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Gastrointestinal Disease and Clinical Nutrition
Gastrointestinal Disease and Clinical Nutrition JAMES A. HALSTED, M.D.*
The purpose of this article is to focus attention on the relationship of gastrointestinal disease to nutrition. Clinical nutrition as an entity is a neglected area in medical thinking, medical education, and research, even though many aspects of medicine and clinical research do, in fact, involve nutrition. Malnutrition may arise from an inadequate or insufficient diet, in which case it can be termed primary. It may also arise from disordered gastrointestinal function. In this instance the term "conditioned malnutrition" seems an appropriate one. Conversely, a faulty diet may lead to lesions of the gastrointestinal tract or to disordered function. Although it will not be possible to document all instances either of faulty intake of nutrients leading to gastrointestinal disorder, or of malnutrition stemming from gastrointestinal disease, outstanding examples of each will be cited in order to call attention to the importance of clinical nutrition in gastroenterology. Both gastroenterology and clinical nutrition are broad headings, neither being easy to define with entire satisfaction. Therefore it seems worthwhile to attempt definitions which are at least plausible and to discuss some of the close relationships of nutrition and gastrointestinal disease. It may be obvious that essentially all aspects of biology and medicine are intimately related to nutrition at one level or another. However, a certain area can be delineated, called clinical nutrition. Such delineation as it is proposed to make will not be agreed upon by everyone concerned with nutrition and it is undoubtedly arbitrary. Nevertheless it may be useful as a means of defining a clinical area if not a true scientific discipline. Thus clinical nutrition may be defined as the area of human disease states or malnutrition brought about by (1) faulty intake of nutrients, or factors which cause their unavailability for absorption; (2) faulty digestion, absorption, or excretion of nutrients; or (3) faulty metabolism of nutrients. "'Associate Chief of Staff for Research and Education, Veterans Administration Hospital; Professor of International Health, Department of Epidemiology and Environmental Health, George Washington University School of Medicine, Washington, D.C.
Medical Clinics of North America- Vo!. 52, No. 6, November, 1968
1397
1398
JAMES
A.
HALSTED
The first criterion in this definition of clinical nutrition is more the concern of the dietitian, the agriculturalist, the Public Health officer, the health educator, and the psychologist than it is of the gastroenterologist. Nevertheless, primary dietary defects may cause gastrointestinal disorders, examples of which will be cited. The third criterion, faulty metabolism of nutrients, is generally beyond the realm wherein gastrointestinal disease is involved in nutrition. It falls chiefly in the province of the biochemist, the specialist in metabolism or diabetes, the endocrinologist, and often the hematologist. In discussing the relationship of gastroenterology to clinical nutrition we must be concerned chiefly with the second of the three identified criteria, namely abnormalities of digestion, absorption, or excretion of nutrients. However, the relationships between nutrition, metabolic and hormonal processes, and gastroenterology are close. The more that is understood the more blurred become the lines demarcating disciplines and the more important it is for collaboration to take place between workers in different areas of scientific research, especially between gastroenterologists and those interested in clinical nutrition. It is unnecessary to belabor a definition of gastroenterology. It consists of the physiology, pathology, and clinical aspects of the tubular gastrointestinal tract and of the solid organs - the pancreas and liver. Abnormalities which lead to faulty digestion, absorption, or excretion usually lead to malnutrition. This is why it is reasonable to define malnutrition secondary to gastrointestinal disease as "conditioned malnutrition." Thus it becomes a major component of the area of medicine called clinical nutrition. Liver disease is, of course, closely involved with malnutrition. Through its involvement with metabolic processes it may be the cause of malnutrition, and, conversely, malnutrition may be one causative factor in cirrhosis. However, liver disease will not be considered in this article since it is well covered elsewhere in this volume. Disorders of the pancreas often lead to conditioned malnutrition through interference with aspects of the digestive process. These also are considered elsewhere so will not be dealt with further.
