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Functional Gastro-Intestinal Disturbances
FUNCTIONAL GASTRO·INTESTINAL DISTURBANCES CHESTER
M.
JONES,
M.D.-
THAT emotional disturbances and states of nervous tension can be responsible for somatic symptoms is a fact that is generally accepted by the majority of practicing physicians. Too frequently, however, the practical application of such a concept in the actual handling of problems as they are presented by the patient is lacking. The steadily increasing tempo of modern life, with its stresses and strains, is reflected in the vast majority of histories that can be obtained in office and hospital practice. In no system of the body is there a more obvious and at times more dramatic manifestation of the close relationship between organic symptoms and psychological disturbances than in the gastro-intestinal tract. Alterations of function on the basis of psychological factors, affecting as they do secretory, motor and absorptive processes, can be easily determined by adequate study and particularly by a careful history. It is still true that most erroneous diagnoses are due to the lack of a meticulous history, rather than to the lack of other forms of clinical investigation, particularly those relating to laboratory procedures. Too often diagnosis and therapeutic measures are predicated upon an attempted assay of innumerable and frequently unnecessary laboratory studies, when a really thorough history would provide the logical diagnosis and indication for therapy. It goes without saying that in patients complaining of serious symptoms adequate studies are needed in order to rule out the more serious forms of organic disease, but many times such studies fail to reveal the true cause of the patient's disability and suffering. PATHOLOGICAL MECHANISMS
Innumerable papers have been written on the subject, and the profound observations of men like Weir Mitchell, Pavlov, Alvarez and many others point clearly to the mechanism underlying a large pro'portion of digestive tract symptoms. The actual visualization of alterations in gastric or intestinal physiology during periods of abnormal nervous stimulation has been clearly described by various authors. Beaumont, in his classical studies on gastric physiology, observed striking changes in the appearance of the stomach under various emotional and mood changes. Intense hyperemia, "aphthous patches" in the stomach and increased mucus secretion were frequently noted. More recently the very excellent studies of Wolff and his collab• Clinical Professor of Medicine, Harvard University; Physician, Massachusetts General Hospital. 1154
FUNCTIONAL GASTRO-INTESTINAL DISTURBANCES
1155
orators on another patient with a gastric fistula demonstrated even more clearly the very definite relationship between gastric physiology and the function of the higher nervous centers. Extreme pallor of the gastric mucosa and diminished secretion accompanied states of fear or anxiety, whereas extreme rese~tment was usually associated with an intense increase in the vascularity of the mucous membrane and with increased gastric secretion. Similarly, White and Jones demonstrated by sigmoidoscopy analogous changes in the appearance of the normal mucosa of the rectum and sigmoid following overstimulation of the parasympathetic nervous system. Cholinergic drugs even in moderate doses produced in normal individuals such extreme occluding spasm of the sigmoid that the passage of a sigmoidoscope was rendered impossible. Under these circumstances all normal vascular markings were obliterated, and diffuse marked hyperemia was noted, with a definite increase in the secretion of mucus. An extreme example of such a physiological change was observed in one normal individual who became suddenly embarrassed during the sigmoidoscopic examination, with an almost immediate change in the color of the mucosa from a pale salmon pink to a bright red color. The change was so intense that it was described as a "rectal blush." Such observations indicate clearly the close integration between the autonomic nervous system and higher emotional centers and the actual functioning of the digestive system. The term "functional disease" is not particularly precise in its application to various clinical problems. It is undoubtedly true, however, that the exaggeration of normal physiological responses as described above can readily form the basis of important symptoms that create diagnostic and therapeutic difficulties. The actual borderline between organic disease and a functional disturbance is so tenuous and so shifting that it is frequently all but impossible to state that no organic disease exists. The symptoms, physical findings, and roentgenologic and sigmoidoscopic abnormalities that can be demonstrated in patients with so-called mucous colitis are a good example of such a difficulty. Nearly all experienced observers are agreed that this condition does not represent a true colitis. Yet in innumerable instances there is not only a history of repeated attacks of intense abdominal pain, but one can easily demonstrate a tender, palpable sigmoid on physical examination. Because of the intensity of the symptoms and the apparent definiteness of physical findings, many ill-advised operations have been performed only to find no organic disease. The secretion of mucus in such instances is at times amazing, and the mucous casts so closely resemble tissue that not infrequently both the patient and the physician are alarmed by their appearance. Such phenomena certainly mimic organic disease in many instances and possess many of its physical and symptomatic characteristics. . Smooth Muscle Spasm Mimicking Organic Disease.-An extreme exam-
1156
CHESTER M. JONES
pIe of the intense smooth muscle spasm that can occur under periods of extreme emotional stress was seen in the following case: An elderly man of 74 years was subjected to an abdominal operation because of recurrent attacks of diverticulitis of the lower sigmoid. The predominating element in the entire clinical picture was one of intense anxiety, which increased to a state of abject fear on the day of operation. Because of the age of the patient and his general physical condition, a low spinal anesthesia had been chosen for the particular operation in question, thus leaving the patient still in possession of his faculties when he reached the operating table, in spite of fairly heavy doses of sedatives. On opening the abdomen, a hard, avascular tumor was observed involving the antrum and pylorus. Inasmuch as a careful x-ray study preceding the operation had shown no evidence of disease of the stomach, the exploring surgeon was extremely surprised and felt that there had been a possible error in diagnosis and that there might be an infiltrating carcinoma of the stomach which had not been recognized. The operation on the sigmoid proceeded, however, and after about 30 minutes it was noted that the pale, hard tumor of the stomach had completely disappeared and that the entire antrum and pylorus were not only normal in color but of normal consistency. It was undoubtedly true that the intense pylorospasm occasioned by fear of surgery was responsible for this curious phenomenon.
