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Serum gastrin concentrations in infants with short gut syndrome
Serum Gastrin Concentrations in Infants With Short Gut Syndrome By J. Michael Scully, Frank J. Lynch, Edward Passaro, Jr., and David L. Dudgeon
G
A S T R I C H Y P E R S E C R E T I O N developing after massive small bowel resection (MSBR) has been reported.~-5 Some investigators have noted acid hypersecretion for 2-3 wk postoperatively, but have not demonstrated any long-term acid hypersecretion. 6 This early hypersecretory state has been attributed to histamine release secondary to shock and acute hepatic injury accompanying bowel infarction. Little information is available on gastric hypersecretion in infants with MSBR. Avery et al. 7 noted significant hyperacidity in three infants following bowel resections for atresia. The purpose of this study was to determine the degree o f acid hypersecretion in infants with MSBR and correlate these levels with serum gastrin values.
METHODS Seven babies ranging in age from 27 days to 10 mo, weighing 1.7 kg to 10.45 kg, and with remaining small bowel lengths of 15 cm to 90 cm, had gastric juice specimens taken after a 3-hr fast according to the method of Avery et al. 7 After the last gastric samples were obtained, 2 cc of venous blood were drawn from the anticubital vein for gastrin determinations. Two babies, 148 and 288 days old, and weighing 4.74 kg to 7.78 kg, with 35 cm and 100 cm of gut, respectively, were fed. Gastric juice specimens were obtained 1 hr postprandially and every half hour thereafter for 3 hr. Total acid was titrated automatically to pH 7.0. Gastrin concentrations were determined by radioimmunoassay. RESULTS
We failed to demonstrate any hyperacidity in either the fasting babies or those that were fed. The a m o u n t of total acid ranged from 0.12 m E q / h r to 0.70 m E q / h r in the fasting group. Gastrin levels ranged from 15 to 239 p g / m l (Table 1). Two babies were tested after feeding. One baby's postprandial acids were 0.9 m E q / h r (after 1 hr) and 0.86 m E q / h r (after 3 hr). The second baby's ranged from 0.70 m E q / h r to 0.68 m E q / h r at similar times. Corresponding gastrin levels were 90 pg/ml (1 hr) and 66 p g / m l (3 hr) in the first baby, and were unchanged at 140 p g / m l in the second baby (Table 2). There was no correlation between the length of gut remaining and the acid levels. The highest acid production (0.72 m E q / h r ) was found in a baby with 47.5 cm of gut remaining, while the child with 15 cm of gut remaining had 0.31 From the Surgical Service, VA Wadsworth Hospital Center, Los Angeles, Calif., the Department of Surgery, UCLA School of Medicine, Los Angeles, Calif., and the Department of Surgery, Childrens Hospital of Los Angeles, University of Southern California School of Medicine, Los Angeles, Calif. Presented before the 24th Annual Meeting of the American Academy of Pediatrics, Surgical Section, Washington, D.C., October 19-21, 1975. Address for reprints: J. Michael Scully, M.D., Department of Surgery, UCLA School of Medicine, Los Angeles, Calif. 90024. 9 1976 by Grune & Stratton, Inc. Journal of Pediatric Surgery, Vol. 11, No. 3 (June), 1976
315
316
SCULLY ET AL.
Table 1. Age (Days)
Sex
Weight (Kg)
Remaining Gut Length (cm)
K.E.
225 D.O.
F
7.5
15
0.31
28
Small massive atresia
M.M. C.M. T.J. D.M.
49 38 54 144
M M M M
1.7 2.95 3.06 3.32
31 35 47.5 70.0
0.21 0.26 0.70 0.38
72 86 14 26
B.M.
27
M
2.55
90
0.19
239
Necrotizing enterocolitis Midgut volvulus Jejunal atresia Ileal atresias omphalocele imperfect anus Multiple small bowel
S.C.
300
M
10.45
90
0.12
15
T.K.
