The neuromuscular basis for normal gastric emptying is complex and involves the coordinated interaction of the central nervous system, peripheral nervous system, enteric nervous system, pacemaker cells (called interstitial cells of Cajal (ICCs)), and gastric smooth muscle. The interactions of nerve and muscle allow the stomach to perform three major tasks in order to accomplish gastric emptying after the ingestion of food. First, the fundus relaxes in order to accommodate the food bolus presented from the esophagus. Second, the corpus and antrum mill the ingested food into chyme, 1–2 mm bits of food in suspension. Third, the nutrient suspension is emptied through the pylorus via corpus-antral peristaltic waves and antropyloroduodenal coordination.

Fundic accommodation is regulated by the vagus nerve in coordination with intramuscular ICCs located within the fundic wall. The fundus normally maintains a state of sustained contraction (high tone) via vagal efferents. This is in contrast to the antrum which has low tone. Ingested solids stimulate mechanoreceptors within the fundus, initiating a vagovagal reflex using nitric oxide, leading to smooth muscle relaxation within the fundus. In some gastroparesis patients a loss of neuronal nitric oxide synthetase impairs normal fundic relaxation. This same reflex arc may be injured in those patients who develop gastroparesis secondary to vagal nerve damage after fundoplication.

The second major function of the stomach is trituration, which refers to the mixing of ingested food to form chyme. This takes place in the corpus/antrum and is mediated primarily by the interaction between ICCs within the myenteric plexus (MY-ICCs), IM-ICC, enteric neurons, and circular smooth muscle cells. MY-ICCs located between the circular and longitudinal layers of smooth muscle are responsible for the generation of slow waves and act as pacemaker cells to coordinate circular muscle contraction. MY-ICCs establish a frequency of slow waves which occur normally at three cycles per minute. In the appropriate neurohumoral setting, gastric peristalsis occurs, which means that a wave of circular muscle contraction migrates from the proximal corpus to the pylorus at a rate of 3 contractions per minute. Thus, normal 3 cpm electrical pattern recorded in the EGG signal indicates normal integrated enteric neuron and ICC activity. The peristaltic contractions mix the ingested food with gastric acid, gastric lipase, and other various enzymes and break it down to form to chyme, the nutrient suspension that will empty into the duodenum. Loss of ICCs contributes to gastric dysrhythmias and uncoordinated and/or reduced gastric peristalsis which results in impaired emptying and the clinical diagnosis of gastroparesis.

The final step in emptying chyme from the gastric antrum into the duodenum is regulated by antral peristalsis coordinated with pyloric sphincter relaxation and reduced duodenal contractions, all of which is termed antropyloroduodenal coordination. Antral peristalsis and the emptying of chyme are affected by the size of food particles. Undigested solids require high-amplitude antral contractions to empty. Normally, pyloric tone increases to prevent large particles from emptying prematurely. Ordinarily, nitric oxide stimulates pyloric sphincter relaxation. Reduced nitric oxide has been implicated in the mechanism of pylorospasm or tonic contraction of the pylorus.

Gastric emptying is affected by many factors ranging from meal characteristics to pathologic changes in key gastric neuromuscular components. Neuromuscular disorders which tend to delay gastric emptying include gastric dysrhythmias, impaired fundic accommodation, antral hypomotility, and pylorospasm. Meal-related factors which tend to delay gastric emptying include increased acidity of ingested foods, fat content in foods, and indigestible fibers. Fats delay emptying more than carbohydrates or proteins. When high fat-containing meals are consumed, gastric lipases help break triglycerides into fatty acids and mono- and diglycerides which then enter the duodenum. Longer-chain fatty acids stimulate cholecystokinin (CCK) release which causes fundic relaxation, diminished antral contractions, and an increase in pyloric tone, the end result being a delay in gastric emptying. Monosaccharides stimulate the duodenum to release incretins (e.g., glucagonlike peptide (GLP-1)). These promote insulin secretion and induce antral hypomotility further delaying gastric emptying. Indigestible fibers delay gastric emptying due to their size, while hyperglycemia decreases antral contractions and induces gastric dysrhythmias leading to a delay in gastric emptying.

Gastroparesis is a syndrome characterized by a documented delay in gastric emptying in the absence of mechanical obstruction. Symptoms associated with gastroparesis are nonspecific and include early satiety, postprandial fullness, nausea, vomiting, bloating, and upper abdominal pain. Note that there is significant symptom overlap with functional dyspepsia (see Chap. 5—this will be added at final edit).