Such intense spasm undoubtedly occurs in many clinical conditions and, as a rule, is the occasion for extremely painful sensations. In the gastro-intestinal tract, localized spasm is apt to occur at or near the sphincters or in the narrower portions of the alimentary tube. Thus the cardiac end of the esophagus, the pylorus, the ileocecal junction and the sigmoid are sites where localized spasm frequently occurs with major symptoms. Anatomical defects, although not constituting actual organic disease, are also trigger points where focal disturbances may occur which form the basis of patients' complaints. Thus esophageal diverticula, para-esophageal hernias, Meckel's diverticula, diverticula of the large bowel, and minor areas of narrowing due to inflammatory adhesions may serve as the basis for focal changes in the vascular bed and local smooth muscle tone as the· result of abnormal stimulation of the autonomic nervous system. In most instances the distressing symptoms resulting from such irritable foci do not require surgical treatment. Rather, the control of the individual, with his numerous reactions to the ordinary or extraordinary wear and tear of daily living may provide the most logical and the most satisfactory therapeutic approach. Gastro-intestinal Bleeding of Functional Origin.-Most physicians visualize the concept of smooth muscle spasm, with or without focal disease, as a basis for chronic symptoms. It is less commonly understood that at times associated changes occur in the local blood supply of the mucosal lining of the digestive tract in areas of spasm, which may simulate an inflammatory process and may even result in minor bleeding episodes. These changes have been visualized and described in detail in well illustrated articles by the various authors mentioned
FUNCTIONAL GASTRO-INTESTINAL DISTURBANCES
1157
above. The following clinical examples may serve as illustrations of the foregoing discussion. CASE REPORTS
I.-The patient was a 56-year-old married woman, with a history of previous operations for subdeltoid bursitis, malposition of the uterus, and trifacial neuralgia over a period of approximately 15 years. Some months after a ventral suspension of the uterus (1919) the patient had a severe attack of lower abdominal pain without any preceding symptoms. There was no nausea or vom~ iting. Physical examination was negative, and there was no elevation of temperature. She was seen by both a medical advisor and a surgeon, who decided that no operation was necessary but were unable to make an immediate diagnosis. Hypodermic injections of morphine were given with symptomatic relief. A few days later the patient passed a very large amount of mucus by rectum, and a diagnosis of mucous colitis was made. Following that episode there was a constant recurrence of left-sided abdominal pain, always associated with the passage of typical loose stools with large amounts of mucus. These episodes seemed more or less to correspond with periods of fatigue or prolonged nervous tension. During the ensuing years occasional studies were made of the entire gastro-intestinal tract, but no evidence could· be obtained of any local disease. During the years 1925 to 1931 the patient's symptoms were less severe and were more easily controlled once a relatively smooth diet with antispasmodic and mild sedatives were employed. In 1930 the patient began to be bothered by attacks of severe substernal oppression, with a feeling of tightness radiating up to the throat and what was described as local esophageal cramps. When these symptoms occurred there was apt to be a return of the bowel symptoms. The substernal distress occurred somewhat more frequently and was more intense during the following months, and at times, after eating, the patient experienced extreme distress under the region of the xiphoid and a feeling as if she had eaten a very large bolus of food. Following a rather fatiguing Christmas and New Year period, her symptoms increased and were described as follows: (1) difficulty in swallowing, with a marked feeling of constriction at the lower end of the sternum; (2) epigastric distress just under the xiphoid, going to the precordium; and (3) extreme breathlessness. The patient recognized clearly that these symptoms might be brought on by any acute emotional disturbance or by fatigue. With the increase in symptoms suggesting esophageal disease, the colonic symptoms diminished in intensity. Finally, a very distressing attack of substernal, precordial distress occurred, associated with extreme difficulty in swallowing. This attack came on shortly after the death of a close friend. Because of the severity of the symptoms the patient was brought to the hospital, and a swallow of barium was given. At this time x-ray examination of the esophagus, which had been normal in previous studies, showed definite occluding spasm in the lower third about an inch and a half above the cardiac orifice. Extreme pain was experienced during the x-ray examination. The inhalation of a small amount of amyl nitrite under fluoroscopic observation resulted in the rapid disappearance of the area of spasm and a complete relief of the substernal distress. After the esophageal spasm had relaxed there was no obstruction either to thin or to thick barium mixtures. No deformity in the outline of the esophagus could be seen, and no fleck could be noted suggesting an ulcer. A year later x-rays of the same area revealed the same phenomenon. The symptom had recurred on numerous occasions in association with periods of emotional tension or fatigue. During the following year, however, the patient gained a good deal of insight into the cause of her symptoms and was helped CASE
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CHESTER M. JONES
somewhat by psychiatric advice and somewhat by the use of sedatives and antispasmodics, with the result that x-rays taken in 1933 revealed no esophageal spasm. During the year 1932 there had been periods when it was necessary for the patient to take nitroglycerin as a means of enabling her to swallow adequate amounts of food. It was of interest that at this time the bowel symptoms were essentially nonexistent. The year preceding these x-rays had been a particularly distressing one on account of various incidents, such as prolonged sickness in the family and anxiety. Finally, an interesting episode occurred in the year 1933 at the outset of an ocean voyage to which the patient had looked forward with a good deal of pleasure. In preparing for the voyage she became tense and unduly tired, and shortly after embarking had definite colonic symptoms and passed black tarry stools. There was no associated diarrhea and no fresh blood. For psychological reasons x-rays were not·· taken on her arrival in Europe, but on her return to this country adequate studies were carried out, which apparently ruled out any form of disease of the gastro-intestinal tract at any level. From 1933 to the present time no further episodes of tarry stools have occurred, although from time to time there have been attacks of substernal pressure, dysphagia and breathlessness, and periods of typical mucous colitis.
Cormnent.- This case is of interest in relation to one subsequently to be mentioned in that it combined symptoms of smooth muscle spasm with probable vascular changes in the bowel productive of actual bleeding. No absolute proof was obtained as to the source of the bleeding, but in comparison with examples given below it seems reasonable to suspect that there was not only intense spasm but also intense hyperemia at some level of the digestive tract, resulting in capillary oozing. In this particular case the relationship between emotional disturbances and striking gastro-intestinal symptoms was always obvious. The first episode in 1919 simulated an acute abdominal attack and only after careful consultation was surgical intervention avoided. After the nature of the symptoms became more apparent, measures calculated to relieve local spasm and to enable the patient to live at a satisfactory emotional level were employed with varying degrees of success. As is true in many instances, more than one level of the gastrointestinal tract was involved. At times the esophageal spasm was so intense that it actually necessitated a sharp modification in diet, forcing the patient to take merely liquid food in small amounts. Repeated studies were necessary before the fear of organic esophageal obstruction was finally ruled out. The symptom of breathlessness was undoubtedly of nervous origin and will be commented upon again. It was entirely comparable to the paroxysmal episodes of intense sighing so frequently seen in overreactive, hypersensitive individuals. It is of interest to point out that on numerous occasions in this particular individual over the entire period of many years, symptomatic relief was frequently obtained by the use of nitroglycerin, a drug that is still not used with sufficient frequency in the handling of gastro-intestinal complaints.
