Medicine: Other Gastroenterology

Question 1

What is Hereditary Haemochromatosis?

Answer 1

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.
Often asymptomatic in early disease and initial symptoms often non-specific

Question 2

What is the epidemiology of Hereditary Haemochromatosis?

Answer 2

• 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

Question 3

What are the presenting features of Hereditary Haemochromatosis?

Answer 3

•fatigue
erectile dysfunction
arthralgia
•’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

Question 4

What are investigations for Hereditary Haemochromatosis?

Answer 4

• Diagnostic tests
o molecular genetic testing for the C282Y and H63D mutations
o liver biopsy: Perl’s stain
• Joint x-rays characteristically show chondrocalcinosis
• Typical iron study profile in patient with haemochromatosis
o transferrin saturation > 55% in men or > 50% in women
o raised ferritin (e.g. > 500 ug/l) and iron
o low TIBC

Question 5

What is the treatment for Hereditary Haemochromatosis?

Answer 5

Venesection is the first-line treatment

Question 6

What are complications of Hereditary Haemochromatosisi?

Answer 6

• Reversible Complications
• Cardiomyopathy, Skin pigmentation
• Irreversible Complications
• Liver cirrhosis, Diabetes mellitus, Hypogonadotrophic hypogonadism, Arthropathy

Question 7

What is

Peutz-Jeghers syndrome?

Answer 7

An autosomal dominant condition characterised by numerous hamartomatous polyps in the gastrointestinal tract.
associated with pigmented freckles on the lips, face, palms and soles. Around 50% of patients will have died from a gastrointestinal tract cancer by the age of 60 years.

Question 8

What are features and management of Peutz-Jeghers syndrome?

Answer 8

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 9

What is niacin and the result of deficiency?

Answer 9

Niacin is a water soluble vitamin of the B complex group. It is a precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells.

Biosynthesis
Hartnup’s disease, carcinoid syndrome: increased tryptophan metabolism to serotonin

Consequences of niacin deficiency is pellagra: dermatitis, diarrhoea, dementia

Question 10

What can causes Clostridium Difficile to increase excessively?

Answer 10

Clostridium difficile develops when the normal gut flora are suppressed by broad-spectrum antibiotics.

Clindamycin is historically
Second and third generation cephalosporins
• proton pump inhibitors

Question 11

What are features of C.difficile disease?

Answer 11

• diarrhoea
• abdominal pain
• a raised white blood cell count is characteristic
• if severe toxic megacolon may develop

Question 12

What is the management of C-difficile disease?

Answer 12

• 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

Question 13

What is Primary sclerosing cholangitis associated with?

Answer 13

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

Question 14

What are features of Primary Sclerosing Cholangitis?

Answer 14

• cholestasis: jaundice and pruritus
• right upper quadrant pain
• fatigue

Question 15

What are investigations of Primary Sclerosing Cholangitis?

Answer 15

• ERCP is the standard diagnostic tool, 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’

Question 16

What are complications of Primary Sclerosing Cholangitis?

Answer 16

• cholangiocarcinoma (in 10%)

* increased risk of colorectal cancer

Question 17

What is Wilsons disease?

Answer 17

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

Question 18

What are features of Wilsons Disease?

Answer 18

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
• Kayser-Fleischer rings
• renal tubular acidosis (esp. Fanconi syndrome)
• haemolysis
• blue nails

Question 19

How is diagnosis of Wilsons disease made?

Answer 19

• reduced serum caeruloplasmin
• reduced serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)
• increased 24hr urinary copper excretion

Question 20

What is the management of Wilsons Disease?

Answer 20

• 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

Question 21

What is melanosis coli?

Answer 21

Melanosis coli is a disorder of pigmentation of the bowel wall. Histology demonstrates pigment-laden macrophages
It is associated with laxative abuse, especially anthraquinone compounds such as senna

Question 22

What are features of Spontaneous Bacterial Peritonitis?

Answer 22

Features
• ascites
• abdominal pain
• fever

Question 23

What is the diagnosis of Spontaneous Bacterial Peritonitis made by and how is it management?

