6.5 mmol/L). Prior
Alkaline phosphatase These biliary enzymes usually indicate cholestatic liver disease
and GGT
or biliary tract disease
GGT levels are disproportionately raised in alcohol-related liver
disease, or where an enzyme-inducing drug such as phenytoin or
phenobarbital is used
Segmental non-obstructive damage to the biliary tree, as in
metastatic or infiltrative disease, often produces elevated biliary
enzymes, mildly elevated transaminases and normal serum bilirubin
Alkaline phosphatase can arise from liver, bone and intestine:
determination of isoenzymes can be used to distinguish between
these sources
to starting her on simvastatin
Bilirubin
Where hyperbilirubinaemia is due to excess haem breakdown serum

bilirubin is predominantly unconjugated. Unconjugated
bilirubinaemia also occurs with inherited disorders of bilirubin
conjugation (Gilberts and CriglerNajjar syndromes)
Conjugated bilirubinaemia can occur with any form of liver damage
that interferes with hepatocyte function (intrahepatic cholestasis),
but in chronic liver disease is typically a late feature and usually
signifies hepatic decompensation
Primary diseases of bile canaliculi, ducts and the gallbladder and
large bile ducts (PBC, PSC, stones) produce hyperbilirubinaemia and
elevated biliary enzymes
Albumin
Albumin is produced in the liver and synthesis declines with

worsening liver function. As the half-life of serum albumin is about
30 days, it is days before changes in synthesis are detectable
Prothrombin time
This is a sensitive test of hepatic synthetic capacity as the liver is

responsible for the synthesis of factors II (prothrombin), V, VII and IX.
The prothrombin time responds rapidly to changes in hepatic
synthesis as the serum half-life of clotting factors is of the order of
hours
50 years
Thank you for seeing this woman
who has recently been diagnosed
as having diabetes. She has a
history of long-standing obesity
and more recently of high
I noted slightly deranged

liver function tests [alanine
transaminase 85 U/L
(normal range 540), glutamyltransferase 150 U/L
(normal range 735)], which
have remained abnormal
on repeat testing. Physical
examination is unrevealing.
I would value your opinion as to
the cause of these abnormalities.
Yours sincerely,
ALT, alanine transaminase; AST, aspartate transaminase; GGT, -glutamyltransferase; PBC,

primary biliary cirrhosis; PSC, primary sclerosing cholangitis.
Introduction
Reduced liver function is hard to
detect clinically, except when the
liver is severely impaired. The liver
can be markedly damaged without
any overt clinical manifestation.
The standard liver function tests can
provide early warning of potentially
serious pathology (Table 8), but
significant liver disease, including
cirrhosis, can be present with
normal liver enzymes. The
detection of liver disease relies on
the combination of careful clinical
assessment, a variety of blood tests,
18
radiological investigations, and often

on histological examination of a
liver biopsy.
Significant liver damage,

including cirrhosis, may exist
with little or no change in serum liver
enzyme levels.
Interpretation of liver function

tests
A normal GGT essentially excludes
the liver as the source of a raised
alkaline phosphatase.
Reduced serum albumin is part of
the acute-phase response, hence
levels may be reduced in severe
infection even if hepatic function is
otherwise normal.
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Prolongation of the prothrombin

time may not be due to hepatic
synthetic dysfunction: it can be
prolonged by vitamin K deficiency
resulting from prolonged cholestasis
and malabsorption of fat-soluble
vitamins.

It is very common for minor
abnormalities in liver function to
be uncovered by routine screening,
particularly prior to initiation of
new drugs. Many patients will have
no specific symptoms, but ask about
general malaise, tiredness, weight
loss or gain, loss of libido and
sexual potency (in men), and right
hypochondrial pain or discomfort.

In enquiring about relevant history
bear in mind the commoner causes
of liver enzyme abnormalities [fatty
liver (steatosis), alcohol, hepatitis C]
and the well-described risk factors
for liver disease (previous blood
transfusion, previous intravenous
drug abuse, diabetes, medication
use). Although the history-taking
station of PACES is not primarily
designed to test communication
skills, some of the matters that
need to be discussed are potentially
sensitive and the examiners (and
patients in routine clinical practice)
will not be impressed if they are
handled in a brutal manner.
This woman has diabetes mellitus,
obesity and hyperlipidaemia, which
are all associated with hepatic
steatosis, but in addition to these
important risk factors there may be
other reasons why the woman may
have abnormal liver function tests.
Ask about the following.
Previous liver disease or jaundice:
has the woman had any problem
with her liver or with jaundice
before? Chronic viral hepatitis
may follow a poorly remembered

episode of jaundice, and recurrent
episodes of jaundice may
signify cholelithiasis. If the
only abnormality is mild
hyperbilirubinaemia, consider
Gilberts syndrome.
Alcohol: the most common cause
of liver disease in the Western
world. Even moderate intake may
cause liver damage in susceptible
individuals. Be aware of a
tendency to minimise drinking
when the patient perceives it
as morally or socially awkward
to be accurate.
Drugs and medications:
prescription drugs, oral
contraceptive pill, over-thecounter medications, herbal
remedies, traditional medications
and recreational drugs should
all be considered. Also ask
about surgery: recent exposure
to anaesthetic agents may
have provoked hepatitis, and
gastrointestinal surgery for obesity
may provoke a steatohepatitis.
Disease associations: diseases
such as primary biliary cirrhosis,
primary sclerosing cholangitis and
other autoimmune liver diseases
are not infrequently associated
with other conditions. Ask about
coeliac disease, inflammatory
bowel disease, thyroid disease,
and autoimmune rheumatic
disorders (eg scleroderma, Sjgrens
syndrome, Raynauds disease).
Multisystem disorders: sarcoidosis
and various vasculitides can all
involve the liver, as may lymphoma
and other neoplastic diseases, and
infections such as tuberculosis.
Infections: enquire about travel
to or residence in areas endemic
for hydatid disease, amoebiasis,
schistosomiasis and liver flukes.
A patient may not regard it as
relevant that he or she lived
in India for 20 years, and the

surrogate in PACES may be told
not to mention it unless asked
directly.
Family history: ask particularly
about a family history of liver
disease, inflammatory bowel
disease, coeliac disease,
hyperlipidaemia and diabetes
mellitus (which this woman has).
Each of these can be familial
and associated with liver
abnormalities.
Exceedingly unlikely in a patient of
this age, but in a younger patient
with unexplained liver disease it
is important to consider Wilsons
disease and take a neurological/
psychiatric history. About 40% of
patients with this condition present
with liver disease, but in others
the first symptoms are either
neurological or psychiatric or
both, and include tremor, rigidity,
drooling, difficulty with speech,
abrupt personality change, grossly
inappropriate behaviour and an
inexplicable deterioration in school
work, neurosis or psychosis.
Relevant in a younger woman might
be pregnancy, which is associated
with a number of hepatic disorders,
including cholestasis of pregnancy,
HELLP syndrome (haemolysis,
elevated liver enzyme levels and a
low platelet count) and acute fatty
liver of pregnancy.

management
you would examine her to confirm
her GPs findings, you would plan
as follows.
Blood tests
There are a large number of causes
of abnormal liver function tests. The
commonest causes of chronic liver
disease should always be looked
19
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for, including hepatitis B and C,

haemochromatosis and autoimmune
liver disease, with others depending
on clinical suspicion if the diagnosis
remains elusive (Table 9).
Imaging
The first-line imaging test should
be an abdominal ultrasound scan
to look at the liver (is it large, are
there abnormal areas, does it look
fatty, are its blood vessels normal?),
the gallbladder (is there evidence of
gallstones?) and spleen (is it large?).
Liver biopsy
Sometimes the information
from blood tests and ultrasound
examination is not enough to make
a confident diagnosis, or the degree
of liver damage needs to be more
thoroughly assessed in order to stage
disease, assess prognosis and guide
therapy, in which case a liver biopsy
may be indicated (Fig. 8).
Management
Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease
(NAFLD) is probably the most
common liver disease in the
developed world. It consists of two
stages, fatty liver and non-alcoholic
steatohepatitis (NASH), and a liver
biopsy is needed to distinguish
between them. A fatty liver is
generally considered a benign and
reversible condition characterised
by fat deposits in hepatocytes.
NASH describes the progression
of fat deposition to inflammation
or so-called steatohepatitis, which
can lead to fibrosis, cirrhosis and
the associated risks of end-stage
liver disease (portal hypertension,
hepatocellular carcinoma).
The combination of obesity,
hyperinsulinaemia, insulin
resistance, diabetes,
20
TABLE 9 DIAGNOSTIC
BLOOD TESTS FOR CHRONIC LIVER DISEASE
Alcohol-induced liver disease
May be a raised IgA level, relatively higher AST than

ALT, and disproportionately raised GGT
Fatty liver, hepatic steatosis

and non-alcoholic steatohepatitis
Associated with diabetes mellitus, so check fasting

glucose/glucose tolerance test in patient without
known diabetes
Chronic viral hepatitis1
HBsAg is the correct screening test; if positive, test for

HBeAg, HBV DNA. Note that antibodies to hepatitis B
antigens may reflect previous infection or immunisation
Anti-HCV antibody is the correct screening test; if
positive, test for HCV RNA
Genetic haemochromatosis
Raised serum iron, transferrin saturation and ferritin

levels
Genetic testing for the common HFE mutation may be
helpful (positive in 95% of affected individuals)
Autoimmune liver disease
Raised IgG levels, positive autoantibodies (anti-nuclear,

anti-smooth muscle, anti-liver and kidney microsomal
antigens)
Primary biliary cirrhosis
Positive anti-mitochondrial antibody
1-Antitrypsin deficiency
Reduced circulating 1-antitrypsin, mutant form of

protein on electrophoresis
Wilsons disease
Raised serum copper, lowered serum caeruloplasmin

level (and increased urinary copper excretion basally
and after oral penicillamine challenge)
1. Note that in some cases acute viral hepatitis can be subclinical, so check IgM to
hepatitis A, E or B antigens if there is possible exposure.
ALT, alanine transaminase; AST, asparate transaminase; GGT, -glutamyltransferase; HBsAg,
hepatitis B surface antigen; HBeAg, hepatitis B envelope antigen; HBV, hepatitis B virus;
HCV, hepatitis C virus.
hypertriglyceridaemia and
hypertension is known as the
metabolic syndrome. NAFLD
appears to be the liver component of
this syndrome. Treatment of patients
with NAFLD is still typically focused

on the management of associated
conditions such as obesity, diabetes
mellitus, hyperlipidaemia and
discontinuation of hepatotoxic
Fig. 8 Microscopic appearance of hepatic steatosis (fatty liver). Fat droplets are seen filling most of the
hepatocytes, with the nuclei in the centres of the cells.
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drugs known to produce NAFLD

(steroids, amiodarone, tamoxifen,
methotrexate). There are no specific
therapies.
The use of liver biopsy in diagnosing
steatohepatitis is still controversial
but clinical indicators predicting the
diagnosis of the steatohepatitic
subset include BMI >30, being
diabetic and age over 45 years.
1.1.8 Abdominal swelling

gastroenterology
outpatient clinic
Dear Doctor,
Re: Mrs Bhavani Patel, aged
60 years
This woman came to see me
today complaining of increasing
abdominal distension. She has no
very significant past medical
history but has been seen
intermittently over the past
3 years with complaints of
lethargy and more recently has
had difficulty sleeping due to
itching. I am grateful for your
assessment and advice.
Yours sincerely,
Introduction
It is unusual for abdominal swelling
to be an isolated problem: there will
often be additional symptoms or an
easily identifiable associated history.
The most important diagnostic
consideration is ascites, the
differential diagnosis of which
and of other causes of abdominal
swelling is given in Table 10.

The following features need to be
determined: duration of the swelling,
and the presence of associated
symptoms such as pain, vomiting,
constipation, weight loss or
jaundice.
Duration: intestinal obstruction,
paralytic ileus and volvulus
typically develop rapidly. Most
cases of ascites develop over days
to weeks. Fat, faeces, fetal tissue
and tumours accumulate over
months. Fluctuation in the
distention may suggest bloating
associated with irritable bowel
syndrome.
Pain: the presence of discomfort
due to distension with ascites is
common, but constant pain
may indicate inflammation or
malignancy. A sudden severe pain
associated with the development
of jaundice would suggest hepatic
vein thrombosis (BuddChiari

syndrome). Colicky pain may
suggest intestinal disease,
particularly obstruction, and the
association of pain with ingestion
of food (particularly high fibre)
would further support this
diagnosis. Pain radiating to the
back is typical of pancreatitis,
a rare but important cause of
ascites.
Vomiting: the presence of
vomiting suggests intestinal
obstruction, particularly if in large
volume, faeculent, projectile or
persistent.
Change in bowel habit: ask about
constipation, particularly in the
elderly, mentally ill or those in
residential or nursing homes. Ileus
or intestinal obstruction results in
diminished bowel movements or
even total constipation (absence
of passage of faeces or flatus). In
some instances, particularly in the
presence of a stoma, the patient
may notice a slowing of bowel
function followed by explosive
defecation in the instance of
subacute obstruction.
Weight loss: the accumulation of
fluid in ascites will obviously lead
to weight gain, but if the patient
has lost weight or muscle bulk
DIAGNOSIS OF ASCITES/ABDOMINAL SWELLING
Common
Uncommon
Rare
Non-ascitic causes of
abdominal swelling
Decompensated
chronic liver disease
Alcoholic hepatitis
Acute liver failure (ascites is

relatively uncommon at the
time of presentation)
BuddChiari syndrome (acute
hepatic vein occlusion)
Peritoneal carcinomatosis
Ovarian carcinoma
Peritoneal tuberculosis
Right-sided heart failure/
constrictive pericarditis
Acute pancreatitis
Nephrotic syndrome
Myxoedema
Chronic constipation
Gaseous distension
Acute bowel obstruction/
paralytic ileus
Massive organomegaly
Obesity
Pregnancy
21
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then this may indicate an

underlying malignant process.
Patients with advanced alcoholic
liver disease are also likely to have
lost significant body mass.
The presence of jaundice

suggests a hepatic cause for
ascites, but remember that the absence
of jaundice does not exclude it.
Other symptoms suggesting

liver disease: fatigue and pruritis
are often presenting features of
chronic liver disease (and present
in this scenario).

Given that ascites related to chronic
liver disease is the most likely
diagnosis, it is essential to probe
tactfully for evidence that the
patient may have, or may be at
risk of, chronic liver disease. After
preliminary questions such as
Have you ever had jaundice or
liver disease in the past? it will
be necessary to explore a careful
alcohol history and explore risk
factors for hepatitis C (and B),
including blood transfusion (pre1992 and abroad), intravenous drug
use and high-risk sexual behaviour.
Ask about other diseases associated
with liver disease: inflammatory
bowel disease (especially ulcerative
colitis) is associated with primary
sclerosing cholangitis; coeliac
disease and other autoimmune
diseases are associated with primary
biliary cirrhosis. A family history
of liver disease should lead to
consideration of haemochromatosis
(and other rare conditions).
Clearly not relevant in this case, but
a menstrual history should be taken
from a younger woman, looking
both for unexpected pregnancy
and gynaecological malignancy;
22
postmenopausal bleeding could

clearly be significant in this case.

management
Many patients associate the

term cirrhosis with alcohol: it is
important to state that it represents
scarring and can have many causes,
which the tests will help to determine.
Blood tests
Routine blood tests will include the
following.
FBC: hypersplenism (low platelet
count, pancytopenia), alcoholic
aetiology (raised mean
corpuscular volume).
-glutamyltransferase. In brief this

would include the following.
Viral serology: hepatitis B and C.
Immunology: autoantibodies
including anti-nuclear antigen
(ANA), anti-mitochondrial
antibody (AMA), smooth muscle
antibody (SMA) and
immunoglobulin levels.
Serum ferritin, iron and
iron-binding studies: a ferritin
level persistently greater than
1000 g/L is highly suggestive of
haemochromatosis and should
prompt genetic testing for the
HFE gene (abnormal in ~95%
of cases).
1-Antitrypsin level.
Copper evaluation (Wilsons
disease).
Electrolytes, urea and creatinine.

Transaminases, alkaline
phosphatase and
-glutamyltransferase
(see Section 1.1.7).
Beware of the patient with

alcoholic liver disease and urea
or creatinine at the upper limit of
normal: very low levels are expected
and a normal value almost certainly
indicates significant renal impairment.
Alpha-fetoprotein (AFP): in
patients with known liver disease
who decompensate (become
jaundiced, encephalopathic or
develop ascites) unexpectedly
consider hepatocellular
carcinoma.
Ferritin levels are often

elevated in liver disease
irrespective of causation.
Assessment of liver function

The best indicators of liver function
are prothrombin time, serum
albumin and bilirubin: it would
be highly unlikely that there is a
hepatic cause for ascites if these
are all normal.
Assessment directed to the cause

of liver disease
A non-invasive liver screen
would be indicated if there were
abnormalities of transaminases,
alkaline phosphatase or
AFP may be normal in 1020%

of cases of hepatocellular
cancer.
Imaging
Plain abdominal radiograph: if
bowel obstruction or ileus is
suspected.
Abdominal ultrasound: this may
confirm the diagnosis of ascites,
especially if the amount of free
fluid is small. It will also provide
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evidence on the nature of the liver

(size, texture) and the presence of
focal lesions. The flow through the
portal vein should be requested
(retrograde flow is usually
indicative of portal hypertension
and cirrhosis and will also
determine the presence or
absence of thrombus here,
which may have implications
for future management since it
may preclude shunt placement or
transplantation). Splenomegaly is
suggestive of portal hypertension.
CT/MRI: the suspicion of
hepatocellular carcinoma
requires imaging by either
MRI or triphasic CT scanning
and referral to the relevant
hepatobiliary specialist. Other
causes of ascites may be revealed,
including ovarian masses and
peritoneal thickening due to
malignant infiltration.
Ascitic aspiration
Send for leucocytes, microscopy
and culture, albumin, amylase and
cytology. Spontaneous bacterial
peritonitis (SBP) is a serious
complication of ascites associated
with chronic liver disease and is
diagnosed by a leucocyte count
>250 cells/mL in the ascitic
fluid. Compare ascitic albumin
concentration with serum albumin
concentration: a gradient >11 g/L
suggests portal hypertension; a
gradient <11 g/L suggests an
exudative cause (neoplastic,
infective or pancreatitis).
Liver biopsy
Percutaneous liver biopsy

should not be performed in the
presence of ascites. It is questionable
whether any approach to liver biopsy
is safe, but the best would be to drain
the ascites and proceed to transjugular
biopsy if a tissue diagnosis is needed.
Management
In most patients the presence of
ascites should prompt admission for
investigation and treatment.
Specific treatment Any specific
underlying cause of chronic
liver disease should be treated if
possible, including abstinence in
alcoholic liver disease, steroids
in autoimmune hepatitis and
venesection in haemochromatosis.
Decompensated cirrhosis may

improve if the insult (eg
alcohol) is removed.
Antibiotic therapy with a

quinolone or a third-generation
cephalosporin should be initiated
immediately in the presence of
SBP. A patient with chronic liver
disease and a history of previous
SBP or a low ascites protein level
(<10 g/L) should be treated with
prophylactic antibiotics to avoid
the condition.
Cultures in spontaneous
bacterial peritonitis are often
negative and waiting for them should
not delay treatment.
Symptomatic management of
ascites The following therapies may
be appropriate.
Diuretics: most ascites should be
treated initially with a diuretic.
Begin with spironolactone, and
note that here is usually a delay of
23 days between introduction of
the drug and initial effect. Careful
use of furosemide may be required
but can precipitate dramatic
hyponatraemia.
Significant renal impairment

as well as hyperkalaemia can be
induced by diuretics: progress should
be monitored by daily weights (reduce
diuretics if weight loss >1 kg/day) and
fastidious renal monitoring.
Fluid and salt restriction:

restriction of fluid intake
to 11.5 L/day is often
recommended, as is salt
restriction, but patients
often fail to comply.
Paracentesis: in the distressed
patient or those who fail to
respond to diuretics therapeutic
paracentesis is required.
Recurrent reaccumulation of
ascites may be an indication
for referral for consideration
of transplantation or
portosystemic shunting (eg
transjugular intrahepatic
portosystemic shunt).
Further discussion
Varices
Any patient with suspected
cirrhosis or portal hypertension
should be screened for oesophageal
varices.
Albumin infusion
The benefits of human albumin
solution in patients with ascites
and renal dysfunction, or in
those undergoing paracentesis,
are controversial and poorly
understood. In simplistic terms
it acts as a small-volume plasma
expander, improving renal perfusion
and function in hepatorenal
syndrome (2 units/day) and prevents
circulatory collapse and hepatorenal
syndrome after large-volume
paracentesis. For paracentesis,
100 mL of 20% human albumin
solution per 23 L drained is
usually administered.
23
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1.2 Clinical examination

disease
Instruction
This man has inflammatory
bowel disease. Please examine
his abdomen.
General features
In routine clinical practice the
first concern is always whether the
patient is well, unwell or extremely
unwell, but patients who are acutely
unwell are not likely to appear in a
PACES examination. Important
issues to comment on before
proceeding to examination of
the abdomen itself include the
following.
Nutritional status: does the patient
look well-nourished? If given the
opportunity to ask, say that you
would like to know his
weight/height/BMI.
Hands: clubbing, leuconychia.
Eyes: anaemia is a frequent
complication of Crohns disease
and iritis an association.
Mouth: aphthous ulceration.
Legs: erythema nodosum;
peripheral oedema due to
hypoproteinaemia.
Features of chronic liver disease
(see Section 1.2.2): primary
sclerosing cholangitis (PSC) may
complicate ulcerative colitis or
Crohns disease.
Abdominal examination
External examination of the
abdomen may be unremarkable,
but look and palpate carefully for
the following.
24
Scars: about 80% of patients

with Crohns disease and 20%
of those with ulcerative colitis
undergo abdominal surgery
over a lifetime.
Palpable bowel: a thickened
fibrosed segment of sigmoid colon
may be felt in ulcerative colitis;
Crohns disease (also ileocaecal
tuberculosis) may cause an illdefined tender mass in the right
iliac fossa.
If this man presented with

bloody diarrhoea, how would
you manage him?
See Sections 1.1.3 and 1.4.2.

Instruction
This 51-year-old man presented
with a brisk, painless, largevolume haematemesis. Please
examine his abdomen.
Rectal examination
This is mandatory in clinical
practice and should be commented
on, although not performed, in the
setting of the PACES examination.
Features to look for would include
signs of:
excoriation at the anal verge
(may result from excess
secretions);
ulceration, fissuring and scarring
(signs of anorectal involvement);
blood and pus (indicative of active
proctitis/colitis).
Further discussion
Abdominal examination may be
completely normal in cases of
inflammatory bowel disease, but it is
likely that at least some features of
the general or specific examination
will be abnormal in a patient
appearing in PACES (although a
patient with no abnormal physical
signs can be included).
If you could feel a mass, what is

the differential diagnosis of the
findings?
Could colorectal neoplasia mimic
inflammatory bowel disease?
As cancer can complicate longstanding active colitis, this is an
important practical question and
the presence of a mass would
require investigation with CT
and/or colonoscopy.
Station 1: Abdominal Examination
General features
The only common cause of
haematemesis associated with
abnormal physical signs is chronic
liver disease and the statement that
the patient had a brisk, painless,
large-volume haematemesis is
clearly a pointer to varices. In
routine practice your first concern
would be to assess the state of the
circulation, but patients who are
actively bleeding will not (or should
not) appear in PACES. What
evidence of chronic liver disease
might be apparent from the end
of the bed?
General appearance: is the patient
cachectic? If given the opportunity
to ask, say that you would like
to know his weight/height/BMI.
Gynaecomastia, loss of secondary
sexual hair (in men); tanned
appearance (consider
haemochromatosis).
Skin: jaundice, spider naevi,
bruising, scratch marks; tattoos,
signs of intravenous drug abuse
(risk factors for hepatitis B and C).
Hands: liver flap, clubbing,
leuconychia, palmar erythema,
Dupuytrens contracture.
Eyes: jaundice, anaemia.
Mouth: angular cheilosis, poor
dentition.
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Abdomen: may be obviously

distended.
Legs: tissue paper skin; peripheral
oedema due to hypoproteinaemia.
TABLE 11 CAUSES
OF CHRONIC LIVER DISEASE
Frequency
Condition
Common
Cushingoid features: suggest
long-term steroid treatment.
Alcoholic liver disease

Chronic viral hepatitis: hepatitis C or hepatitis B
Non-alcoholic steatohepatitis
Less common
Pigmentation: consider
haemochromatosis (bronze
diabetes).
Autoimmune liver diseases: primary biliary cirrhosis, autoimmune

hepatitis, primary sclerosing cholangitis
Cryptogenic or idiopathic (represents probably <20% of cases now)
Rare
Metabolic and genetic liver diseases: 1-antitrypsin deficiency,

haemochromatosis, Wilsons disease
Infiltrative liver disease: sarcoidosis, amyloidosis
Miscellaneous: secondary biliary cirrhosis, prolonged total parenteral
nutrition, cystic fibrosis, chronic heart failure
Also look for the following.
Telangiectasiae on the face,

lips and within the mouth: these
would indicate that the patient
almost certainly has hereditary
haemorrhagic telangiectasiae,
a rare autosomal dominant
condition associated with
gastrointestinal bleeding that
appears in medical examinations,
including PACES, with inordinate
frequency.
Comment on the presence or
absence of the following.
Distension.
Prominent anterior abdominal
wall veins with flow away from
the umbilicus (caput medusa).
Hepatomegaly: but remember
that most causes of chronic liver
disease are associated with a
shrunken liver. Listen for a bruit.
Splenomegaly: the key physical
sign indicating the presence
of portal hypertension in a
patient with chronic liver
disease, although the absence
of splenomegaly does not mean
that portal hypertension can be
excluded.
Ascites: test for shifting dullness.
Rectal examination for the formal
assessment of melaena remains
essential in routine clinical practice,
and a comment to this effect would
be appropriate in PACES.
Further discussion
Thus it is possible to have normal

liver function and still bleed from
varices, the commonest causes of
this in practice being portal and
splenic vein thrombosis.
What are the common causes of

chronic liver disease?
See Table 11.
1.2.3 Splenomegaly
How would you investigate if you

suspected chronic liver disease?
Instruction
See Section 1.1.7.
How would you manage the

patient if presenting with a further
gastrointestinal bleed?
This 35-year-old woman has

upper abdominal discomfort.
Please examine her abdomen.
See Section 1.4.3.
In what diseases can patients have

variceal haemorrhage but not
chronic liver disease?
Portal hypertension can be
divided into prehepatic, hepatic
and posthepatic types (Table 12).
TABLE 12 CAUSES
General features
Look for features of chronic
liver disease (as described in
Section 1.2.2) and for evidence
of haematological disease:
pallor/polycythaemia, indwelling
OF PORTAL HYPERTENSION
Prehepatic
Hepatic
Posthepatic
Increased flow (eg

arteriovenous fistula,
massive splenomegaly)
Portal or splenic vein
thrombosis (eg pancreatitis,
malignancy, sepsis,
thrombophilia)
Portal vein stenosis
(eg post liver transplant)
Presinusoidal (eg primary

biliary cirrhosis,
schistosomiasis, congenital
hepatic fibrosis)
Sinusoidal (eg cirrhosis,
acute alcoholic hepatitis,
fulminant hepatitis)
Postsinusoidal (eg venoocclusive disease)
Hepatic vein outflow

obstruction (eg BuddChiari
syndrome, heart failure, inferior
vena cava web)
25
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tunnelled line (for chemotherapy),

lymphadenopathy.
Observe for scars and obvious
swellings before beginning to
palpate. After gentle palpation
in all quadrants to detect very
obvious masses and to see if the
patient is tender anywhere, examine
for hepatomegaly, splenomegaly
and renal enlargement using
standard technique. Look for
the other features described in
Section 1.2.2.
Radiological investigation: CXR

(hilar lymphadenopathy), CT
abdomen.
Other tests: as determined
by clinical suspicion, eg bone
marrow, screen for causes of
chronic liver disease.
1.2.4 Abdominal swelling

Instruction
This man has abdominal
swelling. Please examine his
abdomen.
Further discussion
What are the common causes of
splenomegaly?
See Table 13.
How would you investigate a

patient found to have
splenomegaly or
hepatosplenomegaly?
Blood tests: FBC and blood film,
routine biochemistry (especially
liver and bone profiles),
inflammatory markers.
General features
In routine clinical practice the first
priority would be determine whether
the patient was acutely unwell,
in which case acute intestinal
obstruction would be the immediate
concern. Patients with ileus,
pseudo-obstruction or constipation
are generally less unwell, although
they may vomit (look for a sick
bowl). Patients with ascites can
be moribund (acute hepatitis,
BuddChiari syndrome), quite
well (chronic diuretic-resistant

ascites) or anything in between.
Massive organomegaly
(hepatomegaly, splenomegaly,
hepatosplenomegaly or very
large kidneys) can also cause
abdominal swelling. In the
context of a PACES examination,
ascites and organomegaly are
much the most likely diagnoses.
From the foot of the bed comment
on the following.
General appearance: is the patient
well-nourished? Alcoholic liver
disease is often associated with
muscle wasting, as is malignant
disease, although this would be
uncommon in PACES.
Signs of chronic liver disease:
see Section 1.2.2.
Signs of chronic renal disease:
arteriovenous fistulae in the
wrist(s) or elbow(s), or signs of
previous surgery relating to these;
central venous dialysis catheter.
Signs of haematological disease:
petechiae/purpura; indwelling
central line for chemotherapy.
TABLE 13 CAUSES
OF SPLENOMEGALY
Frequency1
Condition
Common
Myeloproliferative diseases (chronic myeloid leukaemia, polycythaemia

rubra vera, myelofibrosis)
Lymphoproliferative diseases (Hodgkins disease/non-Hodgkins
lymphoma, chronic lymphoid leukaemia)
Portal hypertension
Less common
Chronic infections (eg malaria2, schistosomiasis2)

Systemic disease (eg sarcoidosis, amyloidosis, SLE)
Thalassaemia major
Rare
Acute infections (eg infectious mononucleosis, bacterial endocarditis,

typhoid)
Storage diseases (eg Gauchers, NiemannPick)
Acute leukaemia
Haemolytic anaemia
1. Frequency refers to the context of a PACES examination in the UK.

2. Very common causes in parts of the world where these diseases are endemic.
SLE, systemic lupus erythematosus.
26
The specific features of chronic liver

disease and hepatosplenomegaly are
covered in Sections 1.2.2 and 1.2.3.
What is the nature of the
swelling? Is the abdomen
doughy (chronic constipation),
gassy (tense, tympanic: ileus,
pseudo-obstruction or acute
obstruction) or fluid filled (ascites,
dialysate), or is the swelling due to
organomegaly? In this scenario in
PACES ascites is much the most
likely diagnosis.
Is there ascites? Check for shifting
dullness; look for dressings,
stitches or scars that might
indicate recent paracentesis;
note if there is umbilical eversion
and/or herniation.
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Is the patient on peritoneal

dialysis (Tenckhoff catheter) or
does he have a renal transplant
(hockey-stick scar in right or left
iliac fossa with transplant kidney
palpable beneath this)? If so,
take particular care to palpate
bimanually for polycystic kidneys,
and note that a large midline
abdominal scar or extensive flank
incision may indicate that one or
both native kidneys have been
removed.
If the patient has ascites, then it
would be appropriate to look for
evidence of right heart failure

(is the JVP grossly elevated?) and
say that you would like to perform
urinalysis to exclude nephrotic
syndrome (heavy proteinuria).
Also, note if the patient looks
hypothyroid, although this would be
a very rare cause of ascites indeed.
How would you investigate a

patient presenting with ascites?
See Section 1.1.8 and Table 15.
1.3 Communication
skills and ethics
Further discussion

What is the differential diagnosis
of a patient presenting with
ascites?
See Table 14.
Scenario
Role: you are a junior doctor
working on a medical ward.
TABLE 14 CAUSES
Miss Fiona Davies is the
OF ASCITES
daughter of one of your

patients. She is concerned
Frequency
Causes
Common
Cirrhosis with portal hypertension

Malignancy1
Severe congestive cardiac failure
about the current condition of
Less common
Rare
her father, Mr Harry Davies, a

72-year-old man with a history
BuddChiari syndrome
Constrictive pericarditis
Nephrotic syndrome
of hypertension and mild short-
Pancreatic disease
Hypothyroidism
Malabsorption (or other cause of hypoalbuminaemia)
a stroke that has left him with a
term memory problems who

was admitted 2 weeks ago with
marked left-sided weakness and
poor swallowing. Over the past
week there have been no signs of
1. Rare in PACES.
improvement in his swallowing

when assessed by the speech and
language therapists. Plans for his
TABLE 15 DIAGNOSTIC
long-term care are in progress
APPROACH TO THE PATIENT WITH ASCITES
and early indications are that

he will require full care in a
Test
Details
Ascitic fluid
Microscopy: malignant cells, infection

Chemistry: gradient of serum albumin from serum to ascitic fluid of >11 g/L
suggests portal hypertension; gradient of <11 g/L suggests an exudative
cause (neoplastic, infective)
Culture: including for tuberculosis
nursing home setting.
Blood tests
Imaging
He has been receiving nutrition

via a nasogastric tube, but this
has been intermittent as he has
FBC
Liver function tests: bilirubin, transaminases, alkaline phosphatase,
-glutamyltransferase, albumin, prothrombin time
not tolerated it well and the tube
CXR: looking for evidence of malignancy

Ultrasound: to confirm ascites and to look at the liver and spleen and (if
appropriate) Doppler studies of the portal and hepatic veins
have been discussed and the
has become dislodged on several

occasions. Plans for his feeding
multidisciplinary team have
considered that a percutaneous
Further investigations will be dictated by clinical suspicion and the results of initial
laboratory tests, eg to pursue the cause of chronic liver disease (see Section 1.2.2),
possible malignancy (CT scan, biopsy of abnormal tissue) or cardiac dysfunction (ECG,
echocardiography).
endoscopic gastrostomy (PEG)

would be appropriate. The
medical team think that
Station 4: Communication Skills and Ethics
27
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Mr Davies is able to consent to

the procedure. Miss Davies has
come to the ward by appointment
to discuss long-term feeding
issues.
Your task: to explain to Miss
Davies what options there are
for feeding her father and the
recommendation that he has
a PEG.
Key issues to explore

Begin by establishing what the
daughters main concerns are.
Things that she might want to
discuss include different options for
maintaining hydration and feeding,
her fathers capacity to understand
and consent to an intervention such
as a PEG, and long-term plans for
care in the event of his condition
deteriorating.
Key points to establish

That you will listen to any of the
daughters concerns, but that
providing artificial hydration and
nutrition is a medical intervention
and the decision about whether to
do so is a medical one, informed
by the multidisciplinary team.
Daughter: but a PEG tube into the

stomach sounds horrible. Isnt there
anything else that would be better?
Doctor: I understand what youre
saying. A PEG tube does sound
rather alarming, but it sounds worse
than it is. Weve already tried feeding
him with a tube through the nose
into the stomach a nasogastric
tube and he found that very
irritating and kept dislodging it:
many people do. A PEG tube
obviously doesnt go through
the nose, but straight through
the abdominal wall and into the
stomach, so patients find it much
less irritating.
Daughter: how can you be sure that
he understands what having a PEG
tube means?
Daughter: I dont think hed want to

be messed about. Why cant you just
keep letting him try to eat and drink?
Doctor: I agree that it can be

difficult to know exactly what a
patient understands sometimes.
However, we have talked to your
father about the reasons for
recommending that he has a PEG
on several occasions, and we think
that he understands the issues: he
knows that he needs to have food
and drink, he knows that he cant
eat and drink normally, and he
knows that the tube through the
nose is uncomfortable and keeps
falling out. Weve explained to him
how a PEG tube is put in, and the
problems that can sometimes arise.
Doctor: this is something that we

have considered. We always prefer a
Daughter: so how is a PEG tube

put in?
That the view of the medical team

is that her father has the capacity
to make a decision about his
feeding.
That any decision made will be
reviewed if there is any change
in her fathers condition.
Appropriate responses to likely

questions
28
patient to drink and eat normally

if they can, but Im afraid that the
stroke has damaged the nerves that
control his swallowing. This means
that when he tries to eat or drink he
coughs and splutters, and some of
the food or drink goes down the
wrong way and is in danger of
landing up in the lungs. If this
happens he will get pneumonia,
from which hed be unlikely to
recover.
Doctor: a PEG is inserted in the

endoscopy department using a
special telescope that is passed
through the mouth into the
stomach. The patient is given a
sedative injection if they need one,
and local anaesthetic is used in the
throat and stomach wall. When the
telescope is in the stomach its light
can be seen through the skin. A
small needle and guidewire are
then put through the skin into the
stomach from the outside, which
the telescope can catch and which
is then used to pull the PEG tube
into position (Fig. 9).
Daughter: will he need this PEG for
the rest of his life?
Doctor: I dont know, but its
possible that he will. Some patients
with swallowing difficulties caused
by a stroke can improve as time goes
on. Sometimes they improve to the
point of not needing the PEG any
more, in which case it can be
removed very simply by pulling
it out.
Daughter: what are the risks of
putting in a PEG?
Doctor: in most cases the business
of putting in a PEG is very
straightforward, but you are right
in thinking that this isnt always
the case. The risks are related to
having the telescope inserted into
the stomach and to the procedure
itself: in a very few cases it isnt
possible to put in a PEG; some
patients experience bleeding from
the stomach afterwards, but this is
usually very minor and settles on its
own; and sometimes the PEG tube
falls out of the stomach into the
stomach cavity which can cause
irritation. But 18 or 19 out of 20
people have a PEG put in without
any problems.
Daughter: will he be able to do things
in the day if he is attached to his PEG
for feeding?
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Mrs Agnes Keane, a 93-year-old

woman resident in a nursing
home, presents with a massive
haematemesis on a background
of long-standing heart failure
and chronic renal failure. She
requires full care in the home
for all activities of daily living,
both because of her heart disease
and her advanced dementia.
On arrival in the Medical
Assessment Unit she is
unresponsive, has an unrecordable
BP and is pale, with fresh blood
around her mouth and melaena
stool evident in the bed. An
intravenous drip has been put
Fig. 9 View of a PEG feeding tube in the stomach at endoscopy.
in and resuscitation with colloid

commenced by the Emergency
Department staff, who ask you
Doctor: yes, we try to do all the

feeding overnight so that the day is
freed up for other things such as
physiotherapy.
Daughter: will the PEG be obvious?
Doctor: not when it is not being
used. When your father is not
attached to the feeding bag and
tube, the PEG tube lies close to the
skin and is not usually visible under
clothes.
Daughter: what would happen if we
chose not to put in a PEG?
Doctor: if we cannot give him
adequate nourishment and
hydration, he will deteriorate
and would find activities such
as physiotherapy more difficult.
We think that other methods of
trying to give him food and drink
will be less effective and have more
problems than a PEG.
to assess her. You contact the

on-call medical consultant who
The question of artificial
nutrition in a patient in a
persistent vegetative state was
considered by the High Court in 1993,
and four principles were established:
the best interests of the patient is to
be the guiding principle;
artificial nutrition is considered a
medical intervention;
withholding and withdrawing
artificial nutrition are equivalent
acts;
it is not unlawful to withhold or
withdraw artificial nutrition.
Anorexia nervosa is considered a
psychiatric condition and a patient
may be detained and treated (eg
artificially fed) under the terms of the
Mental Health Act.
1.3.2 Limitation of
management
not undergo further investigation

or treatment but should be kept
comfortable.
Your task: to explain the
situation and management
plan to Mrs Keanes daughter.

Begin by finding out the daughters
understanding of her mothers
condition: although the situation
seems clear-cut, it cannot safely
be assumed that the daughter
will recognise this. Therefore,
you need to explore the daughters
expectations of what the outcome
is likely to be, and also what she
believes her mother would want
with regard to treatment and
investigation.
Scenario
Further discussion
Any form of artificial feeding is
a therapeutic intervention and
informed consent from the patient
or carers with legal authority must
be sought.
decides that Mrs Keane should

working on a general medical
take.
That Mrs Keane is dying.

The inappropriateness of
aggressive medical interventions
29
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in the context of a patient who is

dying.
That you will listen to the
daughters concerns, but that
you will not ask her to make
decisions about offering or
declining particular treatments,
which are medical decisions.
That doctors are not obliged to
provide treatments that they
consider to be futile.

questions
Daughter: why is my mother bleeding
from her mouth?
Doctor: Im afraid that we dont
know for certain. The blood is
coming from her gut, and it is
most likely that she has developed
an ulcer in her stomach or the top
of her small bowel: this has probably
developed over a small blood vessel
which is now bleeding.
Daughter: why is my mother
unconscious?
Doctor: she has bled so much that
her blood pressure has dropped very
low. This means that blood is not
getting to her brain properly.
Daughter: how are you going to stop
the bleeding?
Doctor: there isnt an easy way to
do this, and we dont think it would
be right to put her through a lot of
investigations and treatments that
wouldnt do any good and which
would cause her distress. The most
important thing is that we make
sure that she is comfortable.
Daughter: so are you just going to let
her bleed to death?
Doctor: Im sorry, but Im afraid that
your mother is dying. As you know,
she has problems with a poor heart,
poor kidneys and her mind has gone
with dementia, and in the situation
30
she is in now she would be very

unlikely to survive for more than a
short while whatever we did. We
are going to make sure that she is
comfortable: it would be wrong for
us to prolong her dying.
Daughter: but I know that you can
do telescope tests. Wouldnt it be right
to find out what is wrong for sure?
Doctor: at the moment it wouldnt
be safe to have a look into your
mothers stomach with a telescope.
She is unconscious and could not
protect her airway, and her blood
pressure is too low for the heart to
take the strain. If we were to try to
do a telescope test we would have to
begin by putting her on a breathing
machine and giving her a lot of
fluid to bring up her blood pressure.
Even if we did that it wouldnt be
guaranteed that the test could be
done safely, or that it would be able
to find out whats going on. It really
wouldnt be kind or sensible to
do this.
Daughter: have you talked to your
consultant about this?
Doctor: yes I have, and what Im
explaining to you is what he has
asked me to say. If you want to speak
to him directly then I can try to
arrange this. Would you like me to?
Daughter: how long will it be before
she dies?
Doctor: I cannot say for sure, not
because Im hiding anything but
because I dont know. She has bled
a lot and her blood pressure is very
low. She could die very soon over
the next few minutes or it could be
longer if the bleeding slows down,
which it can sometimes do.
Daughter: are you sure that shes not
in any distress?
Doctor: yes, she isnt responding
at all at the moment. She is
unconscious and cant feel anything.
But if she did seem to become

distressed, if she seemed to be in
any pain, then we would give her
something to make sure she was
comfortable.
1.3.3 Limitation of
investigation
Scenario
working in a gastroenterology
outpatient clinic.
Mr David Chan is a 25-year-old
man who has experienced
symptoms of irritable bowel
syndrome for 8 years and has
been extensively investigated
previously. He is convinced that
his symptoms have worsened
considerably and is particularly
worried about a recent bout of
constipation because he thinks it
might indicate cancer. A physical
examination is unremarkable
and routine tests such as FBC
are entirely normal. He wishes
to have a colonoscopy, but
the consultant who saw him
previously said that this was not
indicated and declined to perform
the investigation.
Your task: to explain to the
patient the reasons why the test
is not indicated nor on offer, and
what the nature of irritable
bowel syndrome is.

This is clearly going to be a difficult
discussion. Begin by asking the
patient to explain to you what he
thinks is causing his problems, and
what his fears and concerns are.
Constipation is a common symptom
in irritable bowel syndrome (IBS),
so is there any particular reason why
he is worried about cancer now?
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You recognise that IBS causes
distressing symptoms, but it is
benign in the long term, ie it does
not lead to excess mortality or
predispose to developing other
conditions such as colorectal
cancer and inflammatory bowel
disease.
Decisions about investigations
depend on balancing benefits and
risks, and colonoscopy is not
without hazards.
Doctors are not obliged to offer
tests or treatments that they do
not think are clinically indicated.

questions
Patient: how can you be sure that
I dont have cancer?
Doctor: even if you do every test
possible, it cannot be proved that
cancer is impossible. But everything
we know about you, including the
fact that your symptoms have been
going on for a long time, that
everything is as it should be on
examination and that routine blood
tests are normal, are reassuring that
you do not have a serious disorder
such as cancer.
Doctor: no, thats not the main

reason for me saying that we wont
do the test. The main reason is
because the test stands more chance
of doing you harm than doing you
good, although I agree that it isnt
right to spend healthcare money on
something that isnt justified.
Patient: I have a right to have the
test, havent I?
Doctor: no, thats not true. No
patient has a right to a test or a
treatment that is not clinically
indicated. You do have a right to
have a second opinion if you want it,
and if youd like me or your GP to
recommend someone then we can
do, but you cant insist that we do a
test that we dont think is justified.
Patient: you think Im just a whinger,
dont you?
Doctor: no, thats not what Ive said
and its not what I think. There is no
doubt that the symptoms of irritable
bowel syndrome exist and can be
really severe and worrying; and I
and the other doctors in the clinic
will help as much as we can to
control them. However, we wont do
things that we dont think will help.

want to give a history
Patient: why dont you just organise

a colonoscopy? Ill feel better, and you
can get on with your other work.
Doctor: no, this wouldnt be the
right thing to do. Deciding about
tests or procedures is a matter of
balancing benefits and risks, and
colonoscopy does carry a small risk
of serious complications, such as
perforation of the bowel. It wouldnt
be right to put you or any patient at
risk of this if there wasnt a proper
reason for doing the test.
Patient: youre just trying to save
money by not doing the test,
arent you?
Scenario
working on a general medical
ward.
Ms Cathy Evans, a 34-year-old
woman who says that she has
recently moved to the area and
is not registered with a GP, is
admitted with episodic severe
abdominal pain. At times this
seems to be excruciating, such
that she rolls around in agony
and calls out for pethidine, but
between attacks she seems well

and appears unconcerned about
her condition. Examination
reveals two laparotomy scars,
the indications for which are
unclear. Routine laboratory
tests and plain radiographs are
normal. She has been on the
ward for 3 days and matters do
not seem to be improving. It is
the opinion of your consultant
that the woman has factitious
abdominal pain and that no
further investigations should
be performed. Ms Evans is
unhappy with the lack of
investigation since admission
and has demanded to see
someone to discuss this. Your
consultant has asked you to
get more information regarding
her background history, which
Ms Evans has been unwilling to
provide.
Your task: to explain to
Ms Evans that further details
of her medical background
are required and that further
investigation is not indicated.

This is clearly going to be a difficult
discussion. Begin by asking the
patient to explain to you what she
thinks is causing her pain and what
she thinks should be done about it.
Use comments made by her, which
she will almost certainly intend as
justification for investigation, as
reasons for needing precise details
of her past medical history.

Reassure her that the progress
of her illness and the results of
investigation do not indicate
serious intra-abdominal
pathology.
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Be firm and persistent in

requesting specific details:
when, which hospital and which
doctor, etc? But do not become
confrontational.
Doctors are not obliged to offer
tests or treatments that they do
not think are clinically indicated.

questions
Patient: you havent found out whats
wrong with me yet? Dont I need a
CT scan?
Doctor: you are right that we
havent got to the bottom of things
yet, but the tests that we have
done have not revealed anything
worrying, which is good news. We
dont think that a CT scan will add
anything useful at this time, but we
do need to find out as much as we
can about the previous problems
youve had in your abdomen, just
in case these are relevant to whats
happening now.
Patient: my past isnt relevant, why
do I have to tell you about it?
Doctor: you dont have to tell
me anything that you dont want
to, but it is very difficult for us
to manage you safely without
knowing about your past medical
history, in particular about the
operations that you have had.
These details may help us get
to the bottom of your current
problems and we could miss
things if we do not have all the
information. Can you remember
in which hospital you had them
done, and when?
Patient: do you think Im mad?

Doctor: no, I havent said that. I
dont know whats causing your pain,
but you are right that psychological
problems can sometimes present in
this way and are a potential cause
for stomach pain. They do need to
be considered in order to enable us
to get expert help if this is indeed
the case.
Patient: why cant I just have
pethidine to make the pain go away?
Doctor: we do not think that giving
you lots of pethidine to mask the
problem is going to help us get you
better. But if the pain is continuing
to be troublesome, then we would be
more than happy to obtain specialist
advice from the doctors in the pain
clinic.
1.4 Acute scenarios

1.4.1 Nausea and vomiting
Scenario
A 77-year-old woman was
initially admitted with chest
pain, and during the course of
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The scenario described is very

suggestive of intestinal obstruction
that has been precipitated by the
bowel preparation, but it is
important to consider other causes.
Some preparations used for bowel
preparation have an unpleasant
taste and many patients experience
nausea whilst taking them. There is
also a history of chest pain, about
which no details are given, but this
may be cardiac and hence it will be
important to exclude the rare but
important diagnosis of painless
myocardial infarction presenting
with vomiting.
investigation is found to have

iron-deficiency anaemia. She is
given bowel preparation for a

colonoscopy and starts to vomit.
You are asked to assess her.
Introduction
Patient: what is causing the pain?

Doctor: were not sure, but we dont
think there is a serious problem in
your abdomen. Pain can be caused
by a number of things, not all of
which can be demonstrated on
blood or X-ray tests.
Nausea and vomiting are very

common non-specific symptoms that
occur in many medical situations.
Nausea is a feeling of inclination to
vomit and may be associated with
hypersalivation and/or regurgitation
of small amounts of material from
the stomach. Vomiting is not always
associated with nausea. Both may
be stimulated via many mechanisms
within the body, ranging from
the higher centres (eg unpleasant
visual stimulus) to toxic causes
(eg chemotherapeutic agents) to
mechanical causes (eg intestinal
obstruction). Table 16 shows causes
of nausea and vomiting classified
with respect to mechanism.
There are many causes of

nausea and vomiting: serious
causes must be excluded rapidly, but
thorough consideration of the patients
medical and drug history may be
needed to make a diagnosis.
When did the symptoms start?

A long history of recurrent
vomiting may suggest that this is
an acute-on-chronic exacerbation
of a known condition such as
diabetic gastropathy. Identifying
a temporal association with a
procedure, new drug or other
event may be crucial in diagnosing
the underlying problem.
What was in the vomitus? Vomit
is usually partially digested food
mixed with gastric juice. The
presence of small amounts of
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TABLE 16 CAUSES
OF NAUSEA AND VOMITING
Mechanism
Type of problem
Example
Central nervous system
Anxiety
Nociceptive event
Metabolic changes
Raised intracranial pressure
Drugs
Prior to procedure
Phlebotomy
Hyponatraemia
Cerebral tumour
Chemotherapeutic agents,
digoxin, theophyllline, opiates
Balance centre
Labyrinthitis
Mnires disease
Benign positional vertigo
Viral infection
Mechanical
Gastric outlet obstruction

Intestinal obstruction
Dysmotility
Impacted foreign body
Antral gastric cancer

Caecal carcinoma
Diabetic gastropathy
Gallstone ileus
Gut receptors
Ingested toxin
Infection
Drug side effect, eg digoxin

Viral gastroenteritis
blood is not unusual, particularly

if there has been considerable
retching, but large volumes of
blood should lead to consideration
of causes of haematemesis (see
Section 1.4.3). Bilious vomiting
may occur in patients who have
had previous gastric bypass
surgery. Vomiting of food from
several meals ago may suggest
gastric stasis or gastric outlet
obstruction.
What was the volume of the
vomitus? Large-volume vomiting
occurs in small bowel obstruction.
Is there any abdominal pain?
Abdominal pain and vomiting
should lead to consideration of
other specific causes such as
peptic ulceration, acute
pancreatitis or perforated viscus
(see Section 1.4.4). Radiation of
the pain towards the chest or
down the arms would raise
suspicions of a cardiac cause.
Has there been any change in
bowel habit? This may suggest
serious underlying pathology such
as colonic neoplasia but is also
seen in patients with infective
gastroenteritis.
Has the patient passed

stool/flatus? Reduced bowel
opening or absolute constipation
is suggestive of intestinal
obstruction.
Intestinal obstruction leads to

different symptoms depending
on the level of the block.
Oesophageal obstruction: dysphagia
and inability to swallow saliva.
Gastric obstruction: may cause
vomiting with little or no pain.
Small intestinal obstruction: usually
causes vomiting, but the colon may
still function.
Colonic obstruction: often causes
pain and constipation, but vomiting
may be a late feature.
Is there any associated dizziness,

light-headedness, tinnitus or
change in conscious level? These
may indicate a central cause for
nausea/vomiting from either the
vestibular system or central
nervous system, but may also
suggest severe fluid depletion
leading to impaired cerebral
perfusion.
Has there been any previous

abdominal surgery, which could
lead to adhesions that might cause
intestinal obstruction? Does the
patient have any other medical
or surgical conditions? She was
admitted with chest pain, which
might be attributable to angina
provoked by anaemia, and since
acute intestinal obstruction may
require surgical intervention it is
very important to identify comorbid
risks such as ischaemic heart disease
at an early stage.
It will be important to ask carefully
about current medications and any
recent changes in these: drugs are
a common cause of nausea and
vomiting, and patients taking drugs
that affect vascular responses (eg
beta-blockers) may be susceptible to
smaller losses in circulating volume
than would otherwise be the case.
An alcohol history is also important:
alcohol excess/abuse is associated
with nausea and vomiting, as are
many of its complications (eg acute
pancreatitis).
Examination
General features
Does the patient look well, ill,

very ill or nearly dead? If the
latter, then urgent attention and
intervention are required. Get senior
help early: an experienced hand carries
extra authority when negotiating with
other colleagues, eg in intensive care
or surgical services, and is also
important when decisions to limit
intervention are appropriate.
If the patient is in extremis,

summon the cardiac arrest team:
do not wait for the heart to stop. Often
more can usefully be done in the periarrest period than after a cardiac arrest.
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Check vital signs: look in

particular for evidence of volume
depletion (cool peripheries,
tachycardia, hypotension/postural
hypotension, low JVP) and of
sepsis, which can cause vomiting.
Check pulse oximetry.
If the patient is peripherally

shut down and hypotensive,
insert two large-bore cannulae and
start resuscitation immediately
whilst completing the history and
examination.
Check Glasgow Coma Scale (GCS)

score: reduction in conscious level
may occur in the very ill or it may
indicate the underlying cause of
vomiting (eg intracerebral lesion).
Patients in coma (GCS <8/15) need
definitive airway protection as
they are at high risk of aspiration
of gastric contents.
Given the clinical suspicion of
possible malignancy, look for
clubbing, cachexia and
lymphadenopathy. General
examination should also focus on
any significant comorbidities that
might influence or preclude
subsequent investigations or
treatments.
Palpation: signs of peritonism,

abdominal mass.
Auscultation: high-pitched bowel
sounds (obstruction); absent
bowel sounds (perforation);
succussion splash (gastric
outlet obstruction).
Digital rectal examination:
presence of malaena, mass
lesion or faecal impaction.
dehydration, when urea is

proportionally elevated to a
greater extent than creatinine,
also in excluding acute (or
acute-on-chronic) renal
impairment; abnormal liver
blood tests may suggest a
biliary cause for vomiting;
elevated amylase would clearly
raise suspicion of acute
pancreatitis.
Investigation
Routine imaging tests
The appropriate strategy for

investigation will clearly depend on
the clinical context: the patient who
begins to vomit after being given a
new medication may not require
any investigation at all, but in the
scenario described the following
would be appropriate.
An erect CXR should be performed

in those with abdominal pain to
exclude a perforation by looking
for free air under the diaphragm,
and may also reveal evidence of
aspiration pneumonia. A plain
abdominal radiograph is essential in
those whose vomiting might be due
to intestinal obstruction, as in this
case (Fig. 10).
Routine blood tests

Check FBC.
Electrolytes, renal/liver/bone
profiles, amylase: may sometimes
reveal the cause of nausea and
vomiting (eg hyponatraemia,
hypercalcaemia) or its effects
(eg hypokalaemia); useful in
estimating the degree of
Other tests
Given the patients history of
chest pain, a 12-lead ECG should
be performed to look for evidence of
myocardial ischaemia, and this may
need repeating after 812 hours to
assess for evolving changes; also
check serum troponin.
Never lose sight of the

whole patient: after initial
resuscitation do not focus exclusively
on the main problem.
Abdomen
Systematically consider the
following.
Inspection: scars (consider
adhesions), distension, abnormal
bruising (Cullens or Grey Turners
sign in acute severe pancreatitis).
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Fig. 10 Plain abdominal radiograph showing dilated stomach and small bowel in a patient with colonic
obstruction.
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Other investigations will be

determined by the clinical context
and the results of preliminary
tests. Arterial blood gas analysis
is required in any patient who is
very ill and may reveal metabolic
alkalosis if vomiting has been
long-standing. Other structural
investigations may be useful in
selected cases.
Ultrasound scanning: particularly
good for imaging the gallbladder
and proximal biliary tree and can
be useful in excluding intraabdominal fluid collections.
CT scanning: increasingly used
in the investigation of acute
abdominal pathology; particularly
useful in imaging the pancreas
and distal biliary tree but can
also reveal other gastrointestinal
or non-gastrointestinal pathology.
Endoscopic retrograde
cholangiopancreatography
(ERCP)/magnetic resonance
(MRCP): imaging of the biliary
tree by these techniques may be
required in some specific settings,
eg acute gallstone pancreatitis,
where emergency ERCP with
duct drainage is essential in
reducing further complications.
This should preferably be
performed within the first
24 hours as oedema at the papilla
worsens over time, reducing
the likelihood of successful
intervention and increasing
the risk of ERCP-related
complications.
Contrast studies: patients with
persisting symptoms may require
either barium meal or small bowel
enema/enteroclysis, which can
give information relating to the
extent of strictures in the small
intestine in addition to assessment
of the degree of small bowel
obstruction.
If in doubt, get a surgical

opinion: this can wait until
blood test results and preliminary
imaging studies are available if the
patient is not very ill, but if the patient
is shocked call for advice as soon as
resuscitation is underway.
Upper gastrointestinal
endoscopy contributes little
to the investigation of nausea and
vomiting (without haematemesis) and
is not without risk: the patient may
have a stomach full of fluid, increasing
the risk of aspiration and reducing the
chance of visualising any significant
pathology.
repeat until the peripheries are

warming, pulse is settling, BP is
restored (without postural drop) and
JVP can be seen;
insert urinary catheter to monitor
urine output.
Many doctors worry about

administering fluid boluses,
particularly in the elderly or in those
with a history of heart failure. It is true
that both groups will not cope well
with fluid overload, but both tolerate
hypovolaemia poorly and so prompt
volume replacement is important. Give
rapid boluses of 500 mL rather than 1 L
and check regularly for signs of fluid
overload.
Management
Specific management will clearly be
dictated by the particular cause of
vomiting, but there are three main
areas to consider in the management
of all patients with this symptom:
resuscitation, control of pain, and
control of nausea and vomiting.
Central venous lines Central venous

catheters take time to insert, do not
themselves make anyone better, and
attempts to insert them are much
more likely to cause harm than
benefit in a patient who is clearly
hypovolaemic.
Resuscitation
Resuscitation is the most

important aspect of immediate
management. If the patient is shocked,
ie has cool peripheries, tachycardia,
hypotension or severe postural
hypotension (lying and sitting)
and a low JVP, then give high-flow
oxygen and:
insert large-bore cannulae into both
forearms/antecubital fossae;
give a rapid uid bolus (1 L of 0.9%
saline or colloid);
check peripheral perfusion, pulse
rate, BP and JVP in response to uid
bolus;
if there is still evidence of
hypovolaemia, give another
rapid uid bolus;
Do not attempt to insert an

internal jugular or subclavian
central line into someone who is
obviously hypovolaemic. When they
have been resuscitated a central line
may aid continuing fluid management.
Pain control
Patients with pain should be given
sufficient analgesia. If they are
vomiting, then the drug should be
delivered by a parenteral route,
either intramuscularly/intravenously
or subcutaneously depending on the
circumstances. Opiates titrated to
the level of adequate analgesia will
often be necessary for severe pain.
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Opiates cause nausea and

vomiting in many patients
and should therefore always be
administered with an antiemetic.
(Fig. 11 and Table 17). In the patient

who is nauseous but not vomiting
oral medication may be sufficient,
but once the patient starts to vomit
this route is no longer viable.
1.4.2 Acute diarrhoea

Scenario
A 22-year-old man who has just
returned from a trip to Thailand
is sent to the Emergency
Control of nausea and vomiting

Control of nausea and vomiting is
best achieved by identifying the
underlying cause and treating this
specifically. However, in most cases
the exact cause may not be instantly
obvious or there may be delay in
obtaining relevant information, in
which case effective symptom
control depends on determining
the mechanism or mechanisms
of nausea and vomiting in the
particular case and selecting the
relevant therapeutic intervention
Insertion of a nasogastric tube

may be necessary to relieve the
symptoms of large-volume vomiting
and also allows accurate measurement
of fluid loss.
Department by ambulance after

being seen by the out-of-hours GP
service. He looks acutely unwell
and is barely responsive to your
questions, saying that he has
had terrible diarrhoea for
Other useful drug therapies include

hyoscine butylbromide, which can
be employed to reduce intestinal
secretions, and octreotide may be
used in a similar fashion. These
drugs are used most commonly in
patients with complications of
advanced cancer.
several days.
Introduction
This is an emergency: the patient
seems to be suffering circulatory
failure and neurological disturbance.
In a recently returned traveller from
Fig. 11 Pathways involved in nausea and vomiting with specific examples of potential antiemetics for relevant pathways.
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Other symptoms: vomiting, fever.
TABLE 17 ANTIEMETIC
DRUGS AND RECOMMENDED DOSAGE
Antiemetic drug
Dosage per 24 hours
Anxiolytics
Lorazepam
4 mg
Dopamine antagonists
Metoclopramide
Domperidone
Haloperidol
Levomepromazine (methotrimeprazine)
3080 mg
3080 mg
1.510 mg
12.575 mg
5HT3 receptor antagonists

Ondansetron
816 mg
Antimuscarinics
Prochlorperazine
530 mg
Antihistamines
Cyclizine
50150 mg
Steroids
Dexamethasone
820 mg
Have travelling companions been

similarly affected? This would
make an infective cause very likely.
Medications: antidiarrhoeal agents
may prevent the natural expulsion
of stool and can worsen bacterial
dysentery; use of antibiotics may
result in antibiotic-associated
diarrhoea and psuedomembranous
colitis caused by C. difficile
infection; has the patient taken
antimalarial prophylaxis (and if
so, what)?
abroad with severe diarrhoea

the most likely diagnosis is an
acute infection such as bacterial
dysentery, although the other
conditions listed in Table 18 require
consideration.

