One function of the stomach is to grind food into smaller particles and mix it with digestive juices so the food can be absorbed when it reaches the small intestine. The stomach normally empties its contents into the intestine at a controlled rate. Delayed gastric emptying gastroparesis The symptoms of delayed gastric emptying include nausea and vomiting. Poor emptying of the stomach can occur for several reasons:. Read More about Gastropareis.
Twitter Facebook YouTube. A sensitivity analysis with logistic regression models. Categories : Stomach disorders. Tack, J. About Motod article Publication history Published 06 April The [13C]acetate dysfunchions test accurately reflects gastric emptying of liquids in both liquid and Motor dysfunctions of the stomach test meals. Article Google Scholar However, as the WMC is a large, non-digestible, solid object, it does not empty with the meal but rather is most often cleared from the stomach by powerful interdigestive migrating motor complex MMC phase III Fig.
Sexual attraction to unconcious women. MOTOR DISORDERS OF THE STOMACH
Brauty pageants in georgia presence of certain breakdown products in the chyme, especially breakdown products of proteins and perhaps to a lesser extent of fats. However, rapid propulsion by increase in the frequency of GMCs deprives the fecal material of adequate exposure to mucosa, resulting in loose stools. The motility dysfunction in adult rats who received neonatal inflammatory insult occurs in the absence of any inflammation or structural damage. The contractile response to ACh in circular muscle strips from idiopathic chronic constipation patients is significantly less than that in normal strips from patients with normal colon transit [ ]. Therefore, an increase in the frequency of GMCs could be one of the factors inducing visceral hypersensitivity. The balance between the actions of these enzymes is a key regulatory mechanism for gene expression and governs numerous developmental processes and disease states [ ]. Hard straining may not be enough to Orgasm tremor feces against the closed internal and external anal sphincters. The Motor dysfunctions of the stomach nerves mediate the gastrocolonic response to ingestion of a meal. Our current understanding of risk factors for the formation of diverticula are:. The slow-wave frequency and its spatial organization are not different between IBS patients and healthy controls under resting conditions and after stimulation with a meal or neostigmine [ ]. The increase in colonic tone by either stimulus is impaired in patients with slow-transit constipation [ ].
The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive function so that digestion is normally not perceived.
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One function of the stomach is to grind food into smaller particles and mix it with digestive juices so the food can be absorbed when it reaches the small intestine. The stomach normally empties its contents into the intestine at a controlled rate. Delayed gastric emptying gastroparesis The symptoms of delayed gastric emptying include nausea and vomiting. Poor emptying of the stomach can occur for several reasons:. Read More about Gastropareis.
Cyclic vomiting syndrome CVS Cyclic vomiting syndrome CVS is a disorder with recurrent episodes of severe nausea and vomiting interspersed with symptom free periods. CVS occurs in all ages. Patients may struggle for many years before a correct diagnosis is made.
Read More about CVS. Rapid gastric emptying dumping syndrome Rapid gastric emptying, or dumping syndrome, happens when the upper end of the small intestine jejunum fills too quickly with undigested food from the stomach. Many people have both type. Read More about Dumping Syndrome. Functional dyspepsia Many patients have pain or discomfort that is felt in the center of the abdomen above the belly button. Some examples of discomfort that is not nonpainful are:.
There is no single motility disorder that explains all these symptoms, but about a third of patients with these symptoms have delayed gastric emptying usually not so severe that it causes frequent vomiting , and about a third show a failure of the relaxation of the upper stomach following a swallow abnormal gastric accommodation reflex. About half of the patients with these symptoms also have a sensitive or irritable stomach, which causes sensations of discomfort when the stomach is filled with even small volumes.
Read More about Functional Dyspepsia. We provide a wide range of topics and tools dedicated to providing information about chronic disorders of the digestive tract and how improve living with these conditions. Publication Library. Books of Interest. Medical Definitions. This information is in no way intended to replace the guidance of your doctor.
International Foundation for Gastrointestinal Disorders, Inc. All Rights Reserved. Twitter Facebook YouTube. Search Search Join eNewsletter. The stomach has three types of contractions: There are rhythmic, 3 per minute, synchronized contractions in the lower part of the stomach, which create waves of food particles and juice which splash against a closed sphincter muscle the pyloric sphincter to grind the food into small particles.
The upper part of the stomach shows slow relaxations lasting a minute or more that follow each swallow and that allow the food to enter the stomach; at other times the upper part of the stomach shows slow contractions which help to empty the stomach.
Between meals, after all the digestible food has left the stomach, there are occasional bursts of very strong, synchronized contractions that are accompanied by opening of the pyloric sphincter muscle. These are sometimes called "housekeeper waves" because their function is to sweep any indigestible particles out of the stomach. Another name for them is the migrating motor complex. Examples of stomach gastric motility disorders include: Delayed gastric emptying gastroparesis Rapid gastric emptying dumping syndrome Functional dyspepsia Delayed gastric emptying gastroparesis The symptoms of delayed gastric emptying include nausea and vomiting.
