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Effects of Changes in Dietary Lipids on Intestinal Fluid Loss in the Short-Bowel Syndrome WIESLAW BOCHENEK, M.D., JOHN B. RODGERS, JR., M.D., and JOHN A. BALINT, M.B., M.R.C.P., Albany, New York Seven patients underwent massive intestinal resection. Fecal losses of water and electrolytes were life threatening in four patients, who required constant or repeated intravenous replacement. All patients received symptomatic treatment and vitamin replacement. Lowering the amount of dietary fat, bile salt replacement, and supplementation of diet with micellar fat were ineffective. A regimen consisting of 50 to 7 5 % replacement of dietary long-chain fat with medium-chain triglyceride proved beneficial, leading to gradual decline in fecal loss of water and electrolytes and great improvement in nutritional status. Gastric secretory studies showed minimal increase in basal and 12-hr overnight acid output in two patients and no increase in maximal acid output. Pyloroplasty and vagotomy attempted in one patient and directed toward reduction of gastric secretion proved disastrous. Such treatment should be reserved for patients demonstrating massive gastric hypersecretion unresponsive to medical management, and a conservative program should be followed. MASSIVE SMALL-BOWEL resection performed for inflammatory bowel disease or for other reasons can create serious therapeutic problems. In recent years the term "short-bowel syndrome" has been used to describe a situation in patients who are unable to maintain their metabolic balance because of a short residual intestinal tract. Typically such patients demonstrate severe diarrhea and lose excessive amounts of water and electrolytes in their stools to a degree that endangers life. Problems of malabsorption and related malnutrition are often of secondary importance. • From the Department of Medicine Medical College, Albany, N. Y. (Gastroenterology), Albany The amount of bowel removed and the site of resection determines the clinical status. Normally most constituents in the diet are absorbed by the proximal small bowel (1). The distal small bowel, however, has certain important absorptive functions such as active transport of sodium (2), absorption of water, reabsorption of conjugated bile salts (3), and absorption of vitamin B i 2 (4). With removal of the proximal small intestine the ileum is often able to compensate at least partially for the loss of jejunum and take over the function of absorption of dietary materials. However, with distal small-bowel resection, fluid and electrolyte losses are often great because the jejunum has a limited capacity to absorb these substances. The jejunum cannot actively transport conjugated bile salts, and with distal ileal resection steatorrhea develops from bile salt deficiency (5). Excessive loss of water and electrolytes in the short-bowel syndrome may have another source. Patients with massive small-bowel resection were found by some (6) to have gastric hypersecretion. This in itself increases the fluid volume presented to the intestinal tract for absorption and lowers intestinal pH, which may interfere with digestive and absorptive processes. Malabsorption created in this way can lead to increased fecal loss of water and electrolytes. The studies reported here were undertaken to determine whether changes in quantity and mode of administration of dietary fat would control fluid and electrolyte losses, and to determine what role, if any, gastric hypersecretion plays in the pathogenesis of the short-bowel syndrome. Materials and Methods During 1967 and 1968 four patients who had undergone extensive small bowel resection presented with massive fecal losses of water and electrolytes. All re205 Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 termined using the method of Mosbach and associates (7). Duodenal samples were collected from the same tube through which the oil was administered. During trials of bile salt replacement a crude bile salt preparation was made up in skim milk to contain 1.5 g of bile salts per 100 ml (30 mM), and was given q.Ld. with meals. During trials of micellar fat supplementation micellar fat solution was prepared in skim milk using 30 mM bile salt, 35 mM oleic acid, and 14 mM monoolein, and was given in amounts of 100 ml q.i.d. with meals. Each dose contained 1.5 g of bile salts, 15 g of oleic acid, and 7.5 g of monoolein. The bile salt used was Ox Bile Extract purchased from Nutritional Biochemicals Corp., Cleveland, Ohio. Oleic acid (USP grade) was purchased from Fisher Chemical Co., Springfield, N.J. It was extracted and subjected to thin-layer and gas-liquid chromatography and found to be 85% pure. Monoolein was purchased from Eastman Organic Chemicals, Rochester, N.Y. More than 85% was found in the monoglyceride spot on thin-layer chromatography. Medium-chain triglyceride oil was purchased from Mead Johnson Research Center, Evansville, Ind. It was prepared according to the method of Shizas and associates (8) and used