Gastrointestinal motility and perception disorders re-visited

J.-R. Malagelada

Department of Digestive Diseases. University Hospital Vall d’Hebron. Autonomous University of Barcelona. Barcelona, Spain

 

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Malagelada JR. Gastrointestinal motility and perception disorders re-visited. Rev Esp Enferm Dig 2004; 96: 477-483.

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Recibido: 22-01-04.
Aceptado: 27-01-04.

Correspondencia: Juan R. Malagelada. Servicio Aparato Digestivo. Hospital General Universitario Vall d'Hebrón. Pg. Vall d' Hebrón, 119-129. 08035 Barcelona. Fax (34) 93 209 62 05. e-mail: jrmalagelada@vhebron.net

 

INTRODUCTION

The importance of gastrointestinal motility and gut perception in medicine has been long recognized. Physiologically, these key functions ensure normal unperceived feeding and digestion, crucial aspects of health and well-being. Conversely, pathophysiological disturbances may produce digestive symptoms, which are common in the general population and may range from the simply annoying to the incapacitating. In fact, major disturbances may lead to malnourishment, metabolic imbalance and general deterioration of the body. Altered normal gut motility may also disrupt gut homeostasis, induce changes in the gut flora and facilitate bacterial translocation from the intestine to other viscera (Fig. 1).

Clinical recognition of gastrointestinal motility and perception disorders is largely based on the anatomic localization of their symptomatic expression (1-4). Thus, dysphagia, reflux symptoms and chest pain are normally associated with esophageal or gastroesophageal disturbances. Upper abdominal pain or discomfort, early satiety, nausea and vomiting, and other dyspeptic-like symptoms are usually ascribed to dysfunction of the stomach and/or upper small bowel. Bloating is a somewhat mysterious symptom that may be generated by motor/sensorial disturbances throughout the gastrointestinal tract. Diarrhea and/or constipation usually result from small bowel and/or colonic disorders. Ano-rectal symptoms usually derive from dysfunction of the pelvic floor, distal colon or sphincteric structures.

Traditionally, clinical conditions were divided into somatic gastrointestinal motility disorders: achalasia, gastroparesis, chronic intestinal pseudo-obstruction and so on, and functional disorders: dyspepsia, irritable bowel syndrome and a myriad of clinical syndromes and descriptions. The distinction between both groups was largely based on whether a propulsive failure was or not demonstrated by conventional imaging tests. Thus, a patient with recurrent abdominal pain and distension could be categorized either as a chronic intestinal pseudoobstruction (if dilated loops of bowel were visualized on X-rays) or irritable bowel syndrome (if nothing obviously abnormal was found). Application of more sophisticated and discriminating diagnostic tests (intestinal manometry, barostat, etc.) and histology increasingly showed that patients long considered functional have demonstrable physiological and/or morphological abnormalities. Thus, caution is advised against precipitously classifying a patient into the organic or functional category.

But, regardless of regional or diagnostic specificity, is there a common mechanism to all these abdominal symptoms? In this regard, medical opinions have gradually shifted. Reasoning has evolved from presenting the question as a dilemma between either the gut or the brain as the source of clinical manifestations, to a more integrated concept. Today we favour the hypothesis that both the brain and gut are responsible for symptom generation in most patients (5,6). This evolution in our concept of the origin of gastrointestinal motility and perception disorders derives largely from research data showing that key disease mechanisms (inflammation, hyperalgesia, and dysmotility) may be indistinctly induced at central or peripheral levels (Fig. 2). In other words, both the brain and the gut, and possibly intermediate structures as well, can potentially originate local inflammation, disrupt normal propulsion, and amplify conscious perception of mechanical stimuli, all of which are the clinical hallmarks of these gut disorders (6,7). In addition, information is now beginning to surface and indicate that genetic predisposition is an important factor, even though a firm identification of the responsible genes is not yet possible (8). In summary, gastrointestinal motility and perception disorders, like many other medical conditions, probably derive from a combination of genetic and environmental factors that determine the development of the clinical disease through a multiplicity of mechanism disruptions.