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CAsE 11.-The patient was a physician's wife, aged 55 years, who was admitted the hospital because of nausea, heartburn, vomiting, peristaltic unrest and loss of weight, the symptoms being of 10 years' duration. Her past history was important because of the evidence of overreaction to excitement, emotional difficulties, and the like as shown by the fact that she vomited as a child after going to the circus. Her symptoms became aggravated 10' years before admission after the death of her husband, for whom she had constAntly grieved. Physical examination, except for underweight, was entirely negative. Examination of the entire gastro-intestinal tract by x-ray revealed no abnormality. During the patient's stay in the hospital there were J6ng periods of crying, which represented the obvious reaction to anxiety, uncettainty, extreme loneliness and frustration. Only after prolonged reassurance; some sedation and 'a gradual increase in diet was it possible to eliminate nausea and vomiting. On discharge the patient was eating a fairly adequate diet. Her story is of interest in the present discussion because one year before her admission to the hospital, immediately after attending the funeral of a dear friend, she had had an attack of acute diarrhea, with day and night movements, mucu$ in large quantities, and after 24 hours the passage of blood, over a period of 3 days. Endoscopic examination at that time and subsequently failed to show any source of the bleeding in the anal canal or in the rectum or rectosigmoid. During the year following her discharge from the hospital the patient had numerous relapses, with a return of upper gastro-intestinal symptoms. These coincided with emotional outbursts in every instance. At the end of this period she returned to the hospital, at which time she exhibited a new symptom, namely extreme breathlessness and at times overbreathing, with actual tetany. Reassurance and a gradual reorganization of her life, combined with regulation of diet and smoking and the periodic use of antispasmodics, gradually resulted in improvement in symptoms and a gain in weight. No further episodes of bleeding occurred in the next 6 years.
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CASE III.-This patient was a dentist 39 years of age, who said that he had always been well, except for the limitations imposed by' a congenital club foot. One year before his first hospital admission he noted the appearance of blood with his bowel movements. The blood appeared to be on the outside of the movements, and there was no anal pain. He was examined by his brother, a physician, who was unable to demonstrate any fissure or hemorrhoids on anoscopy, and he was advised to have adequate x-rays. No further examinations were made during the following 12 months, although the bleeding continued periodically. Failure to have a proper examination was due to the fact that the patient was extremely fearful of finding cancer. During this year .it was noted that the bowel movements were more frequent and were looser in consistency at times, at other times the' patient being definitely constipated. There was no loss of weight. X-rays taken at the expiration of this time suggested the possibility of several polyps in the sigmoid colon. Because of the x-ray findings the patient was admitted to the hospital, at which time physical examination was entirely negative, except for the presence of a small anal fissure and an internal hemorrhoid. Blood was seen in the fissure but further studies were carried out because material was obtained from the interior of ~ach formed stool giving a test for occult blood. A barium enema at .this time done by ordinary routine and also using the double contrast method failed to reveal any polypi or any other abnormalities of the colon. Sigmoidoscopy was performed and revealed local pin-point areas of bleeding in the rectum. and rectosigmoid, and intense hyperemia. Four years later he again entered the hospital because of anxiety over a moderate amount of weight loss and because of two episodes of abdominal, griping pain, with loose movements. Again the ga$trointestinal studies, both of the upper and lower digestive tract, were entirely normal.
1160
CHESTER M. ]ONES
Comment.-A careful analysis of this patient's history at the time of each hospital admission revealed that his bowel symptoms were very definitely associated with periods of very profound anxiety, overwork and real fatigue. These factors were much more marked at the time of the first admission than four years later, but it is interesting to note that on the second hospital admission he was having, in addition to occasional bowel disturbances, vasomotor disturbances of tachycardia, exc"essive paroxysmal sweating, and flushing similar to the menopausal symptoms experienced by his wife at the same time. The latter volunteered the information that during her pregnancy the patient had vomited as much or more than she. At an insurance examination just prior to the second hospital admission at a time of unusual stress, sugar had been found in the urine, but subsequent fasting blood sugars and sugar tolerance tests revealed nothing abnormal. In other words, this patient also represented a hyperreactive type of individual with symptoms involving several systems but most striking as related to the gastro-intestinal tract. CASE IV.-A housewife of 46 years entered the hospital with a story of gradually increasing lower abdominal distress associated with the passage of hard, inspissated feces and rectal blood and mucus. After about 3 weeks of these symptoms she noted an increase in rectal discharges, many of which consisted in nothing but mucus and blood. Just prior to admission to the hospital, because of the use of milk of magnesia she was having six to eight bowel movements a day, with the frequent appearance of fresh blood in the stools and an associated loss of 11 pounds in weight. Her previous history was negative, except for the fact that she had always been a very emotional, overconscientious, introspective individual, who in spite of her marriage had been more closely attached to her mother than to her husband. A complete physical examination was absolutely negative, aside from hyperactive reflexes, moist skin and dilated pupils. Examination of the anal canal was normal. Sigmoidoscopy revealed extreme hyperemia of the rectum and rectosigmoid, with superficial bleeding areas but no true ulcerations. The walls of the bowel were extremely contractile so that almost occluding spasm was produced by attempts to sponge the mucosa. Complete gastro-intestinal x-rays failed to reveal any evidence of organic disease. There was no evidence of any other systemic disturbance. With sedation, a smooth diet and reassurance, the symptoms gradually subsided and the patient was discharged, to return 3 months later, at which time sigmoidoscopy showed no evidence of bleeding, although the sigmoid was still extremely spastic and hyperemic. Afer the second examination rectal symptoms disappeared completely and there was no further bleeding for some months. Shortly thereafter, however, the patient began to complain of frequent paroxysms of sighing and inability to get a deep breath, with a feeling of choking and constriction around the neck as though "a valve had been suddenly shut off." Palpitation, sweating and giddiness occasionally accompanied these episodes. One such attack had occurred when she and her husband were starting off on a week-end excursion, and the appearance of symptoms had necessitated their return home to the close proximity of the patient's mother. Physical examination in the office was negative, but at the end of the examination the patient suddenly gasped, choked and called for help, desiring her husband and the physician to hold her ,up in order to prevent her falling over. Her husband, who was an extremely excitable individual, was very much alarmed, and his apprehension
