CHARACTERIZATION OF A HYPERACTIVE SEGMENT AT THE RECTOSIGMOID JUNCTION

Transcription

1 GU'I'IIO&H'I'DOLOOY 71: Coyriiht 11> 1976 by The William, & Wilkin, Co. Vol. 71. No.4 Printed in U.S.A. CHARACTERIZATION OF A HYPERACTIVE SEGMENT AT THE RECTOSIGMOID JUNCTION A. RAB CHOWDHURY, M.D., VICENTE P. OINOSO, M.D., AND STANLEY H. LORBER, M.D. Deartment of GlJ8troenterology, Temle University Hosital and School of Medicine, Philadelhia, Pennsylvania During a study of intraluminal motor atterns of the colon and rectum, sontaneous wave activity of a continuous comlex tye was observed at the rectosigmoid junction in constiated subjects. To assess the frequency and characteristics of this hyeractive segment, 39 subjects with colonic motor disorders and 12 healthy controls were studied. Eighteen of 24 atients with constiation (75%) and 1 of 7 subjects with asymtomatic diverticulosis exhibited a ersistent hyeractive segment at the rectosigmoid junction. Neither secretin nor cholecystokinin influenced the wave activity of the hyeractive segment. In contrast, atroine and glucagon inhibited markedly all wave activity and decreased the motility index of this segment significantly, suggesting overactivity of the muscarinic effector cells. It is concluded tnat a seginental area of overactivity exists at the rectosigmoid junction in most constiated subjects regardless of their underlying disorders. Abnormal motor wave activity of the colon has been described in a variety of disorders including diverticulosis of the colon and irritable colon syndrome.'- In diarrheal states colonic motor activity is decreased, in contrast to chronic constiation, in which hyeractivity of the colon has been described.' In the latter, there is segmentation of the lumen roduced by narrow contraction rings or haustra. I. '. In studies of the motor resonses of the sigmoid colon and rectum, we observed a hyeractive segment at the rectosigmoid junction in some subjects, characterized by sontaneous wave activity of a comlex tye. 1 Chronic constiation was the major comlaint of these atients. We have extended our reliminary observations and determined the frequency and characteristics of the hyeractive segment in atients with colonic diverticulosis and functional bowel disorders, and in healthy controls. Materials and Methods Subjects. Fifty-one subjects divided into four grous were included in this study (table 1). Controls had no evidence of gastrointestinal disease. Constiation, defined as the assage of hard and/or insufficient stools at a rate of twice weekly or less, was the only comlaint in the grou of atients with functional constiation. A third grou had diverticulosis of the colon with or without constiation. The final grou had irritable colon syndrome. a diagnosis made by exclusion and Received December 8, Acceted March 5, This aer was resented in art before the lenary session at the Annual Meeting of the American Gastroenterological Association (San Francisco, 1974) and ublished in abstract form. I Addreu requests for rerints to: A. Rab Chowdhury, M.D., Temle University Hosital, 3401 North Broad Street, Philadelhia, Pennsylvania based on acceted clinical criteria." 11 This grou's redominant symtoms were altered bowel habits with or without ostrandial lower abdominal ain or distention, often relieved by defecation or the assage of flatus. Bowel symtoms usually occurred during the day and were often reciitated by emotional stress. Two atients in this grou had normal bowel function during the eriod of study. To exclude the ossibility of isolated lactase deficiency, which may mimic irritable colon. It a lactose tolerance test was erformed on 5 of the 6 atients with irritable colon with associated diarrhea. Organic lesions and diseases caused by infection or infestation were excluded by aroriate stool examinations, sigmoidoscoy, and radiograhic examinations of the gastrointestinal tract. Additionally,S ofthe 7 atients had a satisfactory colonoscoy. Excet for sasm, tenderness, and excessive mucus, which were observed in:3 cases, the rocedure was unremarkable. Procedure. All subjects were studied cuter an overnight fast. A cleansing enema was administered 1 hr before each study. A trile lumen olyvinyl tube assembly with side orifices saced at 5-cm intervals was introduced through a sigmoidoscoe so that the distal. middle, and roximal orifices were 25 to 20, 20 to 15. and 15 to 10 cm from the anal verge (fig. 1). For accurate localization of the tube assembly, the distal 10 cm were oacified with mercury and its osition was checked