The patient cannot give a detailed
or reliable history, but from any
source available (family, friends,
GP letter, ambulance crew notes)
try to ascertain the following.
Travel: when did the patient

return from abroad, how long
was he there, and what precisely
was he doing?
Diarrhoea: when did it start, how
many times today and what is it
like? Is the diarrhoea watery,
suggesting a non-invasive organism
such as Giardia, Cryptosporidium
or cholera, or bloody, suggesting
bacterial or amoebic dysentery or
inflammatory bowel disease?
Is there any possibility that the

patient may have a non-infectious
cause of diarrhoea: has he ever had
any similar problems before, which
would suggest that inflammatory
bowel disease might be the diagnosis?
Does he have any pre-existing
medical condition such as diabetes,
immunodeficiency (including HIV
infection) or relevant family history
of illness, eg of inflammatory bowel
disease? Was the patient vaccinated
against Salmonella and cholera
before travelling?
Just because a patient has

been abroad, do not assume
that it must be an infectious condition.
TABLE 18 CAUSES
OF SEVERE DIARRHOEA IN THE
RETURNING TRAVELLER
Type of cause
Condition
Enteral infection
Bacterial: Campylobacter, Salmonella, Shigella, Escherichia

coli, Vibrio cholerae (if travel to an endemic area),
Clostridium difficile
Protozoal: amoebic dysentery, cryptosporidiosis, giardiasis
Viral: rotavirus, Norwalk agent (CMV in the
immunocompromised)
Systemic infection with

diarrhoeal component
Malaria, pneumonia (especially atypical),

septicaemia, meningitis
Non-infectious
Inflammatory bowel disease, drug side effects (especially

antibiotics), laxative overuse
CMV, cytomegalovirus.
Examination
General features
Get help from the intensive

care unit urgently if the patient
looks very ill or nearly dead.
Vital signs: look in particular for

evidence of intravascular volume
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hypotension, low JVP) and

dehydration (reduced skin turgor,
dry mucosae). Check pulse
oximetry.
If resuscitation is required,
start immediately.
Systemic signs of sepsis: skin rash,

which may accompany typhoid
fever and Gram-negative sepsis
from bacterial dysentery. Is the
body temperature abnormally
high or low, both of which can be
signs of sepsis? Uveitis or arthritis
can complicate dysentery.
Glasgow Coma Scale (GSC) score:
is the fact that the patient barely
responds to questions the result
of general debilitation or does
it indicate pathology such as
cerebral malaria or meningitis?
Abdomen
Routine blood tests

FBC looking for anaemia,
leucocytosis, thrombocytopenia:
a possible feature of sepsis
but also consider haemolytic
uraemic syndrome caused by
E. coli 0157.
Electrolytes (hypokalaemia,
hypernatraemia).
Creatinine/urea (renal function,
hydration status).
Liver function tests.
Inflammatory markers.
Blood culture.
Stool
Submit a stool sample for
microbiological assessment
(microscopy, culture, sensitivity;
testing for ova, cysts and
parasites; C. difficile toxin).
A freshly evacuated specimen needs
to be examined if amoebiasis is
suspected.
Imaging
Abdominal radiograph, looking in
particular for colonic dilatation,
toxic megacolon being defined as
a diameter of the transverse colon
>6 cm (Fig. 12).
Sigmoidoscopy
Rigid sigmoidoscopy with rectal
biopsy should be performed if the
patient has bloody diarrhoea or
is passing mucopus, suggesting
dysentery or colitis, and particularly
in an immunocompromised
individual, where there may be
viral colitis (eg caused by CMV)
or cryptosporidial infection. This
allows direct visualisation of colonic
mucosa and biopsy (see Fig. 4).
Other investigations
The need for other investigations
is determined by clinical progress
and the results of routine testing, eg
serological tests for amoebiasis and
yersiniosis (also for coeliac disease)
may be appropriate.
Is the abdomen tender or

distended? This might indicate
colonic dilatation, and possibly
precede perforation. Are the liver
and spleen enlarged or tender?
Bacterial dysentery may result in
splenomegaly, while amoebiasis can
be associated with liver abscess.
Is the rectal examination normal
or is there a bloody or purulent
discharge? This indicates probable
dysentery or inflammatory bowel
disease, and once the patient is
stabilised rigid sigmoidoscopy
should be considered to obtain a
tissue diagnosis.
Investigation
Always check thick films for

malaria in a patient returning
from the tropics with a febrile illness.
Fig. 12 Plain abdominal radiograph showing a very dilated colon (toxic megacolon).
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Management
In a sick patient with an acute

diarrhoeal/colitic illness, start
treatment before the results of tests
are available.
Resuscitate: as described in
Section 1.4.1.
Ciprofloxacin (500 mg iv bd) and
metronidazole (500 mg iv tds): to
treat presumed bacterial or amoebic
dysentery.
Hydrocortisone (200 mg iv qds): to
cover possibility of inflammatory
bowel disease.
Surgical review: in case there is
actual or impending colonic
perforation.
If dealing with acute

gastroenteritis in the field,
remember the World Health
Organization/UNICEF oral rehydration
fluid: 1 L water, 10 g (2 teaspoons)
sugar, 2.5 g (1/2 teaspoon) salt, 2.5 g
(1/2 teaspoon) baking soda (sodium
bicarbonate).

melaena
Scenario
by ambulance to the Emergency

after walking to the bathroom,
where he vomited some blood.
He gives a history of melaena
Further comments
Is there a public health issue: are
others affected, and was the airlines
caterer rather than the roadside food
vendor in Bangkok to blame?
over the last 2 days.
Introduction
Haematemesis is due to bleeding
from the oesophagus, stomach or
duodenum; it is very unusual for
bleeding distal to the duodenojejunal
junction to return to the stomach.
The history of melaena (dark tarry
faeces containing blood) indicates
the patient has had a gastrointestinal
haemorrhage from a lesion
anywhere from the oesophagus to
the terminal ileum (Table 19), with
Public health issues

Food poisoning and dysentery
cases should be notified to the
Public Health Laboratory Service,
which will consider instigating
case-finding and source-tracing of
any outbreak.
The attending doctor could
reasonably offer testing and
treatment to known contacts
of the index case.
Important issues are to determine

the severity of the haemorrhage, the
likely cause of bleeding, and whether
there is continued bleeding. It is also
important to assess for the presence
of comorbidities such as a chronic
liver disease or ischaemic heart
disease, which increase the mortality
associated with gastrointestinal
bleeding.
A 75-year-old man is brought

Department after he collapsed
Obtain a surgical opinion

(preferably from an experienced
gastroenterological surgeon)
immediately if there is peritonism or
the abdominal radiograph shows toxic
megacolon or free air, or if patient does
not improve rapidly with rehydration
and the treatment listed above.
Emergency colectomy may be required.
the most likely cause being peptic

ulceration. More distal haemorrhage
results in fresh rectal bleeding,
although occasional patients with
caecal malignancies present with
melaena.

Nature of the vomit: find out
if this was fresh blood, which
suggests a proximal source of
bleeding (eg oesophagus), a large
gastrointestinal haemorrhage or
persistent bleeding, or was coffee
grounds, suggestive of altered and
therefore old blood. Patients who
say it might have looked a bit like
coffee grounds are extremely
unlikely to have had significant
gastrointestinal bleeding and
should be managed as if vomiting
is the problem rather than
haematemesis (see Section 1.4.1).
Quantity of blood loss: patients
are most unlikely to be able to
give a more precise estimate than
DIAGNOSIS OF MELAENA
Common
Less common
Rare
Duodenal ulceration
Gastric ulceration/erosions
Gastric carcinoma
NSAID-induced enteropathy
Oesophagitis
Oesophageal/gastric varices
Dieulafoy lesion1
Angiodysplasia
Aortoenteric fistulae2
Small bowel tumour
1. Bleeding from an arteriole protruding through a minute mucosal defect, usually in the
proximal stomach.
2. Rare complication of abdominal aortic aneurysm repair, very rare in other circumstances.
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that there was a lot or a little.

Dizziness or syncope suggests
significant bleeding.
what caused them, the key issues

to pursue are drug history, the
possibility of chronic liver disease,
history of previous abdominal
surgery, and history of
comorbidities.
Syncope suggests a significant

gastrointestinal haemorrhage
or a lesser bleed against the
background of chronic anaemia.
Drug history
Persistent life-threatening
bleeding can occur with
melaena in the absence of
haematemesis.
Anticoagulation with warfarin

clearly has the potential to make
any bleeding worse.
Vomiting before bleeding:

recurrent or forceful vomiting
followed by haematemesis
typically occurs with a Mallory
Weiss tear. A peptic ulcer in the
pyloric canal causing gastric
outflow obstruction may cause
vomiting after eating before
melaena.
Abdominal pain: recent
retrosternal discomfort with
acid reflux into the mouth
suggests oesophagitis. Gastric
and duodenal ulcers may be
associated with epigastric
discomfort or indigestion and
pain radiating through to the
back typically occurs with a deep
posterior duodenal ulcer. The
possibility of perforation must be
considered if pain is severe, but it
is uncommon for perforation and
haematemesis to coexist.
NSAIDs and aspirin can cause

either ulceration or erosions in
the stomach, duodenum or small
bowel.
Beta-blockers may mask a

tachycardia associated with
hypovolaemia.
Chronic liver disease

Are there any features suggestive of
chronic liver disease, which clearly
increases the risk of oesophageal
or gastric varices? Recognising
that some patients may find the
necessary questions embarrassing
or offensive, explain why you need
to know the information: Liver
disease can cause bleeding like this,
so I need to know whether you have
liver disease or are at risk of liver
disease. Explore the following.
History of liver disease: Have you

ever been told you have cirrhosis,
liver disease or a scarred liver?
Have you ever been jaundiced?
Have you ever had a distended
abdomen due to fluid (ascites)?
Risk of liver disease: The things
that put you at risk of liver disease
are alcohol and some viruses. Are
you at risk of these? How much
alcohol do you normally drink?
Have you ever been a heavy drinker
in the past? Are you at risk of
hepatitis B or hepatitis C? The
things that put you at risk are blood
transfusions, intravenous drug
use, and some sexual practices.
Previous abdominal surgery

If the patient has had surgery for
bleeding gastric or duodenal ulcers
in the past, then if possible it is
important to establish the nature
of the operation. Current practice is
almost invariably to simply oversew
a bleeding ulcer, but formerly a
partial gastrectomy with or without
a gastroenterostomy (Billroth I or II)
used to be performed (Figs 13 and
14). There is an increased incidence
of stomal ulceration and carcinoma
of the stoma following partial
gastrectomy, and knowledge of
Weight loss: raises suspicion of

an underlying carcinoma but can
occur through reduced oral intake
due to pain from a peptic ulcer.

Aside from the obvious point of
establishing whether the patient
has had any previous episodes of
gastrointestinal bleeding and, if so,
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Fig. 13 Schematic diagram of the anatomy following a partial gastrectomy (Billroth I).
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The severity of the bleeding and risk

of death can be assessed clinically
on the basis of the patients age,
pulse, systolic BP and comorbidity
(Table 20). As would be expected,
hypotension (systolic BP <100
mmHg) and tachycardia (pulse
>100 bpm) in association with old
age and comorbidity indicate a poor
prognosis.
When dealing with a patient

with gastrointestinal bleeding,
do not forget to look specifically for
features of chronic liver disease (see
Section 1.2.2) and for evidence of
hepatic encephalopathy (see
Section 1.4.6).
Fig. 14 Schematic diagram of the anatomy following a partial gastrectomy with a gastroenterostomy
(Billroth II).
previous intervention aids

endoscopic diagnosis.
It is very important to elicit a history
of aortic aneurysm surgery: patients
with gastrointestinal bleeding
and an aortic graft may have an
aortoenteric fistula and merit
emergency endoscopy and/or
cross-sectional imaging.
Pulse: tachycardia.
Hypotension/postural hypotension
(lying and sitting): if BP falls
significantly on sitting up, then the
patients homeostatic mechanisms
are nearly overwhelmed.
JVP: can you see it?
Abdomen
Apart from confirming the presence
of melaena on rectal examination,
abdominal examination will
be normal in most cases of
gastrointestinal bleeding, but
check for any abdominal mass
and for features of portal
hypertension/chronic liver
disease (see Section 1.2.2).
Comorbidities
The presence of ischaemic heart
disease, chronic pulmonary disease
and/or organ failure (renal, cardiac
or liver) increases the morbidity
and mortality associated with
gastrointestinal bleeding. Risk scores
have been developed to take these
into account in determining the
management of gastrointestinal
bleeding.
If resuscitation is required,
start immediately.
TABLE 20 CLINICAL
GASTROINTESTINAL HAEMORRHAGE BASED ON INITIAL CLINICAL

FINDINGS PRIOR TO ENDOSCOPY
Clinical parameter
Examination
General features
How much blood has the

patient lost?
Cool peripheries: how far up the
fingers/hands/arms do you have to
feel before the skin feels warm?
ASSESSMENT OF THE SEVERITY OF
(ROCKALL
SCORE)
Score
0
Age (years)
Shock
Systolic BP (mmHg)
Pulse (bpm)
Comorbidity
<60
6079
>80
<100
<100
Nil
>100
>100
Other
<100
Total score
Mortality (%)
0
0.2
2
5
Cardiac failure
IHD
4
24
Renal failure
Liver failure
6
49
IHD, ischaemic heart disease.
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Investigation
Immediately organise crossmatch of at least 4 units of

blood for anyone who appears to have
had a substantial gastrointestinal
bleed.
Routine blood tests

FBC (haemoglobin, mean
corpuscular volume: reduced in
chronic iron-deficiency anaemia),
electrolytes, creatinine/urea (urea
is elevated out of proportion to
creatinine due to blood in the
bowel), liver function tests,
clotting screen.
Fig. 15 Small gastric ulcer and adjacent erosion viewed at gastroscopy.
The haemoglobin may initially

be normal following an acute
gastrointestinal bleed. However, a
normal haemoglobin should not be
reassuring in the patient who is
tachycardic and hypotensive and
the value should be rechecked after
812 hours.
Gastrointestinal endoscopy
endoscopy is useful in the
management of upper gastrointestinal
bleeding but does not replace
adequate resuscitation and
management of comorbid illnesses.
It is dangerous to perform
endoscopy on a patient who is
hypovolaemic.
Upper gastrointestinal endoscopy

should ideally be performed within
24 hours of admission in anyone
with a substantial gastrointestinal
bleed. Urgent endoscopy is indicated
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Fig. 16 Small oesophageal varices.
if oesophageal varices are suspected

or the patient continues to bleed
actively. It may be necessary for this
to be performed in theatre with the
surgical team on standby, when
endoscopy will hopefully define the
lesion and also exclude variceal
haemorrhage or an inoperable
gastric cancer (Figs 15 17).
Endoscopic stigmata of recent

haemorrhage
Blood in the stomach.
Clot over an ulcer.
Actively bleeding vessel.
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Venous access
If you cannot establish

peripheral venous access in a
patient with gastrointestinal bleeding,
then cannulate the femoral vein, which
lies medial to the femoral artery
(remembered by the acronym NAVY:
nerve, artery, vein and Y-fronts). Do not
attempt to insert an internal jugular or
subclavian line.
Fig. 17 Varices at the gastro-oesophageal junction with surface ulceration and clot.
Endoscopic stigmata of recent

haemorrhage help in stratifying risk
of rebleeding and mortality. If an
adherent clot is seen in a peptic ulcer,
there is a 20% chance of rebleed;
if a visible vessel is seen in a peptic
ulcer, there is up to a 50% chance of
rebleeding; if neither of these are
found, then the chance of rebleeding
is <10%. Endoscopy will be normal
in 30% of patients with suspected
upper gastrointestinal bleeds. Ongoing
bleeding should always prompt
consideration of repeat endoscopy as
small bleeding points can be missed.
Radiological imaging
Most patients with gastrointestinal
bleeding do not require radiological
tests. An abdominal radiograph is
almost never indicated. An erect
CXR is appropriate if a perforation
is suspected (free air under the
diaphragm), if the patient has
vomited and there is the possibility
of aspiration pneumonia, or if
required for anaesthetic assessment
prior to theatre. In the very rare
circumstance of the patient with
an abdominal aortic graft and the
possibility of an aortoenteric fistula,
then CT of the abdomen may be
indicated.
Management
Management of the patient

with gastrointestinal
haemorrhage
Resuscitate first, ask questions
afterwards.
Early liaison with the surgical team.
If the patient is shocked, ie has

cool peripheries, tachycardia,
hypotension (lying and sitting) and a
low JVP, then give high-flow oxygen
and:
give a rapid fluid bolus of 1 L of 0.9%
saline or colloid, or 2 units blood
(O negative or cross-matched) if
available;
rate, BP and JVP in response to fluid
bolus;
hypovolaemia, give more blood;
JVP can be seen;
urine output.
Resuscitation is the most important

aspect of management: remember
that a central line, like an endoscopy,
does not replace adequate
resuscitation, so do not attempt
to insert one into a patient who is
clearly hypovolaemic. A central line
never made anyone better in this
circumstance but has killed quite a
few: insertion is difficult when veins
are constricted, making the chance
of complications much higher, and
knowing exactly how low the CVP is
will not alter management.
Once intravascular volume has been
restored, a central line should be
considered in the following
situations:
hypotensive on admission and age
over 60 years;
rebleed;
if transfusion requirements exceed
4 units;
accompanying severe
cardiorespiratory or renal disease;
initial Rockall score 2 (in patient
under 60 years of age) or 3 (in
patients over 60 years of age).
Diagnosing rebleeding is not

always straightforward but is
suggested by:
overt fresh haematemesis or melaena,
although melaena can persist for a
few days following a bleed;
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development of new tachycardia of

>100 bpm with drop of systolic BP to
<90 mmHg;
development of new tachycardia of
>100 bpm with fall in CVP;
drop in haemoglobin concentration
of >2 g/dL over a period of 24 hours
or less.
Is surgical or radiological
intervention required?
Inform surgical colleagues sooner
rather than later: as a rule of thumb
discuss any patient who merits
emergency endoscopy, has an initial
Rockall score over 3 or requires
significant transfusion. The decision
regarding the appropriateness and
timing of surgery can be very
difficult and should be made by
experienced, senior colleagues. Early
surgery, especially in older patients,
is associated with a lower overall
mortality and may be indicated for
those who meet criteria such as:
transfusion requirements of
>8 units (age <60 years) or >4 units
(age >60 years) in 24 hours; or
one rebleed; or
TABLE 21 THE
MOST COMMON CAUSES OF HAEMATEMESIS
IN PATIENTS WITH LIVER CIRRHOSIS
Cause
Frequency (%)
Bleeding oesophageal varices

Bleeding peptic ulcer
Portal hypertensive gastropathy
Bleeding gastric varices
Other causes and undiagnosed
60
20
5
5
10
bleeding peptic ulcers (eg

omeprazole 80 mg iv bolus followed
by infusion at 8 mg/hour). Similarly,
oral proton pump inhibitors may be
indicated for oesophagitis or in the
healing of a documented ulcer.
Eradication of Helicobacter pylori
is indicated if infection is present
with a gastric or duodenal ulcer.
Any clotting disorder should
be corrected, and if significant
gastrointestinal haemorrhage occurs
in a patient on aspirin or warfarin,
the riskbenefit for continued use
of these medications should be
considered carefully.
Further comments
Interventional radiology may be

appropriate and should also be
explored in tandem with a surgical
consult. It has a particularly
important role in those with
significant comorbidities associated
with poor postoperative outcomes.
Other treatments
There is no strong evidence for the
initiation of acid suppression until
after an endoscopic diagnosis has
been made. High-dose intravenous
proton pump inhibitor reduces
rebleeding in those who have
received endoscopic treatment of
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Variceal haemorrhage is a lifethreatening emergency: patients

are at risk of further bleeding,
particularly immediately following
an initial haemorrhage, and the
overall mortality in the short and
long term is high. As for any other
cause of gastrointestinal bleeding
the immediate priority is to
recognise shock and resuscitate.
Other aspects of management are
detailed below.
Bleeding from oesophageal varices
Treatments to stop bleeding

The following therapies should be
considered for those with variceal
bleeding.
endoscopy can be both
diagnostic and therapeutic in the
patient with bleeding oesophageal
varices and should be performed as
soon as it is safe to do so when these
are suspected.
Pharmacological measures to
reduce variceal haemorrhage
by reducing splanchnic blood
flow: octreotide and vasopressin
analogues (eg terlipressin 2 mg
iv 4-hourly) should be used
when variceal haemorrhage
is suspected.
spurting vessel at endoscopy not

controlled by injection therapy; or
continued bleeding.
Section 1.2.2), and also remember

that other causes of bleeding,
particularly peptic ulcer disease,
can and do occur in the context of
portal hypertension (Table 21).
A large-volume painless
haematemesis is very suspicious
of oesophageal variceal bleeding,
particularly if there is any indication
of chronic liver disease. However,
portal hypertension and variceal
haemorrhage may occur in patients
without cirrhosis, eg as a result
of portal vein thrombosis (see
Correction of haemostatic/clotting
abnormalities: patients with
decompensated cirrhosis typically
have low platelet counts and a
prolonged prothrombin time.
It is usual practice to attempt to
correct any concomitant vitamin
K deficiency, to maintain platelet
counts above 50 109/L, and to
transfuse 2 units of fresh frozen
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performed with radiological

guidance and is particularly
valuable for cases where
bleeding is from gastric or
ectopic varices, which can be
difficult or impossible to control
by other means.
Emergency surgery: rarely
indicated, but surgical shunts
(eg splenorenal) are occasionally
performed (eg for bleeding in
the presence of portal vein
thrombosis or failed TIPSS
insertion). Surgical transection
of the oesophagus is now very
seldom, if ever, practised.
Rebleeding from varices

Patients remain at increased risk
of rebleeding for about 7 days, when
their risk returns to that of any patient
with chronic liver disease and portal
hypertension. It is therefore usual to
monitor patients in hospital, and to
maintain infusions of octreotide or a
vasopressin analogue for 48 hours
after acute haemorrhage has been
controlled.
Fig. 18 Oesophageal varices: (a) large varices; (b) banded varices with superficial banding ulcers.
plasma for every 4 units of blood

or packed cells.
Endoscopic therapy: both
diagnostic and therapeutic; should
be performed as soon as it is safe
to do so. Bleeding oesophageal
varices may be injected with
sclerosant or ligated with rubber
bands to stem bleeding (Fig. 18).
Balloon tamponade: when
haemorrhage is torrential or other
factors prevent effective and safe
emergency endoscopy, balloon
tamponade of the gastric fundus
and oesophagus may achieve
haemostasis. A Sengstaken
Blakemore or Minnesota tube

is employed in some specialist
units as a temporary measure
(Fig. 19). This should not be used
continuously for longer than 24
hours, risks including inadvertent
intubation of the trachea and
oesophageal perforation.
Emergency transjugular
intrahepatic portosystemic shunt
(TIPSS): reserved for those failing
endoscopic treatment. Reduces
portal hypertension by deploying a
stent to maintain a shunt between
the portal vein and a major
hepatic vein. The procedure is
In the longer term, patients with

oesophageal varices should be
enrolled in a programme of
endoscopic variceal obliteration
using sclerotherapy or band ligation.
Where these measures fail, elective
surgical or radiological (TIPSS)
shunting should be considered, and
also liver transplantation in selected
cases.
Other treatments The following
additional therapies should also be
considered.
Variceal haemorrhage may

precipitate more widespread
hepatic decompensation with
ascites, jaundice, coagulopathy and
encephalopathy (see Section 1.4.6).
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1.4.4 Acute abdominal pain

Scenario
A 44-year-old woman is admitted
to the Emergency Department
with a 12-hour history of severe
abdominal pain. Her husband
called the ambulance because she
seemed to be getting confused.
Introduction
Fig. 19 SengstakenBlakemore tube. This particular tube has a gastric (inflated) balloon, an oesophageal
(deflated) balloon, a gastric aspiration channel and an oesophageal aspiration channel. In most cases
tamponade can be achieved by just inflating the gastric balloon. The gastro-oesophageal junction is
40 cm from the mouth.
Physicians need to know

how to manage a patient
with abdominal pain, even if this is
traditionally regarded as a surgical
problem.
Consider the possible causes of

abdominal pain given in Table 22.
Antibiotics: there is an association
of bleeding oesophageal varices
with sepsis, and patients are at
risk of aspiration pneumonia, so it
is standard practice to administer
broad-spectrum antibiotics after
performing a septic screen (eg
cefotaxime 1 g iv twice daily).
Ascites frequently develops over a
period of 35 days in patients who
have had a variceal haemorrhage,
and prophylactic antibiotics on
admission also reduce the risk of
spontaneous bacterial peritonitis.
Laxatives (lactulose) and enemas:
are essential to reduce the risk of
hepatic encephalopathy, which is
aggravated by the enteric protein
load of blood.
Nutrition: patients with
chronic liver disease are often
malnourished and should be
allowed to eat as soon as possible.
Protein restriction is rarely
indicated. Sodium intake should
be less than 100 mmol/day, which
can be achieved most simply by
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not adding salt to food at the

table. Thiamine replacement
should be used where there is
a history of excess alcohol use.
Avoidance of alcohol withdrawal:
a reducing regimen of a
benzodiazepine should be
prescribed if appropriate,
eg chlordiazepoxide 30 mg qds
on day 1, gradually reducing to
none on day 7.
Is the patient ill, very ill or

nearly dead? What are the vital
signs? Are there signs of peritonitis?
Your initial assessment should be
complete in a few minutes. Start
resuscitation immediately. Call for
surgical assistance without delay if
there is shock or peritonitis. Do not
delay treatment chasing irrelevant
minutiae.
DIAGNOSIS OF SEVERE ABDOMINAL PAIN
Common
Less common
Rare
Acute appendicitis
Biliary colic/acute
cholecystitis
Small bowel obstruction
Acute pancreatitis
Acute gynaecological
disease (including ectopic
pregnancy)
Perforated peptic ulcer

Acute diverticulitis
Intestinal infarction
Renal colic
Leaking abdominal aortic
aneurysm
Gastric volvulus
Myocardial infarction2
Lower lobe pneumonia2
Other medical causes, eg
diabetes, herpes zoster (before
the rash), acute porphyria
(very rare)
1. In up to one-third of cases no clear diagnosis will be made.

2. Rarely present with abdominal pain.
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The patient is not likely to be able
to give a detailed history, and trying
to extract one is unlikely to be
rewarding. Focus on the key issues.
angina. An infarcted bowel may be

preceded by symptoms of mesenteric
angina (postprandial epigastric pain
and weight loss).
Examination
General features
Vomiting
Type of pain
Pancreatic pain is usually constant,
epigastric and radiates through to
the back. Peptic ulcer pain is often
similar, and there may well be a
preceding history of indigestion,
but pain in the back would be an
unusual feature unless the ulcer
involves the posterior wall of the
duodenum. Biliary pain is typically
colicky, often focused in the right
upper quadrant and epigastrium,
and there may be radiation to the
shoulder or shoulder blade due to
diaphragmatic irritation. Small
bowel disease (obstruction or
infarction) is usually associated
with central or low abdominal pain,
whilst renal colic typically affects
the loin area (sometimes with classic
radiation to the groin). Appendicitis
typically begins with central colicky
abdominal pain that then moves to
the right iliac fossa. Rarely thoracic
problems can present as an acute
abdomen, so remember to check
for radiation in a cardiac pattern,
and for symptoms suggestive of
pneumonia.
Onset and duration of the problem

Sudden onset of epigastric pain
would suggest perforation of a
peptic ulcer. Most acute abdomens
present within 24 hours of onset
of symptoms. Biliary colic may
occasionally present with a more
prolonged prodrome, including
discoloration of urine (indicating
biliary obstruction) and fevers/rigors
(indicating acute cholecystitis/
cholangitis). There may be a
preceding history of increasing
dyspepsia with peptic ulcer disease.
A myocardial infarction may present
on a background of increasing
Haematemesis is most likely to be

seen in ulcer disease. Faeculent
vomit can be seen in any small
bowel obstruction or in severe cases
of ileus (including pancreatitis).
Be wary of the term coffee grounds
and do not talk the patient and the
medical team into thinking that
the problem is haematemesis: if
asked enough times, almost all
patients/relatives will eventually say
that the vomitus did look a bit like
coffee grounds.
Bowels
Absolute constipation (faeces and
flatus) suggests bowel obstruction.

Find out if there is there a history
of alcohol excess (associated with
acute pancreatitis), gallstone disease
(associated with biliary colic,
cholangitis and pancreatitis),
indigestion/peptic ulcer disease,
previous abdominal surgery
(may cause adhesions and bowel
obstruction), urinary symptoms,
gynaecological history/symptoms
(when was the last menstrual period,
could the woman be pregnant, has
there been a vaginal discharge?).
Is the patient taking any antacid
preparations or on any ulcerogenic
medications, eg aspirin, NSAIDs?
Is there a history of ischaemic heart
disease or of symptoms suggestive of
unstable angina? Firstly, this might
be relevant for diagnosis (atypical
presentation with abdominal pain);
secondly, the presence of severe
coronary disease (or any other major
medical comorbidity) could certainly
influence management of the patient
with abdominal pain of any cause.
If the patient is nearly dead

(unrecordable BP, thready pulse,
depressed conscious level), call
immediately for help from the
intensive care unit.
Young patients can sustain

a significant insult before
showing obvious signs of
cardiovascular compromise, but once
they decompensate they can do so
very rapidly. Be particularly alert for
postural hypotension, which is often a
warning that the patient is about to
go off in a big way.

hypotension, low JVP). Check
pulse oximetry. Fever might
suggest a perforated viscus/
peritonitis, acute cholecystitis/
cholangitis or pancreatitis, but
remember that a very ill patient
can be profoundly septic with a
normal temperature, or even
hypothermia.

start resuscitation immediately whilst
completing the history and
examination.
Check Glasgow Coma Scale (GCS)

score: reduction in conscious level
indicates significant decrease in
cerebral perfusion in this context.
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Other features to look for

specifically include jaundice
(suggests cholangitis or biliary
obstruction), evidence of chronic
alcohol use or liver disease (see
Section 1.2.2: would increase the
likelihood of acute pancreatitis)
and evidence of peripheral
vascular disease (absent pulses,
bruits: would increase the
likelihood of intestinal infarction).
The presence of jaundice early

on is useful in identifying a
biliary cause for an acute abdomen;
at a later stage it is much less
discriminating.
Abdomen
Does the patient have

peritonitis? If so, call a surgeon
immediately.
The presence of generalised

tenderness on palpation is to be
expected in any patient with acute
abdominal pain and is not of great
diagnostic help. Far more significant
is the presence of guarding and
rebound tenderness of localised
peritonitis. Is there an abdominal
aortic aneurysm? You may not make
the diagnosis unless you specifically
consider it when palpating the
abdomen.
Abdominal distension in this setting
is likely to indicate intestinal
obstruction or ileus. Pancreatitis
can rarely cause ascites, but this
would be exceedingly uncommon at
presentation. High-pitched tinkling
bowel sounds suggest intestinal
obstruction; absent bowel sounds
suggest ileus. Look for abdominal
wall bruising: periumbilical bruising
(Cullens sign) or flank bruising
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Fig. 20 Plain abdominal radiograph showing pancreatic calcification in a patient with chronic
pancreatitis.
(Grey Turners sign) is seen in severe

acute pancreatitis.
Rectal examination may reveal
tenderness (on the right side with
retrocaecal appendicitis) and
(rarely in this context) melaena.
Investigation
Routine blood tests
Check FBC (anaemia, leucocytosis),
electrolytes, renal/liver/bone profiles,
amylase, clotting screen, group and
save. An amylase three times the
upper limit of the laboratory
normal range is diagnostic of acute
pancreatitis; lesser elevations are
common in other causes of acute
abdominal pain and are not
diagnostically useful. Check arterial
blood gases if the patient is very ill.
Imaging tests
A plain CXR may demonstrate free
air under the diaphragm if there
is perforation, a pleural effusion
(consider pancreatitis as well as
chest pathology) or occasionally
pneumonia. An abdominal
radiograph may show widespread
small bowel distension, an isolated
(sentinel) loop (associated with
acute pancreatitis) or pancreatic
calcification (usually associated

with alcoholic chronic pancreatitis,
Fig. 20).
Abdominal ultrasound
This may be used to visualise
the biliary tree (gallstones, tender
thick-walled gallbladder due to
cholecystitis, or biliary dilatation)
and pancreas (although of limited
use in diagnosing pancreatitis). Free
intra-abdominal fluid can also be
identified.
Abdominal CT scan
The use of CT in acute abdominal
pain is becoming more frequent,
particularly in the diagnosis of
appendicitis (ultrasound is an
alternative), small bowel
obstruction, acute pancreatitis,
as well as in cases of suspected
abdominal aortic aneurysm
(Fig. 21).
The correct management for

the patient with peritonitis is
usually an urgent laparotomy: harm
can come from delay caused by
organisation of unnecessary
imaging tests.
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Fig. 21 Abdominal CT scan. (a) Normal pancreas (arrow). (b) Acute pancreatitis: the pancreas is swollen and oedematous (arrow) and a thrombus can be seen in
the splenic vein behind the pancreas ( just below point of arrowhead).
Management
Resuscitation is the most

important aspect of immediate
management. If the patient is shocked,
ie has cool peripheries, tachycardia,
hypotension (lying and sitting)
and a low JVP, then give high-flow
oxygen and:
give a rapid fluid bolus (1 L of 0.9%
saline or colloid);
rate, BP and JVP in response to fluid
bolus;
hypovolaemia, give another rapid
fluid bolus;
JVP can be seen;
urine output.
The patient with an acute

abdomen requires a surgical
opinion as soon as resuscitation is
underway: surgery may be the
definitive treatment.
Pain should be promptly and

efficiently relieved with an NSAID,
eg diclofenac 75 mg im, or opioid,
eg morphine 5 mg sc plus 5 mg im
(with antiemetic such as cyclizine
50 mg iv).
Further comments
Management of acute pancreatitis
In some hospitals patients with
acute pancreatitis are managed on
medical wards by physicians, and
many hospitals have their own
protocols for doing so. Issues to
consider are as follows.
Analgesia: pethidine is preferred
in pancreatitis as morphine may
cause spasm of the sphincter of
Oddi and worsen the condition.
Antibiotics: their role in

management of acute pancreatitis
is unclear. They should always be
given if infection is proven, and
many would use a second- or
third-generation cephalosporin
and metronidazole in severely ill
patients.
Nutrition: early feeding is
associated with a significant
survival benefit in acute
pancreatitis. Enteral feeding
(oral, nasogastric or nasojejunal)
is recommended, but intravenous
feeding should be considered early
if the gut is not working
adequately.
cholangiopancreatography:
should be considered urgently
where there is evidence of
cholangitis or if gallstones are
implicated in the development of
pancreatitis, but after 24 hours of
pancreatitis oedema around the
ampulla makes this technically
very difficult.
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Acute pancreatitis may be due
to alcohol abuse: be vigilant for
signs of alcohol withdrawal and treat
this appropriately (see Section 1.4.3).
The presence of persistent pain,

fever and raised inflammatory
markers may suggest the
development of a pancreatic
abscess or infection of necrotic
pancreatic tissue. These
complications, which may require
surgical or radiological drainage,
are best diagnosed by CT scanning.
After recovery from an attack
of gallstone-related pancreatitis,
cholecystectomy should be
performed when all intra-abdominal
inflammation has settled. After
recovery from an attack of
pancreatitis of any cause abstinence
from alcohol is recommended,
particularly where alcohol was the
precipitating factor, and patient
and doctor should be aware of the
possibility that both endocrine and
exocrine pancreatic insufficiency
might develop.
1.4.5 Jaundice
Scenario
Common
Less common
Rare
Acute alcoholic hepatitis

Acute hepatitis A
Drug-induced hepatotoxicity
Intrahepatic cholestasis
due to sepsis
Acute hepatitis B
Acute hepatitis E
Autoimmune chronic
active hepatitis
Hepatic venous outflow

obstruction (BuddChiari
syndrome, right heart failure)
Weils disease
Wilsons disease
Pregnancy-associated liver
disease
DIAGNOSIS OF OBSTRUCTIVE JAUNDICE
Common
Less common
Rare
Choledocholithiasis
Carcinoma of pancreas
Cholangiocarcinoma
External compression from
malignant hilar lymph nodes
Primary sclerosing
cholangitis
posthepatic (eg biliary obstruction)

causes are most likely (Tables 23 and
24). History, examination and liver
function tests usually give a good
indication of which of these broad
categories applies to the patient,
but liver ultrasound is virtually
mandatory. Dilated common and
intrahepatic bile ducts indicate
obstruction; parenchymal liver
disease is more likely if the ducts
are normal sized (in the absence
of pain).
A 52-year-old woman with

a history of a previous
cholecystectomy presents with
This is accompanied by a dull
quadrant. She admits to drinking
at least one bottle of wine every
Not all jaundice in the alcohol

abuser is due to alcoholic
hepatitis.
other day for the last 2 years.
Introduction
Jaundice in adults is very rarely
due to a prehepatic cause
(eg haemolysis); hepatic
(eg parenchymal disease) or
50
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classically presents with painless

jaundice. Parenchymal liver
disease occasionally results in
right upper quadrant discomfort
due to stretching of the liver
capsule.
Pain is unusual in obstructive

jaundice that is not due to
CBD stones, but biliary pain must
be differentiated from abdominal
discomfort that can occur in a case of
hepatitis.
jaundice of 1 weeks duration.

ache in her right upper
DIAGNOSIS OF JAUNDICE DUE
TO INTRINSIC LIVER DISEASE
Important features to pursue include

the following.
Pain: the presence of pain can
indicate obstruction of the
common bile duct (CBD) with a
stone. Carcinoma of the pancreas
Weight loss: an ominous

symptom that may indicate
pancreatic carcinoma or
cholangiocarcinoma.
Change in colour of stool and
urine: in obstructive jaundice the
stool becomes paler (because bile
is unable to flow into the intestine
and colour the stool) and the
urine darker (excess conjugated
bilirubin). Remember, however,
that similar (though less extreme)
changes can also occur in
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parenchymal disease because

inflammation of the liver
parenchyma can cause local
obstruction of the bile cannaliculi
and interlobular bile ducts.
Fever: together with pain and
jaundice forms Charcots triad,
which is characteristic of
ascending cholangitis due
to bacterial infection in the
biliary system. This is usually a
complication of CBD stones and
rarely occurs with pancreatic
carcinoma.
offence (see Clinical Skills for PACES)

you need answers to the following
questions if the information does not
emerge without prompting: when
did you last drink any alcohol? Do
you drink daily or binge drink (have
months alcohol-free)? What type of
alcohol do you drink (spirits, beer)?
How much do you drink each week
now, and how much in the past?
(Figure 22 allows you to calculate
the number of units.) Have you ever
been told you have an alcohol
problem and told to stop drinking?
Relevant past medical and surgical

history
The details given here state that the
patient has had a cholecystectomy,
but it is always relevant to ask
jaundiced patients if they are known
to have gallstones. Patients can still
have retained stones in the CBD
despite cholecystectomy, as well
as forming new stones in situ, and
jaundice can develop as a result
of inadvertent biliary or vascular
complications following
cholecystectomy.

Alcohol history
The details given in this clinical
scenario clearly indicate that
alcohol may be the cause of the
problem, but this possibility is often
concealed. Sometimes a history that
includes head injuries, rib or other
peripheral fractures, unexplained
epileptic seizures, recurrent acute
pancreatitis and/or gastrointestinal
bleeding can suggest long-standing
alcohol excess. Without causing
The CAGE questionnaire can

be a useful aide-memoire for
confirming suspicion of alcohol excess,
particularly if the patient denies
having an alcohol problem. With
respect to drinking ask the patient
if he or she has ever:
C felt a need to Cut down?
A been Annoyed at the suggestion of
a drinking problem?
G felt Guilty about your drinking?
E had to have a drink (Eye opener) in
the morning?
Choledocholithiasis may
present some time after
previous cholecystectomy for
gallstones: this may be due to silent
stones having been missed in the CBD
at the time of operation, or possibly
formation of new stones in situ.
Drug history
It is essential to determine details of
all prescribed and non-prescribed
medications used by the patient
in the 6 weeks before jaundice
developed. Apparently innocent
medications can cause drug-induced
hepatotoxicity, common culprits
including Augmentin (co-amoxiclav)
and ibuprofen. Herbal and Chinese
medications have also been
implicated.
Travel history
Travel is a risk factor for jaundice: it
is essential to know if patients have
been abroad to a country where
hepatitis A or hepatitis E is endemic,
also if they have they been in contact
with anyone else with viral hepatitis.
Other causes of liver disease
Fig. 22 Number of units of alcohol present in various alcoholic beverages (10 g of alcohol = 1 unit).
It is important and appropriate to

take a sensitive history relating to
previous intravenous drug abuse and
a thorough sexual history. It is also
relevant to enquire about a family
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history of liver disease. Previous

blood transfusions, a history of
childhood jaundice or a history of
pregnancy-associated jaundice
occasionally give contributory
information.
Is the patient developing hepatic

encephalopathy?
A history of any change in the
ability to concentrate, eg read the
newspaper or do the crossword, can
suggest early hepatic encephalopathy,
as can reversal in the sleepwake
cycle with daytime sleepiness.
Examination
General features
As always when dealing with an
acute case, the first priority is to
decide if the patient is well, ill, very
ill or nearly dead, and to begin
resuscitation and get help from the
intensive care unit immediately if
required (as described in Sections
1.4.1 and 1.4.3). Then, in a patient
presenting with jaundice, consider
the diagnoses listed in Tables 23 and
24 and look for evidence of:
sepsis (fever, tachycardia,
hypotension, confusion);
malignancy (cachexia,
lymphadenopathy);
chronic liver disease (see
Section 1.2.2);
alcohol withdrawal (agitation,
hallucinations, tremor);
hepatic encephalopathy (see
Section 1.4.6);
Wernickes encephalopathy
(nystagmus, ophthalmoplegia).
pancreatitis or pancreatic
carcinoma.
Liver: usually firm, tender and
enlarged up to 10 cm in acute
alcoholic hepatitis; may be irregular
if there is associated cirrhosis, but
firm irregular hepatomegaly must
raise suspicion of malignancy
(primary or secondary). A hepatic
bruit may be heard in severe
alcoholic hepatitis as well as
with hepatocellular carcinoma.
Splenomegaly: suggests portal
hypertension in this context.
Gallbladder: if palpable,
remember Courvoisiers law,
which states that in the
presence of jaundice an enlarged
gallbladder is unlikely to be due
to gallstones (carcinoma of the
pancreas or the lower biliary tree
are more likely).
Ascites: suggests chronic liver
disease or malignancy.
Melaena: indicates upper
gastrointestinal bleeding.
Investigation
Ultrasound examination of the

abdomen
The key imaging test is ultrasound
examination of the abdomen to help
differentiate between hepatic and
biliary causes of jaundice, and to
provide evidence of chronic liver
disease/portal hypertension.
Liver, gallbladder and biliary
tree: appearance of the liver
parenchyma (fat infiltration,
heterogeneous suggesting
cirrhosis, focal lesion such as
new hepatoma), intrahepatic
and extrahepatic biliary ducts
(dilation), gallbladder (stones,
thick-walled suggesting
inflammation), liver vasculature
(portal vein thrombosis, hepatic
vein abnormalities).
Pancreas: not always well
visualised, but is there a focal
lesion?
Spleen: enlargement suggests
portal hypertension in this
context; splenic varices may
be seen.
Ascites: consistent with portal
hypertension or malignancy.
Routine blood tests and CXR

Check FBC, electrolytes, renal/liver/
bone profiles, clotting screen, blood
cultures, group and save. The
pattern of abnormality on liver
function tests is used to distinguish
between a hepatitic process (raised
alanine transaminase, ALT) and
an obstructive biliary process
(raised alkaline phosphatase, ALP),
although distinction on these
grounds is not infallible. The
CXR may show evidence of lung
cancer or metastatic disease.
In the patient presenting with

obstructive jaundice, consider
the following:
Gallstones.
Pancreatic carcinoma/
cholangiocarcinoma: usually
painless.
Pancreatitis: oedema/swelling of the
pancreatic head can compress the
bile duct.
BuddChiari syndrome: acute
hepatic vein obstruction results in
painful hepatomegaly, ascites and
jaundice (usually mild).
Abdomen
Look in particular for evidence of
the following.
Scars: previous cholecystectomy,
previous resection of colorectal
malignancy, previous surgery for
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Further blood tests

Gallstones can present acutely
with ALT higher than ALP, and in
end-stage liver disease liver enzymes
can be normal.
These will be dictated by clinical

suspicion and by the results of the
routine investigations described
above. If an acute infective hepatitis
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is thought most likely, then

testing for hepatitis A, B and E,
cytomegalovirus and EpsteinBarr
virus will be appropriate. If it is
thought that the patient has chronic
liver disease, then investigation
should be pursued as described in
Section 1.1.7.
Further imaging
If there is a focal lesion in the liver
or pancreas, then an abdominal
CT scan should usually be the
next investigation. In contrast, if
ultrasonography suggests biliary
pathology, then either endoscopic
retrograde cholangiopancreatography
(ERCP) (Fig. 23) or magnetic
resonance cholangiopancreatography
(MRCP) (Fig. 24) is indicated. In
centres where both of these tests
are available, ERCP should only
be performed if it is likely that a
therapeutic procedure is likely to be
performed because of the associated
morbidity and mortality.
Tissue biopsy
Broad indications for a liver
biopsy are when the aetiology of
liver disease is unclear, where the
degree of liver damage determines
the treatment (eg hepatitis B or C,
autoimmune hepatitis) or where
the nature of a focal lesion is
unclear.
Liver biopsy carries a

significant risk of bleeding: the
British Society of Gastroenterology
suggests transjugular liver biopsy if
the platelet count is <40 109/L and/or
the prothrombin time is prolonged by
more than 6 seconds.
Fig. 23 (a) Cholangiogram showing the CBD packed with stones. (b) The stones are seen within the
duodenum following a sphincterotomy and trawling of the CBD with a balloon.
Cholangitis
Management
If the patient is very ill, then
resuscitate as described in
Section 1.4.1. Specific management
will depend on the diagnosis.
Urgent drainage of the biliary

system is required in acute
ascending cholangitis with obstruction.
If the patient has high fever, rigors

or is obviously septicaemic, then
treat for septicaemia with the
working diagnosis of ascending
cholangitis. Most commonly gut
organisms are the culprits, eg
Escherichia coli, Klebsiella and
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Accumulation of sedatives
occurs in the presence of
alcoholic hepatitis and/or cirrhosis
and there is a risk of precipitating
encephalopathy: review dosing on a
daily basis and stop if the patient
becomes drowsy.
Have a very low threshold for

administering intravenous
thiamine to any patient at risk of
thiamine deficiency: the consequence
of untreated or unrecognised
Wernickes encephalopathy are
very serious.
Fig. 24 Magnetic resonance cholangiogram showing a stone in the CBD.
Enterobacter species, enterococci

and group D streptococci.
Antibiotics with broad-spectrum
cover should be given in accord with
local antimicrobial guidelines, but
these would typically comprise a
third-generation cephalosporin, a
quinolone such as ciprofloxacin or
an antipseudomonal penicillin such
as piperacillin/tazobactam (Tazocin).
failure may develop with rising

prothrombin time, increasing
jaundice, encephalopathy,
(varices or gastropathy) and
hepatorenal failure despite
abstinence and good supportive
medical care. Early active treatment
is essential, as is early referral to a
hepatologist.
The patient with an obstructed

infected biliary tree will not get
better until the obstruction is
relieved. Insertion of a stent allows
drainage around stones and can
produce temporary clinical
improvement in the ill patient with
deranged clotting. Alternatively,
sphincterotomy and stone extraction
may be achieved at initial endoscopy
(Fig. 23). Cholecystectomy is usual
at a later date to remove the focus,
unless comorbidity/frailty dictates
otherwise.
Important aspects of treatment

include assessment of prognosis
based on clinical presentation and
previous history of alcohol use,
careful attention to fluid balance,
scrupulous diagnosis and treatment
of infection, aggressive nutrition,
and prevention of alcohol
withdrawal. Corticosteroids are
used by some in the treatment
of alcoholic hepatitis, but the
timing and selection of patients
who should receive these are
controversial. UK liver centres do
not offer liver transplantation for
acute alcoholic hepatitis and those
with chronic decompensated
alcoholic liver disease need to
demonstrate 6 months abstinence
and a commitment to lifelong
alcohol avoidance.
The alcoholic with jaundice

The patient with jaundice in the
context of alcoholic liver disease
can be difficult to manage. If the
patient deteriorates in hospital, the
prognosis is poor. Progressive liver
54
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Scenario
A 23-year-old woman is brought
to the Emergency Department by
her parents with agitation and
confusion. After returning from
a weekend away they found her
at home with a suicide note and
six empty packets of paracetamol
by her side. On examination she
is dehydrated, agitated, confused
and has a tender liver edge.
Introduction
Acute liver failure is characterised
by rapid deterioration of liver
function resulting in altered
mentation and coagulopathy in
previously normal individuals:
the simplest definition requires
evidence of coagulopathy, usually
an INR >1.5, and any degree of
encephalopathy in a patient without
pre-existing cirrhosis and with an
illness of <26 weeks duration.
It is most commonly caused by
paracetamol overdose, other
drug-induced liver injury or viral
hepatitis, but in 20% of cases the
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DIAGNOSIS OF ACUTE LIVER FAILURE
Common
Less common
Rare
Paracetamol (acetaminophen)
overdose
Drug or toxin induced1
Cryptogenic (cause unknown)
Hepatitis A/hepatitis E
Hepatitis B2
Wilsons disease2
Autoimmune chronic
active hepatitis2
Hypotension/shock
Venous outflow obstruction
Hepatic veins (BuddChiari
syndrome)
Hepatic venules (venoocclusive disease)
Weils disease (leptospirosis)
Halothane
Acute fatty liver of pregnancy
1. Including NSAIDs, ecstasy (methylenedioxymethamfetamine, MDMA), herbal remedies,

mushroom poisoning, food contaminated with Bacillus cereus emetic toxin.
2. Patients with Wilsons disease, vertically acquired HBV or autoimmune hepatitis may be
included despite the possibility of cirrhosis if their disease has only been recognised for
<26 weeks.
failure, if so what the likely cause is,

and whether there is a background
of chronic liver disease.
Is the problem acute liver failure?

The differential diagnosis of
confusion/impaired consciousness
is wide (Tables 26 and 27), so for
fuller discussion of the clinical
approach to the patient presenting
with these problems see various
clinical scenarios in Acute Medicine
and Medicine for the Elderly.
Further discussion here will be
limited to the patient with acute
liver failure.
Cause of acute liver failure

cause remains unknown (Table 25).
Overall short-term survival with liver
transplantation is greater than 65%.
Acute liver failure is rare and

carries a high mortality: early
recognition, early and aggressive fluid
resuscitation, and early liaison with
a specialist liver unit improves
outcomes.

If severe encephalopathy is present
the patient will not be able to give a
reliable history, and information, if
any is available, will have to come
entirely from family or friends. In
this case the diagnosis and cause of
the problem seem reasonably clearcut, but this will not always be so
and it is necessary to determine if
the presenting problem is acute liver
DIAGNOSIS OF CONFUSION
Frequency1
Condition
Common
Hypoglycaemia
Urinary or chest infection
Drug side effect/drug withdrawal
Alcohol/alcohol withdrawal
Post ictal
Stroke
Unreported discomfort, eg urinary retention
Any cause of circulatory shock
Any cause of hypoxia
Less common/rare
Electrolyte disturbance: hyponatraemia, hypercalcaemia

Thiamine deficiency (Wernickes encephalopathy)
Other cerebral causes: metastases, haemorrhage (various),
head injury2 (concussion)
Organ failure: hepatic encephalopathy, renal failure
Other infective: meningitis, malaria
Other endocrine: hyperthyroidism, hypothyroidism
1. Frequency refers to UK practice.

2. Head injury usually obvious, but not always.
Has there been exposure to viral

infection, drugs or other toxins? In
this case the circumstances strongly
suggest paracetamol overdose, but it
is always appropriate to explore the
following: is there any possibility the
patient may have taken paracetamol,
and if so how much and over how
long a period? Has the patient
recently been suicidal? Any
previous overdoses?
Consider the other diagnoses listed
in Table 25: is the patient at risk
of any of these? A full drug history
is required. What medications
(prescribed and over-the-counter)
have been taken in the last few
weeks? Is the patient at risk of viral
hepatitis? Has she travelled overseas
recently?
Occasionally paracetamol
overdose can occur
unintentionally, with the drug taken
over several days for medicinal
purposes. Liver damage due to
paracetamol is potentiated by
concomitant alcoholic liver disease,
malnutrition and some regular
medications, eg phenytoin. Always
take a very careful history of drug use.
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DIAGNOSIS OF COMA
Frequency1
Condition
Common
Hypoglycaemia
Opioid toxicity
Head injury2
Post ictal
Subarachnoid haemorrhage
Stroke
Alcohol
Less common/rare
Other poisoning: benzodiazepine, tricyclic antidepressant,

carbon monoxide
Other intracranial haemorrhage: extradural, subdural
Hypothermia
Electrolyte disturbance: hyponatraemia
Organ failure: hepatic encephalopathy, advanced renal failure
Infective: encephalitis, meningitis, malaria
Non-convulsive status
or family history of other

autoimmune conditions, eg thyroid
disease, rheumatoid arthritis.
Leptospirosis (Weils disease):
if occupational or recreational
exposure to stagnant water;
look for myalgia and red eyes.
Heart failure/ischaemic hepatitis:
can mimic acute liver failure; when a
patient develops acute liver failure
in hospital, always look carefully in
the medical and nursing records for
documented periods of hypotension
prior to presentation.
Malignant infiltration of the
liver by cancer or lymphoma: can
occasionally present as acute liver
failure.
1. Frequency refers to UK practice.

2. Head injury usually obvious, but not always.
Acute liver failure: other important

questions
Visual hallucinations: if these
are associated with confusion,
consider alcohol withdrawal in
the differential diagnosis.
Epileptic fits: these usually
reflect alcohol withdrawal or
focal cerebral disease, but seizures
can occur at any stage of
encephalopathy, and unrecognised
hypoglycaemia must be excluded.
Onset of confusion in relation to
any history of jaundice: hepatic
encephalopathy usually follows
jaundice, and the time from onset
of jaundice to encephalopathy is
of prognostic significance. In
paracetamol hepatotoxicity,
encephalopathy typically occurs
within 2448 hours of jaundice
and within 4896 hours of the
overdose.
Abdominal pain: acute liver failure
rarely causes pain, but there may
be mild right-sided abdominal
discomfort. If pain is prominent,
consider hepatic vein occlusion
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(BuddChiari syndrome). In
paracetamol overdose the pain
typically subsides as the patient
gets better.
Differential diagnosis of the

patient with acute liver failure:
important issues in the history
Drug hepatotoxicity: exposure
to any new drug, particularly an
NSAID, in the 2 weeks preceding
onset of jaundice; remember that
it is important to exclude nonproprietary drugs such as herbal
remedies.
Viral hepatitis: risk factors for
exposure to hepatitis B, eg in
prostitutes, homosexuals,
intravenous drug abusers and
with use of potentially infected
blood products from abroad.
Wilsons disease: if less than 40
years old; there may be a family
history and/or chronic neurological
symptoms, eg tremor, change in
handwriting.
Autoimmune chronic active
hepatitis: must always be excluded,
particularly in middle-aged women;
look for a previous medical history
Is there a history of chronic

confusion and/or poor
concentration? This does not occur
in acute liver failure and suggests
chronic liver disease in this context.
Has the patient got chronic liver
disease or is she at risk of this
(see Section 1.1.7)?

