Gastroenterology

Author: Damien O’Brien MPSI

Many GI issues can be extremely troublesome and have life-long consequences. However, research and treatments are constantly evolving in this area. After reading this module, it is expected the reader will have an enhanced understanding of certain GI conditions, how preventative measures can help, and the diagnostic and treatment options for some of these conditions.

Introduction

Gastroenterology is the branch of medicine that focuses on the digestive system and the conditions associated with it. The function of the digestive system is to move material through the gastrointestinal (GI) tract via peristalsis, process the food, absorb nutrients, and remove waste from the body. The main components of the digestive system are the mouth, oesophagus, stomach, small intestine, large intestine (colon), rectum and anus. The gallbladder, liver and pancreas are also organs that are vital for digestion.¹

Anatomy of the gastrointestinal system

The GI tract is made up of several components that have certain functions. The mouth is the entry point of the digestive system where mechanical digestion begins. Chemical digestion, through enzymes in the saliva, also begins to occur. The mouth also lubricates food with mucus and saliva.

The oesophagus is a muscular tube that moves food from the mouth to the stomach via peristalsis. The stomach is a muscular organ that further helps mechanically and chemically digest food. The muscular layer of the stomach assists in mixing and churning, which are important in the mechanical digestion of food. Food is also mixed with hydrochloric acid and digestive enzymes which helps break food down into a semi-liquid form called chyme.¹

The small intestine has villi, each with multiple microvilli, which increase surface area for nutrient absorption. There is an extensive network of capillaries that optimise absorption. The intestine also has exocrine and endocrine glands that produce hormones and enzymes. The small intestine consists of three parts — the duodenum, jejunum and ileum. The large intestine has the function of absorbing electrolytes and water from indigestible food to form solid waste called faeces. The rectum and anus are where faeces are stored and then eliminated from the body.¹

The liver, pancreas and gallbladder are other organs that are important in the digestive process. The liver produces bile, which is important in digesting and absorbing fats. The gallbladder stores bile and releases it into the small intestine as required. The pancreas produces enzymes and hormones, such as insulin.¹

Preventive strategies in gastroenterology

There are several preventive strategies that are vital in GI health. There are many lifestyle modifications that individuals can make to manage digestive symptoms. Many foods and drinks can irritate the GI tract and trigger conditions such as gastroesophageal reflux disease (GERD), coeliac disease, and inflammatory bowel disease (IBD). These foods can include gluten, acidic, spicy and fatty foods. Dietary modifications, including minimising alcohol and caffeine intake, can improve the management of these conditions. A balanced diet, rich in fruits, vegetables and fibre, with limited red meats can improve GI health. Furthermore, smoking cessation can improve GI health. Maintaining a healthy weight is also important in improving the management of many conditions, and regular exercise can help with this.²

Vaccination can also help prevent certain disorders in gastroenterology. Vaccination against hepatitis A and B viruses can prevent liver infections, while the human papillomavirus (HPV) vaccination can reduce the risk of HPV-related cancers, including anal and liver cancer.

Screening and surveillance are important for early detection of conditions, as well as regular monitoring of patients with certain conditions.² A bowel screening service is available for 59-to-61 year-old individuals in Ireland. Individuals will receive a home screening test, with the objective of early detection of bowel cancer before symptoms are present.³

Overview of common conditions

Gastroesophageal reflux disease

GERD is a condition that develops due to retrograde flow of the contents of the stomach back into the oesophagus. It is a very common disorder, with a prevalence of approximately 20 per cent. It can be classified into three different types: Non-erosive reflux disease, erosive oesophagitis, and Barrett’s oesophagus.

There is no known cause of GERD, but many different mechanisms have been identified that cause the oesophagus to be exposed to acidic gastric contents. Anatomical factors such as hiatal hernia or increased intra-abdominal pressure are associated with an increase in GERD. Motor abnormalities such as impaired oesophageal acid clearance, impairment in the tone of the lower oesophageal sphincter, and delayed gastric emptying are also associated with GERD.