FUNCTIONAL GASTRO-INTESTINAL DISTURBANCES
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increased hers, although it was quite obvious that the attack had all the earmarks of being hysterical in nature. It was of incidental interest that a white blood count done at this time was elevated, with a value of 14,000 cells. The patient was immediately hospitalized and was studied thoroughly from the point of view of trachea, lungs and esophagus. All of these studies were negative, both x-ray and otherwise, and a throat consultant was unable to find any evidence of bulbar palsy, recurrent laryngeal nerve pressure, or local disease in the throat, pharynx, hypopharynx or larynx. Although there was no elevation of temperature and no evidence of any infection either on physical examination or urinary studies, the white blood count remained moderately elevated during this hospital admission. She was seen by a psychiatrist, who felt that the diagnosis was that of anxiety state with some hysterical features. At the time, the patient was anxious to discuss surgical interference for spasm of the larynx, an indication of the extreme apprehension under which she was living. She remained in the hospital for a period of two weeks and then returned home, for the time being relieved of all symptoms. In reviewing the previous hospital and office studies in this case, it is interesting to note that a transient elevation of white blood count had been noted on previous occasions, without any evidence of infection whatever. Several months later a letter from her home physician related that there had been a return of her previous intestinal symptoms, with bowel frequency and the passage of some mucus and blood. These symptoms cleared up under appropriate treatment, but on their disappearance there was again a return of the episodes of severe choking and difficulty in breathing. During the acute episodes her white blood count was noted to be at a level of about 12,000. Her home physician gradually gave her adequate reassurance, and for the following year and a half she was relatively symptom-free. At the end of this time there was again a return of the bowel difficulties, with the passage of blood and mucus and associated episodes of difficult breathing.
Comment.-A careful analysis of the entire history revealed that aside from the evidences of obvious emotional instability, no positive findings were made except that of a hyperemic, extremely spastic sigmoid which oozed blood in slight amounts on the slightest trauma associated with wiping gently with a sponge, or on the passage of hard fecal material. The nature of the emotional difficulties became exceedingly clear during the period under which the patient was observed and was associated with two factors: (1) real anxiety over her husband's health and financial affairs; and (2) a constant deep urge to be with her mother even at the expense of leaving her husband, to whom she appeared to be devoted. These episodes of emotional conflict invariably precipitated either the intestinal or the upper respiratory symptoms of which she complained. Inasmuch as she was followed over a period of 3 years, there is little reason to believe that the leukocytosis was anything more than an unusual expression of a somlltic response to psychological unrest. Such a mechanism has been carefully studied and reported by various observers, including Garrey and his co-workers. GENERAL COMMENT
The foregoing examples illustrate clearly the important relationship existing between the higher emotional levels and the functioning
1162
CliESTER M. JONES
of the gastro-intestinal tract or other systems. They are of particular interest becaus,e of the evidence of bleeding from the gastro-intestinal tract that occurred as a result of profound emotional experiences. It is of the utmost clinical importance that such an explanation for digestive tract bleeding should be accepted only after the most thorough studies and prolonged observation. Failure to exclude any form of organic disease capable of producing bleeding would at once invalidate any conclusions as to the "functional" nature of the symptom. In these cases, however, the individual patients were followed over a sufficient period of time and had sufficiently adequate repeated studies to warrant such an 'assumption. It is probable that the bleeding represents merely an exaggeration of the normal physiological response of one or another portion of the digestive tract to excessive stimulation. Such stimulation could come from an irritable focus at any level in the nerve pathways from the endings of the autonomic nervous system in the bowel wall to the higher centers. In these instances there seemed little doubt that abnormal emotional states produced periodic changes in the gastro-intestinal tract by means of stimuli carried over the pathways from the higher levels through the hypo thalamic area to the final autonomic fibers. The instances of acute respiratory embarrassment associated with evidences of change in gastro-intestinal tone and vascularity are of some additional interest. The transient episodes of leukocytosisare also of interest and are probably analogous to the leukocytosis observed during drug withdrawal in morphine addicts. TREATMENT
Once adequate studies have been performed and the nature of the cause of the symptoms is determined, therapeutic measures can be simply outlined, although they are difficult of performance. The fundamental principles to be followed are those to be employed in any unstable, overreactive individual. Whether or not intensive psychotherapy is indicated is dependent upon individual circumstances. More frequently than not the family physician who knows the patient and his surroundings best is in the best position to provide reassurance and stability. Artificial regulation of living habits, with adequate attention to periodic rest and regularity of living, is frequently an essential maneuver. In the face of gastro-intestinal symptoms nonirritating foods form the basis of any dietary control, but dietary measures in themselves are far from adequate unless combined with the effective handling of the individual in question. Antispasmodics and sedatives offer additional help in the control of individual episodes or over long periods of time. For acute episodes, very often the repeated administration of nitroglycerin is extremely helpful in relieving the pain or discomfort incident to smooth muscle spasm. Over a long period of time atropine
FUNCfIONAL GASTRO-INTESTINAL DISTURBANCES
1163
or its derivatives or synthetic spasmolytic drugs are frequently of great benefit. In the case of atropine or belladonna, it is important to point out that nothing but tolerance doses are effective. Too frequently minimal or "safe" doses are employed, with no physiological effect whatever. Only by a combination of all of these therapeutic measures over long periods of time can individual patients be brought under control and freed from the discomfort of such distressing symptoms as those described.
