MALABSORPTION IN COELIAC SPRUE

Transcription

1 MALABSORPTION IN COELIAC SPRUE

2 MALABSORPTION IN COELIAC SPRUE O. J. J. CLUYSENAER M.D. and J. H. M. VAN TONGEREN M.D. Department of Medicine, Division of Gastroenterology, Sint Radboud Hospital, University of Nijmegen, The Netherlands. with a foreword by C. C. BOOTH M.D., F.R.C.P. Professor of Medicine, Royal Postgraduate Medical School, London MARTINUS NIJHOFF MEDICAL DIVISION - THE HAGUE

3 ISBN-13: e-isbn-13: DOl: / by Martinus Nijhoff, P.O. Box 442, The Hague, The Netherlands. All rights reserved, including the right to translate or to reproduce this book or parts thereof in any form. Cover illustration from Andreas Vesalius (De humani corporis fabrica V, 1543).

4 FOREWORD For at least three centuries, Holland has been at the centre of research on intestinal malabsorption. In the 17th and 18th centuries, early descriptions of coeliac disease and tropical sprue were published by physicians trained in Holland, and it was in 1950 that Dicke published his painstaking and vital observations that coeliac disease in children was caused by the ingestion of wheat flour. Subsequent careful work with van de Kamer and Weijers showed that the harmful agent was gluten. Since these discoveries were made, research in intestinal malabsorption, particularly in the adult, has continued in several centres in Holland. At Nijmegen, for example, dr. Cluysenaer, dr. van Tongeren and their associates have been involved in long-term studies of patients with intestinal disease for the past fifteen years. In this book they describe their experience of the investigation and treatment of fifty patients with the adult form of coeliac disease. Their monograph gives an account of the history, definition and incidence of the disorder, and then goes on to undertake a critical review of the pathogenesis of the coeliac lesion. Before embarking on the different patterns of malabsorption seen in adult coeliac disease, the authors describe the normal small intestine, its morphology and function. Coeliac disease is associated with a wide range of nutritional deficiencies and the authors have therefore concentrated not only on the more obvious intestinal lesion, but also on how vitamins and minerals are absorbed and on how deficiencies may arise in clinical practice. Their clinical experience enables them to define the widely different modes of presentation of the disease. They also describe the important association of coeliac disease with other disorders such as dermatitis herpetiformis. Treatment of malabsorption in the adult may be particularly difficult in those patients who do not respond to the withdrawal of gluten from their diet, a situation recognised by these authors who wisely separate this group of disorders from coeliac disease. The understanding of human disease, from which successful treatment must stem, is based on observation and experiment. This monograph is an admirable example of careful clinical observation coupled with a detailed review of the experimental work upon which modern intestinal physiology

5 and pathology are based. It is a further addition to the literature on intestinal malabsorption to which Dutch physicians have contributed so much. c. C. Booth VI

6 ACKNOWLEDGMENTS We gratefully acknowledge all persons who contributed to the realization of this monograph. The assistance of the nursing staff of the gastrointestinal unit (head: miss A. M. Th. W. van der Belt; previously miss J. M. T. Dekkers), and of the out-patients' department (heads: miss Th. Th. M. Hoogenbosch, miss L. M. J. Schreppers and mr. G. C. Th. Delisse) is greatly appreciated. A great deal of work was done by the technicians of the laboratories for Clinical Chemistry, Haematology, Isotopic Investigations, Amino acids, Histochemistry and Bacteriology, for which the authors feel indebted. The dieticians miss H. A. van der Heijden and miss H. J. W. Lamers have provided much help. We would like to express our thanks for the assistance of our colleagues from the departments of Pathology (Prof. dr. P. H. M. Schillings, drs. M. J. J. Koene-Bogtmans, dr. U. J. G. van Haelst, drs. K. J. M. Assmann), Radiology (dr. G. Rosenbusch) and Dermatology (dr. W. J. B. M. van de Staak, Prof. dr. J. W. H. Mali). Special thanks are due to ir. H. J. J. van Lier and drs. Ph. van Elteren for help with the statistical evaluation. We are grateful to the authors and publishers who gave us permission to reproduce several figures. We personally admire the splendid illustrations by mr. H. M. Berris, and the photographs by mr. A. Th. A. Reynen and mr. Th. C. van Hout. Special thanks are due to mrs. B. J. R. Grootendorst-Lieve for her cheerful patience in typing the manuscript. The text was translated by mr. Th. van Winsen, for which the Jan Dekker and dr. Ludgardine Bouwman Foundations provided financial support. Dr. Adrian and mrs. June Roberts helped with grammatical corrections. We greatly appreciated the help or advice of dr. J. T. M. Burghouts, miss W. C. A. M. Buys, drs. F. H. M. Corstens, dr. J. F. M. Fennis, dr. J. C. M. Hafkenscheid, dr. P. H. K. Jap, dr. R. A. P. Koene, dr. C. B. H. W. Lamers, dr. E. de Nobel, dr. J. M. F. Trijbels, dr. J. M. C. Wessels and dr. S. H. Yap. This book is dedicated to all persons who have put accuracy, empathy and enthousiasm in their contribution. VII