288
F
4.73
100
0.29
15
Patient
TotalHd (mEq)
Gastrin (pg/ml)
Comment
infarction
atresias Omphalocele ileal atresia Necrotizing enterocolitis Hirschsprung's colostomy
m E q / h r of gastric acid. Conversely, the baby with the highest acid had a gastrin level of 14 pg/ml; the baby with the shortest gut and mid-range acid (0.31 m E q / hr) had a gastrin level of 15 pg/ml. In the postprandial group, one child with 100 cm of gut had a rise in acid production of 0.0 m E q / h r to 0.72 m E q / h r over 3 hr; the child with 35 cm of gut dropped from 0.86 m E q / h r at the end of 1 hr to 0.58 m E q / h r at the end of 3 hr. We noted no correlation between gastric acid secretion and weights (Table 1). The two youngest babies had the highest acids: 0.70 m E q / h r at 54 days old and 0.38 m E q / h r at 144 days old. N o correlation between serum gastrin levels was noted when either weights or ages were compared. DISCUSSION
Gastrin hypersecretion following M S B R was not demonstrated in our study. In addition, we could not demonstrate hypergastrinemia in these patients as has been described in adults. 8 One explanation for the gastric hyperacidity that others have observed in some patients with M S B R is that there is a loss or decrease of a gastric inhibitor substance as a result of the massive resection. Ernst 9 demonstrated an increased basal acid output in patients with ileal resection for regional enteritis, but no increase in serum gastrin concentrations. Strauss et al. 8 demonstrated marked hypergastrinemia in four patients with massive intestinal resection in both a Table 2.
Patient
Age (Days)
Sex
Weight (kg)
Remaining Gut Length (cm)
C.M.
149
M
3.36
35
T.K.
288
F
4.73
100
1~
3~
0.85
0.58
0
.72
Gastrin 1~ 3~ 1~ 3~
140 140 90 66
Feeds Progestamil Vivonex and Portagen
SERUM GASTRIN CONCENTRATIONS
317
fasting state a n d after a test m e a l . T h e y c o u l d n o t d e m o n s t r a t e s i m i l a r c h a n g e s in 1 p a t i e n t with a j e j u n o i l e a l b y p a s s . I n infants, the r e l a t i v e a b u n d a n c e o f g a s t r i c s e c r e t i o n i n h i b i t o r s such as gastric i n h i b i t o r y p o l y p e p t i d e ( G I P ) is u n k n o w n . I t is p o s s i b l e t h a t t h e acid h y p e r secretion o c c a s i o n a l l y n o t e d in a d u l t s a n d n o t n o t e d in infants in this s t u d y m a y be due to a large q u a n t i t y o f G I P in infants. N o d a t a is a v a i l a b l e r e g a r d i n g t h e n a t u r e o f i n t e s t i n a l a u t o r e g u l a t i o n o f gastric s e c r e t i o n in n o r m a l i n f a n t s , n o r has t h e g a s t r i c r e s p o n s e to feeding been studied. I n f a n t s with M S B R m a t c h e d closely w i t h c o n t r o l s for g e s t a t i o n a l age a n d weight m u s t be s t u d i e d o v e r a p e r i o d o f m o n t h s to d e t e r m i n e the i n c i d e n c e o f gastric h y p e r s e c r e t i o n a n d p e r h a p s to s h e d s o m e light o n t h e n a t u r e o f intestinal/gastric feedback mechanisms. Finally, maternal intestinal hormone levels s h o u l d be d e t e r m i n e d in b o t h g r o u p s to see w h a t , if any, c o n t r o l t h e y have o v e r the early d e v e l o p m e n t o f a u t o r e g u l a t o r y a u t o n o m y in n o r m a l infants a n d t h o s e with m a s s i v e s m a l l b o w e l r e s e c t i o n . SUMMARY
Seven b a b i e s with 100 cm o r less r e m a i n i n g s m a l l b o w e l h a v e been e v a l u a t e d for evidence o f g a s t r i c h y p e r a c i d i t y a n d / o r h y p e r g a s t r i n e m i a . T w o b a b i e s w e r e also s t u d i e d after feeding. N o p a t i e n t d e m o n s t r a t e d h y p e r a c i d i t y o r h y p e r g a s t r i n e m i a . T h i s i n f a n t d a t a is d i s c u s s e d in r e g a r d s to r e p o r t e d c o n t r a d i c t o r y d a t a in a d u l t studies. ACKNOWLEDGMENT
The authors wish to thank Drs. Gianfranco Frittelli, Stephen Gans, Neal Sherman, and Hossein Mahour for their help in making this work possible. REFERENCES
