Medicine

Question 1

What is the treatment of choice for prophylaxis of variceal haemorrhage?

Answer 1

Propanolol

Question 2

What causes achalasia?

Answer 2

Failure of oesophageal peristalsis and of relaxation of the lower oesophageal sphincter (LOS) due to degenerative loss of ganglia from Auerbach’s plexus i.e. LOS contracted, oesophagus above dilated.

Question 3

What are the clinical features of achalasia?

Answer 3

• 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

Question 4

What are the investigations of achalasia?

Answer 4

• oesophageal manometry (excessive LOS tone which doesn’t relax on swallowing, considered the most important diagnostic test)
• barium swallow shows grossly expanded oesophagus, fluid level, ‘bird’s beak’ appearance)
• chest x-ray (wide mediastinum, fluid level)

Question 5

What are the treatments available for achalasia?

Answer 5

1. pneumatic (balloon) dilation is increasingly the preferred first-line option
   - less invasive and quicker recovery time than surgery
   - patients should be a low surgical risk as surgery may be required if complications occur
2. surgical intervention with a Heller cardiomyotomy should be considered if recurrent or persistent symptoms
3. intra-sphincteric injection of botulinum toxin is sometimes used in patients who are a high surgical risk
4. drug therapy (e.g. nitrates, calcium channel blockers) has a role but is limited by side-effects

Question 6

Inheritance mode of wilson’s disease

Answer 6

Autosomal recessive

Question 7

What is Wilson’s disease?

Answer 7

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.

Question 8

Gene and chromosome defective in Wilson’s disease?

Answer 8

ATP7B chromosome 13

Question 9

Age of onset and characteristics of Wilson’s disease

Answer 9

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: in the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus
- speech, behavioural and psychiatric problems are often the first manifestations
- also: asterixis, chorea, dementia, parkinsonism
- Kayser-Fleischer rings
- green-brown rings in the periphery of the iris
- due to copper accumulation in Descemet membrane
- present in around 50% of patients with isolated hepatic Wilson’s disease and 90% who have neurological involvement
- renal tubular acidosis (esp. Fanconi syndrome)
- haemolysis
- blue nails

Question 10

What are the investigations for wilson’s disease?

Answer 10

• slit lamp examination for Kayser-Fleischer rings
• reduced serum caeruloplasmin
• reduced total serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)
  - free (non-ceruloplasmin-bound) serum copper is increased
• increased 24hr urinary copper excretion
• the diagnosis is confirmed by genetic analysis of the ATP7B gene

Question 11

What’s the management for Wilson’s disease?

Answer 11

• 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 12

What are the features of Crohn’s disease?

Answer 12

• Diarrhoea usually non-bloody
• Weight loss more prominent
• Upper gastrointestinal symptoms, mouth ulcers, perianal disease
• Abdominal mass palpable in the right iliac fossa
• Gallstones are more common secondary to reduced bile acid reabsorption. Oxalate renal stones are formed as the impaired bile acid rebsorption (ileum) increases the loss calcium in the bile. Calcium normally binds oxalate.

Complications
- Obstruction, fistula, colorectal cancer (risk higher in UC)

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 13

What are the features of Ulcerative colitis?

Answer 13

• Bloody diarrhoea more common than in crohns
• Abdominal pain in the left lower quadrant
• Tenesmus
• Primary sclerosing cholangitis more common

Complications
- Risk of colorectal cancer high in UC than CD

Pathology
- Inflammation always starts at rectum and never spreads beyond ileocaecal valve
- Continuous disease

Histology
- 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

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

Radiology (Barium enema)
- loss of haustrations
- superficial ulceration, ‘pseudopolyps’
- long standing disease: colon is narrow and short -‘drainpipe colon’

Question 14

Bacterial classification of c diff

Answer 14

Gram positive bacillus
Clostridium difficile

It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis.

Question 15

Risk factors for c diff

Answer 15

• Second and third-generation cephalosporins are now the leading cause of C. difficile
• clindamycin
• PPIs

Question 16

Pathophysiology of c diff

Answer 16

• anaerobic gram-positive, spore-forming, toxin-producing bacillus
• transmission: via the faecal-oral route by ingestion of spores
• releases two exotoxins (toxin A and toxin B) that act on intestinal epithelial cells and inflammatory cells resulting in colitis

Question 17

What are the features of c diff?

Answer 17

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

Question 18

What’s the severity scale for c diff?

