Lecture ILO’s Flashcards

Question

Gastro oesophageal reflux disease

Answer 1

• Dysfunction of lower oesophageal sphincter • Causes reflux of food from stomach to lower oesophagus • Risk Factors – Hiatus hernia, Obesity, Gastric acid hypersecretion, smoking, alcohol, pregnancy, systemic sclerosis, H.Pylori, surgery in achalasia, Drugs (TCA, nitrates) • If recurrent can lead to: – Oesophagitis – Baretts Oesophagus (metaplasia of lower oesophagus) – Oesophageal stricture

Answer 2

- Metaplasia of cells of lower oesophagus from squamous epithelium to columnar epithelium (mucus secreting) Complete surveillance OGD’s to check not getting ademocarcinoma

Answer 3

– Inflammatory Bowel Disease mainly describes two conditions: Crohn’s Disease and Ulcerative Colitis – Long-term conditions involving inflammation of the bowel – Ulcerative Colitis only affects the colon (large intestine), whereas Crohn’s can affect anywhere from the mouth to the anus

Answer 4

– Diarrhoea/urgency – Weight loss/failure to thrive – Abdominal pain and tenderness – Fever – Malaise – Anorexia – Unlike in ulcerative colitis, there is unaffected bowel between areas of active disease – skip lesions (diseased part then normal part)

Answer 5

– Bloods: FBC, ESR, CRP, U&E, LFT, INR, Ferritin, TIBC, B12, Folate – Stool: MC&S and CDT (infection) – Colonoscopy and rectal biopsy: even if mucosa looks normal, biopsy is needed – Small bowel enema: detects ileal disease – Barium enema: cobblestoning, ‘rose-thorn’ ulcers +/- colon strictures (common exam question) – Colonoscopy is used to establish disease extent – MRI can assess pelvic disease

Answer 6

– Small Bowel Enema: high sensitivity and specificity for examination of the terminal ileum – Strictures: Kantor’s string sign is the string-like appearance of a contrast-filled bowel loop caused by severe narrowing – Proximal bowel dilation – ‘Rose-thorn’ ulcers – Fistulae – A colonoscopy will show diffuse erythema with deep ulcers in a patchy distribution

Answer 7

– Stop smoking!!! – To induce remission: 1. IV hydrocortisone 2. Budesonide (if hydrocortisone give bad side effects) 3. Mesalazine – To maintain remission: 1. Azathioprine or Mercaptopurine 2. Methotrexate 3. Infliximab/adalimumab

Answer 8

– Stop smoking!!! – To induce remission: 1. IV hydrocortisone 2. Budesonide 3. Mesalazine

Answer 9

1. Azathioprine or Mercaptopurine (immunosuppressive) 2. Methotrexate 3. Infliximab/adalimumab

Answer 10

– Under specialist supervision, monoclonal antibody therapies, adalimumab and infliximab, are options for the treatment of severe, active Crohn's disease, following inadequate response to conventional therapies. – Adalimumab and infliximab can be used as monotherapy or combined with an immunosuppressant although there is uncertainty about the comparative effectiveness and long-term side-effects of therapy. – Side effects: numbness or tingling, vision problems, leg weakness, chest pain, shortness of breath, new joint pain, hives and itching.

Answer 11

– ~80% Crohn’s patients will eventually have surgery – ileocaecal resection (usually worst affected part) – About half of all patients who undergo surgery will develop recurrent disease within ten years

Answer 12

– Bloody diarrhoea – Urgency – Tenesmus (rectus pain) – Abdominal pain, especially in the left lower quadrant – Extra-intestinal features include: – Arthritis – Uveitis (painful, red eye) – Primary Sclerosing Cholangitis

Answer 13

– Bloods: FBC, ESR, CRP, U&E, LFT, Blood Culture – Stool: MC&S and CDT – Abdominal X-ray: No faecal shadows – Chest X-ray: Perforation – Barium enema: Do not do during severe attacks or for diagnosis – Colonoscopy: Shows disease extent and allows for biopsy

Answer 14

– Loss of haustrations – featureless , superficial ulceration, pseudopolyps – Long-standing disease: colon is narrow and short a.k.a drainpipe colon – Sacroiliitis – Whole colon, without skips, irregular mucosa, loss of normal haustra markings

Answer 15

Common EQ Mild <4 stools a day +/- blood No systemic symptoms Normal ESR and CRP Moderate 4-6 stools a day with moderate rectal bleeding Minimal systemic symptoms e.g. temperature of 37.1- 37.8, HR of 70-90bpm, Hb of 105-110g/L Severe 6 stools a day with severe rectal bleeding Fever of >37.8, tachycardia >90bpm, Hb <105 g/L abdominal tenderness, distension, decreased bowel sounds Hypoalbuminemia Moderate: Topical 5-ASA +/- Oral 5-ASA +/- Oral Steroids -> Treat as severe if no better in 2 weeks Severe: Admit, IV Hydrocortisone, IV Fluids -> Step-down to oral when well

Answer 16

– To induce remission: 1. Oral aminosalicyates – mesalazine, sulfasalazine 2. Distal disease: rectal mesalazine – To maintain remission: 1. Oral mesalazine 2. Azathioprine

Answer 17

Acute pancreatitis

Answer 18

Pathology Crohns disease Lesions anywhere from mouth -> anus ‘Skip’ lesions Ulcerative colitis Inflammation always starts at the rectum and never spreads beyond the ileocaecal valve Continuous Disease

Answer 19

Histology Crohn’s disease Inflammation in all layers from mucosa to serosa Increased goblet cells Granulomas Ulcerative colitis No inflammation beyond submucosa Depletion of goblet cells and mucin Granulomas are infrequent

Answer 20

Endoscopy Crohn’s disease Deep ulcers Skip lesions – cobblestone appearance Ulcerative colitis Widespread ulceration with preservation of adjacent mucosa - pseudopolyps

Answer 21

Features Crohn’s disease Diarrhoea (non-bloody) Weight loss Mouth ulcers Perianal disease Mass in RIF Ulcerative colitis Bloody Diarrhoea Tenesmus – cramping rectal pain Abdominal pain in LLQ

Answer 22

Crohn’s disease Extra-Intestinal Gallstones – secondary to reduced bile acid reabsorption Oxalate renal stones Ulcerative colitis Primary sclerosing cholangitis – chronic liver disease with ++ pain

Answer 23

Complications Crohn’s disease Bowel obstruction Fistula Colorectal cancer Ulcerative colitis Risk of colorectal cancer increased in ulcerative colitis

Answer 24

– Stoma formation (ileostomy or colostomy) - this may be needed after an operation to remove part of the bowel – Persistent blood loss causing anaemia – Perforation of the bowel wall – Narrowing of the bowel causing obstruction (stricture), more common with Crohn's disease. – Ulceration and abnormal passages (fistulae) around the anus – Severe dilatation of the colon - called toxic megacolon, this is more common with ulcerative colitis than Crohn's disease – Greatly reduced absorption of food from the bowel -> malnutrition – Increased risk of bowel cancer, especially in ulcerative colitis

Answer 25

Ulcerative colitis

Answer 26

– C. Barium follow through

Answer 27

– E. More than six bowel motions per day with large amounts of rectal bleeding

Answer 28

Ulcerative colitis

Answer 29

– A. Cigarette smoking reduces incidence

Answer 30

– B. Topical 5-ASA +/- Oral 5-ASA +/- Oral steroids + discharge

Answer 31

O Common condition affecting the digestive system O Symptoms: O Abdominal cramping O Bloating O Flatulence O Diarrhoea O Constipation

Answer 32

O Mixed group of abdominal symptoms with no clear organic cause O The specific cause of IBS is currently unknown, but it has been linked to: O Food passage being too fast/slow O Oversensitive nerves in the large intestine O Stress O Family history of IBS

Answer 33

Common Exa Question O Consider IBS if >6 months of O Abdominal pain, and/or O Bloating, and/or O Change in bowel habit O Remember: ABC O Positive diagnosis if abdominal pain is relieved by defecation or is associated with altered bowel frequency/stool form plus 2/4 of: O Altered stool passage (straining, incomplete) O Abdominal bloating/distension O Symptoms worse with eating O Passage of mucus

Answer 34

O Coeliac Disease O Inflammatory Bowel Disease O Crohn’s Disease O Ulcerative Colitis O Cancer O Ovarian Cancer O Bowel Cancer

Answer 35

O Rectal bleeding O Unexplained weight loss O Family history of bowel/ovarian cancer O If onset is >60 years old

Answer 36

A: CA125 ?Ovarian Cancer Tumour marker blood test

Answer 37

O Full Blood Count O Erythrocyte Sedimentation Rate O C-Reactive Protein O Liver Function Tests O Tissue Transglutaminase Antibodies O Coeliac Screen

Answer 38

O Upper GI Endoscopy – Dyspepsia, Reflux O Small Bowel Radiology – Crohn’s O Duodenal Biopsy – Coeliac disease O Giardia Tests – Can trigger IBS O ERCP/MRCP - Pancreatitis

Answer 39

O Patient may need referral to various specialties; gastro, surgery, dieticians, psychology, dermatology, pain clinic O If diagnosis is unclear O If changing symptoms in established IBS O Rectal mucosal prolapse O Food intolerance O Stress/Depression O Chronic pain

Answer 40

O Diarrhoea-predominant (D-IBS) – may require further testing if ?small bowel disease, O Constipation-predominant (C-IBS), and O Alternating constipation and diarrhoea (A- IBS).

Answer 41

O No known cure – treatment is rarely even 50% successful. Management aims to reduce symptoms O Initial therapy should always be with lifestyle modification – centrally surrounding diet O If lifestyle modifications alone are unsuccessful, targeted pharmacological approaches can be used

Answer 42

O Regular meals – eaten slowly O Avoid missing meals/having long gaps between meals O 8 cups of liquid a day – water/uncaffeinated drinks O Restrict tea, coffee, alcohol and fizzy drinks O Limit fresh fruit to 3/day O To reduce wind and bloating, increase intake of oats

Answer 43

O First-line pharmacological treatment is according to the predominant symptom: O Pain: Antispasmodic agents O Constipation: Laxatives O Diarrhoea: Loperamide

Answer 44

O Avoid insoluble fibre, such as bran – as it can worsen flatulence and bloating O Bisacodyl and sodium picosulfate can aid constipation relief O Ispaghula (fibre gel) should be used instead of lactulose, as lactulose can increase gas production O For patients with constipation who are not responding to conventional laxatives, consider Linaclotide if: O Maximum tolerated doses of previous laxatives from different classes have not helped, AND O Constipation has been present for 12 months

Answer 45

O Avoid sorbitol sweeteners O Bulking agents – limited evidence O Loperamide 2mg after each loose stool – max. 16mg/day O Side effects: O Colic O Bloating O Ileus

Answer 46

O Oral antispasmodics, e.g: O Mebeverine 135mg/8hr (OTC) O Alverine Citrate 60-120mg/8hr O Dicycloverine 10-20mg/8hr O Can also add simeticone – this is found in Imodium Plus!

Answer 47

• Defecation that is unsatisfactory because of infrequent stools, difficulty in passing stools or sensation of incomplete emptying • Bowel movement less than 3 times a week Can be : • Short term • Chronic constipation - > 3months • Faecal impaction – retention of faeces

Answer 48

Acute <14 days – usually bacteria, viral, food , anxiety Persistent >14 days - Chronic > 4 weeks – IBS, Diet, IBD, Coeliac , bowel cancer SICK day rules- stoping medication due to kidney function

Answer 49

Noravirus • Diarrhoea and projectile vomiting • “Winter vomiting bug” • Most common cause of viral gastroenteritis • Outbreaks typically occur in semi-closed communities e.g. Care homes, cruise ships • Causes watery diarrhoea with vomiting, fever, abdominal pain Rotavirus

Answer 50

Endoscopy with duodenal-jejunal biopsy Tissue transglutaminase autoantibodies

Answer 51

Symptoms: Epigastric pain, radiates to back, eased lying forward, pain typically relapse and remit – Symptoms of malabsorption (reduced pancreatic enzyme secretion): Bloating, steatorrhoea, weight loss

Answer 52

Causes – Commonest: Alcohol – Rarer causes: Cystic fibrosis, familial, haemochromatosis, pancreatic duct destruction (stones, tumor), Hyperparathyroidism

Answer 53

Exocrine (digestive tissue approx 90%) Endocrine (blood glucose tissue approx 10%)

Answer 54

1) Hepatic Steatosis - Accumulation of fat globules within hepatocytes 2) Steatohepatitis -Necrosis of hepatocytes -Neutrophil-dominant inflammatory reaction -Mallory bodies: Eosinophilic accumulations -Continued exposure causes development of fibrosis mainly around central vein (initially) 3)Fibrosis and Cirrhosis -Irreversible architectural disturbance -Normal liver architecture replaced by nodules of regenerated liver cells separated by bands of collagenous fibrosis

Answer 55

• Protein synthesis • Carbohydrate Metabolism • Lipid metabolism • Degradation of Ammonia -> urea • Formation and excretion of bilirubin • Hormone inactivation e.g. insulin, oestrogen • Immunological functions • Drug metabolism

Answer 56

Blood Supply • The liver receives blood from two different sources • Hepatic portal vein 2/3 : carries venous blood from the intestines, pancreas and spleen. • Hepatic artery 1/3 : brings oxygenated blood to the liver. • With the bile duct, these two blood vessels form the portal triad.

