Ultrastructure Atlas of Human TissuesFRED E. HOSSLER

ULTRASTRUCTUREATLAS OF

HUMAN TISSUES

ULTRASTRUCTUREATLAS OF

HUMAN TISSUES

Fred E. Hossler, PhDProfessor Emeritus of Biomedical Sciences

J.H. Quillen College of MedicineEast Tennessee State UniversityJohnson City, Tennessee, USA

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Hossler, Fred E., author.Ultrastructure atlas of human tissues / Fred E. Hossler.

p. ; cm.Includes bibliographical references and index.ISBN 978-1-118-28453-7 (cloth)

I. Title.[DNLM: 1. Histology–Atlases. 2. Tissues–ultrastructure–Atlases. 3. Microscopy, Electron–Atlases.

QS 517]QM557611′.018–dc23

2013042704

Cover image: © Fred E. HosslerCover design by Nicole Teut

Printed in Malaysia

10 9 8 7 6 5 4 3 2 1

This atlas is dedicated to my parents, Leroy E. and Mildred E. Hossler, who taught me toappreciate the beauty of living things and the value of fine, detailed images of them. Mildred wasa well-known water color artist and school teacher in Hamburg, Berks County, Pennsylvania.

CONTENTS

Preface xiAcknowledgments xiiiNote to Readers xiv

I. CELLULAR ORGANELLES AND SURFACE SPECIALIZATIONS 1A. NUCLEI AND NUCLEOLI 1

B. MITOCHONDRIA 6

C. GOLGI COMPLEX 8

D. ROUGH ENDOPLASMIC RETICULUM AND SMOOTHENDOPLASMIC RETICULUM 10

E. LYSOSOMES 12

F. CYTOPLASMIC INCLUSIONS 13

G. PLASMA MEMBRANE JUNCTIONS 16

H. MICROVILLI 18

I. CILIA AND CENTRIOLES 21

J. PLASMA MEMBRANE INFOLDINGS 25

II. BLOOD CELLS 27A. BLOOD COMPOSITION 27

B. RED BLOOD CELLS 39

C. SICKLE CELL ANEMIA 39

D. GRANULAR LEUKOCYTES—NEUTROPHILS, EOSINOPHILS,AND BASOPHILS 44

E. NONGRANULAR LEUKOCYTES—LYMPHOCYTES AND MONOCYTES 55

F. BLOOD PLATELETS—BLOOD CLOTS 70

III. CONNECTIVE TISSUES 77A. COMPOSITION 77

B. RESIDENT CELLS—FIBROBLASTS, ADIPOCYTES, MAST CELLS 90

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viii C O N T E N T S

C. BLOOD CELL DERIVATIVES—NEUTROPHILS, EOSINOPHILS,LYMPHOCYTES, MACROPHAGES, AND PLASMA CELLS 125

D. LOOSE CONNECTIVE TISSUE EXAMPLE: LAMINA PROPRIA 132

E. DENSE IRREGULAR CONNECTIVE TISSUE EXAMPLES: DERMISAND CAPSULES OF ORGANS 132

F. DENSE REGULAR CONNECTIVE TISSUE 132

G. CARTILAGE—HYALINE CARTILAGE AND FIBROCARTILAGE 144

H. BONE—COMPACT BONE AND CANCELLOUS BONE 161

IV. MUSCLE TISSUES 179A. OVERVIEW 179

B. SMOOTH MUSCLE—WALL OF COLON, BRANCHED FIBERS IN WALLOF URETER, WALLS OF BLOOD VESSELS 179

C. SKELETAL MUSCLE 201

D. CARDIAC MUSCLE—ATRIUM 227

V. NERVE TISSUES 253A. OVERVIEW 253

B. PERIPHERAL NERVES—OPTIC NERVE, SCIATIC NERVE, NERVE IN WALLOF COLON, MYELINATED AND UNMYELINATED NERVES 253

C. CENTRAL NERVOUS SYSTEM—CEREBRUM 287

VI. CARDIOVASCULAR SYSTEM 303A. OVERVIEW 303

B. ARTERIES 303

C. VEINS 328

D. CAPILLARIES 336

E. HEART-ATRIUM 354

VII. LYMPHATIC TISSUES 359A. OVERVIEW 359

B. SPLEEN 361

C. THYMUS 365

D. LYMPH NODES, LYMPH NODULES/DIFFUSE LYMPHATIC TISSUE 365

E. TONSILS 374

C O N T E N T S ix

VIII. GASTROINTESTINAL TRACT 385A. ORAL CAVITY 385

B. OVERVIEW OF THE ALIMENTARY CANAL 405

C. ESOPHAGUS 405

D. STOMACH 408

E. SMALL INTESTINES—DUODENUM, JEJUNUM, AND ILEUM 441

F. LARGE INTESTINE (COLON) AND APPENDIX 474

IX. LIVER AND GALL BLADDER 507A. LIVER 507

B. GALL BLADDER 520

X. PANCREAS 543

XI. RESPIRATORY TRACT 561A. OVERVIEW 561

B. TRACHEA, BRONCHI, AND BRONCHIOLES 562

C. LUNGS 579

XII. URINARY TRACT 609A. OVERVIEW 609

B. KIDNEY 609

C. URETERS, BLADDER, AND URETHRA 656

XIII. SKIN 671A. OVERVIEW 671

B. EPIDERMIS 671

C. DERMIS AND HYPODERMIS 725