7 CONTENTS CHAPTER 1. INTRODUCTION 1.1 History 1.2 Terminology 1.3 Definition of coeliac sprue 1.4 Incidence CHAPTER 2. PATHOGENESIS OF COELIAC SPRUE Introduction l3 2.2 Causative factor Pathogenesis Peptidase deficiency theory (15); Immunological theory (15); Other theories (17). CHAPTER 3. MORPHOLOGY OF THE SMALL INTESTINE UNDER NORMAL CONDITIONS AND IN COELIAC SPRUE General introduction The normal small intestine Macroscopic anatomy (18); Stereomicroscopic aspect of the mucosa (19); Microscopic morphology of the mucosa (20); Ultrastructure of the enterocyte (21). 3.3 The small intestine in coeliac sprue Macroscopic anatomy (23); Stereo microscopic aspect of the mucosa (23); Microscopic morphology of the mucosa (25); Ultrastructure of the enterocyte (25). 3.4 Morphogenesis of the coeliac mucosa Morphometry of the mucosa 28 CHAPTER PHYSIOLOGY OF THE SMALL INTESTINE General introduction Motility Innervation 4.4 Circulation IX

8 4.5 Lymphatic system Digestive secretions Introduction (41); Gastric secretion (41); Pancreatic secretion (42); Bile secretion (43). 4.7 Intestinal hormones Intestinal mucus Exfoliation of enterocytes Enteric plasma protein loss Intestinal flora 50 CHAPTER 5. INTESTINAL DIGESTION AND ABSORPTION General introduction Surface (53); Mucosal contact time (53); Digestion (54); Translocation (54); Unstirred layer (55); Absorption (56); Secretion (57). 5.2 Water and electrolytes Carbohydrate Fat Introduction (63); Triglycerides (64); Cholesterol (67); Phospholipids (67); Fat-soluble vitamins (68) Introduction (68); Vitamin A (68); Vitamin D (69); Vitamin E (69); Vitamin K (69). 5.5 Protein Calcium Magnesium Haematopoietic factors Iron (77); Vitamin B12 (80); Folates (81). 5.9 Water-soluble vitamins Vitamin C (83); Thiamine (83); Riboflavin (84); Niacin (84); Vitamin B. (84); Pantothenic acid (85). CHAPTER 6. PATHOPHYSIOLOGY OF COELIAC SPRUE Introduction Composition of the group of patients studied Motility Innervation Circulation Lymphatic system Introduction (93); Protein leakage and lymphocyte count (93); Influence of restriction of LCT fat on protein leakage (93); Abnormalities of the mesenteric lymph nodes (94); Comment (94). x

