European Journal of Clinical Investigation (1 987) 17, 189-1 93
Seeking clues for a positive diagnosis of the irritable bowel syndrome
P. VERNIA, G. LATELLA, F. M. MAGLIOCCA, G. MANCUSO* & R. CAPRILLIT, Cattedre di Gastroenterologia, e tAquila and *Istituto di Pediatria, Unversita di Roma, Italy
Received 3 April 1986 and in revised form 27 November 1986
Abstract. Despite its high prevalence the irritable bowel syndrome (IBS) lacks acceptable pathophysio- logical markers and its diagnosis largely depends on the exclusion of underlying organic disease. Systemic acid-base balance, serum electrolytes and the compo- sition of faecal water (electrolytes and organic anions), were studied in thirty-eight diarrhoea1 patients out of a series of ninety-three consecutive IBS patients. Only patients with diarrhoea as the predominant symptom were included in the study to evaluate whether this subgroup could provide the clue for a positive diagno- sis of the syndrome. Serum electrolytes and systemic acid-base balance were within the normal range. Faecal electrolytes were also normal (Na 26.6 & 19.3 SD; K 66.8f28.3; C1 19.1 15.2 mEq 1-I), despite the finding of a moderately increased 24-h faecal output. The K:Na ratio was also within the normal range. These data are in agreement with the lack of systemic changes observed in IBS patients even with profuse or longstanding diarrhoea. Both faecal short chain fatty acids and lactic acid were increased in patients vs. controls, but a considerable overlap with normal values was observed (1 3 1.4 f 62.6 SD vs. 108.5 f 58.3 mEq 1 - I ) . Only lactic acid concentration was signifi- cantly higher than in controls (1.3 f 1.2 vs. 0.5 f 0.2). Despite these findings i t is concluded that the subgroup of IBS patients with diarrhoea also appears to lack a pathophysiological marker and does not provide clues for a positive diagnosis of this syndrome.
Keywords. Irritable bowel syndrome, faeces, fatty acids, volatile.
Introduction The irritable bowel syndrome (IBS) affects 15-30% of the otherwise normal population in western countries [ 1-31 and is the most common disease category seen by gastroenterologists in out-patients [4,5]. Despite the
Correspondence: P. Vernia. MD, Cattedrd di Gastroenterologia ( I ) , 2a Clinica Medica, Universitd di Roma. Policlinico Umberto I, 00100 Roma, Italy.
high prevalence, attempts to identify positive diagnos- tic features [6,7] have so far been unrewarding.
Some symptoms such as abdominal pain preceeding evacuation, abdominal distension, irregularity of bowel pattern, sense of incomplete evacuation and mucus in the stool have consistently been shown to be associated with IBS. However, when these symptoms and simple laboratory findings were evaluated to estimate their relative diagnostic value, the most heavily weighed items were found to be those pathog- nomonic for non-functional diseases . Thus, the diagnosis of IBS still largely depends on the exclusion of underlying organic disease .
The lack of acceptable pathophysiological markers and of a precise definition of the syndrome leads to the inclusion in IBS of patients with varying clinical presentation ranging from spastic colon, scybalous constipation and abdominal pain to atonic colon and painless diarrhoea. A more precise classification of the clinical subgroups within IBS may thus prove useful for understanding this syndrome better.
The present study was focused only on the subgroup of IBS patients in whom the major complaint was diarrhoea, as this is one of the most common symp- toms in IBS, affecting 20-35% of patients [7,10]. Furthermore, since diarrhoea might be expected to induce deviations from the norm in terms of systemic electrolyte and acid-base balance it might provide the clue for a positive diagnosis of IBS.
Patients and methods
Patients The investigation was carried out on thirty-eight
patients in whom the major complaint was diarrhoea, selected from a series of ninety-three IBS attending the out-patient department of the GI Unit of the Univer- sity of Rome, during the period 1982-1984. Diagnosis of IBS was based on a typical longstanding history of abdominal symptoms (diarrhoea, constipation or alternation of the two, hypersecretion of colonic mucus, abdominal pain, flatulence and general lack of subjective well being), normal finding of barium enema
190 P. VERNIA et al.
and upper GI series, pancreas and biliary tract echo- graphy, and fibersigmoidoscopy with biopsies. Nor- mal values for ESR, haemoglobin, WBC, ALT, AST, yGT, alkaline phosphatase, amylase, thyroid hor- mones, serum proteins, urine sediment and stool examination for pathogenic bacteria, parasites and occult blood were also included in the diagnostic criteria.
