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Functional dyspepsia: from motility to sensitivity
DIGEST LIUER DIS 2000;32lSUPPL.3kS255-7
Functional dyspepsia: to sensitivity F. Mearin
Digest
Liver
4is 2000;32ISuppl.31:S255-7
Key words: fatty food; wceral hypersensitivity
gastric
hypomotility;
From:
Digestive System Research Unit, Hospital General L/all dHebron. Barcelona, Spain. Address
fer correependeece:
Dr. F. Maarin, Digestive Research System Unit, Hospital General Vail d’Hebron, Barcelona, Spain.
from
motility
For many centuries, western medicine had a purely organicist basis. Understanding of anatomy and its alterations was the cornerstone of disease diagnosis, to such an extent that the presence of anatomical lesions was indicative of disease and, their absence, of health. Pathophysiological concepts and measurement of the functions of different organs and systems were introduced later; thus, possible disorders of function (which actually corresponded to the so-called functional disorders) were added to anatomical disorders. Nevertheless, disturbances often do exist, without evident alteration of anatomy or function. For many years, these subjects were considered as not suffering from any disease and that their complaints were due exclusively to psychological disorders, if not to genuine medical fraud. This absolute separation between what is organic, what is functional and what is psychological has caused great difficulties in the understanding of many disorders and has hampered research on this type of disturbances. These three facets cannot be considered as distinct, since the outcome of the disorders depends on all three. Furthermore, what today is considered as purely psychological (e.g., visceral hypersensitivity) may result from currently unknown anatomical (neuronal) changes or functional (neurofunctional) alterations. Functional dyspepsia is a clear example of how the division between what is seen, what is measured and what is felt has hampered the understanding of this syndrome. Dyspeptic disorders, without any organic correlate (normal endoscopy), were for a long time considered of little importance. Later, digestive motility measurement opened new doors to the understanding of this syndrome; if gastric hypomotility on manometry or emptying delay on scintigraphy were present, there appeared to be an explanation for the disorders referred to by the patient. However, later studies showed the existence of a poor correlation between gastrointestinal function alterations and the clinical manifestations described by the patient. It is indisputable that modern medicine should not contemplate only what physicians are able to see or measure, but also the information provided by the patient. Efforts must be directed not only to curing the organic alterations or restoring the altered function, but to relieving the patient’s symptoms. What is felt is just as important, or more, as what is seen or measured (Fig. 1).
Visceral sensitivity in patients withj.unctional
dyspepsia
After many years, there seems to be some agreement over the fact that dyspeptic symptoms (and other digestive or non-digestive disorders) may be due to anatomical alterations (e.g., duodenal ulcer), functional disorders (such as gastric hypomotility or impaired fundic accommodation) or perception alterations (visceral hypersensitivity). An increase in intragastric perception to mechanical stimuli has been described. Thus, progressive distension of the stomach produced symptoms in dyspeptic subjects at pressures hardly noticed by healthy volunteers ’ (Fig. 2). Similar results were obtained when distensions of the stomach were achieved by increasing volume instead of pressure 2 j. Nevertheless, it should be borne in mind that the increase in sensitivity to
5255
Functional dyspepsia: from motility to sensitivity
Perceptive
gastric distension occurs when inter-group comparisons are made (dyspepsia vs healthy controls), but may not be present in all patients with functional dyspepsia”. It would be illogical to think that, in a syndrome as heterogeneous as dyspepsia, a pathophysiological finding would be present in all cases. The possible topographical specificity of this hypersensitivity should also be emphasized. It seems obvious that the increase in perception is limited to visceral sensitivity and that somatic perception is normal, or even decreased ’ 5. The question of whether the hypersensitive region is specific to each functional disorder is controversial. Some authors have reported that patients with functional dyspepsia are hypersensitive to stomach distension but not to duodenal distension 5. In contrast, in other studies duodenal distension also induced greater discomfort in dyspeptic subjects than in healthy controls 6. Furthermore, it has been suggested that the visceral hypersensitivity present in functional dyspepsia is not topographically specific but generalized to the whole digestive tract, since both oesophageal distension and rectal distension manifested the increase in perception 7. These differences might be due to different patient selection criteria and, particularly, to whether cases in which functional dyspepsia is accompanied by manifestations of other functional disorders (a common occurrence) are included or not. However, the symptomatic response to small bowel distension is of little value in differentiating between functional dyspepsia and irritable bowel syndrome, since it is increased equally in both cases, and also when both coincide in the same patient *. On the other hand, it is peculiar that the capacity of visceral sensitivity - evaluated during gastric distension - to distinguish between functional and organic dyspepsia is greater than symptomatic or psychological assessment 9.
disease
Fig. 1. Proposed model of disease.
