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Gastrointestinal and hepatobiliary systems
The cause of their symptoms is unclear but is likely to
be multifactorial and include acid, dysmotility, H. pylori
infection and depression. Satisfactory management is often
difficult for the patient and clinician to achieve. Lifestyle
advice is given regarding smoking, alcohol consumption,
obesity, etc. Use of culprit drugs, such as NSAIDs, should be
stopped if possible. Antisecretory therapy is used and is titrated to the lowest-cost preparation that achieves symptom
control. Those who are H. pylori-positive should undergo
eradication therapy.
HINTS AND TIPS
In irritable bowel syndrome it is important to
gain the patient’s confidence. Investigations
should be sufficient to exclude other important
diagnoses. The diagnosis should then be made
with appropriate explanation and advice, otherwise
patients may move from doctor to doctor seeking
further investigation.
Inflammatory bowel disease
HINTS AND TIPS
Extraintestinal manifestations of inflammatory
bowel disease include aphthous ulcers, pyoderma
gangrenosum, iritis, erythema nodosum, sclerosing
cholangitis, arthritis and clubbing. A helpful
mnemonic to remember these is A PIE SAC.
General overview
Ulcerative colitis and Crohn disease are collectively
termed ‘inflammatory bowel disease’ (IBD). The two conditions differ in their natural history and response to treatment, but both follow a relapsing and remitting course
(Table29.4).
The primary cause of IBD is unknown, although 10% of
patients have a first-degree relative with the disease, suggesting a combination of environmental and genetic factors. It
may result from a genetically determined, inappropriately
severe and/or prolonged inflammatory response to a dietary
or microbial product. Abnormalities of colonic epithelial cell
metabolism have also been reported in ulcerative colitis, and
there are associations with long-term use of NSAIDs and antibiotics, although the significance is uncertain. Stress tends
to exacerbate symptoms rather than cause the disease.
Table29.4 Features of Crohn disease and ulcerative
colitis
Feature Crohn disease Ulcerative colitis
Pathology Transmural
inflammation
Fissuring ulcers:
cobblestone
mucosa
Noncaseating
granulomata
Can involve
whole GI tract.
Skip lesions
Clinical Diarrhoea with
or without rectal
bleeding
Abdominal
pain and fever
prominent
Anal/perianal and
oral lesions
Narrowing causing
obstructive
symptoms
Associations Increased
incidence in
smokers
Cholelithiasis Increased primary
Extraintestinal
manifestations of
IBD (see below)
Complications Fistulas
(enteroenteral,
enterovaginal,
enterovesical,
perianal)
Strictures causing
bowel obstruction
Carcinoma
(related to colitis)
Iron-deficiency
anaemia
Abscess formation
Vitamin B12
deficiency
(terminal ileum
commonly
involved)
GI, Gastrointestinal; IBD, inflammatory bowel disease.
Only mucosa and
submucosa inflamed
Mucosal ulcers:
pseudopolyps
Crypt abscesses
Continuous
involvement proximally
from rectum to affect
variable length of
colon
Diarrhoea: often with
blood and mucus
Abdominal pain less
prominent. Fever may
be present
Decreased incidence
in smokers
biliary cirrhosis,
sclerosing cholangitis,
chronic active hepatitis
Other extraintestinal
manifestations of IBD
are less common than
in Crohn disease
No fistulas
Toxic megacolon (in
acute colitis)
Carcinoma
Iron-deficiency
anaemia
238
Lower gastrointestinal tract
2929
There may be a history of atopy, autoimmune disease
and the presence of circulating immune complexes and
antibodies to colonocytes and neutrophils in ulcerative
colitis. The presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) indicates ulcerative colitis,
whereas the presence of anti-saccharomyces cerevisiae
antibody (ASCA) indicates Crohn disease.
Ulcerative colitis
This is an idiopathic chronic relapsing inflammatory disease
that always involves the rectum and extends proximally in
continuity to affect a variable length of the colon. Although
the small bowel is spared, there may be some ‘backwash ileitis’ secondary to ileocaecal valve incompetence. It is commoner in the Western world, with an incidence of about
10–20 in 100,000 per year. It is most commonly diagnosed
at the age of 15–25years, with a smaller peak at 55–65years.
There is no major sex difference. Patients with ulcerative
colitis have no change in the overall standardized mortality ratio compared with the general population, although
subgroups, such as those with extensive acute colitis, have
higher mortality. The lifetime risk of developing colorectal cancer in people with ulcerative colitis is increased
about twofold. The cumulative incidence is around 18% at
30years.
Clinical features—The severity of diarrhoea and systemic upset depends on the extent of the disease and depth
of mucosal ulceration.
Active subtotal or total ulcerative colitis causes frequent bloody diarrhoea, often with fever, malaise, anorexia,
weight loss, abdominal pain, tenesmus, anaemia and tachycardia. With proctitis, the characteristic symptoms are
rectal bleeding and mucus discharge, but the stool is well
formed and general health is maintained. The patient is
usually symptom-free between relapses.
Patients may present with complications. These can be
local or extraintestinal. Local complications include:
• toxic megacolon;
• perforation;
• massive haemorrhage (rare).
Extraintestinal complications include:
• erythema nodosum, pyoderma gangrenosum, vasculitis
(skin);
• anterior uveitis, episcleritis, conjunctivitis (eyes);
• large joint arthropathy, sacroiliitis, ankylosing
spondylitis (joints);
• pericholangitis, sclerosing cholangitis, cirrhosis,
autoimmune hepatitis, cholangiocarcinoma (liver);
• arterial and venous thrombosis (vasculature).
Investigations—Sigmoidoscopy and rectal biopsy
show inflamed mucosa. If the disease is active, there may
be pus and blood, visible ulceration and contact bleeding.
