SUMMARY BackgroundThe wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner.
The study provides a large healthy volunteer dataset and parameters of traditional measures of anorectal function. A number of novel phenomena are appreciated, the significance of which will require further analysis and comparisons with patient populations.
In the last 15 years, our understanding of the cellular basis of gastrointestinal function has been altered irreversibly by the discovery that normal gastrointestinal motility requires interstitial cells of Cajal (ICC). Research in this relatively short time period has modified our original concept that the core unit that controls motility is made up of nerves and smooth muscle, to one that now includes ICC. This concept has now expanded to beyond the gastrointestinal tract, suggesting that it may be a fundamental property of the regulation of smooth muscle function that requires rhythmic contraction. ICC are distributed throughout the gastrointestinal tract, have important functions in the control of gastrointestinal motility and are often abnormal in diseased states. Recently, significant steps forward have been made in our understanding of the physiology of ICC as well as mechanisms of injury and recovery. These advances will be the focus of this review.
The physiology of ICCUnique motor patterns are intrinsic to every organ of the gastrointestinal tract, which suit their functions related to mixing, absorption and anally directed movement. ICC are an integral part of the control of these motor activities. The distribution of ICC throughout the musculature is associated with nerve structures. ICC surround the Auerbach's or myenteric plexus and are associated with nerve varicosities throughout the muscle layers, the so called intramuscular ICC (Figures 1,2). Other subpopulations of ICC are associated with non-ganglionated plexuses of nerve varicosities at the inner borders of the circular muscle layers in the intestine and colon (Figures 1,2). The best understood function is that of pacemaker activity in the stomach and small intestine where the ICC generate a periodic depolarization at a characteristic frequency in each of these organs that is called the slow wave or pacemaker activity. This involves rhythmic oscillations of intracellular calcium and activation of membrane ion channels that causes depolarization. Ion channels viewed as important in the generation of pacemaker activity include non-selective cat-ion channels 1 calcium-activated chloride channels [2][3][4] Interstitial cells of Cajal are not unique to the gut; they are present in other rhythmically active structures, such as the portal vein 6 and the bladder 7 . This phenomenon, however, leads to a discussion on properties of cells that are essential to give them the identity of ICC 8 . Genetic abnormalities to the Kit receptor that lead to loss of ICC in the gut, may not equally influence ICC in other organs 9 .The rhythmic depolarization generated by pacemaker ICC propagates into the circular and longitudinal muscle layers, resulting in periods of low and high excitability of the smooth muscle cells at the pacemaker frequency. Under unstimulated conditions, i.e. much of the nocturnal period, this generally does not result in muscle contraction. However, under stimulated conditions, such as a meal, distention and/or neural excitation, ...
The segmentation motor activity of the gut that facilitates absorption of nutrients, was first described in the late 19th century but the fundamental mechanisms underlying it remain poorly understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by ICC associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in ICC.
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Pancolonic, 24 h, spatiotemporal pressure mapping readily identifies characteristic disorganization among consecutive PS, regions of diminished activity and absent or deficient fundamental motor patterns and responses to physiological stimuli. These features are all likely to be important in the pathophysiology of slow transit constipation.
Gut 2003;52:966-970 Delayed gastric emptying can be due to muscular, neural, or humoral abnormalities. In the absence of an identified cause, gastroparesis is labelled as idiopathic. We present the case of a patient with severe idiopathic gastroparesis. Pharmacological approaches failed, as well as reduction in gastric emptying resistance with pyloric injection of botulinum toxin and pyloroplasty. Therefore, subtotal gastrectomy was performed. Histological and immunohistochemical study of the resected specimen showed hypoganglionosis, neuronal dysplasia, and a marked reduction in both myenteric and intramuscular interstitial cells of Cajal. To our knowledge, this is the first time these rare histological findings have been described in a patient with idiopathic gastroparesis. U nderstanding of both normal and abnormal gastrointestinal function has gained momentum in recent decades. However, gastric motility and, in particular, the relative contribution of all of the factors involved in the coordination of food propulsion are still poorly understood. Gastric emptying reflects the integration of tonic contractions of the proximal stomach (fundic tone), phasic contractions of the antrum, and the inhibitory forces of pyloric and duodenal contractions. These complex phenomena require cooperation between smooth muscle, enteric and autonomic nerves, and interstitial cells of Cajal (ICC).
Achalasia is dominated by injury to inhibitory nerves. As intramuscular interstitial cells of Cajal (ICC-IM) are proposed to form functional units with nitrergic nerves, their fate in achalasia may be critically important. We studied the relationship between loss of nitrergic nerves and injury to ICC-IM in patients with achalasia and determined associations between ICC-IM and mast cells (MC), using quantitative immunohistochemistry and electron microscopy. Loss of neuronal nitric oxide synthase (nNOS) immunoreactivity was completed within 3 years of acquiring achalasia. Thereafter, progressive ultrastructural injury to remaining nerve structures was evident. Within the first 2 years, the number of ICC-IM did not decline although ultrastructural injury was already present. Thereafter, loss of ICC-IM occurred unrelated to duration of disease. Damage to ICC-IM appeared unrelated to nerve injury. A significant MC infiltration was observed in the musculature; the number of MC was positively related to the persistent number of ICC-IM. Mast cell formed close contacts with ICC-IM and piecemeal-degranulation occurred towards ICC-IM. In conclusion, injury to ICC-IM in achalasia is variable, but not related to duration of disease and injury to nitrergic nerves. MC are prominent and form close functional contact with ICC-IM which may be responsible for their relatively long survival.
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