In this study, diarrhoea was defined as the presence of three or more, liquid or semi-liquid, bowel move- ments per day. Only those IBS patients presenting diarrhoea more than 50% of the time during the month prior to the study were included in the investigation. All patients were in a diarrhoea1 state at the time of the study. They were all on a free diet, which did not include fibre supplements. Patients with known lactose intolerance or who showed a clear benefit from a non- milk diet were not included in the present series. No patient in this series had severe postprandial watery diarrhoea, nor showed high faecal pH associated with a reversed faecal K:Na ratio [ I I], thus ruling out the presence of patients with idiopathic bile salt catharsis
Each patient was interviewed concerning the pres- ence or absence of abdominal pain, straining at stools, mucus in the stool, abdominal distension and flatu- lence, looser stools with pain onset, irregular bowel pattern or persistent diarrhoea.
Patients were instructed to collect faeces over a 24-h period in preweighed plastic containers. Thiomersal (15 ml, 1 : 10 000 solution) was added immediately after the first evacuation to minimize bacterial over- growth. Faeces were brought to the laboratory at the end of the 24-h period and processed immediately or frozen at - 12C for 1-5 days. Upon completion of the 24-h collection, arterial and venous blood samples were drawn in all patients in order to measure systemic acid-base balance and the serum electrolyte concen- trations. Informed consent was obtained in all cases.
Analytical methods Arterial blood pH and pCO2 were measured by
means of a blood gas analyser (Radiometer Mod. 25, Copenhagen, Denmark). Bicarbonate concentration was calculated using the Henderson-Hasselbach equa- tion.
Faecal samples were weighed, and faecal water extracted using an in-riitro dialysis method, as de- scribed elsewhere [ 131.
Sodium and potassium were analysed in blood and faecal water by flame photometry; chloride by poten- tiometric titration. Short chain fatty acids (SCFA) were extracted in ether from the faecal water of eighteen patients and twenty-nine normal controls using the procedure described by Holdeman et al. [I41 and analysed by means of a Varian Model 3700 thermal conductivity gas-liquid chromatograph employing Supelco (SP 1000, 1 % H3P04, 100-120 mesh packed) columns. Solution of volatile SCFA at
10 mEq 1 - ' were made from 90-98% pure commercial preparations (Gold Label, Aldrich Chemical Co., Milwaukee, WS) of the following acids: acetic, propio- nic, isobutyric, isovaleric, valeric and caproic. The extracts of the 10 mM solution ofeach SCFA submitted to the same procedure as faecal water samples were used as standards. D- and L-lactic acid were measured with an enzymatic method using specific L- and D- lactate dehydrogenase [ 151. The concentration of fae- cal water electrolytes in IBS patients was compared to that in fifty normal subjects. Control subjects were selected from healthy volunteers with normal bowel habits, who did not experience adverse abdominal symptoms. They were all on a free diet, which did not include fibre supplements. Sex incidence and age were comparable in the control and patient group (38.2 f 12 SD vs. 2 & 14 years; female : male ratio 1.8 and 2.1 in the control and in the patient group, respectively).
In order to exclude the possibility that some clues might become apparent only in some subgroups of patients, data from IBS patients were analysed in relation to the presence or absence of the individual symptoms sought during the interview, and of the 24-h faecal weight. Faeces of 225 g per day were considered as the upper normal limit being in excess of the mean value plus one standard deviation of the fifty control subjects.
Stat istical unalysis Data were analysed using the Mann-Whitney test.
The linear regression test was used for correlation analysis.
Systemic. acid-base balance and serum electrolytes The mean values for systemic acid-base balance
were within the normal range in the present series of patients (pH 7.41 f0.03 SD; pC0236.1 k 8.2 SD mmHg; HC03- 23.3 f 2.4 SD mEq 1 - I ) . Four patients showed slight respiratory alkalosis, which may be attributed to hyperventilation due to the arterial blood sampling. One patient showed mild metabolic acidosis
Table 1. Faecal water electrolytes in irritable bowel syn- drome and normal controls
24-h weight* Nd K CI K Nd
IBS 224 266 668 19 I 4 8 (11=38) +I31 0 t 5 1 9 3 i 2 8 3 + I 5 2 k5X P 0005 N S NS NS NS Controls I47 219 611 1 4 0 5 2 01-50) i 8 0 6 1 1 7 7 + 2 6 6 * I 0 4 i 4 8
~~ - ~- .. ~ -~
* Twenty-four hour faecal weight expressed in g 24 h - I
t Mean values+SD. electrolyte concentrations expressed in mEq I I.