Patients with acute liver failure may
eventually need super-urgent liver
transplantation. Particularly in
paracetamol overdose it is useful to
gather as much history as possible
from relatives, friends and the
patients own GP about previous
health and contact with the medical
profession.
Examination
General features
If the patient is nearly dead

(unrecordable BP, thready pulse,
depressed conscious level), call
immediately for help from the
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hypotension, low JVP). Check
pulse oximetry. In the early stages
of acute hepatic failure vital signs
are normal; late features include
tachycardia and hypotension.
A rising BP and a falling pulse
rate are very late signs that
indicate cerebral oedema and are
associated with a poor prognosis.

start resuscitation immediately
whilst completing the history and
examination.
Check Glasgow Coma Scale

(GCS) score/grade hepatic
encephalopathy: this is the
hallmark of fulminant hepatic
failure and comprises a spectrum
of neuropsychiatric abnormalities
in patients with liver dysfunction
in the absence of other known
brain disease. There are
characteristic personality changes,
intellectual impairment and a
depressed level of consciousness.
Note that focal neurological
signs are not expected and their
presence should alert to the
possibility of a focal cerebral
lesion, with intracerebral
haemorrhage likely in this context.
Decorticate/decerebrate posture
and fixed pupils are late signs of
irreversible cerebral oedema.
Grades of hepatic
encephalopathy
Grade I: altered mood, impaired
concentration and psychomotor
function.
Grade II: drowsy, inappropriate

behaviour, able to talk.
Grade III: very drowsy, disorientated,
agitated, aggressive.
Grade IV: coma, may respond to
painful stimuli.
Note that ascites would be very

unusual in paracetamol poisoning
but may occur with more gradual
onset of acute hepatic insufficiency,
ie so-called subacute liver failure.
Investigation
Routine tests in any very ill patient
The onset of confusion or
drowsiness in a patient with
acute liver injury is ominous and
necessitates advice from a liver unit.
Stigmata of chronic liver disease

(see Section 1.2.2): jaundice is
often but not always seen at
presentation with acute liver
failure. Look for clues to risk
behaviour, eg tattoos, injection sites,
previous evidence of self-harm. If
the patient is less than 40 years
old, consider an ophthalmic slit
lamp examination for Kayser
Fleischer rings of Wilsons disease.
Look for signs of masquerading
non-hepatic illnesses such as
sepsis, heart failure and
disseminated malignancy.
Development of bilateral
subconjunctival haemorrhages
seems to be a feature peculiar to
paracetamol-associated liver failure
and should raise suspicion of this
diagnosis in patients presenting late.
Abdomen
Right upper quadrant tenderness
may be present. If the liver cannot
be palpated, or the normal hepatic
dullness cannot be detected by
percussion, this may be indicative
of decreased liver volume due to
massive hepatocyte loss. An enlarged
liver may be seen early in viral
hepatitis or with malignant
infiltration, congestive heart failure
or acute BuddChiari syndrome.
FBC, clotting screen/INR,

electrolytes, glucose, renal/liver/
bone function tests, magnesium,
amylase/lipase, C-reactive protein
(CRP), blood group and save.
Blood, urine and sputum cultures.
Arterial blood gases and lactate.
Pregnancy test (if appropriate).
In the context of the patient with
acute liver failure, look particularly
for evidence of synthetic failure
(coagulopathy, hypoglycaemia) and
concurrent renal and/or respiratory
failure. Hyponatraemia is common.
One-third of patients with acute liver
failure have pancreatitis at autopsy.
Note that marked elevations in CRP
are not in keeping with fulminant
liver failure; if found, consider the
possibility of sepsis as the primary
illness and remember that this is a
leading cause of death in acute liver
failure. In paracetamol overdose
an arterial lactate concentration
>3.5 mmol/L early (4 hours)
after admission to a liver unit or
>3.0 mmol/L after fluid resuscitation
(12 hours after admission) identifies
patients who are likely to die early
and who would therefore potentially
benefit from transplantation. There
is a high mortality of fulminant
hepatitis E in pregnant women.
The liver function tests

themselves may aid in
understanding the aetiology of the
liver disease, but the transaminase
level itself is of no prognostic significance
and just indicates liver cell damage.
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Abdominal imaging
Where the prothrombin time
(PT) in seconds is greater than
the time after a paracetamol overdose
(in hours), eg a PT of 40 seconds
30 hours after the overdose as opposed
to a PT of 50 seconds 60 hours after
the overdose, there is a particular risk
of developing liver failure.
Blood tests to determine the cause

of acute liver failure
These should clearly be determined
by the clinical context. In some
instances, such as the case described
here, the diagnosis will be clear-cut
and extensive investigation is not
required to establish the cause of
liver failure, but where the cause is
not obvious the following would be
appropriate.
Paracetamol level.
Toxicology screen as appropriate.
Viral hepatitis serology: anti-HAV
IgM, HBsAg, anti-HBc IgM, antiHEV, anti-HCV (extended screen
if these are negative and no other
diagnosis established, including
herpes simplex virus (HSV),
cytomegalovirus (CMV),
EpsteinBarr virus, adenovirus,
parvovirus B19).
Caeruloplasmin level (if patient
<40 years).
Autoimmune markers: antinuclear
antibodies, liver antibodies,
immunoglobulin levels.
HIV status.
Leptospiral serology.
Surface antigen is cleared

from the serum by the time of
presentation with jaundice in up to 5%
of patients with fulminant hepatitis
due to hepatitis B virus: diagnosis
therefore rests on an appropriate
pattern of antibody response (eg
IgM anti-core) or DNA levels.
58
MMC Core Curriculum
Ultrasound is particularly useful

to look for evidence of background
chronic liver disease (splenomegaly,
varices, ascites, portal vein
thrombosis), and it is also the
first-line investigation if Budd
Chiari syndrome is suspected.
Cross-sectional imaging with CT
should be performed if the patient
is stable enough and the diagnosis
is at all in doubt.
Management
Early involvement of specialist
hepatology services is important
in managing patients with acute
liver failure. The key aspects of
management include the following.
Oxygenation: give high-flow
oxygen to maintain arterial
saturation >92%.
Treat/prevent hypovolaemia: use
4.5% albumin (rather than 0.9%
saline in this context).
Treat/prevent hypoglycaemia: give
10% dextrose (or, if needed, and
by a central line, 50% dextrose) at
a rate to keep fingerprick blood
glucose in the range 4 7 mmol/L.
Correct electrolyte abnormalities,
including phosphate: but note
that hyponatraemia is due to
water excess and not to sodium
deficiency and should not be
treated by infusion of saline.
Monitor renal function closely:
renal replacement therapy should
be instituted sooner rather than
later if the patient develops renal
failure.
Avoid unnecessary medications:
in particular NSAIDs, diuretics,
opiates and sedatives.
Enteral or parenteral nutrition:
should be initiated without delay.
N-Acetylcysteine: give 150 mg/kg
in 1 L 5% dextrose over 24 hours
(note different regimen if given as

a specific antidote to paracetamol
toxicity; see below).
Prophylaxis against sepsis: give
broad-spectrum antibiotics and
fluconazole.
Prophylaxis against
gastrointestinal stress ulceration,
eg ranitidine or omeprazole.
Consider treatments to minimise
absorption of nitrogenous
substances from the gut (not used
in all liver centres): disaccharide
laxative, eg lactulose, in dose
sufficient to produce two to
three soft stools daily; enemas;
broad-spectrum poorly absorbed
antibiotic, eg neomycin 1 g qds
by mouth.
Avoid precipitating Wernickes

encephalopathy: if there is
a history of high alcohol intake or
malnourishment, give thiamine
intravenously before giving glucose,
eg Pabrinex (thiamine) intravenous
high potency, 10 mL over 10 minutes
three times daily.
Do not routinely correct

coagulopathy: bleeding is rare
in acute liver failure and the PT is an
important prognostic indicator.
Hepatic encephalopathy
The patients neurological status
must be reviewed regularly: if
hepatic encephalopathy develops,
progression from grade I to grade IV
and development of cerebral oedema
may occur within an hour or two.
Patients who are agitated or
aggressive may need ventilation to
enable care to be given; those with
grade III or IV encephalopathy
should be ventilated electively
because of the risk of cerebral
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oedema; and those with grade

II encephalopathy should be
considered for ventilation to
facilitate safe transfer to a liver unit.
Cerebral oedema is not likely
in patients with grade III
encephalopathy, but with
progression to grade III the risk
increases to 2535% and with
grade IV coma to 6575% or more.
The signs of hypertension,
bradycardia and irregular
respirations (Cushings triad) are
not uniformly present; these and
other neurological changes such
as pupillary dilatation or signs of
decerebration are typically evident
only late in the course. Liver units
vary in their monitoring for, and
management of, this condition, but
many will directly measure cerebral
perfusion pressure (CPP) and
intracranial pressure (ICP),
maintaining ICP below 2025 mmHg
and CPP above 5060 mmHg
if possible. Strategies for care
include nursing at 2030,
hyperventilation to reduce CO2,
controlled hypothermia, mannitol
boluses (0.51 g/kg repeated
as long as serum osmolality
<320 mosmol/L), controlled
hypernatraemia (boluses of 30%
hypertonic saline to maintain
serum sodium 145155 mmol/L),
and occasionally short-acting
barbiturates such as thiopental.
Specific treatments
Paracetamol overdose Liver
failure from paracetamol overdose
is preventable if the patient presents
early and N-acetylcysteine is
correctly administered, and this
treatment improves prognosis even
in those who present over 16 hours
afterwards. Following loading
TABLE 28 GUIDELINES
FOR REFERRAL TO SPECIALIST CENTRES IN
CASES OF PARACETAMOL TOXICITY ACCORDING TO FINDINGS

ON DAYS
24
FOLLOWING THE OVERDOSE
Day 2 (2448 hours)
Day 3 (4872 hours)
Day 4 (7296 hours)
Arterial pH <7.3
INR >3
Encephalopathy
Creatinine >200 mol/L
Hypoglycaemia
Arterial pH <7.3
INR >4.5
Encephalopathy
Any rise in INR

Encephalopathy
(150 mg/kg iv over 15 minutes

followed by 50 mg/kg over 4 hours)
continue maintenance dose of
150 mg/kg for 24 hours, which can
be given as a concentrated solution
if there is a problem with fluid
overload. If appropriate refer the
patient to a specialist centre
(Table 28).
Paracetamol overdose
If in doubt, give N-acetylcysteine.
Other causes of acute liver failure

Other specific therapies will depend
on the particular diagnosis, eg
prednisolone in autoimmune
hepatitis, lamivudine in hepatitis B,
aciclovir in HSV or varicella
infection, ganciclovir in CMV
infection, delivery in pregnancyassociated disease. Clearly such
management needs to be carefully
discussed with a hepatologist.
Further comments
Criteria for liver transplantation
Urgent hepatic transplantation is
indicated in acute liver failure where
prognostic indicators suggest a

high likelihood of death. Classically,
those listed for super-urgent liver
transplantation are predicted to
have a survival of less than 3 days
without a new organ. The Kings
College Criteria recommend
transplantation in the following
circumstances.
Paracetamol-induced acute liver
failure: arterial pH <7.3 following
adequate volume resuscitation
(irrespective of coma grade) or
PT >100 seconds (INR >6.5) and
serum creatinine >300 mol/L in
patients in grade III/IV coma.
Non-paracetamol-induced acute
liver failure: PT >100 seconds
(irrespective of coma grade)
or any three of the following
(irrespective of coma grade): drug
toxicity/indeterminate cause of
acute liver failure; age <10 years
or >40 years; jaundice to coma
interval >7 days; PT >50 seconds
(INR >3.5); serum bilirubin
>300 mol/L.
Amendments continue to be
suggested and prognostic markers
such as lactate, alpha-fetoprotein,
phosphate and factor V levels have
been used by some.
MMC Core Curriculum
59
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DISEASES AND TREATMENTS
2.1 Oesophageal
disease
reflux disease
Aetiology/pathophysiology/
pathology
Reflux of gastric acid into the
lower oesophagus can cause
mucosal injury (reflux oesophagitis).
Chronic reflux oesophagitis may
induce the appearance of ectopic
gastric and intestinal mucosa in
the lower oesophagus (gastric or
intestinal metaplasia), a change
termed Barretts oesophagus
that is considered premalignant
because it is associated with an
increased risk of oesophageal
adenocarcinoma. Chronic reflux
oesophagitis may also lead to
fibrotic healing and the formation
of a peptic stricture.
Incompetence of the lower
oesophageal sphincter is the main
factor in reflux of acid. Gastric
acid secretion is usually normal.
Hiatal hernias, occurring in
1015% of the general population,
are more prevalent with increasing
severity of reflux disease and may
contribute to abnormal reflux by
both reducing basal lower
oesophageal pressure and impairing
effective oesophageal clearance
of acid (Fig. 25).
Reflux may result in a spectrum
of damage to the oesophagus,
ranging from microscopic changes
only through to circumferential
60
Fig. 25 CXR showing a hiatus hernia behind the heart.
oesophagitis with ulceration and

stricture formation. This can be
graded using the SavaryMiller
classification.
Grade I: one or more nonconfluent erosions.
Grade II: confluent but not
circumferential erosions.
Clinical presentation
Common
Burning retrosternal pain aggravated
by lying down or bending forwards,
and by spicy foods, citrus fruits and
alcohol. Regurgitation of acid, water
brash, chest pain, odynophagia
(painful swallowing) and dysphagia.
Grade III: circumferential erosive

oesophagitis.
Grade IV: grade III plus
ulceration, stricture formation
or Barretts oesophagus.
Epidemiology
Gastro-oesophageal reflux
symptoms (retrosternal
burning, acid regurgitation)
are common and occur on a
daily basis in up to 10% of the
population. Only about one-third
of patients will have endoscopic
evidence of oesophagitis. Peptic
strictures occur in 723% of
patients with untreated reflux
oesophagitis.
Oesophagitis and Barretts

oesophagus can be entirely
asymptomatic. Conversely, reflux
symptoms can be severe without
endoscopic or histological evidence
of oesophagitis.
Uncommon
Haematemesis or iron-deficiency
anaemia.
Physical signs
Usually no physical signs.
Occasionally, severe acid reflux into
the pharynx can lead to hoarseness
and pharyngitis. Weight loss if there
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GASTROENTEROLOGY AND HEPATOLOGY: DISEASES AND TREATMENTS
has been a delayed presentation of

an oesophageal stricture.
Radiotherapy-induced
oesophagitis (eg treatment of
bronchial carcinoma).
Investigation/staging
Long-term
Treatment

Indicated if troublesome or
refractory reflux symptoms.
Gastroscopy is mandatory
in those who have alarm
symptoms (haematemesis,
dysphasia, weight loss, anaemia)
and desirable in middle-aged or
elderly patients with new onset of
symptoms.
Patients in their twenties or early
thirties who require infrequent,
intermittent courses of acidsuppressing therapy probably do not
warrant endoscopy, but those with
persistent symptoms requiring longterm therapy should be examined
to define the extent and severity
of oesophagitis (or presence of
Barretts oesophagus) and thereby
guide therapy.
Oesophageal manometry and

24-hour ambulatory pH monitoring
This is useful in patients with
atypical symptoms, in those who
do not respond to acid-suppressant
therapy, and as part of the work-up
for patients considered for antireflux
surgery (along with oesophageal
manometry).
Differential diagnosis
Common differential diagnoses
include the following.
Cardiac pain.
Oesophageal carcinoma: benignlooking peptic strictures must be
brushed and biopsied to exclude
malignancy.
Infections with herpes simplex or
Candida.
Drugs (eg alendronate, NSAIDs,
ferrous sulphate, potassium salts)
that may cause oesophagitis.
complications such as stricture

formation or Barretts metaplasia.
Emergency
Patients with dysphagia need rapid
assessment with either a barium or
Gastrograffin swallow followed
by endoscopy. Barium swallow is
usually performed first to define
the position and extent of any
stricture. Patients with a stricture
demonstrated on barium swallow
should proceed to endoscopy for
biopsy and brushings to exclude
malignancy. All patients with benign
peptic oesophageal strictures should
be commenced on a proton pump
inhibitor (PPI) to prevent further
acid reflux and damage. Concurrent
oesophagitis per se may contribute
to the dysphagia. If symptoms are
significant, oesophageal dilatation
should be performed. Initial
improvement occurs in >80%,
although one-third require repeat
dilatation within 12 months despite
acid-suppression therapy.
Short-term
Treatment of uncomplicated
gastro-oesophageal reflux should be
directed at alleviating the symptoms.
A graded approach is usual, starting
with antacids and lifestyle measures
(stopping smoking, avoiding
precipitants), then histamine
H2 receptor antagonists with or
without prokinetic agents (eg
metoclopramide), and finally
PPIs or antireflux surgery. When
oesophagitis is demonstrated
endoscopically or microscopically,
aggressive initial treatment with a
PPI, followed by an H2 receptor
antagonist, and eventually
symptomatic treatment with
antacids should be initiated. Healing
of oesophagitis (grade II or more
severe) is desirable to prevent
Many patients with symptomatic

gastro-oesophageal reflux relapse
following cessation of medical
therapy. PPIs are the most effective
agents in the initial healing of reflux
oesophagitis (8090% within 8
weeks with standard doses) and in
subsequent maintenance therapy.
Aggressive acid-suppression therapy
with PPIs has been shown to
decrease the need for repeat
dilatation of oesophageal peptic
strictures.
Complications
Common
Most patients with gastro oesophageal
reflux disease can be well controlled
with acid-suppression therapy.
Relapse of symptoms is common
on withdrawal of treatment. It is
estimated that up to one-quarter
of patients with untreated reflux
oesophagitis will develop strictures.
Long-term acid reflux is important
in the development of Barretts
oesophagus.
Prognosis
The advent of the powerful PPI
agents means the vast majority
of patients can be rendered
asymptomatic. Antireflux surgery is
an alternative where medical therapy
fails, or if the patient is young and
unwilling to take medications
indefinitely. Although reflux disease
has little effect on life expectancy, it
may predispose to the development
of oesophageal adenocarcinoma.
Long-term severe reflux predisposes
to Barretts oesophagus with its
malignant potential.
Prevention
Aggressive control of acid
secretion is likely to be important
61
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in preventing peptic stricture

formation in those with significant
reflux oesophagitis. Once a stricture
has formed, long-term therapy with
a PPI is indicated.
or pleuritic chest pain. Chagas

disease, caused by South American
trypanosomal infection, is rare but
may present with identical clinical,
endoscopic and radiological features
to achalasia.
Common
Treatment
gastro-oesophageal reflux disease

without documented acid reflux or
response to acid-suppressive
treatment.
Disease associations
Scleroderma may result in
severe oesophagitis and stricture
formation.
FURTHER READING
Katz PO, ed. Gastroesophageal reflux
disease. Gastroenterol. Clin. North Am.
1999; 28.
Vigneri S, Termini R, Leandro G, et al.
A comparison of five maintenance
therapies for reflux esophagitis.
N. Engl. J. Med. 1995; 333: 110610.
Dysphagia (difficulty in swallowing)

and odynophagia (painful swallowing)
are typical. Regurgitation may cause
nocturnal cough and respiratory
complications in achalasia.
Physical signs
Often absent, but weight loss may be
evident.
Barium or Gastrograffin swallow
Wu AH, Tseng CC and Bernstein L.

Hiatal hernia, reflux symptoms, body
size, and risk of esophageal and gastric
adenocarcinoma. Cancer 2003; 98:
9408.
2.1.2 Achalasia and

oesophageal dysmotility
pathology
The cause of disordered oesphageal
motility is generally unknown.
Achalasia is the most severe form,
characterised by a hypertensive
lower oesophageal sphincter (LOS)
with failure of LOS relaxation in
response to swallowing. Peristalsis
is absent in the body of the
oesophagus, which becomes
progressively dilated. Histological
examination reveals loss of
myenteric plexus ganglia.
Epidemiology
Achalasia is rare, with an
approximate incidence of 1 in
100,000 in the West. Less severe
forms of oesophageal dysmotility
may be more widespread and may
account for some cases of apparent
62
This should be performed before

endoscopy, showing food debris in
the oesophagus with dilatation in
later stages and a smooth, tapered
birds beak at the distal end (Fig. 26).
Gastroscopy should always

be performed to exclude
malignancy at the gastro-oesophageal
junction: this can mimic achalasia,
particularly in elderly people.
Medical
Explanation and reassurance are
essential. Prokinetic agents such
as metoclopramide may provide
some symptomatic relief. Calcium
antagonists (eg nifedipine 10 mg
tds) or nitrates (eg isosorbide) can
be tried, but response is variable. It
is pragmatic to offer a proton pump
inhibitor to minimise any effect
of gastro-oesophageal reflux.
Endoscopic and surgical treatments
should be explored if achalasia
progresses to cause dysphagia and
regurgitation.
Pneumatic (balloon) dilatation or

surgical myotomy (Hellers)
Results are comparable, with
7585% having excellent relief
of their symptoms. Perforation
occurs in 15% after dilatation.
Late stricture formation occurs
in about 3% of surgically treated
patients.
Manometry
The typical pattern of progressive
peristaltic contraction waves in
the oesophagus in response to
swallowing is lost. There may be
diffuse spasm (diffuse oesophageal
spasm) or intense prolonged
contractions (nutcracker
oesophagus). In achalasia the
body of the oesophagus fails to
contract peristaltically and there
is increased pressure at the LOS,
which fails to relax in response to
swallowing.
Intrasphincteric injection of
botulinum toxin
Reflux oesophagitis and stricture

formation (<1%) may occur after
pneumatic dilatation.
The pain associated wth oesophageal

dysmotility may mimic cardiac
This is as effective as pneumatic

dilatation at 4 weeks but not at
6 months, when repeat injection
is often required.
Complications
Common
Risk of oesophageal carcinoma is
increased about 15-fold in patients
with achalasia.
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Prognosis
Over 90% of patients with achalasia
are improved following pneumatic
dilatation or surgical myotomy.
Repeat dilatation is frequently
required.
FURTHER READING
Leyden JE, Moss AC and MacMathuna
P. Endoscopic pneumatic dilation
versus botulinum toxin injection in
the management of primary achalasia.
Cochrane Database Syst Rev 2006; (4):
CD005046.
Seelig MH, DeVault KR, Seelig SK,
et al. Treatment of achalasia: recent
advances in surgery. J. Clin.
Gastroenterol. 1999; 28: 2027.
2.1.3 Oesophageal cancer and

Barretts oesophagus
pathology
Risk factors for carcinoma of
oesophagus are shown in Table 29.
Oesophageal carcinoma is
microscopically squamous
cell or adenocarcinoma.
Barretts oesophagus is defined
as replacement of the normal
squamous epithelial lining of the
oesophagus by metaplastic columnar
epithelium. It is strongly associated
with chronic gastro-oesophageal
reflux of acid, which is thought to
damage the normal lining with
replacement by columnar, acidresistant lining. The main importance
of Barretts oesophagus is that it
is probably a precursor lesion of
oesophageal adenocarcinoma,
with a 40% lifetime risk of this
complication in patients with a
segment of Barretts >3 cm long.
Fig. 26 (a) CXR of achalasia: note the widened mediastinum due to the grossly distended oesophagus.
(b) Barium swallow of achalasia: the distal end of the dilated oesophagus has a characteristic beaked
appearance.
Epidemiology
Worldwide, squamous cell
carcinoma is most common. There
are geographical variations in its
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TABLE 29 RISK
FACTORS FOR CARCINOMA OF OESOPHAGUS
Squamous cell carcinoma
Adenocarcinoma
CT of the thorax and abdomen
Smoking
Alcohol
Malnutrition
Achalasia
Postcricoid web1
Familial tylosis2
Barretts oesophagus
Gastro-oesphageal reflux
Undertaken to look for evidence of

local invasion into mediastinal
structures and for hepatic or
pulmonary metastases.
1. BrownKellyPaterson/PlummerVinson syndrome.
2. Hyperkeratosis of palms of hands and soles of feet.
incidence, with the highest rates

(>100 per 100,000) in China, Iran and
South Africa. In the Western world
the incidence of adenocarcinoma of
the oesophagus is rising rapidly for
reasons that are unknown, and it is
more common than squamous cell
carcinoma.
The true prevalence of Barretts
oesophagus is unknown since many
cases are silent and therefore not
detected. About 10% of patients
undergoing upper gastrointestinal
endoscopy for reflux symptoms are
found to have a columnar-lined
oesophagus (Barretts), and half
will have specialised intestinal-type
lining. Autopsy studies suggest a
prevalence of around 1%.
Common
Progressive dysphagia with weight
loss is the usual presentation of
oesophageal cancer. Initially subjects
may have dysphagia only for solids
such as meat and bread, eventually
reporting difficulty swallowing
purees and liquids. May be
discovered as part of the work-up
of iron-deficiency anaemia.
Barretts oesophagus may be
asymptomatic, or it may be
discovered as a result of diagnostic
tests for gastro-oesophageal reflux
symptoms.
64
rugal folds), with biopsy confirming

columnar metaplasia (Fig. 28).
Uncommon
Dyspepsia or heartburn.
Pain due to local invasion into the
spine or intercostal nerves.
Hoarseness due to involvement
of the recurrent laryngeal nerve
by middle and upper third
oesophageal carcinomas.
Rare
Tracheo-oesophageal fistulae.
Physical signs
Signs may reflect the extent and
duration of disease, with weight loss,
evidence of complications such as
aspiration pneumonia, and rarely
hoarseness due to tumour invasion
of the recurrent laryngeal nerve.
Endoscopic ultrasound
If available this provides more
accurate local staging of the tumour.
Unfortunately most are advanced at
presentation: T3, with invasion
through the oesophageal wall into
the adventitia; or T4, with spread
into adjacent structures, eg aorta,
pulmonary vessels.
Benign oesophageal stricture:
usually obvious at endoscopy,
confirmed with biopsy and
brushings, but repeat sampling if
clinical suspicion but histology
negative.
Gastric carcinoma (usually from
the cardia) invading the lower
oesophagus.
Note that biopsy from a point distal
to the squamouscolumnar junction
(eg from the proximal end of a hiatus
hernia) will lead to a false-positive
diagnosis of Barretts oesophagus.
Treatment
This is the initial investigation of
choice for patients presenting with
dysphagia (Fig. 27).

The key test for obtaining multiple
biopsies for histology and brushings
for cytology for a tissue diagnosis.
In Barretts, the oesophagus has a
characteristic red, velvety, columnar
epithelium extending proximally
from the gastro-oesophageal
junction (proximal end of gastric
Emergency
Presentation with complete or
near-complete obstruction (liquids/
liquidised food) is not unusual, in
which case dilatation may be needed
at the time of diagnostic endoscopy.
The risk of oesophageal

perforation is higher with
dilatation of malignant compared
with benign strictures.
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Short-term
Aim is rapid work-up to select
appropriate candidates (less than
one-third) for curative surgery,
usually with thoracoabdominal
CT and endoscopic ultrasound
if available. Preoperative enteral
or parenteral nutrition and
physiotherapy are important.
Subtotal oesophagectomy with
anastomosis to fashioned gastric
tube is often employed.
Long-term
Palliation indicated in most cases,
with either endoscopic or
radiological positioning of
expandable metal stents, laser
photocoagulation or radiotherapy
(internal or external).
Complications
Oesophagectomy
Anastomosis may leak or dehisce
(has less rich blood supply
compared with rest of intestine).
Oesophageal stent
Perforation during stent placement
and laser photocoagulation. Stent
migration.
Prognosis
Fig. 27 Barium swallow showing an irregular malignant stricture in the distal oesophagus.
Morbidity
Aim with the majority is palliation,
ie ensuring reasonable swallowing.
Mortality
Overall median survival <1 year;
5-year survival rate 5%. Earlier
stage and absence of lymph node
involvement yields better results.
There is 510% mortality with
oesophagectomy.
Fig. 28 Barretts oesophagus. The squamous

columnar junction lies above the gastrooesophageal junction.
65
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Prevention
2.2 Gastric disease
Primary
Aggressive suppression of acid
secretion in patients with Barretts
oesophagus or reflux oesophagitis.
Long-term acid suppression may
arrest or reverse Barretts changes.
Endoscopic surveillance for

adenocarcinoma
This involves yearly endoscopy
with multiple quadrantic biopsies,
particularly if the segment of Barretts
is long (>3 cm) and shows intestinaltype metaplasia. Junctional and
gastric-type metaplasia probably
have very low malignant potential
and are not usually surveyed.
Endoscopic ablative therapy

The role of laser, photodynamic
therapy or electrocoagulation to
ablate Barretts oesophagus is
unclear, but may be considered for
those who have high-grade dysplasia
or carcinoma in situ and whose
comorbidity prevents surgery.
FURTHER READING
Allum WH, Griffin SM, Watson A
and Colin-Jones D (on behalf of the
Association of Upper Gastrointestinal
Surgeons of Great Britain and Ireland,
the British Society of Gastroenterology,
and the British Association of Surgical
Oncology). Guidelines for the
management of oesophageal and
gastric cancer. Gut 2002; 50 (Suppl. 5):
v1v23. Full text available at
http://www.bsg.org.uk/

Helicobacter pylori
Physical signs
Anaemia.
Epigastric tenderness.
Investigations/staging
pathology
Helicobacter pylori infection
and NSAID use are the two most
common aetiological factors. Risk
of peptic ulceration appears to be
higher in NSAID users if they are
also infected with H. pylori. There
are different H. pylori strains, Cag-A
being associated with more severe
gastritis and intestinal metaplasia.
H. pylori is unique in that it
produces a urease that is made
use of in diagnostic tests.
Endoscopy
To establish the diagnosis and to
take biopsies from a gastric ulcer
to ensure it is benign.
Antral and gastric body biopsies
for H. pylori.
Risk of rebleeding can also be
assessed in those presenting with
haematemesis or melaena.
Some gastric ulcers are

malignant despite appearing
benign endoscopically, hence biopsy
is vital.
Epidemiology
In the UK, serological testing for
H. pylori shows that up to 50% of
50 year olds and up to 20% of
20 year olds have been infected.
This is a cohort effect and does
not mean that 1% acquire the
infection each year. H. pylori causes
90% of duodenal ulcers and 60%
of gastric ulcers.
The lifetime risk of duodenal ulcer
is 410% and of gastric ulcer
34%, males more than females.
H. pylori detection
There are many methods by
which H. pylori can be identified.
Serological testing for IgA or IgG
antibodies to H. pylori is only useful
if previously untreated. Samples
taken at endoscopy can be subjected
to a CLO test or histological
examination (silver stain) (Figs 29
and 30).
Serology cannot be used to
assess whether the infection
has been successfully eradicated with
treatment, as antibodies persist often
for decades.
Common
Epigastric pain or indigestion.
Enzinger PC and Mayer RJ. Esophageal

cancer. N. Engl. J. Med. 2003; 349: 224152.
Lethargy from anaemia.

Melaena and/or haematemesis.
Spechler SJ. Clinical practice: Barretts

esophagus. N. Engl. J. Med. 2002; 346:
83642.
Watson A, Heading RC and Shepherd
NA, eds. Guidelines for the Diagnosis
and Management of Barretts Columnarlined Oesophagus. London: British Society
for Gastroenterology, 2005. Full text
available at http://www.bsg.org.uk/
66
13
Uncommon
If present in the pylorus there may
be gastric outlet obstruction with
vomiting.
Rare
Perforation with abdominal pain
and signs of an acute abdomen.
C urea breath test
A non-invasive method of assessing

whether H. pylori has been
successfully eradicated.
More novel methods of detecting
H. pylori include measurement of
bacterial antigens within stool
samples.
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Reinfection following eradication of

H. pylori is rare in adults. Antibiotic
resistance to metronidazole and/or
clarithromycin occurs in 1020%.
Some patients require further tripletherapy regimens, which may require
modification using culture and
sensitivities from gastric aspiration.
Ulcer healing Six weeks of PPI to
heal the ulcer.
Long-term
Fig. 29 CLO test. This relies on the fact that H. pylori produces a urease. A gastric biopsy is placed on the
test card. If H. pylori is present, the indicator turns from yellow to red. A result is obtained in 1 hour.
A patient who has had a

complicated peptic ulcer (bleeding
or perforation) should probably
remain on long-term antisecretory
therapy (PPI or histamine H2
receptor blocker). If an NSAID is
required following a gastrointestinal
bleed, then a cyclooxygenase (COX)2 inhibitor combined with a PPI has
been suggested, although COX-2
inhibitors are not currently in
favour. If NSAID therapy is required
after an uncomplicated peptic ulcer,
consider using misoprostol or a PPI
in addition.
Complications
Perforation and bleeding.
Gastric carcinoma: less than 3% of
gastric ulcers are malignant.
Fig. 30 Histology of gastric mucosal biopsy showing the presence of H. pylori on the epithelial surface.
Oesophageal reflux: there is

concern that eradication of
H. pylori may be associated with
an increased incidence of
oesophageal reflux.
Prognosis
If abdominal pain, see

Sections 1.1.6 and 1.4.4.
If gastrointestinal haemorrhage,
see Section 1.4.3.
Treatment
Emergency
See Section 1.4.3. Endoscopic
therapy can be used to try to control
bleeding using injection (adrenaline)

and thermal contact devices
(electrocoagulation).
Short-term
Eradication of H. pylori
Triple-drug regimens are effective
in 8095% of cases, eg 7 days of
twice-daily proton pump inhibitor
(PPI), clarithromycin 500 mg
bd or amoxicillin 1 g bd, and
metronidazole 500 mg bd.
Most peptic ulcers heal when a

PPI is used, but 20% will develop
recurrent ulceration even if H. pylori
infection is eradicated.
Prevention
Primary
Avoidance of NSAIDs and smoking.
Use misoprostol or PPI with an
NSAID.
67
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Gastrinoma is associated with
multiple peptic ulcers. May occur in
isolation or associated with multiple
endocrine neoplasia (MEN) type 1.
FURTHER READING
Malfertheiner P, Megraud F, OMorain
C, et al. Current concepts in the
management of Helicobacter pylori
infection: the Maastricht III Consensus
Report. Gut 2007; 56: 77281.
Common
Small superficial tumours are
often asymptomatic. Later
symptoms are weight loss (61%),
abdominal pain (51%), nausea
(34%) and dysphagia (26%). Malaise
due to iron-deficiency anaemia.
Acute upper gastrointestinal
haemorrhage.
Rare
Rostom A, Dube C, Wells G, et al.
Prevention of NSAID-induced
gastroduodenal ulcers. Cochrane
Database Syst Rev 2002; (4): CD002296.
Vomiting from pyloric obstruction.
Physical signs
Common
2.2.2 Gastric carcinoma

pathology
Gastric carcinomas are
adenocarcinomas and can be
classified histologically as diffuse
or intestinal. They are associated
with atrophic gastritis and intestinal
metaplasia, but there is no evidence
that long-term drug-induced
achlorhydria is associated with
gastric cancer. Distal gastrectomy is
associated with a 12-fold increased
risk of gastric cancer after 15
20 years. There is also increasing
evidence of an association between
Helicobacter pylori and gastric
cancer, with prospective serological
studies showing a three- to six-fold
increased risk, mainly of distal
tumours. Countries with high rates
of gastric cancer also have a high
incidence of H. pylori infection.
Epidemiology
The highest incidence is in Japan and
China; in the USA, incidence is 10 per
100,000. Overall the incidence is
falling, but adenocarcinoma affecting
the cardia and gastro-oesophageal
junction is becoming more common.
It rarely occurs before the age of
40 years, peaking in the seventies.
68
Usually there are no abnormal

clinical findings.
Abdominal CT: used for staging

to assess whether a tumour is
surgically resectable. Staging is
graded from I to IV, dependent
on the TNM (tumour, nodes,
metastases) classification.
Endoscopic ultrasound: useful in
the staging of gastric neoplasia as
it gives information on depth of
invasion locally as well as lymph
node involvement and may
identify tumours that can be
removed endoscopically by
endomucosal resection.
Treatment
Surgery
Indicated if early tumour confined to
stomach (ie stage I).
Uncommon
Epigastric mass.
Malignant ascites due to
peritoneal seeding.
Rare
Enlarged supraclavicular lymph
node (Virchows).
Chemotherapy
Neoadjuvant chemotherapy
may reduce tumour bulk
and invasion prior to surgery.
Combined surgery and
chemotherapy are better
than chemotherapy alone.
Conservative
The red flag symptoms for

urgent referral for suspected
gastric cancer all suggest advanced
disease; there are no symptoms of
early gastric cancer.
Indicated for linitus plasticus

(involving whole of stomach) or
those with locally invasive and
widespread metastatic disease.
Complications
Haemorrhage.
Investigations
FBC: an iron-deficiency anaemia
is present in 42%.
Tumour markers:
carcinoembryonic antigen is
not helpful diagnostically. It is
elevated in 1020% of patients
with resectable tumour.
Endoscopy: essential for
histological diagnosis and
assessment of size and position
of the tumour (Fig. 31).
Prognosis
The 5-year overall survival rates
are poor in the UK at 15%. Stage I
(confined to stomach) with surgery
has a 5-year survival rate of 50% in
the UK and 90% in Japan.
Prevention
Screening by endoscopy is advocated
in Japan, where 4060% of early
gastric cancers can be identified,
but this is not the case in the UK,
Europe and the USA.
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leiomyomas have a characteristic

endoscopic appearance with
central ulceration. Around 1%
are malignant. Endoscopic
ultrasound can also be used to
further characterise the lesion.
If bleeding occurs, surgical
resection is indicated.
Gastric and MALT lymphomas

Around 36% of gastric tumours
are lymphomas, predominantly
extranodal B-cell non-Hodgkin
type. Low-grade lymphomas are
associated with Helicobacter pylori
infection in 7298% of cases, H.
pylori infection probably having
resulted in the migration of B cells
into the gastric mucosa as the
stomach is usually devoid of
mucosal-associated lymphoid
tissue (MALT).
Most patients present over the
age of 50 years, with non-specific
dyspepsia, nausea and vomiting.
There are usually no physical signs
and weight loss is rare. There may
be no macroscopic abnormality or
simply gastritis. Endoscopic biopsies
are needed to make the diagnosis.
Fig. 31 Endoscopic appearance of (a) normal gastro-oesophageal junction and (b) gastric carcinoma.
Pernicious anaemia is associated
with a two- to three-fold increased
risk of carcinoma of stomach.
Cunningham D, Allum WH, Stenning

SP, et al. Perioperative chemotherapy
versus surgery alone for resectable
gastroesophageal cancer. N. Engl. J.
Med. 2006; 355: 1120.
FURTHER READING
Allum WH, Griffin SM, Watson A
and Colin-Jones D (on behalf of the
the British Society of Gastroenterology,
and the British Association of Surgical
Oncology). Guidelines for the
management of oesophageal and
gastric cancer. Gut 2002; 50 (Suppl. 5):
Long-term follow-up studies show

that eradication of H. pylori can
cause resolution of most low-grade
MALT lymphomas confined to the
mucosa. Non-responsive MALT
lymphomas may have undergone
high-grade transformation and
require chemotherapy with
chlorambucil. Surgery is only
necessary for those with
complications such as
haemorrhage or perforation.
Leiomyoma
This is a benign tumour of smooth
muscle. Most tumours less than
2 cm are asymptomatic. In contrast,
tumours greater than 2 cm may
ulcerate and cause profuse
gastrointestinal haemorrhage.
Submucosal endoscopic biopsy
is often non-diagnostic, but
Gastrinoma
Gastrinoma causes multiple
duodenal ulcers and is associated
with steatorrhoea due to acidic
destruction of pancreatic lipase. It
may be sporadic or associated with
multiple endocrine neoplasia type 1.
Sporadic tumours are usually single
69
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and found in the duodenal wall or

pancreas; 50% are benign. Treatment
is by resection or with high-dose
proton pump inhibitor. There is
a good 10-year prognosis.
FURTHER READING
Banks PM. Gastrointestinal
lymphoproliferative disorders.
Histopathology 2007; 50: 4254.
Hong SS, Jung HY, Choi KD, et al.
A prospective analysis of low-grade
gastric malt lymphoma after
Helicobacter pylori eradication.
Helicobacter 2006; 11: 56973.

Dieulafoy lesion
Fig. 32 Angiodysplastic lesion found in the duodenum of a patient with severe iron-deficiency anaemia.
This is due to an artery in the

submucosa with an overlying
mucosal defect that results in
massive upper gastrointestinal
haemorrhage. It is usually found
within 6 cm of the gastro-oesophageal
junction. The mean age at
presentation is 50 years. The lesion
may be missed at endoscopy when
air inflates the stomach. Endoscopic
banding can be employed to stop the
bleeding, but some require surgical
oversewing of the artery.
Vascular ectasia (angiodysplasia)

These are dilated, distorted,
thin-walled vessels which are usually
multiple (Fig. 32). They occur
anywhere along the gastrointestinal
tract, but commonly in the caecum
and descending colon. They usually
present in middle age, most typically
with iron-deficiency anaemia, but
15% are associated with massive
bleeding. Treatments include medical
therapies such as oestrogens,
endoscopic electrocoagulation and
surgical resection (Fig. 33). They
are associated with aortic stenosis
(for reasons unknown).
70
Fig. 33 Appearance of angiodysplastic lesion following argon plasma coagulation therapy.
Hereditary haemorrhagic
telangiectasia
This is an autosomal dominant
condition associated with skin and
mucosal haemorrhage. The vascular
lesions commonly occur in the
stomach and small bowel and
lead to recurrent gastrointestinal

haemorrhage and transfusiondependent anaemia. Cutaneous
manifestations include telangiectasia
over the lips, fingers and oral
mucosa. Treatment is with
oestrogens.
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Meckels diverticulum
This congenital abnormality is
present in 0.33% of the population.
It is found on the antimesenteric
border of the small bowel within
100 cm of the ileocaecal valve.
Most are asymptomatic, but 80%
contain ectopic gastric mucosa.
Complications include haemorrhage
(melaena or dark red blood
per rectum), obstruction or
intussusception. The diagnosis is
made by small bowel enema or
technetium-99 scan (which detects
parietal cells).
micelle formation and thus impair

fat absorption. Other mechanisms
may include direct damage to the
enterocytes/mucosal surface or
brush border enzymes, or indirect
damage by deconjugated bile salts.
Bacteria also metabolise vitamin B12.
Epidemiology
Incidence and prevalence are
unknown but may be decreasing
as a result of reduced surgical
intervention for peptic ulcer disease.
Common
Chronic diarrhoea or steatorrhoea.
2.3 Small bowel disease

2.3.1 Malabsorption
Malabsorption occurs when the
constituents of the small intestine
are either transported too quickly
or not adequately broken down,
or there is reduced capacity for
absorption. The most common
cause of malabsorption in the UK is
coeliac disease (see Section 2.3.2);
other causes are described below.
2.3.1.1 Bacterial overgrowth

pathology
Akin to fresh water in a free-flowing
river compared with stagnant water
in a pond, bacterial overgrowth is
promoted by any condition that
impedes the normal flow of
intestinal contents. The normal
small intestine is not sterile but
houses <104 organisms/mL; in
bacterial overgrowth this rises to
104109 organisms/mL. The
mechanisms by which such
bacterial overgrowth produces
diarrhoea (usually steatorrhoea)
are not completely clear, but
deconjugation of bile salts by
bacteria may interfere with fat
Uncommon
Neurological disorder, eg peripheral
neuropathy, subacute combined
degeneration of the spinal cord
(secondary to B12 deficiency). Folic
acid deficiency in the elderly is
sometimes the only indicator of
malabsorption.
and cause a rise in breath hydrogen

or methane. Lactulose is a nonabsorbable synthetic disaccharide
that is metabolised by colonic
bacteria. Bacterial overgrowth of the
small bowel causes an early rise, but
false positives may occur with rapid
small intestinal transit.
Jejunal aspiration and culture

The gold standard for diagnosis, but
invasive and rarely used, although it
does give bacterial sensitivities that
can be useful for optimising
antibiotic regimens in those
patients with resistant bacteria.
Small bowel follow-through

Small bowel radiology is indicated
to look for diverticula in those
patients who do not have a known
underlying structural small bowel
abnormality.
Other causes of diarrhoea and
steatorrhoea (see Sestions 1.1.3
and 1.4.2).
Physical signs
Treatment
None due to bacterial overgrowth

per se. Look for neuropathy and
associated diseases, eg Crohns,
previous peptic ulcer disease surgery.
Antibiotic treatment with the aim of

suppressing bad bacteria in favour
of good bacteria. Augmentin (coamoxiclav) or a 5-fluoroquinolone
has been shown to be effective. Some
patients require cyclical rotating
courses of antibiotics. Vitamin B12
injections may be required.
Investigation
Bacterial overgrowth
Be alert to the diagnosis in
patients developing diarrhoea who
have a predisposition for this problem,
eg those with structural abnormalities
of the small bowel.
Glucose or lactulose hydrogen

breath test
This is the usual diagnostic test.
Glucose is absorbed completely in
the upper small bowel; if bacteria
are present they will metabolise
glucose to hydrogen and methane
Complications
Malnutrition, neuropathy and
deficiencies of fat-soluble vitamins.
Prognosis
Most of the predisposing conditions
are not correctable, so is often a
chronic recurring condition unless
cyclical antibiotics are employed.
Morbidity probably mostly due to
lack of diagnosis. Unlikely to have
any effect on mortality.
See Table 30.
71
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Hypolactasia
TABLE 30 CAUSES
OF BACTERIAL OVERGROWTH
Anatomical
Functional
Immune deficiency
Surgical blind loops

Billroth II
Roux-en-Y
Jejunal diverticula
Strictures
Crohns disease
Radiation enteritis
Enterocolic fistulae
Autonomic neuropathy
Amyloid
Diabetes mellitus
Systemic sclerosis
Hypogammaglobulinaemia
Achlorhydria
FURTHER READING
Quigley EM and Quera R. Small
intestinal bacterial overgrowth:
roles of antibiotics, prebiotics, and
probiotics. Gastroenterology 2006;
130 (2 Suppl. 1): S78S90.
Singh VV and Toskes PP. Small bowel
bacterial overgrowth: presentation,
diagnosis, and treatment. Curr. Treat.
Options Gastroenterol. 2004; 7: 1928.

malabsorption
Chronic pancreatitis/pancreatic
insufficiency
May occur following repeated
acute attacks of pancreatitis,
alcohol being the most common
culprit, or without any identifiable
cause. Steatorrhoea develops when
less than 10% of pancreatic exocrine
function remains. Diagnosis is made
by a combination of imaging and
dynamic function tests. Treatment is
with pancreatic enzyme supplements
titrated against response.
Whipples disease
A rare disease caused by Tropheryma
whippelii that usually occurs in
white middle-aged or elderly men.
It is characterised by malabsorption,
migratory polyarthritis, anaemia
and weight loss. Neurological and
cardiac involvement may occur, as
well as pigmentation and clubbing.
Jejunal biopsy shows large foamy
72
macrophages in the lamina propria

which contain material positive for
periodic acidSchiff (PAS) stain.
Treatment is with sulfamethoxazole
and trimethoprim for 1 year.
Prognosis is good.
Primary hypolactasia is common

in most races apart from northern
Europeans. Lactase, a brush border
enzyme that breaks lactose into
glucose and galactose, disappears
after weaning. Subsequent lactose
ingestion (milk) causes an osmotic
diarrhoea. It is diagnosed on clinical
grounds or by lactose hydrogen
breath test.
Secondary hypolactasia can be
caused by anything that damages
the small bowel mucosa (eg viral
gastroenteritis, coeliac disease,
Crohns disease) and reverses on
treatment of the underlying disorder.
Short bowel syndrome

Tropical sprue
Occurs in residents of the tropics
(India, Asia, Central America) but is
rare in Africa. It usually follows an
acute diarrhoeal illness. There is
persistent bacterial overgrowth
in the small bowel, resulting
typically in steatorrhoea, weight
loss, anaemia, hypoproteinaemia
and glossitis. Small bowel biopsy
( jejunal) shows partial villous
atrophy and round cell infiltration
of the lamina propria. The mortality
is 1020% within months if
untreated, but it responds readily
to tetracycline 250 mg qds and folic
acid 5 mg tds.
Giardiasis
Caused by the flagellated protozoan
Giardia lamblia. It is usually
contracted abroad, although it
can occur in UK. It has faecaloral
transmission and is characterised by
persistent diarrhoea after an acute
diarrhoeal episode. Malabsorption
is unusual but can occur. Diagnosis
is made by finding trophozoites in
jejunal aspiration and biopsy (stool
culture is less sensitive). Tinidazole
2 g as a single dose or metronidazole
800 mg tds for 3 days is very effective.
Malabsorption occurs when the

length of effective small intestine
is reduced to less than 100 cm
by surgical resection, mesenteric
infarction, severe Crohns disease or
radiation injury. Absorptive capacity
is overwhelmed and diarrhoea and
malabsorption ensue. Adaptation
occurs, with improvement for up
to 2 years. The colon contributes
to energy supplies via fermentation
of non-absorbed dietary fibre to
short-chain fatty acids which are
then absorbed. Treatment is difficult
and includes dietary modification,
attempts to slow intestinal transport
and increase absorption, parenteral
nutrition, and bowel transplantation
in severe cases.
Post gastric surgery

Frank malabsorption following gastric
surgery is rare. Iron deficiency is
common. The cause is multifactoral
and includes hypoacidity, chronic
bleeding from friable anastomosis,
and decreased intake. Vitamin B12
deficiency may also occur due to
lack of intrinsic factor or bacterial
overgrowth. Fat malabsorption is
caused by an impaired pancreatic
response due to bypassing of the
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duodenum in a Billroth II
gastrectomy, vagal denervation, or
rapid gastric emptying preventing
optimal mixing with pancreatic juices.
FURTHER READING
Nightingale J and Woodward JM
(on behalf of the Small Bowel and
Nutrition Committee of the British
Society of Gastroenterology).
Guidelines for management of
patients with a short bowel. Gut 2006;
55 (Suppl. 4): iv1iv12. Full text available
at http://www.bsg.org.uk/
2.3.2 Coeliac disease

pathology
Coeliac disease or gluten-sensitive
enteropathy is a state of heightened
immunological responsiveness
to ingested gluten in genetically
susceptible individuals. It is
characterised by damage of the
small intestinal mucosa due to
intolerance to a group of proteins
present in wheat, barley and rye. The
aetiology is unknown but probably
requires both environmental and
genetic factors: 1012% of firstdegree relatives of an affected
individual have the disease;
8590% of patients carry major
histocompatibility complex (MHC)
class II markers HLA-DR3 and HLADQ2, and the remainder are DQ8
positive (these HLA markers are
present in a large proportion of the
population and less than 0.1% of
individuals with this haplotype
actually develop coeliac disease,
but it is not possible to have coeliac
disease without one of these HLA
markers). Tissue transglutaminase
has recently been identified as
the autoantigen towards which
endomysial antibodies are directed.
Gliadin peptides are rich in glutamic
acid residues that are modified
by tissue transglutaminase and
TABLE 31 MODIFIED MARSH
CRITERIA FOR HISTOLOGICAL
CLASSFICATION OF COELIAC DISEASE
Marsh grade
Histological findings
0
1
2
3a
3b
3c
Normal
Increased intraepithelial lymphocytes
1+ crypt hyperplasia
2+ partial villous atrophy
2+ subtotal villous atrophy
2+ total villous atrophy
presented to intraepithelial T cells by

antigen-presenting cells via the HLADQ2 molecule. Activation of T cells
results in patchy damage to the
small intestinal mucosa, with the
proximal small bowel more severely
affected. Changes in the intestinal
lining are graded using the modified
Marsh criteria shown in Table 31.
described in China or the Caribbean.

It occurs more commonly in females
(2:1). In adults, diagnosis peaks in
the fourth and fifth decades in
women, and the fifth and sixth
decades in men.
Coeliac disease may present

for the first time in the seventh
or eighth decade of life.
Epidemiology
Coeliac disease was once thought to
be rare but has been shown by large
screening studies in Europe and the
USA to affect 1 in 100200 people.
It is rare in Africa and has not been
TABLE 32 SYMPTOMS
Symptoms and signs are as shown in
Table 32.
AND SIGNS OF COELIAC DISEASE
Common
Less common
Rare
Anaemia1,2: iron, folate or mixed

deficiency, often found by chance
Diarrhoea1,2: typically pale,
bulky, offensive and difficult
to flush
Weight loss1,2/failure to
thrive1/short stature
Irritable bowel-type symptoms2
(eg distension, pain, bloating,
borborygmi)
Anorexia, nausea, vomiting1
Aphthous oral ulceration,
glossitis, stomatitis
General malaise, lethargy
Mood change1,2, anxiety,
depression
Infertility/amenorrhoea
Bone pain: osteomalacia,
osteoporosis
Dermatitis herpetiformis
Neurological: peripheral
neuropathy, cerebellar
ataxia, etc.
Tetany: hypocalcaemia
Rickets
Bruising and nightblindness: deficiencies of
fat-soluble vitamins A and K
Constipation
1. Commonest signs and symptoms in infancy.

2. Commonest signs and symptoms in adults.
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The diagnosis of coeliac

disease should be seriously
considered in any patient with
diarrhoea/steatorrhoea or with ironor folate-deficiency anaemia.
Barium follow-through
The most important issue is to have

a high index of suspicion for the
diagnosis.
This is often abnormal but is

not usually needed to make the
diagnosis. The normal fine feathery
appearance of the mucosa is replaced
by a coarser pattern (transverse
barring) or a tubular featureless
appearance in severe disease.
Blood tests
Investigation
An FBC may show anaemia (iron

and/or folate deficiency) and the
blood film a dimorphic population
of red blood cells with HowellJolly
bodies (associated hyposplenism).
Occasionally there is isolated B12 or
folic acid deficiency. Some newly
diagnosed patients have raised
transaminases, but these usually
normalise after treatment.
Serology
Anti-gliadin antibodies are
commonly present but have a lower
sensitivity than other serological
markers. The combination of antiendomysial antibody (anti-EMA)
and anti-tissue transglutaminase
antibody (anti-tTG) has a sensitivity
and specificity above 95%. Some
patients have an associated IgA
deficiency that can render these
tests negative as they are IgA based.
However, one of the anti-gliadin
antibodies is IgG based and there
are IgG versions of anti-EMA and
anti-tTG.
Histology
Histological examination of small
bowel biopsies remains the gold
standard for diagnosing coeliac
disease, and should be performed
if the condition is suspected whilst
the subject is on a gluten-containing
diet. Previously jejunal material was
obtained via a Crosby capsule, but
74
now the standard technique is

to obtain four duodenal biopsies
because of the patchy nature of the
intestinal findings.
If diarrhoea: giardiasis, infection,

inflammatory bowel disease.
If abdominal pain and/or weight
loss: Crohns disease and
thyrotoxicosis.
If steatorrhoea: exocrine
pancreatic insufficiency.
If iron-deficiency anaemia:
consider other reasons for
blood loss.
Other causes of villous
atrophy include giardiasis,
hypogammaglobulinaemia, bacterial
overgrowth, tropical sprue, cows
milk sensitivity, Whipples disease,
lymphoma and NSAIDs.
routine follow-up duodenal biopsies

may not be useful.
Persistence of anti-EMA
6 weeks after starting dietary
therapy suggests non-compliance.
Dietary supplementation
Iron, folate, vitamin D and calcium
supplementation may be required at
diagnosis depending on the degree
of abnormality and symptoms.
Non-responsive coeliac disease

Some patients do not respond
adequately to a gluten-free diet
and this may indicate the presence
of associated conditions or
complications. The most common
reason for continued symptoms
in coeliac disease is continued
gluten exposure and therefore
reassessment of the diet (perhaps
best performed by a dietitian) is
essential. Associated conditions
include exocrine pancreatic
insufficiency (up to one-third),
new thyroid disease (12%) and
lactose intolerance. Alternatively
one of the complications may have
arisen.
Immunosuppression
Treatment
Gluten-free diet
Strict withdrawal of gluten from
the diet is advocated: 85% of cases
respond to this and relapse on its
reintroduction. Physicians and
dietitians should be involved in
educating the patient about the
condition, and membership of
Coeliac UK encouraged. Compliance
can be assessed using serial antibody
measurements, which usually
diminish once gluten is withdrawn
from the diet. The small intestinal
mucosa may take many years to
normalise, if at all, and therefore
In those patients who do

not respond to dietary
treatment, steroids and other
immunosuppressants, such as
azathioprine, may be required
to induce remission.
Important information for

patients
Symptoms of coeliac disease are
usually relieved and complications
reduced by permanent adoption of
strict gluten-free diet: join Coeliac UK
(see http://www.coeliac.co.uk/ for
details).
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TABLE 33 CONDITIONS
2.4.1 Acute pancreatitis

ASSOCIATED WITH COELIAC DISEASE
Condition
Prevalence of coeliac disease (%)
Type 1 diabetes mellitus
Thyroid disease
Idiopathic dilated cardiomyopathy
Rheumatoid arthritis
Sjgrens syndrome
Infertility
Osteoporosis
IgA deficiency
Epilepsy (with cerebral calcifications)
Downs syndrome
70
37
Up to 7
5
36
3
3
3
23
3
2.5
2.3
2
Complications
Bone disease in up to 40%
(osteoporosis and osteomalacia).
Increased risk of gastrointestinal
malignancy (enteropathyassociated T-cell lymphoma,
squamous cell carcinoma of the
pharynx and oesophagus, and
small intestinal adenocarcinoma).
Associated diseases are shown in
Table 33.
FURTHER READING
Al-Toma A, Verbeek WH and Mulder CJ.
Update on the management of
refractory coeliac disease. J.
Gastrointest. Liver Dis. 2007; 16: 5763.
Hyposplenism: common and

related to duration and severity
of disease, but rarely causes
problems.
Ciclitira P. Guidelines for the

Management of Patients with Coeliac
Disease. London: British Society for
Gastroenterology, 2002. Full text
Ulcerative enteritis: a rare

complication that may be an
early manifestation of malignant
lymphoma.
Goddard CJ and Gillett HR. Complications

of coeliac disease: are all patients at
risk? Postgrad. Med. J. 2006; 82: 70512.
Osteopenia and osteoporosis

are relatively common at
diagnosis, but malignant complications
are rare.
Prognosis
Mortality
Mortality is increased in coeliac
disease, chiefly due to an excess of
malignant disease. Adoption of a
gluten-free diet appears to protect
against this complication and results
in a normal lifespan.
2.4 Pancreatic disease
Diseases of the pancreas

provide an enormous challenge
to the clinician, and although patients
with the more common forms of
pancreatic disease (ie acute
pancreatitis and pancreatic carcinoma)
have historically been managed by
surgical teams, there is a growing
trend for non-surgical (ie medical)
management.
pathology
This is an acute inflammatory
process of the pancreas with variable
involvement of other regional tissues
or remote organ systems. Once the
process has started, the degree of
pancreatic necrosis is variable and
in part related to proteolytic
autodigestion of the gland.
The most common causes of acute
pancreatitis in the UK are gallstones
(3050%) and alcohol (1040%), but
a significant number of cases do not
have an immediately obvious cause
(15%).
In the absence of gallstones or

alcohol, consider the following
rare causes of acute pancreatitis before
making an idiopathic diagnosis.
Drugs: steroids, azathioprine,
sulfasalazine, furosemide.
Pancreas divisum: congenital
malfusion of the dorsal and ventral
pancreatic buds.
Sphincter of Oddi dysfunction: high
pressure sphincter causing duct
hypertension.
Hypertriglyceridaemia: may be
associated with alcohol abuse or
diabetes.
Hypercalcaemia/
hyperparathyroidism.
Viral: mumps, coxsackievirus B,
EpsteinBarr virus, cytomegalovirus.
Hereditary pancreatitis (see
Section 2.4.2).
Hypothermia: rewarming injury to
the pancreas.
Common
Abdominal pain, usually epigastric
and radiating through to the back.
Vomiting.
Hypovolaemia, circulatory
collapse, hypoxia.
75
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Uncommon
Jaundice suggests the presence of an
associated cholangitis and raises the
probability of gallstones.
Rare
No pain (consider hypothermia).
Physical signs
Common
In mild acute pancreatitis there
may be few physical signs.
Otherwise expect abdominal/
epigastric tenderness or infrequent
or absent bowel sounds.
Assessment of cause
Glasgow/Ranson criteria
Three or more positive criteria,
based on initial admission score and
subsequent repeat tests over 48 hours,
constitutes severe disease.
Age >55 years.

White blood cell count >15 109/L.
Glucose >10 mmol/L.
Urea >16 mmol/L.
PaO2 <8 kPa (60 mmHg).
Calcium <2 mmol/L.
Albumin <32 g/L.
Lactate dehydrogenase >600 U/L.
Aspartate/alanine aminotransferase
>100 U/L.
Uncommon
In patients with more severe
disease there will be clinical
evidence of hypovolaemia and
systemic inflammation. Other
features may include:
mental state (the patient may be
agitated and delirious);
tachycardia;
hypotension;
fever;
peripheral cyanosis;
The Acute Physiology and Chronic

Health Evaluation (APACHE II)
scoring system is used in many
intensive care units. An APACHE II
score of 9 or more is considered to
constitute a severe attack of acute
pancreatitis.
A peak C-reactive protein level
>210 mg/L in the first 4 days of the
attack (or >120 mg/L at the end of
the first week) indicates severe
disease.
An abdominal ultrasound should

be performed within 24 hours of
admission. This will determine
whether there are gallstones present
and may demonstrate biliary
dilatation, suggesting common
bile duct obstruction.
Assessment for complications

Depending on the method of
presentation, some patients will
undergo abdominal CT as their first
imaging investigation to exclude
other causes of acute abdomen.
A CT with contrast should be
performed in cases of severe
pancreatitis between 3 and 10 days
after admission. In addition to
identifying secondary complications
such as pseudocyst formation
(Fig. 34), the extent of pancreatic
necrosis carries prognostic value
(Table 34).
This includes perforated peptic
ulcer, intestinal ischaemia/infarction,
ectopic pregnancy, aortic dissection,
myocardial infarction (see
Section 1.4.4).
peritonism.
Rare
Cullens sign (periumbilical bruising)
and Grey Turners sign (flank
bruising) are both associated with
severe haemorrhagic pancreatitis.
Diagnosis with serum amylase
Serum amylase is diagnostic of
pancreatitis if more than three times
the upper limit of normal for the
laboratory. Alternatives include
serum lipase and possibly urinary
trypsinogen.
Assessment of severity
Severity can be assessed using the
Glasgow/Ranson criteria.
76
Fig. 34 Pancreatic pseudocyst complicating acute pancreatitis. The stomach is stretched over the large
pseudocyst (arrow). (Courtesy of Dr N.D. Derbyshire, Royal Berkshire Hospital.)
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TABLE 34 CONTRAST-ENHANCED CT
GRADING OF
ACUTE PANCREATITIS
Grade
CT morphology
Normal
Focal or diffuse gland enlargement; small intrapancreatic fluid collection
Any of the above plus peripancreatic inflammatory changes and <30%

gland necrosis
Any of the above plus single extrapancreatic fluid collection and

3050% gland necrosis
Any of the above plus extensive extrapancreatic fluid collection,

pancreatic abscess and >50% gland necrosis
Treatment
Emergency
Resuscitation Intravenous fluids
to restore circulating volmue (may
require central venous pressure
monitoring) and oxygen. Patients
with severe pancreatitis (as defined
above) should be managed in either
a high-dependency unit or an
Short-term
(ERCP) If gallstones are present
on ultrasound or if the patient has
clinical features of cholangitis (fever,
jaundice), early ERCP (ie within the
first 24 hours) should be considered
on the principle that early relief
of biliary obstruction will reduce
complications. If this is not
performed within 2448 hours,

oedema of the papilla makes ERCP
technically difficult. ERCP can also
be employed in pseudocyst drainage
if there is communication with the
pancreatic duct.
Endoscopic ultrasound (EUS)
The advent of EUS has enhanced
endoscopic interventions for
pancreatic disease. A pseudocyst
that does not resolve spontaneously
within 6 weeks usually needs
draining to prevent complications
(infection, rupture or bleeding).
This can be done into the stomach
using EUS guidance, which
identifies a suitable tissue plane
and helps avoid vessels in the area
(Fig. 35).
EUS may also reveal a cause for
acute pancreatitis that cannot
be identified by other imaging
modalities, eg microlithiasis,
small tumours or cysts.
Other Surgery may be indicated in
cases of infected necrosis. Pancreatic
abscess may require CT-guided
drainage.
Analgesia The pain of acute

pancreatitis is usually intense and
requires opiate analgesia. Pethidine
is usually used because it has less
effect on the sphincter of Oddi than
morphine.
Nutrition Although historically
patients with acute pancreatitis
were fasted with gastric aspiration
(drip and suck), early nasojejunal
feeding is now favoured once
vomiting has settled.
Antibiotics Use of blind
broad-spectrum antibiotics is
controversial, although recent
studies have suggested a reduction
in septic complications. Antibiotics
should be used in cases of proven
infection or organ failure, with a
third-generation cephalosporin
generally recommended.
Fig. 35 Drainage of a pancreatic pseudocyst into the stomach showing the internal transgastric drain in
situ. (Courtesy of Dr N.D. Derbyshire, Royal Berkshire Hospital.)
77
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Long-term
Management of the appropriate risk
factor helps to prevent recurrent
attacks:
abstinence from alcohol;
early cholecystectomy if gallstones
are confirmed to be the underlying
cause;
control lipids/calcium.
Complications
TABLE 35 PROGNOSIS
Scoring system
Glasgow/Ranson criteria1
<2
35
>6
APACHE II 2
<9
>13
FROM ACUTE PANCREATITIS
Mortality (%)
5
10
60
low
high
1. Scored at 48 hours from the onset of symptoms: sensitivity 5785%; specificity

6885%.
2. Can be scored at any time: sensitivity at admission 3470%, at 48 hours <50%;
specificity at admission 7698%, at 48 hours 100%.
Common
Pancreatic pseudocyst/abscess
(5%): persistent pain and/or fever
suggests the development of a
pancreatic pseudocyst or abscess,
as does a persistently raised
amylase.
Paralytic ileus.
Hypovolaemic shock.
Renal failure.
Hypocalcaemia.
Hypoxia.
Uncommon
prognosis may be worse in

idiopathic pancreatitis.
Morbidity and mortality

This depends on the severity of the
attack (Table 35).
Prevention
Primary
Other than a reduction in alcohol
consumption there is little scope
for primary prevention of acute
pancreatitis.
Portal vein/mesenteric thrombosis.
Secondary
Adult respiratory distress

syndrome.
Cholecystectomy.
Ascites.
Ascites due to pancreatitis has

a high amylase content.
Abstinence from alcohol.

Management of risk factors.
FURTHER READING
Prognosis
Thirty per cent of patients have
recurrent attacks, which are more
likely in pancreatitis related to
alcohol consumption. Overall
78
pathology
Chronic pancreatitis is defined as a
progressive inflammatory condition
of the pancreas characterised by
irreversible changes that typically
cause pain and/or permanent loss
of both endocrine and exocrine
function. This evolution usually
occurs over a period of several years.
Clinically, this helps to distinguish
between acute first-onset
pancreatitis, recurrent acute
pancreatitis and chronic pancreatitis.
However, it is often difficult to
classify pancreatitis: histology is not
routinely used, but it does remain
the gold standard for the early stage
of chronic pancreatitis, where there
is loss of normal acinar cells, fibrosis
and lymphocytic infiltrate.
Whitcomb DC. Clinical practice: acute

pancreatitis. N. Engl. J. Med. 2006; 354:
214250.
Rare
External pancreatic fistulae may
follow percutaneous drainage of
pseudocyst.
2.4.2 Chronic pancreatitis
Working Party of the British Society

of Gastroenterology, Association of
Pancreatic Society of Great Britain and
Ireland and Association of Upper GI
Surgeons of Great Britain and Ireland.
UK guidelines for the management
of acute pancreatitis. Gut 2005; 54
(Suppl. 3): iii1iii9. Full text available
Cause of chronic pancreatitis

(TIGAR O)
Toxic/metabolic: most notably
alcohol (>60% of cases) and
hyperlipidaemia.
Idiopathic: accounts for 1030% of
cases.
Genetic: cystic fibrosis gene
mutations, cationic trypsinogen
gene mutations (PRSS1) and serine
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protease inhibitor Kazal type 1

(SPINK1) mutations.
Autoimmune: more common in
Far East.
Recurrent and severe acute
pancreatitis: progressive
parenchymal tissue damage.
Obstruction: congenital
malformations, eg annular pancreas.
Epidemiology
Rare. Estimated incidence varies
between 1.6 and 23 per 100,000,
with prevalence about four times
higher.
duct or development of pancreatic

carcinoma.
Both exocrine and endocrine

insufficiency may be absent
in mild chronic pancreatitis: their
presence indicates substantial
pancreatic damage.
Physical signs
Common
There are no specific physical signs
until there has been sufficient
destruction of the gland to cause
pancreatic failure (either exocrine
or endocrine).
Common
Abdominal pain, typically epigastric
radiating through to the back. It is
often precipitated by eating fatty
foods or drinking alcohol.
Uncommon
Erythema ab igne may be evident
on the anterior abdominal wall in
patients with chronic pancreatic
pain.
Uncommon
Exocrine pancreatic insufficiency:
steatorrhoea and weight loss.
Endocrine pancreatic
insufficiency: diabetes.
Rare
Jaundice: due to either fibrosis
encroaching on the common bile
Serum amylase is often normal or
at most only modestly elevated
and therefore only of value during
attacks of acute abdominal pain
to exclude acute-on-chronic
pancreatitis (although serum
amylase level may not reach
diagnostic levels).
Tests of pancreatic anatomy

Abdominal radiograph, ultrasound
and CT Plain abdominal radiograph
may show pancreatic calcification.
Ultrasound has a sensitivity of about
70% for detecting parenchymal
pancreatic changes via transabdominal scanning, but the pancreas
is often obscured by overlying bowel
gas. On abdominal CT, the features
of chronic pancreatitis include
parenchymal calcification, duct
irregularities and cysts.
(ERCP)/magnetic resonance
cholangiopancreatography (MRCP)
Chronic pancreatitis can be classified
using the Cambridge system, which
looks at main pancreatic duct
integrity, duct size dilatation, presence
of calculi or stones and any cavities.
It can be applied to ultrasound, CT,
ERCP and MRCP, with the latter
having the advantage of being noninvasive, although early changes
may be missed because the duct
is not filled by contrast injection.
ERCP (Fig. 36) has the option of
therapeutic intervention.
Endoscopic ultrasound (EUS)
This is less invasive than ERCP and
therefore has fewer complications
Fig. 36 Chronic pancreatitis shown on ERCP: (a) dilated pancreatic duct with loss of side branches in severe disease compared with (b) minimal duct changes.
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whilst allowing high-resolution

images of the pancreatic
parenchyma and the ductal
system. EUS also has therapeutic
capabilities (see below under
analgesia).
Tests of exocrine pancreatic

function
Deterioration in exocrine function
occurs when >90% of pancreatic
tissue or >85% of lipase output is
lost. There are many methods of
assessing exocrine pancreatic
function, which can be divided
into direct and indirect tests (see
Section 3.2 for further information).
Others
Pancreatic diabetes has the same
complication rate as any other type
of diabetes and therefore requires
global assessment: although
hyperglycaemia may be relatively
mild, early treatment with insulin is
often useful. Ensure abstinence from
alcohol.
Glucose tolerance test, but note that

this is not helpful in staging chronic
pancreatitis.
There is some evidence that

antioxidant therapy can improve
pain and morbidity associated with
chronic pancreatitis (particularly
alcohol related).
Common
Malabsorption and diabetes.
Of steatorrhoea and weight

loss: coeliac disease, small
bowel bacterial overgrowth,
giardiasis.
Treatment
Pancreatic enzyme replacement
Preparations such as Creon and
Pancrex often improve both the pain
and the malabsorption associated
with chronic pancreatitis. Some
patients have a partial response
and may require addition of acid
suppression to reduce enzyme
destruction by the stomach.
Analgesia
Where pain is the dominant
feature, opiate analgesia and local
approaches such as coeliac axis
block may be necessary. EUS can
be employed to guide coeliac plexus
blockade.
80
Gupta V and Toskes PP. Diagnosis and

management of chronic pancreatitis.
Postgrad. Med. J. 2005; 81: 4917.
2.4.3 Pancreatic cancer

pathology
Most primary malignant tumours of
the pancreas are adenocarcinoma.
Risk factors include increasing age,
male sex, smoking, alcohol, chronic
pancreatitis, diabetes (within 2 years
of diagnosis of type 2 diabetes
mellitus) and hereditary pancreatitis.
Uncommon
Common bile duct obstruction.
Of pain: peptic ulcer, pancreatic

cancer.
Ahmed SA, Wray C, Rilo HL, et al.