GASTROINTESTlNAL DISORDERS CAUSED BY FAULTY DIET Zubira.n 19 has called attention to a number of gastrointestinal abnormalities stemming from primary malnutrition in Mexico. Most of these examples are seen in poverty areas in underdeveloped countries where crowding, a high incidence of infectious diseases, impoverished education, and illiteracy are the rule. The syndrome of protein-calorie malnutrition - kwashiorkor or protein deficiency -leads to a fatty liver, pancreatic dysfunction, and often intestinal malabsorption. Diarrhea is common. A thorough study by Zubiri'm of 92 patients with primary malnutrition revealed tongue abnormalities, diarrhea, abdominal pain, nausea, vomiting, and distention in from 29 to 86 per cent. Blood and mucus were found in 41 per cent of the patients with diarrhea, although parasites and intestinal pathogens were not present. In 28 per cent stea-
GASTROINTESTINAL DISEASE AND CLINICAL NUTRITION
1399
torrhea and creatorrhea occurred. Intestinal biopsies showed findings ranging from normal to partial villous atrophy. d-Xylose tests were frequently abnormal. Radiologic study often revealed dilated loops with segmentation of barium and the "moulage sign." Not all instances of faulty diet leading to gastrointestinal disease occur in the underdeveloped areas of the world. Thus N aiman et al. 14 studied the effects of a milk diet on 14 infants in Boston. This produced severe iron-deficiency anemia and was associated with achlorhydria in 4 of 8 patients, impaired d-xylose absorption in 6 of the 14, low serum carotene in 5 of the 14, and a flat vitamin A tolerance curve in 10. Stool fat excretion was increased in 4 of the group, and positive tests for occult blood occurred in 4 patients. Intestinal biopsy showed abnormalities in 7 of the 11 patients in which it was performed. Most of these abnormalities of intestinal integrity and function reverted to normal after adequate treatment with iron. It was concluded that nutritional iron deficiency in infants on an exclusively milk diet may lead to a diffuse enteropathy with malabsorption and achlorhydria. Although severe iron deficiency of nutritional origin was seen in 11 patients with dwarfism and hypogonadism studied in Iran, this group did not have abnormalities of intestinal absorption. There were normal dxylose tests, absence of excess fat in the stools, normal absorption tests for iron, negative tests for occult blood, and normal gastrointestinal x-ray studies. Intestinal biopsies performed in six of the group showed normal structure. However histamine-fast achlorhydria occurred in six out of eight of the patients in whom the test was performed. In only two of the six could the test be repeated after 6 weeks and 6 months respectively, when the anemia was cured by iron therapy. In these two gastric secretion had not reverted to normal.7 Achlorhydria has long been noted in patients with iron-deficiency anemia. 4. 12 Whether achlorhydria is the result rather than an etiologic factor in iron-deficiency anemia is debatable, although most workers believe it is a result. 1 Chronic iron lack has been known since 1893 2 to be related to dysphagia. This can be cured by iron therapy and dilatation of the esophagus, which may contain webs or strictures. Known in this country as the Plummer-Vinson syndrome,17 it has been termed sideropenic dysphagia in Sweden - probably a better term.18 Vitamin deficiencies from faulty intake are well known to produce gastrointestinal disorders. Thus niacin deficiency is associated with diarrhea in pellagra. Cheilosis and changes in the tongue occur with deficiencies of riboflavin and other B vitamins. Folic acid and vitamin B'2 deficiencies are related to tropical sprue, since treatment with these vitamins is usually quite beneficial (see p. 1367). Although intestinal parasites are a major cause of illness, their relationship to gastrointestinal disease might be considered to be one of harmless guest or resident in many instances. However there are, of course, many parasites of which this is not the case. Giardia lamblia may cause malabsorption and steatorrhea. Ancylostoma duodenale and Necator americanus both cause chronic gastrointestinal bleeding with anemia. If this is prolonged from childhood years, dwarfism, hepatosple-
1400
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A.
HALSTED
nomegaly, and hypogonadism may result. The first example of this was reported in 1910.1:1 (The endocrine abnormalities might actually be caused by zinc deficiency because red blood cells contain considerable zinc. Animals with experimental zinc deficiency have growth failure and hypogonadism.) Finally Chagas' disease (Trypanosoma cruzi, South American trypanosomiasis) may cause megacolon or megaesophagus from damage to Auerbach's plexus.
