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THE ILEOCECAL SPHINCTER
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N T H E FOLLOWING DISCUSSION I SHALL USE T H E term "sphincter" in preference to "valve" because all those who have observed this structure in living, unanesthetized persons with a fistula into the cecum have emphasized the fact that there was no sign of the valve-like lips which appear in the cadaver. What they saw was a dome-like papilla with a dimpled orifice at the summit (Fig. 138). Elliott (1904) concluded that in animals also, the structure is a sphincter and not a valve. Rutherford, Mace wen, White et al., Short and Palmieri each studied the behavior of the ileocecal sphincter in patients with a large right-sided fecal fistula. Looking through the fistula, Rutherford saw a papilla about 1.8 cm. in diameter, projecting about 1 cm. from the wall of the cecum. The mucous membrane covering this eminence was smooth and glistening and had a red color deeper than that of the surrounding mucous membrane. From time to time there were rhythmic changes in the height and width of the papilla, and swaying movements which were associated with the to-and-fro contractions of the terminal segment of ileum. With each enlargement of the eminence there came a relaxation of the circular fibers, and some semi-fluid material (about 4 c.c. at a time) ran into the cecum. Under the influence of excitement, these little jets would appear as often as once every second or two. There was no sign of a valve until the patient was placed under deep anesthesia and then the papilla relaxed; it became more and more oval, and changed into a slit 2.5 cm. long. Usually the sphincter was tightly closed, and then any attempt to pass a catheter caused so much pain that Rutherford had to desist. Macewen had a patient similar to Rutherford's in whom he watched the behavior of the sphincter. He was impressed with the 548
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FIG. 138. A. Papilla of ileocecal sphincter from a man dead twenty-four hours. B. A similar papilla, more relaxed and valve-like. c. Diagrammatic illustration made from a section through the papilla, c.m.c, circ. muscle of cecum; c.m.i., circ. muscle of ileum; l.m.c, longit. muscle of the cecum; c.m.i., longit. muscle of the ileum; i.c.m.v., int. circ. muscle coat of the valve mammilla; ex.c.m.v., ext. circ. muscle coat; 3rd cm.v., third circ. muscle coat. (From Rutherford.)
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increase in muscular activity and in the flow of mucus which occurred after the taking of food. He also commented, first, on an outflow of fluid from the appendix just before material came through the ileocecal sphincter; second, on the jetlike emptying of the terminal ileum; and third, on the drying of the mucous membrane of the cecum which appeared one day when the patient's digestion was upset by the receipt of bad news. In Short's case the tonus of the ileocecal sphincter was not so good as it was in Rutherford's, and instead of being perfectly round the papilla was somewhat oval. Furthermore, when digestion was in progress and jets of ileal contents were appearing at frequent intervals, the sphincter remained relaxed so that it had the appearance of a slit about 3 cm. long. At such times Short was able to pass his finger into the ileum without producing pain. In spite of this occasional slit formation, Short still felt that the opening "should rather be regarded as a sphincter than a valve." He noticed that the coils of ileum were always active, but when the patient was fasting and lying quietly on his side, nothing came through the sphincter for hours at a time. Within from one and a half to four minutes after taking food, little gushes appeared, consisting first of succus entericus and later of food residues, about 15 c.c. every half minute or so. Short could not inhibit the emptying of the ileum through the sphincter by putting either acid or alkali into the cecum. He could slow the emptying by pinching the cecum, but he could not stop it. Heile, Cannon and White found also that they could slow the progress of material through the sphincter by irritating the colon or by distending the cecum with a balloon. Conditions seem, therefore, to be somewhat similar here and at the pylorus, and, for that matter, everywhere else in the bowel. As I have pointed out before, the law seems to be that stimulation at any point tends to hold back the progress of material coming down from above. Another study of the ileocecal sphincter of man was made by White, Rainey, Monaghan and Harris (1934). They studied the behavior of this region in a colored woman who had a large intestinal prolapse following colostomy. The receptive relaxation of the proximal part of the colon as described by Lyman was only occasionally observed. The sphincter was relaxed much of the time. It could be
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closed tightly by distending the proximal colon, if such distention resulted in contraction of the bowel. The sphincteric muscle frequently showed rhythmic contractions, the rate being sometimes
FIG. 139. A contracted ileocecal sphincter as seen in a roentgenogram.
higher and sometimes lower than that of the distal portion of the ileum. A traveling wave in the lower portion of the ileum came down
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several times an hour. When there were no traveling waves, rhythmic segmentations could be seen. The traveling wave of contraction was not preceded by an inhibition. Often it failed to reach the lower
FIG. 140.
The ileocecal sphincter of man, as it appears during life (From Palmieri.)
