Gastroenterology

Question 1

Achalasia

Answer 1

Failure of oesophageal peristalsis and of relaxation of lower oesophageal sphincter (LOS) due to degenerative loss of ganglia from Auerbach’s plexus i.e. LOS contracted, oesophagus above dilated. Achalasia typically presents in middle-age and is equally common in men and women.

Clinical features

dysphagia of BOTH liquids and solids

typically variation in severity of symptoms

heartburn

regurgitation of food - may lead to cough, aspiration pneumonia etc

malignant change in small number of patients

Investigations

oesophageal manometry: excessive LOS tone which doesn’t relax on swallowing - considered most important diagnostic test

barium swallow shows grossly expanded oesophagus, fluid level, ‘bird’s beak’ appearance

CXR: wide mediastinum, fluid level

Treatment

intra-sphincteric injection of botulinum toxin

Heller cardiomyotomy

pneumatic (balloon) dilation

drug therapy has a role but is limited by side-effects

Question 2

Mesenteric Ischaemia

Answer 2

Common features in bowel ischaemia

Common predisposing factors

increasing age

atrial fibrillation - particularly for mesenteric ischaemia

other causes of emboli: endocarditis, malignancy

cardiovascular disease risk factors: smoking, hypertension, diabetes

cocaine: ischaemic colitis is sometimes seen in young patients following cocaine use

Common features

abdominal pain - in acute mesenteric ischaemia this is often of sudden onset, severe and out-of-keeping with physical exam findings

rectal bleeding

diarrhoea

fever

bloods typically show an elevated white blood cell count associated with a lactic acidosis

Diagnosis

CT is the investigation of choice

Question 3

Alcohol Units

FAST

1

MEN: How often do you have EIGHT or more drinks on one occasion?
WOMEN: How often do you have SIX or more drinks on one occasion?

2

How often during the last year have you been unable to remember what happened the night before because you
had been drinking?

3

How often during the last year have you failed to do what was normally expected of you because of drinking?

4

In the last year has a relative or friend, or a doctor or other health worker been concerned about your drinking or
suggested you cut down?

Answer 3

Men and women should drink no more than 14 units of alcohol per week

‘if you do drink as much as 14 units per week, it is best to spread this evenly over 3 days or more’

pregnant women should not drink.

One unit of alcohol is equal to 10 mL of pure ethanol. The ‘strength’ of an alcoholic drink is determined by the ‘alcohol by volume’ (ABV).

Examples of one unit of alcohol:

25ml single measure of spirits (ABV 40%)

a third of a pint of beer (ABV 5 to 6%)

half a 175ml ‘standard’ glass of red wine (ABV 12%)

To calculate the number of units in a drink multiply the number of millilitres by the ABV and divide by 1,000.

For example: half a 175ml ‘standard’ glass of red wine = 87.5 * 12 / 1000 = 1.05 units

Question 4

Autoimmune hepatitis

Answer 4

Autoimmune hepatitis is condition of unknown aetiology which is most commonly seen in young females. Recognised associations include other autoimmune disorders, hypergammaglobulinaemia and HLA B8, DR3. Three types of autoimmune hepatitis have been characterised according to the types of circulating antibodies present

Type I - Anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)
Affects both adults and children

Type II Anti-liver/kidney microsomal type 1 antibodies (LKM1)
Affects children only

Type III - Soluble liver-kidney antigen
Affects adults in middle-age
Features

may present with signs of chronic liver disease

acute hepatitis: fever, jaundice etc (only 25% present in this way)

amenorrhoea (common)

ANA/SMA/LKM1 antibodies, raised IgG levels

liver biopsy: inflammation extending beyond limiting plate ‘piecemeal necrosis’, bridging necrosis

Management

steroids, other immunosuppressants e.g. azathioprine

liver transplantation

Question 5

Clostridium difficile

Answer 5

Clostridium difficile is a Gram positive rod often encountered in hospital practice. It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis. Clostridium difficile develops when the normal gut flora are suppressed by broad-spectrum antibiotics. Clindamycin is historically associated with causing Clostridium difficile but the aetiology has evolved significantly over the past 10 years. Second and third generation cephalosporins are now the leading cause of Clostridium difficile.

Other than antibiotics, risk factors include:

proton pump inhibitors

Features

diarrhoea

abdominal pain

a raised white blood cell count is characteristic

if severe toxic megacolon may develop

Diagnosis

is made by detecting Clostridium difficile toxin (CDT) in the stool

Clostridium difficile antigen positivity only shows exposure to the bacteria, rather than current infection

Management

first-line therapy is oral metronidazole for 10-14 days

if severe or not responding to metronidazole then oral vancomycin may be used

fidaxomicin may also be used for patients who are not responding , particularly those with multiple co-morbidities

for life-threatening infections a combination of oral vancomycin and intravenous metronidazole should be used

bezlotoxumab is a monoclonal antibody which targets Clostridium difficile toxin B - it is not in widespread use

Question 6

Coagulopathy

Answer 6

Liver failure: all clotting factors are low except for factor VIII which is supra-normal. Both PT and APTT can be prolonged.

Haemophilia B would have low levels of factor VIII.

Haemophilia A would have low levels of factor IX but the other clotting factors are not affected.

Von Willebrand disease would have low levels of Von Willebrand factor but the other factors are not affected. Factor VIII may be low or normal.

Question 7

Coeliac Disease

Answer 7

NICE issued guidelines on the investigation of in 2009. If patients are already taking a gluten-free diet they should be asked, if possible, to reintroduce gluten for at least 6 weeks prior to testing.

Immunology

tissue transglutaminase (TTG) antibodies (IgA) are first-choice according to NICE

endomyseal antibody (IgA)

needed to look for selective IgA deficiency, which would give a false negative coeliac result

anti-gliadin antibody (IgA or IgG) tests are not recommended by NICE

anti-casein antibodies are also found in some patients

Duodenal biopsy*

villous atrophy

crypt hyperplasia

increase in intraepithelial lymphocytes

lamina propria infiltration with lymphocytes

Rectal gluten challenge has been described but is not widely used

Question 8

Crohn’s Disease Treatment

Answer 8

General points

patients should be strongly advised to stop smoking

some studies suggest an increased risk of relapse secondary to NSAIDs and the combined oral contraceptive pill but the evidence is patchy

Inducing remission

glucocorticoids (oral, topical or intravenous) are generally used to induce remission. Budesonide is an alternative in a subgroup of patients

enteral feeding with an elemental diet may be used in addition to or instead of other measures to induce remission, particularly if there is concern regarding the side-effects of steroids (for example in young children)

5-ASA drugs (e.g. mesalazine) are used second-line to glucocorticoids but are not as effective

azathioprine or mercaptopurine* may be used as an add-on medication to induce remission but is not used as monotherapy. Methotrexate is an alternative to azathioprine

infliximab is useful in refractory disease and fistulating Crohn’s. Patients typically continue on azathioprine or methotrexate

metronidazole is often used for isolated peri-anal disease

Maintaining remission

as above, stopping smoking is a priority (remember: smoking makes Crohn’s worse, but may help ulcerative colitis)

azathioprine or mercaptopurine is used first-line to maintain remission

methotrexate is used second-line

5-ASA drugs (e.g. mesalazine) should be considered if a patient has had previous surgery

Surgery

around 80% of patients with Crohn’s disease will eventually have surgery

see below for further detail

Question 9

Crohn’s Features

Answer 9

Crohn’s disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus.

