Current insights into the pathophysiology of irritable bowel syndrome

Recent reports have emphasized the possible role of mucosal immune activation and inflammation in neuropathic changes in the pathophysiology of irritable bowel syndrome (IBS). However, novel findings using functional brain imaging techniques have underlined the importance of altered perception of visceral stimuli to symptom generation in IBS. These new developments have rekindled an old debate on peripheral versus central mechanisms in the pathophysiology of IBS. In this review we discuss the latest findings in light of these two concepts. In addition, we provide evidence for the hypothesis that, in the absence of alterations in endogenous pain modulation systems and changes in visceral perception, chronic inflammatory mucosal changes in the gut are not a plausible mechanism to explain the presence of chronic abdominal pain, a cardinal IBS symptom.     

New insights into the pathophysiology of irritable bowel syndrome: Implications for future treatments

Irritable bowel syndrome (IBS) is a multifactorial disorder characterized by abdominal pain and altered bowel habits. Chronic symptoms may occur due to changes in gastrointestinal motor function, enhanced perception of gut stimuli, and psychosocial factors. Recent data suggest that abnormal processing of afferent signals occurs in IBS patients. A newly recognized causative factor in a subset of IBS patients is postinfectious IBS. Altered transport of intestinal gas and bowel distention may contribute to abdominal discomfort, pain, and bloating. Changes in gut microflora have also been reported, but data remain scant. Advances have been made in our understanding of serotonin signaling and metabolism in IBS patients, in part due to the introduction of specific receptor agonists and antagonists. Finally, exciting data are emerging on genetic alterations that may contribute to the pathophysiology and treatment of IBS. Increasingly novel mechanisms are being identified that should aid in better understanding of the complex pathophysiology of IBS and developing new therapies.     

New insights into the psychosocial aspects of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common condition varying in severity from trivial to incapacitating. The more severe cases are associated with poor quality of life, absenteeism from work, frequent consultation with medical professionals, and psychosocial distress. Historically the disorder was often considered as purely psychosomatic in origin, but we now know that this is a gross oversimplification. Gastrointestinal disorders are better understood using the biopsychosocial model, which emphasizes the importance of biologic and psychosocial factors. This article reviews the epidemiologic association of IBS with psychological and social stresses and explores how such stresses may influence consulting behavior and outcome. This review also describes physiologic mechanisms that may be involved in IBS and discusses the role of psychological therapies and psychotropic medication in the treatment of this condition.     

New insights into the pathogenesis of inflammatory bowel disease

Several important advances have been made over the past few years that have expanded our knowledge of the immunology of the gut and its complex interactions with commensal organisms. Critical developments in our understanding of the pathogenesis of inflammatory bowel diseases include the discovery of Toll-like receptors and the identification of not one but two susceptibility genes for Crohn’s disease. We have furthered our understanding significantly concerning the role of dendritic cells in the development of gut inflammation. In addition, a novel hypothesis suggesting a protective role for helminthic infections is gaining experimental evidence and direct clinical applicability. In this review we summarize these key developments in the pathophysiology of inflammatory bowel disease and attempt to ascribe clinical relevance where applicable.     

Bartter's syndrome. New insights into pathogenesis and treatment.

Discussed here is a patient with normotension, hypokalemic alkalosis, hyperreninemia, hyperaldosteronism, juxtaglomerular cell hyperplasia and insensitivity to the pressor effects of angiotensin (Bartter's syndrome). The hyperreninemia and hyperaldosteronism were both suppressible with volume expansion. Hypokalemia was correctible both short-term with potassium chloride infusions and long-term with spironolactone. Nevertheless, the abnormal pressor response to infused angiotensin could not be corrected by these maeuvers, suggesting that this defect is likely to be of primary pathophysiologic significance. We found that potassium loading markedly stimulated aldosterone excretion. This may explain the inadequacy of potassium supplementation alone to correct the hypokalemia and the observed "escape" from the potassium conserving effects of spironolactone seen in patients with Bartter's syndrome. The administration of propranolol in large doses only partially suppressed the marked hyperreniemia of our patient and failed to prevent a subsequent rise in the renin level which was associated with spironolactone therapy. In contrast, suppression of the renin level to normal was demonstrated by sodium loading. It is suggested that patients with Bartter's syndrome be treated simultaneously with large doses of spironolactone and a high sodium intake.     

Traditional thoughts on the pathophysiology of irritable bowel syndrome

The pathogenesis of symptoms in irritable bowel syndrome (IBS) is multifactorial and varies from patient to patient. Disturbances of motor function in the small intestine and colon and smooth-muscle dysfunction in other gut and extraintestinal regions are prominent. Abnormalities of sensory function in visceral and somatic structures are detected in most patients with IBS, which may relate to peripheral sensitization or altered central nervous system processing of afferent information. Contributions from psychosocial disturbances are observed in patients from tertiary centers and primary practice. Proof of causation of symptom genesis for most of these factors is limited.     

