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Pathogenesis of delayed gastric emptying

Pathogenesis of delayed gastric emptying
Author:
Michael Camilleri, MD
Section Editor:
Nicholas J Talley, MD, PhD
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF
Literature review current through: Oct 2022. | This topic last updated: Sep 16, 2021.

INTRODUCTION — Normal gastrointestinal motor function is a complex sequence of events that is controlled by an extrinsic nerve supply from the brain and spinal cord, the complex plexi and other intrinsic or enteric pathways within the wall of the stomach and intestine (the enteric brain), and the effects of locally released transmitters, such as amines and peptides, that alter the excitability of the smooth muscle of the stomach and intestine. Abnormalities in any of these locations can lead to delayed gastric emptying (gastric stasis), a disorder that is often expressed clinically as nausea, vomiting, early or easy satiety, bloating, and weight loss. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis".)

The normal physiology of gastric motor function and the pathogenesis of delayed gastric emptying will be reviewed here. Treatment of this disorder is discussed separately. (See "Treatment of gastroparesis".)

ANATOMY AND PHYSIOLOGY OF GASTRIC MOTOR FUNCTION — An understanding of the pathogenesis of delayed gastric emptying requires comprehension of the physiology of normal gastric motor function.

Control of gut motor function — The motor function of the gut is controlled at three main levels (figure 1) [1]:

Parasympathetic and sympathetic nervous systems

Enteric neurons and interstitial cells of Cajal (ICC)

Smooth muscle cells

Autonomic nervous system — Extrinsic neural control by parasympathetic pathways is conveyed to the stomach and upper intestine through the vagus nerves. Vagal efferents arise in the dorsal motor nucleus of the vagus nerve and, to a lesser extent, from the nucleus ambiguus and tractus solitarius. They form characteristic bead-chain-like terminals in the myenteric plexus throughout the stomach but do not directly innervate muscle [2].

The sympathetic supply reaches the stomach from the intermediolateral columns of the spinal cord at the T5 to T10 levels via the celiac ganglia. Splanchnic efferents to the stomach have cell bodies in the celiac ganglia; they supply the myenteric ganglia, give a few fibers to non-sphincteric muscle of the stomach [3], and densely supply the pyloric sphincter [4,5]. Splanchnic efferents innervating blood vessels contain norepinephrine and neuropeptide Y; those innervating the submucous ganglia and circular muscle contain norepinephrine and somatostatin; and fibers to the myenteric ganglia contain only norepinephrine [6].

Enteric nervous system — The enteric nervous system constitutes a vast network of ganglionated plexi that serves as the integrative circuitry between extrinsic modulation of gastrointestinal motility (via the sympathetic and parasympathetic nervous systems), and sensory afferents in the gastric wall (stimulated by luminal stimuli). These neuronal networks, or plexi, are organized in five layers which are interspersed throughout the wall of the gut; the best characterized are the myenteric, deep muscular, and submucosal plexi.

The deep muscular plexus is made up of the ICC, pacemakers for the sheets of muscle within the wall of the gut. Other cells with pacemaker functions are fibroblast-like cells that are positive for platelet-derived growth factor receptor alpha (PDGFRa). The neurons within the myenteric plexus may contain more than one transmitter [7]. The neural plexi are involved in propulsion, the interdigestive migrating motor complex, sensation, and secretion. The most common gastric cellular defects in gastroparesis are loss of expression of neuronal nitric oxide and ICC [8]. The loss of these cells may be related to the effects of immune injury or reactive oxygen species in animal models of gastroparesis [8-10].

Nitric oxide (NO) regulation may be important in gastric emptying [11,12]. NO synthase was reduced in a murine model of diabetic gastropathy and was restored with insulin treatment [13]. The cellular basis for the dysfunction of enteric neurons is the subject of ongoing research. Specifically, there is a cytoprotective role for heme oxygenase-1 (HO-1) in the pathophysiology of diabetic gastroparesis, and CD206-positive M2 macrophages, which express HO-1 protect against the development of diabetic gastroparesis in two validated animal models of diabetes mellitus that demonstrate delayed gastric emptying, and damage to ICCs by tumor necrosis factor alpha (TNF-alpha) derived from classically activated "M1" macrophages [14,15]. There are also human data supporting the reduction in numbers of these "protective macrophages", and a shift by macrophages towards a pro-inflammatory phenotype has been documented with aging, that causes inflammation-mediated degeneration of the enteric nervous system [16]. Unfortunately, promising results in diabetic mice, as observed with administration of interleukin-10 which activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein, have not been replicated in a human study. Thus, in a single-center, double-blind, placebo-controlled, randomized clinical trial of hemin, which induces HO-1, was not successful in relief of symptoms or acceleration of gastric emptying although a poorly sustained effect on HO-1 by the administered hemin could explain the lack of efficacy in the clinical trial [17-20].

