General Considerations

Altered gastric and small bowel motility result in either delayed gastric emptying or rapid transit. Among the disorders of gastric and small bowel motility discussed in this chapter are gastroparesis, CIPO, dumping syndrome, and rapid transit dysmotility of the small bowel.

Gastroparesis and CIPO are chronic long-term problems that have a variety of causes and can be neuropathic or myopathic. Treatment of these conditions includes dietary, medical, and, rarely, surgical therapies. Research in gastroparesis is ongoing with a focus on improving diagnostics and newer therapeutic agents. Dumping syndrome is a postsurgical iatrogenic problem that is occurring less often in relation to gastric ulcer surgery, but may be increasing among bariatric surgery patients in tandem with the increase in surgical treatment of obesity. Patient education, dietary change, and treatment of underlying medical problems are important factors in the overall management of these motility disorders.

Pathogenesis

Normal gastric emptying requires coordinated efforts by the muscles that control the four regions of the stomach, nerves that modulate the actions of these muscles, and chemical mediators. Important events that occur during gastric filling and emptying include fundic relaxation (accommodation) in response to food ingestion, antral contractions and churning (trituration) of large food particles, and finally pyloric relaxation.

The neurogenic network of the stomach includes elements of both the central nervous system (CNS) and the enteric nervous system (ENS). The CNS elements involve both sympathetic and parasympathetic fibers. Sympathetic fibers arise from the thoracic spinal nerves, extending to postganglionic nerves that run along the celiac plexus and the vascular supply to the stomach. The sympathetic innervation includes afferent pain fibers that arise from the stomach, as well as motor fibers that innervate the pyloric sphincter. The parasympathetic innervation stems from the right and left vagal trunks, which eventually divide into multiple branches that course throughout the stomach wall and synapse with the ENS.

The ENS is an independent branch of the peripheral nervous system that is divided into two plexuses: the submucosal (Meissner) and the myenteric (Auerbach) plexuses. The submucosal plexus receives only parasympathetic input and innervates the cells of epithelial layer and muscular externa. The myenteric plexus, on the other hand, is situated between the middle circular and the outer longitudinal muscle layers, receiving both sympathetic and parasympathetic input. It mediates the motor function of both muscle layers and the secretory functions of the mucosa.

The interstitial cells of Cajal (ICCs) are the “pacemaker cells” of the stomach. They are located in the myenteric plexus and are responsible for basal slow-wave activity, which occurs at 3 cycles per minute. This slow-wave activity is also called the electronic control activity or the pacesetter potential. The ICCs are also responsible for bridging the myogenic and neurogenic control mechanisms.

The migrating motor complex (MMC) is the pattern of motility activity that occurs in the fasted state. It is a 1–2 hour cycle beginning in the stomach or small intestine and divided into three phases. Phase I (45–60 minutes) is a quiescent period. Phase II (30 minutes) is a period of random intermittent contractions. Lastly, phase III (5–15 minutes), also called the activity front, is a period in which bursts of rapid, even-paced uninterrupted peristaltic contractions occur.

Upon ingesting a meal, the MMC is abolished. Gastric accommodation occurs with distention of the fundus to make room for the incoming ingested contents. This response is mediated by the parasympathetic activity from the vagal nerve through cholinergic neurotransmitters, and inhibitory input by neurotransmitters such as nitric oxide, vasointestinal peptide, and serotonin.

The ingested contents upon entering the stomach are distributed, triturated, and then emptied into the duodenum. Liquids are usually dispersed and emptied immediately. The rate of liquid emptying is slowed by increased osmolarity, nutrient content, and carbonation. Solids, on the other hand, are stored in the fundus, churned in the antrum, and emptied in two phases: a lag period and a linear emptying period. The two periods occur over 3–4 hours, with the lag period lasting 1–3 hours. During the lag period, food particles move proximally to distally and undergo trituration and redistribution. Trituration occurs in the antrum with high-amplitude contraction waves that propagate proximally to distally. The food particles are reduced to a size of approximately 1–2 mm in diameter prior to emptying. The pylorus ultimately regulates how much content is emptied into the duodenal bulb by coordinated contractions and maintenance of the lumen with fixed tone.