Answer 57

• Increased hydrostatic pressure: – portal hypertension + splanchnic vasodilation • Salt and Water retention • Reduced oncotic pressure: – Hypoproteinaemia • Treatment: – Salt and fluid restriction – Propanol – Ascitic tap – Oral diuretic (Spironalactone- 100mg/day, Furosemide- 40mg/day – Large volume paracentesis (with Albumin) – TIPSS for refractory ascites

Answer 58

Oesophageal varices

Answer 59

• Ammonia toxic to brain cells • Precipitated by: • sedatives, constipation, dehydration, infection, GI bleed, TIPSS • Treatment: • Treat underlying cause • Lactulose + daily enemas(aim for 3 bowel motions/day) • Rifaximin (non-absorbitive antibiotic, reduces gut bacteria and hence gut ammonia production): Can be used in second episode encephalopathy

Answer 60

Acute liver failure is a syndrome of acute liver dysfunction without underlying chronic liver disease. ALF is characterised by the presence of coagulopathy (INR > 1.5) and hepatic encephalopathy. This is usually accompanied by transaminitis (i.e. deranged liver function tests ALT/AST) and hyperbilirubinaemia. ALF is usually initiated following a severe acute liver injury (ALI).

Answer 61

Hyperacute: HE within 7 days of noticing jaundice. Best prognosis as much better chance of survival and spontaneous recovery. Acute: HE within 8-28 days of noticing jaundice Subacute: HE within 5-12 weeks of noticing jaundice (ALF may be defined up to 28 weeks). Worst prognosis as usually associated with shrunken liver and limited chance of recovery.

Answer 62

Viruses (A, B, E) Paracetamol Non-paracetamol medications (e.g. Statins, Carbamazepine, Ecstasy) Toxin-induced (e.g. Amanita phalloides - death cap mushroom that contains amatoxins and phallotoxins) Budd-chiari syndrome Pregnancy-related (e.g. fatty liver of pregnancy, HELLP syndrome) Autoimmune hepatitis Wilson’s disease

Answer 63

ALF is characterised by jaundice, confusion and coagulopathy.

Answer 64

Coeliac disease is an autoimmune condition triggered by eating gluten. It can develop at any age and is thought to be caused by genetic and environmental factors. There is a link with other autoimmune conditions, particularly type 1 diabetes and thyroid disease. TOM TIP: Remember for your exams that we test all new cases of type 1 diabetes and autoimmune thyroid disease for coeliac disease, even if they do not have symptoms.

Answer 65

In patients with coeliac disease, autoantibodies are created in response to exposure to gluten. These autoantibodies target the epithelial cells of the small intestine, leading to inflammation. These antibodies relate to disease activity and will rise with more active disease and may disappear with effective management. There are three antibodies related to coeliacs (particularly worth remembering the first two): • Anti-tissue transglutaminase antibodies (anti-TTG) • Anti-endomysial antibodies (anti-EMA) • Anti-deamidated gliadin peptide antibodies (anti-DGP) Inflammation affects the small bowel, particularly the jejunum. The surface of the small intestine is covered in projections called villi, which increase the surface area and help with nutrient absorption. Coeliac disease causes atrophy of the intestinal villi, resulting in malabsorption.

Answer 66

Presentation Coeliac disease is often asymptomatic and is under-diagnosed, so have a low threshold for testing for coeliac disease in patients where it is suspected. Presenting symptoms can include: • Failure to thrive in young children • Diarrhoea • Bloating • Fatigue • Weight loss • Mouth ulcers Dermatitis herpetiformis is an itchy, blistering skin rash, typically on the abdomen, caused by coeliac disease. Anaemia occurs secondary to malabsorption and deficiency of iron, B12 or folate. Rarely coeliac disease can present with neurological symptoms: ○ Peripheral neuropathy ○ Cerebellar ataxia ○ Epilepsy

Answer 67

Diagnosis The patient must continue eating gluten while being investigated. Antibodies and histology may be normal if the patient is gluten-free. The first-line blood tests are: • Total immunoglobulin A levels (to exclude IgA deficiency) • Anti-tissue transglutaminase antibodies (anti-TTG) Anti-endomysial antibodies (anti-EMA) are a second-line option where there is doubt (e.g., a borderline result). TOM TIP: Initial anti-TTG and anti-EMA antibody tests are IgA. Some patients have an IgA deficiency. When you test for these antibodies, it is important to test for total immunoglobulin A levels because if the total IgA level is low, the antibody test will be negative, even in a patient with coeliac disease. In this circumstance, you can test for the IgG version of anti-TTG or anti-EMA antibodies. Patients with a positive antibody test are referred to a gastroenterologist to confirm the diagnosis by endoscopy and jejunal biopsy. Typical biopsy findings are: ○ Crypt hyperplasia ○ Villous atrophy

Answer 68

Complications If someone with coeliac disease continues eating gluten, even in tiny amounts, it can lead to: • Nutritional deficiencies • Anaemia • Osteoporosis • Hyposplenism (with immunodeficiency, particularly to encapsulated bacteria such as Streptococcus pneumoniae) • Ulcerative jejunitis • Enteropathy-associated T-cell lymphoma (EATL) • Non-Hodgkin lymphoma • Small bowel adenocarcinoma

Answer 69

Crohn’s Disease • Chronic inflammatory disorder characterised by patchy, transmural inflammation of intestinal mucosa • Can affect any part of the gastrointestinal tract from mouth to anus • Skip lesions are the main identifier • Inflammation is found in all layers from mucosa to serosa, with increased goblet cells and granulomas C - Cobblestone appearance R - Rosethorn ulcers O - Obstruction H - Hyperplasia of lymph nodes N - Narrowing of lumen S - Skip lesions N – No blood or mucus (less common) E – Entire GI tract S – “Skip lesions” on endoscopy T – Terminal ileum most affected and Transmural (full thickness) inflammation S – Smoking is a risk factor (don’t set the nest on fire)

Answer 70

Macroscopic = seen on endoscopy • Cobblestone appearance - caused by superficial ulcers which become deep and sepiginous (wavy margin) • Bowel wall thickening • Lumen narrowing • Deep ulcers • Fistulae • Fissures Microscopic = seen on histology • Inflammatory infiltration: ○ Hyperplasia of lymph nodes ○ Granulomas • Skip lesions • Transmural ulceration (from mucosa to serosa) • Increased goblet cells

Answer 71

Complications • Bowel obstruction (stricture) ○ Thickened wall of intestines causes narrowing of the bowel ○ This is more common in Crohn's than UC • Fistula ○ Inflammation goes through the wall and creates tunnels ○ Abnormal passage between 2 organs or an organ and the outside of your body ○ Can become infected • Abscesses ○ Swollen, pus-filled pockets of infection in intestinal walls • Anal fissures ○ Small tears in the anus that may cause itching, pain or bleeding • Ulcers • Malnutrition • Inflammation in other areas of the body • Colorectal cancer

Answer 72

Presentation Symptoms Nausea & vomiting Fatigue Low-grade fever Weight loss Abdominal pain Diarrhoea (+/- blood) Rectal bleeding Perianal disease Signs Pyrexia Dehydration Angular stomatitis Aphthous ulcers Pallor Tachycardia Hypotension Abdominal pain, mass and distension

Answer 73

Inducing Remission • First line: Steroids (e.g. oral prednisolone or IV hydrocortisone) • If steroids alone don’t work, consider adding immunosuppressant medication under specialist guidance: ○ Azathioprine ○ Mercaptopurine ○ Methotrexate ○ Infliximab ○ Adalimumab • Apply nutritional alterations ○ Exclusive enteral nutrition (EEN) is a liquid diet that excludes all food + drink expect water. ○ Supplement drink at 25kcal/kg/day ○ 1g/kg/day of protein

Answer 74

Maintaining Remission • Tailored to individual patients based on risks, side effects, nature of the disease and patient’s wishes. It is reasonable not to take any medications whilst well. • First line = thiopurines: ○ Work through purine synthesis inhibition in lymphocytes -> immunosuppressive properties ○ E.g.Mercaptopurine + Azathioprine ○ SE: pancreatitis + hepatotoxicty • Alternatives: ○ Methotrexate ▪ Inhibits dihydrofolate reductase ▪ Immunomodulatory + anti-inflammatory properties ▪ SE: bone marrow suppression, hepatotoxicity + pulmonary toxicity ○ Monoclonal antibodies ▪ E.g. Infliximab + Adalimumab ▪ SE: numbness/tingling, vision problems, leg weakness, chest pain, SOB, new joint pain, hives/itching

Answer 75

Surgery • Ileocaecal resection = when the disease only affects the distal ileum it is possible to surgically resect this area and prevent further flares of the disease. ○ Often recurs within 10 years • Stoma ○ May be needed after an operation to remove part of the bowel ○ Colostomy = created with loop of large intestine, solid waste ○ Ileostomy = created with end of small intestine, liquid waste + undigested food • Surgery can also be used to treat strictures and fistulas secondary to Crohns disease.

Answer 76

UC is a disease of the colonic mucosa, which has a relapsing-remitting course. It is characterised by inflammation of the mucosa, affecting the rectum (rectal sparing occurs but is rare) and may progress proximally through the colon. The terminal ileum may be affected ('backwash ileitis') in those with extensive colitis.

Answer 77

Diagnosis is based on macroscopic assessment (e.g. endoscopy) and histological evidence (e.g. biopsy) of colonic inflammation. Imaging Abdominal X-rays are useful for looking at dilatation of the bowel and perforations. Dilatation is said to be present if: • Small bowel: diameter > 3cm • Large bowel: diameter > 6cm • Caecum: diameter > 9cm Computed tomography may be organised where there is concern regarding complications (e.g. toxic megacolon) and prior to surgery. Endoscopy Colonoscopy is considered the diagnostic investigation of choice as it allows assessment of the whole colon. Biopsies can be taken for histological assessment of the mucosa. Caution should be taken during acute flares due to the increased risk of perforation. Sigmoidoscopy may be used as an alternative endoscopic test.

Answer 78

Presentation: The hallmark of UC is bloody diarrhoea / rectal bleeding. Patients with UC may become acutely unwell with features of hypovolaemic shock, so it is important to resuscitate patients with respect to airway, breathing and circulation. Symptoms • Weight loss • Fatigue • Abdominal pain • Loose stools • Rectal bleeding • Tenesmus (incomplete emptying) • Urgency Signs • Febrile • Pale • Dehydrated • Abdominal tenderness • Abdominal distension/mass • Tachycardic, hypotensive

Answer 79

Extra-colonic manifestations Approximately 25% of patients will develop extra-colonic manifestations during their lifetime. Musculoskeletal Arthritis is the most common extracolonic manifestation, which may be a simple peripheral arthritis or more complex spondyloarthropathy (e.g. ankylosing spondylitis). Eyes, mouth & skin Uveitis (inflammation of the uvea) is strongly associated with UC. Extracolonic manifestations of the mouth commonly include aphthous ulcers. The skin is another organ widely affected by UC, leading to erythema nodosum, which is a type of panniculitis that classically results in multiple, painful, purple nodules on the anterior aspect of the shins. Hepatobiliary Numerous hepatobiliary pathologies are associated with UC including fatty liver disease and autoimmune liver disease. Haematological Two common haematological problems associated with UC are anaemia and thromboembolism.

Answer 80

Acute gastritis is inflammation of the stomach and presents with nausea and vomiting. Enteritis is inflammation of the intestines and presents with diarrhoea. Gastroenteritis is inflammation all the way from the stomach to the intestines and presents with nausea, vomiting and diarrhoea.

Answer 81

A sample of the faeces can be tested with microscopy, culture and sensitivities to establish the causative organism and antibiotic sensitivities. Assess patients for dehydration. Attempt a fluid challenge and if they are able to tolerate oral fluid and are adequately hydrated consider outpatient management. If not vomiting and tolerated then rehydration solutions (e.g. dioralyte) can be used. If dehydrated then intravenous fluids can be used to rehydrate them and prevent dehydration until oral intake is adequate again. Slowly introduce a light diet in small quantities once oral intake is tolerated again. Advise them to stay off work or school for 48 hours after symptoms have completely resolved. Antidiarrhoeal medication such as loperamide and antiemetic medication such as metoclopramide are generally not recommended but may be useful for mild to moderate symptoms. Antidiarrhoeals should be avoided in e. coli 0157 and shigella infections and where there is bloody diarrhoea or high fever. Antibiotics should only be given in patients that are at risk of complications and once the causative organism is confirmed.

Answer 82

Post-Gastroenteritis Complications There are possible post-gastroenteritis complications: • Lactose intolerance • Irritable bowel syndrome • Reactive arthritis • Guillain–Barré syndrome

Answer 83

Viral Gastroenteritis Viral gastroenteritis is the most common. Viral gastroenteritis is highly contagious. • Rotavirus • Norovirus • Adenovirus is a less common cause and presents with a more subacute diarrhoea

Answer 84

E. coli Escherichia coli (E. coli) is a normal intestinal bacteria. Only certain strains cause gastroenteritis. It is spread through contact with infected faeces, unwashed salads or water. E. coli 0157 produces the Shiga toxin. This causes abdominal cramps, bloody diarrhoea and vomiting. The Shiga toxin destroys blood cells and leads to haemolytic uraemic syndrome(HUS). The use of antibiotics increases the risk of haemolytic uraemic syndrome therefore antibiotics should be avoided if E. coli gastroenteritis is considered.