ileum. The sphincter sometimes contracted when a peristaltic wave started or when it arrived, but at other times there was no contraction of the sphincter at any time during the passage of a wave. The responses of the ileocecal sphincter seemed to be identical with those of the terminal segment of ileum. A good roentgenogram of the contracted sphincter in man is shown in Figure 139. Palmieri (1938) observed the sphincter in a woman who had a carcinoma of the cecum which grew through the anterior abdominal wall. Much of this tumor was cut away so as to give a view of the sphincter. He published a colored plate which shows a wine-red mammillary eminence about 1.5 cm. in diameter (Fig. 140). It was a little hard to stick the finger into the opening and the impression gained then was similar to that felt when sticking the
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finger into a tight anal sphincter. With this the patient did not feel anything. As Palmieri said, he certainly couldn't see any sign of lips or of a valve. He agreed with Rutherford in his description of the sphincter. It would seem that a valvelike appearance is to be seen only in roentgenograms or after death. According to Oppenheimer (1940) the ileocecal sphincter, when closed, appears in roentgenograms to consist of a pair of lips. Occasionally the terminal segment of ileum, when filled with barium, appears to end in a sort of funnel with material protruding between the lips of the "valve." See Fig. 139. As barium-containing material passes through the sphincter, this opens to a diameter of about 8 mm. Longitudinally running folds of mucosa can be seen in it. Normally the sphincter opens while the terminal segment of ileum is being emptied by the stripping tonic contractions, and it remains closed the rest of the time. It could not be determined whether there was active relaxation or the sphincter merely yielded to the pressure of advancing material. Normally the sphincter is competent and does not leak under pressure from the colon. Material that comes down from the mouth never goes back. As everyone knows, it usually goes back when it is injected as an enema, but then the conditions are decidedly unphysiologic. Using a roentgenologic cinematographic apparatus and patients, Barclay (1939) studied the region of the ileocecal sphincter. Usually the movements in the terminal segment of ileum were very slow, but occasionally they were fairly rapid, as when the terminal segment emptied into the cecum. Barclay presented illustrations showing examples of these emptying contractions. He observed local nontraveling movements and also peristaltic waves. Some of the records show that at times when the ilecocecal sphincter appeared to be open nothing was going through it. Material in the ileum did not come down and pack up against it. Barclay noticed slow systolic contractions of the cecum. Buirge (1944) found that the ileocecal valve, the ileocecal sphincr
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ter and the small intestine are all fundamentally similar in their motor activities. An excellent study of the ileocecal sphincter in animals was made by Hinrichsen and Ivy. Using dogs and watching through a fistula into the cecum, they saw the sphincter relax at intervals to allow the passage of small quantities of material, usually from 2 to 10 c.c. Stimulation of the colonie mucosa caused the sphincter to contract tightly. When fluid containing barium was injected into the terminal segment of ileum, a little would pass immediately into the cecum. Then the sphincter would contract tightly so as to allow no further passage for some time. Active rhythmic segmentation, longitudinal shortening, and peristaltic waves, would then appear in the ileum. This activity would continue usually for from a half to one and a half hours without producing any relaxation of the sphincter. If the animal was then given a meal, the last ileal segment usually became very active, and after about fifteen minutes the sphincter relaxed and opened before an advancing wave of constriction in the small bowel. This wave then almost emptied the lower end of the ileum. This gastro-ileac "reflex" did not appear to be a psychic one, because neither the sight nor the smell of food was ever sufficient to activate the mechanism. Even the giving of a small amount of food was insufficient to start the "réflexe The response was most easily obtained when the animal was hungry and was not obtainable when the animal had been recently fed. As Hannes found, fasting decreased the tonus of the sphincter. Distention of the stomach, duodenum, ileum, or colon all caused contraction of the sphincter. This response was abolished by sectioning both the vagus and the splanchnic nerves, or by cutting through the ileum and colon a few inches away from the sphincter. Obviously, the stimuli which cause contraction of the sphincter have their choice of nerves in the bowel and in the mesentery. Tönnis studied dogs with two fistulas into the ileum and colon, one a few centimeters above and the other the same distance below the sphincter. Normally, material came through at intervals of from six to thirty seconds. Changes in the temperature of the fluids injected had no influence on the rate of passage, and he could see no difference
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in the behavior of the sphincter after putting N 10 HCl or NaOH into the colon. The one thing that did put a stop to the opening of the sphincter was the filling of the colon with feces. That this is not so effective in man was shown by Donaldson, who found in four subjects that the small bowel continued to empty normally into the large bowel even when defecation was restrained voluntarily for four days. Tönnis (1924) cut all the nerves going to the ileocecal region and found that the sphincter was paralyzed for only four or five days. He concluded, therefore, that like the rest of the digestive tract, the sphincter is largely autonomous and dependent on the nerves only for regulatory impulses. He found also that if any part of the ileum was anastomosed with its end to the side of the colon, the new opening would take over satisfactorily the functions of the sphincter. This is what one would expect from the experience of surgeons operating on man; they too have found that there is no disturbance in health after the making of a simple anastomosis between the ileum and colon. This fact suggests strongly that the somewhat complicated ileocecal sphincter is not so important as some have thought. Certainly it would seem that surgeons have been wise in dropping Kellogg's operation for the reconstruction of a presumably leaky ileocecal sphincter. THE GASTRO-ILEAC REFLEX
So far as I know, Macewen (1904) was the first to call attention to the great increase in the rate of passage of the ileal contents into the colon, which is seen when food is taken. This gastro-ileac or gastrocolic "reflex" was rediscovered by Hurst (1913 b ), and it has since been seen by all those who have taken the trouble to look for it (Larson). The fact that food put into the stomach through a fistula did not have much effect on the ileocecal region caused Welch and Plant and Slive and Fogelson to conclude that the "reflex" is caused by the psychic rise in tonus that comes when food is eaten with relish. Against this idea are the observations of Hinrichsen and Ivy, and the observations of Douglas (1939) who used Biebl's type of loop in unanesthetized dogs. Douglas saw an increase in the activity in the ileum within from one to four minutes after feeding, even when the food was given through a gastric fistula. There was no change after
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double vagotomy in the thorax. The fact that the "reflex" was not easily demonstrated when the bowel was cut across, that it was demonstrable at times and not at others, and that it was elicited more easily in some animals than in others may well account for differences of opinion among research workers. AN ILEO-GASTRIC REFLEX There is some evidence also of an ileo-gastric "reflex," that is, if, because of inflammation in the cecum or appendix the progress of material in the terminal segment of ileum is delayed or stopped, there will be a slowing of the progress in the duodenum. This development of what I call "back-pressure" is discussed at length in Chapter vu. The phenomenon probably has clinical importance. I have reasons for suspecting that a certain type of hunger pain is due to back-pressure from the ileum or actual cramping contractions of an ileum which finds it hard to force material through a tight ileocecal sphincter. RECEPTIVE RELAXATION OF THE COLON Lyman described a receptive relaxation of the colon, preparatory to the arrival of ileal contents, similar to the receptive relaxation of the cardia associated with swallowing. THE NERVOUS CONTROL OF THE SPHINCTER The classic article on the innervation of the ileocolic sphincter is by Elliott ( 1904). He could not see that either the vagus or the pelvic visceral nerves had any control over it. In the cat, he saw no change in the tonus of the sphincter after stimulation of the inferior mesenteric nerves, but there was strong, steady contraction after stimulation of the splanchnics. Similar observations were made by Magnus (quoted by Koennecke) and Smets. This fits in with Gaskell's theories about the origin of the muscle in this region (1916, p. 46) and with the fact that some observers, notably Elliott (1904; 1905, p. 415), Kuroda, and Hinrichsen and Ivy have found that epinephrine stimulates the sphincteric muscle whereas it causes relaxation almost everywhere else in the tract. Similar findings at the pylorus were mentioned in Chapter xvn.
