RECOVERY OF EXOCRINE PANCREATIC FUNCTION IN ADULT PROTEIN CALORIE MALNUTRITION

Transcription

1 GASTROENTEROLOGY Copyright e 1970 by The Williams & Wilkins Co. Vol. 58, No.3 Printed in U.S.A. RECOVERY OF EXOCRINE PANCREATIC FUNCTION IN ADULT PROTEIN CALORIE MALNUTRITION B. N. TANDON, M.D., P. A. BANKS, M.D., P. K. GEORGE, M.D., S. K. SAMA, M.D., K. RAMACHANDRAN, AND P. C. GANDHI Gastroenterology Unit, Department of Medicine and PrevlJTltive and Social Medicine, All-India Institute of Medical Sciences, Ne:w Delhi, India Eight adult patients with protein-calorie malnutrition underwent a pancreozymin-secretin test of exocrine pancreatic function and then were treated with a high protein diet for 12 to 14 weeks. Repeated studies of pancreatic function indicated almost complete recovery of bicarbonate and lipase secretion and improvement of protease secretion. The persistence of a normal amylase response in protein-calorie malnutrition suggests adaptation to a high carbohydrate intake. Studies in experimental animals have shown that the pancreas has a remarkable ability to regenerate its parenchyma and to recover its exocrine secretory capacity.1 A similar phenomenon has not been well documented in man. The present study was performed to determine the effect of a high protein diet on exocrine pancreatic function in adult patients with proteincalorie malnutrition. Methods Five male and 3 female patients aged 22 to 55 years (average age, 38) were studied. Dietary history indicated prolonged intake of food low in calories and deficient in protein. The average daily diet consisted of 1600 cal, 40 g of low biological value vegetable protein,' 40 g of fat, and 270 g of carbohydrate. All patients presented with symptoms of diarrhea, progressive weakness, and peripheral edema. None had significant associated diseases. There was no clinical history of alcoholism or disease of the pancreas or biliary tract. Plain film of the abdomen, barium meal studies, and evocative serum enzyme studies provided no evidence of chronic pancreatitis. The mean weight was 42.5 kg. Physical examination showed pallor, dry scaly skin, glossitis, cheilosis, Received June 13, Accepted September 24, Address requests for reprints to: Dr. Peter A. Banks, 1101 Beacon Street, Brookline, Massachusetts muscular wasting, and generalized edema. The mean hemoglobin was 7.0 g per 100 ml; serum protein was 6.2 g per 100 ml; serum albumin was 2.6 g per 100 ml. -secretin tests were performed by the method of Sun and Shay." Patients were fasted overnight and in the morning a double lumen tube was passed into the stomach and was localized in the duodenal loop under fluoroscopic control. Gastric and duodenal samples were collected separately by continuous suction. A basal 20-min pancreatic collection was followed by the intravenous administration of 90 U of pancreozymin (Boots Pure Drug Company, Nottingham, England). After a lo-min collection period, 80 U of secretin (Boots Pure Drug Company) were administered intravenously. Four additional collections then were obtained, the first two of 10-min duration and the latter two of 20-min duration. At the end of each study, correct localization of the duodenal tube was confirmed fluoroscopically. Each sample of duodenal drainage was analyzed for volume, bicarbonate concentration,' protease," lipase, and amylase: Patients were treated and studied on the research ward. The daily diet consisted of 50 cal per kg, 1.5 g per kg of animal protein of high biological value,' 80 g of fat, and remainder of the calories from carbohydrates. Supplemental iron and vitamins were given by mouth. -secretin tests were repeated 12 "to 14 weeks after institution of dietary therapy. Ten healthy volunteers weighing an average of 54.5 kg were explained the purpose of the study and underwent a pancreozymin-secretin

