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I di Fiore's I

Atlas of
with Functional Correlations

Victor R Eroschenko, Ph.D.

Professor of Anatomy
Department of Biological Sciences
WAMI Medical Program
University of Idaho
Mosco\/\/, Idaho

Williams & Wilkins


Executive Editor: Donna Balado
Managing Editor: Victoria Rybicki Vaughn
Production Coordinator: Peter J. Carley
Manus,ript Editor: Rebecca Krumm

Copyright @ 1996
Williams & Wilkins
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All rights reserved. This book is protected by copyright. No part of this book may be reproduced in
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retrieval system without written pennission from the copyright owner.
Printed in Canada

FIRST EDITION, 1957 Reprinted 1958, 1959, 1960, 1961, 1962

SECOND EDITION, 1963 Reprinted 1964, 1965
THIRD EDITION, 1967 Reprinted 1968, 1969, 1970, 1971,1972,1973
FOURTH EDITION, 1974 Reprinted 1975, 1976, 1977, 1978, 1979, 1980, 1981
FIFTH EDITION, 1981 Reprinted 1981, 1982, 1983, 1985, 1987
SIXTH EDITION, 1989 Reprinted 1989, 1992
SEVENTH EDITION, 1993 Reprinted 1994

97 98 99
3 4 5 6 7 8 9 to

Library of Congress Cataloging-in-Publication Data

Eroschenko, Victor P.
Di Fiore's atlas of histology with functional correlations/
Victor P, Eroschenko, - 8th ed.
p. cm,
Includes index.
ISBN 0-683-09671-0
1. Histology-Atlases. I. Fiore, Mariano S. H. di. II. Title.
III. Title: Atlas of histology with functional correlations,
[DNLM: 1. Histology-atlases, WS 517 E71d 1995]
QM557,F5513 1995
611 '.018-dc20
for Library of Congress 94-47275

Reprints of chapters may be purchased from Williams & Wilkins in

quantities of 100 or more, Call Isabella Wise, Special Sales Department,
(800) 358-3583.


Major changes in format, binding, contents, and the introduction of function-

al correlations characterized the seventh edition of this atlas. These changes
were welcomed and acclaimed by both students and instructors of histology.
The publication of the eighth edition of the Atlas of Histology brings additional
changes designed to further improve the use and versatility of this atlas.
Histologic structures must first be recognized under a microscope and then
correctly interpreted. To this end, the most noticeable changes in this edition are
the replacement of older figures with 47 new illustrations and text. New art for
this edition has been prepared by illustrator E. Roland Brown of Lewiston,
Idaho. In preparing the new illustrations, the artist and I have attempted to
maintain the same accuracy and detail of the composite histologic drawings that
have made past editions of this atlas so unique and valuable to histology stu-
In addition to the creation of new illustrations, the presentation of text and
figures has been altered. The atlas has been organized into chapters, and each
chapter is introduced with a section on the functional correlations of that partic-
ular tissue or organ. The illustrations have likewise been numbered according to
chapter number rather than plate number, as had been the practice in past edi-
Histologic sections observed under a microscope appear flat. However, each
such section represents a portion of a tissue or organ that once had depth and
dimension in a living organism. One of the first difficulties that beginning stu-
dents encounter in histology is the recognition-in terms of three dimensions-
of structures viewed under the microscope in flat sections. To assist the student
in this endeavor, an introduction on the interpretation of histologic sections has
been added to this edition of the atlas. The introduction explains how to visual-
ize, understand, and interpret the dimensions of a solid object and of a tube sec-
tioned in different planes. This addition to the atlas should better prepare the
student beginning a histology course to correctly interpret the shapes of cells,
blood vessels, and fibers in any histologic section.
Other changes in the atlas include a section on glands in Chapter I. Several
types of glands in the body are first presented diagrammatically, and then are
illustrated as histologic sections. This presentation will allow the student to
understand the differences between the ducts and acini of various glands, and
then to see the actual histologic structures of the glands.
An important portion of any histology course is function, because structure
without function has little meaning. To maintain this aspect of the Atlas of
Histology, the functional correlations that found much favor with the audience
in the previous edition have been revised and updated. New information on the
functions of cells and tissues of different organs has been included for each
chapter. The dynamics of structure and function thus have been maintained and
improved in this edition.

Preface v
Because the previous three editions of the atlas have undergone major alter-
ations in form and content, this edition is the last that will carry di Fiore's name
as part of the title.
Since publication of the seventh edition of this atlas, there have also been
significant changes in the publisher, editor, and production staff, all of whom
have become directly involved with me in the preparation of this text. Their
valuable assistance in this endeavor is hereby gratefully acknowledged. I
express my appreciation to Donna Balado, Becky Krumm, Pete Carley, and
others of the production staff of Williams & Wilkins.

Moscow, Idaho Victor P. Eroschenko, Ph.D.

VI Preface



Introduction-Interpretation of Histologic Sections

Fig. J Planes of Section of a Round Object 4
Fig. 2 Planes of Section of a Tube 4

Chapter 1 - Epithelial Tissue 7

Section J-Classification of Epithelial Tissue
Fig. J-J Simple Squamous Epithelium: Surface View of
Peritoneal Mesothelium ]0
Fig. J-2 Simple Squamous Epithelium: Peritoneal Mesothelium
(transverse section) 10
Fig. J-3 Simple Columnar Epithelium: Stomach JO
Fig. J-4 Simple Columnar Epithelium: Cells with Striated Borders and
Goblet Cells (small intestine) J2
Fig. ]-5 Stratified Squamous Epithelium: Esophagus
(transverse section) 12
Fig. ]-6 Pseudostratified Columnar Ciliated Epithelium:
Respiratory Passages 14
Fig. J-7 Transitional Epithelium: Bladder (contracted) J4
Section 2-Glandular Tissue
Fig. J-8 Unbranched Simple Tubular Exocrine Glands: Intestinal
Glands 18
Fig. ]-9 Simple Branched Tubular Exocrine Glands: Gastric Glands 18
Fig. ]-10 Coiled Tubular Exocrine Glands: Sweat Glands 20
Fig. ]-1 J Compound Acinar (Exocrine) Gland: Mammary Gland 22
Fig. J-12 Compound Tubuloacinar (Exocrine) Gland: Salivary Gland 24
Fig. ]-13 Endocrine Gland: Pancreas 24

Chapter 2 - Connective Tissue 27

Fig. 2-1 Loose Connective Tissue (spread) 30
Fig. 2-2 Individual Cells of Loose Connective Tissue (sections) 30
Fig. 2-3 Loose Connective Tissue 32
Fig. 2-4 Dense Irregular Connective Tissue 32
Fig. 2-5 Dense Regular Connective Tissue: Tendon
(longitudinal section) 34

Contents VII
Fig. 2-6 Dense Regular Connective Tissue: Tendon
(transverse section) 34
Fig. 2-7 Dense Irregular and Loose Connective Tissue (elastin stain) 36
Fig. 2-8 Adipose Tissue 36
Fig. 2-9 Embryonic Connective Tissue 36

Chapter 3 - Cartilage 39
Fig. 3-1 Fetal Hyaline Cartilage 40
Fig. 3-2 Mature Hyaline Cartilage 40
Fig. 3-3 Hyaline Cartilage of the Trachea 40
Fig. 3-4 Fibrous Cartilage: Intervertebral Disk 42
Fig. 3-5 Elastic Cartilage: Epiglottis 42

Chapter 4 - Bone 45
Fig. 4- J Compact Bone, Dried (transverse section) 48
Fig. 4-2 Compact Bone, Dried (longitudinal section) 48
Fig. 4-3 Compact Bone, Dried: An Osteon (transverse section) 50
Fig. 4-4 Cancellous Bone: Sternum (transverse section, decalcified) 52
Fig. 4-5 Intramembranous Ossification: Developing Mandible
(transverse section, decalcified) 52
Fig. 4-6 Endochondral Ossification: Developing Long Bone
(panoramic view, longitudinal section) 54
Fig. 4-7 Endochondral Ossification: Zone of Ossification 56
Fig. 4-8 Formation of Bone: Secondary (epiphyseal) Ossification
Centers (decalcified, longitudinal section) 58
Fig. 4-9 Formation of Bone: Development of Osteons (Haversian
Systems) (transverse section, decalcified) 60

Chapter 5 - Blood 63
Fig. 5-) Human Blood Smear 64
Fig. 5-2 Erythrocytes and Platelets 64
Fig. 5-3 Neutrophils 64
Fig. 5-4 Eosinophils 66
Fig. 5-5 Lymphocytes 66
Fig. 5-6 Monocytes 66
Fig. 5-7 Basophils 66
Fig. 5-8 Hemopoietic Bone Marrow of a Rabbit (section) 68
Fig. 5-9 Bone Marrow of a Rabbit, India Ink Preparation (section) 70
Fig. 5-10 Bone Marrow: Smear 72

Chapter 6 - Muscle Tissue 75

Fig. 6-J Smooth Muscle Layers of the Small Intestine 78
Fig. 6-2 Skeletal (Striated) Muscles of the Tongue 78

VII' Contents
Fig. 6-3 Cardiac Muscle 80
Fig. 6-4 Skeletal Muscle (longitudinal section) 80
Fig. 6-5 Cardiac Muscle (longitudinal section) 80
Fig. 6-6 Skeletal Muscle and Muscle Spindle (transverse section) 82
Fig. 6-7 Skeletal Muscle and Motor Endplates 82

Chapter 7 - Nervous Tissue 85

Fig. 7-1 Motor Neurons: Anterior Horn of the Spinal Cord 88
Fig. 7-2 Gray Matter: Anterior Horn of the Spinal Cord 88
Fig. 7-3 Fibrous Astrocytes of the Brain 90
Fig. 7-4 Oligodendrocytes of the Brain 90
Fig. 7-5 Microglia of the Brain 90
Fig. 7-6 Myelinated Nerve Fibers 92
Fig. 7-7 Peripheral Nerve (transverse section) 92
Fig. 7-8 Nerve: Sciatic (panoramic view, longitudinal section) 94
Fig. 7-9 Nerve: Sciatic (longitudinal section) 94
Fig. 7- J0 Nerve: Sciatic (transverse section) 94
Fig. 7-] 1 Nerve: Sciatic (longitudinal section) 94
Fig. 7-12 Nerve: Sciatic (transverse section) 94
Fig. 7-13 Nerve: Branch of the Vagus (transverse section) 94
Fig. 7-14 Dorsal Root Ganglion (panoramic view, longitudinal section) 96
Fig. 7- J5 Section of a Dorsal Root Ganglion 96
Fig. 7-J 6 Section of a Sympathetic Trunk Ganglion 96
Fig. 7-17 Spinal Cord: Cervical Region (transverse section) 98
Fig. 7-J 8 Spinal Cord: Anterior Gray Horn, Motor Neurons, and
Adjacent White Matter 98
Fig. 7-19 Spinal Cord: Midthoracic Region (transverse section) 100
Fig. 7-20 Spinal Cord: Anterior Gray Horn, Motor Neurons, and
Adjacent Anterior White Matter 100
Fig. 7-21 Cerebellum (sectional view, transverse section) 102
Fig. 7-22 Cerebellum: Cortex 102
Fig. 7-23 Cerebral Cortex: Section Perpendicular to the
Cortical Surface 104
Fig. 7-24 Central Area of the Cerebral Cortex 104


Chapter 8 - Circulatory System 109

Fig.8-J Blood and Lymphatic Vessels J 12
Fig. 8-2 Large Vein: Portal Vein (transverse section) 112
Fig. 8-3 Neurovascular Bundle (transverse section) J 14

Contents IX
Fig. 8-4 Large Artery: Aorta (transverse section) 114
Fig. 8-5 Heart: Left Atrium and Ventricle (panoramic view,
longitudinal section) 116
Fig. 8-6 Heart: Pulmonary Trunk, Pulmonary Valve, Right Ventricle
(panoramic view, longitudinal section) 118
Fig. 8-7 Heart: Purkinje Fibers (Impulse-conducting fibers) 118
Fig. 8-8 Heart: Purkinje Fibers (Impulse-conducting fibers) 118

Chapter 9 - Lymphoid System 121

Fig. 9-1 Lymph Node (panoramic view) 124
Fig. 9-2 Lymph Node (sectional view) 126
Fig. 9-3 Lymph Node: Reticular Fibers of the Stroma 126
Fig. 9-4 Lymph Node: Proliferation of Lymphocytes 128
Fig. 9-5 Palatine Tonsil 128
Fig. 9-6 Thymus Gland (panoramic view) 130
Fig. 9-7 Thymus Gland (sectional view) 130
Fig. 9-8 Spleen (panoramic view) 132
Fig. 9-9 Spleen: Red and White Pulp 132

Chapter 10 - Integument 135

Fig. 10- I Thin Skin 138
Fig. 10-2 Thick Skin, Palm: Superficial Layers 138
Fig. 10-3 Sweat Glands 140
Fig. 10-4 Skin: Scalp 142
Fig. 10-5 Sebaceous Gland and Adjacent Hair Follicle 144
Fig. 10-6 Bulb of Hair Follicle and Adjacent Sweat Gland 144
Fig. 10-7 Glomus in the Dermis of Thick Skin 144
Fig. 10-8 Pacinian Corpuscles in the Deep Dermis of Thick Skin 146

Chapter 11 - Digestive System: Tongue and Salivary 149

Fig. 11-1 Lip (longitudinal section) 150
Fig. 11-2 Tongue: Apex (longitudinal section, panoramic view) 152
Fig. 11-3 Tongue: Circumvallate Papilla (cross section) 154
Fig. 11-4 Tongue: Taste Buds 156
Fig. 11-5 Posterior Tongue Near Circumvallate Papilla (longitudinal
section) 158
Fig. 11-6 Lingual Tonsils (transverse section) 158
Fig. 11-7 Dried Tooth (panoramic view, longitudinal section) 160
Fig. 11-8 Dried Tooth: Layers of the Crown 160
Fig. 11-9 Dried Tooth: Layers of the Root 160
Fig. 11-10 Developing Tooth (panoramic view) 162

x Contents
Fig. 11-11 Developing Tooth (sectional view) 162
Fig. 11-J2 Salivary Gland: Parotid 164
Fig. 11-13 Salivary Gland: Submandibular 166
Fig. 11-14 Salivary Gland: Sublingual 168

Chapter 12 - Digestive System: Esophagus and Stomach 171

Fig. 12- I Upper Esophagus: Wall (transverse section) 174
Fig. 12-2 Upper Esophagus: Mucosa and Submucosa (transverse
section) 176
Fig. 12-3 Upper Esophagus (transverse section) 178
Fig. J2-4 Lower Esophagus (transverse section) 178
Fig. 12-5 Esophageal-Stomach Junction 180
Fig. 12-6 Stomach: Fundus and Body Regions (transverse section) 182
Fig. 12-7 Stomach: Mucosa of the Fundus and Body (transverse
section) 184
Fig. 12-8 Stomach: Superficial Region of the Gastric Mucosa 186
Fig. 12-9 Stomach: Deep Region of the Mucosa 186
Fig. 12-10 Stomach: Mucosa of the Pyloric Region 188
Fig. 12-11 Pyloric-Duodenal Junction (longitudinal section) J90

Chapter 13 - Digestive System: Small and Large Intestines 193

Fig. 13-1 Small Intestine: Duodenum (longitudinal section) 196
Fig. 13-2 Small Intestine: Jejunum-Ileum (transverse section) 198
Fig. 13-3 Intestinal Glands with Paneth Cells and Enteroendocrine
Cells 198
Fig. 13-4 Small Intestine: Ileum with Lymphatic Nodules (peyers Patch)
(transverse section) 200
Fig. J3-5 Small Intestine: Villi 200
Fig. 13-6 Large Intestine: Colon and Mesentery (panoramic view,
transverse section) 202
Fig. 13-7 Large Intestine: Colon Wall (transverse section) 204
Fig. 13-8 Appendix (panoramic view, transverse section) 206
Fig. 13-9 Rectum (panoramic view, transverse section) 208
Fig. J3-1 0 Anal Canal (longitudinal section) 210

Chapter 14 - Digestive System: Liver and Pancreas 213

Fig. 14-1 Pigs Liver (panoramic view, transverse section) 216
Fig. 14-2 Primate Liver (panoramic view, transverse section) 2J6
Fig. 14-3 Hepatic (Liver) Lobule (sectional view, transverse section) 218
Fig. 14-4 Liver: Kupffer Cells (India Ink Preparation) 218
Fig. J4-5 Liver: Bile Canaliculi (Osmic Acid Preparation) 218
Fig. 14-6 Mitochondria and Fat Droplets in Liver Cells (Altmanns stain) 220

Contents XI
Fig. 14-7 Glycogen in Liver Cells (Bests Carmine stain) 220
Fig. 14-8 Reticular Fibers in a Hepatic Lobule (Del Rio Hortegas stain) 220
Fig. 14-9 Gallbladder (panoramic view) 222
Fig. 14-10 Pancreas (sectional view) 224
Fig. 14-11 Pancreatic Islet 224
Fig. 14-12 Pancreatic Islet (special preparation) 224

Chapter 15 - Respiratory System 227

Fig. 15-1 Olfactory Mucosa and Superior Concha (panoramic view) 230
Fig. 15-2 Olfactory Mucosa: Detail of a Transitional Area 230
Fig. 15-3 Epiglottis (longitudinal section) 232
Fig. 15-4 Larynx (frontal section) 234
Fig. 15-5 Trachea (panoramic view, transverse section) 236
Fig. 15-6 Trachea (sectional view) 236
Fig. 15-7 Trachea: Elastic Fiber Stain (sectional view) 236
Fig. 15-8 Lung (panoramic view) 238
Fig. 15-9 Intrapulmonary Bronchus 240
Fig. 15-10 Terminal Bronchiole 240
Fig. I 5-1 1 Respiratory Bronchiole 240
Fig. 15-12 Alveolar Walls: Interalveolar Septa 240

Chapter 16 - Urinary System 243

Fig. 16-1 Kidney: Cortex and Pyramid (panoramic view) 246
Fig. 16-2 Kidney: Deep Cortical Area and Outer Medulla 248
Fig. 16-3 Kidney Cortex: Juxtaglomerular Apparatus 250
Fig. 16-4 Kidney Medulla: Papilla (transverse section) 252
Fig. 16-5 Kidney Medulla: Papilla Adjacent to a Calyx (longitudinal section) 252
Fig. 16-6 Ureter (transverse section) 254
Fig. 16-7 Ureter Wall (transverse section) 254
Fig. 16-8 Urinary Bladder: Wall (transverse section) 256
Fig. 16-9 Urinary Bladder: Mucosa (transverse section) 256

Chapter 17 - Endocrine System 259

Section 1-Hypophysis (pituitary Gland)
Fig. 17-1 Hypophysis (panoramic view, sagittal section) 262
Fig. 17-2 Hypophysis (sectional view) 262
Fig. 17-3 Hypophysis: Pars Distalis (sectional view) 264
Fig. 17-4 Hypophysis: Various Cell Groups 264

XII Contents
Section 2-Thyroid Gland, Parathyroid Gland, and Adrenal Gland
Fig. 17-5 Thyroid Gland: Canine (general view) 268
Fig. J7-6 Thyroid Gland Follicles: Canine (sectional view) 268
Fig. 17-7 Thyroid and Parathyroid Glands: Canine (sectional view) 270
Fig. J7-8 Adrenal (Suprarenal) Gland 272

Chapter 18 - Male Reproductive System 275

Fig. 18-1 Testis (sectional view) 278
Fig. 18-2 Seminiferous Tubules, Straight Tubules, Rete Testis, and
Ductuli Efferentes (Efferent Ductules) 278
Fig. 18-3 Primate Testis: Spermatogenesis in Seminiferous Tubules
(transverse section) 280
Fig. J8-4 Primate Testis: Stages of Spermatogenesis 280
Fig. 18-5 Ductuli Efferentes and Transition to Ductus Epididymis 282
Fig. 18-6 Ductus Epididymis 282
Fig. J8-7 Ductus Deferens (transverse section) 284
Fig. 18-8 Ampulla of the Ductus Deferens (transverse section) 284
Fig. 18-9 Prostate Gland with Prostatic Urethra 286
Fig. 18-10 Prostate Gland (sectional view, prostatic glands) 286
Fig. 18-1 ] Seminal Vesicle 288
Fig. J8-12 Bulbourethral Gland (sectional view) 288
Fig. 18-13 Penis (transverse section) 290
Fig. J8-14 Cavernous Urethra (transverse section) 290

Chapter 19 - Female Reproductive System 293

Section 1-0varies, Uterine Tubes, and Uterus
Fig. 19-1 Ovary: Dog (panoramic view) 296
Fig. ] 9-2 Ovary: Ovarian Cortex, Primary and Growing Follicles 298
Fig. 19-3 Ovary: Wall of a Mature Follicle 298
Fig. 19-4 Human Ovary: Corpora Lutea and Atretic Follicles 300
Fig. J9-5 Corpus Luteum (panoramic view) 302
Fig. 19-6 Corpus Luteum: Peripheral Wall 302
Fig. 19-7 Uterine Tube: Ampulla (panoramic view, transverse section) 304
Fig. J9-8 Uterine Tube: Mucosal Folds (Early Proliferative Phase) 304
Fig. 19-9 Uterine Tube: Mucosal Folds (Early Pregnancy) 304
Fig. 19-1 0 Uterus: Proliferative (Follicular) Phase 306
Fig. J9-J 1 Uterus: Secretory (Luteal) Phase 308
Fig. 19-12 Uterus: Menstrual Phase 310

Contents XII'
Section 2-CeNix, Vagina, Placenta, and Mammary Glands
Fig. 19-13 CeNix, CeNical Canal, and Vaginal Fornix (longitudinal
section) 314
Fig. 19-14 Vagina (longitudinal section) 316
Fig. 19-15 Glycogen in Human Vaginal Epithelium 316
Fig. 19-16 Vaginal Smears During Various Reproductive Phases 318
Fig. 19-17 Placenta at Five Months (panoramic view) 320
Fig. 19-18 Chorionic Villi: Placenta at Five Months 320
Fig. 19-19 Chorionic Villi: Placenta at Term 320
Fig. 19-20 Mammary Gland, Inactive 322
Fig. 19-21 Mammary Gland During First Half of Pregnancy 322
Fig. 19-22 Mammary Gland During Late Pregnancy 324
Fig. 19-23 Mammary Gland During Lactation 324
Chapter 20 - Organs of Special Senses 327
Fig. 20-1 Eyelid (sagittal section) 330
Fig. 20-2 Lacrimal Gland 332
Fig. 20-3 Cornea (transverse section) 332
Fig. 20-4 Whole eye (sagittal section) 334
Fig. 20-5 Retina, Choroid, and Sclera (panoramic view) 336
Fig. 20-6 Layers of the Choroid and Retina (detail) 336
Fig. 20-7 Inner Ear: Cochlea (vertical section) 338
Fig. 20-8 Inner Ear: Cochlear Duct (Scala Media) 338
h.s. - horizontal section
I.s. - longitudinal section
o.s. - oblique section
tg.s. - tangential section
t.s. - transverse section
v.s. - vertical section

Magnification of the Illustrations

Because the illustrations presented in this atlas are in the form of art, it is difficult to list
their exact magnification. To assist the student in this matter, however, four general ranges of
magnifications are listed for the illustrations in the atlas. These are as follows: low magnifi-
cation indicates that the final illustration is between lOX and 75X; medium magnification
indicates 75X to 250X; high magnification indicates 250X to 600X; and oil immersion indi-
cates magnification of over 600X.

XIV Contents
( Part One )


Interpretat of
Histologic Section
Histologic sections are thin,Zflat slices of fixed and stained tissues or organs
moVnfed on glass siides. These sections are normally composed of cellular,
fibrous, or tubular structures. The cells exhibit a variety of shapes, sizes, and lay-
ers. The fibrous structures are solid and are found in the connective, nervous, and
muscle tissues. The tubular structures are h'tllbW and represent various types of
blood vessels, ducts, and glands of the body.In the tissue or organ, the cells, fibers,nd
space and are parts of three-dimensional structures. The thin slices of histology
slides, however, do not have depth. In addition, the plane of section does not
always cut these structures exactly in the transverse or cross section. This pro-
duces a variation in the appearance of cells, fibers, and tubes, that depends on the
angle of the sectional plane. As a result of these factors, it is difficult on a flat
slide, to perceive correctly the three-dimensional structure from which the sec-
tions were prepared. Therefore, correct visualization and interpretation of these
sections in their, pr'6per three-dimensional persp~ctive becomes an important cri-
(teria for mastering histology
of tissues and organs on the histology slide, the first two figures of this atlas have
been especially prepared to illustrate how the appearance of cells and tubes
changes with the plane of section.

Introduction 3
Figure 1 Planes of Section of a Round Object

To illustrate how the shape of a three-dimensional cell can longitudinal (b) and transverse plane (e), still show the
be altered in a histologic section, a hard-boiled egg has been external shape of the egg. However, because the sections
sectioned in longitudinal and transverse (cross) planes. The were cut peripheral to the midline, the internal contents of
composition of a hard-boiled egg serves as a good example the egg are not seen in their correct size or distribution with-
of a cell, with the yellow yolk representing the nucleus and in the egg white. In addition, the size of the egg appears
the surrounding egg white representing the cytoplasm. smaller.
Enclosing these structures are the soft egg shell membrane The tangential planes (c and 1) of section graze or pass
and a hard egg shell (red). At the rounded end of the egg is through only the outermost periphery of the egg. These sec-
the air space (blue). tions reveal the egg as an oval (c) or a small, round (1) object.
The midline sections of the egg in the longitudinal (a) The egg yolk is not seen in either section because it was not
and transverse plane (d) disclose its correct shape and size, located in the plane of section. As a result, such tangential
as they appear in these planes of section. In addition, these sections do not reveal sufficient detail for correct interpreta-
two planes of section reveal the correct appearance, size, and tion of the egg's size, contents, or distribution of contents
distribution of the internal contents within the egg. within the internal membrane.
Similar but more peripheral sections of the egg in the

Figure 2 Planes of Section of a Tube

Tubular structures are often seen in histologic sections. duces a solid, multicellular, oval structure that does not
Tubes are most easily recognized when they are cut in trans- resemble a tube. This is because the plane of section grazed
verse (cross) sections. However, if the tubes are sectioned in the outermost periphery of the tube as the tube made a turn
other planes, they must be visualized as three-dimensional in space; the lumen was not present in the plane of section.
structures in order to be recognized as tubes. To illustrate An oblique (c) plane of section through the tube and its cells
how a blood vessel, duct, or glandular structure may appear produces an oval structure that includes an oval lumen in the
in a histologic section, a curved tube with a simple (single) center and multiple cell layers at the periphery.
epithelial cell layer is sectioned in longitudinal, transverse, A transverse (1) section in the region of a sharp curve in
and oblique planes. the tube grazes the innermost cell layer and produces two
A longitudinal (a) plane of section that cuts the tube in oval structures connected by a multiple, solid layer of cells
the midline produces a U-shaped structure. The sides of the (f). These sections of the tube also contain an oval lumen,
tube are lined by a single row of cuboidal (round) cells indicating that the plane of section passed at an angle to the
around an empty lumen except at the bottom, where the tube structure.
begins to curve; in this region the cells appear multilayered. Thus, in a histologic section, individual structure shape
Transverse (d and e) planes of section of the same tube and size may vary, depending on the plane of section. Some
produce round structures lined by a single layer of cells. The cells may exhibit full cross sections of their nuclei and they
variations that are seen in the cytoplasm of some cells are appear prominent in the cells. Other cells may exhibit only a
due to the planes of section through the individual cells, as fraction of the nucleus and the cytoplasm appears large. Still
explained above. A transverse section of a straight tube can other cells may appear only as clear cytoplasm, without any
produce a single image (e). The double image (d) of the same nuclei. All of these variations are due to varying the plane of
structure can represent either two tubes running parallel to section through the nuclei. Understanding these variations in
each other or a single tube that has curved within the space cell and tube morphology will result in a better interpretation
of the tissue or organ that is sectioned. of histologic sections.
A tangential (b) plane of section through the tube pro-

4 Tissues
Fig. 1. Planes of Section of a Round Object

Fig. 2. Planes of Section of a Tube

Introduction 5

Epithelial Tissue

Section 1 Classification of Epithelial Tissue

There are four basic tissue types in the body: epithelial, The simple cuboidal epithelium consists of cells that are
connective, muscular, and nervous. These tissues exist and as tall as they are wide. Its function is primarily secretory or
function in close association with one another in the organs. absorptive (for example, in the proximal and distal convolut-
The epithelial tissue, or epithelium, consists of sheets of ed tubules in the kidneys).
cells. These cells form glands and line all body surfaces, cav- The simple columnar epithelium consists of cells that are
ities, and ducts. The classification of the epithelium is based taller than they are wide. In the small intestine, the cells
on (1) the number of cell layers, and (2) the morphology of exhibit a striated border (microvilli) and their major function
the surface cells. Based on these criteria, the simple epitheli- is absorption of fluids and nutrients. Some simple columnar
um consists of a single layer of cells; pseudostratified epithe- epithelial cells are secretory, such as the mucous cells of the
lium consists of a single layer of cells in which all cells stomach, intestines, trachea, and bronchi, and the secretory
attach to the basement membrane, but not all cells reach the cells of the oviduct and uterus.
surface; and stratified epithelium consists of two or more cell The pseudostratified columnar epithelium in the respira-
layers. tory passages is ciliated, and its major function is to clean the
The epithelium is normally separated from the connective respiratory passages by moving mucus and dust particles
tissue by a basement membrane. The epithelium is non-vas- across cell surfaces to the exterior. In the epididymis, this
cular; that is, there are no blood vessels within the epitheli- epithelium is lined by stereocilia whose main function is to
um itself. As a result, oxygen, nutrients, and metabolites absorb t1uids secreted in the testes.
must diffuse from the blood vessels that supply the underly-
ing connective tissue. Stratified Epithelia
Some epithelial tissue has cilia, stereocilia, or microvilli The stratified squamous epithelium contains numerous
on its free surfaces. The cilia are motile and function to trans- cell layers. The basal cells are cuboidal to columnar in shape;
port material across the ciliated cell surfaces. Ciliated epithe- these give rise to cells that migrate toward the free surface
lium is found on the cells of the uterine tubes and in most of and become squamous.
the respiratory passages. The stereocilia, on the other hand, There are two types of stratified squamous epithelia:
are long, non-motile, branched microvilli found on the sur- nonkeratinized and keratinized. The nonkeratinized type
face of cells in the epididymis. The microvilli usually are vis- exhibits live superficial cells with nuclei. It lines the moist
ible as striated brush borders on the epithelium of the small cavities of the mouth, pharynx, esophagus, vagina, and anal
intestine and on the proximal convoluted tubules of the kid- canal. The multilayered composition of this epithelium is
ney. The main function of microvilli and stereocilia is well adapted to withstand wear and tear or abrasion in these
absorption. regions of the body. The keratinized type, which lines the
skin, contains nonliving, cornified superficial cells made of
Simple Epithelia the protein keratin. The major function of the keratinized
The simple squamous epithelium is common in the body epithelium is to protect the body from abrasion, desiccation,
and consists of a single layer of irregular, flattened, or squa- bacterial invasion, and other insults.
mous cells. The simple squamous layer of cells lining the The stratified cuboidal epithelium and stratified columnar
cardiovascular system and lymphatic vessels is called the epithelium have limited distribution in the body. Both types
endothelium. The epithelium in the lining of the peritoneal, are found in the ducts of larger glands: the pancreas, the sali-
pleural, and pericardial cavities is called the mesothelium. vary glands, and the sweat glands. In the ducts of these
The cells of the simple epithelium are extremely thin. As glands, the epithelium usually consist of two or three layers
a result, its main functions are to allow passive transport of of cells. The main function of the epithelium in these ducts is
fluids, nutrients, or metabolites across capillary walls, or also protection.
gases across the alveoli in the lungs. The transitional epithelium is designed to change shape

Epithelial Tissue 7
Figure 1-1 Simple squamous Epithelium: Surface View of peritonea'

To visualize the surface of the simple squamous epitheli- characteristic mosaic pattern. The blue-gray cell nuclei (2)
um, a small piece of mesentery was fixed and treated with exhibit a central location in the yellow- to brown-stained
silver nitrate and counterstained with hematoxylin. The cells cytoplasm (3).
of the simple squamous epithelium (mesothelium) appear The simple squamous epithelium is common in the body.
flat, adhere tightly to each other, and form a sheet with the It is found lining the surfaces that allow passive transport of
thickness of a single cell layer. The irregular cell boundaries gases or fluids, and lining the pleural, pericardial, and peri-
(1) are highly visible because of silver deposition and form a toneal cavities.

Figure 1-2 Simple Squamous Epithelium: Peritoneal Mesothelium

,transverse section)

Examination of the simple squamous epithelium, the Mesothelium and the underlying connective tissue (4)
mesothelium (1) of jejunum, in transverse section, illustrates form the serosa of the peritoneal cavity, which is the outer-
that the cells are spindle-shaped with prominent, oval nuclei. most layer of the jejunal wall. Serosa is attached to the mus-
Cell boundaries are not seen distinctly but are indicated at cularis externa, which consists of smooth muscle fibers (6).
cell junctions (2). A thin basement membrane (3) is In the connective tissue are small blood vessels, lined by a
observed under the mesothelium (1). In surface view, these simple squamous epithelium called the endothelium (5).
cells appear similar to those illustrated in Figure 1-1.

Figure 1-3 Simple Columnar Epithelium: Stomach

In a simple columnar epithelium (2), as seen on the sur- The surface cells of the stomach secrete mucus, which
face of the stomach, the cells are arranged in a single row. protects the stomach lining from its acidic contents. The pale
Their ovoid nuclei (7) are located in the basal region and appearance of the cell cytoplasm in these cells is due to the
exhibit a perpendicular orientation. A thin basement mem- routine preparation of the tissues. The mucigen droplets that
brane (3) separates the epithelium from the underlying con- filled these cell apices (9) were lost during section prepara-
nective tissue (4, 10), the lamina propria of the gastric tion. The more granular cytoplasm is located basally (8) and
mucosa. Small blood vessels (5), lined with endothelium, are stains more acidophilic.
seen in the connective tissue. Examples of other columnar epithelia may be seen in the
In some areas the epithelium has been sectioned trans- lining of the gallbladder (Fig. 14-9:14); in salivary gland
versely or obliquely. When a plane of section passes close to ducts (Fig. 11-12:4, IV; Fig. 11-13:17, IV); in bile ducts of
the free surface of the epithelium, the sectioned apical the liver (Fig. 14-3:7, 14).
regions (1) of these cells resemble a mosaic of enucleated A simple cuboidal epithelium is illustrated in the smallest
polygonal cells. When a plane of section passes through ducts of the pancreas (Fig. 11-14) and in the follicles of the
basal regions (6) of the epithelial cells, the nuclei are cut thyroid gland (Fig. 17-5:3; Fig. 17-6:5).
transversely and resemble a stratified epithelium.

10 Tissues
Epithelial Tissue

2 Nuclei (2)

Fig. 1-1 Simple Squamous Epithelium: Surface View of Peritoneal Mesothelium. Stain: silver
nitrate with hematoxylin. High magnification.

, ... ,
5 Endothelium in venule
and arteriole

6 Smooth muscle It.s.)

Fig. 1-2 Simple Squamous Epithelium: Peritoneal Mesothelium (transverse section). Stain:
hematoxylin-eosin. High magnification.

5 Capillaries (t.s. and I.s.}

1 Apices of
epithelium It.s.)

6 Nuclei of epithelium

2 Columnar epithelium
(I.s.) 7 Nuclei of columnar
epithelial cells (I.s.)
3 Basement membrane
8 Basal cytoplasm

4 Connective tissue
(lamina propria) =- 9 Apical cytoplasm

-10 Connective tissue

11 Connective
" tissue cells

Fig. 1-3 Simple Columnar Epithelium: Stomach. Stain: hematoxylin-eosin. Medium magnification.

Epithelial Tissue 11
Figure 1-4 Simple Columnar Epithelium: Cells with Striated Borders and
Goblet Cells (small intestine)

The intestinal villi (1) are lined by simple columnar the cell apices and the nucleus remains in the basal region of
epithelium, which consists of two types of cells: columnar the cytoplasm (8).
cells with striated borders (2, 13) and goblet cells (8, 12). The epithelium at the tip of the villus in the lower center
The striated border (13) is seen as a reddish outer membrane of the figure has been sectioned in an oblique plane. As a
with faint vertical striations; these are the microvilli on the result, the apices of the columnar cells appear as a mosaic (7)
apices of the columnar cells. In an area of contiguous cells, of enucleated cells while the basal regions, where the plane
the striated border appears continuous. The cytoplasm of of section passed through the nuclei, appear stratified (7).
these cells is finely granular and the oval nuclei are in the The basement membrane (5) is more visible in this illus-
basal portions of the cells. tration than in Figure 1-3. Visible in the connective tissue
The goblet cells (8, 12) are interspersed among the colum- (the lamina propria) (10) are a lymphatic vessel, the central
nar cells. During routine histologic preparation, the mucus is lacteal (3), a capillary (9) lined with endothelium, and
lost; hence, the goblet cell cytoplasm appears clear or only smooth muscle fibers (4, 11), seen as either single fibers or
lightly stained (12). Normally, the mucigen droplets occupy a small group of fibers.

Figure 1-5 Stratified Squamous Epithelium: Esophagus (transverse section)

The'stratified squamous epithelium is composed of surface of the epithelium (I), giving it a characteristic wavy
numerous cell layers. Its thickness varies among the regions appearance. The connective tissue contains collagen fibers
of the body and, as a result, the cell arrangement is altered. (11), fibroblasts (10), capillaries (6, 9, 14) and arterioles
Illustrated in this figure is an example of a moist, nonker- (13). Other examples of moist stratified squamous epitheli-
atinized epithelium (1), which lines the oral cavity, esopha- um may be seen in Figures 11-3, 12-1, 12-2, 19-16, and
gus, vagina, and anal canal. The basal cells (5) are cuboidal I9- I7 .
or low columnar. The cytoplasm is finely granular and the When stratified squamous epithelium is exposed to
oval, chromatin-rich nucleus occupies most of the cell. Cells increased wear and tear, the outermost layer, the stratum
in the intermediate layers are polyhedral (4) with round or corneum, becomes thick and keratinized, as illustrated in the
oval nuclei and more visible cell membranes. Mitoses (7) are epidermis of the palm in Fig. 10-2.
frequently observed in cells of the deeper layers and in the An example of thin, stratified squamous epithelium with-
basal cells. Above the polyhedral cells are several rows of out connective tissue papillae indentation is illustrated in the
squamous cells (3). Cells and nuclei become progressively cornea of the eye, Figure 20-3; the surface underlying the
flatter as the cells migrate toward the free surface. epithelium is smooth. This type of epithelium is only a few
A fine basement membrane (8) separates the epithelium cell layers thick but shows the characteristic arrangement of
(1) from the underlying connective tissue, the lamina pro- basal columnar, polyhedral, and squamous cells, the most
pria (2). Papillae (12) of connective tissue indent the lower superficial cells on the cornea.

12 Tissues
Epithelial Tissue

8 Goblet cell: basal nucleus

and cytoplasm

9 Capillary

10 Connective tissue
(lamina propria)

- 11 Smooth muscle fibers


- 12 Goblet cell

- 13Striatedborder

Fig. 1-4 Simple Columnar Epithelium: Cells with Striated Borders and Goblet Cells (Small
Intestine). Stain: hematoxylin-eosin. Medium magnification.

3 Squamous cells

4 Polyhedral cells
1 Epithelium

5 Basal cells

6 Capillary
7 Mitoses

2 Connective tissue
(lamina propria)
, 8 Basement membrane
9 Capillary (t.s.)

14 Capillary (I.s.)

Fig. 1-5 Stratified Squamous Epithelium: Esophagus (transverse section). Stain: hematoxylin-
eosin. Medium magnification.

Epithelial Tissue 13
figure 1-6 Pseudostratified Columnar Ciliated Epithelium:
Respiratory Passages

The pseudostratified columnar ciliated epithelium (1) The short, motile cilia (3) are numerous and closely
is characteristic of the upper respiratory passages such as the spaced at the cell apices. Each cilium arises from a basal
trachea and variously sized bronchi. In this epithelium, the body (4), which is identical to the centriole. The basal bod-
cells appear in several layers because their nuclei are at dif- ies are located beneath the cell membrane and adjacent to
ferent levels. Serial sections show that all cells reach the each other; they often give the appearance of a continuous
basement membrane (8); however, because the cells are of membrane (4).
different shapes and heights, not all reach the surface. For The clearly visible basement membrane (8) separates
this reason this type of epithelium is called pseudostratified the surface epithelium (1) from the underlying connective
rather than stratified. tissue of the lamina propria (2, 11).
The deeper nuclei belong to the intermediate and short Visible in the connective tissue (11) are collagen fibers,
basaf ceffs (1). The more superficial, oval nuclei belong to cells (fibroblasts), scattered lymphocytes, and small blood
the columnar ciliated cells (5). Interspersed among these vessels (10). Deeper in the connective tissue are found
cells are goblet cells (6). The small, round, heavily stained glands with serous acini (12) and mucous acini (13).
nuclei, without any visible surrounding cytoplasm, are those Other examples of pseudostratified columnar ciliated
of lymphocytes (9), which migrate from the connective tis- epithelium are seen in Figures 15-2, 15-3, and 15-6.
sue through the epithelium.

Figure 1-7 Transitional Epithelium: Bladder 'contracted)

The transitional epithelium (2) is found exclusively in ogy differentiates this epithelium from stratified squamous
the excretory passages of the urinary system. It lines the epithelium, in which cells of various layers have different
renal calyces, pelvis, ureters, and bladder. This stratified shapes.
epithelium is composed of several cell layers of similar cells, Transitional epithelium (2) rests on a connective tissue
and changes its shape in response to stretching or contraction (4, 10) layer, composed primarily of cells, the fibroblasts
during the passage of urine. In relaxed, unstretched condi- (lOa) and collagen fibers (lOb). Between the connective tis-
tion, the surface cells (8) are usually cuboidal and bulge out. sue (4, 10) and the transitional epithelium (2) a thin base-
Frequently, binucleate (two nuclei) cells (1, 7) are visible in ment membrane (3, 9) is visible. The base of the epithelium
the superficial or surface cells (8) in the bladder. When the is not indented by connective tissue papillae, and it exhibits
transitional epithelium (2) is distended or stretched, the num- an even contour. Small blood vessels (venules) (5) and
ber of cell layers is reduced. The cells in the outer layers are arterioles (11) of various sizes are present in the connective
then more elongated or flattened, but not to the degree seen tissue (4, 10). Visible deeper in the connective tissue are
in squamous epithelium. In the stretched condition, the tran- strands of smooth muscle fibers (6, 12), sectioned in differ-
sitional epithelium may resemble stratified squamous epithe- ent planes, from muscle layers that are located below the
lium found in other regions of the body. (Compare transi- connective tissue (4, 10).
tional epithelium with stratified squamous epithelium of the Other examples of transitional epithelium are illustrated
cornea, Fig. 20-3.) However, the similarity in cell morphol- in Chapter 16, Figures 16-6 to 16-9.

14 Tissues
Epithelial Tissue

3 Cilia
4 Basal bodies
5 Columnar ciliated cell

1 Epithelium 6 Goblet cell

7 Basal cells (nuclei)

8 Basement membrane

9 Migrating lymphocytes
10 Venule
11 Connective tissue
2 Connective tissue
(lamina propria)

12 Serous acinus

13 Mucous acinus

Fig. 1-6 Pseudostratified Columnar Ciliated Epithelium: Respiratory Passages. Hematoxylin-

eosin. High magnification.

1 Binucleate cell 7 Binucleate cell

8 Surface cell

2 Transitional
9 Basement
3 Basement

4 Connective 10 Connective tissue

tissue a. Fibroblast
b. Collagen fibers
5 Venule

11 Arterioles

12 Smooth muscle
6 Smooth muscle fibers (longitudinal
fibers (cross section) section)

Fig. 1-7 Transitional Epithelium: Bladder (Contracted). Stain: hematoxylin-eosin. High


Epithelial Tissue 15
Section 2 Glandular Tissue

The body contains a variety of glands. They are classified tory products of their cells. Glands that contain cells which
as either exocrine glands or endocrine glands. The cells or produce a viscous secretion that lubricates and/or protects
parenchyma of these glands develop from epithelial tissue. inner lining of organs are mucous glands. Glands with cells
Exocrine glands secrete their products into ducts, whereas that produce watery secretions that are often rich in enzymes
endocrine glands deliver their secretory products into the cir- are serous glands. ~n glands in the body contain a mix-
culatory system. ture of both mucous and serous secretory cells; these are the
The figures on the pages that follow illustrate the mor- mixed glands (Figs. 1-12A and l-12B).
phology of various glands. The figures on the left are dia- The exocrine glands may also be classified according to
grams of the glands and those on the right illustrate examples the method of discharging their secretory product. The
of their histology. 2fJ.ine...glands release their secretion by exocytosis with-
out any loss of cellular components. Most exocrine glands in
Simple Tubular Exocrine Glands the body secrete their product in this manner. In holocrine
glands, the cells themselves become the secretory product.=--
There are unicellular and multicellular exocrine glands.
The unicellular glands consist of single cells. The mucus- These gland cells accumulate lipid, die, and degenerate to
secreting ~bl~t cells found in the epithelia of the small or become sebum in the sebaceous gla nds of the skin. In the
large intestines or in the respiratory passages are the best intermediate type, apocrine, it was believed that parts of the
examples of unicellular glands. cell was discharged as the secretory product. Almost all
The multicellular glands are characterized by a secretory glands that were once classified apocrine are now regarded
portion, an end-piece where the epithelial cells secrete a as merocrine glands.
product, and an epithelium-lined ductal portion, through
which the secretion from the secretory regions is delivered to Endocrine Glands
the exterior of the gland. ~ger ducts are usually lined_by The endocrine glands differ from the exocrine glands in
tified epithelium. that they do not have ducts to'€~vey their secretory products
Multicellular exocrine glands are divided into two major out of the organ. Instead, such glands are ductless, highly
categories, depending on the structure of their ductal portion. vascularized, and the secretory cells are surrounded by rich
A simple exocrine gland exhibits an unbranched duct, capillary networks. The close proximity of the secretory cells
which may be straight or coiled. Also, if the terminal secre- to the capillaries allows the release of the secretory products
tory portion of the gland is shaped in a form of a tube, the into the blood stream and their distribution to different
gland is called aJ,ubular gland (Figs. 1-8 to 1-10). organs by way of the systemic circulation (Figs. 1-13A and
Coihp~E~ocrine Glands The endocrine glands can be represented by individual
An exocrine gland that shows a repeated branching pat- cells (unicellular glands) in certain organs, as endocrine tis-
tern of the ducts that drain the secretory portions is called a sue in larger exocrine glands that are mixed glands
compound exocrine gland. Furthermore, if the secretory (endocrine and exocrine glands), or as separate and distinct
portions of the gland are shaped in a form of a flask or a tube, endocrine organs. Examples of individual endocrine cells
the glands are called acinar (alveolar) glands or tubular can be found in the digestive organs as part of the enteroen-
glands, respectively. Certain exocrine glands exhibit a mix- docrine cells. Endocrine tissues can be seen in such mixed
ture of both tubular and acinar secretory portions. Such glands as the pancreas and the reproductive organs of both
glands are called tubuloacinar glands (Figs. 1-11 and sexes. The endocrine tissues or glands are characterized by
1-12). the absence of excretory ducts and by increased vascularity
Exocrine glands may also be classified based on the secre- around the cells.

Epithelial Tissue 17
Figure 1-8 Unbranched Simple Tubular Exocrine Glands: Intestinal Glands

Jffcc<7t7cked simple tubular glands that do not have excre- glands are lined with numerous goblet cells; these represent
tory ducts are best represented by the intestinal glands the unicellular exocrine glands. Similar but shorter intestinal
(crypts of Lieberkiihn) in the large intestine (Figs. I-SA glands are found in the small intestine (Fig. 13-1); these
and I-SB) and rectum. The surface epithelium and the glands also contain goblet cells.