Pathology

cause is unknown but there is a strong genetic susceptibility

inflammation occurs in all layers, down to the serosa. This is why patients with Crohn’s are prone to strictures, fistulas and adhesions

Crohn’s disease typically presents in late adolescence or early adulthood. Features include:

presentation may be non-specific symptoms such as weight loss and lethargy

diarrhoea: the most prominent symptom in adults. Crohn’s colitis may cause bloody diarrhoea

abdominal pain: the most prominent symptom in children

perianal disease: e.g. Skin tags or ulcers

extra-intestinal features are more common in patients with colitis or perianal disease

Investigations

raised inflammatory markers

increased faecal calprotectin

anaemia

low vitamin B12 and vitamin D

Question 10

Cyclical vomiting syndrome

Answer 10

Epidemiology

Rare

More common in children than adults

Females are slightly more affected than males

Aetiology

Unknown

80% of children and 25% of adults who develop CVS also have migraines

Presentation

Severe nausea and sudden vomiting lasting hours to days

Prodromal intense sweating and nausea

Well in between episodes

The following may be present:

Weight loss

Reduced appetite

Abdominal pain

Diarrhoea

Dizziness

Photophobia

Headache

Investigations

Clinical Diagnosis

A pregnancy test may be considered in women

Routine blood tests to exclude any underlying conditions

Management

Avoidance of triggers

Prophylactic treatments include amitriptyline, propranolol and topiramate.

Ondansetron, prochlorperazine and triptans in acute episodes.

Question 11

Diarrhoea

Diarrhoea: > 3 loose or watery stool per day

Acute diarrhoea < 14 days

Chronic diarrhoea > 14 days

Answer 11

Usually acute

Condition

Notes

Gastroenteritis

May be accompanied by abdominal pain or nausea/vomiting

Diverticulitis

Classically causes left lower quadrant pain, diarrhoea and fever

Antibiotic therapy

More common with broad spectrum antibiotics

Clostridium difficile is also seen with antibiotic use

Constipation causing overflow

A history of alternating diarrhoea and constipation may be given

May lead to faecal incontinence in the elderly

Usually chronic

Condition

Notes

Irritable bowel syndrome

Extremely common. The most consistent features are abdominal pain, bloating and change in bowel habit. Patients may be divided into those with diarrhoea predominant IBS and those with constipation-predominant IBS.

Features such as lethargy, nausea, backache and bladder symptoms may also be present

Ulcerative colitis

Bloody diarrhoea may be seen. Crampy abdominal pain and weight loss are also common. Faecal urgency and tenesmus may be seen

Crohn’s disease

Crampy abdominal pains and diarrhoea. Bloody diarrhoea less common than in ulcerative colitis. Other features include malabsorption, mouth ulcers, perianal disease and intestinal obstruction

Colorectal cancer

Symptoms depend on the site of the lesion but include diarrhoea, rectal bleeding, anaemia and constitutional symptoms e.g. Weight loss and anorexia

Coeliac disease

In children may present with failure to thrive, diarrhoea and abdominal distension

In adults lethargy, anaemia, diarrhoea and weight loss are seen. Other autoimmune conditions may coexist

Other conditions associated with diarrhoea include:

thyrotoxicosis

laxative abuse

appendicitis

radiation enteritis

Answer 12

The following drugs tend to cause a hepatocellular picture:

paracetamol

sodium valproate, phenytoin

MAOIs

halothane

anti-tuberculosis: isoniazid, rifampicin, pyrazinamide

statins

alcohol

amiodarone

methyldopa

nitrofurantoin

The following drugs tend to cause cholestasis (+/- hepatitis):

combined oral contraceptive pill

antibiotics: flucloxacillin, co-amoxiclav, erythromycin*

anabolic steroids, testosterones

phenothiazines: chlorpromazine, prochlorperazine

sulphonylureas

fibrates

rare reported causes: nifedipine

Liver cirrhosis

methotrexate

methyldopa

amiodarone

Question 13

Dyspepsia

Answer 13

he 2015 NICE guidelines ‘Suspected cancer: recognition and referral’ further updated the advice on who needs urgent referral for an endoscopy (i.e. within 2 weeks). The list below combines the advice for oesophageal and stomach cancer, with the bold added by the author, not NICE.

Urgent

All patients who’ve got dysphagia

All patients who’ve got an upper abdominal mass consistent with stomach cancer

Patients aged >= 55 years who’ve got weight loss, AND any of the following:

upper abdominal pain

reflux

dyspepsia

Non-urgent

Patients with haematemesis

Patients aged >= 55 years who’ve got:

treatment-resistant dyspepsia or

upper abdominal pain with low haemoglobin levels or

raised platelet count with any of the following: nausea, vomiting, weight loss, reflux, dyspepsia, upper abdominal pain

nausea or vomiting with any of the following: weight loss, reflux, dyspepsia, upper abdominal pain

Managing patients who do not meet referral criteria (‘undiagnosed dyspepsia’)

This can be summarised at a step-wise approach

1. Review medications for possible causes of dyspepsia
2. Lifestyle advice
3. Trial of full-dose proton pump inhibitor for one month OR a ‘test and treat’ approach for H. pylori

Testing for H. pylori infection

initial diagnosis: NICE recommend using a carbon-13 urea breath test or a stool antigen test, or laboratory-based serology ‘where its performance has been locally validated’

test of cure: carbon-13 urea breath te

Question 14

Dysphagia

Answer 14

Oesophagitis

There may be a history of heartburn
Odynophagia but no weight loss and systemically well

Oesophageal candidiasis

There may be a history of HIV or other risk factors such as steroid inhaler use

Achalasia

Dysphagia of both liquids and solids from the start
Heartburn
Regurgitation of food - may lead to cough, aspiration pneumonia etc