M.
JONES,
M.D.-
THAT emotional disturbances and states of nervous tension can be responsible for somatic symptoms is a fact that is generally accepted by the majority of practicing physicians. Too frequently, however, the practical application of such a concept in the actual handling of problems as they are presented by the patient is lacking. The steadily increasing tempo of modern life, with its stresses and strains, is reflected in the vast majority of histories that can be obtained in office and hospital practice. In no system of the body is there a more obvious and at times more dramatic manifestation of the close relationship between organic symptoms and psychological disturbances than in the gastro-intestinal tract. Alterations of function on the basis of psychological factors, affecting as they do secretory, motor and absorptive processes, can be easily determined by adequate study and particularly by a careful history. It is still true that most erroneous diagnoses are due to the lack of a meticulous history, rather than to the lack of other forms of clinical investigation, particularly those relating to laboratory procedures. Too often diagnosis and therapeutic measures are predicated upon an attempted assay of innumerable and frequently unnecessary laboratory studies, when a really thorough history would provide the logical diagnosis and indication for therapy. It goes without saying that in patients complaining of serious symptoms adequate studies are needed in order to rule out the more serious forms of organic disease, but many times such studies fail to reveal the true cause of the patient's disability and suffering. PATHOLOGICAL MECHANISMS
Innumerable papers have been written on the subject, and the profound observations of men like Weir Mitchell, Pavlov, Alvarez and many others point clearly to the mechanism underlying a large pro'portion of digestive tract symptoms. The actual visualization of alterations in gastric or intestinal physiology during periods of abnormal nervous stimulation has been clearly described by various authors. Beaumont, in his classical studies on gastric physiology, observed striking changes in the appearance of the stomach under various emotional and mood changes. Intense hyperemia, "aphthous patches" in the stomach and increased mucus secretion were frequently noted. More recently the very excellent studies of Wolff and his collab• Clinical Professor of Medicine, Harvard University; Physician, Massachusetts General Hospital. 1154
FUNCTIONAL GASTRO-INTESTINAL DISTURBANCES
1155
orators on another patient with a gastric fistula demonstrated even more clearly the very definite relationship between gastric physiology and the function of the higher nervous centers. Extreme pallor of the gastric mucosa and diminished secretion accompanied states of fear or anxiety, whereas extreme rese~tment was usually associated with an intense increase in the vascularity of the mucous membrane and with increased gastric secretion. Similarly, White and Jones demonstrated by sigmoidoscopy analogous changes in the appearance of the normal mucosa of the rectum and sigmoid following overstimulation of the parasympathetic nervous system. Cholinergic drugs even in moderate doses produced in normal individuals such extreme occluding spasm of the sigmoid that the passage of a sigmoidoscope was rendered impossible. Under these circumstances all normal vascular markings were obliterated, and diffuse marked hyperemia was noted, with a definite increase in the secretion of mucus. An extreme example of such a physiological change was observed in one normal individual who became suddenly embarrassed during the sigmoidoscopic examination, with an almost immediate change in the color of the mucosa from a pale salmon pink to a bright red color. The change was so intense that it was described as a "rectal blush." Such observations indicate clearly the close integration between the autonomic nervous system and higher emotional centers and the actual functioning of the digestive system. The term "functional disease" is not particularly precise in its application to various clinical problems. It is undoubtedly true, however, that the exaggeration of normal physiological responses as described above can readily form the basis of important symptoms that create diagnostic and therapeutic difficulties. The actual borderline between organic disease and a functional disturbance is so tenuous and so shifting that it is frequently all but impossible to state that no organic disease exists. The symptoms, physical findings, and roentgenologic and sigmoidoscopic abnormalities that can be demonstrated in patients with so-called mucous colitis are a good example of such a difficulty. Nearly all experienced observers are agreed that this condition does not represent a true colitis. Yet in innumerable instances there is not only a history of repeated attacks of intense abdominal pain, but one can easily demonstrate a tender, palpable sigmoid on physical examination. Because of the intensity of the symptoms and the apparent definiteness of physical findings, many ill-advised operations have been performed only to find no organic disease. The secretion of mucus in such instances is at times amazing, and the mucous casts so closely resemble tissue that not infrequently both the patient and the physician are alarmed by their appearance. Such phenomena certainly mimic organic disease in many instances and possess many of its physical and symptomatic characteristics. . Smooth Muscle Spasm Mimicking Organic Disease.-An extreme exam-
1156
CHESTER M. JONES
pIe of the intense smooth muscle spasm that can occur under periods of extreme emotional stress was seen in the following case: An elderly man of 74 years was subjected to an abdominal operation because of recurrent attacks of diverticulitis of the lower sigmoid. The predominating element in the entire clinical picture was one of intense anxiety, which increased to a state of abject fear on the day of operation. Because of the age of the patient and his general physical condition, a low spinal anesthesia had been chosen for the particular operation in question, thus leaving the patient still in possession of his faculties when he reached the operating table, in spite of fairly heavy doses of sedatives. On opening the abdomen, a hard, avascular tumor was observed involving the antrum and pylorus. Inasmuch as a careful x-ray study preceding the operation had shown no evidence of disease of the stomach, the exploring surgeon was extremely surprised and felt that there had been a possible error in diagnosis and that there might be an infiltrating carcinoma of the stomach which had not been recognized. The operation on the sigmoid proceeded, however, and after about 30 minutes it was noted that the pale, hard tumor of the stomach had completely disappeared and that the entire antrum and pylorus were not only normal in color but of normal consistency. It was undoubtedly true that the intense pylorospasm occasioned by fear of surgery was responsible for this curious phenomenon.