Figure 1-9 Simple Branched Tubular Exocrine Glands: Gastric Glands

The simple or slightly branched tubular glands without highly specialized for secreting hydrochloric acid and the
ducts are found in the stomach. These are the gastric glands precursor for the proteolytic enzyme pepsin (Figs. 12-6,
(Figs. 1-9A and 1-9B). In the fundus and body of the stom- 12-7).
ach, they are lined with modified columnar cells that are

18 Tissues
Simple Tubular Exocrine Glands


Epithelial Tissue 19
Figure 1-10 Coiled Tubular Exocrine Glands: Sweat Glands

Coiled tubu]ar glands with long, unbranched ducts are duct that delivers the secretory product to the skin surface is
found in the skin (Figs. 10-3; 10-4); these are the sweat lined by a stratified cuboidal epithelium.
glands (Figs. I-lOA and I-lOB). Note that the excretory

20 Tissues
Simple Tubular Exocrine Glands

A ~
Fig. 1-10 Coiled Tubular Exocrine Glands: Sweat Glands. (A) Diagram of gland. (B) Cross
section. Stain: hemotoxylin-eosin. Medium magnification.

Epithelial Tissue 21
Figure 1-11 Compound Acinar (Exocrine) Gland: Mammary Gland

The mammary gland is a good example of compound filled with milk products. Draining these acini (alveoli) are
acinar (alveolar) gland (Figs. l-11A and I-lIB; Figs. excretory ducts, some of which contain secretory products
19-22, 19-23). The lactating mammary gland contains and are lined by stratified epithelium.
enlarged secretory acini (alveoli) with large lumina that are

22 Tissues
Exocrine Glands

1h..~~", ,..1",:

Fig. 1-11 Compound Acinar (Exocrine) Gland: Mammary Gland. (A) Diagram of gland. (B)
During lactation. Stain: hematoxylin-eosin. Left: Low magnification. Right: medium magnification.

Epithelial Tissue 23
frgure 1-12(:mpound Tubuloacinar (Exocrine) Gland: Salivary Gland

The histology of major salivary glands (parotid, sub- of serous and mucous acini are described in detail on pages
mandibular, and sublingual) are best examples of compound 164-166 and are present in glands illustrated in Figures
tubuloacinar glands (Figs. 1-12A and 1-12B; Figs. 11-12 11-12 to 11-14. Ducts are distinct structures in the salivary
to 11-14). The secretory elements of these glands are shaped glands. They are lined with cuboidal, columnar or stratified
in the form of acini and tubes. In addition, the submandibu- epithelium, and are named according to their location in the
lar and sublingual salivary glands contain two major types of gland.
secretory acini: serous and mucous. Details and comparisons

Figure 1-13 Endocrine Gland: Pancreatic islet

An example of the endocrine gland is illustrated as a pan- The structure and function of other endocrine organs
creatic islet from the pancreas. This organ is a mixed gland, (glands) are presented in greater detail and illustrated in
containing exocrine and endocrine portions. Note that in the Chapter 17.
illustration the exocrine acini surround the endocrine islet
(Figs. 1-13A and 1-13B).

24 Tissues
Exocrine and Endocrine Glands

Fig. 1-12 Compound Tubuloacinar (Exocrine) Gland: Salivary Gland. (A) Diagram of gland.
(B) Submandibular salivary gland. Stain: hematoxylin-eosin. Low magnification.

(A) Diagram of gland. (B) High magnification.

Epithelial Tissue 25

Connective Tissue

With the exceptions of blood and lymph, the connective ies (immunoglobulins) into circulation, aiding the body in its
tissue consists of cells and of extracellular material, known defense against bacterial infections.
as the matrix. The matrix, in turn, consists of connective tis- The white blood cells, or leukocytes, migrate into the con-
sue fibers, ground substance, and tissue fluid. The main func- nective tissue from the blood vessels. Their main function is
tion of the connective tissue is to bind, anchor, and provide to defend the organism against bacterial invasion or the pres-
support for various body parts and organs. ence of foreign material. The neutrophils are active phago-
cytes, found in great numbers at the sites of bacterial invasion
Cells of the Connective Tissue and infection. They readily engulf and destroy bacteria at
The connective tissue comprises a variety of cell types these sites. The eosinophils increase in number following par-
that perform different functions. The fusiform-shaped fibro- asitic infections or allergic reactions. Their main function is
blasts are the most common connective tissue cells; these the phagocytosis of antigen-antibody complexes formed dur-
cells are young and exhibit synthetic activity. The main func- ing allergic reactions. The basophils are filled with basophilic
tion of the fibroblasts is to synthesize collagen; reticular and granules, which contain heparin and histamine. Their function
elastic fibers, and the extracellular matrix. The fibrocytes are is similar to that of the mast cells; they respond to antigens by
mature cells and are smaller than the fibroblasts. liberating histamine and inducing an inflammatory response.
The adipose (fat) cells store fat and may occur singly or in The lymphocytes are most numerous in the respiratory and
groups. When adipose cells predominate, the tissue is called gastrointestinal tracts. Their main function is to respond to
adipose tissue. In addition to storing fat, the adipose cells invasion of pathogens and foreign material. The lymphocytes
provide protective packing material in and around numerous mediate immune responses to antigens.
organs. The fibroblasts and the adipose cells are permanent con-
nective tissue cells. On the other hand, leukocytes, plasma
The macrophages, or histiocytes, are numerous in the con-
cells, mast cells, and macrophages are cells that migrate into
nective tissue regions, especially in the loose connective tis-
and take residence in the connective tissue regions.
sue. In fact, macrophages may resemble the fibroblasts.
Macrophages are phagocytic and their main function is to Fibers of the Connective Tissue
ingest bacteria, cell debris, and other foreign matter in the
There are three types of connective tissue fibers: collagen,
connective tissue.
elastic, and reticular. The amount, arrangement, and concen-
The mast cells are spherical to ovoid cells filled with fine,
tration of these fibers varies depending on the function of the
dark-staining granules. These cells are widely distributed in
tissues or organs.
the connective tissue of the skin and the digestive and respi-
The collagen fibers are most abundant and are found in
ratory organs, and usually are closely associated with blood
almost all types of connective tissue. They exhibit great ten-
vessels. The main function of the mast cells is to synthesize sile strength and are most highly concentrated in those areas
and release heparin and histamine. Heparin from human mast of the body where strong support is needed. Collagen fibers
cells is a weak anticoagulant of the blood. Histamine is a do not branch.
potent mediator of inflammation: it dilates blood vessels, The elastic fibers are thin and small, exhibit branching,
increases their permeability to fluid, and produces edema. and have less tensile strength than the collagen fibers. When
The plasma cells are numerous in the connective tissue stretched, they return to their original size (recoil) without
regions of the respiratory and digestive tracts. Because the deformation. The elastic fibers are found in the lung, bladder,
plasma cells arise from the lymphocytes that migrate into the and skin, as well as in the elastic cartilages of such large
connective tissue, they are found in great abundance in the blood vessels as the aorta, where stretching without breaking
connective tissue and lymphatic tissue of the body. The main or distortion is essential for proper function of the organs.
function of plasma cells is to synthesize and secrete anti bod- The reticular fibers are thin and form a delicate net-like

Connective Tissue 27
framework in the liver, lymph nodes, spleen, hemopoietic axis. Dense regular arrangement of fibers is best seen in the
organs, and others. They provide support for capillaries, tendons that surround the muscles and ligaments that attach
nerves, and muscle cells. These fibers normally are not visi- bones. These organs are constantly subject to strong pulling
ble with histologic stains unless they are stained with silver. forces.

Classification of Connective Tissue The Ground Substance

The connective tissue is normally divided into loose con- The ground substance in the connective tissue is an amor-
nective tissue and dense connective tissue, depending on the phous, transparent, colorless material with the properties of a
amount, type, arrangement, and abundance of cells, fibers, semi-fluid gel and high water content. It surrounds the cells
and ground substance. and fibers of, and provides structural support for, the con-
The loose connective tissue is more abundant in the body. nective tissue. The ground substance mainly consists of gly-
It is characterized by a loose, irregular arrangement of vari- cosaminoglycans and glycoproteins. Hyaluronic acid is the
ous fibers, and may contain all types of connective tissue principal glycosaminoglycan.
cells in its matrix. Although reticular and elastic fibers may The ground substance facilitates diffusion of oxygen,
be present, collagen fibers, fibroblasts, and macrophages pre- electrolytes, nutrients, fluids, metabolites, and other products
dominate. between the cells and the blood vessels. Waste products from
In contrast, the dense connective tissue contains thicker the cells diffuse through the ground substance back into the
and more densely packed collagen fibers. As a result, there blood vessels. The ground substance also serves as a barrier:
are fewer cell types present and less ground substance. In it prevents the spread of pathogens from the connective tis-
dense irregular connective tissue, the collagen fibers have a sue into the bloodstream. However, certain bacteria produce
random orientation and, therefore, can resist pulling forces hyaluronidase, an enzyme that hydrolyzes hyaluronic acid
from all directions. Dense irregular connective tissue is pre- and reduces the viscosity of the ground substance, allowing
sent in the skin, in capsules of different organs, and in other pathogens to invade the surrounding tissues.
areas where strong support is needed. Dense regular connec- The density of ground substance varies depending on the
tive tissue exhibits a dense packing of collagen fibers in a amount of tissue fluid or water content. Mineralization of
characteristically parallel arrangement. As a result, these ground substance changes its density, rigidity, and perme-
fibers offer strong resistance to forces pulling along a single ability to diffusion, as seen in cartilage and developing bone.

28 Tissues

Figure 2-1 Loose Connective Tissue (spread)

Figure 2-2 Individual Cells of Connective Tissue (sections)

Connective Tissue 29
Figure 2-1 Loose Connective Tissue (spread)

The plate illustrates subcutaneous connective tissue from histiocytes (4, 11, II), are always present in varying num-
a rat, stained by injection of a dilute solution of neutral red in bers. When inactive, the macrophages appear similar to
saline. This solution not only permits the tissue elements to fibroblasts, although their processes may be more irregular
remain in their natural state but also separates them farther and their nuclei smaller. Phagocytic inclusions, however,
from each other than would be seen under normal conditions give the cytoplasm of the macrophages a different appear-
or when prepared in histologic sections. Fibers and cells thus ance. In the illustration, the phagocytic vacuoles in the cyto-
aTeTeaGi\y ioentified. plasm are filled with neutral red (small vacuoles in 4, larger
The unstained collagen fibers (2, 9) are thickest, largest, vacuoles in 11 and II: 17).
and the most numerous. These fibers course in all directions, Mast cells (7, III) are generally present in loose connec-
are thick and somewhat wavy, and exhibit faint longitudinal tive tissue; they are seen either as single cells or grouped
striations (parts of their component fibrils). along small blood vessels (7). They are usually ovoid, with a
The elastic fibers (1, 10) are thin, fine, single fibers that small, pale, centrally placed nucleus (18) and cytoplasm
are usually straight; however, after a section is cut, the fibers filled with fine, closely packed granules (7, 19, III) that
may become wavy because of release of tension. Elastic stain deep red with neutral red stain.
fibers form branching and anastomosing networks. Although Present also are groups of adipose (fat) cells (3). Each
unstained, the fibers are highly refringent, an appearance in cell is a spherical, colorless globule; the small, eccentric
contrast to the dull appearance of collagenous fibers. nucleus is not visible.
The fine reticular fibers are also present in loose connec- Blood and other connective tissue cells may also be seen
tive tissue but are not included in this illustration. in small numbers. These cells are not stained with neutral
The fixed permanent cells of this and other connective tis- red; however, eosinophils (5) may be identified by lobulated
sues are the fibroblasts (8, I). In this preparation, the fibro- nuclei and coarse, cytoplasmic granules. In the small round
blasts (8) are illustrated as flattened, branching cells with an lymphocytes (6), the nucleus occupies most of the cell.
oval nucleus in which chromatin is sparse but one or two The faint background stain is the ground substance, which
nucleoli (14, 15) may be present. Fixed macrophages, or has been infiltrated with injected fluid.

Figure 2-2 Individual Cells of Connective Tissue (sections)

This figure illustrates some cells of loose connective tis- lymphocytes have condensed chromatin clumps but no nu-
sue as they appear in histologic sections after fixation and cleoli.
hematoxylin-eosin staining. The plasma cells (6) are distinguished from large lym-
The free macrophages (1) usually appear round with phocytes (4) by a smaller, eccentrically placed nucleus with
slightly irregular cell outlines. Macrophages are variable in condensed, coarse chromatin clumps distributed in a charac-
appearance: in the illustration, the macrophage exhibits a teristic radial pattern and one central mass. A prominent,
sma!! nucleus rich in chromatin and slightly acidophilic cyto- clear area in the cytoplasm is seen adjacent to the nucleus.
plasm. The fibroblast (2) is elongated with cytoplasmic pro- Eosinophils (7) of the circulating blood are readily dis-
jections, an ovoid nucleus with sparse chromatin, and one or tinguished by their large size, a bilobate nucleus, and large,
two nucleoli. The fibrocyte (3) is a more mature, smaller cell cytoplasmic granules that stain intensely with eosin.
without cytoplasmic projections; the nucleus is similar but Occasional pigment cells (8) may be seen. The adipose
smaller than that in the fibroblast. cells (9) are large cells with a narrow rim of cytoplasm and
The large (4) and small (5) lymphocytes are spherical eccentric nuclei. In histologic sections, the large fat globule
cells that differ principally in the greater amount of cy- in the living cell has been dissolved by reagents used in sec-
toplasm in the former. The dark-staining nuclei of the tion preparation, leaving a large, empty space.

30 Tissues
Loose Connective Tissue

Fig. 2-1 Loose Connective Tissue (spread). Supravital staining with neutral red.
Upper: high magnification. Lower: oil immersion.

Connective Tissue 31
Figure 2-3 Loose Connective Tissue

Collagen fibers (6) predominate in loose connective tis- Also present in loose connective tissue are various blood
sue, course in many directions, and form a loose meshwork. cells such as the neutrophils (3), with lobulated nuclei, and
In the illustration, these fibers are sectioned in various small lymphocytes (2), with dense nuclei and sparse cyto-
planes, and transverse ends may be seen. Collagen fibers plasm. The fat or adipose cells (11, 12) appear characteristi-
have various diameters and appear longitudinally striated cally empty with a thin rim of cytoplasm (11) and peripher-
because of their fibrillar structure. The fibers are acidophilic ally displaced flat nuclei (12).
and stain pink with eosin. Thin elastic fibers are also present The connective tissue is highly vascular. Capillaries (7,
in loose connective tissue, but are difficult to distinguish 13) are visible, sectioned in several planes and lined with
with this stain and at this magnification. endothelium. Larger blood vessels, such as the arterioles (4,
The fibroblasts (1) are the most numerous cells in the loose 9, 10) and venules (5, 8) sectioned in several planes, are also
connective tissue and may be sectioned in various planes, so seen in the loose connective tissue.
that only parts of the cells may be seen. Also, during section Other examples of loose connective tissue in organs are
preparation, the cytoplasm of these cells may shrink. A typical illustrated in Figure 16-7.
fibroblast (I) shows an oval nucleus with sparse chromatin and
lightly acidophilic cytoplasm, with few short processes.

Figure 2-4 Dense Irregular Connective Tissue

This figure illustrates dense irregular connective tissue (10), which form fine networks.
from the dermis of the skin. The arrangement of fibers and The fibroblasts (5, 11) are often found compressed
cells is similar to that in loose connective tissue; however, among the collagen fibers. Also illustrated are a perivascu-
this is modified for areas in the body where more firm sup- lar cell (6) along a small blood vessel and a few blood cells,
port and strength are required. neutrophils (3) with lobulated nuclei, and lymphocytes (9)
The collagen fibers (1, 2) are large, typically found in with large round nuclei without visible cytoplasm. Small
thick bundles, and sectioned in several planes because they blood vessels (4, 8) are also illustrated.
course in various directions. This type of fiber arrangement Additional illustration of dense irregular connective tissue
is compact. Also present here are thin, wavy elastic fibers in the dermis of the skin is found in Figure 10-1:3.

32 Tissues
Connective Tissue

Fig. 2-4 Dense Irregular Connective Tissue. Stain: hematoxylin-eosin. High magnification.

Connective Tissue 33
Figure 2-5 Dense Regular Connective Tissue: Tendon (longitudinal section)

Dense regular connective tissue is present where great Dense regular connective tissue with less regular fiber
tensile strength is required, such as in ligaments and tendons. arrangement than in the tendon also forms fibrous mem-
A section of a tendon is illustrated. branes or capsules around various organs in the body.
The collagen fibers (2,3) are arranged in compact, paral- Examples of such connective tissue are perichondrium
lel bundles. Between these bundles are thin partitions of around the tracheal cartilage (Fig. 15-5:2), the dura mater
looser connective tissue that contain parallel rows of fibro- around the spinal cord (Fig. 7-19:2), and the tunica albu-
blasts (1, 4, 5). These cells have short processes (not visible ginea surrounding the testis (Fig. 18-1: 1).
here) and nuclei ovoid that appear when seen in surface view
(4) or rod-like in lateral view (5).

Figure 2-6 Dense Regular Connective Tissue: Tendon (transverse section)

A tendon in transverse section is illustrated at a lower connective tissue (3). Collagen bundles are grouped into fas-
magnification than that in Figure 2-1. Within each large cicles, with larger partitions (septa or trabeculae) of interfas-
bundle of collagen fibers (1, 10) are fibroblasts (nuclei) (2, cicular connective tissue (4, 8) coursing between them.
9) sectioned transversely. The fibroblasts are located These partitions contain blood vessels (5), nerves, and, occa-
between small bundles of collagen fibers. These are better sionally, lamellated Pacinian corpuscles (6), which are sen-
distinguished at the higher magnification in the inset, which sitive pressure receptors. Also illustrated in the figure is a
shows bundles of collagen fibers (10) and the branched shape transverse section of skeletal muscle (7), which is adjacent
of fibroblasts (9) in transverse section. to the tendon but separated from it by connective tissue.
Between the large collagen bundles are thin partitions of

34 Tissues
Dense Regular Connective Tissue

Fig. 2-5 Dense Regular Connective Tissue: Tendon (longitudinal section). Stain: hematoxylin-
eosin. Medium magnification.

- - .- - - - - ~..,...,. --- ... - -- ~
Fig. 2-6 Dense Regular Connective Tissue: Tendon (transverse section). Stain: hematoxylin-eosin.
Low magnification (inset: high magnification).

Connective Tissue 35
Figure 2-7 Dense Irregular and Loose Connective Tissue (elastin stain)

This figure illustrates an area with dense irregular con- The characteristic features of dense irregular and loose
nective tissue on the left side, a transition zone in the middle, connective tissues become apparent with this staining tech-
and loose connective tissue on the right. nique. In dense irregular connective tissue the collagen fibers
The elastic fibers (1, 4) are selectively stained a deep blue (2) are larger, more numerous, and more concentrated.
using Verhoeff's method. Using Van Gieson's as a counter- Elastic fibers are also larger and more numerous (1). In con-
stain, acid fuchsin stains collagen fibers red (2, 5). Cellular trast, in the loose connective tissue, both fiber types are
details of fibroblasts are not revealed but the fibroblast smaller (4, 5) and more loosely arranged. Fine elastic net-
nucJej (3, 6) stain deep blue. works are seen in both types of connective tissue.

Figure 2-8 Adipose Tissue

A small section of a mesentery is illustrated in which large Individual adipose cells appear as empty cells (2) because
accumulations of adjpose (fat) cells (2, 8) are organized into the fat was dissolved by chemicals used during routine his-
adipose tissue. The connective tissue of the peritoneum (6) tologic preparation of the tissue. Their nuclei (8) are com-
serves as a capsule around the adipose tissue. pressed in the peripheral rim of the cytoplasm, and in certain
Adipose cells (2) are closely packed and separated by thin sections, it is difficult to distinguish between fibroblast
strips of connective tissue, which contains the compressed nuclei (7) and adipose cell nuclei (8).
fibroblasts (7). Lobules of adipose tissue are separated by
connective tissue septa (3), in which are found blood ves-
sels (1, 4), nerves, and capillaries (5).

Figure 2-9 Embryonic Connective Tissue

The embryonic connective tissue resembles the mes- At higher magnification, a primitive fibroblast (5) is seen
enchyme or mucous connective tissue, which is loose and as a large, branching cell with abundant cytoplasm, promi-
irregular. The difference in ground substance (semi-fluid ver- nent cytoplasmic processes, an ovoid nucleus with fine chro-
sus jelly-like) is not apparent in these sections. matin, and one or more nucleoli. The widely separated colla-
The fibroblasts (2) are numerous, and fine collagen gen fibers (6) are more apparent at this magnification.
fibers (3) are found between them, some coming in close
contact with fibroblasts. Embryonic connective tissue is vas-
cular (1, 4).

36 Tissues
Connective Tissue

1 Elastic fibers

2 Collagen fibers

3 Fibroblast nucleus

Fig. 2-7 Dense Irregular and Loose Connective Tissue (elastin stain). Stain: Verhoeffs elastin stain
and Van Giesons. Medium magnification.

Fig. 2-9 Embryonic Connective Tissue. Stain: hematoxylin-eosin. Medium magnification (inset: oil

Connective Tissue 37


Cartilage is a special form of connective tissue whose Types of Cartilage: Hyaline, Elastic, and
main function is to support soft tissues. It consists of cells Fibrocartilage
(chondrocytes and chondroblasts) and matrix (fibers and There are three types of cartilage in the body: hyaline,
ground substance). The matrix contains collagen or elastic elastic, and fibrocartilage. This classification is based on the
fibers, which give the cartilage its firmness and resilience. amount and types of fibers present in the matrix.
As a result, cartilage exhibits tensile strength, provides The hyaline cartilage is the most common type in the
structural support, and allows flexibility without distor- body. In the embryo, hyaline cartilage serves as a skeletal
tion. model for most bones, which form by the process of endo-
The cartilage forms from mesenchyme cells that differ- chondral ossification. In adults, most of the hyaline cartilage
entiate into chondroblasts. These cells divide mitotically, has been replaced by bone, except on the articular surfaces of
grow, and synthesize the cartilage matrix and the extracel- bones, ends of ribs (costal cartilage), nose, larynx, trachea,
lular material. Gradually, individual chondroblasts become and in the bronchi. In these organs, hyaline cartilage provides
surrounded by the extracellular matrix and are trapped in a important structural and flexible support.
space called a lacuna (plural, lacunae). The trapped cells Elastic cartilage is similar to hyaline cartilage, except for
are the mature cartilage cells and are called chondrocytes. the presence of numerous elastic fibers in its matrix. This
Some lacunae may contain more than one chondrocyte; type of cartilage allows increased flexibility and support to
these groups of chondrocytes are called isogenous groups. the organs. Elastic cartilage is found in the external ear, in the
Like the epithelial tissue, cartilage is non-vascular. It is, walls of the auditory tube, in the epiglottis, and in the larynx.
however, surrounded by vascular connective tissue. As a Fibrocartilage is characterized by the presence of irregu-
result, all nutrients enter and metabolites leave the carti- lar, dense bundles of collagen fibers. It is found in the inter-
lage by diffusion through the matrix. Also, because the vertebral disks, the symphysis pubis, and certain joints. The
matrix is not hard or rigid, as it is in bone, cartilage grows fibrocartilage is important in the areas of the body where
by two different means simultaneously: interstitially and durability, tensile strength, weight bearing, and resistance to
appositionally. Interstitial growth involves mitosis of the stretch or compression are essential.
chondrocytes within the matrix and the deposition of new Most of the cartilage in the body is surrounded by a layer
matrix between the cells. This process increases the carti- of connective tissue called the perichondrium. An exception
lage size from within. Appositional growth occurs periph- to this is the hyaline cartilage on the articulating surfaces of
erally: chondroblasts differentiate from the inner connec- the bones. Also, because the fibrocartilage is always associ-
tive tissue perichondrium and deposit a layer of cartilage ated with dense connective tissue, it does not exhibit an iden-
that is apposed to the existing cartilage layer. tifiable perichondrium.

Cartilage 39
Figure 3-1 Fetal Hyaline Cartilage

This figure illustrates a cartilage model of a bone in an enchymal cells are concentrated and exhibit a parallel
early stage of development. Most of the model consists of arrangement (2). The nuclei of these cells are elongated and
young chondroblasts (1) that still resemble mesenchymal flattened, and the cell membranes are not distinct. This
cells, having spherical nuclei and cytoplasmic processes. peripheral area of the cartilage develops into perichondrium,
Lacunae have not developed at this stage. The chondroblasts a sheath of dense connective tissue that surrounds hyaline
are numerous, crowded into a specific area, and randomly and elastic cartilage. The inner portion of perichondrium is
distributed in the cartilage without forming isogenous the chondrogenic layer from which chondroblasts (2) devel-
groups. At this stage of development, cartilage matrix (3) is op; there is some indication of such transition in the illustra-
secreted. tion.
On the periphery of the cartilage model (left side), mes-

Figure 3-2 Mature Hyaline Cartilage

This section illustrates an interior or central region of the the matrix are observed either singly or in isogenous groups.
hyaline cartilage. Distributed throughout the homogeneous The matrix (6) appears homogeneous and is usually
ground substance, the matrix (5, 6), are ovoid spaces called basophilic; however, this condition can vary. The matrix
lacunae (2) with mature cartilage cells, the chondrocytes between cells or groups of cells is called interterritorial
(1). In intact cartilage, chondrocytes fill the lacunae. Each matrix (6). The more basophilic matrix around the cartilage
cell has a granular cytoplasm and a nucleus (3). During his- cells is the territorial matrix (5). Around each of the lacu-
tologic preparations, however, the chondrocytes (1) shrink nae, the matrix forms a thin cartilage capsule (4).
and the lacunae (2) appear as clear spaces. Cartilage cells in

Figure 3-3 Hyaline Cartilage of the Trachea

This illustration depicts lacunae with chondrocytes The interterritorial (intercellular) matrix (14) stains
appearing either singly (12) or in isogenous groups (13). lighter, whereas the territorial matrix (15) stains deeper.
Because the chondrocytes fill their lacunae, only margins of A perichondrium (4, 9, 18) of dense connective tissue
lacunae, the cartilage capsules (16), are visible. Lacunae surrounds the entire cartilage plate. Its inner layer is chon-
and chondrocytes in the middle of the cartilage are large and drogenic (10) where the chondrocytes are formed by prolif-
spherical (12, 13), but become progressively flatter in the eration and differentiation of mesenchymal cells (17).
periphery; these flat cells are young chondrocytes (11).

40 Tissues
Hyaline Cartilage


Cartilage 41
Figure 3-4 Fibrous Cartilage: Intervertebral Disl<

In fibrous cartilage, the matrix (6) is permeated with col- elastic cartilage, is absent because fibrous cartilage usually
lagen fibers (5), which frequently exhibit parallel fiber forms a transitional area between hyaline cartilage and ten-
arrangement, as is seen in tendons. Small chondrocytes (2, don or ligament.
4) in lacunae (1) are usually distributed in rows (3) within The proportion of collagen fibers to matrix, the number of
the fibrous matrix, rather than at random or in isogenous chondrocytes, and their arrangement may vary. The collagen
groups, as is normally seen in hyaline or elastic cartilage. All fibers may be so dense that matrix becomes invisible; in such
chondrocytes and lacunae are of similar size; there is no gra- cases, chondrocytes and lacunae appear flattened. Fibers
dation from larger central chondrocytes to smaller and flatter within a bundle may be parallel, but bundles may course in
peripheral cells. many directions.
A perichondrium, normally present around hyaline and

Figure 3-5 Elastic Cartilage: Epiglottis

Elastic cartilage differs from hyaline cartilage principally erable thickness (3, middle leader). The density of fibers in
by the presence of elastic fibers (1, 3) in its matrix. After the matrix varies among elastic cartilages as well as among
staining the cartilage with orcein (3), these are visible as different areas of the same cartilage.
deep purple fibers. The fibers enter the cartilagenous matrix As in hyaline cartilage, larger chondrocytes (2, 5) in lacu-
from the perichondrium (4), usually as small fibers, and are nae are seen in the interior of the plate. The smaller ones are
distributed in the interior as branching and anastomosing more peripheral; the latter finally become fibroblasts in the
fibers of varying size (3). Some of the fibers exhibit con sid- perichondrium (4).

42 Tissues

Fig. 3-4 Fibrous Cartilage: Intervertebral Disl<. Stain: hematoxylin-eosin. High magnification.

1 Matrix with elastic

4 Perichondrium

2 Chondrocytes
5 Small and larger

3 Elastic fibers 6 Nucleus of


Fig. 3-5 Elastic Cartilage: Epiglottis. Stain: hematoxylin-orcein. High magnification.

Cartilage 43


Bone is also a special form of connective tissue. Like Osteoblasts are immature bone cells, present on the sur-
other connective tissues, bones consist of cells, fibers, and faces of bone tissue. Their main function is to synthesize,
matrix. However, because the bone matrix is mineralized, secrete, and deposit the organic components of new bone
bones become hard, dense, and rigid. Because of mineral matrix called osteoid. Osteoid is uncalcified, newly formed
deposition in the matrix, bones can bear weight and serve as bone matrix that does not contain any minerals; however,
a rigid skeleton of the body, provide sites of attachment for shortly after its deposition, it undergoes rapid mineralization
muscles and organs, and provide protective cover for numer- and becomes bone.
ous soft organs. The brain is protected by the skull, the heart Osteocytes are the main cells of the bone. Like the chon-
and lungs are surrounded by the thoracic rib cage, and the drocytes in cartilage, osteocytes are trapped by the surround-
urinary and reproductive organs are located between the ing bone matrix and lie within lacunae. In contrast to carti-
pelvic bones. In addition, the bones function in hemopoiesis lage, however, only one osteocyte is found in each lacuna.
(blood cell formation), and serve as reservoirs for calcium, The osteocytes are responsible for the maintenance of the
phosphate, and other minerals.
bone matrix.
Minerals can be either stored in the bones or released into Osteoclasts are large, multinucleated cells that are found
body fluids when proper mineral homeostasis becomes
along the bone surfaces where resorption, remodeling, and
essential. Almost all (99%) of the calcium in the body is
repair of bone take place. Their main function is to resorb
stored in bones. The body receives some of its daily calcium
bone during remodeling. Osteoclasts are often located on the
needs from this source. Calcium is essential for muscle con-
resorbed or enzymatically etched shallow depressions in the
traction, blood coagulation, cell membrane permeability,
bone called Howship's lacunae. Osteoclasts originate from
transmission of nerve impulses, and other vital functions.
the fusion of the circulating blood monocytes.
Bones are also dynamic structures; they are continually
being renewed, remodeled, or both in response to mineral
Bone Matrix
needs of the body, mechanical stresses put on the bone, bone
thinning during aging or disease, or healing during a fracture Because the mineralized bone matrix is much harder than
or break in the bone. cartilage, nutrients and metabolites cannot freely diffuse
Calcium release into the blood stream from the bones, or through it to the bone cells. Consequently, bones are highly
its deposition in the bones, depends on the hormones vascular and exhibit a unique system of channels or canals
released from either the parathyroid glands or the thyroid called canaliculi. Cytoplasmic processes from osteocytes
gland, respectively. This is discussed in more detail in extend into the canaliculi, which radiate in all directions
Chapter 17, the Endocrine System. from each lacuna. The canaliculi contain extracellular fluid,
and the cytoplasmic extensions allow individual osteocytes
Bone Cells to communicate with adjacent osteocytes and with materials
Developing and adult bones contain four different types present in the blood vessels that supply the bone matrix. In
of cells: osteogenic (osteoprogenitor) cells, osteoblasts, this manner, the canaliculi allow for a very efficient
osteocytes, and osteoclasts. exchange mechanism: nutrients are brought to the osteo-
Osteogenic cells are undifferentiated, pleuropotential cytes, gaseous exchange takes place between the blood and
stem cells derived from the connective tissue mesenchyme. cells, and metabolic wastes are removed from the osteocytes.
During bone development, osteogenic cells proliferate by
mitosis and differentiate into osteoblasts. In mature bones, The Process of Bone Formation (Ossification)
the osteogenic cells are found in the external periosteum and Bone development begins in the embryo by two distinct
in the single layer of the internal endosteum. The periosteum processes: intramembranous ossification and endochondral
and endosteum provide a continuous supply of new ossification. Bones produced by the two different methods
osteoblasts for growth, remodeling, and repair of the bones. do not differ histologically.

Bone 45
Intramembranous Ossification cartilage model begins to calcify and the chondrocytes
In intramembranous ossification, bone develops from the hypertrophy and mature. As cartilage calcifies, diffusion of
connective tissue mesenchyme. Some cells differentiate nutrients and gases through the calcified matrix decreases.
directly into osteoblasts and produce the bony matrix. The As a result, the chondrocytes die and the fragmented calci-
mandible, the maxilla, the clavicles, and most of the flat fied matrix then serves as a structural framework for the
bones of the skull are formed by the intramembranous deposition of the developing bone.
method. In the developing skull, the centers of bone devel- Osteoprogenitor cells and blood vessels from the sur-
opment grow radially, replace the connective tissue, and then rounding connective tissue penetrate and invade the degen-
fuse. In newborns, the fontanelles in the skull are the soft erating cartilage model to supply its interior. Osteoprogenitor
membranous regions where ossification of skull bones has cells proliferate and give rise to osteoblasts. Mesenchyme
not yet been completed. tissue, osteoblasts, and blood vessels form an ossification
center in the developing bone. Osteoid matrix is then pro-
Endochondral Ossification duced and mineralized into bone. Expansion of the ossifica-
Endochondral ossification forms the remaining bones of tion center completely replaces the cartilage model with bone
the skeleton. Each bone is first preceded by a temporary hya- tissue, except over the free ends of the long bones. Here, a
line cartilage model. Bone tissue then slowly replaces most layer of hyaline cartilage covers the bone as the articular car-
of the cartilage model. The cartilage matrix in center of the tilage.

46 Tissues

Figure 4-1 Compact Bone, Dried (transverse section)

Figure 4-2 Compact Bone, Dried (longitudinal section)

Bone 47
Figure 4-1 Compact Bone, Dried (transverse section)

Dried bone is prepared by grinding a small piece of bone teum along the marrow cavity) is composed of internal
to a thin section. This method removes the bone cells and circumferential lamellae (1). Between the internal and
only empty spaces become visible-the canals for blood ves- external circumferential lamellae (I, 7) are the osteons
sels, lacunae where osteocytes or bone cells reside, and (Haversian systems) (3, 10), the structural units of the bone.
canaliculi that connect the adjacent lacunae. Each osteon (10) consists of a number of concentric lamel-
Compact bone is characterized by the arrangement of the lae (3b) that surround a central (Haversian) canal (3a).
bone matrix into layers called lamellae (3b, 8). These are These are shown in both transverse (3a) and oblique planes
thin plates of bony tissue that contain osteocytes or bone of section (10, middle leader) in this illustration. The small
cells in almond-shaped spaces called lacunae (3c, 9). irregular areas of bone between osteons (3, 10) are intersti-
Radiating from the lacunae in all directions are tiny canals, tiallamellae (5, 12).
the canaliculi (2). These penetrate the lamellae (3b, 8), anas- In living bone, the lacunae (3c, 9) contain the osteocytes,
tomose with canaliculi (2) from other lacunae (3c, 9), and and the central canals (3a) of the osteons (3, 10) contain
provide communication links with other osteocytes. Some of reticular connective tissue, blood vessels, and nerves. The
the canaliculi (2) open into central (Haversian) canals (3a) boundary between each osteon (3, 10) is outlined by a refrac-
of the osteon (3) and marrow cavities of the bone. tile line called the cement line (11), which consists of modi-
The external wall of the compact bone (beneath the con- fied matrix. Anastomoses between central canals (3a) are
nective tissue periosteum) is formed by the external cir- frequently seen in the cross section of the bone, and are
cumferentiallamellae (7); these run parallel to each other called perforating (Volkmann's) canals (6).
and to the long axis of the bone. The internal wall (the endos-

Figure 4-2 Compact Bone, Dried (longitudinal section)

This figure represents a small area of compact bone, pre- indicate the extent of an osteon, as seen in longitudinal sec-
pared in a longitudinal section. Because the central canals tion.
(1, 9) course in the longitudinal direction in the bone, each Other canals in the longitudinal section of the bone extend
central canal is seen as a tube, often branched, and sectioned in either a transverse or oblique direction. These are the per-
parallel to the long axis of the bone. The central canal is sur- forating (Volkmann's) canals (7). They join the central
rounded by numerous lamellae (2), within or between which canal (I, 9) of one osteon with the central canal of the adja-
are the lacunae (4), and from which radiate numerous cent osteon or with the marrow cavity. The perforating canals
canaliculi (5). The lamellae (2), lacunae (4), and the osteon (7) do not have concentric lamellae; instead, they penetrate
boundaries (the cement lines) (8) are, in general, parallel to directly through the lamellae (2).
the corresponding central canals (1, 9). The cement lines (8)

48 Tissues
Compact Bone

Bone 49
Figure 4-3 Compact Bone, Dried: An Osteon (transverse section)

A higher magnification of a compact bone in transverse lacunae (1, 7) to contact the adjacent lacunae. In this manner,
section illustrates the characteristic features of one osteon a system of complex communicating canaliculi (2) is formed
and portions of adjacent osteons. Located centrally in the throughout the bony matrix, with connections to the central
osteon is the prominent, dark-staining central (Haversian) canals (3). Each of the canaliculi (2) contain tiny cell
canal (3), around which are seen the concentric arrange- processes of the osteocytes. In this manner, the osteocytes
ments of lamellae (4). Situated between adjacent osteons are around the osteon come in contact with each other and the
tlle interstitkil lamellae (5). The dark, fusiform-shaped struc- central canal~ whkh contajn the blood vessels. Located on
tures between the lamellae (4) are the lacunae (1, 7). In liv- the outer boundary of the osteon is a layer formed by amor-
ing bone, bone cells or osteocytes reside in these spaces. phous material, the cement line (6).
Numerous tiny canaliculi (2) radiate from individual

50 Tissues
Compact Bone

Bone 51
Figure 4-4 Cancellous Bone: Sternum (transverse section, decalcified)

Cancellous bone consists primarily of slender, bony tra- more apparent on the margins of bony areas. Lacunae with
beculae (6), which ramify, anastomose, and enclose irregular osteocytes (9) are visible in all regions of the bone.
marrow cavities (5). Peripherally, these trabeculae merge The reticular connective tissue in the marrow cavities is
with a thin layer of compact bone (3), which contains scat- obscured by adipose cells (10) and hemopoietic (blood
tered osteons (Haversian systems) (4, 7). The surrounding forming) tissue (11). Arteries are clearly visible in this illus-
periosteum (2) may descend into the bone at intervals or tration but sinusoids are too small to distinguish. Marrow (5)
merge with adjacent connective tissue (1). fills the cavities; however, a thin, inner layer of cells, the
Except for concentric lamellae in the osteons (4, 7), the endosteum (12), becomes visible when marrow separates
peripheral bone (3) and the trabeculae of bone (6) exhibit from the bone.
parallel lamellae (8). In this illustration the lamellae (8) are

Figure 4-5 Intramembranous Ossification: Developing Mandible (transverse

section, decalcified)

The upper left part of this illustration depicts the gum that beculae (18). Osteoclasts (5, 8) are multinucleated giant
covers the developing mandible. The mucosa of the gum cells associated with bone resorption and remodeling. The
consists of stratified squamous epithelium (1) situated osteocytes (4, 9) are bone cells located in lacunae of the bone
above the lamina propria (2), a wide connective tissue with trabeculae (18).
blood vessels and nerves. Although collagen fibers embedded in the bony matrix are
Below the lamina propria (2) is the developing bone. The obscured, the continuity with embryonic connective tissue
cells in the periosteum (3) have differentiated into fibers in the marrow cavities may be seen at the margins of
osteoblasts (12) and formed the numerous anastomosing numerous trabeculae (13).
trabeculae of bone (18). These trabeculae surround the Formation of new bone is not a continuous process.
primitive marrow cavities (14) of various sizes. Located Inactive areas appear where ossification has temporarily
within the marrow cavities are embryonic connective tissue, ceased; osteoid (newly synthesized bony matrix) and
blood vessels, and nerves (16). Peripherally, collagen fibers osteoblasts are not present in these areas. In some primitive
of the periosteum (3) are in continuity with the fibers of the marrow cavities, fibroblasts enlarge and differentiate into
embryonic connective tissue of adjacent marrow cavities (6) osteoblasts (12). In other areas, osteoid (11, 17) is seen on
and with collagen fibers within the bone trabeculae (10). the margins of bone trabeculae; osteoblasts may (II) or may
Osteoblasts (7, 15) actively deposit the bony matrix and not (17) be present.
are seen in linear arrangement along the developing bone tra-

52 Tissues
Cancellous Bone and Intramembranous Ossification

Fig. 4-4 Cancellous Bone: Sternum (transverse section, decalcified). Stain: hematoxylin-eosin.
Low magnification.

9 Osteocytes
1 Stratified squamous
10 Periosteum and bone

2 lamina propria
(connective tissue) 11 Osteoid

3 Periosteum
12 Developing
4 Osteocytes
13 Bone and marrow
cavity continuity

5 Osteoclasts
14 Primitive marrow
15 Osteoblasts
6 Periosteum and
marrow cavity
16 Artery, nerves, vein

7 Osteoblasts
17 Osteoid
8 Osteoclast
18 Trabeculae of
Fig. 4-5 Intramembranous Ossification: Developing Mandible (transverse section,
decalcified). Stain: Mallory-azan. Low magnification.

Bone 53
Figure 4-6 Endochondral Ossification: Developing Long Bone 'panoramic
view, longitudinal section)

In the process of endochondral ossification, the future ing cartilage matrix calcify (20). The calcified cartilage
bone is first formed as a model composed of embryonic hya- stains a deep purple.
line cartilage. As development progresses, the cartilage Tufts of vascular marrow (5) invade the zone of calcify-
model is gradually replaced by bone. In the center of the ing cartilage (20), erode the lacunar walls and the calcified
illustration, this process has already begun. In addition, most cartilage (20), and form new, small marrow cavities.
of the original spongy bone that was formed has been Osteoprogenitor cells from the inner periosteum (9) differ-
replaced and resorbed to form the central marrow cavity, entiate into osteoblasts and deposit osteoid and bone (6)
leaving only scattered, thin spicules of bone of endochon- around the remaining spicules of calcified cartilage (6). This
dral origin (11, 30). Red marrow (13) now fills the cavity region in the developing bone is now the zone of ossification
of newly formed bone with hemopoietic (blood forming) (21).
cells. The fine reticular connective tissue fibers are obscured The lower, lateral two-thirds of the illustration shows the
by masses of developing erythrocytes, granulocytes, development of periosteal bone. Osteoblasts differentiate
megakaryocytes (14), numerous sinusoids (12), capillaries, from osteoprogenitor cells in the inner layer of the perios-
and blood vessels. teum (9) and form a bone collar (10). Formation of new
The process of endochondral ossification can be followed periosteal bone (22) keeps pace with formation of new
from the upper part of the illustration downward to the cen- endochondral bone. The bone collar (10) increases in thick-
tral marrow cavity. In the uppermost region is seen the zone ness and compactness as development of bone proceeds. The
of reserve hyaline cartilage (17), in which the chondro- thickest portion of the bone collar (10) is seen in the central
cytes in lacunae (2) are distributed singly or in small groups. part of the diaphysis at the initial site of periosteal bone (29)
Chondrocytes then proliferate rapidly and become arranged formation around the primary ossification center.
in columns (3, 18); cells and lacunae increase in size toward Surrounding the shaft of the developing bone are soft tis-
the lower area of this zone of proliferating cartilage (18). sues: muscle (7), subcutaneous connective tissue, and der-
The chondrocytes then hypertrophy (19) because of the mis of skin (15, 25). The skin, lined on the external surface
swelling of nucleus and cytoplasm. The lacunae enlarge (4), by the epidermis (24), contains a few hair follicles (26),
the cells then degenerate and the thin partitions of interven- sebaceous glands (28), and sweat glands (16).

54 Tissues
Endochondral Ossification: Developing Long Bone

1 Perichondrium
17 Zone of reserve
2 Chondrocytes in cartilage
lacunae 18 Zone of proliferating
hyaline cartilage
3 Column of 19 Zone of
chondrocytes hypertrophying cells
and lacunae

4 Hypertrophied 20 Zone of calcifying

chondrocytes and cartilage
calcified matrix

5 Vascular tufts of
osteogenic marrow

21 Zone of erosion and

6 Osteoid and bone ossification
around calcified
7 Muscle 22 New periosteal
23 Younger and older
8 Periosteum (outer bony spicules

9 Periosteum (inner layer

with osteoblasts)

- 25 Dermis and
10 Periosteal bone subcutaneous layer
(bone collar)

26 Hair follicles

11 Spicules of bone

12 Sinusoid
27 Primitive marrow
13 Red bone marrow cavities in periosteal
14 Megakaryocytes 28 Sebaceous gland

15 Subcutaneous
connective tissue
and dermis
16 Sweat gland - 29 Periosteal bone

30 Spicules of bone
Fig. 4-6 Endochondral Ossification: Developing Long Bone (panoramic view, longitudinal
section). Stain: hematoxylin-eosin. Low magnification.

Bone 55
Figure 4-7 Endochondral Ossification: Zone of Ossification

A higher magnification of endochondral ossification illus- calcified cartilage (5, 17), and lay down osteoid (19) and
trates the process in greater detail. The region shown in this bone. Osteoblasts trapped in the osteoid or bone become
figure corresponds to the zone of ossification and adjacent osteocytes (9, 21).
areas (JabeHed 3 through 6 in Fig. 4-6). The marrow cavity (10) contains pluripotential stem cells
Proliferating chondrocytes (1, 14) are arranged in distinct which give rise to blood cells (23) belonging to the erythro-
columns. Below the proliferating chondrocytes is the zone of cytic and granulocytic series, as well as megakaryocytes
hypertrophied chondrocytes (2, 15). Hypertrophy of chon- (13, 24). Multinucleated osteoclasts (11, 22), which lie in
drocytes occurs because of increased glycogen and lipid shallow depressions called the Howship's lacunae (11, 22),
accumulations in the cytoplasm and nuclear swelling; lacu- are situated adjacent to bone that is being resorbed.
nae also hypertrophy simultaneously. The cytoplasm of On the left side of the illustration is an area of periosteal
hypertrophied chondrocytes then becomes vacuolized (16), bone (7) with osteocytes (9) in their lacunae. The new bone
the nuclei become pyknotic, and the thin cartilage partitions is added peripherally by osteoblasts (6), which develop from
become surrounded by calcified matrix (5, 17). osteoprogenitor cells of the inner periosteum (12). The
Tufts of capillaries (8, 18) from the marrow cavity (10) outer layer of periosteum continues as the connective tissue
invade this area and form the zone of erosion. Osteoblasts perichondrium (3), passing superiorly over the cartilage
(6, 20) are formed and line up along remaining spicules of that has not changed into bone.

56 Tissues
Endochondral Ossification: Zone of Ossification

14 Proliferating

15 Hypertrophied

=- 16 Vacuolized

17 Calcified

18 Capillary
19 Osteoid
20 Osteoblasts

21 Osteocytes

22 Osteoclast
(in Howship's

23 Oeveloping
blood cells

- 24 Megakaryocyte

Fig.4-7 Endochondral Ossification:Zone of Ossification. Stain: Hematoxylin-eosin. Medium


Bone 57
Figure 4-8 Formation of Bone: Secondary (epiphyseal) Ossification Centers
(decalcified, longitudinal section)

The cartilage in the epiphyseal ends (articular cartilages) bone. Bony spicules (13) are larger and more numerous
of two developing bones is illustrated. Both bones contain a because the secondary center of ossification (6) is in a more
secondary center 'of ossification (2, 6). The ossification advanced stage of development than that in the upper bone.
center (2) in the upper bone is in an earlier stage of develop- A small area of ossification is apparent in the metaphysis
ment than that in the lower bone (6). The synovial or joint (9), a transitional zone where cartilage is being replaced by
cavity (5, 11) is located between the two developing carti- bone. This area illustrates the typical features of the zone of
lage models. ossification (8,9,16,17). The connective tissue periosteum
In the upper epiphysis the peripheral or superficial artic- surrounds the developed bone on the right side (18) and on
ular cartilage (3) with t1attened chondrocytes and lacunae is the left side (8, 9).
visible. Toward the center of the cartilage, the chondrocytes The synovial or joint cavity (5, I I) is covered by a joint
and lacunae are rounder. At the margins of the ca1cification capsule (a diarthritic joint). A portion of the outer fibrous
center, the chondrocytes show hypertrophy (10) in prepara- layer of the articular capsule (7) is illustrated. The inner
tion for ossification. Small spicules of red-stained bone and synovial membrane of squamous cells lines the cavity,
primitive marrow cavities are seen in the center of ossifica- except over the articular cartilages (3). The synovial mem-
tion (2). brane, together with the connective tissue of the capsule, may
Similar structural components and changes are visible in extend into the joint cavity as a simple synovial projection
the secondary center of ossification (6, 13-15) in the lower (12) or as more complex synovial folds (4).

