Digestion 15: 9 0 -9 5 (1977)
Exocrine Pancreatic Insufficiency and Primitive Malnutrition L. Descos, J . Duclieu and Y. Minaire' Unité de Recherches de Physiopathologie Digestive, Inserm U 45, Hôpital Edouard-Herriot, Lyon
Key Words. Pancreatic juice • Enzymes • Bicarbonate • Malnutrition - Lipase • Amylase • Trypsin • Chymotrypsin
Abstract. Pancreatic function tests were performed before and after dietary therapy in four patients suffering from primitive malnutrition. Maximal bicarbonate concentrations and lipase activity were the parameters most clearly affected by malnutrition and those showing the fastest recovery following therapy. With reference to this quick recovery it seems unlikely that, at least in Western countries, malnutrition could be a cause o f chronic pancreatitis. Interpretation o f pancreatic function tests requires an exact knowledge o f the nutritional status.
Owing to the high turnover o f protein in the pancreas, it is not surprising that this organ might be affected in protein calorie malnutrition; structural changes and functional alterations are well documented in children living in tropics and suffering from severe malnutrition such as kwashiorkor (6). By contrast, similar facts are scarcely reported in adults (3, 5, 7) and when they are, it is always from countries with endemic malnutrition; they have never been reported from Western countries if one excepts cases in which the malnutrition is obviously secondary to a malabsorption o f medical or surgical origin (10). We have had the opportunity to observe four patients suffering of pancreatic insuffi ciency due to a primitive protein calorie malnutrition and we were able to study their stimulated pancreatic secretion before and after dietary therapy.
1 The helpful criticism o f R. Lambert as well as the skillful technical assistance o f M.B. Bererd are gratefully acknowledged.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
Received: June 21, 1976; accepted: July 10, 1976.
Deseos/Duclieu/Minaire
91
Methods Patients Four male patients, 3 7 -5 9 years old, were studied (table I). Dietary history reveals prolonged period (3 -1 2 months) o f low food intake with a weight loss ranging from 9 to 29 %. All patients presented symptoms o f weakness, muscular wasting, pallor, anemia, and a lowering o f the plasma albumin/globulin ratio. None had biological symptoms o f alcoholic hepatitis although two o f them (A and B) might be suspected o f an alcohol intake larger than normal. None had clinical symptoms o f pancreatic disease and plain film o f the abdomen did not reveal pancreatic calcification. No evidence o f intestinal disease was found except in one o f them (C) who complained o f diarrhea. The follow-up o f these patients after dietary therapy confirmed the absence o f organic digestive disease. At admission the patients were submitted to a pancreatic function test and received dietary therapy providing more than 45 keal/kg body weight (1.2 g/kg body weight o f animal protein) for 4 weeks. Then a second pancreatic function test was performed. By this time the weight gain was inconstant and always less than the initial loss, ranging from 0 to 16%.
Pancreatic Tests Pancreatic function tests were performed after an overnight fast. A Camus tube was passed into the third duodenum and a Levine tube into the antrum under radiological control. Duodenal contamination by gastric juice and instillation every 5 min o f 5 ml o f a BSP solution (0.03 %). Every duodenal sample containing BSP was discarded. Duodenal juice was collected in 10-min samples. After a 2 X 10 min basal period, C C K (G IH , 3 U/kg/h) was intravenously infused at a constant rate for 4 X 10 min. Then secretin (G IH , 1 CU/kg) was intravenously injected and 6 X 10 min samples were obtained. Each sample was collected in an ice-chilled tube. Measurements o f enzymatic concentrations were per formed within 1 h after sampling by the kinetic pH stat technique using benzoylarginineethyl ester for trypsin, acetyltyrosineethyl ester for chymotrypsin and an olive oil suspen sion for lipase (4). Amylase was estimated using the method o f Norby (4) and bicarbonate concentration was measured by titrimetry. The mean value o f enzymatic activities in the 3rd and 4th samples during C C K stimulation and the highest value for volume and bicarbonate concentration in any sample obtained during secretin stimulation were selected as represen tative parameters o f pancreatic functions. It is generally acknowledged that enzyme outputs provide a better estimation of pan creatic function than enzyme concentrations. However, when C C K is used alone, without secretin, as it is in present study, the volumes are very small and the errors on recovery are, therefore, too large to obtain outputs with a good accuracy.