CONDITIONED MALNUTRITION IN GASTROINTESTINAL DISEASE Most of the significant instances of malnutrition secondary to, or conditioned by, gastrointestinal abnormalities have been considered in the articles in this volume on Malabsorption, Disaccharidase Deficiency, and Tropical Sprue. The article on Inflammatory Disease of the Bowel makes mention of the nutritional effects of regional enteritis, where steatorrhea and malabsorption of vitamin BI2 may occur. Likewise in granulomatous colitis, which involves the ileum, vitamin Bl2 deficiency may result, since this is the site of absorption of that vitamin. Ulcerative colitis is usually associated with malnutrition, although not because malabsorption occurs, the colon being an organ of excretion. Fever, toxicity, anorexia, and loss of blood and nitrogen from colonic exudate may all combine to lead to severe malnutrition in chronic ulcerative colitis. Diseases of the stomach which lead to specific types of malnutrition should be considered. In 1957 Citrin, Sterling, and Halsted:1 described protein loss from the stomach in a patient with Menetrier's disease who had severe hypoproteinemia. Studies with radioactive iodinated serum albumin (RI SA) demonstrated that a large amount of radioactivity was excreted into the stomach and that there was a much reduced protein pool. This led to further studies by Gordonl; and by many others resulting in the concept of protein-losing enteropathy.11 The nutritional effects of subtotal and of total gastrectomy have been analyzed.H,lo Significantly, it has been demonstrated that gastrectomy results in steatorrhea and weight loss in a large proportion of patients. After total gastrectomy these occur in practically all cases. The mechanism of steatorrhea is not clear. However, poor mixing with bile and pancreatic juice from loss of the reservoir function of the stomach, and perhaps (in the case of subtotal gastrectomy) deleterious effects of an abnormal bacterial flora residing in the blind loop of duodenum which is produced in the Billroth 11 anastamosis,:; are important factors. The cause of the weight loss is chiefly a reduction in caloric intake due to the small or absent stomach remnant, with early satiety and discomfort when normal-sized meals are taken. Iron deficiency of mild degree is the rule after both subtotal and total gastrectomy. The mechanism of this is not clear. Depletion of iron stores by chronic blood loss from the lesion for which the operation was performed may be a significant factor. Achlorhydria resulting from the operation may be another; reduction of food iron to the absorbable divalent ferrous form takes place optimally in an acid medium. Finally, rapid
GASTROINTESTINAL DISEASE AND CLINICAL NUTRITION
1401
passage through the upper bowel must be an important additonal factor, because iron is normally absorbed in the duodenum. Treatment of steatorrhea which follows gastrectomy is difficult and unsatisfactory. Frequent small feedings, up to 8 or 10 per day, may help. U se of antibiotics to change the abnormal bacterial flora in the duodenal loop has been shown to lessen steatorrhea." Treatment of iron deficiency may be most effective when a liquid iron preparation is given in a large dose at bedtime while the patient is recumbent. This may allow more time for the iron to be in contact with absorbing surfaces and to obviate the necessity of digesting coated iron tablets. It was long believed that intrinsic factor was secreted in the duodenum as well as the stomach because hog intestine had been shown to have intrinsic factor properties of facilitating absorption of vitamin B 12 . However, absorption of radioactive vitamin B12 was shown not to occur at all after total gastrectomy; this demonstrated that intrinsic factor was limited to the stomach in man. 9 • 16 Further studies by Swendseid et al. 15 demonstrated that the liver contained on the average about 1 mg. of vitamin B 12 . Because the dc:.ily requirement of this vitamin is between 0.5 and 1.0 JLg., this would provide a storehouse sufficient to last 3 to 6 years after absorption ceases, as it does following total gastectomy. It is generally agreed that all patients surviving a total gastrectomy long enough for the liver stores to be used up will develop megaloblastic anemia, indistinguishable from Addison's pernicious anemia, unless prophylactic (replacement) therapy is instituted. Both clinical observations and theoretical considerations substantiate this fact. Theoretically, vitamin BI2 ought to be absorbed normally after subtotal gastrectomy because the proximal end of the stomach is a rich source of intrinsic factor secretion. However, assays of vitamin BI2 in the serum of patients who have had subtotal gastrectomy often show a deceasing concentration as time goes on, indicating that deficiency with megaloblastic anemia may ultimately occur unless replacement therapy is instituted. Clinically, however, this is quite rare. As a result of these studies of the relationship of gastrectomy to vitamin BI2 deficiency, all patients who have had a total gastrectomy should receive an intramuscular injection of 50 JLg. of vitamin BI2 once a month to prevent the development of megaloblastic anemia. This is not recommended for the patient with a subtotal gastrectomy unless periodic blood study reveals an increasing anemia. Then a bone marrow examination is indicated. Assay of serum for vitamin B 12 , if the test is available, should be done, as well as a Schilling test for vitamin BI2 absorption. If these examinations indicate vitamin BI2 deficiency, treatment should be instituted.