Such intense spasm undoubtedly occurs in many clinical conditions and, as a rule, is the occasion for extremely painful sensations. In the gastro-intestinal tract, localized spasm is apt to occur at or near the sphincters or in the narrower portions of the alimentary tube. Thus the cardiac end of the esophagus, the pylorus, the ileocecal junction and the sigmoid are sites where localized spasm frequently occurs with major symptoms. Anatomical defects, although not constituting actual organic disease, are also trigger points where focal disturbances may occur which form the basis of patients' complaints. Thus esophageal diverticula, para-esophageal hernias, Meckel's diverticula, diverticula of the large bowel, and minor areas of narrowing due to inflammatory adhesions may serve as the basis for focal changes in the vascular bed and local smooth muscle tone as the· result of abnormal stimulation of the autonomic nervous system. In most instances the distressing symptoms resulting from such irritable foci do not require surgical treatment. Rather, the control of the individual, with his numerous reactions to the ordinary or extraordinary wear and tear of daily living may provide the most logical and the most satisfactory therapeutic approach. Gastro-intestinal Bleeding of Functional Origin.-Most physicians visualize the concept of smooth muscle spasm, with or without focal disease, as a basis for chronic symptoms. It is less commonly understood that at times associated changes occur in the local blood supply of the mucosal lining of the digestive tract in areas of spasm, which may simulate an inflammatory process and may even result in minor bleeding episodes. These changes have been visualized and described in detail in well illustrated articles by the various authors mentioned
FUNCTIONAL GASTRO-INTESTINAL DISTURBANCES
1157
above. The following clinical examples may serve as illustrations of the foregoing discussion. CASE REPORTS
I.-The patient was a 56-year-old married woman, with a history of previous operations for subdeltoid bursitis, malposition of the uterus, and trifacial neuralgia over a period of approximately 15 years. Some months after a ventral suspension of the uterus (1919) the patient had a severe attack of lower abdominal pain without any preceding symptoms. There was no nausea or vom~ iting. Physical examination was negative, and there was no elevation of temperature. She was seen by both a medical advisor and a surgeon, who decided that no operation was necessary but were unable to make an immediate diagnosis. Hypodermic injections of morphine were given with symptomatic relief. A few days later the patient passed a very large amount of mucus by rectum, and a diagnosis of mucous colitis was made. Following that episode there was a constant recurrence of left-sided abdominal pain, always associated with the passage of typical loose stools with large amounts of mucus. These episodes seemed more or less to correspond with periods of fatigue or prolonged nervous tension. During the ensuing years occasional studies were made of the entire gastro-intestinal tract, but no evidence could· be obtained of any local disease. During the years 1925 to 1931 the patient's symptoms were less severe and were more easily controlled once a relatively smooth diet with antispasmodic and mild sedatives were employed. In 1930 the patient began to be bothered by attacks of severe substernal oppression, with a feeling of tightness radiating up to the throat and what was described as local esophageal cramps. When these symptoms occurred there was apt to be a return of the bowel symptoms. The substernal distress occurred somewhat more frequently and was more intense during the following months, and at times, after eating, the patient experienced extreme distress under the region of the xiphoid and a feeling as if she had eaten a very large bolus of food. Following a rather fatiguing Christmas and New Year period, her symptoms increased and were described as follows: (1) difficulty in swallowing, with a marked feeling of constriction at the lower end of the sternum; (2) epigastric distress just under the xiphoid, going to the precordium; and (3) extreme breathlessness. The patient recognized clearly that these symptoms might be brought on by any acute emotional disturbance or by fatigue. With the increase in symptoms suggesting esophageal disease, the colonic symptoms diminished in intensity. Finally, a very distressing attack of substernal, precordial distress occurred, associated with extreme difficulty in swallowing. This attack came on shortly after the death of a close friend. Because of the severity of the symptoms the patient was brought to the hospital, and a swallow of barium was given. At this time x-ray examination of the esophagus, which had been normal in previous studies, showed definite occluding spasm in the lower third about an inch and a half above the cardiac orifice. Extreme pain was experienced during the x-ray examination. The inhalation of a small amount of amyl nitrite under fluoroscopic observation resulted in the rapid disappearance of the area of spasm and a complete relief of the substernal distress. After the esophageal spasm had relaxed there was no obstruction either to thin or to thick barium mixtures. No deformity in the outline of the esophagus could be seen, and no fleck could be noted suggesting an ulcer. A year later x-rays of the same area revealed the same phenomenon. The symptom had recurred on numerous occasions in association with periods of emotional tension or fatigue. During the following year, however, the patient gained a good deal of insight into the cause of her symptoms and was helped CASE
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CHESTER M. JONES
somewhat by psychiatric advice and somewhat by the use of sedatives and antispasmodics, with the result that x-rays taken in 1933 revealed no esophageal spasm. During the year 1932 there had been periods when it was necessary for the patient to take nitroglycerin as a means of enabling her to swallow adequate amounts of food. It was of interest that at this time the bowel symptoms were essentially nonexistent. The year preceding these x-rays had been a particularly distressing one on account of various incidents, such as prolonged sickness in the family and anxiety. Finally, an interesting episode occurred in the year 1933 at the outset of an ocean voyage to which the patient had looked forward with a good deal of pleasure. In preparing for the voyage she became tense and unduly tired, and shortly after embarking had definite colonic symptoms and passed black tarry stools. There was no associated diarrhea and no fresh blood. For psychological reasons x-rays were not·· taken on her arrival in Europe, but on her return to this country adequate studies were carried out, which apparently ruled out any form of disease of the gastro-intestinal tract at any level. From 1933 to the present time no further episodes of tarry stools have occurred, although from time to time there have been attacks of substernal pressure, dysphagia and breathlessness, and periods of typical mucous colitis.
Cormnent.- This case is of interest in relation to one subsequently to be mentioned in that it combined symptoms of smooth muscle spasm with probable vascular changes in the bowel productive of actual bleeding. No absolute proof was obtained as to the source of the bleeding, but in comparison with examples given below it seems reasonable to suspect that there was not only intense spasm but also intense hyperemia at some level of the digestive tract, resulting in capillary oozing. In this particular case the relationship between emotional disturbances and striking gastro-intestinal symptoms was always obvious. The first episode in 1919 simulated an acute abdominal attack and only after careful consultation was surgical intervention avoided. After the nature of the symptoms became more apparent, measures calculated to relieve local spasm and to enable the patient to live at a satisfactory emotional level were employed with varying degrees of success. As is true in many instances, more than one level of the gastrointestinal tract was involved. At times the esophageal spasm was so intense that it actually necessitated a sharp modification in diet, forcing the patient to take merely liquid food in small amounts. Repeated studies were necessary before the fear of organic esophageal obstruction was finally ruled out. The symptom of breathlessness was undoubtedly of nervous origin and will be commented upon again. It was entirely comparable to the paroxysmal episodes of intense sighing so frequently seen in overreactive, hypersensitive individuals. It is of interest to point out that on numerous occasions in this particular individual over the entire period of many years, symptomatic relief was frequently obtained by the use of nitroglycerin, a drug that is still not used with sufficient frequency in the handling of gastro-intestinal complaints.
