Biblthca Nutr. Dieta, No. 23, pp. 14-18 (Karger, Basel 1976)
Malnutrition in Patients with Gastric Resection N.N. BRATANOVA and N.P. NIKOLOV Centre of Hygiene (Director: Prof. T.A. TAsHEv) and Institute of Gastro-Enterology at the Medical Academy (Director: Prof. K. BRAILSKI), Sofia
Malnutrition in patients with gastric resection has been studied by many research workers [NEALEetal., 1967; NEDKOVA-BRATANOVA et al., 1970]. In recent years, attention has been directed to the small intestines on whose compensatory functions largely depends the favourable outcome of the operation. The results obtained are quite controversial. CORSINI et al. [1966] found insignificant morphologic changes in the efferent loop, while other authors [RUNCAN et ai., 1972; NIKOLOFF and KALATCHEWA, 1968] found marked morphologic changes, as well as lactase or combined disaccharidase deficiencies [TASCHEFF et ai., 1968]. In an effort to elucidate the role of the small intestines in the pathogenesis of the frequently observed malnutrition syndrome, especially after Billroth II resection of the stomach, we attempted a parallel study of the morphologic, the disaccharidase and some hydrolase changes in the small intestinal mucosa.
Materials and Methods
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We examined a group of 45 patients operated on for gastric or duodenal ulcer at different surgical clinics. The study was performed in the clinic and was aimed both at elucidating the diagnosis and at testing pathogenetic dietary schedules. The clinical characteristics of our patients are shown in table I. It is seen that most patients were severely ill and had a considerable loss of weight (between 10 and 30 kg); a few of them were plainly cachectic. In all patients the operation has been performed more than 3 years ago; one third of them have been subsequently subjected to different correcting operations. The initial or su bsequent 'correcting' operation in seven patients was Billroth I resection. An area of the efferent loop, 60-80 cm distally from the anastomosis, was biopsied. The biopsy specimens were examined histologically, some of them electron-microscopi-
BRATANOVA/NIKOLOV
15
Table l. Clinical characteristics Clinical diagnosis
Sex
Billroth I
Billroth II Total
M
F
Dumping syndrome Anastomositis Recurrent or anastomotic ulceration Chronic enteritis With malabsorption Without malabsorption Gastrocolic fistula Afferent loop syndrome
10 6 2
7
3 1 1
14 5
17 6 2
8 2 2 4
3 1
2
9 3 2 4
11 3 2 4
Total
34
11
7
38
45
cally. The enzymatic study included three disaccharidases and from three to nine dipeptidases. Disaccharidase activity was determined by the quantitative method of DAHLQIDsT [1968], modified by IVANOV et al. [1974], and dipeptidase by the method of JOSEFSSON and LINDBERG [1965] in homogenate from just obtained intestinal mucosa.
Results
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The histologic changes and the values of the three disaccharidases lactase, maltase, and invertase - are shown in table II. Lactase deficiency was found in 45.5%, invertase deficiency in 33.3% and maltase deficiency in 25% of the patients. The decrease in enzymatic activity was more pronounced in patients with Billroth II resection, especially if there was partial mucosal atrophy. The clinical diagnosis in these cases of enzymatic deficiency was Billroth II + dumping syndrome, whereas patients with afferent loop syndrome and anastomositis had normal disaccharidase activity. No direct relationship was recorded between morphologic lesions and enzymatic activity changes, except the advanced partial or subtotal atrophy. The following dipeptidases were investigated: glycyl-I-alanine, glycyl-Ileucine, glycyl-I-valine, glycyl-I-isoleucine, leucyl-I-Ieucine, alanyl-I-glycine, alanyl-I-leucine, alanyl-I-proline and glycyl-I-glutamic acid. They all belong (with the exception of glycyl-I-isoleucine) to the 'endopeptidases' and decompose neutral amino acid dipeptides. In table III we compare the values of the former four enzymes in three subgroups (17 cases) with the values in the control group. Similar correlations were observed with the latter five enzymes.