D. SKIN PARASITES 743

XIV. EYE 749

XV. EAR 797A. OVERVIEW 797

B. MIDDLE EAR 797

C. INNER EAR 802

x C O N T E N T S

XVI. MALE REPRODUCTIVE SYSTEM 819A. TESTIS AND EPIDIDYMIS 819

B. VAS DEFERENS 841

C. SEMINAL VESICLE 844

D. PROSTATE GLAND 849

E. BULBOURETHRAL GLANDS, GLANDS OF LITTRE, ANDTHE PENIS 856

XVII. FEMALE REPRODUCTIVE SYSTEM 857A. OVERVIEW AND OVARY 857

B. OVIDUCT 860

C. UTERUS AND CERVIX 873

D. VAGINA 888

E. PLACENTA 896

F. MAMMARY GLAND (INACTIVE) 903

XVIII. THYROID, PARATHYROID, AND ADRENALGLANDS—EXAMPLES OF ENDOCRINE ORGANS 911A. THYROID GLAND 911

B. PARATHYROID GLANDS 924

C. ADRENAL GLANDS 930

References 941Index 943

PREFACE

B ecause of the complexity of the human body andbecause of the difficulty in obtaining useful sam-

ples of some tissues for electron microscopy, this atlasis not completely comprehensive. For example, only afew images of the human brain were obtained, and noimages of the human pituitary gland, the pineal gland,and the inner ear are included. However, in regard tothe inner ear, several images of the cochlea of the guineapig, which show many similarities to that of the human,are included here. However, the atlas presents a vari-ety of scanning and transmission electron microscopeimages of most of the major systems of the human body,and except for some images of the inner ear (guineapig) and a few images of the liver (rat), the imagesin the atlas were prepared exclusively from human tis-sues. Many of the scanning electron microscopic imageswere also recorded as stereo pairs. These are includedin the atlas with a folding viewer for 3D viewing. Thusthe two unique features of this atlas are: (1) the imageswere prepared almost exclusively from human tissues;and (2) the atlas includes a number of viewable 3Dimage pairs. In most cases microscopic-sized human tis-sue samples were recovered from biopsies obtained forthe purpose of disease diagnoses or from organ donortissues. In no case were tissue samples obtained for thesole purpose of preparing images for this atlas. In everycase, permission for tissue use was obtained from alldonors, and this was properly monitored by the Institu-

tional Review Board at the College of Medicine. Exceptfor the sex and age of the tissue donor (when rele-vant), no information on the source of the tissues wasrecorded. All tissues were fixed in a sodium cacody-late buffered formaldehyde–glutaraldehyde mixture. Forscanning electron microscopy all samples were criticalpoint dried, and for transmission electron microcopy allsamples were embedded in epon–araldite resin for thinsectioning.

“Photography with the electron microscope recordsviews of the intricate substructures and micro-designs ofobjects and tissues, and reveals details within them inac-cessible to the naked eye or light microscope. Many ofthese views have significance in our understanding ofnormal structure and function and of disease processes.Just as the size of objects increase by powers of ten asone compares our human realm with the earth, our solarsystem, the milky way, and beyond, it is natural to antic-ipate that the substructure of objects similarly diminishesby orders of magnitude in the opposite direction, eachsubunit being composed of its own subunits, and soforth. Evidence indicates that increasing our understand-ing of the structure and function of tissues at the sub-cellular and molecular levels improves our chances offinding cures for diseases.”