Pharyngeal pouch

More common in older men
Represents a posteromedial herniation between thyropharyngeus and cricopharyngeus muscles
Usually not seen but if large then a midline lump in the neck that gurgles on palpation
Typical symptoms are dysphagia, regurgitation, aspiration and chronic cough. Halitosis may occasionally be seen

Systemic sclerosis

Other features of CREST syndrome may be present, namely Calcinosis, Raynaud’s phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia

As well as oesophageal dysmotility the lower oesophageal sphincter (LES) pressure is decreased. This contrasts to achalasia where the LES pressure is increased

Myasthenia gravis

Other symptoms may include extraocular muscle weakness or ptosis
Dysphagia with liquids as well as solids

Globus hystericus

There may be a history of anxiety
Symptoms are often intermittent and relieved by swallowing
Usually painless - the presence of pain should warrant further investigation for organic causes

Question 15

Eosinophilic oesophagitis

Eosinophilic oesophagitis is characterised by an allergic inflammation of the oesophagus. An oesophageal biopsy will show dense infiltrate of eosinophils in the epithelium. Although this disease is relatively poorly understood, it is thought to be caused by an allergic reaction to ingested food. The resulting oesophageal inflammation results in pain and dysphagia, amongst other symptoms.

Answer 15

Epidemiology:

3:1 male:female ratio

Average age at diagnosis is 30-50 years old

Risk factors for developing eosinophilic oesophagitis:

Allergies/ asthma: suffering from food/ environmental allergies or atopic dermatitis and asthma increases the risk of diagnosis

Male sex

Family history of eosinophilic oesophagitis or allergies

Caucasian race

Age between 30-50

Coexisting autoimmune disease e.g. coeliac disease

Patients typically present with a subacute onset of:

In children, disease presents with failure to thrive due to food refusal

Adults often experience dysphagia, strictures/ fibrosis (56%), food impaction (55%), regurgitation/ vomiting, anorexia

Signs:

Signs are minimal and suspicion of this diagnosis relies mainly on the reported symptoms, past medical history and exclusion of other differential diagnoses e.g. GORD

Weight loss

Investigations:

Endoscopy: diagnosis can only be made on the histological analysis of an oesophageal biopsy. There must be more than 15 eosinophils per high power microscopy field to diagnose the condition. Other findings on endoscopy include reduced vasculature, thick mucosa, mucosal furrows, strictures and laryngeal oedema. Histologically, the diagnosis is made more likely in the presence of epithelial desquamation, eosinophilic microabscesses, and abnormally long papillae

PPI trial: persistence of eosinophilia and no improvement of symptoms after trialling a proton pump inhibitor. This can help the clinician differentiate between eosinophilic oesophagitis and GORD, which can be a tricky task

As eosinophilic oesophagitis is a relatively little-known condition that is still widely misunderstood, it is recommended that patients are referred to a gastroenterologist to receive specialist care.

Management:
- Dietary modification: This is both effective in adults and children. There are three methods available to begin excluding food from the diet. The elemental diet (involves taking an amino acid mixture for six weeks), exclusion of six food groups (involves avoiding foods commonly associated with allergy e.g. nuts, soy, egg, seafood), and the targeted elimination diet (involves excluding

Topical steroids e.g. fluticasone and budesonide are options when dietary modification fails. This requires the patient to swallow solutions of the steroid to line the oesophagus. This should be done for eight weeks before being reassessed

Oesophageal dilatation: 56% of patients require this at some point in their treatment to reduce the symptoms associated with oesophageal strictures

Complications:

Strictures of the oesophagus (56%)

Impaction: 55% of patients experience this, and 38% of these require endoscopic removal of the impaction

Mallory-Weiss tears

Prognosis:

Eosinophilic oesophagitis is a chronic condition. It is recognised that this condition is likely to come back in patients that stop treatment so it important to gain a good balance of dietary modifications and additional pharmacological treatments when necessary.

Question 16

Ferritin

Increased ferritin levels. This is typically defined as > 300 µg/L in men/postmenopausal women and > 200 µµg/L in premenopausal women.

Ferritin is an acute phase protein and may be synthesised in increased quantities in situations where inflammatory activity is ongoing. Falsely elevated results may therefore be encountered clinically and need to be taken in the context of the clinical picture and blood results.

The best test to see whether iron overload is present is transferrin saturation. Typically, normal values of < 45% in females and < 50% in males exclude iron overload.

Because iron and ferritin are bound the total body ferritin levels may be decreased in cases of iron deficiency anaemia.

Answer 16

Ferritin is an intracellular protein that binds iron and stores it to be released in a controlled fashion at sites where iron is required.

We can split the causes of increased ferritin levels into 2 distinct categories;

Without iron overload (around 90% of patients)

Inflammation (due to ferritin being an acute phase reactant)
Alcohol excess
Liver disease
Chronic kidney disease
Malignancy

With iron overload (around 10% of patients)

Primary iron overload (hereditary haemochromatosis)

Secondary iron overload (e.g. following repeated transfusions)

Question 17

Gallstones

Up to 24% of women and 12% of men may have gallstones. Of these up to 30% may develop local infection and cholecystitis. In patients subjected to surgery, 12% will have stones contained within the common bile duct. The majority of gallstones are of a mixed composition (50%) with pure cholesterol stones accounting for 20% of cases.

Answer 17

The aetiology of CBD stones differs in the world, in the West most CBD stones are the result of migration. In the East, a far higher proportion arise in the CBD de novo.

The classical symptoms are of colicky right upper quadrant pain that occurs postprandially. The symptoms are usually worst following a fatty meal when cholecystokinin levels are highest and gallbladder contraction is maximal.

Investigation
In almost all suspected cases the standard diagnostic workup consists of abdominal ultrasound and liver function tests. Of patients who have stones within the bile duct, 60% will have at least one abnormal result on LFT’s. Ultrasound is an important test, but is operator dependent and therefore may occasionally need to be repeated if a negative result is at odds with the clinical picture. Where stones are suspected in the bile duct the options lie between magnetic resonance cholangiography and intraoperative imaging. The choice between these two options is determined by the skills and experience of the surgeon. The advantages of intraoperative imaging are less useful in making therapeutic decisions if the operator is unhappy about proceeding the bile duct exploration, and in such circumstances, preoperative MRCP is probably a better option.