Gastric distension
Increase in digestive sensitivity to chemical patients with ,functional dyspepsia
J MDP+2
+4
Intragastric
6
+8
+lO
pressure (mmHg1
Fig. 2. Dyspeptic patients are hypersensitive to intragastric distension n Dyspeptic patients q Healthy volunteers.
S256
stimuli in
As mentioned previously, dyspeptic patients often associate their symptoms with ingestion. However, clinical observations indicate that patients relate their symptoms not only to the amount of food consumed but also to the type. Patients usually state that the discomfort appears or worsens with fatty food, but for decades physicians have discounted this notion. Studies showing the existence of a symptomatic hypersensitivity to lipids in functional dyspepsia patients are relatively recent, although Taggart and Billington studied this possibility in 1966 lo; however, they were unable to demonstrate a correlation between the consumption of fatty food and induction of dyspeptic symptoms. More recently, it has been demonstrated that intraduo-
L Mearin
denal lipid infusion, in quantities well tolerated by healthy volunteers, may induce nausea and vomiting in patients with functional dyspepsia ‘l; furthermore, intraduodenal lipids increase gastric sensitivity to distension I*. This sensitivity appears to be specific for lipids, since it is not produced with equicaloric amounts of carbohydrates I3. The mechanism of symptom production is not related to an alteration in gallbladder contraction, as its emptying in response to intestinal lipid perfusion is normal 14. Intragastric lipid instillation may also be used to study visceral sensitivity to chemical stimuli in different clinical interactions, and to assess the possible efficacy of certain drugs Is.
References ’ Mearin F, Cucala M, Azpiroz F, Malagelada J-R. The origin of symptoms on the brain-gut axis in functional dyspepsia. Gastroenterology 1991;101:999-1006. z Bradette M, Pare P, Douville, P, Morin A. Visceral perception in health and functional dyspepsia. Crossover study of gastric distension with placebo and domperidone. Dig Dis Sci 1991;36:52-8. ’ Lemann M, Dederding JP, Flourie B, Franchisseur C, Rambaud JC, Jian R. Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Dig Dis Sci 1991;36:1249-54. 4 Klatt S, Pieramico 0, Guethner C, Glasbrenner B, Beckh K, Adler G. Gastric hypersensitivity in nonulcer dyspepsia: An inconsistent finding. Dig Dis Sci 1997;42:720-3. 5 Coffin B, Azpiroz F, Guarner F, Malagelada J-R. Selective gastric
hypersensitivity and reflex hyporeactivity in functional dyspepsia. Gastroenterology 1994; 107: 1345-5 1. 6 Holtmann G, Talley NJ, Goebell H. Association between H. pylori, duodenal mechanosensory thresholds, and small intestinal motility in chronic unexplained dyspepsia. Dig Dis Sci 1996;41:1285-91. ’ Trimble KC, Farouk R, Pryde A, Douglas S, Heading RC. Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995;40:1607-13. * Holtmann G, Goebell H, Talley NJ. Functional dyspepsia and irritable bowel syndrome: Is there a common pathophysiological basis? Am J Gastroenterol 1997;92:954-9. 9 Mertz H, Fullerton S, Naliboff B, Mayer EA. Symptoms and visceral perception in severe functional and organic dyspepsia. Gut 1998;42:814-22. lo Taggart D, Billington BP. Fatty foods and dyspepsia. Lancet 1966;ii:465-6. I’ Castro A, Mearin F, Romero I, Torn& M, Varas MJ, Malagelada, J-R. Symptomatic hypersensitivity to intragastric lipid infusion and i.v. CCK in functional dyspepsia: Role of gastric accommodation and gallbladder emptying. Gastroenterology 1997;112:A709. ” Barbera R, Feinle C, Read NW. Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia. Eur J Gastroenterol Hepatol 1995;ll: 1051-7. ” Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci 1995;8:1636-41. ‘? Castro A, Mearin F, Romero I, Tome M, Varas MJ, Malagelada JR. Vaciamiento de la vesfcula biliar en 10s pacientes con dispepsia funcional. Rev Esp Enf Digest 1997;89:A35. ” Castro A, Mearin F, Larish J, Malagelada J-R. Gastric relaxatory and emetic sequences in healthy humans: Central versus peripheral induction. Submitted for publication.