Poor emptying of the stomach can occur for several reasons: The outlet of the stomach the pylorus and duodenum may be obstructed by an ulcer or tumor, or by something large and indigestible that was swallowed. The pyloric sphincter at the exit of the stomach may not open enough or at the right times to allow food to pass through. This sphincter is controlled by neurological reflexes to ensure that only very tiny particles leave the stomach and also to insure that not too much acid or sugar leaves the stomach at one time, which could irritate or injure the small intestine.
These reflexes depend on nerves that sometimes become damaged. The normally rhythmic, 3 per minute contractions of the lower part of the stomach can become disorganized so that the contents of the stomach are not pushed towards the pyloric sphincter.
This also usually has a neurological basis; the most common known cause is longstanding diabetes mellitus, but in many patients the cause of delayed gastric emptying is unknown, so the diagnosis given is idiopathic meaning cause unknown gastroparesis. Read More about Gastropareis Cyclic vomiting syndrome CVS Cyclic vomiting syndrome CVS is a disorder with recurrent episodes of severe nausea and vomiting interspersed with symptom free periods.
Read More about CVS Rapid gastric emptying dumping syndrome Rapid gastric emptying, or dumping syndrome, happens when the upper end of the small intestine jejunum fills too quickly with undigested food from the stomach.
Read More about Dumping Syndrome Functional dyspepsia Many patients have pain or discomfort that is felt in the center of the abdomen above the belly button. Some examples of discomfort that is not nonpainful are: Fullness Early satiety feeling full soon after starting to eat Bloating Nausea There is no single motility disorder that explains all these symptoms, but about a third of patients with these symptoms have delayed gastric emptying usually not so severe that it causes frequent vomiting , and about a third show a failure of the relaxation of the upper stomach following a swallow abnormal gastric accommodation reflex.
Resources We provide a wide range of topics and tools dedicated to providing information about chronic disorders of the digestive tract and how improve living with these conditions.
Summary of the Control of Stomach Emptying. In the absence of a driving force for expulsion of feces and descending more The internal anal sphincter relaxation depends on descending inhibitory signal generated by GMCs propagating up to it. Stomach Emptying and Regulation of Stomach Emptying. Therefore, the suppression of contractility in inflammation is due, in part, to a defect in the excitation-contraction coupling in smooth muscle cells. 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. However, we do not know the cause-and-effect relationship between individual mediators of stress and transient sensitization of visceral afferents.
Motor dysfunctions of the stomach. GMCs and Visceral Pain of Gut Origin
Additional abnormalities in enteric neuromuscular function or in autonomic nerves regulating the puborectalis and external anal sphincter may worsen constipation in these patients. We do not know whether abnormalities in GMCs and impairments in pelvic floor regulation occur independently or whether one leads to the other.
Rectal motor complexes are absent in some constipated patients, indicating enteric neuromuscular dysfunction Figure The rectal motor complexes were nearly absent in a patient with constipation.
Reproduced with permission from Waldron, DJ, Gut , —, . The total incidence of RPCs measured as area under contractions in constipation is variable; it depends on the severity of constipation.
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 [ ]. Note that these data, obtained by a wireless capsule, have less fidelity than those obtained by manometric tube.
Another study, using the manometric method of recording, found that the area under contractions in slow-transit constipation is less than that in healthy subjects throughout the day Figure It is worth noting that, in the absence of GMCs or a reduction in their frequency, colonic propulsion occurs primarily by propagating RPCs. Therefore, having more RPCs does not necessarily mean that propulsion will be faster.
Propulsion is faster only if the incidence of propagating RPCs increases. These data are not available. However, as noted earlier, the contribution of RPCs to colonic propulsion is relatively minor. They may influence the consistency of stools by regulating the intensity of turning over of luminal contents. Twenty-four-hour mapping of total colonic motor activity area under contractions in slow-transit constipation patients.
The total colonic motor activity is suppressed in constipated patients throughout the day. Note that the increases in motor activity more We do not know the precise motor patterns during the two opposite conditions of motility function. Two major risk factors predispose individuals to developing postinfectious IBS symptoms following an enteric infection: 1 enteritis lasting more than 3 weeks significantly increases the risk for developing IBS-PI over a duration lasting less than 1 week and 2 the presence of comorbid psychiatric disorders or a lifetime history of anxiety and depression at the time of infection increases the risk of developing IBS-PI.
The longer duration of enteritis reflects severity of inflammation [ ]. While motility recordings from these patients are not available, their motility dysfunction is likely similar to that in IBS-D patients. 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.
