Atlas of the Ultrastructure of Diseased Human Muscle
By W G P Mair and F M S Tomé
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Atlas of the Ultrastructure of Diseased Human Muscle - W G P Mair
Atlas of the Ultrastructure of Diseased Human Muscle
WGP Mair, MD FRCPath.
Consultant Neuropathologist, The National Hospital for Nervous, Diseases, Queen Square, London
Lecturer in Neuropathology, Institute of Neurology, University of London
FMS Tomé
Neurologist, Faculty of Medicine, University of Lisbon
Lecturer, in Neuropathology, Institute of Neurology, The National Hospital for Nervous Diseases, Queen Square, University of London
Table of Contents
Cover image
Title page
Inside Front Cover
Copyright
Foreword
Preface
Chapter 1: Normal Striated Muscle
Publisher Summary
SKELETAL MUSCLE FIBRES
PLASMA AND BASEMENT MEMBRANES
SATELLITE CELLS
TYPES OF MUSCLE FIBRES
BLOOD CAPILLARIES, FIBROBLASTS AND COLLAGEN
MYOTENDINOUS JUNCTION
NERVES AND MOTOR END PLATES
MUSCLE SPINDLES
EXTRA-OCULAR MUSCLE
FOETAL SKELETAL MUSCLE
CARDIAC MUSCLE. ADULT AND FOETAL
PLATE 1 LONGITUDINAL SECTION OF NORMAL MUSCLE
PLATE 2 TRANSVERSE SECTION OF NORMAL MUSCLE
PLATE 3 TRANSVERSE SECTION OF NORMAL MUSCLE SATELLITE CELL. INTRAMUSCULAR BLOOD CAPILLARY
PLATE 4 TYPES OF MUSCLE FIBRES
PLATE 5 MYOTENDINOUS JUNCTION
PLATE 6 NORMAL NERVE FIBRES IN SKELETAL MUSCLE
PLATE 7 NORMAL NERVE FIBRES IN SKELETAL MUSCLE
PLATE 8 NORMAL MOTOR END PLATE
PLATE 9 MUSCLE SPINDLE
PLATE 10 EXTRA-OCULAR MUSCLE
PLATE 11 NERVES AND MOTOR END PLATE IN EXTRA-OCULAR MUSCLE
PLATE 12 HUMAN FOETAL MUSCLE
PLATE 13 HUMAN FOETAL MUSCLE
PLATE 14 HUMAN FOETAL MUSCLE MYOBLAST IN MITOSIS
PLATE 15 HUMAN CARDIAC MUSCLE
PLATE 16 HUMAN FOETAL CARDIAC MUSCLE CENTRIOLES AND A MITOTIC FIGURE IN MYOCARDIAL CELLS
Chapter 2: Changes in Muscle Fibres
Publisher Summary
MYOFIBRILS
NUCLEI AND GOLGI APPARATUS
MITOCHONDRIA
GLYCOGEN
LIPID BODIES
SARCOPLASMIC RETICULUM AND T-SYSTEM (HONEYCOMB STRUCTURES)
VACUOLES. AUTOPHAGIC VACUOLES
MYELIN AND MEMBRANOUS BODIES
CONCENTRIC LAMINATED BODIES
TUBULAR STRUCTURES
CRYSTAL AND VIRUS-LIKE PARTICLES
PLASMA AND BASEMENT MEMBRANES
SATELLITE CELLS AND REGENERATION OF MUSCLE
PLATE 17 RING FIBRE
MAGNIFICATION 7,500 ×
PLATE 18 RING FIBRES
MAGNIFICATION 21,000 ×
MAGNIFICATION 25,000 ×
PLATE 19 MYOFIBRILLARY DEGENERATION
MAGNIFICATION 11,000 ×
MAGNIFICATION 14,500 ×
PLATE 20 MYOFIBRILLARY DEGENERATION UNDULATIONS OF THE SURFACE OF MUSCLE FIBRES
MAGNIFICATION 8,000 ×
MAGNIFICATION 10,000 ×
PLATE 21 MYOFIBRILLARY DEGENERATION
MAGNIFICATION 9,000 ×
MAGNIFICATION 7,000 ×
PLATE 22 CHANGES IN SHAPE AND SIZE OF DEGENERATE MUSCLE FIBRES
MAGNIFICATION 10,000 ×
MAGNIFICATION 12,000 ×
PLATE 23 ‘STREAMING’ OF THE Z-LINES
MAGNIFICATION 6,500 x
MAGNIFICATION 12,000 ×
MAGNIFICATION 25,000 ×
PLATE 24 TARGET FIBRES
MAGNIFICATION 8,500 ×
MAGNIFICATION 8,000 ×