Colonoscopy will show the extent of the disease. Ulcers and
pseudopolyps may be seen. Other types of colitis should be
excluded, and stool microscopy and culture are needed to
exclude infection. Blood tests may show anaemia and raised
levels of inflammatory markers (white cell count (WCC),
ESR, CRP).
Histology shows inflammatory cells infiltrating the lamina propria with crypt abscesses. There is little involvement
of the muscularis mucosae, and there is a reduction in the
number of goblet cells.
In the patient with acute colitis, abdominal X-ray
should be performed to look for colonic dilatation and
evidence of mucosal oedema. An erect CXR is often performed in the acute setting to exclude perforation (60%–
80% sensitive).
Management—A multidisciplinary approach is preferred with gastroenterologists, nursing staff and stoma
therapists in collaboration with primary healthcare teams.
Liaison with the colorectal surgical team at an early point is
encouraged. Specific nutritional, haematinic and electrolyte
deficiencies may require correction. Use of NSAIDs should
be avoided, and opiates should be used only on specialist
advice.
Patient mortality with acute colitis increases significantly in the case of perforation. In order to minimalize the
risk of complications, management is directed at stratifying
patients in terms of severity, treating them accordingly to
induce remission and carefully selecting those requiring
emergency colectomy (Table29.5).
Drug therapy—The mainstay of therapy in the acute
phase is steroids (with bone protection) with the addition of
a 5-aminosalicylic acid such as mesalazine. Patients should
be weaned off steroids after the acute episode. Steroids
are not used as a maintenance agent. Tacrolimus can be
added in cases of inadequate response to steroid treatment.
Ciclosporin is used as a salvage therapy in persistent disease; however, it is associated with high toxicity levels and
severe side effects.
Mesalazine is used to maintain remission in mild to
moderate disease. Thiopurines such as azathioprine or mercaptopurine are used if aminosalicylates alone are not effective or if the patient has two or more exacerbations per year
Table29.5 Truelove and Witts classification for severity
of ulcerative colitis
Activity Mild Moderate Severe
No. of bloody
stools/day
Temperature
(°C)
Heart rate
(bpm)
Hb (g/dL) >11 10.5–11 <10.5
ESR (mm/h) <20 20–30 >30
ESR, Erythrocyte sedimentation rate; Hb, haemoglobin.
<4 4–6 >6
Normal 37–37.8 >37.8
Normal Intermediate >90
239
Gastrointestinal and hepatobiliary systems
requiring steroid treatment or after a single severe episode.
It may take up to 4months to effect a noticeable clinical benefit with azathioprine. Serious adverse effects include bone
marrow suppression (resulting in, e.g., neutropenia) and
cholestatic jaundice, necessitating blood checks fortnightly
for 1month, then monthly for 2months, then 2–3monthly.
Thiopurine methyltransferase (TPMT) activity should be
measured before commencement of treatment with thiopurines. TPMT is an enzyme that metabolizes these drugs, and
its activity differs greatly amongst the population.
Anti-TNF-α monoclonal antibodies such as infliximab,
adalimumab and golimumab are effective agents used
in moderate to severe disease refractory to conventional
therapy.
If patients are systemically unwell (tachycardia, hypotension, fever, dehydration, tender abdomen) and have more
than eight bowel movements per day, they should be admitted to hospital:
• Nil by mouth, intravenous fluids, close monitoring of
observations, stool record.
• Intravenously administered hydrocortisone in divided
doses throughout the day.
• Antibiotics for any accompanying infection (usually
gram-negative).
• If improved at 5days, commence oral steroid therapy.
• If failing to respond, some advocate the careful use of
ciclosporin or infliximab to induce remission.
• Indications for emergency colectomy: continuing
deterioration despite medical therapy; toxic dilatation
of the colon; perforation.
Surgical intervention—Surgery is curative for colonic disease, although not for extraintestinal complications. Options
include proctocolectomy with ileoanal pouch, permanent
ileostomy or rarely subtotal colectomy with ileorectal anastomosis. Surgery may be considered electively for chronic
intractable ulcerative colitis, colonic carcinoma, persistent
mucosal dysplasia or growth retardation in children. The
emergency indications are summarized in the last point of the
preceding list. Many cases can now be done laparoscopically.
Prognosis and monitoring—Approximately 70% of untreated patients relapse annually, and up to 30% eventually
require surgery, although the overall mortality is close to
that of the general population. The main risks to life are
severe attacks of the disease and colonic cancer. NICE recommends that patients with the disease extending beyond
the rectum should be offered colonoscopic surveillance at
10years. Additionally, the person-specific risk of neoplastic
metaplasia should be calculated. Low-risk patients should
be offered colonoscopy at 5years, intermediate-risk patients
should be offered colonoscopy at 3years and high-risk patients should be offered colonoscopy at 1year.
Crohn disease
Crohn disease can affect any part of the GI tract from
the mouth to the anus. The involvement is not confluent
(‘skip lesions’) (Table 29.4). It most frequently affects the
ileocaecum or colon or ileum alone. The prevalence is
approximately 50–100 in 100,000. Patients with Crohn disease have increased overall mortality compared with the
general population. Peak onset is at the age of 15–30years.
The risk of colorectal cancer is comparable to that of people
with ulcerative colitis.
Clinical presentation—The patient has diarrhoea and
abdominal pain. There may be a fever, anaemia and weight
loss. Associated complications are as with ulcerative colitis,
and also clubbing, renal stones, amyloidosis and granulomata around body organs.