for cooking and as a spread on toast. quired continuous or repeated parenteral supplementation with electrolyte solutions. Data are also presented from three other patients who also had extensive smallbowel resection. However, they did not represent a therapeutic problem of the magnitude of the first four patients. The seven patients were put on controlled diets on a metabolic ward. All intake and output measurements were recorded on a 24-hr basis. Parenteral fluids were given in amounts necessary to keep urine output in excess of 500 ml/24 hr. Composition of the intravenous fluid supplements was varied depending on serum electrolyte values and consisted of sodium, potassium, chloride, calcium, and magnesium. Medications included tincture of belladonna, lomotil, deodorized tincture of opium or codeine and pancreatic extract (cotazyme), multivitamins and folic acid given orally, and vitamin B12 given parenterally. Frequent determinations of blood count, serum electrolytes and other serum chemistries, and urinary and fecal electrolytes and pH were carried out by routine methods. Forty-eight- to 72-hr stool collections were analyzed for fat and nitrogen content by Bio-Science Laboratories, Van Nuys, Calif. Bile salt -concentration in the intestinal content and in the stool after intraduodenal administration of 20 e of olive oil was deTable 1. Clinical Data Patient O.N. J.A. A.J. F.F. J.G. G.K. G.B. Length of Bowel Beyond Ligature of Treitz _ 41 cm of proximal jejunum and 15 cm of colon 67 cm of proximal jejunum and 15 cm of colon 100 cm of proximal jejunum 24-hr Feces Dietary Basal Maximal 12-hr Serum* Hematocrit* Weight* Output Output OverFat Fat Nitrogen Total IProtein Albumin Adm. Dis. Adm. Dis. per per night Hour Hour Adm. Dis. Adm. Dis. 48 39 g 8.2 40.0 22.0 21 33 4.2 4.1 *19 35 228 15 cm 37 proximal jejunum 98 cm of proximal jejunum and 25 cm of colon All remaining but distal 116 cm ileum and cecum Transverse, 25 descending sigmoid colon and _ _ _ _ _ _ • _ *MJ7V* - TnHiQ ' 1.3 50 6.6 5.3* 25.3 25.91 100 5.8 48 32.8 100 0.9§ 2.4§ 1.92 19.0 22.3 21.6§ 34.5J 23.5 0.4 0.9 14.5 13.8 54.5 1.1 11.9 50 28.1 21* No acid, No acid, pH7.2 pH7.0 • Adm—admission; Dis—discharge. t Patient died. t Medium chain triglyceride on program. 9 After reanastomosis. 206 5.8* 1.8 2.3*' 22 40f 99 lb 105t 4.8 7.8 1.9 4.5 31 41 103 122 7.5 6.9 2.7 3.5 46 42 189 157 6.7 7.0 3.7 4.4 35 38 92 96 — — 50 Fmbrumry 1970 • Annals of Internal Medicine • Volume 72 • Numbmr 2 Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 * 4.6 ^^ a/ 1()()ml - g/ lUUFni % During a control period of at least 2 weeks patients were given diets containing 50 to 100 g of fat, 100 g of protein, and 300 g of carbohydrates. Although the diet was kept constant, no attempt was made to monitor strictly daily calorie intake. Daily fluid intake was measured carefully. Gastric analysis using the augmented histamine test of Kay (9), oral glucose tolerance test, and X-ray contrast studies of the entire remaining gastrointestinal tract were obtained during this period. In Patients A.J. and J.A. gastric analysis was repeated after intestinal reanastomosis and while on medium-chain triglyceride regimen, respectively. Trials of experimental regimens lasted for at least 7 days unless the clinical course deteriorated, as shown by increasing fecal volume and negative fluid balance. In this event the patients were put back on the control program. Therapeutic trials included decreasing total fat intake to 25 g of long-chain triglycerides per 24 hr and trials of bile salt replacement while on the control diet, supplementing the control diet with micellar fat, and substitution of 25 to 50 g of medium-chain triglycerides per 24 hr for the corresponding amount of long-chain fat. In the presentation of the data, stool volumes are given in absolute figures and also as a percent of oral fluid intake in order to make the data comparable regardless of oral intake, which varied not only from patient to patient but also in the same patient during different dietary regimens. Case Histories (Table 1) Patient O.N., a 49-year-old white woman, had suffered from Crohn's disease for 16 years. There was also a past history of peptic ulcer disease. During the last 4 years she had been treated by successive resections of the distal small intestine and colon and was admitted to the study 8 weeks after the fourth operation. At that time her intestinal tract consisted of an intact stomach, duodenum, and 41 cm of proximal jejunum anastomosed to 15 cm of sigmoid colon with a colostomy. She presented a severe metabolic problem with tetany from hypocalcemia and hypomagnesemia, and gross emaciation and dehydration. Stool volumes ranged from 3 to 11 liters per 24 hr, and she required constant intravenous supplementation with electrolyte solutions. Therapeutic efforts were primarily directed toward reduction of the large stool volume. During 1 year of continuous intravenous supplementation she developed seven episodes of gram-negative bacillus septicemia and two fungal