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Transit through the proximal colon influences stool weight in the irritable bowel syndrome
GASTROENTEROLOGY
1992;102:102-108
Transit Through the Proximal Colon Influences Stool Weight in the Irritable Bowel Syndrome MARIO VASSALLO, MICHAEL CAMILLERI, SIDNEY MANUEL L. BROWN, NICHOLAS J. CHAPMAN, and GEORGE M. THOMFORDE
F. PHILLIPS,
Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota
The inherent variability of symptoms and motor abnormalities in patients with the irritable bowel syndrome has hampered the demonstration of motor abnormalities that could underlie symptoms. The aim in the current study was to evaluate whether altered regional capacitance or transit of solid residue through the unprepared human gut were factors in the diarrhea of patients with the irritable bowel syndrome. In 10 such patients and in 5 healthy controls, gastric and smal1 bowel transits were evaluated scintigraphically by means of a mixed meal containing gsmTc-labeled resin pellets. Regional colonic transit was quantitated by “‘Inlabeled pellets delivered to the ileocecal region by a pH-sensitive, methacrylate-coated capsule. Symptomatic patients did not have significantly altered gastric or smal1 bowel transits, but colonic transit was accelerated in 7 of 10 persons with the irritable bowel syndrome (P < O.OZ),in the proximal colon of five patients and in the left colon of two patients. The 24hour stool weight was positively correlated with the rate at which solid residue emptied from the ascending and transverse colons (r = 0.78; P c 0.01). There was also an inverse relationship between emptying rates and maxima1 volumes accommodated by the proximal colon (r = -0.58; P < O.O5),although the maximum volume of the proximal colon was not significantly different in patients and healthy subjects. Thus, accelerated transit through the proximal colon is a factor in the pathophysiology of the irritable bowel syndrome and influences the stool weight of such patients. The capacitance of the proximal colon presumably influences its storage capacity and, hence, the rate at which it empties.
abnormalities,4*5 but the episodic nature of symptoms has hindered the identification of motor disorders that might explain the clinical features.‘,’ In addition to abnormal manometric patterns,4’5 rapid transit through the smal1 bowela or whole gut8sQhas been described in patients with IBS and diarrhea, and ileal emptying was delayed” in patients who complained of bloating. A variety of methods has been used to measure gastrointestinal transit, but no report has described movement of the same marker through each region of the gut in IBS. However, regional differences are wel1 established; the proximal and distal colon respond differently to many stimuli, including stretch,l’ electrical field stimulation,” meals,13 and pharmacological doses of cholinergic agonists and serotonin.14 Therefore, it is conceivable that colonic function may be altered selectively by disease and that overall assessments of whole gut or whole colon transit could overlook important regional abnormalities. Indeed, using novel, noninvasive, scintigraphic methods to measure transit through the colon, Proano et a1.15showed storage in the ascending and transverse colons of healthy humans, whereas the left colon acted chiefly as a conduit. Our hypothesis was that disturbed storage in the proximal colon, not previously reported in IBS, would be demonstrable by noninvasive radioscintigraphic methods. Our aims were to evaluate transit of solid residue through the entire, unprepared gut in patients with diarrhea-predominant IBS and to assess the relationships among colonic transit, large bowel capacitance, and stool weights. Materials and Methods Patients and Healthy
he irritable bowel syndrome (IBS), the most common reason for referral of patients to gastroenterologists,‘~2 is characterized by abdominal pain and an altered, often unpredictable, bowel habit. Subsets of patients may have different manometric
T
Controls
Ten patients (7 women and 3 men; mean age, 39 years; age range, 25-55 years) and 5 healthy subjects (3 0 1992 by the American
Gastroenterological
0016-5085/92/$3.00
Association
TOTAL GUT TRANSIT IN IBS WITH DIARRHEA 103
January 1992
men and 2 women; mean age, 34 years; age range, 24-57 years) were recruited for these studies, which were approved by the Mayo Clinic Institutional Review Board and Radiation Control Committee. Al1 participants gave signed informed consent. Women were studied during the follicular phase of the menstrual cycle and had a negative plasma @-human chorionic gonadotrophin pregnancy test within 48 hours of the procedures. Patients were selected according to the symptomatic criteria of Manning et aL3 and an international working team of experts in the field.‘” Symptoms were present for at least 6 months, with at least three bowel movements per day for 22 days most weeks. Investigations directed toward excluding other conditions included hematology and chemistry group studies; stool examinations for excess fat, leucocytes, parasites, and occult blood; colonoscopy or colon radiograph examination and flexible sigmoidoscopy; and colonic biopsy. None of these investigations showed abnormalities. Experimental
Procedure
After an overnight fast, participants were admitted to the Clinical Research Center on the morning of the study. They ingested a gelatin capsule coated with one layer of the pH-sensitive polymer methacrylate, containing 0.8 g of Amberlite IR-120 Plus resin pellets (average diameter, 1 mm) labeled with up to 0.25 mCi of [“‘In]Cl, (Amersham, Arlington Heights, IL).15 External radioactive markers were placed over the xiphisternum and both anterior superior iliac spines. By comparing the position of the capsule with these landmarks on stans taken every 10 minutes we were able to determine when the capsule passed into the smal1 bowel. A breakfast consisting of scrambled eggs, whole wheat bread, and skimmed milk (35% protein, 52% carbohydrate, and 13% fat; 219 kcal) was ingested after the capsule was seen to leave the stomach. Two millicuries of ggmTc-labeled Amberlite 410 resin pellets (average diameter, 1 mm) were mixed with the eggs, which were cooked to a firm consistency to provide a solid medium with which to assess gastric emptying and smal1 bowel transit. The radiolabel was placed on the resin pellets rather than the meal itself to ensure that our measurements of smal1 bowel transit reflected the passage of undigestible solid residue through this region. Previous studies using similar methods showed that >90% of the radiolabel was stil1 bound to pellets after transit through the entire gut.17 Four hours after breakfast, a standardized nonradiolabeled lunch was eaten (chicken, potato, pudding, and water; 18% protein, 47% carbohydrate, and 35% fat; 536 kcal). Similarly, al1 subjects ate a standardized dinner (steak, salad, and dessert; 21% protein, 49% carbohydrate, and 30% fat; 561 kcal) 8 hours after the radiolabeled breakfast. Meals were not regulated after the first day. Gamma camera imaging. Imaging started immediately after ingestion of the radiolabeled breakfast and was performed with a large field-of-view gamma camera with a medium-energy, parallel-hole collimator (GE Starcam; Genera1 Electric, Milwaukee, WI). Anterior and posterior images were acquired with the subjects erect. The radioac-
tive markers over bony landmarks facilitated consistent positioning of the subjects and served as reference points for delineation of colonic regions of interest. Images were obtained at regular intervals for the first 12 hours (every 10 minutes after each meal and at 15-60-minute intervals according to a standard protocol at other times). Between images, participants were allowed to relax in a comfortable chair. Further images were acquired 24 and 36 hours after the initial labeled meal. The total body radiation exposure with these isotopes was 60 mrad. Quantitation of radioactivity in gastric and colonic regions. Two-minute acquisitions were used for each image during the first 12 hours and 5-minute acquisitions subsequently. The data were stored on an on-line computer (GE Starcam) for later analysis. Two energy windows of acquisition were used, 140 keV (*ZO% window) for ggmTc counts (labeled meal, for gastric emptying and smal1 bowel transit) and 245 keV (tZO% window) for “‘In counts (for colonic transit). Using variable regions of interest, radioactivity was quantitated in the stomach and ascending co10n17 for g9mTc and in four regions of the colon15 for “‘In (ascending, transverse, descending, and rectosigmoid). Geometrie means of the counts obtained from anterior and posterior images of each region were corrected for radionuclide decay and the downscatter of “‘In into the ggmTc window. Quantitation of radioactivity in stool. Stools were collected for 2 days, and the time of each bowel movement was recorded by the subjects. Each stool sample was weighed, and radioactivity was measured for “‘In counts in a Capintech Radioisotope Dose Calibrator (CRC-5; Capintech, Montvale, NJ). Counts were corrected for decay using standard tables. Data Analysis The weight and timing Stool weight and frequency. of each stool were recorded during the first 24 hours after ingestion of the radiolabeled capsule to calculate the 24hour weight and frequency. Scintigraphic colonic transit data. Overall colonic transit of radiolabeled solid residue was assessed in two ways. First, the percentages of counts in each colonic region at 12 and 36 hours were compared for patients and healthy controls using nonparametric Wilcoxon’s rank sum test, because values for emptying from the ascending colon were not normally distributed in patients with IBS. Significante was assessed at a = 0.05. A second assessment of overall colonic transit was the geometrie center, i.e., the weighted average of proportions of counts in each of the four colonic regions and in the stool at 4, 12, 24, and 36 hours.” For this analysis, the following regions were designated by numbers 1-5, respectively: ascending, transverse, descending, and rectosigmoid colons and stool. At any time point, a low geometrie center implied that most radiolabel was closer to the cecum; a higher geometrie center implied that most radiolabel was closer to the stool. Overall colonic transit of each patient was compared with data for healthy controls. In view of the storage function of ascending and transverse colons,” we combined the scintigraphic data from