The presentation depends on the site of the disease and
on the tendency to perforate or fistulate rather than to fibrose and stricture, which is probably determined by genetic factors. Terminal ileal disease presents with right iliac
fossa pain, often with an associated mass. This may present
acutely, mimicking appendicitis, or chronically, mimicking
IBS. Strictures lead to GI obstruction.
Colonic Crohn disease is distinguishable from ulcerative
colitis by the presence of skip lesions (multiple lesions with
normal bowel in between), rectal sparing, perianal skin tags
or fistulas with or without granulomata on biopsy, although
the distinction is unclear in up to 10% of patients.
Investigations—Diagnosis is made by endoscopy and
biopsy of lesions. Histology demonstrates transmural inflammation with an inflammatory cell infiltrate and noncaseating granulomata (in 30%). CT (or MRI) of the small and
large bowel shows skip lesions, a coarse cobblestone appearance of the mucosa and, later, fibrosis producing narrowing
of the intestine with proximal dilatation. MRI is particularly
useful for evaluation of fistulas and abscesses, and should be
used as the first-line imaging investigation in pelvic disease.
Blood tests may show anaemia (potentially due to terminal
ileum involvement and a resulting inability to absorb vitamin B12). Serum CRP level can be elevated in active disease
and is a useful marker of response to treatment. ESR has a
similar role. Stool samples should be sent for microscopy
and culture to exclude infection. Faecal calprotectin level
reflects the degree of intestinal inflammation.
Management—In most cases of active Crohn disease,
there are three therapeutic alternatives: drugs, diet and surgery. These options should be discussed with the patient.
Drug and diet therapy—Some patients manage with
symptomatic therapy alone (e.g., loperamide or codeine
phosphate) provided there is no evidence of obstruction
or active colitis. Cholestyramine (an ion-exchange resin) is
useful for diarrhoea due to terminal ileal disease or previous resection as it prevents conjugated bile acids from entering the colon. However, it should not be given at the same
time as other medications as it impairs their absorption.
Haematinics may require replacement, although anaemia
often abates as disease activity falls.
Acute attacks are often treated with corticosteroids, but
as with ulcerative colitis, these have no effect on reducing the rate of relapse. Their inappropriate use must be
avoided because of their side-effect profile. Budesonide is
240
Hepatobiliary system
2929
a corticosteroid analogue with rapid hepatic conversion,
and therefore reduced systemic side effects. It is less effective and should be used only if conventional steroids
are contraindicated. Azathioprine therapy is often started
during the acute attack and used as maintenance treatment.
Methotrexate should be considered if thiopurines cannot
be used. Infliximab and adalimumab are recommended for
use in severe cases resistant to other drugs. Vedolizumab
(anti-α4β7 integrin monoclonal antibody) should be used
only when anti-TNF-α agents fail.
Patients with colonic involvement may benefit from a
5-aminosalicylic acid compound. Antibiotics also have a
role. Metronidazole is effective in colonic and perianal disease and in prevention of recurrence following bowel resection. If it is used for longer than 3months, there is a risk of
peripheral neuropathy. Other antibiotics are also used.
Elemental or polymeric diets are useful for inducing remission in small bowel disease but are expensive and unpalatable, so adherence is often poor.
Some patients can be maintained in remission without
drug therapy—the importance to patients with Crohn disease of stopping smoking must be emphasized.
Surgical intervention—Surgery should be avoided if possible. It is indicated for:
• patients in whom the disease is limited to distal portion
of the ileum;
• failure of medical therapy with acute or chronic illness
causing ill health;
• complications: abscess, obstruction, perforation, toxic
dilatation, fistulas not responding to conservative
treatment with antibiotics;
• failure to grow (children).
Small bowel strictures can be widened (stricturoplasty),
whereas those elsewhere need resection. Postoperative fistulas used to be a common complication but are now rare,
partly because of the use of perioperative antibiotics, particularly metronidazole. After surgical resection, approximately half of patients remain symptom-free for 5years and
half require further surgery within 10years.
Prognosis—Around 10%–20% of patients remain
asymptomatic for 20years after the first or second episode
of symptomatic disease. Around 50% of patients need at
least one surgical resection within their lifetime, particularly if the small and large bowel are involved. The principles for colorectal cancer screening are the same as for
ulcerative colitis.
HEPATOBILIARY SYSTEM
Gallbladder disorders
Gallstones and biliary colic
Approximately 15% of the UK population have gallstones,
but 80% are asymptomatic. Risk factors include increasing
age, obesity and weight-cycling, smoking, diabetes mellitus,
female sex and oral contraceptive or hormone replacement
therapy use. Gallstone-related disease is a common diagnosis in those admitted to hospital with abdominal pain.
Bile contains cholesterol, bile pigments and phospholipids; the relative concentrations of these determine the kind
of stone that is formed. Pigment stones (10%) are small and
radiolucent, and they are occasionally associated with haemolytic anaemia due to increased formation of bile pigment
from haemoglobin.
Cholesterol stones (10%) are large, often solitary, and
radiolucent. Mixed stones (80%) contain calcium salts,
pigment and cholesterol. Only 15%–20% of gallstones are
radio-opaque, whereas approximately 90% of renal stones
are radio-opaque.
Clinical features
Approximately 80% of gallstones are asymptomatic. The
commonest complications are biliary colic, acute cholecystitis and obstructive jaundice. Other presentations are
uncommon or rare, and include cholangitis (infection of
the bile ducts causing right upper quadrant pain, jaundice
and fever with rigors—Charcot triad), chronic cholecystitis
(chronic inflammation secondary to repeated episodes or
acute cholecystitis), pancreatitis, empyema and gallstone ileus, where the gallstone perforates the gallbladder, ulcerates
into the duodenum and passes on to obstruct the terminal
ileum.