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Against Gaskell's idea is the fact that White, Rainey, Monaghan and Harris found that the ileocolic sphincter of man was relaxed by epinephrine. Pituitrin usually produced an increase in the activity of the colon and a diminution in the tonus and rhythmic activity of the ileum. Hinrichsen and Ivy found that, in the cat, the constrictor fibers to the sphincter issued chiefly from the thirteenth thoracic and first and second lumbar roots. Epinephrine had the same effect as sympathetic stimulation. Removal of the spinal cord permanently abolished the power of the sphincter to separate the contents of the ileum and colon. Smets found that stimulation of the central end of the cut splanchnic nerve of the dog causes contraction of the muscle about the ileocecal sphincter. Studies indicated that the afferent nerves involved enter the posterior roots of the spinal cord between the tenth thoracic and third lumbar segments. Elliott stated that the tonus of the ileocolic sphincter diminished slowly after the cord was destroyed, and that it was permanently lost after the splanchnics were cut. According to Magnus (quoted by Koennecke) the paralysis lasted for weeks. Hinrichsen and Ivy found that stimulation of either vagus nerve usually produced, first, slight relaxation or inhibition, and second, contraction of the sphincter. Stimulation of the superior mesenteric ganglion, the hypogastric nerves and the pelvic nerve caused contraction. Stimulation of the sciatic nerve had no effect. REGURGITATION THROUGH THE SPHINCTER
Cannon (1911 a , p. 156) found in his early studies on cats that, if an enema is held in the colon long enough, some of it will run back into the ileum. In one case he saw the animal vomit part of the enema containing round worms from the small bowel. I made similar observations in 1913 and felt as Cannon did that the conditions under which this régurgitation took place were abnormal, and that material which reaches the colon normally through the sphincter rarely goes back again. It is now well known that in perhaps all of the cases in which a barium enema is given to patients, if the operator runs in enough fluid and makes the patient wait long enough, some of the material runs
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back into the ileum. Some sphincters are doubtless more relaxed than others, but there is only a little evidence to indicate that such sphincters ordinarily leak or that leakage produces symptoms. It must also be remembered that the patients when roentgenoscoped have not only been purged the night before, but often they have been denied breakfast. This failure to eat is probably an important factor because Hannes found in cats and dogs with an ileal fistula that enemas regurgitated when the animal was fasting, but not when it had recently been fed. Because the ileocecal sphincter held firmly even when the animal's food was allowed to run out through a fistula made just below the pylorus, he concluded that the resultant increase in tonus was of psychic origin. The régurgitation of material that has once reached the colon from the ileum is probably rare, but it may be that it would be seen more often if men were always on the watch for it and if it were easier to distinguish definitely between small masses of barium in the ileum and in the pelvic colon. Case (1914 a , 1915C) and Groedel have reported cases in which they saw a return of fecal material into the small bowel. In the eighteenth century, when it was the fashion to take large medicated enemas, the sphincter was apparently assumed to be competent, judging from its whimsical nickname of "Le barrière des apothicaires." Many attempts have been made to ascribe the origin of certain syndromes to an incompetent ileocolic sphincter, but, as N . W. Jones pointed out in his study of 1,000 cases, it is generally hard to be sure that other, perhaps constitutional and nervous causes are not at work. For a while Kellogg advised operating on some of these patients to tighten the lips of the "valve," but later Case (1915 b ), who worked with him, advised that the operation be given up. THE FUNCTION OF THE SPHINCTER
The purpose of the ileocecal sphincter is probably, first, to prevent the reflux of foul bacteria-laden feces from the colon where absorption is slight into the ileum where absorption is probably much better, and second, to prevent too rapid passage of food residues through the terminal segment of the small bowel. In this second function of holding back material coming down through the lower ileum, the
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sphincter is doubtless helped by contractions arising in those muscle fibers that reinforce the wall in the last few centimeters of the intestine. This accessory sphincter, which has been described by Luschka, Keith (1903) and Elliott (1904), acts probably very much like those bands of highly rhythmic muscle that take the place of definite sphincters in some of the lower forms of life (Bottazzi; von Brücke, 1905, p. 202). In the rabbit, the sphincter is surrounded by a muscular organ called the "sacculus rotundus." As I showed years ago, this not only tends to contract with a rate a little higher than that of the muscle in the terminal segment of the ileum, but, in the last 25 cm. of the bowel, there is generally a gradient of rhythmicity extending upward toward the ileocecal sphincter (Alvarez, 1915 a ). This arrangement probably serves to somewhat reverse the current in this segment, so that material will not pack up against the sphincter as hard as it otherwise would. Perhaps most of the rush waves down the small bowel are stopped in the terminal ileum, but in the rabbit it can be seen that some of them run on down the colon. Motion pictures of rush waves in a rabbit show that one of them, after reaching the sphincter, was reflected so that it ran backward 2 5 cm. or more up the ileum. Child has often seen a similar reflection of waves at the ends of the rows of swimming plates in Ctenophores. The fact that the intestinal contents remain for some time quietly in the terminal ileum is well known both to physiologists and roentgenologists. In man, material whisks through the jejunum, leaving a little barium sprayed along the tips of the Kerkringian folds, while in the last 50 cm. of ileum, the slowing of progress causes the barium to appear in sausage-shaped masses. If it were not for the ileocecal sphincter, nutrition might suffer and men and women might more often be bothered by diarrhea. Also, if the colonie contents were to flow back into the ileum, we physicians might more often see symptoms of intestinal "auto-intoxication," whatever they may be (Alvarez, 1924 b ). When an ileal fistula is made in an animal or man, the bowel near the artificial anus after a time succeeds somehow in slowing the progress of material coming down and in dehydrating it so that it