Answer 18

Mild
Normal WCC

Moderate
↑ WCC ( < 15 x 109/L)
Typically 3-5 loose stools per day

Severe
↑ WCC ( > 15 x 109/L)
or an acutely ↑ creatinine (> 50% above baseline)
or a temperature > 38.5°C
or evidence of severe colitis(abdominal or radiological signs)

Life threatening
Hypotension
Partial or complete ileus
Toxic megacolon, or CT evidence of severe disease

Question 19

How do you diagnose c diff?

Answer 19

• is made by detecting C. difficile toxin (CDT) in the stool
• C. difficile antigen positivity only shows exposure to the bacteria, rather than current infection

Question 20

How is c diff managed?

Answer 20

Current antibiotic therapy should be reviewed and antibiotics stopped if possible.

First episode of C. difficile infection
- first-line therapy is oral vancomycin for 10 days
- second-line therapy: oral fidaxomicin
- third-line therapy: oral vancomycin +/- IV metronidazole

Recurrent episode
- recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode
- within 12 weeks of symptom resolution:
- oral fidaxomicin
- after 12 weeks of symptom resolution: oral vancomycin OR fidaxomicin

Life-threatening C. difficile infection
- oral vancomycin AND IV metronidazole
- specialist advice - surgery may be considered

Other therapies
- bezlotoxumab is a monoclonal antibody which targets C. difficile toxin B
NICE do not currently support its use to prevent recurrences as it is not cost-effective
- faecal microbiota transplant
may be considered for patients who’ve had 2 or more previous episodes

Question 21

How do you prevent the spread of c diff?

Answer 21

• isolation in side room: the patient should remain isolated until there has been no diarrhoea (types 5-7 on the Bristol Stool Chart) for at least 48 hours
• all staff should wear disposable gloves and an apron during any contact with patients known to have C. difficile
• hand washing is also essential - alcohol gel does not kill the spores of C. difficile

Question 22

How do aminosalicylate drugs work? What are they used for?

Answer 22

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

Use: colitis and crohns

Question 23

What is sulphasalazine? What are the side effects?

Answer 23

• 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 (GI upset, headache, agranulocytosis, pancreatitis, interstitial nephritis)
• Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.

Question 24

What is mesalazine and what are the side effects?

Answer 24

• 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
  *pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine
• Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.

Question 25

What is osalazine?

Answer 25

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

Question 26

Features of whipples disease

Answer 26

Diarrhoea, weight loss, lymphadenopathy, arthralgia, fever D WALF

Question 27

What is the underlying aetiology of Budd-Chiari syndrome?

Answer 27

Thrombosis of the hepatic vein

Question 28

Severe vomiting --> haematemesis in a question is most likely to indicate:

Answer 28

Mallory Weiss syndrome

Question 29

What is gardners syndrome? What are the features of gardner's syndrome?

Answer 29

A variant of FAP called Gardner's syndrome can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin Multiple colonic polyps, osteomas, epidermoid cysts

Question 30

What are the types of colon cancer?

Answer 30

- sporadic (95%) - hereditary non-polyposis colorectal carcinoma (HNPCC, 5%) - familial adenomatous polyposis (FAP, <1%)

Question 31

What's the most common form of inherited colon cancer? And what's its inheritance mode

Answer 31

HNPCC (Lynch syndrome) Autosomal dominant Around 90% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive.

Question 32

What are the most common genes mutated in HNPCC?

Answer 32

MSH2 (60% of cases) MLH1 (30%) Mismatch repair genes

Question 33

What's the second most common cancer in HNPCC patients?

Answer 33

Endometiral

Question 34

Which criteria aids diagnosis of HNPCC?

Answer 34

The Amsterdam criteria are sometimes used to aid diagnosis: - at least 3 family members with colon cancer - the cases span at least two generations - at least one case diagnosed before the age of 50 years

Question 35

What is FAP?

Answer 35

FAP is a rare autosomal dominant condition which leads to the formation of hundreds of polyps by the age of 30-40 years. Patients inevitably develop carcinoma. It is due to a mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5. Genetic testing can be done by analysing DNA from a patient's white blood cells. Patients generally have a total proctocolectomy with ileal pouch anal anastomosis (IPAA) formation in their twenties.

Question 36

How is IBS diagnosed?

Answer 36

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

Question 37

What are the red flag features of IBS you should ask about?