MAGNIFICATION 9,500 ×
PLATE 25 RODS IN SKELETAL MUSCLE
MAGNIFICATION 14,500 ×
MAGNIFICATION 15,000 x
RODS IN EXTRA-OCULAR MUSCLE
MAGNIFICATION 9,000 ×
MAGNIFICATION 110,000 ×
PLATE 27 CYTOPLASMIC BODIES
MAGNIFICATION 9,500 ×
MAGNIFICATION 10,000 ×
PLATE 28 FILAMENTOUS BODIES
MAGNIFICATION 24,000 ×
MAGNIFICATION 16,000 ×
PLATE 29 CENTRAL NUCLEI IN MUSCLE FIBRES
MAGNIFICATION 10,000 ×
MAGNIFICATION 15,000 ×
PLATE 30 MITOCHONDRIAL ABNORMALITIES
MAGNIFICATION 24,000 ×
MAGNIFICATION 30,000 ×
PLATE 31 MITOCHONDRIAL ABNORMALITIES
MAGNIFICATION 26,000 ×
MAGNIFICATION 21,000 ×
PLATE 32 MITOCHONDRIAL ABNORMALITIES
MAGNIFICATION 41,000 ×
PLATE 33 GLYCOGEN IN INCREASED AMOUNT
MAGNIFICATION 18,000 ×
MAGNIFICATION 38,000 ×
PLATE 34 LIPID BODIES IN DEGENERATING MUSCLE FIBRES
MAGNIFICATION 7,000 ×
MAGNIFICATION 13,000 ×
PLATE 35 TRIADS IN DEGENERATING MUSCLE FIBRES
MAGNIFICATION 45,000 ×
MAGNIFICATION 36,000 ×
PLATE 36 COLLECTIONS OF TRIADS
MAGNIFICATION 16,000 ×
MAGNIFICATION 35,000 ×
PLATE 37 DISTENSION OF THE SARCOPLASMIC RETICULUM
MAGNIFICATION 25,000 ×
MAGNIFICATION 80,000 ×
MAGNIFICATION 45,000 ×
MAGNIFICATION 27,000 ×
PLATE 38 HONEYCOMB STRUCTURES
MAGNIFICATION 72,000 ×
MAGNIFICATION 64,000 ×
MAGNIFICATION 72,000 ×
PLATE 39 AUTOPHAGIC VACUOLES
MAGNIFICATION 6,000 ×
MAGNIFICATION 52,000 ×
PLATE 40 EXTRUSION OF THE AUTOPHAGIC VACUOLE CONTENTS INTO THE BASEMENT MEMBRANE
MAGNIFICATION 15,500 ×
MAGNIFICATION 20,000 ×
PLATE 41 MYELIN BODIES IN DEGENERATING MUSCLE FIBRES
MAGNIFICATION 10,000 ×
MAGNIFICATION 17,500 ×
PLATE 42 MEMBRANOUS BODIES IN SKELETAL MUSCLE
MAGNIFICATION 20,000 ×
MAGNIFICATION 30,000 ×
MAGNIFICATION 35,000 ×
PLATE 43 MEMBRANOUS BODIES IN EXTRA-OCULAR MUSCLE
MAGNIFICATION 9,000 ×
MAGNIFICATION 15,000 ×
PLATE 44 CONCENTRIC LAMINATED BODIES IN DEGENERATING MUSCLE FIBRES
MAGNIFICATION 11,000 ×
MAGNIFICATION 60,000 ×
MAGNIFICATION 31,000 ×
PLATE 45 CONCENTRIC AND PARALLEL TUBULES IN MUSCLE FIBRES
MAGNIFICATION 42,000 ×
PLATE 46 TUBULAR AGGREGATES IN MUSCLE FIBRES
PLATE 47 TUBULAR AGGREGATES IN MUSCLE FIBRES
MAGNIFICATION 26,000 ×
MAGNIFICATION 50,000 ×
MAGNIFICATION 40,000 ×
MAGNIFICATION 41,000 ×
MAGNIFICATION 48,000 ×
PLATE 48 TUBULAR AGGREGATES IN MUSCLE FIBRES
MAGNIFICATION 31,000 ×
MAGNIFICATION 45,000 ×
PLATE 49 PLASMA AND BASEMENT MEMBRANES IN DEGENERATING MUSCLE FIBRES
MAGNIFICATION 8,000 ×
MAGNIFICATION 15,000 ×
PLATE 50 BASEMENT MEMBRANE PROJECTIONS FROM AN ATROPHYING MUSCLE FIBRE
MAGNIFICATION 14,500 ×
PLATE 51 SATELLITE CELLS IN MUSCLE FIBRES
MAGNIFICATION 14,000 ×
MAGNIFICATION 15,000 ×
PLATE 52 REGENERATION OF MUSCLE
MAGNIFICATION 24,000 ×
MAGNIFICATION 26,500 ×
PLATE 53 REGENERATION OF MUSCLE
MAGNIFICATION 28,000 ×
MAGNIFICATION 36,000 ×
PLATE 54 REGENERATION OF MUSCLE
MAGNIFICATION 16,000 ×
MAGNIFICATION 17,000 ×
PLATE 55 REGENERATION OF MUSCLE
MAGNIFICATION 17,000 ×
