Chronische Motilitätsstörungen des oberen Gastrointestinaltrakts im Alter

Primary motility disorders of the upper gastrointestinal (GI) tract result from an impairment of the motor function of the esophagus, stomach, and duodenum by malfunction of the enteric nervous system or degeneration of the gastrointestinal muscle layer. Other forms of upper GI motility disorders occur secondary to underlying systemic diseases. The exact pathophysiology of the disturbances within the enteric nervous system of the upper GI tract is not yet clearly understood. For motility disorders resulting from systemic diseases the lack of knowledge with respect to the underlying pathomechanism is even greater. The term functional dyspepsia summarizes some symptoms of the upper abdomen, suggesting a disorder of upper GI motility or perception; however, this link to disturbed physiology has never been convincingly demonstrated. This overview describes therapeutic options for motility disorders of the upper GI tract regarding medicinal, endoscopic and surgical targets. The efficacy of medicinal therapy of upper GI motility disorders is low due to the lack of understanding of the pathophysiology. Therefore, endoscopic and other interventional therapies have to be applied also in the elderly patient group. The restrictions for metoclopramide published by the European Medicines Agency (EMA) in July 2013 have limited the armentarium of medicinal therapy of chronic motility disorders of the upper GI tract.     

Gastrointestinal motility disorders: an update

Gastrointestinal motility disorders encompass a wide array of signs and symptoms that can occur anywhere throughout the luminal gastrointestinal tract. Motility disorders are often chronic in nature and dramatically affect patients' quality of life. These prevalent disorders cause a tremendous impact both to the individual patient and to society as a whole. Significant progress has been made over the last 5 years in understanding the etiology and pathophysiology of gastrointestinal motility disorders. This clinical update will focus on seven of the most common gastrointestinal motility disorders (achalasia, non-achalasia esophageal motility disorders, dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome, and chronic constipation) with an emphasis on current treatment options and new therapeutic modalities.     

Relationship of Helicobacter pylori infection with gastrointestinal motility

The interest of gastroenterologists in the relationship between Helicobacter pylori and gastrointestinal motility emerges from the observation that Helicobacter pylori may be involved in the pathogenesis of functional dyspepsia and that a relatively large percentage of patients with dyspepsia may show impaired gastrointestinal motility. A number of studies have been published on the interaction between Helicobacter pylori infection and gastrointestinal motility with controversial results, and, therefore, there are no definite conclusions, as yet, as to whether Helicobacter pylori is able, at all, or in which degree, to influence the motility of the upper gastrointestinal tract. Motility of the upper gastrointestinal tract has been studied in Helicobacter pylori positive and negative individuals by means of manometry, scintigraphy, radio-opaque markers or by other, recently developed, procedures such as breath tests, ultrasonography, and barostat. The vast majority of studies do not support the hypothesis that Helicobacter pylori may influence gastrointestinal motility. Nearly all these studies are, however, affected by methodological problems related to the small numbers of patients, different methodological approaches, and to the well-known difficulties in studying both gastrointestinal motility and functional dyspepsia.     

Gastrointestinal motility and the brain‐gut axis

The role of the brain‐gut axis in gastrointestinal motility is discussed according to the specific organs of the gastrointestinal tract. Not only clinical studies but basic animal research are reviewed. Although the mechanism of functional gut disorders remains to be clarified, recent data suggest that there is evidence that the brain‐gut axis has significant effects on gastrointestinal motility. The major role of endoscopy in the diagnosis of functional gastrointestinal disorders is to exclude organic gastrointestinal disorders. In the esophagus, the lower esophageal sphincter and a gamma‐aminobutyric acid B mechanism are considered to play important roles in gastroesophageal reflux disease. In the stomach, corticotropin‐releasing factor, neuropeptide Y and other substances might be involved in the pathogenesis of non‐ulcer dyspepsia. In the small intestine, corticotropin‐releasing factor, gamma‐aminobutyric acid B and other substances are considered to modulate intestinal transit via central mechanisms. In the colon, it is known that psychiatric factors are related to the onset and clinical course of irritable bowel syndrome. Serotonin, corticotropin‐releasing factor, gamma‐aminobutyric acid, orphanin FQ and neuropeptide Y have been reported as putative neurotransmitters. More efforts in basic science studies and animal and human studies of physiology of the gastointestinal tract are still required. These efforts will elucidate further mechanisms to clarify the etiology of motility disorders and encourage the investigation of new therapies in this field.     