Question 18

Specific gallstone and gallbladder related disease

Answer 18

Disease

Features

Management

Biliary colic

Colicky abdominal pain, worse postprandially, worse after fatty foods

If imaging shows gallstones and history compatible then laparoscopic cholecystectomy

Acute cholecystitis

Right upper quadrant pain
Fever
Murphys sign on examination
Occasionally mildly deranged LFT’s (especially if Mirizzi syndrome)

Imaging (USS) and cholecystectomy (ideally within 48 hours of presentation) (2)

Gallbladder abscess

Usually prodromal illness and right upper quadrant pain
Swinging pyrexia
Patient may be systemically unwell
Generalised peritonism not present

Imaging with USS +/- CT Scanning
Ideally, surgery although subtotal cholecystectomy may be needed if Calot’s triangle is hostile
In unfit patients, percutaneous drainage may be considered

Cholangitis

Patient severely septic and unwell
Jaundice
Right upper quadrant pain

Fluid resuscitation
Broad-spectrum intravenous antibiotics
Correct any coagulopathy
Early ERCP

Gallstone ileus

Patients may have a history of previous cholecystitis and known gallstones
Small bowel obstruction (may be intermittent)

Laparotomy and removal of the gallstone from small bowel, the enterotomy must be made proximal to the site of obstruction and not at the site of obstruction. The fistula between the gallbladder and duodenum should not be interfered with.

Acalculous cholecystitis

Patients with intercurrent illness (e.g. diabetes, organ failure)
Patient of systemically unwell
Gallbladder inflammation in absence of stones
High fever

If patient fit then cholecystectomy, if unfit then percutaneous cholecystostomy

Question 19

Gastric cancer

There are 700,000 new cases of gastric cancer worldwide each year.

Epidemiology

overall incidence is decreasing, but incidence of tumours arising from the cardia is increasing

peak age = 70-80 years

more common in Japan, China, Finland and Colombia than the West

more common in males, 2:1

Answer 19

Histology

signet ring cells may be seen in gastric cancer. They contain a large vacuole of mucin which displaces the nucleus to one side. Higher numbers of signet ring cells are associated with a worse prognosis

Associations

H. pylori infection

blood group A: gAstric cAncer

gastric adenomatous polyps

pernicious anaemia

smoking

diet: salty, spicy, nitrates

may be negatively associated with duodenal ulcer

Features

dyspepsia

nausea and vomiting

anorexia and weight loss

dysphagia

Investigation

diagnosis: endoscopy with biopsy
staging: CT or endoscopic ultrasound - endoscopic ultrasound has recently been shown to be superior to CT

Surgical aspects

There is some evidence of support a stepwise progression of the disease through intestinal metaplasia progressing to atrophic gastritis and subsequent dysplasia, through to cancer. The favoured staging system is TNM. The risk of lymph node involvement is related to size and depth of invasion; early cancers confined to submucosa have a 20% incidence of lymph node metastasis. Tumours of the gastro-oesophageal junction are classified as below:

Type 1

True oesophageal cancers and may be associated with Barrett’s oesophagus.

Type 2

Carcinoma of the cardia, arising from cardiac type epithelium
or short segments with intestinal metaplasia at the oesophagogastric junction.

Type 3

Sub cardial cancers that spread across the junction. Involve similar nodal stations to gastric cancer.

Image sourced from Wikipedia

Upper GI endoscopy performed for dyspepsia. The addition of dye spraying (as shown in the bottom right) may facilitate identification of smaller tumours

Staging

CT scanning of the chest abdomen and pelvis is the routine first line staging investigation in most centres.

Laparoscopy to identify occult peritoneal disease

PET CT (particularly for junctional tumours)

Treatment

Proximally sited disease greater than 5-10cm from the OG junction may be treated by sub total gastrectomy

Total gastrectomy if tumour is <5cm from OG junction

For type 2 junctional tumours (extending into oesophagus) oesophagogastrectomy is usual

Endoscopic sub mucosal resection may play a role in early gastric cancer confined to the mucosa and perhaps the sub mucosa (this is debated)

Lymphadenectomy should be performed. A D2 lymphadenectomy is widely advocated by the Japanese, the survival advantages of extended lymphadenectomy have been debated. However, the overall recommendation is that a D2 nodal dissection be undertaken.

Most patients will receive chemotherapy either pre or post operatively.

Prognosis

UK Data

Disease extent

Percentage 5 year survival

All RO resections

54%

Early gastric cancer

91%

Stage 1

87%

Stage 2

65%

Stage 3

18%

Question 20

Gastro-oesophageal reflux disease: management

Answer 20

Gastro-oesophageal reflux disease (GORD) may be defined as symptoms of oesophagitis secondary to refluxed gastric contents

NICE recommend that GORD which has not been investigated with endoscopy should be treated as per the dyspepsia guidelines

Endoscopically proven oesophagitis

full dose proton pump inhibitor (PPI) for 1-2 months

if response then low dose treatment as required

if no response then double-dose PPI for 1 month

Endoscopically negative reflux disease

full dose PPI for 1 month

if response then offer low dose treatment, possibly on an as-required basis, with a limited number of repeat prescriptions

if no response then H2RA or prokinetic for one month

Complications

oesophagitis

ulcers

anaemia

benign strictures

Barrett’s oesophagus

oesophageal carcinoma

Question 21

Haemochromatosis features

Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*. It is often asymptomatic in early disease and initial symptoms often non-specific e.g. lethargy and arthralgia

Answer 21

Epidemiology

1 in 10 people of European descent carry a mutation in the genes affecting iron metabolism, mainly HFE

prevalence in people of European descent = 1 in 200, making it more common than cystic fibrosis

Presenting features

early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)

‘bronze’ skin pigmentation

diabetes mellitus

liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)

cardiac failure (2nd to dilated cardiomyopathy)

hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)

arthritis (especially of the hands)

Questions have previously been asked regarding which features are reversible with treatment:

Reversible complications

Irreversible complications

Cardiomyopathy

Skin pigmentation

Liver cirrhosis**

Diabetes mellitus

Hypogonadotrophic hypogonadism

Arthropathy

*there are rare cases of families with classic features of genetic haemochromatosis but no mutation in the HFE gene
**whilst elevated liver function tests and hepatomegaly may be reversible, cirrhosis is not