Risk factors for GERD include obesity, increasing age, tobacco use, excessive consumption of alcohol, pregnancy, and medications, including non-steroidal anti-inflammatory drugs (NSAIDs), anticholinergics, benzodiazepines and calcium channel blockers. GERD presents with typical symptoms of heartburn and regurgitation, while atypical and extra-oesophageal symptoms include chronic cough, chest pain, dental erosions, laryngitis and asthma.⁴

There is no gold standard test in the diagnosis of GERD. The diagnosis is usually made based on presenting symptoms or in combination with other methods, including responsiveness to therapy, esophagogastroduodenoscopy, or ambulatory reflux monitoring. GERD may be diagnosed in most cases when a patient presents with typical symptoms of heartburn and regurgitation. If there are no warning symptoms, the patient may be initiated on empiric therapy. Esophagogastroduodenoscopy may be used if the patient has one or more warning symptoms, which include dysphagia, anaemia, weight loss and hematemesis. Ambulatory reflux monitoring may be used if the patient does not respond to treatment.

Lifestyle modifications are an important aspect of GERD treatment. Patients should be counselled on the importance of maintaining a healthy weight, as this can reduce GERD symptoms. Avoiding meals for at least three hours before sleeping and maintaining good sleep hygiene are also important points. Diet modifications, including reducing caffeine, chocolate and spicy foods may help some individuals, but the evidence is inconclusive.

Pharmacological treatment may be initiated in patients who don’t respond to lifestyle modifications. Proton pump inhibitor (PPI) therapy is the cornerstone of pharmacological treatment. PPIs have been shown to improve symptoms and heal esophagitis. They work by inhibiting the H+/K+ ATPase proton pump in the stomach and therefore inhibit acid secretion. Patients should be initiated on once-daily dosing on an empty stomach, at least 30 minutes before the first meal of the day. Patients who don’t fully respond to treatment may be treated with twice-daily dosing.

Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole are all examples of PPIs. Histamine 2 receptor antagonists, such as famotidine and cimetidine, may also be used to treat GERD. These may be used as add-on therapy if symptoms are not fully resolved with maximal PPI therapy. Antacids are a group of drugs that include salts of calcium, magnesium and aluminium as active ingredients. They neutralise stomach acid, but use is restricted to relieving mild symptoms of GERD.^4,5

Inflammatory bowel disease (IBD)

IBD is a group of autoimmune conditions that are characterised by repeated episodes of inflammation of the GI tract. IBD consists of two separate conditions  — Crohn’s disease (CD) and ulcerative colitis (UC). The exact aetiology of IBD is unknown, but genetics plays a role. Extraintestinal manifestations of IBD can include arthritis, osteoporosis, uveitis, and ankylosing spondyloarthropathy.

CD and UC share similarities, but they also differ in many ways. CD can affect any part of the GI tract, from the mouth to the anus. Symptoms are commonly in the intestine, but symptoms can also affect the mouth, oesophagus and stomach. Inflammation in CD is non-continuous, with healthy patches of tissues often present between lesions. On the other hand, UC only affects the colon and rectum, while the inflammation is continuous with no healthy areas between lesions.

Symptoms of CD and UC include diarrhoea, abdominal pain, rectal bleeding and weight loss. UC is associated with blood or mucus in the stool, rectal bleeding and tenesmus. Rectal bleeding is not as common in CD, but anal fistula is common. Malnutrition and weight loss are more common in CD due to the fact that damage to the small intestine can reduce absorption of nutrients.

The diagnosis of IBD is based on a combination of clinical findings, inflammatory laboratory markers, imaging findings and endoscopic biopsies. Laboratory blood testing can show raised erythrocyte sedimentation rates and white cell counts, which are associated with intestinal inflammation. Imaging techniques such as ultrasound, computed tomography (CT) scans and magnetic resonance imaging (MRI) are also useful in the diagnosis of IBD or to assess for intra-abdomen complications. Endoscopy evaluation is necessary to obtain a biopsy to confirm diagnosis of IBD.⁶

There is no pharmacological or surgical cure for IBD, with the treatment objectives to reduce symptoms of the disease and induce remission. Treatment will depend on the disease severity, presence of extraintestinal manifestations, and the portion of the GI tract affected. A stepwise approach is required for IBD management, and treatment for flare-ups may also be necessary.

Aminosalicylates are often used in treating IBD, with mesalazine and sulfasalazine commonly used for treating mild-to-moderate disease. These drugs can be administered either orally or rectally. The exact mechanism of aminosalicylates is not fully clear, but it is thought that they reduce the synthesis of prostaglandin and leukotriene, which modulates the inflammatory response. Immunomodulators can also be used to treat IBD and include thiopurines, methotrexate, and calcineurin inhibitors. These immunomodulators all have different mechanisms of action but generally work by reducing the immune response by inhibiting T-lymphocyte proliferation and activation.  Azathioprine and 6-mercaptopurine are thiopurines that are effective in treating IBD. Methotrexate is effective in achieving remission in CD patients, but not as effective in UC.