S257
Functional dyspepsia: to sensitivity F. Mearin
Digest
Liver
4is 2000;32ISuppl.31:S255-7
Key words: fatty food; wceral hypersensitivity
gastric
hypomotility;
From:
Digestive System Research Unit, Hospital General L/all dHebron. Barcelona, Spain. Address
fer correependeece:
Dr. F. Maarin, Digestive Research System Unit, Hospital General Vail d’Hebron, Barcelona, Spain.
from
motility
For many centuries, western medicine had a purely organicist basis. Understanding of anatomy and its alterations was the cornerstone of disease diagnosis, to such an extent that the presence of anatomical lesions was indicative of disease and, their absence, of health. Pathophysiological concepts and measurement of the functions of different organs and systems were introduced later; thus, possible disorders of function (which actually corresponded to the so-called functional disorders) were added to anatomical disorders. Nevertheless, disturbances often do exist, without evident alteration of anatomy or function. For many years, these subjects were considered as not suffering from any disease and that their complaints were due exclusively to psychological disorders, if not to genuine medical fraud. This absolute separation between what is organic, what is functional and what is psychological has caused great difficulties in the understanding of many disorders and has hampered research on this type of disturbances. These three facets cannot be considered as distinct, since the outcome of the disorders depends on all three. Furthermore, what today is considered as purely psychological (e.g., visceral hypersensitivity) may result from currently unknown anatomical (neuronal) changes or functional (neurofunctional) alterations. Functional dyspepsia is a clear example of how the division between what is seen, what is measured and what is felt has hampered the understanding of this syndrome. Dyspeptic disorders, without any organic correlate (normal endoscopy), were for a long time considered of little importance. Later, digestive motility measurement opened new doors to the understanding of this syndrome; if gastric hypomotility on manometry or emptying delay on scintigraphy were present, there appeared to be an explanation for the disorders referred to by the patient. However, later studies showed the existence of a poor correlation between gastrointestinal function alterations and the clinical manifestations described by the patient. It is indisputable that modern medicine should not contemplate only what physicians are able to see or measure, but also the information provided by the patient. Efforts must be directed not only to curing the organic alterations or restoring the altered function, but to relieving the patient’s symptoms. What is felt is just as important, or more, as what is seen or measured (Fig. 1).
Visceral sensitivity in patients withj.unctional
dyspepsia
After many years, there seems to be some agreement over the fact that dyspeptic symptoms (and other digestive or non-digestive disorders) may be due to anatomical alterations (e.g., duodenal ulcer), functional disorders (such as gastric hypomotility or impaired fundic accommodation) or perception alterations (visceral hypersensitivity). An increase in intragastric perception to mechanical stimuli has been described. Thus, progressive distension of the stomach produced symptoms in dyspeptic subjects at pressures hardly noticed by healthy volunteers ’ (Fig. 2). Similar results were obtained when distensions of the stomach were achieved by increasing volume instead of pressure 2 j. Nevertheless, it should be borne in mind that the increase in sensitivity to
5255
Functional dyspepsia: from motility to sensitivity
Perceptive
gastric distension occurs when inter-group comparisons are made (dyspepsia vs healthy controls), but may not be present in all patients with functional dyspepsia”. It would be illogical to think that, in a syndrome as heterogeneous as dyspepsia, a pathophysiological finding would be present in all cases. The possible topographical specificity of this hypersensitivity should also be emphasized. It seems obvious that the increase in perception is limited to visceral sensitivity and that somatic perception is normal, or even decreased ’ 5. The question of whether the hypersensitive region is specific to each functional disorder is controversial. Some authors have reported that patients with functional dyspepsia are hypersensitive to stomach distension but not to duodenal distension 5. In contrast, in other studies duodenal distension also induced greater discomfort in dyspeptic subjects than in healthy controls 6. Furthermore, it has been suggested that the visceral hypersensitivity present in functional dyspepsia is not topographically specific but generalized to the whole digestive tract, since both oesophageal distension and rectal distension manifested the increase in perception 7. These differences might be due to different patient selection criteria and, particularly, to whether cases in which functional dyspepsia is accompanied by manifestations of other functional disorders (a common occurrence) are included or not. However, the symptomatic response to small bowel distension is of little value in differentiating between functional dyspepsia and irritable bowel syndrome, since it is increased equally in both cases, and also when both coincide in the same patient *. On the other hand, it is peculiar that the capacity of visceral sensitivity - evaluated during gastric distension - to distinguish between functional and organic dyspepsia is greater than symptomatic or psychological assessment 9.
disease
Fig. 1. Proposed model of disease.