However, clues from clinical and animal studies suggest potential cellular mechanisms. The following sections highlight the insights obtained from these studies and from recently available models of IBS-D. Clinical studies show that the increase of motor activity— including the incidence of GMCs—in the sigmoid colon following ingestion of a meal is significantly greater in IBS-D patients than in healthy controls [ 22 ].
The greater increase of GMCs after a meal in IBS-D patients associates with faster postprandial transit than in healthy subjects [ ]. By contrast, the increase of postprandial colonic motor activity is significantly less in constipated patients than in healthy controls [ , , — ].
Antral distension by a balloon and duodenal instillation of lipids mimic the gastrocolonic response by increasing tone in the distal colon [ ]. The increase in colonic tone by either stimulus is impaired in patients with slow-transit constipation [ ]. The parasympathetic nerves mediate the gastrocolonic response to ingestion of a meal. The parasympathetic nerves synapse on nicotinic receptors on the excitatory and inhibitory motor neurons.
Accumulating evidence shows that the physiologic stimulation of parasympathetic nerves by ingestion of a meal [ 22 ] or experimental electrical stimulation enhances colonic motor activity by release of ACh from excitatory cholinergic motor neurons in the myenteric plexus [ 42 , 44 , , ].
Although the postprandial increase of plasma CCK after ingestion of a normal meal in healthy subjects is not enough to stimulate colonic motor activity [ ], duodenal instillation of lipids and pharmacologic doses of CCK stimulate colonic motor activity [ 22 , ].
CCK acts on presynaptic interneurons or directly on motor neurons to release ACh and stimulate colonic contractions, while atropine blocks the contractile response to CCK in human colonic circular muscle strips [ 22 ]. Findings in patients with constipation are just the opposite of those in IBS-D patients. The contractile response to ACh in circular muscle strips from idiopathic chronic constipation patients is significantly less than that in normal strips from patients with normal colon transit [ ].
Interestingly, the muscle strips from constipated patients also show smaller contractile responses to electrical field stimulation EFS. EFS induces in vitro contractions by releasing ACh from the cholinergic motor neurons. These findings suggest that the impaired colonic motor function in constipated patients is due to a reduction in the expression of ChAT, synthesis or release of ACh, or a defect in excitation-contraction coupling in circular smooth muscle cells.
A decrease in the evoked release of 3H choline confirms the defect in the activity of cholinergic neurons in constipated patients [ ]. An impairment in excitation-contraction coupling in smooth muscle cells follows from the finding that the contractile response to edrophonium chloride—a short acting choline esterase inhibitor—is significantly lower in slow-transit constipation patients than in healthy controls [ ]. ACh accumulation at the neuromuscular junction acts directly on muscarinic M 3 receptors to stimulate smooth muscle contractions.
Smooth muscle dysfunction in idiopathic chronic constipation patients is evident from the inability of cathodal current to generate spikes, which suggests impairment of Ca v 1. Constipated patients also display subclinical autonomic and sensory neuropathy [ , ]. These observations may explain the hyposensitivity to colorectal distension in some constipated patients.
The perception of pain occurs in the higher centers of the brain when they receive signals from a noxious stimulus from the periphery. Noxious signals reach the higher centers due to an unphysiological condition in the periphery, such as inflammation, amplification of a physiological signal during its transmission to the CNS visceral hypersensitivity , or impaired supraspinal processing. IBS patients do not have any organic abnormality such as inflammation. Consequently, visceral hypersensitivity and supraspinal processing have received much attention in understanding the etiology of abdominal cramping in IBS patients.
These investigators have proposed visceral hypersensitivity as a biomarker of IBS. However, they could not relate most symptoms of IBS to visceral hypersensitivity. They also suggested, without any scientific evidence, that visceral hypersensitivity is the source of motility dysfunction in IBS patients. The concept was that the amplified afferent signals reflexively send aberrant efferent signals to the colon to cause motility dysfunction [ — ]. In proposing these hypotheses, the investigators ignored an important fact: visceral hypersensitivity or impaired central processing does not by itself induce the sensation of pain; a peripheral signal is required.
The visceral hypersensitivity hypothesis does not explain abdominal cramping in normosensitive patients [ , ]. In fact, none of the symptoms of IBS adequately distinguish hypersensitive from normosensitive patients [ ]. This hypothesis also does not explain which reflexes alter motility function in response to visceral hypersensitivity, which alterations in colonic contractions they produce, or how the same reflexes cause diarrhea in some patients and constipation in others.
This hypothesis ignores the wealth of knowledge we have about the regulation of contractions by smooth muscle cells and enteric neurons, the types of contractions they generate, and the specific functions of those contractions. Several publications have challenged this simplistic hypothesis of visceral hypersensitivity alone as the basis of IBS symptoms [ , ].
