Ultrastructure of the Small Intestinal Mucosa: Normal and Disease-Related Appearances

170 Pages·1983·13.78 MB·English

by  Margot Shiner FRCP, FRCPath, DCH (auth.)

Margot Shiner
Ultrastructure of
the Small Intestinal
Mucosa
Normal and disease-related appearances
Foreword by Sir Francis Avery Jones
With 165 Figures
Springer-Verlag
Berlin· Heidelberg New York 1983
Margot Shiner FRCP, FRCPath, DCH
Member, Scientific Staff, Medical Research Council,
Clinical Research Centre, Harrow, Middlesex
Hon. Consultant in Gastroenterology,
Central Middlesex Hospital, Park Royal, London
and Northwick Park Hospital, Harrow, Middlesex, UK
ISBN-13: 978-1-4471-1340-9 e-ISBN-13:978-1-4471-1338-6
DOl: 10.1007/978-1-4471-1338-6
Library of Congress Cataloging in Publication Data
Shiner, Margot, 1923-Ultrastructure of the Small Intestinal Mucosa
Bibliography: p. Includes index. 1. Intestine, Small-Diseases. 2. Ultrastructure (Biology).
3. Diagnosis, Electron microscopic. I. Title. [DNLM: 1. Intestinal mucosa - Ultrastructure.
2. Intestine, Small-Ultrastructure. 3. Microscopy, Electron. WI 500 S556s] RC802.9.S48 1982
616.3'482-10333
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© Springer-Verlag Berlin Heidelberg 1983
Softcover reprint of the hardcover 1s t edition 1983
The use of registered names, trademarks etc. in this publication does not imply, even in the
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and regulations and therefore free for general use.
2128/3916543210
To my mother,
husband and children,
and in memory of my father
Foreword
This book represents the culmination of the major aspect of Dr. Margot
Shiner's professional career. It was she who devised the technique of jejunal
biopsy which opened up whole new fields of small intestinal research, including
microbiology, immunology, histochemistry and histopathology, thus greatly
expanding our knowledge of fundamental aspects of absorptive patho
physiology. Later the application of electron microscopy demonstrated the
individual cell with its mechanisms both for absorption and for the production
of so many chemicals such as mucus, enzymes and hormones. Like the vision
from the peak in Darian, it opened up new worlds. The contribution to our
understanding of cell structure and function has been greater than the direct
elucidation of specific diseases but nevertheless, there are pointers to different
mechanisms which could have wide applications.
It is a book which serves a double function: On the one hand it is highly
technical and a publication for the super expert, recording new landmarks of
knowledge and interpretation. On the other hand, it is a book which can indeed
fire the imagination of the rising generation of gastroenterologists,
paediatricians, pathologists and medical scientists.
Having seen the emergence of the art and science of present-day gastro
enterology within my professional lifetime and having been able to provide the
facilities for her work in the very early days, it is with particular pleasure and
pride that I write this foreword.
London, October 1982 Sir Francis Avery Jones,
CBE, MD(London), FRCP(London)
Consulting Gastroenterologist
Central Middlesex Hospital
Acknowledgements
It is with intense gratitude that I acknowledge all the physicians who kindly
referred their patients to me for study and all scientific and nursing staff whose
help has made it possible to carry out this work.
To my former teachers, Sir Francis Avery Jones, Professor Dame Sheila
Sherlock, Dr. E. N. Rowlands and Dr. P. D. Kellock, lowe a debt which words
are inadequate to express. Without their generous support and encouragement
over the years of gastroenterological investigation and research, this work
would not have been possible. I can only hope that this book will justify their
trust in me. .
I also gratefully and specifically acknowledge the help of my associates, Mrs.
E. E. Cox, Mrs. J. Ballard and Mr. R. Sapsford, in the technical execution of
this study.
Lastly my thanks go to my husband Alex, who for 35 years of 'coexistence'
with my professional activities has patiently borne my eccentricities, which go
inevitably with the medical profession and research. His help and encourage
ment in writing this book have been invaluable.
Preface
No comprehensive book on the electron microscopy of the human jejunal
mucosa in disease has been published to date. This atlas of normal and
pathological ultrastructure is aimed at extending present knowledge in this
field [5], though it is recognised that the gastrointestinal diseases studied are
necessarily limited.
With the development of peroral small bowel biopsy [1-4], the human jejunal
mucosa became the subject of intense biological and morphological interest.
Though the technique is recognised today as an important tool in the diagnosis
of gastrointestinal disease and much is known about the histopathological
changes affecting the mucosa, less attention has been paid by clinicians and
pathologists to advance that knowledge to the field of the electron microscope
(EM). This book therefore aims to correlate a brief clinical and histological
presentation of diseases such as coeliac disease (adults and children), cow's
milk protein intolerance in infants, protein-energy malnutrition in childhood
and a variety of other gastrointestinal diseases with the representative
ultrastructural illustrations, and thereby hopes to provide an insight into the
organisation of specialised cells of the mucosa essential for an appreciation of
the derangement in functions which results when cells undergo pathological
changes.
The EM should be used first and foremost to complement and extend the
field of light microscopy, for only at higher magnification can the intricate
structure of the enterocyte (villous columnar epithelium) and its microvilli,
forming the histologist's brush border, be appreciated. These microvilli vastly
increase the surface area of each enterocyte and the numerous digestive
enzymes located in or on their membranes facilitate the transport of luminal
substances through the cell itself. The fine structure of the organelles of the
enterocyte allows an appreciation of its function as a 'factory' where organised
information is passed from the nucleus to the endoplasmic reticulum and the
mitochondria by ribosomes and from there to the Golgi complex, which
elaborates material necessary for the protection and function of the cell. A very
different picture is seen when the function and ultrastructure of normal
enterocytes is altered, as in coeliac disease. The EM clearly shows the loss as
well as the structural deformity of the microvilli which undoubtedly results in
defects in their digestive-absorptive function. It further demonstrates the
cellula.t; immaturity and lack of organisation of its organelles. We cannot be
certain that these are specific for coeliac disease, for excessive extrusion of
