Gastric motor disorders constitute an important part of clinical gastroenterological practice. Normal gastric motor function includes gastric accommodation which provides a reservoir during meal ingestion, gastric emptying at a rate that matches small bowel absorptive function and interdigestive motility that eliminates indigestible particles. Disorders of gastric motor function include impaired accommodation, gastroparesis and dumping syndrome. This review summarises current knowledge on the pathophysiology, diagnostic approach and treatment for these disorders.
Citation s : Park S-Y et al. Hence, the volume of air within the bag reflects the degree of contraction of the stomach: at a constant pressure, a large volume reflects a gastric relaxation and a small volume represents a contraction. Stool consistency, but not frequency, correlates with total gastrointestinal transit time in children. Moreover, in patients with autoimmune dysautonomia and gastroparesis, antibodies to glutamic acid decarboxylase have been described Basically in gastroparesis, Motor dysfunctions of the stomach stomach motility disappears and food remains stagnant in the stomach. Thorn, S. Thus, avoidance of Hoty ass and excess alcohol consumption can help prevent the majority of chronic stomach disorders.
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We do not know the cellular mechanisms by which colonic inflammation enhances the frequency of GMCs. The colon is the last major organ in the gastrointestinal tract. Motor Functions of the Stomach. Take-home Messages The volume Motor dysfunctions of the stomach ICC is decreased in the colon of slow-transit constipation patients. A mechanism- based criterion, using hour recordings of GMCs, might be more objective. Junior model panty photo is partly due to the qualitative nature of analysis in these methods and the heterogeneity of tissues and observations at the microscopic level. Progesterone levels in females with slow-transit constipation are normal. Freshly obtained full-thickness rat colon tissues were immersed in Motor dysfunctions of the stomach, carbogenated Krebs solution more Differential effects of RPCs and GMCs on the compression of the gut wall, propulsion of luminal contents, and distension of the descending segments. A recent study has demonstrated that ICC do not mediate the neuronal input to smooth muscle cells [ ]. Yet the opening of the pylorus is still small enough that only a few milliliters or less of antral contents are expelled into the duodenum with each peristaltic wave.
Stomach diseases include gastritis , gastroparesis , diarrhea , Crohn's disease and various cancers.
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Propulsion of the gastrointestinal GI luminal contents requires coordinated contractions of the intestinal smooth muscle in response to input from the enteric neurons. The enteric nervous system is capable of independent function, which is modulated by motor input from the brain through the sympathetic and parasympathetic branches of the autonomic nervous system. Thus, it is not unusual for preterm infants to have poor gastric emptying GE and feeding intolerance. GI motility disorders result from weak or uncoordinated contractions due to abnormalities of the neuromuscular apparatus or abnormal sensory and motor input from the brain.
These disorders range in severity from mild, recurrent abdominal pain to severe chronic intestinal pseudo-obstruction syndrome CIP with intestinal failure. Motor disorders of the stomach can result from either gastric emptying that is too rapid or too slow. The stomach is a complex electromechanical chamber, and the rate of gastric emptying is influenced by the meal consistency, calorie concentration, and central neural and hormonal input mechanisms.
The act of swallowing initiates gastric accommodation receptive relaxation such that the stomach fundus expands to receive the ingested food. This reflex is mediated by vagal pathways and can also be initiated by gastric distension, duodenal distension, or nutrient infusion into the small bowel.
Pharmacological inhibition of gastric accommodation induces early satiety and weight loss. A gradual increase in the proximal stomach muscle tone transfers the food into the distal stomach. Liquids are transferred rapidly from the proximal to the distal stomach and emptied into the duodenum by series of antral peristaltic contractions.
In contrast, solids are emptied at a relatively slower rate. There is a significant lag phase in the delivery of solids from the stomach into the duodenum, as food particles first need to be grounded into a thick chyme, consisting of particles 1 to 2 mm in diameter. The strong antral contractions that typically occur at a rate of 3 per minute help to ground and mix the food before it is emptied into the duodenum. Disorders that can cause slow emptying are listed in Table ; drug-induced, postsurgical, and postviral gastroparesis are the 3 most common causes.
GE can be delayed in preterm infants due to immaturity of the enteric nervous system. In older children, it can follow infections such as rotavirus, Epstein-Barr virus, and cytomegalovirus. Delayed GE also has been reported in children with eosinophilic gastroenteropathy and following injury to the vagal nerve or its branches during surgery.
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The ascending colon in colitis patients shows stasis, while the sigmoid colon shows rapid transit [ ]. Breakdown products of protein digestion also elicit inhibitory enterogastric reflexes; by slowing the rate of stomach emptying, sufficient time is ensured for ade-quate protein digestion in the duodenum and small intestine. DNA Methylation. Balloon distension in in vitro experiments in the intact human colon stimulates contractions above and relaxation below it [ 47 ]. Impairment of descending inhibition prevents relaxation of the receiving segment ahead of it. The area under contractions in patients with normal colonic transit, with moderately slow transit, or in patients with IBS-C is higher than that in healthy controls [ ]. The link between abnormal motility and altered bowel habits is obvious.