104 VASSALLO ET AL.
GASTROENTEROLOGY Vol. 102, No. 1
these two regions into one value. Time-activity curves were plotted for health and IBS for 36 hours after release into the colon of al1 “‘In radiolabel contained within the methacrylate-coated capsule. The time-activity plot for each participant was also summarized by a slope that expressed the hourly fractional emptying rate of isotope from the proximal (ascending and transverse) colon, expressed as a percentage of the maximum counts delivered to the ascending colon by the methacrylate-coated capsule. Proximal colonic volume. The volumes of the ascending and transverse colons were estimated by a previously validated method. 1g*20 The stans selected for the calculations of maxima1 proximal colonic volume were those that showed the greatest surface area of the ascending and transverse regions. The volume of these regions was calculated as aA2/4L, where A is the surface area of the combined regions, and L is the total length of the two regions, both measured in pixels (1 pixel = 3.2 mm) and subsequently converted to millimeters. Gastric emptying, smal1 bowel transit, and ileocolonic jílling. Gastric emptying was summarized as in previous studiesI by the duration of the lag phase and by the fractional emptying rate, expressed as the slope of the post-lag phase as determined by linear regression analysis. The tlO% for smal1 bowel transit (i.e., time for 10% of the radiolabel to traverse the smal1 bowel) was measured by subtracting the time for 10% gastric emptying from the time for 10% colonic filling.‘l The rate of ileocolonic filling was expressed as the percentage of the radiolabel ingested with the meal that was transferred to the colon per minute; these rates were summarized as the slopes of the colonic filling curves. Statistical sample
Analysis
Statistical evaluations were performed by twot test or Wilcoxon’s rank sum tests for normally
Table 1. Individual
24-Hour Data on Stook, Proximal Stool wt
Wz
h)
distributed and nonparametric data, respectively. Unless otherwise stated, comparisons were made between patients with IBS and the five healthy controls evaluated prospectively in the present study. Comparison of stool frequency between IBS and health was by a Yates’ corrected x2 test; in this test, we compared the number of subjects in each group with one or less or more than one bowel movement per day. Interquartile data from healthy subjects studied previously in our laboratory’5~‘7~2’~22 by an identical method are also included in the tables.
Results Stool Weight
Mean 24-hour stool weights in the IBS group (130 + 20 g) were not different from those of healthy subjects (84 f 25 g; P > 0.10). There was a significant differente (P < 0.05) between the 24-hour stool frequency in IBS (2.2 f 0.4) and health (1 + 0); however, one patient with IBS passed no stools during the 48hour study. Individual subjects’ data are shown in Table 1.
Colonic Transit Proportion oj’radiolabel in different colonic regions at 12 and 36 hours. There was no significant differente between health and IBS in the proportional distribution of solid radiolabel through the four colonic regions and the stool at 12 hours (data not shown). However, at 36 hours (Figure l), patients with IBS had significantly less radiolabel in the transverse (P < 0.05) and descending colons (P < 0.01) and significantly more radiolabel in stool (P < 0.05). Representative examples of time activity
Colonic Transit,
Stool frequency (no./24 h)
and Frequency
and Volume Calculated proximal colon volume (mL)
Proximal colon emptying ratea (%/h)
Healthy subjects 1 2 3 4 5 IBS patients 1 2 3 4 5 6 7 8 9 10 Laboratory control interquartile range ' Emptying rate calculated
40 63 67 67 183
1 1 1 1 1
556 590 406 1202 397
1.37 0.02 1.45 0.25 2.53
0 68 70 115 120 128 132 154 232 285
0 2 4 1 1 2 3 2 4 3
717 816 544 602 454 409 387 697 308 266
1.53 0.68 2.26 4.08 3.34 2.50 2.60 3.83 3.33 5.60 0.51-2.53
during 36 hours.
January
TOTAL
1992
50 s ‘$n L.L 8
25
Ascending
Transverse
Descending
Rectosigmoid
SIOOI
Region Figure 1. Proportion of radiolabel in different colonic regions at 36 hours in healthy and IB!3groups. Note the smal1 proportion of counts in the transverse and descending regions and the greater proportion in stool (*P < 0.05) in the IBS group.
