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CASE 44: CHRONIC DIARRHOEA AND
FLATULENCE
A 25-year-old Irish woman is referred by her general practitioner to the gastroenterology
clinic with a 3-month history of diarrhoea, accompanied by flatulence and weight loss. She
reports that her bowels open up to three times each day. She does not report any other symp-
toms, and there is no history of foreign travel. She has a family history of Graves’ disease in
her brother.
Examination
Physical examination reveals a thin young woman with evidence of mild conjunctival pallor.
Abdominal examination is unremarkable.
INVESTIGATIONS
Baseline blood tests show a mild microcytic anaemia but nothing else of note.
Serological tests are requested, and a biopsy is planned.
QUESTIONS
1.
What serological investigations and biopsy are likely to be requested?
2. What is the underlying disorder, and how is it managed?
3. What long-term risks are associated with this condition?
DOI: 10.1201/9781003242697-46
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ANSWERS
The clinical presentation of diarrhoea, flatulence and weight loss is fairly typical of coeliac
disease.
Coeliac disease results from sensitivity to gluten, the protein component (gliadin) of grains
such as wheat, oat, barley and rye. There is a strong association of coeliac disease with cer-
tain human leukocyte antigen (HLA) haplotypes. Deaminated gluten peptides bind strongly
to HLA-DQ2 and DQ8, presenting an HLA-gluten peptide complex that activates CD4+
T cells, which produce inflammatory cytokines, including interferon gamma, which leads to
flattening of the intestinal mucosa. Indeed, association with these various HLA haplotypes is
also seen with other autoimmune conditions, such as type 1 diabetes and autoimmune thy-
roid disease. The positive autoimmune family history in this case therefore provides a clue to
the coeliac diagnosis.
The diagnosis of coeliac disease can be made in the following ways. Firstly, the presence
of autoantibodies, namely anti-endomysial or anti–tissue-transglutaminase (TTG) antibod-
ies, favour the presence of coeliac disease. The gold standard, however, is a small intestinal
biopsy, typically of the duodenum or jejunum. This would be expected to show atrophy
and blunting of villi, accompanied by intraepithelial lymphocytosis. The changes are more
marked in the proximal small intestine, as it is exposed to the highest concentration of gluten;
hence this is the preferred site for biopsy.
The small intestine is the site of absorption of various nutrients, and hence, coeliac disease
can lead to malabsorption of these, leading to various deficiencies. Iron, vitamin B
12
, and
folate deficiencies may produce an anaemia, whilst calcium malabsorption leads to osteo-
malacia. Lack of fat absorption causes steatorrhea, and also interferes with the absorption of
fat-soluble vitamins (A, D, E and K).
Clinical management includes withdrawal of gluten from the diet and demonstration of a
subsequent improvement in symptoms and histological findings. Indeed, this would prove the
diagnosis. Management of the various features of malabsorption (e.g., iron, vitamin, and folic
acid deficiencies) may also be required.
With regard to the complications of coeliac disease, there is a small increase in the long-term
risk of malignancies such as intestinal lymphomas (enteropathy-associated T-cell lymphoma
[EATCL]) and gastrointestinal and breast carcinomas as well.
KEY POINTS
•
Coeliac disease is caused by sensitivity to the gliadin component of gluten result-
ing in villous atrophy and blunting in the small intestine.
•
The gold standard for diagnosis is jejunal biopsy. Anti-endomysial and anti-TTG
are highly specific.
•
Treatment involves lifelong abstinence from gluten, including barley (including
beer), oats, flour, wheat and rye.
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CASE 45: A YOUNG MAN WITH BLOODY
DIARRHOEA
A 22-year-old Caucasian male presents to his general practitioner with bloody diarrhoea and
mucus on and o over the last few weeks. He does not report a fever or any history of recent
foreign travel. On direct questioning, he denies any extra-intestinal symptoms.
Examination
General and abdominal examination is unremarkable. Digital rectal examination is also
unremarkable.
INVESTIGATIONS
Baseline blood tests ordered by the GP show a mild normocytic anaemia. The patient
is referred for a fast-track colonoscopy, which shows moderate inflammation in the
rectum and sigmoid, but the proximal large bowel appears normal. A biopsy series is
taken from the rectum to terminal ileum. A stool sample is also sent for culture.
