Gastrointestinal Tract

The alimentary canal is a long tube which runs from the mouth to the ****. It is part of the digestive system which also includes the liver and the pancreas. 

Functions of the alimentary canal:

• Mouth: food is digested here and saliva is added containing amylase to begin the breakdown of starch.
• Oesophagus: food passes through by peristalsis, from the mouth to stomach.
• Stomach: muscular walls squeeze on food to make it semi-liquid and gastric juice is secreted which contains protease to digest protein and HCl to maintain an optimum pH.
• Duodenum: the first part of the small intestine which receives pancreatic juice containing protease, lipase and amylase and also contains sodium hydrogen carbonate to neutralise acid from the stomach, producing a pH of 7-8.
  
• Liver: makes bile, which contains salts that emulsify fats, forming droplets with a large surface area to make digestion by lipase more efficient.
• Ileum: second part of the small intestine where enzymes in the epithelial lining, break down lactose and peptides and the surface area is increased by the presence of villi which allows the efficient absorption of digested food molecules.
• Large Intestine: reabsorbs water from indigestible products allowing solid waste to be expelled.
• Rectum: stores faeces until it is egested.
• Anus: has a muscle to control when faeces are egested from the body.

• Parietal Cells: epithelial cells that secrete HCl and Intrinsic Factor.
• Chief Cells: release Pepsinogen (activated by pepsin) and Gastric Lipase.
• Mucous Cells: produces Mucus and Bicarbonate and they line the digestive tract.
• ECL Cells: neuroendocrine cells that produce gastric acid by the release of Histamine.
• G-Cells: found deep with the stomach antrum and secrete Gastrin.
• D Cells: produce Somatostatin.

• Parietal cells in the stomach secrete two liters of acid a day in the form of HCl.
• The acid in the stomach functions to kill bacteria, and aid digestion by solubilising food.
• The protein pump for acid secretion is the H+/K+ ATPase which is found on the apical membrane of parietal cells. It uses the energy derived from ATP hydrolysis to pump hydrogen ions into the lumen in exchange for potassium ions.
• There are three regulatory molecules that stimulate acid secretion: acetylcholine; histamine; and gastrin as well as one that inhibits acid secretion: somatostatin. 

A peptic ulcer is defined as a full-thickness breach of the mucosa in the lower oesophagus, stomach or duodenum that hails to heal over a reasonable period.

Symptoms are:

• Epigastric pain which may sometimes wake the patient in the night.
  
• Nausea.
• Oral flatulence, bloating, distension and intolerance of fatty food.
  
• Heartburn.
• A posterior ulcer may cause pain radiating to the back.

Complications include:

• Haemorrhage: typically in duodenal ulcers which erode into the gastroduodenal artery leading to haematemesis. 
• Perforation: acute abdominal pain and generalised outflow.
• Fibrous Structure: obstructs gastric outflow.

Drug treatment heals by: reduces acid secretion; increases mucosal resistance; or eradicates H pylori.

1. Corpus Gastritis: H pylori induced inflammation leads to atrophy of oxyntic glands, which predominate in the corpus, and reduced acid secretion. The tissue damage leads to a gastric ulcer.

2. Pyloric Gastritis: H pylori induced inflammation leads to increased gastrin secretion and decreased somatostatin secretion. This leads to parietal cell proliferation and hypersecretion. Excess acid in the duodenum overwhelms mucosal and acid-neutralising protective mechanisms leading to duodenal ulcers.

3. Autoimmune Gastritis: an organ-specific autoimmune disease, causing the destruction of gastric parietal cells in the glands of the fundus and corpus. The inflamed area is different from H pylori induced gastritis. In time an extensive area is destroyed so there is a risk of cancer. 

4. Reactive Gastritis: due to gastric irritants e.g. alcohol and NSAIDs and occurs in the antrum, due to bile reflux from the duodenum. 

5. Erosive/Haemorrhagic Gastritis: a bleeding defect in the gastric mucosa, usually due to ingestion of large quantities of NSAIDs, aspirin or alcohol. In acutely unwell patients there is a significant risk of haemorrhage.

NSAID-Induced Peptic Ulcers:

• NSAID Mode of Action: inhibition of prostaglandin production from arachidonic acid.
• Endogenous Prostaglandins: reduce HCl production and increase mucus and bicarbonate production leading to better protection of gastric epithelium.
• Aspirin doses as low as 10mg/day inhibit prostaglandin production and cause stomach damage. The higher the dose the more change of GI damage.