SUMMARY The relationships of gastrointestinal disease and nutrition are discussed. An attempt has been made to define and delineate the field of clinical nutrition. Examples of the effect of primary or dietary malnutrition on gastrointestinal structure and function are given.
1402
lAMES
A.
HALSTED
The mechanisms of examples of conditioned malnutrition secondary to gastrointestinal dysfunction in certain pathologic states are discussed. Treatment is discussed briefly where pertinent.
REFERENCES 1. Badenoch, J., Evans, J. R, and Richards, W. C. D.: The stomach in hypochromic anaemia. Brit. J. Haemat., 3:175-185,1957. 2. Blankenstein, P.: Dysphagia hysterica. Dissertation, University of Bonn, 1893. 3. Citrin, Y, Sterling, K., and Halsted, J. A.: The mechanism of hypoproteinemia associated with giant hypertrophy of the gastric mucosa. New Eng. J. Med., 257:906-912,1957. 4. Davidson, W. M. B., and Markson, J. L.: Gastric mucosa in iron deficiency anemia. Lancet, 2:639, 1955. 5. Goldstein, F., Wirts, C. W., and Kramer, S.: The relationship of afferent limb stasis and bacterial flora to the production of postgastrectomy steatorrhea. Gastroenterology, 40:47-55,1961. 6. Gordon, R S., Jr.: Exudative enteropathy. Abnormal permeability of the gastrointestinal tract demonstrable with labeled polyvinylpyrrolidone. Lancet, 1 :325, 1959. 7. Halsted, J. A., Prasad, A. S., and Nadimi, M.: Gastrointestinal function in iron-deficiency anemia. Arch. Int. Med. 116:253-256, 1965. 8. Halsted, J. A., Briggs, J. D., and Gasster, M.: Nutritional problems after total gastrectomy. New York State J. Med., 57:223-230,1957. 9. Halsted, J. A., Gasster, M., and DreniCk, E. J.: Absorption of radioactive vitamin B" after total gastrectomy: Relation to macrocytic anemia and to the site of origin of Castle's intrinsic factor. New Eng. J. Med., 251 :161-168,1954. 10. Hastings, N., Halsted, J. A., Woodward, K R., Gasster, M., and Hiscock, K A.: Subtotal gastric resection for peptic ulcer. A.M.A. Arch. Surg., 76:74-80, 1958. 11. Jarnum, S.: Protein-Losing Gastroenteropathy. Philadelphia, F. A. Davis Co., 1963. 12. Lees, F., and Rosenthal, F. D.: Gastric mucosal lesions before and after treatment in iron deficiency anemia. Quart. J. Med., 27:19,1958. 13. Lemann, I. I.: A study of the type of' infantilism in hookworm disease. Arch. Int. Med., 6:139-146,1910. 14. Naiman, J. L., Oski, F. A., Diamond, L. K., Vawter, G. F., and Schwachman, H.: The gastrointestinal effects of iron-deficiency anemia. Pediatrics, 33:83-99, 1964. 15. Swendseid, M. K, Hvolball, K, Schick, G., and Halsted, J. A.: The vitamin B12 content of human liver and its nutritional significance. Blood, 12:24-28, 1957. 16. Swendseid, M. K, Halsted, J. A., Libby R L.: Excretion of Co""-labeled vitamin Bl2 after total gastrectomy. Proc. Soc. Exp. BioI. Med., 83:226-228,1953. 17. Vinson, P. P.: Hysterical dysphagia. Minn. Med., 5:107-108,1922. 18. Waldenstrom, J., and Kjellberg, S. R.: Roentgenological diagnosis of sideropenic dysphagia (Plummer-Vinson's syndrome). Acta radiol., 20:618-638,1939. 19. Zubirim, S.: Nutritional aspects of gastrointestinal disease. Amer. J. Digest. Dis., 6:336350, 1961. Veterans Administration Hospital 50 Irving Street, N.W. Washington, D.C. 20422
The purpose of this article is to focus attention on the relationship of gastrointestinal disease to nutrition. Clinical nutrition as an entity is a neglected area in medical thinking, medical education, and research, even though many aspects of medicine and clinical research do, in fact, involve nutrition. Malnutrition may arise from an inadequate or insufficient diet, in which case it can be termed primary. It may also arise from disordered gastrointestinal function. In this instance the term "conditioned malnutrition" seems an appropriate one. Conversely, a faulty diet may lead to lesions of the gastrointestinal tract or to disordered function. Although it will not be possible to document