Effects o f Malnutrition The maximal volume of pancreatic flow during secretin stimulation was irregularly lowered in malnourished patients while the maximal bicarbonate con centration dropped always under the lower value observed in control subjects. Lipase was the more affected o f the enzyme and was below the lower control
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
Results
Table I Age Malnutrition years length causes months
A B C
59 53 37
D
56
social social mental anorexia social
Body weight, kg'
Blood
X
protein RB C X 106/mm3 g/1
g/1
hemoglobin iron g/100 ml Mg/1
Y
Z
albumin
3 8 6
65 57 51
50 51 36
58 51 38
3.25 3.35 4.40
63 62 48
24 36 23
9.6 11.6 13.3
12
77
70
71
3.06
69
34
9.4
Ca mg/1
1,000
87 90 80
610
93
310 -
Deseos/Duclieu ¡Minaire
Patient
to
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
' Body weight: X at the beginning o f the malnutrition period (normal weight); Y at the end o f the malnutrition period (first test), and Z at the end o f the renutrition period (second test 4 weeks after).
Exocrine Pancreatic Insufficiency and Primitive Malnutrition
93
value in each o f these patients. Trypsin and chymotrypsin were respectively lowered in 3 and 1 out o f 4 patients and amylase was always above control value. Effect o f Dietary Therapy The institution o f a high-protein-calorie diet during 4 weeks regularly im proved maximal bicarbonate concentration and lipase activity. The effect was less obvious upon pancreatic flow, trypsin and chymotrypsin activities, the re coveries of which were irregular.
As a whole, these results agree with those obtained by Tandon et al. (7) and Kumar et al. (3) in 8 and 9 malnourished Indian adult patients, respectively, and showing that the secretory volume was not clearly affected by malnutrition, while the maximal bicarbonate concentration was regularly low and returned to the normal range by dietary therapy. Bicarbonate secretion was also reduced in adult malnourished patients living in Colombia (5) as well as in British patients with gastrectomy for gastric ulcer (10). By opposition Barhezat and Hansen (1) reported that the ability to raise the duodenal pH level was not changed in children suffering from kwashiorkor and marasmus, suggesting that the pan creatic ducts are spared in kwashiorkor. Among the enzymes o f the duodenal content, amylase was not clearly af fected by malnutrition or dietary therapy. This result agrees with those of Tandon et al. (7) and Kumar et al. (3) while it differs from those collected in malnourished adults (5) and children (1, 2, 8). The most likely explanation for this difference is that the amylase secretion is affected only in severe form o f malnutrition, such as in children in whom the requirements for growth worsen the malnutrition deficit. This hypothesis is supported by the fact that during malnutrition the enzymes o f the exocrine pancreas disappeared one by one. first lipase, then trypsin and finally amylase (9). Lipase secretion was reduced in each of these four malnourished patients. Actually this enzyme is the most sensitive towards malnutrition (7, 9) as it is towards acute alcoholic intoxication and chronic or acute pancreatitis (4). Among proteases, trypsin is probably more sensitive than chymotrypsin to a reduction in the protein calorie intake. Examination o f tire data collected 4 weeks after the start of dietary therapy (table II) confirms that the recovery is faster for pancreatic function than for body weight (3). The responsiveness to renutrition is greater for bicarbonate and lipase secretions than for trypsin, the concentration o f which remaining low in 2 out o f 4 patients.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
Discussion
Table II
Control1 *3
after
Lipase IU
before
before
26
after
after
before
1,000
75
Trypsin IU
Amylase LU after
before
3.2
Chymotrypsin IU after
before
28
after
60
Patients A B C D
49 28 16 14
26 50 19 76
74 60 58
88 76 110
677 647 500 860
760 1,030 1,115 1,563
18.5 10.4 4.5 9.8
3.5 8.6 17.5 12.0
16 21 22 32
19 32 21 50
53 228 62 94
110 123 70 225
Ratio3
2/4
1/4
3/3
0/3
4/4
1/4
0/4
0/4
3/4
2/4
1/4
0/4
1 Before and after 4 weeks o f dietary therapy. ! Lower value observed in control patients. 3 Number o f patients under the control value/total number o f patients.
VO
■n.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
before'
Bicarbonate mM
Descos /Duelieu /Mina ire
Volume ml/10 min
Exocrine Pancreatic Insufficiency and Primitive Malnutrition
95
The concept o f nutritional pancreatitis has been recently discussed by Pitchumoni (6). It appears that the disease requires a long-term history o f food deprivation, specially during childhood. Therefore, it is unlikely that in Western countries, malnutrition by itself could be a noticeable cause o f pancreatitis. Finally, it must be kept in mind that a reduction in pancreatic secretion cannot be directly accepted as a symptom o f pancreatic disease as long as there is a state o f chronic protein calorie deprivation.