58 Tissues
Formation of Bone: Secondary 'epiphyseal) Ossification Centers

1 Articular cartilage:
deeper area of rounded
chondrocytes and

2 Secondary ossification 10 Zone of

center hypertrophied
and lacunae
3 Articular cartilage

11 Synovial

4 Synovial


5 Synovial

13 Spicule
of bone
6 Secondary 14 Calcified
ossification cartilage
center 15 Primitive

7 Fibrous

8 Zone of
chondrocytes and
16 Calcifying
and lacunae
9 Zone of
ossification in 17 Spicules
metaphysis of bone

18 Periosteum

Bone 59
Figure 4-9 Formation of Bone: Development of Osteons (Haversian Systems)
(transverse section, decalcified)

This illustration represents a late stage in the development of these primitive osteons (8), as indicated by the presence of
of compact bone. Primitive osteons (Haversian systems) osteoblasts (9) along the central (Haversian) canal (8)
have already formed and others are in the process of devel- periphery and the margin of the innermost bone lamella. In
opment. In a long bone, such as in Figure 4-6, the initial some of the primitive osteons, the osteoclasts (2) have
compact bone is formed by deposition in the subperiosteal already formed and are resorbing and remodeling the bone.
region (Fig. 4-6:29). Vascular tufts of connective tissue from A longitudinal channel of osteogenic connective tissue
periosteum or endosteum then invade and erode this bone (10) passes through the bone. From it arise tufts of vascular
and form primitive osteons, visible in this illustration. Bone connective tissue, which give rise to new central (Haversian)
reconstruction will continue as these initial osteons, and then canals (4). Osteoblasts (9) are already found along the
later ones, are broken down, followed by the formation of periphery of the canal.
new osteons. In the lower part of the figure is a large bone marrow
This figure illustrates a section of immature compact bone cavity (14), in which hemopoiesis (blood cell formation) is
whose matrix (11) is stained deep with eosin. Primitive in progress; this is the red marrow. Also present in the bone
oseons are visible in transverse section, with large central marrow cavity (14) are developing erythrocytes and granulo-
(Haversian) canals (8) surrounded by a few concentric cytes, megakaryocytes (16), blood vessels (7), bone
lamellae (3) of bone and osteocytes (1). The central spicules (15), and osteoclasts (13) in Howship's lacunae
(Haversian) canals contain primitive connective tissue and (12) along the wall of the bone.
blood vessels (6, 8). Bone deposition is continuing in some

60 Tissues
Formation of Bone: Development of Osteons

Fig. 4-9 Formation of Bone: Development of Osteons (Haversian Systems) (decalcified).

Stain: hematoxylin-eosin. Medium magnification.

Bone 61


Blood is a unique form of connective tissue that consists carried to tissues in the form of oxyhemoglobin. Carbon
of three major types of cells: red blood cells (erythrocytes), dioxide from the cells and tissues is carried to the lungs part-
white blood cells (leukocytes), and platelets (thrombocytes). ly dissolved in the blood and partly in combination with
These cells or the formed elements are suspended in a liquid hemoglobin, as carbaminohemoglobin.
medium called plasma. The blood cells transport gases, nutri- During differentiation and maturation processes, erythro-
ents, waste products, hormones, antibodies, cells, various cytes synthesize large amounts of hemoglobin. Before ery-
chemicals, ions, and other substances in the plasma to cells throcytes are released into the systemic circulation, the
in different parts of the body. nucleus is extruded from cytoplasm, and the mature erythro-
cytes assume a biconcave shape. This shape provides more
Blood Cells
surface area for carrying respiratory gases. Thus, mature
Blood cells are formed by a process called hemopoiesis. mammalian erythrocytes in the circulation are non-nucleated
In this process, all blood cell types are derived from pluripo- biconcave discs that are surrounded by a membrane and con-
tential stem cells; these multiply, differentiate, and develop tain hemoglobin and some enzymes.
into the various forms of mature blood cells. Hemopoiesis Leukocytes are nucleated cells and are subdivided into
occurs in different sites of the body, depending on the stage granulocytes or agranulocytes, depending on the presence or
of development of the individual. In the embryo, hemo- absence of granules in their cytoplasm. The leukocytes func-
poiesis occurs in the yolk sac, and later in the development,
tion primarily as a defense system against bacterial invasion
it takes place in the liver, spleen, and the lymph nodes. After
or the presence of foreign material in the body. Because most
birth, hemopoiesis continues almost exclusively in the red
of the leukocytes are concentrated in the connective tissue,
marrow of different bones. (In the newborn, all bone marrow
the specific functions of different leukocytes were described
is red). In adults, red marrow is found primarily in the fiat
in detail in the connective tissue section.
bones of the skull, sternum and ribs, vertebrae, and pelvi~
bones. The remaining bones gradually accumulate fat, their
marrow becomes yellow, and they lose the hemopoietic func-
tions. Platelets or thrombocytes are the smallest formed ele-
Microscopic examination of a stained blood smear reveals ments that are found in the blood. They are non-nucleated
the major cell types. The erythrocytes and platelets perform cytoplasmic fragments of megakaryocytes. These are the
their major functions in the blood vessels. The leukocytes, on largest, multilobed cells that are observed in the bone mar-
the other hand, perform their major functions outside of the row. Platelets are produced when small, uneven portions of
blood vessels. These cells leave the blood vessels through the the cytoplasm separate or fragment from the peripheries of
capillary walls and enter connective tissue, lymphatic tissue, the megakaryocytes. The main function of platelets is to pro-
and bone marrow. mote blood clotting. When the wall of the blood vessel is
Mature erythrocytes are highly specialized to transport broken or damaged, the platelets adhere to the damaged
oxygen and carbon dioxide. The ability to transport respira-\ region of the wall and release chemicals that initiate the com-
tory gases depends on the presence of protein hemoglobin in plex process of blood clotting. After a blood clot is formed
the erythrocytes. Iron molecules in hemoglobin bind with and the bleeding ceases, the aggregated platelets contribute
oxygen molecules, and most of the oxygen in the blood is to the clot retraction.

Blood 63
Figure 5-1 Human Blood Smear

A smear of human blood examined under lower magnifi- blood cells or leukocytes are visible in the blood smear.
cation illustrates various formed elements of the blood. The Leukocytes are subdivided into different categories accord-
most abundant elements of the blood are the red blood cells ing to the shape of their nuclei, the absence or presence of
or erythrocytes (1). These cells are enucleated (without cytoplasmic granules, and the staining affinities of their
nucleus) and stain pink with eosin. They are uniform in size, granules. Two neutrophils (2, 4), one eosinophil (7), and
approximately 7.5 .urn in diameter, and can be used as a size one small lymphocyte (5) are shown in this illustration.
reference for other cell types. The erythrocytes (1) are the Scattered around these cells are small, blue-staining frag-
most prevalent elements in the blood smear and are the easi- ments of a blood cell, the platelets (3, 6). All of these formed
est to identify. blood elements are illustrated in greater detail and higher
In addition to numerous erythrocytes (I), several white magnification.

Figure 5-2 Erythrocytes and Platelets

This illustration shows numerous erythrocytes (1) and ocyte, which is found in red bone marrow. Platelets (2)
the tiny platelets (2) that usually are seen in a blood smear. appear as irregular masses of basophilic (blue) cytoplasm,
Blood platelets (2) are the smallest of the formed elements; and they tend to form clumps in blood smears
they are ,cytoplasmic remnants of a large-cell megakary-

Figure 5-3 Neutrophils

The leukocytes that contain granules and a lobulated of neutrophils (I) consists of several lobes that are connect-
nucleus are the polymorphonuclear granulocytes, of which ed by narrow chromatin strands; a fewer number of nuclear
the neutrophils (1) are the most abundant. The cytoplasm of lobes in these cells indicates that the neutrophils (1) are
neutrophils (I) contains fine violet or pink granules; these are immature. The neutrophils (I) constitute approximately
difficult to see with a normal light microscope. As a result, 60-70% of the leukocyte population in the blood and are
the cytoplasm of neutrophils (1) appears clear. The nucleus easy to locate in a blood smear.

64 Tissues
Human Blood Smear

Fig. 5-1 Human Blood Smear. Wrights stain. High magnification.

Fig. 5-2 Erythrocytes and Platelets. Wrights stain. Oil immersion.

Fig. 5-3 Neutrophils. Wrights stain. Oil Immersion.

Blood 65
Figure 5-4 Eosinophils

Eosinophils (1) constitute approximately 2-4% of the is filled with distinct, large, eosinophilic (bright pink) gran-
leukocytes in the blood. These cells usually can be identified ules. The nucleus in eosinophils (1) typically is bilobed, but
without difficulty in a blood smear because their cytoplasm a small third lobe may be present.

Figure 5-5 Lymphocytes

Agranular leukocytes have few or no cytoplasmic gran- In small lymphocytes (2), the densely stained nucleus occu-
ules and exhibit round to horseshoe-shaped nuclei. pies most of the cytoplasm, and the cytoplasm is seen as a
Lymphocytes (1, 2) constitute approximately 20-30% of the thin basophilic rim around the nucleus. The cytoplasm is
blood leukocytes. They vary from cells smaller than erythro- agranular but may contain a few azurophilic granules. In
cytes to those almost twice as large. For size comparison large lymphocytes (I), basophilic cytoplasm is more abun-
among different lymphocytes and erythrocytes, this illustra- dant around the nucleus, and the larger and paler nucleus
tion of a human blood smear depicts a large lymphocyte (1) may contain one or two nucleoli.
and a small lymphocyte (2), surrounded by the erythrocytes.

Figure 5-6 Monocytes

Monocytes (1) are the largest leukocytes. The nucleus and often contains a few fine azurophilic granules.
varies from round or oval to indented or horseshoe-shaped Monocytes (1) constitute approximately 3-8% of the blood
and stains lighter than in lymphocytes. Chromatin is more leukocytes.
finely dispersed; abundant cytoplasm is lightly basophilic

Figure 5-7 Basophils

The granules in the basophils (1) are not as numerous as pale basophilic, it is usually obscured by the density of the
in eosinophils (Fig. 5-4); however, they are more variable in granules. The basophils constitute less than 1% of the blood
size, less densely packed, and stain dark blue or brown. leukocytes and are, therefore, the most difficult cells to find
Although the nucleus is not markedly lobulated and stains and identify in a blood smear.

66 Tissues
Human Blood Smear

1 Large

2 Small

Fig. 5-4 Eosinophils. Wrights stain. Oil Fig. 5-5 Lymphocytes. Wrights stain. Oil
immersion. immersion.

1 Monocyte -

1 Basophil

Fig. 5-6 Monocytes. Wrights stain. Oil
immersion. immersion.

Blood 67
Figure 5-8 Hemopoietic Bone Marrow of a Rabbit ,section)

In a section of red bone marrow, all types of developing most easily recognizable of the earlier erythrocytic cells are
blood cells are difficult to distinguish. The cells are packed the normoblasts (16), which are characterized by small,
densely, and different cell types are intermixed, although dark-staining nuclei (as in 28); numerous normoblast cells
some of the erythrocytic forms often occur in groups or also exhibit mitotic activity (16). Polychromatophilic ery-
"nests" (6, 18). throblasts (20) may also occur in groups or "nests." These
This section is stained with hematoxylin-eosin. At low cells are larger than normoblasts (16), with a larger nucleus
magnification, little differentiation of cytoplasm is visible, that exhibits a more evident "checkerboard" distribution of
except for bright-staining eosinophilic granules (4) in the chromatin (as in 27). Basophilic erythroblasts (3) are larg-
precursor eosinophilic cells. Different individual blood cells er cells that exhibit a large, less-dense nuclei and basophilic
from a bone marrow smear are illustrated below the figure at cytoplasm (as in 26).
a higher magnification to show more details of the cyto- In the granulocytic series of blood cells, the most easily
plasm, its contents, and nucleus. recognizable cells are the polymorphonuclear heterophils
The stroma of the reticular connective tissue in the mar- (15) (corresponding to neutrophils in humans) and
row is obscured largely by hemopoietic cells. In less dense eosinophils. Their earlier forms, the metamyelocytes (19),
areas, the reticular connective tissue (8) can be seen, and the have a bean- or horseshoe-shaped nuclei (as in 25).
elongated reticular cells (22) often are recognized. Different Heterophilic myelocytes (1, 4, 24) have larger, round, or
types of blood vessels (9, 10, 17,23) that contain erythro- ovoid nuclei. Less easily recognizable in a section are the
cytes and leukocytes in their lumina also are seen in the bone pale-staining primitive reticular cells (11).
marrow. Also conspicuous in the bone marrow are large adi- An alternate terminology for the developing erythrocytic
pose cells (2, 13), each exhibiting a large vacuole (because forms, in use clinically, is as follows:
of fat removal during routine section preparation) and small, Proerythroblast = rubriblast
peripheral cytoplasm that surrounds the nucleus (2). Other Basophilic erythroblast = prorubricyte
cells that are identified easily in the bone marrow are large Polychromatophilic erythroblast = rubricyte
megakaryocytes (5, 21) with varied nuclear lobulation. Normoblast (orthochromatophilic erythroblast) =
Erythrocytes (12) are abundant in the bone marrow. The metarubricyte

68 Tissues
Bone Marrow

1 Heterophilic myelocyte -::

2 Nucleus of adipose celr

. 12 Erythrocytes
3 Basophilic *
4 Eosinophilic myelocyte - -13 Adipose cell
5 Megakaryocyte
-14 Primitivereticular cells
;J 15 Heterophilic
6 Erythroblasts

- 16 Mitosis (normoblast)

7 Plasma cell ~ 17 Venule

8 Stroma of reticular
connective tissue
18 Normoblast

~ 19 Heterophilic
9 Small artery I
;... 20 Polychromatophilic


10 Vein :- 21 Megakaryocyte

~~ 22 Reticular cells

11 Reticular cells ~
23 Sinusoid

-~ 2
Heterophilic Heterophilic Basophilic Polychromatophilic Normoblast
myelocyte metamyelocyte erythroblast erythroblast
Fig. 5-8 Hemopoietic Bone Marrow of a Rabbit (section). Stain: hematoxylin-eosin. Upper: high
magnification. Lower: oil immersion.

Formerly called hemocytoblast; no longer considered mOlphologically identifiable.


Blood 69
Figure 5-9 Bone Marrow of a Rabbit, India Inl( Preparation (section)

A section of a hemopoietic bone marrow from a rabbit, Reticular cells (10) of the connective tissue may be seen
injected with India ink, is illustrated. Carbon particles have occasionally, but are obscured frequently by developing
been ingested by the stromal macrophages (1, 7) and by blood cells. Various cells of the erythrocytic and granulo-
fixed macrophages (3) that are adjacent to the endothelium cytic series (4, 6, 11) as well as megakaryocytes (9) can be
of the sinusoids (3, 5). Ingestion and accumulation of dense identified.
carbon particles in some phagocytic cells can obscure their
nuclei (1, 7).

70 Tissues
Bone Marrow

7 Stromal
1 Macrophages in macrophages
the stroma
2 Sinusoid 8 Adipose cell

3 Fixed

9 Megakaryocyte

10 Reticular cells (nuclei)
11 Heterophilic

Fig. 5-9 Bone Marrow of a Rabbit, India Ink Preparation (section). Stain: hematoxylin-eosin.
Medium magnification.

Formerly called hemocytoblast; no longer considered morphologically identifiable.


Blood 71
Figure 5-10 Bone Marrow: Smear

A microscopic field of human bone marrow smear that The granulocytes also originate from the pluripotential
was obtained by sternal puncture is represented in the center stem cell, and the myeloblast (2, 25) is the first recognizable
of the illustration. Around the periphery, the typical bone precursor in the granulocytic series. The myeloblasts (2, 25)
marrow cells are illustrated in greater detail. The formed ele- are small cells (10 to 13 pm in diameter) with a large nucle-
ments that are normally found in the blood easily are recog- us that contain two or three nucleoli and a distinctly
nized: erythrocytes (18, 31), granulocytes (eosinophil 32; basophilic cytoplasm that lacks specific granules. During its
neutrophils 33), and platelets (24). development, the cell enlarges, acquires azurophilic gran-
It currently is believed that a common stem cell gives rise ules, and is now called a promyelocyte (19, early, 23, later).
to different hemopoietic cell lines from which arise such The cell measures approximately 15 to 20 pm in diameter.
functional blood cells as the erythrocytes, granulocytes, lym- The chromatin in the oval nucleus is dispersed, and multiple
phocytes, and megakaryocytes. Because of its ability to dif- nucleoli are evident. In more advanced promyelocytes (neu-
ferentiate into all blood cells, this cell is called pluripoten- trophilic, 23), the cells are smaller, nucleoli become incon-
tial hemopoietic stem cell (1). Although this cell cannot be spicuous, azurophilic granules increase, and specific gran-
recognized microscopically, it resembles a large lymphocyte. ules appear with different staining properties in the perinu-
In adults, the greatest concentration of pluripotential stem clear region.
cells is found in the bone marrow. Myelocytes are smaller than promyelocytes. The nucleus
In the erythrocytic series, the precursor cell is the proery- is eccentric, and the chromatin is more condensed. The cyto-
throblast* (3, 8); it measures 20 to 30 pm in diameter and plasm is less basophilic, with few azurophilic granules evi-
contains a thin rim of basophilic cytoplasm and a large, oval dent, and specific granules (neutrophilic early myelocyte,
nucleus that occupies most of the cell. Azurophilic granules 26; basophilic early myelocyte, 20) increase. More mature
are absent in all cells of this series. The chromatin is dis- myelocytes (12, 21, 22, 27, 29, 34, 35) have an abundance of
persed uniformly, and two or more nuclei may be present. specific granules, slightly acidophilic cytoplasm, and a
Early proerythroblasts divide to form smaller basophilic ery- smaller nucleus. The myelocyte is the last cell of granulocyt-
throblasts approximately 15 to 17 pm in size. ic series capable of mitosis; myelocytes then mature into
Basophilic erythroblasts (4, 7) exhibit less intensely metamyelocytes.
basophilic cytoplasm; however, sufficient basophilia is pre- In the metamyelocytes, the shape of the nucleus changes
sent in the cytoplasm to obscure the small amount of hemo- from oval to that with deep indentation, which is seen in
globin that is being synthesized by these cells. The nucleus mature cells; the greatest change takes place in the neu-
has decreased in size; the chromatin is coarse and exhibits trophilic forms (in succession: 30 and 36, 28, 33). Similar
the characteristic "checkerboard" pattern. Nucleoli are either structural alterations can be seen in eosinophils and
inconspicuous or absent. The progeny of mitotic divisions of basophils (27 lower leader, 27 upper leader, 32; 20, 12).
basophilic erythroblasts (4, 7) are the polychromatophilic Megakaryoblasts (37) are large cells that measure
erythroblasts (5, 13, 14). These cells are similar in size (12 approximately 40 to 60 pm in diameter. The cytoplasm is
to 15 pm in diameter). Their cytoplasm becomes progres- basophilic and largely free of specific granules. The volumi-
sively less basophilic and more acidophilic as a result of nous nucleus is ovoid or indented and exhibits a loose chro-
increased hemoglobin accumulation. The nuclei are smaller matin pattern and poorly defined nucleoli. The mature cells,
and exhibit the coarse "checkerboard" pattern. megakaryocytes (15, 38), are giant cells approximately 80
When the cells acquire an acidophilic cytoplasm because to 100 pm in diameter and have a large, slightly acidophilic
of an increased amount of hemoglobin, they are called nor- cytoplasm that is filled with fine azurophilic granules. The
mob lasts (6, 11) and their size is approximately 8 to 10 pm nucleus of these cells is large and convoluted, with multiple,
in diameter. Initially, the nucleus exhibits a concentrated irregular lobes interconnected by constricted regions. The
"checkerboard" chromatin pattern (6, 11), and the cell divi- chromatin is condensed and coarse, and nucleoli are not vis-
sion continues. The nucleus then decreases in size, becomes ible. In mature megakaryocytes (38), plasma membrane
pyknotic, and is extruded from the cytoplasm. The resulting invaginates the cytoplasm and forms demarcation mem-
flattened cell is the reticulocyte (9, 16, 17) or a young ery- branes. This delimits the areas of the megakaryocyte cyto-
throcyte, exhibiting a bluish-pink cytoplasm. With special plasm that is shed into the blood as small cell fragments in
supravital staining, a delicate reticulum is demonstrated in the form of platelets (39). The platelets measure approxi-
their cytoplasm. Mature erythrocytes (18, 31) are smaller mately 2 to 4 pm in diameter.
and have a homogenous acidophilic cytoplasm.
*For alternate terminology, see page text accompanying Fig. 5-8.

72 Tissues
Bone Marrow: Smear

Fig. 5-10 Bone Marrow: Smear. Stain: May-Grunwald-Giemsa. Oil immersion.

Blood 73

Muscle Tissue

The major function of the muscle tissue in the body is to junctions. These gap junctions provide close contacts
produce motion. Externally, this is seen as movement of between individual cells and allow the passage of stimuli
limbs; internally, as heartbeat, blood vessel contraction, between them. Smooth muscles are also innervated by nerves
intestinal peristalsis, sphincter activity, and others. The mus- from the sympathetic and parasympathetic divisions of the
cle tissue consists of elongated cells called fibers, and the autonomic nervous system; these innervations influence their
cytoplasm of these fibers contains different amounts of the contractility.
contractile protein filaments called actin and myosin.
There are three types of muscle tissue in the body. Based Skeletal Muscle
on its location, structure, and function, muscle tissue is divid- The major type of muscle tissue in the body is the skele-
/ ed into three general categories: skeletal muscle, cardiac tal muscle. Skeletal muscles attach to and move different
muscle, and smooth muscle. Each muscle category has cer- bones of the skeleton. Other skeletal muscles attach to and
tain structural and functional similarities as well as differ- move the facial skin, tongue, eyeball, or deep fascia. Skeletal
ences with each other. muscles are voluntary because they contract and relax as a
A special terminology is used to describe certain parts of result of a conscious control. In the sarcoplasm of a skeletal
muscle fibers that are different from other cells. The plasma muscle, the arrangement of contractile protein filaments
or cell membrane in muscle fiber is called the sarcolemma, actin and myosin is very regular. As a result, contractile fila-
cytoplasm is called sarcoplasm, and endoplasmic reticulum ments form distinct cross-striations, which are seen with the
is called sarcoplasmic reticulum. light microscope as the light I bands and the dark A bands
across each muscle fiber. Because of these distinct cross-stri-
Smooth Muscle ations in their fibers, skeletal muscles are also called striated
Smooth muscle fibers do not contain any visible cross muscles.
striations. Although smooth muscle fibers contain the con- Skeletal muscles are long, multinucleated fibers. They
tractile protein filaments actin and myosin, they are not exhibit longitudinal and parallel arrangements that are held
arranged in striated patterns as seen in skeletal or cardiac together by connective tissue. Skeletal muscles also are
muscles. As a result, the cross-striations are not visible in innervated richly by large motor nerves or axons. As the ter-
these fibers, and the muscles appear smooth or nonstriated. minal end of the motor nerve nears the skeleton muscle, it
Smooth muscle fibers are small, fusiform in shape, and con- branches, and each smaller axon branch then innervates a
tain a single nucleus. single muscle fiber. Because of this direct innervation, each
Smooth muscles are also involuntary muscles. Although skeletal muscle fiber contracts only when stimulated by the
smooth muscles are found in numerous organs of the body as nerve.
individual fibers or slender bundles or fascicles, they are Each skeletal muscle fiber exhibits a specialized site
found predominantly lining the visceral organs and blood ves- where the axon terminates. This is called the neuromuscular
sels. The smooth muscles occur in large sheets, as in the walls junction or motor endplate, a site where the impulse from the
of the hollow viscera such as in the digestive tract, uterus, axon is transmitted to the skeletal muscle fiber. The terminal
ureters, and others. In the blood vessels, smooth muscle fibers end of each axon exhibits numerous vesicles; these vesicles
are arranged in a circular pattern and participate in controlling contain the neurotransmitter chemical acetylcholine.
the blood pressure by altering the size of the lumina. Between the axon terminal and the muscle fiber is a shallow
Smooth muscles usually have spontaneous activity in a trough that separates the two structures. This trough is called
wavelike manner that passes in slow, sustained contraction the synaptic cleft.
over the entire muscle. This type of action produces a con- The arrival of a nerve impulse or the action potential at
tinuous contraction of low force. Smooth muscles make con- the axon terminal causes the synaptic vesicles to fuse with
tact with each other by specialized zones of contact, the gap the plasma membrane and release the acetylcholine into the

Muscle Tissue 75
synaptic cleft. The released acetylcholine then diffuses Cardiac muscles usually have one or two nuclei that are
across the synaptic cleft, combines with acetylcholine recep- located centrally. Cardiac muscle fibers are also shorter than
tors on the muscle fiber membrane, and stimulates the mus- skeletal muscle fibers and exhibit branching; this forms a
cle fiber. This stimulatory action of acetylcholine produces complicated network of muscle fibers. The terminal ends of
the contraction of the skeletal muscle fiber. An enzyme adjacent cardiac muscle fibers form unique and distinct end-
called acetylcholinesterase, located on the membrane of the to-end junctional complexes called intercalated disks. In
muscle fiber, then inactivates the released acetylcholine. This these regions, the opposing cell membranes come into close
inactivation of acetylcholine prevents further muscle stimu- contact with each other and form small gap junctions. The
lation and muscle contraction until the arrival of the next main function of intercalated disks is to bind and functional-
impulse at the axon terminal. ly couple all cardiac muscle fibers and to allow a rapid
Sensitive stretch receptors called neuromuscular spindles spread of stimuli for contraction of the heart. The diffusion
are located within all skeletal muscles. These spindles con- of ions through the pores in the gap junctions allows for the
sist of special muscle fibers called intrafusal fibers and nerve functional coupling and coordination of the activities in the
endings, which are surrounded by a connective tissue cap- entire cardiac muscle. As a result of this type of coupling and
sule. The main function of the neuromuscular spindles is to coordination, the cardiac muscle acts as a functional syn-
detect changes in length of the muscle fibers. An increase in cytium.
the length or stretching of these muscle fibers stimulates the In contrast to the skeletal muscles, the impulse-generating
neuromuscular spindle and causes a conduction of impulses and impulse-conducting system in the cardiac muscles is
to the spinal cord. This produces a muscle reflex, which then located within the heart wall itself. This system consists of
causes a contraction and shortening of the stretched muscle. specialized or modified cardiac muscle fibers that are found
A decrease in muscle length then decreases or ceases the in the sinoatrial (SA) node and atrioventricular (AV) node,
stimulation of the fibers in the neuromuscular spindle. bundle of His, and Purkinje fibers. The cardiac cells in the
All skeletal fibers are innervated. Consequently, the prop- SA node exhibit the most rapid rhythm of producing stimuli
er function of skeletal Jlluscles depends on the intact nerve for heart contraction. As a result, the SA node sets the
supply. If the nerve to a given muscle is severed or damaged, pace for the heart rate and is, therefore, the pacemaker of the
the muscle eventually can undergo atrophy and degeneration heart.
into fibrous tissue unless proper therapy is initiated. Purkinje fibers are thicker and larger than cardiac muscle
fibers and contain an increased amount of glycogen. Also,
Cardiac Muscle they contain fewer contractile filaments. The function of
The cardiac muscle is found primarily in the walls and Purkinje fibers is to deliver stimulatory impulses from the
septa of the heart and in the walls of the large vessels that are nodes to the rest of the heart musculature that produces ven-
attached to the heart. Like the skeletal muscles, the cardiac tricular contraction and ejection of blood.
muscles exhibit distinct cross-striations because the contrac- Both the parasympathetic and sympathetic divisions of
tile protein filaments actin and myosin have similar distribu- the autonomic nervous system innervate the heart in the
tion patterns. In contrast to the skeletal muscle, however, the vicinity of the nodes. Nerve fibers of the parasympathetic
cardiac muscle is involuntary and contracts rhythmically and division, by way of vagus nerves, slow the heart and decrease
automatically during the life of the individual. The rate of blood pressure. Nerve fibers of the sympathetic division pro-
this rhythm, however, is influenced by the innervation of the duce the opposite effect; they increase the rhythmicity of
nerve fibers from the autonomic nervous system (sympathet- the pacemaker cells and, consequently, heart rate and blood
ic and parasympathetic divisions) and different hormones. pressure.

76 Tissues

Figure 6-1 Smooth Muscle Layers of the Small Intestine

Figure 6-2 Skeletal (Striated) Muscles of the Tongue

Muscle Tissue 77
Figure 6-1 Smooth Muscle Layers of the Small Intestine

In the muscular region of the small intestine, smooth mus- places along their length, the cells exhibit different shapes
cles are arranged in two concentric layers, an inner circula- and sizes. The large nuclei (5, 9) are seen only in those sec-
tion and an outer longitudinal. In these layers, muscle fibers tions where the smooth muscle fibers (3, 5, 9) have been
are packed tightly, with the cells of one layer arranged at sectioned in the middle. The muscle fibers that were not sec-
right angles to those of the adjacent layer. tioned in the center appear only as deeply stained areas of
The upper region of the illustration shows the smooth clear cytoplasm (sarcoplasm) (3, lower leader; 9, lower
muscle fibers in the inner circular layer cut in the longitudi- leader).
nal section. Smooth muscle fibers (1, 7) are spindle-shaped In the wall of the small intestine, the smooth muscle lay-
cells with tapered ends. The cytoplasm (sarcoplasm) of each ers are applied closely to each other with only a minimum
muscle is stained deeply with an elongated or ovoid nucleus amount of connective tissue fibers and fibroblasts (2, 4, 8,
(7) present in the center. 10) visible between the two layers. The smooth muscles also
The lower region of the figure shows the muscles of the have a rich blood supply, as seen by the presence of numer-
adjacent longitudinal layer cut in a transverse section. ous capillaries (6,11) between individual fibers and between
Because the spindle-shaped cells are sectioned at different the layers.

Figure 6-2 Skeletal (Striated) Muscles of the Tongue

Skeletal muscle fibers are much longer and larger in and surrounded by connective tissue fibers (5). The connec-
diameter than smooth muscle fibers. In the tongue, these tive tissue (5) sheath around each muscle fascicle is the per-
muscle fibers course in different directions. This figure illus- imysium (12). From the perimysium (12), thin partitions of
trates the tongue muscle fibers in both the longitudinal connective tissue (5), called the endomysium (4,7), extend
(upper region) and transverse (lower region) sections. into each muscle fascicle (15) and invest individual muscle
Skeletal muscles fibers (9, in transverse section; 11, in fibers (9, 11). Small blood vessels (8) and capillaries (2, 14)
longitudinal section) are multinucleated, with the nuclei (1, are present throughout the connective tissue sheaths (5) that
6) situated peripherally and immediately below the sar- surround each muscle fiber.
colemma. (Sarcolemma is not illustrated in the figure.) Each Skeletal muscle fibers that have been sectioned longitudi-
skeletal muscle fiber shows distinct cross-striations (3), nally (II) show light and dark cross-striations, the A bands
which are visible as alternating dark or A bands (3a) and and I bands (3a, 3b). The muscle fibers that were sectioned
light or I bands (3b). With higher magnification, additional transversely (9) exhibit cross sections of myofibril bundles
details of the cross-striations are visible in Figure 6-4. (13) and peripheral nuclei (6).
Skeletal muscle fibers are aggregated into fascicles (15)

78 Tissues

1 Smooth muscle
6 Capillary

7 Nuclei of
smooth muscle

2 Connective
tissue 8 Connective
tissue and

3 Smooth muscle 9 Nucleus and

fibers cytoplasm of
smooth muscle
4 Fibroblast
10 Connective
5 Nucleus of tissue
smooth muscle
-fiber 11 Capillary

Fig. 6-1 Smooth Muscle Layers of the Small Intestine. Stain: hematoxylin-eosin. High magnification.

1 Nucleus

2 Capillary
10 Fibroblast in
3 Cross striations endomysium
a. A band
b. I band 11 Muscle fiber
(light) }
4 Endomysium

12 Perimysium

5 Connective

6 Nuclei of
13 Myofi brils
muscle fibers
7 Endomysium
14 Capillary
8 Blood vessel

9 Muscle fiber 15 Muscle fascicle

Fig. 6-2 SI<eletal (Striated) Muscles of the Tongue. Stain: hematoxylin-eosin. High magnification.

Muscle Tissue 79
Figure 6-3 Cardiac Muscle

Cardiac muscle fibers exhibit some of the features seen in the nucleus. Also visible in transverse sections are the
the skeletal muscles. This figure iIlustrates a section of a car- myofibrils (14) of individual cardiac muscle celIs.
diac muscle cut in both the longitudinal (upper portion) and A distinguishing and characteristic feature of the cardiac
transverse (lower portion) section. The cross-striations (2) muscles are the intercalated disks (4, 9). These disks (4,9)
in cardiac muscle fibers closely resemble those seen in skele- are dark-staining structures that are found at irregular inter-
tal muscles; however, cardiac muscles branch (5, 10) with- vals in the cardiac muscle; they represent the specialized
out much change in their diameters. Also, unlike the multi- junctional complexes between adjacent cardiac muscle
nucleated, elongated skeletal muscles, each cardiac muscle fibers.
fiber is shorter and contains a single, centralIy located nucle- The cardiac muscle has a vast blood supply. Numerous
us (3,7). Binucleate (two nuclei) muscle fibers (8) also are smalI blood vessels are found in the connective tissue (11)
seen occasionally. The location of the nuclei (7) in the center that surrounds the muscle fibers. Capillaries (6) are abun-
clearly is visible when the muscle fibers are cut in a trans- dant in the delicate endomysium (12) between individual
verse section. Around these nuclei (3, 7, 8) are the clear muscle fibers.
zones of nonfibrilIar perinuclear sarcoplasm (1, 13). In Other examples of cardiac muscles are seen in Chapter 8
transverse sections of the cardiac fibers, the perinuclear sar- (Figs. 8-5 to 8-8).
coplasm (13) appears as a clear space if the cut is not through

Figure 6-4 SI(eletal Muscle (longitudinal section)

High magnification of muscle fibers demonstrates the nally striated appearance to the muscle fibers. Where the
cross-striations. The anisotropic or A bands (2) are the myofibrils (6) are separated because of rupture of the sar-
prominent, dark-staining bands; a lighter middle region, the colemma, the A, I, and Z lines are visible on the myofibrils,
H band, is not visible. The isotropic or I bands are equalIy aligned next to each other on adjacent myofibrils.
prominent and are lightly stained acidophilic bands. Crossing Slender ovoid or elongated nuclei (4) of muscle fibers are
each central portion of the I bands are distinct, narrow lines, seen peripherally. In the endomysium (1) between muscle
the Z lines (3). fibers, fibroblasts (5) and a capillary (7) are seen.
The closely arranged paralIel myofibrils give a longitudi-

Figure 6-5 Cardiac Muscle (longitudinal section)

Comparison of cardiac muscle with skeletal muscle at the area between two intercalated disks represents one cardiac
same magnification and the same stain iIlustrates the simi- muscle cell.
larities and differences between the two types of muscles. Large, oval nuclei (1), usualIy one per celI, occupy the
Branching cardiac fibers (3) are in distinct contrast to central position and much of the width of the cardiac fibers,
individual skeletal fibers. Cross-striations (2, 5) are similar in contrast to the many elongated peripheral nuclei of the
to both but less prominent in cardiac muscle fibers. The skeletal fibers. The perinuclear sarcoplasm (6) region is
prominence of the intercalated disks (7) and their irregular distinct. Endomysium (4) filIs the spaces between fibers.
structure are seen more clearly at higher magnification. The

80 Tissues

8 Binucleate
1 Perinuclear fiber

9 Intercalated
2 Cross-striations disks

3 Central nucleus 10 Branching

cardiac fiber

4 Intercalated

6 Capillary - 13 Perinuclear

7 Central nuclei
14 Myofibrils

Fig. 6-3

1 Nucleus of
cardiac fiber
1 Endomysium ~~.~
. 2 A band (dark band)
2 A band 3 Branching of
(dark band) cardiac fibers
3 Z line crossing
I band
(light band) 4 Fibroblasts in
4 Nuclei of
muscle fibers
5 Z lines on I bands

5 Fibroblasts in
endomysium , 6 Perinuclear
6 Exposed
myofibrils 7 Intercalated
7 Capillary in

Fig. 6-4 Skeletal Muscle (longitudinal Fig. 6-5 Cardiac Muscle (longitudinal
section}. Stain:Ironhematoxylin-eosin.Oil section}. Stain: Iron hematoxylin-eosin. Oil
immersion. immersion.

Muscle Tissue 81
Figure 6-6 Skeletal Muscle and Muscle Spindle (transverse section)

A transverse section of the skeletal muscle shows individ- fibers called intrafusal fibers (7) are surrounded by the cap-
ual muscle fibers (1) grouped into fascicles by interfascicu- sule. Intrafusal muscle fibers are smaller in diameter and
lar connective tissue septa, the perimysium (2). In one septa, stain somewhat lighter (more sarcoplasm) than the ordinary
a muscle spindle (3) is seen, and a very small artery (4) is muscle fibers, extrafusal fibers (10). Small nerves (6) asso-
present in the transverse section. The muscle spindle is an ciated with the muscle/spindles represent incoming myeli-
encapsulated sensory end organ. nated and terminal unmyelinated fibers (axons). Very small
When viewed at a higher magnification, the muscle spin- blood vessels are present also in the capsule of the muscle
dle is surrounded by an ovoid connective tissue capsule (5), spindle. These small blood vessels come from blood vessels
which is derived from the perimysium (9). The capsule that are located in the connective tissue septa of the muscle
encloses several components of the spindle, all of which are proper.
surrounded by loose connective tissue. Specialized muscle

Figure 6-7 Skeletal Muscle and Motor Endplates

A group of skeletal muscle fibers (6, 7) have been teased branches, and distributes its axons (1, 5, 10) to the individual
apart and stained to illustrate the nerve terminations or muscle fibers (7). As the axons (I, 5, 10) reach the muscle
myoneural junctions on the muscle fibers. In this illustration, fibers, they terminate on individual muscle fibers as special-
the characteristic cross-striations (2, 8) of the skeletal mus- ized junctional regions called motor end plates (4, 9). The
cle fibers (7) are seen readily. The dark-stained, string-like small, round structures seen in the motor endplates (4, 9) rep-
structures between the separated muscle fibers (7) are the resent the terminal expansion of the axons (1, 5, 10).
myelinated motor nerve (3) and its terminal branches, the Axon terminals (1), whose motor endplates are not pre-
axons (1, 5, to). The motor nerve (3) courses to the muscle, sent in this section, are seen also in this figure.

82 Tissues
Nerve Terminations in S'{e'eta' Muscle

1 Skeletal
fibers (t.s.)

2 Perimysium
3 Muscle
- 10 Extrafusal

- 5 Capsule of the

4 Very small
muscle spindle
= 6 Nerves inthe

7 Intrafusal muscle
8 Very small artery

9 Perimysium

Fig. 6-6 Skeletal Muscle and Muscle Spindle (transverse section). Stain: hematoxylin-eosin.
Medium magnification (inset: oil immersion).

1 Axon terminals
2 Cross-striations -- 7 Skeletal muscle

3 Myelinated

8 Cross-striations
4 Motor end plates

5 Axons 9 Motor endplates

1 D Axons
6 Skeletal muscle
Fig. 6-7 SI(eletal Muscle and Motor Endplates. Stain: silver. High magnification.

Muscle Tissue 83

Nervous Tissue

The perception of internal and external stimuli is the pri- neurotransmitters and neurohormones. During a mechanical
mary function of the cells in the nervous tissue and the ner- or chemical stimulus, these specializations allow the neurons
vous system. Anatomically, the nervous system is divided to react (irritability) to the stimulus and to transmit (conduc-
into the central nervous system (CNS) and the peripheral ner- tivity) the information to other neurons in different regions of
vous system (PNS). The CNS consists of the brain and the the nervous system. Strong stimuli create a wave of excita-
spinal cord and is the integrating and communicating center tion or nervous impulses from the neurons that are then self-
of the body. The PNS consists of the nervous tissue that is propagated along the entire length of the axon (nerve fiber)
located outside of the CNS. Its function is to interconnect all over a long distance.
ollier nervous tissues with the CNS.
Neuroglia are the highly branched, supportive, non-neu-
The nervous tissue consists of two principal cell types:
ronal cells in the CNS that are located between the neurons.
nerve cells or neurons and supporting cells or neuroglia. The
These cells do not conduct impulses and are morphological-
structural and functional cells of the nervous tissue are the
ly and functionally different from the neurons. Three types of
neurons. Neurons form the highly complex intercommuni-
neuroglia cells exist: astrocytes, oligodendrocytes, and
cating network of nerve cells that receive and conduct
impulses along their neural pathways or axons to the CNS for
Astrocytes are the largest neuroglia cells and consist of
analysis, integration, interpretation, and response. The
two types: fibrous astrocytes and protoplasmic astrocytes. In
appropriate response to a given stimulus is provided by the
the CNS, both types of astrocytes are attached to the walls of
action of muscles or glands of the body.
the capillaries. The astrocytes support the neurons, repair the
Functionally, neurons are classified as sensory (afferent),
CNS tissue after injury or disease, and form scar tissue after
motor (efferent), or interneurons. Sensory neurons conduct
neuronal damage. In addition, the astrocytes may be
impulses from internal or external receptors to the CNS.
involved in energy metabolism and supporting metabolic
Motor neurons convey impulses from the CNS to the effec-
exchanges between neurons and the capillaries of the CNS.
tor muscles or glands. Interneurons serve as intermediary
Oligodendrocytes function by forming myelin sheaths
cells and are located between sensory and motor neurons in
around the axons in the CNS. Because oligodendrocytes
the CNS. Anatomically, three major groups of neurons exist:
have several processes, a single oligodendrocyte can sur-
multipolar, bipolar, and unipolar. Their anatomic classifica-
round and myelinate numerous axons. This same function of
tion is based on the number of dendrite and axon processes
myelination of the axons in the PNS is carried out by a dif-
that originate from the cell body.
ferent type of supporting cells called Schwann cells.
Multipolar neurons are the most common type in the CNS
Microglia are considered the macrophages of the CNS
and include motor neurons and interneurons of the brain and
and are found throughout the CNS. When nervous tissue is
spinal cord. Bipolar neurons are not as common and are
injured or damaged, microglia proliferate, become phagocyt-
purely sensory neurons. Bipolar neurons are the receptor
ic, and remove dead tissue from the CNS.
cells that are found in the retina of the eye, the organ of hear-
ing in the inner ear, and the olfactory epithelium in the upper
region of the nose. Most neurons in adults that exhibit only Nerve Fibers: Myelinated and Unmyelinated
one process leaving the cell body are originally bipolar. Axons
These unipolar neurons are also sensory and are found in Nerves contain axons of various size and their surround-
numerous craniosacral ganglia of the body. ing sheaths. In the PNS, all axons are surrounded by
Neurons are highly specialized for irritability, conductivi- Schwann cells. These cells extend along the length of periph-
ty, and the synthesis of such neuroactive substances as the eral axon, from its origin or its termination in the muscle or

Nervous Tissue 85
gland. The Schwann cells form the sheath of Schwann or the Schwann cells along the axon. In these nodal regions, the
neurilemma. In the CNS, the cells that surround the axons of axon is exposed to the extracellular environment.
different size are the oligodendrocytes. Myelination of the axons and the presence of the nodes of
The smaller axons, such as those of the autonomic ner- Ranvier accelerate the conduction of the nerve impulses
vous system, are surrounded only by the cytoplasm of the along the axons. Small unmyelinated axons conduct nerve
Schwann cell. Such axons do not have a myelin sheath impulses at a slower rate than the larger myelinated axons. In
around them and are considered unmyelinated. As the axons larger myelinated axons, the nerve impulse jumps from node
become progressively larger in diameter, they become sur- to node, resulting in a much more efficient and faster con-
rounded or sheathed by an increased number of successive duction of the impulse. This type of impulse conduction in
layers of the plasma membrane of the Schwann cell. These myelinated axons is called saltatory conduction. In unmyeli-
membranes then form the myelin sheath that surrounds and nated axons, the impulse travels along the entire length of the
insulates the axon. Axons that are surrounded by myelin axon and, as a result, conduction efficiency of the impulse
sheath are considered myelinated. Along the entire length of and velocity is reduced. Thus, the larger, heavy-myelinated
a myelinated axon are small gaps in the myelin sheath axons have the highest velocity of impulse conduction. This
between individual Schwann cells. These gaps are the nodes rate of conduction depends directly on the axon size and the
of Ranvier, and they represent the discontinuity between the myelin sheath.

86 Tissues
Figure 7-1 Motor Neurons: Anterior Horn of the Spinal Cord

Figure 7-2 Gray Matter: Anterior Horn of the Spinal Cord

Nervous Tissue 87
Figure 7-1 Motor Neurons: Anterior Horn of the Spinal Cord

The large, multipolar motor neurons (7) of the CNS have The Nissl bodies (4, 8) extend into the dendrites (10, 16) but
a large central nucleus (11), a prominent nucleolus (12), and not into the axon hillock (6, 13) or into the axon (5, 14). This
several radiating cell processes, the dendrites (10, 16). A feature distinguishes the axons (5, 14) from the dendrites (10,
single, thin axon (5, 14) arises from a cone-shaped, clear 16). The nucleus of the neuron (11) is outlined distinctly and
area of the neuron; this is the axon hillock (6, 13). The axons stains light because of the uniform dispersion of the chro-
(5, 14) that leave the motor neurons (7) are thinner and much matin. The nucleolus (12), on the other hand, is prominent,
longer than the thicker but shorter dendrites (10, 16). dense, and stains dark. The nuclei (2, 9) of the surrounding
The cytoplasm or perikaryon of the neuron is character- neuroglia (2, 9), are stained prominently, whereas their
ized by numerous clumps of coarse granules (basophilic small cytoplasm remains unstained. The neuroglia (2, 9) are
masses). These are the Nissl bodies (4, 8), and they represent non-neural cells of the central nervous system; they provide
the granular endoplasmic reticulum of the neuron. When the the structural and metabolic support for the neurons (7).
plane of section misses the nucleus (4), only the dark-stain- Surrounding the neurons (7) and the neuroglia (2, 9) are
ing Nissl bodies (4) are seen in the perikaryon of the neuron. numerous blood vessels (1, 3, 15) of various sizes.

Figure 7-2 Gray Matter: Anterior Horn of the Spinal Cord

This section of the anterior horn of the spinal cord was silver impregnation technique. As a result, the nuclei of these
prepared by silver impregnation (Cajal's method) to demon- neurons (3, 11, 14) appear as lightly stained or almost clear
strate neurofibrils. Typical neurofibril (2, 13) arrangements spaces. The nucleolus (15) may stain light (II) or dark (15).
are seen in the perikaryon (cytoplasm) of the motor neu- In the intercellular areas, many fibrillar processes, some of
rons (3, 6, 11) and in their dendrites (7, 12). Axons are not which arise from the anterior horn neurons or the associated
illustrated in this figure, but neurofibrils would be seen in adjacent neuroglia, are seen.
similar parallel arrangement. The nuclei (1, 4, 5, 8, 9, 10) of neuroglial cells are stained
Other details of the motor neurons are not revealed with and show same characteristics as described in Figure 7-1.