septicemias, which complicated the patient's clinical course and caused her death. Initial treatment consisted of lowering dietary fat to 50 g per 24 hr. During this control period her enterostomy output averaged 5,260 ml on an average oral intake of 5,330 ml/24 hr (Table 2). She was subsequently put on micellar fat. This caused some reduction in stool output but did not permit discontinuation of intravenous fluid therapy (Table 3). Because of the low stool pH, which ranged from 4.5 to 5.5, and the results of gastric analysis, which were at the upper limit of normal, it was decided to subject the patient to vagotomy and pyloroplasty. After the operation, enterostomy output almost doubled, and there was no response to any of the therapeutic regimens (Table 4). Subsequently the patient underwent reversal of an intestinal segment to slow down intestinal transit. This also failed to improve her condition, and she died several weeks later. Patient J.A., a 50-year-old white woman, had multiple small-bowel resections for Crohn's disease during a 12-year period. The last operation left the patient with the intestinal tract consisting of stomach, duodenum, 67 cm of proximal jejunum, and 15 cm of transverse colon with a colostomy (Table 1). Postoperative stool volumes ranged from 3 to 5 liters daily, and she required constant intravenous fluids. The clinical course was complicated by development of enterocutaneous fistulae and wound abscess. On several occasions the Table 2. Control Period Patient Days Intake (by Mouth) * Enterostomy Output* « O.N. Before vagotomy Net Volume ml • Enterostomy Output % of intake 99 14 5,330 (3,600-6,900) 5,260 (3,590-6,260) +70 O.N. After vagotomy 6 5,620 (4,530-7,790) 9,050 (6,210-11,515) -3,430 161 O.N. After intestinal reversal 9 3,360 (2,200-4,550) 3,100 (2,200-4,000) 4,770 (3,395-6,945) 5,930 (3,200-6,980) 3,510 (2,300-5,320) 4,640 (3,170-5,590) -2,570 176 -410 113 + 130 97 J.A. 26 A.J. 10 F.F. First admission 17 3,900 (3,400-4,200) 2,280 (1,540-2,970) + 1,620 58 F.F. 7nH admission 8 4,240 (4,000-4,800) 3,390 (2,900-3,850) + 850 80 • Mean. Ranges are in parentheses. Bochenek, et a/. • Dietary Lipids and Short-Bowl Syndrome Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 207 Table 3. Effect of Micellar Fat Patient Days Intake (by Mouth) * < O.N. Before vagotomy Net Volume > mi 4,590 (3,820-5,700) 13 Enterostomy Output* 3,980 (2,280-5,620) +610 Enterostomy Output On Micellar Fat During Control Period % of intake 87 99 O.N. After vagotomy 6 4,540 (4,060-5,000) 8,320 (7,400-9,180) -3,780 183 161 AJ. Oral administration 7 4,770 (3,900-7,290) 6,480 (5,600-7,680) -1,710 136 97 9 4,170 (3,400-5,010) 3,850 (3,39CM,380) +320 92 97 +700 83 58 AJ. Administered via distal enterostomy F.F. First admission 4,100 (4,(XXM,148) 3 3,400 (2,980-3,820) * Mean. Ranges are in parentheses. patient demonstrated musculai hyperexcitability and was found to be hypocalcemic and hypomagnesemic. Three months after the operations the fistulae and wound healed. However, colostomy output was still high and electrolyte solutions had to be given intravenously on a routine basis. She was admitted to the study at this time and started on a 50 g fat diet. The enterostomy output averaged 3,510 ml, exceeding oral intake by 410 ml (Table 2). Substitution of 50% of dietary fat with medium-chain triglycerides resulted in marked decrease in stool volume, and parenteral fluids could be discontinued (Table 5). Six months after the operation the patient was able to take care of herself and was discharged. Three months later she was readmitted for follow-up studies (Table 5). By that time she looked and felt much better and had gained 20 lb. The patient has now been followed for a full year. She is leading an active life and doing her own housework. Patient A.J., a 53-year-old white, obese, diabetic man with polycythemia vera, was admitted because of diffuse abdominal pain. On the day after admission an exploratory laparotomy was performed, and a diagnosis of venous mesenteric thrombosis was made. Approximately 130 cm of jejunum were resected. Two days later the patient again developed abdominal symptoms and was found to have a new area of jejunal infarction. Further resection of the small intestine was performed. It was judged unwise at that time to do an end-to-end anastomosis. The distal end of the remaining jejunum and the proximal end of the ileum were brought out on the anterior abdominal wall, creating proximal and distal enterostomies. The total amount of resected intestine was 227 cm, and the length of the jejunum between the ligament of Treitz and proximal enterostomy was estimated surgically and radiologically to be 100 cm (Table 1). This operation gave a rare opportunity to study a patient having a short proximal small intestine with high enterostomy output, in whom supplementation of nutrients, water, and elec- Table 4. Effect of Bile Salts Patient Days Intake (by Mouth)* « O.N. After vagotomy AJ. Administered via distal enterostomy F.F. First admission Enterostomy Output* ml • 5 4,550 (4,000-5,700) 8,240 (6,320-9,615) -3,870 6 4,110 (3,590-5,390) 3,560 (2,890-4,140) 9 4,000 (3,900-4,050) 2,200 (1,720-2,820) * Mean. Ranges are in parentheses. 