References 1 2
3
4
5 6 7 8 9
10
Barbezat, G.O . and Hansen, J .D .L .: The exocrine pancreas and protein-calorie mal nutrition. Pediatrics, Springfield 47: 7 7 -9 2 (1968). Gomez, Galvan, R .R .; Cravioto, J ., and French, S .: Enzym atic activity o f the duodenal contents in children affected with third degree malnutrition. Pediatrics, Springfield 13: 548 (1954). Kumar, R .; Banks, P .A .; George, P .K ., and Tandon, B.N .: Early recovery o f exocrine pancreatic function in adult protein-calorie malnutrition. Gastroenterology 68: 1593-1595 (1975). Minaire, Y.; Deseos, L .; Daly, J.P .; Bererd, M .B., and Iximbert, R .: The interrelation ships o f pancreatic enzymes in health and diseases under cholecystokinin stimulation. Digestion 9: 8 -2 0 (1973). Pelaez, J .: Gonzalez, P.A. y Velez, H .: Estudio de la función pancreático en pacientes desnutridos. Antioquía med. 16: 41 -4 8 (1966). Pitchumoni, C .S .: Pancreas in primary malnutrition disorders. Am . J . clin. Nutr. 26: 374-379 (1973). Tandon, B.N.; Banks, P .A ., and George, P .K .: Recovery o f exocrine pancreatic func tion in adult protein calorie malnutrition. Gastroenterology 58: 35 8 -3 6 2 (1970). Thompson, M.D. and Trowell, H .C .: Pancreatic enzyme activity in duodenal contents o f children with a type o f kwashiorkor. Lancet i: 1031-1035 (1952). Veghelyi, P.V. and Kemeny, T.T.: Protein metabolism and pancreatic function; in de Reuck and Cameron Ciba Foundation Symposium on the Exocrine Pancreas, pp. 3 29-352 (Churchill, London 1962). Wormsley, K .G .: Pancreatic exocrine function in patients with gastric ulceration before and after gastrectomy. Lancet ii: 6 82-684 (1972).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
L. Deseos, Pavillon Hbis. Hôpital Edouard-Herriot, F-69374 Lyon Cedex 2 (France)
Exocrine Pancreatic Insufficiency and Primitive Malnutrition L. Descos, J . Duclieu and Y. Minaire' Unité de Recherches de Physiopathologie Digestive, Inserm U 45, Hôpital Edouard-Herriot, Lyon
Key Words. Pancreatic juice • Enzymes • Bicarbonate • Malnutrition - Lipase • Amylase • Trypsin • Chymotrypsin
Abstract. Pancreatic function tests were performed before and after dietary therapy in four patients suffering from primitive malnutrition. Maximal bicarbonate concentrations and lipase activity were the parameters most clearly affected by malnutrition and those showing the fastest recovery following therapy. With reference to this quick recovery it seems unlikely that, at least in Western countries, malnutrition could be a cause o f chronic pancreatitis. Interpretation o f pancreatic function tests requires an exact knowledge o f the nutritional status.
Owing to the high turnover o f protein in the pancreas, it is not surprising that this organ might be affected in protein calorie malnutrition; structural changes and functional alterations are well documented in children living in tropics and suffering from severe malnutrition such as kwashiorkor (6). By contrast, similar facts are scarcely reported in adults (3, 5, 7) and when they are, it is always from countries with endemic malnutrition; they have never been reported from Western countries if one excepts cases in which the malnutrition is obviously secondary to a malabsorption o f medical or surgical origin (10). We have had the opportunity to observe four patients suffering of pancreatic insuffi ciency due to a primitive protein calorie malnutrition and we were able to study their stimulated pancreatic secretion before and after dietary therapy.
1 The helpful criticism o f R. Lambert as well as the skillful technical assistance o f M.B. Bererd are gratefully acknowledged.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
Received: June 21, 1976; accepted: July 10, 1976.
