The UES is a 3–4 cm-long high-pressure zone that forms a barrier between the esophagus and the pharynx. It opens and closes intermittently to allow the passage of food or liquid. The UES closure muscles comprise the cervical esophagus, cricopharyngeus, and interior pharyngeal constrictor. The UES opening muscles consist of the superior and inferior hypoid muscles and superior pharyngeal muscles [1]. All UES muscles are striated and are innervated by the glossopharyngeal, branches of the vagus, ansa cervicalis, and sympathetic nerves from the cervical ganglion. The vagus nerve is the major motor nerve of the UES. Nerve cell bodies of the vagus efferent fibers are located in the nucleus ambiguus (medulla oblongata). Between swallows, the UES is tonically contracted to prevent reflux of esophageal contents and entry of air from the pharynx during inspiration. During swallowing, the cricopharyngeal and inferior pharyngeal constrictor muscles relax and the suprahyoid muscles contract.

The esophageal body extends from the UES to the LES and measures 18–24 cm. The esophageal wall consists of mucosa, submucosa, and the tunica muscularis and adventitia. The esophageal body is not surrounded by a tunica serosa. The esophageal mucosa is of the stratified squamous epithelium type, except for the distal 2 cm, where columnar epithelium of the gastric cardia type may be encountered. More proximal extension of gastric-type epithelium or the presence of intestinal-type columnar epithelium defines the pathological entity known as Barrett’s esophagus (Fig. 16.2). Outside the epithelial lining is a thin layer of longitudinally oriented smooth muscle fibers, the muscularis mucosa. Below the muscularis mucosa is the submucosa, which consists of connective tissue. The muscularis propria is made up of an inner, circular, muscle layer and an outer, longitudinal, muscle layer. In the proximal 5 % of the esophageal body, the muscularis propria is made up of striated muscle fibers. The distal 50–60 % consists entirely of smooth muscle. The middle 35–40 % is composed of a mixture of smooth and striated muscle fibers.

Neuronal control of esophageal body motility is complex [2]. The esophageal wall receives extrinsic innervation via the vagus nerve. Striated muscle fibers are directly innervated by postganglionic neurons originating in the nucleus ambiguus and terminating on the motor end plate. Smooth muscle fibers are controlled by preganglionic nerve fibers originating in the dorsal motor nucleus. These cholinergic nerve fibers terminate on the intrinsic neurons of the myenteric plexus located between the circular and longitudinal muscle layers. Within the myenteric plexus, two types of neurons have been identified. Excitatory neurons mediate contraction of both longitudinal and circular muscle layers via nicotinic cholinergic nerve receptors. Inhibitory neurons mediate the relaxation of mainly circular muscle fibers via noncholinergic, nonadrenergic neurotransmitters, most probably nitrous oxide and vasoactive intestinal peptide (VIP) [3]. Intrinsic sensory (afferent) neurons are within Meissner’s plexus located in the submucosa. Sensory impulses are conveyed to the central nervous system via both vagal and thoracic sympathetic nerve fibers.

Swallowing initiates a progressive series of coordinated propulsive contractions throughout both the striated and the smooth muscle portions of the esophageal body. This form of esophageal motor activity is referred to as primary peristalsis. Intraluminal distention of the esophageal body results in a peristaltic wave at or proximal to the site of distention. This wave is termed secondary peristalsis and serves to clear the esophagus from contents that have not been cleared by primary peristalsis, or refluxed gastric contents. Primary and secondary peristaltic waves have similar amplitudes and travel at a velocity of 3–5 cm/s.

Deglutitory inhibition is a unique physiological phenomenon whereby repetitive swallowing inhibits all esophageal body activity while the LES is relaxed. A normal peristaltic contraction will follow the last swallow of such a series and clear the esophagus completely [4].