Treatment of NSAID Peptic Ulcer:

1. NSAID should be withdrawn.

2. Full dose PPI should be given for 2 months.

3. Smoking Cessation: smoking increases the risk of peptic ulcer, delays healing and opposes the action of H2-receptor antagonists.

For those continuing to take NSAIDs after a peptic ulcer has healed, they should be warned of the potential harm from NSAID treatment, review NSAID use regularly (at least every 6 months) and consider reducing the dose or substituting with paracetamol or an alternative analgesic. In people at a high risk, those with previous ulceration, they should consider a COX-2 selective NSAID and prescribe with a PPI.

It is present in 100% of patient's with duodenal ulcers who are not taking NSAIDs. H.pylori can increase gastrin production and can also produce enzymes which damage the mucosa.

Testing for H.pylori Infections:

• Non-infective Tests: 12C urea breath test, stool antigen test, and serology.
• Invasive Tests: rapid urease test, histology, and culture. (Treatment with PPIs must be discontinued two weeks before the test to prevent a false negative result occurring.)

Treatment of H.pylori Associated Ulcers:

• Antibiotics and PPIs are the main courses of treatment.
• Offered a one week course of PPI and amoxicillin and either clarithromycin and metronidazole.
• PAC 500: amoxicillin 1g BD, clarithromycin 500mg BD and omeprazole 20mg BD.
• If they are allergic a one week course of PPI and clarithromycin and metronidazole should be given.
• PMC250: metronidazole 400mg BD, clarithromycin 250mg BD and omeprazole 20mg BD.

Concordance can cause treatment failure due to nausea and vomiting occurring. After two months, a gastric ulcer should be rescoped due to the risk of bleeding. If the ulcer is fully healed on re-scoping and no further symptoms then the patients may be prescribed a low dose PPI to be taken when required.

Drugs: Omeprazole, Lansoprazole, Esomeprazole, Rabeprazole, Pantoprazole

Indications: Reflex Oesophagitis, Peptic Ulcers, H.pylori Infection, Zollinger-Ellison Syndrome

How do they work? They stop cells in the lining of the stomach producing too much acid which can help to prevent ulcers from forming or assist the healing process. 

Pharmacokinetics: Half-life is 1-2 hours and long duration of action (2-3 days) due to accumulation in the canaliculi of the gland and binds irreversibly to the pump.

Side Effects: constipation, diarrhoea, wind, headaches, nausea, abdominal pain and vomiting.

Cautions: Can mask gastric malignancy, liver disease, pregnant and breastfeeding women.

Interactions: Inhibit P50 which is usually minor at normal doses but can be important for patients taking phenytoin or warfarin.

Advice for Patients: Omeprazole and Pantoprazole can be bought OTC but should only be used for four weeks max. PPIs are well absorbed by the body and may provide quick relief for some problems such as heartburn, however, if they are used for an ulcer, it may take longer.

                       UNIONISED                                                         IONISED

At neutral pH Omeprazole is in the unionised state.          At pH < 4 Omeprazole is in the ionised state.

Freely membrane permeable.                                             Membrane permeability is much reduced.

Easily enters parietal cells.                                                Trapped in parietal cells.

Therefore Omeprazole accumulates in parietal cells at a pH at less than 4.

Drugs: Ranitidine, Cimetidine, Nizatidine, Famotidine

Indications: Gastric Ulcers, Duodenal Ulcers, Reflux Oesophagitis

Pharmacokinetics: Half life of about 2 hours.

Adverse Drug Reactions: Cimetidine antagonises the androgen receptor and causes gynaecomastia and sexual dysfunction in men. Dizziness, muscle pain, rashes, and hypergastrinaemia.

Cautions: Can mask gastric malignancy.

Drug Interactions:

• Cimetidine inhibits p450 so there is a potential interaction with several drugs e.g. oral anticoagulants and tricyclic antidepressants.
• Cimetidine inhibits liver blood flow so reduces clearance of drugs that have a high hepatic metabolism, increasing their concentration e.g. propranolol.
• Ranitidine doesn't cause either of these.

Drugs: Magnesium Silicate or Hydroxide and Aluminium Hydroxide

How do they work? They directly neutralise acids, raising gastric pH thus inhibiting pepsin above pH5.

Indications: Symptomatic relief of dyspepsia and can provide sufficient alkalinisation to allow healing.

Pharmacokinetics: Mg and Al salts are poorly absorbed and the duration of action depends on gastric emptying: 30 minutes on an empty stomach; or 2 hours after eating. Liquid formulations have a faster onset of action but a shorter duration.