Deseos/Duclieu/Minaire
91
Methods Patients Four male patients, 3 7 -5 9 years old, were studied (table I). Dietary history reveals prolonged period (3 -1 2 months) o f low food intake with a weight loss ranging from 9 to 29 %. All patients presented symptoms o f weakness, muscular wasting, pallor, anemia, and a lowering o f the plasma albumin/globulin ratio. None had biological symptoms o f alcoholic hepatitis although two o f them (A and B) might be suspected o f an alcohol intake larger than normal. None had clinical symptoms o f pancreatic disease and plain film o f the abdomen did not reveal pancreatic calcification. No evidence o f intestinal disease was found except in one o f them (C) who complained o f diarrhea. The follow-up o f these patients after dietary therapy confirmed the absence o f organic digestive disease. At admission the patients were submitted to a pancreatic function test and received dietary therapy providing more than 45 keal/kg body weight (1.2 g/kg body weight o f animal protein) for 4 weeks. Then a second pancreatic function test was performed. By this time the weight gain was inconstant and always less than the initial loss, ranging from 0 to 16%.
Pancreatic Tests Pancreatic function tests were performed after an overnight fast. A Camus tube was passed into the third duodenum and a Levine tube into the antrum under radiological control. Duodenal contamination by gastric juice and instillation every 5 min o f 5 ml o f a BSP solution (0.03 %). Every duodenal sample containing BSP was discarded. Duodenal juice was collected in 10-min samples. After a 2 X 10 min basal period, C C K (G IH , 3 U/kg/h) was intravenously infused at a constant rate for 4 X 10 min. Then secretin (G IH , 1 CU/kg) was intravenously injected and 6 X 10 min samples were obtained. Each sample was collected in an ice-chilled tube. Measurements o f enzymatic concentrations were per formed within 1 h after sampling by the kinetic pH stat technique using benzoylarginineethyl ester for trypsin, acetyltyrosineethyl ester for chymotrypsin and an olive oil suspen sion for lipase (4). Amylase was estimated using the method o f Norby (4) and bicarbonate concentration was measured by titrimetry. The mean value o f enzymatic activities in the 3rd and 4th samples during C C K stimulation and the highest value for volume and bicarbonate concentration in any sample obtained during secretin stimulation were selected as represen tative parameters o f pancreatic functions. It is generally acknowledged that enzyme outputs provide a better estimation of pan creatic function than enzyme concentrations. However, when C C K is used alone, without secretin, as it is in present study, the volumes are very small and the errors on recovery are, therefore, too large to obtain outputs with a good accuracy.
Effects o f Malnutrition The maximal volume of pancreatic flow during secretin stimulation was irregularly lowered in malnourished patients while the maximal bicarbonate con centration dropped always under the lower value observed in control subjects. Lipase was the more affected o f the enzyme and was below the lower control
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
Results
Table I Age Malnutrition years length causes months
A B C
59 53 37
D
56
social social mental anorexia social
Body weight, kg'
Blood
X
protein RB C X 106/mm3 g/1
g/1
hemoglobin iron g/100 ml Mg/1
Y
Z
albumin
3 8 6
65 57 51
50 51 36
58 51 38
3.25 3.35 4.40
63 62 48
24 36 23
9.6 11.6 13.3
12
77
70
71
3.06
69
34
9.4
Ca mg/1
1,000
87 90 80
610
93
310 -
Deseos/Duclieu ¡Minaire
Patient
to
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
' Body weight: X at the beginning o f the malnutrition period (normal weight); Y at the end o f the malnutrition period (first test), and Z at the end o f the renutrition period (second test 4 weeks after).
Exocrine Pancreatic Insufficiency and Primitive Malnutrition
93
value in each o f these patients. Trypsin and chymotrypsin were respectively lowered in 3 and 1 out o f 4 patients and amylase was always above control value. Effect o f Dietary Therapy The institution o f a high-protein-calorie diet during 4 weeks regularly im proved maximal bicarbonate concentration and lipase activity. The effect was less obvious upon pancreatic flow, trypsin and chymotrypsin activities, the re coveries of which were irregular.