The LES is a high-pressure zone measuring 2–5 cm in length located between the esophageal body and the stomach. Ultrastructural studies show that this high-pressure zone consists of a specialized thickened region of the circular muscles layer of the distal esophagus, albeit the muscle fibers are not circular, rather they are organized as clasp and sling fibers [5]. At rest the sphincter is tonically contracted with a normal pressure ranging from 10 to 45 mmHg. The basal LES tones are determined by three factors: myogenic tone that is independent of neural influences, cholinergic excitatory tone, and nitrergic inhibitory tone. The LES relaxes after swallowing. Relaxation is mediated by the nitrergic inhibitory neurons. The LES may also relax without swallowing, a phenomenon referred to as transient lower esophageal sphincter relaxation (TLESR). These relaxations are believed to play a major role in the pathogenesis of gastroesophageal reflux disease.

A number of endogenous compounds affect the LES tone when administered in pharmacological doses. For instance, large doses of gastrin increase the tone of LES. Exogenous substances such as beta-adrenergic receptor agonists and calcium channel blockers may induce relaxation of the LES.

Motor disorders affecting the skeletal (proximal) part of the esophagus result from either neurological abnormalities affecting the extrinsic innervation of the proximal esophagus, or skeletal muscle or neuromuscular disorders. More specifically these include:

Because of the difficulty of transferring food bolus from the hypopharynx into the esophageal body across the UES, most patients experience choking or regurgitation of liquids and/or solids. Videofluoroscopy is the best diagnostic modality for diagnosing oropharyngeal dysphagia. Scintigraphy is of limited value.

Disorders of the distal esophageal body (smooth muscle) and LES can be broadly classified into achalasia and nonspecific esophageal dysmotility according to conventional stationary esophageal manometry (Table 16.1).

Gastroesophageal reflux disease (GERD) involves the reflux of chyme from the stomach to the esophagus. The LES may relax spontaneously and transiently 1–2 h after the patient has eaten, allowing gastric contents to regurgitate into the esophagus. The acid is normally neutralized and cleared by peristalsis from the esophagus within 3 min and the tone of the sphincter is stored. When the reflux does not cause symptoms, it is known as physiological but in some individuals it may cause a spectrum of inflammatory responses in the esophagus. GERD is the most prevalent condition originating from the gastrointestinal tract. It is estimated than 20 % of the Western adult population suffers from heartburn more than three times a month [9]. It is particularly important in the pediatric age group. Also, GERD is common among pregnant women, especially during the third trimester.

The typical symptom of GERD is heartburn. However, a number of atypical symptoms are also linked to GERD, such as noncardiac chest pain, hoarseness, asthma, water brash, teeth erosion, and halitosis.

Most children affected with gastroesophageal reflux (GER) are between 6 months and 2 years old; they suffer from poor weight gain, vomiting, aspiration, choking, asthmatic episodes, stridor, apnea, and failure to thrive. A small amount of physiological reflux occurs in infants and resolves spontaneously by 8 months of age. The Tuttle acid reflux test is generally considered the reference standard but is technically demanding. The radionuclide method has a number of potential advantages. It is physiological, easily performed, well tolerated by the patient, and quantitative and involves a low radiation dose to the child.

The stomach is a storage sac located between the esophagus and duodenum (Fig. 16.1). The proximal stomach consists of the cardia, fundus, and body. The antrum forms the distal stomach and is separated from the duodenum by the pyloric ring. The wall structure of the stomach is similar to that of the rest of the gastrointestinal tract, i.e., it consists of the mucosa, submucosa, muscularis propria, and serosa. However, unlike other parts of the gastrointestinal tract, the muscularis consists of three layers – circular, longitudinal, and oblique. This facilitates distension of the stomach and storage of food. The muscle layer in the antrum is modified to aid the mixing of food. The pyloric ring regulates the emptying of the stomach.

Besides storage, the stomach has a number of exocrine, paracrine, and endocrine functions. The exocrine secretions consist of HCI and pepsin produced by the mucosal parietal cells and chief cells respectively. These cells are located in the fundus and body of the stomach. Most cells within the lamina propria and submucosa are responsible for the main paracrine function, namely, the release of histamine, which in turn stimulates the parietal cells to secrete acid. The antrum secretes the hormone gastrin which enhances gastric emptying and acid secretion.