Fred E. Hossler

xi

ACKNOWLEDGMENTS

T he author wishes to thank the following indi-viduals for unselfishly providing their advice,

knowledge, support, and guidance with regard to thepreparation and description of the tissues used in thisatlas.

S.H. Aharinejad, MD, PhDMarc Aiken, MDRonald H. Baisden, PhDLuke A. Barker, MDPaul M. Benson, MDRobert J. Clemons, MDJames P. Craig, MDJames W. Denham, MDJulie Dunn, MDRichard A. Feit, MDPaul W. Gorman, MDTony O. Haley, MD

Howard E. Herrell, MDMary A. Hooks, MDEric W. Hossler, MDKurt E. Hossler, PAFrederick R. Jelovsek, MDFrank N. Low, PhDWilliam R. MayberryShannon ModlaLarry W. Schmidt, MDJohn B. Schweitzer, MDPhillip C. SholesRichard G. Skalko, PhDKen W. Smith, MDDavid Soike, MDRoger C. Wagner, PhDDavid N. Walters, MDCharles E. Witkowski, DDS, PhDMark F. Young, MD

xiii

NOTE TO READERS

A unique feature of this atlas is that most of thechapters contain sets of 3D images that should

be viewed with 3D glasses. Folding 3D glasses areavailable for purchase at SPI Supplies, Structure Probe,

West Chester, PA, USA. The item number is 04001-ABand the 3D glasses are also available at the website:www.2SPI.com.

xiv

CHAPTER

CELLULAR ORGANELLES ANDSURFACE SPECIALIZATIONS

A. NUCLEI AND NUCLEOLI

Cell nuclei vary somewhat with regard to size, shape,chromatin pattern, and number among the varioustypes of human tissues, as is shown in the images in thissection (Figs. I-1 to I-14). Probably the most commonmorphology consists of a round to oval shape, with asingle eccentric nucleolus, and a mixture of inactive(heterochromatin) and active (euchromatin) DNA. Thedarker staining heterochromatin is scattered throughoutthe lighter staining euchromatin, but is often concen-trated along the edge of the inner nuclear membrane.The ratio of heterochromatin to euchromatin is oftenaltered with cell maturation and with changes in cellularsynthetic activity. While most cells contain a singlenucleus, liver cells and myocardial muscle cells often

contain two nuclei, skeletal muscle cells are multinucle-ated (Figs. I-13 and I-14), and red blood cells (Fig. I-10)discard their nuclei at maturity. Nuclei may be indented(Fig. I-11), lobed (Figs. I-10 and I-12), or distorted inshape (Figs. I-8 and I-9) to match the outline of a cell.There is usually one nucleolus in each nucleus, and itssize may increase with cellular synthetic activity. Thenucleolus appears to be made up of a three-dimensionalnetwork of fibrils with which are associated lighter stain-ing regions as well as heterochromatin-like material.DNA within the nucleolus codes for ribosomal RNA andthe nucleolus functions in the synthesis and assemblyof ribosomal subunits. Ribosomal proteins enter thenucleus and ribosomal subunits formed in the nucleolusleave the nucleus through complex, selective nuclearpores (Figs. I-61 and I-62) in the nuclear envelope.

Ultrastructure Atlas of Human Tissues, First Edition. Fred E. Hossler.© 2014 John Wiley & Sons, Inc. Published 2014 by John Wiley & Sons, Inc.

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2 U L T R A S T R U C T U R E A T L A S O F H U M A N T I S S U E S

F I G U R E S I-1 and I-4. I-1 Nucleus of epithelial cell from human jejunum. ×14 167. I-2 Nucleus of cell from human gallbladder. ×8409. I-3 Nucleus (N) of human kidney tubule cell. ×25 000. I-4 Nucleus of fibroblast from human kidney. ×20 521.N, nucleolus; E, euchromatin; H, heterochromatin.

C H A P T E R I C E L L U L A R O R G A N E L L E S A N D S U R F A C E S P E C I A L I Z A T I O N S 3

F I G U R E S I-5 and I-6. I-5 Plasma cell from human colon. Note “spoke wheel” pattern of nucleolus (N) and heterochromatin(H). ×15286. I-6 Plasma cell cluster from human jejunum. Again note peripheral heterochromatin pattern in nuclei. ×2250.E, euchromatin; R, rough endoplasmic reticulum; H, heterochromatin.