In summary, while the macrophage imbalance hypothesis is potentially relevant to the role of enteric nervous system or ICC dysfunction in gastroparesis, it has not yet impacted management (diagnostic or therapeutic of patients with gastroparesis).

Smooth muscle cells — The third level of control of gastrointestinal motility is in the excitable membrane of smooth muscle cells. Specific receptors in the cell membrane bind to amines, peptides, and other transmitters that reach the smooth muscle membrane via neurocrine, endocrine, or paracrine routes. Pacemaker cells which are characterized by spontaneous depolarization of the resting membrane potential fire action potentials that contract the cell. Electrical coupling of the neighboring muscle cells, organized in a syncytium, results in the spread of the contraction around the circumferential and longitudinal axes of the stomach. There is evidence of increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells in the smooth muscle of patients with diabetic gastroparesis [21,22].

Peristaltic reflex — The peristaltic reflex is responsible for propulsion of food from the stomach into the intestine. There are two components to the peristaltic reflex:

The first change is ascending contraction above the level of luminal stimulation, usually due to distention by a food bolus. The main transmitters involved in excitation of gastric muscle are acetylcholine (and, indirectly, serotonin through 5HT4 receptors located on cholinergic interneurons) and tachykinins, such as substance P and substance K.

Descending inhibition below the level of distention is essential for the oncoming bolus to encounter a minimum of resistance to flow. The main inhibitory transmitters are nitric oxide and vasoactive intestinal peptide (VIP), although several other transmitters modulate the interneurons involved in this descending inhibitory pathway, including opiates, somatostatin, and the excitatory transmitter, gamma-aminobutyric acid [7].

Motor functions of the stomach regions — The stomach muscle has three muscular layers with fibers organized in different axes: circular, oblique, and longitudinal. The stomach has traditionally been regarded as having two functional segments: the fundus and the antrum. The mid-portion of the greater curvature of the stomach is the functional site of the gastric electrical pacemaker.

During fasting, the stomach participates in the cyclical activity front that propagates through the gastrointestinal tract and serves as a "housekeeper," propelling nondigestible solid residue towards the colon. There is some evidence in dogs that the hormone motilin, released from the duodenal loop, stimulates this gastric component of the migrating motor complex [23]. Laboratory based studies in healthy humans suggest that only about 50 percent of intestinal migrating motor complexes during fasting are associated with an antral component [24,25]. This may reflect the efficiency of antral contractions during phase III of the migrating motor complex in clearing nondigestible solids from the stomach.

Postprandially, the fundus relaxes during swallowing to start the process of accommodation in which the stomach assumes reservoir functions, facilitating the initial chemical digestion of food by acid and proteases before transfer toward the antrum [26]. The antrum produces high amplitude contractions that pulverize solids by physical and liquid shearing forces. Once solids have been reduced in size to particles of 1 to 2 mm in size (trituration), they are able to empty through the pylorus [27]. Larger particles are repetitively propelled and retropulsed from the distal stomach by an occluded gastric outlet segment until liquid shearing and chemical digestion achieve trituration.

Thus, antral motor function is critical for the grinding, mixing, and emptying of solids from the stomach. Antral motility also significantly correlates with the rate of emptying of liquids from the stomach, after the lag time required for trituration to sufficiently reduce particle size so that pyloric sieving is no longer required [28]. Interdigestive (between meals) antral motor function clears the stomach of undigestible solid particles whose size has not been reduced by trituration (figure 2).

The recovery of proximal gastric tone during the postprandial period is associated with gastric emptying, with the driving force being provided by the pressure gradient between the stomach and duodenum. Most non-nutrient liquids have emptied before tone is restored to normal, suggesting that emptying of liquids may be partly a passive process aided by gravity and the absence of resistance in the gastric outlet.

The pylorus is radiologically 0.6 to 1.6 cm long. It presents functionally as a zone of high resting pressure or tone, upon which are superimposed phasic contractions at a rate of three per minute. These contractions sweep across the antroduodenal junction. There is evidence of control of pyloric contractions by opiates, acetylcholine, and nitric oxide.