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CAsE 11.-The patient was a physician's wife, aged 55 years, who was admitted the hospital because of nausea, heartburn, vomiting, peristaltic unrest and loss of weight, the symptoms being of 10 years' duration. Her past history was important because of the evidence of overreaction to excitement, emotional difficulties, and the like as shown by the fact that she vomited as a child after going to the circus. Her symptoms became aggravated 10' years before admission after the death of her husband, for whom she had constAntly grieved. Physical examination, except for underweight, was entirely negative. Examination of the entire gastro-intestinal tract by x-ray revealed no abnormality. During the patient's stay in the hospital there were J6ng periods of crying, which represented the obvious reaction to anxiety, uncettainty, extreme loneliness and frustration. Only after prolonged reassurance; some sedation and 'a gradual increase in diet was it possible to eliminate nausea and vomiting. On discharge the patient was eating a fairly adequate diet. Her story is of interest in the present discussion because one year before her admission to the hospital, immediately after attending the funeral of a dear friend, she had had an attack of acute diarrhea, with day and night movements, mucu$ in large quantities, and after 24 hours the passage of blood, over a period of 3 days. Endoscopic examination at that time and subsequently failed to show any source of the bleeding in the anal canal or in the rectum or rectosigmoid. During the year following her discharge from the hospital the patient had numerous relapses, with a return of upper gastro-intestinal symptoms. These coincided with emotional outbursts in every instance. At the end of this period she returned to the hospital, at which time she exhibited a new symptom, namely extreme breathlessness and at times overbreathing, with actual tetany. Reassurance and a gradual reorganization of her life, combined with regulation of diet and smoking and the periodic use of antispasmodics, gradually resulted in improvement in symptoms and a gain in weight. No further episodes of bleeding occurred in the next 6 years.
to
CASE III.-This patient was a dentist 39 years of age, who said that he had always been well, except for the limitations imposed by' a congenital club foot. One year before his first hospital admission he noted the appearance of blood with his bowel movements. The blood appeared to be on the outside of the movements, and there was no anal pain. He was examined by his brother, a physician, who was unable to demonstrate any fissure or hemorrhoids on anoscopy, and he was advised to have adequate x-rays. No further examinations were made during the following 12 months, although the bleeding continued periodically. Failure to have a proper examination was due to the fact that the patient was extremely fearful of finding cancer. During this year .it was noted that the bowel movements were more frequent and were looser in consistency at times, at other times the' patient being definitely constipated. There was no loss of weight. X-rays taken at the expiration of this time suggested the possibility of several polyps in the sigmoid colon. Because of the x-ray findings the patient was admitted to the hospital, at which time physical examination was entirely negative, except for the presence of a small anal fissure and an internal hemorrhoid. Blood was seen in the fissure but further studies were carried out because material was obtained from the interior of ~ach formed stool giving a test for occult blood. A barium enema at .this time done by ordinary routine and also using the double contrast method failed to reveal any polypi or any other abnormalities of the colon. Sigmoidoscopy was performed and revealed local pin-point areas of bleeding in the rectum. and rectosigmoid, and intense hyperemia. Four years later he again entered the hospital because of anxiety over a moderate amount of weight loss and because of two episodes of abdominal, griping pain, with loose movements. Again the ga$trointestinal studies, both of the upper and lower digestive tract, were entirely normal.
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CHESTER M. ]ONES
Comment.-A careful analysis of this patient's history at the time of each hospital admission revealed that his bowel symptoms were very definitely associated with periods of very profound anxiety, overwork and real fatigue. These factors were much more marked at the time of the first admission than four years later, but it is interesting to note that on the second hospital admission he was having, in addition to occasional bowel disturbances, vasomotor disturbances of tachycardia, exc"essive paroxysmal sweating, and flushing similar to the menopausal symptoms experienced by his wife at the same time. The latter volunteered the information that during her pregnancy the patient had vomited as much or more than she. At an insurance examination just prior to the second hospital admission at a time of unusual stress, sugar had been found in the urine, but subsequent fasting blood sugars and sugar tolerance tests revealed nothing abnormal. In other words, this patient also represented a hyperreactive type of individual with symptoms involving several systems but most striking as related to the gastro-intestinal tract. CASE IV.-A housewife of 46 years entered the hospital with a story of gradually increasing lower abdominal distress associated with the passage of hard, inspissated feces and rectal blood and mucus. After about 3 weeks of these symptoms she noted an increase in rectal discharges, many of which consisted in nothing but mucus and blood. Just prior to admission to the hospital, because of the use of milk of magnesia she was having six to eight bowel movements a day, with the frequent appearance of fresh blood in the stools and an associated loss of 11 pounds in weight. Her previous history was negative, except for the fact that she had always been a very emotional, overconscientious, introspective individual, who in spite of her marriage had been more closely attached to her mother than to her husband. A complete physical examination was absolutely negative, aside from hyperactive reflexes, moist skin and dilated pupils. Examination of the anal canal was normal. Sigmoidoscopy revealed extreme hyperemia of the rectum and rectosigmoid, with superficial bleeding areas but no true ulcerations. The walls of the bowel were extremely contractile so that almost occluding spasm was produced by attempts to sponge the mucosa. Complete gastro-intestinal x-rays failed to reveal any evidence of organic disease. There was no evidence of any other systemic disturbance. With sedation, a smooth diet and reassurance, the symptoms gradually subsided and the patient was discharged, to return 3 months later, at which time sigmoidoscopy showed no evidence of bleeding, although the sigmoid was still extremely spastic and hyperemic. Afer the second examination rectal symptoms disappeared completely and there was no further bleeding for some months. Shortly thereafter, however, the patient began to complain of frequent paroxysms of sighing and inability to get a deep breath, with a feeling of choking and constriction around the neck as though "a valve had been suddenly shut off." Palpitation, sweating and giddiness occasionally accompanied these episodes. One such attack had occurred when she and her husband were starting off on a week-end excursion, and the appearance of symptoms had necessitated their return home to the close proximity of the patient's mother. Physical examination in the office was negative, but at the end of the examination the patient suddenly gasped, choked and called for help, desiring her husband and the physician to hold her ,up in order to prevent her falling over. Her husband, who was an extremely excitable individual, was very much alarmed, and his apprehension