Answer 85

Campylobacter Jejuni Campylobacter is a common cause of travellers diarrhoea. It is the most common bacterial cause of gastroenteritis worldwide. Campylobacter means “curved bacteria”. It is a gram negative bacteria that is curved or spiral shaped. It is spread by: ○ Raw or improperly cooked poultry ○ Untreated water ○ Unpasteurised milk Incubation is usually 2-5 days. Symptoms resolve after 3-6 days. Symptoms are: § Abdominal cramps § Diarrhoea often with blood § Vomiting § Fever Antibiotics can be considered after isolating the organism where patients have severe symptoms or other risk factors such as HIV or heart failure. Popular antibiotic choices are azithromycin or ciprofloxacin.

Answer 86

Shigella Shigella is spread by faeces contaminating drinking water, swimming pools and food. The incubation period is 1-2 days and symptoms usually resolve within 1 week without treatment. It causes bloody diarrhoea, abdominal cramps and fever. Shigella can produce the Shiga toxin and cause haemolytic uraemic syndrome. Treatment of severe cases is with azithromycin or ciprofloxacin.

Answer 87

Salmonella Salmonella is spread by eating raw eggs or poultry and food contaminated with infected faeces of small animals. Incubation is 12 hours to 3 days and symptoms usually resolve within 1 week. Symptoms are watery diarrhoea that can be associated with mucus or blood, abdominal pain and vomiting. Antibiotics are only necessary in severe cases and guided by stool culture and sensitivities.

Answer 88

Bacillus Cereus Bacillus cereus is a gram positive rod that is spread through inadequately cooked food. It grows well on food not immediately refrigerated after cooking. The typical food is fried rice left out at room temperature. Whilst growing on the food it produces a toxin called cereulide that causes abdominal cramping and vomiting within 5 hours of ingestion. When it arrives in the intestines it produces different toxins that cause a watery diarrhoea. This occurs more than 8 hours after ingestion. All of the symptoms usually resolves within 24 hours. Therefore the typical course is vomiting within 5 hours, then diarrhoea after 8 hours, then resolution within 24 hours. TOM TIP: The typical exam patient develops symptoms soon after eating leftover fried rice that has been left at room temperature. It has a short incubation period after eating the rice and they then recover within 24 hours. Examiners like this question because the course of bacillus cereus is easy to distinguish from the other causes of gastroenteritis. Side Note: The other place you may come across bacillus cereus is in intravenous drug users(IVDU) that develop infective endocarditis. Staphylococcus is the most common cause of IE in IVDUs but Bacillus cereus is one to keep in mind.

Answer 89

Yersinia Enterocolitica Yersinia is a gram-negative bacillus. Pigs are key carriers of Yersinia and eating raw or undercooked pork can cause infection. It is also spread through contamination with the urine or faeces of other mammal such as rat and rabbits. Yersinia most frequently affects children causing watery or bloody diarrhoea, abdominal pain, fever and lymphadenopathy. Incubation is 4-7 days and the illness can last longer than other causes of enteritis with symptoms lasting 3 weeks or more. Older children or adults can present with right-sided abdominal pain due to mesenteric lymphadenitis (inflammation in the intestinal lymph nodes) and fever which can give the impression of appendicitis. Antibiotics are only necessary in severe cases and guided by stool culture and sensitivities.

Answer 90

Staphylococcus aureus can produce enterotoxins when growing in food such as eggs, dairy and meat. When eaten these toxins cause small intestine inflammation. This causes symptoms of diarrhoea, perfuse vomiting, abdominal cramps and fever. These symptoms start within hours of ingestion and settle within 12-24 hours. It is not actually the bacteria causing the enteritis but the staphylococcus enterotoxin.

Answer 91

Giardiasis Giardia lamblia is a type of microscopic parasite. It lives in the small intestines of mammals. These mammals may be pets, farmyard animals or humans. It releases cysts in the stools of infected mammals. These cysts then contaminate food or water and are eaten to infect a new host. This is called faecal-oral transmission. Infection may not cause any symptoms or it may cause chronic diarrhoea. Diagnosis is made by stool microscopy. Treatment is with metronidazole.

Answer 92

Peptic ulcers involve ulceration of the mucosa of the stomach (gastric ulcer) or the proximal duodenum (duodenal ulcer). Duodenal ulcers are more common. Pathophysiology: The mucosa, also known as the mucous membrane, is the inner lining of the stomach and duodenum. It secretes mucus that coats the surface and forms a barrier that protects it from the stomach’s contents, particularly stomach acid and digestive enzymes. It secretes bicarbonate into this mucus coating to neutralise the stomach acid. Factors that disrupt the mucus barrier or increase stomach acid increase the risk of mucosal ulceration.

Answer 93

Risk Factors The risk key factors that disrupt the mucus barrier are: • Helicobacter pylori • Non-steroidal anti-inflammatory drugs (NSAIDs) The risk key factors that increase stomach acid are: • Stress • Alcohol • Caffeine • Smoking • Spicy foods The risk of bleeding from a peptic ulcer is increased with the use of: • Non-steroidal anti-inflammatory drugs (NSAIDs) • Aspirin • Anticoagulants (e.g., DOACs) • Steroids • SSRI antidepressants

Answer 94

Eating typically worsens the pain of gastric ulcers. The pain of duodenal ulcers tends to improve immediately after eating, followed by pain 2-3 hours later. Patients with gastric ulcers tend to lose weight due to the fear of pain on eating, whereas with duodenal ulcers, the weight is stable or increases.

Answer 95

Peptic ulcers present with non-specific symptoms of: • Epigastric discomfort or pain • Nausea and vomiting • Dyspepsia The signs of upper gastrointestinal bleeding are: ○ Haematemesis (vomiting blood) ○ Coffee ground vomiting ○ Melaena (black, tarry stools) ○ Fall in haemoglobin on a full blood count

Answer 96

Diagnosis Peptic ulcers can be diagnosed on endoscopy. During endoscopy, a rapid urease test (CLO test) can be performed to check for H. pylori. A biopsy is considered during endoscopy toexclude malignancy.

Answer 97

Management The core aspects of treating peptic ulcers are: • Stopping NSAIDs • Treating H. pylori infections • Proton pump inhibitors (e.g., lansoprazole or omeprazole) Repeat endoscopy (at 4-8 weeks) may be performed to ensure the ulcer heals.

Answer 98

Complications Bleeding from the ulcer is a common and potentially life-threatening complication. Perforation results in acute abdominal pain and peritonitis, requiring urgent surgical repair (usually laparoscopic). Scarring and strictures can lead to a narrowing of the exit of the stomach, causing difficulty in emptying the stomach contents. This is known as gastric outlet obstruction and presents with early fullness after eating as well as upper abdominal discomfort, abdominal distention and vomiting, particularly after eating. This may be treated with balloon dilatation during an endoscopy or surgery.

Answer 99

Causes The key sources of bleeding are: • Peptic ulcers (the most common cause) • Mallory-Weiss tear (a tear of the oesophageal mucosa) • Oesophageal varices (secondary to portal hypertension in liver cirrhosis) • Stomach cancers

Answer 100

Presentation The presenting features of an upper gastrointestinal bleed are: • Haematemesis (vomiting blood) • Coffee ground vomit (caused by vomiting digested blood with the appearance of coffee grounds) • Melaena (tar-like, black, greasy and offensive stools caused by digested blood) Haemodynamic instability occurs with significant blood loss, causing low blood pressure, tachycardia and other signs of shock. Young, fit patients may compensate well with normal observations until they have lost a lot of blood. Peptic ulcers are associated with a history of epigastric pain and dyspepsia. They may be taking non-steroidal anti-inflammatory drugs (NSAIDs). Mallory-Weiss tears tend to occur after heavy retching or vomiting, which may be caused by binge drinking, gastroenteritis or hyperemesis gravidarum (in early pregnancy). Oesophageal varices are associated with liver cirrhosis and portal hypertension. The patient will have signs of these conditions, such as ascites, jaundice and caput medusae. Stomach cancer is associated with a history of weight loss, epigastric pain, treatment-resistant dyspepsia, low haemoglobin (anaemia) and a raised platelet count.

Answer 101

Rockall Score The Rockall score is used after endoscopy to estimate the risk of rebleeding and mortality. It takes into account: • Age • Features of shock (e.g., tachycardia or hypotension) • Co-morbidities • Cause of bleeding (e.g., Mallory-Weiss tear or malignancy) • Endoscopic findings of recent bleeding (e.g., clots and visible bleeding vessels)

Answer 102

Management As with any medical emergency, get senior support early and follow the local policies. The initial management can be remembered with the ABATED mnemonic: • A – ABCDE approach to immediate resuscitation • B – Bloods • A – Access (ideally 2 x large bore cannula) • T – Transfusions are required • E – Endoscopy (within 24 hours) • D – Drugs (stop anticoagulants and NSAIDs) Send bloods for: ○ Haemoglobin (FBC) ○ Urea (U&Es) ○ Coagulation (INR and FBC for platelets) ○ Liver disease (LFTs) ○ Crossmatch 2 units of blood TOM TIP: “Group and save” is where the lab checks the patient’s blood group and saves a blood sample to match blood if needed. “Crossmatch” is where the lab allocates units of blood, tests that it is compatible, and keeps it ready in the fridge. Transfusion is based on the individual presentation: § Blood, platelets and clotting factors (fresh frozen plasma) are given to patients with massive bleeding § Transfusing more blood than necessary can be harmful § Platelets are given in active bleeding plus thrombocytopenia (platelet count less than 50) § Prothrombin complex concentrate can be given to patients taking warfarin that are actively bleeding There are some additional steps if oesophageal varices are suspected (e.g., in patients with liver cirrhosis): □ Terlipressin □ Broad spectrum antibiotics Oesophago-gastro-duodenoscopy (OGD) (endoscopy) is required to diagnose and treat the source of the bleeding. Non-variceal bleeding can be treated in various ways, such as with clips or thermal coagulation. Variceal band ligation is used to treat bleeding oesophageal varices. The NICE guidelines (updated 2016) recommend against using a proton pump inhibitor until after endoscopy in patients with non-variceal upper GI bleeding.

Answer 103

Pancreatitis refers to inflammation of the pancreas. It can be categorised as acute pancreatitis or chronic pancreatitis. Acute pancreatitis presents with a rapid onset of inflammation and symptoms. After an episode of acute pancreatitis, normal function usually returns. Chronic pancreatitis involves longer-term inflammation and symptoms with a progressive and permanent deterioration in pancreatic function.

Answer 104

Causes The three key causes of pancreatitis to remember are: • Gallstones • Alcohol • Post-ERCP Gallstone pancreatitis is caused by gallstones getting trapped at the end of the biliary system (ampulla of Vater), blocking the flow of bile and pancreatic juice into the duodenum. The reflux of bile into the pancreatic duct, and the prevention of pancreatic juice containing enzymes from being secreted, results in inflammation in the pancreas. Gallstone pancreatitis is more common in women and older patients. Alcohol is directly toxic to pancreatic cells, resulting in inflammation. Alcohol-induced pancreatitis is more common in men and younger patients. I GET SMASHED is a popular mnemonic for remembering a long list of causes of pancreatitis: ○ I – Idiopathic ○ G – Gallstones ○ E – Ethanol (alcohol consumption) ○ T – Trauma ○ S – Steroids ○ M – Mumps ○ A – Autoimmune ○ S – Scorpion sting (the one everyone remembers) ○ H – Hyperlipidaemia ○ E – ERCP ○ D – Drugs (furosemide, thiazide diuretics and azathioprine)

Answer 105

Presentation Acute pancreatitis typically presents with an acute onset of: • Severe epigastric pain • Radiating through to the back • Associated vomiting • Abdominal tenderness • Systemically unwell (e.g., low-grade fever and tachycardia) Acute pancreatitis is a clinical diagnosis, based mainly on the presenting features and the amylase level.

Answer 106

Investigations Initial investigations are required as with any presentation of an acute abdomen. Importantly these need to include those required for calculating the Glasgow score: • FBC (for white cell count) • U&E (for urea) • LFT (for transaminases and albumin) • Calcium • ABG (for PaO2 and blood glucose) Amylase is raised more than 3 times the upper limit of normal in acute pancreatitis. In chronic pancreatitis it may not rise because the pancreas has reduced function. Lipase is also raised in acute pancreatitis. It is considered more sensitive and specific than amylase. C-reactive protein (CRP) can be used to monitor the level of inflammation. Ultrasound is the initial investigation of choice in assessing for gallstones. CT abdomen can assess for complications of pancreatitis (such as necrosis, abscesses and fluid collections). It is not usually required unless complications are suspected (e.g., the patient is becoming more unwell).

Answer 107

Glasgow Score The Glasgow score is used to assess the severity of pancreatitis. It gives a numerical score based on how many of the key criteria are present: • 0 or 1 – mild pancreatitis • 2 – moderate pancreatitis • 3 or more – severe pancreatitis The criteria for the Glasgow score can be remembered using the PANCREAS mnemonic (1 point for each answer): ○ P – Pa02 < 8 KPa ○ A – Age > 55 ○ N – Neutrophils (WBC > 15) ○ C – Calcium < 2 ○ R – uRea >16 ○ E – Enzymes (LDH > 600 or AST/ALT >200) ○ A – Albumin < 32 ○ S – Sugar (Glucose >10)

Answer 108

Management of Acute Pancreatitis Patients with acute pancreatitis can become very unwell rapidly. They require admission to supportive management. Moderate or severe cases should be considered for management on the high dependency unit (HDU) or intensive care unit (ICU). Management involves: • Initial resuscitation (ABCDE approach) • IV fluids • Nil by mouth • Analgesia • Careful monitoring • Treatment of gallstones in gallstone pancreatitis (ERCP / cholecystectomy) • Antibiotics if there is evidence of a specific infection (e.g., abscess or infected necrotic area) • Treatment of complications (e.g., endoscopic or percutaneous drainage of large collections) Most patients will improve within 3-7 days.