PATHOGENESIS OF DELAYED GASTRIC EMPTYING — There are several abnormalities that may result in motor dysfunction of the stomach and thereby in delayed gastric emptying. Each of the stomach regions may be affected by different pathologic processes.

Abnormalities of the fundus — There are several diseases that are associated with abnormal proximal gastric motor function. The accommodation response can significantly influence the rate of emptying of food from the stomach, even the emptying of the proximal stomach [29]. Thus, greater accommodation is associated with retardation of gastric emptying.

Postvagotomy gastric motor dysfunction — The stomach's accommodation response and phasic contractility in response to distention are abolished following vagotomy and partial gastric resection [26]. This probably accounts for the observation that there is immediate early transfer of the liquid phase of the meal to the distal stomach and beyond, but delayed emptying of solids [30]. One of the most common causes of impaired fundal accommodation is fundoplication; the impaired relaxation may be aggravated by concomitant vagal injury [31].

Diabetes mellitus — Patients with diabetes mellitus have impaired antral motor function and coordination (see 'The antrum and antroduodenal coordination' below), and show evidence of abnormal postprandial proximal gastric accommodation [32] and contraction. One study, for example, evaluated eight patients with type 1 diabetes, cardiovascular autonomic neuropathy, and dyspepsia, and 10 healthy volunteers [33]. Blood glucose levels were maintained in the normal range during the experiment. An intragastric bag connected to a barostat was inflated and deflated by stepwise pressure increments, creating pressure volume curves. There was a larger volume during the pressure increase in the diabetics than in the controls; this resulted in a significant difference in compliance (dV/dP): 57.2 mL/mmHg in diabetics versus 43.7 mL/mmHg in controls. In addition, gastric distension induced more nausea, bloating, and upper abdominal pain in the patients than the volunteers. The post-meal relaxation response of the stomach is quite variable even in patients with evidence of cardiovagal dysfunction [34,35]; experimental data also suggest that adaptive mechanisms may restore gastric relaxation to normal after vagal injury [36]. These observations may explain the unpredictability of the motor abnormalities over time in patients with diabetic gut dysmotility.

Increased compliance may explain the prolongation of lag time for emptying solids that is observed in patients with diabetes. Solids are selectively retained within the stomach during this time, often in the proximal compartment. Increased fundic contractions are responsible for accelerated gastric emptying of liquids in this setting [37]. It is important to recognize that the presence of upper gastrointestinal symptoms in a diabetic does not automatically imply delayed gastric emptying. In a study of 108 patients with diabetes mellitus and upper gastrointestinal symptoms (most common symptoms in the cohort being nausea in 80 percent), gastric emptying was rapid in 37 percent, slow in 19 percent and gastric accommodation was reduced in 39 percent [38].

Inadequate gastric accommodation in diabetes may be due to a defective nitric oxide (NO) pathway. In one study, for example, gastric relaxation was impaired in rats mainly by decreased expression of NO synthase in the gastric myenteric plexus [39]. This inadequate gastric accommodation has also been documented in patients with diabetes, and may contribute to increased gastric sensitivity resulting in symptoms such as pain, satiation, or bloating [31,32].

Motility disturbances in functional dyspepsia — Functional dyspepsia (also called nonulcer or motility-like dyspepsia) is a disorder in which patients complain predominantly of nausea, early satiety, postprandial fullness, bloating, and pain without obvious evidence of organic disease (eg, by upper endoscopy or upper gastrointestinal studies). Indeed, a study from the Gastroparesis Clinical Research Consortium documented the interchangeable symptoms and baseline characteristics between gastroparesis and functional dyspepsia with variation of gastric emptying over time that results in criteria that "modify" the diagnosis [40]. Such variation should not be surprising given the prior evidence that the intra-individual coefficient for gastric T1/2 and the emptied proportion of the meal from the stomach at four hours were respectively 23.8 and 12.6 percent based on repeat scintigraphic measurements of gastric emptying of an egg meal in healthy participants [41].

Gastric compliance is lower in patients with motility-like dyspepsia than in healthy controls, an abnormality that may contribute to the associated symptoms [31,42]. Reduced compliance was associated with significant weight loss in another report, suggesting that it resulted in early satiety and reduced food intake [43]. A summary of the motor and sensory dysfunctions reported in the literature in nonulcer dyspepsia is shown in the following figure (figure 3) [44]. Disturbances in proximal gastric function (accommodation or a reduced gastric volume response to feeding, and gastric hypersensitivity) have also been described in children with dyspepsia or chronic functional abdominal pain that may result in similar symptoms to those that result in impaired gastric emptying [45,46]. (See "Functional dyspepsia in adults", section on 'Epidemiology and pathophysiology'.)

