A significant delay in emptying of solids and liquids from the stomach. A delay in gastric emptying may be asymptomatic but may also be associated with nausea, vomiting, bloating, fullness and pain.
Rome II defines functional dyspepsia as the presence of abdominal pain or discomfort centered in the epigastrium and present for at least 12 weeks over the last 12 months, which cannot be explained by upper gastrointestinal investigation. Rome III requires symptoms to be present for the last 3 months, with symptom onset at least 6 months before diagnosis. Rome III proposed that functional dyspepsia comprises at least 2 distinct subgroups: the postprandial distress syndrome which features postprandial fullness and early satiety, and the epigastric pain syndrome, which features a more constant and less meal-related pain syndrome. Patients with significant heartburn are excluded from the diagnosis.
Diabetic and idiopathic forms are the most common forms of gastroparesis; other less common forms include post-surgical, and medication related. Published data from specialized centers suggest that gastroparesis can develop in 20-55% of patients with Type I diabetes and up to 30% of patients with Type II diabetes, however the incidence and prevalence appears to be significantly lower in the general community of diabetics who do not seek specialized care. Furthermore, delayed gastric emptying is seen in up to 30-40% of patients with functional dyspepsia, although the degree of delay is usually milder than that seen in the gastroparesis associated with other forms including diabetics. The prevalence of functional dyspepsia is 11-29% with most US studies in the 15-21% range. Functional dyspepsia, like gastroparesis is more common in females.
Functional Dyspepsia and Visceral Hypersensitivity
Given that a cardinal feature of functional dyspepsia is pain without a clear underlying cause, it is not surprising that visceral hypersensitivity has emerged as a leading candidate as a cause for functional dyspepsia. Visceral pain is fundamentally different from somatic pain; the mechanisms that give rise to visceral pain are different than somatic pain and the processing of the pain signal also different. The stimuli that give rise to visceral pain include distension, mesenteric stretch, inflammation and ischemia. Stimuli that evoke somatic pain such as cutting or crushing are not as effective in evoking visceral pain. It is therefore usually not possible to infer visceral pain mechanism of action from the somatic pain literature. Two main hypotheses have been advanced for visceral pain. One is that visceral pain is transduced by low or high threshold receptors; the other is that a large component of visceral pain is through receptors that require activation by a non mechanical stimulus (inflammation) prior to signaling. In this regard, a recent area of considerable interest is the role of infections in setting up longstanding sub-clinical intestinal inflammation that primes pain receptors. Other etiological factors in dyspepsia include impaired accommodation and alterations in the brain gut axis by stress.
The Role of Neuronal Nitric Oxide Synthase and Interstitial Cells of Cajal in Gastroparesis
The most consistent histological findings in gastroparesis are loss of neuronal nitric oxide synthase (nNOS) and loss or disrupted interstitial cells of Cajal (ICC). Loss of nNOS is usually not accompanied by neuronal death suggesting that it is, at least in part, reversible. Mouse models of diabetic gastroparesis strongly suggest that central to the development of slow gastric emptying are loss of ICC.
A diagnosis of gastroparesis requires documentation of delayed gastric emptying, either by radionuclide tests or by 13 or 14C based breath tests. A 4 hr test is required to make an accurate diagnosis. Before a diagnosis is made one needs to exclude obstruction (usually by endoscopy). Vomiting associated with gastroparesis must be differentiated from regurgitation due to reflux or rumination syndrome, cyclic vomiting syndrome, self induced vomiting with bulimia, and vomiting in superior mesenteric artery syndrome.
A diagnosis of functional dyspepsia requires a careful history to exclude reflux and irritable bowel syndrome. Alarm symptoms (prominent weight loss, recurrent vomiting, bleeding, anemia, dysphagia, jaundice, palpable mass) should be looked for. Endoscopy is usually required for patients with more severe symptoms as are satiety and accommodation tests.
1. Dietary: Reducing meal size and increasing the number of meals to 4-6 per day are reasonable initial recommendations to minimize postprandial gastric distention. A diet low in indigestible, insoluble fiber is advocated as fiber delays gastric emptying and can contribute to bezoar formation in those with profound gastric stasis. Fatty foods should be restricted as lipids delay emptying. However, fat-containing liquids may be tolerated and provide needed calories. A daily multivitamin/mineral supplement can be taken if dietary intake is inadequate. If these measures are ineffective it is best to advise consumption of the bulk of calories as liquid since gastric emptying of liquids often is preserved in gastroparesis. Homogenized solid meal supplements such as blenderized foods may be used as a liquid nutrient source. Poor tolerance of a liquid diet is predictive of a future poor success with more solid food, even if puréed.
2. Prokinetics: Erythromycin (motilin receptor agonist), metoclopramide (dopamine receptor antagonist, also acts as a serotonin 5-HT4 receptor agonist to stimulate cholinergic neural pathways in the stomach as well as a weak 5-HT3 receptor antagonist), bethanechol (cholinergic muscarinic receptor agonist).
3. Antiemetics: Phenothiazines (both dopamine and cholinergic receptor antagonists). These agents include prochlorperazine and thiethylperazine, which are believed to act primarily in the area postrema. Transdermal scopolamine (cholinergic muscarinic M1 receptor antagonist) is occasionally used to treat nausea and vomiting in gastroparesis, although there is no published data to support this practice. The serotonin 5-HT3 receptor antagonists have efficacy in chemotherapy-induced emesis, post-operative emesis, and radiation therapy-induced vomiting. One unpublished study reported that ondansetron produced small but statistically significant reductions in nausea, vomiting, and abdominal pain in 17 patients with refractory unexplained nausea and vomiting. Cannabinoids exhibit potency equal to or slightly greater than dopamine receptor antagonist antiemetic drugs in chemotherapy-induced emesis, and may have additional appetite stimulatory effects. The most recently introduced antiemetics are the neurokinin NK1 receptor antagonists. Tricyclics such as nortriptyline are often of use to treat both pain and nausea.
4. Other: Botulinum toxin: no benefit has been found in blinded studies. Tube feedings are helpful to bypass the stomach and decompress it. Gastric electrical stimulation is effective in relieving nausea and vomiting but not in reversing delayed gastric emptying.
1. Address delayed gastric emptying as above
2. Treat visceral hypersensitivity with tricyclic antidepressants and ?probiotics (latter not proven but appear to be useful in irritable bowel syndrome)
3. Exclude reflux and treat if present
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