9 6.6 Digestive secretions Introduction (95); Gastric secretion (96); Pancreatic secretion (96); Comment (96). 6.7 Intestinal hormones Intestinal mucus Exfoliation of enterocytes Enteric plasma protein loss Introduction (100); Determination of enteric protein loss (100); Comment (102) Intestinal flora Introduction (103); Culture of intestinal fluid (103); 'Breath' test with 14C-glycocholic acid (104); Urinary indican excretion (104); Effect of the glutenfree diet (104); Comment (107); Conclusions (109). CHAPTER 7. MALABSORPTION IN COELIAC SPRUE 7.1 Introduction 7.2 Water and electrolytes 7.3 Carbohydrate Introduction (113); Microscopic examination of faeces for starch (113); Glucose tolerance test (113); Lactose tolerance test (113); Lactase activity of the jejunal mucosa (115); Tolerance tests with other disaccharides (115); D-xylose test (115); Effect of the gluten-free diet (116); Comment (116); Conclusions (121). 7.4 Fat Introduction (121); Fat absorption coefficient (122); Serum cholesterol concentration (124); Serum vitamin A concentration (124); Vitamin A tolerance test (125); Serum vitamin E concentration (125); Thrombotest (126); Effect of the gluten-free diet (126); Comment (132); Conclusions (135). 7.5 Protein Introduction (136); Serum albumin concentration (137); Enteric protein loss (137); Albumin synthesis (138); Effect of the gluten-free diet (139); Comment (139); Conclusions (143). 7.6 Calcium Introduction (144); Plasma calcium concentration (145); Calcium absorption (147); Alkaline phosphatase activity (147); Hydroxyproline excretion (149); Histological examination of bone tissue (149); Two-hour phosphate clearance (149); Radiographs of the hand skeleton (149); Amino-aciduria study (149); Effect of the gluten-free diet (149); Comment (152); Conclusions (155) IX

10 7.7 Magnesium Introduction (156); Serum magnesium concentration (156); Effect of the gluten-free diet (157); Comment (157); Conclusions (159). 7.8 Haematopoietic factors Iron (160) Introduction (160); Haemoglobin concentration (161); Bone marrow study (162); Serum iron concentration (162); Iron absorption (163); Effect of the gluten-free diet (163); Comment (163); Conclusions (165) Vitamin B12 (166) Introduction (166); Serum vitamin B12 concentration (166); Vitamin B12 absorption (168); Effect of the gluten-free diet (168); Comment (169); Conclusions (171) Folates (171) Introduction (171); Serum folate concentration (172); Effect of the gluten-free diet (172); Comment (172); Conclusions (175). 7.9 Water-soluble vitamins Introduction (176); Vitamin C (176); Thiamine (177); Riboflavin (177); Niacin (177); Vitamin B6 (177); Pantothenic acid (77). 176 CHAPTER 8. CLINICAL FEATURES 8.1 Introduction 8.2 Incidence of the various symptoms 8.3 General complaints and symptoms 8.4 Gastrointestinal tract 8.5 Haematopoiesis and blood coagulation 8.6 Musculoskeletal system 8.7 Skin, hair and nails 8.8 Reproductive functions 8.9 Nervous system 8.10 Psyche CHAPTER 9. CLINICAL COURSE AND RESPONSE TO TREATMENT 9.1 Spontaneous course 9.2 Treatment by the gluten-free diet Nature of the diet (190); Adherence to the diet (191); Effect on clinical symptoms (192); Effect on biochemical parameters (194); Effect on mucosal morphology (197) XII

11 9.3 Additional measures Further dietary restrictions (199); Replacement therapy (201); Parenteral feeding (202); Administration of glucocorticosteroids (202). 9.4 Complications Introduction (204); Abnormal bacterial flora (204); Other complications (205); Malignant degeneration and malignancies (207). 9.5 Conclusions 209 CHAPTER 10. ASSOCIATION WITH OTHER DISEASES Introduction Dermatitis herpetiformis Personal observations (210); Comment (213) Concomitant diseases Personal observations (216); Comment (216). CHAPTER 11. SPECIAL FORMS OF SPRUE 11.1 Introduction 11.2 Ulcerative duodenojejunoileitis Introduction (219); Personal observations Comment (222) 'Collagenous' sprue Introduction (223); Personal observations Comment (224) Refractory sprue Introduction (226); Personal observations Comment (229). (219); (224); (226); CHAPTER 12. METHODS AND PROCEDURES Biochemical assays Determinations in blood (232); Determinations in urine (233); Absorption tests (234); Other determinations (235) Statistical analysis Calculation of normal values (236); Calculation of significances (237) Biopsy of the small intestine 237 REFERENCES 238 SURVEY OF REFERENCES TO PATIENTS 272 INDEX 274 XIII