It is noteworthy that the symptom of abdominal cramping usually follows alterations in bowel habits. In addition, repetitive high-pressure mechanical sigmoid stimulation develops hyperalgesia in normosensitive IBS patients [ — ]. GMCs that strongly compress the colon wall send afferent signals similar to those of distension of the wall by a balloon. Therefore, an increase in the frequency of GMCs could be one of the factors inducing visceral hypersensitivity.
A unifying hypothesis, based on accumulated basic science and clinical data, is that GMCs are the source of abdominal cramping. Visceral hypersensitivity, if present, worsens the sensation of abdominal cramping.
Figure 37 explains the sensation of abdominal cramping with and without visceral hypersensitivity. First, the afferent signals generated by a GMC in health are below the nociceptive threshold Figure 37A , so they do not cause the sensation of abdominal cramping. The afferent signals they generate are noxious Figure 37B.
Each GMC may induce the sensation of abdominal cramping; however, concurrent visceral hypersensitivity will exaggerate the pain [ , ]. Figure 37C shows a scenario in which abdominal cramping is entirely due to visceral hypersensitivity. In this case, a GMC of normal or below-normal amplitude will induce the sensation of cramping. The intensity of pain will relate to the degree of hypersensitivity. There is no evidence that the nociceptive threshold decreases to levels where the afferent signals generated by RPCs become noxious.
Were this to happen, patients would feel a continuous sensation of pain, because RPCs are always present somewhere in the colon. Therefore, abdominal cramping occurs intermittently and only for the duration of a GMC. Figure 37D illustrates another scenario in which abdominal cramping may occur with or without visceral hypersensitivity. Impairment of descending inhibition prevents relaxation of the receiving segment ahead of it. Receptive relaxation decreases in some IBS patients [ ].
In this situation, the afferent signals due to ballooning of the receiving segment will add to those of the GMCs to become a noxious signal. This is likely to happen when impairment of descending inhibition prevents relaxation of the internal anal sphincter as the GMC is attempting to push feces through for defecation or when voluntary relaxation of the puborectalis muscle and the external sphincter are impaired. Another potential scenario is when a GMC attempts to push fecal material past compacted stool in constipated patients Figure GMCs in the ascending colon of a severely constipated patient.
Each GMC induced a discrete sensation of pain. The recording ports were 12 cm apart. According to the authors, a kink in the manometric tube located distal to the bottom port stimulated these more Stress is an adaptive physiological response of living systems to real or perceived life-threatening situations. This response begins in the CNS. The release of corticotrophin-releasing hormone CRH from the paraventricular nucleus of the hypothalamus is an early and essential step in the stress response [ ].
The central release of CRH and other mediators, such as arginine vasopressin AVP , stimulate the neuroendocrine system comprised of autonomic neurons and the HPA axis, which modulate the adaptive and maladaptive responses of peripheral organs in a stress- and cell-type-specific manner. Nontranscriptional mechanisms largely mediate the immediate and short-term effects of acute stress. For example, acute stress releases norepinephrine in the amygdala and hypothalamus to sharpen focus and attention [ ].
The HPA axis and the sympathetic nervous system show subtle alterations in IBS patients in the resting state and after stressors [ — ]. Acute psychological as well as physical stress modestly stimulate colonic motor activity. Animal studies show that hypothalamic release of CRH and vagal nerves mediate the stimulation of colonic motor function by acute stress [ — ]. Acute stress modestly reduces the thresholds to colorectal distension in IBS patients relative to normal subjects, presumably due to baseline alterations in the HPA axis and the autonomic nervous system [ , , ].
However, we do not know the cause-and-effect relationship between individual mediators of stress and transient sensitization of visceral afferents.
The effects of acute stress are transient, lasting more or less for the duration of the stressor. This is not surprising, because stress targets some of the same physiological functions already impaired in IBS patients, i. The mechanisms by which chronic stress relapses or exaggerates the symptoms of IBS are not investigable in patients due to ethical considerations and lack of availability of neuromuscular tissues.
Animal studies show that heterotypic or homotypic intermittent chronic stress HeICS and HoICS, respectively induces visceral hypersensitivity in rats that persists after the stress is over by the following mechanisms [ , ] Figure Cartoon showing the mechanisms of HeICS-induced visceral hypersensitivity to colorectal distension CRD in relation to the well-established elements of the stress response.
Step 1: Stress releases CRH and angiotensin vasopressin from the paraventricular more The systemic upregulation of norepinephrine by HeICS also enhances the reactivity of colonic circular smooth muscle cells to ACh in muscle strips as well as in single isolated cells, resulting in an increase in colonic transit and pellet defecation, producing diarrhealike conditions in rats [ ] Figure Adrenalectomy, but not the depletion of sympathetic neurons by guanethidine, blocks these effects.