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1161
increased hers, although it was quite obvious that the attack had all the earmarks of being hysterical in nature. It was of incidental interest that a white blood count done at this time was elevated, with a value of 14,000 cells. The patient was immediately hospitalized and was studied thoroughly from the point of view of trachea, lungs and esophagus. All of these studies were negative, both x-ray and otherwise, and a throat consultant was unable to find any evidence of bulbar palsy, recurrent laryngeal nerve pressure, or local disease in the throat, pharynx, hypopharynx or larynx. Although there was no elevation of temperature and no evidence of any infection either on physical examination or urinary studies, the white blood count remained moderately elevated during this hospital admission. She was seen by a psychiatrist, who felt that the diagnosis was that of anxiety state with some hysterical features. At the time, the patient was anxious to discuss surgical interference for spasm of the larynx, an indication of the extreme apprehension under which she was living. She remained in the hospital for a period of two weeks and then returned home, for the time being relieved of all symptoms. In reviewing the previous hospital and office studies in this case, it is interesting to note that a transient elevation of white blood count had been noted on previous occasions, without any evidence of infection whatever. Several months later a letter from her home physician related that there had been a return of her previous intestinal symptoms, with bowel frequency and the passage of some mucus and blood. These symptoms cleared up under appropriate treatment, but on their disappearance there was again a return of the episodes of severe choking and difficulty in breathing. During the acute episodes her white blood count was noted to be at a level of about 12,000. Her home physician gradually gave her adequate reassurance, and for the following year and a half she was relatively symptom-free. At the end of this time there was again a return of the bowel difficulties, with the passage of blood and mucus and associated episodes of difficult breathing.
Comment.-A careful analysis of the entire history revealed that aside from the evidences of obvious emotional instability, no positive findings were made except that of a hyperemic, extremely spastic sigmoid which oozed blood in slight amounts on the slightest trauma associated with wiping gently with a sponge, or on the passage of hard fecal material. The nature of the emotional difficulties became exceedingly clear during the period under which the patient was observed and was associated with two factors: (1) real anxiety over her husband's health and financial affairs; and (2) a constant deep urge to be with her mother even at the expense of leaving her husband, to whom she appeared to be devoted. These episodes of emotional conflict invariably precipitated either the intestinal or the upper respiratory symptoms of which she complained. Inasmuch as she was followed over a period of 3 years, there is little reason to believe that the leukocytosis was anything more than an unusual expression of a somlltic response to psychological unrest. Such a mechanism has been carefully studied and reported by various observers, including Garrey and his co-workers. GENERAL COMMENT
The foregoing examples illustrate clearly the important relationship existing between the higher emotional levels and the functioning
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CliESTER M. JONES
of the gastro-intestinal tract or other systems. They are of particular interest becaus,e of the evidence of bleeding from the gastro-intestinal tract that occurred as a result of profound emotional experiences. It is of the utmost clinical importance that such an explanation for digestive tract bleeding should be accepted only after the most thorough studies and prolonged observation. Failure to exclude any form of organic disease capable of producing bleeding would at once invalidate any conclusions as to the "functional" nature of the symptom. In these cases, however, the individual patients were followed over a sufficient period of time and had sufficiently adequate repeated studies to warrant such an 'assumption. It is probable that the bleeding represents merely an exaggeration of the normal physiological response of one or another portion of the digestive tract to excessive stimulation. Such stimulation could come from an irritable focus at any level in the nerve pathways from the endings of the autonomic nervous system in the bowel wall to the higher centers. In these instances there seemed little doubt that abnormal emotional states produced periodic changes in the gastro-intestinal tract by means of stimuli carried over the pathways from the higher levels through the hypo thalamic area to the final autonomic fibers. The instances of acute respiratory embarrassment associated with evidences of change in gastro-intestinal tone and vascularity are of some additional interest. The transient episodes of leukocytosisare also of interest and are probably analogous to the leukocytosis observed during drug withdrawal in morphine addicts. TREATMENT
Once adequate studies have been performed and the nature of the cause of the symptoms is determined, therapeutic measures can be simply outlined, although they are difficult of performance. The fundamental principles to be followed are those to be employed in any unstable, overreactive individual. Whether or not intensive psychotherapy is indicated is dependent upon individual circumstances. More frequently than not the family physician who knows the patient and his surroundings best is in the best position to provide reassurance and stability. Artificial regulation of living habits, with adequate attention to periodic rest and regularity of living, is frequently an essential maneuver. In the face of gastro-intestinal symptoms nonirritating foods form the basis of any dietary control, but dietary measures in themselves are far from adequate unless combined with the effective handling of the individual in question. Antispasmodics and sedatives offer additional help in the control of individual episodes or over long periods of time. For acute episodes, very often the repeated administration of nitroglycerin is extremely helpful in relieving the pain or discomfort incident to smooth muscle spasm. Over a long period of time atropine
FUNCfIONAL GASTRO-INTESTINAL DISTURBANCES
1163
or its derivatives or synthetic spasmolytic drugs are frequently of great benefit. In the case of atropine or belladonna, it is important to point out that nothing but tolerance doses are effective. Too frequently minimal or "safe" doses are employed, with no physiological effect whatever. Only by a combination of all of these therapeutic measures over long periods of time can individual patients be brought under control and freed from the discomfort of such distressing symptoms as those described.