88 Tissues
1 Arteriole

2 Nuclei of neuroglia

3 Capillary

4 Nissl bodies

5 Axon

6 Axon hillock 15 Venule

7 Motor neuron

8 Nissl bodies

Nervous Tissue

9 Nuclei of neuroglia

10 Dendrites

11 Nucleus
12 Nucleolus

13 Axon hillock

14 Axon

16 Dendrites

Fig. 7-1 Motor Neurons: Anterior Horn of the Spinal Cord. Stain: hematoxylin-eosin. High

1 Protoplasmic 7 Dendrites with

astrocytes (nuclei) neurofibrils
2 Neurofibrils
8 Microglia (nuclei)
3 Perikaryon of a
motor neuron
4 OIigodendrocytes
(nuclei) 9 OIigodendrocytes

5 Protoplasmic 10 Protoplasmic
astrocytes (nuclei) astrocytes (nuclei)
11 Perikaryon of a
motor neuron
12 Dendrite with
6 Motor neuron 13 Neurofibrils in
Figure 7-3 Fibrous Astrocytes of the Brain

A section of the brain was stained by Del Rio Hortega's long, smooth, slightly branched processes (2) extending in
method to demonstrate the cell outlines, processes, and fibers all directions. A number of these processes (2) from different
of astrocytes and oligodendrocytes. astrocytes, seen in the upper left of the figure, terminate on a
In the center of the figure is a fibrous astrocyte (5). It blood vessel as vascular pedicIes (4) or foot plates.
exhibits a small cell body, a large nucleus, and numerous

Figure 7-4 Oligodendrocytes of the Brain

]n the upper right corner of the figure is a protoplasmic white matter of the CNS. In the white matter, the oligoden-
astrocyte (4). It exhibits a small cell body, large nucleus, and drocytes (2, 5) form myelin sheaths around numerous axons
numerous, thick-branched processes. (6) and are analogous to the Schwann cells that myelinate the
]n comparison, the oligodendrocytes (2, 5) have smaller axons in the nerves of the PNS.
oval cell bodies and nuclei than the astrocytes and exhibit A portion of the neuron (1) in the upper left of the figure
few, thin, short processes without excessive branching. The provides a size contrast with the astrocytes (4) and oligoden-
processes may be extremely thin (5) or somewhat thicker (2). drocytes (2, 5).
The oligodendrocytes (2, 5) are found in both the gray and

Figure 7-5 Microglia of the Brain

In this section of the brain are the microglia (1, 4). Their neuron (3), located superiorly in the figure, provides a size
cell bodies are extremely small, vary in shape, and often contrast with the microglia (I, 4).
exhibit irregular contours. The small, deeply stained nucleus Microglia are usually not numerous, but are found in both
almost fills the entire cell. The cell processes are few, short, the white and gray matter of the CNS. Microglia are the main
slender, tortuous, and covered with small "spines" (5). The phagocytes of the CNS.

90 Tissues

1 Perivascular fibrous

3 Oligodendrocyte
2 Processes of the
perivascular fibrous
4 Vascular pedicle (foot
plate) of a fibrous

5 Fibrous astrocyte: cell

body and nucleus

6 Processes of a fibrous

Fig. 7-3 Fibrous Astrocytes of the Brain. Stain: Del Rio Hortegas method. Medium magnification.

1 Neuron 4 Protoplasmic astrocyte

2 OIigodendrocytes

5 Oligodendrocyte

3 Capillary

6 Oligodendrocyte
processes surrounding
Fig. 7-4 Oligodendrocytes of the Brain. Stain: Modified Del Rio Hortegas method. Medium

3 Neuron
1 Microglia

2 Endothelial cell
of a capillary

6 Erythrocytes in a
Fig. 7-5 Microglia of the Brain. Stain: Del Rio Hortegas method. Medium magnification.

Nervous Tissue 91
Figure 7-6 Myelinated Nerve Fibers

Schwann cells surround the axons of the peripheral nerves A group of nerve fibers or fascicle is also illustrated. The
and form a myelin sheath. To illustrate the myelin sheath, fascicle is surrounded by a light-appearing connective tissue
nerve fibers are fixed with an osmic acid; this preparation layer called the perineurium (3, 5, 8). Each individual nerve
stains the lipid in the myelin sheath black. In this illustration, fiber or axon, in turn, is surrounded by a thin layer of con-
a portion of the peripheral nerve has been prepared in a lon- nective tissue called the endoneurium (7, 11).
gitudinal section (upper figure) and in a cross section (lower In the cross section, different sizes of myelinated axons
figure). are seen. The myelin sheath (9) appears as a thick, black
In the longitudinal section, the myelin sheath (1) appears ring around the light, unstained axon (13), which in most
as a thick, black band surrounding a lighter, central axon (2). fibers is seen in the center.
At intervals of a few microns, the myelin sheath exhibits dis- The connective tissue surrounding individual nerve fibers
continuity between adjacent Schwann cells. This region rep- or the fascicle exhibits a rich supply of blood vessels (6, 12)
resents the node of Ranvier (4). of different sizes.

Figure 7-7 Peripheral Nerve (transverse section)

Several bundles (fascicles) (1) of nerve fibers have been Numerous nuclei are seen between individual nerve
sectioned in transverse (1) or oblique (8) planes. Each nerve fibers. Most of these are Schwann cell nuclei (3); others are
fascicle is surrounded by a connective tissue sheath, the fibroblast nuclei of the endoneurium (5). (See Fig. 7-9).
perineurium (2), which merges with surrounding interfas- Numerous blood vessels (9-12, 16) that course in the
cicular connective tissue (17). Perineurial septa may interfascicular connective tissue send branches into each
separate larger nerve fascicles. From these or directly from fascicle that ultimately divide into capillaries in the endo-
the perineurium, delicate connective tissue strands sur- neurium (5).
round individual nerve fibers in a fascicle and form the
endoneurium (5).

92 Tissues
Nervous Tissue: Nerve Fibers and Nerves

1 Myelin sheath

4 Nodes 01 Ranvier

2 Axons

5 Perineurium
3 Perineurium

6 Blood vessels
7 Endoneurium

8 Perineurium 11 Endoneurium
12 Blood vessel

9 Myelin sheath
13 Axons
Fig. 7-6

9 Arteriole
1 Fascicles 01myelinated
nerve fibers (I.s.)
2 Perineurium
10 Arterial wall (tg. s.)
3 Schwann cell nuclei-
4 Myelinated nerve fibers 11 Lumen of an artery
5 Endoneurium and -
fibroblasts 12 Tunica media of an artery

6 Arteriole (I.s.) - 13 Vasa vasorum and nerve

in the tunica adventitia
14 Internal elastic membrane
15 Endothelium
7 Adipose cell
16 Venule
8 Fascicles of nerve
. 17 Loose interfascicular
fibers (o.s.)
connective tissue
18 Capillary
19 Adipose cell
Fig. 7-7 Peripheral Nerve (transverse section). Stain: hematoxylin-eosin. Medium magnification.

Nervous Tissue 93
Figure 7-8 Nerve: Sciatic (panoramic view, longitudinal section)

A portion of sciatic nerve is illustrated at a low magnifi- Perineurium (4) is the connective tissue sheath that sur-
cation, as it appears in a routine histologic preparation rounds individual nerve fascicles. The numerous nuclei that
stained with hematoxylin-eosin. The complete outer layer of are arranged along nerve fibers are the Schwann cell nuclei
dense connective tissue, the epineurium, is not shown in the (neurolemma nuclei) or fibroblast nuclei of the endoneurium
illustration. The deeper part of the epineurium contains adi- connective tissue. Schwann cells and fibroblasts cannot be
pose tissue (2) and blood vessels (1). Extensions of the differentiated at this magnification
epineurium (3) surround large nerve fascicles (5).

Figure 7-9 Nerve: Sciatic (longitudinal section)

A small portion of the nerve illustrated in Figure 7-8 is tissue; however, in certain areas it is seen as a thin, peripher-
shown at a higher magnification. The axons (1) appear as al boundary and at the node of Ranvier (2) as it descends
slender threads stained lightly with hematoxylin. The sur- toward the axon. Two Schwann cell nuclei (5) and the con-
rounding myelin sheath has been dissolved as a result of rou- nective tissue endoneurium (7) are seen in the illustration.
tine histologic preparation, leaving a distinct neurokeratin The fibroblasts (6) in the endoneurium are distinguished
network (3) of protein. The sheath (4) of Schwann cells is from Schwann cell nuclei (5).
not always distinguishable from the surrounding connective

Figure 7-10 Nerve: Sciatic (transverse section)

The transverse section of sciatic nerve, as seen in Figure Collagen fibers of the endoneurium are faintly distin-
7-9 illustrates the central axons (2), the neurokeratin net- guishable; however, the fibroblasts (5) are seen clearly.
work (3) of protein as peripheral radial lines, and the periph- Perineurium (6) surrounds a fascicle of nerve fibers and
eral Schwann cell sheath (4). Schwann cell nucleus (1) contains a small venule (7).
appears to encircle the axon (2).

Figure 7-11 Nerve: Sciatic (longitudinal section)

This section is stained with Protargol and aniline blue. axon shrinkage. The neurokeratin network is not stained.
The axons (1), stained black, are prominent because of silver Other visible structures are the nodes of Ranvier (4, 8),
impregnation of the neurofibrils. The scattered black droplets Schwann cell nuclei (7), and fibroblast nuclei (5) in the
probably represent remnants of neurofibrils remaining after endoneurium (6).

Figure 7-12 Nerve: Sciatic (transverse section)

As described in Figure 7-11, Protargol stains the axons (1) diameter. The endoneurium (4, 6) is well demonstrated by
black, as seen in the cross section. The surrounding gray area aniline blue staining of the collagen fibers. Other visible
and small, black droplets probably indicate the original axon structures are Schwann cell sheath (3) and fibroblasts (5).

Figure 7-13 Nerve: Branch of the Vagus (transverse section)

This figure illustrates still another staining method for stain red with azocarmine. The endoneurium (7) is demon-
nerve fibers and shows myelinated axons of varying size in a strated clearly, especially in areas where axons are close
branch of the vagus nerve. The fibroblast (1) and Schwann together and within groups of small nerve fibers (8).
cell (6) nuclei, axons (3), and neurokeratin network (4)

94 Tissues
1 Axons
Nervous Tissue: Nerves and Nerve Fibers
2 Node (of Ranvier)

3 Neurokeratin network

4 Schwann's sheath
1 Blood
vessels 5 Schwann cell nuclei
(neurolemma nuclei)

6 Fibroblast (nucleus)

7 Endoneurium

2 Adipose tissue Fig. 7-9 Nerve: Sciatic (longitudinal

in epineurium
3 Extensions
of epineurium
connective tissue)

4 Perineurium

5 Fascicles of 7 Venule
nerve fibers

Fig. 7-10 Nerve: Sciatic (transverse

section'. Stain: hematoxylin-eosin. Oil

1 Axon

2 Myelin sheath

3 Schwann cell sheath

1 Axons 4 Endoneurium

5 Fibroblasts (nuclei)
2 Myelin sheath

6 Endoneurium
3 Schwann cell sheath
Fig. 7-12 Nerve: Sciatic (transverse
4 Schwann cell sheath
at a node of Ranvier
1 Fibroblast (nucleus)
5 Fibroblasts (nuclei)
2 Endoneurium

3 Axons

4 Neurokeratin network
6 Endoneurium 5 Schwann cell sheath

6 Schwann cell nucleus

7 Schwann cell nuclei
7 Endoneurium

8 Node of Ranvier 8 Small myelinated

nerve fibers
Fig. 7-11 Nerve: Sciatic (longitudinal section,. Fig. 7-13 Nerve: Branch of the Vagus
Stain: Protargol and aniline blue. Oil immersion. (transverse section'. Stain: Mallory-azan. Oil

Nervous Tissue 95
Figure 7-14 Dorsal Root Ganglion (panoramic vie longitudinal sectiDn)

A connective tissue layer (1, 13), rich in adipose cells, ganglion cells are conspicuous because of their large size and
nerves, and blood vessels (13), surrounds the nervous tissue staining. Numerous fascicles of nerve fibers (9) are located
of a dorsal root ganglion (8). This layer merges with the between the ganglion cells and course either in the dorsal
external connective tissue capsule of the ganglion, the root (4) or the spinal nerve (11). These nerve fibers repre-
epineurium (2), which is continuous with the epineurium sent, respectively, the central processes and peripheral
of the dorsal root (3) and epineurium of the spinal nerve processes formed by bifurcation of a single axon process,
(10, 11). The perineurium and the endoneurium of the spinal which emerges from each ganglion cell.
nerve are not distinguishable at this magnification. The nerve fibers of the ventral root (7), surrounded by its
The round (pseudo) unipolar neurons (8) of varying size epineurium (6), join the nerve fibers that emerge from the
constitute the majority of the ganglion (8); these neurons or ganglion (8, 12) and form the spinal nerve (11).

Figure 7-15 Section of a Dorsal Root Ganglion

At higher magnification, ganglion cells or unipolar neu- around the ganglion cells (2, 3). An outer capsule (7) of more
rons (2, 3) appear variable in size. The characteristic vesicu- flattened fibroblasts (8) and connective tissue fibers is con-
lar nucleus (2) with its prominent, dark-staining nucleolus tinuous with the endoneurium. In different plane of sections,
(2) is conspicuous. The cytoplasm of these cells is filled with these two layers are not always clearly distinguishable; often
Nissl bodies (3). Each ganglion cell contains an axon the two cell types appear intermingled, as seen around the
hillock; however, it is not visible in this illustration. Some of cell with the lipofuscin pigment (5).
the ganglion cells contain small clumps of lipofuscin pig- Between ganglion cells (2, 3) are numerous fibroblasts
ment (5) in their cytoplasm. (4), randomly arranged in the connective tissue, or in rows in
Within the perineuronal space and in close association the endoneurium between nerve fibers (1). With hema-
with the ganglion cells (2, 3) are the much smaller satellite toxylin-eosin stain, small axons and connective tissue fibers
~t-6}~ ~c.dls..haYe sgherical nuclei, are of neuroecto- are not defined clearly. Large myelinated fibers (1) are rec-
dermal origin, and form a loose inner layer of the capsule ognizable when sectioned longitudinally.

Figure 7-16 Section of a Sympathetic Trunk Ganglion

Similar to the dorsal root ganglion cells, the cells of the Satellite cells (2, 5) are usually less numerous than
sympathetic trunk ganglion exhibit a characteristic nucleus, a around the cells in the dorsal root ganglion. Also, the con-
dark-staining nucleolus (sometimes multiple nucleoli), and nective tissue capsule with its capsule cells (3) may not be
Nissl bodies in their cytoplasm. well defined. Present in the intercellular area (4) are fibro-
In contrast to cells in the dorsal root ganglion, however, blasts, supportive connective tissue, blood vessels, and
the cells in the sympathetic trunk are multipolar neurons and unmyelinated and myelinated axons. Nerve fibers aggregate
are smaller and more uniform in size. As a result, the gan- into bundles (1, 7) and course through the sympathetic trunk.
glion cell outlines and their processes appear often irregular These nerve fibers represent the preganglionic fibers, post-
in the sections. The nuclei of the ganglion cells (6) are often ganglionic visceral efferent fibers, and visceral afferent
eccentric and binucleated cells are not uncommon. Most of fibers.
these cells (6) contain lipofuscin pigment in their cytoplasm.

96 Tissues
Nervous Tissue: Ganglia

Nervous Tissue 97
Figure 7-17 Spinal Cord: Cervical Region (transverse section)

To illustrate the white matter and the gray matter of the roots (9, 21) of the peripheral nerves. The posterior horns (2,
spinal cord, a cross section of the cord was prepared with sil- 13) are the sensory areas and contain cell bodies of smaller
ver impregnation technique. After staining, the dark brown, neurons.
outer white matter (3) and the light-staining, inner gray The spinal cord is surrounded by connective tissue
matter (4, 14) are clearly visible. The white matter (3) con- meninges, consisting of an outer dura mater, a middle arach-
sists primarily of ascending and descending myelinated noid (5), and an inner pia mater (18). The spinal cord is also
nerve fibers or axons. By contrast, the gray matter contains partially divided into right and left halves by a narrow, pos-
the cell bodies of neurons, interneurons, and their axons. The terior (dorsal) groove, the posterior median sulcus (10), and
gray matter also exhibits a symmetrical H-shape, whose two a deep, anterior (ventral) cleft, the anterior median fissure
sides are connected across the midline of the spinal cord by (19). In this illustration, pia mater (18) is best seen in the
the gray commissure (15) in whose center is located the anterior median fissure (19).
central canal (16) of the spinal cord. Between the posterior median sulcus (10) and the posteri-
The anterior horns (6) of the gray matter extend toward or horns (2, 13) of the gray matter are the prominent dorsal
the front of the cord and are more prominent than the poste- columns of the white matter. In the cervical region of the
rior horns (2, 13). The anterior horns contain the cell bodies spinal cord, each dorsal column is subdivided into two fasci-
of the large motor neurons (7, 17). Some axons (8) from the cles, the posteromedial column, the fasciculus gracilis (11)
motor neurons of the anterior horns cross the white matter and the posterolateral column, the fasciculus cuneatus
and exit from the spinal cord as components of the anterior (1, 12).

Figure 7-18 Spinal Cord: Anterior Gray Horn, Motor Neurons, and Adjacent
Anterior White Matter

A small section of the white matter and the gray matter of The white matter contains closely packed groups of
the anterior horn of the spinal cord are illustrated at a higher myelinated axons. In cross sections, the axons (1) appear
magnification. The gray matter of the anterior horn contains dark-stained and surrounded by clear spaces, which are the
large, multipolar motor neurons (2, 3). These are charac- remnants of the myelin sheaths. The axons of the white mat-
terized by numerous dendrites (5, 6) that extend in different ter represent the ascending and descending tracts of the
directions from the parikaryon (cell bodies). In some sections spinal cord. On the other hand, the axons (4) of the anterior
of the neurons, the nucleus (8) is visible with its prominent horn motor neurons aggregate into groups, pass through the
nucleolus (8). In other neurons, the plane of section has white matter, and exit from the spinal cord as the anterior
missed the nucleus and the parikaryon appears empty (2). (ventral) root fibers (Fig. 7-17).
Located in the vicinity of the motor neurons are the small,
lightstaining, supportive cells, the neuroglia (7).

98 Tissues
Spinal Cord: Cervical Region

10 Posterior
median sulcus

1 Fasciculus cuneatus 11 Fasciculus


12 Fasciculus
2 Posterior horn

13 Posterior horn

14 Gray matter
3 White matter

4 Gray matter

5 Arachnoid
~ 15 Gray commissure
16 Central canal

6 Anterior horn 17 Motor neurons

18 Pia mater
7 Motor neurons

19 Anterior median
8 Motor neuron axons
giving rise to anterior
20 Axons giving
rise to anterior

9 Anterior root 21 Anterior root

Fig. 7-17 Spinal Cord: Cervical Region (transverse section). Stain: Silver impregnation (Caja/s
method). Low magnification.

Fig. 7-18 Spinal Cord: Anterior Gray Horn, Motor Neurons, and Adjacent Anterior White
Matter. Stain: silver impregnation (Caja/s method). Medium magnification.

NeNOUS Tissue 99
Figure 7-19 Spinal Cord: Midthoracic Region (transverse section)

A transverse section of a spinal cord cut in the midtho- posterior white column (16, 17), lateral white column (7),
racic region and stained with hematoxylin-eosin is illustrat- central canal (9), and the gray commissure (18).
ed. Although a basic structural pattern is seen throughout the Associated with the posterior gray horns (6) are axons of the
spinal cord, shape and structure of the cord vary at different posterior roots (5) and leaving the anterior gray horns (10,
levels (cervical, thoracic, lumbar, and sacral). 20) are the axons (11, 21) of the anterior roots (11).
The thoracic region of the spinal cord differs from the cer- Surrounding the spinal cord are the connective tissue lay-
vical region illustrated on the previous page in Figure 7-17. ers of the meninges. These are the thick and fibrous outer
The thoracic spinal cord exhibits slender posterior gray dura mater (2), the thinner and middle arachnoid (3), and
horns (6) and smaller anterior gray horns (10, 20) with the delicate inner pia mater (4), which closely adheres to the
fewer motor neurons (10, 20). The lateral gray horns (8, surface of the spinal cord. Located in the pia mater (4) are
19), on the other hand, are well developed in the thoracic numerous anterior and posterior spinal blood vessels (1, 12)
region of the spinal cord. These contain the motor neurons of various sizes. Between the arachnoid (3) and the pia mater
(8, 19) of the sympathetic division of the autonomic nervous (4) is the subarachnoid space (14). Fine trabeculae located
system. in the subarachnoid space (14) connect the pia mater (4) with
The remaining structures in the midthoracic region of the the arachnoid (3). In life, the subarachnoid space (14) is
spinal cord closely correspond to the structures illustrated in filled with circulating cerebrospinal fluid. Between the
the cervical cord region in Figure 7-17. These are the poste- arachnoid (3) and the dura mater (2) is the subdural space
rior median sulcus (15), anterior median fissure (22), fas- (13). In this preparation, the subdural space (13) appears
ciculus gracilis (16) and fasciculus cuneatus (17) (seen in unusually large because of the artifactual retraction of the
the mid to upper thoracic region of the spinal cord) of the arachnoid during the specimen preparation.

Figure 7-20 Spinal Cord: Anterior Gray Horn, Motor Neurons, and Adjacent
Anterior White Matter

A higher magnification of a small section of the spinal The non-neural neuroglia (8) cells, seen only as
cord illustrates the appearance of gray matter, white matter, basophilic nuclei, are small in comparison to the prominent
neurons, neuroglia, and axons stained with hematoxylin- multipolar neurons (2, 4). The neuroglia (8) occupy the
eosin. The cells in the anterior gray horn of the thoracic spaces between the neurons. The anterior white matter of the
region of the spinal cord are multipolar motor neurons (2, spinal cord contains myelinated axons of various sizes.
6). Their cytoplasm is characterized by a prominent vesicu- Because of the histologic preparation of this section, the
lar nucleus (7), a distinct nucleolus (7), and course clumps myelin sheaths appear as clear spaces around the dark-stain-
of basophilic material called the Nissl substance (3). The ing axons (1).
Nissl substance extends into the dendrites (5) but not the In certain neurons (2), the plane of section did not include
axons. One such neuron exhibits the root of an axon from the the nucleus, and the cytoplasm appears enucleated (without
axon hillock (4), which is devoid of the Nissl substance. nucleus).

100 Tissues
Spinal Cord: Midthoracic Region

13 Subdural space

14 Subarachnoid space
15 Posterior median
16 Fasciculus
gracilis Posterior
17 Fasciculus
cuneatus j column

18 Gray commissure

19 Lateral gray horn

with motor neurons

20 Anterior gray horn

21 Axons of
anterior root

22 Anterior median

g. 7-19 Spinal Cord: Midthoracic Region (transverse section). Stain: hematoxylin-eosin. Low

White mailer Gray mailerof anterior horn

1 Axons 5 Dendrites

6 Multipolar motor
2 Multipolar motor neurons
neuron (plane of
section missed 7 Nucleus 2nd nucleolus
nucleus) of multipolar neuron
3 Nissl substance
8 Neuroglia
4 Axon hillock
and axon

Fig. 7-20 Spinal Cord: Anterior Gray Horn, Motor Neurons, and Adjacent Anterior White
Matter. Stain: hematoxylin-eosin. Medium magnification.

Nervous Tissue 101

Figure 7-21 Cerebellum 'sectional view, transverse section)

The cerebellum consists of an outer cortex of gray mat- cell layers can be distinguished in the cortex: an outer mol-
ter (3) and an inner white matter (4, 10). The white matter ecular layer (6) with few cells and horizontally directed
(4, 10) consists of myelinated nerve fibers or axons. These fibers, an inner granular layer (7) with numerous small
fibers are the afferent and efferent fibers of the cerebellar cells with intensely stained nuclei, and a central layer of
cortex. Their ramification (10) forms the core of the numer- Purkinje cells (8). The Purkinje cells are pyriform in shape
ous cerebellar folds. with ramified dendrites that extend into the molecular layer.
n\e gray matter constitutes the cortex, and three distinct

Figure 7-22 Cerebellum: Cortex

Purkinje cells (9) typically are arranged in a single row "basketlike" arrangement. Axons of the granule cells (6) in
at the junction of the molecular (8) and granular cell (10) the granular layer extend into the molecular layer and also
layers. Their large "flask-shaped" bodies give off one or course horizontally (2) as unmyelinated fibers.
more thick dendrites (3), which extend through the molecu- In the granular layer, numerous small granule cells (6, 10)
lar layer to the surface, giving off complex branchings along with dark-staining nuclei (an exception to the usual vesicular
their course. The thin axon (5) leaves the base of the Purkinje nucleus of nerve cells) and little cytoplasm are found. In the
cell, passes through the granular layer, and becomes myeli- granular layer scattered larger stellate cells or Golgi type II
nated as it enters the white matter (12). cells (7) with typical vesicular nuclei and more cytoplasm are
The molecular layer contains scattered outer stellate cells present. Throughout the granular layer are small, irregularly
(8) whose unmyelinated axons normally course in a horizon- dispersed, clear spaces called the "glomeruli" (11). In these
tal direction. Descending collaterals of more deeply placed regions, the cells are absent and synaptic complexes occur.
basket cells (4) arborize around the Purkinje cells (9) in a

102 Tissues

- 6 Cortex: molecular layer

-7 Cortex: granular layer
1 Cerebellar folium -
-8 Purkinje cells (central layer)
(pyriform cells)

2 Interfolial sulcus - - 9 Pia mater

3 Cortex (gray matter)

10 White matter

4 White matter

5 Cortex: granular layer

1&--,.;>1,1; ~' ~.r::."" A -. 1~~ ~.

Fig. 7-21 Cerebellum (sectional view, transverse section). Stain: silver impregnation (Caja/s
method). Low magnification.

8 Outer n
cells iii

n ~
Dr -.
9 Purkinje
cells J -< .E.
~ CD

10 Granule
cells ] :...

11 Glomeruli (islands) in
the granular layer

12 Myelinated fibers of
white matter

Fig. 7-22 Cerebellum: Cortex. Stain: silver impregnation (Cajals method). High magnification.

Nervous Tissue 103

Figure 7-23 Cerebral Cortex: Section Perpendicular to the Cortical Surface

The silver nitrate stain used for this section of cerebral Overlying and covering the molecular cell layer is the deli-
cortex demonstrates the neurofibrils. cate connective tissue of the brain, the pia mater (8).
The different cell types that constitute the cerebral cortex In the next four layers, the predominant cells are the char-
are distributed in layers, with one or more cell types pre- acteristic pyramidal cells of the cerebral cortex; these cells
dominant in each layer. Horizontal fibers associated with exhibit variable sizes. The figure illustrates that the pyrami-
each layer give the cortex a laminated appearance. Fibers dal cells (11, 13) get progressively larger in layers 2, 3, 4,
exhibiting a radial arrangement (14) are also present. and 5. Their dendrites (13) are directed toward the periphery
Although there are variations in arrangement of cells in of the cortex and their axon extends from the cell base. In the
different parts of the cerebral cortex, six distinct layers are internal granular layer (4), numerous smaller and larger
recognized. These layers are labeled on the left side of the stellate cells (12) form numerous complex connections with
figure. the pyramidal cells.
Starting in the periphery of the cortex, the outermost layer The multiform layer (6) lacks the pyramidal cells; how-
is the molecular layer (1). Its peripheral portion is composed ever, the fusiform cells predominate and the granule cells,
predominantly of horizontally directed neuronal processes, stellate cells, and cells of Martinotti are intermixed. All of
both dendrites and axons. Deep in the molecular layer lie the these cells vary in size. Axons of the cells of Martinotti are
infrequent, stellate or spindle-shaped horizontal cells of directed peripherally, whereas the axons from other cells
Cajal (10); their axons contribute to the horizontal fibers. enter the white matter (16).

Figure 7-24 Central Area of the Cerebral Cortex

Higher magnification of the cerebral cortex illustrates the Several collaterals (5) are given off along its course through
large pyramidal cells (1, 8). Neurofibrils (1, 8) in the cell the cortex. Smaller dendrites (6, middle leader) arise from
bodies have a characteristic network arrangement, whereas other parts of the cell body. The axon (7) arises from the base
neurofibrils in the dendrites (6) and the axons (7) exhibit a of the cell body and passes into the white matter.
more parallel arrangement. The typical large vesicular nucle- The intercellular area is occupied by nerve fibers (2) of
us (3) with its prominent nucleolus (3, lower leader) is out- various cells in the cortex, small astrocytes (4), and blood
lined. The most prominent cell process is the apical dendrite vessels.
(6), which is directed toward the surface of the cortex.

104 Tissues
Cerebral Cortex

Fig. 7-23 Cerebral Cortex: Section Perpendicular to the Cortical Surface. Stain: reduced silver
nitrate method of Cajal. Medium magnification.

4 Neuroglial cells
1 Pyramidal cells (astrocytes)

5 Dendritic collaterals of
pyramidal cells
6 Dendrites of pyramidal
2 Intercellular areas
(nerve fibers and
7 Axon of a pyramidal cell

3 Nuclei of pyramidal
cells 8 Pyramidal cell (tg. s.)

Fig. 7-24

NeNOUS Tissue 105

Part Two


Circulatory System

The circulatory system comprises two systems: blood vas- a result of the high proportion of smooth muscle fiber in their
cular and lymph vascular. The blood vascular system con- walls, the muscular arteries control blood flow and blood
sists of the heart, the major arteries, arterioles, capillaries, pressure through vasoconstriction or vasodilation of their
venules, and veins. These blood vessels deliver nutrients, lumina. These effects are produced primarily by the innerva-
oxygen, and hormones to, and remove metabolic waste prod- tion of the smooth muscle walls of the blood vessels by
ucts from, all of the cells in the body. This exchange occurs unmyelinated axons of the sympathetic division of the auto-
at the level of the capillaries. Blood from the capillaries then nomic nervous system.
enters into the venules and veins, and is returned to the heart. The arterioles are the smallest branches of the arterial ves-
The lymphatic system starts as blind-ending tubules or sels. Their walls consist of one to five layers of smooth mus-
lymphatic capillaries. The main function of the lymphatic cle. By autonomic constriction or dilation of their lumen, the
system is to collect the excess interstitial fluid (lymph), filter arterioles regulate the flow of blood into the capillary beds.
it through various lymph nodes, and return it to the blood- The terminal arterioles give rise to capillaries.
Capillaries are the smallest blood vessels in the body. The
The histology of the heart muscle has been described in average diameter of their lumina is about 8 pm, nearly equal-
detail in Chapter 6 as one of the four main tissues (Figs. 6-3 ing the diameter of an erythrocyte. There are three types of
and 6-5). In this chapter, the histology of the heart is illus-
capillaries in the body: continuous capillaries, fenestrated
trated as part of the cardiovascular system.
capillaries, and sinusoids.
The rhythmic contraction of the heart forces the blood out
The continuous capillaries are the most common type and
of its chambers and into the large arteries. The major func-
are found in connective tissue, all muscle tissue, the central
tion of the arterial system is the distribution of blood to the
nervous system, and other organs. In the continuous capillar-
capillary beds of the body. The three major categories of ves-
ies, the endothelial cells are joined and form an uninterrupt-
sels in the arterial system are elastic arteries, muscular arter-
ies, and arterioles. There is a gradual structural and function- ed endothelial lining in the blood vessel.
al transition from one type of vessel to the next. In contrast, the endothelial cells of the fenestrated capil-
The elastic arteries are the largest vessels and include the laries exhibit circular openings or pores (fenestrations) in
aorta and its major branches. The elastic arteries transport the their cytoplasm. The fenestrated capillaries allow a more
blood from the heart and move it along the vascular path. The rapid exchange of molecular substances between blood and
presence of a high proportion of elastic fibers in their walls the tissues than would normally occur in continuous capil-
allows the elastic arteries to expand during heart contraction laries. Fenestrated capillaries are found primarily in the
(systole), when a large volume of blood is ejected into their endocrine organs, the small intestine, and the glomeruli of
lumina. During heart relaxation (diastole), the expanded the kidneys.
elastic walls recoil upon the volume of blood in their lumina. Sinusoids are found in the liver, spleen, and bone marrow.
This forces the blood to move through the vascular channels The sinusoids follow irregular, tortuous paths through the
and maintains the necessary arterial pressure. Also, as a organs and have much wider diameters than other types of
result of elastic fibers in their walls, the elastic arteries pro- capillaries. Endothelial cell junctions are rare, and wide gaps
vide for a less variable systemic blood pressure and a more exist between individual endothelial cells. Also, the base-
even blood flow through the body during the heart cycle. ment membrane is incomplete or absent in the sinusoids. As
The medium-sized muscular arteries are branches of the a result of these gaps in the endothelial lining and the incom-
elastic arteries and constitute the great majority of arteries in plete basement membrane, plasma, as well as formed ele-
the body. They distribute blood to all organs of the body. As ments, can pass through the sinusoids.

Circulatory System J09

Veins The Lymph Vascular System
There is a gradual transition from the capillaries to The lymph vascular system consists of lymph capillaries
venules; venules usually accompany arterioles. The return- and lymph vessels. In contrast to blood capillaries, lymph
ing blood initially flows into postcapillary venules and then capillaries start as blind channels in the connective tissues. In
flows gradually into veins of increasing size. The veins addition, the endothelium in lymph capillaries is extremely
are arbitrarily classified as small, medium, and large. thin, affording greater permeability. The larger lymphatic
Compared to arteries, veins generally are more numerous vessels have a similar structure to that of veins except that
and have thinner walls, larger diameters, and greater struc- their walls are thinner. Lymph movement is similar to the
tural variation. movement of blood in the veins; however, the lymph vascu-
Blood pressure in the veins is lower than in the arteries. lar system includes more valves.
As a result, venous blood flow is passive. Venous blood flow The main function of the lymph vascular system is to pas-
in the head and trunk is primarily due to negative pressure in sively collect excess tissue fluid and proteins, called lymph,
the thorax and abdominal cavities resulting from respiratory from the intercellular spaces of the connective tissue and
movements. Blood return from the extremities is then aided return it into the blood vascular system. Lymph is a clear
by muscle contractions. fluid and an ultrafiltrate of the blood plasma. The lymph ves-
Small- and medium-sized veins, particularly in the sels also carry to the blood stream lymphocytes, fatty acids
extremities, are characterized by valves; these valves prevent absorbed in the small intestine, and antibodies (immunoglob-
the backflow of blood. When the blood in the veins flows ulins) produced in the lymph nodes.
toward the heart, the valves are forced flat against the wall of Lymphatic vessels are found in all tissues except the cen-
the vessel. As the blood begins to flow backward, however, tral nervous system, cartilage, bone and bone marrow, thy-
the valve flaps become distended with blood, closing the mus, placenta, and teeth.
lumen and preventing backflow. Venous blood situated
between the valves in the extremities thus is forced to flow Vasa Vasorum
toward the heart under the force of muscular contractions. The walls of larger vessels are too thick to receive nour-
Valves are absent in veins of the central nervous system, in ishment by direct diffusion from the lumen. As a result, the
large veins such as the inferior or superior vena cava, and in walls of these vessels have their own small blood vessels
veins of the viscera. called the vasa vasorum (vessels of the vessel).

J 10 Organs

Figure 8-1 Blood and Lymphatic Vessels

Figure 8-2 Large Vein: Portal Vein (transverse section)

Circulatory System 1J 1
Figure 8-1 Blood and Lymphatic Vessels

This plate illustrates various types of blood and lymphat- A medium-sized vein (22) is illustrated at the lower cen-
ic vessels, surrounded by loose connective and adipose tis- ter of the plate. It has a relatively thin wall and a large lumen.
sue (13, 28). Most vessels have been cut in a transverse or In cross section, the wall of the vein exhibits the following
oblique plane of section. layers:
A small artery (4), with its basic wall structure, is shown a. tunica intima, composed of endothelium (24) and an
at the top center of the plate. In contrast to a vein (22), an extremely thin layer of fine collagen and elastic fibers, which
artery has a relatively thick wall and a small lumen. In cross blend with the connective tissue of the tunica media.
section, the wall of an artery exhibits the following layers: b. tunica media (25), consisting of a thin layer of cir-
a. tunica intima, composed of an inner layer of endothe- cularly arranged smooth muscle loosely embedded in con-
lium (16), a subendothelial (17) layer of connective tissue, nective tissue. This layer is much thinner in veins than in
and an internal elastic lamina (membrane) (19), which arteries.
marks the boundary between the tunica intima and tunica c. tunica adventitia (26), consisting of a wide layer of
media. connective tissue. In veins, this layer is much thicker than the
b. tunica media (4), composed predominantly of circular tunica media.
smooth muscle fibers. A loose network of fine elastic fibers Arterioles (1, 5, 8) are also illustrated. The smallest arte-
is interspersed among the smooth muscle cells. riole (I) has a thin internal elastic lamina and one layer of
c. tunica adventitia (6), composed of connective tissue smooth muscle cells in the tunica media. One arteriole (8)
containing small nerves (14) and blood vessels (IS). The with a branching capillary (9) is sectioned longitudinally.
blood vessels in the adventitia are collectively called vasa Also illustrated are smaller veins (18, 27), venules (3, 10),
vasorum (15), or "blood vessels of blood vessel." capillaries (9, 11, 20), and small nerves (2, 23).
When arteries acquire about 25 or more layers of smooth A lymphatic vessel (12) can be recognized by the thinnest
muscle in tunica media, they are called muscular or distrib- of its walls and the flaps of a valve in the lumen. Many veins
uting arteries. Elastic fibers become more numerous, but are in the extremities have similar valves.
still present as thin fibers and networks.

Figure 8-2 Large Vein: Portal Vein (transverse section)

In large veins, the outstanding feature is the thick, muscu- In contrast to the thick tunica adventitia, the tunica media
lar adventitia, in which the smooth muscle fibers exhibit a (6) is a thinner layer of circularly arranged smooth muscle
longitudinal orientation. In the illustrated transverse section fibers and a more loosely arranged connective tissue. In other
of the portal vein, the typical arrangement in its wall is visi- large veins, the tunica media may be extremely thin and com-
ble: the smooth muscle fibers (1) are segregated into bun- pact. As seen in other vessels, the tunica intima is part of the
dles and seen mainly in cross section, with varying amounts endothelium (4) and is supported by a small amount of con-
of connective tissue of the tunica adventitia (2) dispersed nective tissue. In addition, large veins usually exhibit an
among them. Vasa vasorum (3, 7) are present in the inter- internal elastic lamina (5), which is not as well developed
vening connective tissue. as in the arteries.

1J2 Organs
Blood and Lymphatic Vessels and Large Vein

2 Nerves (t.s.) - 13Adipose tissue

14 Nerve
3 Venule (o.s.) -
15 Vasa vasorum

16 Endothelium
4 Small artery: tunica
media - 17 Subendothelial
5 Arteriole - - 18 Vein with blood
6 Tunica adventitia
of small artery --- 19 Internal elastic
lamina (membrane)
7 Vein (o.s.) -

>--- 20 Capillaries

8 Arteriole with a
- 21 Small artery
clot (I.s.1
"-- 22 Medium-sized vein

;>--- 23 Nerves (t.s.)

9 Capillary (I.s.1 -
- 24 Endothelium

~ 25 Tunica media
10 Venule

- 26 Tunica adventitia

11 Capillary - 27 Vein (o.s.)

12 lymphatic vessel
- 28 Adipose tissue

- '.
with a valve .
Fig. 8-1 Blood and Lymphatic Vessels. Stain: hematoxylin. Medium magnification.

1 Muscle fibers (l.s.1

of the adventitia 4 Endothelium

5 Internal elastic
2 Connective tissue lamina (membrane)
of the adventitia 6 Muscle (I.s.) of
tunica media
3 Vasa vasorum
(arteriole and venule)

7 Vasa vasorum

Fig. 8-2 Large Vein: Portal Vein (transverse section). Stain: hematoxylin-eosin. Medium

Circulatory System 1J3

Figure 8-3 Neurovascular Bundle (transverse section)

In the center of the figure is a large, elastic artery (18) The veins (4, 7, 22) exhibit a highly variable morphology;
with a thick tunica media (16) consisting primarily of con- however each vein has a thin wall and a large lumen. Some
centric layers of elastic lamina (membrane), between which veins can contain a blood clot or hemolyzed blood (7, 22).
are found thin layers of smooth muscle. The tunica intima Various-sized nerves (2, 8, 10, 25) accompany the blood
consists of endothelium (19) whose round nuclei appear to vessels. Each nerve is surrounded by the connective tissue
project into the lumen of the artery, and a thin layer of suben- perineurium and is composed primarily of unmyelinated
dothelial connective tissue (19) containing fine collagen and axons. Also illustrated in the figure is a sympathetic gan-
elastic fibers. The first visible elastic membrane is the inter- glion (1) surrounded by a connective tissue capsule. It con-
nal elastic lamina (17). The tunica adventitia (15) is a thin tains multipolar neurons, axons, and small blood vessels.
layer of connective tissue with vasa vasorum and the vaso- The figure also shows part of a small lymph node (5), its
motor nerves. hilus, and several efferent lymphatic vessels (6). The larger
Several arterioles (3, 9, 26) are illustrated, distinguished lymph node (11) shows its capsule (14), the subcapsular
by their thin muscular walls and relatively narrow lumina; sinus (13), cortex (12), and medulla (11).
also, numerous capillaries (21) are visible in the vicinity of
the artery.

Figure 8-4 Large Artery: Aorta (transverse section)

The structure of the illustrated artery is similar to that of unstained. The first elastic membrane is the internal elastic
the vessel illustrated in Figure 8-3, however, it has been lamina (membrane) (5). At times, smaller laminae appear in
stained with orcein, which stains elastic fibers (2) dark the subendothelial connective tissue, and a gradual transition
brown. Other tissues in the wall of the aorta remain colorless is made to larger laminae of the tunica media.
or are only lightly stained. The size and arrangement of elas- The tunica adventitia (1), also unstained, is a narrow
tic lamina in the tunica media are clearly demonstrated. zone of collagen fibers. In the aorta and pulmonary arteries,
Smooth muscle cells (3) and fine elastic fibers between the tunica media occupies most of the wall of the vessel, where-
laminae remain unstained. as tunica adventitia is reduced to a proportionately small
The extent of tunica intima (4) is indicated but remains area, as illustrated in the figure.

J 14 Organs
Neurovascular Bundle and Large Artery

16 Tunica media

17 Internal elastic
lamina (membrane)

18 Lumen of large
(elastic) artery
19 Endothelium and
connective tissue

Fig. 8-3 Neurovascular Bundle (transverse section). Stain: hematoxylin-eosin. Low magnification.

1 Adventitia 4 Intima

2 Elastic fibers
in media

5 Internal elastic
3 Smooth muscle in lamina (membrane)
media (unstained)

Fig. 8-4 Large Artery: Aorta (transverse section). Orcein stain: aorta. Elastic fibers selectively stained
dark brown. High magnification.

Circulatory System 115

Figure 8-5 Heart: Left Atrium and Ventricle (panoramic view, longitudinal
section J

This figure illustrates a longitudinal section of the left side sue. The leaflet of the atrioventricular (mitral) valve (4) is
of the heart, showing a portion of the atrium (1), the atri- formed by a double membrane of the endocardium (4a) and
oventricular (mitral) valve (4), and the ventricle (6). In this a core of dense connective tissue (4b), which is continuous
plane of section, the cardiac musculature is seen in various with the annulus fibrosus (3). On the ventral surface of the
planes. valve is seen the insertion of a section of chonda tendinae
In the atrial wall, the endocardium (1) consists of (5) into the valve.
endothelium, a thick subendothelial layer of connective tis- The inner surface of the ventricular wall exhibits the char-
sue, and a thick myocardium (2) of loosely arranged mus- acteristic prominence of myocardium and endocardium: the
culature. The epicardium (13) covers the heart and is lined apex of papillary muscle (18) and trabeculae carnaea (17).
externally by a single layer of mesothelium. A subepicardial The Purkinje fibers (8), or impulse-conducting fibers,
layer (14) contains connective tissue and fat, which vary in are located in the loose subendocardial tissue. They are dis-
amount in different regions of the heart. This layer also tinguished by their larger size and lighter-staining properties.
extends into the coronary (atrioventricular) and interventric- The small area within the rectangle (9) is illustrated in
ular sulcus of the heart. greater detail and higher magnification in Figure 8-7.
In the ventricle, the endocardium (6) is thin in compari- The larger blood vessels, such as the coronary artery
son with that in the atrium (I), whereas the myocardium (7) (10), course in the subepicardial connective tissue (14).
is thick and more compact. The epicardium and subepicar- Below the coronary artery is a section through the coronary
dial (16) connective tissue are continuous with those in the sinus (11). Entering the coronary sinus is a coronary vein
atrium. (12) with its valve. Smaller coronary vessels (15) are seen in
Between the atrium and ventricle is seen the annulus the subepicardial connective tissue (14) and in the perimy-
fibrosus (3), which consists of dense fibrous connective tis- seal septa (15) that extend into the myocardium (7).

116 Organs
Heart: Left Atrium and Ventricle

10 Coronary artery

1 Endocardium of atrium

2 Myocardium of atrium

11 Coronary sinus

12 Coronary vein
with valve

13 Epicardium of atrium

14 Subepicardial
3 Annulus fibrosus
connective tissue
and fat

15 Perimysial septa with

blood vessels
5 Chorda tendinae
16 Epicardium and
subepicardium of
17 Trabeculae carneae
6 Endocardium of

7 Myocardium of
ventricle 18 Apex of papillary

8 Purkinje fibers
(conduction fibers)

9 Area in
Fig. 8-7

Fig. 8-5 Heart: Left Atrium and Ventricle (panoramic view, longitudinal section). Stain:
hematoxylin-eosin. Low magnification.

Circulatory System 1 J7
Figure 8-6 Heart: Pulmonary Trunlc, Pulmonary Valve, Right Ventricle
(panoramic view, longitudinal section)

A portion of the right ventricle and a section of the pul- annulus fibrosus extends into the base of the pulmonary
monary trunk (6) are illustrated. The endothelium of the valve (10) and forms its central core.
tunica intima is visible on the surface to the right. Tunica The thick myocardium (4) of the right ventricle is lined
media constitutes the thickest portion of the wall of the pul- internally by endocardium (11). The endocardium extends
monary trunk; however, its thick, elastic laminae are not over the pulmonary valve (7) and the annulus fibrosus (9),
apparent at this magnification. A thin adventitia merges into and blends in with tunica intima of the pulmonary trunk (8).
the surrounding subepicardial connective tissue (2), which The external surface of the pulmonary trunk (6) is lined
is filled with fat in this specimen. by the subepicardial connective tissue and fat (2), which, in
The pulmonary trunk (8) arises from the annulus fibro- turn, is covered by epicardium (1). Both of these layers
sus (9). One cusp of its semilunar (pulmonary) valve (7) is cover the external surface of the ventricle. Coronary vessels
illustrated. Like the mitral valve, (illustrated in Fig. 8-5), it (3, 5) are seen in the subepicardium (2).
is covered with endocardium. The connective tissue from the

Figure 8-7 Heart: Purkinje Fibers (Impulse-conducting fibers)

The area outlined by a rectangle (9) in Figure 8-5 is illus- clear zone of comparatively clear sarcoplasm. A nucleus is
trated here at higher magnification to show the impulse-con- seen in some transverse sections; in others, a central area of
ducting fibers. Located under the endocardium (1) are clear sarcoplasm is seen, with the plane of section bypassing
groups of Purkinje fibers (2, 4). These fibers are different the nucleus.
from typical cardiac (myocardial) muscle fibers (5) Purkinje fibers merge with cardiac fibers at a transition-
because of their larger size and less intense staining. Some al fiber (3); the upper part of the fiber corresponds to a
Purkinje fibers are sectioned transversely (2) and others lon- Purkinje fiber and the lower part to an ordinary cardiac mus-
gitudinally (4). In transverse section, Purkinje fibers exhibit cle fiber.
fewer myofibrils, distributed peripherally, leaving a perinu-

Figure 8-8 Heart: Purlcinje Fibers (Impulse-conducting fibers)

This figure illustrates a cardiac region with Purkinje fibers With a hematoxylin-eosin preparation, the connective tis-
that are stained with Mallory-Azan; for this preparation, the sue does not stain well. In this preparation, the blue-stained
same magnification as in Figure 8-7 was used. The charac- collagen fibers accentuate the subendocardial connective
teristic features of Purkinje fibers (2) are demonstrated in tissue (3) around the Purkinje fibers (2). A capillary (1) with
both longitudinal and transverse sections. red blood cells is seen near these fibers.

J 18 Organs

6 Pulmonary trunk:
1 Epicardium intima, media,

7 Pulmonary valve:
endocardium and core
of connective tissue

2 Subepicardial -
connective tissue
and fat . 8 Base of pulmonary trunk

3 Coronary arteriole
and venules

9 Annulus fibrosus

! of pulmonary vein

> 11 Endocardium of

Fig. 8-6 Pulmonary trunk, Pulmonary Valve, Right Ventricle (panoramic view, longitudinal
section,. Stain: hematoxylin-eosin. Low magnification.

5 Myocardial fibers
(I.s. and t.s.)

Fig. 8-7 Purkinje Fibers (Impulse- Fig. 8-8 Purkinje Fibers (Impulse-
conducting fibers'. Stain: hematoxylin-eosin. High conducting fibers). Stain: Mallory-azan. High
magnification. magnification.