Let us review in some detail specific information that supports the above concepts. First, gut neurogenic inflammation, including that arising via psychological activities such as stress, is a contention supported by some data. In our laboratory, for instance, we have shown that experimental acute stress in healthy individuals is capable of triggering mast cell degranulation in the intestinal wall with measurable mastocyte tryptase release into the lumen of the intestine, with a parallel increase in luminal histamine and prostaglandin concentrations together with increases in net water flux (9). Mast cells play a special and probably important role in the activation of the pro-inflammatory sequence within the gut wall. Neurogenic inflammation may actually act in concert with local disturbances of bacterial-immunological nature. Thus, a gut inflammatory process originally started by pathogenic bacterial infection, may be reactivated or perpetuated by stress. This is the clinical sequence observed in many patients who present post-gastroenteritic irritable bowel symptoms. Such individuals are more likely to have been under stress or to suffer chronic psychological disorders than other individuals exposed to the same infection who do not develop symptoms after the acute infection heals. At the same time, we know that in some inflammatory forms of IBS there is enterochromapphin cell proliferation in the intestinal mucosa. The abundance of these neuroendocrine cells may possibly lead to an increased synthesis and release of serotonin with a subsequent activation of propulsive activity and luminal water flux (10). Under these conditions the pro-inflammatory effects of the central nervous system may be amplified.

Medullary and autonomic reflexes may also be important. In our laboratory, as an example, we have shown that symphatethic activation enhances visceral perception of mechanical gut stimuli. We performed a study in healthy individuals, using a special device to apply negative pressure to the lower part of the body while simultaneously inflating a tiny balloon inside the small bowel (11). The application of negative pressure to the legs produced a surge in vascular resistance reflecting sympathetic autonomic stimulation and, at the same time, there was an increase in abdominal discomfort elicited by the balloon-mediated distension of the bowel. Interestingly, hand discomfort produced by a cutaneous electrical stimulator remained unchanged. These experiments suggest that sympathetic arousal enhances visceral perception while leaving somatic perception unchanged. Anxiety, mood disturbances and hyper-vigilance may also influence sensorial function and contribute significantly to visceral hypersensitivity (12).

Dietary factors are also important. Specifically, lipids exert an amplifying effect on visceral perception (13) and this phenomenon may explain the typical increase in symptoms that patients with functional gut disorders experience when they consume fatty meals. At the same time, luminal lipids also influence gut motility via neuroendocrine reflexes and may exaggerate some of the motor disturbances that underlie dyspepsia, irritable bowel syndrome and other common functional disorders (14,15). In our laboratory, we have developed an original method to infuse gas into the bowel and collect it as it exits. Normal individuals are able to propel gas along the bowel without significant retention or symptoms. In contrast, we have shown that patients with irritable bowel syndrome abnormally retain infused gas while simulta-neously developing abdominal symptoms. These clinical effects of gas appear to be due both to abnormal gas pooling within the gut and to visceral hypersensitivity. Symptoms induced by gas are exacerbated by the presence of lipids in the intestinal lumen.

What are the main diagnostic tools that clinicians may use to diagnose gastrointestinal motility and perception disorders of various kinds? The physician’s clinical ability facilitated by his/her skills in obtaining a medical history, remains the best. Patients with motility disorders and specially patients with functional disorders are primarily diagnosed on the basis of clinical acumen. Purely clinical considerations such as age, presence or absence of alarm symptoms, patient motivation, interaction with family and relatives, etc., allow the clinician to formulate a tentative diagnosis and to conduct subsequent investigations. Endoscopy and general imaging techniques such as CT, ultrasonography, magnetic resonance, etc., are relatively cumbersome and expensive, but are sometimes a necessary step to exclude various organic disorders, including ulcer, inflammatory bowel disease and tumours that may induce symptoms similar to functional disorders. When clinical features suggest the possibility of inflammatory bowel disease or a potentially lethal malignant condition, such diagnostic resources must be undoubtedly applied. If in doubt, do it. There is another category of tests that may be quite useful in establishing abnormal gut physiology, as opposed to imaging tests that detect mostly morphological lesions. These “physiological” diagnostic techniques include gastrointestinal manometry or barostat measurements, as well as radioscintigraphic assessment of gut transit. Curiously, these techniques, when properly applied, can be extremely useful to make a positive diagnosis of gastrointestinal motility disorders or perception abnormalities. Their main disadvantage is that they require special installations and skills, tend to be only available in specialized tertiary centers, and are relatively insensitive. Thus, failure to pick up an abnormality in contractile or coordinated activity or sensitivity does not exclude the possibility of a defined motor/sensorial gut disorder becoming evident later on in time. Follow-up is, therefore, mandatory in suspected cases. A therapeutic trial with any of the available prokinetic or other pertinent drugs may be useful, provided that patients continue to experience satisfactory long-term relief. Short-term relief may simply represent a placebo effect, which is very common in this group of conditions.