Adverse Drug Reactions: 

• Al3+ salts - cause constipation.
• Mg2+ salts - cause diarrhoea.
• Ca2+ salts - should be avoided as they stimulate gastrin secretion.
• Sodium Bicarbonate - acts rapidly at pH > 7.4 and large doses cause alkalosis.

Drug Interactions: absorption of some drugs, e.g. digoxin and tetracycline, is affected so preferably take drugs greater than 30 minutes apart from other drugs.

GORD is caused by the passage of gastric contents into the oesophagus (squamous epithelial lining which is not designed to resist acidity so inflammation can lead to symptoms of GORD). This is due to structural changes at the gastro-oesophageal junction which allows gastric contents to pass into the oesophagus. It does not have the same protective layers (mucus) as the stomach so damage occurs to the oesophageal lining resulting in symptoms of GORD.

Most patients with GORD have a hiatus hernia. This occurs when the gastric antrum herniates through the diaphragm leaving the oesophagus exposed to large amounts of acids causing symptoms of GORD.

Symptoms:

• Typical: heartburn and acid regurgitation.
• Atypical: dysphagia, non-cardiac chest pain and abdominal pain.
• Extra-oesophageal: a sore throat, sinusitis, chronic cough and non-atopic asthma.

Pathomechanism:

• The presence of a sliding hiatus hernia causes the gastro-oesophageal junction to be drawn upwards.
• Part of the proximal stomach is located in the thorax and not the abdomen.
• The function of the gastro-oesophageal junction is impaired.

Endoscopy Negative Reflux Disease (50% of cases)

• No visible changes to oesophageal mucosa shown during endoscopy.
• It is thought that the mucosa becomes highly sensitive to acid reflux which results in a high burden of both typical and non-typical symptoms.
• It often doesn't respond fully to treatment with PPIs and can be associated with IBS.

Erosive Oesophagitis

• There will be inflamed and ulcerated mucosa visible on endoscopy.
• Patients usually present with typical symptoms e.g. heartburn.
• Greater acid production will increase the severity of the disease.
• Erosive oesophagitis responds well to PPI with full healing of mucosa but there is a risk of stricture with severe disease.

Barrett's Columnar-Lined Oesophagus

• The normal squamous epithelium is replaced by columnar intestinal epithelium which are insensitive to acid.
• The length of the oesophagus is affected increases with increased exposure to acid.
• There is an increased risk of developing oesophageal cancer but symptoms are not as severe.

Many people will present in their local pharmacy with indigestion and often a short course of an antacid or an alginate can be recommended.

Antacids: Alka-Seltzer, Gelusil, Maalox, Mylanta, Pepto-Bismol, Rolaids, and Tums.

Alginates: aluminum hydroxide, magnesium carbonate, and magnesium trisilicate.

H2 Blockers: cimetidine, famotidine, nizatidine, and ranitidine. 

PPIs: lansoprazole, omeprazole, and omeprazole with sodium bicarbonate.

Alarm Symptoms for Immediate Referral:

• Unintentional weight loss.
• Signs of GI bleeding.
• Dysphagia.
• Abdominal swelling and severe abdominal pain
• Persistent vomiting for more than 2 days.
• Patients aged 55 or older should be urgently referred for an endoscopy if they present with unexplained and persistent dyspepsia.
• Patients on medication that could exacerbate GORD e.g. NSAIDs.

1. Treatment at the GP:

• If no symptoms are present then a short course of a PPI is first-line treatment.
• The course should be no more than 1-2 months long and then the need for treatment reassessed.
• An H.pylori test may be carried out in order to eliminate this as a cause of the symptoms.
• If alarm symptoms are present, the patient should be referred for endoscopy

2. Treatment Post-Endoscopy: Endoscopy Negative Oesophagitis and Erosive Oesophagitis:

• Full dose PPI is given for 4-8 weeks.
• If symptoms reoccur then the lowest dose of a PPI, which controls the patient's symptoms, should be prescribed for a limited number of repeat prescriptions.
• If necessary the patient can be maintained on a 'when required' dose of a PPI.
• Alginates are often useful for symptom relief.

3. Treatment Post-Endoscopy: Barrett's Columnar-Lined Oesophagus:

• Long term PPI where dose may be increased to the max licensed dose if inadequate acid suppression occurs.
• An H2 receptor antagonist added at night along with a prokinetic agent for inadequate suppression.

Vomiting is the forceful evacuation of gastric content through the mouth. The emetic reflex is the contraction of abdominal muscles and diaphragm, increasing pressure in the stomach. Also, closure of the glottis prevents the vomit entering the lungs.

