Richard A. Wright, MD and John K. DiBaise, MD
What pathways mediate the control of gastric emptying?
Gastric motor activity is governed by extrinsic neural control from the parasympathetic nervous system, intrinsically by the enteric nervous system, and at the level of the smooth muscle by depolarization of the smooth muscle membrane.
What are the major components of the enteric nervous system?
The enteric nervous system consists of the myenteric (Auerbach’s) plexus, which lies between the circular and longitudinal muscle layers, and the submucosal (Meissner’s) plexus, which lies between the circular muscle layer and the mucosa.
True/False: The stomach has two functional motor components.
True. The proximal stomach represents the accommodating portion of the stomach. It is able to expand to allow large volumes of material to accumulate without causing a resultant increase in gastric pressure. It also receptively relaxes upon deglutition. In contrast, the distal stomach is responsible for trituration and emptying of gastric contents into the duodenum in a controlled manner.
True/False: The gastric pacemaker is located near the incisura.
False. The gastric pacemaker is located on the greater curvature of the stomach in the mid body. The pacemaker generates electrical potentials that sweep circumferentially and distally and correspond to peristaltic contractions during the appropriate stage of digestion.
What is trituration?
Trituration is the process of breaking down solid food to a size less than 1 mm by an antral grinding action. Large particles are repetitively propelled and retropulsed in the antrum, breaking them down to a size compatible with digestion and absorption.
What are the interstitial cells of Cajal?
These are specialized pacemaker cells present within the wall of the gut that transmit electrical signals throughout the gut smooth muscle.
What receptors are present in the prepyloric region that help regulate emptying of materials into the duodenum?
Size and osmole receptors. Size receptors will not allow particles greater than 1 mm to pass through the pylorus in the 2-hour postprandial period. Osmole receptors prevent the passage of hyperosmolar solutions into the duodenum. Hypertonic solutions must be diluted by gastric secretions to isotonicity before they are allowed to pass into the duodenum.
What duodenal mechanisms cause feedback inhibition of gastric emptying?
Acid stimulates the release of secretin from the duodenal mucosa which causes a decrease in gastric emptying. Lipids and amino acids cause release of cholecystokinin-pancreazymin from the duodenal mucosa, also resulting in the inhibition of gastric emptying, thus allowing for graded gastric emptying and preventing rapid transit of gastric contents into the duodenum.
What is the effect of hyperglycemia on gastric emptying?
Hyperglycemia delays gastric emptying in healthy individuals and patients with diabetes.
What is the effect of vagotomy on the gastric fundus?
Both receptive relaxation and accommodation are abolished. This may be partially responsible for the accelerated emptying that occurs after vagotomy (dumping syndrome). This is also the proposed mechanism for rapid gastric emptying that is sometimes seen in patients with diabetes mellitus.
What abnormalities in gastric motor function have been described in patients with nonulcer (functional) dyspepsia?
Altered accommodation, gastric dysrhythmias, antral hypomotility, and delayed gastric emptying have all been described.
True/False: Helicobacter pylori plays a central role in the pathophysiology of nonulcer dyspepsia.
True/False: Diabetic gastroparesis typically develops after diabetes has been present for at least 10 years.
True/False: More individuals with type 1 diabetes with gastroparesis are seen in clinical practice compared with type 2 diabetes.
False. Although gastroparesis appears to be more common in type 1 diabetics, given the higher prevalence of type 2 diabetes, more gastroparesis in type 2 diabetics is seen in clinical practice.
What is the most common gastric motor defect observed in patients with diabetes mellitus?
Autonomic neuropathy with “autovagotomy” results from long-standing diabetes mellitus. The clinical result is usually a delay in gastric emptying with the potential for bezoar formation; however, occasionally rapid emptying, especially of liquids, occurs and results in dumping syndrome.
True/False: Idiopathic gastroparesis affects mostly men who are underweight at the time of diagnosis.
True/False: Severe gastroparesis is typically associated with anorexia and vomiting.
What connective tissue diseases are associated with gastroparesis?
Scleroderma and systemic lupus erythematosus have been most commonly implicated.
True/False: Patients with bulimia or anorexia nervosa and chronic vomiting frequently have gastric emptying abnormalities.
True. In patients with anorexia nervosa or bulimia, impaired gastric emptying of solid foods has been reported, whereas liquid emptying is usually normal. Promotility drugs have been found to be helpful in alleviating gastroparetic symptoms in some of these patients.
What tests are available to measure gastric emptying?
Currently, the most common technique is scintigraphy using radionuclide-labeled meals. Both solid and liquid phases can be measured simultaneously by labeling the solids and liquids with different radionuclides; however, the solid phase seems to be most clinically useful. Transabdominal ultrasonography can be used to measure gastric emptying by determining serial measurements of antral size before and after a standard liquid meal. Magnetic resonance imaging is able to determine gastric emptying rates and the regional distribution of a meal within the stomach. Breath tests utilizing octanoic acid or spirulina, which do not contain radioactivity, are being developed to measure gastric emptying. Finally, an orally ingested capsule that continuously monitors time, pH, temperature, and pressure is available.
What is the role of electrogastrography (EGG) in the evaluation of patients with dysmotilitylike symptoms?
The exact role of EGG remains controversial. While certain dysrhythmias have been described in patients with these symptoms, there remains no consistent correlation between EGG findings, gastric emptying study results, and symptomatic response to promotility agents. EGG has been suggested to be complementary to the more conventional testing of gastric emptying.