Question 22

Helicobacter pylori tests

Answer 22

Urea breath test

patients consume a drink containing carbon isotope 13 (13C) enriched urea

urea is broken down by H. pylori urease

after 30 mins patient exhale into a glass tube

mass spectrometry analysis calculates the amount of 13C CO2

should not be performed within 4 weeks of treatment with an antibacterial or within 2 weeks of an antisecretory drug (e.g. a proton pump inhibitor)

sensitivity 95-98%, specificity 97-98%

may be used to check for H. pylori eradication

Rapid urease test (e.g. CLO test)

biopsy sample is mixed with urea and pH indicator

colour change if H pylori urease activity

sensitivity 90-95%, specificity 95-98%

Serum antibody

remains positive after eradication

sensitivity 85%, specificity 80%

Culture of gastric biopsy

provide information on antibiotic sensitivity

sensitivity 70%, specificity 100%

Gastric biopsy

histological evaluation alone, no culture

sensitivity 95-99%, specificity 95-99%

Stool antigen test

sensitivity 90%, specificity 95%

Question 23

Hepatitis B serology

Answer 23

Interpreting hepatitis B serology is a dying art form which still occurs at regular intervals in medical exams. It is important to remember a few key facts:

surface antigen (HBsAg) is the first marker to appear and causes the production of anti-HBs

HBsAg normally implies acute disease (present for 1-6 months)

if HBsAg is present for > 6 months then this implies chronic disease (i.e. Infective)

Anti-HBs implies immunity (either exposure or immunisation). It is negative in chronic disease

Anti-HBc implies previous (or current) infection. IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months. IgG anti-HBc persists

HbeAg results from breakdown of core antigen from infected liver cells as is, therefore, a marker of infectivity
Example results

previous immunisation: anti-HBs positive, all others negative

previous hepatitis B (> 6 months ago), not a carrier: anti-HBc positive, HBsAg negative

previous hepatitis B, now a carrier: anti-HBc positive, HBsAg positive

HBsAg = ongoing infection, either acute or chronic if present > 6 months

anti-HBc = caught, i.e. negative if immunized

A nurse undergoes primary immunisation against hepatitis B. Levels of which one of the following should be checked four months later to ensure an adequate response to immunisation?

Question 24

Hepatobiliary disease and related disorders

Answer 24

Congestive hepatomegaly

The liver only usually causes pain if stretched. One common way this can occur is as a consequence of congestive heart failure. In severe cases cirrhosis may occur.

Biliary colic

RUQ pain, intermittent, usually begins abruptly and subsides gradually. Attacks often occur after eating. Nausea is common.

It is sometimes taught that patients are female, forties, fat and fair although this is obviously a generalisation.

Acute cholecystitis

Pain similar to biliary colic but more severe and persistent. The pain may radiate to the back or right shoulder.

The patient may be pyrexial and Murphy’s sign positive (arrest of inspiration on palpation of the RUQ)

Ascending cholangitis

An infection of the bile ducts commonly secondary to gallstones. Classically presents with a triad of:

fever (rigors are common)

RUQ pain

jaundice

Gallstone ileus

This describes small bowel obstruction secondary to an impacted gallstone. It may develop if a fistula forms between a gangrenous gallbladder and the duodenum.

Abdominal pain, distension and vomiting are seen.

Cholangiocarcinoma

Persistent biliary colic symptoms, associated with anorexia, jaundice and weight loss. A palpable mass in the right upper quadrant (Courvoisier sign), periumbilical lymphadenopathy (Sister Mary Joseph nodes) and left supraclavicular adenopathy (Virchow node) may be seen

Acute pancreatitis

Usually due to alcohol or gallstones
Severe epigastric pain
Vomiting is common
Examination may reveal tenderness, ileus and low-grade fever
Periumbilical discolouration (Cullen’s sign) and flank discolouration (Grey-Turner’s sign) is described but rare

Pancreatic cancer

Painless jaundice is the classical presentation of pancreatic cancer. However pain is actually a relatively common presenting symptom of pancreatic cancer. Anorexia and weight loss are common

Amoebic liver abscess

Typical symptoms are malaise, anorexia and weight loss. The associated RUQ pain tends to be mild and jaundice is uncommon.

Question 25

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause of cancer worldwide. Chronic hepatitis B is the most common cause of HCC worldwide with chronic hepatitis C being the most common cause in Europe.

Answer 25

The main risk factor for developing HCC is liver cirrhosis, for example secondary* to hepatitis B & C, alcohol, haemochromatosis and primary biliary cirrhosis. Other risk factors include:

alpha-1 antitrypsin deficiency

hereditary tyrosinosis

glycogen storage disease

aflatoxin

drugs: oral contraceptive pill, anabolic steroids

porphyria cutanea tarda

male sex

diabetes mellitus, metabolic syndrome

Features

tends to present late

features of liver cirrhosis or failure may be seen: jaundice, ascites, RUQ pain, hepatomegaly, pruritus, splenomegaly

possible presentation is decompensation in a patient with chronic liver disease

Screening with ultrasound (+/- alpha-fetoprotein) should be considered for high risk groups such as:

patients liver cirrhosis secondary to hepatitis B & C or haemochromatosis

men with liver cirrhosis secondary to alcohol

Management options

early disease: surgical resection

liver transplantation

radiofrequency ablation

transarterial chemoembolisation

sorafenib: a multikinase inhibitor

*Wilson’s disease is an exception

Question 26

Hepatomegaly

Answer 26

Common causes of hepatomegaly

Cirrhosis: if early disease, later liver decreases in size. Associated with a non-tender, firm liver

Malignancy: metastatic spread or primary hepatoma. Associated with a hard, irregular. liver edge

Right heart failure: firm, smooth, tender liver edge. May be pulsatile

Other causes

viral hepatitis

glandular fever

malaria

abscess: pyogenic, amoebic

hydatid disease

haematological malignancies

haemochromatosis

primary biliary cirrhosis

sarcoidosis, amyloidosis

Question 27

Crohn’s disease (CD)

Answer 27

Complications

Obstruction, fistula, colorectal cancer

Pathology

Lesions may be seen anywhere from the mouth to anus
Skip lesions may be present

Histology

Inflammation in all layers from mucosa to serosa

increased goblet cells

granulomas

Endoscopy

Deep ulcers, skip lesions - ‘cobble-stone’ appearance

Radiology

Small bowel enema

high sensitivity and specificity for examination of the terminal ileum

strictures: ‘Kantor’s string sign’

proximal bowel dilation

‘rose thorn’ ulcers

fistulae

Question 28

Ulcerative colitis (UC)

Answer 28

Risk of colorectal cancer high in UC than CD

Inflammation always starts at rectum and never spreads beyond ileocaecal valve

Continuous disease

No inflammation beyond submucosa (unless fulminant disease) - inflammatory cell infiltrate in lamina propria

neutrophils migrate through the walls of glands to form crypt abscesses

depletion of goblet cells and mucin from gland epithelium

granulomas are infrequent

Widespread ulceration with preservation of adjacent mucosa which has the appearance of polyps (‘pseudopolyps’)

