Functional dyspepsia (FD) is a common gastrointestinal disorder defined by symptoms arising from the gastroduodenal region in the absence of an underlying organic disease that could easily explain the symptoms. Characteristic symptoms include epigastric burning, epigastric pain, postprandial fullness, and early satiety. FD was formerly known as non-ulcer dyspepsia, as opposed to "organic dyspepsia" with underlying conditions of gastritis, peptic ulcer disease, or cancer.
The exact cause of functional dyspepsia is unknown however there have been many hypotheses regarding the mechanisms. Theories behind the pathophysiology of functional dyspepsia include gastroduodenal motility, gastroduodenal sensitivity, intestinal microbiota, immune dysfunction, gut-brain axis dysfunction, abnormalities of gastric electrical rhythm, and autonomic nervous system/central nervous system dysregulation. Risk factors for developing functional dyspepsia include female sex, smoking, non-steroidal anti-inflammatory medication use, and H pylori infection. Gastrointestinal infections can trigger the onset of functional dyspepsia.
Functional dyspepsia is diagnosed based on clinical criteria and symptoms. Depending on the symptoms present people suspected of having FD may need blood work, imaging, or endoscopies to confirm the diagnosis of functional dyspepsia. Functional dyspepsia is further classified into two subtypes, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).
Functional dyspepsia can be managed with medications such as prokinetic agents, fundus-relaxing drugs, centrally acting neuromodulators, and proton pump inhibitors. Up to 15–20% of patients with functional dyspepsia experience persistent symptoms. Functional dyspepsia is more common in women than men. In Western nations, the prevalence is believed to be 10–40% and 5–30% in Asian nations.
Signs and symptoms Symptoms of functional dyspepsia include epigastric burning, epigastric pain, postprandial fullness (often described as bloating by those who have FD), and early satiety. Food consumption frequently makes symptoms worse. Although functional dyspepsia is typically chronic, the symptoms are generally sporadic, even during periods of severe symptoms.
Those with FD typically refer to early satiety as a vague abundance of gas after eating or discomfort, but in reality, what they truly mean is that they find it difficult to finish a normal-sized meal because they are uncomfortable or feel full.
While nausea and heartburn are still possible co-occurring symptoms, they are no longer regarded as major dyspeptic symptoms and may originate from different processes. When certain symptoms occur, such as vomiting, a coexisting or alternative condition, like gastroparesis, needs to be evaluated.
Causes Functional dyspepsia has a wide range of complex etiologies. Gastric motor function abnormalities have long been linked to functional dyspepsia. However, a study revealed that there was no relationship between symptoms and stomach physiological abnormalities. The symptoms are significantly influenced by meal consumption, and genetic factors may also play a part.
Risk factors Several epidemiological studies have demonstrated a moderate correlation between dyspepsia in the general population and female sex, smoking, non-steroidal anti-inflammatory medication use, and H pylori infection. In one long-term investigation, a high body mass index was an independent predictor of the emergence of functional dyspepsia.
Since the brain and gut communicate through the hypothalamic-pituitary-adrenal axis and the enteric nerve system, psychological comorbidity plays a significant influence in the development of functional dyspepsia. Anxious participants had an eight-fold increased risk of developing functional dyspepsia compared to those without anxiety in a population-based survey conducted in Sweden. According to two Australian longitudinal investigations, there are reciprocal effects between the stomach and the brain. Specifically, people who had functional dyspepsia at baseline were more likely than those who did not experience anxiety or depression during follow-up.
Triggers Acute gastroenteritis can lead to the development of post-infection functional dyspepsia. According to a meta-analysis of 19 papers, exposed people had nearly three times the chance of developing functional dyspepsia over the course of more than six months following an infection compared to non-exposed people.
Mechanism Because functional dyspepsia symptoms are complicated and vary so much, the underlying pathophysiology of the disorder is still unknown. The causes of dyspeptic symptoms have been attributed to a number of pathophysiologic processes. These include gastroduodenal motility, gastroduodenal sensitivity, intestinal microbiota, immune dysfunction, gut-brain axis dysfunction, abnormalities of gastric electrical rhythm, and autonomic nervous system/central nervous system dysregulation.
Gastroduodenal motility Patients with functional dyspepsia frequently have sensorimotor abnormalities of the gastroduodenum, including altered motility and pathological reactions to mechanical and chemical stimuli.
One of the main pathophysiologic mechanisms thought to underlie the symptoms of functional dyspepsia is delayed stomach emptying. Several studies have looked into the connection between the pattern and intensity of symptoms and delayed stomach emptying. The proportion of dyspeptic individuals with delayed stomach emptying varies from 20% to 50%, depending on the study.