GLJT TRANSIT
IN IBS WITH DIARRHEA
105
h in IBS vs. 1.1% + 0.5%/h in health; P = 0.02). Representative examples of proximal colon emptying curves in health and IBS are shown in Figure 3. Of the seven IBS patients with accelerated overall colonic transit, as judged by the 36-hour geometrie centers (Table 2), five also had rapid emptying of the proximal colon. In the remaining two patients (patients 3 and 7 in Table 1) overall transit was accelerated, despite normal emptying of the proximal colon. This finding implies that transit through the left colon was fast. There was a significant positive correlation (Figure 4) between emptying of the proximal colon and 24hour stool weight (r = 0.80, P < 0.01 for IBS; r = 0.78, P < 0.01 for al1 subjects studied). In contrast, there was no correlation between emptying rate of the proximal colon and 24-hour stool frequency. ProximaJ CoJonic Volume
curves through the five regions of interest in health and disease are shown in Figure 2. Overall colonic transit by geometrie center. The weighted average or geometrie center of counts at 4, 12, 24, and 36 hours (Table 2) reflected the proportional distribution of isotope in the colonic regions. There was no significant differente between health and IBS at 4 and 12 hours. However, the geometric centers at 24 and 36 hours differed for IBS and health (P < 0.05). Three patients (1, 2, and 6) had normal overall colonic transit. Emptying of the ascending and transverse coJons. Table 1 shows the fractional emptying rates of the proximal colon for each individual. The fractional emptying rate of the proximal colon was faster in the whole IBS group than in health (3.0% f O.4%/
There was no significant differente in the calculated maximum volume of the combined ascending and transverse colons in IBS (520 + 59 mL) and health (630 f 148 mL; P > 0.10). However, there were inverse relationships (Figure 5) between proximal colonic emptying rate and colonic volume in patients with IBS (r = -0.66; P < 0.05) and in al1 persons studied (r = -0.58; P = 0.023). Gastric Emptying, CoJonic FiJJing
SmaJJ BoweJ Transit,
and
Gastric emptying (lag times and fractional emptying rates) was not significantly different in IBS (Table 3); however, in four patients, gastric fractional emptying rates were <0.2%/min (normal range in
lYY!kl B
-
Figure 2. Representative examples of time-activity curves showing transit through different colonic regions in a control (number 3) and patient with IBS (number 4). Note the rapid regional emptying in the patient with IBS and diarrhea. (A)Ascendlng, (B)transverse, (C) descending, and (0) rectosigmoid colons; (E) stool.
Control
IBS
100
C
80
%
D
z
20 0 L!x 0
12
24
36
0
12
24
Hours
36
0
12
24
36
106
GASTROENTEROLOGY Vol. 102, No. 1
VASSALLO ET AL.
Table 2. Geometrie Center ofkotope
6r
in Colon at 4, 32, 24,
and 36 Hours 12
4h
h
24 h
36 h
c
Healthy subjects 1
2 3 4 5 Mean SEM IBS patients 1
2 3 4 5 6 7 8 9 10 Mean SEM P vs. control Laboratory control interquartile range
1.17 1.10 1.31 1.27 1.64 1.30 0.09
1.17 1.48 1.41 1.30 1.72 1.42 0.09
1.84 2.01 2.02 1.89 1.95 1.94 0.03
2.32 2.46 2.09 3.17 2.46 0.19
2.29
'S a E
4
Q>
3
0
Health
0
IBS
;
:i’--
ó s
2
3
E ‘E
r=0.70
1 ,o
0
1.34 1.05 1.54 1.85 1.61 1.09 1.55 1.35 1.29 3.84 1.65 0.25 >O.l
1.64 1.06 1.65 2.35 1.86 1.58 1.68 1.40 1.70 3.98 1.89 0.25 >O.l
2.00 1.34 2.51 4.40 3.51 2.99 3.17 4.68 3.78 4.58 3.30 0.35 <0.05
2.49 2.08 4.64 4.30 3.46 3.00 4.85 4.82 3.93 4.79 3.83 0.33 <0.05
1-1.12
1.12-2.12
1.84-3.96
2.28-3.96
P=O.@m
0
2 n
0
50
I
I
I
I
I
100
150
200
250
300
24-hr stool weight, g Figure 4. Correlation plot between fractional emptying rate of the proximal colon and 24-hour stool weight in healthy and IBS groups.
The slopes of the ileocolonic filling curves were not significantly different (P > 0.50) in IBS (0.27% f 0.05%/min) and in healthy subjects (0.33% + O.ll%/min). Discussion
our laboratory, 0.27%-0,5%/min), and in one patient it was >0.5%/min. Smal1 bowel transit (tlO%) was not significantly different in the whole IBS group and healthy controls (Table 3). Individuals with rapid gastric emptying also had rapid smal1 bowel transit; the inverse correlation between fractional gastric emptying rate and smal1 bowel transit time was significant (r = -0.76; P = 0.01).
-
We believe that this study is the first to address in detail the regional transit of solid residue traversing the unprepared gut in patients with IBS and diarrhea. Our patient group showed the wellknown variability in stool weight and frequency described in such patients. Variability was also shown by the observation that three patients with IBS had zero to one stool in 24 hours during the transit study and three had normal overall colonic transit. Our data suggest that accelerated transit through the proximal colon is an important determinant of stool weight in patients with IBS and diarrhea and
Control
0
Health
??IBS
0
0
I
I
I
12
24
36
Hours
0.2
0.3
0.4
0.5
06
0.7
0.6
0.9
1.0
1.1
1.2
1.3
Proximal colon volume, L Figure 3. Proximal (ascending plus transverse) colon emptying profile in a healthy subject (number 3) and a patient with IBS (number 4). Note the rapid emptying of the proximal colon in the patient (4.l%/h) compared with the healthy subject (1.45%/h).
Figure 5. Correlation plot between fractional emptying rate of the proximal colon and maxima1 colonic volume in healthy and IBS groups.
TOTAL GUT TRANSIT IN IBS WITH DIARRHEA
January 1992
TabJe 3. Gastric Emptying
107
and SmaJJ BoweJ Transit Time Gastric emptying Lag duration (min)
Healthy subjects 1 2 3 4 5 IBS patients 1 2 3 4 5 6
8 9 10
Laboratory control interquartile range”
Fractional emptying rate (%/min)
SBTT 10% (min)
Ileocolonic filling rate (%/min)
40 50 40 75 75
0.273 0.251 0.460 0.386 0.314
250 415 170 155 165
0.744 0.173 0.132 0.291 0.308
75 55 40 40 20 55 30 35 50 60
0.303 0.179 0.391 0.258 0.116 0.246 0.392 0.601 0.131 0.170
120 180 135 110 250 190 60 100 310 300
0.241 0.597 0.172 0.266 0.150 0.254 0.308 0.424 0.085 0.192
47-75
0.26-0.49
151-290
SBTT, smal1 bowel transit time. LISee references 15, 17, 21, and 22.
that the accelerated transit resulted from altered motor responses to the arrival of chyme rather than from changes in colonic capacitance or the rate of flow of chyme from the ileum to the colon. The use of a solid marker of standardized size and physical/chemical nature allowed for a clearer assessment of the relative contributions of the different regions of the gut to disorders of transit. A previous study’ used less precise methods (e.g., radiograph of stools for radiopaque markers) to define overall gut transit; on the other hand, the delayed release methodology used in this and other studieP,** allowed US to quantify regional colonic transit. Of particular note with this method is the clear identification of a start time for the assessment of colonic transit, without the need for orocecal intubation.‘* The healthy subjects in this study fel1 within the range established for a larger group of contro1s’5~‘7~2*~22 for the following indices of transit: gastric fractional emptying rate, smal1 bowel transit time, proximal colon emptying rate, and geometrie center of isotope in the colon (see Tables 1-3). The overall acceleration of colonic transit was caused predominantly by fast emptying of the proximal colon in five subjects. Moreover, rapid emptying of the proximal colon was associated with increased stool weight. These results are consistent with the concept that rapid emptying of the proximal colon delivered to distal regions amounts of chyme that overloaded the capacity of the descending colon and rectum and led to increased stool weightz3 Con-
versely, the maximum volume of the proximal colon and the rate of ileocolonic filling were not significantly different in IBS. These observations suggest that capacitance and the rate of flow of chyme into the colon are less important determinants of diarrhea in IBS than the motor response of the proximal colon to the arrival of chyme. The volume accepted by the proximal colon may influence its rate of emptying, in view of the significant inverse relationship between emptying rate and volume of the proximal colon in IBS. On the other hand, there was no correlation between proximal colonic emptying and stool frequency. This suggests that other factors, such as reduced capacitance or increased sensitivity of the rectum,24 may be important determinants of stool frequency in patients with IBS. Fast transit through the smal1 bowel (noted in four of seven patients with accelerated overall colonic transit) may have also influenced the rate at which the proximal colon emptied. Thus, the delivery of unabsorbed bile acids, fatty acids, or large volumes of smal1 bowel contents may have overwhelmed the storage capacity of the proximal coloP or induced propulsive motility.‘g~20~25 Because the geometrie center for colonic transit at 4 and 12 hours was not significantly different in health and IBS, we do not favor the hypothesis that accelerated smal1 bowel transit overwhelmed the storage capacity of the proximal colon. An alternative hypothesis is that the proximal colon in IBS is more sensitive to volume loads than it is in health. This concept is supported
108
VASSALLO ET AL.