Treatment of Vomiting:

• Nausea and vomiting are symptoms, not a diagnosis.
• The preferred treatment is to remove the cause.
• Pharmacological treatment may be essential e.g. during cancer therapy to allow continued treatment.

Causes of Vomiting:

• Motion sickness, postoperative vomiting and drug-induced nausea and vomiting
• Intracranial pathology e.g. a migraine, increased pressure due to inflammation and haemorrhage.
• Emotional causes.
• Pain.
• Drugs and radiation e.g. during cancer therapy.

Emesis is controlled by two brainstem areas: Chemo Trigger Zone (CTZ), where fenestrated capillaries allow detection of circulating chemicals, and the Vomiting Centre, which is the nucleus of the solitary tract.

Anti-histamines: Cinnarizine, Cyclizine, Promethazine (act on vestibular apparatus)

Indications: travel sickness, vestibular disorders (vertigo), space motion sickness and promethazine may be used in pregnancy for severe motion sickness.

ADRs: sedation, anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention) and blocks Ca2+ transport so also causes vasodilation.

Contraindications: significant antimuscarinic activity and use in caution in prostatic hypertrophy, urinary retention, susceptibility, angle-closure glaucoma, and pylori duodenal obstruction.

Antimuscarinic Agent: hyoscine hydrobromide.

Indications: OTC for motion sickness (both prophylaxis and treatment) and GI disorders.

Pharmacokinetics: for motion sickness can use a patch on the skin behind the ear.

ADRs: less drowsiness than antihistamines but still cautioned when driving and can cause typical anticholinergic ADR.

Contraindications: myasthenia gravis, paralytic ileus, pyloric stenosis, toxic megacolon and prostatic enlargement.

Drugs: prochlorperazine, perphenazine, trifluoperazine (less sedating than chlorpromazine)

How do they work? They block access of norepinephrine and dopamine to their receptors in the brain. They act on CTZ so not useful for motion sickness or vestibular disease.

Indications: nausea and vomiting associated with neoplastic disease, radiation sickness and emesis caused by drugs such as opioids, general anaesthetics, and cytotoxics.

ADRs: resulting from DA antagonism, sedative, dizziness, and prochlorperazine can cause anti-cholinergic effects.

Cautions: avoid prochlorperazine in patients with urinary retention or glaucoma and it prolongs QT and promotes hypotension.

Contraindications: Parkinson's disease and phaeochromocytoma as it can cause a hypertensive crisis.

Interactions: prochlorperazine potentiates the effects of other sedatives and increases the effect of other drugs that lower bp or prolong QT.

Mechanism of Action: it facilitates gastric emptying and decreases small bowel transit time by binding to D2 and D3 dopamine receptors, blocking activity at the chemoreceptor trigger zone.

Indications: nausea and vomiting induced by chemotherapy (only to be used for relief of nausea and vomiting).

Pharmacokinetics: dose adjustment is not usually required with hepatic or renal insufficiency; has poor penetration so few extrapyramidal effects; doesn't antagonise antiparkinson's effects of DA agonists.

Contraindications:

• Use in conditions where conduction is or could be impaired. 
• In underlying cardiac disease due to a risk of cardiac side effects.
• When administered concomitantly with drugs that prolong QT interval or potent CYP3A4 inhibitors.
• Severe hepatic impairment.

Indications:

• In adults over 18 years, it should be used for prevention of nausea and vomiting that is postoperative, from radiotherapy, delayed (but not acute) chemotherapy-induced, and symptomatic treatment, including that associated with an acute migraine.
• May also be used in 18+ to improve absorption of oral analgesics.

Pharmacokinetics: metabolised by CYP so reduce dose in hepatic insufficiency.

ADRs: resulting from DA antagonism and there is a risk of neurological adverse effects.

Cautions: avoid in patients with GI obstructions or haemorrhage.

Contraindications: Parkinson's disease and phaeochromocytoma which can cause hypertensive crisis.

Emesis - a protective mechanism which serves to eliminate harmful substances from the stomach and duodenum which occurs due to stimulation of the emetic center situated in the medulla oblongata. 

Pathways that elicit vomiting: vomiting center (VC) and chemoreceptor trigger zone (CTZ).

1. Motion Sickness: hyoscine and cinnarizine.

2. Postoperative Vomiting: phenothiazine and 5HT antagonist.

3. Drug-induced Nausea and Vomiting: try minimising gastric irritation with equal spacing of drug and take with food. Otherwise, try phenothiazine (or another antidopaminergic) or antihistamine.