Chronic pancreatitis: recent advances
and ongoing challenges. Curr. Probl.
Surg. 2006; 43: 127238.
Antioxidants
Complications
Tests of endocrine pancreatic
function
FURTHER READING
Rare
Pancreatic carcinoma.
Prognosis
Morbidity
Although diabetes and
malabsorption can be treated,
chronic pain is a major source of
morbidity with associated loss of
employment, depression and opiate
dependence.
Mortality
Survival is reduced in all causes of
chronic pancreatitis. Outcomes are
often worse in alcoholic chronic
pancreatitis, with death in this group
being due to many different causes.
Prevention
Secondary
Abstinence from alcohol along with
medical management as outlined
above will usually lead to clinical
stabilisation.
Epidemiology
Pancreatic carcinoma is the fourth
commonest gastointestinal tumour.
Its incidence is increasing in the
Western world, in the range of
510 per 100,000. Male to female
ratio is 1.3:1. It is rare in patients
under 45 years old.
Common
Painless cholestatic jaundice
associated with varying degrees
of pruritus, pale stools and dark
urine due to common bile duct
obstruction.
Weight loss.
Abdominal pain.
Uncommon
Vomiting (from duodenal
obstruction).
Malignant ascites.
Unexplained exocrine pancreatic
insufficiency.
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Unexplained episode of acute

pancreatitis.
Rare
Venous thrombosis
(thrombophlebitis migrans).
Diabetes.
Physical signs
Common
Jaundice and cachexia.
Uncommon
Palpable gallbladder (Courvoisiers
sign).
Palpable mass.
Ascites.
Blood tests
Routine blood tests show nonspecific changes related to biliary
obstruction. The pancreaticobiliary
tumour marker CA19-9 may be
elevated but is not specific to
pancreatic tumours.
Non-invasive imaging
Abdominal ultrasound May show
a dilated biliary tree. A pancreatic
mass may be demonstrated, but the
absence of a mass on ultrasound
does not exclude a pancreatic
malignancy. Dilatation of both
the common bile duct and the
pancreatic duct is highly suggestive
of a carcinoma of the pancreatic
head (double duct sign).
The absence of gallstones

on ultrasound in a patient
presenting with acute cholestasis
and a dilated biliary tree suggests
the presence of a common bile duct
stricture due to a carcinoma of the
pancreas or cholangiocarcinoma.
Fig. 37 CT scan showing carcinoma of the head of the pancreas with distal pancreatic duct dilatation.
(Courtesy of Dr N.D. Derbyshire, Royal Berkshire Hospital.)
Abdominal CT or MRI CT scanning

is useful for demonstrating the mass
and for staging, ie demonstration
of invasion into important local
structures or evidence of distant
metastases (Fig. 37).
Invasive imaging
cholangiopancreatography (ERCP)
Duodenoscopy allows assessment
of the ampulla of Vater and
identification and biopsy of a lesion
if present. ERCP allows diagnosis
and placement of an endobiliary
stent to allow relief from biliary
obstruction in patients (the
majority) who are unsuitable
for surgical resection. Carries a
significant morbidity and mortality.
Percutaneous transhepatic
cholangiography (PTC) For cases
where ERCP has failed or is not
possible, eg previous surgery such
as Polya gastrectomy or Roux-en-Y
biliary reconstruction; also allows
placement of an endobiliary stent.
Endoscopic ultrasound (EUS) CT
and transabdominal ultrasound can
miss lesions <2 cm in size. EUS is
particularly good at detecting these
and has the capability of directing

tissue sampling by either fine-needle
aspiration or biopsy. The fact that
it has higher resolution than other
imaging modalities allows clearer
definition of local invasion into
vascular structures and therefore
resectability.
CT-guided biopsy Useful in
selected cases where the diagnosis
remains obscure and where surgical
resection might be considered
if a positive diagnosis of
adenocarcinoma is confirmed,
but there is a risk of seeding along
the track.
Pancreatic tumours are very

fibrotic and biopsy has a higher
sensitivity than aspiration cytology.
Of acute cholestasis:
choledocholithiasis, intrahepatic
cholestasis (eg drug reaction).
Of pancreatic mass: ampullary
carcinoma (tumour arising from
the ampulla of Vater), which has a
better prognosis.
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Treatment
This depends on suitability
for surgery. Patients who have
resectable disease and who will
be operated on in a timely fashion
may not require stenting. Routine
preoperative biliary decompression
has not been shown to be beneficial.
Short-term
Those with extremely symptomatic
jaundice may require stenting prior
to surgery, but the route of delivery
and type of stent is controversial.
The British Society of
Gastroenterology guidelines suggest
plastic stenting via ERCP, although
many centres prefer metal stenting
via PTC as there is a lower risk of
pancreatitis and therefore less risk
of unnecessary delay.
Long-term or according to stage

Curative surgery In about 20% of
patients, pancreaticoduodenectomy
(Whipples procedure) offers the
possibility of a surgical cure. No
other form of therapy is associated
with long-term survival.
Palliative surgery Surgery may
still be beneficial in patients
with advanced disease by
providing combined biliary
and gastroduodenal bypass.
Can be performed laparoscopically
in some cases in some centres.
Chemotherapy/radiotherapy
Oncological therapies in pancreatic
carcinoma are used to help control
symptoms and improve quality of
life. Multimodal therapy (external
beam irradiation combined with
5-flurouracil chemotherapy) has
been shown to have no advantage
over chemotherapy alone, providing
minimal survival advantage (in
the range of weeks). In recent
studies gemcitabine (a pyrimidine
nucleoside analogue) has been
shown to improve quality of life,
and there appears to be a modest
82
but significant increase in response

rate and survival using regimens
containing this agent.
Palliative measures Relief of
jaundice and pain control are
the main objectives in patients
with advanced disease and many
require opiate analgesia. Anorexia
and weight loss remain major
problems.
Nutritional issues The addition
of pancreatic enzyme supplements
(such as Creon) has been shown to
improve quality of life and reduce
cachexia in patients with advanced
pancreatic cancer.
Prognosis
Morbidity
Most patients with pancreatic
cancer have incurable disease at
presentation and will experience
pain in addition to progressive
anorexia and weight loss.
tumours
pathology
Tumours arising from the
specialised neuroendocrine tissue of
the pancreas or intestine. They are
rare but important differentials for
a variety of clinical syndromes
including pancreatic mass lesions.
Epidemiology and genetic

background
All neuroendocrine tumours are
rare. They may occur as part of
several familial cancer syndromes,
notably multiple endocrine neoplasia
(MEN) type 1, MEN type 2,
neurofibromatosis type 1 and
von HippelLindau syndrome.
Clinical presentation and physical

signs
These vary depending on tumour
type (Table 36).
Mortality
Of individuals presenting with

carcinoma of the pancreas, 90%
are dead within 1 year.
Stool weight
This is performed on a normal
diet and then repeated fasting to
distinguish secretory from osmotic
diarrhoea.
FURTHER READING
Choti MA. Adjuvant therapy for
pancreatic cancer: the debate
continues. N. Engl. J. Med. 2004;
350: 124951.
Pancreatic Section of the British
Society of Gastroenterology, Pancreatic
Society of Great Britain and Ireland,
Royal College of Pathologists and
Special Interest Group for GastroIntestinal Radiology. Guidelines for
the management of patients with
pancreatic cancer, periampullary and
ampullary carcinomas. Gut 2005; 54
(Suppl. 5): v1v16. Full text available at
The diarrhoea associated

with hormone excess is
characteristically secretory rather than
osmotic (ie not diminished by fasting).
Blood tests
Serum chromogranin A has an
uncertain role but is produced by
all cells derived from the neural
crest and may be raised in any
neuroendocrine tumour. Most
neuroendocrine hormones can now
be identified on a fasting serum
sample. In the case of gastrin it is
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TABLE 36 NEUROENDOCRINE
TUMOUR TYPE AND COMMON
2.5 Biliary disease
SYMPTOM COMPLEX
2.5.1 Choledocholithiasis
Tumour type
Symptoms
Insulinoma
Confusion, sweating, dizziness, weakness
Gastrinoma (Zollinger
Ellison syndrome)
Severe peptic ulceration and diarrhoea
Glucagonoma
Necrolytic migratory erythema, diabetes, weight loss,

stomatitis, flushing
VIPoma (WermerMorrison
syndrome)
Profuse diarrhoea and hypokalaemia
Somatostatinoma
Cholelithiasis, weight loss, diarrhoea, diabetes
Non-functioning
Pancreatic mass
VIP, vasoactive intestinal polypeptide.
important that the patient is not

taking acid-suppressing medication
at the time of testing.
Gastrinoma: high-dose proton

pump inhibitors improve both the
pain and the diarrhoea.
Pancreatic imaging
Insulinoma: dietary advice,

diazoxide, octreotide.
In most instances the clinical

presentation of neuroendocrine
tumours of the pancreas will be due
to the systemic effect of the secreted
hormone. Identification of the
tumour is important as, with the
exception of insulinomas, a
significant proportion of these
lesions are malignant. Spiral CT,
MRI and increasingly endoscopic
and intraoperative ultrasound are
used.
VIPoma: octreotide.
Treatment
Surgical resection is probably the
best treatment if a focal tumour can
be identified and the patient is fit
enough. Medical treatment depends
on the secreted hormone.
There are three main types of stone:

cholesterol, black pigment (occur in
chronic haemolytic disease) and
brown pigment stones (associated
with infections in the biliary tree).
They are almost always found in the
gallbladder, and if they escape are
usually confined to the extrahepatic
biliary tree. Intrahepatic biliary
stones are rare, but seen more
frequently in the Far East.
Epidemiology
Overall prevalence is 10%. Incidence
increases with age and is twice as
high in women as in men.
Glucagonoma: octreotide.
Common
Prognosis
Asymptomatic (incidental finding

on imaging).
With the exception of insulinoma,

two-thirds of the other tumour types
will be histologically malignant.
However, with improved medical
therapy (proton pump inhibitors and
octreotide) these may still follow a
relatively indolent course.
Cholestatic liver function tests:

raised alkaline phosphatase (ALP)
and -glutamyltransferase (GGT).
Indigestion, particularly
exacerbated by fatty foods.
Biliary colic.
Octreotide scan
Radiolabelled somatostatin binds to
receptors on many neuroendocrine
tumour cells and can help to localise
primary and secondary tumour
deposits.
pathology
FURTHER READING
Kulke MH. New developments in
the treatment of gastrointestinal
neuroendocrine tumours. Curr. Oncol.
Rep. 2007; 9: 17783.
Ramage JK, Davies AHG, Ardill J,
et al. (on behalf of UKNETwork
for neuroendocrine tumours).
Guidelines for the management
of gastroenteropancreatic
neuroendocrine (including carcinoid)
tumours. Gut 2005; 54 (Suppl. 4):
iv1iv16. Full text available at
Acute cholecystitis: fever, right

upper guadrant pain and
tenderness, jaundice.
Ascending cholangitis: high
fever, rigors, jaundice
(Virchows triad).
Acute pancreatitis.
Uncommon
Obstructive jaundice without
symptoms.
Gallstone ileus.
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Elderly patients with

cholangitis and secondary
Gram-negative septicaemia commonly
present with non-specific symptoms,
eg off legs.
Physical signs
Common
There may be no signs, although
jaundice may be present with right
upper quadrant tenderness. In acute
cholecystitis look for Murphys sign.
Rare
The presence of splenomegaly
suggests haemolytic anaemia with
secondary pigmented common bile
duct (CBD) stones.
Investigations
Fig. 38 ERCP showing a stone in the CBD.
Blood tests
FBC and reticulocyte count: an
elevated white cell count occurs
with cholangitis; macrocytic
anaemia and elevated reticulocyte
count suggests haemolysis.
Liver biochemistry: classically
elevated bilirubin and ALP/GGT;
rarely in acute biliary obstruction,
aspartate transaminase (AST)/
alanine transaminase (ALT) may
be >1000 U/L.
Ultrasound
The preferred investigation for
detecting stones in the gallbladder,
but remember that the sensitivity for
stones in the CBD is only 70% and
the only sign may be duct dilatation.
The CBD may not be dilated on

ultrasound in incomplete biliary
obstruction.
84
can both confirm that a stone is
causing biliary obstruction (Fig. 38)
and be employed therapeutically to
remove stones. It will also identify
any distal CBD stricture, benign or
malignant, that may have resulted in
proximal stone formation. However,
ERCP does carry significant risks
and so magnetic resonance
cholangiopancreatography (MRCP)
(see below) should be considered
first (if available) in patients who
do not require immediate/urgent
therapeutic intervention or if
there is diagnostic uncertainty.
Magnetic resonance
This is a non-invasive method of
imaging the CBD and pancreatic
duct without the need for contrast
and therefore has far fewer risks

than ERCP. It can be used to detect
CBD stones and strictures (see
Fig. 24), and consequently ERCP
should be considered a therapeutic
procedure and should not be
performed solely for diagnosis in
centres where MRCP is available.
Other causes of biliary obstruction
such as tumour or congenital
abnormalities such as choledochal
cysts.
Treatment
Emergency
Emergency early ERCP (within
72 hours) with removal of CBD
stones is indicated in patients with
acute pancreatitis associated with
obstructive jaundice (see Section
1.4.5). An alternative approach is
laparoscopic exploration of the
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Clonorchis infection: associated

with intrahepatic stones, but
exceedingly rare in the UK.
Total parenteral nutrition:
associated with sludge and stones.
FURTHER READING
Beckingham IJ. ABC of diseases of liver,
pancreas and biliary system: gallstone
disease. BMJ 2001; 322: 914.
Johnson CD. ABC of the upper
gastrointestinal tract: upper
abdominal pain gall bladder.
BMJ 2001; 323: 11703.
Fig. 39 Plain abdominal radiograph showing a plastic stent within the CBD.
CBD with stone extraction and

cholecystectomy: this may have less
morbidity and mortality than ERCP
but is not widely available.
Short-term
Endoscopic removal of stones
A sphincterotomy or balloon
sphincteroplasty (cutting or dilating
the sphincter of Oddi with a balloon)
is performed and the CBD trawled
with either a balloon or basket
to remove the stones. The
sphincterotomy allows any retained
material to pass. There is a significant
risk of acute pancreatitis, bleeding
or duodenal perforation, with a
0.51% mortality. Larger stones may
require crushing with a mechanical
lithotriptor or, alternatively, a stent
can be inserted to allow bile
drainage and a further attempt at
removal at a later date. Stenting
often causes the stones to shrink
over time. Occasionally a nasobiliary
drain is required to provide
temporary biliary decompression.
Long-term
Interval laparoscopic
cholecystectomy in patients for
whom surgery is appropriate.

In those who are not surgical
candidates, and when it is not
possible to remove large stones
endoscopically, a CBD stent can
be left in the bile duct to provide
adequate biliary drainage (Fig. 39).
This will usually block within 312
months and hence most patients are
brought back for repeat ERCP and
stent exchange every 36 months.
Complications
Cholangitis and secondary
septicaemia are common. Prolonged
asymptomatic biliary obstruction
can rarely lead to secondary biliary
cirrhosis.
Prognosis
Good if CBD stones are removed.
Haemolytic anaemia (eg sickle
cell) or spherocytosis leading to
pigmented large or intrahepatic
stones.
Ileal disease/resection, which
interrupts enterohepatic
circulation of bile acids.
Martin DJ, Vernon DR and Toouli J.

Surgical versus endoscopic treatment
of bile duct stones. Cochrane Database
Syst Rev 2006; (2): CD003327.
2.5.2 Primary biliary cirrhosis

pathology
Primary biliary cirrhosis (PBC)
is a disease of unknown aetiology
leading to progressive destruction
of small intrahepatic bile ducts and
eventually to liver cirrhosis and
failure. It is thought to be immune
mediated as there is a predominantly
T-cell infiltration in the liver.
It is characterised by female
predominance and serum
autoantibodies to mitochondrial
antigens, most typically targeting
the E2 component of the pyruvate
dehydrogenase complex (PDC-E2)
that lies on the inner mitochondrial
membrane. Possible aetiological
factors include failure of immune
regulation, loss of tolerance,
immune complex bile duct damage,
and mitochondrial antibodies
cross-reacting with bacteria.
Epidemiology
Females account for 90% of cases
and most present between the ages
85
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of 40 and 60 years. Prevalence is

25 per 100,000 in women >18 years.
Common
Asymptomatic (diagnosed
as a result of investigation for
abnormal liver function tests).
Itching.
Lethargy.
Anti-mitochondrial antibody
This is present in 95% of cases and
is specific for PBC. Individuals with
anti-mitochondrial antibody (AMA)
and normal liver histology will
eventually develop PBC. Patients
with AMA-negative biopsy-proven
PBC, although rare, behave in the
same clinical manner as AMApositive patients. Anti-nuclear
antibodies and/or smooth muscle
antibodies are more frequently
positive in AMA-negative PBC.
Uncommon
Jaundice.
Haematemesis (from varices).
Abdominal distension (ascites).
Confusion (hepatic
encephalopathy).
Non-E2 AMA positivity can be

seen in syphilis, systemic lupus
erythematosus and other autoimmune
diseases.
Hepatocellular carcinoma.
Immunoglobulins
Physical signs
IgM is often high.
Common
Liver biopsy
Initially none, subsequently

pigmentation, xanthelasma,
hepatomegaly, scratch marks.
The histology is of lymphoid

aggregates and granuloma in portal
tracts, with bile duct damage and
eventually bile duct loss. Progressive
fibrosis results in biliary cirrhosis
(Fig. 40). Note, however, that liver
biopsy is not essential to make the
diagnosis of PBC in a patient who
has high-titre E2 AMA and typical
symptoms and biochemical
abnormalities.
Uncommon
Late signs of portal hypertension
(ascites and hepatic encephalopathy).
Investigations
Liver biochemistry
High alkaline phosphatase and mild
increase in alanine transaminase.
Rising bilirubin is a marker of poor
prognosis. Falling albumin and
rising prothrombin time only occur
at a very late stage in the disease as
it is a biliary cirrhosis.
The level of alkaline

phosphatase does not correlate
with the extent of liver disease:
insidious progression to cirrhosis
may occur without significant changes
in liver blood tests.
Treatment
Short-term
Ursodeoxycholic acid Its role is
controversial but it appears to delay
time to transplantation and death in
late-stage disease. It may improve
itching. Treatment at a dose of
1015 mg/kg should be directed to
symptomatic patients.
Other immunosuppressives
Steroids, azathioprine, ciclosporin
and methotrexate have not
convincingly been shown to be
effective.
Itching Responds to colestyramine.
If persistent, other drugs worth
trying include rifampicin,
benzodiazepines, ondansetron,
serotonin antagonists and naltrexone
(opiate antagonist).
Long-term
Liver transplantation Patients who
develop signs of decompensated liver
disease or in whom bilirubin is
greater than 100 mol/L should be
referred to a liver unit if
appropriate. Recurrence in hepatic
grafts occurs, but this does not have
an adverse effect on outcome in the
first 510 years.
Complications
In PBC the changes in the liver
are focal so a liver biopsy is
not useful for staging liver disease.
Furthermore, diagnosis does not
usually require liver biopsy because of
the specificity of AMA for this disease.
Large bile duct obstruction.
Sclerosing cholangitis.
86
Other causes of intrahepatic

cholestasis (drugs, sepsis, total
parenteral nutrition).
Osteoporosis and portal hypertension

are common in late disease.
Osteomalacia and deficiencies of
other fat-soluble vitamins are rare.
Prognosis
Variable and unpredictable. Some
asymptomatic patients may have a
normal life expectancy. Symptoms
generally develop within 27 years,
with subsequent life expectancy
varying from 2 to 10 years.
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Fig. 40 Liver biopsy of a patient with primary biliary cirrhosis showing (a) portal tract with lymphocytic infiltration and loss of bile ducts, (b) granuloma and
(c) progression to biliary cirrhosis.
Other autoimmune conditions:
rheumatoid arthritis, CREST
syndrome (calcinosis, Raynauds
disease, esophagus (hypomotility),
sclerodactyly, telangiectasia),
hypothyroidism, sicca syndrome
(dry mouth and eyes) and coeliac
disease.
FURTHER READING
Charatcharoenwitthaya P and Lindor
KD. Current concepts in the
pathogenesis of primary biliary
cirrhosis. Ann. Hepatol. 2005; 4: 16175.
Kaplan MM and Gershwin ME. Primary
biliary cirrhosis. N. Engl. J. Med. 2005;
353: 126173.

cholangitis
pathology
There is diffuse inflammation and
fibrosis involving the whole of the
biliary tree, eventually leading to
obliteration of bile ducts and biliary
cirrhosis with portal hypertension.
The disease usually involves the
intrahepatic ducts alone, but there
may also be involvement of the
extrahepatic ducts and occasionally
the disease is limited to these.
The aetiology is unknown, but the
disease is probably immunologically
mediated. Primary sclerosing
cholangitis (PSC) is strongly
associated with coexisting
inflammatory bowel disease,

especially ulcerative colitis, and
also with HLA-DR3. Antibodies
to perinuclear antineutrophil
cytoplasmic antibody are nonspecific but seen in 6080%
of cases.
Epidemiology
Prevalence is 6 per 100,000: 70%
are male and the average age at
diagnosis is 40 years.
Fatigue, intermittent jaundice,
pruritus, right upper quadrant
pain, or no symptoms but abnormal
liver biochemistry (often noted in
patients with ulcerative colitis or
Crohns disease).
87
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Physical signs
There are no signs in about 50% of
symptomatic patients. Jaundice and
hepatomegaly or splenomegaly may
be present.
Investigations
Liver biochemistry
High alkaline phosphatase/glutamyltransferase. Mild elevations
in serum transaminases (aspartate
transaminase/alanine transaminase).
Bilirubin may be raised. A low
albumin and raised prothrombin
time are only found in late-stage
disease (biliary cirrhosis).
Cholangiography
cholangiography or ERCP show
multiple irregular stricturing and
dilatation (beading) of intrahepatic
ducts (Fig. 41), with or without
extrahepatic stricture.
Liver biopsy
May be normal. Periductal onion
skin fibrosis and inflammation with
expansion of portal tracts, bile duct
proliferation and portal oedema.
Late progressive fibrosis with loss
of bile ducts (Fig. 42).
Fig. 41 ERCP showing classical beading of the intrahepatic bile ducts in PSC.
Secondary sclerosing cholangitis
due to cytomegalovirus or
Cryptosporidium infection in
AIDS.
Previous bile duct surgery.
Bile duct stones causing cholangitis.
Post liver transplant recurrent

PSC is hard to distinguish
from biliary stricturing
secondary to hepatic arterial
ischaemia.
Treatment
There is no curative therapy.
Fig. 42 Liver biopsy showing (a) normal portal tract (bile duct, hepatic artery and portal vein) and (b) periductal sclerosis, onion skin fibrosis typical of PSC.
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Management of complications
Pregnancy
Antibiotics (eg oral ciprofloxacin,

which is excreted in bile) for
cholangitis. Well-defined
extrahepatic biliary strictures
can be stented or balloon dilated
at ERCP.
Between 5 and 10% of patients with

ulcerative colitis and 1% of those
with Crohns disease develop PSC.
Up to 70% of patients with PSC will
have clinical or histological evidence
of ulcerative colitis. The colitis may
pre-date the diagnosis of PSC or
present many years later.
Intrahepatic cholestasis of
pregnancy (ICP) affects about
0.7% of pregnancies in the UK
and is associated with prematurity,
fetal distress and intrauterine death.
It is characterised by pruritus,
mostly in the third trimester, and
diagnosis is based on the presence
of itch in association with elevated
levels of serum bile acids and in
the absence of other skin diseases.
Current medical management
is with ursodeoxycholic acid, a
hydrophilic bile acid that alters
the composition of the bile acid
pool in maternal blood. When
ICP is diagnosed, ursodeoxycholic
acid coupled with close
maternalfetal surveillance
is indicated.
Ursodeoxycholic acid
Improves liver biochemistry but
probably has no effect on histology
or survival. Steroids, azathioprine,
methotrexate and ciclosporin have
not been shown to have any effect
on disease outcome.
Liver transplantation
Indicated for end-stage biliary
cirrhosis. Cholangiocarcinoma
is a contraindication.
Complications
These include cholangitis, common
bile duct or intrahepatic stones,
extrahepatic biliary strictures, biliary
cirrhosis with portal hypertension,
cholangiocarcinoma (occurs in
1030%, more commonly if the
patient has ulcerative colitis) and
colorectal carcinoma (25% lifetime
risk, especially if the patient has
ulcerative colitis). Most of these
complications present as increasing
jaundice.
It can be difficult to
differentiate a benign biliary
stricture from a cholangiocarcinoma,
even after cholangiography and
cytology of brushings from the
stricture.
Prognosis
This is variable. In symptomatic
patients the median survival
from presentation to death or
transplantation is 12 years; 75%
of asymptomatic patients are alive
at 15 years.
FURTHER READING
Maggs JR and Chapman RW. Sclerosing
cholangitis. Curr. Opin. Gastroenterol.
2007; 23: 31016.
Olsson R, Boberg KM, de Muckadell OS,
et al. High-dose ursodeoxycholic acid
in primary sclerosing cholangitis:
a 5-year multicenter, randomized,
controlled study. Gastroenterology
2005; 129: 146472.
Inherited

Cholestasis is defined as an
impairment of bile secretion due to
intrahepatic or extrahepatic causes.
Any disease which leads to failure
of synthesis or decreased excretion
of bile acids within the liver can
result in cholestasis. In addition
to intrinsic liver diseases,
intrahepatic cholestasis is notable
in sepsis, with certain drugs (eg
flucloxacillin), following prolonged
total parenteral nutrition (TPN),
during pregnancy and in a few rare
genetic diseases.
Sepsis
Jaundice associated with
cholestatic liver biochemistry
(elevated alkaline phosphatase and
-glutamyltransferase) is common in
patients with extrabiliary bacterial
infections, particularly on the
intensive care unit. Differential
diagnosis is from cholestasis due
to TPN, gallstones and drugs.
Treatment is of the underlying
condition.
Progressive familial intrahepatic

cholestasis (PFIC) and benign
recurrent intrahepatic cholestasis
(BRIC) are rare hereditary disorders:
patients with PFIC suffer from
chronic cholestasis and develop
liver fibrosis; patients with BRIC
experience intermittent attacks
of cholestasis that resolve
spontaneously.
pathology
Chronic inflammation and bile
duct stasis are associated with
increased risk of developing
cholangiocarcinoma, which is a
malignant adenocarcinoma of the
biliary tree with three main
distributions.
1. Intrahepatic or peripheral
tumours arising from bile ducts
within the liver, usually mass
lesions.
2. Extrahepatic tumours that are
classified as proximal (near the
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liver), intermediate or distal (near

the pancreas).
3. Klatskin tumour, which arises at
the bifurcation of the common
hepatic duct, leading to
obstruction of both left and
right hepatic ducts.
Epidemiology
Cholangiocarcinomas comprise
510% of malignant hepatic
tumours and are more common
with increasing age (most patients
>60 years). The incidence is
increasing in the Western world
(cause unknown). Intrahepatic
cholangiocarcinoma may be
mistaken for a liver mass and
therefore be under-reported.
The patient is often asymptomatic
until a late stage, when symptoms
include biliary obstruction, fever,
weight loss and vague abdominal
pain. Some patients describe itching
before jaundice becomes clinically
apparent.
Physical signs
Jaundice, with or without
hepatomegaly.
Weight loss.
Biliary obstruction is usually
proximal to the cystic duct,
so the gallbladder is not usually
palpable (negative Courvoisiers
sign).
and specificity, so it should not

be used diagnostically, although
it may be helpful in assessing
response to therapy. Alphafetoprotein levels will not usually
be raised, which can help to
differentiate intrahepatic
cholangiocarcinomas from
hepatocellular carcinoma.
Ultrasound/CT
Liver biochemistry
Ultrasound detects dilated ducts,

mass in pancreatic head (carcinoma)
and level of obstruction. CT
scanning adds little in these
patients unless looking for distant
metastases.
Elevated bilirubin/alkaline
phosphatase and glutamyltransferase.
Investigations
Tumour markers
CA19-9 rises, but does so in many
causes of jaundice (benign and
malignant) giving a low sensitivity
90
Fig. 43 ERCP showing a cholangiocarcinoma with dilatation of the CBD above the stricture.
This is usually the definitive test and

is both diagnostic and potentially
therapeutic (Fig. 43). The sensitivity
of cytology of brushing from the
stricture is about 5070%.
cholangiography
In the presence of a lower common
bile duct (CBD) stricture it may not
be possible to cannulate the papilla
endoscopically and the biliary tree
has to be accessed percutaneously
using percutaneous transhepatic
cholangiography (PTC) (Fig. 44).
PTC is also particularly useful in
patients with proximal strictures
or Klatskin tumours.
Endoscopic ultrasound
Has been used to take tissue
samples by fine-needle aspiration.
The use of miniprobes allows further
assessment of biliary strictures by
intraductal ultrasound in some
centres.
Extrahepatic tumours must
be differentiated from benign
strictures, eg chronic pancreatitis,
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or endoscopically (Fig. 46) is the

mainstay of treatment for most
patients. Different types of stent can
be employed, selection depending on
the predicted survival of the patient:
metal self-expanding stents remain
patent for longer than cheaper
plastic stents.
Metal stents cannot be

removed and can make
subsequent surgery difficult: it is
therefore important to have made the
correct diagnosis before inserting one.
Long-term
Fig. 44 PTC showing a stricture in the CBD.
primary sclerosing cholangitis.

Intrahepatic tumours must be
differentiated from hepatic lesions,
eg metastases and hepatocellular
carcinoma.
Treatment
Short-term
Relief of biliary obstruction with a
stent placed percutaneously (Fig. 45)
Surgical resection Appropriate

in early disease if no evidence of
spread. The procedure depends
on the location of the tumour.
Distal tumours may be removed by
Whipples procedure, with segmental
resection for intrahepatic lesions.
Klatskin tumours are almost never
Fig. 45 (a) A high CBD stricture with dilated intrahepatic ducts above. A percutaneously inserted guidewire can be seen crossing the stricture and passing out of
the biliary tree into the duodenum. (b) A metal stent has been placed through the stricture allowing contrast to pass into the duodenum.
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2.6 Infectious diseases

gastroenteritis
Vomiting and diarrhoea caused by
ingestion of contaminated food or
water is a common clinical problem.
It is common in travellers to areas
where pathogens are endemic, or
where food and water hygeine is
suboptimal. It can also occur in the
UK due to pathogens endemic in the
food chain and where preparation
and storage of food allows
organisms or toxins to persist.
Fig. 46 Duodenal view of biliary stent showing bile draining freely.
resectable. Roux-en-Y biliary

anastomosis may relieve obstruction
as a palliative procedure for low
CBD cholangiocarcinomas.
Liver transplantation This is
contraindicated in a patient with
primary sclerosing cholangitis who
develops a cholangiocarcinoma due
to the high rate of tumour recurrence
with immunosuppression.
Complications
Secondary bacterial cholangitis, with
or without a blocked stent.
The presence of cholangitis in

the presence of a CBD stent
usually indicates that the stent is
blocked and is an indication for
changing it, even if the liver
biochemistry improves with
treatment of the cholangitis.
Prognosis
This is poor, with an overall survival
rate of 4053% at 1 year and
10 19% at 2 years.
92
Well-recognised associations are
primary sclerosing cholangitis,
parasitic infections with liver
flukes such as Clonorchis and
Opisthorchis (South-east Asia)
and recurrent bacterial cholangitis
with hepatolithiasis. Exposure
to thorium dioxide (thorotrast),
1-antitrypsin deficiency and
choledochal cysts have also been
described in association with
cholangiocarcinoma.
Gastrointestinal infections can be

caused by viruses (most commonly),
bacteria (or their toxins) or
protozoa. They present abruptly
with diarrhoea and/or vomiting and
colicky abdominal pain and are
usually self-limiting. The commonest
causes in the UK are rotavirus,
Norwalk agent, Campylobacter,
Salmonella and Escherichia coli.
All cases of food poisoning

are notifiable by law.
Stool cultures often fail to

grow an organism.
pathology
FURTHER READING
Khan SA, Davidson BR, Goldin R, et al.
Guidelines for the diagnosis and
treatment of cholangiocarcinoma:
consensus document. Gut 2002; 51
(Suppl. 6): vi1vi9. Full text available
Khan SA, Thomas HC, Davidson BR and
Taylor-Robinson SD. Cholangiocarcinoma.
Lancet 2005; 366: 130314.
Causes of food poisoning and

gastroenteritis are shown in
Table 37.
Enterotoxins are usually secreted
bacterial proteins that act on
the intestinal epithelium, or are
absorbed into the bloodstream and
have systemic effects, eg vibrios and
enterotoxigenic E. coli toxins can
stimulate intestinal secretion.
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Prevention
TABLE 37 CAUSES
OF FOOD POISONING AND GASTROENTERITIS
Type of agent
Pathogen
Comment
Viruses
Rotavirus
Norwalk
Outbreaks particularly in young children

Winter vomiting illness: rapidly spread
from person to person
Preformed toxins
Staphylococcus
Vomiting and diarrhoea within a few

hours of ingesting contaminated food
Particularly likely to be present in
reheated cooked food
Bacillus cereus
Intestinal production
of enterotoxins
Vibrio cholerae
Vibrio parahaemolyticus
Invasive bacterial
infection
E. coli 0157:H7
Salmonella, Shigella,
Campylobacter
Parasites
Giardia intestinalis
Entamoeba histolytica
Enteropathogenic bacteria such as

E. coli, Campylobacter, Salmonella
and Shigella species invade the
epithelium, causing ulceration and
inflammation. The stool contains
blood and leucocytes, and there is
a systemic inflammatory response
resembling inflammatory bowel
disease.
Epidemiology
Worldwide outbreaks, although
poorer parts of the world have
higher rates of endemic infection.
Usually epidemic outbreaks of severe

watery diarrhoea
Vomiting and diarrhoea associated with
ingestion of contaminated seafood
Associated with contaminated beef and
unpasteurised fruit juices
Travellers diarrhoea and contaminated
poultry
Water-borne protozoan causing nausea,
diarrhoea, flatulence
Cause of dysentery and may cause
systemic infection (eg liver abscess)
inflammation and bleeding,

particularly if sigmoidoscopy is
performed.
Investigation
Stool and vomitus should
be collected and analysed for
pathogens by microscopy, culture
and toxin testing. Food poisoning
is a notifiable illness, for obvious
public health reasons.
Treatment
Food hygeine and meticulous

cooking of potentially contaminated
meat and poultry are the key
measures.
2.6.2 Bacterial dysentery

pathology
Infection is spread by consuming
contaminated water or food,
particularly meat and poultry.
Common causes of bacterial
dysentery are Campylobacter jejuni,
Salmonella species, Shigella species
and enteropathogenic E. coli strains.
Epidemiology
Travellers to endemic areas in
the tropics, subtropics and poor
countries with inadequate sanitation
and food hygeine practices are most
affected. Salmonella infection is
endemic in poultry in the UK, and
undercooked or raw eggs and
chicken are a common cause of
infection. E. coli strain 0157:H7
is endemic in cattle and causes
outbreaks associated with ingestion
of contaminated beef.
Bacterial dysentery is not

only a disease of travellers:
Salmonella infection is endemic in
poultry in the UK and can contaminate
the food chain.
Emergency
Vomiting and diarhoea following
exposure are the typical features.
The main danger of acute
gastroenteritis is dehydration and
its consequences, which can include
life-threatening circulatory collapse,
especially in children and in the old
and infirm.
Physical signs
Dehydration is the most likely sign.
Rectal examination may reveal
Dehydration and electrolyte

abnormalities should be corrected.
In acute gastroenteritis antibiotics
have little role, although they may
reduce the duration of illness in
cases of dysentery.
Complications
Reactive arthritis may develop
after a self-limited episode of
food poisoning. GuillainBarr
syndrome may follow infection
with Campylobacter species.
The incubation period is 35 days.
Dysentery typically causes severe,
cramping abdominal pain and
diarrhoea, which may be bloody.
There is frequently associated
malaise, headache and myalgia.
Infection with E. coli strain 0157:H7
may be associated with severe renal
dysfunction and haemolysis, and
may be rapidly fatal. Bacterial
dysentery may be indistinguishable
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from idiopathic inflammatory bowel

disease (IBD) and may occur in
patients who already have a
diagnosis of IBD.
Sigmoidoscopic and
histological appearances
in gastrointestinal infections
and idiopathic IBD may be
indistinguishable, and the two
conditions can also coexist.
Complications
Bacterial dysentery may cause
Reiters syndrome (uveitis or
conjunctivitis, urethritis and
arthritis). GuillainBarr syndrome
may follow infection with
Campylobacter species. Salmonella
infection may become systemic
(eg causing osteomyelitis or septic
arthritis), and a chronic carrier
state associated with colonisation
of the biliary tree is sometimes
established.
Infection with E. coli strain

0157:H7 can follow ingestion of
contaminated food, especially beef,
and is associated with a severe lifethreatening haemolyticuraemic
syndrome.
Treatment
Fluoroquinolones such as
ciprofloxacin are usually highly
effective. Haemolyticuraemic
syndrome caused by E. coli 0157:H7
infection requires high-intensity
supportive treatment.
diarrhoea
pathology
Use of antibiotics alters the enteric
bacterial population and frequently
causes diarrhoea. In some cases this
94
is caused by overgrowth of
enterotoxin-producing Clostridium
difficile. Most antibiotics are
implicated, including clindamycin,
with the widespread use of thirdgeneration cephalosporins and
broad-spectrum penicillins
responsible for many cases.
Diarrhoea may be mild, with
frequent watery stools, or more
severe, with passage of blood and
mucus and a marked systemic
inflammatory response (fever,
tachycardia, hypotension). The
most severe consequence of
toxigenic C. difficile infection,
pseudomembranous colitis, may
lead to intestinal perforation and
is life-threatening.
Investigations
C. difficile can be cultured from the
stool and its enterotoxins can be
detected by a sensitive and rapid
enzyme-linked immunosorbent assay
(ELISA). Sigmoidoscopy reveals
punctate yellow-white plaques
adhering to inflamed mucosa in
pseudomembranous colitis.
C. difficile enterotoxin can

be detected by a rapid and
specific ELISA performed on stool
specimens.
Prevention and treatment

Strategies to minimise the use
of broad-spectrum antibiotics
reduce the incidence of C. difficile
infection. First-line treatment is
with metronidazole, administered
orally or parenterally. Relapse is
common (up to 30%) and can be
treated by vancomycin 125 mg qds
orally. Probiotics may reduce the
incidence of further relapses.
FURTHER READING
Bricker E, Garg R, Nelson R, et al.
Antibiotic treatment for Clostridium
difficile-associated diarrhea in adults.
Cochrane Database Syst Rev 2005; (1):
CD004610.
Hurley BW and Nguyen CC. The
spectrum of pseudomembranous
enterocolitis and antibiotic-associated
diarrhea. Arch. Intern. Med. 2002; 162:
217784.

the intestine
pathology
Intestinal parasitic infestations are
widespread throughout the world. In
the UK the commonest infestations
are with Giardia intestinalis and
Enterobius vermicularis (pinworm).
Hookworm and roundworm
infections may cause chronic
diarrhoea, malabsorption, growth
retardation and intestinal blood loss.
Infection with Giardia

intestinalis and Enterobius
vermicularis are widespread in the UK.
Giardiasis is spread by the fecaloral
route and by ingesting contaminated
water. The organism is relatively
resistant to chlorine. Infection
typically causes nausea and
diarrhoea with excessive flatus after
an incubation period of 14 weeks.
Malabsorption may occur, with pale,
bulky, offensive stools and weight
loss. Symptoms may persist for
months.
Pinworm infection is spread by the
fecaloral route from human to
human. It is particularly prevalent
among children and may cause
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perianal pruritis as the organisms

and eggs are shed.
such as ultrasound, and may require

aspiration and microscopy.
Investigations
Complications
Giardiasis is diagnosed by finding

trophozoites in jejunal aspirates or
biopsies taken at endoscopy, or cysts
in the stool. Pinworms or oocytes
might be detected in the stool.
Liver abscesses occur in 13% of

cases.
Treatment
Metronidazole or tinidazole are
highly effective for giardiasis, while
pinworm infections are treated with
mebendazole or albendazole.
Household contacts should be
treated.

amoebiasis
pathology
Entamoeba histolytica is a freeliving protozoan that spreads via
person-to-person contact and by
ingestion of contaminated water
or food. It can cause dysentery
when localised to the large intestine.
The organisms are distributed
haematogenously to distant organs,
particularly the liver, where they
may cause inflammatory masses
(amoeboma) and abscesses.
The incubation period for amoebic
dysentery is 14 weeks. Symptoms
range from mild diarrhoea to
severe bloody diarrhoea (colonic
ulceration). Amoebic liver abscess
may present many months after
infection with abdominal pain,
fever and abnormal liver
function tests.
Investigations
Dysentery is diagnosed by
examination of the stool, which may
demonstrate live parasites, or by
rectal biopsy or serology. Amoebic
abscesses are visualised by imaging,
Treatment
Metronidazole is effective in
treating amoebic dysentery.
Liver abscesses should be treated
with metronidazole followed by
diloxanide to eliminate carriage
of the organism.

HIV infection
Despite progress in treating
HIV infection, infection rates are
increasing worldwide as well as in
the UK. Up to one-third of HIVpositive individuals in the UK may
be unaware of their infected status.
Untreated HIV progresses to cause
a profound immune deficiency,
and with immunodeficiency the
gastrointestinal tract may be
involved by oropharyngeal
and oesophageal candidiasis,
cryptosporidiosis, microsporidiosis,
atypical mycobacterial infection,
tuberculosis, cytomegalovirus and
herpesvirus infections. HIV-positive
patients may also be at greater risk
of enteric pathogens such as
amoebiasis and dysentery-causing
bacteria.
Gastroenteritits caused
by unusual organisms,
oropharyngeal candidiasis, and severe
and persistent herpesvirus infection
raise the possibility of HIV infection.
HIV infection itself may cause an

enteropathy, manifest as diarrhoea,
malabsorption and weight loss,
which histologically has the
appearance of partial villous atrophy
with crypt hyperplasia and
polymorph infiltration. Depletion of

lymphocytes in the gastrointestinal
tract is an early feature of HIV
infection, and in patients on
antiretroviral drug treatment a
reservoir of latent virus may persist
in gastrointestinal lymphoid tissue.
Co-infection with HIV and hepatitis
C or B viruses causes more severe
and rapidly progressive liver disease.
Antiretroviral drug treatment may
cause severe drug-induced hepatitis,
hence (for instance) nevirapine
should not be used in individuals
with a high or normal CD4 count
because it can induce a lifethreatening hepatitis.
HIV and the liver

Chronic viral hepatitis is
usually more severe in the presence
of HIV co-infection.
Antiretroviral drug treatment may
cause severe liver disease.
2.7 Inflammatory bowel

disease
2.7.1 Crohns disease
pathology
The aetiology is unknown, but there
is a presumed autoimmune process
(association with perinuclear
antineutrophil cytoplasmic antibody
and antibodies to Bakers yeast).
There is a measurable genetic
component, with family studies
showing 50% concordance in
identical twins and linkage studies
incriminating a number of loci.
There is also a possible association
with infectious agents, eg
Mycobacterium paratuberculosis.
There is an increased incidence
in cigarette smokers.
95
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(erythema nodosum, pyoderma

gangrenosum).
Investigations
Blood tests
Fig. 47 Histological specimen from Crohns colitis showing intense inflammation and granuloma.
The characteristic histological

features are transmural
inflammation with ulceration and
granuloma formation (Fig. 47).
This may affect any part of the
gastrointestinal tract (mouth to
anus), but predominantly the
terminal ileum, right colon or
rectum and perianal region.
Affected areas are often separated
by normal bowel (skip lesions).
The process may cause strictures
or fistulae to adjacent structures
and is usually accompanied by a
vigorous systemic response, with
raised C-reactive protein (CRP) and
erythrocyte sedimentation rate
(ESR).
Epidemiology
Incidence is 68 per 100,000 and
prevalence is 2656 per 100,000 in
northern Europe, the USA and
Australia. Slightly more common
in females. There is a bimodal age
incidence: 1540 years is most
common, with a second peak at
around 70 years of age. Ten per
cent of patients have a first-degree
relative with the disease. The
risk for siblings is 30-fold increased
compared with the general
population. Smoking increases
relative risk three-fold.
96
FBC often shows anaemia, which

may be normochromic, normocytic
(chronic disease) or result from iron,
B12 or folate deficiency. The platelet
count is often high in active disease
(regard as an inflammatory marker).
Serum inflammatory markers are
raised (CRP and ESR). Serum
albumin is often low (due to chronic
inflammatory disease process, not
malnutrition). Vitamin B12 may be
low due to terminal ileitis.
Other tests
Common
Diarrhoea, abdominal pain and
weight loss (often >10% body mass)
are all expected, with Crohns
disease the presumed diagnosis in a
young patient with this triad. May
be associated with general malaise,
lassitude, fever and anorexia. A
careful history may reveal a lengthy
preceding history of bowel upset, a
previous diagnosis of irritable bowel
syndrome, or previous perianal
disease (fissure or abscess).
Rare
Sigmoidoscopy/colonoscopy can
show colonic or ileal inflammation
(may be patchy), granulomas on
biopsy and is the investigation of
choice. Small bowel follow-through
can show segmental inflammation,
strictures and fistulae (Fig. 48). MRI
scanning is particularly useful for
assessing complex perianal disease,
including fistulae.
Rectal biopsy in Crohns

disease may show granuloma
even when macroscopically normal.
Occasionally mistaken for anorexia

nervosa.
Physical signs
Common
There may be few physical signs, or
the patient may be thin and unwell
with clubbing, aphthous ulceration,
abdominal tenderness, and perianal
skin tags, ulceration or fistulae.
Ulcerative colitis if colonic

involvement.
Abdominal tuberculosis,
particularly if terminal ileal
disease and the patient is in
an at-risk group.
Malignancy/intestinal lymphoma.
Uncommon
Abdominal mass.
Treatment
Rare
Emergency
Fistulae, seronegative arthritis,

sacroiliitis, iritis and skin rashes
Patients who are very ill will require

emergency admission to hospital for
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weekly for the first month, then

monthly for 2 months, and
3-monthly for the duration of
treatment.
Methotrexate In those intolerant
of, or failing to respond to,
azathioprine, methotrexate may be
tried. In steroid-dependent patients
it has been shown to achieve both
remission and withdrawal of
steroids in 39% compared with
19% given placebo.
Fig. 48 Barium follow-through showing several tight strictures in the terminal ileum in a patient with
Crohns disease.
resuscitation followed by treatment

as described in Sections 1.4.2 and
1.4.4.
Short-term
Corticosteroids In severe disease
start hydrocortisone 100 mg iv qid.
Following clinical response, or if the
attack is less severe, commence oral
prednisolone at 3040 mg daily and
taper down by approximately 5 mg
per fortnight depending on clinical
progress; 70% will be in remission
in 34 months. Budesonide, a
topically acting steroid with high
potency and extensive first-pass
metabolism, is equivalent to
prednisolone in inducing remission
in terminal ileal disease and has
fewer side effects, but is much more
expensive and relapse rates within
1 year are disappointingly high.
5-Aminosalicylic acids These
compounds have only marginal
benefit in acute disease.
Dietary Elemental and polymeric
diets containing low-molecularweight nutrients may induce
remission in up to 70% of patients
(particularly in small bowel disease).
They need to be taken cold as

a sip feed and may have to be
given by nasogastric tube
(for 6 weeks).
Other Metronidazole or
ciprofloxacin may be useful in
treating perianal sepsis, but the
evidence for this is not strong.
Long-term
About 50% of Crohns disease
patients will have relapsed 1 year
after initial treatment.
5-Aminosalicylic acids Have at
best a modest effect in maintaining
remission, with the postsurgical
subgroup benefiting most.
Azathioprine This
immunosuppressant has been
shown to induce remission in
steroid-resistant and steroiddependent patients, to reduce
relapse rates (including post
surgery), and to have steroid-sparing
effects. It takes 612 weeks to
achieve its effects. Side effects
include bone marrow suppression,
liver dysfunction (dose dependent)
and pancreatitis (idiosyncratic).
Patients should have FBC checked
Infliximab This anti-tumour

necrosis factor (TNF)- antibody
is established in the treatment of
refractory Crohns disease. It may
induce long-term remission in up
to 60% of patients and has recently
been licensed for maintenance
therapy, although it remains very
expensive. All patients should
have a CXR to exclude previous
tuberculosis prior to starting
treatment.
Surgery Crohns patients have a 90%
lifetime risk of surgery (Fig. 49).
Indications include failed medical
therapy, abscesses, fistulae, intestinal
obstruction and haemorrhage, and
in limited terminal ileal disease it
may be considered the treatment of
choice. Half will have symptomatic
relapse within 10 years following
surgery, although up to 80% may
have evidence of disease at
endoscopy, but not all will require
further operations. Stricturoplasty
may be performed, rather than
resection, to preserve small
intestinal length.
Complications
Common
Intestinal obstruction Usually
subacute. May be due to active
disease causing oedema and
narrowing, or to chronic fibrotic
stricture. The former usually
responds to steroids.
97
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The National Association for

Colitis and Crohns Disease
provides information and support
for patients: for further details
see http://www.nacc.org.uk
FURTHER READING
Fig. 49 Terminal ileum resected from a patient with Crohns disease showing linear ulceration and
pseudopolyps.
Patients with small bowel

strictures are advised to
maintain a low-fibre diet to avoid
food bolus obstruction.
There is an increased risk of

colonic carcinoma in patients
with colonic Crohns disease.
Free perforation is rare.
Prognosis
Malabsorption Vitamin B12
deficiency and bile salt diarrhoea
are caused by terminal ileal disease.
Extensive involvement of the small
bowel or surgical resections result
in generalised malabsorption
(short bowel syndrome). Bacterial
overgrowth secondary to
enteroenteric fistulae or strictures
results in fat malabsorption.
Perforations Contained perforations
result in abdominal, pelvic and
ischiorectal abscesses and require
drainage.
Uncommon/rare
Chronic blood loss causing
Massive rectal bleeding, almost
always secondary to colonic
disease.
Toxic megacolon can occur, but is
less common than in ulcerative
colitis.
98
Morbidity
Some patients experience
considerable morbidity from
general ill-health, pain, malnutrition,
fistulous disease, abscess formation,
repeated surgery or steroid side
effects, but most are maintained
relatively symptom-free.
Mortality
Overall mortality is twice that
for the general population. Those
diagnosed with the disease before
the age of 20 have more than
10 times the standardised
mortality ratio.
Prevention
Cessation of smoking is of benefit in
active disease and reduces the risk of
relapse.
Weak association with primary
sclerosing cholangitis, arthralgia and
arthritis; also with HLA-B27.
Carter MJ, Lobo AJ and Travis SPL

(on behalf of the IBD Section of the
British Society of Gastroenterology).
Guidelines for the management of
inflammatory bowel disease in adults.
Gut 2004; 53 (Suppl. 5): v1v16. Full text
Caprilli R, Gassull MA, Escher JC, et al.
European evidence based consensus
on the diagnosis and management of
Crohns disease: special situations.
Gut 2006; 55 (Suppl. 1): i36i58.
Stange EF, Travis SPL, Vermiere S, et al.
European evidence based consensus on
the diagnosis and management of
Crohns disease: definitions and
diagnosis. Gut 2006; 55 (Suppl. 1): i1i15.
Travis SPL, Stange EF, Lemann M, et al.
European evidence based consensus on
the diagnosis and management of
Crohns disease: current management.
Gut 2006; 55 (Suppl. 1): i16i35.
2.7.2 Ulcerative colitis

pathology
The aetiology is unknown, but
there is a presumed autoimmune
process with a measurable genetic
component (genetic linkages and
family studies). Enteric bacterial
factors seem to be important. There
is a decreased incidence in cigarette
smokers.
The histopathological features
are of mucosal inflammation only
(contrasting with Crohns disease)
with crypt distortion, crypt abscesses
and goblet cell depletion (Fig. 50).
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abdominal tenderness, blood on

rectal examination, and mucopus
on rigid sigmoidoscopy.
Uncommon
Toxic megacolon, arthritis, iritis and
skin rashes (erythema nodosum,
pyoderma gangrenosum).
Fig. 50 Histology of ulcerative colitis showing inflammatory infiltrate within the mucosa.
Serum inflammatory markers are

markedly raised in severe disease
but may be normal in proctitis or
mild disease. Stool culture and
microscopy are required to exclude
infectious diarrhoea, including
Clostridium difficile.
Rectal inflammation is almost

universal, but the extent of more
proximal disease is variable. Disease
is continuous, ie extends from anus
to wherever the proximal extent lies,
and does not cause fistulae or
strictures, but may rarely result
in fibrotic narrowing of colon.
Epidemiology
Common
Barium enema
Incidence 1020 per 100,000. Affects

any age group, but most typically
youths and young adults.
There may be few physical signs,

but the patient may be thin and
unwell with aphthous ulceration,
This may confirm findings on the

plain abdominal radiograph, but its
use is limited and should be avoided
in severe disease due to the risk of
perforation (Fig. 51).
Bloody diarrhoea and general malaise

are common. Arthritis and arthralgia,
uveitis, skin rashes, abdominal pain
and tenesmus are less common.
Toxic megacolon is rare.
Physical signs
Plain abdominal radiograph

May show proximal faecal loading.
Mucosal oedema and ulcers may be
detected, and in severe disease there
can be colonic dilatation (toxic
megacolon).
Colonoscopy
The investigation of choice in
ulcerative colitis: may show
inflammation extending from the
rectum to the proximal extent of
disease (Fig. 52). In severe disease
this should be limited to flexible
sigmoidoscopy due to the increased
risk of perforation.
Fig. 51 Barium enema showing ulcerative colitis extending to the splenic flexure.
Common differential diagnoses

include Crohns colitis, infectious
colitis (bacterial, amoebic,
viral, eg cytomegalovirus in
immunosuppressed patients),
NSAID-induced colitis, and
microscopic colitis.
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with azathioprine (target dose

22.5 mg/kg) is recommended.
Panproctocolectomy is curative.
Patients may opt for a permanent
ileostomy or formation of a
neorectum using a loop of ileum
(pouch).
Complications
Common complications include
malnutrition, steroid-induced side
effects, arthralgias, arthritis, skin
rash. Less common are uveitis, toxic
megacolon and perforation or sepsis.
Malignancy (colorectal carcinoma)
is rare.
Because of the increased risk

of colorectal cancer, it is now
recommended that all patients with
ulcerative colitis undergo surveillance
colonoscopy every 3 years after 10
years, every 2 years after 20 years, and
yearly from 30 years. However, the use
of regular 5-aminosalicylic acid
compounds may reduce the risk to
near that of the normal population.
Prognosis
Fig. 52 Endoscopic appearance of (a) normal colon and (b) inflamed colon.
Treatment
Emergency
Patients who are very ill will require
emergency admission to hospital for
resuscitation followed by treatment
as described in Sections 1.4.2 and
1.4.4.
Short-term
In mild to moderate disease,
high-dose 5-aminosalicylic acid
compounds (4 g/day) may induce
remission. The addition of topical
preparations can result in more
rapid resolution of rectal bleeding
and are the first-line treatment of
choice in proctitis and colitis not
100
extending beyond the splenic flexure.

In more severe disease, or where
5-aminosalicylic acid compounds
are ineffective, steroids may be used,
eg prednisolone 3040 mg/day,
reduced by 5 mg every 12 weeks.
Intravenous ciclosporin may have
a role to play in severe colitis, but
this remains controversial due to
potential side effects and high
long-term failure rates.
Long-term
5-Aminosalicylic acid compounds
can maintain remission in most
patients. In patients who have
frequent relapses or become steroid
dependent, immunosuppression
Morbidity
About 25% of patients experience
only one attack, 40% are in
remission in any one year, and a
minority have unremitting disease.
About 30% of patients ultimately
undergo colectomy. The longer a
patient remains in remission, the
better the chance of remaining in
remission.
Mortality
Overall mortality is not increased
compared with healthy controls,
possibly due to a lower incidence
of smoking.
Prevention
Secondary prevention is with
5-aminosalicylic acid compounds
and azathioprine.
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Physical signs
Prognosis
Primary sclerosing cholangitis.
There are usually no abnormal

physical signs. Rigid sigmoidoscopy
is typically normal.
Most patients suffer repeated

relapses.
FURTHER READING
Carter MJ, Lobo AJ and Travis SPL (on
behalf of the IBD Section of the British
Podolsky DK. Inflammatory bowel
disease. N. Engl. J. Med. 2002; 347:
41729.
Stein RB and Hanauer SB. Medical
therapy for inflammatory bowel
disease. Gastroenterol. Clin. North Am.
1999; 28: 297321.
Serum inflammatory markers,
macroscopic appearance at
colonoscopy and barium enema
are usually normal. Coeliac
antibodies should be checked
and duodenal biopsies arranged
if these are positive. Microscopic
changes in the colon (raised
intraepithelial lymphocytes or a
thick subendothelial collagen band)
are diagnostic, but there may be a
40% false-negative rate if only leftsided biopsies are taken, so samples
should also be taken from the
ascending colon.
2.7.3 Microscopic colitis

pathology
The aetiology of microscopic
colitis is not known, but there is a
recognised association with coeliac
disease, raising the possiblity of
gluten sensitivity as an aetiological
factor, and also an association with
the use of NSAIDs. Colonoscopy
is macroscopically normal, but
histology may show a marked
rise in intraepithelial lymphocytes
(lymphocytic colitis) or a thick
subepithelial collagen layer
(collagenous colitis).
Epidemiology
Occurs typically in middle-aged and
elderly women. More common than
originally thought, with combined
incidence of about 810 per
100,000.
Most commonly with persistent
watery diarrhoea. Less commonly
weight loss and abdominal pain may
be seen in cases with coexisting
coeliac disease.
Other cause of chronic diarrhoea

Treatment
The condition may be self-limiting.
Antidiarrhoeal agents (eg
loperamide) may be sufficient in
mild disease. 5-Aminosalicylic acid
compounds may be of benefit in
mild to moderate disease, with
improvement seen in up to 50% of
cases. Bismuth subsalicylate has
been advocated, but trial data are
limited and there remain concerns
over potential toxic side effects. In
resistant cases budesonide (a potent
corticosteroid with high first-pass
metabolism and thus low systemic
side-effect profile) seems to be
more efficacious than conventional
corticosteroid therapy with
prednisolone. Colestyramine
may be of value, with some
case series reporting incidence
of concomitant bile salt
malabsorption as high as 60%.
There are no good data for any
of the mentioned drugs in
maintenance of remission.
Arthritis, thyroiditis, diabetes,

coeliac disease.
FURTHER READING
Chande N, McDonald JW and
MacDonald JK. Interventions for
treating lymphocytic colitis. Cochrane
Database Syst Rev 2007; Jan 24:
CD006096.
Stroehlein R. Microscopic colitis. Curr.
Opin. Gastroenterol. 2004; 20: 2731.
2.8 Functional bowel

disorders
There are a range of functional
bowel disorders (Table 38). The rest
of this section concentrates on the
commonest of these, irritable bowel
syndrome.
pathology
The hallmark of the functional
gastrointestinal disorders is altered
(usually increased) visceral pain
sensitivity. This may be associated
with increased release of 5hydroxytryptamine (5HT, serotonin)
from enterochromaffin cells in the
gut, but central (psychosocial,
neurohumoral) factors may be
important, and it has also been
suggested that alterations in the
intestinal bacterial flora may be
involved. This is supported by the
high incidence of patients presenting
with irritable bowel syndrome
following culture-positive
gastroenteritis, use of broadspectrum antibiotics or pelvic
surgery. The role of stress is
uncertain, but there is a higher
101
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TABLE 38 THE
FUNCTIONAL BOWEL DISORDERS
Classification
Examples
Oesophageal disorders
Globus
Functional heartburn
Functional dysphagia
Gastroduodenal disorders
Functional dyspepsia
Functional vomiting
Bowel disorders

Functional constipation
Functional diarrhoea
Functional abdominal pain
Biliary disorders
Sphincter of Oddi dysfunction
Anorectal disorders
Functional faecal incontinence

Proctalgia fugax
Functional paediatric disorders
incidence of psychological disorders

in those who seek medical advice.
Epidemiology
The prevalence of the functional
bowel disorders depends entirely on
definition. It is estimated that only
10 50% of patients with functional
gut symptoms consult medical
practitioners, yet this represents as
much as 5% of all general practice
consultations in the UK and up to
40% of gastroenterology referrals.
There is a female to male
predominance of 23:1. About 75%
of patients diagnosed with irritable
bowel syndrome will continue to
have chronic disease.
Common
The agreed definition of irritable
bowel syndrome is as follows: At
least 12 weeks, which need not be
consecutive, in the preceding 12
months of abdominal discomfort or
pain that has two of the following
three features: relieved with
defecation; and/or onset associated
with a change in frequency of stool;
and/or onset associated with a
change in form (appearance)
of stool.
102
Symptoms that cumulatively support

the diagnosis of irritable bowel
syndrome include abnormal stool
frequency (more than three motions
per day or less than three motions
per week); abnormal stool form;
abnormal stool passage (urgency,
straining or incomplete evacuation);
passage of mucus; bloating or a
feeling of abdominal distension.
There are some clinical

features that should not be
attributed to a functional cause
without careful further investigation,
including:
dysphagia;
anorexia and/or weight loss;
mouth ulcers;
nocturnal diarrhoea;
rectal bleeding.
Physical signs
There are no characteristic physical
signs.
both the correct clinical diagnosis

and subsequent management.
Investigations depend largely on
the patients particular symptom
complex. A recommended screening
panel would include FBC,
erythrocyte sedimentation rate,
thyroid function tests and coeliac
antibodies. Where appropriate
consider stool cultures. Patients
aged over 50 years presenting with
altered bowel habit should have a
colonoscopy.
The following should always
be considered: coeliac disease,
hypolactasia, inflammatory bowel
disease, giardiasis, depressive illness,
gastrointestinal malignancy and
thyroid disease (hyperthyroidism
and hypothyroidism). The diffential
diagnosis for chronic diarrhoea is
described in Section 1.1.3.
Treatment
The most important part of

the management is to listen to
the patient: after a thorough history
and physical examination the qualified
reassurance of being told that there
is no objective evidence of physical
disease may be sufficient to lead to an
improvement in symptoms (or at least
the resulting concern).
The treatment of irritable

bowel syndrome sufferers is often
disappointing but should be tailored
to the predominant symptoms of the
patient (Table 39).
Prognosis
Investigation
The extent of clinical investigation
must be tailored to the individual
patient. A detailed history (including
a good dietary history) is central to
Most patients will continue to

have intermittent gastrointestinal
symptoms and some may develop
more overt psychiatric problems.
Mortality is not increased.
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FURTHER READING
Carter MJ, Lobo AJ and Travis SPL
(on behalf of the IBD Section of the
TABLE 39 TREATMENTS
Main symptom
Treatments
Diarrhoea
Dietary exclusion: common problem foods include wheat, dairy and

eggs; many patients benefit from a low-fibre diet and find their
symptoms worsen with increase in dietary fibre
Antidiarrhoeals (loperamide, diphenoxylate)
5HT3 antagonists, eg alosteron, but concern remains over the
association with ischaemic colitis
Amitriptyline
Constipation
Fibre supplementation: this may be achieved by dietary means, but may

result in increased pain or bloating; non-fermentable bulking agents
(eg Normacol) may be more efficacious
Laxatives: stimulant laxatives (eg senakot) are not recommended for
long-term use; osmotic laxatives, eg Movicol (macrogols) or other
polyethylene glycol-based preparations, are most effective
Biofeedback: particularly if straining is a predominant symptom; retrains
individuals to defecate normally
Pain/bloating
Anitcholinergics (eg mebeverine, alverine): reduce bowel spasm

Amitriptyline: has anticholinergic effects and works on serotonin
pathway; effective at small (1025 mg) doses independently from
presence of depressive symptoms, but side-effect profile may limit use.
SSRIs: act on serotonin pathway; fewer side effects than amitriptyline
but data less convincing
Hypnotherapy
Kennedy T, Rubin G and Jones R.