by observations that, although colonic volumes and ileocolonic rates of filling were not different between IBS and health, the emptying of the proximal colon was more rapid in IBS. The significant negative correlation between fractional gastric emptying rate and smal1 bowel transit time suggests that transit through these regions of the upper gut is similar, i.e., fast, normal, or slow. This argues against an important effect of delivery of unabsorbed carbohydrates or fats to the distal smal1 bowel. Thus, rapid activation of the ileal “brake”26.27 in persons with fast smal1 bowel transit would have been expected to retard gastric emptying. Our observations were quite the opposite: rapid gastric emptying occurred in persons with accelerated smal1 bowel transit. In summary, our study showed that accelerated transit of solid residue through the unprepared proximal colon was a determinant of stool weight in patients with diarrhea-predominant IBS. A minority of patients (2/1O) had accelerated transit through the left colon. References 1. Switz DM. What the gastroenterologist
does al1 day. Gastroenterology 1976;70:1048-1050. 2. Harvey RF, Salih SY, Read AE. Organic and functional disorders in 2000 gastroenterology outpatients. Lancet 1983;1:632-634. 3. Manning AP, Thompson WG, Heaton KW, Morris AF. Towards positive diagnosis of the irritable bowel. Br Med J 1978;2:653-654. 4. Kellow JE, Phillips SF. Altered smal1 bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 1987;92:1885-1893. 5. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome. Physiological and psychologlcal differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci 1980;25:404-413. 6. Kumar D, Wingate DL. The irritable bowel syndrome: a paroxysmal motor disorder. Lancet 1985;2:973-977. 7. Camilleri M, Neri M. Motility disorders and stress. Dig Dis Sci 1989;34:1777-1786. 8. Cann PA, Read NW, Brown C, Hobson N, Holdsworth CD. Irritable bowel syndrome: relationship of disorders in the transit of a single solid meal to symptom patterns. Gut 1983;24:405-411. 9. Hardy JG, Wood E, Clark AG, Reynolds JR. Whole bowel transit in patients with the irritable bowel syndrome. Eur J Nucl Med 1986;11:393-396. 10.Trotman IF, Price CC. Bloated irritable bowel syndrome defined by dynamic ga”Tc-bran scan. Lancet 1986;2:364-366. 11. Gil1 RC, Cote KR, Bowes KL, Kingma YJ. Human colonic smooth muscle: spontaneous contractile activity and response to stretch. Gut 1986;27:1006-1013. 12. Snape WJ Jr, Kim BH, Willenbucher R, Koebel CB, Mayer EA Jr. Walsh JH. Differences in the response of proximal and distal rabbit colonic muscle after electrical field stimulation. Gastroenterology 1989:96:321-326.
GASTROENTEROLOGY Vol. 102. No. 1
13. Dapoigny M, Trolese J-F, Bommelaer G, Tournut R. Myoelectric spiking activity of right colon, left colon, and rectosigmoid of healthy humans. Dig Dis Sci 1988;33:1007-1012, 14. Fink S, Freedman G. The differential effect of drugs on the proximal and distal colon. Am J Med 1960;28:534-540. 15. Proano M, Camilleri M, Phillips SF, Brown ML, Thomforde GM. Transit of solids through the human colon: regional quantification in the unprepared bowel. Am J Physiol 1990;258:G856-G862. 16. Thompson WG, Dotevall G, Drossman DA, Heaton KW, Kruis W. Irritable bowel syndrome: guidelines for the diagnosis. Gastroenterol Int 1989;2:92-95. 17. Camilleri M, Colemont LJ, Phillips SF, Brown ML, Thomforde GM, Chapman NJ, Zinsmeister AR. Human gastric emptying and colonic filling of solids characterized by a new method. AmJPhysiol1989;257:G284-G290. 18. Krevsky B, Malmud LS, D’Ercole F, Maurer AH, Fisher RS. Colonic transit scintigraphy. A physiologic approach to the quantitative measurement of colonic transit in humans. Gastroenterology 1986;91:1102-1112. 19.Spiller RC, Brown ML, Phillips SF. Decreased fluid tolerante, accelerated transit, and abnormal motility of the human colon induced by oleic acid. Gastroenterology 1986;91:100-107, 20. Kamath PS, Phillips SF, O’Connor MK, Brown ML, Zinsmeister AR. Colonic capacitance and transit in man: modulation by luminal contents and drugs. Gut 1990;31:443-449. 21. Greydanus MP, Camilleri M, Colemont LJ, Phillips SF, Thomforde GM. Ileocolonic transfer of solid chyme in smal1 intestinal neuropathies and myopathies. Gastroenterology 1990; 99:158-164. 22. Stivland T, Camilleri M, Vassallo M, Proano M, Rath D, Brown M, Thomforde G, Pemberton J, Phillips S. Scintigraphic measurement of regional gut transit in idiopathic constipation. Gastroenterology 1991;101:107-115. 23. Debongnie JC, Phillips SF. Capacity of the human colon to absorb fluid. Gastroenterology 1978;74:698-703. 24. Prior A, Maxton DG, Whorwell PJ. Anorectal manometry in irritable bowel syndrome: differences between diarrhea and constipation predominant subjects. Gut 1990;31:458-462. 25. Kamath PS, Phillips SF, Zinsmeister AR. Short-chain fatty acids stimulate ileal motility in man. Gastroenterology 1988;95:1490-1502. 26. Spiller RC, Trotman IF, Higgins BE, Ghatei MA, Grimble GK, Lee YC, Bloom SR, Misiewicz JJ, Sulk DBA. The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984;25:365-374. 27. Read NW, MacFarlane A, Kinsman RI, Bates TE, Blackhall NW, Farrar GBJ, Hall JC, Moss G, Morris AP, O’Neill B, Welch 1, Leey Y, Blossom SR. Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology 1984; 86:274-280.
Received October 24,199O.Accepted May 31, 1991. Address requests for reprints to: Michael Camilleri, M.D., Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905. Supported in part by Mayo Foundation and grants DK34988, DK32121, and RR00585 from the National Institutes of Health. The authors thank the dietitians and nursing staff of the Clinical Research Center for excellent patient care and Cindy Stanislav for typing and preparing the manuscript.