Gastric distension
Increase in digestive sensitivity to chemical patients with ,functional dyspepsia
J MDP+2
+4
Intragastric
6
+8
+lO
pressure (mmHg1
Fig. 2. Dyspeptic patients are hypersensitive to intragastric distension n Dyspeptic patients q Healthy volunteers.
S256
stimuli in
As mentioned previously, dyspeptic patients often associate their symptoms with ingestion. However, clinical observations indicate that patients relate their symptoms not only to the amount of food consumed but also to the type. Patients usually state that the discomfort appears or worsens with fatty food, but for decades physicians have discounted this notion. Studies showing the existence of a symptomatic hypersensitivity to lipids in functional dyspepsia patients are relatively recent, although Taggart and Billington studied this possibility in 1966 lo; however, they were unable to demonstrate a correlation between the consumption of fatty food and induction of dyspeptic symptoms. More recently, it has been demonstrated that intraduo-
L Mearin
denal lipid infusion, in quantities well tolerated by healthy volunteers, may induce nausea and vomiting in patients with functional dyspepsia ‘l; furthermore, intraduodenal lipids increase gastric sensitivity to distension I*. This sensitivity appears to be specific for lipids, since it is not produced with equicaloric amounts of carbohydrates I3. The mechanism of symptom production is not related to an alteration in gallbladder contraction, as its emptying in response to intestinal lipid perfusion is normal 14. Intragastric lipid instillation may also be used to study visceral sensitivity to chemical stimuli in different clinical interactions, and to assess the possible efficacy of certain drugs Is.
References ’ Mearin F, Cucala M, Azpiroz F, Malagelada J-R. The origin of symptoms on the brain-gut axis in functional dyspepsia. Gastroenterology 1991;101:999-1006. z Bradette M, Pare P, Douville, P, Morin A. Visceral perception in health and functional dyspepsia. Crossover study of gastric distension with placebo and domperidone. Dig Dis Sci 1991;36:52-8. ’ Lemann M, Dederding JP, Flourie B, Franchisseur C, Rambaud JC, Jian R. Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Dig Dis Sci 1991;36:1249-54. 4 Klatt S, Pieramico 0, Guethner C, Glasbrenner B, Beckh K, Adler G. Gastric hypersensitivity in nonulcer dyspepsia: An inconsistent finding. Dig Dis Sci 1997;42:720-3. 5 Coffin B, Azpiroz F, Guarner F, Malagelada J-R. Selective gastric
hypersensitivity and reflex hyporeactivity in functional dyspepsia. Gastroenterology 1994; 107: 1345-5 1. 6 Holtmann G, Talley NJ, Goebell H. Association between H. pylori, duodenal mechanosensory thresholds, and small intestinal motility in chronic unexplained dyspepsia. Dig Dis Sci 1996;41:1285-91. ’ Trimble KC, Farouk R, Pryde A, Douglas S, Heading RC. Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995;40:1607-13. * Holtmann G, Goebell H, Talley NJ. Functional dyspepsia and irritable bowel syndrome: Is there a common pathophysiological basis? Am J Gastroenterol 1997;92:954-9. 9 Mertz H, Fullerton S, Naliboff B, Mayer EA. Symptoms and visceral perception in severe functional and organic dyspepsia. Gut 1998;42:814-22. lo Taggart D, Billington BP. Fatty foods and dyspepsia. Lancet 1966;ii:465-6. I’ Castro A, Mearin F, Romero I, Torn& M, Varas MJ, Malagelada, J-R. Symptomatic hypersensitivity to intragastric lipid infusion and i.v. CCK in functional dyspepsia: Role of gastric accommodation and gallbladder emptying. Gastroenterology 1997;112:A709. ” Barbera R, Feinle C, Read NW. Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia. Eur J Gastroenterol Hepatol 1995;ll: 1051-7. ” Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci 1995;8:1636-41. ‘? Castro A, Mearin F, Romero I, Tome M, Varas MJ, Malagelada JR. Vaciamiento de la vesfcula biliar en 10s pacientes con dispepsia funcional. Rev Esp Enf Digest 1997;89:A35. ” Castro A, Mearin F, Larish J, Malagelada J-R. Gastric relaxatory and emetic sequences in healthy humans: Central versus peripheral induction. Submitted for publication.
S257