Irritable bowel syndrome. Clin. Evid.
2004; 11: 61525.
Mertz HR. Irritable bowel syndrome.
N. Engl. J. Med. 2003; 349: 213646.
2.9 Large bowel

disorders
Colorectal cancer remains

a major cause of death
worldwide. It commonly presents at
an advanced stage with complications
such as colonic obstruction or
perforation, but recognition that most
cancers arise within adenomatous
polyps of the colon (Fig. 53) has led to
a greater emphasis on early diagnosis.

the colon
pathology
These are benign neoplastic polyps.
The cause is uncertain, but may be
related to genetic abnormalities or
diet. Although slow-growing they
may develop malignant potential,
especially if greater than 1 cm in
diameter or if they demonstrate
high-grade dysplasia on microscopy.
Most commonly an incidental
finding at colonoscopy, but
sometimes can present with iron-
FOR PATIENTS WITH IRRITABLE
BOWEL SYNDROME
SSRIs, selective serotonin reuptake inhibitors.
deficiency anaemia and /or rectal

bleeding.
adenomas, which do have malignant

potential.
Hamartomatous polyps
Polyps found during
colonoscopy for investigation of
iron-deficieny anaemia may not be the
cause but merely an incidental finding.
Not all colonic polyps carry a
significantly increased risk of
colorectal cancer.
Hyperplastic polyps
These are diminutive polyps, usually
less than 5 mm in diameter, found in
the distal colon and rectum. They
are not neoplastic and carry no
significant risk of colorectal cancer.
Hyperplastic polyps found beyond
the splenic flexure should be
followed up as they may be serrated
These are associated with

PeutzJeghers syndrome, and
although they are not themselves
neoplastic, there is an increased risk
of gastrointestinal tumours in these
patients.
Inflammatory pseudopolyps
Representing islands of regenerative
mucosa in a chronically inflamed
bowel, these are seen in Crohns
disease and ulcerative colitis. They
carry no malignant potential.
Treatment
Colonoscopic polypectomy is
recommended for all adenomatous
polyps. Further surveillance for
these patients is discussed in
Section 2.9.2.
103
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Complications
Colorectal carcinoma.
FURTHER READING
Levine JS and Ahnen DJ. Clinical
practice: adenomatous polyps of the
colon. N. Engl. J. Med. 2006; 355: 25517.
Colorectal cancer is a major

public health problem in the
developed world: increasing efforts
are being directed towards early
identification of the condition in
individuals considered to be at risk.
pathology
There are several conditions that
are recognised to predispose to
colorectal cancer.
Adenomatous polyps of the colon

Tubulovillous adenomas carry an
increased risk of colorectal cancer.
It is generally felt that colorectal
cancer usually develops in preexisting adenomatous polyps in
the colon (Fig. 53).
Ulcerative colitis
Patients with a 10-year history of
colitis extending proximal to the
splenic flexure are at increased risk
of colorectal carcinoma. They should
be offered surveillance colonoscopy
with random pancolonic biopsies
to detect dysplastic change (see
Prevention).
Family history
There is a family history in 14%
of new cases of colorectal cancer.
Lifetime risk can be calculated
based on family history and
surveillance recommended
accordingly (Table 40).
104
Fig. 53 The colonic adenomacarcinoma sequence. DCC (deleted in colon cancer), APC, MLH1 and MSH2
are genes.
Familial cancer syndromes
Epidemiology
There are some rare but important

hereditary cancer syndromes.
The incidence of colorectal cancer

increases with age, and overall has
increased over the last 50 years.
Colorectal cancer now accounts for
20,000 deaths per year in the UK.
Familial adenomatous
polyposis (FAP): autosomal
dominant; hundreds of
adenomatous polyps are
seen throughout the colon
and evident from an early age;
the risk of neoplasia is such
that prophylactic colectomy is
performed before the age of 20.
Common
Change in bowel habit: new-onset
constipation or spurious diarrhoea.
Iron-deficiency anaemia.
Hereditary non-polyposis
colon cancer (HNPCC): this
is inherited in an autosomal
dominant fashion and is due to
mutations in DNA mismatch
repair genes; individuals at risk
are offered colonoscopic
screening.
TABLE 40 FAMILY
CANCER. THERE IS
Rectal bleeding.
Uncommon
Large bowel obstruction:
constipation, pain and vomiting.
Evidence of metastatic disease
(ascites).
HISTORY AND LIFETIME RISK OF COLORECTAL

A BENEFIT OF SURVEILLANCE COLONOSCOPY
AT A RISK OF
IN
12
OR GREATER
Family history of colorectal cancer
Lifetime risk
None
One first-degree relative >45 years
One first-degree and one second-degree relative
One first-degree relative <45 years
Two first-degree relatives (any age)
Dominant inheritance (eg HNPCC)
1 in 40
1 in 17
1 in 12
1 in 10
1 in 6
1 in 2
HNPCC, hereditary non-polyposis colon cancer syndromes.
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Weight loss.
Abdominal pain.
Anorexia.
Physical signs
Common
In most cases there will be no
diagnostic physical signs.
Uncommon
Palpable abdominal mass.
Signs of iron deficiency: pallor,
koilonychia, glossitis.
Signs of metastatic disease:
hepatomegaly, ascites.
Fig. 54 Dukes staging for colorectal carcinoma. This was originally used for the staging of rectal cancer
but is now widely adopted for colorectal cancer in general. Stage D was not originally described by Dukes.
Dukes staging of colonic carcinoma
(Fig. 54).
Blood tests
FBC, iron indices: may demonstrate
Liver blood tests may be

normal or there may be
an isolated elevation in alkaline
phosphatase (may be >1000 U/L)
in the presence of liver metastases.
Tumour markers
Carcinoembryonic antigen (CEA) is
not useful for diagnosis but may be
useful in monitoring the patients
response to treatment and for the
identification of disease relapse.
Fig. 55 Barium enema showing an apple-core lesion of colonic carcinoma in the transverse colon.
Colonoscopy
Barium enema
Colonoscopy is the investigation of

choice. Total examination of the
colon should be undertaken, even
in instances of proven distal
tumours, to exclude the presence
of synchronous tumours or polyps.
If this has not been performed
prior to resection, it ought to be
done subsequently.
May be considered in the elderly or

frail, or where colonoscopy has been
unsuccessful. Characteristic applecore lesions may be seen (Fig. 55).
Liver ultrasound, abdominal CT, MRI

Abdominal CT is now the
investigation of choice for
identifying metastatic disease. In
patients with rectal carcinoma MRI

scanning of the pelvis is used to
determine invasion into local
structures and determine suitability
for resection. Chemotherapy or
radiotherapy may be used prior to
surgery in metastatic disease to
down-grade the tumour stage, so
staging should be performed except
in emergency settings.
105
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Diagnoses listed in Table 41 should
be considered.
Treatment
It is not necessary to establish

a tissue diagnosis before
laparotomy if there are signs of
impending bowel obstruction.
Emergency
DIAGNOSIS OF COLORECTAL CARCINOMA
Presentation
Diagnoses to consider
Change in bowel habit
Inflammatory bowel disease
Gastroenteritis
Thyroid disease
Iron-deficiency anaemia
Peptic ulcer disease

Coeliac disease
Upper gastrointestinal malignancy
Colonic angiodysplasia
Dietary deficiency (rare as sole cause)
Rectal bleeding
Haemorrhoids (fresh blood in the pan and on the paper)

Diverticular disease (may cause massive bleeding;
typically acute rather than persistent)
Acute large intestinal obstruction is

a surgical emergency with a high
risk of caecal perforation.
Short-term
Surgery This is required in most
cases of colorectal cancer. The extent
of bowel resection depends on the
site of the tumour: attempts are
made to resect at least 5 cm of
normal bowel either side of it.
Palliative approaches Although
surgery is the usual treatment for
patients with impending colonic
obstruction, stenting of tumours
with self-expanding metal stents
offers an alternative approach for
the palliative relief of obstruction.

Chemotherapy Treatment with
5-fluorouracil improves survival
for Dukes B and C cancers.
Radiotherapy Preoperative
radiotherapy to down-stage rectal
tumours reduces local recurrence
but has limited effect on survival.
Complications
Large bowel obstruction and
metastatic disease are common.
Prognosis
Mortality
Prognosis following surgery depends
on the histological grade of the
106
TABLE 42 THE 5-YEAR
SURVIVAL RATES AFTER RESECTION
OF COLORECTAL CANCER
Dukes stage
5-year survival (%)
A
B
C
Distant metastases
95100
6575
3040
<1
tumour and the Dukes stage

(Fig. 54 and Table 42).
Prevention
Identifying asymptomatic
individuals with premalignant or
early malignant disease offers the
opportunity to reduce the associated
mortality of colorectal carcinoma.
This is loosely referred to as
screening, although it may be
useful to distinguish targeted
screening on the basis of a preexisting disease (surveillance,
eg ulcerative colitis) or positive
family history (case finding) from
population screening of individuals
of average risk.
Surveillance
Indications for surveillance include:
previous diagnosis of colorectal
cancer;
previously identified colonic

polyps (high-grade dysplasia,
more than three adenomas,
any polyp >1 cm);
ulcerative colitis (initial
surveillance colonoscopy at
10 years, then 3-yearly until
20 years, then 2-yearly until
30 years, then yearly);
FAP syndrome;
HNPCC or other familial colon
cancer syndromes.
Case finding
Appropriate in those with a
significant positive family history
(see Table 40).
Population screening
Despite continuing controversy,
population screening for colorectal
cancer is shortly to be introduced in
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the UK. This will currently include

all those over 60 years of age with
a positive faecal occult blood test,
and will eventually be extended to
include those over 50 years old.
Colonoscopy will be offered to all
identified individuals at 5-yearly
intervals.
Epidemiology
The prevalence of diverticular
disease of the colon increases
with age: it is present in 50%
of the population over the age
of 50 years.
Common
Colonoscopy carries a risk of

bleeding or perforation of 1 in
1,000, which is increased if therapeutic
colonoscopy (eg polypectomy) is
performed. Patients should be advised
of this risk, including the potential
need for surgery (perhaps colostomy)
in such an eventuality.
FURTHER READING
Cairns S and Scholefield JH, eds.
(Developed on behalf of the British
Society of Gastroenterology and the
Association of Coloproctology of Great
Britain and Ireland). Guidelines for
colorectal cancer screening in high
risk groups. Gut 2002; 51 (Suppl. 5):
Weitz J, Koch M, Debus J, et al. Colorectal
cancer. Lancet 2005; 365: 15365.
2.9.3 Diverticular disease

pathology
Although there are suspicions that
there may be an underlying genetic
predisposition to diverticular
disease, it is best considered as an
acquired condition. Diverticula form
as herniations of colonic mucosa
through the muscularis layer.
This process tends to occur more
commonly in the distal colon and
usually occurs at the point of entry
of penetrating blood vessels through
the muscle layers (hence the
presentation with acute
haemorrhage).
Diverticula are common in elderly

people, often asymptomatic and
regarded as an incidental finding
at colonoscopy/barium enema.
Acute presentation is usually in
the form of one of the common
complications.
Diverticulitis: an associated
inflammation of the colon, often
related to infection and thought to
result from impaction of faeces
within a diverticulum.
Colonic bleeding: a frequent
presentation of diverticular
disease, thought to result from
the fact that diverticula form at
the point of maximal weakness
in the colon, ie at the point
where blood vessels penetrate
the muscle coat.
Some patients will have non-specific
symptoms such as low abdominal
pain, constipation or diarrhoea.
Uncommon
Diverticular abscess.
Colovesical fistula.
Colonic stricture: after repeated
episodes of inflammation,
resulting in subacute colonic
obstruction.
Investigation
Barium enema/colonoscopy
Diverticular change may be
demonstrated by either barium
enema or colonoscopy.
Abdominal CT
CT is the best way to demonstrate
abscess formation (Fig. 56).
Colovesical fistulae require a high
index of suspicion (recurrent urinary
tract infections, pneumaturia, etc.)
but may be identified on barium
contrast radiology (Fig. 57).
This includes colonic carcinoma,
colonic ischaemia, inflammatory
bowel disease and irritable bowel
syndrome.
Treatment
Short-term
The management of diverticular
disease is determined by the extent
of symptoms or presence of
complications. Acute diverticulitis
requires intravenous fluids,
antibiotics and analgesics, with
diverticular abscess often requiring
drainage in addition; bleeding will
usually settle with supportive
treatment.
Long-term
Avoidance of constipation (high-fibre
diet, bulking laxatives such as
Normacol, and good fluid intake)
is recommended in the belief
that this may reduce the risk of
complications. Surgery is reserved
for complicated diverticular disease
(ie bleeding, abscess, stricture).
Physical signs
There are no specific physical signs
of diverticular change itself. In acute
diverticulitis or in the presence of a
diverticular abscess there may be left
iliac fossa tenderness or a palpable
mass.
Prognosis
Many patients experience recurrent
diverticulitis or bleeding, but
diverticular change is not a
progressive pathology and there is no
increased risk of colonic neoplasia.
107
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Fig. 56 Diverticular disease: (a) CT scan showing a loop of bowel (lumen in black) with diverticula; (b) adjacent collection (identified by tip of white marker line)
due to a perforated diverticulum adjacent to the bladder.
hyperlipidaemia and atrial

fibrillation.
Common
Ischaemic colitis Bloody diarrhoea,
usually of sudden onset and
associated with abdominal pain.
Ischaemia frequently affects

the splenic flexure of the colon,
which is the watershed between areas
supplied by the superior and inferior
mesenteric arteries. The caecum and
distal terminal ileum are also
commonly involved.
Fig. 57 Barium enema showing fistulae complicating diverticular disease.
FURTHER READING
Stollman N and Raskin JB. Diverticular
disease of the colon. Lancet 2004; 363:
6319.

pathology
As with vascular disease elsewhere
in the body, the gut is prone to
108
ischaemia from either progressive

atheromatous narrowing
of the mesenteric arteries or
thromboembolism from intracardiac
or proximal vascular sources.
Epidemiology
Vascular disease in general is
increasing in most developed
countries. Risk factors include age,
male sex, family history, smoking,
diabetes, hypertension,
Small bowel infarction This is

usually due to arterial embolism and
presents as an acute abdomen, often
with severe systemic disturbance
(hypotension, acidosis).
Uncommon
Mesenteric angina: recurrent
postprandial abdominal pain and
weight loss.
Physical signs
Other features of atheroma: arcus,
xanthelasma.
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Potential sources of arterial

embolism: atrial fibrillation,
heart valve disease.
Abdominal bruits and other
evidence of vascular disease.
Investigation
Radiological
Plain abdominal radiograph:
may show aortic calcification
and colonic mucosal oedema,
often with thumb-printing,
which may be of relatively
limited distribution compared
with other forms of colitis
(eg distal transverse colon
and splenic flexure).
CT or MRI angiography: the
presence of significant stenosis
or occlusion of two out of three
(coeliac axis, superior mesenteric
artery and inferior mesenteric
artery) vessels is suggestive of
significant disease; the superior
mesenteric artery needs to be
involved to justify intervention.
Mesenteric angiography: confirms
the radiological diagnosis
and may allow therapeutic
intervention to be performed
(eg angioplasty or stenting).
ischaemia (eg ischaemic colitis) are

usually managed conservatively.
Complications
Intestinal strictures and obstruction.
Prognosis
Excess mortality is associated with
other features of vascular disease
(ischaemic heart disease, stroke,
renal failure, etc.). Acute intestinal
infarction carries a high mortality
rate and significant long-term
morbidity, often requiring parenteral
nutrition.
FURTHER READING
Green BT and Tendler DA. Ischemic
colitis: a clinical review. South. Med. J.
2005; 98: 21722.
2.9.5 Anorectal diseases

See Table 43.
2.10 Liver disease

2.10.1 Acute viral hepatitis
Colonoscopy may reveal ischaemic

changes but carries increased risk of
perforation in this context and is not
recommended if ischaemic colitis is
the most likely diagnosis.
This includes colorectal carcinoma,

diverticular change, inflammatory
bowel disease, peptic ulcer disease
and chronic pancreatitis.
Treatment
Acute intestinal infarction often
requires emergency surgery for
bowel resection. Lesser degrees of
Common
Hepatitis A is an acute hepatitis

caused by an RNA virus that is
spread by the faecaloral route.
Figure 58 shows the histological
picture of acute viral hepatitis.
Epidemiology
Hepatitis A endemic regions

include, but are not limited to,
Mexico, parts of the Caribbean,
South America, Central America,
Africa, Asia (except Japan), the
Mediterranean basin, Eastern
Europe and the Middle East.
Hepatitis A remains the most
common vaccine-preventable
disease in travellers to endemic
regions, who can contract hepatitis
A by ingestion of contaminated
drinking water or ice, uncooked
fruits or vegetables grown with or
washed in contaminated water, or
raw or uncooked shellfish (oysters,
clams or mussels). Outbreaks can
be seen in day-care centres where
children have not been toilet-trained,
after breakdowns in usual sanitary
conditions such as natural disasters,
and occasionally through blood
transfusions or by sharing
contaminated needles and
syringes. The incubation period
is 1545 days.
Aetiology/pathology
Other
Better sanitation means age of first

exposure is increasing. Most cases
are sporadic.
Hepatitis A is the commonest cause

of viral hepatitis in the UK, with an
incidence of symptomatic disease
of about 6 per 100,000, most
commonly between the ages of
20 and 45 years. Asymptomatic
disease is common in childhood: 5%
of children in the UK are immune by
5 years of age, compared with 74%
of people over the age of 50 years.
Most cases are asymptomatic, with

symptoms and severe disease more
common with increasing age. If
symptomatic the presentation is of
an acute hepatitis with non-specific
symptoms of lethargy, arthralgia,
anorexia, nausea and mild upper
quadrant discomfort (prodrome)
followed by jaundice. The latter is
associated with pale stools and dark
urine. Itching can occur in the
cholestatic phase of illness.
Physical signs
Features of an acute hepatitis
(tender mild hepatomegaly, jaundice)
are common. Splenomegaly is seen
in 15% of cases.
109
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TABLE 43 ANORECTAL
Condition
Aetiology,
pathophysiology,
pathology
DISEASES
Investigation
Treatment
Haemorrhoids (piles) Varicose perianal veins;

associated with chronic
constipation and straining
at stool
Common findings are

rectal bleeding (usually
bright red blood on the
toilet paper, but
sometimes dramatic
bleeding), perianal
irritation (itching), pain
(usually associated with
thrombosis)
Proctoscopy
Flexible sigmoidoscopy:
necessary to exclude other
causes of rectal bleeding (eg
proctitis, rectal cancer, polyps)
In some circumstances
investigation of the more
proximal colon by barium
enema or colonoscopy may
be necessary
Conservative: simple advice

on diet, use of aperients and
toilet habits
Injection sclerotherapy
(phenol)
Banding: now replacing
injection therapy
Surgery: haemorrhoidectomy
reserved for very troublesome
haemorrhoids
Anal fissure
Tear in anal mucosa

associated with straining
and passage of a very
hard constipated stool
Anal pain on defecation;

constipation, which is
sometimes secondary to
the pain associated with
defecation
Sigmoidoscopy and
examination under
anaesthetic
Conservative: advice on diet

and hydration to avoid
constipation
GTN paste: when applied to
the anus this leads to
reduction in anal sphincter
tone and healing of fissures
Surgery: lateral
sphincterotomy performed for
resistant cases
Fistula in ano1
A fistulous tract originating

in the rectum and opening
onto the perineum or into
other pelvic organs (most
commonly the vagina)
Discharge: pus, mucus

and blood may
discharge spontaneously
onto the perineum
Pain: if persistent,
usually indicates a
complicating abscess
Sigmoidoscopy: but this may

be very uncomfortable for the
patient and may provide only
limited information
Examination under
anaesthetic: allows thorough
sigmoidoscopy and the
probing of any identified
tracts; biopsies should be
taken to exclude Crohns
disease.
MRI: is of increasing utility in
delineating the course of
fistulae and identifying
associated abscess cavities

constipation
Seton drain: a plastic drain
placed through a fistula will
keep the tract open and
prevent the recurrent
formation of abscess
Fistulotomy: superficial
fistulae may be laid open
Solitary rectal ulcer
Ulceration of the anterior

Tenesmus and rectal
rectal wall due to
bleeding
excessive straining. An
increasing number of
patients are presenting
with rectal ulcers due to
the use of nicorandil, a
potassium channel agonist
used in the treatment of
ishaemic heart disease
Sigmoidoscopy and rectal

biopsy

constipation
1. Fistula in ano may cause faecal incontinence if it passes through the anal sphincter; Crohns disease should always be considered in
patients with recurrent or complex perianal fistulae.
GTN, glyceryl trinitrate.
110
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Fig. 58 Histology of acute viral hepatitis. (a) Unlike cirrhosis the normal hepatic architecture is preserved. (b) Higher power showing mixed (neutrophil and
polymorphonucleocyte) portal tract inflammation and infiltration of the lobule; other findings are hepatocyte necrosis and ballooning of hepatocytes. (c) Hepatitis
B infection with positive immunohistochemical staining for HBsAg in hepatocytes.
Investigation
Liver biochemistry: high serum
transaminases (peak usually
>1000 U/L), with or without
raised serum bilirubin; alkaline
phosphatase raised in cholestatic
phase; normal albumin.
Serology: the presence of hepatitis
A IgM indicates a recent infection
(Fig. 59).
See Table 44.
Fig. 59 Serology in acute hepatitis A. HAV, hepatitis A virus.
111
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DIAGNOSIS OF ACUTE HEPATITIS
Common
Uncommon
Viral hepatitis
Halothane
Hepatitis A
Nitrofurantoin
Hepatitis B ( hepatitis D)
Liver infiltration (adenocarcinoma/lymphoma)
Hepatitis E
Venous hepatic outflow obstruction
Seronegative hepatitis
Pregnancy-associated liver disease
Drugs
Wilsons disease
Paracetamol
NSAIDs
Flucloxacillin/Augmentin (co-amoxiclav)
Dextropropoxyphene
Alcoholic hepatitis
Autoimmune chronic active hepatitis
Ischaemic hepatitis (eg heart failure, septic shock)
Prevention
In those with a typical
hepatitis who are seronegative
for hepatitis A and B, be sure to
specifically request hepatitis E testing.
Passive immunisation
Pooled serum immunoglobulin can
be given to close contacts of a case
of hepatitis A within 2 weeks of
exposure.
Treatment
This is supportive, with intravenous
fluids if vomiting. Rare cases of
acute liver failure need special
management.
Complications
A cholestatic phase in acute

hepatitis is common, can last
between 12 and 18 weeks, and is
associated with rising bilirubin
(ie 400 500 mol/L) and alkaline
phosphatase and falling serum
transaminases. Relapsing disease
is rare, occurring in 6%, but there
is no chronic state.
Active immunisation
Formalin-inactivated vaccine is
indicated for travellers to high-risk
areas, homosexuals, intravenous
drug users and those with chronic
liver disease. It provides protection
for 510 years.
Hepatitis A is self-limiting with no

residual liver damage. Symptoms
and signs usually resolve within
3 weeks. Acute liver failure occurs in
0.140.35%. Death occurs in 0.04%
of patients with symptomatic
disease.
112
Hepatitis E is seen in young adults

and resembles hepatitis A. The
incubation period is 3446 days.
Jaundice is often of sudden onset
and liver biochemistry is cholestatic.
Acute liver failure is rare. It
is diagnosed by IgG and IgM
antibodies to recombinant HEV
proteins. Alternatively HEV RNA
can be detected by polymerase
chain reaction (PCR).
The disease is self-limiting. Acute
haemorrhagic syndrome with
encephalopathy and renal failure
is a complication seen most typically
in women in the last trimester of
pregnancy and is associated with a
20% mortality.
Community-acquired hepatitis E
infection does sporadically occur in
the UK and should be considered
as a cause of seronegative hepatitis.
There is a suggestion that there may
be an animal reservoir as the virus
has been identified in a number of
animal species including swine,
sheep, cattle, poultry and rodents.
FURTHER READING
Kemmer NM and Miskovsky EP.
Hepatitis A. Infect. Dis. Clin. North Am.
2000; 14: 60515.
2.10.1.2 Other acute viral

hepatitis
Hepatitis E
Prognosis
Hong Kong. It is rare in the UK,

with only about 2% of adults being
immune. There is low viral faecal
excretion and hence low secondary
spread.
This is caused by hepatitis E virus

(HEV), an RNA virus transmitted
by the faecaloral route. It accounts
for sporadic and major epidemics
of viral hepatitis, particularly in
developing countries, but also in
other parts of the world, eg 50% of
non-A non-B (NANB) hepatitis in
Cytomegalovirus
Cytomegalovirus (CMV) can
cause an acute hepatitis, most
commonly in those who are
immunosuppressed. Patients may
be asymptomatic, with hepatitis
recognised solely from elevation of
serum transaminases, but symptoms
can range from fever and malaise to
a devastating illness with jaundice
and other features of CMV infection
including pharyngitis, oesophagitis,
gastroenteritis, pneumonitis,
retinitis and bone marrow
suppression. Diagnosis is by
demonstrating CMV on tissue
biopsy, detection of CMV by PCR
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in blood or urine, or by finding

IgM to CMV. Treatment is with
intravenous ganciclovir.
EpsteinBarr virus
Hepatitis B virus (HBV) is a doublestranded DNA virus. The e antigen is

a protein subunit of the core of the
virus that is excreted by hepatocytes.
Excess surface antigen is also found
free in serum. The histological
picture is of an acute hepatitis
with liver damage due to immune
clearance of the virus.
Primary infection in children is

asymptomatic. In young adults
it can mimic viral hepatitis with
fever and right upper quadrant pain
together with elevated bilirubin
(in 50%) and transaminases (up
to 20 times normal). Diagnosis is
made by a positive monospot or
raised IgM to EpsteinBarr virus
capsid antigens. The disease is
self-limiting.
Other
Other rare causes of viral
hepatitis include herpes simplex,
adenovirus and rubella in the
immunosuppressed. Parvovirus
also rarely causes hepatitis in
association with pancytopenia.
Note that hepatitis C is not a cause
of acute liver disease, but is the
commonest cause of chronic
hepatitis in the world.
FURTHER READING
Aggarwal R and Krawczynski K.
Hepatitis E: an overview and recent
advances in clinical and laboratory
research. J. Gastroenterol. Hepatol.
2000; 15: 920.
pathology
Epidemiology
Horizontal transmission is via
parenteral transmission and sexual
contact, and probably by close
contact in young children. Vertical
transmission accounts for the high
rates of infection worldwide. The
prevalence is falling, although
worldwide there are still 350 million
chronic carriers.
Common
Most infected individuals are
asymptomatic. Some will have fever,
malaise, nausea and right upper
quadrant pain. Up to 4 months after
exposure there may be self-limiting
jaundice, which rarely lasts more
than 1 month (Fig. 60).
Rare
A cholestatic phase and relapses
are uncommon (unlike hepatitis A).
The presence of immune complexes
containing hepatitis B antigens leads
to extrahepatic manifestations, eg
polyarteritis, glomerulonephritis
and myocarditis.
Physical signs
The acute phase may produce
signs of an acute hepatitis. Signs of
chronic liver disease develop later in
some cases (see Section 1.2.2).
Investigation
Liver biochemistry
High serum transaminases and an
elevated bilirubin may be seen in the
acute phase.
Evidence of infection
Serological markers of HBV infection
are shown in Table 45. During the
acute phase of illness HBV DNA
can be detected in the blood; this is
cleared by 2 months in >90% of cases.
Hepatitis B core IgM is often

the only marker of infection
in acute liver failure as the virus will
have been eradicated by the immune
system by the time liver failure occurs.

Chronic viral hepatitis refers to
inflammation of the liver (hepatitis)
that is caused by a virus and which
lasts for longer than 6 months.
Hepatitis B and C viruses are the
commonest causes. Presentation
is highly varied: infection may be
asymptomatic, subclinical causing
only vague symptoms like fatigue,
or lead to chronic liver disease and
cirrhosis (about 20% of patients
with chronic hepatitis B or C).
Fig. 60 Time course of acute hepatitis B infection. AST, aspartate transaminases.
113
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TABLE 45 SEROLOGICAL
Acute hepatitis B
Resolved acute infection
Vaccination
MARKERS OF HEPATITIS
INFECTION
HBsAg
HBeAg
HBsAb
HBcAb (IgG)
+/
Treatment
Acute liver failure
Neonates
No treatment is indicated for

most patients with acute infection.
Lamivudine is now being used
in those with acute liver failure,
and liver transplantation may be
needed. In those with chronic active
hepatitis, with evidence of ongoing
inflammation biochemically and
on liver biopsy, treatment with
interferon alfa or lamivudine may be
suggested after review by a specialist.
Adevofir or entecavir may be used in
the event of lamivudine resistance.
Liver transplantation is offered for
patients with decompensated
hepatitis B cirrhosis.
Due to enhanced immune response

with rapid clearance of the virus.
Others
If the mother has HBV, give hepatitis

B immunoglobulin at birth as
passive immunisation, together
with hepatitis B vaccination.
Polyarteritis and glomerulonephritis

are rare.
Complications
Chronicity
Persistence of HBsAg in serum for
longer than 6 months suggests
chronicity. Overall, 10% of adults
and 90% of neonates or those who
become infected in infancy will
become chronic carriers. The carrier
rate in the UK is 0.1% compared
with 1015% in Africa. Chronicity is
less common if the acute attack is
more severe, ie associated with
jaundice.
TABLE 46 INDICATIONS
Prognosis
Good unless acute liver failure ensues.
Prevention
Vaccination along with strategies to
prevent exposure.
Children and adults

Recombinant vaccine is given
intramuscularly; after three injections
94% will become immune. Low
responders (often the elderly, the
immunosuppressed or those on
renal replacement therapy) may
need a further booster/course of
vaccination. For all receiving
vaccination a booster is
recommended every 57 years
to maintain HBsAb levels above
100 IU/L. There is an argument for
universal vaccination in childhood
to eradicate HBV worldwide, but
currently it is recommended for
selected groups only (Table 46).
FOR VACCINATION FOR HEPATITIS
Surgical and dental staff1

Hospital staff in contact with blood products1
Mental abnormality
Close family and sexual contact of HBsAg-positive individual
Drug abusers
Homosexually active men
Travellers to high-risk areas
1. In many hospitals/healthcare settings, vaccination against hepatitis B is a condition of
employment.
114
Remember to tell a patient

with HBsAg to avoid
unprotected sexual intercourse
unless his or her partner is immune
to hepatitis B.
pathology
Hepatitis C virus (HCV) is an
RNA virus that is parenterally
transmitted, most commonly
by percutaneous exposure to
contaminated blood. Sexual
transmission is possible, but not
common. HCV infection occurs
in 28% of infants born to HCVinfected mothers. Most of those
infected develop hepatitis
14160 days after exposure.
Epidemiology
In the UK, 0.10.5% of the
population have been infected, but
in some countries the prevalence is
much higher, eg up to 20% in Egypt.
Most cases are asymptomatic:
perhaps 20% develop a mild acute
hepatitic illness, but jaundice is rare
and symptoms are less severe than
with hepatitis A or hepatitis B. In
the long term, 85% of patients fail to
clear the virus and have persistent
viraemia. Many of these develop
slowly progressive chronic liver
disease, and over the course of
2040 years progress from acute
to chronic persistent hepatitis,
to chronic active hepatitis, to
cirrhosis (in 10%) and eventually
hepatocellular carcinoma (14%).
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Physical signs
Prognosis and complications
There are typically no abnormal

physical signs in the acute stage
of infection. Signs of chronic liver
disease develop later in many cases
Investigation
HCV infection is one of the

commonest causes of chronic
liver failure. Rare extrahepatic
manifestations include
membranoproliferative
glomerulonephritis and mixed
cryoglobulinaemic vasculitis.
Liver biochemistry
Prevention
In acute infection, alanine

transaminase (ALT) typically
rises to about 10 times normal
and the bilirubin may also be
increased. In patients with
persistent HCV infection the
ALT fluctuates indefinitely, but
bilirubin returns to normal (until
the development of advanced
chronic liver disease).
There is no vaccine for hepatitis C,

hence prevention must be by
reducing exposure.
FURTHER READING
Cramp M and Rosenberg W. Guidance
on the Treatment of Hepatitis C
Incorporating the Use of Pegylated
Interferons. London, British Society for
Gastroenterology, 2003. Full text
Evidence of infection
HCV infection is usually diagnosed
by testing for HCV antibodies.
If positive this is followed by
testing for HCV RNA, providing an
independent method of confirming
infection and determining whether
it is persistent.
Ganem D, and Prince AM. Hepatitis B

virus infection: natural history and
clinical consequences. N. Engl. J. Med.
2004; 350: 111829.
Treatment
Pegylated interferon alfa with
ribavarin are effective but
expensive and often difficult for
patients to tolerate because of
side effects. They should only be
administered by specialists in
accordance with recognised
protocols.
Acute liver failure: encephalopathy

occurring within 828 days of
jaundice.
Subacute liver failure
(previously known as late-onset
hepatic failure): defined by
encephalopathy that occurs
between 5 and 12 weeks from
onset of jaundice.
The conditions are characterised
by acute hepatocellular necrosis.
Causes are described in
Section 1.4.6.
Increasing jaundice and confusion,
ie encephalopathy, often following
known precipitant, eg paracetamol
overdose.
Physical signs
Poland GA and Jacobson RM. Clinical
practice: prevention of hepatitis B with
the hepatitis B vaccine. N. Engl. J. Med.
2004; 351: 28328.
Liver biopsy
The acute hepatitis induced by
HCV is generally less severe than
with the other hepatitis viruses. In
patients with persistent infection the
histological findings can fluctuate,
but scoring systems that typically
quantitate necrosis, inflammation
and fibrosis remain the best
predictors of outcome and are
often used to decide whether to
offer antiviral treatment.
Hyperacute liver failure:

encephalopathy occurring within
7 days of onset of jaundice, eg
caused by paracetamol overdose.
Poynard T, Yuen MF, Ratziu V and Lai CL.

Viral hepatitis C. Lancet 2003; 362:
2095100.
Tan J and Lok AS. Update on viral
hepatitis: 2006. Curr. Opin.

pathology
Acute liver failure is distinguished
from chronic liver disease by the
absence of pre-existing clinical liver
disease. Most simply, acute liver
failure is defined as an acute illness
of less than 26 weeks duration,
associated with coagulopathy (INR
>1.5) and encephalopathy. Further
classifications have been described.
Jaundice and mild tender

hepatomegaly. Small amounts
of ascites may develop later. In
hepatic venous outflow obstruction
(BuddChiari syndrome) there
is sudden onset of tender
hepatomegaly and tense ascites.
Investigation and treatment

See Section 1.4.6.
Patients should be discussed

with or referred to a liver
transplant centre sooner rather
than later.
Complications
Common complications include the
following.
Cerebral oedema: occurs in
4070% of patients who develop
grade III/IV hepatic
encephalopathy.
115
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Infection: bacterial in about 82%

and fungal in 34% (often occult).
Acidosis.
Coagulopathy: but bleeding on
account of coagulopathy is
relatively rare.
Renal failure: hepatorenal failure
and/or acute tubular necrosis from
paracetamol.
Acute pancreatitis: seen
particularly in paracetamolinduced toxicity.
Prognosis
Overall with medical treatment
1040% of patients survive, with
outcome best for paracetamol
overdose and hepatitis A and worst
for non-A non-B hepatitis and
idiosyncratic drug reactions. The
time to onset of encephalopathy is
also a prognostic factor: 35% of
patients with hyperacute failure
survive compared with only 15%
of those with subacute failure.
With such figures, selection for
transplantation is important and
the 1-year survival after super-urgent
liver transplantation probably now
exceeds 6575%.
Prevention
Treatment of paracetamol
overdose with N-acetylcysteine
within 16 hours of overdose can
prevent liver failure.
FURTHER READING
Khan SA, Shah N, Williams R and Jalan
R. Acute liver failure: a review. Clin.
Liver Dis. 2006; 10: 23958.
Fig. 61 Metabolic pathways involved in alcohol metabolism; 85% of alcohol is metabolised via the ADH
pathway. ADH, alcohol dehydrogenase; ALDH2, acetaldehyde dehydrogenase 2; P450-II-E1, cytochrome
P450-II-E1.
presentations of liver disease. It is

estimated that 8% of men and 3% of
women are problem drinkers, but
many more people drink excessive
amounts of alcohol (perhaps as
many as 1 in 3 men and 1 in 5
women). About 20% of all adult
inpatients admitted to general
hospital settings are drinking in
a hazardous or harmful way.
pathology
Ethanol is primarily oxidised in the
liver (Fig. 61). Men who drink more
than 52 units or 420 g (1 unit of
alcohol is 10 mL by volume, or
8 g by weight, of pure alcohol) per
week and women who drink more
than 35 units (280 g) per week are
at increased risk of alcohol-related
liver disease (ALD). The three most
widely recognised forms of ALD are
alcoholic fatty liver (steatosis), acute
alcoholic hepatitis and alcoholic
cirrhosis. The histology of alcoholic
liver diseases is shown in Fig. 62.
Epidemiology

disease
In the UK, alcohol-related disease
explains at least half of all clinical
116
At least 80% of heavy drinkers

develop steatosis, 1035% develop
alcoholic hepatitis and about 10%
will develop cirrhosis.
Minor alcoholic hepatitis may
be asymptomatic, with elevated
serum transaminases as the only
abnormality, and many people are
diagnosed when they have routine
liver function tests as part of a
medical check-up. Severe alcoholic
hepatitis presents with hepatic
encephalopathy, jaundice, renal
failure or coagulopathy. Other
than those who present with
decompensated liver disease,
patients tend to have non-specific
features such as nausea, vomiting,
abdominal discomfort or diarrhoea.
They may also present with other
sequelae of alcoholism such as
pneumonia, rib fractures, head
injury, pancreatitis, neuropathy
or heart failure.
Physical signs
This depends on the severity.
Mild/moderate alcoholic hepatitis
causes tender hepatomegaly,
with jaundice in 1015%.
Severe alcoholic hepatitis
causes jaundice, ascites, hepatic
encephalopathy and rarely a hepatic
bruit. Parotid gland enlargement
and testicular atrophy are
sometimes seen.
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Fig. 62 Acute alcoholic hepatitis. (a) Pericellular fibrosis around individual hepatocytes giving a chicken-wire appearance. (b) Mallorys hyaline within
hepatocytes. (c) Megamitochondria and fat within hepatocytes. Other features are predominantly neutrophil infiltration around portal tracts and fibrosis around
the hepatic vein. More extensive fibrosis or established cirrhosis may also be present.
Investigation
Assessment of severity
FBC: there is often a leucocytosis
(more common with viral
hepatitis) and a macrocytosis. An
initial low platelet count is seen
with acute alcohol use in the
absence of portal hypertension.
Low-grade haemolysis is common.
Prothrombin time is an important
prognostic marker.
Liver function tests reveal
aspartate transaminase (AST,
usually >300 U/L) greater than
alanine transaminase (ALT) in
alcoholic liver disease. Alkaline
phosphatase is often elevated,
with levels up to three to four

times normal in the absence
of pancreatic disease (ie lower
common bile duct stricture
from chronic pancreatitis).
Transaminase levels >1000 U/L

are seen if there is associated
paracetamol toxicity, which can occur
with doses of as little as 46 g.
Abdominal ultrasound is needed to

exclude biliary obstruction and signs
of portal hypertension suggestive of
cirrhosis. Liver biopsy is diagnostic
of acute alcoholic hepatitis but
because of abnormalities in
coagulation is not often performed
in the acute context; in the long term
it is needed to establish the extent of
hepatic fibrosis.
Assessment of chronic liver disease
Alcoholic hepatitis can coexist with
other chronic liver diseases, eg
haemochromatosis, hepatitis C
and hepatitis B, which should
be screened for as appropriate
(see Sections 1.1.7 and 1.2.2).
Drugs, viral hepatitis and

autoimmune liver disease.
Treatment
This will depend on the presentation
(see Sections 1.1.7, 1.2.2, 1.4.3 and
1.4.6) but with specific regard to
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alcoholic hepatitis and alcohol

addiction.
Short-term
Corticosteroids should be considered
in severe alcoholic hepatitis as long
as there is no evidence of infection
or renal failure.
Long-term
Abstinence: psychological input
and counselling both reduce
readmission rates.
Drugs: acamprosate and
naltrexone (12 months) may
reduce alcohol dependence.
Disulfiram should probably be
avoided because of side effects.
Complications
Ascites, hepatic encephalopathy,
septicaemia, hepatorenal failure
and chronic liver disease.
Prognosis
Patients admitted to hospital with
alcoholic hepatitis have an overall
15% mortality at 30 days, but those
with severe disease (hepatic
encephalopathy, jaundice, renal
failure or coagulopathy) have a
mortality closer to 1 in 2. There are
a number of ways of quantifying
an individual patients chance of
surviving: the Maddrey discriminant
function involves a formula
including the prothrombin time and
serum bilirubin, with those scoring
highly (worse) often considered
for a trial of steroids; the Glasgow
Alcoholic Hepatitis Score (GAHS)
depends on five variables (age, white
blood cell count, urea, prothrombin
ratio and serum bilirubin) and
appears to perform slightly better.
Overall survival at 5 years is 60%
if the patient remains abstinent,
falling to 40% if the patient
continues to drink.
The development of complications of
cirrhosis reduces life expectancy: a
118
first variceal bleed has an average inhospital mortality of 2030%

and those with ascites have 50%
mortality at 2 years. The treatment
of hepatocellular carcinoma is
usually palliative.
Remember that although

alcoholic liver disease has a
poor prognosis, each patient should be
assessed and managed on his or her
own merits. Do not deny patients
intensive care or organ support just
because they are alcoholics.
Prevention
Men should drink no more

than 21 units of alcohol per
week (and no more than 4 units in any
one day) whereas women should drink
no more than 14 units of alcohol per
week (and no more than 3 units in
any one day). Pregnant women who
drink one or two drinks of alcohol
(1 or 2 units), once or twice a week, are
unlikely to harm their unborn baby,
although the exact amount that is
safe is not known.
Psychological input and counselling

(including referral to Alcoholics
Anonymous) is indicated when there
is alcohol misuse.
These include hypertension,
alcoholic cardiomyopathy, chronic
pancreatitis, duodenal ulceration,
peripheral sensory neuropathy,
cerebellar atrophy, cerebral atrophy,
Wernickes encephalopathy and
Korsakoffs dementia.
FURTHER READING
Bathgate AJ (on behalf of the UK Liver
Transplant Units Working Party).
Recommendations for alcohol-related
liver disease. Lancet 2006; 367: 20456.
Rueben A. Alcohol and the liver. Curr.

Sougioultzis S, Dalakas E, Hayes PC and
Plevris JN. Alcoholic hepatitis: from
pathogenesis to treatment. Curr. Med.
Res. Opin. 2005; 21: 133746.
2.10.5 Drugs and the liver

2.10.5.1 Hepatic drug toxicity
pathology
Drug-induced liver injury is a
potential complication of nearly
every medication (prescribed or
non-prescribed, pharmaceutical or
herbal) since the liver is central to
the metabolic disposition of virtually
all drugs and foreign substances.
Damage can occur to hepatocytes,
bile ducts and hepatic veins,
producing a range of clinical
presentations (Table 47).
The effect of drugs on the liver
may be predictable and dose
dependent, eg paracetamol, but is
more commonly idiosyncratic. Drugs
can cause direct toxic damage, or
indirect damage via the formation
of reactive metabolites, which may
deplete essential enzymes/cofactors,
eg glutathione (paracetamol),
or bind to liver proteins forming
adducts. These adducts can
subsequently mediate an
immunoallergic response, eg
autoantibodies to halothane and
nitrofurantoin have been identified.
Genetic factors are also important,
eg deficiency in certain cytochrome
P450 enzymes is associated with
hepatotoxicity.
Histological features depend on
the type of drug, but in general
drug-induced liver damage may be
differentiated from other causes of
acute liver injury by the presence of
large numbers of eosinophils (Fig. 63).
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Clinical presentation/physical signs
TABLE 47 CLINICAL
PRESENTATIONS OF DRUG HEPATOXICITY
Bilirubin ALP/GGT ALT/AST Drug causes

Acute hepatitis
++
+++
Acute cholestasis
+++
+++
++
++
Hepatic fibrosis
N
No liver disease (enzyme induction)
N
/+
Fatty liver
Steatohepatitis
Granuloma
++
++
N
Paracetamol
NSAIDs
Isoniazid
Halothane
Oestrogens
Flucloxacillin
Chlorpromazine
Dextropropoxyphene
Tetracycline
Amiodarone
Carbamazepine
Allopurinol
Methotrexate
Rifampicin
ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; GGT,
-glutamyltransferase; N, normal liver biochemistry.
Always consider drug toxicity

in the presence of jaundice or
abnormal liver biochemistry: always
ask about over-the-counter and
herbal remedies, and check with the
patients GP.
The clinical presentation depends on

the type of liver injury.
Jaundice: more likely if bile duct
damage or cholestasis, but also
occurs in severe hepatitis.
Symptoms of hypersensitivity
(fever, arthralgia) but these may
be absent.
Acute hepatitis: nausea and upper
abdominal discomfort.
Acute cholestasis: jaundice and
itching.
Fatty liver: usually asymptomatic.
Fig. 63 Bile duct damage due to clavulinic acidamoxicillin. The bile duct epithelium is irregular and
infiltrated with lymphocytes.
Epidemiology
The incidence of hepatic drug toxicity
is under-reported; it is thought to
be 1 in 10,000100,000. Prevalence
increases with age, with drugs
being responsible for 40% of acute
hepatitis in those aged >50 years.
Drugs most commonly implicated in
causing drug toxicity include:
clavulanic acidamoxicillin
(Augmentin);
flucloxacillin;
amiodarone;
statins;
thiopurines, eg azathioprine;
NSAIDs;
HAART (highly active

antiretroviral drugs);
paracetamol/dextropropoxyphene;
herbal remedies.
There is usually a temporal

association between starting
a drug and the occurrence of
hepatotoxicity, although liver
biochemistry may become abnormal
before symptoms develop. However,
note that halothane and clavulanic
acidamoxicillin hepatotoxicity occur
up to 3 weeks after cessation of drug
exposure.
Investigations
FBC may show an eosinophilia.
The pattern of liver biochemistry is
shown in Table 47. Liver injury is
defined as an ALT value more than
three times the upper limit of the
normal range, an ALP value more
than twice the upper limit of
normal, or a total bilirubin level
more than twice the upper limit
of normal if associated with any
elevation of ALT or ALP. Liver injury
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is further classified as hepatocellular

when there is a predominant initial
elevation of ALT or as cholestatic
when there is a predominant initial
elevation of ALP; in a mixed pattern
elevation of both values occurs.
This depends on the type of liver

injury caused by the drug.
The following drugs should be

avoided or used cautiously in
patients known to have chronic liver
disease.
Acute hepatitis: viral hepatitis,

autoimmune chronic active
hepatitis, alcoholic hepatitis.
Steatohepatitis: alcoholic
hepatitis.
Acute cholestasis: biliary
disease, extrahepatic obstruction,
intrahepatic disease (including
primary sclerosing cholangitis,
primary biliary cirrhosis
and intrahepatic cholestasis
of sepsis).
In severe reactions: erythroderma,

bone marrow suppression.
2.10.5.2 Drugs and chronic liver

disease
Narcotics/anxiolytics:
accumulation results in hepatic
encephalopathy.
Codeine: causes constipation and
secondary hepatic encephalopathy.
NSAIDs: may cause haemorrhage
from oesophageal varices and
precipitate hepatorenal failure.
Treatment
Paracetamol: small overdoses can

be fatal, hence caution should be
exercised if the patient has
decompensated liver disease.
Stop the drug. Supportive care.

Ursodeoxycholic acid is often
empirically prescribed for those
with a cholestatic injury.
Gentamicin/radiocontrast agents:
may precipitate hepatorenal
failure.
Complications
Acute liver failure
This is more likely in elderly people.
It occurs in about 20% who are
jaundiced. Overall 1520% of acute
liver failure is due to drugs.
Frequently reported with
antituberculous medication.
Chronic cholestasis
Statins and liver disease

Postmarketing surveillance data
suggest one case of liver failure for
each million person-years of use, but
there is no evidence of increased
toxicity in those with pre-existing liver
disease. Most guidelines recommend a
baseline check of liver function tests
before starting treatment, 8 weeks
later and after any dose increase, then
annual checks if tests are stable.
Loss of bile ducts (ductopenia) has

been reported.
120
Prognosis
FURTHER READING
In the absence of liver failure

most reactions are self-limiting
with no chronic liver damage.
If acute liver failure develops,
outcome is not as good as that
of viral hepatitis.
Arundel C and Lewis JH. Drug-induced

liver disease in 2006. Curr. Opin.

and cirrhosis
pathology
Chronic liver disease is defined
as liver damage persisting for
more than 6 months. It results in
progressive fibrosis and eventually
cirrhosis (Fig. 64), which comprises
fibrotic liver damage with
regenerative nodule formation
and consequent portal venous
hypertension (Fig. 65).
Non-alcholic fatty liver disease can
progress to cirrhosis, particularly
when steatohepatitis is present and
in those with diabetes and other
metabolic syndrome features.
Other common causes of chronic
progressive liver disease are shown
in Table 48.
Autoimmune hepatitis (relatively
common) and Wilsons disease
(very rare) can progress rapidly to
cirrhosis, and indeed patients may
be cirrhotic on presentation. Rapid
progression to cirrhosis due to
recurrent disease in the liver
graft can also occur after liver
transplantation, eg in recurrent
hepatitis C or recidivist alcohol use.
Rarer causes of chronic liver disease
include sarcoidosis, biliary disease
secondary to cystic fibrosis, longstanding biliary obstruction and
chronic BuddChiari syndrome.
Epidemiology
Incidence varies with geographic
region, age and sex. The commonest
cause of chronic hepatitis in the
world is hepatitis C; in the UK the
commonest cause of cirrhosis is
alcohol, followed by hepatitis C.
Common
Lee WM. Drug-induced hepatotoxicity.