1. Frederick PL, Sizer JS, Osborne MP: Relation of massive small bowel resection to gastric secretion. N Engl J Med 272:509-514, 1966 2. Osborne MP, Frederick PL, Sizer JS, et al: Mechanism of gastric hypersecretion following massive intestinal resection: Clinical and experimental observations. Ann Surg 164:626-634, 1966 3. Osborne MP, Sizer J, Frederick PL, et al: Massive small bowel resection and gastric hypersecretion--lts mechanism and a plan for clinical study and management. Am J Surg 114: 393-397, 1967 4. Aber GM, Ashton F, Carmalt MH, et al: Gastric hypersecretion following massive small bowel resection in man. Am J Dig Dis 12:785794, 1967
5. Grundberg AB, Lopez RS, Dragstedt LR: Effect of intestinal reversal and massive resection on gastric secretion. Arch Surg 94:326-329, 1967 6. Windsor CWO, Fejfor J, Waadward DAK: Gastric secretion after massive small bowel resection. Gut 10:779 786, 1969 7. Avery GB, Randolph JG, Weaver T: Gastric response to specific disease in infants. Pediatrics 38:874 878, 1966 8. Strauss E, Gerson C, Yalow RS: Hypersecretion of gastrin associated with short bowel syndrome. Gastroenterology 66:175-180, 1974 9. Earnst DL, Briggs FT, Walsh JH, et al: Gastric acid hypersecretion in patients with ileal regional enteritis. Gastroenterology 64:723, 1973
G
A S T R I C H Y P E R S E C R E T I O N developing after massive small bowel resection (MSBR) has been reported.~-5 Some investigators have noted acid hypersecretion for 2-3 wk postoperatively, but have not demonstrated any long-term acid hypersecretion. 6 This early hypersecretory state has been attributed to histamine release secondary to shock and acute hepatic injury accompanying bowel infarction. Little information is available on gastric hypersecretion in infants with MSBR. Avery et al. 7 noted significant hyperacidity in three infants following bowel resections for atresia. The purpose of this study was to determine the degree o f acid hypersecretion in infants with MSBR and correlate these levels with serum gastrin values.
METHODS Seven babies ranging in age from 27 days to 10 mo, weighing 1.7 kg to 10.45 kg, and with remaining small bowel lengths of 15 cm to 90 cm, had gastric juice specimens taken after a 3-hr fast according to the method of Avery et al. 7 After the last gastric samples were obtained, 2 cc of venous blood were drawn from the anticubital vein for gastrin determinations. Two babies, 148 and 288 days old, and weighing 4.74 kg to 7.78 kg, with 35 cm and 100 cm of gut, respectively, were fed. Gastric juice specimens were obtained 1 hr postprandially and every half hour thereafter for 3 hr. Total acid was titrated automatically to pH 7.0. Gastrin concentrations were determined by radioimmunoassay. RESULTS
We failed to demonstrate any hyperacidity in either the fasting babies or those that were fed. The a m o u n t of total acid ranged from 0.12 m E q / h r to 0.70 m E q / h r in the fasting group. Gastrin levels ranged from 15 to 239 p g / m l (Table 1). Two babies were tested after feeding. One baby's postprandial acids were 0.9 m E q / h r (after 1 hr) and 0.86 m E q / h r (after 3 hr). The second baby's ranged from 0.70 m E q / h r to 0.68 m E q / h r at similar times. Corresponding gastrin levels were 90 pg/ml (1 hr) and 66 p g / m l (3 hr) in the first baby, and were unchanged at 140 p g / m l in the second baby (Table 2). There was no correlation between the length of gut remaining and the acid levels. The highest acid production (0.72 m E q / h r ) was found in a baby with 47.5 cm of gut remaining, while the child with 15 cm of gut remaining had 0.31 From the Surgical Service, VA Wadsworth Hospital Center, Los Angeles, Calif., the Department of Surgery, UCLA School of Medicine, Los Angeles, Calif., and the Department of Surgery, Childrens Hospital of Los Angeles, University of Southern California School of Medicine, Los Angeles, Calif. Presented before the 24th Annual Meeting of the American Academy of Pediatrics, Surgical Section, Washington, D.C., October 19-21, 1975. Address for reprints: J. Michael Scully, M.D., Department of Surgery, UCLA School of Medicine, Los Angeles, Calif. 90024. 9 1976 by Grune & Stratton, Inc. Journal of Pediatric Surgery, Vol. 11, No. 3 (June), 1976
315
316
SCULLY ET AL.