208 Net Volume February 1970 • Annals of Internal Medicine • Volume 72 • Number 2 Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 Enterostomy Output On Bile Salts During Control Period % of intake 185 161 + 550 87 97 + 1,800 55 58 Table 5. Effect of Medium-Chain Triglycerides Patient Days Daily Fat Intake Enterostomy Output* Intake (by Mouth)* — ml 4 J.A. 8 Long-chain triglycerides 25 Medium-chain triglycerides 25 Beginning of program 18 14 F.F. Second admission 7 8 2 months later Long-chain triglycerides 50 Medium-chain triglycerides 50 Long-chain triglycerides 25 Medium-chain triglycerides 50 Net Volume • -10 Enterostomy Output On MediumChain Triglycerides During Control Period % of intake 100 113 2,450 2,400 (1,650-2,060) (2,100-10,190) 2,970 (2,010-3,160) 2,5001 2,040 (1,160-2,900) 1,180 (840-1,300) 4,000 3,030 (3,950-4,020) +930 69 113 +1,320 47 113 +970 76 80 + 1,660 58 80 (2,570-3,370) 3,970 2,310 (3,740-4,010) (1,000-2,800) * Average ranges are in parentheses. t Patient at home; precise volume of oral intake unknown. trolytes could be easily managed via the distal enterostomy. The postoperative course was complicated by gangrene of the gall bladder, which required drainage. Three and one half months after the first operation the patient demonstrated no further complications, and the small bowel was reanastomosed. The patient has now been followed for 24 months. He feels well, and there are no symptoms of malabsorption. While in the hospital he lost 70 lb, but he is now back to his previous weight of 220 pounds. Patient F.F., a 50-year-old man had multiple intestinal resections during a 20-year period for Crohn's disease of the colon and terminal ileum. When admitted to the study the estimated length of his small intestine was 228 cm beyond the ligament of Treitz and ended in an ileostomy (Table 1). Although he could take care of himself and was employable after the last resection, he was in borderline fluid and electrolyte balance and would become dehydrated due to minor increases in ileostomy output or prolonged sun exposure during summer months. He was found to respond to 50% substitution of dietary fat with mediumchain triglycerides and continues to take this diet at home (Table 5). Since the commencement of this regimen the patient appears to be in good metabolic balance and so far has not been readmitted to the hospital. Patients G.K., J.B., and G.B. had varying lengths of intestinal tract remaining (Table 1). Their ability to maintain metabolic balance was not impaired to the extent presented by the former patients, and they only occasionally required intravenous supplementation. Results Table 1 gives the data on the basic disease process, length of the remaining bowel, the values of 24-hr fecal fat and nitrogen and the results of gastric analysis, hematocrit, serum protein, and the patients' weight. All the patients had distal bowel resection, and the results of the 24-hr fecal fat determinations in five patients show a marked degree of steatorrhea. Gastric analysis showed slight elevation of basal values in Patients J.A. and A.J. In addition, 12-hr overnight collections in Patient A.J. gave results above normal on two occasions. The same patient had two more studies after restoration of the continuity of his gastrointestinal tract, which showed normal results for basal secretion. In Patient J.G., although there was no basal hypersecretion, 12-hr overnight collection gave a result above normal. Patient G.B. did not produce acid during the basal hour or after administration of histamine. Secretory studies on Patients O.N., F.F., and G.K. yielded normal results. There was no elevation of maximal acid output in any of the patients. CONTROL PERIOD During the control period (Table 2) Patients O.N. and J.A. were put on a diet containing 50 g of fat, and Patients A.J. and F.F. received 100 g of fat/24 hr. Patients O.N. and J.A. had markedly negative intestinal water balance. Patient A.J. was in marginal positive balance, whereas Patient F.F. was in adequate positive balance. EFFECT OF MICELLAR FAT When micellar fat was used orally it caused a Bochenek, et a/. • Dietary Lipids and Short-Bowl Syndrome Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 209 decrease in enterostomy output in Patient O.N. of 12%, and increase in enterostomy output in Patients F.F. and A.J. (Table 3). On administration via the distal enterostomy in Patient A.J. it produced a minimal improvement in fluid balance (jejunostomy output fell from 97 to 92% of oral intake). SUPPLEMENTATION WITH BILE SALTS Daily doses of 6 g of bile salts were given orally to Patients O.N. and F.F. and via distal enterostomy with supplementary fluids to Patient A.J. (3 g of Ox Bile Extract/100 ml of saline). This program produced only minimal decrease in enterostomy output in two patients and an increase in one (Table 4). SUBSTITUTION OF