N. Engl. J. Med. 2003; 349: 47485.
Non-specific malaise, loss of libido

and mental changes.
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Fig. 64 (a) Normal liver; (b) cirrhotic liver containing a benign cyst.
Treatment
See Sections 1.1.7, 1.2.2, 1.4.3 and
1.4.6 for discussion of the various
clinical presentations that can arise
in patients with chronic liver
disease.
Specific measures
Progressive liver disease can
sometimes be arrested where the
cause is known (Table 49).
Fig. 65 Histological appearance of cirrhosis. There is loss of the normal architecture which is replaced by
nodules.
Hepatic decompensation:
jaundice, ascites, hepatic
encephalopathy, variceal
haemorrhage.
Most patients with chronic

liver disease are asymptomatic
until they become cirrhotic, and
cirrhosis may cause no symptoms
until portal hypertension develops.
Physical signs
See Section 1.2.2.
See Sections 1.1.7 and 1.2.2 for
discussion. Aside from the issues
discussed in these scenarios, note
that osteoporosis and more rarely
osteomalacia are important
complications of chronic liver
disease and associated with
significant morbidity through
fractures resulting in pain, deformity
and immobility. Patients with
chronic liver disease should have
their bone density measured, in
addition to vitamin D and
testosterone levels.
Wilsons disease
Wilsons disease may present
as asymptomatic liver disease
with predominant neurological
abnormalities, as chronic liver disease
with cholestatic features in early
adulthood, or as fulminant liver failure
in younger patients. A clue to Wilsons
disease in these patients is the
presence of significant red cell
haemolysis. Always consider the
diagnosis in patients under the age
of 40 years with unexplained liver
disease: prompt treatment can be
life-saving.
General measures
Treatment is aimed at managing and
preventing complications.
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TABLE 48 IMPORTANT
CAUSES OF CHRONIC LIVER
DISEASE AND CIRRHOSIS
See Section 2.10.4
Chronic viral hepatitis
Lobular lymphocytic infiltration, variable hepatocyte

necrosis and fibrosis progresses to cirrhosis;
damage is most likely due to immune-mediated
mechanisms rather than a viral cytopathic effect
Excess iron absorption from the intestine results in

accumulation in hepatocytes, hepatocyte necrosis
and cirrhosis
Immune cell infiltration and hepatocyte damage

leads to rapidly progressing fibrosis and cirrhosis
See Section 2.5.2
Primary sclerosing cholangitis
See Section 2.5.3
Abnormal protein cannot be adequately exported

from hepatocytes, where it accumulates causing
hepatocyte damage
Wilsons disease
Abnormalities in the biliary copper transporter

results in excess copper accumulation in the liver
and brain, with hepatocyte damage and basal
ganglia disease
The disease is genetically heterogeneous and this
is reflected in variable clinical presentations (eg
rapid neurological deterioration, early-onset
fulminant liver failure, or chronic liver disease
presenting with cirrhosis)
Ascites: diuretics, eg
spironolactone, furosemide,
amiloride.
Portal hypertension: non-selective
beta-blocker (propranolol).
Bone disease: for
osteoporosis/osteomalacia,
treatments include calcium,
bisphosphonates (eg cyclical
etidronate, alendronate,
risedronate), calcitonin and
combined vitamin D/calcium.
To maintain general health:
nutrition.
Refer patients with chronic

liver disease for consideration
of liver transplantation, particularly
if complications develop or there is
a deterioration in markers of liver
function (albumin and prothrombin
time).
Complications
TABLE 49 SPECIFIC
TREATMENT OPTIONS FOR VARIOUS
CAUSES OF CHRONIC LIVER DISEASE
Cause of liver disease
Treatment
Abstinence
Chronic viral hepatitis
Hepatitis C is cleared in more than 40% by a

combination of interferon alfa and ribavirin (a
nucleoside analogue) given for 612 months
Hepatitis B responds to interferon alfa in 30% who
are HBeAg positive with elevated transaminases.
Antivirals including lamivudine, adevofir and
entecavir are also used
Venesection to reduce iron load and return serum

iron indices to normal reduces the rate of
progression of liver disease (each venesection
reduces ferritin by about 50 ng/mL)
Systemic steroid treatment, with or without

azathioprine, maintains long-term remission
No effective treatment exists
Wilsons disease
Penicillamine to increase urinary copper excretion

and prevent hepatic and neurological disease
progression
Oral zinc may also promote copper excretion
HBeAg, hepatitis B e antigen.
122
Common
Coagulopathy Caused by decreased
synthesis of coagulation factors II, V,
VII and IX with worsening liver
function, or as a result of chronic
cholestasis and reduced levels of
vitamin K. It is aggravated by
thrombocytopenia caused by
hypersplenism due to portal
hypertension.
Encephalopathy The cause is
multifactorial and ill-understood.
Abnormal amino acid synthesis and
increased ammonia production may
play a role, as may abnormal enteric
bacterial metabolism and reduced
hepatic clearance of neurotoxic
substances due to portal
hypertension and shunting. Resting
electroencephalogram shows slowed
alpha-wave frequency. Treatments
for encephalopathy are inadequate,
but see Section 1.4.6 for discussion.
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Ascites Results from a combination

of portal hypertension, increased
sodium and water retention, and
hypoalbuminaemia. Spontaneous
bacterial peritonitis (SBP) in
cirrhotic patients with ascites is
common and potentially fatal:
prophylaxis with norfloxacin or
ciprofloxacin should be considered.
Regular paracentesis with human
albumin infusions to maintain
euvolaemia may be needed.
Hepatorenal failure Hepatorenal
failure is a diagnosis of exclusion
to be made only after the following
causes of acute renal failure have
been ruled out (which is often
difficult to do): hypovolaemia
(eg over-diuresis, bleeding), sepsis
(particularly SBP), drug toxicity
(eg NSAIDs, gentamicin, diuretics),
intrinsic renal disease (eg IgA
nephropathy) and urinary
obstruction. The patient typically
has a low urinary volume, with a
low concentration of sodium in the
urine, both persisting in the face
of a fluid challenge. Treatment is
supportive: some administer
Glypressin with human albumin
infusion to try to improve renal
blood flow, but evidence of efficacy
is weak. Prognosis is very poor.
Variceal haemorrhage The most
common site is oesophageal and
gastric varices, but varices can form

at any site of contact between the
portal and systemic circulation.
Cachexia As the liver is the primary
regulator of glucose, lipid and
protein metabolism, profound
abnormalities occur with advanced
liver disease and patients eventually
become profoundly wasted. This is
aggravated by haemorrhage, ascites,
infection and anorexia.
Hepatocellular carcinoma Develops
almost exclusively in cirrhotic livers,
and patients with chronic viral
hepatitis are most at risk, followed
by those with haemochromatosis
(Fig. 66). Hepatocellular carcinoma
is less common in women of

reproductive age. Development
of hepatocellular carcinoma can
precipitate ascites, encephalopathy
and rapid hepatic failure.
Prognosis
Morbidity
There is significant morbidity from
malaise, malnutrition, sepsis and
bleeding. Figure 67 shows the
natural history of hepatitis C
infection.
Mortality
Life expectancy is severely reduced,
but varies depending on the cause
Fig. 66 Haemochromatosis: iron deposition in hepatocytes shown as blue staining with Perls stain.
Fig. 67 Natural history of hepatitis C infection: (a) rate of progression to cirrhosis; (b) different rates of disease progression and factors associated with rapid
progression.
123
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TABLE 50 CHILDSPUGH
Parameter
Bilirubin (mol/L)1
Albumin (g/L)
PT (seconds prolonged)
Encephalopathy
Ascites
2.10.7 Focal liver lesion

CLASSIFICATION
pathology
Score
1
<34
>35
<4
None
None
3450
2835
46
Mild
Mild
>50
<28
>6
Marked
Marked
Common
Abscess: fever, pain and tenderness.
ChildsPugh categories and their prognosis
Class A
Class B
Class C
The causes of focal liver lesions are

shown in Table 51.
Total score
1-year survival
During investigation of abnormal

liver tests.
56
79
1015
100%
80%
50%
Incidental finding on ultrasound

scanning.
1. If there is primary biliary cirrhosis or sclerosing cholangitis, then bilirubin is classified as

1 (<68 mol/L), 2 (68170 mol/L) or 3 (>170 mol/L).
and whether specific treatment is

available (Table 49). Most patients
die from sepsis, bleeding or
progressive liver failure. Successful
liver transplantation much improves
the prognosis.
There are many clinical scoring

systems for liver disease, the
simplest being the ChildsPugh
Classification (Table 50).
Detected on screening ultrasound

in at-risk patients.
Clinical deterioration or
decompensation in cirrhotic
patients.
Iredale JP. Cirrhosis: new research

provides a basis for rational and
targeted treatments. BMJ 2003; 327:
1437.
Moore KP and Aithal GP. Guidelines
on the management of ascites in
cirrhosis. Gut 2006; 55 (Suppl. 6 ):
vi1vi12. Full text available at
Onset of jaundice in patient with

primary sclerosing cholangitis
(PSC).
Uncommon/rare
Weight loss, abdominal pain,
increased ascites secondary to portal
vein thrombosis, and bleeding or
tumour rupture.
FURTHER READING
Gins P, Cardenas A, Arroyo V and
Rodes J. Management of cirrhosis and
ascites. N. Engl. J. Med. 2004; 350:
164654.
Gins P, Guevara M, Arroyo V and
Rodes J. Hepatorenal syndrome. Lancet
2003; 362: 181927.
Grant A, Neuberger J, Day C and
Saxseena S (on behalf the British
British Association for the Study of the
Liver). Guidelines on the Use of Liver
Biopsy in Clinical Practice. London:
British Society for Gastroenterology,
2004. Full text available at
Fig. 68 CT scan showing multiple hepatic cysts in a patient with autosomal dominant polycystic kidney
disease. The scan also shows ascites and absence of kidneys following bilateral nephrectomy.
124
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TABLE 51 CAUSES
OF FOCAL LESIONS IN THE LIVER
Type of cause
Condition
Comments
Infective
Pyogenic abscess
Amoebic abscess
Hydatid cyst
Often related to colonic disease or appendicitis

Requires environmental exposure to Entamoeba histolytica
Mainly in patients from agricultural regions; associated with exposure to
dogs and sheep
Benign tumours
Simple cyst
Haemangioma
Multiple cysts often found in adult polycystic kidney disease (Fig. 68)
Extremely common, occurring in up to 20% of people, and detected
usually as an incidental finding
Occurs in 34 per 100,000 women on oestrogen-containing
contraceptives, and may occur in men on androgen treatment
Hepatic adenoma
Focal nodular hyperplasia/focal
regenerative hyperplasia
Secondary deposits
Colorectal cancer
Other gastrointestinal tract cancer
including pancreatic and carcinoid
tumours (Fig. 69)
Breast, cervix, ovary, prostate,
lung, skin cancer
Primary liver cancer
Hepatocellular carcinoma related

to cirrhosis
Cholangiocarcinoma
Hepatocellular carcinoma
developing in hepatic adenoma
Cell proliferation in regenerating cirrhotic nodules may favour malignant

change, as may the effects of chronic viral infection on the host
genome. Found in about 2030% of patients dying with cirrhosis,
particularly that caused by chronic viral hepatitis or haemochromatosis,
and commoner in men than in premenopausal women
Occurs in up to 15% of patients with primary sclerosing cholangitis
Rare, except in inherited glycogen diseases
Uncommon
Hepatic bruit with hepatocellular
carcinoma.
Blood tests
Any patient with a focal liver lesion
will require routine blood tests
including FBC, liver function tests,
albumin, clotting screen and
inflammatory markers. Some
specific blood tests (Table 52)
may help to confirm or refute a
particular diagnostic possibility.
Imaging
Fig. 69 CT scan showing multiple liver metastases from adenocarcinoma of the pancreas.
Physical signs
Common
There are often few signs but there
may be:
jaundice;
signs of chronic liver disease in

patients with hepatocellular
carcinoma;
hepatomegaly (tender in the case
of liver abscess).
Ultrasound scanning is most useful,

but vascular tumours may have a
diagnostic appearance on CT and
MRI scanning and angiography,
obviating the need for biopsy.
cholangiopancreatography is
useful for evaluating if jaundice
in a patient with PSC is caused by
125
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TABLE 52 BLOOD
TESTS THAT CAN HELP TO ESTABLISH
Decompensated liver failure in

patients with cirrhosis or PSC.
THE DIAGNOSIS OF A FOCAL LIVER LESION
Uncommon
Test
Disease
Alpha-fetoprotein
Hepatocellular carcinoma; also acute hepatitis and

germ cell tumours
Vascular thrombosis, particularly

portal vein thrombosis or inferior
vena cava thrombosis.
CA19-9 tumour antigen
Cholangiocarcinoma; also other pancreatic and

biliary diseases
Rare
Carcinoembryonic antigen
Colorectal carcinoma
Amoebic and hydatid serology
Past infection with amoeba or Echinococcus species
cholangiocarcinoma, and allows

collection of bile and brushings for
cytological examination.
Tissue sampling
Histological diagnosis may be
established by liver biopsy, but
beware of vascular lesions that may
bleed catastrophically on biopsy. If
the patient has ascites, cytological
examination may provide a
diagnosis, particularly if the lesion
is a secondary malignant deposit.
Short-term
Biliary obstruction can be relieved
endoscopically or radiologically.
Small hepatocellular carcinomas
can be treated locally (eg by
percutaneous alcohol injection,
radiofrequency ablation,
transarterial chemoembolisation),
reducing tumour load and
prolonging patient survival. Local
resection of secondary deposits
may be feasible in some cases.
Long-term
Beware of haemangiomas and
hydatid cysts, where biopsy may
result in catastrophic bleeding or
disseminated infection.
Common causes of focal liver lesions
are shown in Table 51.
Treatment
Treatment of a focal liver lesion will
depend on the cause. For benign
lesions the most important aspect is
to reassure patients that they have
not got cancer.
Emergency
Liver abscess requires prompt
antimicrobial treatment, and may
require diagnostic or therapeutic
aspiration or drainage. Rupture of
liver abscess or haemangioma
requires surgical intervention.
126
Pyogenic and amoebic liver abscess

may be cured by antimicrobial
treatment alone or combined with
percutaneous drainage. Hydatid
cysts usually require careful
excisional surgery under
antimicrobial cover.
Cessation of oral contraceptive
use is associated with regression
of adenomas. Benign neoplastic
liver lesions may require surgical
removal (partial hepatectomy or
liver transplant) if there is a risk
of major complications (usually
impending rupture or haemorrhage).
Early hepatocellular carcinoma may
be cured by resection or liver
transplantation.
Complications
Common
Septicaemia in patients with
pyogenic abscess.
Haemorrhage or rupture of
haemangioma or large adenoma.
Malignant transformation of
adenoma.
Prognosis
Morbidity
Incidental liver lesions rarely cause
morbidity. Fever, pain or vague right
upper quadrant discomfort are
common.
Mortality
Without curative resection hepatic
secondaries and hepatocellular
carcinoma usually have a dire
prognosis.
Hepatocellular carcinoma
Usually arises in the setting
of cirrhosis, with untreated 1-year
survival of 50 90% in patients with
ChildsPugh class A cirrhosis and 20%
in those with ChildsPugh class C
disease. Metastases may develop in
the lung, portal vein, periportal nodes,
bones or brain, with 5-year survival
rates less than 5% without treatment.
Alpha-fetoprotein (AFP) is elevated in
75% of cases, and the higher the level
the worse the prognosis. An elevation
of greater than 400 ng/mL predicts
hepatocellular carcinoma with
specificity greater than 95%, and in the
setting of a growing mass, cirrhosis
and the absence of acute hepatitis,
many centres use a level greater than
1000 ng/mL as presumptive evidence
of hepatocellular carcinoma (without
biopsy). However, two-thirds of
hepatocellular carcinomas <4 cm have
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AFP levels below 200 ng/mL, and up to

20% of hepatocellular carcinomas do
not produce AFP even when very large.
AFP values can fluctuate significantly
in chronic hepatitis C and are therefore
less useful for screening in this group
of patients.
The only proven potentially curative
therapy for hepatocellular carcinoma
remains surgical, either hepatic
resection or liver transplantation,
and patients with a single small
hepatocellular carcinoma (<5 cm) or
up to three lesions <3 cm should be
referred for assessment for these
procedures. Hepatic resection should
be considered as primary therapy
in any patient with hepatocellular
carcinoma and a non-cirrhotic liver
(including fibrolamellar variant).
Screening by 6-monthly ultrasound
and AFP measurement is generally
advocated in those with cirrhosis,
although there is no clear evidence
of survival benefit.
FURTHER READING
Choi BY and Nguyen MH. The diagnosis
and management of benign hepatic
tumors. J. Clin. Gastroenterol. 2005;
39: 40112.
Garden OJ, Rees M, Poston GJ, et al.
Guidelines for resection of colorectal
cancer liver metastases. Gut 2006; 55
(Suppl. 3): iii1iii8. Full text available at
Llovet JM, Burroughs A and Bruix J.
Hepatocellular carcinoma. Lancet 2003;
362: 190717.
Ryder SD (on behalf of the British
Guidelines for the diagnosis and
treatment of hepatocellular carcinoma
(HCC) in adults. Gut 2003; 52 (Suppl. 3):
iii1iii8. Full text available at

Prevention
Background
Primary
Low-dose oestrogen formulations
reduce the risk of hepatic adenoma in
patients using the oral contraceptive
pill. The risk of hepatocellular
carcinoma is reduced in patients with
cirrhosis who abstain from alcohol
and in patients with chronic viral
hepatitis in whom viral replication
is suppressed by antiviral therapies.
Pyogenic liver abscess: cholangitis,
diverticular disease, inflammatory
bowel disease, appendicitis,
colorectal neoplasia.
Amoebic liver abscess: amoebic
colitis.
Adenoma: glycogen storage disease.
Hepatocellular carcinoma: liver
cirrhosis.
Cholangiocarcinoma: PSC.
Over 600 adult orthotopic liver

transplantations are carried out
annually in the UK. Donor livers
are matched to the recipient on
the basis of size and ABO blood
group. In contrast with renal
transplantation, human leucocyte
antigen (HLA) matching is not
required. About 10% of those
waiting will die on the list, which
partly reflects a significant shortage
of heart-beating brain-dead donors.
Ways of trying to increase organ
availability include the following.
Living related transplantation:
either a right or left lobe is used
primarily in children who need
small grafts, and in adults in
Japan where cadaveric organs are
not available because the concept
of brain death is not recognised.
This techinque is likely to be
extended to adults in the UK in
the near future.
Split liver transplantation: this

provides two grafts from a single
donor and is useful in children. A
minimum graft-to-donor weight
ratio of 1% is needed to reduce
the chances of so-called small for
size syndrome.
Extending the use of marginal
livers: most centres will now
consider donation from patients
of all ages, in those with evidence
of past viral infection (hepatitis B
and C), and in those with a history
of certain malignancies.
Non-heart-beating donors: the
liver is sensitive to ischaemia, but
criteria for controlled non-heartbeating donors (where death
occurs in a hospital setting) are
being developed and outcomes
are good, although there is an
increased risk of biliary
complications.
Xenotransplantation: this
approach is not likely to be used
in the near future despite all the
research on using pig livers,
mainly due to fears about
transmissible infections.
Indications
Main indications for liver

transplantation
End-stage chronic liver disease.
Acute hepatic failure.
Metabolic liver disease: oxalosis,
glycogen storage disease, hereditary
amyloidosis.
Ethical issues
These are largely related to donor
shortage and include the following.
Should patients with liver failure
due to paracetamol overdose or
alcohol be transplanted?
127
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transplantation with a quality of life

acceptable to the patient.
Should patients who have a worse

post-transplant prognosis be
transplanted (ie acute liver failure
versus chronic liver disease)?
Should patients with acute liver
failure take priority over other
patients already on a waiting list?
Is there a role for
xenotransplantation?
Timing of transplantation
Emergency transplantation
There are two liver transplant
waiting lists in the UK: acute liver
failure (super-urgent list) and
chronic liver disease. Strict criteria
need to be met before an individual
can be placed on the acute liver
failure waiting list as these patients
take priority over all other patients
(Table 53).
Extent of liver dysfunction

The indication for liver
transplantation in chronic liver
disease is cirrhosis in the presence
of hepatic decompensation, eg
diuretic-resistant ascites, one episode
of bacterial peritonitis, uncontrolled
oesophageal variceal or gastric variceal
bleeding, hepatic encephalopathy or
a hepatocellular carcinoma <5 cm in
diameter. Quality of life is also an
important consideration. In the UK,
patients are listed if they meet the
indications for transplantation and
are estimated to have >50%
probability of survival after
Timing is a balance of risk of death

without transplantation against risk
with transplantation. Prognostic
scores to assess mortality in chronic
liver disease have been developed
(eg Mayo score for primary biliary
cirrhosis depending on albumin,
prothrombin time and bilirubin)
but are of limited value in individual
patients. A decision as to when to
list a patient for liver transplantation
is also determined by the likely ease
of organ procurement for that
individual, this being more difficult
if the patient is of small size or has
blood group O or AB. Because of
continued donor shortage it is likely
that patients on the waiting lists
will increasingly be prioritised on
the basis of their probable mortality,
ie the sickest patients will be
transplanted first.
The waiting list for liver

transplantation is up to
12 months, depending on the recipient
blood group, and so early referral to a
liver transplant centre is important.
Patients with chronic liver disease do
best if transplanted from home and
most units will not transplant chronic
patients from an intensive-care setting.
TABLE 53 KINGS COLLEGE HOSPITAL
CRITERIA FOR LISTING FOR
URGENT LIVER TRANSPLANTATION IN ACUTE LIVER FAILURE
128
Cause of acute liver failure
Criteria for listing
Paracetamol
pH < 7.3 or prothrombin time >100 seconds plus

Creatinine >300 mol/L plus
Grade 3/4 encephalopathy
Non-paracetamol
Prothrombin time >100 seconds or any three of the

following:
Aetiology: drug reactions or non-A non-B hepatitis
Age <10 or >40
Jaundice to encephalopathy in less than 7 days
Prothrombin time >50 seconds
Serum bilirubin >300 mol/L
Contraindications
There are very few absolute
contraindications to transplantation
(eg cholangiocarcinoma, active
bacterial infection) and patients
should where possible be given the
opportunity of assessment by a liver
centre, but potential areas of
concern include the following.
Alcohol intake within the last
6 months: liver function can
improve on abstinence, and this
is also a risk factor for recidivism
after transplantation. However,
consideration should be given to
patients who deteriorate before
6 months has elapsed if they are
likely to remain abstinent.
Increasing age, advanced endstage disease, poor nutrition and
Psychiatric disease and absence
of social support: may adversely
affect compliance with
immunosuppressive medication.
Note that HIV is not a
contraindication to transplantation
(if adequately treated).
Practical details
Surgery lasts between 4 and
24 hours and postoperative stays
can be as short as 10 days, but
are more typically 23 weeks.
Anastomoses between donor and
recipient hepatic artery, portal vein,
inferior vena cava and biliary tree
need to be fashioned and are sites
of potential complications. Biliary
anastomosis is usually a duct-to-duct
anastomosis, but in the presence of
recipient biliary disease (eg cystic
fibrosis, primary sclerosing
cholangitis) a Roux-en-Y biliary
anastomosis is fashioned (Fig. 70).
Postoperative immunosuppression is
typically with an initial combination
of prednisolone and azathioprine/
mycophenolate mofetil and
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FURTHER READING
Clavein PA, Petrowsky H, DeOliveira ML
and Graf R. Strategies for safer liver
surgery and partial liver transplantation.
N. Engl. J. Med. 2007; 356: 154559.
Devlin J and OGrady J (on behalf of the
Indications for referral and assessment
in adult liver transplantation: a clinical
guideline. Gut 1999; 45 (Suppl. 6):
vi1vi22. Full text available at
Said A, Einstein M and Lucey MR. Liver
transplantation: an update 2007. Curr.
Fig. 70 Roux-en-Y biliary anastomosis.
2.11 Nutrition
tacrolimus, although many
regimens now seek to avoid
steroids completely. All
patients require long-term
immunosuppression, but this
can often be with a single agent.
of individuals have at least one

episode of acute cellular rejection,
usually occurring in the first few
weeks, but unlike in renal
transplantation this is not a
predictor of chronic rejection, which
only affects 510% of recipients.
Outcome
The 1-year survival rate following
transplantation for chronic liver
disease is now approaching 95%,
falling to 80% at 5 years primarily
due to recurrent disease,
cardiovascular events, malignancy
and renal failure. The 1-year
survival is only 61% following
transplantation for acute liver
failure, reflecting the presence of
infection and multiorgan failure at
the time of transplantation. Survival
is lower following retransplantation,
and in those receiving a liver and
kidney at the same time.
Biliary complications
These affect 1020% of patients
and include anastomotic biliary
strictures and biliary leaks.
Disease recurrence
Complications
The most important late

complication is disease recurrence,
including alcohol abuse; this may
lead to graft loss before 5 years,
particularly in hepatitis C and
primary sclerosing cholangitis.
Recurrent hepatic malignancy can
be predicted by the proliferative
index of the tumour on explant and
the presence or absence of vascular
invasion.
Early complications
Comorbid illness
These include graft non-function

and hepatic arterial or portal vein
thrombosis, problems which usually
require retransplantation. Up to 60%
Malignancy, renal failure and

cardiovascular events are
increasingly being seen as
recipients survive longer.
2.11.1 Defining nutrition

Nutritional requirements in health
A balanced diet supplies energy
(fat and carbohydrate), nitrogen
(protein), electrolytes and
vitamins/trace elements. Fat is
the most efficient storage form
of energy, yielding approximately
10 kcal/g compared with glucose
and protein (both 4 kcal/g).
Nutritional requirements vary
depending on age, weight, degree
of activity, growth, pregnancy and
illness (catabolic states, eg sepsis,
trauma, surgery). In health about
2,0002,500 kcal of energy are
required daily, as well as 1420 g
nitrogen (a minimum of 4050 g
protein). There are eight or nine
essential amino acids (ie cannot be
synthesised by humans) and one
essential fatty acid (linoleic acid).
Vitamins and trace elements are
also required (Tables 5456).
Assessment of nutritional status

The term malnutrition includes
both energy undernutrition and
129
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TABLE 54 VITAMIN
REQUIREMENTS
(VITAMIN B
IS COVERED SEPARATELY IN
TABLE 55)
Vitamin
Requirement
Effect of deficiency
Notes
1000 IU/day
Night blindness, Bitots

spots, hyperkeratosis and
keratomalacia of skin
Found in dairy products, liver, fish. Plasma retinol levels

can be measured
60100 mg/day
Scurvy
Necessary for collagen synthesis (hydroxylation of proline

to hydroxyproline). Deficiency seen in the elderly or people
who do not eat vegetables. Signs are perifollicular
haemorrhages, corkscrew hair, bleeding gums, loose
teeth, spontaneous bruising/haemorrhage, anaemia, poor
wound healing. Vitamin C required to enable iron
absorption
200 IU/day
Osteomalacia, rickets, bone

pain, proximal myopathy,
Loosers zones
Normal or low calcium, low phosphate, high ALP, high

PTH. Main source is from action of sunlight on skin
photoactivating 7-dehydrocholesterol. Dietary vitamin D
hydroxylated in kidneys then liver to produce active
compound
1020 mg/day
Neurological disorders
Found in vegetable oils and fish
1 g/kg daily
Bleeding diathesis
Found in leafy vegetables. Deficiency most commonly

seen in biliary obstruction
ALP, alkaline phosphatase; PTH, parathyroid hormone.
TABLE 55 VITAMIN B
Vitamin
Requirement
Notes
B1 (thiamine)
0.51 mg per
1000 kcal intake
Neuropathy, cardiac failure (beriberi), ophthalmoplegia, (Wernickes)

encephalopathy, severe acidosis
Suspect in alcoholics, intravenous feeding with high

glucose intake
Red cell transketolase levels can be measured
B2 (riboflavin)
0.6 mg per
1000 kcal intake
Angular stomatitis, cheilosis,

glossitis, conjunctival injection
Suspect in alcoholics. Can measure blood and urine levels
B6 (pyridoxine)
1.62 mg/day or
0.038 mg/g protein
intake
Angular stomatitis, cheilosis,

glossitis, neuropathy, sideroblastic
anaemia
Isoniazid, hydralazine and penicillamine are antagonists
Niacin
6.6 mg NE1
Pellagra (classically dermatitis

Casals necklace, diarrhoea,
dementia)
Deficiency found in areas where maize is main dietary

constituent (biologically unavailable niacin and low in
precursor tryptophan)
Biotin
0.030.1 mg/day
Mental changes, myalgia, dermatitis
Deficiency rare
B12 (cobalamin)
2 g/day
Megaloblastic anaemia, glossitis,

stomatitis, peripheral neuropathy,
subacute combined degeneration of
the spinal cord
Found in meat, fish, dairy produce but not plants.

Deficiency may occur in vegans, pernicious anaemia,
gastrectomy, coeliac disease, bacterial overgrowth, ileal
disease/resection, ZollingerEllison syndrome. Average
adult stores may last up to 5 years before deficiency
develops. Treat with 3-monthly vitamin B12 injections
Folic acid
3 g/kg daily
Megaloblastic anaemia, glossitis,

stomatitis
Found in green leafy vegetables and offal. Main cause of

deficiency is poor intake. Deficiency may occur in small
bowel disease (eg coeliac disease). Phenytoin and
methotrexate are antifolate drugs
1. NE, niacin equivalent = niacin + tryptophan (mg)/60.
130
REQUIREMENTS
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TABLE 56 MINERALS
AND TRACE ELEMENTS REQUIRED IN DIET
Mineral
Requirement
Notes
Iron
1 mg/day
Microcytic anaemia, glossitis, cheilosis,

koilonychias
Iron deficiency is very common. Prevalence is

0.2% men, 1.9% postmenopausal women, 2.6%
menstruating women. May be due to poor intake or
excess loss (gastrointestinal tract most commonly)
Calcium
8001000
mg/day is normal
Western intake
Weakness, proximal myopathy, perioral

paraesthesia, tetany
Correct for albumin level (add 0.02 [40 serum

albumin])
Copper
24 mg/day
Hypochromic anaemia, leucopenia, osteoporosis
Magnesium
Zinc
Myopathy
15 mg/day
Deficiency common in alcoholics. Tends to follow

calcium levels. Watch for associated hypokalaemia
Rash (nasolabial, hands), hair loss, infections,

diarrhoea
Selenium
Muscle pain and weakness, cardiomyopathy
Chromium
Glucose intolerance, neuropathy
overnutrition (eg obesity) as well as

specific deficiencies or excesses of
vitamins or trace elements. However,
malnutrition is often used
synonymously with undernutrition.
Nutritional assessment of patients in
hospital is vital: almost half may be
malnourished, and this is associated
with increased mortality, higher
incidence of hospital-acquired
infections and prolonged hospital
stay. There is no single adequate
parameter of nutritional status.
Assessment is mainly made by a
combination of history and
examination.
History
The following features from the
history are important in assessing
the nutritional state.
Altered intake and pattern of
intake.
Recent weight loss (>10%
significant).
Ability to chew or swallow,
presence of dysphagia.
Anorexia, early satiety.
Recent vomiting.
Altered bowel habit suggesting

malabsorption.
Vitamin deficiency: angular
stomatitis, glossitis, night blindness.
A number of screening tools have
been used to identify patients at
risk of malnutrition based on these
features. Most have been shown
to correlate poor nutritional status
with adverse outcomes. Of these,
the Malnutrition Universal
Screening Tool (MUST, Fig. 71)
is the easiest to calculate.
Examination
The following findings suggest
impaired nutrition.
General muscle and fat mass:
hollow cheeks, wasting of
temporalis, squaring of shoulders
(loss of deltoid), wasting of
quadriceps.
Oedema: may indicate
hypoalbuminaemia.
Petechial or subcutaneous
haemorrhage: consider vitamin
C/K deficiencies.
Wrinkling, dryness of conjunctiva:
possible vitamin A deficiency.
Ophthalmoplegia: thiamine
deficiency; may be other signs of
Wernickes encephalopathy.
Cheilosis, angular stomatitis,
glossitis: vitamin B complex
deficiency.
Myelopathy, ataxia, retinopathy,
blindness: vitamin E deficiency.
Body mass index

A nutritional assessment also
involves calculating the body mass
index (BMI) from the height (m) and
weight (kg):
BMI = weight/(height)2
The World Health Organization
classifies BMI as follows:
<18.5
18.524.9
25.030
>30
underweight
normal
overweight
obese
Investigations
Blood tests Malnutrition may
be indicated by albumin <30 g/L
(but this usually reflects coexistent
disease and is a very poor marker
of nutritional state), lymphocytes
131
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Fig. 71 The Malnutrition Universal Screening Tool (MUST). (Reproduced with permission from BAPEN, and available from http://www.bapen.org.uk/.)
132
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<1.5 109/L or transferrin <2 g/L.

Thyroxine-binding prealbumin and
retinol-binding protein have been
used as indicators of proteinenergy
malnutrition, but may be also
affected by other conditions.
Although low albumin levels

may indicate proteinenergy
malnutrition, albumin concentration
often reflects disease activity and may
be regarded as the reciprocal of the
ESR (erythrocyte sedimentation rate).
Albumin has a plasma half-life of
21 days and although fasting affects
albumin synthesis within 24 hours, this
has little impact on albumin levels
because of the low turnover rate and
large pool size. Infection, malignancy,
inflammation, and gastrointestinal,
renal and liver disease may all depress
albumin levels, and yet most anorexic
patients have a normal serum albumin.
Anthropometric measurements
These include triceps and
subscapular skinfold thickness,
which provides an index of body fat,
and the mid-arm circumference
which provides a measure of muscle
mass. However, there are problems
with both the reference database
and considerable interobserver
measurement variability. Generally
only used in trial settings.
Dynamometry This refers to the use
of hand grip strength, which has
been shown to predict postoperative
complications in surgical patients.
Other tests have used electrical
stimulation of the adductor pollicis
muscle in the hand to measure
forcefrequency curves, fatiguability
and relaxation.
Others Delayed cutaneous
hypersensitivity tests may also be
used as indicators of nutritional
status.
Total body water Body composition
may be divided into four
compartments: water, protein,

fat and mineral. Total body water
may be measured by isotope
dilution techniques using tritium-,
deuterium- or 18O-labelled water.
Water has a relatively stable
relationship to fat-free body mass
(protein), with the proportion of
water taken to be a constant at
0.732. Hence measurement of
total body water allows the
following to be calculated:
Protein = fat-free body mass
Fat = [total body weight
(fat-free body mass + water)]
Combined non-invasive methods
for measuring the following are in
developmental stages:
protein (total body nitrogen);
fat (dual photon absorptiometry);
mineral (dual photon
absorptiometry and delayed
neutron activation);
water (isotope water dilution).
Prognosis
There is a near linear relationship of
increasing BMI with morbidity and
mortality. A BMI <15 kg/m2 is also
associated with increased mortality.
malnutrition
Kwashiorkor and marasmus are
the two classical primary nutrition
disorders seen in children. Although
described as distinct entities,
features of both are often present.
Marasmus is defined as present
when weight is less than 60% that
expected for the age, and is termed
marasmic kwashiorkor when
oedema is additionally present. Less
severe proteincalorie malnutrition
is present when weight is 6080%
that expected for age, and is termed
undernutrition in the absence of
oedema, and kwashiorkor in its
presence.
Other causes of undernutrition

include anorexia nervosa, intestinal
disorders (eg Crohns, coeliac),
infections (including parasites),
neoplasms and severe inflammatory
disorders.
2.11.3 Obesity
Sudden death is more

common in those who are
naturally fat than in the lean.
(Hippocrates)
Aetiology/pathophysiology
Obesity, defined as a BMI >30 kg/m2,
is a large and increasing problem. In
addition to the total body-fat mass
(estimated by BMI), the distribution
of fat is also important. Truncal
obesity is associated with
dyslipidaemia, hypertension,
insulin resistance, diabetes mellitus,
cardiovascular disease and stroke.
In clinical practice, the distribution
of fat can be simply assessed by
the waist/hip circumference ratio
(WHR). The WHR should not exceed
1.0 in men and 0.85 in women.
Genetic factors are involved. A signal
protein, leptin, produced by adipose
tissue, has recently been discovered
that may modulate body weight and
energy expenditure.
Epidemiology
In the UK, the prevalence of obesity
increased from 8% in 1980 to 15%
by 1995. In Europe and the USA the
figures are 1525%. As the BMI
increases, so does morbidity and
mortality. Obesity is a result of
energy input exceeding output
over a sustained period.
Treatment
Dietary
The principle of treatment is to
induce negative energy balance,
133
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which should be achieved by

a combination of long-term
low-intensity exercise and diet
(500600 kcal daily deficit),
which should be low in fat. Some
very low calorie diets may cause
micronutrient deficiency, and should
be monitored. Ketogenic diets such
as the Atkins diet restrict the intake
of carbohydrates and encourage
eating fat and protein, which could
have adverse long-term effects on
health even if body weight is
reduced.
Behaviour modification
Behaviour modification is important
and includes a diary of food intake,
meal frequency and separating
eating from other activities. Regular
exercise probably raises the basal
metabolic rate and favours energy
expenditure.
Reducing energy intake by

dietary modification and
increasing energy expenditure by
regular exercise are key to controlling
obesity. Regular exercise probably
acts partly by increasing the basal
metabolic rate and favouring energy
expenditure.
Drug treatments
These are considered if diet, exercise
and behaviour modification has
failed, and the risks of obesity
outweigh the risks of the drug in
that individual. Serotoninergic
agonists suppress appetite but may
cause pulmonary hypertension and
pulmonary valve disease. Orlistat is
a potent pancreatic lipase inhibitor
that causes malabsorption of fats
and has recently been shown to be
effective in treating obesity, although
a limiting side effect is that it
produces a high incidence of
steatorrhoea. Administration of
appetite-suppressing hormones may
provide an effective pharmacological
treatment of obesity in the future.
134
Surgery
Vertical banded gastroplication,
reducing the reservoir capacity of
the stomach, is reserved for morbid
obesity (BMI >35 kg/m2). Jejunoileal
bypass surgery is no longer
performed because it causes
severe hepatic abnormalities.
Other issues
Other cardiovascular risk factors
present in the obese patient
should be addressed (eg
smoking, hypertension, diabetes,
hyperlipidaemia), and alcohol intake
should be minimised (7 kcal/g).
Hypothyroidism should be excluded.
Indications
Enteral nutrition
Enteral nutrition is the preferred
option in all malnourished patients
who have a normal or near-normal,
functioning, accessible gut. It is
trophic for the upper intestinal
mucosa, maintains epithelial barrier
integrity, and is cheaper and safer
than parenteral feeding. If the upper
gastrointestinal tract is obstructed,
for example by oesophageal disease,
a percutaneous enterogastrostomy
(PEG) tube can be used to bypass
the obstruction and maintain enteral
feeding.
Parenteral nutrition
FURTHER READING
Dietz WH and Robinson TN. Clincal
practice: overweight children and
adolescents. N. Engl. J. Med. 2005; 352:
21009.
Farooqi S and ORahilly S. Genetics of
obesity in humans. Endocr. Rev. 2006;
27: 71018.
Li Z, Maglione M, Tu W, et al. Metaanalysis: pharmacologic treatment of
obesity. Ann. Intern. Med. 2005; 142:
53246.
McNatt SS, Longhi JJ, Goldman CD and
McFadden DW. Surgery for obesity: a
review of the current state of the art
and future directions. J. Gastrointest.
Surg. 2007; 11: 37797.
Parenteral nutrition is indicated in

those malnourished patients who
have a non-functioning gut (eg short
bowel syndrome, prolonged ileus).
Traditionally, parenteral nutrition is
administered via the large central
veins (subclavian or internal
jugular), which allows rapid
dilution of the hyperosmolar
solutions and reduces the incidence
of thrombophlebitis and subsequent
line failure. The introduction of lipid
suspensions allowed total nutritional
supplementation intravenously in a
realistic infusion volume over a
realistic time-frame, ie total
parenteral nutrition (TPN).
Contraindications

nutrition and special diets
Principle
Nutritional support is indicated for
malnourished patients and those at
risk of malnutrition, for example
through debilitation, surgery,
reduced consciousness or disease
of the gastrointestinal tract.
Support may be given enterally
(gastrointestinal) or parenterally
(intravenous).
Enteral nutrition
This is contraindicated in paralytic
ileus, mechanical obstruction and
major intra-abdominal sepsis, and in
those with complex fluid balance
problems.
Practical details
Enteral nutrition
Many patients can take oral
supplements (eg Fortisip, Fortijuice)
by mouth. In those with swallowing
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problems or those who lack appetite,

nasogastric feeding may be initiated
via a fine-bore feeding tube. A PEG
or percutaneous enterojejunostomy
(PEJ) tube may be sited if long-term
enteral feeding is required, as
these are more convenient and
comfortable than a nasogastric
tube and not prone to removal/
displacement. Nasojejunal feeding
may be the preferred option in
patients in whom aspiration is a
potential problem, eg gastric
dysmotility.
Special diets
Elemental diet
This comprises low-molecularweight nutrients, usually
with 10% free amino acids, 85%
oligosaccharides and <5% fat. It is as
effective as steroids in the treatment
of active Crohns disease, but many
patients find it distasteful and need
nasogastric feeding over a 6-week
period. Its mechanism of action is
unknown, but it may exert its effect
by reducing immunogenic load and
altering bacterial flora.
Venous access is secured via the
internal jugular, subclavian or
antecubital veins. A tunnelled
central venous catheter should be
sited unless it is anticipated that
feeding is only required for a few
days.
Complications
The complications of parenteral
nutrition include central venous
access-related complications,
metabolic complications, vitamin
and trace element deficiencies and
hepatobiliary dysfunction. The
metabolic complications include
hyperglycaemia/hypoglycaemia,
hypernatraemia/hyponatraemia,
hypercalcaemia/hypocalcaemia and
magnesaemia, hypophosphataemia,
mineral/vitamin/trace element
deficiency and cholestatic jaundice.
Enteral nutrition is always

preferred to parenteral
nutrition: even small volumes of
enteral feeding can help to maintain
intestinal health and hasten the
ultimate return to normal feeding.
advocates avoidance of
carbohydrates and favours a
relatively high intake of fats
and proteins, with the lack of
carbohydrate promoting ketogenesis
from fats and the high protein
content possibly suppressing
appetite and resulting in loss of
weight. Long-term consequences
may include dyslipidaemia, vitamin
and mineral deficiencies, and
possibly an increased risk of
colorectal cancer, which is
associated with a diet rich
in meat products and deficient
in insoluble fibre.
Exclusion diets
The most common conditions
requiring exclusion of specific
foods from the diet are coeliac
disease (where gluten provokes
an immunological response),
cows milk protein intolerance
and hypolactasia. Some patients
with irritable bowel syndrome
seem to benefit from avoiding
certain foods.
Diets for weight loss

Restricting calorie intake reduces
body weight, although homeostatic
mechanisms probably act to
counteract changes in the long
term, frequently resulting in
rebound weight gain after a few
months. Some diets restrict fluid
intake, with dehydration causing
rapid but spurious weight loss.
To maintain weight control, diets
must be sustainable, nutritionally
adequate, and not lack
essential vitamins, minerals or
macronutrients. Very low calorie
diets carry the risk of undernutrition
and should be supervised by a
physician, while low-calorie diets
such as those advocated by Weight
Watchers are safer. The Atkins diet
FURTHER READING
Baldwin C, Parsons T and Logan S.
Dietary advice for illness-related
malnutrition in adults. Cochrane
Database Syst Rev 2007; (1): CD002008.
Milne AC, Potter J and Avenell A.
Protein and energy supplementation
in elderly people at risk from
malnutrition. Cochrane Database
Syst Rev 2005; (2): CD003288.
National Collaborating Centre for
Acute Care. Nutrition Support for
Adults: Oral Nutrition Support, Enteral
Tube Feeding and Parenteral Nutrition.
Methods, Evidence and Guidance. NICE
guideline CG32. London: National
Institute for Health and Clinical
Excellence, 2006. Full text available
at http://www.nice.org.uk/
Stroud M, Duncan H and Nightingale J.
Guidelines for enteral feeding in adult
hospital patients. Gut 2003; 52 (Suppl.
7): vii1vii12. Full text available at
Zaloga GP. Parenteral nutrition in
adult inpatients with functioning
gastrointestinal tracts: assessment of
outcomes. Lancet 2006; 367: 110111.
135
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GASTROENTEROLOGY: INVESTIGATIONS AND PRACTICAL PROCEDURES
INVESTIGATIONS AND PRACTICAL

PROCEDURES
3.1 General
investigations
The main function of the
gastrointestinal tract is to absorb
nutrients, hence disease of the
intestine frequently manifests
with nutritional deficiency. Loss of
weight, which can be assessed by
estimating BMI, is a useful general
test. Low body mass may arise from
general debilitation, cachexia due to
malignancy, malabsorption caused
by intestinal or pancreaticobiliary
disease, chronic liver disease, or
chronic inflammatory disease such
as Crohns or ulcerative colitis.
Anaemia and nutritional deficiency
The FBC is an extremely

useful general test in
gastroenterology: anaemia may be
caused via many mechanisms that
involve the gastrointestinal tract.
Deficiency of a number of key

nutrients can manifest as anaemia.
Iron deficiency is the most common
nutritional defect worldwide.
It may be due to inadequate
intake, malabsorptive disease
such as coeliac disease, occult
gastrointestinal bleeding due to
peptic ulceration, colorectal cancer
or blood loss due to intestinal
helminth infestation. Furthermore,
chronic inflammation, including
inflammatory bowel disease, can
result in relative malabsorption of
iron and anaemia.
136
Anaemia may also be caused by

deficiency of vitamin B12 or folic
acid. Deficiency of vitamin B12 may
reflect disease of the stomach (post
gastrectomy, atrophic gastritis) or
terminal ileum (post resection, or
due to ileal Crohns disease), and is
very rarely due to inadequate intake
(eg in vegans). Folic acid is found
mainly in green leafy vegetables
and predominantly absorbed in the
jejunum. Deficiency may be dietary
or caused by chronic infestation and
inflammation of the jejunum,
eg giardiasis.
Serum biochemical tests
In gastroenterological practice
hypoalbuminaemia may reflect
nutritional disease, liver disease or
inflammatory disease.
Hypoalbuminaemia may be a sign

of severe nutritional deficiency, be
part of the acute-phase response to

systemic inflammation or may be
due to severe liver dysfunction. The
serum alkaline phosphatase level
may be raised due to disease of the
intestine. Acute-phase proteins such
as C-reactive protein are sensitive
markers of inflammation that can
reflect the activity of conditions
such as Crohns disease.
Stool examination
Determining relevant facts about
the amount and composition
of stool is a key aspect of the
gastroenterological assessment.
Stool may also be examined for
occult blood, fat globules,
leucocytes, erythrocytes and
pathogens. Normal stool volume
is about 200 mL per day, and the
normal frequency of defecation
varies from approximately three
times a day to once every 3 days.
Examples of abnormalities in the
stool and their interpretation are
shown in Table 57.
TABLE 57 ABNORMALITIES
OF THE STOOL
Abnormality
Interpretation
Volume >200 mL/day
Diarrhoea: may indicate secretory diarhoea if this

persists during an enforced fast
Fat globules visible (steatorrhoea)
Fat malabsorption: pancreatic or biliary disease

is likely
Fecal occult blood test positive
Ingestion of raw meat products, excessive red

meat consumption, occult intestinal bleeding
Leucocytes present
Intestinal inflammation or dysentery
Pathogenic bacteria, ova or

cysts of parasitic species
Intestinal infection or infestation
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3.2 Tests of
gastrointestinal and
liver function
The main measure of gastrointestinal
function is determined by clinical
history-taking. Most blood tests,
radiological investigations and
endoscopic modalities do not give
a measure of function but quantify
structural abnormalities and
damage. However, there are a
number of tests used to determine
whether there has been disruption
of normal physiology, which will be
considered in anatomical order.
Oesophageal manometry and

pH monitoring
Gastro-oesophageal reflux and
associated pathology (especially
Barretts oesophagus and
oesophageal adenocarcinoma) are
assuming greater public health
importance. Measuring gastrooesophageal motility and acid reflux
are important adjuncts to endoscopy
and radiology and can be performed
simply in an outpatient setting. A
nasogastric tube is passed and pH
or pressure measurements taken
through an appropriate transducer
and recording apparatus. The results
are used to determine whether
oesophageal symptoms (heartburn,
pain, dysphagia or odynophagia) are
related to acid reflux or abnormal
oesophageal motility and whether
surgical intervention may be useful.
Pancreatic function tests

Direct tests
Secretincaerulein test Duodenal
intubation test where pancreatic
juice enzyme concentration and
bicarbonate are analysed following
injection of secretin. This test is
considered the gold standard but is
invasive, time-consuming and not

routinely performed in many UK
centres.
Lundh test meal A duodenal
intubation test similar to the secretin
caerulein test but the stimulus is
a specially formulated test meal.
Similarly invasive to the secretin
caerulein test but gives information
about gut signalling to the pancreas.
Indirect tests
Faecal fat Either by Sudan staining
of stool sample or microscopy.
This has gone out of favour as it
involves the patient consuming a
large volume of fat in the diet for
3 days after stopping any pancreatic
supplements. It is insensitive in mild
to moderate pancreatic insufficiency
as greater than 90% of acinar tissue
needs to be lost before the test
becomes abnormal.
PABA test/mixed triglyceride breath
test/pancreolauryl test/triolein
breath test A complex substrate
is administered orally, which is
hydrolysed by the pancreatic
enzymes and then absorbed by gut,
with products measured in blood,
urine or breath.
Faecal enzyme measurement
Pancreatic chymotrypsin and
elastase have both been developed
into commercial tests, although
faecal elastase appears to be
superior. Enzymes are released from
the pancreas, pass through the
intestine without degradation and
can be measured in a single stool
sample. Low levels are associated
with reduced exocrine pancreatic
function.
Small bowel function

Measuring small bowel function is
challenging and many methods are
currently still research tools. Two
types of test are most commonly
employed.
Stool tests: collecting samples

over a period of days and measuring
weights and volume can help to
determine the difference between
osmotic diarrhoea and secretory
diarrhoea. This can be enhanced by
fasting the patient.
Breath tests: bacterial metabolism
or intestinal absorption of orally
administered substrates forms the
basis of a number of functional
tests. In some cases the products
of metabolism result in the release
of H2 or CO2 gas, which is detected
on the breath; alternatively, renal
excretion of substrate is measured.
Some commonly performed tests are
described in Table 58.
Other tests of small bowel function
include gut permeability tests,
using chromium-labelled EDTA
administered orally. Motility
disorders can be investigated using
small bowel manometry, when a long
catheter with pressure transducers
along its length is passed
fluoroscopically or endoscopically
and then left to take measurements
throughout a determined time
period. The migrating motor
complex (MMC) is propagated in the
stomach and passes down the small
intestine with gathering intensity,
with different periods of activity
such as the interdigestive period
and nocturnal patterns. Pressure
measurements can be used to
characterise different types of
pseudo-obstruction and other
clinical applications are being
developed, but it is not in routine
use in many centres.
Liver function tests and liver

damage tests
The conventional liver function
tests do not reflect liver function:
bilirubin, the transaminases and
alkaline phosphatase give information
on liver damage more than function.
The most sensitive and specific
137
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TABLE 58 FUNCTIONAL
Investigation
Indications
Substrate
Metabolite/read-out
Notes
Urease breath test
Helicobacter pylori infection
13
13
Most sensitive and specific

test for H. pylori infection
Lactose breath test
Hypolactasia
Lactose
Excess H2 from
bacterial fermentation
of lactose
Lactulose breath test
Intestinal bacterial
overgrowth and intestinal
hurry
Lactulose
Early release of excess

H2 by bacteria in the
small intestine, or as a
result of rapid intestinal
transit
Glycocholate breath test
Intestinal bacterial
overgrowth
Labelled glycineglycocholate
Early release of labelled

glycine by bacteria in
the small intestine
results in absorption of
glycine and release of
labelled CO2 in the
breath
Xylose excretion test
Malabsorption due to small

intestinal disease
Xylose
Urinary xylose excretion
Most ingested xylose is

normally excreted unchanged
by the kidneys, unless it is not
absorbed
Schilling test
Cause of vitamin B12

deficiency
Labelled
hydroxocobalamin
(vitamin B12) tracer
administered after
body stores are
saturated by an
intramuscular dose of
unlabelled vitamin B12
Urinary excretion of
labelled vitamin B12
Normal: complete absorption

and excretion of vitamin B12.
Pernicious anaemia:
incomplete absorption and
excretion of vitamin B12,
corrected by co-administration
of intrinsic factor
Terminal ileal disease:
incomplete absorption and
excretion of vitamin B12, not
corrected by co-administration
of intrinsic factor
measure of liver function is the

prothrombin time (PT), which is
simple to measure and reproducible.
Other tests of liver function include
the plasma urea (the urea cycle
predominantly occurs in the liver),
serum glucose concentration
(gluconeogenesis) and serum
albumin, but all are also affected by
factors other than liver function.
Urea is affected substantially by
renal function and protein intake,
glucose can be altered by comorbid
conditions, and albumin falls in
many acute severe illnesses as the
liver switches to production of
acute-phase proteins.
138
AND BREATH TESTS USED IN GASTROENTEROLOGY
C-labelled urea
C-labelled CO2
3.3 Diagnostic and

therapeutic endoscopy
Endoscopy of the intestinal tract is
one of the most powerful diagnostic
and therapeutic manoeuvres
available to the physician and can
be safely performed under light
sedation even in frail and ill
patients. Originally flexible fibreoptic
devices with a light
source and a channel for suction,
insufflation and instrumentation
were used, but these are now
increasingly replaced by devices
Lactulose is not absorbed or

metabolised by the intestine
and normally reaches the
large intestine intact
that collect visual information

through a charge-coupled device
located at the end of the instrument.
Channels for insufflation, suction
and instrumentation are still
present, but the visual information
is transmitted electronically and
viewed on a video-display unit.
The main endoscopic procedures
are shown in Table 59 (apart
from endoscopic retrograde
cholangiopancreatography:
see Table 61).
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TABLE 59 ENDOSCOPIC
TECHNIQUES FOR EXAMINING THE INTESTINAL LUMEN
Investigation
Indications/abnormalities
Contraindications/notes
Oesophagogastroduodenoscopy
(upper gastrointestinal
endoscopy)
Causes of dyspepsia, including peptic ulcer

Causes of heartburn, including gastrooesophageal reflux disease
Causes of haematemesis, melaena and
iron-deficiency anaemia
Ensure that endoscopy is safe (eg that the patients airway is

protected, and the patient understands the procedure)
A frail patient with cardiac failure or respiratory compromise
should not be endoscoped without due attention to these
problems
Dysphagia may be caused by carcinoma of the oesophagus,
which could be perforated on endoscopy: consider a barium or
gastrograffin swallow first
Endoscopy may be therapeutic as well as diagnostic,
particularly in the treatment of upper gastrointestinal
haemorrhage, including adrenaline injection, thermal or
mechanical treatment of bleeding ulcers, or the banding of
oesophageal varices. May also enable dilatation of benign
strictures or the stenting of obstructing tumours. Biopsy
obtained for urease assay (CLO test) can diagnose H. pylori
infection at the bedside. Patients should preferably abstain from
acid-suppressing medications for 2 weeks prior to the test
Duodenal biopsy should always be performed when
investigating iron-deficiency anaemia to exclude coeliac disease
Enteroscopy
A special long endoscope may be

introduced beyond the duodenum, but the
technique is unreliable
There is no reproducible and reliable endoscopic means of

examining the small intestine between the second part of the
duodenum and the terminal ileum. The advent of wireless
capsule endoscopy has altered the potential to visualise the
small bowel. Predominantly of use in the investigation of iron
deficiency and/or recurrent gastrointestinal haemorrhage that
defies other diagnostic techniques. May enable targeted
endoscopic therapy by enteroscopy or surgery. May occasionally
diagnose small bowel diseases such as Crohns disease. Should
be avoided in patients with obstructive symptoms
Colonoscopy and
terminal ileoscopy
Colitis, colorectal polyps, carcinoma,

diverticulosis
Terminal ileitis, ileal Crohns disease and
tuberculosis
Mucosal lesions such as angiodysplasia
that are not detected radiologically
Requires adequate colonic clearance (eg with polyethylene

glycol-containing purgative)
There is a risk of colonic perforation and bleeding of ~1 per
1,000 cases, particularly if laser treatment, electrocautery or
polypectomy is performed
May be diagnostic (eg altered bowel habit, iron deficiency) or
therapeutic (eg polypectomy, colonic stenting of obstructing
tumours)
Flexible sigmoidoscopy
Colonic lesions distal to the splenic flexure
Does not require extensive colonic purging: may be performed

after an enema. May be useful as a screening test, or to assess
the extent of ulcerative colitis
CLO, Campylobacter-like organism.
3.4 Diagnostic and

therapeutic radiology
Choosing the best imaging

modality can be difficult. If in
doubt, discuss with a radiologist.
Luminal radiology
Pancreaticobiliary investigations
The lumen of the intestine can be

imaged by introduction of radioopaque contrast or air (Table 60).
Although still images are usually
studied, much of the information
comes from dynamic changes, so
consultation with the radiologist
supervising the procedure is
essential to obtain maximal
diagnostic information (Fig. 72).
The main pancreaticobiliary

investigations are summarised in
Table 61.
Radiological investigations for

occult blood loss and irondeficiency anaemia
(oesophago-gastroduodenoscopy)
and colonoscopy will provide a
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TABLE 60 RADIOLOGICAL
INVESTIGATION OF THE GASTROINTESTINAL LUMEN
Investigation
Oesophageal dysmotility, stricture,

neoplasia, rupture or fistula
Barium should be avoided if there is high suspicion of

rupture, fistula or potential for aspiration, when
Gastrograffin (water-soluble contrast) is preferred
Barium swallow should precede endoscopy when
investigating dysphagia
Barium meal
Stomach and duodenal ulcers, gastric

outlet obstruction, surgical anastomoses
Endoscopy is the preferred modality to investigate most

gastric and duodenal pathology, but barium meal may be
useful particularly in the postsurgical stomach
Barium meal and follow-through

or small bowel enema
Diseases of the small intestine:

lymphoma, tumours, Crohns disease,
Meckels diverticulum
Relatively insensitive and non-specific; dependent on expert

interpretation
Barium enema
Colorectal carcinoma, polyps,

diverticulosis, complications of IBD
Contraindicated in frail or immobile patients who are unable

to position themselves on the radiology table and who may
be overcome by the strong purgative necessary beforehand
Contraindicated for 24 hours after rectal or colonic biopsy
Alternative to colonoscopy that does not allow therapeutic
manoeuvres such as polypectomy or collection of tissue for
histology
Defecating proctogram
Assessment of obstructive defecation
Useful in planning whether surgical intervention may be

needed
Endoanal ultrasound
Assessment of faecal incontinence
Identification of sphincter damage
Transabdominal ultrasound
May demonstrate thickening of the

intestinal wall in IBD
Location and characterisation of intraabdominal collections
User dependent
May be used to direct drainage of collections or target
biopsy of masses
Contrast CT scanning and

virtual colonoscopy
Colorectal carcinoma, polyps,

diverticulosis, complications of IBD
Used interchangeably with barium enema

Air insufflation of the colon is well tolerated and allows
delineation of the lumen
Abnormalities of the wall can be detected
Imaging is improving rapidly as image-processing software
evolves
MRI scanning
Assessment of Crohns disease
Particularly useful for identifying fistulous tracks in the

perineum
IBD, inflammatory bowel disease.
diagnosis in most cases of

gastrointestinal bleeding, but may
need to be repeated if the bleeding is
intermittent or due to a small, easily
missed lesion. Other techniques may
also be used, particularly for blood
loss from the small intestine, which
is inaccessible to endoscopy
(Table 62).
140
3.5 Rigid sigmoidoscopy

and rectal biopsy
Indications
Altered bowel habit.
Rectal bleeding of unknown cause.
The rectum and distal sigmoid colon

can be viewed directly with a rigid
instrument and a light source. Many
symptomatic colorectal carcinomas
occur distally, and patients with
ulcerative colitis almost universally
have rectal involvement.
Diarrhoea and rectal bleeding in

patients with ulcerative colitis.
Tenesmus, proctalgia.
To obtain rectal mucosal
biopsy, eg for diagnosis of
schistosomiasis, amyloidosis.
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Fig. 72 Normal barium studies: (a) barium meal; (b) barium follow-through; and (c) barium enema.
TABLE 61 PANCREATICOBILIARY
INVESTIGATIONS
Investigation
Ultrasound scan
Dilated intrahepatic ducts

Dilated extrahepatic ducts
Stones
Gallbladder wall abnormalities
Pancreatic abnormalities
Initial investigation of choice for suspected biliary and pancreatic

disease, although pancreas often obscured by overlying bowel (Fig. 73).
Fasting avoids postprandial gallbladder emptying and increases
sensitivity
CT and MRI scanning may add further information, especially with
intravenous contrast agents
(ERCP)
Dilated or strictured bile ducts

Typical features of PSC (beads on
a string stricturing)
Carcinoma of the head of the
pancreas
Stones
Contraindications as for any upper gastrointestinal endoscopy

Side-viewing endoscope allows cannulation of the ampulla of Vater,
with radiocontrast injection demonstrating biliary tree on fluoroscopy
Allows sampling/brushing/biopsy
May be therapeutic, eg retrieval of stones, sphincterotomy, insertion of
stent
CT scanning
Cancer staging
Further delineation of pancreatic
abnormalities
Gives more detailed information than ultrasound especially in

pancreatic disease
Can be used to direct biopsy
cholangiography (PTC)
Dilated or strictured ducts
Caution if there is disordered coagulation or low platelet count

Radiocontrast is introduced into the biliary system by percutaneous
injection
Indicated when ERCP is difficult or impossible
May be therapeutic as well as diagnostic, eg allows cutaneous
drainage of bile from an obstructed system and stent insertion
Magnetic resonance
(MRCP) (see Fig. 24)
Intrahepatic and extrahepatic

biliary and pancreatic anatomy
Can also detect solid parenchymal
lesions and thickening of bile ducts
Cannot be performed in some patients with metallic implants and

electrical devices
Claustrophobia is a relative contraindication
Increasingly used as it is non-invasive and does not use X-rays
Imaging is improving as software and machines evolve
Functional testing
HIDA (radionuclide) scanning

Bromsulphthalein excretion test
HIDA scanning demonstrates functional biliary excretion and is useful

for delineating complicated surgical anastomoses, biliary leaks, etc.
Bromsulphthalein excretion is a measure of biliary excretory function
PSC, primary sclerosing cholangitis.
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TABLE 62 INVESTIGATION
OF OCCULT GASTROINTESTINAL BLOOD LOSS
Investigation
Details/indications/abnormalities
Notes
Red cell scanning
Patients red cells are radiolabelled and

reinjected. A gamma camera is used to
locate the site of radioactive accumulation,
which corresponds to extravasation of blood
Requires relatively brisk bleeding, eg 100 mL per 24 hours

May not provide sufficient anatomical detail to direct therapy
Meckels scanning
Technetium label directed to parietal cells
Detects ectopic gastric mucosa, which may be associated

with a Meckels diverticulum
Selective visceral angiography
Brisk bleeding from the coeliac or

mesenteric arterial territories
Requires fairly brisk bleeding to be detected, eg 750 mL/day

May be therapeutic (embolisation of vascular lesion)
Exploratory laparotomy
Reserved for young patients where an

anatomical lesion such as Meckels
diverticulum is more likely
Often inadequate to locate subtle mucosal abnormalities

such as angiodysplasia
May be combined with on table endoscopy, especially for
the small intestine
Contraindications
Sigmoidoscopy cannot be
performed if:
the patient is unwilling,
apprehensive or uncooperative;
there are inadequate facilities
(lack of privacy, nurse escort or
chaperone, biopsy forceps);
severe anorectal pain (consider
examination under anaesthetic);
biopsy contraindicated in
prescence of bleeding diathesis.
Practical details
Fig. 73 Normal ultrasound of the liver. The liver has normal texture and the bile ducts are not dilated.
Before the procedure

The procedure can usually be
performed without an enema
beforehand. Ensure that the
patients clotting and platelet
count are satisfactory. Sedation
or intravenous cannula are
unnecessary.
Fig. 74 Disposable plastic sigmoidoscope with obturator removed, light source and insufflator with
rubber bulb, and sterilised packaged crocodile biopsy forceps.
142
Essential equipment (Fig. 74)

includes a sigmoidoscope with
obturator, light source, insufflating
bulb with functioning ball valve,
and biopsy forceps. Lubricating
jelly, swabs, towels, gloves and a
specimen pot with histological
fixative should be at hand.
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Ensure that the patient understands

the procedure, and that a nurse
or assistant is present to reassure
the patient, hand you additional
equipment and act as a chaperone.
The procedure
Explain the procedure and place
the patient comfortably in the left
lateral position, with the buttocks
close to the edge of the couch and
the knees slightly extended. Perform
a gentle rectal digital examination.
Lubricate the sigmoidoscope and
obturator. With the obturator fully
inserted in the sigmoidoscope,
insert the first 5 cm of the
instrument into the anus, pointing
anteriorly and cranially (towards the
umbilicus). Withdraw the obturator
and attach the light-source head and
insufflator. Gently insufflate air and
direct the instrument posteriorly
(towards the sacroiliac joint) until a
luminal view is obtained. Insert the
instrument gently, insufflating and
manoeuvring to maintain a luminal
view. Examine the mucosa in all
directions by angling the instrument
gently. The instrument may safely
be inserted to 20 cm provided a
mucosal view is maintained and
the patient does not complain of
discomfort. If indicated obtain
a mucosal biopsy by inserting a
forceps through the viewing port,
and gently shearing a sample
of mucosa under direct vision.
Withdraw the instrument to 5 cm,
carefully examining the mucosa.
Replace the obturator and remove
the instrument.
It is safest to take a biopsy

posteriorly and from the distal
10 cm where the rectum lies outside
the peritoneum. The procedure should
be painless provided the anal mucosa
is avoided.
After the procedure

Warn the patient that there may
be minor rectal bleeding for about
24 hours if a biopsy has been taken.
Complications are rare, but may
include pain, bleeding and
perforation.
3.6 Paracentesis
Paracentesis can be diagnostic
or therapeutic. A diagnostic
paracentesis involves the removal of
50 mL ascitic fluid using a sterile
green needle and syringe. The fluid
should be analysed for albumin,
amylase, cytology and a quantitative
white count. Inoculate blood culture
bottles with ascites to increase the
chance of growing pathogens. If
the fluid is cloudy, then chylous
ascites is confirmed by an ascitic
triglyceride level greater than the
serum level.
Indications
All patients with ascites must

have a diagnostic ascitic tap.
Therapeutic paracentesis is used as

treatment of tense diuretic-resistant
ascites in patients with portal
hypertension.
Contraindications
Absolute contraindications are small
or large bowel obstruction with
dilated loops of bowel, and clinically
evident fibrinolysis/disseminated
intravascular coagulation. Most
physicians routinely correct
coagulation if the INR is >2 and/or
transfuse platelets if the platelet count
is <50 109/L, but there is no evidence
that this is required if the patient
has no clinical evidence of bleeding.
Practical details
Lie the patient flat on the back.
Prepare the following equipment:
suprapubic bladder drainage
catheter or paracentesis catheter
(Fig. 75), lidocaine 1 or 2%, blade,
suture, urine catheter bag, 10-mL
syringe and 18G needle.
The procedure
Insert the catheter into either the
right or left iliac fossa. Clean the
skin and infiltrate with lidocaine
through to the peritoneum: do not
continue with the procedure if you
are unable to draw back ascitic
fluid while anaesthetising. Make
an incision in the skin. Insert the
catheter through the skin and angle
it obliquely for 1 cm or so before
entering the peritoneum at 90 to
the skin and a little way from the
skin entry site. This reduces the risk
of an ascitic leak on removal of the
catheter. Secure the catheter with
adhesive dressings: most liver units
remove paracentesis catheters after
about 6 hours so a suture is not
usually indicated. Attach the end
of the catheter to the urine bag.
Tape the catheter securely to the
abdominal wall.
Allow 510 L of ascites to drain
over 16 hours: if the fluid does not
drain, change the patients position.
In patients with portal hypertension
give 6 g albumin intravenously per
litre of fluid drained (100 mL 4.5%
albumin = 4.5 g; 100 mL 20%
albumin = 20 g).
After the procedure
Remove catheter after 6 hours

irrespective of the amount of
fluid drained to reduce the risk of
bacterial peritonitis.
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Indications
Indications for liver biopsy include
acute hepatitis, drug-related hepatitis,
chronic liver disease, cirrhosis, post
liver transplantation, space-occupying
lesions, unexplained hepatomegaly
or liver enzyme elevations. Ultrasoundguided biopsy is specifically
indicated in focal liver lesion, small
liver or emphysema. Transjugular
liver biopsy (Fig. 76) is specifically
indicated in ascites, prolonged
prothrombin time (PT) >4 seconds
or a platelet count <60 109/L.
Contraindications
A percutaneous liver biopsy is
usually contraindicated where
there is ascites, coagulopathy
or an uncooperative patient.
Fig. 75 Paracentesis catheter. Normally used for suprapubic catheterisation, the catheter is easily
introduced and when inserted its end curls up in the abdominal cavity. Fluid drains through side holes in
the distal catheter.
Practical details
Details are for percutaneous nonradiologically guided liver biopsies.
Note that an assistant is needed.