MAGNIFICATION 10,000 ×
Chapter 3: Changes in Blood Capillaries and Interstitial Tissue of Muscle
Publisher Summary
BLOOD CAPILLARIES
LEUCOCYTIC INFILTRATION AND PHAGOCYTOSIS OF THE MUSCLE FIBRES
FIBROBLASTS AND COLLAGEN
AMYLOID FIBRILS
PLATE 56 CENTRIOLE IN THE ENDOTHELIAL CELL OF AN INTRAMUSCULAR BLOOD CAPILLARY
PLATE 57 CENTRIOLES IN THE ENDOTHELIAL CELL OF AN INTRAMUSCULAR BLOOD CAPILLARY
PLATE 58 LAMINATED LIPID INCLUSION IN THICKENED CAPILLARY ENDOTHELIUM
PLATE 59 HYPERTROPHY AND HYPERPLASIA OF THE ENDOTHELIAL CELLS OF THE BLOOD CAPILLARIES
PLATE 60 LEUCOCYTES IN POLYMYOSITIS
PLATE 61 PLASMA CELLS IN POLYMYOSITIS
PLATE 62 LEUCOCYTES IN POLYMYOSITIS A LEUCOCYTE IN MITOSIS
PLATE 63 PHAGOCYTOSIS OF MUSCLE FIBRES IN POLYMYOSITIS
PLATE 64 AMYLOID FIBRILS
Chapter 4: Changes in Nerves, Motor End Plates and Muscle Spindles
Publisher Summary
CHANGES IN NERVES
CHANGES IN MOTOR END PLATES
CHANGES IN MUSCLE SPINDLES
PLATE 65 MOTOR END PLATES IN DENERVATED MUSCLE
PLATE 66 MOTOR END PLATE IN MUSCULAR DYSTROPHY
PLATE 67 MOTOR END PLATES IN POLYMYOSITIS
Chapter 5: Changes in Various Muscle Diseases
Publisher Summary
DENERVATION ATROPHY OF MUSCLE
MUSCULAR DYSTROPHIES
POLYMYOSITIS AND ALLIED CONDITIONS
METABOLIC, ENDOCRINE AND TOXIC MYOPATHIES
CONGENITAL MYOPATHIES
PLATE 68 ABNORMALITIES OF MUSCLE FIBRES IN DENERVATION
MAGNIFICATION 13,500 X
MAGNIFICATION 21,000 x
PLATE 69 ATROPHIED MUSCLE FIBRE IN DENERVATION
MAGNIFICATION 9,000 x
PLATE 70 MUSCULAR DYSTROPHY (DUCHENNE TYPE)
MAGNIFICATION 19,000 x
MAGNIFICATION 9,000 x
PLATE 71 MUSCULAR DYSTROPHY DOUBLE Z-LINES
MAGNIFICATION 9,500 x
PLATE 72 MUSCULAR DYSTROPHY ATROPHIED MUSCLE FIBRES
MAGNIFICATION 6,500 x
PLATE 73 MUSCULAR DYSTROPHY PHAGOCYTOSIS OF A DEGENERATING MUSCLE FIBRE
MAGNIFICATION 7,000 x
PLATE 74 MUSCULAR DYSTROPHY ELECTRON DENSE PARTICLES IN DEGENERATING MUSCLE FIBRES
MAGNIFICATION 13,000 x
MAGNIFICATION 125,000 x
MAGNIFICATION 58,000 x
PLATE 75 POLYMYOSITIS LEUCOCYTIC INFILTRATION
MAGNIFICATION 5,500 x
MAGNIFICATION 5,000 x
PLATE 76 POLYMYOSITIS DEGENERATING MUSCLE FIBRE
MAGNIFICATION 14,000 x
PLATE 77 POLYMYOSITIS RODS IN A DEGENERATING MUSCLE FIBRE
MAGNIFICATION 8,000 x
PLATE 78 STEROID MYOPATHY
MAGNIFICATION 50,000 x
MAGNIFICATION 75,000 x
PLATE 79 VINCRISTINE NEUROMYOPATHY
MAGNIFICATION 22,000 x
MAGNIFICATION 66,000 x
MAGNIFICATION 15,000 x
PLATE 80 VINCRISTINE NEUROMYOPATHY
MAGNIFICATION 34,000 x
MAGNIFICATION 44,000 x
PLATE 81 CHLOROQUINE MYOPATHY
MAGNIFICATION 16,000 X
MAGNIFICATION 25,000 x
PLATE 82 CHLOROQUINE MYOPATHY
MAGNIFICATION 15,000 x
MAGNIFICATION 18,000 x
PLATE 83 VITAMIN E DEFICIENCY DEGENERATING MUSCLE FIBRES
MAGNIFICATION 26,000 x
MAGNIFICATION 16,000 x
PLATE 84 VITAMIN E DEFICIENCY DEGENERATING MUSCLE FIBRES
MAGNIFICATION 12,000 x
MAGNIFICATION 10,000 x
References
Index
Inside Front Cover
‘After all, muscle moves the world’.