As a whole, these results agree with those obtained by Tandon et al. (7) and Kumar et al. (3) in 8 and 9 malnourished Indian adult patients, respectively, and showing that the secretory volume was not clearly affected by malnutrition, while the maximal bicarbonate concentration was regularly low and returned to the normal range by dietary therapy. Bicarbonate secretion was also reduced in adult malnourished patients living in Colombia (5) as well as in British patients with gastrectomy for gastric ulcer (10). By opposition Barhezat and Hansen (1) reported that the ability to raise the duodenal pH level was not changed in children suffering from kwashiorkor and marasmus, suggesting that the pan creatic ducts are spared in kwashiorkor. Among the enzymes o f the duodenal content, amylase was not clearly af fected by malnutrition or dietary therapy. This result agrees with those of Tandon et al. (7) and Kumar et al. (3) while it differs from those collected in malnourished adults (5) and children (1, 2, 8). The most likely explanation for this difference is that the amylase secretion is affected only in severe form o f malnutrition, such as in children in whom the requirements for growth worsen the malnutrition deficit. This hypothesis is supported by the fact that during malnutrition the enzymes o f the exocrine pancreas disappeared one by one. first lipase, then trypsin and finally amylase (9). Lipase secretion was reduced in each of these four malnourished patients. Actually this enzyme is the most sensitive towards malnutrition (7, 9) as it is towards acute alcoholic intoxication and chronic or acute pancreatitis (4). Among proteases, trypsin is probably more sensitive than chymotrypsin to a reduction in the protein calorie intake. Examination o f tire data collected 4 weeks after the start of dietary therapy (table II) confirms that the recovery is faster for pancreatic function than for body weight (3). The responsiveness to renutrition is greater for bicarbonate and lipase secretions than for trypsin, the concentration o f which remaining low in 2 out o f 4 patients.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
Discussion
Table II
Control1 *3
after
Lipase IU
before
before
26
after
after
before
1,000
75
Trypsin IU
Amylase LU after
before
3.2
Chymotrypsin IU after
before
28
after
60
Patients A B C D
49 28 16 14
26 50 19 76
74 60 58
88 76 110
677 647 500 860
760 1,030 1,115 1,563
18.5 10.4 4.5 9.8
3.5 8.6 17.5 12.0
16 21 22 32
19 32 21 50
53 228 62 94
110 123 70 225
Ratio3
2/4
1/4
3/3
0/3
4/4
1/4
0/4
0/4
3/4
2/4
1/4
0/4
1 Before and after 4 weeks o f dietary therapy. ! Lower value observed in control patients. 3 Number o f patients under the control value/total number o f patients.
VO
■n.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
before'
Bicarbonate mM
Descos /Duelieu /Mina ire
Volume ml/10 min
Exocrine Pancreatic Insufficiency and Primitive Malnutrition
95
The concept o f nutritional pancreatitis has been recently discussed by Pitchumoni (6). It appears that the disease requires a long-term history o f food deprivation, specially during childhood. Therefore, it is unlikely that in Western countries, malnutrition by itself could be a noticeable cause o f pancreatitis. Finally, it must be kept in mind that a reduction in pancreatic secretion cannot be directly accepted as a symptom o f pancreatic disease as long as there is a state o f chronic protein calorie deprivation.
References 1 2
3
4
5 6 7 8 9
10
Barbezat, G.O . and Hansen, J .D .L .: The exocrine pancreas and protein-calorie mal nutrition. Pediatrics, Springfield 47: 7 7 -9 2 (1968). Gomez, Galvan, R .R .; Cravioto, J ., and French, S .: Enzym atic activity o f the duodenal contents in children affected with third degree malnutrition. Pediatrics, Springfield 13: 548 (1954). Kumar, R .; Banks, P .A .; George, P .K ., and Tandon, B.N .: Early recovery o f exocrine pancreatic function in adult protein-calorie malnutrition. Gastroenterology 68: 1593-1595 (1975). Minaire, Y.; Deseos, L .; Daly, J.P .; Bererd, M .B., and Iximbert, R .: The interrelation ships o f pancreatic enzymes in health and diseases under cholecystokinin stimulation. Digestion 9: 8 -2 0 (1973). Pelaez, J .: Gonzalez, P.A. y Velez, H .: Estudio de la función pancreático en pacientes desnutridos. Antioquía med. 16: 41 -4 8 (1966). Pitchumoni, C .S .: Pancreas in primary malnutrition disorders. Am . J . clin. Nutr. 26: 374-379 (1973). Tandon, B.N.; Banks, P .A ., and George, P .K .: Recovery o f exocrine pancreatic func tion in adult protein calorie malnutrition. Gastroenterology 58: 35 8 -3 6 2 (1970). Thompson, M.D. and Trowell, H .C .: Pancreatic enzyme activity in duodenal contents o f children with a type o f kwashiorkor. Lancet i: 1031-1035 (1952). Veghelyi, P.V. and Kemeny, T.T.: Protein metabolism and pancreatic function; in de Reuck and Cameron Ciba Foundation Symposium on the Exocrine Pancreas, pp. 3 29-352 (Churchill, London 1962). Wormsley, K .G .: Pancreatic exocrine function in patients with gastric ulceration before and after gastrectomy. Lancet ii: 6 82-684 (1972).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 11:49:46 PM
L. Deseos, Pavillon Hbis. Hôpital Edouard-Herriot, F-69374 Lyon Cedex 2 (France)