Complications
3.7 Liver biopsy
Major
Peritoneal varices are rare but can
be ruptured by the insertion of an
ascitic drain. Severe haemorrhage
after abdominal paracentesis
occurs in 0.2% of patients with
liver disease. This is more likely in
those with severe liver failure or
with significant renal dysfunction,
but bleeding is not related to
operator experience, elevated
INR or low platelets.
Minor
Failure to drain ascites: if
the patient has had previous
paracenteses the abdominal
fluid often becomes loculated
and the drain may need to be
inserted under ultrasound
guidance.
Infection at exit site.
144
The aim is to obtain a core of liver

tissue of sufficient length (about
2 cm, with six to eight portal tracts)
to allow the histopathologist to
establish a diagnosis. The procedure
can be performed blind without
imaging at the bedside, ultrasound
guided or via the transjugular route.
There is a move away from blind
biopsies to all biopsies being
ultrasound guided, which is
probably associated with a higher
success rate and less pain, although
there is no evidence that significant
life-threatening complications are
reduced.
Platelet count should be >60 109/L

and PT <3 seconds prolonged: if
34 seconds prolonged, give
fresh frozen plasma just prior to
procedure. Sedation is usually
avoided as the patient has to
cooperate with breathing, but
if sedation is required then use
midazolam with monitoring of
oxygen saturations. If the patient
has renal failure, then desmopressin
acetate (DDAVP) should be given.
Equipment comprises the following:
Menghini needle 1.9 mm diameter
80100 mm long (Fig. 77), or a
Tru-cut needle;
saline 10 mL;
blade;
lidocaine 1 or 2% (10 mL);
Liver biopsy can be performed

as a day case in patients without
cirrhosis who have normal coagulation.
needles for instillation of local

anaesthetic;
formalin in a sterile container.
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If using the Menghini needle a cut

is made in the skin. A track is then
made down to the liver capsule
using the metal needle in the
Menghini pack. The biopsy is now
performed by inserting the Menghini
needle (attached to a syringe of
saline) down the preformed track as
far as the liver capsule. Then, while
the patient is holding his or her
breath in expiration, the needle is
advanced quickly 23 cm in and
out of the liver while continuously
aspirating back on the syringe.
No more than two passes into

the liver should be made.
Fig. 76 Transjugular biopsy. Contrast is seen in a hepatic vein with the biopsy needle in the vein.
After the procedure

Ensure analgesia with paracetamol
or codeine; narcotics are
occasionally needed. The patient
lies flat for 2 hours, with 6 hours
bed-rest. BP and pulse recorded
every 15 minutes for the first
2 hours and then half-hourly for
2 hours and then hourly.
Handling of specimens The tissue
should go into formaldehyde for
routine histology. If Wilsons disease
is suspected, part of the biopsy is
sent fresh for biochemical analysis.
If tuberculosis is suspected, part of
the biopsy should be placed in a
sterile vial for microbiology.
Fig. 77 Menghini biopsy needle.
The procedure
Lie the patient flat on the back.
Mark the first dull intercostal space
on expiration in the mid-axillary
line: the needle should be inserted
over the top of a rib, avoiding the
intercostal vessels below the rib.
Clean the skin with antiseptic.
Anaesthetise down to the liver
capsule with lidocaine: do this
by advancing the needle slowly
perpendicular to the skin with the
patient holding their breath in
expiration. You will feel the needle

pass through skin and muscle and
over the rib, and you will hear it
moving against the liver capsule
when the patient breathes. It is
important that you fully anaesthetise
the liver capsule.
If you cannot identify the

capsule, do not continue.
Complications
Mortality rate is 0.01%.
Major
Haemorrhage occurs in 0.5%,
usually in the first 34 hours post
biopsy. There is a higher rate in
malignancy and it is rare in the nonjaundiced patient. If there is major
bleeding, angiography followed by
transcatheter hepatic embolisation
may be needed. Intrahepatic
haematomas are rare, but may be
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seen up to 24 hours after biopsy

and should be considered if there
is severe pain, fever or right upper
quadrant tenderness. Pneumothorax/
haemothorax are uncommon.
Cholangitis can occur after a biopsy,
particularly if there is underlying
biliary disease, but it usually settles
well with antibiotics.
146
Minor
A small amount of bleeding is
universal and minor discomfort is
common. Pain is more likely during
and after the procedure if the
capsule is inadequately
anaesthetised.
FURTHER READING
Grant A, Neuberger J, Day C and
Saxseena S (on behalf the British
British Association for the Study of the
Liver). Guidelines on the Use of Liver
Biopsy in Clinical Practice. London:
British Society for Gastroenterology,
2004. Full text available at
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SELF-ASSESSMENT
4.1 Self-assessment
questions
Question 1
Clinical scenario
A 24-year-old student with wellcontrolled ulcerative colitis treated
with sulfasalazine and azathioprine
develops acute diarrhoea during a
brief visit to Thailand.
Question
Which is the most seriously incorrect
response from the list below?
Answers
A The most likely diagnosis is an
acute exacerbation of ulcerative
colitis, which could be treated
with a higher dose of
sulfasalazine, or with oral or
parenteral corticosteroids
B The most likely diagnosis is
infectious diarrhoea, which
could be treated with a course of
antibiotics such as ciprofloxacin
or metronidazole
C Long-term treatment with
azathioprine might predispose
the patient to opportunistic
infection and broad-spectrum
antimicrobial, antiviral,
antiprotozoal and antifungal
therapy might be indicated
D The likely diagnosis is acute
exacerbation of ulcerative
colitis or infectious diarrhoea,
which could be treated with
antidiarrhoeals such as codeine
or loperamide, used judiciously
for a short time to provide
symptomatic relief
E The likely diagnosis is acute

exacerbation of ulcerative colitis
or infectious diarrhoea, which
could be treated with a
combination of antibiotics and oral
corticosteroids, until a definitive
diagnosis can be established
bouts of diarrhoea and constipation.

He has no other significant
symptoms, but his father was found
to have colon cancer at the age of
70 years and he is anxious about the
possibility that he may have early
bowel cancer.
Question
Question 2
Clinical scenario
A 50-year-old woman who is
generally well apart from having
troublesome osteoarthritis of the
knees complains of profuse watery
diarrhoea that has steadily worsened
over the last 3 months.
Question
Select the most appropriate response
from the list below:
Answers
A A full clinical evaluation, followed
by blood tests and colonoscopy
are probably required
B It is likely that this is an adverse
event related to medications she
might be taking, such as NSAIDs
C Watery diarrhoea with
hypokalaemia, caused by a
vasoactive intestinal peptide
(VIP)-secreting tumour, is the
likely diagnosis
D The progressive nature of the
symptoms suggests a malignant
process
E Microscopic colitis is the most
likely diagnosis
Question 3
Clinical scenario
A 40-year-old man presents to your
clinic with a history of alternating
Which two of the following

statements are correct?
Answers
A The risk of colon cancer increases
markedly after the age of 50 years
B Alternating constipation and
diarrhoea are highly suspicious
of neoplastic obstruction
C Screening for mutations in the
APC and HNPCC genes has
significantly altered the routine
management of familial colon
cancer
D A screening colonoscopy is a
reasonable first step in the
diagnostic algorithm, and should
be arranged as soon as possible
E If the FBC and tumour markers
are normal, there is little chance
that he has colon cancer
F Faecal occult blood testing should
be performed to exclude colon
cancer
G It is likely that the patients father
has a sporadic form of colon
cancer, and the patient is at no
increased risk
H Annual colonoscopy is likely to be
necessary if the patient is found
to have adenomatous polyps
I Regular use of aspirin could halve
the patients risk of developing
adenomatous polyps of the colon
J Regular use of folic acid
supplements could halve the
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GASTROENTEROLOGY AND HEPATOLOGY: SELF-ASSESSMENT
patients risk of developing

adenomatous polyps of the colon
B
Question 4
Clinical scenario
A young white woman is referred for
investigation of low BMI. She denies
any gastrointestinal symptoms and
seems generally quite healthy,
although thin and with a BMI of 17.
Question
Which of the following statements is
probably not correct?
Answers
A Coeliac disease is a cause of low
body weight and may be
asymptomatic
B Anorexia nervosa should be
considered in the differential
diagnosis
C Thyroid disease is unlikely and
isolated biochemical
abnormalities in the absence of
symptoms should be interpreted
with caution, as they can lead to
over-diagnosis and treatment
D Crohns disease is unlikely to
cause low body weight unless it is
very severe, when it is likely to be
symptomatic
E Occult colorectal cancer is highly
unlikely in this scenario
Question 5
Clinical scenario
You are devising a management
algorithm to be used in a rapidaccess, nurse-led clinic for patients
complaining of dysphagia.
Question
Which of the following
recommendations would you
support?
Answers
A Patients with a history of weight
loss and progressive dysphagia
should be assessed urgently with
a water-soluble contrast swallow
148
C
D
test, followed by upper endoscopy

if indicated
Empiric treatment with a proton
pump inhibitor may be offered
for up to 4 weeks
Urgent upper endoscopy, biopsy
and brushings should be arranged
Achalasia is the most likely
diagnosis in younger patients
and the first test to be performed
should be oesophageal
manometry
Peptic stricture secondary to acid
reflux is the most likely diagnosis
in middle-aged patients, and the
first test to be performed should
be 24-hour oesophageal pH
monitoring
Question 6
Clinical scenario
A 70-year-old woman with
pneumonia who has been
treated with a third-generation
cephalosporin develops profuse
diarrhoea.
Question
Which of the following statements
about her situation is correct?
Answers
A The patient is likely to have
developed pseudomembranous
colitis due to infection with
Clostridium difficile
B Significant infection with
C. difficile is associated with
enterotoxin A, which can be
rapidly detected by a sensitive
ELISA test
C Rectal bleeding associated with
diarrhoea makes it unlikely that it
is related to the use of antibiotics
D Her antibiotic treatment should
be broadened to include a
fluoroquinolone such as
ciprofloxacin to cover infection
with dysentery-causing organisms
E The concurrent use of antibiotics
means that it will be impossible
to determine if her diarrhoea is
caused by infection with

C. difficile
Question 7
Clinical scenario
A 20-year-old man with HIV
infection develops profuse
watery diarrhoea.
Question
Which of the following statements
regarding HIV infection and
the gastrointestinal tract is
correct?
Answers
A HIV infects CD4-positive
lymphocytes and is therefore
minimally present in the
gastrointestinal tract, which is
predominantly populated with
CD8-positive lymphocytes
B HIV infection reduces adaptive
immunity by reducing the
number of CD4-positive cells
and therefore has minimal
effects on intestinal immunity
because it is mainly mediated by
innate defence mechanisms
C Opportunistic infections such
cryptosporidiosis are unlikely if
the patient has a CD4-positive
lymphocyte count >200 cells/mL
D The most likely cause of
diarrhoea is an opportunistic
infection, even if the patients
CD4-positive lymphocyte count
is normal
E If the diarrhoea is profuse,
there is a small risk of fecaloral
transmission of HIV infection to
carers
Question 8
Clinical scenario
An obese patient reports to you
that he has recently been following
the Atkins diet, in which all forms
of carbohydrate are avoided and
subjects eat high-protein, high-fat
meals.
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Question
Which of the following statements is
correct?
Answers
A It is unlikely that the subject will
lose weight because of the high
energy density of the foods
consumed
B The long-term consequences of
following this diet might include
vitamin and micronutrient
deficiency, dyslipidaemia,
accelerated atherosclerosis
and neoplasia
C The absence of carbohydrate in
the diet results in significant
hypoglycaemia
D The absence of carbohydrate in
the diet inhibits the absorption
of other nutrients, such as amino
acids and triglycerides
E The diet has not been tested in
clinical trials
Question 9
Clinical scenario
A 56-year-old woman presents to
her GP with lethargy and tiredness.
Her routine blood tests are normal
apart from an alkaline phosphatase
twice the upper limit of normal.
Subsequent testing of liver
antibodies show her to be positive
for anti-mitochondrial antibody
(M2 subtype).
Question
What should the patient be told?
Answers
A That she has primary biliary
cirrhosis and will urgently
need referral to a liver transplant
unit
B That she has symptomatic
primary biliary cirrhosis and will
need a liver biopsy to stage her
disease
C That she has primary biliary
cirrhosis and will need follow-up
in a liver clinic
D That no treatment is available for

primary biliary cirrhosis
E That no further investigation or
treatment will be needed
Question 10
Clinical scenario
A 25-year-old heavily pregnant
woman returns to the UK from a
holiday in Bangladesh where she
visited family. Two weeks later she
presents jaundiced and confused to
casualty with an INR of 2, alanine
transaminase (ALT) of 2,000 U/L and
bilirubin of 200 mol/L.
Question
Which viral infection is most likely
to have caused this illness?
Answers
A
B
C
D
E
Hepatitis
Hepatitis
Hepatitis
Hepatitis
Hepatitis
A
B
C
D
E
Question 11
Clinical scenario
Prior to starting medical school, a
prospective student is tested for
hepatitis B. Her liver tests show
alanine transaminase (ALT) 120 U/L
and serology shows her to be
positive for HBsAg, HBcAb and
HBeAg, with a viral load of 105
genome equivalents/mL. A liver
biopsy is reported as showing early
fibrosis with evidence of moderate
inflammation.
Question
Treatment should be offered to this
patient in the form of:
Answers
A Interferon beta
B Interferon alfa 2b
C Pegylated interferon alfa 2a and
ribavirin
D Basiliximab
E Entecavir
Question 12
Clinical scenario
An 18-year-old man admits to
having taken 12 g of paracetamol
1 day prior to presentation in the
Emergency Department with
abdominal pain.
Question
Which of the following factors is
most important in determining
treatment?
Answers
A
B
C
D
E
His
His
His
His
His
paracetamol level
serum bilirubin
serum alanine transaminase
history
serum creatinine
Question 13
Clinical scenario
You are looking after a 35-year-old
woman with a 10-year history of
alcohol abuse (>50 units/week).
She has been given a diagnosis of
alcoholic hepatitis based on her
history, and investigations show a
bilirubin of 250 mol/L, alanine
transaminase (ALT) of 120 U/L
and INR of 2. Her creatinine has
increased over the last 2 days from
90 to 250 mol/L.
Question
In managing her further which
single investigation would be most
helpful?
Answers
A Urine osmolality
B Urine microscopy
C Serum antineutrophil cytoplasmic
antibody
D Creatinine clearance
E Spot urine sodium
Question 14
Clinical scenario
You are reviewing an 80-year-old
man who presents to clinic with
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a 2-week history of jaundice, not

associated with any pain. He feels
lethargic but is otherwise well.
Initial hepatitis serology is
negative, ultrasound shows no
duct dilatation, and liver function
tests are cholestatic in nature. His
medications have not changed over
the last 2 years, apart from a recent
course of Augmentin (co-amoxiclav)
for cellulitis.
Question
Which of his medications may
explain his jaundice?
Answers
A
B
C
D
E
Atorvastatin
Aspirin
Augmentin (co-amoxiclav)
Amiodarone
Diclofenac
Question 15
Clinical scenario
A 35-year-old woman has an
ultrasound scan for investigation
of epigastic pain. Her liver function
tests are all normal, and by the time
of her scan her symptoms have
abated on ranitidine. The report
reads as follows: There are multiple
small hyperechoic lesions in both
lobes of the liver. No other focal
lesions. No features to suggest
cirrhosis or portal hypertension.
Intrahepatic and extrahepatic biliary
tree normal. Pancreas, kidneys,
spleen normal.
Clinical scenario
You admit a 45-year-old man who
had a liver transplant just over
3 months ago for primary sclerosing
cholangitis. He complains of fever,
abdominal pain and diarrhoea,
which has come on over the last
week. He has a platelet count of
60 109/L and alanine transaminase
(ALT) of 300 U/L with a normal
bilirubin. He is taking tacrolimus
and prednisolone for
immunosuppression. He tells you
that he recently stopped taking
valganciclovir.
Question
What is the most likely diagnosis?
Answers
A
B
C
D
E
Acute rejection
Chronic rejection
Donor-acquired toxoplasmosis
Donor-acquired cytomegalovirus
Recurrence of his primary
sclerosing cholangitis
H Faecal elastase-1 level

I Thyroid function tests
J Small bowel meal
Question 18
Clinical scenario
A 45-year-old man presents
with chronic epigastric pain
radiating through to the back
and steatorrhoea. He consumes
45 units of alcohol per week and
has no family history of pancreatic
disease. He has no other significant
past medical history. CT scanning
of the abdomen reveals a dilated
pancreatic duct with associated
calcification of the gland.
Subsequent endoscopic retrograde
shows similar findings with no
dominant structure. He is started
on Creon (pancreatin) 3 tablets tds
and there is improvement in his
steatorrhoea.
Question
Question 17
Which test might be helpful in

determining the cause of his
pancreatic disease?
Clinical scenario
Answers
A 35-year-old woman, diagnosed

18 months previously with coeliac
disease (biopsy-proven), now
presents to outpatients with
unresolved diarrhoea. Her bowels
are open up to six times per day.
There is no blood in the stools and
she does not have abdominal pain.
A Magnetic resonance
(MRCP)
B Serum lipid profile
C Endoscopic ultrasound
D Serum amylase
E Pancreatic biopsy
Question
Question
Question 19
The most likely diagnosis is:
What are the two most useful tests

to perform to investigate her
diarrhoea?
Answers
A
B
C
D
E
150
Question 16
Multiple metastasis
Focal nodular hyperplasia
Adenomas
Haemangiomas
Liver abscesses
Answers
A
B
C
D
E
F
G
Lactose hydrogen breath test

Repeat coeliac antibodies
Repeat duodenal biopsy
Colonoscopy
Dietitian review
Ultrasound of the abdomen
Glucose hydrogen breath test
Clinical scenario
A 66-year-old woman is referred
urgently with painless jaundice and
weight loss. Bilirubin is 212 mol/L,
alanine transaminase (ALT) 60 U/L,
alkaline phosphatase (ALP) 605 U/L,
albumin 34 g/L and prothrombin
time 17 seconds. Ultrasound scanning
of the abdomen shows a grossly
dilated biliary tree and a dilated
pancreatic duct, but no mass is seen.
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Question
What is the next most appropriate
step in her management?
Answers
A Endoscopic retrograde
(ERCP)
B Abdominal CT scan
C Pancreatic endoscopic ultrasound
D Check CA19-9
E Laparoscopy
Question 20
Clinical scenario
A 30-year-old man is admitted
with haemoglobin 5.2 g/dL, mean
corpuscular volume 55.4 fL and
ferritin 3 g/L (normal range
14200). B12 and folate levels
are normal. He has had no
haematemesis or malaena and no
abdominal symptoms. An upper
gastrointestinal endoscopy is
performed. Figure 78 shows the
appearance in the second part
of the duodenum.
Question
What should be the next step in
management?
Answers
A Sclerotherapy with alcohol and
adrenaline
B Angiography and embolisation
C Thermal ablation with argon
plasma coagulation
D Application of endoscopic bands
E Biopsy
Fig. 78 Question 20.
alanine transaminase (ALT) 26 U/L

and albumin 39 g/L. Transabdominal
ultrasound shows normal liver
architecture, but there are several
small stones in the gallbladder and
the common bile duct measures
10 mm in diameter. The pancreas
and the main pancreatic duct are
normal.
Question
What would be the most appropriate
next step?
Answers
Question 21
Clinical scenario
A 40-year-old woman presents to the
outpatient clinic with intermittent
epigastric discomfort. FBC, urea
and electrolytes are normal. Liver
function tests reveal alkaline
phosphatase (ALP) 600 U/L,
-glutamyltransferase (GGT)
768 U/L, bilirubin 13 mol/L,
A Endoscopic retrograde
cholangiopancreatography and
bile duct trawl
B CT scan
C CA19-9
D Magnetic resonance
(MRCP)
E Refer for laparoscopic
cholecystectomy and bile duct
exploration
Question 22
Clinical scenario
A 79-year-old man presents
with obstructive jaundice and is
found to have a non-resectable
adenocarcinoma of the pancreatic
head. The decision at the
multidisciplinary team meeting
is that he should receive palliative
care and that his jaundice should be
relieved by inserting a biliary stent.
Question
Which of the following factors
would favour stent insertion
via percutaneous transhepatic
cholangiography (PTC) rather
than endoscopic retrograde
cholangiopancreatography (ERCP)?
Answers
A
B
C
D
E
Prothrombin time of 17 seconds

Presence of ascites
Underlying chronic liver disease
Platelet count of 70 109/L
Previous Polya gastrectomy
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Question 23
Clinical scenario
A 48-year-old man with type 1
diabetes mellitus of 8 years duration
attends outpatients with a history of
opening his bowels five to six times
per day over the last 6 months.
There is no blood or mucus in
the stool and he has not had any
abdominal pain. His HbA1c is 7.0%.
FBC, urea and electrolytes, liver
function tests, thyroid function
tests, abdominal ultrasound and
colonoscopy with random biopsies
are all normal.
Question
Which two of the following tests are
most likely to lead to a diagnosis?
Answers
A Autonomic function tests
B Helicobacter serology
C Stool for microscopy, culture and
sensitivity
D Abdominal CT scan
E Small bowel enema
F Stool for faecal elastase
G Lactose hydrogen breath test
H Small bowel manometry
I Glycocholate hydrogen breath test
J Rigid sigmoidoscopy and rectal
deep rectal biopsy
Question 24
Clinical scenario
A 40-year-old man is referred
with a 12-month history of
diarrhoea.
Question
Which one of the following features
would be against a diagnosis of
irritable bowel syndrome?
Answers
A Passage of mucus with the
motions.
B Nocturnal diarrhoea
152
C Abdominal discomfort relieved

by defecation
D Abdominal bloating
E Onset of symptoms following an
episode of Campylobacter
diarrhoea
4.2 Self-assessment
answers
Answer to Question 1
D
Question 25
Clinical scenario
A 66-year-old man is referred to the
gastroenterology outpatient clinic
for investigation of a 6-month
history of diarrhoea.
Question
Which two of the following
statements are true?
Answers
A Colonoscopic investigation should
only be offered if alert symptoms
such as weight loss or rectal
bleeding are present
B Rigid sigmoidoscopy and rectal
biopsy will exclude microscopic
colitis
C Normal inflammatory markers
(ESR/CRP) do not exclude
inflammatory bowel disease
as a cause of his symptoms
D Coeliac antibodies should only be
performed if the patient gives a
history of symptoms worsening
on exposure to wheat
E Crohns disease is an unlikely
diagnosis in a man of his age
F A history of cholecystectomy
preceding the onset of his
symptoms may suggest a
diagnosis of microscopic colitis
G The presence of abdominal pain
is highly suggestive of ulcerative
colitis
H Colorectal cancer is a possible
diagnosis
I Nocturnal diarrhoea is common
in the elderly
J Peptic ulceration is a likely cause
Acute diarrhoea is usually infectious

in aetiology, although other
causes such as medications, food
intolerance and inflammatory bowel
disease (IBD) need to be considered.
In patients with a known history of
IBD it is often difficult to distinguish
an exacerbation of disease activity
from an infectious gastroenteritis,
and it is pragmatic to treat for
both until the diagnosis can be
established, which often cannot
be achieved with any certainty.
Symptomatic treatment with
antidiarrhoeals can be highly
dangerous because it can both
mask the severity of the illness
and potentially aggravate it by
inhibiting the excretion of
pathogens. Azathioprine is used at
a relatively low dose in IBD and is
unlikely to cause life-threatening
immunosuppression unless there is
severe myelosuppression, which may
develop after months and/or years of
uneventful treatment; hence patients
on thiopurine treatment should have
regular FBC.
A
Chronic diarrhoea may be due to a
large number of different causes,
hence a full evaluation of patients
presenting in this way is mandatory.
This patient may well have used
NSAIDs that are associated with
the development of microscopic
or lymphocytic colitis, which is a
typical cause of watery diarrhoea
in middle-aged and elderly women.
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However, without a full history,

examination and supportive
investigations, this possibility
is not necessarily highly or most
likely. VIPoma is exceedingly rare,
and there is no evidence in favour of
a malignant process in this patient.
A, F
Colorectal cancer is the third
commonest cause of cancer-related
death, and the lifetime risk of
developing the condition is about
1 in 50. However, this risk is very
low in early life and rises steeply
after the age of 50 years. Typically,
colorectal cancer may be
asymptomatic or it may present
with constipation, diarrhoea,
rectal bleeding, abdominal pain,
unexplained iron deficiency or
anaemia. Alternating constipation
and diarrhoea, especially if longstanding, is more indicative of
irritable bowel syndrome.
Germline mutations in the APC
gene are exceedingly rare, although
when they occur, they cause an
autosomally dominant form of
hereditary colorectal cancer.
Hereditary non-polyposis colon
cancer (HNPCC) is a clinical
syndrome describing an inherited
tendency to develop cancer without
a preceding history of adenomatous
polyps. It is associated with
mutations in a number of different
genes, particularly those associated
with correcting defects in DNA
replication at the cellular level
(mismatch-repair genes). Genetic
testing for HNPCC is complex and
not easily applied in clinical practice.
Even in cases of apparently sporadic
colorectal cancer there is probably
an increased risk in first-degree
relatives, probably as a consequence
of genetic and environmental factors
such as diet. Strategies for screening
the population at risk for colorectal

cancer are evolving and are
currently focused on those older
than 50 years, or in cases of familial
cancer at an age 10 years younger
than the youngest affected family
member. In these cases, faecal
occult blood testing followed by
sigmoidoscopy or colonoscopy, or
colonoscopy on its own, at 5-yearly
intervals are favoured options.
Use of NSAIDs and aspirin
significantly slows the development
of adenomatous polyps, which are
the precursors of colorectal cancer,
although the relative benefit may
be offset by an increased risk of
intestinal bleeding due to peptic
ulceration. Folic acid has no
proven effect.
patients presenting with symptoms

of oesophageal obstruction to
provide guidance to the endoscopist
and to avoid inadvertent perforation
of a malignant lesion. Patients
with oesophageal obstruction are
at risk of aspiration pneumonia,
which might be reduced by using
a water-soluble contrast medium
rather than barium. Empiric acid
suppression may be appropriate
for simple reflux symptoms but
is inappropriate when patients
complain of difficulty swallowing,
which may be due to malignant
or benign stricturing, or dysmotility
of the oesophagus. Physiological
tests such as manometry and
pH monitoring can help to refine
the diagnosis, but they are best
used after more common or
serious conditions have been
excluded.
C
Low body weight or weight loss may
be caused by many processes,
including dietary habits, exercise,
smoking and undiagnosed medical
illnesses such as coeliac disease,
Crohns disease and thyrotoxicosis.
The symptoms and signs of these
conditions may be very mild, and
with an insidious onset the patient
may complain of few or no
symptoms at all. This is most
true for coeliac disease and
hyperthyroidism, which might only
be detected by special tests (coeliac
serology and thyroid function tests).
Crohns disease is unlikely to cause
significant weight loss without
also causing abdominal pain and
diarrhoea, which might be mistaken
for symptoms of irritable bowel
syndrome. At this age, occult
colorectal cancer is highly unlikely.
A
A barium swallow should be
obtained before endoscopy in
B
Antibiotic-associated diarrhoea
frequently develops after use of
broad-spectrum antibiotics. In
many cases it is not associated
with toxigenic C. difficile infection
and may clear simply on withdrawal
of the antibiotics. Significant
C. difficile infection is associated
with production by the bacteria
of enterotoxins, which can be
rapidly detected in the stool using
tests such as ELISA. Detection
of C. difficile infection is not
compromised by concurrent
use of antibiotics. In severe
cases, toxigenic C. difficile infection
can cause pseudomembranous
colitis, which is associated with
the passage of blood and mucus
per rectum. In these cases the
appropriate first line of treatment
is withdrawal of broad-spectrum
antibiotics if possible, and
administration of metronidazole
or oral vancomycin.
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predispose to atherogenesis and

colorectal cancer.
C
There is increasing evidence that
HIV infection has profound effects
on the gastrointestinal immune
system, despite the relative
predominance of CD8-positive T
lymphocytes in this compartment.
Patients on long-term antiretroviral
treatment may harbour a reservoir
of infection in the intestine that
allows reactivation when
medications are withdrawn.
Defence mechanisms in the intestine
are critically dependent on the
function of T lymphocytes, including
a specialised group of intraepithelial
lymphocytes confined to the
intestine. Opportunistic intestinal
infections are rare when the CD
count is satisfactory and more
frequent when the count is low.
Despite the high levels of virus in
gastrointestinal secretions, including
saliva, HIV does not seem to infect
via the oral route, although infection
by rectal, vaginal and parenteral
routes occurs readily.
B
Anecdotal reports and clinical
studies demonstrate that ketogenic
diets such as the Atkins diet can lead
to substantial loss of weight. This
probably occurs through ketogenic
metabolism of fat and suppression
of appetite by the high intake of
protein. The relative paucity of
carbohydrate in the diet is unlikely
to affect the absorption of other
nutrients, although the lack of fruit,
vegetables and starchy foods may
lead to deficiencies of calcium, iron,
folate and other vitamins. With the
paucity of glucose in the diet, blood
levels can be maintained by
gluconeogenesis. The relatively high
intake of fats and red meat and low
intake of vitamins and fibre may
154
C
Primary biliary cirrhosis (PBC)
is a disease characterised by
inflammatory destruction of the
small bile ducts within the liver,
eventually leading to cirrhosis
of the liver. The cause of PBC is
unknown, but because of the
presence of autoantibodies it
is generally thought to be an
autoimmune disease. In the
presence of typical symptoms,
liver enzyme abnormalities and
positive M2 anti-mitochondrial
antibodies, the diagnosis can
confidently be made without a liver
biopsy. Most patients with PBC do
not come to liver transplantation,
which is reserved for those with
documented decompensated liver
disease or (very occasionally)
uncontrollable symptoms (usually
pruritus). In symptomatic patients
ursodeoxycholic acid prolongs
survival, and because of this along
with the need for surveillance for
progressive liver disease patients
should have ongoing follow-up,
usually performed by their local
gastroenterologist/hepatologist.
E
Infective hepatitis can be caused
by a variety of different viruses
such as hepatitis A, B, C, D and E.
The incubation period following
exposure to hepatitis E ranges
from 3 to 8 weeks, with a mean
of 40 days. Hepatitis E is usually
a self-limiting infection followed
by complete recovery; prolonged
viraemia or faecal shedding is
unusual and there is no chronic
infection. A fulminant form of
hepatitis E can develop, most
frequently in pregnancy and with a

mortality rate of 20% in the third
trimester. The condition should
therefore be suspected in outbreaks
of water-borne hepatitis occurring
in developing countries, especially
if the disease is more severe in
pregnant women, or if hepatitis
A has been excluded. A correct
diagnosis can only be made by
testing for the presence of specific
viral antigens and/or antiviral
antibodies (with or without
polymerase chain reaction for
active viral replication).
B
Government estimates are that
about 180,000 people in the UK
have chronic hepatitis B and the
prevalence of hepatitis B surface
antigen (HBsAg) among blood
donors is around 1 in 1,500.
Around one-fifth of HBsAg-positive
individuals are HBeAg positive, with
720% spontaneously losing HBeAg
positivity per year.
There are five therapies for chronic
hepatitis B that are currently
approved: interferon alfa-2b,
lamivudine, adefovir, entecavir
and pegylated interferon
(peginterferon) alfa-2a. Given
the need for long-term treatment,
current guidelines recommend
treatment only for patients with
elevated aminotransferase levels or
histological evidence of moderate or
severe inflammation or advanced
fibrosis. For patients with HBeAgpositive chronic hepatitis B who do
not yet have cirrhosis, the goal is
to achieve HBeAg seroconversion,
and interferon alfa alone has the
best chance of achieving this.
Viral suppression without HBeAg
clearance is invariably associated
with relapse, whereas viral
suppression with HBeAg clearance
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is associated with sustained

responses in 5090% of patients.
Students found to be infected with
a blood-borne virus such as hepatitis
B are allowed to continue their
medical course leading to full
medical registration provided they
accept the requirement that they
will not be allowed to perform
exposure-prone procedures while
infectious (HBeAg positive or
HBeAg negative with >103 genome
equivalents/mL HBV DNA), and that
careers in some specialties may not
be open to them. Registered medical
students who are HBeAg negative
and who have virus loads that do not
exceed 103 genome equivalents/mL
will be tested annually in order to
confirm that their virus load has
not exceeded the threshold at
which they would be prohibited
from conducting exposure-prone
procedures. Those who have
undergone a course of treatment
need to show that they have a
viral load that does not exceed 103
genome equivalents/mL 1 year after
cessation of treatment before a
return to unrestricted working
practices can be considered.
D
The history is most important
in determining the risk of
hepatotoxicity: a dose of
paracetamol of as little as
75 mg/kg in someone at risk
can be fatal. Risk factors include:
regular ethanol consumption in
excess of 21 units/week in males
and 14 units/week in females;
regular use of enzyme-inducing
drugs (carbamazepine, phenytoin,
phenobarbital, rifampacin);
conditions causing glutathione
depletion (malnutrition, HIV,
eating disorders, cystic fibrosis).
In all scenarios you are strongly

advised to treat with Nacetylcysteine if in doubt.
E
Although not diagnostic, a low
spot urinary sodium (<5 mmol/L)
is in keeping with a diagnosis of
hepatorenal syndrome (HRS),
assuming that the patient does
not have intravascular volume
depletion. HRS is defined as an
acute, functional and progressive
reduction in renal blood flow and
glomerular filtration rate (GFR)
secondary to intense renal cortical
vasoconstriction in the setting of
decompensated liver disease. Other
aetiologies for renal failure in liver
disease must be excluded. HRS
can be classified as type 1, with a
rapidly progressive decline in GFR
(<2 weeks), or type 2, which is not
as rapidly progressive (>2 weeks).
C
Virtually all drugs can cause liver
injury. In this case the most recently
introduced medication is most likely
to be the cause of liver injury,
assuming other investigations for
chronic liver disease are negative.
The prescription drugs to be
particularly aware of when assessing
a patient with an undiagnosed liver
disorder include Augmentin (coamoxiclav), diclofenac, isoniazid,
erythromycin, sodium valproate,
amiodarone and phenytoin.
D
Liver imaging must always be
interpreted in the context of the
clinical information, particularly
the presence or absence of relevant
symptoms, the presence or absence
of liver function test abnormalities,

and the presence or absence of
cirrhosis. Liver masses with typical
imaging features of simple cyst or
haemangioma in patients not known
to have, or not suspected of having,
a malignancy may be classified as
benign.
Haemangiomas, the commonest of
the focal benign liver lesions, arise
from the endothelial cells that line
the blood vessels and consist of
multiple large vascular channels
lined by a single layer of endothelial
cells and supported by collagenous
walls. They are more common in
women and occur at all ages, but
most frequently in the third, fourth
and fifth decades of life. Most are
seen incidentally and are usually
less than 1 cm in diameter. They
are generally asymptomatic,
although if large (>5 cm) may
cause symptoms/signs such as pain,
nausea or enlargement of the liver;
very rarely they can rupture, causing
severe pain and bleeding into the
abdomen, or become infected.
On ultrasound imaging hepatic
haemangiomas are hyperechoic in
6070% of cases, hypoechoic in 20%
of cases, and have a mixed pattern
with discrete margins in 20%; they
are multiple in 10% of cases.
D
Cytomegalovirus (CMV) infection
is an important consideration in
any organ transplant recipient,
particularly where the recipient has
never had infection but the donor is
a carrier, since the recipient is then
at risk of primary infection. For this
reason close attention is given to
prophylaxis, particularly in the first
3 months after transplantation.
When prophylaxis is stopped there is
still a chance of infection, which in
the case of liver transplant recipients
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will often present as fever,

abdominal pain, diarrhoea
(colitis), breathlessness
(pneumonitis) and hepatitis.
Other features of the illness
can include haematological
abnormalities, retinitis and
oesophagitis. Diagnosis is by
quantifying CMV viraemia in the
blood. Treatment is with intravenous
ganciclovir and reduction of
immunosuppression if possible.
congenital abnormalities, but

ERCP and CT scan did not
reveal either of these. Endoscopic
ultrasound is unlikely to
demonstrate the cause of
pancreatitis at this stage. Pancreatic
biopsy will show evidence of chronic
pancreatitis but is unlikely to reveal
the aetiology. It is possible that his
pancreatitis may be caused by
hyperlipidaemia.
E, H
The most common cause of
ongoing gastrointestinal symptoms
in patients with coeliac disease
is continued gluten exposure.
Dietitians are best equipped to
assess this and therefore should
be involved in assessment. Up to
30% of patients with coeliac disease
and unresolved diarrhoea have
associated exocrine pancreatic
insufficiency. The faecal elastase-1
test is cheap, non-invasive and
simple to use in an outpatient
setting. Positive coeliac antibodies
may suggest continued gluten
exposure but are not diagnostic.
Repeat duodenal biopsy may still
show villous atrophy even in
compliant patients. Colonoscopy in a
patient under 45 years is unlikely to
demonstrate a significant cause for
diarrhoea. Although thyroid disease
is associated with coeliac disease
and should be screened for, only
12% of patients develop new
thyroid dysfunction over a
12-month period.
B
Chronic pancreatitis is most
commonly caused by alcohol but
this man consumes only small
quantities. MRCP may help to
exclude obstructive causes or
156
B
This scenario is highly suspicious
of cancer in the pancreatic head as
there is obstructive jaundice and
ultrasound demonstrates the double
duct sign. The absence of a mass
on ultrasound does not exclude
this diagnosis and therefore a CT
scan is required to further image the
pancreatic head and simultaneously
stage the disease. ERCP would
demonstrate the stricture but
gives no staging information,
and endoscopic ultrasound may
not pick up liver metastases. CA19-9
is not specific for pancreatic cancer
and is often raised in obstructive
jaundice of any aetiology.
Laparoscopy is too invasive at this
stage without further imaging.
C
This is duodenal angiodysplasia and
very likely to be the source of blood
loss in this patient. It can be dealt
with directly by applying argon
electrocoagulation, with minimal
time added to the procedure.
Sclerotherapy and banding
techniques are not appropriate
for such a lesion. Angiography may
not identify this lesion if it is not
actively bleeding and embolisation
may not be possible. Biopsy is
hazardous as it may lead to
torrential bleeding.
D
As this woman is not acutely ill,
there is time to perform further
investigations of the biliary tree
without moving directly to invasive
procedures. MRCP has a higher
sensitivity than CT for detecting
distal bile duct stones, which are the
most likely cause of this womans
presentation. CA19-9 is useless in
this situation. If her MRCP is
negative, then laparoscopic removal
of the gallbladder would be
appropriate.
E
ERCP is usually preferable to PTC
for insertion of biliary stents, unless
ERCP has previously failed or there
is altered anatomy. Patients who
have had a Billroth II gastrectomy
have grossly different anatomy
and ERCP can be impossible to
perform. Impaired clotting (raised
prothrombin time, low platelets or
liver disease) are contraindications
to a percutaneous approach, as is
the presence of ascites.
F, I
The three most likely associations
with type 1 diabetes mellitus that
cause diarrhoea are coeliac disease
(up to 5%, so check coeliac
serology), exocrine pancreatic
insufficiency (over 30% in some
studies) and small bowel bacterial
overgrowth (SBBO). SBBO
commonly occurs when there is
autonomic dysfunction, but tests of
the autonomic nervous system may
be normal, and SBBO may not be
present in those with dysfunction.
This patient also has good metabolic
control of his diabetes as judged by
HbA1c of 7.0%. It will be appropriate
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to send stool for microscopy, culture

and sensitivity, but after a history of
6 months this is likely to be normal.
CT scanning or small bowel imaging
will have a low yield. Lactose
hydrogen breath testing may be
falsely positive due to SBBO.
Further colonic biopsies are
unlikely to add anything.
B
The Rome II diagnostic criteria for
irritable bowel syndrome require
the presence of abdominal pain
for 12 weeks (not necessarily
consecutive) with two of the
following: relieved by defecation;
onset associated with change in
form of stool; onset associated
with change in frequency of stool.
Associated features may include
the passage of mucus and the

presence of abdominal bloating.
Postinfectious irritable bowel
syndrome is well recognised after
an episode of culture-positive
gastroenteritis. The presence of
nocturnal diarrhoea or pain, weight
loss, or abnormalities on blood tests
should alert the physician to the
possibility of inflammatory bowel
disease or other organic disease.
C, H
All patients over the age of 50 years
with a persistent change in bowel
habit should undergo colonoscopy
(or double-contrast barium enema)
to exclude colonic neoplasm.
Rectal biopsies alone do not
exclude microscopic colitis: it is
recommended that biopsies are
taken from the right and left colon.

Mild or limited (eg proctitis)
ulcerative colitis may present
with normal inflammatory markers.
Coeliac antibodies should be
routinely performed in any patient
with chronic diarrhoea. Many
patients with irritable bowel
syndrome exhibit intolerance
to wheat. Crohns disease has
a bimodal distribution, with
peaks between 1540 years and
6070 years. Cholecystectomy
is associated with bile salt
malabsorption. Abdominal
pain is commonly seen in
Crohns disease but should alert
the physician to complications
in ulcerative colitis. Nocturnal
diarrhoea should always be
aggressively investigated as
this is not a feature of functional
disease.
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THE MEDICAL MASTERCLASS SERIES
Scientific Background
to Medicine 1
GENETICS AND
MOLECULAR
MEDICINE
Nucleic Acids and
Chromosomes 3
Inammation 120
Nucleotides 61
Immunosuppressive Therapy
125
Self-assessment 66
CELL BIOLOGY
Ion Transport 71
1.1 Ion channels 72
1.2 Ion carriers 79
Techniques in Molecular
Biology 11
Receptors and Intracellular

Signalling 82
Molecular Basis of Simple

Genetic Traits 17
Cell Cycle and Apoptosis 88
More Complex Issues 23

Self-assessment 30
BIOCHEMISTRY
AND METABOLISM
Requirement for Energy 35
Carbohydrates 41
Fatty Acids and Lipids 45
3.1 Fatty acids 45
3.2 Lipids 48
Cholesterol and Steroid

Hormones 51
Amino Acids and Proteins 53
5.1 Amino acids 53
5.2 Proteins 56
158
Haem 59
Self-assessment 130
ANATOMY
Heart and Major Vessels 135
Lungs 138
Liver and Biliary Tract 140
Spleen 142
Kidney 143
Haematopoiesis 94
Endocrine Glands 144
Self-assessment 97
Gastrointestinal Tract 147
IMMUNOLOGY AND
IMMUNOSUPPRESSION
Eye 150
Nervous System 152
Overview of the Immune

System 103
Self-assessment 167
The Major Histocompatibility

Complex, Antigen Presentation
and Transplantation 106
PHYSIOLOGY
T Cells 109
B Cells 112
Tolerance and Autoimmunity
115
Cardiovascular System 171

1.1 The heart as a pump 171
1.2 The systemic and pulmonary
circulations 176
1.3 Blood vessels 177
1.4 Endocrine function of the
heart 180
Respiratory System 182

Complement 117
2.1 The lungs 182
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Gastrointestinal System 187

3.1 The gut 187
3.2 The liver 190
3.3 The exocrine pancreas 193
Brain and Nerves 194

4.1 The action potential 194
4.2 Synaptic transmission 196
4.3 Neuromuscular transmission
199
Endocrine Physiology 200

5.1 The growth hormone
insulin-like growth factor 1
axis 200
5.2 The hypothalamicpituitary
adrenal axis 200
5.3 Thyroid hormones 201
5.4 The endocrine pancreas 203
5.5 The ovary and testis 204
5.6 The breast 206
5.7 The posterior pituitary 207
Renal Physiology 209

6.1 Blood flow and glomerular
filtration 209
6.2 Function of the renal tubules
211
6.3 Endocrine function of the
kidney 217
Self-assessment 220
Scientific Background
to Medicine 2
CLINICAL
PHARMACOLOGY
Introducing Clinical
Pharmacology 3
1.1 Risks versus benefits 4
1.2 Safe prescribing 4
1.3 Rational prescribing 5

1.4 The role of clinical
pharmacology 5
Pharmacokinetics 7
2.1
2.2
2.3
2.4
2.5
2.6
Introduction 7
Drug absorption 7
Drug distribution 11
Drug metabolism 12
Drug elimination 17
Plasma half-life and steadystate plasma concentrations 19
2.7 Drug monitoring 20
Pharmacodynamics 22
3.1 How drugs exert their effects
22
3.2 Selectivity is the key to the
therapeutic utility of an agent
25
3.3 Basic aspects of the
interaction of a drug with
its target 27
3.4 Heterogeneity of drug
responses, pharmacogenetics
and pharmacogenomics 31
5.5 Non-dose-related adverse

drug reactions (type B) 51
5.6 Adverse reactions caused by
long-term effects of drugs
(type C) 56
5.7 Adverse reactions caused
by delayed effects of drugs
(type D) 57
5.8 Withdrawal reactions (type E)
58
5.9 Drugs in overdose and use of
illicit drugs 59
Drug Development and

Rational Prescribing 60
6.1 Drug development 60
6.2 Rational prescribing 65
6.3 Clinical governance and
rational prescribing 66
6.4 Rational prescribing:
evaluating the evidence for
yourself 68
6.5 Rational prescribing,
irrational patients 68
Self-assessment 70
Prescribing in Special
Circumstances 33
4.1 Introduction 33
4.2 Prescribing and liver disease
33
4.3 Prescribing in pregnancy 36
4.4 Prescribing for women of
childbearing potential 39
4.5 Prescribing to lactating
mothers 39
4.6 Prescribing in renal disease 41
4.7 Prescribing in the elderly 44
Adverse Drug Reactions 46

5.1 Introduction and definition 46
5.2 Classification of adverse drug
reactions 46
5.3 Clinical approach to adverse
drug reactions 47
5.4 Dose-related adverse drug
reactions (type A) 48
STATISTICS,
EPIDEMIOLOGY,
CLINICAL TRIALS
AND METAANALYSES
Statistics 79
Epidemiology 86
2.1 Observational studies 87
Clinical Trials and

Meta-Analyses 92
Self-assessment 103
159
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Clinical Skills
CLINICAL SKILLS
FOR PACES
Introduction 3
History-taking for PACES
(Station 2) 6

ethics 65
1.2.1 Pain 65
1.2.2 Breathlessness 66
1.2.4 Bowel obstruction 69
1.2.5 End of life 70
1.3.1 Pain 71
1.3.2 Breathlessness 74
1.3.4 Bowel obstruction 79

Communication Skills and
Ethics for PACES (Station 4) 10
Examination for PACES
Stations 1, 3 and 5: General
Considerations 12
Station 1: Respiratory
System 15
Station 1: Abdominal
System 20
Station 3: Cardiovascular
System 26
Station 3: Central Nervous
System 35
Station 5: Brief Clinical
Consulations 53
PAIN RELIEF AND

PALLIATIVE CARE
Scenarios 61
1.1.1 Pain 61
1.1.2 Constipation/bowel
obstruction 63
160
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
Pain 82
Breathlessness 87
Nausea and vomiting 88
Constipation 89
Bowel obstruction 90
Anxiety and depression 91
Confusion 93
End-of-life care:
the dying patient 94
2.9 Specialist palliative care
services 96
Self-assessment 98
MEDICINE FOR
THE ELDERLY
Scenarios 107
1.1.1 Frequent falls 107
1.1.2 Recent onset of confusion
110
1.1.3 Urinary incontinence and
immobility 114
1.1.4 Collapse 116
1.1.5 Vague aches and pains
119
1.1.6 Swollen legs and back
pain 121
1.1.7 Failure to thrive: gradual
decline and weight loss
127

1.2.1 Confusion (respiratory)
129
1.2.2 Confusion (abdominal)
130
1.2.3 Failure to thrive
(abdominal) 131
1.2.4 Frequent falls
(cardiovascular) 131
1.2.5 Confusion
(cardiovascular) 132
(neurological) 132
1.2.7 Confusion (neurological)
134
1.2.8 Impaired mobility
(neurological) 135
1.2.9 Confusion (skin) 135
(locomotor) 136
1.2.11 Confusion (endocrine)
136
1.2.12 Confusion (eye) 136
ethics 137
1.3.1 Frequent falls 137
1.3.2 Confusion 138
1.3.3 Collapse 139
1.4.1 Sudden onset of
confusion 141
1.4.2 Collapse 143

2.1
Why elderly patients are

different 147
2.2 General approach to
management 149
2.3 Falls 151
2.4 Urinary and faecal
incontinence 155
2.4.1 Urinary incontinence 155
2.4.2 Faecal incontinence 157
2.5 Hypothermia 158
2.6 Drugs in elderly people 161
2.7 Dementia 162
2.8 Rehabilitation 165
2.9 Aids, appliances and
assistive technology 166
2.10 Hearing impairment 168
2.11 Nutrition 170
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2.12 Benefits 174

2.13 Legal aspects of elderly care
175

Procedures 178
3.1 Diagnosis vs common sense
178
3.2 Assessment of cognition,
mood and function 178
Self-assessment 181
Acute Medicine
ACUTE MEDICINE
Scenarios 3
ethics 3
1.1.1 Cardiac arrest 3
1.1.2 Stroke 4
1.1.3 Congestive cardiac
failure 5
1.1.4 Lumbar back pain 6
1.1.5 Community-acquired
pneumonia 7
1.1.6 Acute pneumothorax 7
1.2.1 Cardiac arrest 8
1.2.2 Chest pain and
hypotension 12
1.2.3 Should he be
thrombolysed? 15
1.2.4 Hypotension in acute
coronary syndrome 20
1.2.5 Postoperative
breathlessness 21
1.2.6 Two patients with
tachyarrhythmia 23
1.2.7 Bradyarrhythmia 27
1.2.8 Collapse of unknown
cause 30
1.2.9 Asthma 33
1.2.10 Pleurisy 36
1.2.11 Chest infection/

pneumonia 39
1.2.12 Acute-on-chronic
airways obstruction 42
1.2.13 Stridor 44
1.2.14 Pneumothorax 46
1.2.15 Upper gastrointestinal
haemorrhage 48
1.2.16 Bloody diarrhoea 51
1.2.17 Abdominal pain 54
1.2.18 Hepatic encephalopathy/
alcohol withdrawal 56
1.2.19 Renal failure, fluid
overload and
hyperkalaemia 59
1.2.20 Diabetic ketoacidosis 62
1.2.21 Hypoglycaemia 65
1.2.22 Hypercalcaemia 67
1.2.23 Hyponatraemia 69
1.2.24 Addisonian crisis 71
1.2.25 Thyrotoxic crisis 74
1.2.26 Sudden onset of severe
headache 75
1.2.27 Severe headache with
fever 77
1.2.28 Acute spastic paraparesis
79
1.2.29 Status epilepticus 81
1.2.30 Stroke 83
1.2.31 Coma 86
1.2.32 Fever in a returning
traveller 89
1.2.33 Anaphylaxis 90
1.2.34 A painful joint 91
1.2.35 Back pain 94
1.2.36 Self-harm 96
1.2.37 Violence and aggression
97

2.1 Overdoses 100
2.1.1 Prevention of drug
absorption from the
gut 100
2.1.2 Management of overdoses
of specific drugs 100

Procedures 103
3.1 Central venous lines 103
3.1.1 Indications,
contraindications, consent
and preparation 103
3.2
3.3
3.4
3.5
3.6
3.7
3.8
3.1.2 Specific techniques for

insertion of central lines
104
3.1.3 Interpretation of central
venous pressure
measurements 106
Lumbar puncture 106
Cardiac pacing 107
Elective DC cardioversion 109
Intercostal chest drain
insertion 109
Arterial blood gases 112
3.6.1 Measurement of arterial
blood gases 112
3.6.2 Interpretation of arterial
blood gases 113
Airway management 113
3.7.1 Basic airway
management 113
3.7.2 Tracheostomy 116
Ventilatory support 117
3.8.1 Controlled oxygen
therapy 117
3.8.2 Continuous positive
airway pressure 117
3.8.3 Non-invasive ventilation
118
3.8.4 Invasive ventilation 118
Self-assessment 120
Infectious Diseases and

Dermatology
INFECTIOUS
DISEASES
Scenarios 3
1.1.1 A cavitating lung lesion 3
1.1.2 Fever and
lymphadenopathy 5
1.1.3 Still feverish after
6 weeks 7
1.1.4 Chronic fatigue 10
161
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1.1.5 A spot on the penis 12

1.1.6 Penile discharge 15
1.1.7 Woman with a genital
sore 17
ethics 20
1.2.1 Fever, hypotension and
confusion 20
1.2.2 A swollen red foot 21
1.2.3 Still feverish after
6 weeks 22
1.2.4 Chronic fatigue 23
1.2.5 Malaise, mouth ulcers
and fever 24
1.2.6 Dont tell my wife 25
1.3.1 Fever 27
1.3.2 Fever, hypotension and
confusion 30
1.3.3 A swollen red foot 33
1.3.4 Fever and cough 34
1.3.5 Fever, back pain and
weak legs 37
1.3.6 Drug user with fever and
a murmur 40
1.3.7 Fever and heart failure
44
1.3.8 Persistent fever in the
intensive care unit 47
1.3.9 Pyelonephritis 49
1.3.10 A sore throat 52
1.3.11 Fever and headache 55
1.3.12 Fever with reduced
conscious level 60
1.3.13 Fever in the neutropenic
patient 62
1.3.14 Fever after renal
transplant 65
1.3.15 Varicella in pregnancy
68
1.3.16 Imported fever 70
1.3.17 Eosinophilia 74
1.3.18 Jaundice and fever after
travelling 76
1.3.19 A traveller with
diarrhoea 78
1.3.20 Malaise, mouth ulcers
and fever 81
1.3.21 Breathlessness in a
HIV-positive patient 83
1.3.22 HIV positive and blurred
vision 86
162
1.3.23 Abdominal pain and

vaginal discharge 88
1.3.24 Penicillin allergy 91
2.10.6
Pathogens and Management 94

2.1
2.2
2.3
2.4
2.5
Antimicrobial prophylaxis 94
Immunisation 95
Infection control 97
Travel advice 99
Bacteria 100
2.5.1 Gram-positive
bacteria 101
2.5.2 Gram-negative
bacteria 104
2.6 Mycobacteria 108
2.6.1 Mycobacterium
tuberculosis 108
2.6.2 Mycobacterium leprae
113
2.6.3 Opportunistic
mycobacteria 114
2.7 Spirochaetes 115
2.7.1 Syphilis 115
2.7.2 Lyme disease 117
2.7.3 Relapsing fever 118
2.7.4 Leptospirosis 118
2.8 Miscellaneous bacteria 119
2.8.1 Mycoplasma and
Ureaplasma 119
2.8.2 Rickettsiae 120
2.8.3 Coxiella burnetii
(Q fever) 120
2.8.4 Chlamydiae 121
2.9 Fungi 121
2.9.1 Candida spp. 121
2.9.2 Aspergillus 123
2.9.3 Cryptococcus
neoformans 124
2.9.4 Dimorphic fungi 125
2.9.5 Miscellaneous fungi
126
2.10 Viruses 126
2.10.1 Herpes simplex
viruses 127
2.10.2 Varicella-zoster virus
128
2.10.3 Cytomegalovirus 130
2.10.4 EpsteinBarr virus
130
2.10.5 Human herpesviruses
6 and 7 130
2.11
2.12
2.13
2.14
Human herpesvirus 8
131
2.10.7 Parvovirus 131
2.10.8 Hepatitis viruses 132
2.10.9 Influenza virus 133
2.10.10 Paramyxoviruses 134
2.10.11 Enteroviruses 134
2.10.12 Coronaviruses and
SARS 135
Human immunodeficiency
virus 135
2.11.1 Prevention following
sharps injury 140
Travel-related viruses 142
2.12.1 Rabies 142
2.12.2 Dengue 143
2.12.3 Arbovirus infections
143
Protozoan parasites 144
2.13.1 Malaria 144
2.13.2 Leishmaniasis 145
2.13.3 Amoebiasis 146
2.13.4 Toxoplasmosis 147
Metazoan parasites 148
2.14.1 Schistosomiasis 148
2.14.2 Strongyloidiasis 149
2.14.3 Cysticercosis 150
2.14.4 Filariasis 151
2.14.5 Trichinosis 151
2.14.6 Toxocariasis 152
2.14.7 Hydatid disease 152

Procedures 154
3.1 Getting the best from the
laboratory 154
3.2 Specific investigations 154
Self-assessment 159
DERMATOLOGY
Scenarios 175
1.1 History taking 175
1.1.1 Blistering disorders 175
1.1.2 Chronic red facial rash
177
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1.1.3 Pruritus 178

1.1.4 Alopecia 180
1.1.5 Hyperpigmentation 181
1.1.6 Hypopigmentation 183
1.1.7 Red legs 185
1.1.8 Leg ulcers 187
1.2.1 Blistering disorder 189
1.2.2 A chronic red facial
rash 193
1.2.3 Pruritus 198
1.2.4 Alopecia 200
1.2.5 Hyperpigmentation 202
1.2.6 Hypopigmentation 205
1.2.7 Red legs 207
1.2.8 Lumps and bumps 210
1.2.9 Telangiectases 212
1.2.10 Purpura 214
1.2.11 Lesion on the shin 216
1.2.12 Non-pigmented lesion
on the face 217
1.2.13 A pigmented lesion on
the face 219
1.2.14 Leg ulcers 221
1.2.15 Examine these hands
223
ethics 225
1.3.1 Consenting a patient to
enter a dermatological
trial 225
1.3.2 A steroid-phobic patient
227
1.3.3 An anxious woman
with a family history
of melanoma who wants
all her moles removed
228
1.3.4 Prescribing isotretinoin to
a woman of reproductive
age 229
1.4.1 Acute generalised rashes
231
1.4.2 Erythroderma 238

2.1
2.2
2.3
Acne vulgaris 243

Acanthosis nigricans 245
Alopecia areata 245
2.4
2.5
2.6
2.7
2.8
2.9
2.10
2.11
2.12
2.13
2.14
2.15
2.16
2.17
2.18
2.19
2.20
2.21
2.22
2.23
2.24
2.25
2.26
2.27
2.28
Bullous pemphigoid 246

Dermatomyositis 248
249
Drug eruptions 249
Atopic eczema 251
Contact dermatitis 252
Erythema multiforme,
StevensJohnson syndrome
and toxic epidermal
necrolysis 253
Erythema nodosum 254
Fungal infections of skin,
hair and nails (superficial
fungal infections) 255
HIV and the skin 257
Lichen planus 258
Lymphoma of the skin:
mycosis fungoides and
Szary syndrome 260
Pemphigus vulgaris 261
Psoriasis 263
Pyoderma gangrenosum
265
Scabies 266
Basal cell carcinoma 268
Squamous cell carcinoma
270
Malignant melanoma 271
Urticaria and angio-oedema
274
Vitiligo 275
Cutaneous vasculitis 276
Topical therapy:
corticosteroids and
immunosuppressants 277
Phototherapy 278
Retinoids 279

Procedures 281
3.1 Skin biopsy 281
3.2 Direct and indirect
immunofluorescence 282
3.3 Patch tests 282
3.4 Obtaining specimens for
mycological analysis 284
Self-assessment 285
Haematology and
Oncology
HAEMATOLOGY
Scenarios 1
1.1.1 Microcytic hypochromic
anaemia 3
1.1.2 Macrocytic anaemia 5
1.1.3 Lymphocytosis and
anaemia 8
1.1.4 Thromboembolism
and fetal loss 11
1.1.5 Weight loss and
thrombocytosis 12
1.2.1 Normocytic anaemia
14
1.2.2 Thrombocytopenia
and purpura 14
1.2.3 Jaundice and anaemia
16
1.2.4 Polycythaemia 17
ethics 19
1.3.1 Persuading a patient
to accept HIV testing 19
1.3.2 Talking to a distressed
relative 20
1.3.3 Explaining a medical
error 22
1.3.4 Breaking bad news 23
1.4.1 Chest syndrome in sickle
cell disease 25
1.4.2 Neutropenia 27
1.4.3 Leucocytosis 29
1.4.4 Spontaneous bleeding
and weight loss 31
1.4.5 Cervical
lymphadenopathy and
difficulty breathing 32
1.4.6 Swelling of the leg 35
163
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2.1
2.2
2.3
2.4
164
Causes of anaemia 37
2.1.1 Thalassaemia
syndromes 38
2.1.2 Sickle cell syndromes 39
2.1.3 Enzyme defects 41
2.1.4 Membrane defects 41
2.1.5 Iron metabolism and
iron-deficiency
anaemia 43
2.1.6 Vitamin B12 and folate
metabolism and
deficiency 44
2.1.7 Acquired haemolytic
anaemia 44
2.1.8 Bone-marrow failure
and inflitration 46
Haematological malignancy
46
2.2.1 Multiple myeloma 46
2.2.2 Acute leukaemia: acute
lymphoblastic leukaemia
and acute myeloid
leukaemia 49
2.2.3 Chronic lymphocytic
leukaemia 52
2.2.4 Chronic myeloid
leukaemia 54
2.2.5 Malignant lymphomas:
non-Hodgkins
lymphoma and
Hodgkins lymphoma 55
2.2.6 Myelodysplastic
syndromes 58
2.2.7 Non-leukaemic
myeloproliferative
disorders (including
polycythaemia vera,
essential
thrombocythaemia
and myelofibrosis) 60
2.2.8 Amyloidosis 62
Bleeding disorders 64
2.3.1 Inherited bleeding
disorders 64
2.3.2 Aquired bleeding
disorders 67
2.3.3 Idiopathic
throbocytopenic
purpura 68
Thrombotic disorders 69
2.4.1 Inherited thrombotic

disease 69
2.4.2 Acquired thrombotic
disease 72
2.5 Clinical use of blood
products 74
2.6 Haematological features of
systemic disease 76
2.7 Haematology of pregnancy
79
2.8 Iron overload 80
2.9 Chemotherapy and related
therapies 82
2.10 Principles of bone-marrow
and peripheral blood stemcell transplantation 85

Procedures 87
3.1 The full blood count
and film 87
3.2 Bone-marrow examination 89
3.3 Clotting screen 91
3.4 Coombs test (direct
antiglobulin test) 91
3.5 Erythrocyte sedimentation
rate versus plasma viscosity
92
3.6 Therapeutic anticoagulation
92
1.3.3 Consent for

chemotherapy (2) 114
1.3.4 Dont tell him the
diagnosis 116
1.4.1 Acute deterioration
after starting
chemotherapy 117
1.4.2 Back pain and
weak legs 119
1.4.3 Breathless, hoarse, dizzy
and swollen 121

2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
2.9
2.10
2.11
2.12
2.13
2.14
Breast cancer 124

Central nervous system
cancers 126
Digestive tract cancers 129
Genitourinary cancer 132
Gynaecological cancer 136
Head and neck cancer 139
Skin tumours 140
Paediatric solid tumours 144
Lung cancer 146
Liver and biliary tree
cancer 149
Bone cancer and sarcoma 151
Endocrine tumours 157
The causes of cancer 159
Paraneoplastic conditions
162
Self-assessment 94

Procedures 167
ONCOLOGY
Scenarios 109
1.1.1 A dark spot 109
1.2.1 A lump in the neck 110
ethics 111
1.3.1 Am I at risk of cancer?
111
1.3.2 Consent for
chemotherapy (1) 113
3.1 Investigation of unknown

primary cancers 167
3.2 Investigation and
management of metastatic
disease 169
3.3 Tumour markers 171
3.4 Screening 173
3.5 Radiotherapy 175
3.6 Chemotherapy 176
3.7 Immunotherapy 179
3.8 Stem-cell transplantation 180
3.9 Oncological emergencies 180
Self-assessment 185
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Cardiology and
Respiratory Medicine
CARDIOLOGY
Scenarios 3
1.1.1 Paroxysmal
palpitations 3
1.1.2 Palpitations with
dizziness 6
1.1.3 Breathlessness and
ankle swelling 9
exertional presyncope
12
1.1.5 Dyspnoea, ankle
oedema and cyanosis 14
1.1.6 Chest pain and
recurrent syncope 16
1.1.7 Hypertension found at
routine screening 19
1.1.8 Murmur in pregnancy
23
1.2.1 Irregular pulse 25
1.2.2 Congestive heart
failure 27
1.2.3 Hypertension 29
1.2.4 Mechanical valve 29
1.2.5 Pansystolic murmur 30
1.2.6 Mitral stenosis 31
1.2.7 Aortic stenosis 32
1.2.8 Aortic regurgitation 33
1.2.9 Tricuspid regurgitation
34
1.2.10 Eisenmengers
syndrome 35
1.2.11 Dextrocardia 36
ethics 37
1.3.1 Advising a patient against
unnecessary
investigations 37
1.3.2 Explanation of
uncertainty of
diagnosis 38
1.3.3 Discussion of the need

to screen relatives for
an inherited condition
38
1.3.4 Communicating news
of a patients death to a
spouse 39
1.3.5 Explanation to a
patient of the need for
investigations 40
1.3.6 Explanation to a
patient who is
reluctant to receive
treatment 41
1.4.1 Syncope 42
1.4.2 Stroke and a murmur
46
1.4.3 Acute chest pain 49
1.4.4 Hypotension following
acute myocardial
infarction 52
collapse 54
1.4.6 Pleuritic chest pain 57
1.4.7 Fever, weight loss and a
murmur 60
1.4.8 Chest pain following a
flu-like illness 64