Barium enema

loss of haustrations

superficial ulceration, ‘pseudopolyps’

long standing disease: colon is narrow and short -‘drainpipe colon’

Question 29

Irritable bowel syndrome

Answer 29

NICE published clinical guidelines on the diagnosis and management of irritable bowel syndrome (IBS) in 2008

The diagnosis of IBS should be considered if the patient has had the following for at least 6 months:

abdominal pain, and/or

bloating, and/or

change in bowel habit

A positive diagnosis of IBS should be made if the patient has abdominal pain relieved by defecation or associated with altered bowel frequency stool form, in addition to 2 of the following 4 symptoms:

altered stool passage (straining, urgency, incomplete evacuation)

abdominal bloating (more common in women than men), distension, tension or hardness

symptoms made worse by eating

passage of mucus

Features such as lethargy, nausea, backache and bladder symptoms may also support the diagnosis

Red flag features should be enquired about:

rectal bleeding

unexplained/unintentional weight loss

family history of bowel or ovarian cancer

onset after 60 years of age

Suggested primary care investigations are:

full blood count

ESR/CRP

coeliac disease screen (tissue transglutaminase antibodies)

Question 30

Malabsorption Syndrome

very common complication of scleroderma (systemic sclerosis). The bloods show evidence of impaired absorption of some vitamins (B12, folate), nutrients (iron) and protein (low albumin).

Answer 30

Malabsorption is characterised by diarrhoea, steatorrhoea and weight loss. Causes may be broadly divided into intestinal (e.g. villous atrophy), pancreatic (deficiency of pancreatic enzyme production or secretion) and biliary (deficiency of bile-salts needed for emulsification of fats)

Intestinal causes of malabsorption

coeliac disease

Crohn’s disease

tropical sprue

Whipple’s disease

Giardiasis

brush border enzyme deficiencies (e.g. lactase insufficiency)

Pancreatic causes of malabsorption

chronic pancreatitis

cystic fibrosis

pancreatic cancer

Biliary causes of malabsorption

biliary obstruction

primary biliary cirrhosis

Other causes

bacterial overgrowth (e.g. systemic sclerosis, diverticulae, blind loop)

short bowel syndrome

lymphoma

Question 31

Metoclopramide

Answer 31

Metoclopramide is a D2 receptor antagonist* mainly used in the management of nausea. Other uses include:

gastro-oesophageal reflux disease

prokinetic action is useful in gastroparesis secondary to diabetic neuropathy

often combined with analgesics for the treatment of migraine (migraine attacks result in gastroparesis, slowing the absorption of analgesics)

Adverse effects

extrapyramidal effects: oculogyric crisis. This is particularly a problem in children and young adults

hyperprolactinaemia

tardive dyskinesia

parkinsonism

Metoclopramide should be avoided in bowel obstruction, but may be helpful in paralytic ileus.

*whilst metoclopramide is primarily a D2 receptor antagonist, the mechanism of action is quite complicated:

it is also a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist

the antiemetic action is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone. At higher doses the 5-HT3 receptor antagonist also has an effect

the gastroprokinetic activity is mediated by D2 receptor antagonist activity and 5-HT4 receptor agonist activity

Question 32

Non-alcoholic fatty liver disease

Answer 32

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease in the developed world. It is largely caused by obesity and describes a spectrum of disease ranging from:

steatosis - fat in the liver

steatohepatitis - fat with inflammation, non-alcoholic steatohepatitis (NASH), see below

progressive disease may cause fibrosis and liver cirrhosis

NAFLD is thought to represent the hepatic manifestation of the metabolic syndrome and hence insulin resistance is thought to be the key mechanism leading to steatosis.

Non-alcoholic steatohepatitis (NASH) is a term used to describe liver changes similar to those seen in alcoholic hepatitis in the absence of a history of alcohol abuse. It is relatively common and thought to affect around 3-4% of the general population. The progression of disease in patients with NASH may be responsible for a proportion of patients previously labelled as cryptogenic cirrhosis.

Associated factors

Obesity

type 2 diabetes mellitus

hyperlipidaemia

jejunoileal bypass

sudden weight loss/starvation

Features

usually asymptomatic

hepatomegaly

ALT is typically greater than AST

increased echogenicity on ultrasound

NICE produced guidelines on the investigation and management of NAFLD in 2016. Key points:

there is no evidence to support screening for NAFLD in adults, even in at risk groups (e.g. type 2 diabetes)

the guidelines are therefore based on the management of the incidental finding of NAFLD - typically asymptomatic fatty changes on liver ultrasound

in these patients, NICE recommends the use of the enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis

the ELF blood test is a combination of hyaluronic acid + procollagen III + tissue inhibitor of metalloproteinase 1. An algorithm based on these values results in an ELF blood test score, similar to triple testing for Down’s syndrome

An excellent review by Byrne et Al1 in 2018 reviewed the diagnosis and monitoring of NAFLD. It made the following suggestions if the ELF blood test was not available:

non-invasive tests may be used to assess the severity of fibrosis

these include the FIB4 score or NALFD fibrosis score

these scores may be used in combination with a FibroScan (liver stiffness measurement assessed with transient elastography)

this combination has been shown to have excellent accuracy in predicting fibrosis

Patients who are likely to have advanced fibrosis should be referred to a liver specialist. They will then likely have a liver biopsy to stage the disease more accurately.

Management

the mainstay of treatment is lifestyle changes (particularly weight loss) and monitoring

there is ongoing research into the role of gastric banding and insulin-sensitising drugs (e.g. metformin, pioglitazone)

Question 33

Oesophageal cancer

Answer 33

Until recent times oesophageal cancer was most commonly due to a squamous cell carcinoma but the incidence of adenocarcinoma is rising rapidly. Adenocarcinoma is now the most common type of oesophageal cancer and is more likely to develop in patients with a history of gastro-oesophageal reflux disease (GORD) or Barrett’s.

The majority of adenocarcinomas are located near the gastroesophageal junction whereas squamous cell tumours are most commonly found in the middle third of the oesophagus.

Risk factors

smoking

alcohol

GORD

Barrett’s oesophagus

achalasia

Plummer-Vinson syndrome

squamous cell carcinoma is also linked to diets rich in nitrosamines

rare: coeliac disease, scleroderma

Features

dysphagia: the most common presenting symptom

anorexia and weight loss

vomiting

other possible features include: odynophagia, hoarseness, melaena, cough

Diagnosis

Upper GI endoscopy is the first line test

Contrast swallow may be of benefit in classifying benign motility disorders but has no place in the assessment of tumours

Staging is initially undertaken with CT scanning of the chest, abdomen and pelvis. If overt metastatic disease is identified using this modality then further complex imaging is unnecessary

If CT does not show metastatic disease, then local stage may be more accurately assessed by use of endoscopic ultrasound

Staging laparoscopy is performed to detect occult peritoneal disease. PET CT is performed in those with negative laparoscopy. Thoracoscopy is not routinely performed.