Corticosterone, CRH, or vagal nerves do not mediate these effects. Effects of HeICS on colonic smooth muscle contractility and motor function. A The contractile response to ACh in colonic circular muscle strips increased significantly at 4 hours and 8 hours after 9-day heterotypic intermittent chronic stress protocol more These effects peak at about 8 hours after the last stressor and return to baseline by 24 hours [ ].
These findings show that prolonged upregulation of plasma norepinephrine by chronic stress remodels the cellular regulatory mechanisms, resulting in organ dysfunction. Similar remodeling occurs in CNS neurons and cardiac muscle cells [ — ]. Acute chronic stress does not induce these effects. By contrast, HoICS induces hyperalgesia in rats that lasts up to 40 days [ ].
The prolonged effects of chronic stress in animal models is consistent with clinical observations that the symptoms of IBS improve with the resolution of major life stressors. Retrospective studies show that prenatal, infant, or childhood trauma predisposes to developing the symptoms of IBS at an early age, which continue in adulthood [ — ]. Mechanical or chemical irritation in neonates results in persistent sensitization of the spinal afferents and visceral hypersensitivity to colorectal distension in adulthood [ ].
Maternal separation of neonatal rats induces allodynia and hyperalgesia in adulthood by enhancing expression of NGF in the colon wall [ , ]. In this model, the proliferation and degranulation of mast cells increase the expression of NGF, which mediates hypersensitivity to colorectal distension.
The maternally separated rats also show heightened response to acute water avoidance stress. A randomized double-blind placebo-controlled study found little improvement in symptoms of IBS- PI patients by prednisone treatment [ ]. Regardless, we do not know yet the epigenetic mechanisms, described later, that underlie colonic motor dysfunction and visceral hypersensitivity in response to adverse early life experiences. The enhanced expression of each of these cell-signaling proteins favors increased reactivity to ACh see Figure As a result, the contractile responses of single smooth muscle cells and of circular smooth muscle strips from affected rats are greater than those from control rats.
The faster colonic transit and greater pellet output in these rats simulate the diarrhealike conditions of IBS-D patients. The neonatal insult in these rats also enhances the VIP content of muscularis externa and plasma concentrations of norepinephrine. The motility dysfunction in adult rats who received neonatal inflammatory insult occurs in the absence of any inflammation or structural damage.
Of note, a similar inflammatory insult in adult rats does not result in enhancement of smooth muscle reactivity to ACh or faster colonic transit [ ]. Note that there is seldom a perfect animal model of human disease. However, these models closely mimic specific features of IBS and their regulatory mechanisms.
They are indispensable in identifying the underlying mechanisms of organ dysfunction, allowing for testing of hypotheses in humans and development of therapeutic agents. Balloon distension in in vitro experiments in the intact human colon stimulates contractions above and relaxation below it [ 47 ].
However, the descending relaxation—mediated by NO—is not different between slow-transit constipation patients and healthy controls, suggesting a normal function of inhibitory motor neurons. In vitro findings in muscle strips from patients with idiopathic chronic constipation support the notion that their nitrergic neurons are functioning near normal [ ]. The normality of inhibitory neuronal function, however, may not be universal in constipation.
One study found enhanced NO-induced and ATP-induced relaxation in a group of idiopathic chronic constipation patients [ ]. The prevalence and severity of slow-transit constipation are higher in females than in males [ , ]. Alterations in cell-signaling proteins of excitation-contraction coupling in smooth muscle cells in response to progesterone partly explain this disparity. Progesterone levels in females with slow-transit constipation are normal.
However, the contribution of these pathways in spontaneous colonic motor function is unknown. The shortening of single isolated smooth muscle cells obtained from normal controls and from patients with chronic constipation.
Upregulation of progesterone B receptors in smooth muscle cells in the human colon explain the higher incidence of slow-transit constipation in female patients. Some reports found a deficiency in the volume of ICC throughout the colon of patients with slow-transit constipation [ 99 , — ].
However, these publications did not establish a cause-and-effect relationship between the reduction in the volume of ICC and patient symptoms, disorders in colonic motor activity, or its regulatory mechanisms. According to numerous clinical studies cited above, the slow transit in these patients is primarily due to the reduction in GMCs.
A recent study has demonstrated that ICC do not mediate the neuronal input to smooth muscle cells [ ]. The normal function of inhibitory nitrergic motor neurons in descending inhibition is additional evidence that reduction in the volume of ICC in constipated patients does not mediate neuronal input to smooth muscle cells [ 79 , ].
The RPCs regulated by slow waves play a relatively smaller role in slow-transit constipation. However, the slow waves do not show a defect in in vitro recordings from the colonic smooth muscle cells of slow-transit patients [ ].