In some patients, there is a clear association with acute onset and a febrile illness suggesting the possibility that dyspepsia is a post-infectious or post-inflammatory disorder [47]. Such patients appear to have the same sensory or motor disorders that characterize the pathophysiology of other dyspeptic patients who do not report this acute onset with a febrile illness. As in diabetic patients, the upper gastrointestinal symptoms may result from delayed gastric emptying or reduced gastric accommodation (roughly 25 percent each), and another 25 percent have both abnormal gastric emptying and reduced gastric accommodation [48].

The molecular mechanisms leading to impaired gastric accommodation include NO, adrenergic, cholinergic, and 5-HT mechanisms as evidenced by pharmacodynamic or therapeutic effects of agents that modulate gastric compliance or postprandial accommodation, such as clonidine (alpha-2 adrenergic agonist), acotiamide (acetylcholinesterase inhibitor), or buspirone (5-HT1A agonist) [49].

The antrum and antroduodenal coordination — As previously mentioned, antral motor function is critical for the grinding, mixing, and emptying of solids from the stomach. Thus, in the absence of well-coordinated antral interdigestive motor function, as in the postvagotomy state or in diabetic autonomic neuropathy, undigestible solid particles may accumulate over time and eventually form a bezoar.

Abnormalities of antral function can occur by several mechanisms:

A decreased frequency of antral contractions is the most common form of gastric motor dysfunction; this is associated with a reduced rate of gastric emptying in patients with gastroparesis [50]. In neuropathic disorders, this is usually manifested by a lower frequency of normal amplitude distal antral contractions (>40 mmHg) in response to a meal. Thus, the frequency averages 0.5 to 0.75 per minute in neuropathic diseases versus at least 1 per minute in healthy controls [51].

Reduced antral contractile amplitude is rarely observed in infiltrative disorders such as progressive systemic sclerosis. The average amplitude of contractions is typically less than 40 mmHg [52]. This abnormality more often results in vomiting because of the absence of peristaltic forces in the small intestine. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)

There is increasing evidence that several mechanisms of antral motor dysfunction frequently coexist in patients with diseases that cause gastric stasis or pharmacologic models of stasis. These mechanisms include antral hypomotility, "pylorospasm" or isolated pyloric pressure waves (IPPW), and failure of proximal gastric contraction; the last abnormality inhibits the redistribution of intragastric content for trituration by the antral segment [53]. The potential impact of pylorospasm is supported by the evidence, largely in uncontrolled trials, that botulinum toxin injection at the pylorus [54], or peroral endoscopic myotomy appear to be efficacious in the treatment of gastroparesis [55]. Further controlled studies are needed to demonstrate efficacy, and to identify biomarkers of response to these treatments (eg, isolated pylorospasm versus combined pylorospasm with antral hypomotility); female sex and underlying disease (diabetes) appear to be predictive of failure based on limited data currently available [56].

Diabetes mellitus and scleroderma are examples of diseases that may affect multiple areas of antral function (image 1).

Abnormal electrical slow wave rhythms in the stomach may result in reduced antral motor function. The normal pacemaker function of three contractions per minute is replaced by a reduced (bradygastria) or increased (tachygastria) frequency, or a mixed brady/tachygastria (figure 4). These rhythm alterations have been measured intraoperatively in patients with gastric atony, in vitro in muscle strips prepared from atonic stomachs [57], and in vivo in a number of disease states including diabetic gastroparesis, anorexia nervosa, motion sickness, and vomiting of pregnancy. The precise mechanism for these dysrhythmias is unclear; prostaglandins have been implicated since prostaglandin synthesis inhibitors restore normal electrical control activity both in vitro and in vivo [58,59].

Other abnormalities that may result in impaired antral function are autonomic neuropathy and hyperglycemia in patients with diabetes mellitus. The concept of "autovagotomy" in diabetes was introduced in the late 1970s [59]. Gastric acid secretion in response to a swallowed meal was normal in this initial review, suggesting intact parietal cell function; however, the acid secretory response to modified sham feeding (chewing but not swallowing a meal, which is a normally potent vagal stimulus) was reduced. Subsequent morphologic studies of the vagus nerve and enteric nervous system were normal in a report of patients with diabetic gastroparesis [60]. Nevertheless, the clinical association with autonomic and, particularly, vagal dysfunction is frequent in both type 1 and type 2 diabetes [61,62]. (See "Diabetic autonomic neuropathy of the gastrointestinal tract".)