Circulatory System 119


Lymphoid System

The lymphoid system includes all cells, tissues, and then synthesize and secrete specific antibodies against the
organs that contain aggregates of lymphocytes. The lympho- particular antigen into the blood and lymph.
cytes are distributed throughout the body either as isolated T lymphocytes arise from lymphocytes that are carried
aggregates of cells, as distinct non-encapsulated lymphatic from the bone marrow to the thymus gland. Here, they
nodules in the loose connective tissue, or as encapsulated mature and acquire immunocompetence before migrating to
individual lymphoid organs. The major lymphoid organs are other peripheral lymphoid tissues and organs. Production of
the thymus, tonsils, spleen, and lymph nodes. Because the mature T lymphocytes by the thymus gland takes place early
bone marrow produces lymphocytes, it can also be consid- in the life of the individual. After their stay in the thymus
ered a lymphoid organ. gland, T lymphocytes are then distributed throughout the
The lymphoid cells, tissue, and organs are important com- body in the blood stream and populate the lymph nodes,
ponents of the immune system. They protect the internal spleen, and different lymphoid aggregates in the connective
environment of the body against any foreign substances or tissue. In these regions, the T lymphocytes are able to carry
antigens. This crucial protective function of the immune sys- out immune responses when stimulated.
tem is performed by the lymphocytes because these cells There are two types of closely allied immune responses.
have the ability to recognize antigens and, by producing anti- The first type is the cell-mediated immune response, in
bodies, react specifically against them. An antigen is any for- which the T lymphocytes proliferate, attack, and directly kill
eign macromolecule in the body that can provoke an immune the invading foreign microorganisms or antigens. T lympho-
response. Antibodies are circulating plasma glycoproteins, cytes may also attack indirectly by activating B lymphocytes
also called immunoglobulins, that are specialized to react or macrophages. In the second type of response, the humoral
with the antigens, initiating a complex immune response that immune response, the B lymphocytes differentiate into plas-
protects the body from damage by eventually destroying the ma cells and secrete specific antibodies. These antibodies
foreign substance. then bind to, inactivate, and/or destroy the particular foreign
Many types of lymphocytes exist in the various organs of substance or antigen. The activation and proliferation of B
the body. Morphologically, these lymphocytes appear very lymphocytes requires the cooperation (help) of T lympho-
similar, but functionally they differ greatly. Lymphoid tissue cytes that respond to the same antigen.
consists mainly of two types of lymphocytes: T lymphocytes
and B lymphocytes. These are two functionally distinct types Lymphoid Organs
of lymphocytes that play central roles in the immune system Thymus Gland. The thymus gland is an important compo-
and are found in the blood, lymph, and lymphoid tissues. nent of the immune system. During fetal development and
Like all blood cells, both types of lymphocytes originate early childhood, the thymus gland is large. It reaches its
from precursor hemopoietic stem cells in the bone marrow largest size during puberty, but is most functional in early
and enter the blood stream. Whether the developing lympho- childhood. As the body ages, the thymus gland gradually
cytes become B lymphocytes or T lymphocytes depends on atrophies and degenerates into connective tissue and adipose
where in the body they mature and become immunocompe- tissue.
tent. Although all of its functions are not completely under-
B lymphocytes mature and become immunocompetent in stood, the thymus gland performs an important role in devel-
the bone marrow. After they mature, B lymphocytes are car- oping the immune system of the organism. Undifferentiated
ried by the blood to the non-thymic lymphoid tissue, where lymphocytes are carried by blood to the thymus gland, where
they reside, primarily in the lymph nodes, spleen, and con- they proliferate and then differentiate into immunocompetent
nective tissue. When the immunocompetent B lymphocytes T lymphocytes. The T lymphocytes then leave the thymus
encounter a specific antigen, they become activated, prolif- gland by way of the blood stream and populate other lym-
erate, and differentiate into plasma cells. The plasma cells phoid organs and tissues. T lymphocytes carry out the cell-

Lymphoid System 121

mediated immune response and assist B lymphocytes in The T lymphocytes migrate to and concentrate below the
humoral immunity. The epithelial cells of the thymus gland lymphoid nodules in the deep cortical or paracortical regions
also secrete various hormones and humoral growth factors of the lymph node.
that are believed necessary for proliferation, differentiation, Spleen. The spleen is the largest lymphoid organ. One of
and maturation of T lymphocytes. These hormones are thy- its main functions is to filter the blood. As a result, the sinus-
mulin, thymopoietin, thymosin-I, and thymic humoral factor. es of the spleen are filled with blood cells. The dense reticu-
Under experimental conditions, if the thymus gland is lar network of the spleen's interior functions as an effective
removed in a newborn, the lymphoid organs will not become filter for antigens, microorganisms, platelets, and aged or
populated by the immunocompetent T lymphocytes. As a abnormal red blood cells. The trapped material in the reticu-
result of this deficiency, the organism does not acquire the lar meshwork is then removed from the blood by macro-
necessary immunological competence to fight invading phages and phagocytic reticular cells.
pathogens and may die early from the complications of an The spleen is also involved in recycling iron in the body.
infection. Spleen macrophages remove iron from the hemoglobin of
Lymph Nodes. Lymph nodes are distributed throughout the worn-out red blood cells and return it to the bone marrow,
body and along the paths of lymphatic vessels. They also are where the iron is reused during the synthesis of new hemo-
an important part of the defense mechanism of the body. The globin by the developing red blood cells. The heme from the
nodes are most prominent in the inguinal and axillary regions breakdown of hemoglobin is then degraded and excreted in
of the body. They filter the lymph, removing particulate mat- bile by the liver cells.
ter and oacteria before it enters the cardiovascular system. In fetal life, the spleen has an important role as a hemo-
The phagocytic function of the lymph nodes is directly poietic organ. In produces blood cells such as granulocytes
associated with lymph filtration. Within the mesh of the and erythrocytes. This hemopoietic capability, however,
reticular fiber network in each node are fixed or free ceases after birth. The spleen also serves as an important
macrophages. By filtering and phagocytizing bacteria or for- reservoir for blood. Because it has a sponge-like structure,
eign substances from the lymph, the lymph nodes assist in increased amounts of blood volume can be stored in its inte-
localizing and preventing the spread of infection into the rior. When the need arises, the stored blood is returned from
general circulation. the spleen to the general circulation.
Lymph nodes are also important in the formation of anti- The spleen is also imp0l1ant in defending the body against
bodies and in the immunological defense of the body in invasion by bacteria and viruses. This is due to the presence
response to regional antigens. Antibodies are produced and in the spleen of large quantities of both B lymphocytes and T
released into the lymph by the numerous plasma cells that are lymphocytes, as well as macrophages. The presence of anti-
concentrated in the lymph nodes. gens stimulate the proliferation of B lymphocytes, which
Lymph nodes also produce and recirculate B lymphocytes then give rise to plasma cells. The plasma cells in the spleen
and T lymphocytes. As these cells enter the lymph node, the then produce large quantities of antibodies.
B lymphocytes aggregate and proliferate in the germinal cen- Although the spleen performs various important functions
ter (central pale area) of the lymphoid nodules in the cortex. in the body, it is not essential to life.

122 Organs

Figure 9-1 Lymph Node (panoramic view)

Lymphoid System 123

Figure 9-1 Lymph Node (panoramic view)

The lymph node consists of lymphocyte aggregations tive tissue trabeculae (7) extend into the node, initially
intenneshed with lymphatic sinuses, supported by a reticular between the cortical nodules (7, upper leader) and then ram-
fiber framework and surrounded by a connective tissue cap- ifying throughout the medulla (15) between medullary cords
sule (2). The lymph node has a cortex (5) and a medulla (6). and sinuses. The trabeculae contain the major blood vessels
The cortex (5) of the lymph node contains lymphocytes (15) of the lymph node.
that are aggregated into lymphatic nodules (5, 16). In many Afferent lymphatic vessels (4) course in the connective
of the cortical nodules (16) the centers are lightly stained. tissue of the lymph node and, at intervals, pierce the capsule
These ljghter-stained areas represent the germinal centers to enter the subcapsular sinus (9, 17). From here, the tra-
(18), which are the active sites of lymphocyte proliferation. becular sinuses (cortical sinuses) extend along the trabeculae
In the medulla (6) of the lymph node, the lymphocytes are to pass into medullary sinuses (13).
arranged as irregular cords of lymphatic tissue, the At the upper right section are the hilus (12) of the lymph
medullary cords (14). The medullary sinuses (13) course node and the efferent lymphatic vessels (11), which drain
between these cords. lymph from the node. Also found here are nerves, small
The capsule (2) of the node is surrounded by connective arteries, and veins, which supply and drain the node.
tissue and pericapsular fat (1). From the capsule, connec-

124 Organs
Lymph Node

2 Capsule
10 Arterioles

3 Lymphatic tissue
11 Efferent lymphatic

12 Hilus

5 Cortex

13 Medullary sinuses

6 Medulla

14 Medullary cords

15 Trabeculae (1.s.1 in
the medulla with
7 Trabeculae
blood vessels

16 Lymphatic nodules

8 Blood vessels
in trabeculae
17 Subcapsular
sinus (marginal!

18 Germinal centers
9 Subcapsular sinus

19 Veins

Fig. 9-1 Lymph Node (panoramic view). Stain: hematoxylin-eosin. Low magnification.

Lymphoid System 125

Figure 9-2 Lymph Node (sectional view)

A small section of a cortical region of the lymph node is medullary cords. The medulla consists of anastomosing
illustrated at a higher magnification. cords of lymphatic tissue, the medullary cords (12, 20),
The lymph node capsule (5) is surrounded by loose con- interspersed with medullary sinuses (11, 21), which drain
nective tissue (1) containing blood vessels (2, 3, 4) and into the efferent lymphatic vessels located at the hilus.
afferent lymphatic vessels (13); the latter are lined with Reticular connective tissue forms the stroma of the corti-
endothelium and contain valves (14). Arising from the inner cal nodules, the medullary cords, and all sinuses. Relatively
surface of the capsule (5), connective tissue trabeculae few lymphocytes are seen in the sinuses (6, II, 16, 21); thus,
(15) extend through the cortex and medulla. Associated with it is possible to distinguish the reticular framework (21) of
these connective tissue partitions are trabecular blood ves- the node. In the lymphatic nodules (7) and the medullary
sels (18). cords (12, 20) lymphocytes are so abundant that the reticu-
The cortex (7) of the lymph node is separated from the lum is obscured unless it is specially stained, as shown in
connective tissue capsule (5) by the subcapsular (marginal) Figure 9-3. Most of the lymphocytes are small and contain
sinus (6). The cortex consists of lymphatic nodules situated large, deep-staining nuclei with condensed chromatin. The
adjacent to each other but incompletely separated by inter- cells exhibit either a small amount of cytoplasm or none
nodular trabeculae (15) and trabecular (cortical) sinuses at all.
(16). In this figure, one complete lymphatic nodule (7, Lymphatic nodules often exhibit germinal centers (8),
lower leader; 8; 17, lower leader) and portions of two other which stain less intensely than the surrounding peripheral
nodules (7, upper leader; 17, upper leader) are illustrated. portion of the nodule (7). In the germinal center (8), the cells
The deeper portion of the cortex, the paracortical region are more loosely aggregated and the developing lymphocytes
(19), is the thymus-dependent zone and is occupied by T have larger, lighter nuclei with more cytoplasm than the
lymphocytes. This is a transition area from the nodules to the small lymphocytes (see Fig. 9-4).

Figure 9-3 Lymph Node: Reticular Fibers of the Stroma

A section of a lymph node has been stained with the ognizable: the cortex (1), subcapsular (marginal) sinus (2),
Bielschowsky-Foot silver method to illustrate the intricate medullary cords (5), and medullary sinuses (6). All of
arrangement of the reticular fibers (4, 7). these regions contain a stroma of delicate reticular fibers (4,
The various zones illustrated in Figure 9-2 are readily rec- 7), which form the fine meshwork of the lymph node.

126 Organs
Lymph Node

3 Capillary
13 Lymphatic vessels
4 Veins

14 Valve
5 Capsule

6 Subcapsular

7 Cortex:
lymphatic 15 Internodular
nodules trabecula

8 Germinal
(.) center in 16 Trabecular sinuses
a lymphatic

9 Capillaries

17 Cortex

18 Trabecular blood
10 Trabeculae vessels
19 Paracortex
(deep cortex)

20 Medullary cords
.!!! 11 Medullary
.", sinus
12 Medullary
21 Reticulum of the
medullary sinuses

Fig. 9-2 Lymph Node (sectional view). Stain: hematoxylin-eosin. Medium magnification.

1 Cortex
5 Medullary
2 Subcapsular
sinus (marginal)
6 Medullary

3 Capsule and
trabecula 7 Reticular
fibers in
4 Reticular sinuses

Fig. 9-3 Lymph Node: Reticular Fibers of the Stroma. Stain: Bielschowsky-Foot silver method.
Medium magnification.

Lymphoid System 127

Figure 9-4 Lymph Node: Proliferation of Lymphocytes

This figure illustrates, at a higher magnification than that lower leader), which are characterized by dark-staining
in Figure 9-2, a portion of the lymph node capsule (1), the nuclei, condensed chromatin, and little or no cytoplasm.
subcapsular (marginal) sinus (2), a lymphatic nodule with The germinal center (6) contains a majority of cells that
its peripheral zone (5), and a germinal center (6) contain- are medium-sized lymphocytes (12). These are character-
ing developing lymphocytes. ized by larger, lighter nuclei and more cytoplasm than is seen
The reticular connective tissue of the node is seen in the in the small lymphocytes; the nuclei exhibit variations in size
subcapsular sinus (2), where reticular cells (9) and their and density of chromatin. The largest lymphocytes, with less
processes and associated delicate fibers are distinguishable. condensed chromatin, are derived from lymphoblasts (14).
Small lymphocytes (11, upper leader) and free mac- With successive mitosis (8), chromatin condenses and cell
rophages (3, 10) are also visible in the subcapsular sinus. size decreases, resulting in the formation of small lympho-
Endothelial cells (limiting cells) (4) form an incomplete cytes.
cover over the surface of the node. Occasional reticular cells The lymphoblasts (14) are visible in small numbers in the
(15) and free macrophages (3, 7, 10) may be seen in differ- germinal center (6). These are large, round cells with a broad
ent regions of the node. band of cytoplasm and a large vesicular nucleus with one or
The peripheral zone (5) of the lymphatic nodule is dense more nucleoli. Mitotic divisions of lymphoblasts (13) pro-
because of the accumulations of small lymphocytes (11, duce other lymphoblasts and medium-sized lymphocytes.

Figure' 9-5 Palatine Tonsil

The surface of the palatine tonsil is covered with strati- The fibroelastic connective tissue underlies the tonsil and
fied squamous epithelium (1), which also lines the deep forms its capsule (11). The septa (trabeculae) (5, 9) arise
invaginations or tonsillar crypts (3, 10). In the underlying from the capsule (II) and pass upward as a core of connec-
connective tissue are numerous lymphatic nodules (2) dis- tive tissue between the lymphatic nodules that form the walls
tributed along the crypts. The lymphatic nodules are embed- of the crypts. Skeletal muscle fibers (6, 12) form an under-
ded in reticular connective tissue stroma and diffuse lym- lying layer of the tonsil.
phatic tissue. The nodules frequently merge with each other
(8) and usually exhibit a germinal center (7).

128 Organs
Lymph Node and Palatine Tonsil

1 Capsule of the node

2 Subcapsular sinus
9 Reticular cells

3 Free macrophage

10 Free macrophage
4 Limiting cells
(endothelial cells)

11 Small lymphocytes
5 Lymphatic nodule:
peripheral zone

6 Germinal center 12 Medium-sized


13 Mitosis in a
7 Free macrophage lymphoblast

14 Lymphoblasts

15 Reticular cells
8 Mitosis in

Fig. 9-4 Lymph Node: Proliferation of Lymphocytes. Stain: hematoxylin-eosin. High magnification.

1 Stratified squamous

2 Lymphatic nodules 7 Germinal center

8 Merging nodules
3 Tonsillar crypts

Fig. 9-5 Palatine Tonsil. Stain: hematoxylin-eosin. Low magnification.

Lymphoid System 129

Figure 9-6 Thymus Gland (panoramic view)

The thymus gland is a lobulated lymphoid organ. It is phocytes but more epithelial reticular cells. The medulla also
enclosed by a connective tissue capsule (1) from which arise contains numerous thymic (HassaIl's) corpuscles (6, 9),
numerous trabeculae (2, 10). The trabeculae extend into and which are highly characteristic features of the thymus gland.
subdivide the thymus gland into incomplete lobules (8). The histology of the thymus gland varies with the age of
Each lobule consists of a dark-staining outer cortex (3, 13) the individual. The gland attains its greatest development
and a light-staining inner medulla (4, 12). Because the lob- shortly after birth; however, by puberty, it begins to involute.
ules are incomplete, the medulla exhibits continuity between Lymphocyte production declines and the thymic (Hassall's)
neighboring lobules (4, 12). Numerous blood vessels (5,14) corpuscles (6, 9) become larger. In addition, the parenchyma
pass into the thymus gland by way of the connective tissue of of the gland is gradually replaced by loose connective tissue
the capsule (I) and the trabeculae (2, 10). (10) and adipose cells (7, 11). The thymus gland depicted in
The cortex (3, 13) of each lobule contains numerous this illustration exhibits involution changes associated with
densely packed lymphocytes without forming lymphatic age.
nodules. In contrast, the medulla (4, 12) contains fewer Iym-

Figure 9-7 Thymus Gland (sectional view)

A small section of the cortex and medulla of a thymus epithelial cells. The corpuscles also exhibit calcification or
gland lobule is illustrated at a higher magnification. The degeneration centers (9), which stain as highly eosin-
thymic lymphocytes in the cortex (1, 5) exhibit dense aggre- ophilic. The functional significance of these corpuscles is
gations. In the medulla (3), there are fewer lymphocytes but unknown.
more epithelial reticular cells (7, 10). Blood vessels (6) and adipose cells (4) are seen in both
The thymic (Hassall's) corpuscles (8) are oval structures the lobules and the connective tissue trabecula (2).
consisting of round or spherical aggregations of flattened

130 Organs

1 Capsule

2 Trabeculae --=::
8 Lobule

3 Cortex

9 Thymic
4 Medulla - corpuscles

10 Connective
tissue of
11 Adipose cells

5 Blood vessels "'"

12 Medulla

6 Thym ic -.::::::::::
(Hassall's) 13 Cortex

7 Adipose cells -
14 Blood vessel
Fig. 9-6 Thymus Gland (panoramic view). Stain: hematoxylin-eosin. Low magnification.

. 5 Cortex (with thymic


. 6 Blood vessels
1 Cortex (with thymic ......

lymphocytes) 7 Epithelial reticular cell

2 Trabecula - - 8 Thymic (Hassall's) corpuscle
3 Medulla
4 Adipose cells: . 9 Degenerating centers of
thymic corpuscles

10 Epithelial reticular
Fig. 9-7 Thymus Gland (sectional view). Stain: hematoxylin-eosin. High magnification.

Lymphoid System 131

Figure 9-8 Spleen (panoramic view)

The spleen is enclosed by a dense connective tissue cap- Surrounding the lymphatic nodules (4, 6) and intermeshed
sule (1), from which connective tissue trabeculae (3) extend with the trabeculae (3) is a diffuse cellular meshwork that
deep into the spleen's interior. The main trabeculae enter the makes up the bulk of the organ and collectively forms the red
spleen at the hilus and branch throughout the organ. Located or splenic pulp (12, 13). In fresh preparations, red pulp
in the trabeculae (3) are the trabecular arteries (5b) and exhibits a red color because of its vascular tissue. The red
trabecular veins (Sa). Trabeculae that are cut in transverse pulp also contains pulp arteries (14), venous sinuses (13)
section (II) appear round or nodular. and splenic cords (Billroth's) (12); these appear as diffuse
The spleen is characterized by the presence of numerous strands of lymphatic tissue between the venous sinuses (13).
aggregations of lymphatic nodules (4, 6); these nodules The splenic cords (12) form a spongy meshwork of reticular
constitute the white pulp of the organ. The lymphatic nod- connective tissue. This is usually obscured by the density of
ules contain germinal centers (8, 9); these progressively other tissue.
decrease in number as the individual ages. Passing through The spleen does not exhibit a cortex and a medulla, as
each lymphatic nodule (4, 6) is a central artery (2, 7, 10); seen in lymph nodes; however, lymphatic nodules (4, 6) are
however, these arteries are usually displaced to one side, thus found throughout the spleen. In addition, the spleen contains
losing the central position. Central arteries are branches of venous sinuses, in contrast to lymphatic sinuses found in the
trabecular arteries (5b) that become ensheathed with lym- lymph nodes. However, the spleen does not exhibit subcap-
phatic tissue as they leave the trabeculae. This sheath also sular or trabecular sinuses. The capsule (I) and trabeculae (3)
forms the lymphatic nodules (4, 6), which then constitute the in the spleen are thicker than those around the lymph nodes
white pulp of the spleen. and contain some smooth muscle cells.

Figure 9-9 Spleen: Red and White Pulp

A higher magnification of a section of the spleen illus- splenic cords (1, 8) are thin aggregations of lymphatic tissue
trates a small area of red and white pulp along with such containing small lymphocytes, associated cells, and various
associated structures as the connective tissue trabeculae, var- blood cells. Venous sinuses (2, 9) are dilated vessels lined
ious blood vessels, venous sinuses, and the splenic cords. with modified endothelium; their elongated cells appear
The large lymphatic nodule (3) represents the white pulp cuboidal in transverse sections.
of the spleen. Each nodule normally exhibits a peripheral Also present in the red pulp are pulp arteries (10); these
zone, the periarterial lymphatic sheath, densely packed small are the branches of the central artery (4) as it leaves the lym-
lymphocytes, a germinal center (5), which may not always phatic nodule (3). Capillaries and pulp veins (venules) are
be present, and an eccentric central artery (4). The cells also present.
found in the periarterial lymphatic sheath are mainly T lym- Trabeculae containing trabecular artery (6) and tra-
phocytes. In the more lightly stained germinal center (5) are becular vein (7) are also clearly illustrated. These vessels
found the B lymphocytes, mainly medium-sized lympho- have the endothelial tunica intima and the muscular tunica
cytes, some small lymphocytes, and Iymphoblasts. media but no apparent connective tissue adventitia; connec-
The red pulp contains the splenic cords (1, 8) (Billroth's) tive tissue of the trabeculae surrounds the tunica media.
and venous sinuses (2, 9) that course between the cords. The

]32 Organs

1 Capsule

2 Central artery

3 Trabeculae
4 Lymphatic nodule
(white pulp) 9 Germinal center

10 Central artery

5 Trabecular 11 Trabeculae
a. vein
b. artery
12 Splenic cords
(in red pulp)
13 Venous sinuses
(in red pulp)
6 Lymphatic nodule
(white pulp)

7 Central artery 14 Pulp arteries

B Germinal center

Fig. 9-8 Spleen (panoramic view). Stain: Hematoxylin-eosin. Low magnification.

7 Trabecular vein

B Splenic cords

9 Venous sinuses

10 Pulp arteries

Fig. 9-9 Spleen: Red and White Pulp. Stain: Hematoxylin-eosin. Medium magnification.

Lymphoid System 133



Skin and its derivatives or appendages form the integu- external environment. Numerous encapsulated and free sen-
mentary system. In humans, skin derivatives include the sory nerve endings within the skin respond to stimuli for
nails, hair, and several types of sweat and sebaceous glands. temperature (heat and cold), touch, pain, and pressure.
Skin, or integument, is composed from two distinct regions, Excretory Organ. Through production of sweat by the
the epidermis and dermis. The epidermis is the superficial, sweat glands, water, sodium salts, and nitrogenous wastes are
nonvascular layer that consists of cornified, stratified squa- excreted to the surface of the skin.
mous epithelium. The dermis, deeper, thicker, and the more Formation of Vitamin D. When the skin is exposed to the
vascular layer of the skin under the epidermis, consists of ultraviolet rays from the sun, vitamin D is formed from pre-
connective tissue and contains blood vessels, nerves, and cursors synthesized in the epidermis.
skin derivatives.
The histology of the skin is similar in different regions of Skin Derivatives or Appendages
the body, though the thickness of the epidermis varies. In the The nails, hairs, and glands are derivatives of the skin that
regions of the palms and soles, for example, where there is develop directly from the surface epithelium of the epider-
an increased amount of wear, tear, and abrasion, the epider- mis. During development, the appendages grow into and
mis is thick. These are the thick skin regions. The remainder reside deep within the connective tissue of the dermis. Often
of the body is covered by thin skin. In these regions, the epi- the sweat glands extend deeper into the hypodermis, a con-
dermis is thinner and its cellular composition simpler than in nective tissue layer situated below the dermis.
the thick skin. Hairs are the hard, cornified, cylindrical structures that
The skin is the outer covering of the body and comes in arise from the hair follicles of the skin. One portion of the hair
direct contact with the external environment. As a result, the projects through the epithelium of the skin to the exterior sur-
skin performs numerous important functions: protection, face; the other portion remains embedded in the dermis. Hair
temperature regulation, sensory perception, excretion, and grows in the expanded portion at the base of the hair follicle
formation of vitamin D. called the hair bulb. The base of the hair bulb is indented by
Protection. The cornified, stratified epithelium of the skin a connective tissue papilla. This papilla is highly vascularized
epidermis protects the body from mechanical abrasion and and serves an important function by bringing the essential
forms a physical barrier to pathogenic microorganisms that nourishments to the cells of the hair follicle. In this region, the
may otherwise enter the body. The epidermis is impermeable hair cells divide, grow, cornify, and form the hair.
to water and also prevents the loss of body fluids through Associated with each hair follicle are one or more seba-
dehydration. ceous glands that produce an oily secretion called sebum.
Temperature Regulation. The skin participates in regulat- Extending from the connective tissue around the hair follicle
ing the temperature of the body. Physical exercise or a warm to the papillary layer of the dermis is a bundle of smooth
environment will cause increased sweating. This mechanism muscle called the arrector pili. The sebaceous glands are
allows some of the heat to be lost from the body by evapora- located between the arrector pili muscle and the hair follicle.
tion of sweat from the skin surfaces. In addition to sweating, The functions of the arrector pili muscle are controlled by the
thermoregulation also occurs as a result of increased dilation nerves of the autonomic nervous system. These muscles con-
of blood vessels for maximum blood flow to the skin; this tract under such conditions as fear, strong emotions, or cold.
dilation increases the dissipation of heat from the body core The contraction of arrector pilli muscle bundle erects the hair
to the exterior. Conversely, in cold climates, sweating does shaft, depresses the skin where it inserts, and produces a
not occur and the core body heat is conserved by constriction small bump on the surface of the skin often called a "goose-
of blood vessels and decreased blood flow to the skin. bump". In addition, contraction of the arrector pili muscle
Sensory Perception. The skin is a large sense organ, pro- forces the sebum from the sebaceous glands onto the hair fol-
viding the main source for general sensations of the body's licle and the skin. Sebum functions to oil and keep the skin

Integument 135
smooth, to prevent it from drying, and to provide some tion, which acquires a distinct odor following bacterial
antibacterial protection to the skin. decomposition.
The sweat glands, widely distributed in the skin, are sub-
divided into two types, eccrine and apocrine. Eccrine sweat Cells of the Skin
glands are simple, coiled tubular glands. Their secretory por- Four different types of cells are found in the epidermis of
tion is found deep within the connective tissue of the dermis, the skin: keratinocytes, melanocytes, Langerhans' cells, and
from which a coiled excretory duct leads to the surface of the Merkel cells. Keratinocytes, the most dominant epithelial
skin. The eccrine sweat glands contain two types of cells; cells in the epidermis, divide, grow, undergo keratinization,
clear cells without secretory granules and dark cells contain- and form a protective cell covering for the body.
ing secretory granules. Surrounding the secretory cells of the Melanocytes, located in the basal layer of the epidermis, syn-
sweat gland are myoepithelial cells, whose contraction thesize the pigment melanin, which is then incorporated into
expels the secretion (sweat) from the sweat glands. The keratinocytes. Melanin imparts a dark color to the skin and
eccrine sweat glands are most numerous in the skin of the exposure of the skin to sunlight promotes increased synthe-
palms and soles. The sweat consists primarily of water and sis of melanin. Langerhans' cells are epidermal cells that par-
some sodium salts, ammonia, uric acid, and urea. The main ticipate in the body's immune responses and play an impor-
function of the sweat is to assist the body in regulating the tant role in skin immunological reactions. A small number of
core temperature. Merkel cells are also found in the epidermis. Although they
The aeocrine sweat glands have a limited distribution in contain numerous granules, their exact function is not
the skin, limited primarily to the axillary, anal, and areolor known.
breast regions of the body. Apocrine sweat glands are larger Unless the skin is prepared with special stains,
than eccrine sweat glands and their ducts open into the hair melanocytes, Langerhans' cells, and Merkel cells are not eas-
follicle. The apocrine sweat glands produce a viscous secre- ily seen with routine histologic preparations.

136 Organs

Figure 10-1 Thin SI<in

Figure 10-2 Thicl< Skin, Palm: Superficial Layers

Integument 137
Figure 10-1 Thin SI<in

Skin is composed of two principal layers: epidermis (I) mis. A small portion of hypodermis (4), the superficial
and dermis (2, 3). The epidermis (I) is the most superficial region of the underlying subcutaneous tissue, is also illus-
and cellular layer. The dermis (2, 3) is located directly below trated.
the epidermis (I) and consists of connective tissue (2, 3) Most of the skin appendages are located in the dermis.
components. This illustration depicts a section of skin from Illustrated in this figure are parts of hair follicles and a sweat
the general body surface, where wear and tear are minimal. gland, which is illustrated in greater detail on the next page
In this type of skin, the epidermis (I) consists of stratified in Figure 10-3. The lower portion of the hair follicle is in
squamous epithelium and a thin layer of keratinized cells. longitudinal section and exhibits the hair bulb and papilla
This type of skin is thin and is in contrast to thick skin found (13) at its base; these structures are located deep in the der-
on the palms and soles, which are covered with a thick layer mis. The section of the upper portion of another hair follicle
of keratinized cells. (9) exhibits the smooth muscle, arrector pili muscle (10),
The single layer of low columnar cells at the base of the and a sebaceous gland (11). An oblique section of the hair
epidermis (I) is the stratum basale or germinativum (7). follicle (14) is illustrated deep in the subcutaneous tissue.
Located directly above this layer are a few rows of polygo- The dermis (2, 3) contains numerous examples of the
nal-shaped cells that form the stratum spinosum (6). Above cross sections of a coiled portion of the sweat gland (12).
these cells are usually found one or two layers of granular The sections with light-staining epithelium are from the
cells; these blend with the elongated, cornified cells of the secretory (12a) portion of the gland, whereas the darker-
stratum corneum (5). staining sections are from the duct (12b) portion.
The narrow zone of dense, irregular connective tissue This illustration of the skin has been prepared with Cajal's
below the epidermis (I) is the papillary layer (2) of the der- trichrome stain, which allows a view of the variations in col-
mis. This papillary layer (2) indents into the base of the epi- lagen fiber density and distinguishes between the muscle and
dermis and forms the dermal papillae (8). The deeper retic- connective tissue. The nuclei are stained bright red, the cyto-
ular layer (3) of the dermis consists of dense, irregular con- plasm orange, and the collagen fibers deep blue.
nective tissue; and this layer comprises the bulk of the der-

Figure 1 0-2 Thicl< Skin, Palm: Superficial Layers

A section of palm skin is illustrated here at higher magni- stratum basale (5), consisting of columnar cells that rest on
fication. The epidermis is much thicker and more complex the basement membrane.
than in the thin skin illustrated in Figure 10-1 and exhibits Cells of stratum spinosum (4, 8) are connected by spin-
five distinct cell layers. The outermost layer, the stratum ous processes or intercellular bridges (9 in the insert),
corneum (1), is a wide layer of flattened, dead cells that are which represent the desmosomes (macula adherens). Mitotic
constantly desquamated or shed (10) from the surface. activity (12) is normally seen in the deeper layers of stratum
Beneath the stratum corneum is a narrow, lightly stained spinosum (4) and stratum basale (5).
stratum lucidum (2). At higher magnification, outlines of Ducts of sweat glands (11) penetrate the epidermis
flattened cells and eleidin droplets in this layer are occasion- between two dermal papillae, lose their epithelial wall, and
ally seen. Located under the stratum lucidum is the stratum spiral through the cell layers of the epidermis (1-5) to the
granulosum (3), whose cells contain dark-staining kerato- skin surface as small channels with a thin cuticular lining.
hyalin granules (7), better seen at a higher magnification in Dermal papillae (6) are prominent in thick skin. Some of
the insert (bottom left). Below this layer is the thick stratum the dermal papillae contain tactile corpuscles (13)
spinosum (4), composed of several layers of polyhedral- (Messner's corpuscles); other papillae have capillary loops.
shaped cells. The deepest cell layer is the basal layer, the

138 Organs

1 Epidermis

2 Papillary layer


3 Reticular layer

Fig. 10-1 Thin SI<in. Stain: Cajals trichrome. Cytoplasm: orange, nuclei: bright red; collagen fibers: deep
blue. Low magnification.

L 10 Desquamating layer

11 Excretory duct
01 a sweat gland

12 Cell in mitosis

13 Tactile corpuscle
(Meissner's corpuscle) in
a dermal papilla

14 Papillary layer of
the dermis

Fig. 10-2 Thick SI<in, Palm: Superficial Layers. Stain: hematoxylin-eosin. Medium magnification.

Integument 139
Figure 1 0-3 Sweat Glands

The sweat gland is a simple, highly coiled tubular gland Leaving the secretory region of the sweat gland is a thin-
that extends deep into the dermis or the upper portion of the ner, darker-staining excretory duct (2, 7). The cells of the
hypodermis. To illustrate this, the sweat gland is shown in excretory duct are smaller than the cells of the secretory
both cross-sectional (left side) and diagrammatic views acini. Also, the duct is smaller in diameter and is lined by two
'(ITgT[' syJ-eJ. layers of deep-staining cuboidal cells. There are no myoep-
The coiled portion of the sweat gland located deep in the ithelial cells around the excretory duct. As the excretory duct
dermis represents its secretory (8) region. The secretory ascends through the dermis, it straightens out and penetrates
cells (3, 4) in this region are large, columnar, and stain light the cell layers of the epidermis (1, 6), where it loses its
eosinophilic. Surrounding the secretory cells are thin, spin- epithelial wall. In the epidermis (I, 6), the duct follows a spi-
dle-shaped myoepithelial cells (5); these are located ral course through the cells to the surface of the skin.
between the base of the secretory cells (3, 4) and the base-
ment membrane (not illustrated).

140 Organs
Sweat Glands

1 Excretory duct 6 Excretory duct

(in epidermis) (in epidermis)

7 Excretory duct
(in dermis)
2 Excretory duct
(in dermis)

3 Secretory cells

8 Secretory portion

Fig. 10-3 Sweat glands. Stain: hematoxylin-eosin. Low magnification.

Integument 141
Figure 1 0-4 SI<in: Scalp

This low magnification section of the scalp skin illustrates are aggregated clusters of clear cells; they are connected to a
some of the cell layers in the epidermis (1, 2, 13) and the duct that opens into the hair follicle (see Fig. 10-5).
contents of the underlying layers. In the epidermis (I, 2, 13), The arrector pili muscles (7) are smooth muscles that are
me most visible layers are the stratum corneum (1) with aligned at an oblique angle to the hair follicles (5). These
cells, stratum spinosum (2), and stra- muscles bind to the papillary layer of the dermis and to the
iUl1T il-J~-i1k. connective tissue sheath of the hair follicle. The contraction
The dermal papillae (3) form typical indentations on the of arrector pili muscles (7) moves the hair shaft to a more
underside of the epidermis (l, 2, l3). The thin papillary layer vertical position.
of the dermis, located immediately under the epidermis, is Deep in the dermis or in the subcutaneous layer are the
not visible at this magnification. The thick reticular layer basal portions of the sweat glands (11). Sections of the sweat
(4) of the dermis extends from just below the epidermis (I, gland (II) that exhibit lightly stained columnar epithelium
2, 13) to the subcutaneous layer (19), which contains are the secretory portions (11) of the gland. These are dis-
increased amounts of adipose tissue (19). Beneath the sub- tinct from sections of the excretory ducts (9) of the sweat
cutaneous layer (19) is found the skeletal muscle (12). glands (II), which exhibit two layers of smaller, darker-
Hair follicles (8, 10, 16, 17) in the skin of the scalp are stained cells; these excretory ducts have stratified cuboidal
very numerous, closely packed together, and placed at an epithelium. Each sweat gland duct (9) is coiled and located
angle to the surface of the skin. A complete hair follicle (16, in the deep dermis, then straightens out in the upper dermis
17d) in longitudinal section is illustrated in the center of the (15) and follows a spiral course through the epidermis (13).
figure. Parts of other hair follicles, sectioned in different The skin is highly vascular (20, 21) and has a rich senso-
planes, are also visible (5, 8, 17). Each hair follicle consists ry innervation. Some of these sensory endings, the Pacinian
of the following structures: cuticle, internal root sheath corpuscles (18), are located in the subcutaneous tissue.
(17a), external root sheath (17c), connective tissue sheath These corpuscles are important sensory receptors, for such
(17b), hair bulb (lOa), and connective tissue papillae perception as pressure and vibration. The Pacinian corpus-
(lOb). The hair passes upward through the follicle (16, 17) cles (18) are illustrated in greater detail and higher magnifi-
and to the surface of the skin. The sebaceous glands (6, 14) cation in Figure 10-8.

142 Organs

12 Skeletal muscle 21 Arteriole

Fig. 10-4 Skin: Scalp. Stain: hematoxylin-eosin. Low magnification.

Integument 143
Figure 10-5 Sebaceous Gland and Adjacent Hair Follicle

This figure illustrates a sebaceous gland (2-6) sectioned cytolysis (3) and, together with the secretory product sebum,
through the middle. The potential lumen is filled with secre- pass through the short duct (2) of the gland into the lumen of
tory cells undergoing cyto\ysis (3) (holocrine secretion), a the hair follicle. The sebaceous glands (2-D) lie in the con-
process in which the cells degenerate to become the oily nective tissue of the dermis and in the angle between the hair
secretory product of the gland, called sebum. The sebaceous follicles and the arrector pili muscles (11).
g\and (2-D) is lined with a stratified epithelium that has con- The various layers of the hair follicle at the level of the
tinuity with the external root sheath (1) of the hair follicle. sebaceous gland (2-6) may be identified. The follicle is sur-
The gland's epithelium is modified, and along its base is a rounded by a connective tissue sheath (7) of the dermis. The
single row of columnar or cuboidal cells, the basal cells (5), external root sheath (8) is composed of several cell layers;
whose nuclei may be flattened. These cells rest on a base- these layers are continuous with the epithelial layer stratum
ment membrane, which is surrounded by the connective tis- spinosum of the epidermis. The internal root sheath (9) is
sue of the dermis. The basal cells (5) exhibit mitotic activity composed of a thin, pale epithelial stratum (Henle's layer)
and fill the acinus of the gland with larger, polyhedral cells, (9) and a thin, granular epithelial stratum (Huxley's layer)
which enlarge, accumulate secretory material, and become (9). The latter is in direct contact with the cortex of the hair
round (4, 6). The cells in the interior of the acinus undergo (10), illustrated as a pale yellow layer with cells.

Figure 1 0-6 Bulb of Hair Follicle and Adjacent Sweat Gland

This figure illustrates the bulb of a hair follicle and its sur- cells of the hair matrix (12), which caps the connective tis-
rounding cell layers. A sheath of fibrous connective tissue sue papilla (11) of the hair follicle. Cell mitosis (10) can be
(7) surrounds the bulb. The external root sheath (1) at this seen in the matrix cells.
level of the bulb is a single layer of cells. The cells are In the dermal connective tissue and adjacent to the hair
columnar above the bulb and flat at the base of the bulb, follicle are sections through the basal portion of a coiled
where they cannot be distinguished from the matrix cells of sweat gland (8,9). The secretory cells (9) of the sweat gland
the hair follicle. Above the bulb is the internal root sheath are tall, columnar, and stain light. Along their bases may be
(2,3) composed of a thin, pale epithelium stratum (Henle's seen the flattened nuclei of the contractile myoepithelial
layer) (2), and a thin, granular stratum (Huxley's layer) cells (14). The excretory ducts (8) of the sweat gland are
(3). These two cell layers become indistinguishable as their smaller in diameter, are lined with a stratified cuboidal
cells merge with the cells of the bulb. Internal to these cell epithelium, and stain characteristically darker than the secre-
layers are the cuticles (4), cortex (5), and medulla (6) of the tory cells.
hair. In the bulb, these layers merge into undifferentiated

Figure 10-7 Glomus in the Dermis of Thick Skin

Arteriovenous anastomoses are numerous in the thick skin becomes thin again before the arteriole empties into a venule.
of fingers and toes. Some anastomoses form direct connec- The small artery (3, middle leader) may represent the termi-
tions; in others, the arterial portion of the anastomosis forms nal part of the glomus.
a specialized thick-walled structure called the glomus (2). Small nerves and capillaries are present in the glomus and
The vessel is coiled and, as a result, more than one lumen a connective tissue sheath (6) encloses the entire structure.
may be seen in a transverse section. The smooth muscle cells The dermis that surrounds the glomus contains blood ves-
in the tunica media have hypertrophied and the specialized sels (3), nerves (4), and ducts (1, 7) of sweat glands. The
muscle cells with the epithelioid appearance are now called PAS and hematoxylin (PASH) stains demonstrate the base-
the epithelioid cells (5). The tunica media wall, however, ment membrane of these ducts.

144 Organs

Integument 145
Figure 1 0-8 Pacinian Corpuscles in the Deep Dermis of Thick Skin

Pacinian corpuscles (1, 6) in the thick skin are located by concentric lamellae (10) of compact collagenous fibers,
deep in the dermis and subcutaneous tissue. The corpuscles which become denser peripherally (inner and outer lamel-
are important sensory receptors for pressure and possibly lae). Between the lamellae is a small amount of loose con-
"immitillt. G\\e. corpuscle is illustrated in a transverse section nective tissue with flat fibroblasts (6). A thin, dense connec-
,{}\.aar.m\7taerin an oblique section (6). tive tissue sheath (9) encloses the Pacinian corpuscle.
The Pacinian corpuscles are ovoid structures when seen in In a transverse section of the corpuscle (I), the layers of
longitudinal or oblique sections (6) and contain an elongated lamellae surrounding the inner bulb resemble a sliced onion.
central core, the inner bulb (8). This area usually appears In the dense irregular connective tissue of the dermis (3),
empty in sections, but in life, the corpuscle contains a termi- adipose cells (5), blood vessels (7), nerves (2, 11), and a
nal myelinated nerve fiber. The inner bulb (8) is surrounded sweat gland (4) surround the Pacinian corpuscle.

146 Organs

.: ,
5 Adipose Cells

6 Pacinian

1 Pacinian

7 Venules

8 Inner bulb
of the
2 Nerve (o.s.) (o.s.)
..l. 9 Sheath
of the

10 Inner
and outer
lamellae of
.'. the corpuscle
4 Duct and
secretory 11 Nerve (o.s.)
portion of
sweat gland

Fig. 10-8 Pacinian Corpuscles in the Deep Dermis of Thicl, Skin. Stain: Pash. High magnification.

Integument 147

Digestive System: Tongue and

Salivary Glands

The digestive system consists of a long hollow tube or tract There are four primary taste sensations to which the cells
that extends through the body from the oral cavity to the anus. in the taste buds respond: sour, salt, bitter, and sweet. All
Associated with this tube are such accessory organs as the sali- other taste sensations are combinations of these four. Certain
vary glands, liver, and pancreas. These organs produce numer- regions of the tongue exhibit more sensitivity to certain taste
ous secretions that are delivered to the digestive tract through sensations than do others. Thus, the tip of the tongue is most
the excretory ducts. These secretions facilitate the digestion and sensitive to sweet and salt, the posterior portion of the tongue
absorption of nutrients from the ingested material. to bitter, and the lateral edges to sour taste sensations.

The Oral Cavity The Salivary Glands

The oral cavity is the initial portion of the digestive sys- There are three major salivary glands: the parotid, sub-
tem. Here food is ingested, masticated (chewed), and lubri- mandibular, and sublingual. These glands, located outside of
cated for swallowing. The major structures of the oral cavity the mouth, produce a watery secretion called saliva. Saliva
are the lips, tongue, teeth, oral lining, and the salivary glands. is a mixture of mucus, enzymes, immunoglobulins, and
Because food is physically broken down in the oral cavity, ionic secretions that are produced by cells in different sali-
this cavity is lined by a protective, nonkeratinized, stratified vary glands, although the major composition of saliva is
squamous type of epithelium. The same type of epithelium water. The sight, smell, thought, taste, or the actual presence
extends over and covers the inner surface of the lips. of food in the mouth cause an autonomic increase of saliva
secretion from the salivary glands and its release into the
The Tongue
oral cavity.
The tongue consists of a core of interlacing bundles of Saliva performs numerous functions in the oral cavity. It
skeletal muscle fibers covered by a mucous membrane. The moistens the chewed food and lubricates the bolus to facili-
epithelium on the lower surface of the tongue is smooth, tate its swallowing and passage through the esophagus
whereas its dorsal surface is irregular and covered with toward the stomach. Saliva also contains numerous elec-
numerous epithelial elevations called papillae. The main trolytes (calcium, potassium, sodium, chloride, bicarbonate
functions of the tongue during digestion are to perceive taste ions, and others). The digestive enzyme amylase, produced
and to assist in chewing and swallowing food (bolus). The
mainly by the serous acini of the salivary glands, is also
sensation of taste is detected by specialized cells located in
found in the saliva. This salivary amylase initiates the break-
numerous taste buds that are found in the stratified squamous
down of starch into smaller carbohydrates during the short
epithelium of the fungiform, circumvallate, and foliate papil-
time that the food is present in the oral cavity.
lae of the tongue; in humans, the foliate papillae are rudi-
Saliva also controls bacterial flora in the mouth and pro-
mentary. In addition to the tongue, where the taste buds are
most numerous, the taste buds are also found in the mucous tects the oral cavity against pathogens. The enzyme lyso-
membrane of the soft palate, pharynx, and epiglottis. zyme, secreted also by the cells of the serous glands into the
Substances that stimulate the taste buds must first be dis- saliva, hydrolyzes the cell walls of bacteria and inhibits their
solved in saliva, which is normally present in the oral cavity growth in the oral cavity. Also, the immunoglobulins in sali-
and increased during food intake. In addition, taste buds in va, primarily the IgA produced by the lymphocytes and plas-
the circumvallate papillae are washed continuously by ma cells in the connective tissue of the glands, assist in
watery secretions produced by the serous (von Ebner's) immunological defense against bacteria found in the mouth.
glands located below the surface in the connective tissue of As the saliva flows through the duct systems of the sali-
the tongue. This continuous secretory process and washing vary glands, its ionic content is modified. Sodium and chlo-
of the taste buds allow different chemicals in the solution to ride ions are actively reabsorbed from the fluid in the lumen
enter the taste pores in the taste buds and to stimulate their while potassium and bicarbonate ions are added to the sali-
receptor cells. vary secretions.

Digestive System: Tongue and Salivary Glands 149

Figure 11-1 Lip (longitudinal section)

The core of the lip contains fibers of the striated muscle, lamina propria (2), the counterpart of the dermis as related
orbicularis oris (8). Special stains would reveal the presence to the epidermis. In the submucosa are found tubuloacinar
of intermixed dense fibroelastic connective tissue in the core. labial glands (4), which are predominantly mucous with
The right side illustrates the skin of the lip and the left side occasional serous demilunes. Their secretion moistens the
the mucosal lining of the mouth. oral mucosa and their small ducts (4, lower leader) open into
The skin of the lip is lined with epidermis (9) composed the oral cavity.
of stratified squamous, keratinized epithelium. Beneath the Transition of the skin epidermis to epithelium of oral
epidermis (9) is the dermis (10) with sebaceous glands (11), mucosa illustrates a mucocutaneous junction. The "red line"
hair follicles (12), and sweat glands (14); all of these are or vermilion border of the lip (6) is illustrated. Epithelium
epidermal derivatives. The dermis also contains the arrector (I) of the lip and oral mucosa is relatively smoother than that
pili muscles (13, 15) and a neurovascular bundle (7) on the of the epidermis (9). The underlying papillae of the lip and
lip periphery. oral mucosa are high, numerous, and abundantly supplied
The labial mucosa is lined with a stratified squamous, with capillaries. The color of the blood shows through the
nonkeratinized epithelium (1). The surface cells, without overlying cells, giving the lips a characteristic red color. The
becoming cornified, slough off in the fluids of the mouth. epithelium of the labial mucosa (I) is also thicker than the
Underlying the mucosal epithelium is the connective tissue epidermis of the skin (9).