Current understanding of pathogenesis of functional dyspepsia

Functional dyspepsia (FD) is a disorder in which upper abdominal symptoms occur in the absence of organic disease that explains them. Many pathogenic factors have been proposed for FD, including motility abnormalities, visceral hypersensitivity, psychosocial factors, excessive gastric acid secretion, Helicobacter pylori, genetics, environment, diet, lifestyle, and post-infectious FD. Many of those pathogenic factors are also common to irritable bowel syndrome and other functional gastrointestinal disorders, so understanding FD offers a glimpse into the nature of functional gastrointestinal disorders in general. Motility abnormalities and visceral hypersensitivity are thought to be important in the manifestation of FD symptoms, but the other factors are also thought to contribute by interacting and modifying motility and visceral hypersensitivity.     

13 Dyspepsia in infants and children

Pathological processes and diseases of the upper gastrointestinal tract have become increasingly recognized over recent years as childhood entities responsible for a variety of upper gastrointestinal symptoms previously labelled as functional or non-organic. The term ‘dyspepsia’ is an adult one whose definition requires clarification before use in the paediatric context, but it encompasses age-dependent symptoms such as feedassociated irritability in the infant, peri-umbilical pain in the younger child, and heartburn, nausea, and indigestion in the older child as in adults. The possible organic conditions giving rise to such symptoms are multiple and multiorgan and include: gastro-oesophageal reflux; peptic ulcer disease; upper gastrointestinal Crohn's disease; antroduodenal motility disorders; pancreatitis; cholecystitis; cholelithiasis; biliary dyskinesia; and abdominal migraine. However, Munchausen syndrome by proxy must not be forgotten. Non-ulcer dyspepsia, it is now clear, has a basis in altered gastroduodenal motility and may be amenable to propulsion agents. In many individuals the dyspeptic symptoms of recurrent abdominal pain may be altered by psychotherapeutic intervention. Indeed there remains a proportion of children who undoubtedly have a behavioural or psychological base to their complaint. Nevertheless, with the recent increase in diagnostic yield from improved technical investigative aids available to paediatrics in the last 5–10 years, it is clear that the responsibility of the paediatrician to the child to find a cause of their symptoms is paramount. The variety of presenting features, possible causes of these symptoms, and appropriate investigation and treatment will be discussed, and management algorithms based on published literature and personal practice will be offered.     

3 Is functional dyspepsia just a subset of the irritable bowel syndrome?

To determine whether functional dyspepsia and irritable bowel syndrome are different entities, epidemiological data, factor analysis studies, physiological data and associated psychological symptoms were reviewed. Between 30% and 60% of patients with either diagnosis also meet the criteria for the other diagnosis, a level greater than expected to occur by chance but not sufficient to infer an identity. Most factor analysis studies identify independent clusters of symptoms corresponding to functional dyspepsia and irritable bowel syndrome. Visceral hypersensitivity is seen throughout the gastrointestinal tract in both disorders, but the motility patterns seen in association with functional dyspepsia (principally antral hypomotility and delayed gastric emptying) differ from the motility patterns seen in irritable bowel syndrome. Psychological symptoms are similar in these two disorders but are not believed to be aetiological for either of them. Thus, based on a factor analysis of gastrointestinal symptoms and differences in intestinal motility, functional dyspepsia and irritable bowel syndrome appear to be different entities.     

Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract

It has been demonstrated that nitric oxide (NO) is a major inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter in the gastrointestinal (GI) tract. NO released in response to nerve stimulation of the myenteric plexus causes relaxation of the smooth muscle. NO is synthesized by the activation of neuronal NO synthase (nNOS) in the myenteric plexus. Released NO plays an important physiological role in various parts of the GI tract. NO regulates the muscle tone of the sphincter in the lower esophagus, pylorus, sphincter of Oddi, and anus. NO also regulates the accommodation reflex of the fundus and the peristaltic reflex of the intestine. Previous studies have shown that NOS inhibitors delay gastric emptying and colonic transit. The reduction of nNOS expression, associated with impaired local production of NO, may be responsible for motility disorders in the GI tract. There is accumulated evidence that dysfunction of NO neurons in the myenteric plexus may cause various GI diseases. These reports are reviewed and possible mechanisms of altered nNOS expression are discussed in this article. In particular, impaired nNOS synthesis of the myenteric plexus seems to be an important contributing factor to the pathogenesis of achalasia, diabetic gastroparesis, infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and Chagas' disease. Reduced NO release and/or nNOS expression are suspicious in a subset of patients with functional dyspepsia. Although the etiology of intestinal pseudo-obstruction remains unknown, it is conceivable that extrinsic denervation may upregulate nNOS expression, resulting in enhanced muscular relaxation and disturbed peristalsis. An animal model of colitis showed impaired nNOS expression in the colonic myenteric plexus. Antecedent infection may be associated with the impaired NO pathways observed in functional dyspepsia, colitis, and Chagas' disease.     