Several studies have suggested a role for hyperglycemia in the pathogenesis of antral dysfunction. Acute hyperglycemia can significantly slow gastric motility and the emptying of solids in normals and patients with diabetes [62,63]. In one study of normal subjects, for example, gastric contractions were nearly absent at a serum glucose concentration of 250 mg/dL (13.9 mmol/L) and were markedly reduced at concentrations of 140 and 175 mg/dL (7.8 and 9.7 mmol/L) [63]. However, even physiologic changes in blood glucose within the normal postprandial range can increase gastric retention of a solid meal [64]. (See "Diabetic autonomic neuropathy of the gastrointestinal tract", section on 'Gastroparesis'.)

The effect of chronic hyperglycemia is less clear. In one study of 87 randomly selected diabetic patients, gastric emptying of a liquid meal was slower in those with blood glucose values above 270 mg/dL (15 mmol/L) [61]. However, there are no data showing that a chronic improvement in glycemic control enhances gastric emptying. Furthermore, the precise contribution of chronic hyperglycemia in diabetics, separate from the effects of simultaneous autonomic dysfunction, remains uncertain. Data suggest that sustained (six month) improvements in glycemic control do not affect gastric emptying [65]; on the other hand, a study of 78 patients with type 1 diabetes who participated in the Epidemiology of Diabetes Interventions and Complications study showed that delayed gastric emptying is associated with early and long-term hyperglycemia in type 1 diabetes mellitus [66]. Despite this somewhat contradictory information, it is important to maintain optimal control of diabetes as uncontrolled diabetes is a risk factor for the development of complications including neuropathy both peripherally and in the autonomic nervous system.

Is there a cellular basis for the development of gastroparesis? — Experimental models of gastroparesis show a reduction or remodeling in the number of interstitial cells of Cajal (ICC) in the deep muscle plexus. This leads to secondary effects in gastric muscles because of the lack of trophic factors (eg, stem cell factor) [67-69]. There are a few case reports documenting the same deficiency in patients with gastroparesis [70-73].

Loss of ICC results from imbalance between the processes that injure ICC networks and processes that generate and maintain ICC [74]. The relative insulinopenia and IGF-1 deficiency in diabetes leads to reduced production of smooth muscle cell-produced stem cell factor, an important ICC survival factor [69]. Diabetes is associated with high oxidative stress which may result from upregulation of macrophage heme oxygenase-1 [9].

Detailed studies of full thickness biopsies of the stomach in patients with idiopathic and diabetic gastroparesis show no significant differences in nerve or smooth muscle or inflammatory cell markers on light microscopy, except for greater reduction in expression of neuronal NO synthase neurons in diabetic compared with idiopathic gastroparesis [8]. At the ultrastructural level, diabetic gastroparesis was associated with a thickened basal lamina around smooth muscle cells, and other changes (altered neuronal bodies and nerve endings and fibrosis around nerves) were more severe in idiopathic than diabetic gastroparesis [75]. The precise functional significance of these changes is unclear, and therefore histological studies remain predominantly research tools.

The loss of ICC in patients with gastroparesis is significantly associated with delayed gastric emptying; overall clinical severity and nausea in idiopathic gastroparesis are associated with the degree of immune cell infiltrate [76].

Does inflammation or oxidative stress contribute to the abnormal cellular functions in gastroparesis?

Morphology studies – Loss of antiinflammatory macrophages and increased expression of genes associated with proinflammatory macrophages have been reported in full-thickness gastric biopsies from patients with gastroparesis. However, there may be differences in the morphologic abnormalities in diabetic and idiopathic gastroparesis in the different studies reported to date. The candidate mechanism leading to loss of these different pacemaker cells is oxidative stress, possibly resulting from the depletion of antiinflammatory resident M2 macrophages expressing heme oxygenase-1, which would protect the pacemaker cells by neutralizing the oxidative mechanisms [9].

Proteomics and RNA expression studies – Based on full-thickness gastric body biopsies and deep RNA sequencing, it was shown that granulocyte adhesion and diapedesis, as well as a macrophage-based immune dysregulation pathway, are the most significantly affected pathways altered in both diabetic and idiopathic gastroparesis. In addition, proteins involved in the complement and prostaglandin synthesis pathway were associated with diabetic gastroparesis. In the same study, immune cell analysis revealed no significant differences in enrichment of genes associated with M1 or M2 macrophages in the biopsies from patients with diabetic gastroparesis and diabetic control samples [77-79].  