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comes to look more like feces (BeuttenmüUer). In one patient who submitted to colectomy, this constipating effect was so marked that about once a year the unfortunate woman had to have a segment of hypertrophied ileum removed surgically. REASON FOR BLOCKAGE OF WAVES AT THE ILEOCECAL SPHINCTER In many ways the conditions at the ileocecal sphincter resemble those at the pylorus; again there is a barrier, not only between the contents of the two parts of the tract, but also between the waves on the two sides; and again the barrier is not complete. Again, also it appears to be due mainly to a folding of the muscle layers and an interposition of connective tissue. As can be seen from the descriptions and illustrations of Luschka, Lebon and Aubourg, Toldt, Engelmann and Van Brakel, Elliott (1904), and Rutherford (1914), the layers of circular muscle from the ileum and colon run out to the top of the papilla, with a layer of longitudinal muscle between them. Apparently there is not the discontinuity of the fibers which is to be seen at the pylorus, but it is possible that the folding of the muscle layers accomplishes the same purpose by leading approaching waves into a blind pocket and losing them there (Fig. 138). Just as at the pylorus, so here, the blockage of the waves may perhaps be ascribed partly to differences in the characteristics of the muscle above and below the sphincter and partly to peculiarities in the sphincter itself. The muscle of the colon appears to be more sluggish than that of the ileum, and its rhythmic activities are different. I have evidence pointing also to a greater irritability of the sphincter muscle which enables it to contract a little ahead of its turn. Thus if a cat's colon is tied off at the rectum and filled with soapy water, it will contract powerfully in its efforts to empty itself. Under such conditions I have often seen a deep wave running orad and threatening to force material into the ileum, but suddenly, before it reached the sphincter, the muscle there picked up the advancing stimulus, contracted powerfully ahead of its turn, and the advancing wave either faded out or broke ineffectively against the barrier. According to Bayliss and Starling (1900, p. 109), in the dog,
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waves often run from the ileum over onto the colon, but in this animal the two segments of the tract meet end-to-end without much sign of a division between them.
FIG. 141. Types of ileocolic junction seen in several vertebrate animals. (From Huntington.)
ANATOMY AND EMBRYOLOGY
Figure 141, taken from Huntington's splendid work, gives an idea of the many different ways in which, in the animal kingdom the ileum joins the colon. One of the peculiar things about this region is the presence of large masses of lymphoid tissue. In man, this tissue is massed in the appendix whereas in the dog, it is largely in the mesentery. In addition there are the patches of Peyer, which are particu-
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larly plentiful in the lower part of the ileum. This lymphoid tissue is probably placed at this point to protect the body from invasion by the micro-organisms which grow so freely in this one segment where the f eces are sufficiently liquid to supply a good culture medium. The embryology of the sphincter was studied by Beattie who found that the structure develops early as a swelling of the muscle fibers. At a certain stage in its development the ileocecal sphincter looks much like the pylorus. Plesch (1928) studied the structure in many species of animal and concluded that in some there is a flap which acts as a valve to prevent régurgitation. A study of what he called the "fremila valvulae coli" was made by Rutherford (1926). SUMMARY
The term "sphincter" is here used in preference to "valve" because all who have observed this structure in living unanesthetized men and women with a fistula into the cecum have emphasized the fact that it is a dome-like papilla without any sign of valve-like lips. The lips appear only after death has brought relaxation to the muscle fibers. Palmieri, who watched the sphincter work in a woman with a big opening into the cecum, agreed emphatically with Rutherford in stating that the opening was on a mammillary eminence which had no sign of lips. Oppenheimer who studied the sphincter with the roentgen rays, saw what looked like lips. Barclay studied the functions of this region with roentgen motion pictures. The mode of control of the sphincter seems to be something like that of the pylorus, where irritation of the bowel about it or caudad to it causes material coming down from above to be held back. The sphincter muscle shows rhythmic contractions which sometimes occur at a rate faster than that of the rhythmic movements of the terminal segment of ileum. Waves come down the ileum, usually several times an hour, and as they arrive, material may come through the sphincter in little jets. Stimulation of the colonie mucosa causes contraction of the sphincter and delay in the emptying of the ileum. Experiences with both animals and man show that the ileocecal
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sphincter is not essential to health. A man can get along well with a simple anastomosis between ileum and colon. When food is taken into the stomach there is a greater tendency for material to pass from the terminal ileum into the colon, and when there is a delay in the passage of material from the ileum to the colon, there may be a holding back of material in the stomach or upper bowel. A receptive relaxation of the colon has been described as taking place when material is about to come through from the ileum. Destruction of the spinal cord or section of the splanchnic nerves causes a marked loss of tonicity in the sphincter with loss of function. Stimulation of the vagus nerves may produce slight inhibition followed by contraction of the sphincter. Stimulation of the sympathetic nerves or the injection of epinephrine usually causes contraction. Régurgitation through the sphincter can easily be produced by filling the colon with an enema. It is questionable whether such regurgitation takes place in man when the material in the colon has come down from the stomach. The régurgitation after enemas is so nearly universal in its occurrence that no clinical significance can be attached to the fact as observed in the case of a particular patient. It is doubtful if disease is produced in man by the presence of a particularly incompetent sphincter. The function of the sphincter is not only to prevent the reflux of bacteria-laden feces from the colon into the ileum, but also to keep the ileum from emptying too often and too fast into the colon. In man, there is some interruption of the muscular coats of the bowel at the sphincter and this may help to keep every wave in the ileum from running on down the colon. There is evidence also that the sphincter muscle is more irritable than is the bowel on either side. This would help to keep it contracted and the sphincter tightly closed.