Electrical therapies for gastrointestinal motility disorders

Introduction: Gastrointestinal (GI) motility disorders are common in clinical settings, including esophageal motility disorders, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, post-operative ileus, irritable bowel syndrome, diarrhea and constipation. While a number of drugs have been developed for treating GI motility disorders, few are currently available. Emerging electrical stimulation methods may provide new treatment options for these GI motility disorders.

Areas covered: This review gives an overview of electrical therapies that have been, and are being developed for GI motility disorders, including gastroesophageal reflux, functional dyspepsia, gastroparesis, intestinal motility disorders and constipation. Various methods of gastrointestinal electrical stimulation are introduced. A few methods of nerve stimulation have also been described, including spinal cord stimulation and sacral nerve stimulation. Potentials of electrical therapies for obesity are also discussed. PubMed was searched using keywords and their combinations: electrical stimulation, spinal cord stimulation, sacral nerve stimulation, gastrointestinal motility and functional gastrointestinal diseases.

Expert commentary: Electrical stimulation is an area of great interest and has potential for treating GI motility disorders. However, further development in technologies (devices suitable for GI stimulation) and extensive clinical research are needed to advance the field and bring electrical therapies to bedside.     

Aktuelle Konzepte zur funktionellen Dyspepsie

The term “dyspepsia” describes chronic or intermittent complaints of the upper gastrointestinal tract that are characterized by epigastric pain, anorexia, fullness, belching, heartburn, nausea, and/or vomiting. In the general population, the prevalence of dyspeptic symptoms is about 15–20%. Most of these individuals suffer from functional dyspepsia (FD), with organic diseases such as peptic ulcer, esophagitis caused by gastroesophageal reflux, and neoplasia being much less common. The precise etiology of FD remains unknown. According to Rome III criteria, FD is defined as distinct epigastric complaints lacking a structural or biochemical explanation. Current hypotheses consider altered motility or visceral hypersensitivity as the underlying pathomechanism. Hence, the symptomatic pharmacological treatment mainly consists of compounds modulating motor activity and visceral nociception.     

Tobacco associated gastrointestinal disorders: smoking cessation therapy - a task for gastroenterologists

Tobacco smoking is an independent risk factor in the etiology of Crohn's disease, functional dyspepsia, GERD, chronic pancreatitis and gastrointestinal carcinomas (oesophagus, stomach, colon, pancreas and liver). The current knowledge of the effects of tobacco smoking on the gastrointestinal tract is summarised. Non-smoking should be recommended to everybody as primary prevention against cardiopulmonary and gastrointestinal diseases. Despite lacking of clinical studies tobacco abstinence should be recommended as a secondary preventive therapy of Crohn's disease, functional dyspepsia, GERD and chronic pancreatitis because of epidemiological studies and pathophysiological considerations. All gastroenterologists should help patients with the above mentioned diseases to stop smoking. Evidence based methods of smoking cessation and methods suited to routine clinical care are presented. Pharmacological (nicotine replacement therapy) and psychological therapies (cognitive behavioural group therapies) should be adapted to the prior experiences of the patient, his stage of motivation to stop smoking and his co-morbidity. In refractory ulcerative colitis controlled tobacco smoking can be recommended to ex-smokers.     

Role of Ghrelin in the Pathophysiology of Gastrointestinal Disease

Ghrelin is a 28-amino-acid peptide that plays multiple roles in humans and other mammals. The functions of ghrelin include food intake regulation, gastrointestinal (GI) motility, and acid secretion by the GI tract. Many GI disorders involving infection, inflammation, and malignancy are also correlated with altered ghrelin production and secretion. Although suppressed ghrelin responses have already been observed in various GI disorders, such as chronic gastritis, Helicobacter pylori infection, irritable bowel syndrome, functional dyspepsia, and cachexia, elevated ghrelin responses have also been reported in celiac disease and inflammatory bowel disease. Moreover, we recently reported that decreased fasting and postprandial ghrelin levels were observed in female patients with functional dyspepsia compared with healthy subjects. These alterations of ghrelin responses were significantly correlated with meal-related symptoms (bloating and early satiation) in female functional dyspepsia patients. We therefore support the notion that abnormal ghrelin responses may play important roles in various GI disorders. Furthermore, human clinical trials and animal studies involving the administration of ghrelin or its receptor agonists have shown promising improvements in gastroparesis, anorexia, and cancer. This review summarizes the impact of ghrelin, its family of peptides, and its receptors on GI diseases and proposes ghrelin modulation as a potential therapy.     