2 March 1970 RECOVERY OF EXOCRINE PANCREATIC FUNCTION 359 test to serve as normal controls. These volunteers had been consuming more than 50 cal per kg and 1.5 to 2.0 g per kg of high biological value animal protein" in their diet for more than 5 years and were actively employed, with excellent annual health records. Results Dietary therapy resulted in complete clinical recovery and improvement in serum hemoglobin, total proteins, and albumin in all patients within 12 to 14 weeks. Weight gain averaged 7 kg in spite of initial weight loss of edema fluid. The volume and bicarbonate responses in exocrine pancreatic secretion are given in table 1. The volume of basal and stimulated pancreatic flow in the patients before dietary therapy was the same as that in the control volunteers. The institution of a high protein diet produced no change in volume output when compared with pre and control volumes. Basal bicarbonate concentration was lower among patients than controls and did not increase significantly after therapy. The secretinstimulated bicarbonate concentration of the patients before was lower than that of the control volunteers; after, the bicarbonate concentration increased significantly and returned almost to normal when compared with that of the control volunteers. Protease and lipase responses are given in table 2. Before, protease and lipase concentrations were lower among patients than among controls in both the basal and poststimulatory periods. Following dietary therapy, concentration of basal protease did not increase appreciably, while that of basal lipase did. The poststimulatory protease concentration increased significantly in only one period, while the lipase did for all periods. The improvement in lipase response almost was complete when compared with control responses. Amylase responses are presented in table 3. The basal and poststimulatory concentrations were similar for patients and controls, except for a lower output of amylase among patients 50 and 70 min after pancreozymin administration. Following dietary therapy, neither the basal nor stimulated amylase showed a significant change. Discussion The characteristic alterations of exocrine pancreatic function in adult protein-calorie malnutrition are reductions in enzyme and bicarbonate concentrations with preservation of a normal volume response.s,9 The present study demonstrates that 3 months of dietary therapy result in considerable improvement in these abnormalities, with almost complete recovery of TABLE 1. Effect of 12 to 14 weeks of high protein diet on the volume and bicarbonate secretion in protein-calorie malnutrition disease" Volume Bicarbonate B C B C Pancreatic secretion A Patients Patients A Patients Patients collection periods Controls before.:loab after.:locb Control before.:loab after.:locb p Mean I SE Mean I SE Mean I SE Mean I SE Mean I SE Mean I SE ml/kg/hr meq/liter Basal secretion NS NS < NS lo-min NS NS NS NS 20-min NS NS < < min NS NS < < min NS NS < < min NS NS < <0.01 a Ten control subjects and 8 patients were evaluated. b Probability determined by Student's I-test..:lo, difference; NS, not significant.

3 360 T ANDON ET AL. Vol. 58, No.3 TABLE 2. Effect of 12 to 14 weeks of high protein diet on protease and lipase secretion in protein-calorie malnutrition disease" Protease Lipase Pancreatic B C B C secretion A Patients Patients A Patients Patients collection Controls \ before <1AB after <1CB Controls before <1AB after <1CB periods p P Mean I SE Meanl SE Mean I SE Mean I SE Mean I SE Mean I SE U/lOOml U/lOO ml Basal secretion < NS < < min < NS < < min < < < < min < NS < < min < NS < < min < NS < <0.01 a Ten control subjects and 8 patients were evaluated. b Probability determined by Student's t-test. <1, difference; NS, not significant. TABLE 3. Effect of 12 to 14 weeks of high protein diet on amylase secretion in proteincalorie malnutrition disease B Amylase Pancreatic A B C secretion Controls Patients before <1AB Patients after collection period <1CB p vafue b Mean I SE Mean I SE Mean I SE U/lOO ml Basal secretion.. 129, , , ,660.6 NS 123, ,209.7 NS lo-min , , , ,506.0 NS 145, ,547.1 NS 20-min , , , ,256.5 NS 131, ,278.4 NS 30-min , , , ,189.2 NS 113, ,582.6 NS 50-min , , , ,718.5 ", , ,231.1 NS 70-min , , , ,911.7 < , ,465.1 NS B Ten control subjects and 8 patients were evaluated. b Probability determined by Student's t-test. a, difference; NS, not significant. bicarbonate and lipase secretion and improved protease secretion. Amylase secretion, which initially was similar to that in the control subjects, showed no increase following therapy. The composition of the diet prior to therapy may have had a direct bearing on the initial pattern of enzyme abnormalities observed in the present study. Before therapy, patients subsisted on a reduced protein and fat intake but a high carbohydrate intake (dietary components were cereals, rice, and potato, exclusively). The pancreatic response to this diet was a marked decrease in lipase and protease secretion, but no significant decrease in amylase output as compared with controls. An attractive explanation for the normal amylase response is that the maintenance of a high carbohydrate intake prevented a decrease in amylase secretion. As such, this response would indicate a process of adaptation by which the composition of the diet governs the pattern of enzyme secre-