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N T H E FOLLOWING DISCUSSION I SHALL USE T H E term "sphincter" in preference to "valve" because all those who have observed this structure in living, unanesthetized persons with a fistula into the cecum have emphasized the fact that there was no sign of the valve-like lips which appear in the cadaver. What they saw was a dome-like papilla with a dimpled orifice at the summit (Fig. 138). Elliott (1904) concluded that in animals also, the structure is a sphincter and not a valve. Rutherford, Mace wen, White et al., Short and Palmieri each studied the behavior of the ileocecal sphincter in patients with a large right-sided fecal fistula. Looking through the fistula, Rutherford saw a papilla about 1.8 cm. in diameter, projecting about 1 cm. from the wall of the cecum. The mucous membrane covering this eminence was smooth and glistening and had a red color deeper than that of the surrounding mucous membrane. From time to time there were rhythmic changes in the height and width of the papilla, and swaying movements which were associated with the to-and-fro contractions of the terminal segment of ileum. With each enlargement of the eminence there came a relaxation of the circular fibers, and some semi-fluid material (about 4 c.c. at a time) ran into the cecum. Under the influence of excitement, these little jets would appear as often as once every second or two. There was no sign of a valve until the patient was placed under deep anesthesia and then the papilla relaxed; it became more and more oval, and changed into a slit 2.5 cm. long. Usually the sphincter was tightly closed, and then any attempt to pass a catheter caused so much pain that Rutherford had to desist. Macewen had a patient similar to Rutherford's in whom he watched the behavior of the sphincter. He was impressed with the 548
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FIG. 138. A. Papilla of ileocecal sphincter from a man dead twenty-four hours. B. A similar papilla, more relaxed and valve-like. c. Diagrammatic illustration made from a section through the papilla, c.m.c, circ. muscle of cecum; c.m.i., circ. muscle of ileum; l.m.c, longit. muscle of the cecum; c.m.i., longit. muscle of the ileum; i.c.m.v., int. circ. muscle coat of the valve mammilla; ex.c.m.v., ext. circ. muscle coat; 3rd cm.v., third circ. muscle coat. (From Rutherford.)
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increase in muscular activity and in the flow of mucus which occurred after the taking of food. He also commented, first, on an outflow of fluid from the appendix just before material came through the ileocecal sphincter; second, on the jetlike emptying of the terminal ileum; and third, on the drying of the mucous membrane of the cecum which appeared one day when the patient's digestion was upset by the receipt of bad news. In Short's case the tonus of the ileocecal sphincter was not so good as it was in Rutherford's, and instead of being perfectly round the papilla was somewhat oval. Furthermore, when digestion was in progress and jets of ileal contents were appearing at frequent intervals, the sphincter remained relaxed so that it had the appearance of a slit about 3 cm. long. At such times Short was able to pass his finger into the ileum without producing pain. In spite of this occasional slit formation, Short still felt that the opening "should rather be regarded as a sphincter than a valve." He noticed that the coils of ileum were always active, but when the patient was fasting and lying quietly on his side, nothing came through the sphincter for hours at a time. Within from one and a half to four minutes after taking food, little gushes appeared, consisting first of succus entericus and later of food residues, about 15 c.c. every half minute or so. Short could not inhibit the emptying of the ileum through the sphincter by putting either acid or alkali into the cecum. He could slow the emptying by pinching the cecum, but he could not stop it. Heile, Cannon and White found also that they could slow the progress of material through the sphincter by irritating the colon or by distending the cecum with a balloon. Conditions seem, therefore, to be somewhat similar here and at the pylorus, and, for that matter, everywhere else in the bowel. As I have pointed out before, the law seems to be that stimulation at any point tends to hold back the progress of material coming down from above. Another study of the ileocecal sphincter of man was made by White, Rainey, Monaghan and Harris (1934). They studied the behavior of this region in a colored woman who had a large intestinal prolapse following colostomy. The receptive relaxation of the proximal part of the colon as described by Lyman was only occasionally observed. The sphincter was relaxed much of the time. It could be
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closed tightly by distending the proximal colon, if such distention resulted in contraction of the bowel. The sphincteric muscle frequently showed rhythmic contractions, the rate being sometimes
FIG. 139. A contracted ileocecal sphincter as seen in a roentgenogram.
higher and sometimes lower than that of the distal portion of the ileum. A traveling wave in the lower portion of the ileum came down
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several times an hour. When there were no traveling waves, rhythmic segmentations could be seen. The traveling wave of contraction was not preceded by an inhibition. Often it failed to reach the lower
FIG. 140.
The ileocecal sphincter of man, as it appears during life (From Palmieri.)
