Aetiology
There are several potential underlying causes for upper gastrointestinal (UGI) tract symptoms, including GORD, peptic ulcer disease, Helicobacter pylori infection, a variety of medications, and, rarely, UGI malignancy. In practice; however, actual aetiology is often not confirmed, and the patient is assessed and managed as having uninvestigated dyspepsia.
Uninvestigated dyspepsia
In patients with uninvestigated dyspepsia, functional dyspepsia (from gut hypersensitivity, motility disturbances, H pylori infection, non-erosive reflux disease with epigastric symptoms only, post-infectious irritability, and psychosocial factors) and reflux oesophagitis will typically be the most common causes. The second most common causes are gastritis and duodenitis (with or without ulcers) due to aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or H pylori infection. Finally, there are patients in whom inflammation or ulcers are found in the stomach or duodenum but without any identifiable cause. UGI malignancy is an uncommon but extremely important cause of dyspepsia.
Functional dyspepsia
Functional dyspepsia refers to symptoms of dyspepsia that have been investigated, but where the investigations have not revealed a potential cause for the dyspepsia.[7] Endoscopy is necessary for establishing a firm diagnosis of functional dyspepsia, but in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy.[14] Guidance from the British Society for Gastroenterology recommends that patients be referred to a consultant for further assessment when there is diagnostic doubt; where symptoms are severe, or refractory to first-line treatments; or where the patient requests a consultant opinion.[7]
Functional dyspepsia may be due to gut hypersensitivity, motility disturbances, H pylori infection, non-erosive reflux disease with epigastric symptoms only, post-infectious irritability, and psychosocial factors.[4][6][15] These changes may be caused by the post-infectious state, may be idiopathic, or may have their origin in complex brain-to-gut interactions. Psychosocial factors (including a history of violence and abuse) have been implicated in the generation of symptoms; psychological therapies, such as cognitive behavioural therapy and psychotherapy, may reduce dyspeptic symptoms in the short term in individual people.[4][6]
Typical GORD
Typical GORD symptoms (heartburn and acid regurgitation) are not always present in patients suffering from GORD.[5] In some cases, patients with GORD will have epigastric pain or burning only, and it will not be possible to identify them as having GORD based on their symptoms. Among those undergoing endoscopy for typical GORD symptoms, normal mucosa is the most common finding.[5] The diagnosis of GORD is based on a combination of symptom presentation, endoscopic assessment of oesophageal mucosa, reflux monitoring, and response to therapeutic intervention.[5]
UGI malignancy
UGI malignancy can cause UGI symptoms indistinguishable from other causes of dyspepsia; however, the mechanisms of symptom production remain obscure.
American College of Gastroenterology / Canadian Association of Gastroenterology (ACG/CAG) guidance on the management of dyspepsia suggests endoscopy to exclude malignancy as the underlying cause of new onset dyspepsia in older patients (≥60 years old).[3]
In the UK, the National Institute for Health and Care Excellence (NICE) recommends urgent UGI endoscopy for those aged 55 years or over with weight loss and dyspepsia.[16] Non-urgent UGI endoscopy should be considered for those aged 55 years or over with:[16]
treatment-resistant dyspepsia, or
dyspepsia with raised platelet count or nausea or vomiting.
In some populations and regions, for example Asia and parts of eastern Europe, UGI malignancies are an important consideration in younger people; therefore, the threshold for investigation should be tailored to local protocols.[3][4]
Drugs
Medications (particularly NSAIDs, cyclooxygenase [COX]-2 inhibitors, and aspirin) can all be irritating to the gastrointestinal tract, particularly in its upper portion where exposure to acidic gastric secretions can add to the problems. COX-1 has a protective maintenance effect in the gastrointestinal mucosa, and, when blocked by aspirin or NSAIDs, the mucosa may become irritated, causing symptoms, erosions, or ulcers. Symptoms can occur without ulcers, and ulcers can occur without symptoms. COX-2 selective inhibitors are about half as likely as non-selective NSAIDs to cause ulceration, and they can also cause dyspepsia symptoms.[17]
Other medications can also cause dyspepsia, often through mucosal irritation and/or motility disturbances. Important potential culprits include bisphosphonates, nitrates, theophyllines, macrolide antibiotics, and calcium channel blockers.
Examples of other drugs that have been reported to cause dyspeptic symptoms include orlistat (an anti-obesity drug), erectile dysfunction drugs (e.g., sildenafil, tadalafil), iron compounds (e.g., ferrous sulfate), antidepressants (e.g., selective serotonin reuptake inhibitors, risperidone), antibiotics (e.g., erythromycin, tetracycline), calcium channel blockers and beta blockers.[18]
Excessive consumption of alcohol can cause gastritis, resulting in dyspeptic symptoms such as abdominal pain and nausea.
Gastroparesis
Nearly half of patients with diabetes (both type 1 and type 2) have delayed gastric emptying, known as diabetic gastroparesis, which leads to the retention of stomach contents.[19] This may cause upper abdominal pain or discomfort, as well as bloating, early satiety, nausea, vomiting, or post-prandial fullness (diabetic dyspepsia).
Post-viral gastroparesis can also occur in young people with no history of diabetes.
Hepatobiliary disorders
Hepatobiliary disease can cause bloating, belching, and upper abdominal pain and discomfort indistinguishable from dyspepsia. When there is hepatobiliary involvement, there is classically a post-prandial delay in onset of 20 to 120 minutes, and symptoms are more likely to be located in the right upper abdomen or right chest, especially the posterior chest near the scapula. Compatible history with tenderness in the right upper quadrant or positive Murphy's sign and supportive investigations raise the likelihood of hepatobiliary disorders.
Pancreatic disorders
With pancreatitis, patients present with an acute or subacute onset (hours, days, or weeks), persistent vomiting, and severe pain in the upper abdomen (particularly with radiation straight through to the back). Patients with malignant pancreatic tumours tend to be older (>50 years old) and often have new onset of progressively worsening symptoms. These symptoms may include anorexia, weight loss, and persistent vomiting. The examination of patients with pancreatic tumours may reveal a mass in the epigastrium or jaundice from biliary tract obstruction. Patients with chronic pancreatitis may have chronic or recurrent epigastric pain.
Cardiac disorders
Disturbances in neighbouring organs (heart, pancreas, liver, or gallbladder) and systems are potential causes of symptoms masquerading as UGI disorders. It is particularly important initially to exclude an acute coronary syndrome as the cause for the symptom because of the potentially catastrophic consequences of misdiagnosis.
Patients with an acute cardiac problem may present for care with symptoms that appear to be originating in the UGI tract. They may describe heartburn, upset stomach, or indigestion. They may also have a sense of bloating, belching, or other dyspepsia symptoms. Great care is needed when documenting the history, along with a high index of suspicion to exclude a cardiac source for the symptoms. Cardiac disorders present with a shorter duration of symptoms (hours, days, or weeks), temporal relationship of symptoms to exertion, and associated features such as dyspnoea, weakness, diaphoresis, or altered cardiovascular vital signs. A burning quality of pain does not exclude cardiac causes.[20][21]
Other conditions
Hypercalcaemia can cause vague abdominal pains, which in turn can simulate dyspepsia. Coeliac disease and lactose intolerance can also cause dyspepsia symptoms (e.g., bloating and distension).[22] Physical examination is typically normal in both these conditions.
Pain emanating from the abdominal wall can be confused with dyspepsia.
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