The broad differential diagnosis of chronic nausea and vomiting, shown in Table 8.2, must be considered when evaluating patients who may have gastroparesis. For example, prominence of abdominal pain in conjunction with nausea and vomiting may herald the presence of peptic ulcer disease, biliary colic, mesenteric ischemia, pancreatitis, sphincter of Oddi dysfunction, or abdominal wall syndrome. The pain may be a trigger for nausea and vomiting, and if the underlying disease is addressed, the nausea and vomiting typically improves. Abdominal pain is the predominant symptom in approximately 20 % of patients with gastroparesis.

In patients with predominant nausea and vomiting, the differential diagnosis includes gastrointestinal entities such as GERD, cyclic vomiting syndrome, and rumination syndrome [2]. As noted in Table 8.2, non-gastrointestinal causes include entities such as medications (e.g., narcotics), Addison’s disease, thyroid disease, uremia in the setting of chronic kidney disease, bulimia nervosa, and diseases originating from the central nervous system such as tumors and infections.

The history and physical examination are paramount to the initial evaluation of these patients. In patients with primary symptoms of pain, the presence of hematemesis, melena, and/or anemia should prompt evaluation for peptic ulcer disease. Postprandial pain associated with fatty food intake or abnormal liver function tests should prompt consideration for possible biliary colic. Sitophobia in a patient with risk factors for vascular disease such as dyslipidemia, smoking, diabetes mellitus, or other vascular disease should prompt consideration of mesenteric ischemia. Patients whose pain is localized to a highly specific location on the abdomen, often associated with a surgical scar, and related to position changes (e.g., twisting and/or bending) should be assessed for Carnett’s sign. Carnett’s sign is elicited by palpating the localized area of tenderness and then asking the patient to left their head off the pillow. With head flexion the abdominal wall contracts and the abdominal pain immediately worsens. This is considered a positive Carnett’s sign and is suggestive of abdominal wall syndrome.

In patients with primary symptoms of nausea and vomiting, the history of forceful ejection of gastric contents is characteristic of vomiting, whereas the effortless return of undigested liquid or solids into the patient’s mouth without burning or nausea is more characteristic of rumination. Regurgitation in the setting of GERD should be clearly differentiated from vomiting and rumination (and see Chap. 20). Cyclic vomiting syndrome is characterized by intense episodes of nausea and vomiting which last for days with periods in between episodes where patients are totally symptom free. GERD is not always accompanied by characteristic heartburn. Nausea may be the atypical manifestation of GERD in the occasional patients. If asked to locate their nausea, these patients will indicate that they feel their nausea in the substernal area.

A careful history is important in elucidating the cause of gastroparesis. Patients with type 1 or 2 diabetes mellitus and non-gastric diabetic complications may have gastroparesis. Prior fundoplication, partial gastrectomies, vagotomy, and other intrathoracic or intra-abdominal procedures can all predispose to the development of gastroparesis. Symptoms that begin after a gastrointestinal febrile illness suggest post-infectious gastroparesis. Medications such as opioids, calcium channel blockers, GLP-1 agonists (exenatide in particular), cannabinoids, potent anticholinergic, and calcineurin inhibitors (e.g., cyclosporine) may all demonstrate delayed gastric emptying as a side effect.

Physical examination should include an assessment of volume status and nutrition. Careful inspection of the patient’s dentition may reveal eroded enamel possibly implicating GERD or bulimia. Abdominal examination may reveal bruits suggestive of underlying vascular stenosis, tenderness suggestive of visceral inflammation, or a positive Carnett’s sign implicating an abdominal wall syndrome.

The initial diagnostic testing performed once gastroparesis is suspected includes a complete blood count, metabolic profile, esophagogastroduodenoscopy (EGD), and gastric scintigraphy. Solid-phase gastric scintigraphy should be performed using a standardized solid meal and a 4 h exam [3]. Medications which could affect gastric emptying should be stopped 48–72 h prior to the exam. Typical offending agents include prokinetics, opioid analgesics, anticholinergics, and GLP-1 agonists. Patients must refrain from smoking the morning of the test and throughout the exam. For diabetic patients, the blood glucose should be less than 270 mg/dL [4]. Meal retention of >60 % at 2 h and >10 % retention at 4 h is considered diagnostic of delayed gastric emptying.