Motor dysfunctions of the stomach. GMCs and Visceral Pain of Gut Origin
Another major limitation is the absence of efforts to establish a cause-and-effect relationship between the findings and functional impairment. However, these approaches seem to be of limited use in complex diseases like IBS. Over the past three decades, discoveries of gene mutations that cause or contribute to simple Mendelian diseases, such as sickle cell anemia, hemophilia, and cystic fibrosis have been reported [ — ].
However, the search for gene mutation that causes complex diseases, such as diabetes, most cancers, asthma, inflammatory bowel disease, and functional bowel disorders has largely been unsuccessful. Differential environmental factors during fetal and neonatal development usually account for discordance of monozygotic twins. The simple diseases progressively worsen after onset, whereas complex diseases, such as major psychosis, inflammatory bowel disease, functional bowel disorders, and rheumatoid arthritis, exhibit relapses and remissions.
Epigenetics plays a prominent role in cancer and autoimmune and inflammatory diseases [ — ]. The inherited genetic code is identical in all cell types in an organism, with the exception of a few, such as the gametes [ ]. During ontogeny, epigenetic mechanisms set the transcription rates of each gene in the genome ranging from complete silence to full activation, imparting phenotype to each cell.
The transcription rates of different genes are set for survival of the fetus and the neonate as well as for optimal responses of the cells to their microenvironment of hormones, neurotransmitters, growth factors, and inflammatory mediators in adulthood. However, if the fetus indirectly through the mother or the neonate is exposed to psychological or inflammatory stress, the transcription rates of genes vulnerable at the time of insult may be set at abnormal levels, ensuring current survival but leading to abnormal cell function in adulthood, causing a complex disease.
Epigenetic regulation during neonatal inflammatory or psychological stress can modify gene expression by post-transcriptional histone modifications and by DNA methylation.
The basic subunit of chromatin is the nucleosome, which contains about bp of DNA wrapped twice around an octomer core of four histones two molecules each of histones H2A, H2B, H3, and H4 in a 1. Nucleosome is the smallest unit of chromatin. On the left, the packing of the first few nucleosomes is tight so that the transcription factors do not have access to the DNA wrapped around these nucleosomes.
Acetylation of the N-terminal histone protein more Normally, the histone proteins are positively charged and form tight electrostatic associations with negatively charged DNA, which results in tight compaction of chromatin and inaccessibility of the DNA to transcription factors and transcriptional machinery.
The N-terminal tails are the main sites of posttranslational modifications including acetylation, methylation, phosphorylation, citrullination, sumoylation, ubiquitination, and ADP-ribosylation by enzymes, and this affects their function in gene regulation [ ]. Acetylation, one of the most widespread modifications of histone proteins, including H2B, H3, and H4, occurs on lysine residues in the N-terminal tail and on the surface of the nucleosome core as part of gene regulation [ ].
The addition of an acetyl group to histone proteins reduces their positive charge to form a more relaxed configuration with DNA, which allows the transcription factors and transcriptional machinery access to their recognition sites on the promoters of specific genes to induce transcription. The HATs are present as part of large protein complexes and act as transcriptional coactivators. The deacetylases HDACs are recruited to target genes via their direct association with transcriptional activators and repressors, as well as their incorporation into large multiprotein transcriptional complexes [ ].
Together, these two classes of enzymes account for the coordinated changes in chromatin structure that carry out its functions [ , ]. The balance between the actions of these enzymes is a key regulatory mechanism for gene expression and governs numerous developmental processes and disease states [ ]. Lysine acetylation is associated with active gene expression and open chromatin.
H3K9ac and H4K16ac are two histone modifications often associated with euchromatin. RNAP II interaction with the Cacna1c core promoter is markedly elevated in the colonic muscularis externa of adult rats subjected to neonatal inflammation.
Freshly obtained full-thickness rat colon tissues were immersed in warm, carbogenated Krebs solution more Methylation of lysine and arginine residues can occur in histones H3 and H4, in the mono-, di-, or tri-methylated form [ ]. Depending on the site and type of histone, the methylation pattern will result in a different transcriptional outcome. Di- and tri-methylation of histone H3 lysine 4 H3K4me2 and H3K4me3 are hallmarks of chromatin at active genes [ ].
DNA methylation occurs at specific dinucleotide sites along the genome, cytosines 5' of guanines CpG sites. DNA methylation affects the correct temporal and spatial silencing of gene expression during development and during disease processes such as tumor progression [ ]. The methylation of CpG islands restricts the access of transcription factors to the promoter region, thereby suppressing transcription of the targeted genes [ ]. Functional bowel disorders do not have the traits of genetic diseases.
Genetic alterations mutations and polymorphisms inherited from parents or mutations due to environmental factors once acquired are irreversible. Mutations in a gene may produce a wrong protein or no protein at all; polymorphisms may produce a variant protein. The functional effects of mutations and polymorphisms are stable. By contrast, the severity and types of symptoms in functional bowel disorders vary, arguing against a genetic component [ , ]. All these characteristics of functional bowel disorders suggest fluctuating expression of proteins causing dysfunction, a result of epigenetic regulation rather than genetic variance.