Answer 23

Diagnosis
• paracentesis: neutrophil count > 250 cells/ul
• the most common organism found on ascitic fluid culture is E. coli

Management
IV cefotaxime/IV tazocin

Question 24

When should Spontaneous Bacterial Peritonitis be prophylactically treated?

Answer 24

• patients who have had an episode of SBP
• patients with fluid protein <15 g/l and either Child-Pugh score of at least 9 or hepatorenal syndrome
• ‘Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less until the ascites has resolved’

Question 25

What is Carcinoid Syndrome?

Answer 25

• usually occurs when metastases are present in the liver and release serotonin into the systemic circulation
• may also occur with lung carcinoid as mediators are not ‘cleared’ by the liver

Question 26

What are features of Carcinoid Syndrome?

Answer 26

• flushing (often earliest symptom)
• diarrhoea
• bronchospasm
• hypotension
• right heart valvular stenosis (left heart can be affected in bronchial carcinoid)
• other molecules such as ACTH and GHRH may also be secreted resulting in, for example, Cushing’s syndrome
• pellagra can rarely develop as dietary tryptophan is diverted to serotonin by the tumour

Question 27

What is the investigations and management of Carcinoid Tumours?

Answer 27

Investigation
• urinary 5-HIAA
• plasma chromogranin A y

Management
• somatostatin analogues e.g. octreotide
• diarrhoea: cyproheptadine may help

Question 28

What are causes of Liver Cirrhosis?

Answer 28

• alcohol
• non-alcoholic fatty liver disease (NAFLD)
• viral hepatitis (B and C)

Question 29

How is diagnosis of Liver Cirrhosis made?

Answer 29

Diagnosis
• traditionally a liver biopsy was used. This procedure is however associated with adverse effects such as bleeding and pain
• other techniques such as transient elastography and acoustic radiation force impulse imaging are increasingly used and were recommended by NICE in their 2016 guidelines
• for patients with NAFLD, NICE recommend using the enhanced liver fibrosis score to screen for patients who need further testing

What is transient elastography?
• brand name ‘Fibroscan’
• uses a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe
• measures the ‘stiffness’ of the liver which is a proxy for fibrosis

Question 30

When should fibroscan/transient elastography be used for screening for cirrhosis?

Answer 30

• people with hepatitis C virus infection
• men who drink over 50 units of alcohol per week and women who drink over 35 units of alcohol per week and have done so for several months
• people diagnosed with alcohol-related liver disease

Further investigations
Upper endoscopy for varices
•liver ultrasound every 6 months (+/- alpha-feto protein) to check for HCC

Question 31

What is Primary Biliary Cholangitis?

Answer 31

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

Question 32

What are clinical features of Primary Biliary Cholangitis?

Answer 32

• early: may be asymptomatic (e.g. raised ALP on routine LFTs) or fatigue, pruritus
• cholestatic jaundice
• hyperpigmentation, especially over pressure points
• around 10% of patients have right upper quadrant pain
• xanthelasmas, xanthomata
• also: clubbing, hepatosplenomegaly
• late: may progress to liver failure

Question 33

What are complications of Primary biliary cholangitis?

Answer 33

• malabsorption: osteomalacia, coagulopathy
• sicca syndrome occurs in 70% of cases
• portal hypertension: ascites, variceal haemorrhage
• hepatocellular cancer (20-fold increased risk)

Question 34

How does Giardia infection present?

Answer 34

Giardia causes fat malabsorption, therefore greasy stool can occur. It is resistant to chlorination, hence risk of transfer in swimming pools

Question 35

What is Ferritin?

Answer 35

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

Question 36

What is the definition of increased Ferritin?

Answer 36

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

Question 37

What are causes of increased ferritin when Iron overloaded?

Answer 37

Primary iron overload (hereditary haemochromatosis)

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

Question 38

What are causes of increased ferritin without Iron overload?

Answer 38

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

Question 39

How is Iron Overload tested?

Answer 39

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.

Question 40

What causes reduced Ferritin levels?

Answer 40

Reduced ferritin levels
• Because iron and ferritin are bound the total body ferritin levels may be decreased in cases of iron deficiency anaemia.
• Measurement of serum ferritin levels can be useful in determining whether an apparently low haemoglobin and microcytosis is truly caused by an iron deficiency state.