SIR CHARLES SHERRINGTON
Copyright
© LONGMAN GROUP LIMITED, 1972
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publishers (Churchill Livingstone, Teviot Place, Edinburgh)
ISBN 0 443 00831 0
Printed in Great Britain by
Butler & Tanner Ltd, Frome and London
Foreword
Studies concerning the pathology and aetiology of muscle diseases in this country have received a considerable impetus from the Muscular Dystrophy Group of Great Britain who have donated large sums for research by prominent scientists.
Just over ten years ago an electron microscope was given by the National Fund for Research into Poliomyelitis (as it then was) to the Muscular Dystrophy Group and it was handed over to me at The Institute of Neurology, The National Hospital, Queen Square. Dr W. G. P. Mair, Consultant Neuropathologist, had the immediate opportunity of using it in diseases of muscle and was one of the earliest to undertake this type of study in this country. Since then he has taught a succession of research workers from many countries, and of these Dr F. Tomé of Lisbon is the most recent and one of the most able. Drs Mair and Tomé have devoted their time and skill during the past year or so to produce this volume which, in view of their wide experience and their most beautiful pictures, will be of the utmost importance as well as of inestimable value to all workers in this field.
Both authors, as well as myself, would desire to express our indebtedness to the Muscular Dystrophy Group of Great Britain, without whose help the work described in the volume would have been impossible.
J.N. CUMINGS, MD, FRCP, FRCPath.
Chairman, Medical Research Committee, Muscular Dystrophy Group of Great Britain
Emeritus Professor of Chemical Pathology, Institute of Neurology, The National Hospital, London
Preface
A great deal of information on the ultrastructure of muscle both in experimental animals and in a wide variety of human muscular disorders is now available but is disseminated in a great many publications which are not readily accessible to the majority of workers. In this book an effort has been made to provide a concise, general view of the ultrastructure of normal and diseased human muscle: brief reference is also made to extra-ocular and cardiac muscle. In addition skeletal and cardiac muscle of the human foetus are also described.
Our main concern has been to illustrate the changes which take place in common pathological conditions, and we have tried to outline the patterns of change which occur in particular diseases. It must be stressed, however, that many of the ultrastructural changes in muscle are common to many different pathological processes.
We have provided a bibliography of the most important reports, but we are well aware that it is far from complete and the omission of any is unintentional.
We are most indebted to the Muscular Dystrophy Group of Great Britain for providing the equipment and the technical and financial assistance of their laboratory at the Institute of Neurology, The National Hospital for Nervous Diseases, Queen Square, London. It is through their generosity that this publication was made possible. We are grateful to the Calouste Gulbenkian Foundation for the Fellowship granted to one of us (F. T.) while part of the work was in progress.
The material on which the study was based consisted of some 250 biopsies. We would like to thank all the physicians and surgeons of The National Hospital, Queen Square, London, and of the Hospital de Santa Maria, Lisbon, for providing the biopsies, and the pediatricians, obstetricians and ophthalmologists of other hospitals who provided some of the material for examination. We are grateful to Drs A. Nordén and F. K.-G. Henriksson for the material from the patient with vitamin E deficiency, and to Drs J. A. Morgan-Hughes and P. M. Le Quesne for the material from rats treated with vincristine. We are indebted to Dr Ross McD. Anderson for his assistance in studying several of the biopsies and for some of the electron micrographs, and to Dr Sverrir B. Bergmann for the electron micrographs of foetal cardiac muscle. These micrographs were prepared while they worked with us.