Epigenetic mechanisms, discussed above, can alter the expression of target proteins in target cells, such as smooth muscle cells and afferent neurons, in response to changes in their microenvironment.
The two types of IBD are clinically, immunologically, and morphologically distinct. In spite of differing etiologies, the primary symptoms of both types of IBD diarrhea, abdominal cramping, and urgency of defecation are strikingly similar.
Stools of ulcerative colitis patients are bloody and contain mucus. IBD patients present with motor diarrhea diarrhee motrice , frequent nonwatery stools [ ]. The daily frequency of unformed stools is about five times per day in mild to moderate pancolitis and four times per day in mild to moderate distal colitis. These numbers increase with severity of colitis. The total gut transit in ulcerative colitis patients is not different from that in healthy controls [ ].
However, the proximal colon shows stasis while the rectosigmoid colon shows rapid propulsion, which counteract each other to produce normal whole colon transit [ — ]. Much of our understanding of motility dysfunction in both types of IBD has come from animal models of inflammation. Studies in IBD patients and in experimental models show that inflammation suppresses RPCs and tonic contractions, at the same time enhancing the frequency of GMCs [ 19 , , , — ]. The degree of suppression of RPCs and increase in the frequency of GMCs are independent variables, but each correlates with the intensity of inflammation and clinical symptoms [ , ].
However, inflammation in one part of a gut organ can reflexively alter motility function at distal locations [ ], which means that colitis in the distal colon may suppress RPCs in the middle and the proximal colon. Note that most studies of ulcerative colitis have recruited patients with mild to moderate colitis.
Patients with severe colitis are likely to have more intense motility dysfunction, as judged by inflammation in experimental models. In one group of patients with moderate colitis, the frequency of GMCs increased about twofold over that in healthy controls [ 39 ]. The increased frequency of GMCs produces frequent mass movements. The concurrent suppression of RPCs facilitates distal propulsion of luminal contents. The GMCs that propagate up to the rectum or the distal sigmoid colon stimulate afferent signals to generate urges to defecate as well as causing descending relaxation of the internal anal sphincter in preparation for defecation.
A strong GMC propagating to the rectum can result in involuntary defecation fecal incontinence. It is noteworthy that even though the frequency of GMCs increases in colonic inflammation, it still occurs no more than 10 to 15 times per day in moderate colitis. The frequent rapid propulsion by GMCs reduces the contact time of fecal material with the inflamed mucosa to reduce absorption of water and electrolytes. In addition, the concurrent suppression of RPCs reduces the mixing and turning over of fecal material to reduce its total exposure to the mucosa.
Together, these two factors result in unformed, but not watery, stools. Note that the degree of stool softness depends on the intensity of inflammation, which stimulates GMCs and suppresses RPCs. Excessive occurrence of GMCs causes hemorrhages, thick mucus secretion, and mucosal erosions in experimental models [ ].
These lesions explain the bloody stools with mucus characteristic of ulcerative colitis. While the GMCs are also the driving force for diarrhea in IBS-D patients, their mucosa is not inflamed and fragile as in ulcerative colitis patients.
So while IBS-D patients have diarrhea, they do not have bloody stools. The higher frequency of GMCs propagating up to the rectum in the inflamed colon induces frequent bowel movements in ulcerative colitis patients motor diarrhea. In a canine model of moderately severe acute pancolitis, the frequency of GMCs increased more than fold [ ]. About half of these GMCs propagated to the sigmoid colon, resulting in uncontrollable defecation urgency.
The rest occasionally expelled gas and caused tenesmus, which may result if a GMC generates the urge to defecate in the absence of any stool in the rectum.
The false urges caused by GMCs in an empty distal colon may also generate the sensation of incomplete evacuation. These symptoms and abnormal motility cease on recovery from inflammation. The ascending colon in colitis patients shows stasis, while the sigmoid colon shows rapid transit [ ]. Concurrent manometric recordings from the ascending and sigmoid colons of these patients are not available.
However, on a speculative note, stasis in the ascending may result if inflammation in the sigmoid colon reflexively suppresses both RPCs and GMCs in the proximal colon, thus prolonging stool transit and forming hard stools. However, when these hard stools reach the inflamed sigmoid colon, the frequently occurring GMCs propel them rapidly, so that the passing of hard stools gives the impression of constipation.
These effects are similar to the colonic motor dysfunction seen in ulcerative colitis patients. Animal models of ileal inflammation confirm these findings [ ]. Ileal inflammation suppresses RPCs in the ileum as well as proximal to it, extending up to the stomach. Many of the GMCs stimulated by ileal inflammation propagate up to the terminal ileum.
The animals are visibly uncomfortable during the passage of an ileal GMC. The frequency of bowel movements increases several-fold due to ileal inflammation [ ].