Name the abnormalities of the gastric rhythm.
The normal discharge (normogastria) from the gastric pacemaker is 3 cycles per minute (cpm). Bradygastria is said to exist when the discharge rate is less than 2 cpm. Tachygastria is defined as a discharge rate of greater than 4 cpm.
True/False: A succussion splash is the most common finding on physical examination in a patient with delayed gastric emptying.
False. Most individuals with gastroparesis will have a normal examination; however, occasionally a succussion splash may be appreciated.
What infectious diseases have been associated with delayed gastric emptying?
Acute infection with Norwalk agent, a parvovirus, has been associated with a delay in gastric emptying. Trypanosoma cruzi causes delayed gastric emptying by damaging the myenteric plexus. Temporary delays in gastric emptying have also been noted in patients with varicella zoster, Epstein–Barr virus, cytomegalovirus, and Clostridium botulinum poisoning. While delayed gastric emptying has been described in patients with HIV infection, the mechanism is not clear. Patients with H. pylori infection have normal gastric emptying.
True/False: Gastroparesis occurs commonly in patients with gastroesophageal reflux disease.
True. Some studies have reported the presence of gastroparesis in up to one-half of these patients. The clinical significance of this delay in most patients remains disputed, however. Gastroparesis is not more prevalent in patients with Barrett’s esophagus than in patients with erosive disease.
What is the mechanism of action of metoclopramide?
Metoclopramide is a centrally and peripherally acting dopamine (D2 receptor) antagonist that enhances myenteric cholinergic transmission. It also has agonist activity at the 5-hydroxytryptamine (5-HT4) receptor.
What is the mechanism of action of domperidone?
Domperidone is a selective dopamine antagonist similar to metoclopramide but with little penetration of the blood-brain barrier.
What is the mechanism of action of erythromycin?
Erythromycin is a motilin receptor agonist that causes stimulation of gastric smooth muscle directly and via cholinergic myenteric neural pathways. Erythromycin’s use as a long-term promotility agent is limited by its antibacterial properties and tachyphylaxis caused by down-regulation of the motilin receptor.
True/False: The risk of tardive dyskinesia with metoclopramide use relates to the dose but not the duration of therapy.
False. The development of this potentially irreversible condition is directly related to the duration of metoclopramide use and the cumulative dose.
What are other potential neurological side effects of metoclopramide?
Pseudoparkinsonism, akathisia, and acute dystonic reactrions. These reactions typically respond to a reduction or cessation of metoclopramide use.
True/False: The intramuscular injection of botulinum toxin into the pylorus has been shown in controlled studies to enhance gastric emptying and improve symptoms in patients with gastroparesis.
False. Despite anecdotal reports and open trials suggesting otherwise, two recent randomized, controlled trials demonstrated no benefit of intrapyloric injections of botulinum toxin compared to placebo.
True/False: Gastric electrical stimulation therapy derives its benefit from enhancing gastric emptying.
False. Instead, its proposed mechanism of action has been suggested to be from a central neuromodulatory effect via vagal afferent stimulation.
True/False: Gastric electrical stimulation is more likely to provide symptomatic benefit to those with idiopathic gastroparesis than those with diabetic gastroparesis.
False. Factors suggested to predict a better outcome with this form of therapy include diabetes as the cause of gastroparesis, an absence of pain as a predominant symptom, and absence of chronic narcotic analgesic use.
True/False: Gastrectomy should be offered to those with refractory gastroparesis.
False. Gastrectomy should generally be reserved for those with refractory postsurgical causes of gastroparesis and, possibly, those with recurrent bezoar formation.
True/False: Rapid gastric emptying (dumping) also commonly occurs in diabetics and produces symptoms virtually identical to those caused by delayed gastric emptying.
What are the characteristic presentations of early and late dumping syndromes?
Early dumping typically presents with gastrointestinal and vasomotor symptoms that occur shortly after eating. Late dumping typically presents with hypoglycemic symptoms. Both forms can be incapacitating.
Describe the pathophysiology of early dumping syndrome.
The enhanced rate of gastric emptying of solids and liquids allows higher volume hypertonic food boluses to be released into the small intestine. This induces a neurohumoral cascade responsible for the gastrointestinal and vasomotor symptoms seen.
What is the primary factor in the pathogenesis of the symptoms of late dumping?
Hypoglycemia resulting from the initial absorption of hyperosmolar carbohydrates producing hyperinsulinemia.
True/False: The diagnosis of dumping syndrome is based on results of a gastric emptying test.
False. Diagnosis is most commonly based on a suggestive symptom profile in the proper clinical context (eg, post gastric surgery).
What is the initial treatment for dumping syndrome?
Dietary maneuvers including low-sugar foods, smaller, more frequent meals, and consuming solids and liquids at separate times. The addition of soluble fiber to the diet to delay gastric emptying may also be of help. Medications that have demonstrated some efficacy in dumping include acarbose (late dumping) and short- and long-acting somatostatin analogues (early and late dumping).
• • • SUGGESTED READINGS • • •
Parkman HP, Yates K, Hasler WL, et al. Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity. Gastroenterology. 2011;140:101-115.
Camilleri M, Bharucha AE, Farrugia G. Epidemiology, mechanisms and management of diabetic gastroparesis. Clin Gastroenterol Hepatol. 2011;9:5-12.
Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R. Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol. 2009;6:583-590.