QUESTIONS
1.
What is the clinical diagnosis based on the above data?
2. Why is it important to enquire about extra-intestinal symptoms in this patient?
3. What are distinguishing pathological features of this condition?
4. What are the long-term complications?
DOI: 10.1201/97810 03242697-47
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ANSWERS
Bloody diarrhoea may be caused by acute infections (viral, bacterial or protozoal). Non-
infectious causes of haemorrhage into the large bowel include inflammatory bowel dis-
ease, ischaemic bowel disease, diverticular disease, polyps, angiodysplasia, haemorrhoids
or a bleeding diathesis. The presentation of bloody diarrhoea intermittently over a period
of weeks and without any features of infection is suggestive of inflammatory bowel disease
(IBD). Left-sided disease on colonoscopy with a sharp demarcation between inflamed and
proximally normal mucosa supports this and favours ulcerative colitis.
A history of extra-intestinal symptoms is important because ulcerative colitis and Crohn’s
disease, the other variant of IBD, may be associated with migrating polyarthritis, ankylosing
spondylitis and sacroiliitis. Hepatic involvement by pericholangitis and primary sclerosing
cholangitis is seen more commonly in ulcerative colitis. Uveitis and renal obstruction due to
retroperitoneal fibrosis may also accompany IBD. Fat and vitamin malabsorption may ensue
with Crohn’s disease due to involvement of the terminal ileum, as this is where these nutrients
are absorbed. IBD is an immunological disorder and with established genetic associations
which are, however, dierent for the two clinical subtypes.
Ulcerative colitis involves the mucosa and submucosa of the rectum, and the inflammation
spreads proximally but is typically confined to the colon with occasional backwash ileitis. No
normal intervening areas remain. With regeneration of the mucosa, pseudopolypoid appear-
ance develops. A diuse chronic inflammatory infiltrate is present in the submucosa, and
crypt abscesses form as neutrophilic infiltration progresses. There is distortion of the crypt
architecture with mucosal ulceration and fibrosis.
Crohn’s disease is characterised by transmural inflammation of segments of the gastrointes-
tinal (GI) tract (from the mouth to anus), accompanied by non-necrotising granulomata and
fissuring of the mucosa. The intervening segments of the GI tract are normal (skip lesions).
Early mucosal lesions (aphthous ulcers) coalesce to produce linear fissures in between surviv-
ing mucosa with a cobblestone appearance. The fissures may extend deeply into the bowel
producing adhesions or even fistulae.
Crohn’s disease may be associated with perforation and strictures, whilst ulcerative colitis
may progress to involvement of deeper layers (muscularis propria and neural plexus) with
resultant toxic megacolon and potential perforation. However, it is the development of dys-
plasia and invasive malignancy that poses a long-term risk, more so in patients with ulcer-
ative colitis.
It is assumed that long-standing chronic inflammation is responsible for this increased risk.
This is supported by the fact that colon cancer risk increases with longer duration of colitis,
the extent of colitis, the concomitant presence of other inflammatory manifestations such as
primary sclerosing cholangitis, and the fact that certain drugs used to treat inflammation,
such as 5-aminosalicylates and steroids, may prevent the development of colorectal cancer.
The major carcinogenic pathways that lead to colorectal cancer (e.g., chromosomal instabil-
ity, microsatellite instability and hypermethylation) are seen in inflamed colonic mucosa.
Oxidative stress also plays a role, as reactive oxygen and nitrogen species produced by
inflammatory cells can interact with key genes involved in carcinogenic pathways such as
p53 and the DNA mismatch repair gene.
The risk of carcinoma is 20–30 times higher in patients with pancolitis of more than 10 years’
duration compared to the normal population.
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123
Case 45: A Young Man with Bloody Diarrhoea
KEY POINTS
•
Bloody diarrhoea may be caused by infectious agents (viral, bacterial and proto-
zoal) as well as non-infectious conditions (e.g., IBD).
•
Ulcerative colitis and Crohn’s disease are the two clinical types of IBD.
•
Long-standing and extensive IBD is associated with an increased risk of dysplasia
and carcinoma of the colon.