Spontaneous GMCs in the ileum occur primarily in the interdigestive state [ 6 ]. However, in ileal inflammation, they also occur after a meal, resulting in rapid emptying of undigested food and bile from the ileum into the colon. The increase in the incidence of GMCs in the ileum, by itself, cannot induce frequent defecation.
Colon involvement is necessary. Animal studies show that many GMCs originating in the ileum propagate to the colon, causing uncontrollable defecation if they propagate to the sigmoid colon [ ].
Furthermore, postprandial GMCs occurring during ileal inflammation rapidly transfer undigested chyme into the colon, which increases its osmotic load to suppress RPCs and stimulate colonic GMCs [ ].
In an animal model of ileal inflammation, a collection cannula located distal to the inflamed segment of the ileum collected copious discharge of mucus with fresh blood [ ]. The sensation of pain in IBD patients is generally located in the lower abdomen and rectal areas. Most information on visceral hypersensitivity in these patients comes from distension studies in the rectum.
There are two schools of thought regarding rectal hypersensitivity in IBD patients. One is that the rectum is hypersensitive to balloon distension in patients with moderate colitis, when compared with healthy subjects or patients in remission [ , , ]. These patients present with diarrhea, urgency, feeling of incomplete evacuation, tenesmus, incontinence, and intermittent lower abdominal pain. The rectum in patients with active colitis is less compliant than in controls or in quiescent colitis.
Data from distension studies in the sigmoid colon are not available. The visceral hypersensitivity that accompanies inflammation is due to the upregulation of neurotrophin growth factor NGF in response to the enhanced production of inflammatory mediators in the colon wall [ , ].
Animal models of inflammation show consistent visceral hypersensitivity, which subsides after inflammation is over [ — ]. Rectal hypersensitivity in moderate to severe inflammation explains the frequent urge to defecate in response to the arrival of smaller volumes of feces in the rectum.
The descending inhibition of the internal anal sphincter in response to rectal distension remains intact in colitis patients [ ], suggesting that the internal anal sphincter does not obstruct the mass propulsion by a propagating GMC preceding defecation. The perception of pain in these patients is therefore entirely due to strong compression of the colon wall and sensitization of the afferent splanchnic neurons.
Colitis patients in remission are relatively free of symptoms because the events precipitating them—excessive frequency of GMCs—are absent. This may happen regardless of whether the afferent sensitization normalizes during remission. Strong compression of the sigmoid colon along with visceral hypersensitivity causes the sensation of intermittent short-lived pain in IBD patients.
Increased expression of NGF in the colon wall mediates visceral hypersensitivity in animal models of colonic inflammation. A great deal of our understanding of the cellular mechanisms of motility dysfunction in colonic inflammation has come from animal models of inflammation [ ].
The animal models of IBD fairly well replicate the acute inflammatory component of human disease; however, they lack the remission and relapse features. While the animal models have these limitations, they have the advantage of having more or less similar lesions within the study group, and they are free of disease modification by medications. In many cases, the animals serve as their own controls. ACh acts directly on muscarinic M 3 receptors on smooth muscle cells to stimulate contractions.
Therefore, the suppression of contractility in inflammation is due, in part, to a defect in the excitation-contraction coupling in smooth muscle cells. Studies in human tissue from ulcerative colitis patients [ ] show little change in the characteristics of slow waves. The nitrergic nerves also seem to function normally in tissue from ulcerative colitis patients, which concurs with normal relaxation of the anal sphincter in response to rectal distension [ ].
A major abnormality contributing to the suppression of contractility by inflammation seems to be in the excitation-contraction coupling in smooth muscle cells. However, this concept is not consistent with the fact that inflammation in both types of IBD similarly suppresses circular muscle contractility [ , — ].
There is no known mechanism by which inflammation confined to the mucosa impairs smooth muscle function, since smooth muscle impairment in inflammation requires local release of inflammatory mediators in the muscularis externa.
Recent studies in animal models of the two forms of IBD and accumulating clinical findings [ , ] suggest that inflammation is transmural in both forms of IBD. The ulcerative colitis—like inflammation is primarily due to transmural generation of oxidative stress. Peptide inflammatory mediators play a minor role in ulcerative colitis—like inflammation.
Both types of inflammation begin with a breakdown of the mucosal barrier, exposing the sterile interior of the colon wall to a pathogenic luminal environment. The breakdown of the mucosal barrier by TNBS results in the translocation of luminal bacteria across the colon wall within 24 hours [ ]. TNBS impairs the epithelial barrier function by necrosis. By contrast, Toll-like receptor 4 TLR4 signaling, which limits bacterial translocation, mediates DSS inflammatory response [ , ].
DSS arrests the epithelial cell cycle, resulting in apoptosis, impaired proliferation, and weak release of peptide inflammatory mediators [ — ]. Consequently, bacterial translocation is marginal and confined to the mucosa, indicating its lesser role in DSS inflammation than in TNBS inflammation.
It is noteworthy that TNBS inflammation in the absence of intestinal flora is also primarily mucosal [ ]. The differences in the nature of the damage to the epithelium e. Together with smooth muscle cells, the enteric neurons play an essential role in regulating motility function. They are in the same hostile inflammatory environment as the smooth muscle cells, but their precise role in impaired motility dysfunction in colonic inflammation remains ambiguous.