Besides mechanical factors, neurohormonal factors also control the rate of emptying. Glucagon and incretins (eg, amylin and glucagon-like peptide 1) slow gastric emptying. The vagus provides both excitatory and inhibitory innervation. The presence of chyme in the duodenum provides negative feedback on the rate of emptying as mediated by duodenal distention, acidification, or perfusion with fats and protein. The regulation of duodenal intake controls the level of postprandial hyperglycemia from nutrient absorption.

General Considerations

Gastroparesis is characterized by delayed gastric emptying that is not associated with the presence of an obstructing structural lesion in the stomach or distally in the gastrointestinal tract. Many disorders that interfere with the normal neuromuscular coordination of the stomach can lead to gastroparesis (Table 18–1). The three most common causes are idiopathic, diabetic, and postsurgical. A tertiary referral series of 146 patients showed the causes of gastroparesis to be 36% idiopathic, 29% diabetic, 14% postgastric surgery, 7.5% Parkinson disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudo-obstruction, and 6% miscellaneous causes (eg, paraneoplastic syndrome, superior mesenteric artery syndrome, and median arcuate ligament syndrome). The idiopathic causes included acute viral-like gastroenteritis (23%), gastroesophageal reflux disease (GERD) and nonulcer dyspepsia (19%), and cholecystectomy.

CIPO is characterized by obstructive symptoms generated from the small or large bowel occurring in the absence of anatomic obstruction. It is a severe form of dysmotility that is considered a failure or insufficiency of the “intestinal pump.” Like gastroparesis, CIPO has a wide variety of causes (Table 18–2). These can generally be separated into congenital versus acquired causes, and myopathic versus neuropathic processes. Because gastroparesis and CIPO have very similar clinical approaches, this section discusses the assessment and treatment of these conditions together.

The true prevalence of gastroparesis has been difficult to study due to underdiagnosis and the lack of inexpensive diagnostic testing that is also widely available. A large population-based study in Olmsted County, Minnesota, estimated the age-adjusted prevalence of definite gastroparesis, defined as delayed gastric emptying on scintigraphy and typical symptoms for more than 3 months, to be 24.4 per 100,000 persons (95% confidence interval [CI], 15.7–32.6). Other population studies have shown upper gastrointestinal symptoms to be present in 11–18% of diabetic patients, with 50–65% of them having delayed gastric emptying. The mean age of gastroparetic patients in one study was 45 years, with a mean age of onset of 33.7 years. The prevalence of gastroparesis per 100,000 persons was 9.6 among men versus 37.8 among women. It is unclear whether gender influences the pathophysiology of gastroparesis or if this represents a difference in health care–seeking behavior between men and women. An overlap syndrome of gastroparesis and functional dyspepsia has been noted, and 25–42% of patients with functional dyspepsia have concomitant gastroparesis.

Clinical Findings

A. Symptoms and Signs

Typical complaints of gastroparesis include postprandial nausea, vomiting, belching, early satiety, bloating, discomfort, or pain. Reflux symptoms are also common. Chronic symptoms include weight loss or electrolyte disturbances, or both. Signs and symptoms of nutritional and vitamin deficiencies that may be noted include temporal wasting and loss of subcutaneous fat (malnutrition), gum bleeding (vitamin C), visual changes with night blindness (vitamin A), neuropathy, or impaired memory and confusion (folate, vitamin B₁₂). Dysphagia or odynophagia may occur as a result of reflux esophagitis. Diarrhea and malabsorption may be a consequence of bacterial overgrowth caused by altered peristalsis. Symptoms to look for include dry mouth, eyes, or vagina; difficulties with visual accommodation in bright light; anhidrosis (absence of sweating); impotence; dizziness on standing; scleroderma symptoms such as Raynaud phenomenon, skin tightening, and peripheral paresthesia; and numbness or focal weaknesses. A medication history can elicit drugs that may contribute to altered gastric motility (Table 18–3).