150 Organs

6 Border of the lip,

transition zone

1 labial Epithelium 7 Neurovascular


8 Orbicularis oris
2 lamina propria

9 Epidermis

3 Superficial 10 Dermis
11 Sebaceous gland

12 Hair follicles
(t.s. and I.s.)
4 labial glands:
mucous acini and Arrector pili muscle

5 Vein

14 Sweat gland: duct

and secreting portions

15 Arrector pili muscle

Fig. 11-1 Lip (longitudinal section). Stain: hematoxylin-eosin. Low magnification.

Digestive System: Tongue and Salivary Glands 151

Figure 11-2 Tongue: Apex (longitudinal section, panoramic view)

The mucosa of the tongue consists of a stratified squa- skeletal muscle (3, 5). As a result, the tongue muscle is typ-
mous epithelium (1) and a thin papillated lamina propria ically seen in longitudinal, transverse, or oblique planes of
(\). which may contain diffuse lymphatic tissue. The dorsal section. In the connective tissue around the muscle bundles
surface of the tongue is characterized by mucosal projections may be seen numerous blood vessels (9, 10, 15, 16) and
called papillae (4, 6, 7). Most numerous are the slender fili- nerves (8, 17).
form papillae (6) with cornified tips. Less numerous are the In the lower half of the tongue near the apex and embed-
fungiform papillae (4, 7), which exhibit a broad, round sur- ded in the muscle (3, 5) a portion of the anterior lingual gland
face of non cornified epithelium and a prominent core of lam- is illustrated. This gland is of a mixed type and contains
ina propria (4). All papillae are located on the dorsal surface serous (11), mucous (13), and mixed acini with serous
of the tongue but are absent on the entire ventral (lower) sur- demilunes (not illustrated). The interlobular ducts (12) pass
face (I8), where the mucosa is smooth. into the larger excretory ducts (14), which then open into
The core of the tongue consists of crisscrossing bundles of the oral cavity on the ventral surface of the tongue.

152 Organs

4 Fungi fDr m Pa p illa:
epithelium a~ d
2 Muscle (I.s.)
lamina propna

3 Muscle (ts.) 5 Muscle (o.s.)

6 Filiform papillae

11 Serous acini

Anterior hngual gland
Fig. 11-2 Tongue. . A p ex - dinal section,
(Iongltu - p anoramlc- view). .
Stal. n . hematoxylin-eosin.

Digestive Syste m". Tongu e and Salivary Glands 153

Figure 11-3 Tongue: Circumvallate Papilla 'cross section)

A cross section of a circumvallate papilla of the tongue is of the tongue are numerous, tubu]oacinar serous (von
illustrated in this figure. The epithelium of the tongue, lin- Ebner's) glands (6, 11), whose excretory ducts (6a, 11a)
gual epithelium (2), and that covering the circumvallate open at the base of the circular furrows (5, ]0) in the cir-
papilla is stratified squamous (1). The underlying connec- cumvallate papilla. The secretory product from these glands
tive tissue, the lamina propria (3), exhibits numerous, sec- acts as a solvent for taste-inducing substances.
ondary papillae (7) that project into the overlying stratified Most of the core of the tongue consists of interlacing bun-
squamous epithelium (1, 2) of the papilla. A deep trench or dIes of skeletal (striated) muscles (12) running in different
furrow (5, 10) surrounds the base of each circumvallate directions. Examples of skeletal muscle fibers sectioned in
papilla. longitudinal (12a) and transverse planes (] 2b) are abundant.
"4lm~m1,L,a.valtaste buds (4, 9) are found in the epithe- This arrangement of muscles allows the tongue great mobi]-
lium of the latera] surfaces of the circumvallate papilla and ity, which is necessary for phonating, chewing, and swallow-
on the outer wall of the furrow (5, ]0). Higher magnification ing of food. The lamina propria (3) surrounding the serous
and greater details of the taste buds (4, 9) are illustrated in glands (6, I I) and muscles also contains an abundance of
Figure I ]--4. Located deep in the lamina propria (3) and core blood vessels (8).

154 Organs

3 Lamina -

4 Taste buds

5 Furrow

6 Serous
(von Ebner's)
a. excretory
b. serous

Fig. 11-3 Tongue: Circumvallate Papilla (cross section). Stain: hematoxylin-eosin. Medium

Digestive System: Tongue and Salivary Glands 155

Figure 11-4 Tongue: Taste Buds

The taste buds (5, 12) at the bottom of a furrow (14) the basal cells (13) are located at the periphery of the taste
(Fig. 11-3) are illustrated at a higher magnification and in bud (5, 12) near the basement membrane.
greater detail. The taste buds (5, 12) are actually embedded At this present time, no consensus exists that defines the
within and extend the full thickness of the stratified lingual specific gustatory role to a certain cell type. However,
epithelium (1) of the circumvallate papilla. The taste buds because unmyelinated nerve fibers are associated with both
(5, 12) are distinguished from the surrounding stratified sustentacular cells (3, 8) and gustatory cells (7, II), both
epithelium (I) by their oval shape and elongated cells (mod- types may serve some taste receptor functions. It is believed
ified columnar) arranged perpendicularly to the surface of that basal cells (13) give rise to both the sustentacular cells
the epithelium (I). (3, 8) and gustatory cells (7, II).
There are several types of cells in taste buds (5, 12). Three The apical surfaces of both the sustentacular cells (3, 8)
different types of cells can be identified in this illustration. and gustatory cells (7, II) have long microvilli (taste hairs)
The dark supporting or sustentacular cells (3, 8) are elon- (4) that extend into and protrude through the taste pore (9)
gated with a darker cytoplasm and slender, dark nucleus. The into the furrow (14) that surrounds the circumvallate papilla.
light taste or gustatory cells (7, 11) exhibit a lighter cyto- The surrounding lamina propria (2) consists of loose con-
plasm and a more oval, lighter nucleus. A third type of cell, nective tissue and numerous blood vessels (6, 10).

156 Organs
Tongue: Taste Buds

1 Lingual epithelium "

2 Lamina propria
j - 8 Sustentacular cell

3 Sustentacularcell . - 9 Taste pore

4 Microvilli (taste hairs) ~ 10 Blood vessel

5 Taste bud } - 11 Gustatory cell

. 4
- 12 Taste bud

7 Gustatorycell ~ - 13 Basal cells

- 14 Furrow

Fig. 11-4 Tongue: Taste Buds. Stain: hematoxylin-eosin. High magnification.

Digestive System: Tongue and Salivary Glands 157

Figure 11-5 Posterior Tongue Near Circumvallate Papilla ,'ongitudina'

The posterior region of the tongue is located behind the blood vessels, and nerves (9).
circumvallate papillae and near the lingual tonsils. Its dorsal Numerous mucous acini (4) of the posterior lingual
surface typically exhibits large mucosal ridges (1) and round mucosal glands lie deep in the lamina propria and connective
elevations or folds (6) that resemble large fungiform papil- tissue between the skeletal muscles (5, 10). The excretory
lae. Lymphatic nodules of the lingual tonsils can be seen in ducts (7) of the lingual glands open onto the dorsal surface
such elevations; however, the typical filiform and fungiform of the tongue, usually between bases of the mucosal ridges
papillae normally seen in the anterior region of the tongue and folds (I, 6); however, in this figure, the duct opens at the
are absent. apex of a ridge. Anteriorly, these glands come in contact with
The lamina propria of the mucosa is wider but similar to the serous glands (von Ebner's) of the circumvallate papilla;
that in the anterior two thirds of the tongue. Under the epithe- posteriorly, the glands extend through the root of the tongue.
lium are seen diffuse lymphatic tissue (2), adipose cells (3),

Figure 11-6 Lingual Tonsils ,transverse section)

This figure depicts a transverse section of the lingual ton- excretory ducts, most of which open into the crypts, although
sils (2) in the posterior tongue. The lymphatic nodules (2) some open on the lingual surface (4, upper leader). Skeletal
are in the lamina propria (7) below the stratified squa- muscles, not shown, lie below the glands.
mous surface epithelium (6). The crypts of the tonsils (3, The lingual tonsils (2) are an aggregation of small, indi-
8) form deep invaginations of the surface. The crypts are also vidual tonsils, each with its own crypt. They are situated in
lined with stratified squamous epithelium (9) and may the lamina propria (7) at the root of the tongue. This arrange-
extend deep into the lamina propria (7). ment may not be apparent in a small section of the tissue. The
Deep in the lamina propria (7) and near the adipose tis- lingual tonsils are not a single encapsulated mass of lym-
sue (11) are mucous acini (5) of the posterior lingual phatic nodules as are the palatine tonsils.
glands (4). Small excretory ducts (4) unite to form larger

158 Organs
Tongue and Tonsils

6 Epithelium and lamina

1 Mucosal ridges propria of mucosal fold

2 Diffuse lymphatic
7 Excretory ducts of
mucous glands
3 Adipose cells
8 Arteriole and venule

4 Mucous acini
(posterior lingual

5 Skeletal muscle (o.s.)

Fig. 11-5 Posterior Tongue Near Circumvallate Papilla (longitudinal section). Stain:
hematoxylin-eosin. Low magnification.

- 6 Stratified squamous

1 Lingual mucosa -7 lamina propria

2 lymphatic nodules . 8 Crypt
of the lingual tonsil
. 9 Stratified squamous
epithelium lining crypt
3 Crypt of the tonsil -

4 Excretory
ducts of
- -10 lymphocytic
infiltration between
glands (I.s. and t.s.)

5 Mucous acini
of posterior
lingual glands

Fig. 11-6 Lingual Tonsils (transverse section). Stain: hematoxylin-eosin. Low magnification.

Digestive System: Tongue and Salivary Glands 159

Figure 11-7 Dried Tooth (panoramic view, longitudinal sectionl

Dentin (3,5) surrounds the pulp cavity (4) and its exten- The dentin in the crown of the tooth is covered with a
sion, the root canal (6). In life, the pulp cavity and root canal thicker layer of enamel (I), composed of enamel rods or
are filled with fine connective tissue, which contains fibro- prisms held together by an interprismatic cementing sub-
blasts, histiocytes, odontoblasts, blood vessels, and nerves. stance. The incremental growth lines (of Retzius) (8) repre-
Dentin (3) exhibits wavy, parallel dentinal tubules. The ear- sent the variations in the rate of enamel deposition. Light
lier or primary dentin (3) is located at the periphery of the rays passing through a dried section of the tooth are refract-
tooth; the later or secondary dentin (5) lies along the pulp ed by twists that occur in the enamel rods as they course
cavity, where it is formed throughout life by odontoblasts. In toward the surface of the tooth. These are the light bands of
the crown of a dried tooth and at the junction of dentin with Schreger (9). At the dentinoenamel junction may be seen
enamel (1) are numerous irregular, air-filled spaces that enamel spindles (10) and enamel tufts (11); these are illus-
appear black in the section. These are the interglobular trated at a higher magnification in Figure 11-8.
spaces (12) which, in life, are filled with incompletely calci- Cementum (7) covers the dentin of the root. In life,
fied dentin (interglobular dentin). Similar areas, but smaller cementum contains lacunae (14) with cementocytes and
and spaced closer together, are present in the root, close to canaliculi.
the dentinal-cementum junction, where they form the gran-
ular layer (of Tomes) (13).

Figure 11-8 Dried Tooth: Layers of the Crown

A section of enamel (1) and dentin (6) are illustrated at a enamel. The enamel tufts (3), which are the poorly calcified,
high magnification. The enamel consists of elongated enam- twisted enamel rods, extend from the dentinoenamel junc-
el rods or prisms (1). In the enamel region, near the junction tion (4) into the enamel. Dentin (6) is clearly visible with its
with dentin (4), are the enamel spindles (2). These are point- dentinal tubules (6) and black, air-filled interglobular
ed or spindle-shaped processes of dentin that penetrate the spaces (5).

Figure 11-9 Dried Tooth: Layers of the Root

Dentin (1) and cementum (4) are illustrated at a high irregular interglobular spaces (3) which are commonly seen
magnification. Near the dentinoenamel junction is the gran- in the crown of the tooth but may also be present in the root.
ular layer (of Tomes) (2). Internal to this layer are the large, Cementum (4) contains lacunae (5) with their canaliculi.

160 Organs
Dried Tooth

8 Incremental growth lines

(of Retzius)
9 Light band of Schreger

1 Enamel
10 Enamel spindles

2 Area shown in Fig. 11-8. 11 Enamel tufts

3 Dentin (primary) 12 Interglobular spaces

4 Pulp cavity

5, Dentin (secondary)
13 Granular layer (of Tomes)

6 Root canal
14 Lacunae with canaliculi
in cementum

7 Cementum

15 Area shown in Fig.11-9.

Fig. 11-7 Dried Tooth (panoramic view, longitudinal section).

1 Enamel rods 1 Dentin

2 Enamel spindles
2 Granular layer
(of Tomes)
3 Enamel tuft
3 Interglobular space

4 Dentinoenamel 4 Cementum

5 Interglobular spaces

6 Dentin 5 lacunae in cementum

Fig. 11-8 Dried Tooth: Layers of the Fig. 11-9 Dried Tooth: Layers of the Root.
Crown. Area Corresponding to (2) in Fig. 1 1-7. Area Corresponding to (15) in Fig. 11-7. Medium
Medium magnification. magnification.

Digestive System: Tongue and Salivary Glands 161

Figure 11-10 Developing Tooth ,panoramic view)

A developing deciduous tooth is shown embedded in a nective tissue and forms the core of the developing tooth.
socket, the dental alveolus (22), in the bone (4) of the jaw. Blood vessels and nerves extend into and innervate the den-
A layer of connective tissue (3) surrounds the developing tal pulp from below. The mesenchymal cells in the dental
tooth and forms a compact layer around the tooth, the dental papilla differentiate into odontoblasts (11) and form the
sac (5). Enclosed within the sac is the enamel organ. It is outer margin of the dental pulp (21). The odontoblasts (II)
composed of the external enamel epithelium (18), the stel- secrete predentin (10, 17), which is an uncalcified dentin.
late reticulum of enamel pulp (6, 19), the intermediate As predentin calcifies (10, 17), it forms a layer of dentin (9,
stratum (20), and the ameloblasts or inner enamel epithe- 16) adjacent to enamel (8, 15).
lium (7). All of these structures differentiate from the down- The oral mucosa (1, 13) covers the developing tooth. An
growth of the gum epithelium (1). The ameloblasts secrete epithelial down growth from the oral epithelium indicates the
enamel around the dentin (9, 16). The enamel (8, 15) germ of a permanent tooth (2). At the base of the tooth, the
appears as a narrow band of deep-staining pink material. outer and inner enamel epithelium form the epithelial root
The dental pulp (21) originates from the primitive con- sheath (of Hertwig) (12).

Figure 11-11 Developing Tooth 'sectional view)

The left side of the figure shows a small area of dental modified epithelial cells, the intermediate stratum (8), a
pulp, fibroblasts (1), and fine fibers, illustrated at a higher transition region, and the tall columnar ameloblasts (6) that
magnification. The odontoblasts (2) are located at the mar- secrete the enamel (5, 10) in the form of enamel rods or
gin of the pulp and secrete the uncalcified predentin (3), prisms. During enamel (5, 10) formation, the apical ends of
which later calcifies as dentin (4). The odontoblasts (2) ameloblast become transformed into a terminal processes
remain in the predentin and dentin as the odontoblast of Tomes. In advanced enamel formation, these proces-
processes (of Tomes) (3). ses appear as a separate layer of enamel processes (of
On the right side of the figure is a small area of stellate Tomes) (9).
reticulum (7) of enamel. Seen here are the processes of its

162 Organs
Developing Tooth

Fig. 11-10 Developing Tooth (panoramic view). Stain: hematoxylin-eosin. Low magnification.

Fig. 11-11 Developing Tooth (sectional view). Stain: hematoxylin-eosin. High magnification.

Digestive System: Tongue and SalivaryGlands 163

Figure 11-12 Salivary Gland: Parotid

The parotid salivary gland is a large serous gland, classi- ithelial cells (14, I), located between the basement mem-
fied as a compound tubuloacinar gland (Fig. 1-14). In this brane and the serous cells; usually, only their nuclei are
illustration, a section of the parotid gland is depicted at lower visible.
magnification, while the specific features of the gland are The secretory acini empty their product into narrow chan-
presented at a higher magnification in separate boxes below. nels, the intercalated ducts (6, 11, II). These ducts have
The parotid gland is surrounded by a connective tissue small lumina, are lined by a simple squamous or low
capsule from which arise numerous septa (2, 8) that subdi- cuboidal epithelium, and are often surrounded by myoep-
vide the gland into several lobes and lobules. Located in the ithelial cells (See Fig. 11-13 :23, III). The secretory product
connective tissue septa (2, 8) between the lobules are small from the intercalated ducts drains into larger striated ducts
arterioles (12), venuies (13), interlobular excretory ducts (7, III). These ducts have larger lumina and are lined by sim-
(1, 4, 9, IV) and numerous adipose cells (3). ple columnar cells that exhibit basal striations (17, III); the
Each lobule consists of closely packed masses of secreto- striations are formed by deep infolding of the basal cell
ry cells, the serous acini (5, 10, 16, I). These acini (1) con- membrane.
sist of pyramid-shaped cells arranged around a small lumen. The striated ducts empty their product into the interlob-
The spherical nuclei of these cells are located at the base of ular excretory ducts (1, 4, 9, IV) that are located in the
the slightly basophilic cytoplasm. In certain sections, the connective tissue septa (2, 8). Their lumina become pro-
lumen is not always visible in all acini. At a higher magnifi- gressively wider and the epithelium taller as the ducts
cation, small secretory granules (15, I) are visible in the cell increase in size. The ductal epithelium (IV) varies from
apices. The number of secretory granules in these cells varies columnar to pseudostratified or stratified columnar in large
with the functional activity of the gland. The serous acini (5, excretory (lobar) ducts that drain the lobes of the parotid
10, 16, I)'are also surrounded by thin, contractile myoep- gland.

164 Organs
Salivary Gland: Parotid

1 Interlobular 6 Intercalated
excretory duct duct
2 Interlobular septum -
7 Striated ducts

8 Interlobular

9 Interlobular
3 Adipose cells -=::::::::::: duct

10 Serous acini

4 Small
excretory duct
(emptying into
11 Intercalated
larger duct)

12 Arteriole

13 Venule

5 Serous acini

14 Myoepithelial -

15 Secretory


I Serous acinus II Intercalated duct III Striated duct IV Interlobular

excretory duct

Fig. 11-12 Salivary Gland: Parotid. Stain: hematoxylin-eosin. Upper: medium magnification; Lower:
high magnification.

Digestive System: Tongue and Salivary Glands J65

Figure 11-13 Salivary Gland: Submandibular

Like the parotid salivary gland, the submandibular is also cell membrane. The mucous acini also have a somewhat larg-
a compound tubuloacinar gland. The submandibular gland, er and more apparent lumina.
however, is a mixed type, being composed predominantly of The mixed acini (serous and mucous) are normally mucous
serous acini. The presence of serous and mucous acini dis- acini surrounded or capped by one or more groups of serous
tinguishes the submandibular gland from the parotid gland, cells, forming a crescent-shaped serous demilune (8,12). The
which is a purely serous gland. This low-power illustration thin, contractile myoepithelial cells (21, 22, 23) surround the
depicts portions of several lobules of the submandibular serous (I), mucous (II), and intercalated duct cells (III).
gland in which a few mucous acini (6, 11, 14) are intermixed The duct system of the submandibular gland is similar to
with serous acini (7, 18). The more detailed features of the that of the parotid gland. The intralobular intercalated ducts
gland are illustrated at higher magnification in separate (9, 13, 15, 19, III) have small lumina and are shorter while
boxes below. the striated ducts (5, 16, IV) are longer than in the parotid
The serous acini (7, 18, I) are similar to those observed gland. Illustrated is a mucous acinus (14) that opens into an
in the parotid gland (Fig. 11-12). These acini are character- intercalated duct (15), which then opens into a larger stri-
ized by smaller size, darker-stained pyramidal cells, spheri- ated duct (16). Numerous interlobular excretory ducts (3,
cal nucleus located basally, and secretory granules (20) in 17) of different sizes are located in the interlobular connec-
the cell apices, visible at higher magnification (I). The tive tissue septa (4). These septa (4) penetrate and divide the
mucous acini (6, 11, 14, II) are larger than the serous acini gland into lobes and lobules. Also located in the connective
(7, 18, I) and are more variable in their size and shape. The tissue septa (4) are nerves and numerous, different-sized
mucous cells are more columnar and exhibit pale or almost arterioles (1) and venules (2). Numerous adipose cells (10)
colorless cytoplasm after routine histologic staining. Their are seen scattered among the various acini and in the con-
nuclei (II) are flattened and pressed against the base of the nective tissue septa.

166 Organs
Salivary Gland: Submandibular

1 Arteriole
2 Venule

3 Interlobular
excretory duct

4 Interlobular

5 Striated ducts

, 6 Mucous

7 Serous acini

8 Serous demilune

9 Intercalated duct

20 Secretory

21 Myoepithelial

I Serous acinus II Mucous acinus III Intercalated duct IV Striated duct

Fig. 11-13 Salivary Gland: Submandibular. Stain: hematoxylin-eosin. Upper: medium magnification;
lower: high magnification.

Digestive System: Tongue and Salivary Glands 167

Figure 11-14 Salivary Gland: Sublingual

The sublingual gland is a compound mixed tubuloacinar are infrequent or are absent. In the sublingual gland, the
gland. This gland resembles the submandibular gland intercalated ducts (2, 10, III) are short and are not readily
hrs.;m.<; is composed of both serous and mucous acini. observed in a given section. The nonstriated intralobular
.M[)5JDf the secretory acini, however, are mucous (5, 15, I, excretory ducts (4, 6, IV) are more prevalent in the sublin-
'll/8na lTillCOUS acini capped with serous demilunes (9, 14, gual glands. These ducts are equivalent to the striated ducts
18, 19, II, III). The light-stained mucous acini (5, ]5, I, II) of the submandibular and parotid glands, but lack the exten-
are conspicuous in this section. Purely serous acini are sive basal striations.
scarce; however, the composition of the gland is variable. In The interlobular connective tissue septa (13) are more
this low-magnification illustration, serous acini (3, 16) abundant in the sublingual than in the parotid and sub-
appear frequently, whereas in other sections of the sublingual mandibular glands. Numerous arterioles (12), venules (8),
gland such serous acini may be absent. At higher magnifica- nerve fibers, and interlobular excretory ducts (1, 11) are
tion, the myoepithelial cells (17, I) are seen around individ- seen in the septa. The epithelial lining of the interlobular
ual acini. excretory ducts (I, II) varies from low columnar in the
In comparison to other salivary glands, the duct system is smaller ducts to pseudostratified or stratified columnar in the
somewhat different. Typical intercalated ducts (2, 10, III) larger ducts.

168 Organs
Salivary Gland: Sublingual

9 Serous
1 Interlobular

10 Intercalated
2 Intercalated
duct 11 Interlobular

12 Arteriole

3 Serous acini
13 Interlobular

4 Intralobular
14 Serous
5 Mucous demilune

15 Mucous

16 Serous acini

7 Adipose
8 Venule

Fig. 11-14 Salivary Gland: Sublingual. Stain: hematoxylin-eosin. Upper: medium magnification; lower:
high magnification.

Digestive System: Tongue and Salivary Glands 169


Digestive System: Esophagus

and Stomach

The Esophagus underlying lamina propria of the mucosa and forms numer-
The esophagus is a long, soft tube that extends from the ous gastric pits. The tubular gastric glands open into these
pharynx to the stomach. Most of the esophagus is located in pits.
the thorax with a short piece extending into the abdominal The main functions of the stomach are to receive, store,
cavity. The major function of the esophagus is to convey liq- mix, and digest the ingested food products. Some of these
uids and chewed food (bolus) to the stomach. The lumen of stomach functions are performed by mechanical and chem-
the esophagus is lined by a protective, nonkeratinized strati- ical actions, which reduce the ingested food material to a
fied squamous epithelium. The mucus secreted by the semi-liquid mass called chyme. The mechanical reduction
esophageal glands located below the epithelium lubricates of food products in the stomach is produced by strong, mus-
the lumen of the esophagus for smoother passage of the swal- cular contractions of its thick wall in the form of peristalsis.
lowed food. This peristaltic activity churns and mixes the food with gas-
The wall of the digestive tube, from the esophagus to the tric juices produced by the gastric glands when the food
rectum, exhibits four common layers: mucosa, submucosa, enters and distends the stomach wall. Nerve cells and nerve
muscularis externa, and serosa. Where the digestive tube is fibers located in the submucosal nerve plexus and myen-
retroperitoneal or adheres to the posterior abdominal wall, teric nerve plexus in the stomach wall regulate the peri-
the outermost layer is the adventitia. staltic activity of the stomach musculature. The stomach
The four layers of the digestive tube, however, show also has some absorptive functions; however, these are lim-
regional variations, depending on the location of the diges- ited to the absorption of water, alcohol, salts, and certain
tive tube and its specific function in the digestive process. drugs.
The characteristic features of each layer are discussed with The chemical reduction of food in the stomach is the
each illustration of the different digestive organ. result of the watery gastric secretions produced by different
cells in the gastric glands, especially those in the fundus and
Stomach body regions of the stomach. The main components of the
The stomach is a dilated, hollow organ of the digestive gastric secretions are pepsin, hydrochloric acid, mucus,
tube that is situated between the esophagus and the small intrinsic factor, water, and different electrolytes.
intestine. Anatomically, the stomach is divided into the car-
dia, fundus, body or corpus, and pylorus. Because the fundus Gastric Glands and the Cell Types
and body have identical histology, the stomach has only three The gastric glands of the cardia and pylorus regions are
histologically distinct regions. The cardia, the most superior located at the opposite ends of the stomach; however, their
region in the stomach, surrounds the entrance of the esopha- cell types have similar histology and are predominantly
gus into the stomach. The fundus and body form the major mucus-secreting. The gastric glands in the fundus and body
portions of the stomach; their mucosa contains deep gastric of the stomach, however, are composed of three major types
glands that produce most of the gastric secretions or juices of cells. Located in the upper region of the gastric gland near
for digestion of food. The pylorus, the most inferior region in the gastric pits are the mucous neck cells. The product of
the stomach, ends at the border of the duodenum of the small these cells, along with that of the cells in the surface epithe-
intestine. lium, is mucus; it covers the stomach lining with its protec-
The luminal surface of the stomach is lined by a single tive layer.
layer of mucus-secreting, columnar epithelium, whose secre- The large, polygonal, distinctive eosinophilic cells locat-
tion forms a thick layer of mucus that lines and protects the ed primarily in the upper half of the gastric glands between
stomach surface from the corrosive action of the gastric other gland cells are the parietal cells. These cells secrete
juices. The surface epithelium of the stomach invaginates the hydrochloric acid, a major component of the gastric juice. In

Digestive System: Esophagus and Stomach J71

humans, the parietal cells produce gastric intrinsic factor, a Enteroendocrine (APUDj Cells
glycoprotein that is necessary for vitamin B l2 absorption in In addition to the cells in the gastric glands described
the small intestine. Vitamin Bl2 is necessary for red blood above, the mucosa of the digestive tract also contains a wide
cell production in the red bone marrow; deficiency of this distribution of enteroendocrine or APUD (amine precursor
vitamin leads to anemia. uptake and decarboxylation) cells. Unless they are prepared
The basophilic, cuboidal cells distributed predominantly with special silver-staining techniques, these cells are poorly
in the lower region of the gastric glands in the body of the seen in histological sections. The enteroendocrine cells secrete
stomach are the chief or zymogenic cells. The cytoplasm of a variety of polypeptides and proteins with hormonal activity
these cells exhibits numerous secretory granules that contain that influence various functions of the digestive tract. APUD
pepsinogen, an inactive form of pepsin. Release of pepsino- cells are not confined to the gastrointestinal tract but are also
gen during gastric secretion into the acidic environment of found in the respiratory organs and other organs of the body.
the stomach converts the inactive pepsinogen into the highly Additional details, description, and illustration of the enteroen-
active, proteolytic enzyme pepsin. docrine (APUD) cells are found in Chapter 13, Figure 13-3.

172 Organs

Figure 12-1. Upper Esophagus: Wall ,transverse section)

Digestive System: Esophagus and Stomach 173

Figure 1 2-1 . Upper Esophagus: Wall 'transverse section,

The esophagus is a long, hollow tube whose wall is com- 12-2). Large blood vessels (13) are present in the connective
posed of the mucosa, submucosa, muscularis externa, and tissue of the submucosa (4).
adventitia. Located beneath the submucosa (4) is the muscularis
The mucosa (1, 2, 3) consists of an inner lining of nonker- extema (5, 6, 7), composed of two well-defined muscle lay-
ziim1zeclstratified squamous epithelium (1); an underlying ers. The inner muscle layer is circular (5) and, in this trans-
thin layer of fine connective tissue, the lamina propria (2); verse section of the esophagus, sectioned longitudinally. The
and a layer of longitudinal smooth muscle fibers, the mus- outer muscle layer is longitudinal (7), and the muscle fibers
cularis mucosae (3), illustrated in either cross or oblique are seen mainly in transverse sections. A thin layer of con-
sections. The connective tissue papillae in the lamina propria nective tissue (6) lies between the two muscle layers.
indent the epithelium. The lamina propria (2) contains small The muscularis extern a of the esophagus is highly vari-
blood vessels, diffuse lymphatic tissue, and a small lym- able in different species. In humans, the muscularis extern a
phatic nodule (9). in the upper third of the esophagus consists primarily of stri-
The submucosa (4) is a wide layer of moderately dense ated skeletal muscles. In the middle third, both layers exhib-
irregular connective tissue that often contains adipose cells it a mixture of smooth muscle, and in the lower third of the
(14). The esophageal glands proper (11) are present in the esophagus, only smooth muscle is found.
submucosa at intervals throughout the length of the esopha- The adventitia (8) of the esophagus consists of a loose
gus. These are the tubuloacinar mucous glands, and their connective tissue layer that blends with the adventitia of the
excretory ducts (12) pass through the muscularis mucosae trachea and the surrounding structures. Adipose tissue (16),
(3, 10) and the lamina propria (2), and open into the large blood vessels (17, 18), and nerves (19) forming the
esophageal lumen. The ductal epithelium merges with strati- neurovascular bundles are present in the adventitia.
fied squamous surface epithelium of the esophagus (see Fig.

174 Organs
Upper Esophagus: Wall 9 Small lymphatic

10 Excretory duct

11 Mucous acini of
esophageal glands

:. 12 Excretory ducts of
esophageal glands
13 Arteriole and venule

14 Adipose cells

15 Venule

5 :

19 Nerves

Fig. 12-1 Upper Esophagus: Wall (transverse section). Stain: hematoxylin-eosin. Low magnification.

Digestive System: Esophagus and Stomach 175

Figure 1 2-2. Upper Esophagus: Mucosa and Submucosa (transverse section)

Higher magnification of the upper esophageal wall illus- esophageal glands proper. Small excretory ducts (16, lower
trates the mucosa (1, 2, 3) with the stratified squamous leaders) from these glands, lined with simple epithelium, join
epithelium (1) and the submucosa (4). In the luminal the larger excretory ducts (16, upper leader) that are lined
epithelium, the squamous cells (6) form the outer layers, the with stratified epithelium. A large duct, sectioned tangential-
numerous polyhedral cells (7) form the intermediate layers, ly (14), reveals that its epithelium is continuous with the
and low columnar cells (9) form the basal layer. Mitotic stratified squamous epithelium of the esophageal lumen.
activity (8) is seen in the deeper layers of the epithelium. In the submucosa (4) are also seen blood vessels (17,18),
The lamina propria (2, 10) contains blood vessels (11) nerves (19), and adipose cells (20). A section of skeletal
and aggregates of lymphocytes (12). The smooth muscle of muscle fibers from the inner circular layer of the muscularis
muscularis mucosae (13) is illustrated as bundles of muscle externa (5) is illustrated in the lower left corner of the
fibers sectioned in a transverse plane. figure.
The submucosa (4) contains mucous acini (15) of the

176 Organs
Upper Esophagus: Mucosa and Submucosa

6 Squamous cells

7 Polyhedral cells

8 Mitosis

9 Columnar cells

10 lamina propria

11 Blood vessels

12 lymphocytes

13 Muscularis mucosae

14 Excretory duct

15 Mucous acini of
esophageal glands

16 Excretory Ducts of
esophageal glands

17 Veins

18 Arteries

19 Nerve

20 Adipose cells

Fig. 12-2 Upper Esophagus: Mucosa and Submucosa 'transverse section). Stain: hematoxylin-
eosin. Medium magnification.

Digestive System: Esophagus and Stomach 177

Figure 12-3. Upper Esophagus (transverse section)

This section of the upper esophagus is similar to the illus- guishable. In the upper esophagus (as in Fig. 12-2), the out-
tration in Figure 12-1 except that it is stained with ermost layer is the adventitia (1), and the muscularis exter-
Heidenhain's modification of Mallory's trichrome (Mallory- na (2, 3) is skeletal muscle. Aniline blue stains the large
azan). Azocarmine stains the nuclei an intense red. A mixture amounts of connective tissue in the submucosa (9) and
of aniline blue and orange G selectively stains other tissues. adventitia (I) and the smaller amounts between (4) and with-
The collagen fibers of the connective tissue (1, 4, 5, 7, 9) in muscle layers (5). The connective tissue of the lamina
stain bright blue, whereas the cytoplasm of epithelium (6) propria (7) appears distinct from the smooth muscle of the
and muscle cells (2, 3, 8) stains orange to red. muscularis mucosae (8).
The different layers of the esophagus are easily distin-

Figure 12-4. Lower Esophagus (transverse section)

This section of the terminal portion of the esophagus (in tions. The outermost layer is the serosa (1) (visceral peri-
the peritoneal cavity near the stomach) is stained with Van toneum). This is in contrast to the adventitia, which lines the
Gieson's trichrome, which uses iron hematoxylin (Wiegert's esophagus in the thoracic region. The muscularis extema
or Heidenhain's) as a nuclear stain and picrofuchsin to stain (2, 4) layers in lower esophagus are entirely smooth muscle,
other components. As a result, cellular details are not well although this is not apparent with this stain and this magnifi-
defined, but the connective tissue (3, 5, 7) and smooth mus- cation. Distribution of the mucous glands (9) in the submu-
cle (2, 4, 8) are nicely differentiated. Nuclei are stained dark cosa is variable, and in some regions, they may be absent;
brown. Collagen fibers (3, 5, 7) are stained red with acid however, some are illustrated in this section.
fuchsin, whereas muscle (and other tissues) (2, 4, 6, 8, 9) are The collagen fibers in the submucosa (5) are abundant.
stained yellow with picric acid. The distribution of finer connective tissue fibers (3, 8) in
The layers in the wall of the lower esophagus are similar lesser amounts is seen between and around smooth muscle
to those in the upper region, except for regional modifica- fibers (2, 3), in serosa (1), and in the lamina propria (7).

178 Organs

Fig. 12-3 Upper Esophagus (transverse section). Stain: Mallorys trichrome. (Nuclei, red; connective
tissue, blue; epithelium and muscle, orange to red.) Low magnification.

1 Serosa (visceral
peritoneum) 6 Epithelium

7 lamina propria
2 Outer longitudinal -
muscle layer (smooth)

8 Muscularis
3 Connective

4 Inner circular
muscle layer (smooth) 9 Mucous acini of
esophageal glands

5 Submucosa

Fig. 12-4 Lower Esophagus (transverse section). Stain: Van Giesons trichrome. (Nuclei, dark brown;
connective tissue, red; epithelium and muscle, yellow.) Low magnification.

Digestive System: Esophagus and Stomach 179

Figure 12-5. Esophageal-StomachJunction

At its terminal end, the esophagus joins the stomach, Iy limited to the transition region, the cardia of the stomach.
forming the esophageal-stomach junction. The nonkera- These glands are lined with a single type of cell, the pale-
tinized stratified squamous epithelium (1) of the esopha- staining, mucus-secreting columnar cell. Below the cardiac
gus abruptly changes to simple columnar, mucus-secreting region of the stomach are the simple tubular gastric glands
gastric epithelium (10) of the cardia of the stomach. (16), some of which exhibit basal branching.
Consequently, this junction between stomach and esophagus In contrast to the cardiac glands (17), the gastric glands
exhibits a distinct histologic mark. (16) contain four different cell types: the pale-staining
At the esophageal-stomach junction, the esophageal mucous neck cells (13), large, eosinophilic parietal cells
glands proper (7) of the esophagus may be seen in the sub- (14), basophilic chief or zymogenic cells (15), and several
mucosa (8). Excretory ducts (4, 6) from these glands course different types of endocrine cells (not illustrated), collective-
through the muscularis mucosae (5) and the lamina pro- ly called the enteroendocrine cells. These cells are illustrated
pria (2) of the esophagus into its lumen. In the lamina pro- in greater detail in Figure 13-3.
pria (2) of the esophagus near the stomach region are also The muscularis mucosae of the stomach (18) is also
seen a group of glands called the esophageal cardiac glands continuous with the muscularis mucosae of the esophagus
(3). Both the esophageal glands proper (7) and the cardiac (5). In the esophagus, the muscularis mucosae (5) is usually
glands (3) are mucus-secreting. a single layer of longitudinal smooth muscle fibers, whereas
The lamina propria of the esophagus (2) is continuous in the stomach, a second layer of smooth muscle is added,
with the lamina propria of the stomach (12), where it called the inner circular layer.
becomes a wide layer filled with glands (16,17) and diffuse The connective tissue of the submucosa (8, 19) and the
lymphatic tissue. The lamina propria of the stomach (12) is smooth muscles of muscularis externa (9,21) of the esoph-
penetrated by numerous shallow gastric pits (11) into which agus are continuous with those of the stomach. Numerous
empty the numerous gastric glands (16, 17) of the mucosa. blood vessels (20) are found in the submucosa (8, 19). From
In the upper region of the stomach are found two types of here, smaller blood vessels are distributed to other regions of
glands. The simple tubular cardiac glands (17) are primari- the organ.

180 Organs
Esophageal-Stomach Junction

10 Gastric

11 Gastric pits

12 Lamina

13 Mucous
neck cells

14 Parietal

15 Zymogenic
(chief) cells

16 Gastric

17 Cardiac

1B Muscularis

19 Submucosa

20 Blood vessels
(venule and

21 Muscularis
..- , I (stomach)
Fig. 12-5 Esophageal-Stomach Junction. Stain: hematoxylin-eosin. Low magnification.

Digestive System: Esophagus and Stomach 181

Figure 12-6. Stomach: Fundus and Body Regions (transverse section)

The human stomach is divided into three distinct histo- the lamina propria may contain small accumulations of lym-
logic areas: the cardia, the fundus and body, and pylorus. The phatic tissue or nodules (16).
fundus and body is the most extensive region in the stomach. The mucosa of an empty stomach exhibits numerous folds
This low magnification figure illustrates a transverse sec- called the rugae (9). These folds are temporary and are
tion of the fundic stomach. The stomach wall exhibits four formed from the contractions of the smooth muscle layer, the
general regions that are characteristic of the entire digestive muscularis mucosae (3, 15). As the stomach fills with solid
tract: the mucosa (1, 2, 3), submucosa (4), muscularis or liquid material, the rugae disappear and the mucosa
externa (5, 6, 7), and serosa (8). appears smooth.
Mucosa (1, 2, 3): The mucosa of the stomach consists of Submucosa (4): The prominent layer directly beneath the
three layers: the epithelium, lamina propria, and muscularis muscularis mucosae (3, 15) is the submucosa (4). In an
mucosae. The luminal surface of the mucosa is lined by a empty stomach, this layer can extend into the folds or the
layer of simple columnar epithelium (1, 11). This epitheli- rugae (9). The submucosa (4) contains denser irregular con-
um also extends into and lines the gastric pits (10), which nective tissue and more collagen fibers (17) than does the
are tubular infoldings of the surface epithelium (11). In the lamina propria (2, 12). In addition to the normal complement
fundic region of the stomach, the gastric pits (10) are not of connective tissue cells, the submucosa (4) contains numer-
deep and extend into the mucosa about one fourth of its ous lymph vessels, capillaries (22), large arterioles (18),
thickness. Beneath the surface epithelium is a layer of loose and venules (19). Isolated or small clusters of the parasym-
connective tissue, the lamina propria (2, 12), which fills the pathetic ganglia of the submucosal (Meissner's) nerve
narrow spaces between the gastric glands. The outer layer of plexus (21) are also seen in the deeper regions of the sub-
mucosa is lined by a thin band of smooth muscle, the mus- mucosa.
cularis ]11ucosae (3, 15), consisting of an inner circular and Muscularis externa (5, 6, 7): In the stomach, the muscu-
an outer longitudinal layer. Thin slips of muscle from the laris externa (5, 6, 7) consists of three layers of smooth mus-
muscularis mucosae (3, 15) extend into lamina propria (2, cle, each oriented in a different plane: an inner oblique (5), a
12) between the gastric glands (13, 14) toward the surface middle circular (6), and an outer longitudinal (7) layer. The
epithelium (1, I I) (See Fig. 12-7:8). oblique layer is not complete and, as a result, this layer is not
The gastric glands (13, 14) are packed tightly in the lam- always seen in sections of stomach wall. In this illustration,
ina propria and occupy the entire thickness of the mucosa (I, the circular layer has been sectioned longitudinally and the
2, 3). These glands open in small groups into the bottom of longitudinal layer transversely. Located between the circular
the gastric pits (10). The surface epithelium of the entire gas- and longitudinal smooth muscle layers is a prominent myen-
tric mucosa contains the same cell type, from the cardiac to teric (Auerbach's) nerve plexus (23) of parasympathetic
the pyloric region; however, there are distinct regional dif- ganglia and nerve fibers.
ferences in the type of cells that comprise the gastric glands. Serosa (8): The outermost layer of the stomach wall is the
At lower magnification, two distinct types of cells can be serosa (8). This is a thin layer of connective tissue that over-
identified in the gastric glands of the fundic stomach. The lies the muscularis extern a (5, 6, 7). Externally, this layer is
acidophilic parietal cells (13) are seen in the upper portions covered by a simple squamous mesothelium of the visceral
of the glands; the more basophilic chief (zymogenic) (14) peritoneum (8). The connective tissue covered by the vis-
cells occupy the lower regions. The subglanduJar regions of ceral peritoneum can contain numerous adipose cells (24).

182 Organs
Stomach: Fundus and Body Regions

9 Rugae


5 Oblique

6 Circular
Muscularis muscle
externa layer

7 Longitudinal
layer {
8 Serosa - -

Fig. 1 2-6 Stomach: Fundus and Body Regions (transverse section). Stain: hematoxylin-eosin. Low

Digestive System: Esophagus and Stomach J83

Stomach: Mucosa of the Fundus and Body

11 Gastric pits
12 Smooth muscle
13 Surface epithelium

14 Isthmus

15 Neck


16 Base (fundus)

17 Lymphatic nodule
18 Collagen fibers
19 Fibroblasts
20 Arteriole
21 Venule

Fig. 12-7 Stomach: Mucosa of the Fundus and Body ,transverse section'. Stain: hematoxylin-
eosin. Medium magnification.

Digestive System: Esophagus and Stomach 185

Figure 12-8. Stomach: Superficial Region of Gastric Mucosa

Higher magnification of the stomach illustrates the char- The prominent parietal cells (7) are interspersed among
acteristic features of different cells that compose the superfi- the mucous neck cells (6); their free surfaces are on the bor-
cial region of the gastric mucosa of the fundus and body. der of the glandular lumen (12). The parietal cells (7) are
The tall columnar surface epithelium (1) exhibits basal most conspicuous in the gastric mucosa and are predomi-
oval nuclei and is lightly stained because of the presence of nantly found in the upper half of the gastric glands. These
mucigen droplets in the cytoplasm. It is delimited from the cells are large and pyramidal in shape with round nucleus
adjacent fibroelastic connective tissue lamina propria (3) by and highly acidophilic cytoplasm; some pyramidal cells may
a thin but distinct basement membrane (2). The surface be binucleate.
epithelium extends downward into the gastric pits (4, 8). Deeper in the gastric glands (5, 12), toward the lower half
The gastric glands (5, 12) lie in the lamina propria (11) or third of the gland, the mucous cells are replaced by
below the gastric pits (4, 9). The necks (5, 10) of the gastric basophilic chief or zymogenic cells (13), which border on
glands are also lined with low columnar mucous neck cells the lumen of the gland. Parietal cells (7) are also seen here;
(6) that have round, basal nuclei. The constricted necks of the however, they are displaced peripherally and lie against the
gastric glands (10) open by a short transition region into the basement membrane without reaching the lumen.
bottom of the gastric pit (8).

Figure 12-9. Stomach: Deep Region of the Mucosa

The gastric glands (1, 10) are branched tubular glands; well demonstrated in several transverse sections of the
the branching is normally seen at the base of the glands. A glands (3, lower leader).
section through the deep region of the mucosa illustrates Also illustrated in this figure are the lamina propria (2)
basal portions of the gastric glands (I, 10) sectioned in vari- between the gastric glands (I, 10) and a narrow zone of sub-
ous planes. glandular lamina propria (5), which is not always distin-
As in the higher region of the gland, the chief or zymo- guishable.
genic cells (4,9, 12) border the glandular lumen. The pari- The two layers, inner circular and outer longitudinal, of
etal cells (3, 8, 11) are wedged against the basement mem- muscularis mucosae (13, 14), are also illustrated.
brane and are not in direct contact with the lumen. This is

186 Organs
Stomach: Fundus and Body

Fig. 12-9 Stomach: Deep Region of the Mucosa. Stain: hematoxylin-eosin. High magnification.

Digestive System: Esophagus and Stomach 187

Figure 12-10. Stomach: Mucosa of the Pyloric Region

In the pyloric region of the stomach, the gastric pits (4, leader). Enteroendocrine or APUD cells are also present in
12) are deeper than those in the body or fundus regions of the this region of the stomach and can be demonstrated usually
stomach. The gastric pits (4, 12) extend into the mucosa to with special training techniques.
about one half or more of its thickness. The simple columnar The remaining structures in this region are similar to those
mucous epithelium (10) that lines the surface of the stomach in the upper stomach. The lamina propria (13) contains dif-
~~Dds into and lines the gastric pits (4, 12). fuse lymphatic tissue, an occasional lymphatic nodule (16)
The pyloric gastric glands (5, 6, 14) are either branched may be seen in its deepest part. The lymphatic nodules may
or coiled tubular mucous glands. As in the cardia region of increase in size and penetrate through the muscularis
the stomach, only one type of cell is normally found in these mucosae (18) into the submucosa (20). Smooth muscle
glands. This is a tall columnar cell, with slightly granular fibers (7, 15) from the circular layer of the muscularis
cytoplasm, lightly stained because of mucigen content, and a mucosae (18) pass upward into the lamina propria (13) be-
flattened or oval nucleus at the base. The pyloric glands (5, tween the pyloric glands (6) and into mucosal ridges (2,3).
6, 14) open into the bottom of the gastric pits (4, lower

188 Organs
Stomach: Mucosa of the Pyloric Region

Fig. 12-10 Stomach: Mucosa of the Pyloric Region. Stain: hematoxylin-eosin. Medium magnification.

Digestive System: Esophagus and Stomach 189

Figure 12-11. Pyloric-Duodenal Junction (longitudinal section)

The pyioric (1) of the stomach is separated from stomach (3) changes abruptly to intestinal epithelium (11).
the duodenum (2) by a pyloric sphincter (7). This sphinc- This epithelium consists of goblet cells and columnar cells
ter is formed by thickened circular layer of the muscularis with striated borders (microvilli), which are present through-
externa. out the length of the small intestine.
As the pylorus joins the duodenum, the mucosal ridges Short, simple tubular intestinal glands (crypts of
(5) wbich surrurround the gastric pits (6), become broader and Lieberkiihn) (12) are now seen in the lamina propria. These
more irregular. As a result, their shape becomes highly vari- glands consist primarily of goblet cells and cells with striat-
able. Coiled tubular pyloric (mucous) glands (4), located in ed borders (microvilli) from the surface epithelium. One or
the lamina propria, open at the bottom of the gastric pits (6). more intestinal glands (17) are shown opening between the
Lymphatic nodules (10) are frequently seen in the transition villi (17).
regIOn. Duodenal (Brunner's) glands (14) occupy most of the
The duodenum (2) exhibits surface modification in the submucosa (9) in the upper duodenum. In this region, the
form of villi (13). Each villus (13) is a leaf-shaped surface muscularis mucosae (15) is disrupted and strands of its
projection with a pointed end. Between individual villi are muscle are dispersed among the glands. Except for the
intervillous spaces (16) that represent the continuation of esophageal (submucosal) glands proper, the duodenal glands
the intestinal lumen. The mucus-secreting epithelium of the (14) are the only submucosal glands in the digestive tract.