The slow-wave frequency and its spatial organization are not different between IBS patients and healthy controls under resting conditions and after stimulation with a meal or neostigmine [ ]. Several immunohistochemical, radioimmunoassay, and ultrastructural studies have identified abnormalities in enteric neurons and smooth muscle cells in tissue from IBS patients [ — ]. Most of these studies are on tissues obtained from severely constipated patients undergoing colonic resection.
Disappointingly, these findings are often divergent; some show a positive change, some show a negative one, and others find no change in the same parameter, such as damage to neurons containing a certain neurotransmitter or global damage to neurons [ ]. This is partly due to the qualitative nature of analysis in these methods and the heterogeneity of tissues and observations at the microscopic level.
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 [ , ].
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.
In summary, hormones, especially CCK, can inhibit gastric emptying when excess quantities of chyme, especially acidic or fatty chyme, enter the duodenum from the stomach. Summary of the Control of Stomach Emptying. Emptying of the stomach is controlled only to a mod-erate degree by stomach factors such as the degree of filling in the stomach and the excitatory effect of gastrin on stomach peristalsis.
Probably the more important control of stomach emptying resides in inhibitory feedback signals from the duodenum, including both enterogastric inhibitory nervous feed-back reflexes and hormonal feedback by CCK. These feedback inhibitory mechanisms work together to slow the rate of emptying when 1 too much chyme is already in the small intestine or 2 the chyme is excessively acidic, contains too much unprocessed protein or fat, is hypotonic or hypertonic, or is irritat-ing.
In this way, the rate of stomach emptying is limited to that amount of chyme that the small intestine can process. Developed by Therithal info, Chennai. Toggle navigation BrainKart. Guyton, John E. The motor functions of the stomach are threefold: 1 storage of large quantities of food until the food can be processed in the stomach, duodenum, and lower intestinal tract; 2 mixing of this food with gastric secretions until it forms a semifluid mixture called chyme; and 3 slow emptying of the chyme from thestomach into the small intestine at a rate suitable for proper digestion and absorption by the small intestine.
Stomach Emptying Stomach emptying is promoted by intense peristaltic contractions in the stomach antrum. Regulation of Stomach Emptying The rate at which the stomach empties is regulated by signals from both the stomach and the duodenum. The types of factors that are continually monitored in the duodenum and that can initiate enterogastric inhibitory reflexes include the following: 1.
The degree of distention of the duodenum 2. The presence of any degree of irritation of the duodenal mucosa 3. The degree of acidity of the duodenal chyme 4. The degree of osmolality of the chyme 5.
Diabetic neuropathy in the gut: pathogenesis and diagnosis | SpringerLink
Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5—10 years have led to this update about indications for and selection and performance of currently available tests.
As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres.
This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.
Disturbances of gastric and intestinal motor functions such as gastroparesis, functional dyspepsia, enteric dysmotility, IBS and constipation affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs 1 , 2. Comprehensive consensus papers published in Ref. Advances in diagnostic techniques for the evaluation of gastrointestinal motor function necessitate an update about indications for and selection and performance of currently available tests, how motility disorders can be differentiated and classified based on these tests and how the results guide treatment decisions, as noted in this Consensus Statement.
A panel of international motility experts has re-examined these issues and provides concise information on test principles, practical performance and interpretation of individual tests Box 1. Further details on these topics will be provided in technical position statements that will be published separately.
This Consensus Statement is part of a series of papers on gastrointestinal motility initiated by the International Working Group for Disorders of Gastrointestinal Motility and Function. Authors were invited based on their experience and reputation in the field and chosen to cover the intended scope of the manuscript; they represent experts from many European countries, North America, Australia and China.
Experts on gastric, small bowel and colonic motility disorders first developed statements regarding evaluation of transit and contractility of the respective segments of the gastrointestinal tract, which were based on already available consensus statements 3 , 4. Consensus statements from other gastrointestinal societies or expert groups were searched for and included when appropriate, for example, if they were published more recently or if they covered relevant areas not specifically addressed in the previous documents 3 , 4.
Moreover, an updated literature search using PubMed and Medline was performed centrally by the corresponding author J.
The literature search started on the date specified as the end date of the literature searches performed for two previously published consensus papers 3 , 4 that is, 1 Jan for intraluminal measurements of gastrointestinal motility and 1 Jan for transit tests ; the search covered the period until 14 Apr and was generally limited to human studies. Low-quality studies were also considered if the topic was deemed relevant and not covered otherwise.
Statements were distributed via e-mail, and each author had to confirm full agreement, minor concerns or disagreement in writing. Concerns or disagreement had to be explained. All statements with at least one author in disagreement or more than three authors with minor concerns were modified after discussion in conference calls and in a face-to-face meeting at United European Gastroenterology Week in Vienna, Austria, in October It was required that no more than one author disagree with the final Consensus Statement for it to be included in the final version of the manuscript.