4 U L T R A S T R U C T U R E A T L A S O F H U M A N T I S S U E S

F I G U R E S I-7 and I-10. I-7 Comparison of nuclei of fibroblast (F) and epithelial lining cells (E) from human colon. I-8 andI-9 Human fibroblasts demonstrating irregular nuclear shapes influenced by cell shapes. ×23 000 and ×21 585. I-10 Cells withina capillary in the wall of the human ureter demonstrate variations in nuclei. The lymphocyte (L) has a somewhat roundedand condensed nucleus, the neutrophil (N), exhibits a highly condensed, multilobed nucleus, while the red blood cell (R) hasgiven up its nucleus. ×15 400.

C H A P T E R I C E L L U L A R O R G A N E L L E S A N D S U R F A C E S P E C I A L I Z A T I O N S 5

F I G U R E S I-11 and I-14. I-11 Human lymphocytes showing rounded, somewhat indented, and condensed nuclei. ×34 367.I-12 Human neutrophil with extensive nuclear lobation. ×7600. I-13 Human skeletal muscle from the tibialis anterior. Skeletalmuscle cells are multinucleated. Seen here are two adjacent muscle cells, each showing a single nucleus along its periphery.×5106. I-14 Cardiac myocytes from the human atrium. Cardiac myocytes may contain one or two nuclei. The cell at the rightcenter may have two nuclei or, more likely, the tissue section may have been cut along the edge of a single nucleus. ×5000.

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B. MITOCHONDRIA

Like nuclei, mitochondria are bound by a double mem-brane. Folds in the inner membrane, called cristae,extend toward the interior, or matrix space, of the mito-chondrion (Figs. I-15 to I-18). Mitochondria are self-replicating and their matrix space contains its ownunique segment of DNA, and unique RNA species(evidence to support the belief that these organelleswere originally derivatives of a symbiotic bacterium).The outer membrane contains pores that facilitatethe free flow of small molecules. The inner mem-

brane is essentially impermeable and is rich in pro-ton pump enzymes (NADH dehydrogenase complexand cytochrome chain complex), and ATP synthase.Enzymes involved in the citric acid cycle as well as someenzymes involved in fatty acid oxidation are locatedwithin the matrix space. This functional relationshipbetween the matrix and the inner membrane definesthe primary function of the mitochondrion, ATP synthe-sis. Because of this basic function, most cells containmitochondria, but this organelle is especially abundantin synthetically active cells and in cells involved in activetransport.

C H A P T E R I C E L L U L A R O R G A N E L L E S A N D S U R F A C E S P E C I A L I Z A T I O N S 7

F I G U R E S I-15 to I-18. Clusters of mitochondria from distal tubule cells in the human kidney. M, matrix space; C, cristae.×45 625, ×61 818, ×81 820, and ×53 500.

8 U L T R A S T R U C T U R E A T L A S O F H U M A N T I S S U E S

C. GOLGI COMPLEX

The Golgi complex consists of a stack of flattened mem-brane vesicles or cisternae (Figs. I-19 to I-24). The stackis usually concave on one side (the forming face or cis-face) and convex on the opposite side (maturing face ortrans-face). The Golgi complex is an essential compo-nent in the process of cell secretion and in the move-ment of membrane vesicles between the cytoplasmic

F I G U R E S I-19 to I-20. I-19 Golgi complex in chief cell of human fundus. ×15 000. I-20 Golgi complex in chief cell of humanfundus. ×26 700. G, Golgi complex; F, forming face of Golgi; M, maturing face of Golgi; R, rough endoplasmic reticulum;SV, secretory vesicle.

organelles and the cell surface. Most cells contain a Golgicomplex, but Golgi complexes are especially well devel-oped and abundant in cells involved in secretion and inlysosome synthesis. In secretory cells the forming faceof the Golgi complex is closely associated with roughendoplasmic reticulum (RER) and the maturing face isassociated with secretory vesicles. As the secretory pro-teins pass through the Golgi complex they are sorted,packaged, and chemically modified.

C H A P T E R I C E L L U L A R O R G A N E L L E S A N D S U R F A C E S P E C I A L I Z A T I O N S 9

F I G U R E S I-21 to I-24. I-21 Golgi complex in distal tubule cell of human kidney. ×55 652. I-22 Golgi complex in epithelialcell in human gall bladder. ×7800. I-23 Epithelial cell in human colon. ×11 923. I-24 Epithelial cell in human gall bladder.×13 000. G, Golgi complex; F, forming face of Golgi complex; M, maturing face of Golgi complex; SV, secretory vesicles;S, smooth endoplasmic reticulum; R, rough endoplasmic reticulum.