Recent developments in the pathophysiology of irritable bowel syndrome

Irritable bowel syndrome(IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.     

肠易激综合征发病机制研究进展

肠易激综合征(irritable bowel syndrome, IBS)是常见的功能性胃肠病, 其发病机制尚未完全阐明.目前认为IBS是由多种因素共同作用的结果, 肠道动力异常, 内脏高敏感性为IBS发病的病理生理基础.本文对IBS的多种发病机制的最新研究作一综述.     

Sepsis syndrome. New insights into its pathogenesis and treatment.

Recent insights into the pathogenesis of sepsis and its sequelae have opened up new approaches to treatment. For maximum effectiveness, however, treatment must be given as early as possible in the course of illness--but only to patients who are at high risk of developing shock. The definition of sepsis syndrome outlined in this article provides a method by which to identify such patients before the onset of shock.     

肠易激综合征发病机制的研究进展

肠易激综合征(IBS)的发病机制虽然仍不十分明确,但近年来除了在内脏高敏、肠动力异常等传统观点认为的病理生理基础上有新的发现外,在其他多方面均有重要的研究进展。此文从基因易感性、神经递质、感染及免疫、肠黏膜屏障、神经系统、精神心理因素、动物模型等方面较完整的对IBS发病机制的研究进展作一综述。     

New insights into the pathophysiology of oedema in nephrotic syndrome

Oedema is a common clinical manifestation of nephrotic syndrome. However, the pathophysiological mechanism of sodium retention in nephrotic syndrome has been intensely debated for decades. Several clinical and experimental observations argue against the classic or "underfill" hypothesis of oedema formation in nephrotic syndrome. In many patients, oedema formation in nephrotic syndrome is due to the kidney being intrinsically unable to excrete salt and is unrelated to systemic factors (i.e. hypoalbuminaemia, decreased “effective” arterial blood volume, and secondary hyperaldosteronism). The cortical collecting duct is the nephron site of sodium retention in nephrotic syndrome. Activation of the epithelial sodium channel in the cortical collecting duct is responsible for sodium retention in nephrotic syndrome. In nephrotic syndrome, a defective glomerular filtration barrier allows the passage of proteolytic enzymes or their precursors, which have the ability to activate the epithelial sodium channel, thereby causing the the subsequent sodium retention and oedema.     

肠易激综合征发病机制的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以腹部不适和排便习惯改变为特征的胃肠功能性疾病.IBS的发病机制仍不清楚,传统观点认为基因、心理社会因素、胃肠动力障碍和内脏高敏感性等是引起IBS的关键因素.近年来,人们陆续发现了一些与IBS发病相关的新病理生理学改变依据,如脑肠轴调节失常、肠道感染、肥大细胞的激活并释放活性物质等.本文总结与IBS发病机制相关的一些最新研究进展.     

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10¹⁴ cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.     

肠易激综合征发病机制研究进展

肠易激综合征（irritable bowel syndrome,IBS）是常见的功能性肠病,以腹痛伴有大便性状和排便习惯改变为主 要表现。IBS 发病机制复杂,包括了增加IBS易感性的因素及与症状发作相关的因素,多种因素相互作用导致了相应 的病理生理变化,从而产生IBS症状,文章就已有的研究结果对IBS的发病机制进行总结。     

Genetic polymorphism in pathogenesis of irritable bowel syndrome

Irritable bowel syndrome(IBS)is a complex symptombased disorder without established biomarkers or putative pathophysiology.IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3mo according to ROMEⅢ:relief by defecation,onset associated with a change in stool frequency or onset with change in appearance or form of stool.Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms,as well as the therapeutic responses in treating IBS patients.This review gives new insights on how genetic determinations influence in clinical manifestations,treatment responses and potential biomarkers of IBS.     

New insights into the pathophysiology of allergic rhinitis.

The immune response to an allergen is dependent on an initial sensitization process, with future exposures triggering a two-part allergic response including an early and a late phase. The process by which an allergen is recognized as such, including which cell types and cytokines are involved in the sensitization process, has become clearer over the last several years. Similarly, the roles of the different preformed mediators responsible for many of the signs and symptoms of the early phase response have been elucidated. Recent work also has shed some light on the multitude of cells and mediators involved in the late-phase reactions, which can lead to priming and long-term inflammation. This article will discuss some of this recent work as well as review the basics behind all of the stages of the allergic response, especially as they apply to the nose and upper airway.     

Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome

Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.     

Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome

Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.