LONG-CHAIN TRIGLYCERIDES WITH MEDIUM-CHAIN TRIGLYCERIDES Fluid balance became positive with no need for further intravenous therapy in the three patients in whom 50% or more of dietary long-chain triglycerides were replaced by medium-chain triglycerides (Table 5). On 50 g of long-chain triglycerides and 50 g of medium-chain triglycerides Patient F.F. showed only minimal improvement. Further decrease in long-chain triglycerides to 25 g/24 hr resulted in 22% decrease in enterostomy output. In Patient J.A. a diet containing 25 g medium-chain triglycerides with 25 g long-chain triglycerides resulted in a 13% decrease in enterostomy output during the first 8 days. During the following month there was further decrease in enterostomy output, resulting in an overall reduction of 44% as compared with the control period. On follow-up studies 2 months later, her enterostomy output measured over 14 days averaged 1,180 ml/ 24 hr on an oral fluid intake of 2,500 ml. At that time discontinuation of medium-chain triglycerides for 6 days, with long-chain triglycerides remaining at 25 g/24 hr and without additional caloric supplements resulted in steady increase in enterostomy output to 2,200 ml/24 hr, which continued for 3 days after reinstitution of the previous mediumchain triglyceride program (Figure 1). Subsequent stool volume declined gradually and attained a steady level after approximately 3 weeks, averaging 1,200 ml/24 hr. Similar effects were observed in Patient J.G. Over a period of 6 weeks after the program was started he gained more than 10 pounds, and his urine output increased more than twofold. Most of this time the patient was at home and at work, and no exact data on oral fluid intake and enterostomy output are available. The increase in urine output was gradual and reached a steady level after 4 weeks of treatment. REFEEDING In Patient A.J., who had both a proximal and a distal enterostomy (Table 1, see Case Histories), the effect of transfer of the proximal enterostomy output into the distal enterostomy was observed. Average oral intake during 5 days was 2,560 ml and proximal enterostomy output, 1,170 ml/24 hr. The net volume gain averaged 1,390 ml/24 hr, and the proximal enterostomy output expressed as percent of oral intake decreased to 46% compared to the control value of 97%. FECAL LOSS OF ELECTROLYTES Fecal losses of sodium, potassium, and chloride were examined in Patients A.J. and J.A. Concentrations of the electrolytes in feces remained fairly constant during the various treatment periods so that electrolyte losses were proportional to stool volumes (Table 6). BILE SALT CONCENTRATIONS IN INTESTINAL CONTENT AND STOOLS Figure 1. Effect on fecal volume of stopping and restarting medium-chain triglyceride in Patient J.A. Oral intake was kept constant at 2,500 m l / 2 4 hr. Bars represent average 24-hr stool volumes during 3-day periods. 210 After intraduodenal administration of 20 g of olive oil to Patient J.A. the highest concentrations of bile salts in the intestinal contents were 0.5 //.mole of dihydroxy, and 0.9 /xmole of trihydroxy bile salts per ml. The values for stools during the same experiment were 0.3 /xmole/ml and 0.6 /Amole/ml, respectively, indicating severe bile salt depletion and malabsorption. February 1970 • Annals of Internal Medicine • Volume 72 • Number 2 Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 Table 6. Fecal Electrolytes Patient J.A. A.J. Regimen Control period On medium-chain triglyceride program* Control period Bile salts via distal enterostomy Micellar fat orally Micellar fat via distal enterostomy Enterostomy Output Concentration Sodium ml 3,500 62 2,040 4,640 61 79 3,560 6,480 3,850 Potassium — Cy, / TMLq/ 14 Daily Output Chloride Sodium lllBr Potassium Chloride J7 fittrr 64 217 22 16 87 78 82 79 15 16 86 16 TtiJu*q ~—~ 49 224 124 367 45 74 117 362 94 86 292 512 53 104 335 557 82 331 62 316 • Patient obtained oral supplementation of potassium. Discussion This study was undertaken to determine whether dietary manipulations would diminish water and electrolyte loss in patients with a short small intestine and to evaluate the importance of gastric hypersecretion in the pathogenesis of the shortbowel syndrome. All patients studied had massive intestinal resection. Large stool volumes were due primarily to loss of the distal small intestine and colon, which are important in water and electrolyte absorption. Excessive diarrhea is a common feature after intestinal resection or bypass. However, after an initial period of approximately 2 to 4 months, adaptation often occurs (10-12), and marked improvement may be observed even in patients who had massive intestinal resection. Dowling (13), using perfusion techniques, found statistically significant increases in absorption of glucose per unit length of intestine in patients with small-bowel resection, as compared with control subjects. This can perhaps be explained by the findings of Poms (14), which showed that after intestinal resection in humans, the number of epithelial cells per unit