In contrast, genes associated with M1 (proinflammatory) macrophages were increased in idiopathic gastroparesis samples compared to their controls. Finally, innate immune mechanisms in diabetic gastroparesis seem to be associated with reduced expression of inflammatory markers on transcriptomics, and paradoxically, they are associated with M2 macrophage deficiency, which would be expected to be proinflammatory in diabetic gastroparesis.

Therefore, further studies are needed to clarify the role of inflammatory mechanisms in gastroparesis and particularly, the impact of vagal denervation, which may be associated with diabetes mellitus. Moreover, there are still no known treatments to effectively inhibit oxidative stress in the gut neuromuscular apparatus, and antiinflammatory approaches or treatments directed at oxidative stress still require controlled trials.

The pylorus — Two disease processes have been associated with pyloric dysfunction: idiopathic hypertrophic pyloric stenosis; and diabetic gastroparesis. In the former, a deficiency of inhibitory NO-containing neurons leads to lack of relaxation or excessive spasm. In diabetes mellitus, excessive tonic and phasic pressure activity at the level of the pylorus is present, contrasting with the postprandial antral hypomotility [80]. Experimental evidence suggests that normalization of blood glucose with insulin treatment or treatment with the phosphodiesterase-5 inhibitor sildenafil restores normal gastric emptying of liquids [13].

The precise contribution of the pylorus alone to impaired gastric emptying in disease is unclear. However, this may be a moot point, since in most diseases and in pharmacologic models of gastric stasis, excessive pyloric contractility is most often associated with significant impairment of antral and probably fundal contractility. Nevertheless, there is increased interest in pursuing measurements of pyloric diameter and distensibility as evidence of a pathophysiologic mechanism contributing to impaired gastric emptying, as well as some evidence showing that these measurements either at baseline or in response to gastric peroral endoscopic myotomy are actually predictive of clinical success of the procedure [81-84].

Abnormal small bowel motility — Abnormalities in small bowel motility can result in delayed gastric emptying of solids [85]. This is true regardless of whether the underlying process is neuropathic or myopathic [86]. Disturbances of intestinal ICC can also affect the small bowel and result in impaired gastric emptying (eg, in paraneoplastic dysmotility) [87]. (See "Chronic intestinal pseudo-obstruction: Etiology, clinical manifestations, and diagnosis".)

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Basics topics (see "Patient education: Gastroparesis (delayed gastric emptying) (The Basics)")

SUMMARY AND RECOMMENDATIONS

The motor function of the gut is controlled at three main levels: the parasympathetic and sympathetic nervous systems, enteric neurons and interstitial cells of Cajal, and smooth muscle cells. (See 'Control of gut motor function' above.)

The peristaltic reflex is responsible for propulsion of food from the stomach into the intestine. The peristaltic reflex includes ascending contraction above the level of luminal stimulation, usually due to distention by a food bolus, and descending inhibition below the level of distention. (See 'Peristaltic reflex' above.)

The stomach has three functional segments: the fundus, the antrum and the pylorus. The mid-portion of the greater curvature of the stomach is the functional site of the gastric electrical pacemaker. (See 'Motor functions of the stomach regions' above.)

During fasting, the stomach participates in the cyclical activity front that propagates through the gastrointestinal tract and serves as a "housekeeper," propelling nondigestible solid residue towards the colon.

Postprandially, the fundus relaxes during swallowing (receptive relaxation) to start the process of accommodation in which the stomach assumes reservoir functions, facilitating the initial chemical digestion of food by acid and proteases before transfer toward the antrum. The antrum produces high amplitude contractions resulting in the grinding, mixing, and emptying of solids from the stomach.

Interdigestive (between meals) antral motor function clears the stomach of undigestible solid particles whose size has not been reduced by trituration.

The recovery of proximal gastric tone during the postprandial period is associated with gastric emptying, with the driving force being provided by the pressure gradient between the stomach and duodenum. (See 'Motor functions of the stomach regions' above.)

Delayed gastric emptying may be due to abnormalities of the fundus (post-vagotomy state, diabetes mellitus, and functional dyspepsia), abnormalities in antroduodenal contraction (low amplitude, frequency, decreased antral motor function or dysfunction), pyloric dysfunction (idiopathic hypertrophic pyloric stenosis and diabetic gastroparesis associated with "pylorospasm") or abnormalities in small bowel motility. (See 'Pathogenesis of delayed gastric emptying' above.)

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Topic 2638 Version 17.0

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