Membership of the Royal College of Physicians (MRCP UK) Gastroenterology and Hepatology Syllabus

What is the first-line pharmacological management of IBS by predominant symptom?

Antispasmodics (e.g. mebeverine, hyoscine) for pain/cramps; loperamide for diarrhoea-predominant IBS; soluble fibre (e.g. ispaghula) or laxatives such as macrogols for constipation (avoid lactulose). A low-dose tricyclic antidepressant is second-line for pain.

What is the autoantibody and HLA association of coeliac disease, and what test is most sensitive?

Coeliac disease is associated with HLA-DQ2 and HLA-DQ8. The most sensitive/specific serological test is anti-tissue transglutaminase (anti-tTG) IgA, with total IgA measured to exclude deficiency. Endomysial antibodies (EMA) are a confirmatory test.

What must a patient do before coeliac serology and biopsy, and what is the gold-standard diagnostic finding?

The patient must be consuming gluten (e.g. >1 meal/day) for at least 6 weeks before testing, otherwise results may be falsely negative. The gold standard is duodenal biopsy showing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.

Name the classic complications and associated conditions of coeliac disease.

Complications: iron/folate/B12 deficiency anaemia, osteoporosis, hyposplenism, dermatitis herpetiformis, and enteropathy-associated T-cell lymphoma (EATL) and small bowel adenocarcinoma. Associations: type 1 diabetes, autoimmune thyroid disease, and IgA deficiency.

What is the UK bowel cancer screening programme, and which test does it use?

The faecal immunochemical test (FIT), which detects human haemoglobin, is offered every 2 years to adults within the screening age range (now being extended down to age 50-74). A positive FIT leads to colonoscopy.

What inherited syndromes predispose to colorectal cancer, and what are their key features?

Familial adenomatous polyposis (FAP): APC gene mutation, hundreds-to-thousands of adenomas, near-100% cancer risk, prophylactic colectomy. Lynch syndrome (HNPCC): mismatch repair gene mutations (MSH2, MLH1), microsatellite instability, right-sided tumours, and extracolonic cancers (endometrial).

How does the location of colorectal cancer influence its presentation?

Right-sided (caecum/ascending) tumours present later with iron-deficiency anaemia, weight loss and an abdominal mass. Left-sided/sigmoid tumours present earlier with change in bowel habit, PR bleeding/blood mixed with stool, and obstruction (narrower lumen, more formed stool).

Compare the typical presentations of upper versus lower GI bleeding.

Upper GI bleed (proximal to ligament of Treitz): haematemesis, 'coffee-ground' vomit, and melaena (black tarry stool); often a raised urea:creatinine ratio. Lower GI bleed: fresh/dark red blood per rectum (haematochezia), usually with a normal urea.

What is the difference between diverticulosis, diverticular disease, and diverticulitis?

Diverticulosis: presence of asymptomatic diverticula (mucosal outpouchings). Diverticular disease: diverticula causing symptoms (e.g. pain). Diverticulitis: inflammation/infection of diverticula, presenting with left iliac fossa pain, fever and raised inflammatory markers ('left-sided appendicitis').

What are the common causes of significant lower GI bleeding in older adults?

Diverticular disease (the most common cause of major lower GI bleeding), angiodysplasia, colorectal cancer/polyps, ischaemic colitis, and haemorrhoids. Most diverticular bleeds stop spontaneously.

What dose-independent mechanism causes paracetamol hepatotoxicity, and what is the antidote?

Paracetamol overdose saturates normal conjugation pathways; excess is metabolised by CYP450 to the toxic intermediate NAPQI, which depletes glutathione and causes centrilobular hepatic necrosis. The antidote is N-acetylcysteine, which replenishes glutathione.

Which criteria identify a paracetamol-poisoned patient who needs transfer for liver transplantation (King's College Criteria)?

Arterial pH < 7.3 after resuscitation; OR all three of: prothrombin time > 100 s (INR > 6.5), creatinine > 300 µmol/L, and grade III/IV hepatic encephalopathy. These predict poor outcome without transplantation.