4 March 1970 RECOVERY OF EXOCRINE PANCREATIC FUNCTION 361 tion. Adaptive changes in pancreatic enzyme responses have been demonstrated in the rat; when a balanced diet is replaced by a carbohydrate-rich (or proteinrich) diet, the activity of amylase (or protease) increases in pancreatic tissue.10, 11 The fundamental histological abnormality in the pancreas in protein-calorie malnutrition is atrophy of acinar cells associated with marked diminution of secretory granules, and eventually fibrosis of the gland with sparing of islet cells,12-17 These abnormalities appear in the experimental animal within 2 weeks of initiating a protein-deficient diet14, and are associated with a striking reduction in pancreatic enzyme secretion.14 Among children deprived of protein for only 3 weeks, marked reduction in basal pancreatic flow has been recorded.12 These studies serve to point out the rapidity with which functional and morphological alterations occur in the pancreas following protein deprivation in both man and experimental animals. The importance of associated vitamin or mineral deficiency in initiating pancreatic exocrine disfunction is not known at present. In children, reversibility of pancreatic structure and function is equally dramatic following protein replacement, with histological recovery within 4 weeks,13 return to normal basal enzyme flow in 3 days to 7 weeks,12, 13 and a significant recovery of stimulated enzyme response.22 In experimental animals, complete functional recovery takes only 3 to 6 weeks following initiation of a high protein diet.14 The response of the pancreas to dietary therapy in adult protein-calorie malnutrition has not been studied previously, other than an observation that 1 patient failed to show improvement.23 The present study indicates that recovery can be substantial among adults even when protein-calorie malnutrition is of long duration. The reason for the failure of protease secretion to return completely to normal in the present study is not clear. The important considerations may be irreversible fibrosis of the pancreas associated with prolonged protein-calorie malnutrition or perhaps the need for additional time for recovery to be complete. In the dog, for example, pancreatic atrophy induced by ductal ligation may require 4 months for functional and histological recovery following ductal reanastomosis.24 A study of this type does not provide information as to the effect of protein depletion and repletion on specific processes of synthesis and secretion of pancreatic enzymes. In the experimental animal, the activity of amylase and protease in pancreatic tissue is quite different on a balanced diet, a carbohydrate-rich diet, and a protein-rich diet; on each diet, however, a constant relationship persists between the activity of an enzyme in acinar tissue and that in pancreatic secretion.10,25 This parallel suggests that dietary changes not associated with nutritional deficits affect synthesis and secretion of enzymes equally. It also suggests that hormonal and cholinergic stimuli ordinarily are well integrated, since pancreozymin primarily increases enzyme secretion, whereas methacholine increases both synthesis and secretion. 26 However, under certain conditions secretion of a preformed enzyme may be increased proportionally more than synthesis. For example, when a trypsin inhibitor is administered to the rat, trypsinogen secretion is increased in pancreatic juice without a corresponding increase in its activity in pancreatic tissue.21 It is intriguing to speculate that a disproportion between tissue and juice levels of pancreatic enzymes may develop during recovery from protein-calorie malnutrition, with levels in juice proportionally greater than in tissue. REFERENCES 1. Tiscornia, O. M., and D. A. Dreiling Does the pancreatic gland regenerate? Gastroenterology 51: Munro, H. N., and J. B. Allison reds:] Mammalian protein metabolism, Vol. 2, p. 47. Academic Press, Inc., New York. 3. Sun, D. C. H., and H. Shay secretin test. The combined study of serum enzyme and duodenal contents in the diagnosis of pancreatic disease. Gastroenterology 38: Lagerlof, H. O Pancreatic functions and pancreatic diseases studied by means of secretin. Acta M ed. Scand. Suppl. 128: 16.