Answer 109

Complications of Acute Pancreatitis • Necrosis of the pancreas • Infection in a necrotic area • Abscess formation • Acute peripancreatic fluid collections • Pseudocysts (collections of pancreatic juice) can develop 4 weeks after acute pancreatitis • Chronic pancreatitis

Answer 110

Chronic Pancreatitis Chronic pancreatitis refers to chronic inflammation in the pancreas. It results in fibrosis and reduced function of the pancreatic tissue. Alcohol is the most common cause. It presents with similar symptoms to acute pancreatitis, but generally less intense and longer-lasting. Key complications are: • Chronic epigastric pain • Loss of exocrine function, resulting in a lack of pancreatic enzymes (particularly lipase) secreted into the GI tract • Loss of endocrine function, resulting in a lack of insulin, leading to diabetes • Damage and strictures to the duct system, resulting in obstruction in the excretion of pancreatic juice and bile • Formation of pseudocysts or abscesses

Answer 111

Management of Chronic Pancreatitis Abstinence from alcohol and smoking is important in managing symptoms and complications. Analgesia can be used to manage the pain, although it can be severe and difficult to manage. Replacement pancreatic enzymes (Creon) may be required if there is a loss of pancreatic enzymes (i.e. lipase). Otherwise, a lack of enzymes leads to malabsorption of fat, greasy stools (steatorrhoea), and deficiency in fat-soluble vitamins. Subcutaneous insulin regimes may be required to treat diabetes. ERCP with stenting can be used to treat strictures and obstruction to the biliary system and pancreatic duct. Surgery may be required by specialist centres to treat: • Severe chronic pain (draining the ducts and removing inflamed pancreatic tissue) • Obstruction of the biliary system and pancreatic duct • Pseudocysts • Abscesses

Answer 112

Liver cirrhosis is the result of chronic inflammation and damage to liver cells. The functional liver cells are replaced with scar tissue (fibrosis). Nodules of scar tissue form within the liver. Fibrosis affects the structure and blood flow through the liver, increasing the resistance in the vessels leading into the liver. This increased resistance and pressure in the portal system is called portal hypertension.

Answer 113

Causes The four most common causes of liver cirrhosis are: • Alcohol-related liver disease • Non-alcoholic fatty liver disease (NAFLD) • Hepatitis B • Hepatitis C Cirrhosis also has many rarer causes: ○ Autoimmune hepatitis ○ Primary biliary cirrhosis ○ Haemochromatosis ○ Wilsons disease ○ Alpha-1 antitrypsin deficiency ○ Cystic fibrosis ○ Drugs (e.g., amiodarone, methotrexate and sodium valproate)

Answer 114

Examination Findings Signs of liver cirrhosis on examination include: • Cachexia (wasting of the body and muscles) • Jaundice caused by raised bilirubin • Hepatomegaly (enlargement of the liver) • Small nodular liver as it becomes more cirrhotic • Splenomegaly due to portal hypertension • Spider naevi (telangiectasia with a central arteriole and small vessels radiating away) • Palmar erythema caused by elevated oestrogen levels • Gynaecomastia and testicular atrophy in males due to endocrine dysfunction • Bruising due to abnormal clotting • Excoriations (scratches on the skin due to itching) • Ascites (fluid in the peritoneal cavity) • Caput medusae (distended paraumbilical veins due to portal hypertension) • Leukonychia (white fingernails) associated with hypoalbuminaemia • Asterixis (“flapping tremor”) in decompensated liver disease

Answer 115

Non-Invasive Liver Screen Abnormal liver function tests without a clear cause require a non-invasive liver screen, which includes: • Ultrasound liver (used to diagnose fatty liver) • Hepatitis B and C serology • Autoantibodies (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis) • Immunoglobulins (autoimmune hepatitis and primary biliary cirrhosis) • Caeruloplasmin (Wilsons disease) • Alpha-1 antitrypsin levels (alpha-1 antitrypsin deficiency) • Ferritin and transferrin saturation (hereditary haemochromatosis)

Answer 116

Blood Tests Liver function tests (LFTs) may be normal in cirrhosis. However, in decompensated cirrhosis, all the liver markers become deranged, with raised: • Bilirubin • Alanine transaminase (ALT) • Aspartate transferase (AST) • Alkaline phosphatase (ALP) Other blood results include: ○ Low albumin due to reduced synthetic function of the liver ○ Increased prothrombin time due to reduced synthetic function of the liver (reduced production of clotting factors) ○ Thrombocytopenia (low platelets) is a common finding and indicates more advanced disease ○ Hyponatraemia (low sodium) occurs with fluid retention in severe liver disease ○ Urea and creatinine become deranged in hepatorenal syndrome ○ Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma

Answer 117

The enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease. It is not used in patients with other causes of liver disease. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates whether they have advanced fibrosis of the liver: • 10.51 or above – advanced fibrosis • Under 10.51 – unlikely advanced fibrosis (NICE recommend rechecking every 3 years in NAFLD)

Answer 118

Child-Pugh Score The Child-Pugh scores uses 5 factors to assess the severity of cirrhosis and the prognosis. Each factor is considered and scored 1, 2 or 3. The minimum overall score is 5 (scoring 1 for each factor), and the maximum is 15 (scoring 3 for each factor). You can remember the features with the “ABCDE” mnemonic: • A – Albumin • B – Bilirubin • C – Clotting (INR) • D – Dilation (ascites) • E – Encephalopathy Liver transplantation is generally considered when there are features of decompensated liver disease. The four key features can be remembered with the “AHOY” mnemonic: • A – Ascites • H – Hepatic encephalopathy • O – Oesophageal varices bleeding • Y – Yellow (jaundice)

Answer 119

Complications and Prognosis The course of the disease is variable. Overall, 5-year survival is about 50% once cirrhosis has developed. The MELD score or Child-Pugh score can be used as prognostic tools. There are several important complications of cirrhosis: • Malnutrition and muscle wasting • Portal hypertension, oesophageal varices and bleeding varices • Ascites and spontaneous bacterial peritonitis • Hepatorenal syndrome • Hepatic encephalopathy • Hepatocellular carcinoma

Answer 120

Malnutrition Cirrhosis leads to malnutrition and muscle wasting. Patients often have a loss of appetite resulting in reduced intake. Cirrhosis affects protein metabolism in the liver and reduces the amount of protein the liver produces. It also disrupts the ability of the liver to store glucose as glycogen and release it when required. Overall, less protein is available for maintaining muscle tissue and muscle tissue is broken down for use as fuel. Management involves nutritional support guided by a dietician, with: • Regular meals • High protein and calorie intake • Reduced sodium intake to minimise fluid retention • Avoiding alcohol

Answer 121

Portal Hypertension and Varices The portal vein comes from the superior mesenteric and splenic veins and delivers blood to the liver. Liver cirrhosis increases the resistance to blood flow in the liver. As a result, there is increased back pressure on the portal system. This is called portal hypertension. The back pressure of blood results in splenomegaly. Back pressure in the portal system causes swollen and tortuous vessels at sites where collaterals form between the portal and systemic venous systems. These collaterals can occur at several locations, notably the: • Distal oesophagus (oesophageal varices) • Anterior abdominal wall (caput medusae) Varices are asymptomatic until they start bleeding. Due to the high blood flow, bleeding from varices can cause patients to exsanguinate (bleed out) very quickly. Prophylaxis of bleeding in stable oesophageal varices involves: ○ Non-selective beta blockers (e.g., propranolol) first-line ○ Variceal band ligation (if beta blockers are contraindicated) Variceal band ligation involves a rubber band wrapped around the base of the varices, cutting off the blood flow through the vessels.

Answer 122

Bleeding Oesophageal Varices Bleeding oesophageal varices is a life-threatening emergency. Initial management involves: • Immediate senior help • Consider blood transfusion (activate the major haemorrhage protocol) • Treat any coagulopathy (e.g., with fresh frozen plasma) • Vasopressin analogues (e.g., terlipressin or somatostatin) cause vasoconstriction and slow bleeding • Prophylactic broad-spectrum antibiotics (shown to reduce mortality) • Urgent endoscopy with variceal band ligation • Consider intubation and intensive care Other options to control the bleeding include: ○ Sengstaken-Blakemore tube (an inflatable tube inserted into the oesophagus to tamponade the bleeding varices) ○ Transjugular intrahepatic portosystemic shunt (TIPS) Transjugular intrahepatic portosystemic shunt (TIPS) is a technique where an interventional radiologist inserts a wire under x-ray guidance into the jugular vein, down the vena cava and into the liver via the hepatic vein. A connection is made through the liver between the hepatic vein and portal vein, and a stent is inserted. This allows blood to flow directly from the portal vein to the hepatic vein, relieving the pressure in the portal system. The two main indications are: § Bleeding oesophageal varices § Refractory ascites

Answer 123

Ascites Ascites refers to fluid in the peritoneal cavity. The increased pressure in the portal system causes fluid to leak out of the capillaries in the liver and other abdominal organs into the peritoneal cavity. The drop in circulating volume caused by fluid loss into the peritoneal cavity causes reduced blood pressure in the kidneys. The kidneys sense this lower pressure and release renin, which leads to increased aldosterone secretion via the renin-angiotensin-aldosterone system. Increased aldosterone causes the reabsorption of fluid and sodium in the kidneys, leading to fluid and sodium retention. Cirrhosis causes transudative (low protein content) ascites.

Answer 124

Management options include: • Low sodium diet • Aldosterone antagonists (e.g., spironolactone) • Paracentesis (ascitic tap or ascitic drain) • Prophylactic antibiotics (ciprofloxacin or norfloxacin) when there is <15 g/litre of protein in the ascitic fluid • Transjugular intrahepatic portosystemic shunt (TIPS) is considered in refractory ascites • Liver transplantation is considered in refractory ascites

Answer 125

Stages There is a stepwise progression of alcohol-related liver disease. 1. Alcoholic fatty liver (also called hepatic steatosis) Drinking leads to a build-up of fat in the liver. This process is reversible with abstinence. 2. Alcoholic hepatitis Drinking alcohol over a long period causes inflammation in the liver cells. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence. 3. Cirrhosis Cirrhosis is where the functional liver tissue is replaced with scar tissue. It is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.

Answer 126

Complications of Alcohol • Alcohol-related liver disease • Cirrhosis and its complications (e.g., hepatocellular carcinoma) • Alcohol dependence and withdrawal • Wernicke-Korsakoff syndrome (WKS) • Pancreatitis • Alcoholic cardiomyopathy • Alcoholic myopathy, with proximal muscle wasting and weakness • Increased risk of cardiovascular disease (e.g., stroke or myocardial infarction) • Increased risk of cancer, particularly breast, mouth and throat cancer

Answer 127

Examination Findings with Excess Alcohol Signs suggestive of excessive alcohol consumption include: • Smelling of alcohol • Slurred speech • Bloodshot eyes • Dilated capillaries on the face (telangiectasia) • Tremor

Answer 128

Blood test results suggesting alcohol-related liver disease include: • Raised mean cell volume (MCV) • Raised alanine transaminase (ALT) and aspartate transferase (AST) • AST:ALT ratio above 1.5 particularly suggests alcohol-related liver disease • Raised gamma-glutamyl transferase (gamma-GT) (particularly notable with alcohol-related liver disease) • Raised alkaline phosphatase (ALP) later in the disease • Raised bilirubin in cirrhosis • Low albumin due to reduced synthetic function of the liver • Increased prothrombin time due to reduced synthetic function of the liver (reduced production of clotting factors) • Deranged U&Es in hepatorenal syndrome

Answer 129

Liver ultrasound may show early fatty changes with “increased echogenicity”. Later, it can show changes related to cirrhosis. Ultrasound is used to screen for hepatocellular carcinoma in patients with cirrhosis. Transient elastography (“FibroScan”) can be used to assess the elasticity of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring). Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected. CT and MRI scans can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites. Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis, particularly in patients where steroid treatment is being considered for alcohol-related hepatitis.

Answer 130

Management The general principles of managing alcohol-related liver disease are: • Stop drinking alcohol permanently (drug and alcohol services are available for support) • Psychological interventions (e.g., motivational interviewing or cognitive behavioural therapy) • Consider a detoxication regime • Nutritional support with vitamins (particularly thiamine – vitamin B1) and a high-protein diet • Corticosteroids may be considered to reduce inflammation in severe alcoholic hepatitis to improve short-term outcomes (but not long-term outcomes) • Treat complications of cirrhosis (e.g., portal hypertension, varices, ascites and hepatocellular carcinoma) • Liver transplant in severe disease (generally 6 months of abstinence is required)

Answer 131

CAGE Questions The CAGE questions can be used to quickly screen for harmful alcohol use: • C – CUT DOWN? Do you ever think you should cut down? • A – ANNOYED? Do you get annoyed at others commenting on your drinking? • G – GUILTY? Do you ever feel guilty about drinking? • E – EYE OPENER? Do you ever drink in the morning to help your hangover or nerves?

Answer 132

Delirium tremens is a medical emergency associated with alcohol withdrawal. There is a 35% mortality rate if left untreated. Alcohol is a depressant substance. It stimulates GABA receptors in the brain. GABA receptors have a relaxing effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors), causing a further relaxing effect on the electrical activity of the brain (glutamate is an “excitatory” neurotransmitter). Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol. When alcohol is removed, the GABA system under-functions and the glutamate system over-functions, causing extreme excitability of the brain and excessive adrenergic (adrenalin-related) activity.