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D. ROUGH ENDOPLASMICRETICULUM AND SMOOTHENDOPLASMIC RETICULUM

Free ribosomes become involved in protein synthe-sis when they attach to a messenger RNA and formpolysomes. Polysomes within the cell cytoplasm (freepolysomes) synthesize proteins for use within the cell.However, when the polysomes are attached to mem-brane complexes (endoplasmic reticulum) within thecytoplasm, they synthesize proteins for secretion, forincorporation into the cell membrane, or for lysosomeformation. Polysomes attached to cytoplasmic mem-branes are referred to as RER (Figs. I-25 to I-30). When

F I G U R E S I-25 to I-26. I-25 Human hepatocyte. I-26 Epithelial cell in human ileum. N, nucleus; R, rough endoplasmicreticulum; arrows, ribosomes.

a cell is stimulated to increase its secretory activity, theamount of RER within a cell’s cytoplasm can increasedramatically. One example of this is the conversion of arelatively dormant lymphocyte into a plasma cell whichthen synthesizes and secretes abundant amounts of anti-body. Endoplasmic reticulum within the cytoplasm thatdoes not have attached ribosomes is smooth endoplas-mic reticulum (SER) (Fig. I-21). SER is less abundant inmost cells than RER, but because it is involved in lipidsynthesis, steroid synthesis, and drug detoxification, SERis found in liver cells and in endocrine glands. A spe-cial form of SER is found in striated muscle cells whereit forms complex networks around muscle fibrils andactively sequesters calcium between contractions.

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F I G U R E S I-27 to I-30. I-27 to I-29 Rough endoplasmic reticulum in human pancreatic islet cells. ×40 000, ×50 000, and×40 000. I-30 Rough endoplasmic reticulum in a human hepatocyte. ×24 000. N, nucleus; M, mitochondria; arrows, ribosomes.

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E. LYSOSOMES

Lysosomes are cytoplasmic membrane-bound vesiclesthat contain a variety of digestive enzymes, includingproteases, lipases, glycosidases, phosphatases, nucle-ases, and sulfatases (Figs. I-31 and I-32). Proteins des-tined for lysosomes contain a phosphorylated mannoseresidue that tags them for delivery into a lysosomal vesi-cle as they are passed through the Golgi complex. The

F I G U R E S I-31 to I-32. I-31 Neutrophil within a capillary in the human lung. ×18 139. I-32 Active macrophage in the laminapropria of the human ileum displaying unusually large lysosomes. ×18 750. N, nucleus; arrows, lysosomes.

marker enzyme for lysosomes is acid phosphatase, andmost of the enzymes in lysosomes exhibit optimal activ-ity at an acid pH. These organelles are most abundant inneutrophils and macrophages where they are involvedin intracellular digestion of phagocytized material suchas bacteria or cellular debris. A few specialized celltypes release lysosomal granules for extracellular diges-tive processes. An example of the latter is the osteoclastthat is involved in bone remodeling.

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F. CYTOPLASMIC INCLUSIONS

In addition to organelles, some cells include inclusionsin their cytoplasm (Figs. I-33 to I-42). Some inclusionsfunction as energy stores while others serve specializedfunctions. Probably the most readily observed form ofenergy storage function is evident as lipid storage in

F I G U R E S I-33 to I-34. I-33 Human hepatocyte. ×6923. I-34 Fibroblast in the lamina propria of the human colon. ×23 000.N, nucleolus; R, rough endoplasmic reticulum; L, lipid droplets.

adipocytes (Figs. I-35 to I-38) and other cells (Figs. I-33and I-34), and as glycogen storage in hepatocytes(Figs. I-39 and I-40). Another example of importantcytoplasmic inclusions is the melanin pigment gran-ules which the skin keratinocytes ingest as protectionagainst potential ultraviolet radiation damage (Figs. I-41and I-42).

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F I G U R E S I-35 to I-38. I-35 Adipose tissue from human dermis. ×77. I-36 Fat cells from human dermis. ×500. I-37 Fatcells from human dermis. ×580. I-38 Cross section of edge of a fat cell from human dermis. ×2500. N, nucleus; F, fat deposit;C, collagen fibrils.