length of intestinal villi is increased. Studies performed on rats with resection of the jejunum showed hypertrophy of the intestinal mucosa of the remaining ileum and also demonstrated increases in the activity of two microsomal enzymes, fatty acid: coenzyme A ligase and acyl-coenzyme A:monoglyceride acyltransferase, which are involved in reesterification of absorbed fatty acids and monoglycerides present in dietary lipids (15). If the bowel remaining after resection is basically healthy, it is reasonable to expect it to adapt at least to some extent, provided good metabolic balance is maintained. In an attempt to reduce water and electrolyte loss diet was manipulated in order to decrease steatorrhea without decreasing caloric intake. A simple reduction in the amount of steatorrhea can readily be achieved by decreasing the amount of fat in the diet This in itself may have a beneficial effect on fecal fluid loss. However, decrease in dietary long-chain triglycerides to SO g/24 hr did not benefit Patients O.N. and J.A.. In Patient J.A. a further reduction of long-chain triglycerides to 25 g was attempted without success. It is now well established that ileal resection or ileal disease interrupts the enterohepatic circulation of bile salts, and, consequently, concentrations of conjugated bile salts in the intestine may fall below the critical micellar concentration (16, 17). Under these conditions malabsorption of fat is observed. Oral administration of bile salts in such patients may result in increased concentration of micellar lipids in the small bowel and decreased fecal loss of fat (18, 19). Since all the patients in this study had distal small bowel resection and colectomy, it was expected that some improvement could be achieved by oral supplementation of bile salts. Malabsorption of bile salts with resultant depletion of the bile salt pool was demonstrated in Patient J.A. Oral administration of crude Ox Bile Extract in two patients produced a slight decrease in enterostomy output in one and an increase in another. Direct ileal administration of bile salts in the third patient, A.J., resulted in some improvement Oral use of micellar fat in Patients A.J. and F.F. was associated with increase in stool volume and in Patient O.N. with decrease. Direct ileal administration in Patient A.J. resulted in only slight reduction in jejunostomy output. It is of interest that in this patient a significant reduction in proximal enterostomy drainage resulted when the proximal enterostomy drainage was instilled into the distal enterostomy. This was probably related to efficient reabsorption of endogenous bile salts and absorption of electrolytes, water, and predigested fat by the distal bowel. By contrast, in only one of three Boehenek, et •/. • Dietary Lipids and Short-Bowl Syndrome Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 211 patients did the oral administration of micellar fat produce any benefit. It is possible that the additional fat represented by the micellar solution proved excessive in these patients. Medium-chain triglycerides have been reported to be useful in many forms of malabsorption (20, 21) and have also been used successfully in patients with a short bowel (6, 22, 23). French (24) reported reduction of stool weight in a patient after massive small-bowel resection while on mediumchain triglyceride supplementation; however, the effects of medium-chain triglycerides on fecal fluid loss have not been well studied. It was decided to substitute part of the dietary fat with medium-chain triglyceride to improve nutrition and to decrease fecal loss in three patients. Considerable benefit was observed in all three. Substitution with mediumchain triglycerides did not result in immediate improvement in any of the three patients, but approximately 7 days on therapy were needed before significant reduction in fecal volume was produced. This may account for the lack of effect in the first period of medium-chain triglyceride therapy in Patient F.F. Similarly, discontinuation of medium-chain triglycerides resulted in only gradual increase in stool volume. Thus, withdrawing medium-chain triglycerides in Patient J.A., while the rest of the diet was kept constant, caused a twofold increase in stool volume over a 5-day period. Reinstitution of medium-chain triglycerides in the program resulted in a decrease of stool volume to the previous level in 20 days. Long-term follow-up of treatment with medium-chain triglycerides led to remarkable improvement in nutritional status. Patient J.A. reached her normal weight, and anemia and hypoalbuminemia present after the last resection were corrected. The mechanism by which medium-chain triglycerides cause a decrease in fecal fluid and electrolyte loss is unknown. Because these effects are not observed for at least several days after initiation of medium-chain triglyceride therapy and persist for several days after its discontinuation it seems unlikely that its only action is secondary to decrease in the degree of steatorrhea. Similarly, inhibition