4. A Migraine: phenothiazine is helpful as it speeds up gastric emptying and facilitates absorption of analgesics. 

5. Chemotherapy: dexamethasone, phenothiazine or 5HT3 antagonists.

What is Vertigo? It is a type of dizziness that can last for a short period of time (minutes) or can last for hours or even days. People who have vertigo have a false feeling that their surroundings are moving or spinning. This is usually accompanied by a feeling of nausea and loss of balance. Vertigo is a symptom and not a condition.

What causes Vertigo?

• Usually a problem with the inner part of the ear - for example, an infection or inflammation. 
• Conditions affecting the inner ear includes: Meniere's disease, motion sickness and toxicity from medicines. 
• A common cause of vertigo in older people is benign paroxysmal positional vertigo. 
• Other causes: stroke, migraine, multiple sclerosis, a growth in the brain, double vision and drinking too much alcohol.

What is the treatment for Vertigo? Betahistine which is an H1 partial agonist, a pre-synaptic H3 antagonist and a precursor to histamine. It works by increasing blood flow to the inner ear.

What is the length of treatment for Vertigo? Only to be taken for a short time which is normally 3-14 days.

Adverse Drug Reactions: a headache and nausea.

What is constipation? It is defined as the feeling of not passing stools enough or that an individual has a strain on defecation (change from what is normal to the patient).

What are the causes of constipation? Drugs, poor diet, inadequate food intake, reduced mobility, being over/underweight, dehydration, suppressing the urge to defecate or underlying medical conditions.

Treatment for Constipation:

• Patients advised to increase the amount of fibre in their diet, avoid becoming dehydrated and regularly exercise.
• If this is ineffective then the patient may be offered either:
  • Bulk-forming laxatives e.g. ispaghula husk, bran, and methylcellulose. They are hydrophilic compounds which swell in the stomach and absorb water, promoting peristalsis. They are used for treating small hard stools.
  • Stool softeners e.g docusate sodium and glycerin suppositories. They are useful when there is a need to avoid bulk forming agents.
  • Osmotic laxatives e.g. lactulose, magnesium hydroxide and polyethylene glycol. They retain water in the bowel causing distension and purgation within one hour.
  • Stimulant Laxatives e.g senna, bisacodyl and castor oil. They are useful for rapid evacuation by stimulating the enteric nerves, increasing electrolyte and water secretion. 

1. Acute Watery Diarrhoea

• Causes: rotavirus, norovirus, V.cholerae, ETEC, C.jejuni, giardia, or cryptosporidium.
• Dangers: dehydration, severe and sometimes life-threatening with V.cholerae.

2. Acute Bloody Diarrhoea

• Causes: EI-EC (developed), EHEC, shigella, C.jejuni, salmonella or E.histolytica.
  
• Dangers: damage of the intestinal mucosa, sepsis, malnutrition and dehydration.

3. Chronic Diarrhoea

• Causes: LA-EC, cryptosporidium (AIDs), IBD, IBS or CA.
• Dangers: malnutrition, serious non-intestinal infection, and dehydration.

Acute: commonly caused by an infection and can last for about several hours or days. It is usually self-limiting so treated with oral rehydration therapy. Any blood in stools should be referred to the GP.

Chronic: can be a symptom of a condition which is experienced for longer than 14 days. Anti-motility agents can be used if there is no infective cause with first-line treatment being loperamide. Codeine may be used.

Treatment of Diarrhoea:

• Identify the cause.
•  Restore fluids/electrolytes and start rehydration therapy.
• Eliminate any infection.
• Use of absorbent agents e.g. kaolin. 
• Antidiarrhoeal drugs:
  • Opioids: cause intestinal motility, secretion, and absorption.
  • Loperamide (Imodium): 40-50 times more potent than morphine as an antidiarrhoeal agent and it increases small intestinal, mouth to cecum transit time, and increases anal sphincter tone. It has antisecretory activity against the cholera toxin and some forms of E.coli toxin. It is effective in traveller's diarrhoea. In overdose, it can cause CNS depression, paralytic ileus, and toxic megacolon. 
  • Co-Phenotrope: it is a combination of diphenoxylate (an opiate) and atropine (an antiperistaltic). It can cause euphoria, respiratory depression, drowsiness, and dizziness so there is less potential for abuse due to large amounts of adverse drug reactions. To be avoided in patients with acute inflammatory disease due to the risk of acute toxic megacolon.