Treatment

Operable disease is best managed by surgical resection.

The most standard procedure is an Ivor- Lewis type oesophagectomy. This procedure involves the mobilisation of the stomach and division of the oesophageal hiatus. The abdomen is closed and a right sided thoracotomy performed. The stomach is brought into the chest and the oesophagus mobilised further. An intrathoracic oesophagogastric anastomosis is constructed. Alternative surgical strategies include a transhiatal resection (for distal lesions), a left thoraco-abdominal resection (difficult access due to thoracic aorta) and a total oesophagectomy (McKeown) with a cervical oesophagogastric anastomosis.

The biggest surgical challenge is that of anastomotic leak.

In addition to surgical resection many patients will be treated with adjuvant chemotherapy.

Question 34

Pancreatic cancer

Over 80% of pancreatic tumours are adenocarcinomas which typically occur at the head of the pancreas.

Answer 34

Associations

increasing age, smoking, diabetes, chronic pancreatitis,, hereditary non-polyposis colorectal carcinoma, multiple endocrine neoplasia, BRCA2 gene

Features

classically painless jaundice

Courvoisier’s law states that in the presence of painless obstructive jaundice, a palpable gallbladder is unlikely to be due to gallstones (

however, patients typically present in a non-specific way with anorexia, weight loss, epigastric pain

loss of exocrine function (e.g. steatorrhoea)

loss of endocrine function (e.g. diabetes mellitus)

atypical back pain is often seen

migratory thrombophlebitis (Trousseau sign) is more common than with other cancers

Investigation

ultrasound has a sensitivity of around 60-90%

high-resolution CT scanning is the investigation of choice if the diagnosis is suspected

Management

less than 20% are suitable for surgery at diagnosis

a Whipple’s resection (pancreaticoduodenectomy) is performed for resectable lesions in the head of pancreas. Side-effects of a Whipple’s include dumping syndrome and peptic ulcer disease

adjuvant chemotherapy is usually given following surgery

ERCP with stenting is often used for palliation

Question 35

Peutz-Jeghers syndrome

Answer 35

Peutz-Jeghers syndrome is an autosomal dominant condition characterised by numerous hamartomatous polyps in the gastrointestinal tract. It is also associated with pigmented freckles on the lips, face, palms and soles. Although the polyps themselves don’t have malignant potential, around 50% of patients will have died from another gastrointestinal tract cancer by the age of 60 years.

Genetics

autosomal dominant

responsible gene encodes serine threonine kinase LKB1 or STK11

Features

hamartomatous polyps in GI tract (mainly small bowel)

pigmented lesions on lips, oral mucosa, face, palms and soles

intestinal obstruction e.g. intussusception

gastrointestinal bleeding

Management

conservative unless complications develop

Question 36

Pharyngeal pouch

Answer 36

A pharyngeal pouch is a posteromedial diverticulum through Killian’s dehiscence. Killian’s dehiscence is a triangular area in the wall of the pharynx between the thyropharyngeus and cricopharyngeus muscles. It is more common in older patients and is 5 times more common in men

Features

dysphagia

regurgitation

aspiration

neck swelling which gurgles on palpation

halitosis

Management

surgery

Question 37

Primary biliary cholangitis

Answer 37

Primary biliary cholangitis - the M rule

IgM, anti-Mitochondrial antibodies, M2 subtype, Middle aged females

Primary biliary cholangitis (previously referred to as primary biliary cirrhosis) is a chronic liver disorder typically seen in middle-aged females (female:male ratio of 9:1). The aetiology is not fully understood although it is thought to be an autoimmune condition. Interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis. The classic presentation is itching in a middle-aged woman

Associations

Sjogren’s syndrome (seen in up to 80% of patients)

rheumatoid arthritis

systemic sclerosis

thyroid disease

Diagnosis

anti-mitochondrial antibodies (AMA) M2 subtype are present in 98% of patients and are highly specific

smooth muscle antibodies in 30% of patients

raised serum IgM

Management

pruritus: cholestyramine

fat-soluble vitamin supplementation

ursodeoxycholic acid

liver transplantation e.g. if bilirubin > 100 (PBC is a major indication) - recurrence in graft can occur but is not usually a problem

Complications

cirrhosis

osteomalacia and osteoporosis

significantly increased risk of hepatocellular carcinoma

Question 38

Primary sclerosing cholangitis

Answer 38

Primary sclerosing cholangitis is a biliary disease of unknown aetiology characterised by inflammation and fibrosis of intra and extra-hepatic bile ducts.

Associations

ulcerative colitis: 4% of patients with UC have PSC, 80% of patients with PSC have UC

Crohn’s (much less common association than UC)

HIV
Features

cholestasis: jaundice and pruritus

right upper quadrant pain

fatigue

Investigation

endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) are the standard diagnostic investigations, showing multiple biliary strictures giving a ‘beaded’ appearance

ANCA may be positive

there is a limited role for liver biopsy, which may show fibrous, obliterative cholangitis often described as ‘onion skin’

Complications

cholangiocarcinoma (in 10%)

increased risk of colorectal cancer

Question 39

Proton pump inhibitors

Answer 39

Proton pump inhibitors (PPI) cause irreversible blockade of H+/K+ ATPase of the gastric parietal cell.

Examples include omeprazole and lansoprazole.

Adverse effects

hyponatraemia, hypomagnasaemia

osteoporosis → increased risk of fractures

microscopic colitis

increased risk of Clostridium difficile infections

Question 40

Clostridium difficile

Answer 40

Clostridium difficile is a Gram positive rod often encountered in hospital practice. It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis. Clostridium difficile develops when the normal gut flora are suppressed by broad-spectrum antibiotics. Clindamycin is historically associated with causing Clostridium difficile but the aetiology has evolved significantly over the past 10 years. Second and third generation cephalosporins are now the leading cause of Clostridium difficile.