all instances either of faulty intake of nutrients leading to gastrointestinal disorder, or of malnutrition stemming from gastrointestinal disease, outstanding examples of each will be cited in order to call attention to the importance of clinical nutrition in gastroenterology. Both gastroenterology and clinical nutrition are broad headings, neither being easy to define with entire satisfaction. Therefore it seems worthwhile to attempt definitions which are at least plausible and to discuss some of the close relationships of nutrition and gastrointestinal disease. It may be obvious that essentially all aspects of biology and medicine are intimately related to nutrition at one level or another. However, a certain area can be delineated, called clinical nutrition. Such delineation as it is proposed to make will not be agreed upon by everyone concerned with nutrition and it is undoubtedly arbitrary. Nevertheless it may be useful as a means of defining a clinical area if not a true scientific discipline. Thus clinical nutrition may be defined as the area of human disease states or malnutrition brought about by (1) faulty intake of nutrients, or factors which cause their unavailability for absorption; (2) faulty digestion, absorption, or excretion of nutrients; or (3) faulty metabolism of nutrients. "'Associate Chief of Staff for Research and Education, Veterans Administration Hospital; Professor of International Health, Department of Epidemiology and Environmental Health, George Washington University School of Medicine, Washington, D.C.
Medical Clinics of North America- Vo!. 52, No. 6, November, 1968
1397
1398
JAMES
A.
HALSTED
The first criterion in this definition of clinical nutrition is more the concern of the dietitian, the agriculturalist, the Public Health officer, the health educator, and the psychologist than it is of the gastroenterologist. Nevertheless, primary dietary defects may cause gastrointestinal disorders, examples of which will be cited. The third criterion, faulty metabolism of nutrients, is generally beyond the realm wherein gastrointestinal disease is involved in nutrition. It falls chiefly in the province of the biochemist, the specialist in metabolism or diabetes, the endocrinologist, and often the hematologist. In discussing the relationship of gastroenterology to clinical nutrition we must be concerned chiefly with the second of the three identified criteria, namely abnormalities of digestion, absorption, or excretion of nutrients. However, the relationships between nutrition, metabolic and hormonal processes, and gastroenterology are close. The more that is understood the more blurred become the lines demarcating disciplines and the more important it is for collaboration to take place between workers in different areas of scientific research, especially between gastroenterologists and those interested in clinical nutrition. It is unnecessary to belabor a definition of gastroenterology. It consists of the physiology, pathology, and clinical aspects of the tubular gastrointestinal tract and of the solid organs - the pancreas and liver. Abnormalities which lead to faulty digestion, absorption, or excretion usually lead to malnutrition. This is why it is reasonable to define malnutrition secondary to gastrointestinal disease as "conditioned malnutrition." Thus it becomes a major component of the area of medicine called clinical nutrition. Liver disease is, of course, closely involved with malnutrition. Through its involvement with metabolic processes it may be the cause of malnutrition, and, conversely, malnutrition may be one causative factor in cirrhosis. However, liver disease will not be considered in this article since it is well covered elsewhere in this volume. Disorders of the pancreas often lead to conditioned malnutrition through interference with aspects of the digestive process. These also are considered elsewhere so will not be dealt with further.