Ultimately, the clinical diagnosis should not be simply a choice between functional and organic. There is considerable overlap between these two possibilities and, moreover, symptom interpretation is commonly a function of the intensity and sophistication of the technology applied to the investigation of a particular individual (Fig. 3). Thus, patients primarily seen and managed within a general medical practice tend to remain either uninvestigated or only so by basic imaging tests such as endoscopy or ultrasonography. They may be ascribed to the functional category but in fact may have demonstrable abnormalities in motility or sensitivity that become evident when referred to a specialized unit and investigated in depth. Vice versa, patients with an apparent lesion on imaging may have symptoms that are in fact related to an underlying and unrecognized disturbance. Consider, for instance, the not-so-rare patient with apparent gastroesophageal reflux symptoms who fails to respond to proton pump inhibitors or the patient with an ulcer who continues to have dyspeptic symptoms after appropriate Helicobacter pylori eradication and antisecretory treatment has been applied, or the patient with gallstones who remains symptomatic after cholecystectomy. Admittedly, such specialized investigation of motility/perception disturbances is the prerogative of a tertiary setting, but may be the only approach that allows the clinician to prove objectively the existence of dysmotility and/or sensorial abnormalities. Such patients with proven physiological gut abnormalities are to be considered completely analogous to those with a conventional “organic” disease. Conversely, a negative in-depth investigation makes it more comfortable for the clinician to refer the patient for specialized evaluation of a possible psycho-visceral disturbance or follow-up observation (16,17).

To use medical resources judiciously, the management of patients with motility and sensorial disorders should be conceived in a step by step progression or decrease along an increasingly complex and expensive ladder (18) (Fig. 4). Patients with suspected motor disorders of a severe or/and incapacitating nature, including for instance those suspected of achalasia/esophageal spasm, gastroparesis, chronic intestinal pseudoobstruction or colonic inertia resistant to usual therapeutic measures, should be directed to the appropriate referral centres to allow full use of all diagnostic resources including the most sophisticated tools. There is an intermediate category of patients with unexplained bacterial overgrowth, post-infectious IBS and standard forms of the main functional disorders, (dyspepsia, IBS-bloating, proctalgia, etc.). These patients may not require tertiary center investigations except in resistant on very severe cases, but they do deserve pharmacological treatment and psycho-social evaluation. At the bottom of the scale there are many patients complaining of vague and non-specific symptoms such as food intolerance and general unhappiness associated with abdominal malaise that blend with psychiatric disturbances including somatization disorders, etc. For this category, more or less formal behavioural medical approaches, as in fact spontaneously administered by many physicians, seem best. Reassurance is important to all categories.

The pharmacological treatment comprises a number of drugs that are not very convincing in terms of providing global improvement, but that may be useful to relieve specific symptoms. These agents include fiber, antispasmodics, tricyclic antidepressants and prokinetics (19). In addition, the pharmaceutical industry is developing and in the process of releasing into the market a new group of drugs that looks more promising (20). These newer agents are based on experimental evidence, tried in controlled studies and aim for global or multi-symptom relief. These include somatostatin analogues, various 5-HT receptor ligands such as Alosetron (diahrrea-predominant IBS), Tegaserod (constipation-predominant IBS) and others. Hypnotherapy and dynamic psychotherapy are also proving useful for certain functional patients, but they tend to be restricted to highly specialized centers. The quest for euthymia is not misdirected for general well being seems a pre-requisite and in equilibrium with a normally functioning and silent gut. William Shakespeare already perceptively noted centuries ago that “unquiet meals make ill digestions”.

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