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Malabsorption in Coeliac Sprue PDF

290 Pages·1977·13.822 MB·English
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MALABSORPTION IN COELIAC SPRUE 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 - 1977 ISBN-13: 978-90-247-2000-2 e-ISBN-13: 978-94-010-1093-1 DOl: 10.1007/978-94-010-1093-1 © 1977 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). 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 inges tion 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 as sociates 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 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 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 Clin ical Chemistry, Haematology, Isotopic Investigations, Amino acids, Histo chemistry and Bacteriology, for which the authors feel indebted. The dieti cians 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 Bouw man 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 CONTENTS CHAPTER 1. INTRODUCTION 1.1 History 1.2 Terminology 3 1.3 Definition of coeliac sprue 4 1.4 Incidence 8 CHAPTER 2. PATHOGENESIS OF COELIAC SPRUE 13 2.1 Introduction l3 2.2 Causative factor 13 2.3 Pathogenesis 15 2.3.1 Peptidase deficiency theory (15); 2.3.2 Immunological theory (15); 2.3.3 Other theories (17). CHAPTER 3. MORPHOLOGY OF THE SMALL INTESTINE UNDER NORMAL CONDITIONS AND IN COELIAC SPRUE 18 3.1 General introduction 18 3.2 The normal small intestine 18 3.2.1 Macroscopic anatomy (18); 3.2.2 Stereomicroscopic aspect of the mucosa (19); 3.2.3 Microscopic morphology of the mucosa (20); 3.2.4 Ultrastructure of the enterocyte (21). 3.3 The small intestine in coeliac sprue 23 3.3.1 Macroscopic anatomy (23); 3.3.2 Stereo microscopic aspect of the mucosa (23); 3.3.3 Microscopic morphology of the mucosa (25); 3.3.4 Ultrastructure of the enterocyte (25). 3.4 Morphogenesis of the coeliac mucosa 26 3.5 Morphometry of the mucosa 28 CHAPTER 4. PHYSIOLOGY OF THE SMALL INTESTINE 30 4.1 General introduction 30 4.2 Motility 31 4.3 Innervation 33 4.4 Circulation 36 IX 4.5 Lymphatic system 39 4.6 Digestive secretions 41 4.6.1 Introduction (41); 4.6.2 Gastric secretion (41); 4.6.3 Pancreatic secretion (42); 4.6.4 Bile secretion (43). 4.7 Intestinal hormones 44 4.8 Intestinal mucus 47 4.9 Exfoliation of enterocytes 48 4.10 Enteric plasma protein loss 48 4.11 Intestinal flora 50 CHAPTER 5. INTESTINAL DIGESTION AND ABSORPTION 53 5.1 General introduction 53 5.1.1 Surface (53); 5.1.2 Mucosal contact time (53); 5.1.3 Diges- tion (54); 5.1.4 Translocation (54); 5.1.5 Unstirred layer (55); 5.1.6 Absorption (56); 5.1.7 Secretion (57). 5.2 Water and electrolytes 58 5.3 Carbohydrate 61 5.4 Fat 63 5.4.1 Introduction (63); 5.4.2 Triglycerides (64); 5.4.3 Cholest- erol (67); 5.4.4 Phospholipids (67); 5.4.5 Fat-soluble vitamins (68). 5.4.5.1 Introduction (68); 5.4.5.2 Vitamin A (68); 5.4.5.3 Vitamin D (69); 5.4.5.4. Vitamin E (69); 5.4.5.5 Vitamin K (69). 5.5 Protein 70 5.6 Calcium 73 5.7 Magnesium 75 5.8 Haematopoietic factors 77 5.8.1 Iron (77); 5.8.2 Vitamin B12 (80); 5.8.3 Folates (81). 5.9 Water-soluble vitamins 83 5.9.1 Vitamin C (83); 5.9.2 Thiamine (83); 5.9.3 Riboflavin (84); 5.9.4 Niacin (84); 5.9.5 Vitamin B. (84); 5.9.6 Pantothenic acid (85). CHAPTER 6. PATHOPHYSIOLOGY OF COELIAC SPRUE 86 6.0 Introduction 86 6.1 Composition of the group of patients studied 86 6.2 Motility 89 6.3 Innervation 91 6.4 Circulation 92 6.5 Lymphatic system 93 6.5.1 Introduction (93); 6.5.2 Protein leakage and lymphocyte count (93); 6.5.3 Influence of restriction of LCT fat on protein leakage (93); 6.5.4 Abnormalities of the mesenteric lymph nodes (94); 6.5.5 Comment (94). x 6.6 Digestive secretions 95 6.6.1 Introduction (95); 6.6.2 Gastric secretion (96); 6.6.3 Pancreatic secretion (96); 6.6.4 Comment (96). 