GASTROINTESTlNAL DISORDERS CAUSED BY FAULTY DIET Zubira.n 19 has called attention to a number of gastrointestinal abnormalities stemming from primary malnutrition in Mexico. Most of these examples are seen in poverty areas in underdeveloped countries where crowding, a high incidence of infectious diseases, impoverished education, and illiteracy are the rule. The syndrome of protein-calorie malnutrition - kwashiorkor or protein deficiency -leads to a fatty liver, pancreatic dysfunction, and often intestinal malabsorption. Diarrhea is common. A thorough study by Zubiri'm of 92 patients with primary malnutrition revealed tongue abnormalities, diarrhea, abdominal pain, nausea, vomiting, and distention in from 29 to 86 per cent. Blood and mucus were found in 41 per cent of the patients with diarrhea, although parasites and intestinal pathogens were not present. In 28 per cent stea-
GASTROINTESTINAL DISEASE AND CLINICAL NUTRITION
1399
torrhea and creatorrhea occurred. Intestinal biopsies showed findings ranging from normal to partial villous atrophy. d-Xylose tests were frequently abnormal. Radiologic study often revealed dilated loops with segmentation of barium and the "moulage sign." Not all instances of faulty diet leading to gastrointestinal disease occur in the underdeveloped areas of the world. Thus N aiman et al. 14 studied the effects of a milk diet on 14 infants in Boston. This produced severe iron-deficiency anemia and was associated with achlorhydria in 4 of 8 patients, impaired d-xylose absorption in 6 of the 14, low serum carotene in 5 of the 14, and a flat vitamin A tolerance curve in 10. Stool fat excretion was increased in 4 of the group, and positive tests for occult blood occurred in 4 patients. Intestinal biopsy showed abnormalities in 7 of the 11 patients in which it was performed. Most of these abnormalities of intestinal integrity and function reverted to normal after adequate treatment with iron. It was concluded that nutritional iron deficiency in infants on an exclusively milk diet may lead to a diffuse enteropathy with malabsorption and achlorhydria. Although severe iron deficiency of nutritional origin was seen in 11 patients with dwarfism and hypogonadism studied in Iran, this group did not have abnormalities of intestinal absorption. There were normal dxylose tests, absence of excess fat in the stools, normal absorption tests for iron, negative tests for occult blood, and normal gastrointestinal x-ray studies. Intestinal biopsies performed in six of the group showed normal structure. However histamine-fast achlorhydria occurred in six out of eight of the patients in whom the test was performed. In only two of the six could the test be repeated after 6 weeks and 6 months respectively, when the anemia was cured by iron therapy. In these two gastric secretion had not reverted to normal.7 Achlorhydria has long been noted in patients with iron-deficiency anemia. 4. 12 Whether achlorhydria is the result rather than an etiologic factor in iron-deficiency anemia is debatable, although most workers believe it is a result. 1 Chronic iron lack has been known since 1893 2 to be related to dysphagia. This can be cured by iron therapy and dilatation of the esophagus, which may contain webs or strictures. Known in this country as the Plummer-Vinson syndrome,17 it has been termed sideropenic dysphagia in Sweden - probably a better term.18 Vitamin deficiencies from faulty intake are well known to produce gastrointestinal disorders. Thus niacin deficiency is associated with diarrhea in pellagra. Cheilosis and changes in the tongue occur with deficiencies of riboflavin and other B vitamins. Folic acid and vitamin B'2 deficiencies are related to tropical sprue, since treatment with these vitamins is usually quite beneficial (see p. 1367). Although intestinal parasites are a major cause of illness, their relationship to gastrointestinal disease might be considered to be one of harmless guest or resident in many instances. However there are, of course, many parasites of which this is not the case. Giardia lamblia may cause malabsorption and steatorrhea. Ancylostoma duodenale and Necator americanus both cause chronic gastrointestinal bleeding with anemia. If this is prolonged from childhood years, dwarfism, hepatosple-
1400
JAMES
A.
HALSTED
nomegaly, and hypogonadism may result. The first example of this was reported in 1910.1:1 (The endocrine abnormalities might actually be caused by zinc deficiency because red blood cells contain considerable zinc. Animals with experimental zinc deficiency have growth failure and hypogonadism.) Finally Chagas' disease (Trypanosoma cruzi, South American trypanosomiasis) may cause megacolon or megaesophagus from damage to Auerbach's plexus.