Table 1. Age (Days)
Sex
Weight (Kg)
Remaining Gut Length (cm)
K.E.
225 D.O.
F
7.5
15
0.31
28
Small massive atresia
M.M. C.M. T.J. D.M.
49 38 54 144
M M M M
1.7 2.95 3.06 3.32
31 35 47.5 70.0
0.21 0.26 0.70 0.38
72 86 14 26
B.M.
27
M
2.55
90
0.19
239
Necrotizing enterocolitis Midgut volvulus Jejunal atresia Ileal atresias omphalocele imperfect anus Multiple small bowel
S.C.
300
M
10.45
90
0.12
15
T.K.
288
F
4.73
100
0.29
15
Patient
TotalHd (mEq)
Gastrin (pg/ml)
Comment
infarction
atresias Omphalocele ileal atresia Necrotizing enterocolitis Hirschsprung's colostomy
m E q / h r of gastric acid. Conversely, the baby with the highest acid had a gastrin level of 14 pg/ml; the baby with the shortest gut and mid-range acid (0.31 m E q / hr) had a gastrin level of 15 pg/ml. In the postprandial group, one child with 100 cm of gut had a rise in acid production of 0.0 m E q / h r to 0.72 m E q / h r over 3 hr; the child with 35 cm of gut dropped from 0.86 m E q / h r at the end of 1 hr to 0.58 m E q / h r at the end of 3 hr. We noted no correlation between gastric acid secretion and weights (Table 1). The two youngest babies had the highest acids: 0.70 m E q / h r at 54 days old and 0.38 m E q / h r at 144 days old. N o correlation between serum gastrin levels was noted when either weights or ages were compared. DISCUSSION
Gastrin hypersecretion following M S B R was not demonstrated in our study. In addition, we could not demonstrate hypergastrinemia in these patients as has been described in adults. 8 One explanation for the gastric hyperacidity that others have observed in some patients with M S B R is that there is a loss or decrease of a gastric inhibitor substance as a result of the massive resection. Ernst 9 demonstrated an increased basal acid output in patients with ileal resection for regional enteritis, but no increase in serum gastrin concentrations. Strauss et al. 8 demonstrated marked hypergastrinemia in four patients with massive intestinal resection in both a Table 2.
Patient
Age (Days)
Sex
Weight (kg)
Remaining Gut Length (cm)
C.M.
149
M
3.36
35
T.K.