fluoroscoically before each study. Patency of each tube was maintained by erfusion with demineralized water at a constant role of 4 ml er hr using a Gorrell and Gorrell infusion aaratus. II Studies were erformed in a quiet room with the atient lying in the left lateral osition. A belt neumograh was alied to the abdomen for recording of resiration. Changes in intraluminal ressure and resiration were transmitted to external transducers (Statham Laboratories, P23B, Cambridge, Mass.) which in turn were connected to a Sanborn Polyviso recorder for amlification and recording. Informed consent was obtained from all articiants. Study design. After a stable base-line recording was obtained for 30 min, the tube assembly was withdrawn at 0.5- to l-cm 584

2 October 1976 HYPERACTIVE SEGMENT AT THE RECTOSIGMOID 585 TABLE 1. Clinical data Grou (no.) Mean age (yr) Males Females Bowel habita' Duration of symtoms (yr) Healthy controls (12) 30 7 Functional constiation (9) 53 4 Colonic diverticulosis (12) 58 8 Irritable colon syndrome (18) Normal (12) Constiation (9) Normal (7) Constiation (5) Constiation (10) Normal (2) Diarrhea (6) Bowel habits during the eriod of study. Figures in arentheses reresent the number of atients in each grou. FIG. 1. Schematic reresentation of the method of study. Arrows indicate the orifices of the catheters at 5'cm intervals. intervals, and motor activity was recorded for 3 min at each level. Segmental withdrawal was continued until wave activity of the comlex tye was observed or until the middle orifice of the tube assembly was 10 to 13 cm from the anal verge. The recording was continued for an additional 30 min to obtain a base line, during which time 0.9% saline solution was infused intravenously. If a hyeractive segment was observed, resonses to the following test substances were studied for 30 min in a randomized fashion on searate days at intervals of 5 to 12 days: (1) secretin 1 U er kg er hr; (2) cholecystokinin (CCK), 1 U er kg er hr; (3) atroine sulfate, 12 ~ er g kg er hr; (4) glucagon, 10 ~ g er kg er hr. The test substances were administered intravenously by a Harvard infusion um. Both secretin and CCK were obtained from the Karolinska In stitutet, Stockholm, Sweden. Quantitative analysis of motor activity. The motor activity of the rectosigmoid in the basal state and in resonse to the test substances was quantitated by determining the number of 91aves, amlitude index (sum of the amlitude of all waves in centimeters of H.O), and motility index (vide infra) er 30 min of observation. As originally suggested by Chaudhary and Truelove," and later modified by Deller and Wangel," the Illotility index (M.!.) was calculated as follows : A x D M.I. - nl- T x 10, in which A = wave amlitude, D = wave duration, T = recorded time in minutes, and n = number of waves during T. To avoid artifactual errors, waves of less than 3 em of water were excluded from analysis." II Student's t-test for aired data was used to analyze the significance of the difference of the mean values between the control eriod and each eriod of administration of a test substance. 17 Results Characterization of the hyeractive segment. The hyeractive segment (fig. 2), characterized by wave activity of a continuous comlex tye or suerimosed reetitive waves, measured 1.5 to 2 cm in length and was located 9 to 15 cm from the anal verge; one-half were located 12 to 14 cm above the anal margin. This narrow segment of hyeractivity was identified by ull-through exeriments and was observed in at least two of the three channels as the recording orifices traversed the zone of increased activity. Resonses to test substances. Changes in the number of waves, as well as in amlitude and motility indices in resonse to the test substances, are summarized in table 2. Secretin did not inhibit the hyeractive segment, although it did deress motor activity of the ad-