Functional disorders of the stomach

Gastroenterologists frequently encounter patients who report vague epigastric discomforts or sensations of fullness, bloating, and distention in the upper abdomen. The discomfort is neither burning in character nor severe in intensity; there is no nocturnal pain. The epigastric location of discomfort and lack of radiation may help to exclude biliary tract and pancreatic diseases. Nausea may be present, but there is little or no vomiting. After these patients ingest liquids or solid foods, the symptoms of easy filling or early satiety and increasing discomfort and nausea are almost always present. The patient may only report "indigestion," but a specific chief complaint, such as pain, discomfort, nausea, or bloating may be elicited with further inquiries. Solid foods usually provoke more symptoms than do liquids. Symptoms of early satiety, nausea, bloating, and abdominal discomfort may culminate in the vomiting of undigested food. These vague upper gastrointestinal (GI) symptoms have been termed "dyspepsia." When peptic diseases of the stomach are excluded, the symptom complex has been called "nonulcer" dyspepsia, a vague syndrome with symptoms attributed to stomach dysfunction. Nonulcer dyspepsia has been reviewed recently. Such symptoms, commonly attributed to a "functional" disorder, are very common in clinical practice, with an incidence of 30% of patients. In this review, we will discuss an approach to the evaluation and treatment of patients with symptoms of nausea, early satiety, bloating, and vague epigastric discomfort--dyspeptic symptoms associated with functional stomach disorders. We will review the anatomy and motility of the stomach and suggest potential neuromuscular malfunctions of the stomach that may result in epigastric symptoms. The potential role of stress and other brain-gut interactions, which may underlie these symptoms, will also be reviewed.     

Gastrointestinal manifestations in myotonic muscular dystrophy

Myotonic dystrophy(MD)is characterized by myotonicphenomena and progressive muscular weakness.Involvement of the gastrointestinal tract is frequentand may occur at any level.The clinical manifestationshave previously been attributed to motility disorderscaused by smooth muscle damage,but histologicevidence of alterations has been scarce and conflicting.A neural factor has also been hypothesized.In the upperdigestive tract,dysphagia,heartburn,regurgitation anddyspepsia are the most common complaints,while inthe lower tract,abdominal pain,bloating and changesin bowel habits are often reported.Digestive symptomsmay be the first sign of dystrophic disease and mayprecede the musculo-skeletal features.The impairmentof gastrointestinal function may be sometimes sogradual that the patients adapt to it with little awarenessof symptoms.In such cases routine endoscopic andultrasonographic evaluations are not sufficient andtargeted techniques(electrogastrography,manometry,electromyography,functional ultrasonography,scintigraphy,etc.)are needed.There is a low correlationbetween the degree of skeletal muscle involvement andthe presence and severity of gastrointestinal disturbanceswhereas a positive correlation with the duration of theskeletal muscle disease has been reported.The drugs recommended for treating thegastrointestinal complaints such as prokinetic,anti-dyspeptic drugs and laxatives,are mainly aimed atcorrecting the motility disorders.Gastrointestinal involvement in MD remains acomplex and intriguing condition since many importantproblems are still unsolved.Further studies concentratingon genetic aspects,early diagnostic techniques and thedevelopment of new therapeutic strategies are neededto improve our management of the gastrointestinalmanifestations of MD.     

Trastornos funcionales y motores digestivos

Functional gastrointestinal (GI) disorders are difficult to live with. Many patients would prefer to have an organic disease and a medical report stating the results of a test providing evidence of a lesion. Therefore, further knowledge of the causes and treatment of these disorders is essential. The present article aims to summarize as simply and usefully as possible the most important studies on functional and motor GI disorders presented at the Congress of the American Gastroenterological Association (Digestive Disease Week 2010).The most notable presentations concerned the pathogenic mechanisms and search for new therapies in highly prevalent disorders such as functional dyspepsia, irritable bowel syndrome and constipation but interesting studies were also presented on incontinence, gastroparesis, cyclic vomiting syndrome and achalasia.It is increasingly clear that functional GI disorders are caused by multiple factors and, therefore, that genetic, environment, psychological, microinflammatory and neuroimmune-endocrine factors form part of this complex puzzle. Each year, advances are made in distinct parts of the world, which will hopefully improve patient well-being.     