Other than antibiotics, risk factors include:

proton pump inhibitors

Features

diarrhoea

abdominal pain

a raised white blood cell count is characteristic

if severe toxic megacolon may develop

Diagnosis

is made by detecting Clostridium difficile toxin (CDT) in the stool

Clostridium difficile antigen positivity only shows exposure to the bacteria, rather than current infection

Management

first-line therapy is oral metronidazole for 10-14 days

if severe or not responding to metronidazole then oral vancomycin may be used

fidaxomicin may also be used for patients who are not responding , particularly those with multiple co-morbidities

for life-threatening infections a combination of oral vancomycin and intravenous metronidazole should be used

Other therapies

bezlotoxumab is a monoclonal antibody which targets Clostridium difficile toxin B - it is not in widespread use

Question 41

Ulcerative colitis management

Answer 41

Treatment can be divided into inducing and maintaining remission. NICE updated their guidelines on the management of ulcerative colitis in 2019.

The severity of UC is usually classified as being mild, moderate or severe:

mild: < 4 stools/day, only a small amount of blood
moderate: 4-6 stools/day, varying amounts of blood, no systemic upset
severe: >6 bloody stools per day + features of systemic upset (pyrexia, tachycardia, anaemia, raised inflammatory markers)

Inducing remission

Treating mild-to-moderate ulcerative colitis

proctitis

topical (rectal) aminosalicylate: for distal colitis rectal mesalazine has been shown to be superior to rectal steroids and oral aminosalicylates

if remission is not achieved within 4 weeks, add an oral aminosalicylate

if remission still not achieved add topical or oral corticosteroid

proctosigmoiditis and left-sided ulcerative colitis

topical (rectal) aminosalicylate

if remission is not achieved within 4 weeks, add a high-dose oral aminosalicylate OR switch to a high-dose oral aminosalicylate and a topical corticosteroid

if remission still not achieved stop topical treatments and offer an oral aminosalicylate and an oral corticosteroid

extensive disease

topical (rectal) aminosalicylate and a high-dose oral aminosalicylate:

if remission is not achieved within 4 weeks, stop topical treatments and offer a high-dose oral aminosalicylate and an oral corticosteroid

Severe colitis

should be treated in hospital

intravenous steroids are usually given first-line

intravenous ciclosporin may be used if steroid are contraindicated

if after 72 hours there has been no improvement, consider adding intravenous ciclosporin to intravenous corticosteroids or consider surgery

Maintaining remission

Following a mild-to-moderate ulcerative colitis flare

proctitis and proctosigmoiditis

topical (rectal) aminosalicylate alone (daily or intermittent) or

an oral aminosalicylate plus a topical (rectal) aminosalicylate (daily or intermittent) or

an oral aminosalicylate by itself: this may not be effective as the other two options

left-sided and extensive ulcerative colitis

low maintenance dose of an oral aminosalicylate

Following a severe relapse or >=2 exacerbations in the past year

oral azathioprine or oral mercaptopurine

Other points

methotrexate is not recommended for the management of UC (in contrast to Crohn’s disease)

there is some evidence that probiotics may prevent relapse in patients with mild to moderate disease

Question 42

Aminosalicylate drugs

5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis

Answer 42

Sulphasalazine

a combination of sulphapyridine (a sulphonamide) and 5-ASA

many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis

other side-effects are common to 5-ASA drugs (see mesalazine)

Mesalazine

a delayed release form of 5-ASA

sulphapyridine side-effects seen in patients taking sulphasalazine are avoided

mesalazine is still however associated with side-effects such as GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis

Olsalazine

two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria

*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine

Question 43

Variceal haemorrhage

Answer 43

Acute treatment of variceal haemorrhage

ABC: patients should ideally be resuscitated prior to endoscopy

correct clotting: FFP, vitamin K

vasoactive agents: terlipressin is currently the only licensed vasoactive agent and is supported by NICE guidelines. It has been shown to be of benefit in initial haemostasis and preventing rebleeding. Octreotide may also be used although there is some evidence that terlipressin has a greater effect on reducing mortality

prophylactic antibiotics have been shown to reduce mortality in patients with liver cirrhosis. Quinolones are typically used. NICE support this in their 2016 guidelines: ‘Offer prophylactic intravenous antibiotics for people with cirrhosis who have upper gastrointestinal bleeding.’

endoscopy: endoscopic variceal band ligation is superior to endoscopic sclerotherapy. NICE recommend band ligation

Sengstaken-Blakemore tube if uncontrolled haemorrhage

Transjugular Intrahepatic Portosystemic Shunt (TIPSS) if above measures fail

Prophylaxis of variceal haemorrhage

propranolol: reduced rebleeding and mortality compared to placebo

endoscopic variceal band ligation (EVL) is superior to endoscopic sclerotherapy. It should be performed at two-weekly intervals until all varices have been eradicated. Proton pump inhibitor cover is given to prevent EVL-induced ulceration. This is supported by NICE who recommend: ‘Offer endoscopic variceal band ligation for the primary prevention of bleeding for people with cirrhosis who have medium to large oesophageal varices.’

Question 44

Vitamin D

Answer 44

Vitamin D is a fat-soluble vitamin that plays a key role in calcium and phosphate metabolism. It is converted into the prohormone calcifediol in the liver. Circulating calcifediol is then converted into calcitriol (the biologically active form of vitamin D) in the kidneys.

Sources

vitamin D2 (ergocalciferol): plants

vitamin D3 (cholecalciferol): dairy products, can be synthesised by the skin from sunlight

Functions

increases plasma calcium and plasma phosphate

increases renal tubular reabsorption and gut absorption of calcium

increases osteoclastic activity

increases renal phosphate reabsorption

Consequences of vitamin D deficiency:

rickets: seen in children
osteomalacia: seen in adults

Question 45

Wilson’s disease

Answer 45

Wilson’s disease is an autosomal recessive disorder characterised by excessive copper deposition in the tissues. Metabolic abnormalities include increased copper absorption from the small intestine and decreased hepatic copper excretion. Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13.

The onset of symptoms is usually between 10 - 25 years. Children usually present with liver disease whereas the first sign of disease in young adults is often neurological disease

Features result from excessive copper deposition in the tissues, especially the brain, liver and cornea:

liver: hepatitis, cirrhosis
neurological: basal ganglia degeneration, speech, behavioural and psychiatric problems are often the first manifestations. Also: asterixis, chorea, dementia, parkinsonism

Kayser-Fleischer rings

renal tubular acidosis (esp. Fanconi syndrome)

haemolysis

blue nails

Diagnosis

reduced serum caeruloplasmin

reduced serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)

increased 24hr urinary copper excretion

Management

penicillamine (chelates copper) has been the traditional first-line treatment

trientine hydrochloride is an alternative chelating agent which may become first-line treatment in the future

tetrathiomolybdate is a newer agent that is currently under investigation