This is largely due to the lack of availability of neuronal cultures until recently [ ], the multiple types of neurons containing more than one neurotransmitter, and our limited ability to correlate neuronal abnormality with motor dysfunction. Immunohistochemical studies on inflamed and normal tissues have yielded mixed results [ — ].
Morphological data show that inflammation does not alter the density of neurons innervating circular smooth muscle cells [ ].
However, it may impair the packaging, storage, and release of neurotransmitters from the nerve endings of motor and sympathetic neurons [ — ]. Electrophysiological studies show that inflammation in guinea pig colon enhances the excitability of AH neurons and facilitates synaptic transmission in S neurons [ , ]. However, we do not know yet how these changes relate to the suppression of neurotransmitter release, suppression of RPCs, and the stimulation of GMCs during inflammation.
However, recent publications have discounted any role of ICC in regulating motility function [ 79 , , ]. In spite of the changes found in the number of ICCs or damage to their processes, the slow waves and nitrergic inhibition seem to be normal in inflammation, as discussed above. Clinically, these patients are divided into three categories: asymptomatic diverticular disease, symptomatic uncomplicated diverticular disease, and symptomatic complicated diverticular disease.
Some complications of diverticular disease—perforation, fistula, or bowel obstruction—relate to the severity and duration of colitis. The following discussion focuses primarily on asymptomatic and symptomatic diverticular disease patients. The symptoms of diverticular disease include recurrent abdominal pain in the lower left quadrant and altered bowel habits: diarrhea, constipation, or alternating diarrhea loose stools and constipation hard stools.
Additional secondary symptoms are bloating, straining, urgency, incontinence, and mucus and blood in stools [ , — ]. These symptoms generally develop in patients over the age of 50 years. Low fiber in the diet is a likely contributor to its higher prevalence in Western counties. However, there is no hard evidence for it. The diverticula form primarily in the sigmoid colon. The severity of the symptoms relates to the degree of diverticulitis [ ].
However, the etiologies of the two conditions may differ to some degree. In IBS-D, inflammation plays little role in the induction of these symptoms. We do not fully understand the events leading up to inflammation in IBD patients. However, in IBD, inflammation evenly covers the affected segment. Prednisone treatment is a major therapy in IBD patients. In diverticulitis, the inflammation starts by the translocation of pathogenic fecal material into the diverticula, causing abscess formation.
Therefore, in diverticular disease, inflammation occurs in pockets centered on diverticula, and it may be unevenly distributed through the muscle layer. The circular muscle layer in diverticulitis shows hypertrophy and hyperplasia [ , , ]. Manometric recordings show a higher incidence of GMCs in the sigmoid colon and distal to it in symptomatic diverticular disease patients than in asymptomatic patients or healthy controls.
Overall motor activity, quantified as total duration of contractions, is also higher in symptomatic complicated or uncomplicated diverticular disease patients than in asymptomatic patients or in normal healthy subjects [ , , ]. Pioneering studies in diverticular disease patients proposed that the diverticula form by high outward pressures generated in the lumen [ , ]. These studies did not identify the source of the pressure. Our current understanding of risk factors for the formation of diverticula are:.
Note that the formation of diverticula by itself does not generate the symptoms of pain and altered bowel habits. The symptoms of intermittent abdominal cramping and altered bowel habits result primarily from the increase in the frequency of GMCs at the site of the inflamed diverticula. The GMCs that propagate to the rectum induce urgency and frequent defecation. As noted earlier [ , , ], frequent GMCs rupture the mucosal barrier in the inflamed colon segment to cause bleeding and exudation of mucus, both expelled with the stool.
The stool is loose because frequent mass movements by GMCs reduce its contact time with the mucosa in the sigmoid colon. Diverticulitis patients show the same phenomena as IBD patients, sometimes passing loose stools, sometimes hard stools. Manometric data during the two conditions are not available. The frequency of GMCs likely fluctuates above and below normal levels to produce alternating diarrhea and constipation.
The amplitude of GMCs in diverticulitis— to mmHg [ ]—is about the same as that in normal subjects: mmHg [ 28 , , ]. Therefore, pain in these patients is likely due to inflammation-induced visceral hypersensitivity to colorectal distension by a balloon or its compression by a GMC see Figure 37C. The sigmoid colon bearing the diverticula and the rectum are hypersensitivity to luminal distension without a change in their compliance [ ].
Diverticular disease patients tend to have raised scores on the Hospital Anxiety and Depression scale [ ]. No data are available on changes in the expressions of these growth factors in symptomatic diverticular disease patients. One may speculate, however, that similar changes might induce thickening of muscle layers in diverticular disease patients [ , ].
Immunofluorescence findings show that inflammation in diverticular disease alters the expressions of several endogenous peptides, including substance P SP , galanin, neuropeptides K NPK , pituitary adenylate cyclase—activating peptide PACAP , and vasoactive intestinal polypeptide VIP.