CONDITIONED MALNUTRITION IN GASTROINTESTINAL DISEASE Most of the significant instances of malnutrition secondary to, or conditioned by, gastrointestinal abnormalities have been considered in the articles in this volume on Malabsorption, Disaccharidase Deficiency, and Tropical Sprue. The article on Inflammatory Disease of the Bowel makes mention of the nutritional effects of regional enteritis, where steatorrhea and malabsorption of vitamin BI2 may occur. Likewise in granulomatous colitis, which involves the ileum, vitamin Bl2 deficiency may result, since this is the site of absorption of that vitamin. Ulcerative colitis is usually associated with malnutrition, although not because malabsorption occurs, the colon being an organ of excretion. Fever, toxicity, anorexia, and loss of blood and nitrogen from colonic exudate may all combine to lead to severe malnutrition in chronic ulcerative colitis. Diseases of the stomach which lead to specific types of malnutrition should be considered. In 1957 Citrin, Sterling, and Halsted:1 described protein loss from the stomach in a patient with Menetrier's disease who had severe hypoproteinemia. Studies with radioactive iodinated serum albumin (RI SA) demonstrated that a large amount of radioactivity was excreted into the stomach and that there was a much reduced protein pool. This led to further studies by Gordonl; and by many others resulting in the concept of protein-losing enteropathy.11 The nutritional effects of subtotal and of total gastrectomy have been analyzed.H,lo Significantly, it has been demonstrated that gastrectomy results in steatorrhea and weight loss in a large proportion of patients. After total gastrectomy these occur in practically all cases. The mechanism of steatorrhea is not clear. However, poor mixing with bile and pancreatic juice from loss of the reservoir function of the stomach, and perhaps (in the case of subtotal gastrectomy) deleterious effects of an abnormal bacterial flora residing in the blind loop of duodenum which is produced in the Billroth 11 anastamosis,:; are important factors. The cause of the weight loss is chiefly a reduction in caloric intake due to the small or absent stomach remnant, with early satiety and discomfort when normal-sized meals are taken. Iron deficiency of mild degree is the rule after both subtotal and total gastrectomy. The mechanism of this is not clear. Depletion of iron stores by chronic blood loss from the lesion for which the operation was performed may be a significant factor. Achlorhydria resulting from the operation may be another; reduction of food iron to the absorbable divalent ferrous form takes place optimally in an acid medium. Finally, rapid
GASTROINTESTINAL DISEASE AND CLINICAL NUTRITION
1401
passage through the upper bowel must be an important additonal factor, because iron is normally absorbed in the duodenum. Treatment of steatorrhea which follows gastrectomy is difficult and unsatisfactory. Frequent small feedings, up to 8 or 10 per day, may help. U se of antibiotics to change the abnormal bacterial flora in the duodenal loop has been shown to lessen steatorrhea." Treatment of iron deficiency may be most effective when a liquid iron preparation is given in a large dose at bedtime while the patient is recumbent. This may allow more time for the iron to be in contact with absorbing surfaces and to obviate the necessity of digesting coated iron tablets. It was long believed that intrinsic factor was secreted in the duodenum as well as the stomach because hog intestine had been shown to have intrinsic factor properties of facilitating absorption of vitamin B 12 . However, absorption of radioactive vitamin B12 was shown not to occur at all after total gastrectomy; this demonstrated that intrinsic factor was limited to the stomach in man. 9 • 16 Further studies by Swendseid et al. 15 demonstrated that the liver contained on the average about 1 mg. of vitamin B 12 . Because the dc:.ily requirement of this vitamin is between 0.5 and 1.0 JLg., this would provide a storehouse sufficient to last 3 to 6 years after absorption ceases, as it does following total gastectomy. It is generally agreed that all patients surviving a total gastrectomy long enough for the liver stores to be used up will develop megaloblastic anemia, indistinguishable from Addison's pernicious anemia, unless prophylactic (replacement) therapy is instituted. Both clinical observations and theoretical considerations substantiate this fact. Theoretically, vitamin BI2 ought to be absorbed normally after subtotal gastrectomy because the proximal end of the stomach is a rich source of intrinsic factor secretion. However, assays of vitamin BI2 in the serum of patients who have had subtotal gastrectomy often show a deceasing concentration as time goes on, indicating that deficiency with megaloblastic anemia may ultimately occur unless replacement therapy is instituted. Clinically, however, this is quite rare. As a result of these studies of the relationship of gastrectomy to vitamin BI2 deficiency, all patients who have had a total gastrectomy should receive an intramuscular injection of 50 JLg. of vitamin BI2 once a month to prevent the development of megaloblastic anemia. This is not recommended for the patient with a subtotal gastrectomy unless periodic blood study reveals an increasing anemia. Then a bone marrow examination is indicated. Assay of serum for vitamin B 12 , if the test is available, should be done, as well as a Schilling test for vitamin BI2 absorption. If these examinations indicate vitamin BI2 deficiency, treatment should be instituted.