Define acute liver failure and list its cardinal features.

Acute liver failure is the rapid development of hepatic dysfunction (coagulopathy, INR ≥ 1.5) with hepatic encephalopathy in a patient without pre-existing chronic liver disease. Cardinal features: jaundice, coagulopathy, encephalopathy, and often cerebral oedema and multi-organ failure.

What are the components and significance of the Child-Pugh score in cirrhosis?

It grades cirrhosis severity using 5 variables: bilirubin, albumin, INR (prothrombin time), ascites, and encephalopathy. Classes A, B and C reflect increasing severity and predict surgical risk and mortality.

What does the MELD score predict, and which variables does it use?

The MELD (Model for End-stage Liver Disease) score predicts 3-month mortality and prioritises liver transplant allocation. It uses serum bilirubin, creatinine, INR, and (in MELD-Na) serum sodium.

How is hepatic encephalopathy managed, and what precipitants should be sought?

First-line: lactulose (reduces ammonia absorption, aim for 2-3 soft stools/day), with rifaximin added for recurrence. Precipitants to identify/treat: GI bleeding, infection (including SBP), constipation, dehydration, electrolyte disturbance, sedatives, and high protein load.

What is spontaneous bacterial peritonitis, how is it diagnosed, and how treated?

Infection of ascitic fluid without an obvious surgical source. Diagnosis: ascitic neutrophil (PMN) count > 250 cells/mm³. Treatment: IV broad-spectrum antibiotics (e.g. cefotaxime) plus IV albumin to reduce hepatorenal syndrome. Prophylaxis with a quinolone follows.

Contrast the serology of acute hepatitis B, chronic hepatitis B, and immunity from vaccination.

Acute HBV: HBsAg positive, IgM anti-HBc positive. Chronic HBV: HBsAg positive > 6 months, IgG anti-HBc positive. Vaccination immunity: anti-HBs positive ALONE (anti-HBc negative). Natural past infection: anti-HBs and anti-HBc both positive.

What does the presence of hepatitis B 'e' antigen (HBeAg) indicate?

HBeAg positivity indicates active viral replication and high infectivity. Seroconversion to anti-HBe with loss of HBeAg suggests reduced replication, although 'precore mutant' HBV can have high viral load despite being HBeAg-negative.

How is chronic hepatitis C diagnosed and treated, and what is the cure target?

Diagnosis: anti-HCV antibody screening, confirmed by HCV RNA (PCR) for active infection; genotype guides therapy. Treatment is with direct-acting antivirals (DAAs) for 8-12 weeks. Cure = sustained virological response (SVR): undetectable HCV RNA 12 weeks after treatment.

Compare primary biliary cholangitis and primary sclerosing cholangitis (autoantibodies, sex, associations).

PBC: anti-mitochondrial antibody (AMA) positive, predominantly middle-aged women, intrahepatic small bile duct destruction, associated with other autoimmune disease; treat with ursodeoxycholic acid. PSC: p-ANCA may be positive (AMA negative), more common in men, intra- and extra-hepatic 'beaded' strictures on MRCP, strongly associated with ulcerative colitis and cholangiocarcinoma.

What are the diagnostic hallmarks of autoimmune hepatitis?

Raised transaminases (hepatitic picture), raised IgG, and positive autoantibodies: ANA and anti-smooth muscle antibody (type 1), or anti-LKM-1 (type 2). Liver biopsy shows interface hepatitis. It responds to corticosteroids and azathioprine.

What are the key features and diagnostic findings of hereditary haemochromatosis?

An autosomal recessive HFE (C282Y) gene disorder causing iron overload. Features: fatigue, arthralgia, bronze skin, diabetes ('bronze diabetes'), cardiomyopathy, hypogonadism, cirrhosis. Findings: raised ferritin and transferrin saturation (> 45%); treat with venesection.

How is Wilson's disease diagnosed and treated?

A defect in copper excretion (ATP7B gene). Findings: low serum caeruloplasmin, raised urinary copper, Kayser-Fleischer rings, neuropsychiatric and hepatic disease, typically in young patients. Treatment: copper chelation with penicillamine (or trientine) and zinc.