5 362 T ANDON ET AL. Vol. 58, No.3 5. Bergmeyers, H. N Determination of trypsin with casein as substrate. In Methods of enzymatic analysis. Academic Press, Inc., New York. 6. Vogel, W. C., and L. Zieve Rapid and sensitive turbidimetric method for serum lipase based on difference between the lipases of normal and pancreatitic serum. Clin. Chem. 9: 16S Wootton, 1. D. P Micro-analysis in medical biochemistry, Ed. 4. J. & A. Churchill Ltd., London. 8. Jorge Palaez, M., P. Antonio Gonzales, and H. Velez Estudio de la function pancreatica en pacientes desnutridos. Antiquia Medica 16: Tandon, B. N., P. K. George, S. K. Sarna, K. Ramachandran, and P. C. Gandhi Exocrine pancreatic function in protein calorie malnutrition disease of adults. Amer. J. Clin. Nutr. 22: Grossman, M. 1., H. Greengard, and A. C. Ivy The effect of dietary composition on pancreatic enzymes. Amer. J. Physiol. 138: Desnuelle, P., J. P. Rebound, and A. Ben Abdeljlil Influence of the composition of diet on the enzyme content of rats' pancreases, p In: A. V. S. de Reuck and M. P. Cameron [eds.), Ciba foundation symposium on the exocrine pancreas. Normal and abnormal functions. J. & A. Churchill Ltd., London. 12. Veghelyi, P. V Nutritional edema. Ann. Paediat. 175: Thompson, M. D., and H. C. Trowell Pancreatic enzyme activity in duodenal contents of children with a type of kwashiorkor. Lancet 1: 'Suzanne, L., and F. L. Iber Pancreatic secretion in rats with protein malnutrition. Johns Hopkins Med. J.120: Davies, J. N. P The essential pathology of kwashiorkor. Lancet 1: Blackburn, W., and K. Vinijchaikul Lesions of the exocrine pancreas in kwashiorkor. Fed. Proc. 28: Scrinshaw, N. S., and M. Behar Protein malnutrition in young children. Science 133: Veghelyi, P. V., T. T. Kemeny, J. Pozonyi, and J. Sos Dietary lesions of the pancreas. Amer. J. Dis. Child. 79: Weisblum, B., L. Herman, and P. J. Fitzgerald Changes in the pancreatic acinar cells during protein deprivation. J. Cell BioI. 12: Paradisi, F., and F. Cavazzuti Exocrine pancreas and experimental dietary lesions. Gastroenterologia 103: Rothman, S. 8., and H. Wells Selective effects of dietary egg white trypsin inhibitor on pancreatic enzyme secretion. Amer. J. Physiol. 216: Barbezat, G. O The exocrine pancreas and protein-calorie malnutrition. S. Afr. Med. J. 41: Banwell, J. G., and J. Campbell Pancreatic exocrine function in African patients. Trans. Roy. Soc. Trop. Med. Hyg. 61: Tiscornia, O. M., and D. A:.Dreiling Recovery of pancreatic exocrine secretory capacity following prolonged ductal obstruction. Bicarbonate and amylase response to hormonal stimulation. Ann. Burg. 164: Abdeljlil, A. B., and P. Desnulle Sur l'adaptation des enzymes exocrines du pancreas it la composition du regime. Biochim. Biophys. Acta 81: Webster, P. D Comparison of metabolic and secretory effects of methacholine and pancreozymin on the pancreas. Gastroenterology 56: 1267.