190 Organs
Pyloric-Duodenal Junction

1 Pylorus

2 Duodenum

Fig. 12-11 Pyloric-Duodenal Junction "ongitudina' section). Stain: hematoxylin-eosin. Low


Digestive System: Esophagus and Stomach 191


Digestive System: Small and

Large Intestines

Small Intestine Interspersed among the columnar absorptive cells are the
The small intestine consists of three parts: the duodenum, goblet cells, which increase in number toward the distal
jejunum, and ileum. It is a long tube that extends from the region of the small intestine (ileum). Goblet cells secrete
junction with the stomach to the junction with the large intes- mucus that lubricates, coats, and protects the intestinal sur-
tine or colon. The small intestine performs many important face from the corrosive action of digestive chemicals and
digestive functions, including (I) completing digestion (ini- enzymes.
tiated in the stomach) of food products (chyme) by chemicals The small intestine also contains numerous intestinal
and enzymes produced in the liver and pancreas, and by cells glands (crypts of LieberkUhn). These glands are located in
in its own mucosa; (2) selective absorption of nutrients into the intestinal mucosa and open into the intestinal lumen at
the blood and lymph capillaries; (3) transportation of chyme the base of the villi. The surface epithelium of the villi also
and digestive waste materia] to the large intestine; and (4) extends into and lines the intestinal glands. Undifferentiated
release of hormones that regulate the digestive processes. cells in the intestinal glands exhibit mitotic activity and pro-
The mucosa of the small intestine is specialized in ways duce the columnar absorptive cells and the goblet cells of the
that increase its surface area for absorption. Specialized intestinal epithelium. Located at the base of the intestinal
structures include the plicae circulares, the villi, and the glands are the Paneth cells, characterized by deep-staining
microvilli. The plicae circulares are permanent, spiral folds eosinophilic granules. Their exact functions are not com-
of the mucosa (with submucosal core) that extend into the pletely known; however, these cells produce lysozyme, an
intestinal lumen; they are most prominent in the proxima] antibacterial enzyme that digests the cell walls of some bac-
portion of the small intestine, where most of the absorption teria and appears to control the microbial flora of the small
takes place, and decrease in prominence closer to the ileum. intestine.
The villi are fingerlike projections that cover the surface of Numerous aggregations of lymphoid nodules, called
the intestine and extend into the lumen. The villi are also Peyer's patches, are found in the ileum of the small intestine.
more prominent in the proximal portion of the small intes- Present in the Peyer's patches are B lymphocytes. T lympho-
tine. The microvilli are cytoplasmic extensions that cover the cytes, and macrophages. Overlying the lymphoid nodules are
apices of the intestinal absorptive cells. They are visible M (membranous epithelial) cells. M cells continually sample
under a light microscope as a striated (brush) border. the antigens of the intestinal lumen, ingest the antigens, and
A]though the epithelium that lines the stomach surface is transport them to the underlying lymphocytes, where specif-
made up of only one type of cell (mucus-secreting), the sur- ic antibodies to the foreign antigens are developed.
face of the mucosa of the small intestine contains numerous Numerous enteroendocrine or APUD (amine precursor
cell types. Most cells in the intestinal epithelium are tall, uptake and decarboxylation) cells are also found in the
columnar absorptive cells with a prominent striated (brush) epithelium of the villi and intestinal glands. These cells
border (microvilli) covered by a thick glycocalyx coat. The secrete numerous regulatory hormones of the intestine,
outer glycocalyx coat not only protects the intestinal surface including gastric inhibitory peptide, secretin, and cholecys-
from digestion, but also contains the enzymes required for tokinin (pancreozymin). These intestinal hormones control
the terminal digestion of carbohydrates and proteins, and the the release of gastric and pancreatic secretions, intestinal
carriers needed for transporting the products of digestion into motility, and contractions of the gall bladder.
the cell. Intestinal cells absorb amino acids, glucose, and A characteristic feature of the first portion of the small
fatty acids-the end products of protein, carbohydrates, and intestine, the duodenum, is the presence of mucus-secreting
fat digestion, respectively. Amino acids and glucose are duodenal (Brunner's) glands in the submucosa. The ducts of
transported through intestinal cells to the blood capillaries. these glands extend through the muscularis mucosae and
Most of the fatty acids, however, enter the lymphatic vessels, open into the bases of the intestinal glands. Duodenal glands
called the ]acteals, that are located in the lamina propria of protect the duodenal mucosa from the highly corrosive
the villi. action of gastric secretions. When acidic chyme enters the

Digestive System: Small and Large Intestines 193

duodenum from the stomach, the glands secrete an alkaline The principal functions of the large intestine are to
fluid rich in bicarbonate ions. This alkaline fluid then neu- absorb water and minerals from the residual contents and
tralizes the acidic chyme from the stomach and protects the form feces. Consistent with these functions, the epithelium
duodenal surfaces from digestion. The alkaline secretion also of the large intestine contains columnar absorptive cells
provides a more favorable environment for the continued (similar to those in the epithelium of the small intestine)
action of the digestive enzymes. and mucus-secreting goblet cells. No digestive enzymes
are produced by the cells of the large intestine.
Large Intestine Goblet cells appear more numerous in the large intes-
The large intestine is situated between the anus and the ter- tine than in the small intestine. They produce mucus for
minus of the ileum. Unabsorbed and undigested food residues lubricating the lumen of the larger intestine to facilitate
in the small intestine are forced into the large intestine by passage of the hardened feces.
peristaltic action of the muscles in muscularis extema of the The intestinal glands of the large intestine do not con-
small intestine. The residues that enter the large intestine are tain plicae circulares, villi, or Paneth cells. The intestinal
in a semifluid state; by the time they have reached the termi- glands of the large intestine are deeper than in the small
nal portion of the large intestine, however, these residues have intestine, and contain different enteroendocrine (APUD)
acquired the semisolid consistency of feces. cells.

194 Organs

Figure 13-1 Small Intestine: Duodenum (longitudinal section)

Digestive System: Small and Large Intestines 195

Figure 13-1 Small Intestine: Duodenum (longitudinal section)

The wall of the duodenum (first part) consists of four lay- tions of the duodenum, the submucosal duodenal glands (13)
ers: the mucosa with its lining epithelium (7a), lamina pro- can be seen extending into the lamina propria (3). The lami-
pria (7b), and the muscularis mucosae (9, 12); the underly- na propria (7b) also contains fine connective tissue fibers
ing connective tissue submucosa with the mucous duodenal with reticular cells, diffuse lymphatic tissue, and/or lym-
(Brunner's) glands (3, 13); the two smooth muscle layers of phatic nodules (5).
the muscularis externa (14); and the visceral peritoneum In the duodenum, the submucosa (13) is almost complete-
serosa (15). These layers are continuous with those in the ly filled with highly branched, tubular duodenal glands (13).
stomach and in the small and large intestine. The muscularis mucosae (9, 12) may be interrupted if the
The small intestine is characterized by numerous finger- duodenal glands penetrate into the mucosal lamina propria
like extensions called villi (7) (singular: villus); a lining (3). The duodenal glands (3) deliver their secretory product
epithelium (7a) of columnar cells lined with microvilli, to the bottom of the intestinal glands (3, 4, 8).
which form the striated borders; light-staining goblet cells In a normal cross section of the duodenum, the muscularis
(2); and short, tubular intestinal glands (crypts of extern a (14) consists of an inner circular layer (14a) and
Lieberkiihn) (4, 8) in the lamina propria (7b). The presence outer longitudinal layer (14b) of smooth muscle. However,
of duodenal glands (3, 13) in the submucosa (13) character- because in this figure the duodenum has been cut in a longi-
izes the upper duodenum. These glands are absent in the rest tudinal plane, the direction of fibers in these two smooth
of the small and large intestine. muscle layers is reversed. Nests of parasympathetic ganglion
The villi (7) are mucosal surface modifications. cells of the myenteric (Auerbach's) nerve plexus (6) are
Intervillous spaces (1) are visible between the villi (7). The also visible in the connective tissue between the two muscle
lining epithelium (7a) covers each villus and continues into layers of the muscularis externa (14). This nerve plexus is
the intestinal glands (4, 8). Each villus (7) has core of lami- found between these muscle layers throughout the small and
na propria (7b), strands of smooth muscle fibers (10) that large intestine. Similar but smaller nests of ganglion cells are
extend upward into the villi from the muscularis mucosae likewise found in the submucosa (not illustrated) throughout
(9, 12), and a central lymphatic vessel, called the lacteal the small and large intestine.
(11). (See Fig. 13-5 for a detailed structure of a villus, the The serosa (visceral peritoneum) (15) contains the con-
central lacteal, and the contents of the lamina propria.) nective tissue cells, blood vessels, and adipose cells; the
The lamina propria (7b) contains the intestinal glands (4, serosa forms the outermost layer of the duodenum (first
8); these open into the intervillous spaces (I). In certain sec- part).

196 Organs
Small Intestine: Duodenum

- 7 Villus
- a. Lining
- b. Lamina
- 8 Intestinal
- 9 Muscularis
- 10 Smooth
- 11 Lacteals
--- 12 Muscularis
13 Duodenal
?" glands in

14 Muscularis
- a.lnner
~ b, Outer
-- 15 Serosa
P":XU5 ',"', "-":"-""'~""~_':,~',:'",:,:',',:,C"'.' .:..',',"-: -.:';','.";'.:,',. '~,-:c:.::>~. '';-: .:"-1
Fig. 13-1 Small Intestine: Duodenum (longitudinal section). Stain: hematoxylin-eosin. Low

Digestive System: Small and Large Intestines 197

Figure 1 3-2 Small Intestine: Jejunum-Ileum 'transverse section,

The histology of the lower duodenum, jejunum, and ileum and small blood vessels; these are illustrated in Figure 13-5.
is similar to that of the upper duodenum illustrated in Figure The intestinal glands (crypts of Lieberkuhn) (5, 12) extend
13-1. The only exception are the duodenal glands into the lamina propria (3). These glands are closely packed,
(Brunner's); these are usually limited to submucosa in the and in the figure are seen in both the longitudinal and cross
upper part of the duodenum. The villi exhibit variable shapes sections. The intestinal glands (5, 12) open into the intervil-
and lengths in different regions of the small intestine; how- lous spaces (11). A lymphatic nodule (14) is visible extend-
ever, this is not usually apparent in histologic sections. Also, ing from the lamina propria (3) of the mucosa into the sub-
in the lower regions of the ileum, large aggregates of lym- mucosa (16), disrupting the surrounding muscularis
phatic nodules (peyer's patches) are visible at intervals (See mucosae (15).
Fig. 13-4). The appearance and distribution of the muscularis
This figure illustrates numerous villi (2) sectioned in dif- mucosae (6, 15), submucosa (4, 16), muscularis externa (7,
ferent planes and a prominent, permanent fold of the small 8), and serosa (18) are typical of the small intestine.
intestine, the plica circulares (10). Both the mucosa and Parasympathetic ganglion cells of the myenteric plexus (17)
submucosa (4, 16) constitute the plica circulares (10). In the are seen in the connective tissue between the inner circular
lumen, each villus (2) exhibits a typical structure: a columnar smooth muscle layer (7) and the outer longitudinal muscle
lining epithelium (1) with striated border and goblet cells, a layer (8) of the muscularis externa. Ganglion cells of the sub-
core of lamina propria (3) with diffuse lymphatic tissue, mucosal plexuses are also present in the small intestine but
and strips of smooth muscle fibers from the muscularis are not illustrated in this figure.
mucosae (6). Within the villi are also seen a central lacteal

Figure 1 3-3 Intestinal Glands with Paneth Cells and Enteroendocrine Cells

Adjacent to the smooth muscle of the muscularis (2), and Paneth cells (4, 9). Enteroendocrine cells are char-
mucosae (5, 10) several intestinal glands (7) are visible. acterized by fine granules located in the basal portions of the
The characteristic goblet cells (2) and cells with striated bor- cytoplasm, with the nucleus situated above the granules.
ders are seen in the glands. Visible at the base of these glands Most enteroendocrine cells take up and decarboxylate pre-
are pyramid-shaped cells with large, acidophilic granules, cursors of biogenic monoamines and are therefore consid-
which fill most of the cytoplasma and displace the nucleus ered part of a larger group of cells designated as the amine
toward the base of the cell. These cells are the Paneth cells precursor uptake and decarboxylation (APUD) cell series.
(4,9) and are found throughout the small intestine. The APUD cell types are found in the epithelia of the gas-
Enteroendocrine cells (3, 8) are interspersed among the trointestinal tract (stomach, small and large intestines), respi-
intestinal gland cells, mitotic gland cells (1, 6), goblet cells ratory tract, pancreas, and thyroid glands.

198 Organs
Small Intestine

. 11 Intervillous

. 12 Intestinal

- 13 Muscularis

. 14 Lymphatic

. 15 Muscularis

- 16 Submucosa

- 17 Myenteric

- 18 Serosa

Fig. 13-2 Small Intestine: Jejunum-ileum (transverse section). Stain: hematoxylin-eosin. Low

.. ~ -"",- ",-_<1t:-"""'" ,. - ~

1 Mitotic cell ---

2 Goblet cells -: - 6 Mitotic cell

3 Enteroendocrine 7 Intestinal
4 Paneth8 Enteroendocrine
cells cell
9 Paneth cell!
5 Muscularis 10 Muscularis

Fig. 13-3 Intestinal Glands w,ith Paneth Cells and Enteroendocrine Cells. Stain: hematoxy/in-
eosin, plastic section. High magnification.

Digestive System: Small and Large Intestines 199

Figure 1 3-4 Small Intestine: Ileum with Lymphatic Nodules ,Peyers Patch)
,transverse section)

This cross section of the ileum illustrates the four layers patch illustrated in this figure shows nine lymphatic nodules
of the intestinal wall (9-16). The villi (1,2,9) have been sec- (4, 5, and others), most of which exhibit germinal centers
tioned in various planes and thus appear irregular. The (5). The lymphatic nodules coalesce and the boundaries
intestinal glands (crypts of Lieberkiihn) (3, 10) are located between them are usually not discernible.
in the lamina propria; two of these glands are illustrated The nodules originate in the diffuse lymphatic tissue of
opening into an intervillous space (upper leader 3, upper the lamina propria (11). Villi are absent in the area of the
leader 10). intestinal lumen where the nodules reach the surface of the
A characteristic feature of the ileum are the aggregations mucosa (4). Typically, the lymphatic nodules extend into the
of lymphatic nodules called Peyer's patches (5). Each submucosa (7,13), disrupt the muscularis mucosae (6), and
Peyer's patch is an aggregation of ten or more lymphatic spread out in the loose connective tissue of the submucosa
nodules, which are located in the wall of the ileum opposite (7, 13).
the attachment of the mesentery. The portion of the Peyer's

Figure 1 3-5 Small Intestine: Villi

The distal parts of villi sectioned in several planes are basement membrane (5) is visible between the surface a higher magnification. The villi on the left and epithelium (2) and the lamina propria (12). In the core of
on the right are sectioned longitudinally. The villus (1) in the the lamina propria (12) are seen reticular cells of the stroma,
center was bent and is sectioned in two parts; the apex has lymphocytes, and smooth muscle fibers (4, 16). Present in
been sectioned transversely (I) and the lower portion tan- each villus (but not always seen in sections) is a central
gentially (7) and longitudinally (8). lacteal (3, 17)-a dilated lymphatic vessel lined with
The surface epithelium (2) contains goblet cells (9, 10, endothelium. Arterioles, one or more venules, and numerous
13) and columnar cells with striated borders (14, 15). A thin capillaries (11) are also visible in the villi.

200 Organs
Small Intestine

9 Villi

1 Villus (I.s.):
epithelium and 10 Intestinal glands
core of lamina propri
11 lamina propria
12 Muscularis
3 Intestinal glands
(crypts of Lieberkiihn) 13 Submucosa
4 lymphatic nodules

5 Germinal centers in 14 Muscularis

lymphatic nodules externa:
--- circular layer
5 Muscularis
7 Submucosa externa:
. longitudinal layer

,\ 6 Serosa (visceral
, peritoneum)

8 Circular muscle
Fig. 13-4 Small Intestine: Ileum with Lymphatic Nodules (peyers Patch) (transverse section).
Stain: hematoxylin-eosin. Low magnification.

1 Villus (l.s.1 - 10 Goblet cell

2 Surface epithelium -
11 Capillaries

3 Central lacteal (I.s.) -

- 12 lamina propria
4 Smooth muscle (I.s.)
5 Basement membrane
6 lymphocyte

- 13 Goblet cell
14 Striated border

7 Epithelium.
- 15 Columnar cells with
tangential section
striated borders
- 16 Smooth muscle (I.s.)

8 Villi(I.s.) -

1 . - 17 Central lacteal (I.s.)

9 Gobletcells - 18 lymphocyte

Fig. 13-5 Small Intestine: Villi. Stain: hematoxylin-eosin. Medium magnification.

Digestive System: Small and Large Intestines 201

Figure 1 3-6 Large Intestine: Colon and Mesentery (panoramic view,
transverse section)

The colon has the same basic layers of epithelium, con- The smooth muscle layers in the muscularis externa (13)
nective tissue, and smooth muscle in its wall as the small of the colon are also modified. The inner circular muscle
intestine. The mucosa (4, 5, 6, 7) consists of columnar sur- layer (16) is continuous in the colon wall, whereas the outer
face epithelium (4), intestinal glands (5), lamina propria smooth muscle layer is condensed into three broad, longitu-
(6), and muscularis mucosae (7). The underlying submu- dinal bands called taeniae coli (1, 10). In the rest of the colon
cosa (8) contains connective tissue cells and fibers, various wall, a very thin outer longitudinal muscle layer (15)
blood vessels, and nerves. Two smooth muscle layers are vis- can be found between the taeniae coli (I, 10); this outer lon-
ible in the muscularis externa (13). The serosa (visceral gitudinal muscle layer, however, is often discontinuous.
peritoneum and mesentery) (3, 17) covers the transverse The parasympathetic ganglion cells of the myenteric
colon and sigmoid colon regions. Several distinct modifica- (Auerbach's) nerve plexus (2, 14) are found between the
tions in the wall of the colon, however, clearly distinguish it two smooth muscle layers of the muscularis externa (13).
from other regions of the digestive tract (tube). Both the transverse and sigmoid portions of the colon are
In contrast to the small intestine, the colon does not have attached to the body wall by a mesentery (18). As a result,
villi or plicae circulares. As a result, the luminal surface of the serosa (3, 17) becomes the outermost layer in these two
the mucosa in the colon is smooth. When the colon is undis- regions of the colon. Within the mesentery loose connective
tended, however, the mucosa (4, 5, 6, 7) and submucosa (8) tissue, adipose cells, blood vessels, and nerves are found.
exhibit numerous temporary folds (12). In the lamina pro- A more detailed description and illustration of each layer
pria (6) and the submucosa (8) of the colon wall various- in the colon wall are presented at a higher magnification in
sized lymphatic nodules (9, 11) may be found. Figure 13-7.

202 Organs
Colon and Mesentery

Fig. 13-6 Large Intestine: Colon and Mesentery (panoramic view, transverse section). Stain:
hematoxylin-eosin. Low magnification.

Digestive System: Small and Large Intestines 203

Figure f 3-7 Large Intestine: Colon Wall (transverse section)

A small section of undistended colon wall is illustrated in tine, contains abundant diffuse lymphatic tissue. A distinct
greater detail. The four layers of the wall are the mucosa (2, lymphatic nodule (13) is visible deep in the lamina propria
3, 4), submucosa (5), muscularis externa (6), and serosa (2). Some of the larger lymphatic nodules may extend
(7). These layers are continuous with those of the small intes- through the muscularis mucosae (4, II) into the submu-
tine. This section of the colon wall shows the temporary cosa (5).
fold (9) of the mucosa (2, 3,4) and submucosa (5). The appearance and distribution of the muscularis
Villi are absent in the colon. The mucosa, however, is mucosae (4, II), submucosa (5), and serosa (7) are typical
indented by long tubular intestinal glands (crypts of for the digestive tract. The muscularis externa (6), however,
Lieberktihn) (1, 10), which extend through the lamina pro- appears atypical. In this section, the longitudinal layer of the
pria (3) to the muscularis mucosae (4, 11). muscularis externa (6) is arranged into strips or bands of
The lining epithelium (2) in the colon is primarily colum- smooth muscle called the taeniae coli (15). The parasympa-
nar, with thin striated borders and numerous goblet cells. thetic ganglia of the myenteric plexus (8, 14) are visible
This epithelium continues into the intestinal glands (I, 10), between the muscle layers in the muscularis externa (6).
where goblet cells are abundant. Some of the intestinal The serosa (7) covers the transverse and sigmoid colon;
glands (I, 10) are visible sectioned in longitudinal, trans- however, the ascending and descending colon are retroperi-
verse, or oblique planes. toneal and the outer layer on their posterior surface is the
The lamina propria (2), similar to that in the small intes- adventitia.

204 Organs
Large Intestine: Colon

Fig. 13-7 Large Intestine: Colon Wall (transverse section). Stain: hematoxylin-eosin. Medium

Digestive System: Small and Large Intestines 205

Figure 1 3-8 Appendix (panoramic view, transverse section,

This figure illustrates a cross section of the vermiform Lymphatic nodules (4, 9) with germinal centers are very
appendix at low magnification. It is structurally similar to the numerous and highly characteristic of the appendix. These
colon except for certain modifications characteristic of the nodules originate in the lamina propria (3); however, because
appendix. of their large size, the nodules may extend from the surface
In comparing the mucosa of the appendix with that of the epithelium (I) to the submucosa (8).
colon, several similar features are apparent: a lining epithe- The submucosa (8) is highly vascular and has numerous
lium (1) with numerous goblet cells; the underlying lamina blood vessels (11). The muscularis externa (7) consists of
propria (3) containing the intestinal glands (5) (crypts of the characteristic inner circular layer (7a) and outer longi-
Lieberkiihn); and the muscularis mucosae (2). The intesti- tudinal layer (7b) of smooth muscle; these muscle layers
nal glands (5) in the appendix are less well developed, short- may vary in thickness. The parasympathetic ganglia (12) of
er, and often spaced farther apart than those in the colon. the myenteric plexus (12) are seen between the inner (7a)
Diffuse lymphatic tissue (6) in the lamina propria (3) and outer (7b) smooth muscle layers. The outermost layer of
is abundant and is often observed in the adjacent submu- the appendix is the serosa (10).
cosa (8).

206 Organs

1 Lining epithelium
with goblet cells

2 Muscularis B Submucosa

3 Lamina propria
9 Lymphatic nodule
with germinal
, 4 Germinal center
(01 lymphatic nodule)

10 Serosa
5 Intestinal glands

11 Blood vessels
(in submucosa)
6 Diffuse lymphatic
tissue 12 Parasympathetic
ganglia (01
nerve plexus)
13 Adipose cells

Fig. 13-8 Appendix (panoramic view, transverse section). Stain: hematoxylin-eosin. Low

Digestive System: Small and Large Intestines 207

Figure 1 3-9 Rectum (panoramic view, transverse section)

The histology of the transverse section through the upper cosa (8) that is covered by the mucosa. Permanent transver-
rectum appears similar to that of the colon; the same layers sal folds of the rectum, if present in a section, contain smooth
are present in the wall of the organ and the same components muscle fibers from the circular layers of the muscularis
are found in each layer. Except for the longitudinal muscle externa. Permanent longitudinal folds (rectal columns) are
layer surrounding the lumen, this figure could be a section of found in the lower rectum, the anal canal.
the colon. Taeniae coli of the colon, illustrated in Figures 13-6 and
The surface epithelium (1) facing the lumen (5) is lined 13-7, continue into the rectum. Here, however, the muscles
by columnar cells with striated borders and goblet cells. The of the muscularis externa (13a, b) again acquire the typical
intestinal glands (4), adipose cells (12), and scattered lym- inner circular (13a) and outer longitudinal (13b) smooth
phatic nodules (10) in the lamina propria (2) are similar to muscle layers that are found in the rest of the digestive tract.
those in the colon; however, the glands are longer, closer Visible between these two smooth muscle layers are the
together, and are mainly filled with goblet cells. Beneath the parasympathetic ganglia of the myenteric (Auerbach's)
lamina propria (2) are the thin smooth muscle layers of mus- plexus (14).
cularis mucosae (11). Adventitia (9) covers a portion of the rectum and serosa
The longitudinal folds (3) seen in the upper rectum and covers the remainder. Numerous blood vessels (6, 7, 15) are
colon are temporary. These folds (3) have a core of submu- visible in both the submucosa (8) and adventitia (9).

208 Organs

9 Adventitia

1 D Lymphatic nodule

11 Muscularis

12 Adipose cells
13 Muscularis
a. inner circular
b. outer
longitudinal layer

14 Parasympathetic
ganglia of
myenteric plexus

15 Arteriole
and venule

Fig. 13-9 Rectum (panoramic view, transverse section). Stain: hematoxylin-eosin. Low

Digestive System: Small and Large Intestines 209

Figure 13-10 Anal Canal ,'ongitudina' section)

The upper portion of the anal canal (A), above the anal (9) of the rectum merges with the connective tissue in the
valves (11), represents the lowermost part of the rectum. The lamina propria of the anal canal, a region that is highly vas-
lower part of the anal canal (B), below the anal valves (I I), cular; the internal hemorrhoidal plexus of veins (15) lies in
shows the transition from the simple columnar epithelium to the mucosa of the anal canal. Blood vessels from this region
the stratified squamous epithelium of the skin. The change continue into the submucosa (9) of the rectum. Internal hem-
from the rectal mucosa to the anal mucosa occurs at the apex orrhoids develop from chronic dilation of these vessels.
of the anal valves (10, II). This region is the anorectal junc- External hemorrhoids develop from vessels of the external
tion (10). venous plexus of the anus (not iIIustrated in this figure).
The rectal mucosa (4-8) is similar to the mucosa of the The circular smooth muscle layer of the muscularis
colon; however, the intestinal glands (7) are shorter and far- extern a (1) increases in thickness in the upper region of the
ther apart. As a result, the lamina propria (8) is more promi- anal canal (A) and forms the internal anal sphincter (1, 14).
nent, diffuse lymphatic tissue is more abundant, and solitary Lower in the anal canal, this sphincter is replaced by skeletal
lymphatic nodules (6) are more numerous. muscles, the external anal sphincter (16). External to this
The muscularis mucosae (5, 12) and the intestinal glands sphincter is the skeletal levator ani muscle (3). The longitu-
(7) of the digestive tract terminate in the vicinity of the anal dinal muscle layer of the muscularis externa (2) becomes
valve (II). The lamina propria (8) of the rectum is replaced thin and disappears in the connective tissue of the external
by the dense irregular connective tissue of the lamina pro- anal sphincter (16).
pria of the anal canal (13, lower leader). The submucosa

210 Organs
Anal Canal

Fig. 13-10 Anal Canal (longitudinal section). Stain: hematoxylin-eosin. Low magnification.

Digestive System: Small and Large Intestines 211


Digestive System: Liver and


The liver, gallbladder, and pancreas are the accessory from the stomach. This action of the bile promotes easier
digestive organs that are connected to the small intestine by digestion of the fats by the fat-digesting enzymes, the pan-
excretory ducts. The cells of the liver and pancreas secrete creatic lipase produced by the pancreas. The digested fats are
numerous chemicals and enzymes for digestion; these secre- subsequently absorbed by the cells in the small intestine. Bile
tions are then delivered into the duodenum by a duct com- salts also solubilize cholesterol and facilitate its excretion
mon to both organs. The gall bladder serves primarily as a from the body.
reservoir for bile secreted by the liver. The endocrine functions of the liver are related to the syn-
thesis of numerous plasma proteins, including albumin and
Liver the blood-clotting factors prothrombin and fibrinogen. Liver
The liver has a highly strategic location in the body. All also stores glucose (as glycogen), fats, and various vitamins.
venous blood that returns from the digestive organs and When the cells of the body need glucose, glycogen stored in
spleen by way of the portal vein first percolates through the the liver is converted back into glucose and released into the
liver. Because venous blood is poor in oxygen, the liver is blood stream. Liver cells also detoxify various drugs and
also supplied by the hepatic artery from the aorta. Thus, the harmful chemicals. Kupffer cells, specialized phagocytic
liver has a dual blood supply. cells that are derived from blood monocytes and located in
The mixing of venous and arterial blood occurs only in the hepatic sinusoids, phagocytize particulate material and
the hepatic sinusoids of the liver. The blood then flows cellular debris and remove it from the blood. In the fetus, the
toward the central vein that is found in the liver lobules. The liver cells perform hemopoiesis-an important function in
liver sinusoids are dilated blood channels lined by a discon- blood cell production. Thus, the liver is an essential organ for
tinuous layer of fenestrated endothelial cells, which are sep- life.
arated from the underlying liver cells, the hepatocytes, by a
perisinusoidal space (of IJisse). As a result of this arrange- Gallbladder
ment, the material carried in the mixed blood percolates
The gallbladder is a small, hollow organ attached to the
through the discontinuous endothelial wall and comes in
inferior surface of the liver. It receives, stores, and concen-
direct contact with the hepatocytes. This allows for a more
trates bile by absorbing its water. In response to the entrance
efficient exchange of materials found in the blood with those
of dietary fats into the small intestine, a hormone, cholecys-
in the hepatocytes and vice versa.
tokinin, is released into the blood stream by the enteroen-
The hepatocytes are highly versatile cells that perform
docrine (APUD-amine precursor uptake and decarboxyla-
numerous vital functions. Because hepatocytes synthesize
tion) cells located in the intestinal mucosa. Cholecystokinin
and release a secretory product (bile) into a system of ducts,
is carried in the blood to the gallbladder and causes rhythmic
they are exocrine cells. The hepatocytes are also endocrine
contractions of the smooth muscles in the wall of the gall-
cells because they release many of their products directly
bladder. This action forces the bile to enter the duodenum by
into the bloodstream as the blood flows through the sinusoids
way of the common bile duct.
and past the hepatocytes. Thus, the liver cells perform both
important endocrine and exocrine functions.
The main exocrine function of the hepatocytes is the Exocrine Pancreas
secretion of bile, which enters tiny bile canaliculi located The pancreas is the main accessory digestive organ. It
between adjacent hepatocytes. In the liver, the bile flows produces an alkaline tluid with numerous digestive enzymes
toward the bile duct located at the periphery of the liver lob- that break down proteins, fats, and carbohydrates into small-
ule and exactly in the opposite direction to the flow of blood. er molecules for absorption in the small intestine. Most of the
The bile salts that are present in the bile are necessary to pancreas consists of exocrine secretory units or acinar cells,
emulsify the fats that enter the small intestine (duodenum) which secrete the pancreatic enzymes. Pancreatic secretions

Digestive System: Liver and Pancreas 213

are regulated by both hormones and vagal stimulation. Two islets (of Langerhans'); these islets constitute the
intestinal hormones, secretin and cholecystokinin, secreted endocrine portion of the pancreas. With special stains,
by the enteroendocrine (APUD) cells of the duodenal three main types of cells can be identified in the pancreat-
mucosa into the blood stream, regulate the pancreatic secre- ic islets: alpha, beta, and delta. These islet cells produce
tions. two very important hormones, insulin and glucagon.
In response to the presence of acidic chyme in the small The alpha cells produce the hormone glucagon, whose
intestine, secretin release stimulates the pancreatic cells to main physiological function is to increase the levels of
secrete large amounts of watery fluid rich in sodium bicar- glucose in the blood. This function is primarily accom-
bonate ions. This fluid, which has little or no enzymatic plished by accelerating the conversion of glycogen, amino
activity, is produced primarily by the epithelial cells that line acids, and fatty acids in the liver into glucose; these con-
the smaller pancreatic ducts. The function of this fluid is to versions elevate the sugar levels in the blood.
neurralize the acidic chyme and create an optimal environ- The beta cells of the pancreatic islets produce the hor-
ment for the activity of the pancreatic enzymes. mone insulin, whose release is stimulated by the elevation
In response to the presence of fats and proteins in the of glucose after a meal. The main physiological function
small intestine, cholecystokinin release stimulates the acinar of insulin is to lower the glucose levels in the blood by
cells in the pancreas to secrete large amounts of different accelerating membrane transport of glucose into cells,
digestive enzymes. The pancreatic enzymes that are pro- especially into the cells of the liver, muscle, and fat.
duced in the acinar cells enter the duodenum in an inactive Insulin also accelerates the conversion of glucose into
form and are then activated by a hormone secreted by intesti- glycogen in the liver. The effects of insulin on the levels
nal mucosa. of blood glucose are just the opposite to that of glucagon.
The delta cells secrete the hormone somatostatin,
Endocrine Pancreas which decreases and inhibits the secretion of both insulin
Scattered throughout the secretory acini in the pancreas and glucagon through local action within the pancreatic
are pale-staining, spherical units of cells called pancreatic islets.

214 Organs

Figure 14-1 Pigs Liver (panoramic view, transverse section)

Figure 14-2 Primate Liver (panoramic view, transverse section)

Digestive System: Liverand Pancreas 215

Figure 14-1 Pigs Liver (panoramic view, transverse sectionJ

The connective tissue from the liver hilus extends and nerves; however, these structures are small, inconspicu-
between the liver lobes as interlobular septa. In the pig's ous, and seen only occasionally.
liver, the individual hepatic (liver) lobules (7) are well In the center of each hepatic lobule (7) is a central vein (I,
defined. To illustrate the boundaries of the hepatic lobules, a 8). Radiating from the central vein (I, 8) toward the periphery
section of pig's liver was stained with Mallory-Azan stain, of the lobule are plates of hepatic cells (6). Located between
which stains the connective tissue septa dark blue. the hepatic plates (6) are the hepatic sinusoids (10). On
This figure illustrates, in transverse section, a complete entering the liver, arterial and venous blood mixes in these
hepatic lobule (on the left) and parts of several adjacent sinusoids and then flows toward the central veins (I, 8) of the
hepatic lobules (7). The blue-staining interlobular septa (5, lobule (7). Bile is formed in the liver cells and flows through
9) contain interlobular branches of the portal vein, bile duct, the minute bile canaliculi in the opposite direction into the
and hepatic artery (2, 3, 4,11,12,13). These regions around interlobular bile ducts (2, 12) (See Fig. 14-5).
the hepatic lobule are collectively considered portal canals The interlobular vessels and bile ducts (2, 3, 4, II, 12, 13)
or areas. Around the periphery of each lobule can be seen exhibit numerous branches in the liver parenchyma. Thus, in a
several portal canals within the interlobular septa (5, 9). The cross section of the liver lobule, it is possible to see more than
interlobular septa (5, 9) also contain small lymphatic vessels one section of each of these structures within a portal area.

Figure 1 4-2 Primate Liver (panoramic view, transverse section)

[n the primate or human liver, the connective tissue septa center of each hepatic lobule (8) is the central vein (6, 9).
between individual hepatic lobules (8) are not as conspicu- The hepatic sinusoids (5) are seen between the plates of
ous as in the pig's liver. As a result, the liver sinusoids are hepatic cells (7) that radiate from the central veins (6, 9)
continuous from one lobule to the next. Despite these differ- toward the periphery of the hepatic lobule (8). As illustrated
ences, portal areas containing the interlobular branches of the in Fig. 14-1, numerous branches of the interlobular vessels
portal veins, hepatic arteries, and bile ducts (I, 2, 3, 11, and bile ducts are seen within the portal areas of a given
12, 13) are visible around the peripheries of different lobules. hepatic lobule (8).
This figure illustrates numerous hepatic lobules (8). [n the

216 Organs

8 Central vein

1 Central vein

Interlobular 9 Interlobular
branches of: septum

2 Bile duct
n; 3 Hepatic
4 Portal vein

5 Interlobular Interlobular
septum branches of:
11 Portal vein ~
6 Plates of 12 Bile duct ~
hepatic cells 13 Hepatic ;;
artery ) ~

7 Hepatic lobule

Fig. 14-1 Pigs Liver (panoramic view, transverse section). Stain: Mallory-Azan. Low magnification.

9 Central vein

10 Interlobular
5 Hepatic septum

6 Central vein

8 Hepatic lobule

Fig. 14-2 Primate Liver (panoramic view, transverse section). Stain: Hematoxylin-eosin. Low

Digestive System: Liver and Pancreas 217

Figure 1 4-3 Hepatic (Liver) Lobule (sectional view, transverse section)

A portion of a hepatic lobule between the central vein (1) portal venules and hepatic arterioles penetrate the connective
and the peripheral interlobular septum (9) is illustrated in tissue to form the sinusoids (2, 5).
greater detail and higher magnification than in Figure 14-2. The hepatic cells (I I) are polygonal, vary in size, contain
The central vein (I) is a venule lined with endothelium a large, round vesicular nucleus, and may occasionally be
(3). At the periphery of the lobule is the interlobular septum binucleate. The cells have a granular acidophilic cytoplasm
(9) with the portal area, which consists of a branch of por- which varies with their functional state (see also Fig. 14-4).
tal vein (8), two branches of the hepatic artery (6, 12), four The sinusoids (2, 5) are situated between plates of hepat-
sections of the bile duct (7, 14) and a lymphatic vessel (13). ic cells, and follow their branchings and anastomoses. The
The hepatic lobule consists of plates of hepatic cells (11). sinusoids (2, 5) are lined with a discontinuous type of
These plates branch and anastomose within the lobule. At the endothelium (3). Also present in the sinusoid wall are fixed
periphery of the lobule, the hepatic cells form a solid limit- macrophages, the Kupffer cells (see Fig. 14-4). The blood in
ing plate (10), which separates the hepatic plates and sinu- the sinusoids, containing erythrocytes (4) and leukocytes,
soids from the interlobular connective tissue septum (9). The drains into the central vein (I).

Figure 14-4 Liver: I<upffer Cells (India Ink preparation)

To demonstrate the phagocytic system in the sinusoids (2) lar or stellate outline. Because of the increased phagocytosis,
of the liver, a rabbit liver was intravenously injected with the nucleus is obscured by the accumulation of ingested car-
India ink. The Kupffer cells (1, 5), because of their phago- bon particles. Endothelial cells (3) are also visible in the
cytosis of carbon particles, appear prominent in the sinusoids sinusoids (2); they are smaller and usually only the nucleus
between the hepatic cells (4). The phagocytic Kupffer cells is visible.
(I, 5) are large with several processes, and exhibit an irregu-

Figure 1 4-5 Liver: Bile Canaliculi (Osmic Acid preparation)

A section of liver was fixed in osmic acid and the sections (I, 6). In this figure, some canaliculi (8) are illustrated in a
prepared and stained with hematoxylin-eosin. Osmic acid transverse plane.
fixation reveals the bile canaliculi (2, 8), which are minute The sinusoids (4, 5) are lined by endothelial cells (7)
channels between individual cells in the hepatic plates (2, with small nuclei and a Kupffer cell (9) with a larger nucle-
6). The canaliculi follow an irregular course between the us and branched cytoplasm. Also illustrated is a sinusoid (4,
hepatic cells (1) and branch freely within the hepatic plates upper leader) opening into a central vein (3).

218 Organs
Digestive System: Liverand Pancreas 219
Figure 1 4-6 Mitochondria and Fat Droplets in Liver Cells (Altmanns stain)

This liver section was fixed in potassium bichromate and droplets (1) usually stain hlack after osmic acid fixation, hut
osmic acid, and then stained with acid fuchsin and picric in this preparation stain hlue.
acid. This preparation stains mitochondria (2) red. The fat

Figure 14-7 Glycogen in Liver Cells (Bests carmine stain)

Staining the liver sections with alcohol and ammonia plasm. If the sections are previously stained with Mcyer's
solution of carmine demonstrates glycogen (1) as red gran- hemalum, the nuclei appear violet.
ules that exhibit an irregular distribution within the cyto-

Figure 14-8 Reticular Fibers in a Hepatic Lobule (Del Rio Hortegas stain)

The Del Rio Hortega modification of ammonium silver between the hepatocytes and the discontinuous endothelial
earbonats method for silver impregnation demonstrates the cells, and form a dense network of fihers (3) around the cen-
fine fibrillar structure of the liver stroma. The reticular fibers tral vein (2).
stain black and the liver cells pale violet. The collagen fihers in the dense irregular connective tis-
The reticular fibers form most of the supporting connec- sue of the interlohular septa (4) stain dark hrown; the retic-
tive tissue of the liver. They line the liver sinusoids (1) ular fibers merge with these fibers.

220 Organs

4 Collagen fibers
in interlobular
1 Reticular fibers in
5 Bile duct
walls of sinusoids

2 Central

3 Reticular fibers
around central vein

Fig. 14-8 Reticular Fibers in a Hepatic Lobule. Stain: Del Rio Hortega. High magnification.

Digestive System: Liver and Pancreas 221

Figure 1 4-9 Gallbladder (panoramic view)

The wall of the gallbladder consists of a mucosa (3, 4, 5), The lining epithelium (5, 14, 20) is a simple tall colum-
a fibromuscular layer (2), a peri muscular connective tissue nar epithelium with lightly stained cytoplasms and basal
layer (1, 10), and a serosa (6) on all of its surface except the nuclei. The lamina propria (4, 17) contains loose connec-
hepatic, where an adventitia attaches it to the liver. tive tissue and some diffuse lymphatic tissue.
The mucosa exhibits temporary folds (15), which disap- The smooth muscle fibers (7) in the fibromuscular layer
pear when the gallbladder is distended with bile. These folds (2) are interspersed within the layers of loose connective tis-
resemble the villi in the small intestine; however, they vary sue that are rich in elastic fibers (8). In contrast to other
in size, shape and irregular arrangement. The crypts or organs in which a serosa or adventitia covers the muscular
diverticula (16) between the folds often form deep indenta- layer, the gallbladder has a wide layer of peri muscular loose
tions in the mucosa. In cross section, these diverticula (18) connective tissue (1, 10), which contain blood vessels (11,
in the lamina propria resemble tubular glands; however, there 13), lymphatics, and nerves (12); serosa (6) is the outermost
are no glands in the gallbladder proper (except in the neck layer and covers all of these structures.

222 Organs

14 Columnar epithelium

15 Fold in mucosa:
epithelium and
lamina propria

16 Diverticulum or crypt
of mucosa (I.s.)

17 lamina propria

18 Diverticulae or crypts

19 Arterioles

20 Columnar epithelium

Fig. 14-9 Gallbladder (panoramic view,. Stain: hematoxylin-eosin. Medium magnification.

Digestive System: Liver and Pancreas 223

Figure 1 4-1 0 Pancreas (sectional view)

The pancreas has both endocrine and exocrine compo- (2). These ducts (2) exhihit small lumina and low cuhoidal
nents, which form the majority of the gland. The exocrine epithelium. The centroacinar cells (0. 10) are continuous
pancreas consists of closely packed secretory serous acini with the epithelium of the intercalated ducts (2). The interC<l-
(1) arranged into numerous small lobules. The lobules are lated ducts (2) then drain into interlohular ducts (12) that
surrounded by thin intralobular and interlobular connective are found in the connective tissue septa (4, 13) that extend
tissue septa (4, 13) with their corresponding blood vessels between the lohules. The small interlohular ducts (12) are
(5), ducts (12), nerves, and occasional Pacinian corpuscle lined by a simple cuhoidal epithelium, which hecomes taller
(11). Within the masses of serous acini (I) are found the iso- and stratified in larger ducts.
lated pancreatic islets (islets of Langerhans) (3, 7). These The pancreatic islets (3, 7) are round masses of
islets represent the endocrine portion of the pancreas and are endocrine cells of varying size that are demarcated from the
its characteristic features. surrounding exocrine acinar tissue hy thin layer of reticular
A pancreatic acinus (I) consists of pyramidal-shaped, pro- fibers. The pancreatic islets 0, 7) are normally larger than
tein-secreting zymogenic cells (I) surrounding a small cen- the acini and appear as compact clusters of epithelial cells
tral lumen. The excretory ducts extend into individual acini permeated by numerous capillaries (8). The cellular compo-
and are visible as pale-staining centroacinar cells (6, 10) sition of individual pancreatic islets 0, 7) are illustrated at
within their lumina. The secretory products from the acini higher magnification in Figures 14-11 and 14-12.
are drained by the narrow intercalated (intralobular) ducts

Figure 14-11 Pancreatic Islet

A pale-staining, spherical pancreatic islet (islet of (5). These cells are part of the duct system that conduct the
Langerhans) (2) is illustrated at a higher magnification. The secretory products of the acini (5) into the intercalated
endocrine cells of the islet (2) are arranged in cords and ducts (1). Myoepithelial cells do not surround the secretory
clumps, between which are found delicate connective tissue acini in the pancreas.
fibers and a rich capillary (3) network. A thin connective The pancreatic islets contain several hormone-secreting
tissue capsule (4) separates the endocrine pancreas from the cells; however, with routine histological preparations. indi-
dark-staining exocrine serous acini (5). In some of the vidual cells cannot he identified and the islets must he pre-
serous acini (5) are seen the pale-staining centroacinar cells pared with special stains.

Figure 14-12 Pancreatic Islet (special preparation)

This pancreatic islet has been prepared with special stain illustrated) is also present in the islets. These cells are least
to distinguish the glucagon-secreting alpha (A) cells (1) abundant, have variahle cell shape, and may occur anywhere
from the insulin-secreting beta (B) cells (3). The cytoplasm in the pancreatic islet.
of the alpha cells (I) stain pink while the cytoplasm of the Numerous capillaries (2) are clearly visihle around the
beta cells (3) stain blue. Generally, the alpha (I) cells are sit- different endocrine cells, demonstrating the rich viscularity
uated more peripherally in the islet and the beta cells (3) of the pancreatic islets. The islet cells are separated from the
deeper or more in the center of the islet. Also, the beta cells serous acini (6) hy a thin connective tissue capsule (4).
(3) are the predominant cell type of the pancreatic islets and Centroacinar cells (5) are clearly visihle in some of the sur-
constitute about 70% of their mass. The delta (D) cell (not rounding acini.

224 Organs

Fig. 14-10 Pancreas (sectional view). Stain: Hematoxylin-eosin. Low magnification.

1 Alpha cells

2 Capillary
3 Beta cells

4 Connective tissue
5 Centroacinar cells

6 Serous acini

Digestive System: Liver and Pancreas 225


Respiratory System

The respiratory system consists of two lungs and numer- monary bronchi; and a series of intrapulmonary bronchi and
ous tubes of various sizes that lead to and from each lung. bronchioles with decreasing diameters, culminating in the
The epithelium in the extrapulmonary passages (outside of terminal bronchioles. Hyaline cartilage plays an important
lungs), trachea, bronchi, and larger bronchioles is pseudo- supporting role in the conducting system by providing sup-
stratified ciliated epithelium containing numerous goblet port for the structures and keeping their passageways patent
cells. As the conducting tubes in the lungs become progres- (open). Incomplete hyaline cartilage rings encircle the lumen
sively smaller, the height of the epithelium and the amount of of the trachea. As the trachea divides into bronchi and the
cilia and goblet cells gradually diminish. In those regions of bronchi enter the lungs, the hyaline cartilage rings are
the lungs where gaseous exchanges take place, the epitheli- replaced by cartilage plates. As the bronchi become smaller,
um is simple squamous and the goblet cells are absent. The the cartilage plates are reduced in size and number. Cartilage
respiratory system can be considered in two parts: air-con- plates disappear from the conducting passageways when the
ducting and respiratory. diameter of the bronchioles is reduced to about I mm. The
final air passageways of the conducting system are the ter-
Olfactory Epithelium minal bronchioles, with diameters ranging from 0.5 mm to
Air that enters the lungs through the nasal passages is 1.0mm.
exposed to sensory epithelium. The roof of the nasal cavity The conducting portion of the respiratory system condi-
contains a highly specialized area of epithelium for detection tions and delivers air from the external environment to the
and transmission of smell. This olfactory epithelium consists respiratory portion in the lungs. Here an exchange of oxygen
of three cell types: supportive (sustentacular), basal, and and carbon dioxide takes place between the blood and
olfactory. The olfactory cells, distributed among the support- inspired air. Mucus plays an important role in conditioning
ive cells, are the sensory bipolar neurons; these cells end at the air. It is continuously produced by the goblet cells in the
the surface of the olfactory epithelium as small olfactory respiratory epithelium and mucous glands in the lamina pro-
bulbs. Radiating from each olfactory bulb are long, non- pria; the mucous layer covers the luminal surfaces in most of
motile olfactory cilia that lie flat on the epithelial surface in the conducting tubes. As a result, air that enters the conduct-
the overlying mucus and function as odor receptors. In order ing portion from the external environment is warmed,
to detect odors, the odoriferous substances must first be dis- humidified, and cleansed of particulate matter, infectious
solved. For this reason, the olfactory epithelium is always microorganisms, or other airborne mater. Goblet cells, how-
kept moist by a thin, watery secretion produced by the serous ever, lack in the epithelium that lines the bronchioles.
tubuloacinar olfactory (Bowman's) glands located below the
epithelium in the lamina propria. The watery secretion from Respiratory Portion of the Respiratory System
these glands washes over the surface of the olfactory epithe- The respiratory portion of the respiratory system is the
lium and, in this manner, allows the receptor cells to contin- distal continuation of the conducting portion. It consists of
uously detect and respond to new odors. the respiratory bronchioles, alveolar ducts, alveolar sacs, and
The unmyelinated afferent axons of the sensory olfactory alveoli. The terminal bronchioles of the conducting system
cells leave the olfactory epithelium and join to form small give rise to the respiratory bronchioles. These bronchioles
olfactory nerve bundles in the lamina propria. From here, represent the transitional structures between the conducting
these nerves pass through the ethmoid bone in the skull, and and respiratory portions of the respiratory system because
synapse in the olfactory bulbs of the brain. the respiratory bronchioles contain thin-walled outpocket-
ings, the alveoli. Respiration or gaseous exchange can only
Conducting Portion of the Respiratory System occur in the alveoli because the barrier between inspired air
The conducting portion of the respiratory system consists in the alveoli and blood in the capillaries is very thin. Thus,
of the nasal cavities; pharynx; larynx; trachea; extrapul- the functional units of the lungs are the alveoli.