1 Crohns Disease - lesions may be found anywhere between the mouth and the **** and it occurs in patches. Features include: thickened bowel walls, with a cobblestone appearance and deep ulcers that cross the muscularis mucosae and granulomas, are common.

2. Ulcerative Colitis - the disease is confined to the colon but is continuous. Ulcers do not cross the muscularis mucosae and associated with crypts.

The complications of Crohn's disease: strictures, fistulas, and fissures.The complications of ulcerative colitis: increased risk of colonic cancer and toxic megacolon. Extra-intestinal features of both conditions includes: arthritis, ocular problems, uveitis, scleritis, conjunctivitis and dermatological conditions.

Drugs: sulfasalazine, mesalazine, balsalazide, olsalazine.

Sulfasalazine is cleaved in the intestine into the active 5-ASA and sulphapyridine group. This group is responsible for the side effects such as hypersensitivity, oligospermia, and nausea so it is therefore removed resulting in mesalazine (5-ASA on its own). Balsalazide and olsalazine are both prodrugs without sulfapyridine. Unmodified mesalazine is rapidly absorbed from the small bowel. 

ADRs: risk of blood dyscrasias with the 5-ASA compound so patients need to report any signs of fever or malaise to their GP immediately. 

Only sulfasalazine, e.g. Asacol and Mesren, are licensed for the treatment of Crohn's disease. Mesren is cheaper and has a similar efficacy in comparison to Asacol.

5-ASA compounds should be prescribed by the brand. 

Useful in the acute phase of a flare up of both Crohn's disease and ulcerative colitis as they reduce the inflammation present. 

• If the patient is admitted to a hospital, they will be given intravenous steroids until a clinical improvement is seen.
• Once this occurs they are changed to oral prednisolone 40mg daily, which should be stepped down very slowly (5mg per week) to prevent relapse. 
• Long-term steroid use should be avoided in IBD due to side effects.
• Budesonide capsules (enterocort or Budenofalk) and beclometasone tablets (clipper) have been licensed for Crohn's and ulcerative colitis. 
• Budesonide has potent effects in the terminal ileum and proximal colon, with fewer systemic side effects than conventional corticosteroids.
• Budesonide is a treatment option for mild to moderate Crohn's in the area of the GIT, however, the patient should be advised that it is less effective at treating exacerbations than conventional corticosteroids such as prednisolone.

Azathioprine:

• Immunomodulating drug is useful for if a patient relapses on a dose of <15mg of prednisolone daily.
• Takes several weeks before a maximum effect is seen.
• Can cause blood dyscrasias and so the patient should be counselled regarding infections.
• Weekly FBCs and LFTs should be taken for four weeks and then monthly thereafter.

Methotrexate:

• Effective in cases of Crohn's disease which are refractory to azathioprine. 
• Dose: 25mg per week given orally or parenterally.
• Weekly FBCs and LFTs should be taken per week and then monthly.
• Side effects may be alleviated by folic acid.
• The appearance of hepatotoxicity and pulmonary fibrosis requires cessation of treatment.
• Regular spirometry is required.

Infliximab: Licensed for the treatment of both severe and Crohn's and ulcerative colitis.

• Administered by IV infusion and so requires the patient to be in the hospital during the dose.
• The risk of hypersensitivity so the patient may receive chlorphenamine and hydrocortisone as premedication.
• Resuscitation facilitates are required.
• It predisposes the patient to infections so they should have a chest x-ray and be screened for TB before starting treatment.
• Dosing depends on the indication.

Adalimumab: Only licensed for Crohn's in the context of IBD.

• Given as subcutaneous injection so it can be given at home.
• The patient should be screened for TB before starting therapy.

Ciclosporin: Only effective in ulcerative colitis and is the final attempt before surgery.

• Dose: 2-4mg/kg daily.
• Used as a bridge to azathioprine therapy because of its severe side effects. 
• Monitor U&Es, BP, FBCs, LFTs, cholesterol and Mg levels.

A stoma is where the bowel is brought to the surface of the skin. Each type of stoma has different characteristics dependent on the site. They may be functional or non-functional.

Ileostomy: normally located on the right-hand side of the body, where the output is fluid and requires a drainable bag. They may have high output with a low pH which means that the contents may damage the skin surrounding the stoma.

Colostomy: normally located on the left-hand side of the body, where the output is semi-solid and requires either a disposable sealed bag or sometimes just a cap. Usually, low output in nature but the contents can increase the risk of skin infection.

Terminal Stomas: created when all distal bowel is removed. They have one lumen that produces the stool and may be reversed by the formation of an ileoanal pouch.