16
BRATANoVA/NIKOLOV
It is seen that all four dipeptidases were decreased (one of them - glycylI-isoleucine - was brush-border peptidase). In cases of Billroth I, enzymatic activity was comparatively higher than in Billroth II resections. While the activities of the former three enzymes were altogether less than 50% of the activities in the control group, the glycyl-I-isoleucine decrease was slighter. The correlation between the results of the histologic study and the results of the enzymatic study is shown in table IV. It is evident that activities of the same four enzymes were by 20-60% lower than in the reference group, in spite of the histologic conclusion of a normal small intestinal mucosa. In cases of partial atrophy the enzymatic activity was even lower, but the difference between the two groups is not statistically significant. Just as in the disacharidases, there is no correlation between the morphologic changes in the mucosa and the hydrolase activity.
Table II. Histologic changes and mean values (",mol/min); wet tissue Diagnosis and histology
Number Lactase of cases
Maltase
Invertase
BiIIroth II + afferent loop syndrome BiIIroth II + dumping syndrome BiIIroth II + anastomositis or stomal ulcer Billroth II + chronic enteritis with malabsorption Reference group Normal mucosa Partial atrophy
4 15 7
6.85 3.03 1.32
23.06 14.70 14.77
29.81 15.04 9.54
6 10 18 16
1.33 9.16 1.82 3.24
9.09 17.8 14.77 10.34
5.94 20.06 13.72 14.03
Type of gastric operation
Number Glycyl-Iof cases alanine
Glycyl-fleucine
Glycyl-fvaline
Glycyl-fisoleucine
BiIIroth I BiIIroth II + dumping syndrome Billroth II + chronic enteritis Reference group
7
64.52
107.42
42.34
95.11
7
45.80
50.23
26.09
71.45
3 12
60.09 153.08
76.73 141.36
78.80 81.28
57.56 100.27 Downloaded by: Université de Paris 193.51.85.197 - 1/24/2020 3:25:55 PM
Table Ill. Mean values (",mol/mg protein nitrogen)
Malnutrition in Patients with Gastric Resection
17
Table IV Histology
Number Glycyl-lof cases alanine
Normal mucosa Partial atrophy Reference group
13 7 12
67.06 43.92 153.08
Glycyl-lleucine
Glycyl-lvaline
Glycyl-lisoleucine
80.61 72.89 141.36
53.90 17.33 81.28
81.34 100.27
Discussion
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Among the causes of malnutrition in patients with gastric resection, impaired intestinal digestion occupies an important place, especially impaired contact and intracellular digestion [UGOLEV, 1972]. The enzymatic activity of the small intestine (efferent loop at a distance of 60-80 cm distally from the anastomosis) was sharply reduced, regardless of the presence or absence of histologic changes. Of the disaccharidase enzymes studied, most common was lactase deficiency (in 45.5% of the patients) closely followed by invertase and maltase deficiency. They were more common in Billroth-II-operated patients, especially if there was partial mucosal atrophy. In our opinion, the intolerance to lactose and other disaccharides may be attributed to these 'acquired' enzymatic deficiencies. Dipeptidase activity disturbances seem to be more complex. We observed a decrease in the hydrolases both in Billroth-I- and in Billroth-II-operated patients, of course with some quantitative differences. Interesting enough, there were no essential quantitative differences between the enzymatic activities in Billroth-I-operated patients, in whom dumping was the leading syndrome, and in Billroth-II-operated with chronic enteritis as leading syndrome. In our opinion, the sharp decrease in dipeptidase activity is responsible for the impaired protein digestion and absorption at enterocyte level (intracellular digestion of dipeptides). Which is the mechanism of these disturbances? It is difficult to give an answer to this question. It may be admitted that they are not necessarily associated with microscopic or ultramicroscopic changes. More essential seem to be the enzyme induction phenomena. The major decrease in dipeptidase than disaccharidase activity should be interpreted in this sense. In conclusion, malnutrition following gastric resection depends much on
18
BRATANOVAjNIKoLOV
