Table Of ContentMALABSORPTION 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).
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