They are marked as bold bulleted points throughout the manuscript. All authors consented to the final version of the manuscript, including comments. Symptoms of gastrointestinal motor disorders are nonspecific: dysmotility cannot be differentiated from inflammatory or malignant disease on the basis of patient history alone.
For example, epigastric pain, early satiety and abdominal fullness are typical symptoms of gastroparesis but can also be due to gastroduodenal ulcers or gastric cancer. Moreover, inflammatory diseases of the small and large bowel are associated with delayed gastric emptying, which can be reversible after treatment of inflammation 5 , 6.
Thus, it is important to first exclude other aetiologies, in particular, mucosal and obstructive lesions, by appropriate investigations such as upper and lower gastrointestinal endoscopy, imaging techniques and laboratory investigation.
Such tests are mandatory in patients with 'red flags' that is, weight loss, low haemoglobin levels and substantial episodes of vomiting but should also be performed if the motility tests are invasive or symptoms are severe. In patients with moderate complaints and no alarm symptoms, noninvasive motility testing might be considered. The selection of tests will also be influenced by availability and the costs of diagnostic procedures in different health-care systems.
In general, motility investigations are usually limited to patients with relevant complaints that can be related to dysmotility and that markedly affect quality of life, nutrition, social function or work productivity and, rarely, to increased mortality 7 , 8.
As with any diagnostic procedure, they are justified only if the results can be expected to influence clinical management. Tests of gastric motor function comprise gastric emptying tests and intraluminal measurements of contractility. Symptoms suggestive of delayed gastric emptying include early satiety, nausea, vomiting, regurgitation, bloating, postprandial fullness, visible upper abdominal distention, abdominal pain and weight loss 1 , 9.
Most patients with rapid gastric emptying present with abdominal symptoms that mimic those of gastroparesis 10 , Suspicion of gastroparesis is further supported by identifying risk factors, for example, long-standing diabetes mellitus 9. Conversely, suspicion of gastric dumping is supported by a history of upper gastrointestinal surgery Furthermore, upper gastrointestinal symptoms had a poor clinical specificity relative to the actual rate of gastric emptying on scintigraphy, underlining the need for function testing to guide treatment.
Because accelerated, normal and delayed gastric emptying cannot be differentiated reliably based on type or severity of gastrointestinal symptoms, objective measurement of clearly delayed gastric emptying gastric emptying time increased above the upper level of normal using well-validated techniques such as gastric emptying scintigraphy Fig. Standardized scintigraphic study of gastric emptying of solids with consumption of a kcal radiolabelled meal scrambled eggs labelled with 99m Tc; Mayo Clinic protocol 30 and imaging over 4 h.
In the individual with normal gastric emptying GE left panel , large amounts of the meal are emptied from the stomach at 2 h, and GE is completed at 4 h. The merit of gastric emptying studies for clinical management has been questioned because of variations in the reports of association between gastric emptying rates and symptoms.
Several studies published during the past 7 years have shown a positive association between symptoms of gastroparesis and gastric emptying times 14 , 15 , 16 , 17 , 18 , Measurement of gastric emptying can also predict responsiveness to different therapeutic options 20 , For example, the presence of slow gastric emptying in patients with functional dyspepsia was associated with poor response to antidepressant medications that target visceral hypersensitivity On the other hand, one systematic literature review that used multiple methods, various symptom instruments and diverse treatments showed that most drugs that improved idiopathic and diabetic gastroparesis failed to show a statistically significant relationship with the degree of symptom improvement and acceleration of gastric emptying across studies Some groups have observed that the association between clinical improvement and acceleration of gastric emptying depends on the aetiology of gastroparesis 20 , 23 , which could partly explain inconsistent findings across studies Moreover, the modes of action of drugs used for acceleration of gastric emptying are extremely heterogeneous and potentially induce dysfunctions that cause symptoms.
For example, motilin receptor agonists markedly accelerate gastric emptying but simultaneously impair gastric accommodation and can induce dyspeptic symptoms 1. Several additional factors other than a global delay in gastric emptying — such as antral distension, antral hypomotility, gastric dysrhythmias, visceral hypersensitivity or psychological disturbances — could explain, in part, the symptoms experienced by patients with gastroparesis In unclear cases, provocation tests that prove dumping syndrome are the basis of diagnosis, which is supported by evidence of accelerated gastric emptying, preferably of liquids.
Dumping syndrome is a common complication of oesophageal, gastric or bariatric surgery and includes early and late dumping symptoms Early dumping occurs within 1 h after eating, when rapid emptying of food into the small intestine triggers rapid fluid shifts into the intestinal lumen and release of gastrointestinal hormones, resulting in gastrointestinal and vasomotor symptoms.