ileum. The sphincter sometimes contracted when a peristaltic wave started or when it arrived, but at other times there was no contraction of the sphincter at any time during the passage of a wave. The responses of the ileocecal sphincter seemed to be identical with those of the terminal segment of ileum. A good roentgenogram of the contracted sphincter in man is shown in Figure 139. Palmieri (1938) observed the sphincter in a woman who had a carcinoma of the cecum which grew through the anterior abdominal wall. Much of this tumor was cut away so as to give a view of the sphincter. He published a colored plate which shows a wine-red mammillary eminence about 1.5 cm. in diameter (Fig. 140). It was a little hard to stick the finger into the opening and the impression gained then was similar to that felt when sticking the
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finger into a tight anal sphincter. With this the patient did not feel anything. As Palmieri said, he certainly couldn't see any sign of lips or of a valve. He agreed with Rutherford in his description of the sphincter. It would seem that a valvelike appearance is to be seen only in roentgenograms or after death. According to Oppenheimer (1940) the ileocecal sphincter, when closed, appears in roentgenograms to consist of a pair of lips. Occasionally the terminal segment of ileum, when filled with barium, appears to end in a sort of funnel with material protruding between the lips of the "valve." See Fig. 139. As barium-containing material passes through the sphincter, this opens to a diameter of about 8 mm. Longitudinally running folds of mucosa can be seen in it. Normally the sphincter opens while the terminal segment of ileum is being emptied by the stripping tonic contractions, and it remains closed the rest of the time. It could not be determined whether there was active relaxation or the sphincter merely yielded to the pressure of advancing material. Normally the sphincter is competent and does not leak under pressure from the colon. Material that comes down from the mouth never goes back. As everyone knows, it usually goes back when it is injected as an enema, but then the conditions are decidedly unphysiologic. Using a roentgenologic cinematographic apparatus and patients, Barclay (1939) studied the region of the ileocecal sphincter. Usually the movements in the terminal segment of ileum were very slow, but occasionally they were fairly rapid, as when the terminal segment emptied into the cecum. Barclay presented illustrations showing examples of these emptying contractions. He observed local nontraveling movements and also peristaltic waves. Some of the records show that at times when the ilecocecal sphincter appeared to be open nothing was going through it. Material in the ileum did not come down and pack up against it. Barclay noticed slow systolic contractions of the cecum. Buirge (1944) found that the ileocecal valve, the ileocecal sphincr
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ter and the small intestine are all fundamentally similar in their motor activities. An excellent study of the ileocecal sphincter in animals was made by Hinrichsen and Ivy. Using dogs and watching through a fistula into the cecum, they saw the sphincter relax at intervals to allow the passage of small quantities of material, usually from 2 to 10 c.c. Stimulation of the colonie mucosa caused the sphincter to contract tightly. When fluid containing barium was injected into the terminal segment of ileum, a little would pass immediately into the cecum. Then the sphincter would contract tightly so as to allow no further passage for some time. Active rhythmic segmentation, longitudinal shortening, and peristaltic waves, would then appear in the ileum. This activity would continue usually for from a half to one and a half hours without producing any relaxation of the sphincter. If the animal was then given a meal, the last ileal segment usually became very active, and after about fifteen minutes the sphincter relaxed and opened before an advancing wave of constriction in the small bowel. This wave then almost emptied the lower end of the ileum. This gastro-ileac "reflex" did not appear to be a psychic one, because neither the sight nor the smell of food was ever sufficient to activate the mechanism. Even the giving of a small amount of food was insufficient to start the "réflexe The response was most easily obtained when the animal was hungry and was not obtainable when the animal had been recently fed. As Hannes found, fasting decreased the tonus of the sphincter. Distention of the stomach, duodenum, ileum, or colon all caused contraction of the sphincter. This response was abolished by sectioning both the vagus and the splanchnic nerves, or by cutting through the ileum and colon a few inches away from the sphincter. Obviously, the stimuli which cause contraction of the sphincter have their choice of nerves in the bowel and in the mesentery. Tönnis studied dogs with two fistulas into the ileum and colon, one a few centimeters above and the other the same distance below the sphincter. Normally, material came through at intervals of from six to thirty seconds. Changes in the temperature of the fluids injected had no influence on the rate of passage, and he could see no difference
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in the behavior of the sphincter after putting N 10 HCl or NaOH into the colon. The one thing that did put a stop to the opening of the sphincter was the filling of the colon with feces. That this is not so effective in man was shown by Donaldson, who found in four subjects that the small bowel continued to empty normally into the large bowel even when defecation was restrained voluntarily for four days. Tönnis (1924) cut all the nerves going to the ileocecal region and found that the sphincter was paralyzed for only four or five days. He concluded, therefore, that like the rest of the digestive tract, the sphincter is largely autonomous and dependent on the nerves only for regulatory impulses. He found also that if any part of the ileum was anastomosed with its end to the side of the colon, the new opening would take over satisfactorily the functions of the sphincter. This is what one would expect from the experience of surgeons operating on man; they too have found that there is no disturbance in health after the making of a simple anastomosis between the ileum and colon. This fact suggests strongly that the somewhat complicated ileocecal sphincter is not so important as some have thought. Certainly it would seem that surgeons have been wise in dropping Kellogg's operation for the reconstruction of a presumably leaky ileocecal sphincter. THE GASTRO-ILEAC REFLEX
So far as I know, Macewen (1904) was the first to call attention to the great increase in the rate of passage of the ileal contents into the colon, which is seen when food is taken. This gastro-ileac or gastrocolic "reflex" was rediscovered by Hurst (1913 b ), and it has since been seen by all those who have taken the trouble to look for it (Larson). The fact that food put into the stomach through a fistula did not have much effect on the ileocecal region caused Welch and Plant and Slive and Fogelson to conclude that the "reflex" is caused by the psychic rise in tonus that comes when food is eaten with relish. Against this idea are the observations of Hinrichsen and Ivy, and the observations of Douglas (1939) who used Biebl's type of loop in unanesthetized dogs. Douglas saw an increase in the activity in the ileum within from one to four minutes after feeding, even when the food was given through a gastric fistula. There was no change after
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double vagotomy in the thorax. The fact that the "reflex" was not easily demonstrated when the bowel was cut across, that it was demonstrable at times and not at others, and that it was elicited more easily in some animals than in others may well account for differences of opinion among research workers. AN ILEO-GASTRIC REFLEX There is some evidence also of an ileo-gastric "reflex," that is, if, because of inflammation in the cecum or appendix the progress of material in the terminal segment of ileum is delayed or stopped, there will be a slowing of the progress in the duodenum. This development of what I call "back-pressure" is discussed at length in Chapter vu. The phenomenon probably has clinical importance. I have reasons for suspecting that a certain type of hunger pain is due to back-pressure from the ileum or actual cramping contractions of an ileum which finds it hard to force material through a tight ileocecal sphincter. RECEPTIVE RELAXATION OF THE COLON Lyman described a receptive relaxation of the colon, preparatory to the arrival of ileal contents, similar to the receptive relaxation of the cardia associated with swallowing. THE NERVOUS CONTROL OF THE SPHINCTER The classic article on the innervation of the ileocolic sphincter is by Elliott ( 1904). He could not see that either the vagus or the pelvic visceral nerves had any control over it. In the cat, he saw no change in the tonus of the sphincter after stimulation of the inferior mesenteric nerves, but there was strong, steady contraction after stimulation of the splanchnics. Similar observations were made by Magnus (quoted by Koennecke) and Smets. This fits in with Gaskell's theories about the origin of the muscle in this region (1916, p. 46) and with the fact that some observers, notably Elliott (1904; 1905, p. 415), Kuroda, and Hinrichsen and Ivy have found that epinephrine stimulates the sphincteric muscle whereas it causes relaxation almost everywhere else in the tract. Similar findings at the pylorus were mentioned in Chapter xvn.