enterocytes; lesser changes in their microvilli, increase in lysosomes and
x Preface
abnormalities in mitochondrial structure are also observed in other diseases
affecting the mucosa. The identification and heterogeneity of the fine structure
of the interepithelial cells (theliolymphocytes) so clearly seen with the light
microscope offer an excellent chance for study with the EM. This also applies
to the structure of cells supported by the connective tissue of the lamina
propria, their relation to each other and to the enterocytes themselves and their
fine structural alteration in the diseased mucosa. The importance of further
study of the lamina propria cells cannot be over-estimated, and their role in
the pathogenesis of gastrointestinal diseases affecting the jejunal mucosa may
await more specialised techniques than conventional EM.
Lastly the EM allows the identification of specific disease-associated
abnormalities denied to light microscopy. A foremost example of this is
Whipple's disease, characterised by the fine structural identification of intact
bacterial forms in the cells and connective tissue of the jejunal mucosa. In
acrodermatitis enteropathica, specific (? lysosomal) abnormalities with Paneth
cells have been identified with this disease. The intimate association of bacteria,
viruses and parasites with mucosal cells in certain diseases can usefully be
studied only with the EM. The recognition of early malignant changes in the
fine structure of mucosal cells deserves special attention. No doubt this list of
indications for ultrastructural investigation in specific gastrointestinal diseases
will be greatly extended in the future.
This collection of EM material represents the personal and subjective study
of a clinician whose overriding interest for the past 25 years has been the
morphology of the human jejunal mucosa and its diagnostic significance. It has
been a natural follow-up of the author's development of the peroral jejunal
biopsy tube, which has opened new horizons in gastroenterology-including
EM. The book is intended to arouse the interest and enthusiasm of gastroen
terologists, paediatricians, pathologists and the medical student.
Harrow, Middlesex, 1982 Margot Shiner
References
l. Crosby WH, Kugler HW (1957 Intraluminal biopsy of the small intestine. The intestinal
biopsy capsule. Am J Dig Dis 2 :236-241
2. Royer M, Croxatto 0, Biempica L, Ballazer-Morrison AJ (1955) Biopsia duodenal por
aspiracion bajo control radioscopico. Prensa Med Argentina 42:2515-2519
3. Shiner M (1956) Duodenal biopsy. Lancet i: 17-19
4. Shiner M (1956) Jejunal biopsy tube. Lancet i:85
5. Toner, PG, Carr KE, Al Yassin TM (1980) Small intestine. In: JohannessenJV (ed) Electron
microscopy in human medicine, vol 7. Digestive system. McGraw-Hill, London, pp 132-168
Contents
Introduction .................................................. 1
Clinical material. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Technique of peroral jejunal biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Technique for electron microscopy. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Comparison of histology, thick and thin ultramicrotome sections
and immunofluorescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Challenge studies .......................................... 4
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Chapter 1. Cells of the Normal Mucosa. . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
The enterocyte. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Crypt cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Precursor cells of the enterocytes . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Goblet cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Paneth cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
APUD cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Theliolymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
The lamina propria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Cells infiltrating the lamina propria. . . . . . . . . . . . . . . . . . . . . . . . 39
Schwann cells and unmyelinated nerve fibres. . . . . . . . . . . . . . . . 50
Endothelial cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Fibrocytes and their fibrillar processes ..................... 56
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Select bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Chapter 2. Coeliac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Untreated. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Comparison of adult and childhood coeliac disease. . . . . . . . . . . . . . 79
Gluten challenge in treated children with normal mucosa ........ 79
Gluten challenge in children with partial repair of the mucosa. . . . . 87
The correlation of structure and function in coeliac disease. . . . . . . 91
Untreated coeliac disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Gluten challenge after treatment with a gluten-free diet . . . . . . . 92
xii Contents
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Select bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Chapter 3. Cow's Milk Protein Intolerance (CMPI) ................. 97
Untreated. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Cow's milk challenge. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100
Histology and immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100
Ultrastructural observations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100
Clinical, morphological and immunological correlation .......... 108
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109
Chapter 4. Protein-Energy Malnutrition (P-EM) ................... 111
Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111
Ultrastructure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
Correlation of clinical and morphological data ................. 126
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 128
Chapter 5. Miscellaneous ....................................... 129
Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 129
Fine structure of involved mucosa with IPSID. . . . . . . . . . . . . .. 129
Fine structure of the mucosa in alpha-chain disease .......... 132
Fine structure of uninvolved mucosa in lymphoma. . . . . . . . . .. 137
Ultrastructural recognition of abnormal inflammatory cells. . .. 139
Giardia lamblia ............................................ 139
Cysts..................................................... 140
Whipple's disease .......................................... 144
Acrodermatitis enteropathica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 148
Multiple sclerosis .......................................... 149
Crohn's disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 153
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 158
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 161