3 586 CHOWDHURY ET AL. Vol. 71. No.4 UH20 2:E ~ C O l O N~ 2 0~ U A- - - J ~ ~ !.EaO SIG.OID IS c. l!, ~ A ~ ~ ~ A ~ ~ ' ~ ~ - A ' ~ ~.ESPlU TION '.IN. ~ FIG. 2. An examle of a ull through study erformed on a atient with functional constiation. Each P reresents withdrawal of 0.5 em. Note the aearance of sontaneous wave activity of a continuous comles tye (hyeractive segment) at 14 em and it, disaearance at 12 cm from the anal verge. No significant change in base line ressure is observed in this area. The ascending or descending limb of a wave is often suerimosed on another wave. Wave amlitude ranges u to 18 em of water. TABLE 2. Effect of test agents on the hyeractive segment and the adjacent,egment8 of colon and rectum in 18 constiated subjects." Area ofotudy Ba8al Secretin Cholecystokinin Atroine Glucagon Colon No. of waves 9 =0.5 5 =0.3 Amlitude indes 42 = = 0.8 Motility indes 4.7 = = 0.2 o <0.01 Hyeractive No. of waves 75 = = 1.3 Amlitude indes 416 = = 10.8 Motility indes = = 7.3 o NS Rectum No. of waves 10 = =0.9 Amlitude indes 52 = = 1.9 Motility indes 4.9 = = 0.6 o NS Shown for motility indes only. Not significant. mean ",SEM 16 = = = = = : = = : 0.03 <0.01 <0.005 < = =0.3 6 = = : = = = = 0.07 NS <0.001 < = =0.1 2 = =2.8 9 =0.1 8 = = = = NS <0.01 <0.01 jacent sigmoid colon significantly (fig. 3), as evidenced by a decrease in the number of waves, amlitude index, and motility index (table 2). Similarly, administration of exogenous CCK did not influence the hyeractive seg ment although it did stimulate the adjacent sigmoid colon. CCK increased significantly all three arameters of motor activity measured. Neither secretin nor CCK influenced motor activity of the rectum significantly (P > 0.05). In contrast, atroine sulfate abolished or suressed almost all wave activity of the colon and rectum includ ing the hyeractive segment of the rectosigmoid junco tion. It decreased the number of waves, the amlitude index, and the motility index of the hyeractive segment markedly. A similar inhibitory effect was observed in resonse to the administration of glucagon (fig. 4). The changes in all three arameters of motor activity were highly significant (table 2). Excet for dryness of the mouth and minimal tachycardia, which occurred in most subjects during the infusion of atroine sulfate, no unleasant side effects were observed with the test substances. Clinical correlation. Table 3 lists the frequency of the hyeractive segment in the different grous of subjects in relation to their bowel habits. None of the healthy subjects had a ersistent hyeractive segment and in only 1 was it recorded intermittently. In contrast, 8 of 10 atients with irritable colon and constiation, as well as 4 of 5 with colonic diverticulosis and constiation, exhibited a ersistent hyeractive segment at the rectosigmoid junction. Thus, of the 24 atients with constiation, 18 (75%) had a ersistent hyeractive segment. Of the 15 atients with irritable colon or colonic diverticulosis who were not constiated, only 1 had a ersistent and 2 an intermittent hyeractive segment, a revalence that did not differ from that observed in the healthy control grou (P > 0.05). Sigmoidoscoic findings. Seven of the 10 atients with irritable colon syndrome and constiation had observa ble changes at sigmoidoscoy which included sasm,

4 . ~ October 1976 HYPERACTIVE SEGMENT AT THE RECTOSIGMOID 587 CM H20 SECRETIN I U/Kg/hr. I.V. S. COLON \8 CM... 2 ~ ~ ~ ~ A ~ E ~ ~ ~ ~ _ lor: Ot:... RECTUM. CM """'--"- ~ ~ ~ N \ ~ ~ RESPIRA non l-...j I MIN. FIG. 3. The effect of secretin on the hyeractive segment of the rectosigmoid junction and the adjacent segments of colon and rectum. Secretin suressed wave activity of the colon but not the hyeractive segment or the rectum. CMH20 GLUCAGON 10 ~ g;k ' gh. ri.v. r-" o ~ t ~ ~ ~ ~ ~ S. COLON 18 CM 2 RECTO-SIGMOID 13 CM o 2 ~ ~ ~ ~ ~ " ' ~ ~ ~ J ' ~ _ ~ RESPIRATION L--J I MIN. FIG. 4. The inhibitory effect of glucagon on the hyeractive segment and adjacent segments of the colon and rectum. TAIlLE 3. Frequency of hyeractive segment in different grous in rei4tion to bowel habits. Hyeractive segment Grou Bowel habits' Inter Persistent Absent mittene Healthy subjects Normal (12) 11 Irritable colon syn- Constiation (10) 8 drome Normal (2) 1 Diarrhea (6) 6 Colonic Normal (7) 5 diverticulosis Constiation (5) 4 Functional Constiation (9) 6 2 constiation Bowel habits during the eriod of study. Figurea in arentheses reresent the number of atients in' each grou. Hyeractive segment observed either intermittently or continuously in one or two studies but not in subsequent studies. excessive mucus, and ain in resonse to maniulation Or distention. Excet for the resence of occasional ~ i v e r t ithe c usigmoidoscoic l a, aearance was normal In the remainder of the grous. Roentgenologic examination. Radiograhic exam ination of the gastrointestinal tract revealed diverticulosis, esecially of the left side of the colon, in the grou with colonic diverticulosis. Segmentation and minimal narrowing of the descending colon including the rectosigmoid region was observed in some atients with irritable colon syndrome and constiation. In 2 atients, uon observation of a hyeractive segment manometrically, a