Biliary colic is the most common presentation, classically with pain in the upper abdomen or right upper quadrant. Typically, the pain lasts for more than 30 minutes, but
less than 8 hours, is colicky in nature, is often severe and
may be associated with nausea and vomiting, but not is associated with fever or abdominal tenderness.
Investigations
• LFTs may show a cholestatic picture if a gallstone
is impacted in the common bile duct (CBD) (see
Chapter14).
• Ultrasound examination is useful in diagnosing
gallstones, cholecystitis and stones in the bile duct.
• Magnetic resonance cholangiopancreatography
(MRCP) should be used if ultrasound examination
has not demonstrated CBD stones but the bile duct is
dilated and/or LFT results are abnormal. Endoscopic
ultrasound examination may be useful if MRI is not
possible.
• Haemolysis screen: if pigment stones are suspected or
found operatively.
Management
Asymptomatic gallstones do not need treatment.
Asymptomatic CBD stones should be treated in the same
way as symptomatic CBD stones as stones in the biliary tree
can cause obstructive jaundice, cholangitis and pancreatitis.
In symptomatic gallstones, treatment is often by
cholecystectomy (ideally laparoscopic), which may be
241
Gastrointestinal and hepatobiliary systems
performed immediately or after a delay. Care should be
taken in patients with nonspecific upper abdominal symptoms to confirm that gallstones found on investigation are
the true cause of symptoms. In biliary colic, cholecystectomy is usually reserved for recurrent episodes.
Patients with symptomatic CBD stones require resuscitation, and intravenous antibiotics for infection in cholangitis. In the presence of duct dilatation or CBD stones,
endoscopic retrograde cholangiopancreatography (ERCP)
with sphincterotomy is usually performed, allowing the removal of stones. A stent may be placed if stones cannot be
retrieved.
Other options include an “on-table” cholangiogram
during open or laparoscopic surgery to assess the presence
of stones in the CBD.
Acute cholecystitis
Clinical features
Acute cholecystitis is most common in overweight,
middle-aged women but may occur at any age. Risk factors include gallstones or biliary sludge (95% of patients),
female sex, increasing age, obesity or rapid weight loss and
pregnancy. It typically follows the impaction of a stone in
the cystic duct or Hartmann pouch (at the junction of the
gallbladder neck and the cystic duct). If the stone moves to
the CBD, jaundice may occur. The signs and symptoms are
like those of biliary colic, but in addition there is fever and
tenderness in the epigastrium or right upper quadrant, and
there may be rigors, vomiting, local peritonism or a gallbladder mass.
Murphy sign may be positive; this is increased pain on
inspiration when the tips of the fingers are placed under
the costal margin in the right upper quadrant, due to an inflamed gallbladder impinging on the examiner’s fingers. The
test is only considered positive when the same manoeuvre
performed in the left upper quadrant does not elicit pain.
CLINICAL NOTES
DIFFERENTIAL DIAGNOSIS OF ACUTE
CHOLECYSTITIS
The differential diagnosis of acute cholecystitis
includes:
• biliary colic;
• cholangitis;
• appendicitis in an anatomical variant of an
appendix located higher than normal within the
abdominal cavity;
• perforated peptic ulcer;
• pancreatitis;
• right basal pneumonia;
• myocardial infarction.
Investigations
WCC is elevated and the levels of inflammatory markers
are raised (unlike in biliary colic). A CXR, an ECG and serum amylase and troponin measurements should be taken
to help exclude differential diagnoses. Ultrasound scan will
commonly show a thickened gallbladder wall and stones
with or without CBD dilatation.
Management
Management is usually conservative initially, unless complications ensue (e.g., perforation of the gallbladder). The
patient should be asked to fast and should be given intravenous fluids, offered effective analgesia and prescribed
antibiotics (e.g., amoxicillin and metronidazole intravenously) followed by oral co-amoxiclav; gentamicin should
also be given intravenously if the patient is showing signs
of sepsis. Laparoscopic cholecystectomy is offered, often
within 1 week of diagnosis, or the inflammation is allowed to settle and a cholecystectomy is performed after
2–3months.
Recurrent cholecystitis
Recurrent episodes of cholecystitis are usually associated
with gallstones, and can lead to intermittent colic and
chronic inflammation. It may be asymptomatic, present as a
more severe case of acute cholecystitis or present as abdominal discomfort, bloating, nausea, flatulence and intolerance
of fats.
Biliary tract cancer
Cholangiocarcinoma
This is a carcinoma arising in any part of the biliary tree,
but most cholangiocarcinomas are extrahepatic. More
than 90% of cholangiocarcinomas are ductal adenocarcinomas, and the remainder are squamous cell tumours.
Patients usually present with obstructive jaundice or
systemic symptoms. Risk factors include increasing age,
primary sclerosing cholangitis and chronic intraductal
gallstones.
Surgery is the only curative option, but less than one-third
are resectable at diagnosis. Prognosis is poor (10%–40% at
5years, average survival of 10–12months from diagnosis).
ERCP and stenting is used for palliation of jaundice, and
chemotherapy is used for locally advanced or metastatic unresectable cholangiocarcinoma.
Gallbladder cancer
This is a rare cancer, and 85% of cases are adenocarcinoma.
It is more common in women, smokers and those with a
family history; the risk increases with age, particularly after 70years. The tumour typically arises in the fundus, and
is often discovered incidentally during cholecystectomy.
Curative treatment requires surgery, the extent depending
on the staging. Prognosis is very poor (10% 5-year survival
rate) as most cases are diagnosed late.