1992;102:102-108
Transit Through the Proximal Colon Influences Stool Weight in the Irritable Bowel Syndrome MARIO VASSALLO, MICHAEL CAMILLERI, SIDNEY MANUEL L. BROWN, NICHOLAS J. CHAPMAN, and GEORGE M. THOMFORDE
F. PHILLIPS,
Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota
The inherent variability of symptoms and motor abnormalities in patients with the irritable bowel syndrome has hampered the demonstration of motor abnormalities that could underlie symptoms. The aim in the current study was to evaluate whether altered regional capacitance or transit of solid residue through the unprepared human gut were factors in the diarrhea of patients with the irritable bowel syndrome. In 10 such patients and in 5 healthy controls, gastric and smal1 bowel transits were evaluated scintigraphically by means of a mixed meal containing gsmTc-labeled resin pellets. Regional colonic transit was quantitated by “‘Inlabeled pellets delivered to the ileocecal region by a pH-sensitive, methacrylate-coated capsule. Symptomatic patients did not have significantly altered gastric or smal1 bowel transits, but colonic transit was accelerated in 7 of 10 persons with the irritable bowel syndrome (P < O.OZ),in the proximal colon of five patients and in the left colon of two patients. The 24hour stool weight was positively correlated with the rate at which solid residue emptied from the ascending and transverse colons (r = 0.78; P c 0.01). There was also an inverse relationship between emptying rates and maxima1 volumes accommodated by the proximal colon (r = -0.58; P < O.O5),although the maximum volume of the proximal colon was not significantly different in patients and healthy subjects. Thus, accelerated transit through the proximal colon is a factor in the pathophysiology of the irritable bowel syndrome and influences the stool weight of such patients. The capacitance of the proximal colon presumably influences its storage capacity and, hence, the rate at which it empties.
abnormalities,4*5 but the episodic nature of symptoms has hindered the identification of motor disorders that might explain the clinical features.‘,’ In addition to abnormal manometric patterns,4’5 rapid transit through the smal1 bowela or whole gut8sQhas been described in patients with IBS and diarrhea, and ileal emptying was delayed” in patients who complained of bloating. A variety of methods has been used to measure gastrointestinal transit, but no report has described movement of the same marker through each region of the gut in IBS. However, regional differences are wel1 established; the proximal and distal colon respond differently to many stimuli, including stretch,l’ electrical field stimulation,” meals,13 and pharmacological doses of cholinergic agonists and serotonin.14 Therefore, it is conceivable that colonic function may be altered selectively by disease and that overall assessments of whole gut or whole colon transit could overlook important regional abnormalities. Indeed, using novel, noninvasive, scintigraphic methods to measure transit through the colon, Proano et a1.15showed storage in the ascending and transverse colons of healthy humans, whereas the left colon acted chiefly as a conduit. Our hypothesis was that disturbed storage in the proximal colon, not previously reported in IBS, would be demonstrable by noninvasive radioscintigraphic methods. Our aims were to evaluate transit of solid residue through the entire, unprepared gut in patients with diarrhea-predominant IBS and to assess the relationships among colonic transit, large bowel capacitance, and stool weights. Materials and Methods Patients and Healthy
he irritable bowel syndrome (IBS), the most common reason for referral of patients to gastroenterologists,‘~2 is characterized by abdominal pain and an altered, often unpredictable, bowel habit. Subsets of patients may have different manometric
T
Controls
Ten patients (7 women and 3 men; mean age, 39 years; age range, 25-55 years) and 5 healthy subjects (3 0 1992 by the American
Gastroenterological
0016-5085/92/$3.00
Association
TOTAL GUT TRANSIT IN IBS WITH DIARRHEA 103
January 1992
men and 2 women; mean age, 34 years; age range, 24-57 years) were recruited for these studies, which were approved by the Mayo Clinic Institutional Review Board and Radiation Control Committee. Al1 participants gave signed informed consent. Women were studied during the follicular phase of the menstrual cycle and had a negative plasma @-human chorionic gonadotrophin pregnancy test within 48 hours of the procedures. Patients were selected according to the symptomatic criteria of Manning et aL3 and an international working team of experts in the field.‘” Symptoms were present for at least 6 months, with at least three bowel movements per day for 22 days most weeks. Investigations directed toward excluding other conditions included hematology and chemistry group studies; stool examinations for excess fat, leucocytes, parasites, and occult blood; colonoscopy or colon radiograph examination and flexible sigmoidoscopy; and colonic biopsy. None of these investigations showed abnormalities. Experimental
Procedure
After an overnight fast, participants were admitted to the Clinical Research Center on the morning of the study. They ingested a gelatin capsule coated with one layer of the pH-sensitive polymer methacrylate, containing 0.8 g of Amberlite IR-120 Plus resin pellets (average diameter, 1 mm) labeled with up to 0.25 mCi of [“‘In]Cl, (Amersham, Arlington Heights, IL).15 External radioactive markers were placed over the xiphisternum and both anterior superior iliac spines. By comparing the position of the capsule with these landmarks on stans taken every 10 minutes we were able to determine when the capsule passed into the smal1 bowel. A breakfast consisting of scrambled eggs, whole wheat bread, and skimmed milk (35% protein, 52% carbohydrate, and 13% fat; 219 kcal) was ingested after the capsule was seen to leave the stomach. Two millicuries of ggmTc-labeled Amberlite 410 resin pellets (average diameter, 1 mm) were mixed with the eggs, which were cooked to a firm consistency to provide a solid medium with which to assess gastric emptying and smal1 bowel transit. The radiolabel was placed on the resin pellets rather than the meal itself to ensure that our measurements of smal1 bowel transit reflected the passage of undigestible solid residue through this region. Previous studies using similar methods showed that >90% of the radiolabel was stil1 bound to pellets after transit through the entire gut.17 Four hours after breakfast, a standardized nonradiolabeled lunch was eaten (chicken, potato, pudding, and water; 18% protein, 47% carbohydrate, and 35% fat; 536 kcal). Similarly, al1 subjects ate a standardized dinner (steak, salad, and dessert; 21% protein, 49% carbohydrate, and 30% fat; 561 kcal) 8 hours after the radiolabeled breakfast. Meals were not regulated after the first day. Gamma camera imaging. Imaging started immediately after ingestion of the radiolabeled breakfast and was performed with a large field-of-view gamma camera with a medium-energy, parallel-hole collimator (GE Starcam; Genera1 Electric, Milwaukee, WI). Anterior and posterior images were acquired with the subjects erect. The radioac-
tive markers over bony landmarks facilitated consistent positioning of the subjects and served as reference points for delineation of colonic regions of interest. Images were obtained at regular intervals for the first 12 hours (every 10 minutes after each meal and at 15-60-minute intervals according to a standard protocol at other times). Between images, participants were allowed to relax in a comfortable chair. Further images were acquired 24 and 36 hours after the initial labeled meal. The total body radiation exposure with these isotopes was 60 mrad. Quantitation of radioactivity in gastric and colonic regions. Two-minute acquisitions were used for each image during the first 12 hours and 5-minute acquisitions subsequently. The data were stored on an on-line computer (GE Starcam) for later analysis. Two energy windows of acquisition were used, 140 keV (*ZO% window) for ggmTc counts (labeled meal, for gastric emptying and smal1 bowel transit) and 245 keV (tZO% window) for “‘In counts (for colonic transit). Using variable regions of interest, radioactivity was quantitated in the stomach and ascending co10n17 for g9mTc and in four regions of the colon15 for “‘In (ascending, transverse, descending, and rectosigmoid). Geometrie means of the counts obtained from anterior and posterior images of each region were corrected for radionuclide decay and the downscatter of “‘In into the ggmTc window. Quantitation of radioactivity in stool. Stools were collected for 2 days, and the time of each bowel movement was recorded by the subjects. Each stool sample was weighed, and radioactivity was measured for “‘In counts in a Capintech Radioisotope Dose Calibrator (CRC-5; Capintech, Montvale, NJ). Counts were corrected for decay using standard tables. Data Analysis The weight and timing Stool weight and frequency. of each stool were recorded during the first 24 hours after ingestion of the radiolabeled capsule to calculate the 24hour weight and frequency. Scintigraphic colonic transit data. Overall colonic transit of radiolabeled solid residue was assessed in two ways. First, the percentages of counts in each colonic region at 12 and 36 hours were compared for patients and healthy controls using nonparametric Wilcoxon’s rank sum test, because values for emptying from the ascending colon were not normally distributed in patients with IBS. Significante was assessed at a = 0.05. A second assessment of overall colonic transit was the geometrie center, i.e., the weighted average of proportions of counts in each of the four colonic regions and in the stool at 4, 12, 24, and 36 hours.” For this analysis, the following regions were designated by numbers 1-5, respectively: ascending, transverse, descending, and rectosigmoid colons and stool. At any time point, a low geometrie center implied that most radiolabel was closer to the cecum; a higher geometrie center implied that most radiolabel was closer to the stool. Overall colonic transit of each patient was compared with data for healthy controls. In view of the storage function of ascending and transverse colons,” we combined the scintigraphic data from