Gastrointestinale Motilitätsstörungen in der Intensivmedizin

Gastrointestinal (GI) motility disorders in critically ill patients are a common clinical problem. These disorders can be the consequence of the underlying disease or result from the medical or interventional intensive care treatment. Despite increasing knowledge of the underlying physiology and pathophysiology of the motility disorders, there is a lack in therapeutic alternatives (prokinetics), which can be used and are approved under these conditions. Swallowing disorders, gastroesophageal reflux and gastroparesis due to various underlying causes comprise the most import clinically relevant disorders in the upper GI tract, with dysphagia, nausea, and vomiting being the leading symptoms. Constipation with delayed passage, paralysis, or ileus, on the one hand, as well as diarrhea due to various causes, on the other hand, are the most important clinical disorders in the lower GI tract. Intestinal pseudo-obstruction is a special form of paralytic ileus with an acute or chronic form occurring in various diseases and post-operative conditions. Improvement in the general intensive care management of critically ill patients can dramatically reduce the incidence of gastrointestinal motility disorders. Reduction of stress and pain, cautious use of medications with inhibitory effects on gastrointestinal motility (e.g., opioids, catecholamines), balancing electrolytes and fluid losses, early mobilization, physical therapy, and early enteral feeding can reduce the overall incidence. Besides cholinomimetics, only a few prokinetic substances (domperidone, metclopramide, erythromycin, cholecystokinin (CCK) agonists) are approved and available for treatment in the upper GI tract. In the lower GI tract, decompression and the use of laxatives are most commonly used for treatment; however, newer substances (lubiprostone, prucalopride) are on the horizon.     

8 Relevance of gastrointestinal motor disturbances in functional dyspepsia

Gastrointestinal motor abnormalities are frequent findings in patients with functional dyspepsia. However, these abnormalities are rather non-specific and seem to be restricted to a proportion of patients. Furthermore, they are not necessarily time-linked to symptom perception. The relationship of digestive motor derangements and symptoms in functional dyspepsia remains, therefore, unsettled. A variety of methodological and conceptual shortcomings characterize many of the studies investigating the relationship between gastrointestinal motility disorders and dyspeptic symptoms, and this obviously contributes to a higher level of uncertainty in the field. Recent reports suggest that gastrointestinal dysmotility is associated with perception of some dyspeptic symptoms, at least in a subset of patients. Well-conducted studies using appropriate methodology are needed to verify whether gastrointestinal motor disorders play a causal role in functional dyspepsia and whether this is of clinical relevance.     

Gastrointestinal motility problems in the elderly patient

Statistics abound demonstrating the aging of the population, and this comes as no news to physicians caring for an increasing number of elderly patients. This group experiences the expected age-related physiologic declines, including systems critical to integrative functions such as immunologic, neurologic, and metabolic systems. Although an increased prevalence of several common gastrointestinal disorders occurs in the elderly person, aging per se appears to have less direct effect on most gastrointestinal functions, in large part because of the functional reserve of the gastrointestinal tract. Although irritable bowel symptoms decrease with aging, there seems to be an increase in many gastrointestinal disorders of function and motility. The gastroenterologist will frequently encounter elderly patients with complaints of dysphagia, anorexia, dyspepsia, and disorders of colonic function. Understanding age-related changes in gastrointestinal physiology and effects of common comorbid illnesses enhances the ability to evaluate and treat these common, troublesome symptoms.     

Large-scale disaster and gastrointestinal diseases

Many medical investigations, including epidemiological studies, case reports and case series have been conducted in association with large-scale disasters worldwide. Gastrointestinal diseases have been identified in many studies on disaster-related diseases with various problems being encountered especially in the acute (the first 3 days after the onset of a disaster), subacute (approximately the first 2 weeks after the onset of a disaster), and chronic phases. The problems in the acute phase concern food security and nutrition, while those in the subacute phase concern constipation and diarrhea. According to each disease site, the clinically important problems in the chronic phase are peptic ulcer and functional dyspepsia affecting the upper gastrointestinal tract, and inflammatory bowel disease and irritable bowel syndrome affecting the lower gastrointestinal tract. In addition, chronic hepatitis B and alcoholic liver diseases/pancreatitis are major hepatobiliary pancreatic diseases.     

Dysmotility disorders of the stomach and possible methods of diagnosis

Gastric dysmotility disorders are markedly heterogeneous group of gastrointestinal tract disorders and their etiology vary substantially. Some clinical manifestations of gastric dyspepsia can be present but they could be clinically silent, too. The authors give an overview of recent possibilities of dysmotility disorders diagnostics and of their relation to diabetes mellitus.