The intrinsic factor (IF) is a glycoprotein secreted by parietal cells. It binds to Vitamin B-12. The IF-B12 complex in turn binds to specific receptors on the terminal ileal epithelium. Without IF, B12 cannot be absorbed and pernicious anemia develops. Usually failure to secrete IF results from gastric atrophy which causes the destruction of parietal cells.

The motor activity of the stomach serves two main functions: (a) to act as a reservoir for ingested meal and ensure timed delivery of food particles to the duodenum at a rate compatible with optimal digestion and (b) to disperse solids into small particles and to mix them with gastric juice. The functions are accomplished by the coordinated activity of three functionally distinct parts of the stomach: (a) the proximal stomach, including the fundus and proximal body; (b) the distal stomach, including distal body and antrum; and (c) the pylorus, as part of the pyloroduodenal unit.

The proximal stomach has three muscle layers – longitudinal, circular, and oblique. No myoelectrical activity is recorded from the fundus during fasting except for the interdigestive migratory motor complexes (see below). In the fed state, the fundus exhibits two forms of motor activity: receptive relaxation and accommodation. Receptive relaxation refers to the reduction in proximal stomach tone initiated by swallowing or pharyngeal stimulation. Accommodation is reflex relaxation of the proximal stomach in response to gastric distention. It is not induced by swallowing or pharyngeal stimulation. Truncal vagotomy abolishes both receptive relaxation and accommodation, suggesting that they are mediated by the vagus nerve. Some gastrointestinal peptides such as cholecystokinin, secretin, VIP, and gastrin induce proximal stomach relaxation, whereas motilin increases fundic pressure [17, 18].

The distal stomach is comprised of two muscle layers: the longitudinal and circular. Slow waves or slow pacer potentials originate in the pacemaker region, located on the greater curvature of the stomach near the junction of the proximal and distal stomach. Slow waves pace the normal 3/min corpus-antral peristalsis, which mixes solid and liquid food with gastric juice and triturates larger particles. The distal gastric motor activity is regulated by cholinergic and noncholinergic, vagal efferent nerve fibers. Cholinergic pathways stimulate antral contraction whereas noncholinergic vagal nerve stimulation inhibits antral activity through VIP and possibly nitrous oxide release from inhibitory neurons within the myenteric plexus.

The pyloric sphincter functions, in coordination with the duodenum, as a sieve allowing particles l mm or smaller to pass into the duodenum in 2- to 4-ml aliquots with each gastric peristalsis [19]. Emptying of inert liquids such as 0.9 % saline follows first-order kinetics; i.e., the volume of liquid emptied into the duodenum in a given time is a constant fraction of the volume that remains in the stomach (Fig. 16.3) [20]. Emptying of digestible solid particles is characterized by a lag phase and a linear phase (Fig. 16.4) [21]. However, the caloric density, viscosity, osmolarity, and volume of any specific meal will influence gastric emptying rates. Fibrous material in the stomach is emptied in the interdigestive state by migrating myoelectrical-contractile complexes comprising 3–10 min of strong lumen-obliterating antral contractions [17].

The small intestine is a hollow muscular cylinder that measures 5–6 m in length. It consists of three regions: duodenum, jejunum, and ileum. The intestinal wall is made up of four layers: the mucosa, the submucosa, the muscularis, and the serosa. The small intestinal mucosa is fashioned into villi and crypts to increase the surface area and enhance the absorptive function of the small bowel. The mucosa of the villi consists of absorptive columnar epithelial cells (enterocytes) and mucus-secreting goblet cells. Within the crypts the most common cell type is the undifferentiated crypt cell which secretes chloride and water into the lumen. The crypt also contains pluripotent stem cells. Furthermore, the small bowel harbors the enteroendocrine cells which secrete a number of hormones including secretin, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, glucagon, vasoactive intestinal peptide, somatostatin, and others. These hormones play an important role in gastrointestinal motility. Finally, the intestinal mucosa and lamina propria contain the largest lymphoid organ in man: the gut-associated lymphoid tissue (GALT) [31]. The latter consists of:

The M-cells are specialized epithelial cells overlying lymphoid follicles. Because they are not covered by mucus, antigens can bind to M-cells which take in the antigens, process them, and present them to lymphocytes and macrophages. However, the binding to antigens is highly selective. For instance, only pathogenic bacteria can attach to M-cells, whereas commensals cannot. IELs are specialized T lymphocytes situated between the basolateral membranes of mucosal epithelial cells and the lamina propria. They appear to have an important immunologic function as they express CD45RO a marker of memory cells. Dendritic cells are derived from the bone marrow and reside beneath M-cells. They capture antigens, carry them across the mucosal barrier, and present them to T lymphocytes.