Answer 133

• Acute confusion • Severe agitation • Delusions and hallucinations • Tremor • Tachycardia • Hypertension • Hyperthermia • Ataxia (difficulties with coordinated movements) • Arrhythmias

Answer 134

Wernicke-Korsakoff Syndrome Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol. Alcoholics often have poor diets and get many of their calories from alcohol. Thiamine deficiency leads to Wernicke’s encephalopathy and Korsakoff syndrome. Features of Wernicke’s encephalopathy include: • Confusion • Oculomotor disturbances (disturbances of eye movements) • Ataxia (difficulties with coordinated movements) Features of Korsakoff syndrome include: ○ Memory impairment (retrograde and anterograde) ○ Behavioural changes Wernicke’s encephalopathy is a medical emergency with a high mortality rate. Korsakoff syndrome is often irreversible and results in patients requiring full-time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.

Answer 135

Gallstones are small stones that form within the gallbladder. The stones form from concentrated bile from the bile ducts. Most stones are made of cholesterol. These may be completely asymptomatic. They can also cause pain and lead to complications, such as acute cholecystitis, acute cholangitis and pancreatitis. Gallstones blocking the drainage of the pancreas (i.e. the pancreatic duct) result in pancreatitis.

Answer 136

Common hepatic duct

Answer 137

Cholestasis: blockage to the flow of bile

Answer 138

• Cholelithiasis: gallstone(s) are present

Answer 139

• Choledocholithiasis: gallstone(s) in the bile duct

Answer 140

Biliary colic: intermittent right upper quadrant pain caused by gallstones irritating bile ducts

Answer 141

• Cholecystitis: inflammation of the gallbladder

Answer 142

Cholangitis: inflammation of the bile ducts

Answer 143

Gallbladder empyema: pus in the gallbladder

Answer 144

Cholecystostomy: inserting a drain into the gallbladder

Answer 145

Cholecystectomy: surgical removal of the gallbladder Cholecystectomy involves surgical removal of the gallbladder. It is indicated where patients are symptomatic of gallstones, or the gallstones are leading to complications (e.g., acute cholecystitis). Stones in the bile ducts can be removed before (by ERCP) or during surgery. Laparoscopic cholecystectomy (keyhole surgery) is preferred to open cholecystectomy (with a right subcostal “Kocher” incision), as it has less complications and a faster recovery.

Answer 146

Fat Fair Female Forty

Answer 147

Presentation Patients with gallstones may be completely asymptomatic. The typical symptom of gallstones is biliary colic. Biliary colic is caused by stones temporarily obstructing drainage of the gallbladder. It may get lodged at the neck of the gallbladder or in the cystic duct, then when it falls back into the gallbladder the symptoms resolve. It causes symptoms of: • Severe, colicky epigastric or right upper quadrant pain • Often triggered by meals (particularly high fat meals) • Lasting between 30 minutes and 8 hours • May be associated with nausea and vomiting Alternatively, patients may present with a complication of gallstones, such as: ○ Acute cholecystitis ○ Acute cholangitis ○ Obstructive jaundice (if the stone blocks the ducts) ○ Pancreatitis TOM TIP: Fat entering the digestive system causes cholecystokinin (CCK) secretion from the duodenum. CCK triggers contraction of the gallbladder, which leads to biliary colic. Patients with gallstones and biliary colic are advised to avoid fatty foods to prevent CCK release and gallbladder contraction. Exams may test this mechanism, so it is worth remembering.

Answer 148

Ultrasound An ultrasound scan is a useful first-line investigation for symptoms of gallstone disease, for example, abdominal pain, right upper quadrant pain and jaundice. It is the most sensitive initial imaging test for gallstones (CT scans are not good at identifying gallstones or biliary disease). Ultrasound is limited by the patient’s weight, gaseous bowel obstructing the view and discomfort from the probe. Ultrasound Findings Ultrasound can be helpful in identifying: • Gallstones in the gallbladder • Gallstones in the ducts • Bile duct dilatation (normally less than 6mm diameter) • Acute cholecystitis (thickened gallbladder wall, stones or sludge in gallbladder and fluid around the gallbladder) • The pancreas and pancreatic duct

Answer 149

A magnetic resonance cholangio-pancreatography (MRCP) is an MRI scan with a specific protocol that produces a detailed image of the biliary system. It is very sensitive and specific for biliary tree disease, such as stones in the bile duct and malignancy. MRCP is used in a number of scenarios for gaining a detailed picture of the biliary system, such as identifying biliary strictures or congenital abnormalities. With gallstone disease, MRCP is typically used to investigate further if the ultrasound scan does not show stones in the duct, but there is bile duct dilatation or raised bilirubin suggestive of obstruction.

Answer 150

Endoscopic Retrograde Cholangio-Pancreatography An endoscopic retrograde cholangio-pancreatography (ERCP) involves inserting an endoscope down the oesophagus, past the stomach, to the duodenum and the opening of the common bile duct (the sphincter of Oddi). This gives the operator access to the biliary system. The main indication for ERCP is to clear stones in the bile ducts. ERCP allows the operator to: • Inject contrast and take x-rays to visualise the biliary system and diagnose pathology (e.g., stones or strictures) • Perform a sphincterotomy on the sphincter of Oddi if it is dysfunctional (blocking flow) • Clear stones from the ducts • Insert stents to improve bile duct drainage (e.g., with strictures or tumours) • Take biopsies of tumours Key complications of ERCP are: ○ Excessive bleeding ○ Cholangitis (infection in the bile ducts) ○ Pancreatitis

Answer 151

CT Scans CT scans are less useful for looking at the biliary system and for gallstones. They may be used to look for differential diagnoses (e.g., pancreatic head tumour) and complications such as perforation and abscesses.

Answer 152

Management Asymptomatic patients with gallstones may be treated conservatively, with no intervention required. Patients with symptoms or complications of gallstones are treated with cholecystectomy, which is surgical removal of the gallbladder (provided they are fit for surgery).

Answer 153

Complications of cholecystectomy include: • Bleeding, infection, pain and scars • Damage to the bile duct including leakage and strictures • Stones left in the bile duct • Damage to the bowel, blood vessels or other organs • Anaesthetic risks • Venous thromboembolism (deep vein thrombosis or pulmonary embolism) • Post-cholecystectomy syndrome

Answer 154

Post-cholecystectomy syndrome involves a group of non-specific symptoms that can occur after a cholecystectomy. They may be attributed to changes in the bile flow after removal of the gallbladder. Symptoms often improve with time. Symptoms include: ○ Diarrhoea ○ Indigestion ○ Epigastric or right upper quadrant pain and discomfort ○ Nausea ○ Intolerance of fatty foods ○ Flatulence

Answer 155

Non-alcoholic fatty liver disease (NAFLD) is characterised by excessive fat in the liver cells, specifically triglycerides. These fat deposits interfere with the functioning of the liver cells. The early stages of NAFLD can be asymptomatic. However, it can progress to hepatitis and liver cirrhosis. Around 25% of adults are estimated to have non-alcoholic fatty liver disease.

Answer 156

The stages of non-alcoholic fatty liver disease are: 1. Non-alcoholic fatty liver disease 2. Non-alcoholic steatohepatitis (NASH) 3. Fibrosis 4. Cirrhosis

Answer 157

Risk Factors Non-alcoholic fatty liver disease shares the same risk factors as cardiovascular disease and diabetes: • Middle age onwards • Obesity • Poor diet and low activity levels • Type 2 diabetes • High cholesterol • High blood pressure • Smoking It is associated with metabolic syndrome, which is a combination of hypertension, obesity and diabetes. Metabolic syndrome is common and dramatically increases the risk of cardiovascular disease and other health problems.

Answer 158

The enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates whether they have advanced fibrosis of the liver: • 10.51 or above – advanced fibrosis • Under 10.51 – unlikely advanced fibrosis (NICE recommend rechecking every 3 years in NAFLD)

Answer 159

Raised ALT is usually the first indication on liver function blood tests Liver ultrasound can confirm the diagnosis of hepatic steatosis (fatty liver), seen as increased echogenicity. Enhanced liver fibrosis (ELF) blood test to assess fibrosis in NAFLD NAFLD Fibrosis Score (NFS) is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, BMI, liver enzymes (AST and ALT), platelet count, albumin and diabetes. Fibrosis 4 (FIB-4) score is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, liver enzymes (AST and ALT) and platelet count. Transient elastography (“FibroScan”) can be used to assess the stiffness of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring) to test for liver cirrhosis. It is used where the enhanced liver fibrosis (ELF) test indicates advanced fibrosis. Liver biopsy may be required to confirm the diagnosis and exclude other causes of liver disease. TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis. The normal ratio is less than 1. A ratio greater than 0.8 in NAFLD suggests advanced fibrosis. An AST:ALT ratio greater than 1.5 (meaning a disproportionately high AST) indicates alcohol-related liver disease rather than NAFLD.

Answer 160

Management Management involves: • Weight loss • Healthy diet (Mediterranean diet is recommended) • Exercise • Avoid/limit alcohol intake • Stop smoking • Control of diabetes, blood pressure and cholesterol • Refer patients where scoring tests indicate liver fibrosis to a liver specialist • Specialist management may include vitamin E, pioglitazone, bariatric surgery andliver transplantation

Answer 161

○ Type 1: occurs in adults § typically affects women in their late forties or fifties. § It presents around or after the menopause with fatigue and features of liver disease on examination. § It takes a less acute course than type 2. § Type 1 Autoantibodies: □ Anti-nuclear antibodies (ANA) □ Anti-smooth muscle antibodies (anti-actin) □ Anti-soluble liver antigen (anti-SLA/LP)

Answer 162

○ Type 2: occurs in children § patients in their teenage or early twenties present with acute hepatitis with high transaminases and jaundice. § Type 2 Autoantibodies: □ Anti-liver kidney microsomes-1 (anti-LKM1) □ Anti-liver cytosol antigen type 1 (anti-LC1)

Answer 163

Clinical Features • Asymptomatic • Acute hepatitis ○ Anorexia ○ Nausea ○ Jaundice ○ Right upper quadrant pain ○ Hepatomegaly • Chronic liver disease (cirrhosis) • Acute liver failure ○ Jaundice ○ Confusion ○ coagulopathy

Answer 164

Investigations will show raised transaminases (ALT and AST), IgG levels and it is associated with many autoantibodies. Diagnosis can be confirmed using a liver biopsy.

Answer 165

Treatment • High dose steroids (prednisolone) that are tapered over time as other immunosuppressants, particularly azathioprine, are introduced. Immunosuppressant treatment is usually successful in inducing remission however it is usually required life long. • Liver transplant may be required in end stage liver disease, however the autoimmune hepatitis can recur in transplanted livers.

Answer 166

• Viral hepatitis (hep A,B,C,D,E) • Alcoholic hepatitis • Non-alcoholic steatohepatitis (NASH) • Autoimmune hepatitis • Drug induced hepatitis (e.g. paracetamol overdose)

Answer 167

Presentation Viral hepatitis may be asymptomatic or present with non-specific symptoms of: • Abdominal pain • Fatigue • Flu-like illness • Pruritus (itching) • Muscle and joint aches • Nausea and vomiting • Jaundice

Answer 168

Liver Function Tests A “hepatitic picture” on liver function tests refers to high transaminases (AST and ALT) with proportionally less of a rise in ALP. Transaminases are liver enzymes released into the blood due to inflammation of the liver cells. Bilirubin can also rise as a result of inflammation of the liver cells. High bilirubin causes jaundice.

Answer 169

Hepatic encephalopathy is also known as portosystemic encephalopathy. It is thought to be caused by the build-up of neurotoxic substances that affect the brain. One toxin particularly worth remembering is ammonia, produced by intestinal bacteria when they break down proteins. Ammonia is absorbed in the intestines. There are two reasons that ammonia builds up in the blood in patients with cirrhosis: Firstly, the liver cells’ functional impairment prevents them from metabolising the ammonia into harmless waste products. Secondly, collateral vessels between the portal and systemic circulation mean that the ammonia bypasses the liver and enters the systemic system directly. Acutely, hepatic encephalopathy presents with reduced consciousness and confusion. It can present more chronically with changes to personality, memory and mood.

Answer 170

Management involves: ○ Lactulose (aiming for 2-3 soft stools daily) ○ Antibiotics (e.g., rifaximin) to reduce the number of intestinal bacteria producing ammonia ○ Nutritional support (nasogastric feeding may be required) Lactulose works in several ways to reduce ammonia: Speeds up transit time and reduces constipation (the laxative effect clearing the ammonia before it is absorbed) Promotes bacterial uptake of ammonia to be used for protein synthesis Changes the pH of the contents of the intestine to become more acidic, killing ammonia-producing bacteria Rifaximin is the usual choice of antibiotic as it is poorly absorbed and stays in the gastrointestinal tract. Neomycin and metronidazole are alternatives.

Answer 171

Primary sclerosing cholangitis is a condition where the intrahepatic and extrahepatic bile ducts become inflamed and damaged, developing strictures that obstruct the flow of bile out of the liver and into the intestines. Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts. Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.