Loop Ostomies: formed when part of the distal bowel needs to be rested. They have two lumina: the active proximal stoma; and inactive distal stoma.They can often be reversed once an anastomosis (a connection made surgically between adjacent blood vessels) has healed.

Common Symptoms: diarrhoea, constipation, abdominal pain (relieved by defecation), bloating/abdominal distension, faecal incontinence and passage of mucus.

GI Symptoms: lethargy, urinary incontinence, nausea, backache, and fibromyalgia. 

Diagnosis of IBS

Patient must have had one or more of the following symptoms for at least six months: abdominal pain or discomfort, bloating and a change in bowel habit. 

They must not have any red flag symptoms: unintentional weight loss, abdominal masses, age over 60 with a change in bowel habits for more than 6 weeks with looser and/or more frequent stools, rectal bleeding and family history of bowel or ovarian cancer. If any red flag symptoms are present then they should be referred.

More serious causes of the patient's symptoms must be ruled out before a diagnosis is made: 

• Check for anaemia: this rules out malignancy, diverticular disease, and peptic ulcers.
• ESR/CRP: this rules out IBD.
• Endomysial antibodies/tissue transglutaminase: this rules out coeliac disease.

First Line Treatment:

• Dietary advice: have regular meals, and take their time to eat, avoid missing meals, drink 8 cups of fluid/day, reduce alcohol/fizzy drinks, limit fruit to 3 a day, reduce the amount of fibre in their diet, and people with wind and bloating may find it useful to eat oats e.g. porridge. 
• Patients should be offered antispasmodic agents, taken alongside dietary and lifestyle advice. 

Diarrhoea Specific Recommendations:

• Antimotility agents are the first line treatment with loperamide being the drug of choice as it does not cross the blood-brain barrier thus reducing the risk of misuse.
• Sorbitol should be avoided.
• The dose of the antimotility agent should be adjusted according to response to produce a soft, well-formed stool (British stool chart should give an idea of exactly what this is).

Constipation Specific Recommendations:

• Laxatives recommended but these should be bulk forming that contain soluble fibre e.g. isphagula husk.
• Lactulose should be avoided due to sugar based content as this tends to cause bloating more frequently.

First Line Treatment:

• Dietary advice: have regular meals, and take their time to eat, avoid missing meals, drink 8 cups of fluid/day, reduce alcohol/fizzy drinks, limit fruit to 3 a day, reduce the amount of fibre in their diet, and people with wind and bloating may find it useful to eat oats e.g. porridge. 
• Patients should be offered antispasmodic agents, taken alongside dietary and lifestyle advice. 

Diarrhoea Specific Recommendations:

• Antimotility agents are the first line treatment with loperamide being the drug of choice as it does not cross the blood-brain barrier thus reducing the risk of misuse.
• Sorbitol should be avoided.
• The dose of the antimotility agent should be adjusted according to response to produce a soft, well-formed stool (British stool chart should give an idea of exactly what this is).

Constipation Specific Recommendations:

• Laxatives recommended but these should be bulk forming that contain soluble fibre e.g. isphagula husk.
• Lactulose should be avoided due to sugar based content as this tends to cause bloating more frequently.

Domperidone (Motilium 10): useful for bloating or nausea symptoms.

Tricyclic Antidepressants: recommended 2nd line by NICE and used for their analgesic effects, low dose (5-10mg amitriptyline per day).

Patients who have not responded to pharmacological treatments after 12 months and have refractory IBS can be considered for referral for:

Within the rectum and anus, there are cushions of vascular and connective tissue which provides sensory information. Haemorrhoids are the enlargement or displacement of this tissue that leads to the problem. Can occur at any age, mid-teens onwards but the prevalence increases with age and is very common in pregnancy. 

Internal haemorrhoids arise above the pectinate (dentate) line whilst external haemorrhoids arise below the dentate line. Internal haemorrhoids are more likely to cause symptoms and are more likely to prolapse. They are classified into four degrees: 1st Degree: project into lumen but don't prolapse. 2nd Degree: prolapse on straining but return spontaneously. 3rd Degree: prolapse and have to be manually returned. 4th Degree: prolapse and cannot be returned.

External haemorrhoids have a few symptoms unless they thrombose which is extremely painful.

Symptoms: bleeding (fresh blood on toilet paper), irritation, discomfort following defecation, mucus associated with stool and faecal incontinence (3rd and 4th-degree haemorrhoids only).

Rare Symptoms: ulceration, maceration of the tissues, ischaemia, gangrene and anaemia.