the morphologic and especially on the enzymatic deficiencies in the small intestinal mucosa. The lactase and other disaccharidase deficiencies underlie the impaired digestion and absorption of milk and carbohydrates. The dipeptidase deficiencies are likely to be responsible for the impaired digestion and absorption of neutral amino acid oligopeptides. It is namely these digestive disturbances in carbohydrate and protein absorption and hence to malnutrition. Proceeding from all this we promoted dietary treatment in conformity with the enzymatic and absorptive disturbances in each case with very favourable results. References CORSINI, G.; GONDOLFI, E.; BONEcm, J., et al: Postgastrectomy malabsorption. Gastroenterology 50 358-365 (1966). DAHLQUIST, A.: Assay of intestinal disaccharidases. Analyt. Biochem. 22: 99-107 (1968). GRAY, G. M. and COOPER, H. L. : Protein digestion and absorption. Gastroenterology 61 : 535-544 (1971). IVANOV, E.; SAVOV, G., and TODORINOVA, E.: The quantitative determination of some disaccharidases in the small intestinal mucosa. Sovrem. Med., Sof. (in press, 1974). JOSEFSSON, L. and LINDBERG, T.: Intestinal dipeptidases. I. Spectrophotometric determination and characterisation of dipeptidase activity in pig intestinal mucosa. Biochim. biophis. Acta 105: 149-161 (1965). NEALE, G.; ANTCLlFF, c.; WELBOURN, R.B.; MOLIN, D.L., and BooTH, C.C.: Protein malnutrition after partial gastrectomy. Q. JI Med. 36: 144,469-494 (1967). NIKOLOFF, N. und KALATCHEWA, J.: Strukturveranderungen der Magenmukosa und des Jejunums nach Magenresektion von Typ Billroth II. Z. ges. inn. Med. 23: 14,437-439 (1968). RUNcAN, V.; GHEORGHESCU, B.; lOVIN, c., et al.: Whole body counter studies of iron absorption patients with subtotal gastrectomy. Revue roum. MM. int. 2: 5, 451-464 (1972). SmNER, M. and DONIACH, l.: Histopathologic studies in steatorrhea. Gastroenterology 38: 419-440 (1960). TASCHEFF, T.; NEDKOWA-BRATANOWA, N.; NIKOLOFF, N.; IWANoFF, E.; KRISTEWA. A. und SAWOFF, G.: Uber Disaccharidasenmangel bei Erwachsenen mit gastrointestinalen Erkrankungen. Z. ges. inn. Med. 27: 99-107 (1968). UGOLEV, A.M.: Membrane digestion. Gut 13: 735-747 (1972).
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Dr. N.N. BRATANOVA, Centre of Hygiene, Boul. Dim. Nestorov 15, Sofia (Bulgaria)
Malnutrition in Patients with Gastric Resection N.N. BRATANOVA and N.P. NIKOLOV Centre of Hygiene (Director: Prof. T.A. TAsHEv) and Institute of Gastro-Enterology at the Medical Academy (Director: Prof. K. BRAILSKI), Sofia
Malnutrition in patients with gastric resection has been studied by many research workers [NEALEetal., 1967; NEDKOVA-BRATANOVA et al., 1970]. In recent years, attention has been directed to the small intestines on whose compensatory functions largely depends the favourable outcome of the operation. The results obtained are quite controversial. CORSINI et al. [1966] found insignificant morphologic changes in the efferent loop, while other authors [RUNCAN et ai., 1972; NIKOLOFF and KALATCHEWA, 1968] found marked morphologic changes, as well as lactase or combined disaccharidase deficiencies [TASCHEFF et ai., 1968]. In an effort to elucidate the role of the small intestines in the pathogenesis of the frequently observed malnutrition syndrome, especially after Billroth II resection of the stomach, we attempted a parallel study of the morphologic, the disaccharidase and some hydrolase changes in the small intestinal mucosa.
Materials and Methods
Downloaded by: Université de Paris 193.51.85.197 - 1/24/2020 3:25:55 PM
We examined a group of 45 patients operated on for gastric or duodenal ulcer at different surgical clinics. The study was performed in the clinic and was aimed both at elucidating the diagnosis and at testing pathogenetic dietary schedules. The clinical characteristics of our patients are shown in table I. It is seen that most patients were severely ill and had a considerable loss of weight (between 10 and 30 kg); a few of them were plainly cachectic. In all patients the operation has been performed more than 3 years ago; one third of them have been subsequently subjected to different correcting operations. The initial or su bsequent 'correcting' operation in seven patients was Billroth I resection. An area of the efferent loop, 60-80 cm distally from the anastomosis, was biopsied. The biopsy specimens were examined histologically, some of them electron-microscopi-
BRATANOVA/NIKOLOV
15
Table l. Clinical characteristics Clinical diagnosis
Sex
Billroth I
Billroth II Total
M
F
Dumping syndrome Anastomositis Recurrent or anastomotic ulceration Chronic enteritis With malabsorption Without malabsorption Gastrocolic fistula Afferent loop syndrome
10 6 2
7
3 1 1
14 5
17 6 2
8 2 2 4
3 1
2
9 3 2 4
11 3 2 4
Total
34
11
7
38
45
cally. The enzymatic study included three disaccharidases and from three to nine dipeptidases. Disaccharidase activity was determined by the quantitative method of DAHLQIDsT [1968], modified by IVANOV et al. [1974], and dipeptidase by the method of JOSEFSSON and LINDBERG [1965] in homogenate from just obtained intestinal mucosa.