2.1
2.2
2.3
2.4
Coronary artery disease 69

2.1.1 Stable angina 69
2.1.2 Unstable angina and
non-ST-elevation
myocardial infarction
71
2.1.3 ST-elevation
myocardial infarction
72
Cardiac arrhythmia 76
2.2.1 Bradycardia 76
2.2.2 Tachycardia 78
Cardiac failure 82
Diseases of heart muscle 86
2.4.1 Hypertrophic
cardiomyopathy 86
2.4.2 Dilated
cardiomyopathy 89
2.4.3 Restrictive
cardiomyopathy 89
2.4.4 Arrhythmogenic right

ventricular
cardiomyopathy 90
2.4.5 Left ventricular noncompaction 90
2.5 Valvular heart disease 90
2.5.1 Aortic stenosis 90
2.5.2 Aortic regurgitation 92
2.5.3 Mitral stenosis 93
2.5.4 Mitral regurgitation 95
2.5.5 Tricuspid valve disease
97
2.5.6 Pulmonary valve
disease 98
2.6 Pericardial disease 98
2.6.1 Acute pericarditis 98
2.6.2 Pericardial effusion
100
2.6.3 Constrictive
pericarditis 102
2.7 Congenital heart disease 104
2.7.1 Acyanotic congenital
heart disease 105
2.7.1.1 Atrial septal
defect 105
2.7.1.2 Isolated
ventricular
septal defect
107
2.7.1.3 Patent ductus
arteriosus 107
2.7.1.4 Coarctation of
the aorta 108
2.7.2 Cyanotic congenital
heart disease 109
2.7.2.1 Tetralogy of
Fallot 109
2.7.2.2 Complete
transposition
of great
arteries 111
2.7.2.3 Ebsteins
anomaly 112
2.7.3 Eisenmengers
syndrome 113
2.8 Infective diseases of the
heart 114
2.8.1 Infective endocarditis
114
2.8.2 Rheumatic fever 119
2.9 Cardiac tumours 120
2.10 Traumatic heart disease 122
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2.11 Disease of systemic arteries

124
2.11.1 Aortic dissection 124
2.12 Diseases of pulmonary
arteries 126
2.12.1 Primary pulmonary
hypertension 126
2.12.2 Secondary pulmonary
hypertension 129
2.13 Cardiac complications of
systemic disease 130
2.13.1 Thyroid disease 130
2.13.2 Diabetes 131
2.13.3 Autoimmune
rheumatic diseases 131
2.13.4 Renal disease 132
2.14 Systemic complications of
cardiac disease 133
2.14.1 Stroke 133
2.15 Pregnancy and the heart
134
2.16 General anaesthesia in heart
disease 136
2.17 Hypertension 136
2.17.1 Hypertensive
emergencies 140
2.18 Venous thromboembolism 141
2.18.1 Pulmonary embolism
141
2.19 Driving restrictions in
cardiology 145

Procedures 147
3.1
3.2
3.3
3.4
3.5
166
ECG 147
3.1.1 Exercise ECGs 151
Basic electrophysiology
studies 152
Ambulatory monitoring 154
Radiofrequency ablation and
implantable cardioverter
defibrillators 156
3.4.1 Radiofrequency
ablation 156
3.4.2 Implantable
cardioverter
defibrillator 157
3.4.3 Cardiac
resynchronisation
therapy 158
Pacemakers 159
3.6
Chest radiograph in cardiac

disease 161
3.7 Cardiac biochemical
markers 163
3.8 CT and MRI 164
3.8.1 Multislice spiral CT 164
3.8.2 MRI 165
3.9 Ventilationperfusion
imaging 166
3.10 Echocardiography 167
3.11 Nuclear cardiology 170
3.11.1 Myocardial perfusion
imaging 170
3.11.2 Radionuclide
ventriculography 170
3.11.3 Positron emission
tomography 171
3.12 Cardiac catheterisation 171
3.12.1 Percutaneous coronary
intervention 172
3.12.2 Percutaneous
valvuloplasty 173
Self-assessment 176
RESPIRATORY
MEDICINE
Scenarios 191
1.1.1 New breathlessness
191
1.1.2 Solitary pulmonary
nodule 193
1.1.3 Exertional dyspnoea
with daily sputum 195
1.1.4 Dyspnoea and fine
inspiratory crackles
197
1.1.5 Nocturnal cough 199
1.1.6 Daytime sleepiness and
morning headache 202
1.1.7 Lung cancer with
asbestos exposure 204
1.1.8 Breathlessness with a
normal chest
radiograph 206

1.2.1 Coarse crackles:
bronchiectasis 209
1.2.2 Fine crackles: interstitial
lung disease 210
1.2.3 Stridor 212
1.2.4 Pleural effusion 213
1.2.5 Wheeze and crackles:
chronic obstructive
pulmonary disease 215
1.2.6 Cor pulmonale 216
1.2.7 Pneumonectomy/
lobectomy 217
1.2.8 Apical signs: old
tuberculosis 218
1.2.9 Cystic fibrosis 219
ethics 220
1.3.1 Lifestyle modification
220
1.3.2 Possible cancer 221
1.3.3 Potentially lifethreatening illness 222
1.3.4 Sudden unexplained
death 224
1.3.5 Intubation for
ventilation 225
1.3.6 Patient refusing
ventilation 226
1.4.1 Pleuritic chest pain 228
1.4.2 Unexplained hypoxia
232
1.4.3 Haemoptysis and
weight loss 234
1.4.4 Pleural effusion and
fever 237
1.4.5 Lobar collapse in nonsmoker 239
1.4.6 Upper airway
obstruction 241

2.1
2.2
2.3
2.4
Upper airway 243

2.1.1 Sleep apnoea 243
Atopy and asthma 245
2.2.1 Allergic rhinitis 245
2.2.2 Asthma 246
Chronic obstructive
pulmonary disease 251
Bronchiectasis 253
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2.5
2.6
Cystic fibrosis 256

Occupational lung disease
258
2.6.1 Asbestosis and the
pneumoconioses 258
2.7 Diffuse parenchymal lung
disease 261
2.7.1 Usual interstitial
pneumonia 261
2.7.2 Cryptogenic organising
pneumonia 262
2.7.3 Bronchiolitis obliterans
263
2.8 Miscellaneous conditions
264
2.8.1 Extrinsic allergic
alveolitis 264
2.8.2 Sarcoidosis 265
2.8.3 Respiratory
complications of
rheumatoid arthritis
267
2.8.4 Pulmonary vasculitis
269
2.8.5 Pulmonary eosinophilia
270
2.8.6 Iatrogenic lung disease
272
2.8.7 Smoke inhalation 274
2.8.8 Sickle cell disease and
the lung 276
2.8.9 Human
immunodeficiency virus
and the lung 278
2.9 Malignancy 279
2.9.1 Lung cancer 279
2.9.2 Mesothelioma 283
2.9.3 Mediastinal tumours
285
2.10 Disorders of the chest wall
and diaphragm 287
2.11 Complications of respiratory
disease 288
2.11.1 Chronic respiratory
failure 288
2.11.2 Cor pulmonale 289
2.12 Treatments in respiratory
disease 290
2.12.1 Domiciliary oxygen
therapy 290
2.12.2 Continuous positive
airways pressure 292
2.12.3 Non-invasive
ventilation 292
2.13 Lung transplantation 294

Procedures 297
3.1 Arterial blood gas sampling
297
3.2 Aspiration of pleural effusion
or pneumothorax 298
3.3 Pleural biopsy 298
3.4 Intercostal tube insertion
300
3.5 Fibreoptic bronchoscopy and
transbronchial biopsy 302
3.5.1 Fibreoptic
bronchoscopy 302
3.5.2 Transbronchial biopsy
302
3.6 Interpretation of clinical data
302
3.6.1 Arterial blood gases 302
3.6.2 Lung function tests 304
3.6.3 Overnight oximetry 306
3.6.4 Chest radiograph 306
3.6.5 Computed tomography
scan of the thorax 307
Self-assessment 312
Gastroenterology and
Hepatology

16
tests 18
disease 24
1.2.2 Chronic liver disease 24
ethics 27
27
1.3.2 Limitation of
management 29
1.3.3 Limitation of
investigation 30
want to give a history
31
1.4.2 Acute diarrhoea 36
melaena 39
1.4.4 Acute abdominal pain 46
1.4.5 Jaundice 50

2.1
GASTROENTEROLOGY
AND HEPATOLOGY
Scenarios 3
3
difficulties 5
1.1.3 Chronic diarrhoea 8
1.1.4 Rectal bleeding 10
2.2
Oesophageal disease 60
reflux disease 60
2.1.2 Achalasia and
oesophageal
dysmotility 62
2.1.3 Oesophageal cancer
and Barretts
oesophagus 63
Gastric disease 66
Helicobacter pylori 66
2.2.2 Gastric carcinoma 68
69
gastrointestinal
haemorrhage 70
167
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2.3
2.4
2.5
2.6
2.7
2.8
2.9
168
Small bowel disease 71

2.3.1 Malabsorption 71
2.3.1.1 Bacterial
overgrowth 71
malabsorption
72
2.3.2 Coeliac disease 73
Pancreatic disease 75
2.4.1 Acute pancreatitis 75
2.4.2 Chronic pancreatitis 78
2.4.3 Pancreatic cancer 80
tumours 82
Biliary disease 83
2.5.1 Choledocholithiasis 83
2.5.2 Primary biliary
cirrhosis 85
cholangitis 87
89
89
Infectious diseases 92
gastroenteritis 92
2.6.2 Bacterial dysentery 93
diarrhoea 94
the intestine 94
amoebiasis 95
HIV infection 95
95
2.7.1 Crohns disease 95
2.7.2 Ulcerative colitis 98
2.7.3 Microscopic colitis 101
Functional bowel disorders
101
Large bowel disorders 103
the colon 103
104
2.9.3 Diverticular disease 107
108
2.9.5 Anorectal diseases 109
2.10 Liver disease 109

2.10.1 Acute viral hepatitis 109
109
2.10.1.2 Other acute
viral hepatitis
112
113
113
114
disease 116
2.10.5 Drugs and the liver 118
2.10.5.1 Hepatic drug
toxicity 118
2.10.5.2 Drugs and
chronic liver
disease 120
and cirrhosis 120
2.10.7 Focal liver lesion 124
127
2.11 Nutrition 129
2.11.1 Defining nutrition 129
malnutrition 133
2.11.3 Obesity 133
nutrition and special
diets 134

Procedures 136
3.1 General investigations 136
3.2 Tests of gastrointestinal and
liver function 137
endoscopy 138
radiology 139
3.5 Rigid sigmoidoscopy and
rectal biopsy 140
3.6 Paracentesis 143
3.7 Liver biopsy 144
Self-assessment 147
Neurology,
Ophthalmology and
Psychiatry
NEUROLOGY
Scenarios 3
1.1.1 Episodic headache 3
1.1.2 Facial pain 6
1.1.3 Funny turns/blackouts 8
1.1.4 Increasing seizure
frequency 11
1.1.5 Numb toes 12
1.1.6 Tremor 15
1.1.7 Memory problems 17
1.1.8 Chorea 19
1.1.9 Muscle weakness and
pain 20
1.1.10 Sleep disorders 21
1.1.11 Dysphagia 24
1.1.12 Visual hallucinations 26
1.2.1 Numb toes and foot
drop 27
1.2.2 Weakness in one leg 28
1.2.3 Spastic legs 32
1.2.4 Gait disturbance 33
1.2.5 Cerebellar syndrome 36
1.2.6 Weak arm/hand 37
1.2.7 Proximal muscle
weakness 40
1.2.8 Muscle wasting 41
1.2.9 Hemiplegia 42
1.2.10 Tremor 44
1.2.11 Visual field defect 45
1.2.12 Unequal pupils 47
1.2.13 Ptosis 48
1.2.14 Abnormal ocular
movements 51
1.2.15 Facial weakness 53
1.2.16 Lower cranial nerve
assessment 55
1.2.17 Speech disturbance 57
ethics 60
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1.3.1 Genetic implications 60

1.3.2 Explanation of the
diagnosis of Alzheimers
disease 61
1.3.3 Prognosis after stroke 62
1.3.4 Conversion disorder 63
1.3.5 Explaining the diagnosis
of multiple sclerosis 64
1.4.1 Acute weakness of legs
65
1.4.2 Acute ischaemic stroke
67
1.4.3 Subarachnoid
haemorrhage 71
1.4.4 Status epilepticus 73
1.4.5 Encephalopathy/coma
78

2.1
2.2
2.3
2.4
2.5
2.6
Peripheral neuropathies and

diseases of the lower motor
neuron 81
2.1.1 Peripheral
neuropathies 81
2.1.2 GuillainBarr
syndrome 85
2.1.3 Motor neuron disease
87
Diseases of muscle 89
2.2.1 Metabolic muscle
disease 89
2.2.2 Inflammatory muscle
disease 91
2.2.3 Inherited dystrophies
(myopathies) 91
2.2.4 Channelopathies 93
2.2.5 Myasthenia gravis 93
Extrapyramidal disorders
95
2.3.1 Parkinsons disease 95
Dementia 99
2.4.1 Alzheimers disease 99
Multiple sclerosis 101
Headache 104
2.6.1 Migraine 104
2.6.2 Trigeminal neuralgia
107
2.6.3 Cluster headache 108
2.6.4 Tension-type headache
109
2.7
2.8
Epilepsy 110
Cerebrovascular disease
116
2.8.1 Stroke 116
2.8.2 Transient ischaemic
attacks 120
2.8.3 Intracerebral
haemorrhage 122
2.8.4 Subarachnoid
haemorrhage 125
2.9 Brain tumours 127
2.10 Neurological complications
of infection 131
2.10.1 New variant
CreutzfeldtJakob
disease 131
2.11 Neurological complications
of systemic disease 132
2.11.1 Paraneoplastic
conditions 132
2.12 Neuropharmacology 133
OPHTHALMOLOGY
Scenarios 161
1.1 Clinical scenarios 161
1.1.1 Examination of the eye
161
1.2.1 An acutely painful red eye
164
1.2.2 Two painful red eyes and
a systemic disorder 166
1.2.3 Acute painless loss of
vision in one eye 168
1.2.4 Acute painful loss of vision
in a young woman 170
1.2.5 Acute loss of vision in an
elderly man 171

Procedures 139
3.1 Neuropsychometry 139
3.2 Lumbar puncture 140
3.3 Neurophysiology 142
3.3.1 Electroencephalography
142
3.3.2 Evoked potentials 142
3.3.3 Electromyography 142
3.3.4 Nerve conduction
studies 143
3.4 Neuroimaging 143
3.4.1 Computed tomography
and computed
tomography angiography
143
3.4.2 Magnetic resonance
imaging and magnetic
resonance angiography
144
3.4.3 Angiography 145
3.5 Single-photon emission
computed tomography and
positron emission tomography
145
3.6 Carotid Dopplers 147
Self-assessment 148
2.1
2.2
2.3
2.4
2.5
2.6
Iritis 173
Scleritis 174
Retinal artery occlusion 175
Retinal vein occlusion 178
Optic neuritis 179
Ischaemic optic neuropathy in
giant-cell arteritis 180
2.7 Diabetic retinopathy 181

Procedures 186
3.1 Fluorescein angiography 186
3.2 Temporal artery biopsy 186
Self-assessment 188
PSYCHIATRY
Scenarios 195
1.1.1 Eating disorders 195
1.1.2 Medically unexplained
symptoms 197
169
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ethics 199
1.2.1 Panic attack and
hyperventilation 199
1.2.2 Deliberate self-harm
200
1.2.3 Medically unexplained
symptoms 201
1.3.1 Acute confusional state
202
1.3.2 Panic attack and
hyperventilation 205
1.3.3 Deliberate self-harm 207
1.3.4 The alcoholic in hospital
208
1.3.5 Drug abuser in hospital
210
1.3.6 The frightening patient
212

2.1
2.2
2.3
Dissociative disorders 215

Dementia 215
Schizophrenia and
antipsychotic drugs 217
2.3.1 Schizophrenia 217
2.3.2 Antipsychotics 218
2.4 Personality disorder 220
2.5 Psychiatric presentation of
physical disease 221
2.6 Psychological reactions to
physical illness (adjustment
disorders) 222
2.7 Anxiety disorders 223
2.7.1 Generalised anxiety
disorder 225
2.7.2 Panic disorder 226
2.7.3 Phobic anxiety
disorders 228
2.8 Obsessivecompulsive
disorder 229
2.9 Acute stress reactions and
post-traumatic stress
disorder 231
2.9.1 Acute stress reaction
231
2.9.2 Post-traumatic stress
disorder 231
2.10 Puerperal disorders 233
2.10.1 Maternity blues 233
170
2.11
2.12
2.13
2.14
2.10.2 Postnatal depressive

disorder 233
2.10.3 Puerperal psychosis
233
Depression 235
Bipolar affective disorder
237
Delusional disorder 238
The Mental Health Act 1983
239
Self-assessment 241
Endocrinology
ENDOCRINOLOGY
Scenarios 3
1.1.2 Polyuria 5
1.1.3 Faints, sweats and
palpitations 8
1.1.4 Gynaecomastia 12
1.1.5 Hirsutism 14
1.1.6 Post-pill amenorrhoea
16
1.1.7 A short girl with no
periods 17
1.1.8 Young man who has not
developed 20
1.1.9 Depression and diabetes
21
1.1.10 Acromegaly 23
1.1.11 Relentless weight gain 24
1.1.13 Tiredness and lethargy 29
1.1.14 Flushing and diarrhoea
32
1.1.15 Avoiding another
coronary 34
1.1.16 High blood pressure and
low serum potassium 37
1.1.17 Tiredness, weight loss
and amenorrhoea 39

1.2.1 Amenorrhoea and low
blood pressure 42
1.2.2 Young man who has
not developed 43
1.2.3 Depression and diabetes
45
1.2.4 Acromegaly 45
1.2.5 Weight loss and gritty
eyes 47
1.2.6 Tiredness and lethargy
48
1.2.7 Hypertension and a
lump in the neck 48
ethics 50
1.3.1 Explaining an uncertain
outcome 50
1.3.2 The possibility of cancer
51
1.3.3 No medical cause for
hirsutism 52
1.3.4 A short girl with no
periods 53
1.3.5 Simple obesity, not a
problem with the
glands 54
1.3.6 I dont want to take the
tablets 55
1.4.1 Coma with
hyponatraemia 56
1.4.2 Hypercalcaemic and
confused 60
1.4.3 Thyrotoxic crisis 61
1.4.4 Addisonian crisis 63
1.4.5 Off legs 65

2.1 Hypothalamic and pituitary
diseases 68
2.1.1 Cushings syndrome 68
2.1.2 Acromegaly 71
2.1.3 Hyperprolactinaemia 73
2.1.4 Non-functioning pituitary
tumours 76
2.1.5 Pituitary apoplexy 77
2.1.6 Craniopharyngioma 78
2.1.7 Diabetes insipidus 80
2.1.8 Hypopituitarism and
hormone replacement 83
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2.2 Adrenal disease 85

2.2.1 Cushings syndrome 85
2.2.2 Primary
hyperaldosteronism 85
2.2.3 Virilising tumours 87
2.2.4 Phaeochromocytoma 89
2.2.5 Congenital adrenal
hyperplasia 92
2.2.6 Primary adrenal
insufficiency 94
2.3 Thyroid disease 97
2.3.1 Hypothyroidism 97
2.3.2 Thyrotoxicosis 100
2.3.3 Thyroid nodules and
goitre 105
2.3.4 Thyroid malignancy 107
2.4 Reproductive disorders 107
2.4.1 Delayed growth and
puberty 107
2.4.2 Male hypogonadism 111
2.4.3 Oligomenorrhoea/
amenorrhoea and
premature menopause
113
2.4.4 Turners syndrome 115
2.4.5 Polycystic ovarian
syndrome 116
2.4.6 Hirsutism 118
2.4.7 Erectile dysfunction 120
2.4.8 Infertility 123
2.5 Metabolic and bone diseases
125
2.5.1 Hyperlipidaemia/
dyslipidaemia 125
2.5.2 Porphyria 128
2.5.3 Haemochromatosis 130
2.5.4 Osteoporosis 131
2.5.5 Osteomalacia 134
2.5.6 Pagets disease 136
2.5.7 Hyperparathyroidism
137
2.5.9 Hypocalcaemia 141
2.6 Diabetes mellitus 143
2.6.1 Management of
hyperglycaemic
emergencies 145
2.6.2 Management of
hypoglycaemic
emergencies 147
2.6.3 Short- and long-term
management of diabetes
147
2.6.4 Complications 153

2.6.5 Important information
for patients 160
2.7 Other endocrine disorders
162
2.7.1 Multiple endocrine
neoplasia 162
2.7.2 Autoimmune
polyglandular
endocrinopathies 163
2.7.3 Ectopic hormone
syndromes 164

Procedures 165
3.1 Stimulation tests 165
3.1.1 Short Synacthen test
165
3.1.2 Corticotrophin-releasing
hormone test 166
3.1.3 Thyrotrophin-releasing
hormone test 166
3.1.4 Gonadotrophin-releasing
hormone test 167
3.1.5 Insulin tolerance test
167
3.1.6 Pentagastrin stimulation
test 168
3.1.7 Oral glucose tolerance
test 169
3.2 Suppression tests 169
3.2.1 Overnight
dexamethasone
suppression test 169
3.2.2 Low-dose
dexamethasone
3.2.3 High-dose
dexamethasone
3.2.4 Oral glucose tolerance
test in acromegaly
171
3.3 Other investigations 171
3.3.1 Thyroid function tests
171
3.3.2 Water deprivation test
172
Self-assessment 174
Nephrology
NEPHROLOGY
Scenarios 3
1.1.1 Dipstick haematuria 3
1.1.2 Pregnancy with renal
disease 5
1.1.3 A swollen young woman
8
1.1.4 Rheumatoid arthritis with
swollen legs 11
1.1.5 A blood test shows
moderate renal failure 13
1.1.6 Diabetes with impaired
renal function 16
1.1.7 Atherosclerosis and renal
failure 18
1.1.8 Recurrent loin pain 20
1.2.1 Polycystic kidneys 22
1.2.2 Transplant kidney 23
ethics 23
1.3.1 Renal disease in
pregnancy 23
1.3.2 A new diagnosis of
amyloidosis 24
1.3.3 Is dialysis appropriate?
25
1.4.1 A worrying potassium
level 26
1.4.2 Postoperative acute renal
failure 30
1.4.3 Renal impairment and
a multisystem disease 33
1.4.4 Renal impairment and
fever 36
1.4.5 Renal failure and
haemoptysis 38
1.4.6 Renal colic 41
1.4.7 Backache and renal
failure 43
1.4.8 Renal failure and coma
47
171
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2.1 Major renal syndromes 49
2.1.1 Acute renal failure 49
2.1.2 Chronic renal failure 51
2.1.3 End-stage renal failure
58
2.1.4 Nephrotic syndromes 60
2.2 Renal replacement therapy 64
2.2.1 Haemodialysis 64
2.2.2 Peritoneal dialysis 66
2.2.3 Renal transplantation 69
2.3 Glomerular diseases 72
2.3.1 Primary glomerular
disease 72
2.3.2 Secondary glomerular
disease 79
2.4 Tubulointerstitial diseases 81
2.4.1 Acute tubular necrosis
81
2.4.2 Acute interstitial
nephritis 82
2.4.3 Chronic interstitial
nephritis 82
2.4.4 Specific
tubulointerstitial
disorders 83
2.5 Diseases of renal vessels 86
2.5.1 Renovascular disease 86
2.5.2 Cholesterol
atheroembolisation 88
2.6 Postrenal problems 89
2.6.1 Obstructive uropathy 89
2.6.2 Stones 90
2.6.3 Retroperitonal fibrosis
or periaortitis 91
2.6.4 Urinary tract infection 92
2.7 The kidney in systemic
disease 92
2.7.1 Myeloma 92
2.7.2 Amyloidosis 93
2.7.3 Thrombotic
microangiopathy
(haemolyticuraemic
syndrome) 94
2.7.4 Sickle cell disease 95
2.7.5 Autoimmune rheumatic
disorders 95
2.7.6 Systemic vasculitis 97
2.7.7 Diabetic nephropathy 99
2.7.8 Hypertension 101
2.7.9 Sarcoidosis 102
172
2.7.10 Hepatorenal syndrome

102
2.7.11 Pregnancy and the
kidney 103
2.8 Genetic renal conditions 104
2.8.1 Autosomal dominant
polycystic kidney
disease 104
2.8.2 Alports syndrome 106
2.8.3 X-linked
hypophosphataemic
vitamin-D resistant
rickets 106

Procedures 108
3.1 Examination of the urine 108
3.1.1 Urinalysis 108
3.1.2 Urine microscopy 109
3.2 Estimation of glomerular
filtration rate 109
3.3 Imaging the renal tract 110
3.4 Renal biopsy 114
Self-assessment 116
Rheumatology and
Clinical Immunology
RHEUMATOLOGY
AND CLINICAL
IMMUNOLOGY
Scenarios 3
1.1.1 Recurrent chest
infections 3
1.1.2 Recurrent meningitis 5
1.1.3 Recurrent facial swelling
and abdominal pain 7
1.1.4 Recurrent skin abscesses
9
1.1.5
1.1.6
Flushing and skin rash 12

Drug-induced
anaphylaxis 14
1.1.7 Arthralgia, purpuric rash
and renal impairment
16
1.1.8 Arthralgia and
photosensitive rash 19
1.1.9 Cold fingers and
difficulty swallowing 23
1.1.10 Dry eyes and fatigue 25
weakness 27
1.1.12 Low back pain 30
1.1.13 Chronic back pain 32
1.1.14 Recurrent joint pain and
stiffness 33
1.1.15 Foot drop and weight
loss in a patient with
rheumatoid arthritis 35
1.1.16 Fever, myalgia,
arthralgia and elevated
acute-phase indices 38
1.1.17 Non-rheumatoid pain
and stiffness 40
1.1.18 Widespread pain 42
1.2.1 Hands (general) 44
1.2.2 Non-rheumatoid pain and
stiffness: generalised
osteoarthritis 45
1.2.3 Rheumatoid arthritis 46
1.2.4 Psoriatic arthritis 47
1.2.5 Systemic sclerosis 49
1.2.6 Chronic tophaceous gout
49
1.2.7 Ankylosing spondylitis 50
1.2.8 Deformity of bone:
Pagets disease 51
1.2.9 Marfans syndrome 51
ethics 52
1.3.1 Collapse during a
restaurant meal 52
1.3.2 Cold fingers and
difficulty swallowing 54
1.3.3 Back pain 55
1.3.4 Widespread pain 56
1.3.5 Explain a
recommendation to start
a disease-modifying
antirheumatic drug 57
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1.4.1 Fulminant septicaemia in
an asplenic woman 59
1.4.2 Collapse during a
restaurant meal 61
1.4.3 Systemic lupus
erythematosus and
confusion 64
1.4.4 Acute hot joints 66
1.4.5 A crush fracture 69

2.1 Immunodeficiency 72
2.1.1 Primary antibody
deficiency 72
2.1.2 Combined T-cell and
B-cell defects 75
2.1.3 Chronic granulomatous
disease 77
2.1.4 Cytokine and cytokinereceptor deficiencies 78
2.1.5 Terminal pathway
complement deficiency 80
2.1.6 Hyposplenism 81
2.2 Allergy 82
2.2.1 Anaphylaxis 82
2.2.2 Mastocytosis 84
2.2.3 Nut allergy 85
2.2.4 Drug allergy 87
2.3 Rheumatology 88
2.3.1 Carpal tunnel syndrome
88
2.3.2 Osteoarthritis 89
2.3.3 Rheumatoid arthritis 91
2.3.4 Seronegative
spondyloarthropathies
94
2.3.5 Idiopathic inflammatory
myopathies 98
2.3.6 Crystal arthritis: gout 99
2.3.7 Calcium pyrophosphate
deposition disease 101
2.3.8 Fibromyalgia 101
2.4 Autoimmune rheumatic
diseases 103
2.4.1 Systemic lupus
erythematosus 103
2.4.2 Sjgrens syndrome 105
2.4.3 Systemic sclerosis
(scleroderma) 106
2.5 Vasculitides 109
2.5.1 Giant-cell arteritis and
polymyalgia rheumatica
109
2.5.2 Wegeners
granulomatosis 111
2.5.3 Polyarteritis nodosa 113
2.5.4 Cryoglobulinaemic
vasculitis 114
2.5.5 Behets disease 115
2.5.6 Takayasus arteritis 117
2.5.7 Systemic Stills disease
119

Procedures 121
3.1 Assessment of acute-phase
response 121
3.2
3.3
3.4
3.5
3.6
3.7
3.1.1 Erythrocyte
sedimentation rate 121
3.1.2 C-reactive protein 121
Serological investigation of
autoimmune rheumatic
disease 122
3.2.1 Antibodies to nuclear
antigens 122
3.2.2 Antibodies to doublestranded DNA 123
3.2.3 Antibodies to extractable
nuclear antigens 124
3.2.4 Rheumatoid factor 125
3.2.5 Antineutrophil
cytoplasmic antibody 125
3.2.6 Serum complement
concentrations 125
Suspected immune deficiency
in adults 126
Imaging in rheumatological
disease 129
3.4.1 Plain radiology 129
3.4.2 Bone densitometry 130
3.4.3 Magnetic resonance
imaging 131
3.4.4 Nuclear medicine 131
3.4.5 Ultrasound 132
Arthrocentesis 132
Corticosteroid injection
techniques 133
Immunoglobulin replacement
135
Self-assessment 138
173
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INDEX
Note: page numbers in italics refer to figures, those in bold refer to tables.
abdominal computed tomography 49

diverticular disease 107
pancreatic carcinoma 81
abdominal distention/bloating 4, 213,
267
differential diagnosis 21
examination 26 7
history of complaint 212
investigation 223
ascitic aspiration 23
blood tests 22
imaging 223
liver biopsy 23
liver function 22
management 23, 103
referral letter 21
abdominal mass 13
abdominal pain 11, 14, 312, 33, 40, 56
acute 4650
bowel habit 47
examination 479, 48, 49
management 49 50
onset and duration 47
type of pain 47
vomiting 47
chronic 16 17
exacerbating/relieving factors 16
history of complaint 16 17
investigation 17
localisation of 16
management 17
nature of 16
referral letter 16
functional 102
abdominal radiography 48
ulcerative colitis 99
abdominal ultrasound
acute liver failure 58
chronic pancreatitis 79
jaundice 52
abscess
amoebic 125
pancreatic 50
pyogenic 125
acamprosate 118
N-acetylcysteine 58, 59
achalasia 6, 623
174
aetiology 62
chest radiograph 63
complications 623
epidemiology 62
investigation/staging 62
pathology 62
pathophysiology 62
treatment 62
aciclovir 59
acid reflux see gastro-oesophageal reflux
disease; reflux
Acute Physiology and Chronic Health
Evaluation (APACHE II) system 76
Addisons disease 17
adenomatous polyps of colon 103 4
colorectal cancer risk 104, 104
adevofir 114
albendazole 95
albumin 18
infusion 23
alcohol abuse 17
jaundice 51, 51, 54
alcoholic hepatitis 54
alcoholic liver disease 20, 22, 26
alcohol intake 19
and dyspepsia 4
alcohol-related liver disease 116 18
aetiology/pathophysiology/pathology
116, 116
clinical presentation 116, 117
complications 118
disease associations 118
epidemiology 116
investigation 117
physical signs 116
prevention 118
prognosis 118
treatment 11718, 122
alcohol withdrawal 52
alkaline phosphatase 18, 83, 136
primary biliary cirrhosis 86
allopurinol, hepatotoxicity 119
alpha-fetoprotein 22, 126
ALT 18
ambulatory pH monitoring 61
5-aminosalicylic acid
Crohns disease 97
amiodarone, hepatotoxicity 119
amoebiasis 19, 38
intestinal 95
liver 95
amoebic abscess 125
anaemia 136
anal fissure 11, 110
analgesia
acute pancreatitis 77
angiodysplasia
duodenal 151, 151, 156
gastric 70, 70
angiography, abdominal pain 17
angular cheilosis 24
anorexia 12, 14, 102
anthropomorphic measurements 133
antibiotic-associated diarrhoea 94, 148, 153
antibiotics
acute pancreatitis 49, 77
oesophageal varices 46
antiemetics 37
antihistamines 37
anti-mitochondrial antibody 86
antimuscarinics 37
antioxidants 80
anti-tissue transglutaminase antibody 74
1-antitrypsin deficiency 20, 122
treatment 122
anxiolytics 37
aphthous ulceration 24
appendicitis 47
appetite 14
appetite suppressants 134
apple-core lesions 105, 105
arthritis 38, 94
artificial feeding 279, 29
ascites 21, 25, 26, 48, 52, 123
aspiration 23
causes 27
diagnostic approach 27
symptomatic management 23
AST 18
Augmentin 51
auscultation 34
autoimmune chronic active hepatitis 56
autoimmune liver disease 20, 122
treatment 122
azathioprine 86
Crohns disease 97
Bacillus cereus 93
bacterial overgrowth 71, 72
balloon dilatation of oesophagus 62
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GASTROENTEROLOGY AND HEPATOLOGY: INDEX
balloon tamponade 45, 46

barium enema 140, 141
colorectal carcinoma 105
diverticular disease 107, 108
rectal bleeding 13
barium meal 140, 141
barium swallow 6, 7, 140, 148, 153
achalasia 62
Barretts oesophagus 64, 65
63
clinical presentation 64
complications 65
epidemiology 63 4
investigation/staging 64, 65
prevention 66
prognosis 65
treatment 64 5
benzodiazepines 86
bile duct obstruction 50
biliary cirrhosis 20, 857, 149, 154
85
complications 86
epidemiology 85 6
investigations 86, 87
physical signs 86
prognosis 86
treatment 86
biliary disease 16, 8392
cholangiocarcinoma 8992
choledocholithiasis 51, 83 5
colic 47
intrahepatic cholestasis 89
primary biliary cirrhosis 85 7
primary sclerosing cholangitis 879
biliary pain 47
biliary stents 91, 92
bilious vomiting 33
bilirubin 18
Billroth I procedure 40
Billroth II procedure 41
biopsy
in jaundice 53
liver 20, 21, 21, 23, 53, 86, 87, 88, 88,
115, 144 6, 145
in pancreatic carcinoma 81
rectal 96
biotin 130
bismuth subsalicylate 101
body mass index 131
botulinum toxin, achalasia 62
bowel habit 4, 8, 11, 16, 21, 33
bronze diabetes see haemochromatosis
Budd-Chiari syndrome 21, 26, 56, 57, 120
budesonide, Crohns disease 97
bulimia 14
C
CA19-9 81, 90, 126
cachexia 34, 123
caeruloplasmin 58
CAGE questionnaire 51
calcium 131
Campylobacter spp. 92, 93, 94
Campylobacter jejuni 93
caput medusa 25
carbamazepine, hepatotoxicity 119
carcinoembryonic antigen 105, 126
central venous lines 35
cerebral oedema 59
cerebral perfusion pressure 59
Chagas disease 62
Charcots triad 51
Childs-Pugh classification 124
chlorpromazine, hepatotoxicity 119
cholangioarcinoma 125
cholangiocarcinoma 81, 89 92
8990
complications 92
differential diagnosis 90 1
epidemiology 90
investigations 90, 90, 91
physical signs 90
prognosis 92
treatment 912
cholangiogram 53, 54
cholangiography, sclerosing cholangitis 88
cholangitis 53 4
cholecystectomy 51
cholecystitis, Murphys sign 84
choledocholithiasis 51, 83 5
aetiology/pathophysiology/pathology 83
clinical presentation 83 4
complications 85
epidemiology 83
investigations 84, 84, 85
physical signs 84
prognosis 85
treatment 84 5
cholelithiasis 19
cholera 37
cholestasis of pregnancy 19
chromium 131
chromogranin A 82
chronic viral hepatitis 20
ciclosporin 86
ciprofloxacin 39, 97
cirrhosis 18, 22, 120 4
decompensated 44
histological appearance 121
management 23
clinical examination
abdominal swelling 26 7
chronic liver disease 245

inflammatory bowel disease 24
splenomegaly 25 6
Clonorchis 92
Clostridium difficile 94, 99
clubbing 24, 34
coagulopathy 122
co-amoxiclav 51
coeliac disease 8, 15, 725, 72, 75, 87,
150, 156
73
complications 75
conditions associated with 75
epidemiology 73
histological classification 73, 74
investigation 74
prognosis 75
treatment
dietary supplementation 74
gluten-free diet 74
immunosuppression 74
non-responsive disease 74
colestyramine 86, 101
colon
adenomatous polyps 1034
hamartomatous polyps 103
hyperplastic polyps 103
inflammatory pseudopolyps 103
colonic obstruction 33
colonoscopy 107, 139, 152, 157
chronic diarrhoea 9, 10
colonic carcinoma 13, 13
colorectal carcinoma 105
diverticular disease 107
ulcerative colitis 99, 100
virtual 140
colorectal carcinoma 12, 13, 13, 24,
104 7, 147 8, 1523
104, 104
case finding 106
complications 106
epidemiology 104
physical signs 105
population screening 1067
prevention 106
prognosis 106, 106
surveillance 106
treatment 106
coma, differential diagnosis 56
computed tomography 141
abdominal 49, 64, 79, 81
choledocholithiasis 84
diverticular disease 107, 108
thoracic 64
175
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confusion 56, 57
conjunctivitis 94
constipation 30 1, 47
functional 102
treatment 103
copper 131
corticosteroids 37
Crohns disease 97
Courvoisiers law 52
Courvoisiers sign 81
C-reactive protein 136
Crohns disease 96
CREST syndrome 87
Crohns disease 9, 12, 15, 16, 72, 95 8
956, 96
complications 97 8
epidemiology 96
physical signs 96
prevention 98
prognosis 98
skip lesions 96
treatment 96 7, 98
Cryptosporidium spp. 37
Cullens sign 34, 48, 76
13
C urea breath test 66
cushingoid features 25
Cushings triad 59
cyclizine 37, 49
cysts, htdatid 125
cytomegalovirus 11213, 150, 155 6
defecating proctogram 140

dexamethasone 37
dextropropoxyphene, hepatotoxicity 119
diabetes mellitus 14, 19, 152, 156 7
diabetic gastropathy 32
diarrhoea 14
acute 369, 147, 152
causes 37
examination 37 8
investigation 38, 38
antibiotic-associated 94, 148, 153
chronic 8 10, 147, 152
investigation 9 10
management 10
referral letter 8
diabetes mellitus 152, 156 7
functional 102
management 39
nocturnal 102
176
osmotic 82
public health issues 39
secretory 82
treatment 103
diclofenac 49
Dieulafoy lesion 70
digital rectal examination 34
disulfiram 118
diuretics, ascites 23
diverticulitis 107
domperidone 37
dopamine antagonists 37
double duct sign 81
drowsiness 57
drug hepatotoxicity see hepatic drug
toxicity
duodenal angiodysplasia 151, 151, 156
duodenal ulcer 16
Dupuytrens contracture 24
dynamometry 133
dysentery 37, 93 4
complications 94
epidemiology 93
treatment 94
dyspepsia see heartburn/dyspepsia
dysphagia 5 7, 62, 102
drug history 6
functional 102
investigation
barium swallow 6, 7
blood tests 6
manometry and pH studies 7
radiological tests 6
management 7
medical history 6
referral letter 5
social history 6
early satiety 4
elemental diet 135
ELISA 94
encephalopathy 122
endoanal ultrasound 140
endoscopic ablative therapy 66
endoscopic electrocoagulation 70, 70
endoscopic retrograde
cholangiopancreatography 35, 49,
53, 53, 141, 151, 156
cholangiocarcinoma 90, 90
chronic pancreatitis 79, 79
endoscopic ultrasound 64

endoscopy 138 9, 139
abdominal pain 17
dyspepsia 4
dysphagia 6
gastrointestinal 423, 42, 43
upper gastrointestinal 61, 64
Entamoeba histolytica 93, 95
entecavir 114
enteral nutrition 134 5
Enterobius vermicularis 94
enteroscopy 139
enti-endomysial antibody 74
enzyme-linked immunosorbent assay see
ELISA
epileptic fits 56
Epstein-Barr virus 53, 113
erythema ab igne 79
erythema nodosum 24
erythrocyte sedimentation rate, Crohns
disease 96
Escherichia coli 92, 93, 93
exclusion diets 135
faecal enzyme measurement 137

faecal fat 137
faecal incontinence, functional 102
familial adenomatous polyposis 104
familial cancer syndromes 104
fatigue 22
fat malabsorption 723
fatty liver 19, 20
fistula in ano 110
flexible sigmoidoscopy 139
flucloxacillin, hepatotoxicity 119
fluid restriction 23
5-fluorouracil 106
focal liver lesion 124 7
complications 126
investigations/staging 1256, 126
physical signs 125
prevention 127
prognosis 126
folic acid 130
food poisoning 923, 93
causes 92
functional bowel disorders 1013, 102
1012
epidemiology 102
investigation 102
physical signs 102
prognosis 102
treatment 102, 103
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G
gallstones 17, 51, 52
gallstone disease 47
gamma-glutamyltransferase 18, 83
ganciclovir 59
gastrectomy, partial 40, 41
gastric carcinoma 68 9
68
complications 68
epidemiology 68
physical signs 68
prevention 68
prognosis 68
red flag symptoms 68
treatment 68
gastric obstruction 33
gastric stasis 33
gastric tumours 69 70
gastric and MALT lymphomas 69
gastrinoma 69 70
leiomyoma 69
gastrinoma 69 70, 83
gastroenteritis 923, 93
causes 92
Gastrograffin swallow 140
achalasia 62
gastrointestinal haemorrhage 70 1
Dieulafoy lesion 70
hereditary haemorrhagic telangiectasia
70
Meckels diverticulum 71
vascular ectasia (angiodysplasia) 70,
70
gastro-oesophageal reflux disease 6,
602
60
common 60
physical signs 60 1
uncommon 60
complications 61
epidemiology 60
prevention 612
prognosis 61
treatment
emergency 61
long-term 61
short-term 61
gastro-oesphageal varices 43
gastroscopy 61, 62
Giardia spp. 37
Giardia intestinalis 93, 94
giardiasis 72
Glasgow Alcoholic Hepatitis Score 118
Glasgow Coma Scale 34, 38, 47, 57
gliadin peptides 73
antibodies 74
globus 102
glucagonoma 83
gluten-free diet 74
gluten-sensitive pathology see coeliac
disease
glycocholate breath test 138
Grey Turners sign 34, 48, 76
Guillain-Barr syndrome 94
gynaecomastia 24
haemangioma 125, 150, 155

haematemesis 24 5, 33, 39 46, 47
causes 44
comorbidities 41
drug history 40
examination 41, 41
history of complaint 39 41, 40, 41
investigation 423, 42, 43
gastrointestinal endoscopy 423,
42, 43
radiological imaging 43
routine blood tests 42
limitation of management 29 30
previous abdominal surgery 40 1, 40,
41
Rockall score 41
surgical/radiological intervention 44
syncope 40
venous access 43 4
haemochromatosis 20, 24, 25, 122, 123
treatment 122
haemorrhoids (piles) 11, 12, 110
haloperidol 37
halothane, hepatotoxicity 119
heartburn, functional 102
heartburn/dyspepsia 3 5
abdominal distention/bloating 4
change in bowel habit 4
early satiety 4
investigation 4
blood tests 4
endoscopy 4
imaging 4, 5
jaundice 4
management 5
medical/surgical history 4
medications and alcohol 4
pain 3
referral letter 3
reflux 3 4
vomiting 3
weight loss 4
Helicobacter pylori 4, 44, 66 8
detection 66
CLO test 66, 67
13
C urea breath test 66
eradication of 67
and gastric lymphoma 69
histology 67
see also peptic ulcer
HELLP syndrome 19
hepatic adenoma 125
hepatic drug toxicity 56, 11820, 14950,
155
118 19, 119
chronic liver disease 120
clinical presentation/physical signs
119, 119
complications 120
epidemiology 119
investigations 119 20
prognosis 120
treatment 120
hepatic encephalopathy 52, 57, 589
hepatitis 56, 109, 11115, 149, 154
autoimmune chronic active 56
chronic 20, 113 14, 122
treatment 122
histology 111
ischaemic 56
hepatitis A 51, 109, 11112
aetiology/pathology 109
epidemiology 109
physical signs 109
prevention 112
prognosis 112
treatment 112
hepatitis B 113 14, 149, 1545
113
complications 114
epidemiology 113
investigation 113
physical signs 113
prevention 114, 114
prognosis 114
serological markers 114
treatment 114
hepatitis C 19, 114 15
114
epidemiology 114
investigation 115
physical signs 115
prevention 115
prognosis and complications 115
treatment 115
177
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hepatitis E 51, 112

hepatocellular carcinoma 123, 123,
1267
hepatomegaly 26
hepatorenal failure 123
hepatorenal syndrome 149, 155
hepatosplenomegaly 26
hereditary haemorrhagic telangiectasia,
and gastric haemorrhage 70
hereditary non-polyposis colon cancer 104
herpetic oesophagitis 6
hiatus hernia 60, 60
HIV, intestinal features 95, 148, 154
hookworm 94
Howell-Jolly bodies, coeliac disease 74
hydatid cyst 125
hydatid disease 19
hydrocortisone 39
Crohns disease 97
hypercalcaemia 75
hyperkalaemia, diuretic-induced 23
hyperlipidaemia 19
hyperparathyroidism 75
hypersplenism 22
hypertriglyceridaemia 75
hypoalbuminaemia 136
hypolactasia 72
hyponatraemia 57
hypoproteinaemia 24
hyposplenism, coeliac disease 75
hypothermia, and acute pancreatitis 75
hypothyroidism 87
isoniazid, hepatotoxicity 119

isosorbide 62
ibuprofen 51
ileus 21
immunosuppression, coeliac disease 74
inflammatory bowel disease 24, 37,
95101
abdominal examination 24
Crohns disease 9, 12, 15, 16, 72, 95 8
idiopathic 8, 94
microscopic colitis 101
rectal examination 24
ulcerative colitis 10, 98 101
infliximab, Crohns disease 97
insulinoma 83
intestinal ischaemia 108 9
intestinal obstruction 21, 32, 33, 47
Crohns disease 97
intrahepatic cholestasis 89
inherited 89
iron 131
iron-deficiency anaemia 15
irritable bowel syndrome 152, 157
limitation of investigation 30 1
treatment 103
see also functional bowel disorders
ischaemic colitis 108
ischaemic heart disease 47
ischaemic hepatitis 56
178
jaundice 4, 19, 22, 24, 50 4

alcohol abuse 51, 51, 54
drug history 51
examination 52
fever 51
hepatic encephalopathy 52
investigation 523
abdominal ultrasound 52
cholangiogram 53
tissue biopsy 53
management 53
obstructive 52
pain 50
stool/urine colour 50 1
travel history 51
weight loss 50
Kayser-Fleischer rings 57
ketogenic diets 148 9, 154
Klatskin tumour 90, 91
Korsakoffs dementia 118
kwashiorkor 133
lactase 72
lactose breath test 138
lactulose breath test 138
lamivudine 59, 114
laparoscopy, rectal bleeding 13
laparotomy
exploratory 142
rectal bleeding 13
large bowel disorders 103 9
adenomatous polyps of colon 103 4
anorectal diseases 110
colorectal carcinoma 12, 13, 13, 24,
1047
diverticular disease 107 8, 108
intestinal ischaemia 108 9
laxatives, oesphageal varices 46
leiomyoma 69
leptospirosis 56
leuconychia 24
levomepromazine 37
liver
amoebiasis 95
examination 52
ultrasound 142
liver biopsy 20, 21, 21, 53, 144 6, 145
abdominal distension 23
complications 145 6
contraindications 144
hepatitis C 115
indications 144
primary biliary cirrhosis 86, 87
procedure 145
sclerosing cholangitis 88, 88
liver disease 109 29
alcohol-related 116 18
autoimmune 20, 122
chronic 24 5, 40, 1204
120, 121
causes 25, 122
Childs-Pugh classification 124
complications 1223, 123
epidemiology 120
investigations/staging 121
prognosis 123 4, 124
treatment 121, 122
see also liver failure
cirrhosis 18, 120 4
causes 122
focal liver lesion 1247
hepatitis 11115
liver function tests 1821
liver failure
acute 54 9, 115 16
115
cause of 55
complications 11516
examination 56 7
investigation 57 8
management 58 9, 59
physical signs 115
prognosis 116
chronic 56
liver flukes 19
liver function tests 18 21, 18, 1378
abdominal pain 17
interpretation of 18 19
investigation 19 20
blood tests 19 20
imaging 20
liver biopsy 20, 21
management 20 1
referral letter 18
liver transplantation 59, 1279
biliary cirrhosis 86
biliary complications 129
comorbid illness 129
contraindications 128
disease recurrence 129
emergency 128, 128
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liver transplantation (continued)

extend of liver dysfunction 128
indications 127 8
living related 127
non-heart-beating donors 127
outcome 129
Roux-en-Y biliary anastomosis 128,
129
sclerosing cholangitis 89
split liver transplantation 127
timing of 128
xenotransplantation 127
loperamide 101
lorazepam 37
Lundh test meal 137
lymphadenopathy 34
lymphoma
gastric 69
MALT 69
magnesium 131
magnetic resonance
cholangiopancreatography 53, 54,
141, 151, 156
major histocompatibility complex 73
malabsorption 713
chronic pancreatitis/pancreatic
insufficiency 72
Crohns disease 98
giardiasis 72
hypolactasia 72
post gastric surgery 723
short bowel syndrome 72
tropical sprue 72
Whipples disease 72
Mallory-Weiss tear 40
Malnutrition Universal Screening Tool
132
MALT lymphoma 69
manometry, oesophageal 62, 137
marasmus 133
mebendazole 95
Meckels scanning 142
melaena 4, 11, 29, 39 46, 52
history of complaint 39 41, 40, 41
mesenteric angiography, rectal bleeding
13
mesenteric ischaemia 17
methotrexate 86
Crohns disease 97
hepatotoxicity 119
metoclopramide 37, 62
metronidazole 39, 72, 94, 95, 97
microscopic colitis 101
Minnesota tube 45
mixed triglyceride breath test 137
morphine 49
mouth ulcers 102
mucosal-associated lymphoid tissue see
MALT
multiple endocrine neoplasia 82
Murphys sign 84
Mycobacterium paratuberculosis 95
naltrexone 86, 118

nausea and vomiting 3, 12, 16, 21,
32 6
abdominal pain 47
causes of 33
control of 36, 37
examination 33 4
abdomen 34
functional 102
investigation 34 5, 34
management 35 6
pain control 35 6
resuscitation 35
neuroendocrine tumours 823, 83
82
epidemiology 82
genetic background 82
prognosis 83
treatment 83
see also individual tumour types
neurofibromatosis type 1 82
niacin 130
nifedipine 62
nitrates 62
nocturnal pain 3, 16
non-alcoholic fatty liver disease 20 1
non-alcoholic steatohepatitis 20, 20
Norwalk agent 92, 93
NSAIDs, hepatotoxicity 119
nutrition 129 35
acute pancreatitis 49, 77
anthropomorphic measurements
133
body mass index 131
Crohns disease 97
enteral 134 5
examination 131
Malnutrition Universal Screening Tool
132
nutritional requirements in health 129,
130, 131
nutritional status 129, 131
obesity 133 4
parenteral 134 5
protein-calorie malnutrition 133

special diets 135
nutritional deficiency 136
obesity 19, 133 4

occult gastrointestinal blood loss 142
octreotide scan 44
neuroendocrine tumours 83
odynophagia 5, 62
oesophageal adenocarcinoma 60
oesophageal candidiasis 6
oesophageal carcinoma 636
complications 65
epidemiology 63 4
prevention 66
prognosis 65
risk factors 64
treatment 64 5
oesophageal dysmotility 623
62
complications 62 3
epidemiology 62
treatment 62
oesophageal manometry 62, 137
oesophageal stent 65
oesophageal stricture 56
oesophageal varices 42, 446
antibiotics 46
balloon tamponade 45, 46
rebleeding 45
terlipressin 44
transjugular intrahepatic portosystemic
shunt 45
oesophagectomy 65
oesophagitis 40
chronic reflux 60
radiation-induced 6
reflux 6, 60
oesophago-gastroduodenoscopy 139
oesophagus
balloon dilatation 62
investigation of 6 7
surgical myotomy 62
oesphageal manometry 61
oesphageal obstruction 33
oestrogens, hepatotoxicity 119
omeprazole 58
ondansetron 37, 86
opiates 36
Opisthorchis 92
orlistat 134
osteomalacia, and biliary cirrhosis 86
osteoporosis, and biliary cirrhosis 86
179
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P
PABA test 137
pain
abdominal see abdominal pain
chronic diarrhoea 9
dyspepsia 3
jaundice 50
nocturnal 3, 16
on swallowing 6
palmar erythema 24
palpation 34
pancreas 52
pancreas divisum 75
pancreatic abscess 50
pancreatic carcinoma 80 2, 150 1,
156
80
epidemiology 80
imaging 81, 81
jaundice 50
physical signs 81
prognosis 82
treatment 82
pancreatic enzyme replacement 80, 82
pancreatic function tests 80, 137
faecal enzyme measurement 137
faecal fat 137
Lundh test meal 137
mixed triglyceride breath test 137
PABA test 137
secretin-caerulein test 137
triolein breath test 137
pancreatic insufficiency 72
pancreaticobiliary investigations 141
pancreatic pain 47
pancreatic pseudocyst 76, 77
pancreatitis 48, 48
acute 75 8
75
cause 76
causes 75
complications 76, 78
CT grading 77
Glasgow/Ranson criteria 76
management 49, 77 8, 77
physical signs 76
prevention 78
prognosis 78, 78
chronic 16, 17, 72, 78 80, 150, 156
78
causes 78 9
180
complications 80
epidemiology 79
investigation/staging 79 80, 79
physical signs 79
prevention 80
prognosis 80
treatment 80
Cullens sign 34, 48, 76
Grey Turners sign 34, 48, 76
hereditary 75
panproctocolectomy 100
paracentesis 23, 143 4, 144
paracetamol
hepatotoxicity 119
overdose 54 9, 116, 149, 155
treatment 59, 59
see also liver failure
paralytic ileus 21
parasitic infections, intestinal 39, 72,
94 5
parenteral nutrition 134 5
parvovirus 113
PEG tube 279, 29
pelvic disease 12
peptic ulcer 4, 66 8
66
complications 67
epidemiology 66
investigations/staging 66, 67
pain 47
prevention 67
prognosis 67
treatment 67
percutaneous transhepatic
cholangiography 141
cholangiocarcinoma 90, 91
peritonitis 46, 48
spontaneous bacterial 23
pernicious anaemia 69
pethidine 49
Peutz-Jeghers syndrome 103
pharyngeal pouch 7
pinworm 94
piperacillin/tazobactam 54
portal hypertension 25, 25, 86
postural hypotension 47
prednisolone 59
pregnancy, intrahepatic cholestasis 89
prochlorperazone 37
proctalgia fugax 102
protein-calorie malnutrition 133
prothrombin time 18, 19
proton pump inhibitors 70
pruritus 22
pyogenic abscess 125
R
radiation-induced oesophagitis 6
radiography
abdominal 48, 79
chest 63
radiology, gastrointestinal lumen
139 40, 140
ranitidine 58
Raynauds disease 19
rectal biopsy 96
rectal bleeding 8 9, 1013, 102
drug history 12
family history 12
management 13
medical/surgical history 12
referral letter 10
rectal ulcer 110
red cell scanning 142
reflux 3 4, 6
reflux oesophagitis 6, 60
regurgitation 6
Reiters syndrome 94
rifampicin 86
hepatotoxicity 119
right iliac fossa mass 11
rigid sigmoidoscopy 140, 1423, 142
Rockall score 41
rotavirus 92, 93
roundworm 94
Roux-en-Y biliary anastomosis 128, 129
Salmonella spp. 92, 93, 93

salt restriction 23
Schilling test 138
schistosomiasis 19
scleroderma 19
sclerosing cholangitis 879
complications 89
epidemiology 87
physical signs 88
prognosis 89
treatment 88 9
secretin-caerulein test 137
selective visceral angiography 142
selenium 131
Sengstaken-Blakemore tube 45, 46
sepsis 52
and intrahepatic cholestasis 89
prophylaxis 58
systemic signs 38
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serotonin antagonists 37, 87

serum biochemical tests 136
Shigella spp. 93, 93
short bowel syndrome 72, 98
sicca syndrome 87
sigmoid diverticulum 13
sigmoidoscopy 38
flexible 139
rigid 140, 1423, 142
Sjgrens syndrome 19
skip lesions 96
small bowel disease 715
coeliac disease 8, 15, 725, 72, 75
malabsorption 713
chronic pancreatitis/pancreatic
insufficiency 72
giardiasis 72
hypolactasia 72
post gastric surgery 723
short bowel syndrome 72
tropical sprue 72
Whipples disease 72
pain 47
small bowel function 137
small bowel infarction 108
somatostatinoma 83
special diets 135
sphincter of Oddi
dysfunction 75, 102
sphincterotomy 85
spleen 52
splenomegaly 25 6, 38, 52
causes 26
spontaneous bacterial peritonitis 23
Staphylococcus 93
statins, and liver disease 120
steatorrhoea 9, 14
and gastrinoma 69
pancreatic insufficiency 72
tropical sprue 72
see also malabsorption
steatosis 19, 20
stool colour 50 1
stool examination 9, 136, 136
stool frequency 8
stool sample 38
stool volume 8
stool weight 82
stroke, artificial feeding 279, 29
sulfamethoxazole 72
telangiectasiae 25, 70
Tenckhoff catheter 27
terminal ileoscopy 139

tetracycline, hepatotoxicity 119
thiamine replacement 46
thrombophlebitis migrans 81
tinidazole 72, 95
tissue paper skin 25
toxic megacolon 38, 98, 99
transabdominal ultrasound 140
transaminases 18
transjugular intrahepatic portosystemic
shunt 45
travel, and jaundice 51
trimethoprim 72
triolein breath test 137
Tropheryma whippelii 72
tropical sprue 72
ulcerative colitis 10, 98 101

98 9, 99
colorectal cancer risk 104
complications 100
epidemiology 99
investigations/staging 99, 99, 100
physical signs 99
prevention 100
prognosis 100
treatment 100
ulcerative enteritis 75
ultrasound
abdominal 52, 79, 81
endoanal 140
liver 142
transabdominal 140
urease breath test 138
urethritis 94
urine colour 50 1
uroseoxycholic acid 86
ursodeoxycholic acid 89
uveitis 38, 94
variceal haemorrhage 123

varices 23, 24 5
vascular ectasia (angiodysplasia) 70,
70
vasoactive intestinal peptide 10
vasopressin analogues 44
venous access 43 4
Vibrio cholerae 93
Vibrio parahaemolyticus 93
VIPoma 83
viral hepatitis see hepatitis
Virchows triad 83
visceral pain 16
visual hallucinations 56
vitamin A 130
vitamin B1 (thiamine) 130
vitamin B2 (riboflavin) 130
vitamin B6 (pyridoxine) 130
vitamin B12 (cobalamin) 130
Crohns disease 96
deficiency 723
vitamin C 130
vitamin D 130
vitamin E 130
vitamin K 130
volvulus 21
vomiting see nausea and vomiting
von Hippel-Lindau syndrome 82
waist/hip circumference ration 133

weight loss 12, 14 15, 40, 102, 148,
153
abdominal distention 212
abdominal pain 16
causes of 14
chronic diarrhoea 9
heartburn/dyspepsia 4
investigation 15
imaging 15, 15
urine and blood tests 15
jaundice 50
management 15
referral letter 14
weight-loss diets 135, 1489, 154
Weils disease 56
Wermer-Morrison syndrome 83
Wernickes encephalopathy 52, 54, 58,
118
Whipples disease 72
Wilsons disease 20, 22, 56, 120, 121, 122
Kayser-Fleischer rings 57
treatment 122
xylose excretion test 138
zinc 131
Zollinger-Ellison syndrome 6970, 83
181

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GAH_A01

Consultant Physician and Nephrologist

MBBC h DP hil FRCP

Consultant Physician and Gastroenterologist

Dr GM Hirschfield MA MB BChir PhD MRCP(UK)

Dr SC Keshav MBBCh DPhil FRCP

Honorary Clinical Lecturer in Gastroenterology

2008, 2010 Royal College of Physicians of London

List of contributors iii

1.4.3 Haematemesis and

Diseases and Treatments 60

PACES Stations and Acute

2.5.4 Intrahepatic cholestasis

2.10.3 Acute liver failure

2.11 Nutrition 129

3.3 Diagnostic and therapeutic

4.1 Self-assessment questions 147

The second edition of Medical Masterclass is produced and published by

Iron-deficiency anaemia with

This icon is used to highlight points of particular importance.

Dietary deficiency is very

This icon is used to indicate common or important drug interactions, pitfalls

RJ Atkinson, GM Hirschfield, SC Keshav and JS Leeds

GASTROENTEROLOGY AND HEPATOLOGY: SECTION 1

PACES STATIONS AND ACUTE

Letter of referral to general

Atypical cardiac pain

1. Testing for and treating Helicobacter pylori is of value in these groups.

1.1.1 Heartburn and dyspepsia

Re: Mr Ben Harrison, aged

abdomen can come from

developed a peptic ulcer, or is

History of the presenting problem

Dyspepsia pain is most frequently

and relieved by food; biliary pain

Station 2: History Taking

GASTROENTEROLOGY AND HEPATOLOGY: PACES STATIONS AND ACUTE SCENARIOS

potentially beneficial lifestyle

Dyspepsia with weight

Episodes of jaundice, dark urine

and steroids can cause peptic ulcer

Past medical and surgical history

Plan for investigation and

Other relevant history

Station 2: History Taking

Key investigations for dyspepsia

Routine blood tests

No matter how likely the

GASTROENTEROLOGY AND HEPATOLOGY: PACES STATIONS AND ACUTE SCENARIOS

in the mouth, pharynx or

Fig. 1 Normal ultrasound appearance of the liver and bile ducts.

may be performed, but this can miss

in swallowing over the last

Although the patient will

of reflux symptoms and uses

ranitidine for this. She has also