Calcineurin inhibitors, such as ciclosporine and tacrolimus, can also be effective in achieving remission in patients with IBD. These drugs don’t have a favourable adverse effect profile, which can include bone marrow suppression, liver damage, renal damage and gastrointestinal intolerance. The adverse effect profile of these drugs has led to a move towards biologics in treating IBD.⁶

Biologic drugs are often initiated in patients with moderate-to-severe disease. Biologic therapy is often introduced earlier in high-risk patients and patients with severe disease, with de-escalation possible when a clinical response is observed. Biologics can be effective in treating IBD and have the advantages of reduced toxicity, high selectivity, and high efficiency when compared to other therapeutic options.⁸

Anti-tumour necrosis factor (TNF) therapy and anti-interleukin (IL) therapy are the two main categories of biologic agents used to treat IBD. TNF and IL are cytokines that can cause chronic inflammation in the GI tract. Infliximab and adalimumab are examples of anti-TNF therapy, while ustekinumab is a commonly used anti-IL agent. Biologics are administered parenterally. The main adverse effects associated with biologic therapy include increased risk of infection, congestive heart disease, malignancies, cardiovascular events and skin reactions.

Corticosteroids can be a useful treatment option if other therapies have failed, or in the case of flare-ups. They are effective in reducing inflammation and inducing remission. Corticosteroids can also be used both orally and rectally, with rectal administration reducing the chance of systemic adverse effects. Surgical intervention can also be used in certain cases, either as monotherapy or in combination with pharmacological treatment. The main indications include heavy bleeding, intestinal perforation, carcinogenesis and highly suspected carcinogenesis. Surgery may also be used in patients with severe IBD who have not responded to medical treatment or can’t tolerate medical treatment.⁶

Irritable bowel syndrome (IBS) is a functional disorder characterised by the presence of abdominal pain or discomfort, accompanied by altered bowel habits. IBS is more commonly diagnosed in females than males, with a decrease in prevalence observed with age.

IBS can be classified into three main categories: IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), and IBS with mixed bowel patterns (IBS-M). The aetiology of IBS is not fully understood, with brain-gut interaction, visceral sensation, motility and psychosocial distress all potential causes. Environmental factors that may contribute to IBS include life stress, enteric infections, food intolerance, and antibiotic use.

The main symptoms of IBS typically include abdominal pain or discomfort, constipation, diarrhoea and altered bowel habits. Other symptoms can include bloating and distention. Diagnosis of IBS can be difficult, but the Rome IV criteria is a validated tool to aid diagnosis. If symptoms are typical of IBS and no warning symptoms are present, routine diagnostic testing may not be required. If warning symptoms are present, further investigations may be necessary. Diagnosis criteria require at least three days per month in the last three months associated with at least two of the following:

• Improvement in abdominal pain or discomfort with defecation.
• Onset associated with a change in frequency of stool.
• Onset accompanied by a change in appearance of stool.⁷

Treatment objectives are aimed at relieving symptoms of pain, cramping, diarrhoea and constipation. A wide range of fibre supplements and laxatives are available both over the counter and on prescription for treating constipation, including stimulant laxatives (bisacodyl and sennosides), bulk forming laxatives (ispaghula husk), and osmotic laxatives (macrogol and lactulose).

In patients with diarrhoea, loperamide is an opioid receptor agonist and decreases the frequency of diarrhoea, without crossing the blood-brain barrier. Mebeverine hydrochloride, hyoscine butylbromide and alverine citrate can be used for the relief of gastrointestinal spasm in IBS. Peppermint oil is generally a safe treatment option and can be effective for symptoms of discomfort and distension.

Patients with chronic symptoms may respond to low-dose tricyclic antidepressants or SSRIs. Rifaximin has also been shown to be effective in treating IBS. Rifaximin is a broad-spectrum antibiotic that is not well absorbed, which allows it to work locally in the gut. The effectiveness of rifaximin gives support to the theory that bacterial overgrowth plays a role in the aetiology of IBS.⁷

Peptic ulcer disease

Peptic ulcer disease (PUD) is a condition characterised by discontinuation in the inner lining of the GI tract due to secretion of gastric acid or pepsin. It usually presents in the stomach and proximal duodenum, but may involve the lower oesophagus, distal duodenum or jejunum.