Late dumping occurs 1—3 h after carbohydrate ingestion and is caused by an incretin-driven hyperinsulinaemia. According to clinical experience, in patients with typical symptoms after surgery, gastric emptying tests Figs 1 , 2 usually add little to the diagnosis. Liquid test meals might better detect acceleration of early gastric emptying; studies using solid meals generally have low sensitivity and specificity for detecting accelerated gastric emptying 12 , The test principle underlying the 13 C-octanoic acid breath test part a is as follows: 13 C-octaonoic acid is rapidly absorbed after gastric emptying and transported to the liver.
Hepatic metabolism leads to production and exhalation of 13 CO 2. Thus, alterations of the 13 C: 12 C ratio in breath samples collected at multiple time points postprandially reflect gastric emptying. Examples part b of values for accelerated, normal and delayed gastric emptying are shown.
In these conditions, delayed gastric emptying can be clinically relevant even without typical symptoms of gastroparesis, as the test identifies gastric dysfunction that could have clinical or therapeutic implications. Thus, impaired coordination between nutrient delivery to the duodenum and onset of insulin effect can impair glycaemic control in patients with insulin-dependent diabetes and gastroparesis 9. Delayed gastric emptying could cause gastro-oesophageal reflux and regurgitation in a subset of patients with GERD 26 and systemic sclerosis Lung transplant recipients can have markedly impaired gastric emptying secondary to vagal injury with a risk of aspiration and post-transplant sequelae Delayed gastric emptying contributes substantially to fluctuations in symptom control in patients with Parkinsonism on long-term levodopa therapy In patients with generalized gastrointestinal motility disorders, particularly in those under consideration for abdominal surgery because of the motility disorder for example, colonic inertia , knowledge of gastric involvement is required to individualize therapy.
Detailed investigation of gastric contractility generally requires invasive techniques such as intraluminal manometry including stomach and small bowel and should, therefore, be limited to patients with severe symptoms. A consensus report 24 has recommended a standardized protocol for the performance of gastric emptying scintigraphy in the USA and has provided normal values. However, even in the USA, despite society guidelines, many centres continue to perform suboptimal studies duration 1—2 h that undermine the quality and utility of the test 4.
In most other countries, including the European ones, there are no widely accepted standard procedures. For interpretation of test results, it has to be taken into account that clinical utility depends on complete consumption of adequate test meals and adequate duration of imaging.
Test meals labelled with the stable, nonradioactive isotope 13 C can be used to measure gastric emptying. The edible blue—green algae, 13 C-labelled Spirulina platensis 31 or the medium-chain fatty acid, 13 C-octanoic acid 13 C-OA 32 , is typically used to label solids; 13 C-acetate is used for liquids Subsequently, it is metabolized, usually in the liver, and finally excreted by the lungs as 13 CO 2. For 13 C-acetate, an interaction has been demonstrated between the rate of 13 C delivery to the duodenum and 13 C recovery in breath Moreover, it has been hypothesized that 13 C-GEBTs might be inaccurate in conditions associated with substantial malabsorption or liver or lung diseases.
Intraindividual and interindividual variabilities of all 13 C-GEBTs are high, but they are similar to the variations observed with scintigraphy 4 , 31 , 38 and, therefore, reflect day-to-day physiological variability in gastric emptying. Results of the 13 C-labelled S. The test kit is commercially available USA only , and the protocol is exactly defined and has been validated in a large group of healthy volunteers and patients When using these tests, it is important to strictly follow a standardized, validated approach.
The WMC for example, SmartPill, Medtronic, USA is a single-use, orally ingested, non-digestible, data-recording capsule that measures pH, pressure and temperature throughout the gastrointestinal tract 4. A marked increase in pH units is used to estimate gastric emptying time Fig. However, as the WMC is a large, non-digestible, solid object, it does not empty with the meal but rather is most often cleared from the stomach by powerful interdigestive migrating motor complex MMC phase III Fig.
Accordingly, passage of the WMC into the duodenum correlates only modestly with gastric emptying of nutrients 41 , These aspects must be taken into consideration for evaluation of the test. Wireless motility recordings in a healthy male participant part a and a female patient with severe constipation part b are shown.
Please note that the timescales are different for the left and right panels. High-resolution gastroduodenal manometry plots are shown for normal fasting part a and postprandial part b motility. During the fasting state part a , there is a constant transition between phases I to III of the interdigestive migrating motor complex MMC with motor quiescence during phase I, irregular contractions that are propagated over only smaller segments during phase II and regular, aborally propagated contractions that usually start in the stomach and traverse long segments of the small bowel during phase III.
Postprandially part b , MMC activity is interrupted and replaced by irregular contractions that serve to mix the luminal contents and to slowly propel them towards the more distal intestine. Catheter-based manometry with multiple pressure sensors located in the antrum, pylorus and duodenum is the only clinically available test that enables detailed assessment of coordinated gastric contraction patterns 3 Fig.