The submucosa consists of connective tissue, lymphocytes, plasma cells, macrophages, mast cells, fibroblasts, eosinophils, nerve fibers, ganglion cells (Meissner’s plexus), blood vessels, and lymphatics.

The muscularis is made of inner circular and an outer longitudinal muscle fibers. Between these two layers of smooth muscle lies the myenteric plexus, the network of intramural neurons that is essential for all coordinated and organized motor activity. The extrinsic (autonomic) nerves affect the gastrointestinal motility by means of these enteric nerves.

Most of the digestion and absorption of nutrients takes place in the small bowel. Moreover, the motor function of the small bowel ensures the mixing of chyme with digestive enzymes and the propulsion of chyme toward the colon. Also, the small bowel plays an important role as a first line of defense against pathogenic microorganisms and harmful food antigens.

In most instances, nutrients cannot be absorbed by the cells that line the gastrointestinal tract in the forms in which they are ingested. Digestion is the breakdown of ingested molecules into small ones via reactions catalyzed by enzymes produced by the gastrointestinal organs.

The small intestinal epithelium participates in digestion by secreting oligosaccharidases such as lactase, enterokinase, and peptidases.

Absorption refers to the process of transporting molecules through the epithelial lining of the gastrointestinal tract into the blood or lymph.

Water, electrolytes, monosaccharides, amino acids, small peptides, glycerol, fatty acid, vitamins, and minerals are all absorbed via a number of mechanisms including passive diffusion, facilitated diffusion, active transport, and endocytosis. Although absorption takes place along the entire length of the small intestine, the mucosa in certain regions selectively absorbs specific molecules. For instance, iron is primarily absorbed in the duodenum and proximal jejunum, whereas the terminal ileal mucosa has specific receptors for binding and absorbing vitamin B-12 and bile salts [32].

Under physiological conditions the small bowel exhibits two main motor patterns. During the fed state, and as a result of contact with nutrients, a number of neuronal and hormonal signals are elicited including afferent vagal stimulation and the release of cholecystokinin which mediate segmentation and peristalsis. Segmentation is the most frequent movement in the small bowel and is characterized by closely spaced contractions of the circular muscle layer. These contractions divide the small intestine into short neighboring segments. Segmentation helps mix chyme with digestive enzymes. Peristalsis, on the other hand, is the progressive contraction of successive sections of circular smooth muscle resulting in the propulsion of chyme toward the colon. Furthermore, during the fed state, the small intestine especially the duodenum exerts negative feedback control on gastric emptying via neural and hormonal mechanisms (secretin, cholecystokinin, and gastric inhibitory peptide).

During the fasting phase, the small intestine exhibits a different pattern of motility characterized by bursts of intense electrical and contractile activity separated by periods of lack of activity. This pattern is called migrating myoelectric complex (MMC). In humans MMC occurs every 90–120 min, originates from the stomach, and sweeps through the small bowel till the terminal ileum. The function of MMC is to clear undigested particles and propagate them to the colon [33].

Motor disorders of the small bowel can lead to symptoms and signs of “functional” as opposed to mechanical small bowel obstruction. Patients frequently complain of abdominal distension, bloating, and abdominal pain, and when small intestinal dysmotility is associated with gastroparesis, nausea and vomiting may be prominent. On physical examination, the abdomen is usually distended and bowel sounds are diminished. Features of bacterial overgrowth may be observed.

Small intestinal dysmotility may be acute or chronic. Acute dysmotility is termed adynamic ileus and is commonly seen following abdominal surgery, severe septicemia, or electrolyte disturbances such as hypokalemia. Chronic dysmotility is termed pseudo-obstruction (Table 16.5).