There are several potential causes of PUD, with Helicobacter pylori and NSAID use the two most common causes. Less-common causes of PUD include Zollinger-Ellison syndrome, viral infection, CD, radiation therapy, chemotherapy and malignancy. H.pylorus is a gram-negative bacterium that is found within the gastric epithelial cells and is responsible for up to 90 per cent of GI ulcers. Symptoms of PUD include epigastric abdominal pain, bloating, nausea, vomiting, hematemesis and abdominal fullness. Epigastric pain will usually occur within 30 minutes following a meal with a gastric ulcer, while the pain will usually occur two-to-three hours after a meal with a duodenal ulcer. Warning symptoms can include weight loss, GI bleeding, anaemia, emesis, progressive dysphagia, and family history of upper GI malignancy.

Diagnosis of PUD is based on patient history and various medical tests. Esophagogastroduodenoscopy is the gold standard in diagnosing PUD, with specificity and sensitivity up to 90 per cent. H.Pylori testing through serologic testing or urea breath testing is useful in diagnosing the presence of the bacterium.

Similarly to GERD, PPIs are the cornerstone of treatment of PUD. They have replaced histamine 2 receptor antagonists due to their superior symptom relief and promotion of healing. PUD due to NSAID use can be treated by withdrawal of the NSAID or reducing the dose. Anticoagulants, bisphosphonates and corticosteroids may also be withdrawn if possible. First-line treatment for H.pylori-induced PUD is a triple-therapy regimen consisting of two antibiotics and a PPI, which work synergistically against H.Pylori. Clarithromycin 500mg every 12 hours, amoxicillin 1g every 12 hours and a PPI every 12 hours is the first-line treatment option. Bismuth may be added for quadruple therapy, while metronidazole may be used in the case of penicillin allergy. Surgery is indicated if the patient does not respond to medical treatment or is at high risk of complications.⁸

Coeliac disease is an autoimmune disease of the small intestine, where the body’s immune system reacts with gluten to cause inflammation and damage to the small intestine. It is a genetic disease and is triggered by exposure to gluten in the diet in susceptible individuals. The local inflammation leads to destruction of the villi in the small intestine. This leads to a decrease in the function of the small intestine and impaired nutrient absorption, leading to malnutrition. This can impact on all body systems and result in general poor health.

Common symptoms include lethargy, diarrhoea, constipation, vomiting, abdominal distension, abdominal pain and failure to thrive. Serological tests are generally one of the first steps involved in diagnosis. A duodenal mucosal biopsy, showing villous atrophy, is the gold standard for diagnosis. Coeliac disease is a chronic disorder, with a strict gluten-free diet the only recommended treatment.⁹

Gallstones, also known as cholelithiasis, are stones that are formed in the gallbladder composed of cholesterol, bilirubin and bile. Gallstones are usually formed from the slow emptying of bile from the gall bladder. Biliary obstruction from a variety of causes can lead impaired draining, which can cause bile to precipitate as sludge and develop into gallstones. The most common cause is the precipitation of cholesterol from cholesterol-rich bile. Risk factors for gallstones include obesity, pregnancy, certain medications, metabolic syndrome and prolonged fasting.

In most cases, gallstones are asymptomatic, with 10 per cent of patients developing symptoms within five years, and 20 per cent of patients developing symptoms within 20 years of diagnosis. The main symptoms of gallstones include pain in the right upper abdomen after eating greasy or spicy food, nausea, vomiting and epigastric pain.

Acute cholecystitis is inflammation of the gall bladder and can be more severe and present as jaundice. A right-upper quadrant abdominal ultrasound has 90 per cent specificity in diagnosing gallstones. Cholecystectomy is indicated to treat symptomatic gallstones, with laparoscopic the preferred approach. Gallstones can be also treated pharmacologically. Ursodeoxycholic acid can be administered once daily for dissolution of radiolucent gallstones in patients with a functioning gall bladder. This has mixed results, but can be effective for some patients.¹⁰

Role of the pharmacist

Pharmacists play a crucial role in the management of GI conditions. They play an important role in patient education, particularly around the proper use of medication, adherence to medication, and lifestyle modifications. Pharmacists also monitor patients to ensure safe and effective use of medications in the treatment of GI conditions.

Many conditions in gastroenterology involve complex drug regimens and pharmacists can help to manage these treatment regimens to improve clinical outcomes for patients, while reducing adverse effects. Pharmacists also collaborate as part of a multidisciplinary team with other healthcare professionals to ensure comprehensive care and continuity of care for patients.

The field of gastroenterology will continue to evolve with new treatment options, and pharmacists are ideally placed to continue to provide comprehensive patient-centred care.^11,12