104 VASSALLO ET AL.
GASTROENTEROLOGY Vol. 102, No. 1
these two regions into one value. Time-activity curves were plotted for health and IBS for 36 hours after release into the colon of al1 “‘In radiolabel contained within the methacrylate-coated capsule. The time-activity plot for each participant was also summarized by a slope that expressed the hourly fractional emptying rate of isotope from the proximal (ascending and transverse) colon, expressed as a percentage of the maximum counts delivered to the ascending colon by the methacrylate-coated capsule. Proximal colonic volume. The volumes of the ascending and transverse colons were estimated by a previously validated method. 1g*20 The stans selected for the calculations of maxima1 proximal colonic volume were those that showed the greatest surface area of the ascending and transverse regions. The volume of these regions was calculated as aA2/4L, where A is the surface area of the combined regions, and L is the total length of the two regions, both measured in pixels (1 pixel = 3.2 mm) and subsequently converted to millimeters. Gastric emptying, smal1 bowel transit, and ileocolonic jílling. Gastric emptying was summarized as in previous studiesI by the duration of the lag phase and by the fractional emptying rate, expressed as the slope of the post-lag phase as determined by linear regression analysis. The tlO% for smal1 bowel transit (i.e., time for 10% of the radiolabel to traverse the smal1 bowel) was measured by subtracting the time for 10% gastric emptying from the time for 10% colonic filling.‘l The rate of ileocolonic filling was expressed as the percentage of the radiolabel ingested with the meal that was transferred to the colon per minute; these rates were summarized as the slopes of the colonic filling curves. Statistical sample
Analysis
Statistical evaluations were performed by twot test or Wilcoxon’s rank sum tests for normally
Table 1. Individual
24-Hour Data on Stook, Proximal Stool wt
Wz
h)
distributed and nonparametric data, respectively. Unless otherwise stated, comparisons were made between patients with IBS and the five healthy controls evaluated prospectively in the present study. Comparison of stool frequency between IBS and health was by a Yates’ corrected x2 test; in this test, we compared the number of subjects in each group with one or less or more than one bowel movement per day. Interquartile data from healthy subjects studied previously in our laboratory’5~‘7~2’~22 by an identical method are also included in the tables.
Results Stool Weight
Mean 24-hour stool weights in the IBS group (130 + 20 g) were not different from those of healthy subjects (84 f 25 g; P > 0.10). There was a significant differente (P < 0.05) between the 24-hour stool frequency in IBS (2.2 f 0.4) and health (1 + 0); however, one patient with IBS passed no stools during the 48hour study. Individual subjects’ data are shown in Table 1.
Colonic Transit Proportion oj’radiolabel in different colonic regions at 12 and 36 hours. There was no significant differente between health and IBS in the proportional distribution of solid radiolabel through the four colonic regions and the stool at 12 hours (data not shown). However, at 36 hours (Figure l), patients with IBS had significantly less radiolabel in the transverse (P < 0.05) and descending colons (P < 0.01) and significantly more radiolabel in stool (P < 0.05). Representative examples of time activity
Colonic Transit,
Stool frequency (no./24 h)
and Frequency
and Volume Calculated proximal colon volume (mL)
Proximal colon emptying ratea (%/h)
Healthy subjects 1 2 3 4 5 IBS patients 1 2 3 4 5 6 7 8 9 10 Laboratory control interquartile range ' Emptying rate calculated
40 63 67 67 183
1 1 1 1 1
556 590 406 1202 397
1.37 0.02 1.45 0.25 2.53
0 68 70 115 120 128 132 154 232 285
0 2 4 1 1 2 3 2 4 3
717 816 544 602 454 409 387 697 308 266
1.53 0.68 2.26 4.08 3.34 2.50 2.60 3.83 3.33 5.60 0.51-2.53
during 36 hours.
January
TOTAL
1992
50 s ‘$n L.L 8
25
Ascending
Transverse
Descending
Rectosigmoid
SIOOI
Region Figure 1. Proportion of radiolabel in different colonic regions at 36 hours in healthy and IB!3groups. Note the smal1 proportion of counts in the transverse and descending regions and the greater proportion in stool (*P < 0.05) in the IBS group.