242
Hepatobiliary system
2929
Cancer of the ampulla of Vater
This tumour arises in the distal 1 cm of the CBD. Patients
present with anorexia, nausea, vomiting, jaundice, pruritus or weight loss. Patients may present relatively early
(compared with pancreatic cancer) because of the tumour
location causing biliary obstruction. A curative Whipple
procedure is preferred for early cancer (proximal pancreaticoduodenectomy with antrectomy). This is best done at a
centre with specific expertise and experience in the procedure. Stenting may be used for palliation. The overall survival rate at 5years is 20%.
Pancreatic disorders
Acute pancreatitis
Acute pancreatitis is an acute inflammatory condition of
the pancreas causing local and systemic reactions. The incidence is approximately 3 cases per 10,000 population in
the United Kingdom. More than 80% of cases are secondary
to either gallstones or alcohol consumption. Other causes
include ERCP, surgery or trauma, toxins and drugs, hyperglyceridaemia, scorpion venom and autoimmune disease.
Alcohol history must be carefully taken and evidence of
gallstone disease should be sought.
HINTS AND TIPS
The causes of pancreatitis can be recalled from the
mnemonic GET SMASHED:
• gallstones;
• ethanol;
• trauma;
• steroids;
• mumps;
• autoimmune diseases;
• scorpion stings;
• hypertriglyceridaemia;
• ERCP;
• drugs (e.g., azathioprine or thiazide diuretics).
Clinical features
Pancreatitis causes acute-onset severe epigastric abdominal
pain radiating to the back. Nausea and vomiting are common. Patients are commonly dehydrated and quite unwell
when they present. Jaundice may be present. On examination, there may be abdominal tenderness with guarding and
rebound tenderness. Tachycardia, fever, hypotension and
sweating may be present. Bruising around the umbilicus
(Cullen sign) or in the flanks (Grey Turner sign) is a classic
signs in pancreatitis.
Pancreatitis can lead to serious complications such as
acute respiratory distress syndrome (ARDS), sepsis or disseminated intravascular coagulation.
Investigations
Bedside:
• Serum amylase: level often markedly raised (more than
three times the normal level). However, a normal amylase
level does not exclude pancreatitis (this is especially true in
acute attacks on a background of previous episodes when
pancreatic tissue mass may be reduced). Amylase level
is also raised with cholecystitis, perforated viscus (e.g., a
duodenal ulcer) and even in ectopic pregnancy, but usually
to a lesser extent. Serum lipase is more sensitive and
specific, but the test is not always available.
• Serum calcium, magnesium and phosphate: levels may
be low and replacement may be needed.
• FBC: WCC is usually raised.
• U&Es: raised urea level is an indicator of severity.
• LFTs: may show an obstructive picture.
• Fasting serum glucose: level often raised in pancreatitis.
• Arterial blood gases: metabolic acidosis. Po2 is also
measured, and this is important in prognosis.
• ECG: to exclude myocardial infarction.
Imaging:
• Abdominal X-ray: gallstones, pancreatic calcification
indicating previous inflammation, an absent psoas
shadow due to retroperitoneal fluid and a distended
loop of jejunum (‘sentinel loop’).
• Erect CXR: widened mediastinum in aortic dissection;
gas under the diaphragm in perforated peptic ulcer. In
severe cases, pleural effusion or ARDS.
• Abdominal ultrasound or endoscopic ultrasound
examination: allows visualization of gallstones and duct
dilatation.
• Abdominal CT scan: within 48 hours for severe
pancreatitis, within 7days for those failing to improve
(suspected pancreatic necrosis), delayed for detection
of pseudocyst.
Multiple prognostic scoring systems have been validated to
determine severity, guide management and predict mortality; the Modified Glasgow Acute Pancreatitis Severity Score
(Imrie score) is the most commonly used (Table 29.6).
An alternative prognostic scoring system is the Acute
Physiology and Chronic Health Evaluation II (APACHE-II)
score, which also considers chronic health problems. Any
patient with severe pancreatitis should be discussed with
staff from the intensive care unit/high-dependency unit as
multiple organ dysfunction syndrome can evolve quickly.
Mortality is 5% in mild disease and around 30% in severe
disease. Recurrence is uncommon in patients who recover.
Death may be from shock, renal failure, sepsis or respiratory failure. Other complications include hypocalcaemia
due to the formation of calcium soaps, transient hyperglycaemia, pancreatic abscess requiring drainage and pseudocyst (fluid in the lesser sac presenting as a palpable mass),
persistently raised serum amylase levels or LFT values and
fever. Patients should be investigated to exclude gallstones,
and alcohol should be avoided.
243
Gastrointestinal and hepatobiliary systems
Table29.6 Modified Glasgow severity scoring in acute
pancreatitis
Mnemonic
Po
2
Age Age >55years
Neutrophils WCC >15×106/L
Calcium Corrected calcium concentration
Renal Urea concentration >16 mmol/L
Enzymes Enzyme concentrations: LDH >600 U/L;
Albumin Albumin concentration <32 g/L
Sugar Fasting glucose concentration >10 mmol/L
Each element scores 1 point: 0 or 1, mild pancreatitis;
2, moderate pancreatitis; 3 or more, severe pancreatitis.
AST, Aspartate aminotransferase LDH, lactate dehydrogenase;
Po2, partial pressure of arterial oxygen; WCC, white cell count.
Arterial Po2 <8 kPa
<2.0 mmol/L
AST >125 mmol/L
Management
Patients with pancreatitis are usually managed conservatively. Aggressive rehydration, analgesia and electrolyte
replacement are important. Careful fluid and electrolyte
balance monitoring should be emphasized. In patients
who are nil by mouth or vomiting severely a nasogastric
tube should be inserted. Enteral feeding should be attempted in all cases of severe acute pancreatitis. Treatment
with antibiotics is commenced if an infective cause is suspected or there is evidence of pancreatic necrosis. Daily
FBC and U&E, calcium and glucose measurements should
be performed. Surgery should be considered if haemorrhagic necrosis of the pancreas is suspected or diagnosed
following imaging.