Results
Downloaded by: Université de Paris 193.51.85.197 - 1/24/2020 3:25:55 PM
The histologic changes and the values of the three disaccharidases lactase, maltase, and invertase - are shown in table II. Lactase deficiency was found in 45.5%, invertase deficiency in 33.3% and maltase deficiency in 25% of the patients. The decrease in enzymatic activity was more pronounced in patients with Billroth II resection, especially if there was partial mucosal atrophy. The clinical diagnosis in these cases of enzymatic deficiency was Billroth II + dumping syndrome, whereas patients with afferent loop syndrome and anastomositis had normal disaccharidase activity. No direct relationship was recorded between morphologic lesions and enzymatic activity changes, except the advanced partial or subtotal atrophy. The following dipeptidases were investigated: glycyl-I-alanine, glycyl-Ileucine, glycyl-I-valine, glycyl-I-isoleucine, leucyl-I-Ieucine, alanyl-I-glycine, alanyl-I-leucine, alanyl-I-proline and glycyl-I-glutamic acid. They all belong (with the exception of glycyl-I-isoleucine) to the 'endopeptidases' and decompose neutral amino acid dipeptides. In table III we compare the values of the former four enzymes in three subgroups (17 cases) with the values in the control group. Similar correlations were observed with the latter five enzymes.
16
BRATANoVA/NIKOLOV
It is seen that all four dipeptidases were decreased (one of them - glycylI-isoleucine - was brush-border peptidase). In cases of Billroth I, enzymatic activity was comparatively higher than in Billroth II resections. While the activities of the former three enzymes were altogether less than 50% of the activities in the control group, the glycyl-I-isoleucine decrease was slighter. The correlation between the results of the histologic study and the results of the enzymatic study is shown in table IV. It is evident that activities of the same four enzymes were by 20-60% lower than in the reference group, in spite of the histologic conclusion of a normal small intestinal mucosa. In cases of partial atrophy the enzymatic activity was even lower, but the difference between the two groups is not statistically significant. Just as in the disacharidases, there is no correlation between the morphologic changes in the mucosa and the hydrolase activity.
Table II. Histologic changes and mean values (",mol/min); wet tissue Diagnosis and histology
Number Lactase of cases
Maltase
Invertase
BiIIroth II + afferent loop syndrome BiIIroth II + dumping syndrome BiIIroth II + anastomositis or stomal ulcer Billroth II + chronic enteritis with malabsorption Reference group Normal mucosa Partial atrophy
4 15 7
6.85 3.03 1.32
23.06 14.70 14.77
29.81 15.04 9.54
6 10 18 16
1.33 9.16 1.82 3.24
9.09 17.8 14.77 10.34
5.94 20.06 13.72 14.03
Type of gastric operation
Number Glycyl-Iof cases alanine
Glycyl-fleucine
Glycyl-fvaline
Glycyl-fisoleucine
BiIIroth I BiIIroth II + dumping syndrome Billroth II + chronic enteritis Reference group
7
64.52
107.42
42.34
95.11
7
45.80
50.23
26.09
71.45
3 12
60.09 153.08
76.73 141.36
78.80 81.28
57.56 100.27 Downloaded by: Université de Paris 193.51.85.197 - 1/24/2020 3:25:55 PM
Table Ill. Mean values (",mol/mg protein nitrogen)
Malnutrition in Patients with Gastric Resection
17
Table IV Histology
Number Glycyl-lof cases alanine
Normal mucosa Partial atrophy Reference group
13 7 12
67.06 43.92 153.08
Glycyl-lleucine
Glycyl-lvaline
Glycyl-lisoleucine
80.61 72.89 141.36
53.90 17.33 81.28
81.34 100.27
Discussion
Downloaded by: Université de Paris 193.51.85.197 - 1/24/2020 3:25:55 PM