We have been greatly assisted by Mr Brian Young who prepared all the specimens used in this publication and we are grateful to him and to Miss Alison Leigh for their goodwill, excellent technical assistance and photographic skill. We are indebted to Mr J. A. Mills for the light micrograph of Plate 9. Finally we would thank Mrs M. Beryl Bailey for her help in the preparation of the bibliography, Miss Margaret C. Wood for typing part of the manuscript, and Messrs Churchill Livingstone, particularly Mr W. G. Henderson, for their assistance and courtesy during the preparation of this atlas.
W.G.P. MAIR and F.M.S. TOMÉ
CHAPTER 1
Normal Striated Muscle
Publisher Summary
This chapter reviews the ultrastructure of muscle. Skeletal muscle fibers are multinucleated cells bounded successively by plasma and a basement membrane. Collagen fibers, blood vessels, and nerves lie between the muscle fibers. The bulk of the muscle fiber consists of myofibrils, which are the contractile elements of muscle. They lie parallel to the long axis of the fiber and run almost its whole length. The myofibrils display alternating dark anisotropic or doubly refractile A-bands and clear isotropic I-bands that are not doubly refractile. Muscle cells arise from undifferentiated mononucleated cells, that is, the myoblasts, which fuse to form multinucleated cells and differentiate into adult muscle fibers. In the same muscle of the fetus from early stages of development, cells occur simultaneously at different stages of differentiation. The chapter discusses cardiac muscle of adult and fetus. Cardiac muscle resembles skeletal muscle in that the myofibrils of both are striated. Cardiac muscle fibers are, however, shorter and smaller in diameter than skeletal muscle fibers.
The structure of skeletal muscle has interested many workers over the past century and a considerable addition to our knowledge of its structure and function followed the introduction of electron microscopy in the pursuit of the study of normal and diseased muscle. Numerous authors studied the ultrastructure of muscle, and important amongst the reports of some of the early investigators in experimental animals are those of Draper and Hodge (1949), H. E. Huxley (1953), Bennett and Porter (1953), Ruska (1954), Hodge, H. E. Huxley and Spiro (1954), Bennett (1955), A. F. Huxley (1957a) and Hodge (1960), and in normal human muscle that of van Breemen (1960a). More recent reviews of the ultrastructure of muscle have been reported by Wilkie (1968), Price (1969) and Fardeau (1969a). The works of many important contributors to our knowledge of the ultrastructure of muscle are mentioned throughout this chapter.
SKELETAL MUSCLE FIBRES
Skeletal muscle fibres are multinucleated cells bounded successively by a plasma and a basement membrane. Collagen fibres, blood vessels and nerves lie between the muscle fibres.
Muscle fibres are fusiform in shape and of varying length depending on the length of the muscle which they form; however, individual fibres in the same muscle may also vary in length. The diameters of the muscle fibres vary between 10 and 100 μ.
The bulk of the muscle fibre consists of myofibrils (Plates 1 and 2) which are the contractile elements of muscle. They lie parallel to the long axis of the fibre and run almost its whole length. In normal human muscle the diameter of the myofibrils varies between 0·5 and 1 μ. The myofibrils display alternating dark anisotropic or doubly refractile A-bands and clear isotropic I-bands which are not doubly refractile. In the middle of the A-band is a lighter zone, the H-zone (Hensen’s stripe), in the centre of which is the M-line (Mittelscheibe). Running through the centre of the I-band is the dense Z-line (Zwischenscheibe). In longitudinal sections of human muscle the Z-lines are commonly 800 Å wide. In cross section the Z-line has a lattice pattern. The ultrastructure of the Z-line has been studied by various authors including Knappeis and Carlsen (1962), Auber and Couteaux (1963), Reedy (1964), Kelly (1967) and Landon (1970). The distance between two Z-lines is called a sarcomere, which in resting human muscle measures about 2·3 μ but may vary from 2 to 3·8 μ, depending on whether the muscle is contracted or relaxed. The A-band is of fixed length about 1·5 μ, whereas the I-band varies in length according to whether the muscle is contracted or relaxed. Normally the Z-lines, and I- and A-bands of adjacent myofibrils lie in series (Plate 1). The Z-lines of adjacent myofibrils are not continuous with each other, nor do they extend to the plasma membrane except at the myotendinous junction. Myofibrils are formed of thick and thin myofilaments. The myofilaments in the I-band are thin, some 60 Å in diameter and about 1·0 μ long; they extend into the A-band, which contains also thick filaments of about 160 Å in diameter and 1·5 μ long. In the A-band the thick filaments are arranged in an hexagonal pattern, and each thick filament is also surrounded by six thin filaments. In relaxed muscle the H-zone is evident since