Chronic pancreatitis
The main cause of chronic pancreatitis is alcohol misuse.
Other causes include cystic fibrosis and haemochromatosis. The patient is generally ill with weight loss and has recurrent abdominal pain radiating to the back. Steatorrhoea
secondary to malabsorption from pancreatic insufficiency
may occur. Diabetes may occur because of involvement of
pancreatic islet beta cells, and there may be intermittent or
persistent obstructive jaundice.
Investigations
These are as for those for acute pancreatitis, although serum
amylase level is not helpful in the diagnosis as it is usually
normal or only slightly raised. In addition, the following investigations should be performed:
• plasma glucose: level raised in diabetes;
• CT scan: to investigate pancreatic atrophy, calcification
and dilated ducts;
• MRCP or endoscopic ultrasound examination.
Management
Alcohol should be avoided. A low-fat diet is advised because
of malabsorption. Fat-soluble vitamins, calcium and pancreatic enzymes (e.g., Creon) are given. Complications such
as diabetes should be managed. ERCP may be useful for
strictures. For recurrent attacks causing unremitting pain,
pancreatectomy should be considered, although this procedure has high mortality.
Pancreatic cancer
Pancreatic cancer is the 11th most common cancer in the
United Kingdom. Risk factors include smoking, poor nutrition, chronic pancreatitis and familial cancer syndromes (e.g.,
BRCA1 and BRCA2 mutations). The clear majority of pancreatic tumours are adenocarcinomas. Approximately threequarters occur in the head, the rest occurring in the body or tail
of the pancreas. Secondary diabetes is uncommon. Pancreatitis
may occur because of obstruction of the pancreatic duct.
Clinical features
General features of malignancy include anorexia, weight loss
and lethargy. Local features include dyspepsia or epigastric
pain radiating to the back and obstructive jaundice with an
enlarged palpable gallbladder (Courvoisier sign). There may
be hepatomegaly from biliary obstruction or metastases.
Thrombophlebitis migrans is a paraneoplastic feature in 10%
of patients. Fever may occur. Pancreatic cancer should be suspected in any patient presenting with painless jaundice.
Investigations
FBC is required to test for anaemia and LFTs should be performed and, if a diagnosis of pancreatic cancer is suspected, the
tumour marker cancer antigen 19-9 (CA19-9) should also be
measured. Ultrasound examination may identify a mass and
dilated bile ducts. CT scan is used to define resectability and
tumour staging. MRCP and endoscopic ultrasound examination can provide valuable information regarding tumour characteristics and local involvement. ERCP allows biopsies to be
taken; stents can be inserted for symptomatic control.
Management
Surgical resection is the only curative treatment, but most patients (85%–90%) present late in the disease after local invasion and spread have occurred (e.g., to portal vessels), making
surgical intervention unsuitable. If the tumour is resectable,
a Whipple procedure is the most commonly performed operation. Adjuvant chemotherapy is recommended for patients postoperatively. Management in unresectable disease is
aimed at symptomatic control. Palliative chemotherapy with
gemcitabine may be given. Despite interventions, prognosis
is poor and the 5-year survival rate is less than 3%.
Liver disorders
Chronic liver disease
Chronic liver disease can be a result of many underlying disorders, several which are discussed in this chapter.
244
Hepatobiliary system
2929
Clinical features include leuconychia, clubbing, Dupuytren
contracture, bruising, gynaecomastia, spider naevi and caput medusa. Liver size is not a reliable sign as livers which
have reached end-stage cirrhosis are often not palpable.
Progression happens over years, but patients may present
acutely with decompensated liver failure, the symptoms of
which are variceal bleeding, ascites, encephalopathy, coagulopathy and hepatorenal syndrome. The principal problems
in severe chronic liver disease are due to the degree of hepatocellular failure (causing hypoglycaemia, failure of synthesis of clotting factors and hypoalbuminaemia) and the
complications of portal hypertension.
Established chronic liver disease
Chronic liver disease is the result of cycles of destruction
and regeneration of liver parenchyma resulting in scarring by means of fibrosis eventually causing cirrhosis.
Often patients may have no or few symptoms, but the degree of hepatocyte destruction reduces hepatic reserve and
minimal events may precipitate hepatic decompensation
(Table29.7), the features of which are discussed next.
Varices—Oesophageal varices result from portal hypertension: a portal–systemic shunt between the left gastric
vein (portal) and lower oesophageal veins (systemic). The
increased pressure in these varices makes them prone to
rupture and consequently bleeding. The management of
variceal bleeding was discussed previously in this chapter.
Ascites—Ascites is the presence of free fluid within the
peritoneal cavity. Factors leading to the formation of ascites include salt and water retention because of cirrhosis,
hypoalbuminaemia resulting in decreased plasma colloid
pressure, portal hypertension and increased hepatic lymph
production.
Clinically, there may be abdominal distension, shifting
dullness and a fluid thrill, if the ascites is tense. Associated
features include hernias, divarication of the recti, abdominal wall venous distension, ankle oedema and distension of
the neck veins.
Investigations include diagnostic paracentesis (ascitic
tap). The ascites is clear and yellow unless it is infected,
when it appears turbid. If the tap is nontraumatic, blood
signifies intraabdominal malignancy. The protein content
is usually less than 15 g/L. Higher values indicate infection,
hepatic venous obstruction or malignancy. Fluid should be
sent for cytology, microscopy and culture.