Referral Symptoms: first presentation of symptoms, unintentional weight loss, fatigue, altered bowel habit, painful haemorrhoids, melaena/large volume bleeding and 3rd/4th degree with bad symptoms.

There are many ointments, creams, and suppositories available for the treatment of haemorrhoids. Choice of preparation depends on the location of haemorrhoids and preference:

Patients should be counselled to eat a high fibre diet.

3rd or 4th-degree haemorrhoids may require surgery.

Treatments of haemorrhoids contain combinations of the following five ingredients:

• Astringents: allantoin, bismuth oxide, zinc oxide.
• Emollients: white soft paraffin.
• Mild Antiseptics: balsam peru, zinc oxide, benzoyl benzoate.
• Local Anaesthetic: cinchocaine, lidocaine, benzocaine.
• Corticosteroids: hydrocortisone, fluocortolone.

An anal fissure is a small tear or ulcer in the anal canal. They occur most commonly posterior to the midline but can occur anteriorly following childbirth. They can be extremely painful with the pain being sharp or burning. There may be a small amount of bleeding.

Most commonly caused by the passage of a hard stool. Causes: mucosal ischaemia secondary to muscle spasm and local injury to the anus.

Treatment of Anal Fissure:

• Bulk-forming Laxatives: will ease the stool passage.
• Pain Relief: paracetamol or local anaesthetics (lidocaine 5% ointment).
• Sitz Baths: sitting in warm or cold water up tot he hips.
• GTN or Calcium Antagonist Ointments: used to improve mucosal blood flow and so aids healing. 

Diverticulae are mucosal balloonings through the muscularis of the colon. They are thought to be caused by a lack of fibre in the diet, which increases stool bulk and transit time which in turn increases intraluminal pressure. Both of these can lead to mini-hernias in the colon. 

Complications: infection, inflammation, fistulas, and perforation. 

It can be divided into three stages:

• Diverticulosis: asymptomatic.
• Diverticular Disease: causes intermittent lower abdominal pain, bloating and relieved by passing stools.
• Diverticulitis: inflammation, infection of diverticulae, severe pain, rectal bleeding, and malaise.

Diverticulitis is a medical emergency as bacterial or faecal contamination of the peritoneum can lead to peritonitis. NSAIDs and opioids increase the risk of perforation by increasing intraluminal pressure. 

Treatment:

• The patient is given a clear fluid diet.
• Broad spectrum antibiotics are prescribed and patients generally improve after 2-4 days of treatment.
• If perforation, sepsis, obstruction or fistulae are involved, surgery may be required. 

This is an autoimmune disease known as gluten-sensitive enteropathy. It is an increased immunological response to gluten found in wheat, bark or rye which causes villous atrophy, decreasing the surface area in the small intestine. This, in turn, leads to malabsorption of nutrients. 

Patients tend to present with non-specific GI symptoms including abdominal pain, diarrhoea, bloating and steatorrhoea. A common presenting symptom is dermatitis herpetiformis which is an intensely itchy, vesicular, pruritic rash. 

A duodenal biopsy (looking for signs of villous atrophy) is still required for confirmation of a diagnosis of coeliac disease. The patient must be kept on a normal diet prior to biopsy and serology to ensure an accurate diagnosis. 

When healthcare professionals request serological tests to investigate suspected coeliac disease in young people and adults, laboratories should: 

• Test for total IgA and IgA tTG as the first choice.
• Use IgA EMA if IgA tTg is weakly positive.

If a patient is suspected of having coeliac disease, serological testing should be offered to those with: persistent unexplained abdominal or gastrointestinal symptoms, faltering growth, severe or persistent mouth ulcers, unexplained weight loss, irritable bowel syndrome, unexplained iron, vitamin B12 or folate deficiency, type 1 diabetes mellitus and autoimmune thyroid disease.

If the patient is undergoing testing for coeliac disease they need to be aware that:

• The test is only accurate if a gluten-containing diet is eaten during the diagnostic process.
• should not start a gluten free diet unless a diagnosis is confirmed by a specialist even if the result of the serological test are positive.

Once a diagnosis is made, the patient must stick to a strict gluten-free diet.

To avoid anaemia:

• Vitamin B12
• Iron
• Folate supplementation 

If DEXA scanning reveals osteoporosis, it is recommended to give either:

• Calcium supplementation
• Bisphosphonate

Once a patient has been stabilised on a gluten-free diet, their bowel starts to heal and recover, therefore they need further dietary advice to prevent considerable weight loss. Treatment failure is often attributed to non-compliance with the diet, which is often due to a high cost and poor palatability of the food.