contrast medium (Gastrografin) was instilled into the rectosigmoid through the recording catheter to determine its radiograhic characteristics. Other than rominent mucosal folds, no significant abnormalities were detected in the vicinity of the recording orifice. Discussion This study demonstrates that sontaneous wave activity of a comlex tye occurred within a narrow zone at the rectosigmoid junction which we,have designated as a hyeractive segment. This motor henomenon is a common finding in atients with constiation irresective of the basic underlying disorder. It does not have the characteristics of a true shincter because there is no significant elevation of its base-line ressure nor is there a ressure gradient roximal or distal to this segment. The comlex wave activity observed in this study is simi-

5 588 CHOWDHURY ET AL. Vol. 71, No.4 lar to that described by Bloom et ai., 11 but the abnormal activity which we observed was continuous or had reetitive waves suerimosed on hasic contractions without any significant change in base line ressure. For years, investigators have suggested the existence of a shincter at the rectosigmoid junction, and have referred to it as "O'Beime's shincter" or the rectosigmoid shincter. Others have been unable to observe any shincteric activity in the sigmoid colon or rectum of healthy subjects. so. II Failure to observe such a segment by these investigators may relate to their excluding subjects with constiation, or to differences in the ressure-sensing units emloyed. Almy et a1.,21 in a study of atients with irritable colon syndrome, observed "heightened motility" also in the form of "unremitting contractions of large amlitude" in the rectosigmoid region. Connell reorted a tendency to more active hasic contractions in constiated subjects than in normal subjects.' Although CCK or secretin did not alter the attern of the hyeractive segment, these hormones did influence the adjacent roximal sigmoid colon but had an insignificant effect on the rectum, as has been reorted reviously. U In contrast, glucagon, which resembles secretin in its molecular form, inhibited or abolished all wave activity of the hyeractive segment as well as the adjacent roximal and distal segments of colon. Similar effects were observed after the administration of atroine sulfate, which is known to deress intestinal motility.1f This suggests that the abnormal motor activity observed at the hyeractive segment may be due to a continuous discharge of a neurotransmitter via cholinergic athways acting erferentially on the muscarinic effector cells. If this interretation is correct, then the question arises as to whether constiation is the cause or the effect of the cholinergic overactivity. Further studies are indicated to determine the significance and the relationshi of this hyeractive segment to bowel function. We conclude that a hyeractive segment characterized by continuous wave activity of a comlex tye without any significant alterations in base line ressure exists at the rectosigmoid junction in a majority of subjects with constiation. This motor abnormality could have an imortant hysiological relationshi to constiation. It may reresent a segment that initiates motor dysynergia between sigmoid and rectum, thus contributing to the genesis of constiation. Although it could not be identified anatomically by the technique emloyed in this study, it robably corresonds to the narrowing at the rectosigmoid junction referred to frequently by anatomists and endoscoists. The athogenesis of this hyeractive segment is not clear at the resent time. REFERENCES 1. Chowdhury AR, Dinoso y, Lorber SH: Hyeractive segment at the rectosigmoid junction in normals and in subjects with func tional constiation and diverticulosis (abstr). Gastroenterology 66:A181, Connell AM: Alied hysiology of the colon: factors relevant to diverticular disease. Clin Gastroenterol 4:23-36, Schuster MM, Mendeloff AI: Characteristics of rectosigmoid motor function. In Progress in Gastroenterology, vol 2. Edited by GBJ Glass. New York, Grune and Stratton 1970, Truelove SC: Movements of the large intestine. Physiol Rev 46: , Code CF, Wilkinson GR Jr, Sauer WG: Normal and some abnormal colonic atterns in man. Ann NY Acad Sci 58: , Connell AM: The motility of the elvic colon. Part II. Paradoxical motility in diarrhea and constiation. Gut 3: , Christensen J: The controls of gastrointestinal movements: some old and new views. N Engl J Med 285:85-98, Misiewicz JJ: Colonic motility. 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