Among the causes of malnutrition in patients with gastric resection, impaired intestinal digestion occupies an important place, especially impaired contact and intracellular digestion [UGOLEV, 1972]. The enzymatic activity of the small intestine (efferent loop at a distance of 60-80 cm distally from the anastomosis) was sharply reduced, regardless of the presence or absence of histologic changes. Of the disaccharidase enzymes studied, most common was lactase deficiency (in 45.5% of the patients) closely followed by invertase and maltase deficiency. They were more common in Billroth-II-operated patients, especially if there was partial mucosal atrophy. In our opinion, the intolerance to lactose and other disaccharides may be attributed to these 'acquired' enzymatic deficiencies. Dipeptidase activity disturbances seem to be more complex. We observed a decrease in the hydrolases both in Billroth-I- and in Billroth-II-operated patients, of course with some quantitative differences. Interesting enough, there were no essential quantitative differences between the enzymatic activities in Billroth-I-operated patients, in whom dumping was the leading syndrome, and in Billroth-II-operated with chronic enteritis as leading syndrome. In our opinion, the sharp decrease in dipeptidase activity is responsible for the impaired protein digestion and absorption at enterocyte level (intracellular digestion of dipeptides). Which is the mechanism of these disturbances? It is difficult to give an answer to this question. It may be admitted that they are not necessarily associated with microscopic or ultramicroscopic changes. More essential seem to be the enzyme induction phenomena. The major decrease in dipeptidase than disaccharidase activity should be interpreted in this sense. In conclusion, malnutrition following gastric resection depends much on
18
BRATANOVAjNIKoLOV
the morphologic and especially on the enzymatic deficiencies in the small intestinal mucosa. The lactase and other disaccharidase deficiencies underlie the impaired digestion and absorption of milk and carbohydrates. The dipeptidase deficiencies are likely to be responsible for the impaired digestion and absorption of neutral amino acid oligopeptides. It is namely these digestive disturbances in carbohydrate and protein absorption and hence to malnutrition. Proceeding from all this we promoted dietary treatment in conformity with the enzymatic and absorptive disturbances in each case with very favourable results. References CORSINI, G.; GONDOLFI, E.; BONEcm, J., et al: Postgastrectomy malabsorption. Gastroenterology 50 358-365 (1966). DAHLQUIST, A.: Assay of intestinal disaccharidases. Analyt. Biochem. 22: 99-107 (1968). GRAY, G. M. and COOPER, H. L. : Protein digestion and absorption. Gastroenterology 61 : 535-544 (1971). IVANOV, E.; SAVOV, G., and TODORINOVA, E.: The quantitative determination of some disaccharidases in the small intestinal mucosa. Sovrem. Med., Sof. (in press, 1974). JOSEFSSON, L. and LINDBERG, T.: Intestinal dipeptidases. I. Spectrophotometric determination and characterisation of dipeptidase activity in pig intestinal mucosa. Biochim. biophis. Acta 105: 149-161 (1965). NEALE, G.; ANTCLlFF, c.; WELBOURN, R.B.; MOLIN, D.L., and BooTH, C.C.: Protein malnutrition after partial gastrectomy. Q. JI Med. 36: 144,469-494 (1967). NIKOLOFF, N. und KALATCHEWA, J.: Strukturveranderungen der Magenmukosa und des Jejunums nach Magenresektion von Typ Billroth II. Z. ges. inn. Med. 23: 14,437-439 (1968). RUNcAN, V.; GHEORGHESCU, B.; lOVIN, c., et al.: Whole body counter studies of iron absorption patients with subtotal gastrectomy. Revue roum. MM. int. 2: 5, 451-464 (1972). SmNER, M. and DONIACH, l.: Histopathologic studies in steatorrhea. Gastroenterology 38: 419-440 (1960). TASCHEFF, T.; NEDKOWA-BRATANOWA, N.; NIKOLOFF, N.; IWANoFF, E.; KRISTEWA. A. und SAWOFF, G.: Uber Disaccharidasenmangel bei Erwachsenen mit gastrointestinalen Erkrankungen. Z. ges. inn. Med. 27: 99-107 (1968). UGOLEV, A.M.: Membrane digestion. Gut 13: 735-747 (1972).
Downloaded by: Université de Paris 193.51.85.197 - 1/24/2020 3:25:55 PM
Dr. N.N. BRATANOVA, Centre of Hygiene, Boul. Dim. Nestorov 15, Sofia (Bulgaria)