However, the cause-and-effect relationship between these changes and the symptoms of diverticular disease are unknown. The influx of calcium, essential for smooth muscle contraction, occurs through these channels. Therefore, an increase in the expression of these channels enhances calcium influx, the amplitude of contractions, and colonic transit [ , ].
The twofold increase of VIP in the circular muscle layer of the colon of symptomatic diverticular disease patients might be a contributing factor in the increased frequency of GMCs in diverticulitis. Turn recording back on. National Center for Biotechnology Information , U.
Show details Sarna SK. Search term. Colonic Motility Dysfunction. The CNS circuitry, which processes this signal and sends the information to the higher centers for perception of pain.
The amplitudes of GMCs increase due to neuromuscular dysfunction so that the afferent signal generated by them exceeds the nociceptive threshold Figure 37B. This scenario is similar to that in which balloon distension in the rectum or sigmoid colon exceeds the nociceptive threshold. The development of hypersensitivity in afferent neurons or impairment of CNS processing effectively lowers the nociceptive threshold Figure 37C so that GMCs of normal amplitude exceed it and induce painful sensation.
Due to impairment of descending inhibition, the descending segment generates tone and sends afferent signals to the CNS. The combined afferent signals, due to strong compression by GMC and distension of the receiving segment, exceed the nociceptive threshold to induce the sensation of pain in the CNS Figure 37D.
This scenario develops particularly when the sphincters, such as the anal sphincters, fail to relax. In this case, a GMC attempts to push feces against a closed sphincter, but due to the closure, the intervening segment balloons up.
Note that, in normal subjects, the release of NO by descending inhibition prevents the generation of tone in the receiving segment, preventing it from generating the afferent signals [ 23 ].
Take-home Messages GMCs are the essential peripheral stimuli that generate the sensation of pain of gut origin. Each GMC from its beginning to its termination lasts for a short period of a few minutes. This explains the sensation of short-lived intermittent abdominal cramping. GMCs can start anywhere in the colon and propagate to various distances. This suggests that the pain may localize in any quadrant of the abdomen or migrate among different quadrants.
Abdominal cramping may occur in the absence of visceral hypersensitivity or impaired CNS processing due to enhancement of GMC amplitudes or impairment of descending inhibition. Visceral hypersensitivity by itself does not cause pain. There has to be a stimulus, such as a GMC, that generates an afferent signal for perception of pain. Diarrhea-Predominant IBS In addition to intermittent abdominal cramping, IBS-D patients have one or more of the following symptoms: 1 more than three bowel movements per day, 2 loose mushy or watery stools, and 3 urgency of defecation.
These increases relate to the severity of symptoms of abdominal cramping and bowel movements per day. Concurrent visceral hypersensitivity exaggerates this sensation. The relief of abdominal cramping may relate to reduction in the incidence of GMCs following defecation. However, if a GMC occurs in the absence of feces in the sigmoid colon, it might initiate an urge to defecate, giving the sensation of incomplete evacuation. Constipation-Predominant IBS, Slow-Transit Constipation, Idiopathic Constipation, and Constipation Due to Pelvic Floor Dysfunction According to the Rome II criteria, IBS-C patients present with one or more of the following symptoms: 1 fewer than three bowel movements per week, 2 hard or lumpy stools, 3 straining during bowel movements, and 4 intermittent short-lived abdominal cramping.
FIGURE 39 GMCs are notably absent, fewer in number, or do not propagate up to the rectum prior to and at the time of defecation in patients with obstructed pelvic floor dysfunction defecation. FIGURE 41 Twenty-four-hour mapping of total colonic motor activity area under contractions in slow-transit constipation patients.
Take-home Messages The amplitude and frequency of GMCs decrease significantly in constipated patients. The suppression of GMCs in the sigmoid colon will impair pelvic floor function, adding to the severity of constipation. There is no consistent change in the parameters of propagating or nonpropagating RPCs in any type of constipation. Diagnosis of motility disturbances in IBS-D, IBS-C, slow-transit constipation, idiopathic constipation, and obstructed defecation could be made simply by analyzing the frequency of GMCs over 24 hours, their amplitude, duration, distance of propagation, and point of origin in the whole colon.
These analyses do not require a computer program. Ambulatory recordings with solid-state transducers would provide more physiological data. GMCs are a reliable biomarker of both primary symptoms of IBS: altered bowel habits and abdominal cramping. The Rome criteria to subdivide IBS patients into different groups are subjective and symptom based.
They have not received universal acceptance after three revisions. A mechanism- based criterion, using hour recordings of GMCs, might be more objective.
The inclusion of objective criteria would spur mechanistic studies followed by development of therapeutic agents to normalize dysfunctional proteins. These observations speak against a genetic mutation, polymorphism role in motility and sensory dysfunctions in IBS. The genetic dysfunctions are stable. Epigenetic changes in gene expression are sensitive to the cellular microenvironment.
Cellular and Molecular Mechanisms of IBS and Other Types of Constipation Our understanding of the cellular mechanisms of motility dysfunction in functional bowel disorders FBD is limited, largely due to the unavailability of neuromuscular tissues from these patients and the paucity of animal models that mimic salient features of these disorders.