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Against Gaskell's idea is the fact that White, Rainey, Monaghan and Harris found that the ileocolic sphincter of man was relaxed by epinephrine. Pituitrin usually produced an increase in the activity of the colon and a diminution in the tonus and rhythmic activity of the ileum. Hinrichsen and Ivy found that, in the cat, the constrictor fibers to the sphincter issued chiefly from the thirteenth thoracic and first and second lumbar roots. Epinephrine had the same effect as sympathetic stimulation. Removal of the spinal cord permanently abolished the power of the sphincter to separate the contents of the ileum and colon. Smets found that stimulation of the central end of the cut splanchnic nerve of the dog causes contraction of the muscle about the ileocecal sphincter. Studies indicated that the afferent nerves involved enter the posterior roots of the spinal cord between the tenth thoracic and third lumbar segments. Elliott stated that the tonus of the ileocolic sphincter diminished slowly after the cord was destroyed, and that it was permanently lost after the splanchnics were cut. According to Magnus (quoted by Koennecke) the paralysis lasted for weeks. Hinrichsen and Ivy found that stimulation of either vagus nerve usually produced, first, slight relaxation or inhibition, and second, contraction of the sphincter. Stimulation of the superior mesenteric ganglion, the hypogastric nerves and the pelvic nerve caused contraction. Stimulation of the sciatic nerve had no effect. REGURGITATION THROUGH THE SPHINCTER
Cannon (1911 a , p. 156) found in his early studies on cats that, if an enema is held in the colon long enough, some of it will run back into the ileum. In one case he saw the animal vomit part of the enema containing round worms from the small bowel. I made similar observations in 1913 and felt as Cannon did that the conditions under which this régurgitation took place were abnormal, and that material which reaches the colon normally through the sphincter rarely goes back again. It is now well known that in perhaps all of the cases in which a barium enema is given to patients, if the operator runs in enough fluid and makes the patient wait long enough, some of the material runs
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back into the ileum. Some sphincters are doubtless more relaxed than others, but there is only a little evidence to indicate that such sphincters ordinarily leak or that leakage produces symptoms. It must also be remembered that the patients when roentgenoscoped have not only been purged the night before, but often they have been denied breakfast. This failure to eat is probably an important factor because Hannes found in cats and dogs with an ileal fistula that enemas regurgitated when the animal was fasting, but not when it had recently been fed. Because the ileocecal sphincter held firmly even when the animal's food was allowed to run out through a fistula made just below the pylorus, he concluded that the resultant increase in tonus was of psychic origin. The régurgitation of material that has once reached the colon from the ileum is probably rare, but it may be that it would be seen more often if men were always on the watch for it and if it were easier to distinguish definitely between small masses of barium in the ileum and in the pelvic colon. Case (1914 a , 1915C) and Groedel have reported cases in which they saw a return of fecal material into the small bowel. In the eighteenth century, when it was the fashion to take large medicated enemas, the sphincter was apparently assumed to be competent, judging from its whimsical nickname of "Le barrière des apothicaires." Many attempts have been made to ascribe the origin of certain syndromes to an incompetent ileocolic sphincter, but, as N . W. Jones pointed out in his study of 1,000 cases, it is generally hard to be sure that other, perhaps constitutional and nervous causes are not at work. For a while Kellogg advised operating on some of these patients to tighten the lips of the "valve," but later Case (1915 b ), who worked with him, advised that the operation be given up. THE FUNCTION OF THE SPHINCTER
The purpose of the ileocecal sphincter is probably, first, to prevent the reflux of foul bacteria-laden feces from the colon where absorption is slight into the ileum where absorption is probably much better, and second, to prevent too rapid passage of food residues through the terminal segment of the small bowel. In this second function of holding back material coming down through the lower ileum, the
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sphincter is doubtless helped by contractions arising in those muscle fibers that reinforce the wall in the last few centimeters of the intestine. This accessory sphincter, which has been described by Luschka, Keith (1903) and Elliott (1904), acts probably very much like those bands of highly rhythmic muscle that take the place of definite sphincters in some of the lower forms of life (Bottazzi; von Brücke, 1905, p. 202). In the rabbit, the sphincter is surrounded by a muscular organ called the "sacculus rotundus." As I showed years ago, this not only tends to contract with a rate a little higher than that of the muscle in the terminal segment of the ileum, but, in the last 25 cm. of the bowel, there is generally a gradient of rhythmicity extending upward toward the ileocecal sphincter (Alvarez, 1915 a ). This arrangement probably serves to somewhat reverse the current in this segment, so that material will not pack up against the sphincter as hard as it otherwise would. Perhaps most of the rush waves down the small bowel are stopped in the terminal ileum, but in the rabbit it can be seen that some of them run on down the colon. Motion pictures of rush waves in a rabbit show that one of them, after reaching the sphincter, was reflected so that it ran backward 2 5 cm. or more up the ileum. Child has often seen a similar reflection of waves at the ends of the rows of swimming plates in Ctenophores. The fact that the intestinal contents remain for some time quietly in the terminal ileum is well known both to physiologists and roentgenologists. In man, material whisks through the jejunum, leaving a little barium sprayed along the tips of the Kerkringian folds, while in the last 50 cm. of ileum, the slowing of progress causes the barium to appear in sausage-shaped masses. If it were not for the ileocecal sphincter, nutrition might suffer and men and women might more often be bothered by diarrhea. Also, if the colonie contents were to flow back into the ileum, we physicians might more often see symptoms of intestinal "auto-intoxication," whatever they may be (Alvarez, 1924 b ). When an ileal fistula is made in an animal or man, the bowel near the artificial anus after a time succeeds somehow in slowing the progress of material coming down and in dehydrating it so that it