The patient should be prescribed bed rest with restricted
salt and fluid intake. The first-choice diuretic is spironolactone. This can cause painful gynaecomastia in men, and
other diuretics can be used instead. If there is a poor response to spironolactone, furosemide may be added. Fluid
balance, weight and U&E levels should be monitored daily.
Ascites can also be treated with therapeutic paracentesis
and albumin infusion.
Overdiuresis may result in dehydration, uraemia and
hyponatraemia and may precipitate hepatic encephalopathy, oliguria and hepatorenal syndrome. Transjugular intrahepatic portosystemic shunt (described previously in this
chapter) is an alternative in patients requiring ascitic taps
frequently.
Hepatic encephalopathy—Hepatic encephalopathy can
either be reversible and episodic or lead to coma and death
(Table 29.8). Liver failure results in diminished hepatic
metabolism of substances derived from the gut, which can
cause neurotoxicity. Clinical features include impaired conscious level, personality disturbances, inversion of the normal sleep pattern, slurred speech, constructional apraxia,
flapping tremor (asterixis), hepatic fetor, brisk tendon reflexes, increased muscle tone and rigidity and hyperventilation in deep coma.
Initial treatment aims to correct or remove the precipitating causes. These may include electrolyte abnormalities,
sepsis, hypovolaemia, hypoxia, bleeding and constipation.
Use of diuretics, sedatives and opiates should be stopped,
and intracranial disease should be excluded, especially in
patients with alcoholism. CT scanning of the brain may be
appropriate to exclude subdural haematomas.
Measures should then be instituted to remove nitrogenous material and bacteria from the bowel. High doses
of lactulose should be used. Antibiotics such as neomycin
can be helpful in reducing gut ammonia-producing bacterial load.
Hepatorenal syndrome—Hepatorenal syndrome is
discussed in Chapter30.
Table29.7 Factors that can precipitate hepatic
decompensation
Constipation
Vomiting and diarrhoea
Gastrointestinal bleeding
Intercurrent infection
Alcohol
Morphine
Surgery
Electrolyte imbalance
Table29.8 Grading of conscious level in hepatic
encephalopathy
Grade Features
1 Confusion, altered
behaviour, psychometric
abnormalities
2 Drowsy, altered behaviour
3 Stupor, obeys single
commands, very confused
4 Coma responding to painful
stimuli
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Gastrointestinal and hepatobiliary systems
Hepatitis
Acute hepatitis
Acute hepatitis is inflammation of a previously healthy
liver lasting less than 6 months. It has multiple causes
(Table 29.9). Treatment and prognosis are dependent on
the underlying cause (see later). However, certain comorbidities will affect overall recovery and disease progression.
These include chronic infection with, for example, HIV or
hepatitis C virus (HCV), long-term alcohol abuse, necessary drug therapy (e.g., methyldopa) or genetic disorders
(e.g., haemochromatosis). Fulminant hepatic failure is a
syndrome that is due to overwhelming hepatocyte necrosis,
leading to severe impairment of liver function.
Acute viral hepatitis
Hepatitis A
Epidemiology—Hepatitis A virus (HAV) is a member
of the picornavirus family. It is an RNA virus. Transmission
is by the faecal–oral route. The incubation period ranges
from 2 to 6weeks. Fever, fatigue, abnormal liver function
and jaundice occur in adults. Clinical disease is uncommon
in infants and young children, and the infection may go
unnoticed.
Serology—At the onset of symptoms, immunoglobulin
M (IgM) anti-HAV antibody is present in serum. High titres
persist for 3–12months, so a positive test in a patient with
acute hepatitis indicates recent acute infection. Previous infection, and therefore immunity, can be illustrated by the
presence of IgG anti-HAV without IgM anti-HAV. IgG is
detectable lifelong.
Prognosis—The disease is usually self-limiting and
treatment is symptomatic. Relapses and cholestatic jaundice may occur but hepatitis A does not progress to chronic
hepatitis.
Prevention and control—Prophylaxis can be obtained
by immune serum immunoglobulin or active immunization. The latter induces higher levels of anti-HAV.
Hepatitis B
Epidemiology—Hepatitis B virus (HBV) is a DNA virus. The complete infectious virion (Dane particle) consists
of the following:
Table29.9 Causes of acute hepatitis
Cause Example
Infection Hepatitis A virus, hepatitis B
virus, hepatitis C virus, EBV,
CMV
Drugs Paracetamol, β-lactams
Toxins Alcohol, carbon tetrachloride
Autoimmune Autoimmune hepatitis, SLE
Metabolic disease Wilson disease
Ischaemia Portal vein thrombosis (70%
of oxygen is delivered through
portal vein)
• Hepatitis B surface antigen (HBsAg): the outer
lipoprotein ‘surface’ envelope.
• Hepatitis B core antigen (HBcAg): the internal core,
which surrounds the viral genome of DNA.
• Hepatitis B e antigen (HBeAg): a subunit of HBcAg;
it can be detected in serum and is a useful marker of
circulating virions and infectivity.
Transmission is parenteral through infected body fluids or
blood, and the incubation period is 40–160days. In developed countries hepatitis B usually occurs sporadically.
Those at risk are intravenous drug users, healthcare
workers, people with haemophilia or patients on haemodialysis, babies of HBsAg-positive mothers, people who have
moved from areas where it is endemic, those engaging in
risky sexual behaviours and individuals resident in longterm care facilities. Infection is characteristically anicteric
(not accompanied by jaundice), asymptomatic and chronic.
Serology—Following exposure to HBV, HBsAg can be
detected throughout the prodromal phase and is not usually cleared from the serum until convalescence. Other
early markers include anti-HBc and HBeAg. A positive IgM
anti-HBc test typically distinguishes acute hepatitis B from
chronic hepatitis B. The presence of HBeAg implies high
infectivity.