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CASE 46: ABDOMINAL DISCOMFORT AND
GENERALISED WEAKNESS
A 58-year-old man presents to his general practitioner with a 4-week history of generalised
weakness and malaise. He also complains of mild abdominal discomfort but cannot identify
any change in his bowel habit (he opens his bowels once a day) nor any blood in his stools.
There is no family history of note.
Examination
General examination reveals conjunctival pallor. His weight has reduced by 5 kg since it was
previously recorded on his last attendance 2 months ago. Abdominal examination is unre-
markable. Digital rectal examination identifies soft stool, but no masses.
INVESTIGATIONS
Baseline blood tests show a mildly microcytic anaemia (Hb 11.5, MCV 78) but no other
abnormalities. As a faecal occult blood test is positive, the GP refers the patient for
further investigations, which identify a polypoid mass in the caecum, and a biopsy is
taken. The remaining large bowel appears normal.
QUESTIONS
1.
What is the likely nature of the polypoid mass and why?
2. What other findings may come to light at colonoscopy?
3. How do right-sided colonic tumours differ in their presentation from left-sided
ones?
4. What factors determine the prognosis of patients with colon carcinoma?
DOI: 10.1201/9781003242697-48
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ANSWERS
The clinical history and examination point to a progressively worsening condition over a
period of a few weeks, which in the absence of features of chronic infection, are suggestive of
malignancy.
Occult blood in the faeces and anaemia are due to chronic blood loss from the polypoid
tumour, which tends to have a friable surface and bleeds easily. The biopsy will confirm
whether the polyp shows epithelial dysplasia only or invasion into the deeper layers of the
bowel wall. Histologically, polypoid tumours may be adenomas with dysplasia, which may be
low grade or high grade. The term adenocarcinoma is used when invasion is seen into the
stalk of the polyp or deeper into the bowel wall. Adenomas may show a tubular, villous or a
combination of architecture. The larger the adenoma and the more villous its architecture,
the higher is the risk of adenocarcinoma.
Colonoscopy may detect synchronous tumours in other parts of the bowel or identify under-
lying conditions such as inflammatory bowel disease. Bowel cancer may arise in familial
syndromes such as polyposis coli in which the bowel is carpeted with polyps and in which
the risk of progressing to invasive malignancy is almost 100%. Long-standing inflamma-
tory bowel disease may also give rise to epithelial dysplasia and progression to malignancy.
Inflammatory bowel disease may be variably symptomatic, but there is usually a suggestive
clinical history.
Right-sided tumours such as those in the caecum may grow into large polypoid masses due to
its large capacity. Those arising in the left-sided colon may give rise to fresh bleeding, mucus
in stools, and rectal pain and therefore are more likely to present early.
The prognostic features in colon cancer include the grade or dierentiation of the carcinoma,
as well as the pathological TNM stage, which includes the depth of invasion (T) and assess-
ment of metastasis to lymph nodes (N ) and other organs (M). Grade 1 corresponds to well-
dierentiated carcinoma and Grade 3 to poorly dierentiated. The higher the grade, the
worse the prognosis. The pathological stage can be fully assessed only after definitive surgery.
Both of these factors are addressed in the modified Dukes’ staging of colorectal carcinoma.
The presence of lymphovascular invasion and distant metastases are other important prog-
nostic features.
The biopsy in this case demonstrated Grade 3 adenocarcinoma with invasion into the muscle
layer of the bowel wall; hence, right hemicolectomy with lymphadenectomy would be the
treatment of choice.
KEY POINTS
•
Anaemia associated with weight loss and positive faecal occult blood are highly
suggestive of bowel cancer.
•
Right-sided tumours often present just with anaemia, whereas left-sided cancers
are more symptomatic.
•
A worse prognosis is rendered by higher-grade tumours (containing less differen-
tiated cells), lymph node involvement and distant metastasis.
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CASE 47: ABDOMINAL PAIN IN A PUBLICAN
A 49-year-old pub owner presents to the emergency department with a progressive 2-week
history of epigastric pain, nausea, and vomiting. He has no other past medical history, in par-
ticular, no previous history of peptic ulcer disease or gallstone disease. On direct questioning,
he admits to drinking up to half a 750 mL bottle of spirits a day, i.e. up to 105 units per week
(one alcohol unit is 10 mL of alcohol, and the strengths of alcoholic beverages are stated as
alcohol by volume or ABV; most spirits are about 40% ABV).