Answer 172

The cause is unclear and thought to be combined genetic and environmental factors. There is a strong association with ulcerative colitis, with around 70% of cases occurring alongside pre-existing ulcerative colitis. Less commonly, it can be associated with Crohn’s disease. The key risk factors for primary sclerosing cholangitis are: • Male • Aged 30-40 • Ulcerative colitis • Family history

Answer 173

Presentation Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with: • Abdominal pain in the right upper quadrant • Pruritus (itching) • Fatigue • Jaundice • Hepatomegaly • Splenomegaly

Answer 174

Investigations Liver function tests show: • Raise alkaline phosphatase (the most notable liver enzyme as with most “obstructive” pathology) • Other liver enzymes and bilirubin are raised later in the disease Magnetic resonance cholangiopancreatography (MRCP) is the diagnostic imaging investigation. It involves an MRI scan that gives a detailed view of the bile ducts, showing bile duct strictures in primary sclerosing cholangitis. Colonoscopy should be performed to assess for ulcerative colitis. Liver biopsy is not usually required but may be used where there is diagnostic uncertainty.

Answer 175

Management There are no treatments proven to be effective for primary sclerosing cholangitis. Endoscopic retrograde cholangio-pancreatography (ERCP) may be used to treat dominant strictures. This involves inserting an endoscope down the oesophagus, past the stomach, to the duodenum and the opening of the common bile duct (the sphincter of Oddi). This gives the operator access to the biliary system. Strictures can be dilated. Stents can be inserted to keep the ducts open. Antibiotics are given alongside ERCP to reduce the risk of infection (bacterial cholangitis). Liver transplant is used in advanced disease, with around 80% survival at five years post-transplantation. Other aspects of management include: • Colestyramine for symptoms of pruritus (a bile acid sequestrant that reduces intestinal absorption of bile acids) • Replacement of fat-soluble vitamins • Monitoring for complications such as cholangiocarcinoma, cirrhosis and oesophageal varices

Answer 176

Complications Complications and associations include: • Biliary strictures • Acute bacterial cholangitis • Cholangiocarcinoma develops in 10-20% of cases • Cirrhosis and the related complications (e.g., portal hypertension and oesophageal varices) • Fat-soluble vitamin deficiency (A, D, E and K) • Osteoporosis • Colorectal cancer in patients with ulcerative colitis TOM TIP: The association between ulcerative colitis, primary sclerosing cholangitis and cholangiocarcinoma is commonly tested in exams. IgG4-Related Sclerosing Cholangitis IgG4-related sclerosing cholangitis is similar to primary sclerosing cholangitis. Elevated IgG4 levels in the blood are the distinguishing feature. Unlikely primary sclerosing cholangitis, IgG4-related sclerosing cholangitis responds well to treatment with steroids. It is associated with autoimmune pancreatitis.

Answer 177

• Two main organs are affected by alpha-1-antitrypsin deficiency, the liver and the lungs. It leads to: ○ Liver cirrhosis after 50 years old - build up of hepatocytes leading to cirrhosis § Normally, alpha-1-antitrypsin is created in the liver. § In alpha-1-antitrypsin deficiency, an abnormal “mutant” version of this protein is produced, rather than the normal alpha-1-antitrypsin protein. § This mutant protein gets trapped in the liver, builds up, and causes liver damage. § This liver damage progresses to cirrhosis over time. It can lead to hepatocellular carcinoma. ○ Bronchiectasis and emphysema in the lungs after 30 years old - absent inhibition of neutrophil elastase causes lung damage leading to COPD § The lack of a normal, functioning alpha-1-antitrypsin protein leads to an excess of protease enzymes that attack the connective tissue in the lungs.

Answer 178

• The clinical features of AATD depends on the underlying genotype. Patients may have features of both COPD and chronic liver disease. • Pulmonary clinical features ○ Dyspnoea ○ Cough ○ Wheeze ○ Ankle swelling (right-sided heart failure from chronic lung disease) • Hepatic clinical features ○ Jaundice ○ Bruising ○ Spider naevi ○ Palmar erythema ○ Hepatomegaly ○ Ascites ○ Leuconychia ○ Confusion ○ Asterixis: flapping tremor (suggests encephalopathy) ○ Cachexia

Answer 179

Primary biliary cholangitis is an autoimmune condition where the immune system attacks the small bile ducts in the liver, resulting in obstructive jaundice and liver disease. It was previously known as primary biliary cirrhosis.

Answer 180

Primary biliary cholangitis affects the small bile ducts inside the liver (the intrahepatic ducts). There is inflammation and damage to the epithelial cells of the bile ducts (the cholangiocytes). Over time, this can lead to obstruction of bile flow through these ducts. Reduced flow of bile is called cholestasis. The back-pressure of bile and the overall disease process ultimately lead to liver fibrosis, cirrhosis and failure. Bile acids, bilirubin and cholesterol are excreted through the bile ducts into the intestines. When obstruction to the outflow of these chemicals means they are not being excreted, they build up in the blood. Raised bile acids cause itching, and raised bilirubin causes jaundice. Raised cholesterol causes cholesterol deposits in the skin called xanthelasma. Xanthomasare larger nodular deposits of cholesterol in the skin or tendons. Raised cholesterol increases the risk of atherosclerosis and cardiovascular disease. Bile acids help with the digestion of fats. Reduced or absent bile acids in the gastrointestinal tract cause abdominal symptoms, malabsorption of fat and greasy stools. Bilirubin is responsible for the darker colour of stools. A lack of bilirubin results in pale stools. Excretion of bilirubin via the urine causes dark urine.

Answer 181

Presentation The typical patient is a white woman aged 40-60 years. Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with: • Fatigue • Pruritus (itching) • Gastrointestinal symptoms and abdominal pain • Jaundice • Pale, greasy stools • Dark urine On examination, there may be: ○ Xanthoma and xanthelasma (cholesterol deposits) ○ Excoriations (scratches on the skin due to itching) ○ Hepatomegaly ○ Signs of liver cirrhosis and portal hypertension in end-stage disease (e.g., splenomegaly and ascites)

Answer 182

Primary biliary cholangitis.

Answer 183

○ Anti-mitochondrial antibodies (AMA) are the most specific to PBC and form part of the diagnostic criteria ○ Anti-nuclear antibodies are present in about 35% of patients Raised immunoglobulin M (IgM) is a non-specific blood result finding. Ultrasound does not show specific changes with primary biliary cholangitis but helps exclude other pathology. Liver biopsy may be used in diagnosing and staging the disease.

Answer 184

Ursodeoxycholic acid is the most essential treatment to remember in primary biliary cholangitis. It is a non-toxic, hydrophilic bile acid that protects the cholangiocytes from inflammation and damage. It makes the bile less harmful to the epithelial cells of the bile ducts. It slows the disease progression and improves outcomes.

Answer 185

Primary hepatocellular carcinoma Upto 1/3 of patients will develop HCC

Answer 186

Spontaneous Bacterial Peritonitis Spontaneous bacterial peritonitis (SBP) occurs in 10-20% of patients with ascites. It has a mortality of 10-20%. It involves an infection developing in the ascitic fluid and peritoneal lining without a clear source of infection (e.g., an ascitic drain or bowel perforation). Spontaneous bacterial peritonitis can be asymptomatic. Presenting features include: • Fever • Abdominal pain • Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis) • Ileus (reduced movement in the intestines) • Hypotension The most common organisms are: ○ Escherichia coli ○ Klebsiella pneumoniae Management involves: § Taking a sample of ascitic fluid for culture before giving antibiotics § Intravenous broad-spectrum antibiotics according to local policies (e.g., piperacillin with tazobactam)

Answer 187

Hepatorenal Syndrome Hepatorenal syndrome involves impaired kidney function caused by changes in the blood flow to the kidneys relating to liver cirrhosis and portal hypertension. The exact pathophysiology is still being debated. A simplified version is that portal hypertension causes the portal vessels to release vasodilators, which cause significant vasodilation in the splanchnic circulation (the vessels supplying the gastrointestinal organs). Vasodilation leads to reduced blood pressure. The kidneys respond to the reduced pressure by activating the renin-angiotensin-aldosterone system, which leads to vasoconstriction of the renal vessels. Renal vasoconstriction combined with low systemic pressure results in the kidneys being starved of blood and significantly reduced kidney function. Hepatorenal syndrome has a poor prognosis unless the patient has a liver transplant. Treatment: Terlipressin (vasoconstrictor)

Answer 188

Pathophysiology • Haemochromatosis is an iron storage disorder that results in excessive total body iron and deposition of iron in tissues. • The human haemochromatosis protein (HFE) gene is located on chromosome 6 - main gene involved but there can be others • The haemochromatosis genetic mutation is autosomal recessive. • This gene is important in regulating iron metabolism. • Patients develop progressive organ dysfunction due to iron overload, especially in the liver • Increase in iron stores, which raises the level of serum ferritin. There is also a rise in transferrin saturation.

Answer 189

Symptoms • Haemochromatosis usually present after the age of 40 when the iron overload becomes symptomatic. It presents later in females due to menstruation acting to regularly eliminate iron from the body. ○ Chronic tiredness ○ Joint pain ○ Pigmentation (bronze / slate-grey discolouration) ○ Hair loss ○ Erectile dysfunction ○ Amenorrhoea ○ Cognitive symptoms (memory and mood disturbance)

Answer 190

Diagnosis • The main diagnostic method is to perform a serum ferritin level. ○ Ferritin is an acute phase reactant, meaning that it goes up with inflammatory conditions such as infection. • Performing a transferrin saturation is helpful in distinguishing between a high ferritin caused by iron overload (in which case transferrin saturation is high) from a high ferritin due to other causes such as inflammation or non alcoholic fatty liver disease. • If serum ferritin and transferrin saturation is high and there is no other reason then genetic testing can be performed to confirm haemochromatosis. • Liver biopsy with Perl’s stain can be used to establish the iron concentration in the parenchymal cells used to be the gold standard but has been surpassed by genetic testing. • A CT abdomen scan can show a non-specific increase in attenuation of the liver. • MRI can give a more detailed picture of liver deposits of iron. It can also be used to look at iron deposits in the heart.

Answer 191

Complications • Type 1 Diabetes (iron affects the functioning of the pancreas) • Liver Cirrhosis • Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility) • Cardiomyopathy (iron deposits in the heart) • Hepatocellular Carcinoma • Hypothyroidism (iron deposits in the thyroid) • Chrondocalcinosis / pseudogout (calcium deposits in joints) causing arthritis

Answer 192

Management • Venesection = a weekly protocol of removing blood to decrease total iron • Iron chelation therapy • Monitoring serum ferritin • Avoid alcohol • Genetic counselling • Monitoring and treatment of complications

Answer 193

Wilson’s disease is an autosomal recessive genetic condition resulting in the excessive accumulation of copper in the body tissues, particularly in the liver. It is caused by mutations in the Wilson disease protein gene on chromosome 13 (also called the ATP7B copper-binding protein). This copper-transporting protein is important in helping remove excess copper from the body via the liver. Copper is excreted in the bile.

Answer 194

Wilson’s disease typically presents in teenagers or young adults. It is rare for symptoms to start after age 40. The presenting features vary significantly between individuals. Liver problems usually arise first. Rarely it can present initially with neurological or psychiatric problems, although these typically occur with more advanced disease. Copper deposition in the liver leads to chronic hepatitis, eventually leading to cirrhosis.Copper deposition in the central nervous system can lead to neurological and psychiatric problems. Neurological symptoms can include tremor, dysarthria (speech difficulties) and dystonia (abnormal muscle tone). Copper deposition in the basal ganglia causes Parkinsonism (tremor, bradykinesia and rigidity). Psychiatric symptoms can include abnormal behaviour, depression, cognitive impairmentand psychosis. Kayser-Fleischer rings in the cornea (deposition of copper in Descemet’s membrane) may be seen in Wilson’s disease. These are green-brown circles surrounding the iris of the eye. They can usually be seen by the naked eye but proper assessment is made using slit lamp examination. Haemolytic anaemia (low haemoglobin caused by red blood cell destruction) may also be a feature.

Answer 195

Diagnosis Serum caeruloplasmin is the initial screening test for suspected Wilson’s disease. A low serum caeruloplasmin is suggestive of Wilson’s disease. Caeruloplasmin is the protein that carries copper in the blood. It can be falsely normal or elevated in cancer or inflammatory conditions. A 24-hour urine copper assay will show high urinary copper. Liver biopsy can be used to assess the liver copper content and assess liver disease. Scoring systems that consider various features and laboratory results are used to establish the diagnosis. Other investigations: • Kayser-Fleischer rings on slit lamp examination • MRI brain may show changes, including the characteristic “double panda sign” • Low haemoglobin with haemolytic anaemia (negative Coombs test) • Genetic testing (including screening family members)

Answer 196

Management Treatment is with copper chelation using either: ○ Penicillamine ○ Trientine Other treatments include: § Zinc salts (inhibit copper absorption in the gastrointestinal tract) § Liver transplantation

Answer 197

Gilbert syndrome Overview Gilbert syndrome is an autosomal recessive disorder that causes abnormal bilirubin processing in the liver. Gilbert syndrome is a benign, inherited cause of abnormal processing of bilirubin within the liver. This leads to recurrent episodes of unconjugated hyperbilirubinaemia.

Answer 198

Epidemiology Gilbert syndrome is the most common cause of inherited jaundice. Gilbert syndrome is seen in all populations and usually presents around the time of puberty. This is thought to be because sex hormones affect bilirubin processing in the liver. Gilbert is seen more commonly in males.

Answer 199

Bilirubin metabolism Bilirubin is a breakdown product of heme metabolism. Bilirubin is a breakdown product of haemoglobin, which is the oxygen-carrying pigment in red blood cells. Bilirubin is carried to the liver for processing where it can then be excreted into bile. Formation of bilirubin Red blood cells that contain haemoglobin are initially broken down by tissue macrophages, especially those located within the spleen. Heme is broken down by the enzyme heme oxygenase to form biliverdin, carbon monoxide and iron. Biliverdin is converted to bilirubin by biliverdin reductase. Bilirubin then binds to albumin within the serum and is carried to the liver for processing. Bilirubin is then taken up by hepatocytes.