of gastric secretion or improvement in water transport in the jejunum would be expected to result in immediate changes. It is possible that medium-chain triglycerides act indirectly by improvement in the patient's nutritional status and bowel function. They may do this by providing readily available calories in a form that does not exert a strong osmotic effect in the bowel lumen. Measurements of fecal sodium, potassium, and chloride indicate that the amount of electrolyte loss 212 is directly related to stool volume. This finding is understandable in view of the fact that in these patients the remaining bowel was jejunum, where electrolytes are absorbed in essentially isotonic solution. Because of steatorrhea, hypocalcemia and hypomagnesemia were common complications. Typical neuromuscular hyperexcitability was observed in two patients and responded only to combined administration of calcium and magnesium (25, 26). In Patient J.A. calcium and magnesium supplementation by the oral route has been steadily reduced with her improvement. Presumably, losses of these cations decreased with the decrease in stool volumes. It has been suggested that patients with massive intestinal resection may have increased gastric secretion (6). This might contribute to fecal fluid loss by presenting more endogenous fluid to the intestine for absorption or because the low pH might interfere with digestion and absorption. No increase in maximal acid output was found in this series of seven patients, but basal acid output was slightly increased in two of them, and 12-hr overnight secretion was somewhat higher in one of these and in one other patient. It is of interest that in Patient A.J., who demonstrated basal hypersecretion initially, gastric analysis performed twice after reanastomosis of his intestinal tract gave normal values. During intestinal digestion and absorption of fat, inhibition of gastric secretion occurs. This has been well documented in studies on animals (27, 28), as well as on humans in this laboratory (29). Experimental studies on dogs suggest that massive intestinal resections can cause gastric hypersecretion (30, 31). However, Salmon and Wright (32), who performed gastric analysis in nine patients before and after small-bowel bypass, did not observe increases in gastric secretion after the operation. Similar results were reported by Shibata and associates (12) on three patients after jejunocolic bypass. Our studies indicate that if intestinal resection does affect gastric secretion, the resulting increase, if any, is in basal secretion and is generally not of great significance. It may be due to loss of a normal inhibitor of basal gastric acid secretion. Patients with massive small-bowel resection have been reported to respond favorably to pyloroplasty and vagotomy (6, 10). This operation actually dramatically worsened the condition of Patient O.N. Subsequently, the patient underwent reversal of an intestinal segment. Followup was too short to draw any definite conclusions, but the procedure did not appear to have been effective. Most of the patients in whom this pro- February 1970 • Annals of Internal Medicine • Volume 72 • Number 2 Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 cedure has been attempted by others (33, 34) had longer lengths of small bowel remaining. Treatment of patients with short-bowel syndrome should be conservative. Therapy should consist of appropriate fluid, electrolyte, and vitamin replacement, with the usual symptomatic measures. In particular, a prolonged trial of substitution of medium-chain triglyceride for long-chain dietary fat is indicated. Surgical therapy directed toward reduction of gastric acid secretion should be reserved for patients demonstrating massive gastric hypersecretion unresponsive to medical management. ACKNOWLEDGMENTS: The authors thank Dr. James F. Long for helpful advice throughout this study and Miss M. Rogers for help with the special diets. This work was carried out in the Clinical Research Unit of Albany Medical College and supported by Public Health Service Research Center grant 5 M01 FR00094 CLR from the Division of Research Facilities and Resources; and supported in part by Training Grant TO-1 AM05597, the National Institutes of Health, Bethesda, Md. Appeared in part in Clinical Research 16:528, 1968. Received July 24, 1969; revision accepted October 14, 1969. • Requests for reprints should be addressed to John A. Balint, M.D., Department of Medicine, Albany Medical College, Albany, N.Y. 12208 12. SHIBATA HR, MACKENZIE JR, LONG RC: Metabolic effects of controlled jejunocolic bypass. Arch Surg (Chicago) 95: 413-428, 1967 13. DOWLING RH, BOOTH CC: Functional compensation after small bowel resection in man. Lancet 2:146-147, 1966 14. PORUS RL: Epithelial hyperplasia following massive small bowel resection in man. Gastroenterology 48:753-757, 1965 15. RODGERS JB, JR: Location of lipid reesterifying enzymes in the small intestine and effects of jejunectomy on ileal enzyme levels (abstract). Clin Res 