288
F
4.73
100
1~
3~
0.85
0.58
0
.72
Gastrin 1~ 3~ 1~ 3~
140 140 90 66
Feeds Progestamil Vivonex and Portagen
SERUM GASTRIN CONCENTRATIONS
317
fasting state a n d after a test m e a l . T h e y c o u l d n o t d e m o n s t r a t e s i m i l a r c h a n g e s in 1 p a t i e n t with a j e j u n o i l e a l b y p a s s . I n infants, the r e l a t i v e a b u n d a n c e o f g a s t r i c s e c r e t i o n i n h i b i t o r s such as gastric i n h i b i t o r y p o l y p e p t i d e ( G I P ) is u n k n o w n . I t is p o s s i b l e t h a t t h e acid h y p e r secretion o c c a s i o n a l l y n o t e d in a d u l t s a n d n o t n o t e d in infants in this s t u d y m a y be due to a large q u a n t i t y o f G I P in infants. N o d a t a is a v a i l a b l e r e g a r d i n g t h e n a t u r e o f i n t e s t i n a l a u t o r e g u l a t i o n o f gastric s e c r e t i o n in n o r m a l i n f a n t s , n o r has t h e g a s t r i c r e s p o n s e to feeding been studied. I n f a n t s with M S B R m a t c h e d closely w i t h c o n t r o l s for g e s t a t i o n a l age a n d weight m u s t be s t u d i e d o v e r a p e r i o d o f m o n t h s to d e t e r m i n e the i n c i d e n c e o f gastric h y p e r s e c r e t i o n a n d p e r h a p s to s h e d s o m e light o n t h e n a t u r e o f intestinal/gastric feedback mechanisms. Finally, maternal intestinal hormone levels s h o u l d be d e t e r m i n e d in b o t h g r o u p s to see w h a t , if any, c o n t r o l t h e y have o v e r the early d e v e l o p m e n t o f a u t o r e g u l a t o r y a u t o n o m y in n o r m a l infants a n d t h o s e with m a s s i v e s m a l l b o w e l r e s e c t i o n . SUMMARY
Seven b a b i e s with 100 cm o r less r e m a i n i n g s m a l l b o w e l h a v e been e v a l u a t e d for evidence o f g a s t r i c h y p e r a c i d i t y a n d / o r h y p e r g a s t r i n e m i a . T w o b a b i e s w e r e also s t u d i e d after feeding. N o p a t i e n t d e m o n s t r a t e d h y p e r a c i d i t y o r h y p e r g a s t r i n e m i a . T h i s i n f a n t d a t a is d i s c u s s e d in r e g a r d s to r e p o r t e d c o n t r a d i c t o r y d a t a in a d u l t studies. ACKNOWLEDGMENT
The authors wish to thank Drs. Gianfranco Frittelli, Stephen Gans, Neal Sherman, and Hossein Mahour for their help in making this work possible. REFERENCES
1. Frederick PL, Sizer JS, Osborne MP: Relation of massive small bowel resection to gastric secretion. N Engl J Med 272:509-514, 1966 2. Osborne MP, Frederick PL, Sizer JS, et al: Mechanism of gastric hypersecretion following massive intestinal resection: Clinical and experimental observations. Ann Surg 164:626-634, 1966 3. Osborne MP, Sizer J, Frederick PL, et al: Massive small bowel resection and gastric hypersecretion--lts mechanism and a plan for clinical study and management. Am J Surg 114: 393-397, 1967 4. Aber GM, Ashton F, Carmalt MH, et al: Gastric hypersecretion following massive small bowel resection in man. Am J Dig Dis 12:785794, 1967
5. Grundberg AB, Lopez RS, Dragstedt LR: Effect of intestinal reversal and massive resection on gastric secretion. Arch Surg 94:326-329, 1967 6. Windsor CWO, Fejfor J, Waadward DAK: Gastric secretion after massive small bowel resection. Gut 10:779 786, 1969 7. Avery GB, Randolph JG, Weaver T: Gastric response to specific disease in infants. Pediatrics 38:874 878, 1966 8. Strauss E, Gerson C, Yalow RS: Hypersecretion of gastrin associated with short bowel syndrome. Gastroenterology 66:175-180, 1974 9. Earnst DL, Briggs FT, Walsh JH, et al: Gastric acid hypersecretion in patients with ileal regional enteritis. Gastroenterology 64:723, 1973