Examination
General examination reveals an overweight gentleman with an identifiable whi of alcohol.
Abdominal examination shows epigastric tenderness, but no peritonism or guarding.
INVESTIGATIONS
Blood tests show:
•
Bilirubin: 28 mol/L
•
Alanine aminotransferase (ALT): 60 IU/L
•
Alkaline phosphatase (ALP): 150 IU/L
•
Gamma glutamyl transferase: 142 IU/L
•
Amylase: 592 IU/L
QUESTIONS
1.
What is the diagnosis?
2. What other differential diagnoses should be considered?
3. What is the most likely cause?
4. What other causes are associated with this diagnosis?
DOI: 10.1201/9781003242697-49
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ANSWERS
This is alcohol-induced acute pancreatitis. Taking the history alone, dierential diagnoses to
be considered include causes of foregut pain such as gastritis, peptic ulcer disease and, given
the deranged liver enzymes, gallstone disease and hepatitis.
Pancreatitis is typically diagnosed with a suitable history and a serum amylase of at least
three times the upper limit of normal (a mild hyperamylasaemia may be seen in various
intra-abdominal pathologies). Lower levels may be consistent with a diagnosis of pancreatitis,
as levels decline after 2–3 days. The level of amylase does not correlate with severity of pan-
creatitis. Lipase is equally valid for diagnosis.
In most series, alcohol and gallstones both account for 30–35% of cases. In the in-patient setting,
pancreatitis occurs in about 10% of patients undergoing endoscopic retrograde cholangiopan-
creatography (ERCP). A significant number of cases, as many as 10–20%, remain idiopathic,
although this may reflect the diminishing returns of exhaustive investigation once alcohol and
gallstones have been excluded. The remaining 1–2% are caused by hypercalcaemia, hyper-
lipidaemia, various drugs and toxins, trauma, hypothermia, mumps and autoimmune disease.
In the normal pancreas, self-digestion is prevented by several mechanisms: the enzymes are stored
as pro-enzymes, requiring activation by trypsin, itself a digestive enzyme. In addition, the intra-
cellular pH and calcium concentration keep the enzymes inactive. Alcohol and several of the
other causes disrupt these mechanisms, resulting in premature activation and leakage of enzymes
into the parenchyma. In gallstone disease, small stones or biliary sludge block the ampulla, pre-
venting drainage of pancreatic secretions and forcing pancreatic secretions into the parenchyma.
Regardless of the initiating cause, there is inappropriate activation of enzymes within the
parenchyma that creates a cascade of further activation of more unreleased enzymes. The
damage caused can be extensive, as the pancreas is a soft, fleshy organ (pan = all, creas = flesh).
The inevitable acute inflammation is usually mild and self-limiting, but in about 10% of cases,
it is sucient to result in widespread systemic inflammation and cause compromise of various
organ systems. Circulatory collapse, renal failure and adult respiratory distress syndrome may
ensue. These severe cases of pancreatitis carry a mortality of up to 10% and should be identi-
fied early through a combination of clinical assessment, imaging, and predictive physiological
scores (e.g., the modified Glasgow score), so they can be given the best supportive care.
Repeated episodes may result in chronic inflammation with destruction of the pancreas with
irreversible morphological changes. The early changes are mainly on a histological level (atro-
phy and fibrosis), but in later stages are detectable radiologically as calcification. Ultimately,
there is both endocrine and exocrine impairment, such that these patients require insulin
and enzyme supplementation with meals. With little residual exocrine pancreas remaining,
serum amylase is rarely raised in chronic pancreatitis.
KEY POINTS
•
Pancreatitis can be diagnosed with severe epigastric pain and a markedly ele-
vated serum amylase or lipase.
•
The most common causes of pancreatitis are excessive alcohol intake and gallstones.
•
Activation of digestive pancreatic enzymes within the pancreatic parenchyma
leads to acute inflammation; chronic inflammation results in irreversible atrophy
and fibrosis.
•
Remember that pancreatitis displays a broad clinical spectrum from mild disease
to pancreatic necrosis that results in multi-organ failure and death. Never under-
estimate diseases of the pancreas.
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