Answer 37

- rectal bleeding - unexplained/unintentional weight loss - family history of bowel or ovarian cancer - onset after 60 years of age

Question 38

What are the investigations for IBS?

Answer 38

- full blood count - ESR/CRP - coeliac disease screen (tissue transglutaminase antibodies)

Question 39

Which conditions are associated with coeliac's disease?

Answer 39

- dermatitis herpetiformis (a vesicular, pruritic skin eruption) - autoimmune disorders (type 1 diabetes mellitus and autoimmune hepatitis). - strongly associated with HLA-DQ2 (95% of patients) and HLA-DQ8 (80%).

Question 40

What are the complications of coeliac disease?

Answer 40

- anaemia: iron, folate and vitamin B12 deficiency (folate deficiency is more common than vitamin B12 deficiency in coeliac disease) - hyposplenism - osteoporosis, osteomalacia - lactose intolerance - enteropathy-associated T-cell lymphoma of small intestine - subfertility, unfavourable pregnancy outcomes - rare: oesophageal cancer, other malignancies

Question 41

SeHCAT is the best investigation for....

Answer 41

bile acid malabsorption

Question 42

What are the causes of bile acid malabsorption?

Answer 42

Primary, due to excessive production of bile acid Secondary causes are often seen in patients with ileal disease, such as with Crohn's. Other secondary causes include: - cholecystectomy - coeliac disease - small intestinal bacterial overgrowth

Question 43

How do you manage bile acid malabsorption?

Answer 43

bile acid sequestrants e.g. cholestyramine

Question 44

Helicobacter pylori is associated with...

Answer 44

- peptic ulcer disease 95% of duodenal ulcers 75% of gastric ulcers - gastric cancer - B cell lymphoma of MALT tissue (eradication of H pylori results causes regression in 80% of patients) - atrophic gastritis

Question 45

How is h pylori treated?

Answer 45

eradication may be achieved with a 7-day course of: - a proton pump inhibitor + amoxicillin + (clarithromycin OR metronidazole) PAC or PAM! - if penicillin-allergic: a proton pump inhibitor + metronidazole + clarithromycin

Question 46

What is the treatment of choice for severe alcoholic hepatitis?

Answer 46

Prednisolone

Question 47

Alcoholic liver disease incorporates which conditions? What would you expect on examination?

Answer 47

Alcoholic liver disease covers a spectrum of conditions: - alcoholic fatty liver disease - alcoholic hepatitis - cirrhosis Selected investigation findings: - gamma-GT is characteristically elevated - the ratio of AST:ALT is normally > 2, a ratio of > 3 is strongly suggestive of acute alcoholic hepatitis

Question 48

A man who presents with intussusception is noticed to have multiple polyps on colonoscopy. These are later shown to be hamartomatous. He also has pigmented lesions on his lips and palms is a stereotypical history of:

Answer 48

Peutz Jeghers Syndrome

Question 49

What's the mode of inheritance of Peutz Jeghers syndrome? What's the mutation?

Answer 49

- autosomal dominant - responsible gene encodes serine threonine kinase LKB1 or STK11 (tumour suppressor gene)

Question 50

What does HbeAg imply?

Answer 50

It's a marker of infectivity. HbeAg results from breakdown of core antigen from infected liver cells as is, therefore, a marker of infectivity. Marker of HBV replication and infectivity

Question 51

Anti HBs implies....

Answer 51

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

Question 52

Anti HBc implies....

Answer 52

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

Question 53

Name 4 inherited causes of jaundice. Which are associated with conjugated bilirubin?

Answer 53

Unconjugated hyperbilirubinaemia Gilbert's syndrome Crigler-Najjar syndrome Conjugated hyperbilirubinaemia Dubin-Johnson syndrome Rotor syndrome Gilbert's syndrome - autosomal recessive - mild deficiency of UDP-glucuronosyl transferase - benign Crigler-Najjar syndrome, type 1 - autosomal recessive - absolute deficiency of UDP-glucuronosyl transferase - do not survive to adulthood Crigler-Najjar syndrome, type 2 - slightly more common than type 1 and less severe - may improve with phenobarbital Dubin-Johnson syndrome - autosomal recessive. Relatively common in Iranian Jews - mutation in the canalicular multidrug resistance protein 2 (MRP2) results in defective hepatic excretion of bilirubin - results in a grossly black liver - benign Rotor syndrome - autosomal recessive - defect in the hepatic uptake and storage of bilirubin - benign

Question 53

HBsAg normally implies.....