A significant increase in GMC frequency causes diarrhea, while a significant decrease causes constipation. Chronic stress releases CRH and angiotensin vasopressin from the paraventricular nucleus in the hypothalamus. In parallel, CRH releases adrenocorticotropic hormone from the pituitary, which releases corticosterone from the adrenal cortex. Activation of the greater splanchnic sympathetic preganglionic neurons releases norepinephrine from the chromaffin cells in the adrenal medulla into the blood stream [ , ].
The increase in plasma norepinephrine persists for several hours [ ]. Take-home Messages Chronic, rather than acute, stress in animal models produces prolonged motor dysfunction and visceral hypersensitivity. Sustained increase in plasma norepinephrine following chronic stress makes a major contribution to the development of visceral hypersensitivity and altered motor function. Increase in the expression of NGF in the colonic muscularis externa mediates the induction of visceral hypersensitivity by norepinephrine.
Early-Life Trauma and IBS Retrospective studies show that prenatal, infant, or childhood trauma predisposes to developing the symptoms of IBS at an early age, which continue in adulthood [ — ]. Take-home Messages Neonatal psychological and inflammatory insults induce visceral hypersensitivity and motor dysfunction in adulthood. The maladaptive effects of chronic stress on gut function—altered motor function and visceral hypersensitivity to motor events in the colon—are the same as those that characterize IBS patients.
However, the mechanisms by which chronic stress exaggerates these effects in IBS patients may be different from those that underlie abnormal functions without stress. Impaired Enteric Reflexes Balloon distension in in vitro experiments in the intact human colon stimulates contractions above and relaxation below it [ 47 ]. Impaired Smooth Muscle Excitation-Contraction Coupling in Slow-Transit Constipation The prevalence and severity of slow-transit constipation are higher in females than in males [ , ].
FIGURE 45 The shortening of single isolated smooth muscle cells obtained from normal controls and from patients with chronic constipation. Take-home Message Upregulation of progesterone B receptors in smooth muscle cells in the human colon explain the higher incidence of slow-transit constipation in female patients.
Role of ICCs Some reports found a deficiency in the volume of ICC throughout the colon of patients with slow-transit constipation [ 99 , — ]. Take-home Messages The volume of ICC is decreased in the colon of slow-transit constipation patients. However, there is no evidence that this decrease causes motility dysfunction or visceral hypersensitivity.
Role of Alterations in the Expression of Neuropeptides in the Myenteric Plexus and Structural Damage to Enteric Neurons and Smooth Muscle Cells Several immunohistochemical, radioimmunoassay, and ultrastructural studies have identified abnormalities in enteric neurons and smooth muscle cells in tissue from IBS patients [ — ].
Epigenetic Dysregulation Over the past three decades, discoveries of gene mutations that cause or contribute to simple Mendelian diseases, such as sickle cell anemia, hemophilia, and cystic fibrosis have been reported [ — ]. Posttranslational Histone Modifications. DNA Methylation. Genetics Functional bowel disorders do not have the traits of genetic diseases. Take-home Messages Epigenetic regulation modifies the expression of selective genes in cells following changes in their microenvironment.
If the changes in microenvironment occur during the vulnerable stages of fetal and neonatal development, the changes in expressions of selective genes may persist into adulthood to cause complex diseases, such as IBS. As the stomach becomes progressively more and more empty, these constric-tions begin farther and farther up the body of the stomach, gradually pinching off the food in the body of the stomach and adding this food to the chyme in the antrum.
These intense peristaltic contractions often create 50 to 70 centimeters of water pressure, which is about six times as powerful as the usual mixing type of peristaltic waves. When pyloric tone is normal, each strong peristaltic wave forces up to several milliliters of chyme into the duodenum.
Role of the Pylorus in Controlling Stomach Emptying. Here the thickness of the circular wall muscle becomes 50 to per cent greater than in the earlier portions of the stomach antrum, and it remains slightly tonically con-tracted almost all the time. Despite normal tonic contraction of the pyloric sphincter, the pylorus usually is open enough for water and other fluids to empty from the stomach into the duodenum with ease. Conversely, the constriction usually prevents passage of food particles until they have become mixed in the chyme to almost fluid con-sistency.
The degree of constriction of the pylorus is increased or decreased under the influence of nervous and humoral reflex signals from both the stomach and the duodenum, as discussed shortly.
The rate at which the stomach empties is regulated by signals from both the stomach and the duodenum. However, the duodenum provides by far the more potent of the signals, controlling the emptying of chyme into the duodenum at a rate no greater than the rate at which the chyme can be digested and absorbed in the small intestine.
Increasedfood volume in the stomach promotes increased emp-tying from the stomach. But this increased emptying does not occur for the reasons that one would expect. It is not increased storage pressure of the food in the stomach that causes the increased emptying because, in the usual normal range of volume, the increase in volume does not increase the pressure much.