The loss of HBeAg is a good prognostic sign, indicating
that the patient will clear HBsAg and is unlikely to develop
chronic infection. The disappearance of HBeAg is usually
followed by the appearance of serum anti-HBe. Anti-HBs is
the last marker to appear in serum (Fig.29.1).
Prognosis—Acute infection rarely leads to fulminant
hepatic failure. Treatment is normally supportive, and
patients are advised to avoid alcohol. Between 8% and
20% of patients will develop cirrhosis without antiviral
treatment within 5years of infection. Patients with established cirrhosis should undergo hepatocellular carcinoma
surveillance.
Prevention and control—Infection can be prevented by
active immunization. Management includes peginterferon
alfa-2a. Treatment is continued for 48 weeks in patients
with compensated liver disease. Antiviral medication is
not routinely offered to infected, otherwise well individuals
with an HBV DNA count lower than 2000 IU/mL.
Hepatitis C
Epidemiology—HCV is an RNA virus, and can be di- vided into many major types and subtypes. Hepatitis C is a slowly progressive liver disease with a varied clinical picture, ranging from asymptomatic to rapidly progressing cirrhosis with hepatocellular carcinoma. Transmission is parenteral through blood and bodily fluids. The incubation period is between 6 and 9weeks.
Serology—Anti-HCV develops 1–3months after the
onset of clinical illness in most cases; however, it may
take up to 9months in some individuals. Identification of
the viral RNA in serum is possible by PCR, and signifies
ongoing infection. HCV antigens cannot be detected in
serum.
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Hepatobiliary system
HBeAg+
Time (years)
ULN
HBeAg–ve/anti-HB+
2929
Immune
tolerance
phase
HBV-DNAALT
Fig.29.1 Natural history of chronic hepatitis B virus (HBV) infection. ALT , Alanine aminotransferase; HBeAg, hepatitis B e
antigen; ULN, upper limit of normal
Prognosis—The acute disease is often asymptomatic,
and leads to chronic infection in around 80% of patients.
In about 20% of patients, cirrhosis may develop insidiously within 10years, and patients may develop a clinical picture resembling autoimmune hepatitis. Systemic
manifestations include cryoglobulinaemia, porphyria
cutanea tarda and membranous glomerulonephritis.
Untreated HIV infection accelerates the progression of
HCV-induced cirrhosis. Success of antiviral treatment
differs with the viral genotype. NICE recommends a
combination therapy of peginterferon alfa and ribavirin.
Genotypes 2 and 3 of HCV tend to respond to this treatment better than genotype 1.
Prevention and control—Unlike for HAV and HBV
there is no effective vaccination. Prevention of transmission
is therefore the mainstay of infection control. Blood bank
screening for anti-HCV and genetically engineered factor
VIII preparations for people with haemophilia limit the occurrence of hepatitis C.
Hepatitis D—Hepatitis D (delta) virus (HDV) is an RNA
virus. The virion particle is encapsulated by the coat protein
of HBV (HBsAg). Thus infection by HDV occurs only in
patients with hepatitis B. Transmission is as for HBV, and
the incubation period is 35days. Diagnosis is through IgM
anti-HD, IgG anti-HD and hepatitis D antigen detection.
The disease is not usually progressive, but outbreaks of fulminant hepatitis caused by HBV plus HDV can occur.
Hepatitis E—This RNA virus is transmitted via the
faecal–oral route, with a peak of epidemic infection
6–7 weeks after primary exposure and low secondary attack rate. Serum IgG and IgM anti-HEV can be detected by
ELISA. The condition is usually self-limiting, and progression to chronic hepatitis is rare. Mortality can be as high as
20% if the infection occurs while the patient is pregnant.
Prevention and disease control are dependent on high standards of public sanitation and sewage elimination.
Immune
clearance
phase
Risk of
cirrhosis
Immune control
phase
Immune escape
phase
Risk of
cirrhosis
Other viruses—Viral hepatitis can be caused by nonhepatic, systemic viruses. Examples include EBV, CMV,
herpes simplex virus, Q fever and arbovirus (yellow fever).
Clinical features differ enormously from asymptomatic
mild hepatitis to rapidly progressive fulminant fatal hepatitis. Diagnosis is through specific viral assays using techniques such as PCR or ELISA. If virology gives negative
results, alternative causes such as autoimmune hepatitis or
Budd–Chiari syndrome must be considered.
Clinical features—In the preicteric phase, symptoms
are nonspecific and include malaise, fatigue, listlessness and
lack of energy. Anorexia, nausea and vomiting may occur.
Right upper quadrant pain, change in bowel habit, myalgia,
fever and headaches may be present.
The prodromal symptoms become less severe as jaundice appears. Dark urine and pale stools may occur.
The physical signs are usually minimal. Common findings include jaundice, hepatic tenderness, hepatomegaly, splenomegaly and lymphadenopathy. Rashes may be
present.
Fulminant hepatitis leads to hepatic encephalopathy
with severe jaundice, ascites and oedema and is usually accompanied by haemorrhage caused by coagulopathies. The
disturbance of consciousness reflects a combination of hepatic coma, hypoglycaemia and cerebral oedema.
Investigations
• LFTs: alanine aminotransferase (ALT)and aspartate
aminotransferase (AST) levels are markedly elevated.
Bilirubin level is raised. During recovery, liver enzyme
levels return to normal. A persistently raised ALT
6months after the acute onset of hepatitis usually
indicates progression of the disease.
• Prothrombin time: may be prolonged with fulminant
hepatic failure.
• Serum albumin: level may be low and serum globulin
level may rise.
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