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comes to look more like feces (BeuttenmüUer). In one patient who submitted to colectomy, this constipating effect was so marked that about once a year the unfortunate woman had to have a segment of hypertrophied ileum removed surgically. REASON FOR BLOCKAGE OF WAVES AT THE ILEOCECAL SPHINCTER In many ways the conditions at the ileocecal sphincter resemble those at the pylorus; again there is a barrier, not only between the contents of the two parts of the tract, but also between the waves on the two sides; and again the barrier is not complete. Again, also it appears to be due mainly to a folding of the muscle layers and an interposition of connective tissue. As can be seen from the descriptions and illustrations of Luschka, Lebon and Aubourg, Toldt, Engelmann and Van Brakel, Elliott (1904), and Rutherford (1914), the layers of circular muscle from the ileum and colon run out to the top of the papilla, with a layer of longitudinal muscle between them. Apparently there is not the discontinuity of the fibers which is to be seen at the pylorus, but it is possible that the folding of the muscle layers accomplishes the same purpose by leading approaching waves into a blind pocket and losing them there (Fig. 138). Just as at the pylorus, so here, the blockage of the waves may perhaps be ascribed partly to differences in the characteristics of the muscle above and below the sphincter and partly to peculiarities in the sphincter itself. The muscle of the colon appears to be more sluggish than that of the ileum, and its rhythmic activities are different. I have evidence pointing also to a greater irritability of the sphincter muscle which enables it to contract a little ahead of its turn. Thus if a cat's colon is tied off at the rectum and filled with soapy water, it will contract powerfully in its efforts to empty itself. Under such conditions I have often seen a deep wave running orad and threatening to force material into the ileum, but suddenly, before it reached the sphincter, the muscle there picked up the advancing stimulus, contracted powerfully ahead of its turn, and the advancing wave either faded out or broke ineffectively against the barrier. According to Bayliss and Starling (1900, p. 109), in the dog,
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waves often run from the ileum over onto the colon, but in this animal the two segments of the tract meet end-to-end without much sign of a division between them.
FIG. 141. Types of ileocolic junction seen in several vertebrate animals. (From Huntington.)
ANATOMY AND EMBRYOLOGY
Figure 141, taken from Huntington's splendid work, gives an idea of the many different ways in which, in the animal kingdom the ileum joins the colon. One of the peculiar things about this region is the presence of large masses of lymphoid tissue. In man, this tissue is massed in the appendix whereas in the dog, it is largely in the mesentery. In addition there are the patches of Peyer, which are particu-
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larly plentiful in the lower part of the ileum. This lymphoid tissue is probably placed at this point to protect the body from invasion by the micro-organisms which grow so freely in this one segment where the f eces are sufficiently liquid to supply a good culture medium. The embryology of the sphincter was studied by Beattie who found that the structure develops early as a swelling of the muscle fibers. At a certain stage in its development the ileocecal sphincter looks much like the pylorus. Plesch (1928) studied the structure in many species of animal and concluded that in some there is a flap which acts as a valve to prevent régurgitation. A study of what he called the "fremila valvulae coli" was made by Rutherford (1926). SUMMARY
The term "sphincter" is here used in preference to "valve" because all who have observed this structure in living unanesthetized men and women with a fistula into the cecum have emphasized the fact that it is a dome-like papilla without any sign of valve-like lips. The lips appear only after death has brought relaxation to the muscle fibers. Palmieri, who watched the sphincter work in a woman with a big opening into the cecum, agreed emphatically with Rutherford in stating that the opening was on a mammillary eminence which had no sign of lips. Oppenheimer who studied the sphincter with the roentgen rays, saw what looked like lips. Barclay studied the functions of this region with roentgen motion pictures. The mode of control of the sphincter seems to be something like that of the pylorus, where irritation of the bowel about it or caudad to it causes material coming down from above to be held back. The sphincter muscle shows rhythmic contractions which sometimes occur at a rate faster than that of the rhythmic movements of the terminal segment of ileum. Waves come down the ileum, usually several times an hour, and as they arrive, material may come through the sphincter in little jets. Stimulation of the colonie mucosa causes contraction of the sphincter and delay in the emptying of the ileum. Experiences with both animals and man show that the ileocecal
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sphincter is not essential to health. A man can get along well with a simple anastomosis between ileum and colon. When food is taken into the stomach there is a greater tendency for material to pass from the terminal ileum into the colon, and when there is a delay in the passage of material from the ileum to the colon, there may be a holding back of material in the stomach or upper bowel. A receptive relaxation of the colon has been described as taking place when material is about to come through from the ileum. Destruction of the spinal cord or section of the splanchnic nerves causes a marked loss of tonicity in the sphincter with loss of function. Stimulation of the vagus nerves may produce slight inhibition followed by contraction of the sphincter. Stimulation of the sympathetic nerves or the injection of epinephrine usually causes contraction. Régurgitation through the sphincter can easily be produced by filling the colon with an enema. It is questionable whether such regurgitation takes place in man when the material in the colon has come down from the stomach. The régurgitation after enemas is so nearly universal in its occurrence that no clinical significance can be attached to the fact as observed in the case of a particular patient. It is doubtful if disease is produced in man by the presence of a particularly incompetent sphincter. The function of the sphincter is not only to prevent the reflux of bacteria-laden feces from the colon into the ileum, but also to keep the ileum from emptying too often and too fast into the colon. In man, there is some interruption of the muscular coats of the bowel at the sphincter and this may help to keep every wave in the ileum from running on down the colon. There is evidence also that the sphincter muscle is more irritable than is the bowel on either side. This would help to keep it contracted and the sphincter tightly closed.