What enzyme deficiency causes alpha-1 antitrypsin deficiency liver and lung disease, and what is the inheritance?

Deficiency of the protease inhibitor alpha-1 antitrypsin (PiZZ phenotype most severe). Misfolded protein accumulates in hepatocytes causing cirrhosis, while lack of the enzyme in lungs leads to early panacinar (basal) emphysema. It is autosomal codominant inheritance.

State the modified Glasgow (Imrie) criteria mnemonic for severity in acute pancreatitis.

PANCREAS: PaO2 < 8 kPa; Age > 55; Neutrophils (WCC > 15); Calcium < 2 mmol/L; Renal (urea > 16 mmol/L); Enzymes (LDH > 600, AST > 200); Albumin < 32 g/L; Sugar (glucose > 10 mmol/L). A score ≥ 3 within 48 h indicates severe pancreatitis.

What are the two most common causes of acute pancreatitis, and how is it diagnosed?

Gallstones and alcohol (the 'GET SMASHED' mnemonic lists others). Diagnosis requires 2 of 3: characteristic epigastric pain radiating to the back; serum amylase or lipase > 3 times the upper limit of normal; and characteristic imaging (CT/US). Lipase is more specific and stays elevated longer.

What is the cornerstone of management of acute pancreatitis?

Aggressive IV fluid resuscitation, analgesia, oxygen, and enteral nutrition as tolerated. There is no role for routine prophylactic antibiotics; antibiotics are reserved for confirmed infected necrosis. ERCP is indicated for gallstone pancreatitis with cholangitis/obstruction.

What triad characterises chronic pancreatitis, and how is exocrine insufficiency managed?

The classic triad: abdominal pain, diabetes (endocrine failure), and steatorrhoea (exocrine failure). Pancreatic calcification may be seen on imaging. Exocrine insufficiency is treated with pancreatic enzyme replacement (e.g. Creon) and fat-soluble vitamin supplementation (A, D, E, K).

What test assesses pancreatic exocrine function in suspected chronic pancreatitis?

Faecal elastase-1: a low level indicates pancreatic exocrine insufficiency. It is a simple, non-invasive marker that remains stable during gut transit and is unaffected by enzyme supplementation.

Define Charcot's triad and Reynolds' pentad in ascending cholangitis.

Charcot's triad: right upper quadrant pain, fever (with rigors), and jaundice. Reynolds' pentad adds hypotension (septic shock) and confusion (altered mental status), indicating severe suppurative cholangitis requiring urgent biliary decompression (e.g. ERCP).

Distinguish biliary colic, acute cholecystitis, and ascending cholangitis.

Biliary colic: RUQ pain after fatty meals, no fever, normal inflammatory markers (cystic duct transiently obstructed). Acute cholecystitis: persistent RUQ pain, fever, positive Murphy's sign, raised inflammatory markers (gallbladder inflammation). Cholangitis: pain, fever and jaundice (Charcot's triad) due to infected obstructed common bile duct.

What is refeeding syndrome, and which electrolyte abnormality is its hallmark?

A potentially fatal shift in fluids/electrolytes when feeding is reintroduced after starvation; insulin surge drives intracellular uptake of phosphate, potassium and magnesium. The hallmark is hypophosphataemia. Also seen: hypokalaemia, hypomagnesaemia, and thiamine deficiency.

How is refeeding syndrome prevented in a high-risk patient?

Identify high-risk patients (e.g. BMI < 16, little intake > 10 days, low baseline K/Mg/PO4); start feeding at a low rate (e.g. 10 kcal/kg/day) and increase slowly; supplement electrolytes (phosphate, potassium, magnesium); and give thiamine and B vitamins before and during refeeding.

When is parenteral nutrition indicated over enteral nutrition?

Enteral nutrition ('if the gut works, use it') is always preferred. Parenteral nutrition is reserved for a non-functioning, inaccessible, or perforated GI tract — e.g. prolonged ileus, short bowel syndrome, high-output fistula, or severe malabsorption — where enteral feeding is impossible or unsafe.