6.7 Intestinal hormones 97 6.8 Intestinal mucus 99 6.9 Exfoliation of enterocytes 99 6.10 Enteric plasma protein loss 100 6.10.1 Introduction (100); 6.10.2 Determination of enteric protein loss (100); 6.10.3 Comment (102). 6.11 Intestinal flora 103 6.11.1 Introduction (103); 6.11.2 Culture of intestinal fluid (103); 6.11.3 'Breath' test with 14C-glycocholic acid (104); 6.11.4 Urinary indican excretion (104); 6.11.5 Effect of the gluten free diet (104); 6.11.6 Comment (107); 6.11.7 Conclusions (109). CHAPTER 7. MALABSORPTION IN COELIAC SPRUE 110 7.1 Introduction 110 7.2 Water and electrolytes 110 7.3 Carbohydrate 113 7.3.1 Introduction (113); 7.3.2 Microscopic examination of faeces for starch (113); 7.3.3 Glucose tolerance test (113); 7.3.4 Lactose tolerance test (113); 7.3.5 Lactase activity of the jejunal mucosa (115); 7.3.6 Tolerance tests with other dis accharides (115); 7.3.7 D-xylose test (115); 7.3.8 Effect of the gluten-free diet (116); 7.3.9 Comment (116); 7.3.10 Conclusions (121). 7.4 Fat 121 7.4.1 Introduction (121); 7.4.2 Fat absorption coefficient (122); 7.4.3 Serum cholesterol concentration (124); 7.4.4 Serum vitamin A concentration (124); 7.4.5 Vitamin A tolerance test (125); 7.4.6 Serum vitamin E concentration (125); 7.4.7 Thrombotest (126); 7.4.8 Effect of the gluten-free diet (126); 7.4.9 Comment (132); 7.4.10 Conclusions (135). 7.5 Protein 136 7.5.1 Introduction (136); 7.5.2 Serum albumin concentration (137); 7.5.3 Enteric protein loss (137); 7.5.4 Albumin syn thesis (138); 7.5.5 Effect of the gluten-free diet (139); 7.5.6 Comment (139); 7.5.7 Conclusions (143). 7.6 Calcium 144 7.6.1 Introduction (144); 7.6.2 Plasma calcium concentration (145); 7.6.3 Calcium absorption (147); 7.6.4 Alkaline phos phatase activity (147); 7.6.5 Hydroxyproline excretion (149); 7.6.6 Histological examination of bone tissue (149); 7.6.7 Two-hour phosphate clearance (149); 7.6.8 Radiographs of the hand skeleton (149); 7.6.9 Amino-aciduria study (149); 7.6.10 Effect of the gluten-free diet (149); 7.6.11 Comment (152); 7.6.12 Conclusions (155). IX 7.7 Magnesium 156 7.7.1 Introduction (156); 7.7.2 Serum magnesium concentration (156); 7.7.3 Effect of the gluten-free diet (157); 7.7.4 Com- ment (157); 7.7.5 Conclusions (159). 7.8 Haematopoietic factors 160 7.8.1 Iron (160). 7.8.1.1 Introduction (160); 7.8.1.2 Haemoglobin concentration (161); 7.8.1.3 Bone marrow study (162); 7.8.1.4 Serum iron concentration (162); 7.8.1.5 Iron absorption (163); 7.8.1.6 Effect of the gluten-free diet (163); 7.8.1.7 Comment (163); 7.8.1.8 Conclusions (165). 7.8.2 Vitamin B12 (166). 7.8.2.1 Introduction (166); 7.8.2.2 Serum vitamin B12 concentration (166); 7.8.2.3 Vitamin B12 absorption (168); 7.8.2.4 Effect of the gluten-free diet (168); 7.8.2.5 Comment (169); 7.8.2.6 Conclusions (171). 7.8.3 Folates (171). 7.8.3.1 Introduction (171); 7.8.3.2 Serum folate concentration (172); 7.8.3.3 Effect of the gluten-free diet (172); 7.8.3.4 Comment (172); 7.8.3.5 Conclusions (175). 7.9 Water-soluble vitamins 176 7.9.0 Introduction (176); 7.9.1 Vitamin C (176); 7.9.2 Thiamine (177); 7.9.3 Riboflavin (177); 7.9.4 Niacin (177); 7.9.5 Vitamin B6 (177); 7.9.6 Pantothenic acid (77). CHAPTER 8. CLINICAL FEATURES 178 8.1 Introduction 178 8.2 Incidence of the various symptoms 179 8.3 General complaints and symptoms 179 8.4 Gastrointestinal tract 181 8.5 Haematopoiesis and blood coagUlation 183 8.6 Musculoskeletal system 183 8.7 Skin, hair and nails 184 8.8 Reproductive functions 185 8.9 Nervous system 186 8.10 Psyche 186 CHAPTER 9. CLINICAL COURSE AND RESPONSE TO TREATMENT 187 9.1 Spontaneous course 187 9.2 Treatment by the gluten-free diet 190 9.2.1 Nature of the diet (190); 9.2.2 Adherence to the diet (191); 9.2.3 Effect on clinical symptoms (192); 9.2.4 Effect on biochemical parameters (194); 9.2.5 Effect on mucosal morphology (197). XII

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