Answer 200

Diagnosis & investigations Diagnosis is based on recurrent unconjugated hyperbilirubinaemia and the absence of obvious liver disease or haemolysis. A formal diagnosis of Gilbert syndrome does not require extensive testing. It can usually be made based on the presence of recurrent episodes of isolated unconjugated hyperbilirubinaemia and the absence of obvious haemolysis or liver disease. Blood tests Liver function tests (LFTs) will show an isolated rise in unconjugated bilirubin that should be confirmed on repeat testing. Total bilirubin is usually given as part of LFTs so it is important to ask for a ‘split bilirubin’ that gives both the conjugated and unconjugated portions. Other liver function tests (e.g. ALP, ALT) will be normal. It is important to exclude haemolysis as a potential cause of a raised unconjugated bilirubin. This involves initial screening with a full blood count +/- a reticulocyte count and peripheral blood film. If the patient is anaemic or there are any signs of haemolysis then a full haemolytic screen should be requested.

Answer 201

Management No specific management is required for patients with Gilbert syndrome. Gilbert syndrome is a benign condition without long-term sequelae. No specific treatment is indicated other than patient education.

Answer 202

Overview Barrett’s oesophagus refers to columnar metaplasia of the distal oesophagus. Barrett’s oesophagus (BO) is defined as any portion of the normal distal oesophageal squamous epithelial lining being replaced by metaplastic columnar epithelium. Metaplasia refers to the transformation one mature cell type into another. This metaplastic change is the consequence of persistent oesophageal injury due to chronic reflux of stomach content. The condition is important because it can predispose to the development of oesophageal adenocarcinoma with a 0.33% annual risk in patients with BO without dysplasia (i.e. abnormal cells).

Answer 203

Risk factors • Long standing gastro-oesophageal reflux • Male sex (male-to-female ratio 2:1) • Caucasian ethnicity • Increasing age • Obesity • Smoking • Family history

Answer 204

Clinical features Patients with BO usually have symptoms of chronic reflux, but the metaplastic columnar epithelium per se is asymptomatic. Signs and symptoms • Heartburn • Regurgitation • Chest discomfort • Dyspepsia • Nausea and/or vomiting • Dysphagia (suggestive of stricture or malignancy in context of BO and reflux) Approximately 40% of patents with BO will have no history of troublesome reflux.

Answer 205

Diagnosis BO is an endoscopic diagnosis, which is subsequently confirmed on oesophageal biopsies. The diagnosis of BO is made during upper gastrointestinal endoscopy by direct visualisation of the lower oesophagus. The squamo-columnar junction, known as the ‘Z’ line, should lie within 1cm of the GOJ, which is marked by the top of the gastric folds. Therefore, if there is evidence of metaplastic columnar epithelium ≥1cm above the GOJ biopsies should be taken to confirm the diagnosis of BO.

Answer 206

Management of BO depends on the extent of disease and presence/absence of dysplasia. Protein pump inhibitors Protein pump inhibitors (PPIs) are recommended in all patients with BO. PPIs prevent acid production within the stomach through inhibition of H+/K+ ATPases in parietal cells. This reduces the acidity of the refluxate and therefore the damage to the lower oesophageal mucosa. PPI reduce risk of both high grade dysplasia and oesophageal carcinoma. Dysplastic vs non - dysplastic Barrett’s oesophagus Following endoscopic identification of BO, patients will have biopsies to confirm the diagnosis. If dysplasia is identified on biopsy, management should follow dysplastic Barrett's surveillance. If no dysplasia is identified on biopsy, management should follow non-dysplastic surveillance.

Answer 207

Gastro-oesophageal reflux disease (GORD) is where acid from the stomach flows through the lower oesophageal sphincter and into the oesophagus, where it irritates the lining and causes symptoms. The oesophagus has a squamous epithelial lining that makes it more sensitive to the effects of stomach acid. The stomach has a columnar epithelial lining that is more protected against stomach acid.

Answer 208

Causes and Triggers Certain factors can exacerbate or worsen the symptoms of GORD: • Greasy and spicy foods • Coffee and tea • Alcohol • Non-steroidal anti-inflammatory drugs • Stress • Smoking • Obesity • Hiatus hernia

Answer 209

Presentation Dyspepsia Dyspepsia is a non-specific term used to describe indigestion. It covers the symptoms of GORD: ○ Heartburn ○ Acid regurgitation ○ Retrosternal or epigastric pain ○ Bloating ○ Nocturnal cough ○ Hoarse voice

Answer 210

Red Flags Patients with symptoms suspicious of cancer get a two week wait referral for further investigation. It is possible to refer from primary care for an urgent direct-access endoscopy. The NICE guidelines on suspected cancer (2021) have criteria for when to refer urgently or routinely. The key red flag features are: • Dysphagia (difficulty swallowing) at any age gets an immediate two week wait referral • Aged over 55 (this is generally the cut-off for urgent versus routine referrals) • Weight loss • Upper abdominal pain • Reflux • Treatment-resistant dyspepsia • Nausea and vomiting • Upper abdominal mass on palpation • Low haemoglobin (anaemia) • Raised platelet count TOM TIP: Remember dysphagia as a critical red flag. Any patient presenting with the feeling that food is getting stuck on the way down needs an urgent two week wait referral for an endoscopy.

Answer 211

Endoscopy An oesophago-gastro-duodenoscopy (OGD) involves inserting a camera through the mouth down to the oesophagus, stomach and duodenum. It can be used to assess for: • Gastritis • Peptic ulcers • Upper gastrointestinal bleeding • Oesophageal varices (in liver cirrhosis) • Barretts oesophagus • Oesophageal stricture • Malignancy of the oesophagus or stomach Patients with evidence of upper gastrointestinal bleeding (e.g., melaena or coffee ground vomiting) need admission and urgent endoscopy.

Answer 212

Hiatus Hernias A hiatus hernia refers to the herniation of the stomach up through the diaphragm. The diaphragm opening should be at the lower oesophageal sphincter level and fixed in place. A narrow opening helps to maintain the sphincter and stops acid and stomach contents from refluxing into the oesophagus. When the opening of the diaphragm is wider, the stomach can enter through the diaphragm, and the contents of the stomach can reflux into the oesophagus. There are four types of hiatus hernia: • Type 1: Sliding • Type 2: Rolling • Type 3: Combination of sliding and rolling • Type 4: Large opening with additional abdominal organs entering the thorax A sliding hiatus hernia is where the stomach slides up through the diaphragm, with the gastro-oesophageal junction passing up into the thorax. A rolling hiatus hernia is where a separate portion of the stomach (i.e., the fundus), folds around and enters through the diaphragm opening, alongside the oesophagus. Type 4 hiatus hernia refers to a large hernia that allows other intra-abdominal organs to pass through the diaphragm opening (e.g., bowel, pancreas or omentum). Hiatus hernias can be intermittent, meaning they may not be seen on investigations. Hiatus hernias may be seen on a: ○ Chest x-ray ○ CT scan ○ Endoscopy ○ Barium swallow test

Answer 213

Management Management of gastro-oesophageal reflux disease can be split into: • Lifestyle changes • Reviewing medications (e.g., stop NSAIDs) • Antacids (e.g., Gaviscon, Pepto-Bismol and Rennie) – short term only • Proton pump inhibitors (e.g., omeprazole and lansoprazole) • Histamine H2-receptor antagonists (e.g., famotidine) • Surgery Lifestyle changes include: ○ Reduce tea, coffee and alcohol ○ Weight loss ○ Avoid smoking ○ Smaller, lighter meals ○ Avoid heavy meals before bedtime ○ Stay upright after meals rather than lying flat Surgery for reflux is called laparoscopic fundoplication. This involves tying the fundus of the stomach around the lower oesophagus to narrow the lower oesophageal sphincter. TOM TIP: The usual medical strategy when someone presents for the first time is to exclude red flags, address potential triggers, offer a 1 month trial of a proton pump inhibitor and consider H. pylori testing.

Answer 214

Helicobacter Pylori Helicobacter pylori (H. pylori) is a gram-negative aerobic bacteria that can live in the stomach. It causes damage to the epithelial lining, resulting in gastritis, ulcers and an increased risk of stomach cancer. It avoids the acidic environment by forcing its way into the gastric mucosa, using flagella to propel itself. It creates gaps in the mucosa, exposing the epithelial cells underneath to damage from stomach acid. H. pylori produces ammonium hydroxide, which neutralises the acid surrounding the bacteria. It also produces several toxins. The ammonia and toxins lead to gastric mucosal damage. We offer a test for H. pylori to anyone with dyspepsia. They need 2 weeks without using a PPI before testing for H. pylori for an accurate result. Investigations for H. Pylori are: • Stool antigen test • Urea breath test using radiolabelled carbon 13 • H. pylori antibody test (blood) • Rapid urease test performed during endoscopy (also known as the CLO test) A rapid urease test involves taking a small biopsy of the stomach mucosa. This is added to a liquid medium containing urea. H. pylori produce urease enzymes that convert urea to ammonia. Ammonia makes the solution more alkaline. A pH indicator (e.g., phenol red) changes colour if the pH rises, giving a positive result. The H. pylori eradication regime involves triple therapy with a proton pump inhibitor (e.g., omeprazole) plus two antibiotics (e.g., amoxicillin and clarithromycin) for 7 days. Routine re-testing is not necessary after treatment.

Answer 215

Zollinger–Ellison Syndrome Zollinger-Ellison syndrome is a rare condition where a duodenal or pancreatic tumour secretes excessive quantities of gastrin. Gastrin is a hormone that stimulates acid secretion in the stomach. Therefore, there is excess production of stomach acid, resulting in severe dyspepsia, diarrhoea and peptic ulcers. Gastrin-secreting tumours (gastrinomas) may be associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant genetic condition, which can also cause hormone-secreting tumours of the parathyroid and pituitary glands.

Answer 216

N-acetylcysteine. Additional management for acute ingestion (<8 hours) • Activated charcoal: consider 50 g for adults if ingestion of >150 mg/kg and presentation within one hour

Answer 217

There are two major types of cancer that arise from the oesophagus, depending on the cell of origin. • Squamous cell carcinoma (SCC): usually located in the upper or middle oesophagus. Accounts for >90% of cases worldwide. • Adenocarcinoma (AC): usually located in the lower oesophagus. Due to chronic reflux and development of a columnar metaplasia, which is a precursor lesion known as Barrett’s oesophagus. Rarer forms of oesophageal cancers include small cell carcinoma, sarcoma, lymphoma, melanoma and choriocarcinoma.

Answer 218

Aetiology Smoking and alcohol consumption are the two major risk factors for the development of SCC. Oesophageal neoplasia develops due to sequential mutations that occur in the oesophageal epithelium, which allows cells to proliferate uncontrollably. Several risk factors for both SCC and AC increase the likelihood of developing these mutations. Squamous cell carcinoma The biggest risk factors for development of SCC include alcohol consumption and smoking. • Smoking • Alcohol consumption • Foods containing N-nitroso compounds • Chewing of areca nuts • Previous partial gastrectomy • Atrophic gastritis • Human papillomavirus (HPV): mainly genotypes 16 and 18 • Tylosis: rare condition leading to hyperkeratosis of hands and feet Adenocarcinoma The majority of AC cases arise from Barrett’s oesophagus, which refers to columnar metaplasia of the lower oesophagus due to chronic reflux. This a pre-malignant lesion. ○ Chronic reflux ○ Barrett’s oesophagus: 30-fold increase risk of AC ○ Smoking ○ Obesity ○ Zollinger-Ellison syndrome: gastrin-secreting tumour leading to excess hydrochloric acid.

Answer 219

Usually in the mid oesophagus Squamous cell carcinoma The majority of SCCs occur due to chronic alcohol consumption and smoking, which damage cellular DNA. This leads to development of genetic mutations that promote abnormal cell growth. Overtime, the cells proliferate uncontrollably leading to invasive cancer. SCC may be seen as an infiltrating and ulcerated mass in the middle oesophagus, especially if advanced. There is early invasion into surrounding lymph nodes and the tumour may metastasize to liver, bone and lung.

Answer 220

Clinical features The hallmark feature of oesophageal cancer is dysphagia, which refers to difficulty swallowing. Symptoms • Constitutional symptoms: fevers, anorexia, lethargy, weight loss • Dysphagia: difficulty swallowing • Weight loss: due to tumour-related anorexia and poor nutrition from swallowing difficulties • Bleeding: haematemesis and melaena • Pain: typically retrosternal pain • Aspiration: cough, shortness of breath, fever • Hoarseness: if there is extension to involve the recurrent laryngeal nerve Signs ○ Lymphadenopathy: if local tumour spread ○ Cachexia ○ Pallor: due to anaemia ○ Hepatomegaly: if metastatic spread

Answer 221

Adenocarcinoma - usually found near the gastro oesophageal junction (GOJ) Typically, chronic reflux leads to inflammation and damage of the lower oesophageal mucosa. This results in columnar metaplasia, which refers to the transformation of the mature squamous cell type to columnar cell type. This metaplastic epithelium may become dysplastic, which refers to cells with abnormal growth and development. The dysplastic epithelium acquires further genetic mutation that promotes development of invasive carcinoma. AC is most commonly located near the GOJ and there is usually early lymph node involvement.