GLJT TRANSIT
IN IBS WITH DIARRHEA
105
h in IBS vs. 1.1% + 0.5%/h in health; P = 0.02). Representative examples of proximal colon emptying curves in health and IBS are shown in Figure 3. Of the seven IBS patients with accelerated overall colonic transit, as judged by the 36-hour geometrie centers (Table 2), five also had rapid emptying of the proximal colon. In the remaining two patients (patients 3 and 7 in Table 1) overall transit was accelerated, despite normal emptying of the proximal colon. This finding implies that transit through the left colon was fast. There was a significant positive correlation (Figure 4) between emptying of the proximal colon and 24hour stool weight (r = 0.80, P < 0.01 for IBS; r = 0.78, P < 0.01 for al1 subjects studied). In contrast, there was no correlation between emptying rate of the proximal colon and 24-hour stool frequency. ProximaJ CoJonic Volume
curves through the five regions of interest in health and disease are shown in Figure 2. Overall colonic transit by geometrie center. The weighted average or geometrie center of counts at 4, 12, 24, and 36 hours (Table 2) reflected the proportional distribution of isotope in the colonic regions. There was no significant differente between health and IBS at 4 and 12 hours. However, the geometric centers at 24 and 36 hours differed for IBS and health (P < 0.05). Three patients (1, 2, and 6) had normal overall colonic transit. Emptying of the ascending and transverse coJons. Table 1 shows the fractional emptying rates of the proximal colon for each individual. The fractional emptying rate of the proximal colon was faster in the whole IBS group than in health (3.0% f O.4%/
There was no significant differente in the calculated maximum volume of the combined ascending and transverse colons in IBS (520 + 59 mL) and health (630 f 148 mL; P > 0.10). However, there were inverse relationships (Figure 5) between proximal colonic emptying rate and colonic volume in patients with IBS (r = -0.66; P < 0.05) and in al1 persons studied (r = -0.58; P = 0.023). Gastric Emptying, CoJonic FiJJing
SmaJJ BoweJ Transit,
and
Gastric emptying (lag times and fractional emptying rates) was not significantly different in IBS (Table 3); however, in four patients, gastric fractional emptying rates were <0.2%/min (normal range in
lYY!kl B
-
Figure 2. Representative examples of time-activity curves showing transit through different colonic regions in a control (number 3) and patient with IBS (number 4). Note the rapid regional emptying in the patient with IBS and diarrhea. (A)Ascendlng, (B)transverse, (C) descending, and (0) rectosigmoid colons; (E) stool.
Control
IBS
100
C
80
%
D
z
20 0 L!x 0
12
24
36
0
12
24
Hours
36
0
12
24
36
106
GASTROENTEROLOGY Vol. 102, No. 1
VASSALLO ET AL.
Table 2. Geometrie Center ofkotope
6r
in Colon at 4, 32, 24,
and 36 Hours 12
4h
h
24 h
36 h
c
Healthy subjects 1
2 3 4 5 Mean SEM IBS patients 1
2 3 4 5 6 7 8 9 10 Mean SEM P vs. control Laboratory control interquartile range
1.17 1.10 1.31 1.27 1.64 1.30 0.09
1.17 1.48 1.41 1.30 1.72 1.42 0.09
1.84 2.01 2.02 1.89 1.95 1.94 0.03
2.32 2.46 2.09 3.17 2.46 0.19
2.29
'S a E
4
Q>
3
0
Health
0
IBS
;
:i’--
ó s
2
3
E ‘E
r=0.70
1 ,o
0
1.34 1.05 1.54 1.85 1.61 1.09 1.55 1.35 1.29 3.84 1.65 0.25 >O.l
1.64 1.06 1.65 2.35 1.86 1.58 1.68 1.40 1.70 3.98 1.89 0.25 >O.l
2.00 1.34 2.51 4.40 3.51 2.99 3.17 4.68 3.78 4.58 3.30 0.35 <0.05
2.49 2.08 4.64 4.30 3.46 3.00 4.85 4.82 3.93 4.79 3.83 0.33 <0.05
1-1.12
1.12-2.12
1.84-3.96
2.28-3.96
P=O.@m
0
2 n
0
50
I
I
I
I
I
100
150
200
250
300
24-hr stool weight, g Figure 4. Correlation plot between fractional emptying rate of the proximal colon and 24-hour stool weight in healthy and IBS groups.
The slopes of the ileocolonic filling curves were not significantly different (P > 0.50) in IBS (0.27% f 0.05%/min) and in healthy subjects (0.33% + O.ll%/min). Discussion
our laboratory, 0.27%-0,5%/min), and in one patient it was >0.5%/min. Smal1 bowel transit (tlO%) was not significantly different in the whole IBS group and healthy controls (Table 3). Individuals with rapid gastric emptying also had rapid smal1 bowel transit; the inverse correlation between fractional gastric emptying rate and smal1 bowel transit time was significant (r = -0.76; P = 0.01).
-
We believe that this study is the first to address in detail the regional transit of solid residue traversing the unprepared gut in patients with IBS and diarrhea. Our patient group showed the wellknown variability in stool weight and frequency described in such patients. Variability was also shown by the observation that three patients with IBS had zero to one stool in 24 hours during the transit study and three had normal overall colonic transit. Our data suggest that accelerated transit through the proximal colon is an important determinant of stool weight in patients with IBS and diarrhea and
Control
0
Health
??IBS
0
0
I
I
I
12
24
36
Hours
0.2
0.3
0.4
0.5
06
0.7
0.6
0.9
1.0
1.1
1.2
1.3
Proximal colon volume, L Figure 3. Proximal (ascending plus transverse) colon emptying profile in a healthy subject (number 3) and a patient with IBS (number 4). Note the rapid emptying of the proximal colon in the patient (4.l%/h) compared with the healthy subject (1.45%/h).
Figure 5. Correlation plot between fractional emptying rate of the proximal colon and maxima1 colonic volume in healthy and IBS groups.
TOTAL GUT TRANSIT IN IBS WITH DIARRHEA
January 1992
TabJe 3. Gastric Emptying
107
and SmaJJ BoweJ Transit Time Gastric emptying Lag duration (min)
Healthy subjects 1 2 3 4 5 IBS patients 1 2 3 4 5 6
8 9 10
Laboratory control interquartile range”
Fractional emptying rate (%/min)
SBTT 10% (min)
Ileocolonic filling rate (%/min)
40 50 40 75 75
0.273 0.251 0.460 0.386 0.314
250 415 170 155 165
0.744 0.173 0.132 0.291 0.308
75 55 40 40 20 55 30 35 50 60
0.303 0.179 0.391 0.258 0.116 0.246 0.392 0.601 0.131 0.170
120 180 135 110 250 190 60 100 310 300
0.241 0.597 0.172 0.266 0.150 0.254 0.308 0.424 0.085 0.192
47-75
0.26-0.49
151-290
SBTT, smal1 bowel transit time. LISee references 15, 17, 21, and 22.
that the accelerated transit resulted from altered motor responses to the arrival of chyme rather than from changes in colonic capacitance or the rate of flow of chyme from the ileum to the colon. The use of a solid marker of standardized size and physical/chemical nature allowed for a clearer assessment of the relative contributions of the different regions of the gut to disorders of transit. A previous study’ used less precise methods (e.g., radiograph of stools for radiopaque markers) to define overall gut transit; on the other hand, the delayed release methodology used in this and other studieP,** allowed US to quantify regional colonic transit. Of particular note with this method is the clear identification of a start time for the assessment of colonic transit, without the need for orocecal intubation.‘* The healthy subjects in this study fel1 within the range established for a larger group of contro1s’5~‘7~2*~22 for the following indices of transit: gastric fractional emptying rate, smal1 bowel transit time, proximal colon emptying rate, and geometrie center of isotope in the colon (see Tables 1-3). The overall acceleration of colonic transit was caused predominantly by fast emptying of the proximal colon in five subjects. Moreover, rapid emptying of the proximal colon was associated with increased stool weight. These results are consistent with the concept that rapid emptying of the proximal colon delivered to distal regions amounts of chyme that overloaded the capacity of the descending colon and rectum and led to increased stool weightz3 Con-
versely, the maximum volume of the proximal colon and the rate of ileocolonic filling were not significantly different in IBS. These observations suggest that capacitance and the rate of flow of chyme into the colon are less important determinants of diarrhea in IBS than the motor response of the proximal colon to the arrival of chyme. The volume accepted by the proximal colon may influence its rate of emptying, in view of the significant inverse relationship between emptying rate and volume of the proximal colon in IBS. On the other hand, there was no correlation between proximal colonic emptying and stool frequency. This suggests that other factors, such as reduced capacitance or increased sensitivity of the rectum,24 may be important determinants of stool frequency in patients with IBS. Fast transit through the smal1 bowel (noted in four of seven patients with accelerated overall colonic transit) may have also influenced the rate at which the proximal colon emptied. Thus, the delivery of unabsorbed bile acids, fatty acids, or large volumes of smal1 bowel contents may have overwhelmed the storage capacity of the proximal coloP or induced propulsive motility.‘g~20~25 Because the geometrie center for colonic transit at 4 and 12 hours was not significantly different in health and IBS, we do not favor the hypothesis that accelerated smal1 bowel transit overwhelmed the storage capacity of the proximal colon. An alternative hypothesis is that the proximal colon in IBS is more sensitive to volume loads than it is in health. This concept is supported
108
VASSALLO ET AL.