SUMMARY The relationships of gastrointestinal disease and nutrition are discussed. An attempt has been made to define and delineate the field of clinical nutrition. Examples of the effect of primary or dietary malnutrition on gastrointestinal structure and function are given.
1402
lAMES
A.
HALSTED
The mechanisms of examples of conditioned malnutrition secondary to gastrointestinal dysfunction in certain pathologic states are discussed. Treatment is discussed briefly where pertinent.
REFERENCES 1. Badenoch, J., Evans, J. R, and Richards, W. C. D.: The stomach in hypochromic anaemia. Brit. J. Haemat., 3:175-185,1957. 2. Blankenstein, P.: Dysphagia hysterica. Dissertation, University of Bonn, 1893. 3. Citrin, Y, Sterling, K., and Halsted, J. A.: The mechanism of hypoproteinemia associated with giant hypertrophy of the gastric mucosa. New Eng. J. Med., 257:906-912,1957. 4. Davidson, W. M. B., and Markson, J. L.: Gastric mucosa in iron deficiency anemia. Lancet, 2:639, 1955. 5. Goldstein, F., Wirts, C. W., and Kramer, S.: The relationship of afferent limb stasis and bacterial flora to the production of postgastrectomy steatorrhea. Gastroenterology, 40:47-55,1961. 6. Gordon, R S., Jr.: Exudative enteropathy. Abnormal permeability of the gastrointestinal tract demonstrable with labeled polyvinylpyrrolidone. Lancet, 1 :325, 1959. 7. Halsted, J. A., Prasad, A. S., and Nadimi, M.: Gastrointestinal function in iron-deficiency anemia. Arch. Int. Med. 116:253-256, 1965. 8. Halsted, J. A., Briggs, J. D., and Gasster, M.: Nutritional problems after total gastrectomy. New York State J. Med., 57:223-230,1957. 9. Halsted, J. A., Gasster, M., and DreniCk, E. J.: Absorption of radioactive vitamin B" after total gastrectomy: Relation to macrocytic anemia and to the site of origin of Castle's intrinsic factor. New Eng. J. Med., 251 :161-168,1954. 10. Hastings, N., Halsted, J. A., Woodward, K R., Gasster, M., and Hiscock, K A.: Subtotal gastric resection for peptic ulcer. A.M.A. Arch. Surg., 76:74-80, 1958. 11. Jarnum, S.: Protein-Losing Gastroenteropathy. Philadelphia, F. A. Davis Co., 1963. 12. Lees, F., and Rosenthal, F. D.: Gastric mucosal lesions before and after treatment in iron deficiency anemia. Quart. J. Med., 27:19,1958. 13. Lemann, I. I.: A study of the type of' infantilism in hookworm disease. Arch. Int. Med., 6:139-146,1910. 14. Naiman, J. L., Oski, F. A., Diamond, L. K., Vawter, G. F., and Schwachman, H.: The gastrointestinal effects of iron-deficiency anemia. Pediatrics, 33:83-99, 1964. 15. Swendseid, M. K, Hvolball, K, Schick, G., and Halsted, J. A.: The vitamin B12 content of human liver and its nutritional significance. Blood, 12:24-28, 1957. 16. Swendseid, M. K, Halsted, J. A., Libby R L.: Excretion of Co""-labeled vitamin Bl2 after total gastrectomy. Proc. Soc. Exp. BioI. Med., 83:226-228,1953. 17. Vinson, P. P.: Hysterical dysphagia. Minn. Med., 5:107-108,1922. 18. Waldenstrom, J., and Kjellberg, S. R.: Roentgenological diagnosis of sideropenic dysphagia (Plummer-Vinson's syndrome). Acta radiol., 20:618-638,1939. 19. Zubirim, S.: Nutritional aspects of gastrointestinal disease. Amer. J. Digest. Dis., 6:336350, 1961. Veterans Administration Hospital 50 Irving Street, N.W. Washington, D.C. 20422