In response to gastric balloon distension during fasting and following meal intake, patients with functional dyspepsia demonstrate impaired proximal stomach accommodation. Due to the poor accommodation, there is a disproportional volume distribution, with the fundus volume being less and the antral volume being bigger than usual. Furthermore, individuals suffering from functional dyspepsia exhibit compromised fundus accommodation in reaction to duodenal distension.
Gastroduodenal sensitivity In functional dyspepsia, the stomach's sensitivity to chemical and mechanical stimuli is changed. After fasting and meal consumption, patients with functional dyspepsia exhibit visceral hypersensitivity following gastric fundus distension. Following stomach distension, even patients with normal accommodation experience discomfort. Additionally, some individuals exhibit hypersensitivity to distension of the duodenum, jejunum, or rectal cavity, indicating a more widespread sensitization of the central and autonomic nervous systems.
Intestinal microbiota The small intestinal microbiota has been identified as a possible contributing factor. In one study, an elevated duodenal mucosal bacterial load was inversely connected with quality of life and correlated with meal-related symptoms during a nutritional challenge test, despite the fact that relative bacterial abundance in the small intestine is difficult to interpret. The bile acid pool may vary as a result of microbiome modifications brought on by small intestine inflammation.
On the other hand, a decrease in primary bile acid levels may have an impact on the small intestine's microbial diversity, which may promote the proliferation of proinflammatory bacteria and low-grade inflammation, both of which may result in the breakdown of the epithelial barrier.
A shift in the ratio of main to secondary bile acids and decreased amounts of total bile acids in certain patients with functional dyspepsia during fasting further suggest the involvement of gastrointestinal microbes.
Immune dysfunction Some other functional gastrointestinal disorders have been linked to low-grade mucosal inflammation and elevated quantities of inflammatory cells, such as intraepithelial lymphocytes and mast cells.
The quantity of cell-surface markers needed for more proliferation or differentiation of specialized cells, however, does not increase in functional dyspepsia; rather, it indicates the active state of these cells.
Reduced expression of two markers—FAS, which is involved in lymphocyte homoeostasis and cell apoptosis, and HLA-DRA, which is involved in B-cell proliferation—has been linked to functional dyspepsia and is thought to reflect changes in duodenal lymphocyte populations.
Moreover, duodenal eosinophilia has been linked to symptoms of postprandial distress syndrome, as opposed to an increase in mast cells.
Gut-brain axis dysfunction There is a subpopulation of people with functional dyspepsia who have involvement in the gut-brain axis. Through the hypothalamic-pituitary-adrenal axis, changes in epithelial barrier function brought on by immune system and gastrointestinal microbiota disruptions can control gut-brain connections. The mechanisms involving corticotropin-releasing hormone and stress play a significant part in gastrointestinal permeability. This impact has been demonstrated in controlled trials including healthy volunteers under stress as well as in animal models of functional dyspepsia. Anatomical and functional connectivity impairments were observed in brain regions important for processing visceral afferent information in patients with functional dyspepsia, according to MRI results.
Abnormalities of gastric electrical rhythm Additionally, there is proof that up to two thirds of patients with functional dyspepsia have anomalies in the underlying stomach myoelectrical activity, as determined by cutaneous electrogastrography. It is yet unknown how this discovery relates to stomach emptying and symptom patterns. There was no association discovered between the pattern of dyspeptic symptoms and the existence of electrogastrography results. There has been good evidence of a relationship between aberrant gastric electrical rhythm and delayed stomach emptying.
Autonomic nervous system/central nervous system dysregulation It has been proposed that certain patients with functional dyspepsia may have anomalies in their autonomic nervous system. Particularly, it has been suggested that efferent vagal dysfunction may be the cause of antral hypomotility and poor adaption to a meal. Additionally, there is proof that psychological variables and both stomach functionality and symptoms of functional dyspepsia are related to psychopathology. Low vagal activity has been suggested as the mediating mechanism in these relationships.
Diagnosis Functional dyspepsia is diagnosed using clinical symptoms and Rome IV criteria, which were recently revised. The clinical examination and patient history should look for alarm symptoms. Alarm symptoms include dysphagia, especially if progressive, or odynophagia, overt gastrointestinal bleeding, such as melena or hematemesis, persistent vomiting, unintentional weight loss, family history of gastric or esophageal cancer, palpable abdominal or epigastric mass or abdominal adenopathy, and signs of iron-deficiency anemia.
The diagnostic criteria for functional dyspepsia is as follows:
At least one of the following:
Troublesome postprandial fullness. Troublesome early satiation. Troublesome epigastric pain. Troublesome epigastric burning.
The criteria must be met over the past three months, with the onset of symptoms occurring at least six months before diagnosis and there must be an absence of structural disease evidence that could account for the symptoms, including upper endoscopy.
Taking a thorough history that includes all relevant symptoms is the first step in the process. Patients are then categorized into the relevant subtype and any alarm symptoms or indicators that might point to a different diagnosis are reviewed.