However, stretching of the stomach wall does elicit local myenteric reflexes in the wall that greatly accen-tuate activity of the pyloric pump and at the same time inhibit the pylorus. This has potent effects to cause secretion of highly acidic gastric juice by the stomach glands. Gastrin also has mild to moderate stimulatory effects on motor functions in the body of the stomach. Most important, it seems to enhance the activity of the pyloric pump.
Thus, it, too, probably promotes stomach emptying. When food enters the duodenum, multiplenervous reflexes are initiated from the duodenal wall that pass back to the stomach to slow or even stop stomach emptying if the volume of chyme in the duo-denum becomes too much. These reflexes are medi-ated by three routes: 1 directly from the duodenum to the stomach through the enteric nervous system in the gut wall, 2 through extrinsic nerves that go to the prevertebral sympathetic ganglia and then back through inhibitory sympathetic nerve fibers to the stomach, and 3 probably to a slight extent through the vagus nerves all the way to the brain stem, where they inhibit the normal excitatory signals transmitted to the stomach through the vagi.
The types of factors that are continually monitored in the duodenum and that can initiate enterogastric inhibitory reflexes include the following:. The degree of distention of the duodenum. The presence of any degree of irritation of the duodenal mucosa. The degree of acidity of the duodenal chyme. The degree of osmolality of the chyme. The presence of certain breakdown products in the chyme, especially breakdown products of proteins and perhaps to a lesser extent of fats.
The enterogastric inhibitory reflexes are especially sensitive to the presence of irritants and acids in the duodenal chyme, and they often become strongly acti-vated within as little as 30 seconds. For instance, when-ever the pH of the chyme in the duodenum falls below about 3. Breakdown products of protein digestion also elicit inhibitory enterogastric reflexes; by slowing the rate of stomach emptying, sufficient time is ensured for ade-quate protein digestion in the duodenum and small intestine.
Finally, either hypotonic or hypertonic fluids espe-cially hypertonic elicit the inhibitory reflexes. Thus, too rapid flow of nonisotonic fluids into the small intestine is prevented, thereby also preventing rapid changes in electrolyte concentrations in the whole-body extracellular fluid during absorption of the intes-tinal contents.
Notonly do nervous reflexes from the duodenum to the stomach inhibit stomach emptying, but hormones released from the upper intestine do so as well. The stimulus for releasing these inhibitory hormones is mainly fats entering the duodenum, although other types of foods can increase the hormones to a lesser degree. In turn, the hormones are carried by way of the blood to the stomach, where they inhibit the pyloric pump and at the same time increase the strength of contraction of the pyloric sphincter.
These effects are important because fats are much slower to be digested than most other foods. Precisely which hormones cause the hormonal feedback inhibition of the stomach is not fully clear.
This hormone acts as an inhibitor to block increased stomach motility caused by gastrin. Secretin is released mainly from the duodenalmucosa in response to gastric acid passed from the stomach through the pylorus.
GIP has a general but weak effect of decreasing gastrointestinal motility. GIP is released from the upper small intestine in response mainly to fat in the chyme, but to a lesser extent to carbohydrates as well. Although GIP does inhibit gastric motility under some conditions, its effect at physiologic concentrations is probably mainly to stimulate secretion of insulin by the pancreas. These hormones are discussed at greater length elsewhere in this text, in rela-tion to control of gallbladder emptying and control of rate of pancreatic secretion.
Disorders of the Stomach
Don't miss out! Create your free JWatch. David J. Am J Gastroenterol Sep Symptomatic patients may have one or more gastric motor dysfunctions and reduced respiratory sinus arrhythmia.
The pathophysiology of dyspepsia is multifactorial. To evaluate the role that motor disorders of the stomach play in dyspepsia, investigators retrospectively analyzed data from approximately dyspepsia patients who were evaluated for gastric emptying GE and gastric accommodation GA at a single tertiary referral center. Data on respiratory sinus arrhythmia RSA; a measure of vagal function were available for patients.
Multivariable analysis showed that gender, body-mass index, GE, diabetes, and prior abdominal surgery, but not GA or other comorbidities, were associated with symptoms. The investigators conclude that delayed GE and reduced RSA are associated with abnormal GA in patients with functional gastroduodenal disorders and that these patients may have one or more gastric motor dysfunctions.
Although the motility changes in the study were statistically significant, there was considerable variation within the groups. Nonetheless, the general associations noted may provide a pathophysiologic explanation for some symptoms and suggest potential therapies.
Unfortunately, the methodology for measuring GA in the study is not universally available. It is not clear if alternative measures are as effective in identifying clinical differences. Park S-Y et al. Gastric motor dysfunction in patients with functional gastroduodenal symptoms. Am J Gastroenterol Sep 12; [e-pub]. Get Your Copy. Am J Gastroenterol Sep 12 Symptomatic patients may have one or more gastric motor dysfunctions and reduced respiratory sinus arrhythmia.
Comment Although the motility changes in the study were statistically significant, there was considerable variation within the groups. Citation s : Park S-Y et al. October 10, Surgery, Neurological. Neurosurgery - Sayre, PA. Sayre, Pennsylvania.
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