Answer 222

Diagnosis Oesophageal cancer is diagnosed using upper GI endoscopy and biopsies of suspected lesions. The principle test for the diagnosis of oesophageal cancer is an upper GI endoscopy known as a gastroscopy. This a camera test that allows direct visualisation of the upper gastrointestinal tract including oesophagus and gastro-oesophageal junction. If cancer is confirmed do a CT chest/abdomen/pelvis to see staging of the cancer

Answer 223

• Surgery: resection of oesophageal or gastro-oesophageal tumours (e.g. oesophagectomy). • Endoscopic techniques: mucosal resection or mucosal dissection. • Radiotherapy: use of high energy rays to destroy cancer cells. • Chemotherapy: use of anti-cancer medications to destroy cancer cells. • Targeted cancer drugs: monoclonal antibodies against certain receptors (e.g. HER2). • Palliative care: use of chemotherapy/radiotherapy or stenting to control disease and/or symptoms without aiming to cure. • Best supportive care: focus primarily on symptoms and quality of life without systemic treatments.

Answer 224

Abdominal u Appendicitis u Obstruction u Perforation u Ectopic pregnancy u Ovarian cancer u Biliary pathology u Pancreatitis u Renal stones/pyelonephritis Non Abdominal u CVS u MI, angina, aneurysm Neurological u Headache (meningitis, encephalitis, sub arachnoid sub dural bleeds etc) u Migraine u Raised ICP u Glaucoma

Answer 225

Infectious Causes: u Ask about recent illnesses (such as possible gastroenteritis) in family members and other contacts such as people at their place of work (or school). u Has there been any recent travel abroad and particularly to developing country where hygiene may be poor? u If there is diarrhoea associated with the vomiting and if so is there any blood or mucus in the stools? u Try to obtain any recent history of any food consumption e.g. out of date food or dodgy takeaways? u Food poisoning and infectious bloody diarrhoea are notifiable diseases. u Consider any history of heartburn as nausea may be only symptom of gastroesophageal reflux. u Obtain an accurate and preferably corroborated alcohol history. u Excess alcohol is a very common cause of nausea and vomiting. u Chronic dependence is associated with early morning nausea and vomiting u Is the patient pregnant as early morning vomiting is associated with pregnancy. Consider any female of child bearing age and if in doubt undertake a pregnancy test u Take a history of any OTC medication and any recent changes in prescribed medication. u Does the patient have diabetes mellitus (type I) as acute vomiting can be a feature of DKA while diabetic gastroparesis can cause chronic vomiting. u Is it any associated vertigo, gait instability or nystagmus? This might suggest labyrinth disorders such as vestibular neuronitis as a cause of the vomiting. u Systems Review u Cough u SOB uMay indicate LRTI or CVD u Neurology – headaches, visual changes, dizziness/vertigo u Urinary symptoms uLRTIs and UTIs often present as vomiting in the elderly and in children

Answer 226

Dipstick urine test for glucose and infection Pregnancy test FBC, U&Es, LFT, magnesium, phosphate and CRP These basic investigations will determine the presence or absence of dehydration, infection, hypokalaemia and more rarely hypomagnesaemia and hypophosphatemia associated with persistent vomiting Serum amylase should be tested (acute pancreatitis), random serum glucose (DKA), serum calcium (hypercalcaemia) and TFT (vomiting can be feature of acute hypo and hyper thyroidism). In seriously ill patients with nausea and vomiting consider arterial blood gas (ABG) to look for metabolic alkalosis (with respiratory compensation) Radiological considerations: u Abdominal X-ray – if considering small or large bowel obstruction u Chest X-ray erect to exclude pneumonia or perforation u Ultrasound of the abdomen and biliary tree in suspected cholecystitis or pancreatitis u CT abdomen and pelvis will help refine the differential diagnosis in the acute abdomen u CT Head should be done if suspected raised intracranial pressure/possible cerebral lesion u Barium studies including barium meal or barium follow through, can be useful in cases of chronic vomiting to confirm delayed gastric emptying u In rare circumstances MRI is used to investigate the small bowel in chronic nausea and vomiting.

Answer 227

Wilson’s disease

Answer 228

Hereditary haemochromotosis

Answer 229

Most common: Colorectal Dermatology Others: Vascular GUM Gastroenterology

Answer 230

 Anal fissures are relatively common, with a lifetime incidence of approx 10%  Sexes are equally affected  Most common in 20s-40s, rarer in the elderly  Acute (<6/52 duration) are far more common than chronic (>6/52 duration) fissures  Can also be considered primary (no apparent cause) or secondary  Vast majority are posterior midline, but can also be anterior midline or lateral (more common with secondary fissures)

Answer 231

 Tearing from passage of hard stools  Anal trauma (sex, surgery)  Drugs (chemo, opiods, nicorandil)  IBD  STIs  Dermatological conditions (psoriasis, eczema, pruritis ani)  Pregnancy/childbirth (anterior midline)

Answer 232

Symptoms  Localised pain on defecation (sharp, can be persistent, tearing sensation)  Bleeding (small amount, bright red, on wiping)

Answer 233

Management  Keep stools soft, regular, easy to pass  Anal hygiene  Avoid straining or stool withholding  Manage underlying causes for secondary fissures  Pain relief – simple analgesia, warm bath, lidocaine ointment  Consider referral if atypical,elderly,secondary, severe,diagnosis unclear (referral to colorectal) Medical Management  GTN 0.4% rectal ointment (Rectogesic) applied BD for 6-8 weeks  Headache main side effect (~third of cases)  Diltiazem 2% topical (unlicensed – seek specialist advice)  Nifedipine (oral – secondary care only)  Botox (secondary care only)  Surgical management (most commonly lateral internal sphincterotomy – 85% cure rate)

Answer 234

 Haemorrhoids are abnormal enlargements of mucosal cushions in the anal canal  These vascular mucosal cushions help to maintain continence  They can either be internal or external, depending on where they arise in relation to the dentate line (which is 2cm above the anal verge)  External piles originate below the dentate line and are often symptomatic due to being covered in modified squamous epithelium  Internal piles originate above dentate line and are covered with columnar epithelium (no pain fibres) therefore usually not symptomatic unless strangulated or thrombosed

Answer 235

Grade 1 No prolapse, just prominent blood vessels Grade 2 Prolapse upon bearing down but spontaneous reduction Grade 3 Prolapse upon bearing down but requiring manual reduction Grade 4 Prolapse but inability to be manually reduced

Answer 236

 Studies suggest 13-65% of the population are affected  Yearly prevalence in the UK of approx. 10%  Most common in those aged 40-65 but can happen at any age  Increased likelihood with straining, constipation, heavy lifting, pregnancy/childbirth, increased intra- abdominal pressure (ie: ascites), aging, chronic cough Old haemorrhoids can also present as new skin tags

Answer 237

 Sometimes asymptomatic and incidental  Most common symptom is bright red, fresh rectal bleeding when opening bowels – can be on wiping, coating stool, or in pan. Usually painless.  Itching or irritation  Feelings of incomplete emptying, rectal fullness, or discomfort  Patient may be aware of a palpable lump  Usually painless unless strangulated or thrombosed  On examination – bluish swellings, internal not visible unless straining.  Need to do DRE (to exclude anything else)

Answer 238

 Refer anyone who has acutely painful, thrombosed or incarcerated haemorrhoids  Refer if symptoms are severe and likely to need surgical management  Refer if diagnosis is unclear, or there is suspicion of other pathology (ie: anal or rectal carcinoma)  Consider referral for proctoscopy or flexible sigmoidoscopy for all patients to confirm diagnosis (internal piles look like pink swellings on proctoscope)

Answer 239

Primary Care Management  Ensure stools are soft and easy to pass  Good anal hygiene, avoid stool withholding  Consider topical treatment (creams or suppositories)  These may have astringents (reduce irritation), anaesthetics (reduce pain), steroids (reduce inflammation)  For example – Anusol (astringent & emollient), Germoloids (lidocaine & astringent), Proctosedyl (anaesthetic & steroid)  Use steroid based treatments for 7 days only, anaesthetics for a few days at a time

Answer 240

Secondary Care Management (Non-Surgical)  Rubber band ligation is most common and involves a band applied to base of pile, which becomes necrotic and sloughs off.Three can be banded at one visit. ~20% risk of recurrence.  Injection sclerotheapy provides short term benefit – phenol in oil is injected around the pedicles of the piles, inducing a fibrotic reaction which obliterates vessels and causes atrophy of the piles  Photocoagulation for 1st and 2nd degree piles – uses infrared energy to induce fibrosis and mucosal fixation, therefore reducing tendency to prolapse  Bipolar diathermy and direct-current electrotherapy involve local application of heat to cause coagulation and fibrosis

Answer 241

Secondary care management (Surgical)  Haemorrhoidectomy involves excision of symptomatic piles and has the best long- term effect with less than 20% recurrence. Complications include bleeding, fistula, abscess, infection, incontinence.  Staple haemorrhoidectomy excises a donut of mucosa from the upper anal canal and lifts the mucosal cushions – more accurately called haemorrhoidopexy as not excised but relocated  Haemorrhoidal artery ligation – using a proctoscope, the arteries are ligated with sutures to remove the blood supply to the piles. Not frequently used as often needs to be repeated and other options are better.

Answer 242

 A collection of pus in the anal or perianal region  90% caused by acute infection in the anal glands  Classified by location – perianal (most common), ischioanal, intersphincteric and supralevator  Risk factors include immunocompromised patients, IBD, diabetics, receptive anal sex  Mean age 40, men twice as affected as women

Answer 243

 Usually present with a painful,hard lump in the anal area  Pain is often constant, throbbing, exacerbated by sitting or defecation  May get discharge of pus from the rectum  Can be systemically unwell with fever  DRE diagnostic but likely painful ++,may need scope or imaging depending on location/severity

Answer 244

 Management is nearly always surgical  Very small abscesses may self-resolve but most need I&D  Antibiotics rarely helpful alone but may be used as adjunct to surgery  From primary care – refer to colorectal surgeons  Complication – can lead to fistula-in-ano

Answer 245

 Fistula (tracts that form between blocked internal gland and skin) occur in 40% of abscess cases  Classified by anatomical relationship to the anal sphincter  Pain, discharge, skin irritation and sometimes bleeding are common presenting symptoms  Usually follow abscesses, also in Crohn’s, diverticulitis, HS,TB,HIV and post-colorectal surgery

Answer 246

Always a surgical treatment  If fistula is straightforward and involves minimal muscle,it can be “unroofed” in a fistulotomy and heal from the inside out  Setons – surgical thread to help drain and heal – can be used and progressively tighter ones to slowly cut through – sometimes left in place permanently  Advancement flap procedure – used if fistulotomy has high risk of incontinence – involves cutting the fistula and covering the hole with a flap of tissue from inside the rectum  LIFT procedure – cut made above fistula and sphincter muscles pulled apart – fistula sealed at both ends and cut open so lies flat  Endoscopic ablation – tiny endoscope inserted in the fistula and electrode passed through to seal  Laser surgery – similar to above  Fibrin glue – seals and heals  Bioprosthetic plug – made from animal tissue, blocks the internal opening of a fistula

Answer 247

 Usually squamous cell cancers histologically (different from bowel Ca)  Not especially common, approx. 1000 cases in the UK annually (compared to 40k bowel)  65% of cases occur in women  5yr survival rate approx. 60%  Most often diagnosed clinically and with direct imaging (proctoscope or flexi sig)  NICE guidelines: “unexplained anal mass or unexplained anal ulceration”

Answer 248

 A benign anal pain syndrome – people often suffer for years before approaching health professionals  Thought to be due to spasm of muscles, either anal sphincter or pelvic floor muscles  Affects about 8% of the population, but only about 1/3rd of these will ever seek help  Characterised by recurrent episodes of severe,cramping pain that often occur at night  Attacks are usually infrequent so drug therapies rarely indicted and not much evidence base  Reassurance often helpful – but make sure to investigate to exclude any other pathology. Abdo and DRE as a minimum, flexi sig advised

Answer 249

(Itchy bum)  More commonly affects men than women, and most commonly in those aged 40-60yrs  Many, many causes but can be divided into primary (idiopathic, functional) or secondary  Assess duration and pattern of itch, any exacerbating or relieving factors, hygiene routines, and any associated sx

Answer 250

(Itchy bum)  Management – treat secondary causes. Avoid scratching, avoid irritants, wash bottom, dry bottom.  Consider relief products – mild steroid cream for a few days, antihistamines.

Answer 251

(Itchy bum)  Approx 50% of cases are caused by dermatological problems including psorarisis, dermatitis, skin tags, lichen sclerosus or planus, seb derm, hidradenitis supparativa  Parasites – threadworm (worse at night time) or scabies.Viral, bacterial, fungal infections including STIs.  Anal/colorectal Ca (20% of anal causes), piles (20%), fissures (12%), fistulas, incontinence, chronic diarrhoea  Diabetes, anaemia, blood Ca, thyroid problems, liver disease  Medications including steroids, colchicine, antibiotics, immunosuppressants

Answer 252

 Pain and inflammation of the last 6 inches of the rectum  Symptoms include: fecal urgency, diarrhoea, constipation, tenesmus (feeling of wanting to go), cramping pain, mucus on stools, PR bleeding or pus PR  More common in those who practice receptive anal intercourse  Usually either as a result of IBD or infections incl. STIs (ghonnarhea). Can also occur as a result of radiation therapy ie prostate/bladder cancer) - monkey pox can also cause  Full hx including sexual – DRE, consider bloods, stool sample MC&S and calprotectin, anal swab, and maybe some imaging. DRE.  Treatment is to manage the underlying condition

Answer 253

Things in the blood Things in the head Things in the ears Things in the gut