by observations that, although colonic volumes and ileocolonic rates of filling were not different between IBS and health, the emptying of the proximal colon was more rapid in IBS. The significant negative correlation between fractional gastric emptying rate and smal1 bowel transit time suggests that transit through these regions of the upper gut is similar, i.e., fast, normal, or slow. This argues against an important effect of delivery of unabsorbed carbohydrates or fats to the distal smal1 bowel. Thus, rapid activation of the ileal “brake”26.27 in persons with fast smal1 bowel transit would have been expected to retard gastric emptying. Our observations were quite the opposite: rapid gastric emptying occurred in persons with accelerated smal1 bowel transit. In summary, our study showed that accelerated transit of solid residue through the unprepared proximal colon was a determinant of stool weight in patients with diarrhea-predominant IBS. A minority of patients (2/1O) had accelerated transit through the left colon. References 1. Switz DM. What the gastroenterologist
does al1 day. Gastroenterology 1976;70:1048-1050. 2. Harvey RF, Salih SY, Read AE. Organic and functional disorders in 2000 gastroenterology outpatients. Lancet 1983;1:632-634. 3. Manning AP, Thompson WG, Heaton KW, Morris AF. Towards positive diagnosis of the irritable bowel. Br Med J 1978;2:653-654. 4. Kellow JE, Phillips SF. Altered smal1 bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 1987;92:1885-1893. 5. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome. Physiological and psychologlcal differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci 1980;25:404-413. 6. Kumar D, Wingate DL. The irritable bowel syndrome: a paroxysmal motor disorder. Lancet 1985;2:973-977. 7. Camilleri M, Neri M. Motility disorders and stress. Dig Dis Sci 1989;34:1777-1786. 8. Cann PA, Read NW, Brown C, Hobson N, Holdsworth CD. Irritable bowel syndrome: relationship of disorders in the transit of a single solid meal to symptom patterns. Gut 1983;24:405-411. 9. Hardy JG, Wood E, Clark AG, Reynolds JR. Whole bowel transit in patients with the irritable bowel syndrome. Eur J Nucl Med 1986;11:393-396. 10.Trotman IF, Price CC. Bloated irritable bowel syndrome defined by dynamic ga”Tc-bran scan. Lancet 1986;2:364-366. 11. Gil1 RC, Cote KR, Bowes KL, Kingma YJ. Human colonic smooth muscle: spontaneous contractile activity and response to stretch. Gut 1986;27:1006-1013. 12. Snape WJ Jr, Kim BH, Willenbucher R, Koebel CB, Mayer EA Jr. Walsh JH. Differences in the response of proximal and distal rabbit colonic muscle after electrical field stimulation. Gastroenterology 1989:96:321-326.
GASTROENTEROLOGY Vol. 102. No. 1
13. Dapoigny M, Trolese J-F, Bommelaer G, Tournut R. Myoelectric spiking activity of right colon, left colon, and rectosigmoid of healthy humans. Dig Dis Sci 1988;33:1007-1012, 14. Fink S, Freedman G. The differential effect of drugs on the proximal and distal colon. Am J Med 1960;28:534-540. 15. Proano M, Camilleri M, Phillips SF, Brown ML, Thomforde GM. Transit of solids through the human colon: regional quantification in the unprepared bowel. Am J Physiol 1990;258:G856-G862. 16. Thompson WG, Dotevall G, Drossman DA, Heaton KW, Kruis W. Irritable bowel syndrome: guidelines for the diagnosis. Gastroenterol Int 1989;2:92-95. 17. Camilleri M, Colemont LJ, Phillips SF, Brown ML, Thomforde GM, Chapman NJ, Zinsmeister AR. Human gastric emptying and colonic filling of solids characterized by a new method. AmJPhysiol1989;257:G284-G290. 18. Krevsky B, Malmud LS, D’Ercole F, Maurer AH, Fisher RS. Colonic transit scintigraphy. A physiologic approach to the quantitative measurement of colonic transit in humans. Gastroenterology 1986;91:1102-1112. 19.Spiller RC, Brown ML, Phillips SF. Decreased fluid tolerante, accelerated transit, and abnormal motility of the human colon induced by oleic acid. Gastroenterology 1986;91:100-107, 20. Kamath PS, Phillips SF, O’Connor MK, Brown ML, Zinsmeister AR. Colonic capacitance and transit in man: modulation by luminal contents and drugs. Gut 1990;31:443-449. 21. Greydanus MP, Camilleri M, Colemont LJ, Phillips SF, Thomforde GM. Ileocolonic transfer of solid chyme in smal1 intestinal neuropathies and myopathies. Gastroenterology 1990; 99:158-164. 22. Stivland T, Camilleri M, Vassallo M, Proano M, Rath D, Brown M, Thomforde G, Pemberton J, Phillips S. Scintigraphic measurement of regional gut transit in idiopathic constipation. Gastroenterology 1991;101:107-115. 23. Debongnie JC, Phillips SF. Capacity of the human colon to absorb fluid. Gastroenterology 1978;74:698-703. 24. Prior A, Maxton DG, Whorwell PJ. Anorectal manometry in irritable bowel syndrome: differences between diarrhea and constipation predominant subjects. Gut 1990;31:458-462. 25. Kamath PS, Phillips SF, Zinsmeister AR. Short-chain fatty acids stimulate ileal motility in man. Gastroenterology 1988;95:1490-1502. 26. Spiller RC, Trotman IF, Higgins BE, Ghatei MA, Grimble GK, Lee YC, Bloom SR, Misiewicz JJ, Sulk DBA. The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984;25:365-374. 27. Read NW, MacFarlane A, Kinsman RI, Bates TE, Blackhall NW, Farrar GBJ, Hall JC, Moss G, Morris AP, O’Neill B, Welch 1, Leey Y, Blossom SR. Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology 1984; 86:274-280.
Received October 24,199O.Accepted May 31, 1991. Address requests for reprints to: Michael Camilleri, M.D., Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905. Supported in part by Mayo Foundation and grants DK34988, DK32121, and RR00585 from the National Institutes of Health. The authors thank the dietitians and nursing staff of the Clinical Research Center for excellent patient care and Cindy Stanislav for typing and preparing the manuscript.