Answer 53

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). HBsAg is the first marker

Question 54

What's the best investigation for pharyngeal pouch?

Answer 54

Dynamic swallow combined with dynamic video fluoroscopy

Question 55

Which antibiotics are given to patients with liver cirrhosis and variceal haemorrhage?

Answer 55

IV quinolones

Question 56

What's the management for suspected variceal haemorrhage?

Answer 56

- ABC - correct clotting: FFP, vitamin K, platelet transfusions may be required - vasoactive agent (terlipressin) - prophylactic antibiotics if liver cirrhosis - both terlipressin and antibiotics should be given before endoscopy in patients with suspected variceal haemorrhage - 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 connects the hepatic vein to the portal vein exacerbation of hepatic encephalopathy is a common complication

Question 57

What's the ELF test? What does it test for?

Answer 57

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. Tests for NAFLD

Question 58

What causes haemachromatosis? What's the inheritance pattern? What chromosome is the gene on?

Answer 58

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

Question 59

What are the features of haemachromatosis?

Answer 59

- early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands) - 'bronze' skin pigmentation (reversible) - diabetes mellitus - liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition) - cardiac failure (2nd to dilated cardiomyopathy) (reversible) - hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism) - arthritis (especially of the hands)

Question 60

What is the Budd Chiari triad?

Answer 60

- abdominal pain: sudden onset, severe - ascites → abdominal distension - tender hepatomegaly

Question 60

What are the causes of Budd Chiari syndrome?

Answer 60

- polycythaemia rubra vera - thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies - pregnancy - combined oral contraceptive pill: accounts for around 20% of cases

Question 60

What's the investigation of choice for Budd Chiari syndrome?

Answer 60

ultrasound with Doppler flow studies is very sensitive and should be the initial radiological investigation

Question 61

Severe vomiting → oesophageal rupture

Answer 61

Boerhaave syndrome

Question 62

Severe vomiting → painful mucosal lacerations at the gastroesophageal junction resulting in haematemesis. Common in alcoholics

Answer 62

Mallory-Weiss syndrome

Question 63

Which drugs cause pulmonary fibrosis?

Answer 63

MANS methotrexate amiodarone nitrofurantoin sulphasalazine

Question 63

What's the Plummer Vinson triad? What's the treatment?

Answer 63

Triad of: - dysphagia (secondary to oesophageal webs) - glossitis - iron-deficiency anaemia Treatment includes iron supplementation and dilation of the webs

Question 63

How long in advance should PPIs be stopped before endoscopy?

Answer 63

2 weeks

Question 64

When would you do an endoscopy for GORD?

Answer 64

Indications for upper GI endoscopy: - age > 55 years - symptoms > 4 weeks or persistent symptoms despite treatment - dysphagia - relapsing symptoms - weight loss If endoscopy is negative consider 24-hr oesophageal pH monitoring (the gold standard test for diagnosis)

Question 65

What's the anatomy of a pharyngeal pouch?

Answer 65

Posteromedial herniation between thyropharyngeus and cricopharyngeus muscles

Question 66

What are the causes of dysphagia?

Answer 66

OOO SAM GP - oesophageal cancer - oesophagitis - oesophageal candidia - systemic sclerosis - achalasia - myasthenia gravis - globus hystericus - pharyngeal pouch Extrinsic - Mediastinal masses - Cervical spondylosis Oesophageal wall - Achalasia - Diffuse oesophageal spasm - Hypertensive lower oesophageal sphincter Intrinsic - Tumours - Strictures - Oesophageal web - Schatzki rings Neurological - CVA (cerebrovascular accident) - Parkinson's disease - Multiple Sclerosis - Brainstem pathology - Myasthenia Gravis

Question 67

What is the investigation of choice for suspected carcinoid tumours?

Answer 67

Urinary 5-HIAA plasma chromogranin A y

Question 68

What are the features of carcinoid syndrome?

Answer 68

- flushing - diarrhoea - bronchospasm - hypotension - weight loss

Question 69

What are the classifications of UC?

Answer 69

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)

Question 70

What are the 2 stages of treating UC patients?

Answer 70

Inducing remission Maintaining remission

Question 71

How is remission induced in UC patients?

Answer 71

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

Question 72

How do you maintain remission for UC patients?

Answer 72

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