17:309, 1969 16. AUSTAD WI, LACK L, TYOR MP: Importance of bile acids and of an intact distal small intestine for fat absorption. Gastroenterology 52:638-646, 1967 17. VAN DEEST BW, FORDTRAN JS, MORAWSKI SG, et al: Bile salt and micellar fat concentration in proximal small bowel content of ileectomy patients. / Clin Invest 47:1314-1324, 1968 18. HOFMANN AF, GRUNDY SM: Abnormal bile salt metabolism in a patient with extensive lower intestinal resection (abstract). Clin Res 13:254, 1965 19. HARDISON WGM, ROSENBERG IH: Bile-salt deficiency in the steatorrhea following resection of the ileum and proximal colon. New Eng J Med 277:337-342, 1967 20. HOLT PR, HASHIM SA, VAN ITALLIE TB: Treatment of mal- absorption syndromes and exudative enteropathy with synthetic medium chain triglycerides. Amer J Gastroent 43:549559, 1965 21. GREENBERGER NJ, RUPPERT RD, TZAGOURNIS MT: Use of medium chain triglycerides in malabsorption. Ann Intern Med 66:727-734, 1967 22. ZURIER 23. PINTER References RB, CAMPBELL RG, HASHIM SA, et al: Use of medium-chain triglyceride in management of patients with massive resection of the small intestine. New Eng J Med 274:490-493, 1966 KG, HYMAN H, BOLANOS O: Fat and nitrogen sodium absorption in the human small intestine. / Clin Invest 47:884-900, 1968 balance with medium chain triglycerides after massive intestinal resection. Amer J Clin Nutr 22:14-20, 1969 24. FRENCH AB: Effects of graded increments of medium chain triglycerides on nutrient balance in subjects with intestinal resection in Medium Chain Triglycerides, edited by J. B. SENIOR, Philadelphia, University of Pennsylvania Press, 1968, p. 109-119 3. BOROSTROM B, LUNDH G, HOFMANN A: The site of absorp- 25. FLETCHER RF, HENLY AA, SAMMONS HG, et al: A case of tion of conjugated bile salts in man. Gastroenterology 45: 229-238, 1963 4. BOOTH CC, MOLLIN DL: The site of absorption of vitamin B 12 in man. Lancet 1:18-21, 1959 magnesium deficiency following massive intestinal resection. Lancet 1:522-525, 1960 BALINT JA, HIRSCHOWITZ BI: Hypomagnesemia with tetany in nontropical sprue. New Eng J Med 265:631-633, 1961 MENGUY R: Studies on the role of pancreatic and biliary secretions in the studies of gastric inhibition by fat. Surgery 48:195-200, 1960 LONG JF, BROOKS FP: Relation between inhibition of gastric secretion and absorption of fatty acids. Amer J Physiol 209:447-451, 1965 BOCHENEK W: Unpublished data 1. BOROSTROM G, DAHLQVIST A, LUNDH G, et al: Studies of intestinal digestion and absorption in the human. / Clin Invest 36:1521-1536, 1957 2. FORDTRAN J, RECTOR F, JR, CARTER N: The mechanisms of 5. PLAYOUST MR, LACK L, WEINER IM: Effect of intestinal resection on bile salt absorption in dogs. Amer J Physiol 208:363-369, 1965 6. OSBORNE MP, SIZER J, FREDERICK PL, et al: Massive bowel resection and gastric hypersecretion. Its mechanism and a plan for clinical study and management. Amer J Surg 114: 393-397, 1967 7. MOSBACH EH, HALINSKY HJ, HALPERN E, et al: Determina- tion of deoxycholic acid and cholic acid in bile. Arch Biochem Biophys 51:402-410, 1954 8. SHIZAS AA, CREMIN JA, LARSON E, et al: Medium chain triglycerides—use in food preparations. / Amer Dietetic Assoc 51:228-232, 1967 9. KAY A: Effect of large doses of histamine on gastric secretion of HC1; augmented histamine test. Brit Med J 2:77-80, 1953 10. LEONARD AS, LEVINE AS, WITTNER R, et al: Massive small bowel resections. Operative and dietary management Arch Surg (Chicago) 95:429-435, 1967 11. WINAWER SJ, BROITMAN SA, WOLOCHOW DA, et al: Success- ful management of massive small bowel resection based on assessment of absorption defects and nutritional needs. New Eng J Med 274:72-78, 1966 26. 27. 28. 29. 30. FREDERICK PL, SIZER JS, OSBORNE MP: Relation of massive bowel resection to gastric secretion. New Eng J Med 272: 509-514, 1965 31. GRUNDBERG AB, LOPEZ AS, DRAGSTEDT LR: Effect of in- testinal reversal and massive resection on gastric secretion. Arch Surg (Chicago) 94:326-329, 1967 32. SALMON PA, WRIGHT WJ: Effect of small-bowel bypass on gastric secretion in obese patients. Canad J Surg 11:365-368, 1968 33. THOMAS J, JORDAN GL JR: Massive resection of small bowel and total colectomy: use of reversed segment Arch Surg (Chicago) 90:781-786, 1965 34. BRAASCH JW, SEDGWICK CE: Reversed loops in the short bowel syndrome: preliminary clinical experience. Lahey Clinic Foundation Bulletin 14:27-32, 1965 Bochenek, et a/. • Dietary Lipids and Short-Bowl S y n d r o m * Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 213 Question of the Month: Rheumatology Question 98 The patient whose roentgenograms are shown below most likely has which of the following: (A) (B) (C) (D) (E) Scleroderma Hyperparathyroidism Rheumatoid arthritis Psoriatic arthritis Chondrocalcinosis [This Question of the Month- is from the Medical Knowledge SelfAssessment Program of the AC P. The answer and a reference are given on p. 270 of this issue—Ed J 214 February 1970 • Annals of Internal Medicine • Volume 72 • Number Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/11/2016 2