Respiratory System 227

The alveoli consist of two types of cells. The most abun- diameters and prevents their collapse during respiration by
dant cells are squamous alveolar cells (type 1). These thin reducing collapsing forces to a minimum. During fetal devel-
cells line all of the alveolar surfaces. The remaining cells, opment, sufficient surfactant is secreted by type II cells dur-
which are interspersed among the squamous alveolar cells ing the last weeks (28 to 32) of gestation to prevent alveolar
either singly or in small groups, are the great alveolar cells collapse during respiration.
(type II). These cells are secretory in nature: they synthesize Alveolar macrophages, or dust cells, are derived from the
and secrete a phospholipid-rich product called pulmonary circulating blood monocytes that originate in the bone mar-
surfactant. As surfactant is released from type II cells, it row. They are found in the connective tissue of alveolar septa
spreads over the alveolar cell surfaces, moistens them, and and on the surface of the alveoli. The primary function of the
lowers the surface tension in the alveoli. By decreasing sur- alveolar macrophages is protection: they clean the alveoli of
face tension in the alveoli, surfactant stabilizes alveolar invading microorganisms and inhaled particulate matter.

228 Organs

Figure 15-1 Olfactory Mucosa and Superior Concha (panoramic view)

Figure 1 5-2 Olfactory Mucosa: Detail of a Transitional Area

Respiratory System 229

Figure 1 5-1 Olfactory Mucosa and Superior Concha (panoramic view'

The olfactory mucosa (2, 5) is illustrated on the surface The underlying lamina propria (2) contains the branched
of the superior concha (1), one of the bony shelves in the tubuloacinar olfactory glands (Bowman's glands) (3, 6).
nasal cavity. These glands produce a serous secretion, in contrast to the
The respiratory epithelium in the nasal cavity is pseudo- mixed mucous and serous secretions produced by glands in
stratified ciliated columnar epithelium with goblet cells. The the rest of the nasal cavity. Numerous small nerves found in
olfactory epithelium (2, 5; Fig. 15-2) is specialized for the connective tissue of the lamina propria are the olfactory
reception of smell and therefore differs from the respiratory nerves or fila olfactoria (4, 7). These nerves represent the
epithelium; it is pseudostratified tall columnar epithelium aggregated axons of the olfactory cells. The lamina propria
without goblet cells. The olfactory epithelium is found in the (2) merges with the periosteum of the bone.
roof of each nasal cavity, on each side of the septum, and in
the upper nasal conchae.

Figure 1 5-2 Olfactory Mucosa: Detail of a Transitional Area

This illustration depicts a transitional area between the the olfactory bulbs at the base of the brain. The basal cells
olfactory (1) and respiratory epithelia (9). In this region, (5) are short, small cells located at the base of the epithelium
the histologic differences between these two important between the bases of supportive (3) and olfactory cells (4).
epithelia become obvious. The olfactory epithelium (I) is The transition from the olfactory epithelium (I) to the res-
tall, pseudostratified columnar epithelium, composed of piratory epithelium (9) is abrupt. In this illustration, the res-
three different cell types: supportive, basal, and neuroepithe- piratory epithelium (9) is pseudostratified columnar epitheli-
lial olfactory cells. The individual cell outlines are difficult to um with distinct surface cilia (10) and an abundance of gob-
distinguish in a routine histologic preparation; however, the let cells (11); the goblet cells are not present in the olfactory
location and shape of nuclei allow some identification of the epithelium (I). Also, in the transition area, the height of the
cell types that comprise the olfactory epithelium. respiratory epithelium appears similar to that of the olfacto-
The supportive, or sustentacular cells (3) are elongated, ry; however, in other regions of the respiratory tract, the
with oval nuclei situated mor~iCallY or superficially in the epithelial height is much reduced in comparison to olfactory
epithelium than the nuclei of the olfactory cells (4). The api- epithelium.
cal surfaces of the olfactory cells contain slender microvilli Beneath the olfactory epithelium (I) is the lamina propria
that protrude into the overlying layer of surface mucus (2); (6), containing a rich supply of capillaries, lymphatic vessels.
basally, the cells are slender. arterioles (8), and venules (13). In addition to olfactory
The olfactory cells (4) have ovaloI' round nuclei that nerves (14), the lamina propria also contains branched, tubu-
occupy a region in the epithelium that is somewhat between loacinar olfactory glands (Bowman's glands) (7). These
the nuclei of the supportive cells (3) and basal cells (5). The serous glands deliver their secretions through narrow ducts
apices of the olfactory cells (4) are slender and pass to the (12), which penetrate the olfactory epithelium (I) and open
epithelial surface. Extending from the slender cell bases are onto the surface. The secretions from these glands moisten
axons that pass into the underlying connective tissue, or lam- the olfactory mucosa and provide the solvent necessary to
ina propria (6), where they aggregate into small bundles of dissolve odoriferous substances and stimulate the olfactory
unmyelinated olfactory nerves, the fila olfactoria (14). receptor cells (3).
These nerves ultimately leave the nasal cavity and pass into

230 Organs
Olfactory Mucosa

5 Olfactory epithelium:

Fig. 15-1 Olfactory Mucosa and Superior Concha (panoramic view). Stain: hematoxylin-eosin.
Low magnification.

1 OIlactory epithelium - - 9 Respiratory

10 Citia
2 Surlace mucus - 11 Goblet cells

3 Nuclei 01 supportive cell:

4 Nuclei 01 olfactory cells

12 D uc t s 0 I 0 II ac t ory
(Bowman's) glands
5 Nuclei 01 basal cells -
6 Lamina propria -----
13 Venule
7 Dlfactory (Bowman's)
14 Olfactory nerves
(fila olfactoria)
8 Arteriole

Fig. 15-2 Olfactory Mucosa: Detail of a Transitional Area. Stain: hematoxylin-eosin. High

Respiratory System 231

Figure 1 5-3 Epiglottis ,'ongitudina' section)

The epiglottis is the superior portion of the larynx; it pro- surface (2). The stratified squamous epithelium (3), how-
jects upward from the larynx's anterior wall as a flat flap. ever, is lower; the connective tissue papillae disappear, and a
A central epiglottic (elastic) cartilage (7) forms the transition is made to a respiratory epithelium, which is pseu-
framework of the epiglottis. Its anterior or lingual surface dostratified ciliated columnar epithelium (5) with goblet
(6) is covered with a noncornified stratified squamous cells.
epithelium (9). The underlying lamina propria (4) merges Tubuloacinar mucous, serous, or mixed glands are present
with the perichondrium (8) of the epiglottic cartilage (7). in the lamina propria (4). Occasional taste buds (1) are seen
The anterior, or lingual, mucosa (6) covers the apex of the in the epithelium. Solitary lymphatic nodules may be present
epiglottis and more than half of the posterior or laryngeal in the lingual (6) or laryngeal mucosa (2).

232 Organs

6 Lingual Mucosa

1 Taste buds

2 Laryngeal Mucosa

3 Stratified
squamous epithelium 7 Epiglottic lelastic)

8 Perichondrium
4 Mixed glands in
the lamina propria

5 Pseudostratified
ciliated columnar
9 Stratified squamous

Fig. 15-3

Respiratory System 233

Figure 1 5-4 Larynx (frontal section)

A vertical section through the larynx shows the two propria (3) blends with the perichondrium (9) of the thy-
prominent vocal folds (13, 18-20), supporting cartilages (8, roid cartilage (8); there is no distinct submucosa. The lower
11), and muscles (10, 20). wall of the ventricle makes the transition to a true vocal fold
The superior, or false, vocal fold (13) of the larynx is ( 18-20).
formed by the mucosa and is continuous with the posterior The mucosa of the true vocal fold (18-20) consists of
surface of the epiglottis (12). The lining epithelium is pseu- noncornified, stratified squamous epithelium (18) and a
dostratified ciliated columnar epithelium (14) with goblet thin, dense lamina propria devoid of glands, lymphatic tis-
cells. Visible below the epithelium, in the lamina propria sue, or blood vessels. At the apex of the true vocal fold is the
(3), are mixed glands (15), which are predominantly vocal ligament (19), consisting of dense elastic fibers that
mucous. Excretory ducts (16), which open onto the epithe- spread out into the adjacent lamina propria and the skeletal
lial surface, are visible among the acini of the glands (15). vocalis muscle (20). The skeletal thyroarytenoid muscle
Lymphatic nodules (7) are located in the lamina propria (3) (10) and the thyroid cartilage (8) comprise the remaining
on the ventricular side of the vocal fold. wall.
The ventricle (17) is a deep indentation and recess sepa- The epithelium in the lower larynx changes to pseudo-
rating the false vocal fold (13) from the true vocal fold stratified ciliated columnar epithelium (21), and the
(18-20). The mucosa in the lateral wall (3, 4, 5, 6) of the underlying lamina propria contains mixed glands (22). The
ventricle (17) is similar to that of the false vocal fold (13). cricoid cartilage (11) is the lowermost cartilage of the
Lymphatic nodules are more numerous in this area and are larynx.
sometimes called the "laryngeal tonsils" (7). The lamina

234 Organs

1 Adipose tissue

2 Arteriole and

3 lamina propria
of ventricular wall

4 Serous acini

5 Mucous acini

6 Excretory duct

7 lymphatic
nodules 16 Excretory duct
(laryngeal tonsils)

17 Ventricle

18 Stratified
epithelium True
19 Vocal ligament
8 Thyroid cartilage fold
20 Vocalis muscle

9 Perichondrium

10 Thyroarytenoid
muscle (skeletal)
21 Pseudostratified
ciliated columnar

22 Mixed glands in
lamina propria
(lower larynx)

11 Cricoid

Fig. 1 5-4 Larynx (frontal section). Stain: hematoxylin-eosin. Low magnification.

Respiratory System 235

Figure 1 5-5 Trachea (panoramic view, transverse section)

The wall of the trachea consists of mucosa, submucosa, tive tissue, the perichondrium (2), which merges with the
hyaline cartilage, and adventitia. The cartilage in the trachea submucosa (\6) on one side and the adventitia (I) on the
is a series of C-shaped rings between whose ends lies the other side. Numerous blood vessels and nerves (6) course in
smooth trachealis muscle (9), the adventitia (I) and provide smaller branches to the outer
The mucosa consists of pseudostratified ciliated colum- layers.
nar epithelium (13) with goblet cells. The lamina propria The mucosa (12) exhibits folds along the posterior wall of
(11, 14) contains fine connective tissue fibers, diffuse lym- the trachea where the cartilage is absent. The tracheal is mus-
phatic tissue (14), and occasional solitary lymphatic nod- cle (9) lies deep to the elastic membrane (15) of the mucosa
ules. Deep in the lamina propria (\ I), the elastic fibers form and is embedded in the fibroelastic tissue that occupies the
a longitudinal elastic membrane (15). In the loose connec- area between the ends of the cartilage rings. Most of the tra-
tive tissue of the submucosa (16) are mixed tubuloacinar cheal is muscle fibers (9) insert into the perichondrium of the
glands (4, 5) whose ducts (10, 17) pass through the lamina cartilage (2, upper leader). Mixed glands (8) are present in
propria (II) to the tracheal lumen. the submucosa; these can intermingle with the muscle fibers
The hyaline cartilage (3) is surrounded by dense connec- and extend into the adventitia.

Figure 1 5-6 Trachea (sectional view)

A small section of trachea is illustrated at a higher magni- tration, the fibers are cut in transverse plane. Also seen in the
fication to show details of the wall. The pseudostratified sur- lamina propria are a group of mucous acini (9) of the tra-
face epithelium contains ciliated (5) and goblet cells (10) cheal glands and their duct (8). ]n the adjacent cartilage (2),
with irregularly located nuclei. Note the thickened basement the larger lacunae and chondrocytes (3) in the interior
membrane (6). A longitudinal elastic membrane (7) is vis- become progressively flatter toward the perichondrium (I)
ible in the deeper region of the lamina propria; in this illus- while the matrix gradually blends with the connective tissue.

Figure 15-7 Trachea: Elastic Fiber Stain (sectional view)

This section of the trachea has been stained with where they intermix with the elastic fibers. Collagen fibers
Gallego's method to visualize elastic fibers (8) in the elastic are also visible in the perichondrium (I, lower leader),
membrane, which stain red with carbolfuchsin. Collagen submucosa (3), and superficial lamina propria (9).
fibers stain blue with aniline blue and provide a contrast

236 Organs


1 Adventitia (fibrosa)

2 Perichondrium

13 Epithelium: pseudostratified
ciliated columnar with
goblet cells

14 lamina propria with diffuse

lymphatic tissue
3 Tracheal cartilage
15 Elastic membrane

16 Submucosa with tracheal

4 Serous acini

5 Mucous acini
17 Duct of tracheal glands

Fig. 15-5 Trachea (panoramic view, transverse section). Stain: hematoxylin-eosin. Low

1 Perichondrium

Fig. 15-6

1 Cartilage and
2 Mixed acinus;
mucous acinus;
serous acinus

3 Submucosa

4 Duct of tracheal glands

Fig. 15-7 Trachea: Elastic Fiber Stain (sectional view). Stain: Gallegos method for elastic fibers.
Medium magnification.
Figure 1 5-8 Lung 'panoramic view)

The respiratory system, consisting of the lungs and the air The respiratory bronchioles (5, 8, 17, 23, 26, 27) are
passages, is divided into conducting and respiratory portions. directly connected to the alveolar ducts and alveoli. In these
The conducting portion consists of the nasal cavity, bronchioles, the epithelium is low columnar or cuboidal (S,
nasopharynx, larynx, trachea, bronchi, bronchioles, and ter- 8) and may be ciliated in the proximal portion of the tubules.
minal bronchioles. The respiratory portion consists of the A minimal amount of connective tissue supports the band of
respiratory bronchioles, alveolar ducts, alveolar sacs, and intermixed smooth muscle, the elastic fibers of the lamina
alveoli. The characteristic features of the lung are illustrated propria, and the accompanying blood vessels. Individual
in this panoramic view. Figures IS-9 through I S-12 illus- alveoli (25) appear in the wall of the respiratory bronchioles
trate the histology of these divisions in greater detail and (26) as small outpockets. Alveoli increase in number distally
higher magnification. All cartilage in the lung is hyaline. in the tubules. The epithelium and smooth muscle in the dis-
The histology of the extrapulmonary bronchi is similar to tal respiratory bronchioles appear as small, intermittent areas
that of the trachea. In the intrapulmonary bronchi, the C- between the openings of the numerous alveoli (S, upper
shaped cartilage rings are replaced by cartilage plates that leader; 17, 23, 24, 2S).
encircle the bronchi. The smooth muscle spreads out from The terminal portion of each respiratory bronchiole
the trachealis muscle to surround the lumina of the bronchi. branches into several alveolar ducts (2, 15,22); in histolog-
The intrapulmonary bronchus (33) is normally identi- ic sections only one such alveolar duct may be seen (2 and S,
fied by several cartilage plates (30) located in close prox- lower leaders; 22, middle leader; 23, upper leader). The walls
imity to each other. The epithelium (32) is pseudostratified of the alveolar ducts (2, IS, 22) are formed by a series of
columnar ciliated epithelium with goblet cells. The rest of alveoli situated adjacent to each other. A cluster of alveoli
the wall consists of a thin lamina propria, a narrow layer of that open into an alveolar duct is called an alveolar sac (14,
smooth muscle (31), a submucosa with scattered bronchial 20). The alveoli (4, 21, 25) form the parenchyma of the lung,
glands, hyaline cartilage plate (30), and adventitia. gi ving it the appearance of fine lace (see Fig. IS-12 for
As the intrapulmonary bronchi branch and become small- details). In this illustration, a plane of section shows a con-
er bronchi, the epithelial height and the amount of cartilage tinuous passageway from the terminal bronchiole (6) to the
decreases. Farther down the airway tube, only occasional respiratory bronchiole (S, 26, 27) into the alveolar duct (2,
small pieces of cartilage are seen. In bronchi that are about I lowest leader; 22, middle leader).
mm in diameter, cartiJage is no longer visible. The pulmonary artery (28) branches repeatedly to
In bronchioles (16), the epithelium is low, pseudostrati- accompany the divisions of the bronchial tree. Large pul-
fied columnar ciliated epithelium with occasional goblet monary vein branches also accompany the bronchi and bron-
cells. The mucosa is normally folded and the smooth muscle chioles; numerous small branches of the vein are seen in the
surrounding the lumen is prominent. Glands and cartilage lung trabeculae (3). Pulmonary arterioles (7, 10) supply the
plates are no longer present, and adventitia surrounds these walls of various bronchi, bronchioles, (6, 12) and other areas
structures. of the lung. Small bronchial veins (29) may be seen in the
The terminal bronchioles (6, 12) exhibit a wavy mucos- walls of the larger bronchi (33).
al lining and columnar ciliated epithelium; goblet cells are The visceral pleura (1) adheres closely to lungs. It is
lacking in the terminal bronchioles. Still present, however, composed of a thin layer of pleural connective tissue (19)
are a thin lamina propria, a layer of smooth muscle, and an and pleural mesothelium (18).

238 Organs
Figure 15-9 Intrapulmonary Bronchus

The primary, or extrapulmonary, bronchi divide and give smaller and farther apart as the bronchi continue to divide
rise to a series of smaller intrapulmonary bronchi. Such and their size continues to decrease. Between the cartilage
bronchi are lined by pseudostratified columnar ciliated plates (4), the submucosal connective tissue blends with the
epithelium (12), a thin lamina propria (13) of fine connec- well-developed adventitia (3).
tive tissue with many elastic fibers (not illustrated), and a The accompanying branch of the pulmonary artery (15)
few lymphocytes. Ducts (2) from the submucosal bronchial is located either adjacent to the bronchi or in the outer adven-
glands (5, 8, 10) pass through lamina propria (13) to open titia (14). A smaller branch of another pulmonary artery (7)
into the bronchial lumen. A thin layer of smooth muscle (6) probably accompanies a small bronchus or bronchiole locat-
surrounds the lamina propria (13). The submucosa contains ed in another plane of section.
glands of either serous (5, 8), mucous, or mucoserous acini Bronchial vessels visible in the connective tissue of the
(10). In the mixed glands, serous demilunes may be seen. bronchus include an arteriole (16), a venule (11), and capil-
The cartilage plates (4) are distributed close together laries (9).
around the periphery of the bronchus; the plates become

Figure 15-10 Terminal Bronchiole

The terminal bronchioles have small diameters, about I na propria which is, in turn, surrounded by the adventitia
mm or less. Mucosal folds (4) are prominent and the epithe- (2). Cartilage plates, glands, and goblet cells are absent.
lium is low pseudostratified columnar ciliated with few gob- Adjacent to the bronchiole is a small branch of the pul-
let cells. In the terminal bronchioles, the epithelium (5) is monary artery (6); the bronchiole is surrounded by the
columnar ciliated and the goblet cells are absent. A well- alveoli (7) of the lung.
developed smooth muscle (3) layer surrounds the thin lami-

Figure 15-11 Respiratory Bronchiole

The wall of the respiratory bronchiole is lined with located adjacent to the epithelium. A small branch of the pul-
cuboidal epithelium (4). Cilia may be present in the epithe- monary artery (5) accompanies the respiratory bronchiole.
lium of the proximal portion but disappear in the distal por- An alveolar duct (2) arises from the respiratory bronchi-
tion of the respiratory bronchiole. Smooth muscle (3) is ole and numerous alveoli (1) open into the alveolar duct (2).

Figure 15-12 Alveolar Walls: Interalveolar Septa

The oval alveoli (5) are lined by simple squamous epithe- preparation of lung tissue, it is difficult to distinguish
lium, which is not very obvious at this magnification. between the nuclei of squamous cells in the alveoli (5),
Adjacent alveoli share a common interalveolar septum (4). endothelial cells in the blood vessels (capillaries) (1,3), and
Located in the thin septum (4) are capillary plexuses (1, 3) the fibroblasts (6) in the interalveolar septuIll (4).
supported by fine connective tissue fibers, fibroblasts, and At the free ends of the interalveolar septa (4) and around
other cells. As a result of the thin interalveolar septum (4) the open ends of the alveoli are narrow bands of smooth
and its contents, the capillaries are in close proximity to the muscle (2), which is a continuation from the Illuscle layer of
squamous cells of the adjacent alveoli, separated from the the respiratory bronchiole.
epithelium only by the sparse connective tissue. In routine

240 Organs

1 Pulmonary alveoli 7 Pulmonary artery

8 Serous acini

3 Adventitia and 9 Bronchial capillaries

10 Mucous acinus

4 Cartilage plate 11 Bronchial venule

(hyaline) 12 Bronchial epithelium

13 lamina propria
5 Serous acini in the
14 Adventitia

6 Smooth muscle
15 Pulmonary artery

16 Bronchial artery

Fig. 15-9

1 Alveolar wall 1 Alveoli opening into

(interalveolar septuml alveolar duct
2 Adventitia 2 Alveolar duct

3 Smooth muscle
3 Smooth muscle in
wall of respiratory
4 Mucosal folds
5 Columnar epithelium
4 Cuboidal epithelium

6 Pulmonary artery

7 Pulmonary alveoli 5 Pulmonary artery (I.s.)

Fig. 15-10 Terminal Bronchiole. Stain: Fig. 15-11 Respiratory Bronchiole. Stain:
hematoxylin-eosin. Low magnification. hematoxylin-eosin. Low magnification.

4 Alveolar walls
(interalveolar septa)

5 Alveoli (I.s.1

6 Nuclei of epithelial
or endothelial cells
or fibroblasts

Fig. 15-12 Stain: hematoxylin-eosin. Oil immersion.

Respiratory System 241


Urinary System

The urinary system consists of kidneys, ureters, the uri- consists of the proximal convoluted tubule, the loop of
nary bladder, and the urethra. The kidneys are vital in main- Henle, and the distal convoluted tubule.
taining homeostasis of the body. They regulate blood pres- Each renal corpuscle has a vascular pole, where the arter-
sure, blood composition, and fluid volume of the body; pro- ial blood vessels of the glomerulus enter and exit, and a uri-
duce urine; and maintain acid-base balance. In addition, the nary pole, where the proximal convoluted tubule arises. The
cells of the kidney produce two important hormones, renin proximal convoluted tubule absorbs all of the glucose and
and erythropoietin. Renin regulates blood pressure to main- amino acids, and about 75% of water and sodium chloride
tain proper filtration pressure for the kidneys and erythro- ions, from the glomerular filtrate. It does this by means of the
poietin promotes red blood cell formation in the red bone microvilli in the brush border of its cells. In addition, the
marrow. proximal convoluted tubule excretes certain metabolites,
dyes, and drugs from the body into the glomerular filtrate.
The Uriniferous Tubule and Nephron Such metabolic waste products as urea and uric acid remain
The functional unit of the kidney is the uriniferous tubule, in the proximal convoluted tubule and are eliminated from
which consists of a nephron and a collecting duct into which the body in the urine.
empty the filtered contents of the nephron. The nephron, in The loop of Henle comprises a thick, descending portion
turn, is subdivided into two components, the renal corpuscle of the proximal tubule, a thin descending and a thin ascend-
and the renal tubule. The renal corpuscle consists of a tuft of ing segment, and a thick, ascending portion of the distal
capillaries (the glomerulus) surrounded by an inner visceral tubule. In the juxtamedullary nephrons, the loop of Henle is
and an outer parietal layer of epithelial cells, the glomerular long; it descends from the cortex of the kidney deep into the
[Bowman's] capsule. medulla and then loops back to ascend into the cortex. The
There are two types of nephrons in the kidney. The corti- loop of Henle is necessary for the production of hypertonic
cal nephrons are located in the cortex of the kidney and the urine. Sodium chloride and urea are concentrated in the
juxtamedullary nephrons are situated near the corti- interstitial tissue of the kidney medulla by means of a com-
comedullary junction. All nephrons participate in urine for- plex countercurrent multiplier system. The hypertonicity
mation. The juxtamedullary nephrons produce a hypertonic (high osmotic pressure) of the extracellular fluid in the
environment in the interstitium of the kidney medulla, a con- medulla produced by this process removes the water from the
dition that is necessary for the production of concentrated glomerular filtrate as it flows through these tubules.
(hypertonic) urine. The distal convoluted tubule is shorter and less convolut-
The renal corpuscle filters blood through the capillaries of ed than the proximal tubule. It actively resorbs sodium ions
the glomerulus into the capsular (urinary) space that is locat- from the glomerular filtrate. This resorptive activity is cou-
ed between the two epithelial cell layers in the glomerular pled with excretion of hydrogen or potassium ions into the
capsule. Filtration of blood is facilitated by the glomerular filtrate or tubular urine. Sodium reabsorption in the distal
endothelium. This endothelium is porous (fenestrated) and convoluted tubule is controlled by the hormone aldosterone
highly permeable to many substances in the blood but not to secreted by the adrenal cortex. The distal convoluted tubules
the formed elements and plasma proteins. Thus, the glomeru- are vital for maintaining a proper acid-base balance in the
lar filtrate that enters the capsular space is similar to plasma, body fluids.
except for the absence of proteins. Glomerular filtrate flows from the distal convoluted
The glomerular filtrate first enters and then flows from the tubule to the collecting tubule; this tubule normally is not
glomerular capsule into the renal tubule, which extends from permeable to water. During certain conditions, however, an
the glomerular capsule to the collecting tubule. The renal antidiuretic hormone (ADH) is released from the neurohy-
tubule that leaves the renal corpuscle is highly convoluted pophysis of the pituitary gland in response to decreased
and has several distinct histologic and functional regions. It water intake in the body. As a result of ADH presence in the

Urinary System 243

system, the epithelium of the collecting tubule becomes fied cells of the distal convoluted tubule situated adjacent to
highly permeable to water. Consequently, as the glomerular the afferent arteriole with the juxtaglomerular cells. The jux-
filtrate in the collecting tubule flows through the medulla, taglomerular cells and macula densa are functionally inte-
water is drawn from the filtrate because of increased tubular grated.
permeability and high osmotic pressure created by the hyper- The juxtaglomerular apparatus performs an important role
tonic extracellular fluid. The retained water in the extracellu- in maintaining normal blood pressure. The juxtaglomerular
lar region is then returned to the general circulation via the cells monitor changes in the systemic blood pressure by
blood vessels, and the glomerular filtrate in the collecting responding to stretching in the wall of the afferent arteriole.
tubules becomes hypertonic (concentrated) urine. In the The cells in the macula densa probably respond to changes in
absence of circulating ADH, water does not leave the col- the sodium chloride concentration in the glomerular filtrate
lecting tubule because the epithelium remains impermeable as it flows past them in the distal convoluted tubule.
to water. As a result, the expelled filtrate is a dilute urine, A decrease in systemic blood pressure induces the juxta-
containing more water. glomerular cells to release the hormone renin into the blood
Urine formation in the kidney thus involves filtration, stream. Renin converts the plasma protein angiotensinogen
reabsorption, and secretion. About 99% of the glomerular fil- to angiotensin I, which in turn is converted to angiotensin II
trate produced by the kidneys is reabsorbed into the system by enzyme present in the endothelial cells of the lung.
in the nephron and about I % is voided as urine. Angiotensin II is an active hormone and a powerful vaso-
constrictor that initially produces arterial constriction, there-
by increasing the systemic blood pressure. In addition,
The Juxtaglomerular Apparatus angiotensin II stimulates release of the hormone aldosterone
Adjacent to the renal corpuscle and the distal convoluted from the adrenal cortex. Aldosterone acts primarily on the
tubule lie a special group of cells called the juxtaglomerular cells of the distal convoluted tubules in the kidney to increase
apparatus, consisting of juxtaglomerular cells and macula their reabsorption of sodium and chloride ions from the
densa. The juxtaglomerular cells are a group of modified glomerular filtrate. As water follows sodium chloride osmot-
smooth muscle cells that are located in the wall of the atTer- ically, fluid volume in the circulatory system increases. This
ent arteriole just before it enters the glomerular capsule to raises the systemic blood pressure and increases the
form the glomerulus. The macula densa is a group of modi- glomerular filtration rate in the kidney.

244 Organs

Figure 16-1 I(idney: Cortex and Pyramid (panoramic view)

Urinary System 245

Figure 16-1 Kidney: Cortex and Pyramid ,panoramic view}

The kidney is subdivided into an outer region, the cortex (straight or descending proximal tubules, thin segments, and
(20) and an inner region, the medulla (21). Externally, the straight or ascending distal tubules) and collecting tubules.
cortex is covered with a connective tissue capsule (19) and The collecting tubules join in the medulla to from large pap-
the perirenal connective and adipose tissues (18). illary ducts (Figs. 16-4 and 16-5).
In the cortex convoluted tubules (3), glomeruli (2, 8), The papilla (16) usually is covered with a simple colum-
straight tubules (4), and medullary rays (5) are found. nar epithelium (12). As this epithelium reflects on to the
The cortex also contains renal corpuscles (glomerular outer wall of the calyx, it becomes transitional epithelium
[Bowman's] capsules and glomeruli), adjacent proximal and (13). A thin layer of connective tissue and smooth muscle
distal convoluted tubules (3) of the nephrons, interlobular (not illustrated) is found under this epithelium, which then
arteries (6) and interlobular veins (7). The medullary rays merges with the connective tissue of the renal sinus (17).
(5) contain straight portions of nephrons and collecting In the renal sinus (17), between the pyramids, are branch-
tubules. Medullary rays do not extend to the kidney capsule es of the renal artery and vein, the interlobar vessels (15).
because of a narrow zone of convoluted tubules (1). These vessels enter the kidney and then arch over the base of
The medulla comprises a number of renal pyramids. Each the pyramid at the corticomedullary junction as the arcuate
pyramid is situated with its base (11) adjacent to the cortex vessels (9). The arcuate vessels give rise to smaller, inter-
(20) and its apex directed inward. The apices of renal pyra- lobular arteries and veins (6, 7, 10). The arcuate arteries (9)
mids form the papilla (16), which projects into a minor pass radially into the kidney cortex (20) and extend numer-
calyx (14). The medulla also contains the loops of Henle ous afferent glomerular arteries to the glomeruli.

246 Organs

Kidney: Cortex and Pyramid

18 Perirenal adipose
1 Subcapsular 19 Capsule
convoluted tubules
2 Glomeruli

3 Convoluted tubules

4 Straight tubules

5 Medullary rays

20 Cortex
6 Interlobular arteries
7 Interlobular veins

8 Glomeruli

9 Arcuate artery

10 Interlobular artery
and vein

11 Base of pyramid
(with straight tubules)

12 Columnar epithelium
covering a papilla 21 Medulla

13 Transitional epithelium
covering the minor calyx
14 Minor calyx; lumen
and wall

15 Interlobar artery and


16 Renal papilla

17 Connective tissue of
the renal sinus

Fig. 16-1 Kidney: Cortex and Pyramid (panoramic view). Stain: hematoxylin-eosin. Low

Urinary System 247

Figure 16-2 Kidney: Deep Cortical Area and Outer Medulla

A higher magnification of the kidney cortex reveals cuboidal cells with intensely eosinophilic, granular cyto-
greater details of the renal corpuscle. Each corpuscle consists plasm. The well-developed brush borders (IS) are present
of a glomerulus (3) and a glomerular (Bowman's) capsule but are not always well preserved in sections.
(2, 17). The glomerulus (3) is a tuft of capillaries formed Distal convoluted tubules (14) are fewer in number and
from the afferent glomerular arterioles and supported by fine exhibit a larger lumen with smaller, cuboidal cells. The cyto-
connective tissue. plasm stains less intensely and the brush borders are not pre-
The visceral layer (17) of the glomerular capsule consists sent (14, compare with 15).
of modified epithelial cells called the podocytes. These cells Renal corpuscles and their associated tubules constitute
closely follow the contours of the glomerulus and invest the the kidney cortex. The cortex surrounds the medullary rays,
capillary tufts. At the vascular pole, the visceral epithelium which are composed of straight portions of the nephrons and
reflects to become the parietal layer (17) of the glomerular collecting tubules. The medullary rays include three types of
capsule. The space between the visceral and parietal layers of tubules: straight (descending) segments of the proximal
the capsule is the capsular space, which becomes continuous tubules (6), straight (ascending) segments of the distal
with the lumen of the proximal convoluted tubule at the uri- tubules (11, 20), and collecting tubules (5, 19). The straight
nary pole (see Fig. 16-3). At the urinary pole, the squamous segments of the proximal tubules are similar to the proximal
epithelium of the parietal layer changes to cuboidal epitheli- convoluted tubules and the straight segments of the distal
um of the proximal convoluted tubule (9). tubules are similar to distal convoluted tubules. Collecting
Numerous tubules, sectioned in various planes, lie adja- tubules are distinct because of lightly stained cuboidal cells
cent to the renal corpuscles. The tubules are primarily of two and visible cell membranes.
types, the proximal convoluted (4, 10, 15, 21) and distal The medulla contains only straight portions of tubules and
convoluted (1, 14, 21); these tubules are the initial and ter- thin segments of loops of Henle. Illustrated in the outer
minal segments of the nephron, respectively. The proximal medullary region are thin segments of loops of Henle (13,
convoluted tubules are numerous in the cortex, exhibit a 23) lined with squamous epithelium, straight segments of
small, uneven lumen, and contain a single layer of large distal tubules (20), and collecting tubules (12, 22).

248 Organs

14. Distal convoluted tubules

15 Proximal convoluted
tubules with brush

16 Glomerular arteriole (I.s.)

17 Visceral and parietal

layers of glomerular

18 Interlobular artery
sectioned obliquely:
wall and lumen

19 Collecting tubules

10 Proximal convoluted

11 Straight (ascending)
segments of distal 20 Straight (ascending)
tubules segments of distal tubules

12 Collecting tubules -- 21 Proximal and distal

convoluted tubules

22 Collecting tubules

13 Thin segments of
loops of Henle
23 Thin segments of
loops of Henle

24 Capillaries

Fig. 16-2 Kidney: Deep Cortical Area and Outer Medulla. Stain: hematoxylin-eosin. Low

Urinary System 249

Figure 16-3 Kidney Cortex: Juxtaglomerular Apparatus

A still higher magnification of a small area of the kidney mal convoluted tubule (6, 14). The plane of section through
cortex illustrates the renal corpuscle, adjacent tubules, and the renal corpuscle illustrated in this figure is seen only occa-
juxtaglomerular apparatus. sionally in the kidney cortex; however, illustration of both
The renal corpuscle exhibits the glomerular capillaries vascular and urinary poles represents an important structural
(2), parietal (lOa) and visceral (lOb) epithelium of association of the renal corpuscle with the region of blood
glomerular (Bowman's) capsule (10), and the capsular filtration, glomerular filtrate accumulation, and initial stages
space (13). Conspicuous brush borders and acidophilic cells of filtrate modification in urine formation.
distinguish the proximal convoluted tubules (6, 14) from At the vascular pole, smooth muscle cells in the tunica
the distal convoluted tubules (1, 15), whose smaller, less media of the afferent glomerular arteriole (12) are replaced
intensely stained cells lack brush borders. The cells of the by highly modified epithelioid cells with cytoplasmic gran-
collecting tubules (8) are cuboidal with distinct cell outlines ules. These are the juxtaglomerular cells (4). In the adjacent
and clear, pale cytoplasm. Distinct basement membranes segment of the distal convoluted tubules, the cells that bor-
(9) surround these tubules. der the juxtaglomerular area are narrow and more columnar
Each renal corpuscle exhibits a vascular pole on one side than elsewhere in the tubules. This area of darker, more com-
where the afferent glomerular arterioles (12) enter and pact cell arrangement is called the macula densa (5). The
efferent glomerular arterioles exit. On the opposite side of juxtaglomerular cells in the afferent glomerular arteriole (12)
the corpuscle is the urinary pole (11), where the capsular and the macula densa (5) cells in the distal convoluted tubule
space (13) becomes continuous with the lumen of the proxi- together constitute the juxtaglomerular apparatus.

250 Organs

15 Distal convoluted

Fig. 16-3 Kidney Cortex: Juxtaglomerular Apparatus. Stain: periodic acid-Schiff and hematoxylin.
Medium magnification.

Urinary System 251

Figure 1 6-4 I<idney Medulla: Papilla (transverse section)

The papilla of the kidney contains the terminal portions of (7). Connective tissue (10) is more abundant in this region
the collecting tubules, the papillary ducts (2, 5, 6). These than elsewhere in the kidney, and the collecting tubules are
ducts have large diameters and wide lumina and are lined by not as close together. Numerous small blood vessels (4, 9)
tall, pale-staining columnar cells. Also seen in this region are are also present. The thin segments of loops of Henle (3, 8)
cross sections of the thin segments of the loops of Henle (3, in cross section resemble capillaries or venules (4, 9).
8) and the ascending straight portions of the distal tubules

Figure 1 6-5 Kidney Medulla: Papilla Adjacent to a Calyx (longitudinal


Several collecting tubules merge in the medulla to form however, the covering epithelium usually is a simple colum-
large, straight tubules called papillary ducts (5), which open nar epithelium continuous with the lining of the papillary
at the tip of the papilla. Their numerous openings on the sur- ducts. Also illustrated are thin segments of loops of Henle (3,
face of the papilla produce a sievelike appearance; this is the 4, 6) and ascending straight portion of the distal tubule (1).
area cribrosa. In this illustration, the papilla is covered by a Abundant connective tissue (7) and many capillaries (2) are
stratified cuboidal epithelium (8). At the area cribrosa, also seen.

252 Organs
.<idney Medulla: Papilla

6 Papillary ducts

3 Thin segments
of loops of Henle
7 Straight (ascending)
segment of loops of Henle

8 Th in segments of
loops of Henle
9 Capillaries

10 Connective tissue stroma

Fig. 16-4

5 Papillaryducts (I.s.)

6 Thin segments of
loops of Henle

7 Connective tissue stroma

8 Epithelium covering
the papilla

Fig. 16-5 Kidney Medulla: Papilla Adjacent to a Calyx (longitudinal section). Stain:
hematoxylin-eosin. Medium magnification.

Urinary System 253

Figure 16-6 Ureter (transverse section)

An undistended ureter exhibits a convoluted lumen, epithelium and looser near the muscularis. Diffuse lymphat-
formed by the longitudinal mucosal folds. The wall of the ic tissue and occasional small lymphatic nodules may be
ureter consists of mucosa, muscularis, and adventitia. observed in the lamina propria.
The mucosa consists of transitional epithelium (9, 10) In the upper ureter, the muscularis consists of an inner
and a wide lamina propria (5). The transitional epithelium longitudinal (3) smooth muscle layer and an outer circular
has several cell layers, the outermost layer characterized by (2) smooth muscle layer; these layers are not always distinct.
large cuboidal cells (9). The intermediate cells are polyhedral An additional outer longitudinal layer of smooth muscle is
in shape, whereas the basal cells are low columnar or found in the lower third of the ureter.
cuboidal (10). The basal surface of the epithelium is smooth The adventitia (6) blends with the surrounding fibroelas-
and there are no indentations by the connective tissue pa- tic connective tissue and adipose tissue (1, 12), which
pillae. contain numerous arteries (8), venules (11), and small
The lamina propria (5) contains fibroelastic connective nerves (7).
tissue, which is denser with more fibroblasts under the

Figure 16-7 Ureter Wall (transverse section)

A higher magnification of the ureter wall illustrates ous in the connective tissue under the epithelium than in the
greater structural details and layers. The transitional epithe- deeper region.
lium (8, 9, 10) exhibits the same cell layers as described in The muscularis layer (7, 11) often appears as loosely
Figure 16-6. The outermost cells often stain deeper than the arranged smooth muscle bundles surrounded by abundant
remaining cells. The surface membrane, illustrated as a nar- connective tissue, as illustrated in the inner longitudinal
row acidophilic band (9), serves as an osmotic barrier layer (11).
between urine and tissue fluids. The adventitia (5) merges with the connective tissue (6) of
In the lamina propria (12), fibroblasts are more numer- the posterior abdominal wall in which the ureter is embedded.

254 Organs

1 Adipose tissue

3 longitudinal
muscle layer

4 lumen

5 lamina propria

6 Adventitia

Fig. 16-6

7 Circular muscle layer

8 Transitional epithelium

9 Surface membrane

10 Basal layer of
epithelial cells

11 longitudinal muscle

12 lamina propria

Fig. 16-7 Ureter Wall Itransverse section). Stain: hematoxylin-eosin. Medium magnification.

Urinary System 255

Figure 1 6-8 Urinary Bladder: Wall (transverse section)

The smooth muscle (1) layers in the bladder wall are sim- The loose connective tissue in the deeper zone contains more
ilar to those in the ureter except for their thickness. The blad- elastic fibers.
der wall consists of a mucosa (6, 7, 8), a muscularis (1, 9), The muscularis (I, 9) is thick, and the three layers in the
and a serosa (4,5) on the superior surface of the bladder. The neck of the bladder are arranged in anastomosing bundles (I)
inferior surface of the bladder is covered by adventitia, between which is found loose connective tissue (2). In this
which merges with the connective tissue of adjacent struc- section, muscle bundles are visible in various planes of sec-
tures. tion (I) and the three distinct muscle layers are difficult to
The mucosa in an empty bladder exhibits numerous folds distinguish. The interstitial connective tissue merges with the
(6); however, these folds disappear during bladder disten- connective tissue of the serosa (4); mesothelium (5) is the
sion. The transitional epithelium (7) contains more cell lay- outermost layer.
ers and the lamina propria (8) is wider than in the ureter.

Figure 1 6-9 Urinary Bladder: Mucosa (transverse section)

The mucosa of the bladder is illustrated at a higher mag- round (5) and basal cells are more columnar (see also Figure
nification. 1-9).
In an empty bladder, the superficial cells of the transi- In the lamina propria (2) are two zones, as in the ureter,
tional epithelium (5) are low cuboidal or columnar (6). but more pronounced. The subepithelial region is denser with
When the bladder is full and the transitional epithelium is fine fibers and numerous fibroblasts (2, upper leader). The
stretched, cells exhibit a squamous (9) appearance. The aci- deeper zone (2, lower leader) typically contains loose or
dophilic surface membrane (7) of the superficial cells may moderately dense irregular connective tissue, which extends
be prominent. The deeper layers of cells in the epithelium are between the muscle fibers as interstitial connective tissue.

256 Organs

Urinary Bladder

1 Smooth muscle
bundles (sectioned
in various planes)
6 Folds in the
2 Interstitial connective

3 Capillaries
7 Transitional

4 Superficial connective

8 lamina
5 Peritoneal propria

9 Smooth

Fig. 16-8 Urinary Bladder: Wall (transverse section). Stain: hematoxylin-eosin. Low magnification.

1 Smooth muscle
bundles of the

2 lamina propria

3 Arterioles

4 Vein

Urinary System 257


Endocrine System

Section 1 Hypophysis (Pituitary Gland)

Introduction the hypothalamus, carried by axonal transport to neurohy-

The endocrine system consists of cells, tissues, and organs pophysis, stored in the axon terminals, and released into sys-
that synthesize and secrete chemicals and hormones into the temic circulation from these terminals when the need arises.
blood and lymph capillaries. These chemicals are then trans-
ported by the vascular system to distant target organs, where, Adenohypophysis
via specific surface receptors, they exert an influence on the The cells of the adenohypophysis have been traditionally
structure and function of their cells and tissues. classified into chromophils and chromophobes, based on the
The distinct endocrine organs are the hypophysis, or pitu- affinity of their granules for specific stains. The chromophils
itary gland (described below), and the thyroid gland, adrenal are subdivided into acidophils and basophils because of their
(suprarenal) glands, and parathyroid glands (described in staining properties. Specific immunocytochemical tech-
Section 2). Other individual endocrine cells or tissues are niques now allow identification of two kinds of acidophils,
associated with numerous exocrine organs. These organs are somatotrophs and mammotrophs. The pale-staining chromo-
the pancreas, kidney, reproductive organs of both sexes, pla- phobes are believed to be partially degranulated acidophils
centa, and the gastrointestinal tract. Endocrine cells and tis- or basophils. The hormones that are produced by these cells
sues are discussed with the exocrine organs in their respec- and their specific effects on organs of the body are described
tive chapters of this atlas. below.
Acidophils and their Hormones.
Hypophysis (Pituitary Gland) Somatotrophs are cells that secrete growth hormone
The structure and function of the hypophysis reflect its (somatotropin or GH). Growth hormones stimulate general
embryological origin from two distinct regions of the body. body growth, uptake of amino acids, and protein synthesis.
The epithelium of the pharyngeal roof (oral cavity) forms an Growth hormone also induces proliferation of cartilage cells
outward outpocketing, the hypophyseal (Rathke's) pouch. in the epiphyseal plates of developing or growing long
This pouch detaches from the oral cavity and becomes the bones.
glandular portion of the hypophysis, the adenohypophysis. Mammotrophs produce the lactogenic hormone pro-
At the same time, the downgrowth of the developing brain lactin, which stimulates development of the mammary gland
forms the neural portion of the hypophysis, the neurohy- during pregnancy. Following parturition (birth), prolactin
pophysis. The developed hypophysis remains attached to the maintains milk production in the mammary glands during
base of the brain by a neural stalk and a vascular connection. lactation.
As a result of this dual origin, the structure and function of Basophils and their Hormones. There are three types of
these two portions of the hypophysis differ. basophils: thyrotrophs, gonadotrophs, and corticotrophs.
Although the hypophysis produces numerous hormones Thyrotrophs secrete the thyroid-stimulating hormone
and/or factors, their synthesis and release from the hypoph- (thyrotropin or TSH). It stimulates synthesis and secretion of
ysis are directly controlled by the hypothalamus of the brain. the thyroid hormones thyroxin and triiodothyronine from the
The hypothalamic hormones that control the function of the thyroid gland.
adenohypophysis are the releasing factors or the inhibitory Gonadotrophs are cells that secrete follicle-stimulating
factors. From the hypothalamus, the releasing factors are car- hormone (FSH) and luteinizing hormone (LH). In females,
ried to the adenohypophysis by way of blood vessels of the FSH promotes estrogen secretion and growth and maturation
hypophyseal portal system. On reaching the adenohypoph- of the ovarian follicles. In males, FSH stimulates spermato-
ysis, these factors then stimulate certain cells to secrete and genesis and secretion into the seminiferous tubules of the
release specific hormones into the circulation. testes of androgen-binding protein by the Sertoli cells.
On the other hand, the hormones that are released from In females, LH functions in association with FSH to
the neurohypophysis are first synthesized by specific cells in induce ovulation and to promote the final maturation of the

Endocrine System 259

ovarian follicles. LH is also responsible for the formation of whose cell bodies are found in the hypothalamus. Two hor-
the corpus luteum in the ovary following ovulation and the mones, oxytocin and vasopressin (antidiuretic hormone or
secretion of estrogen and progesterone from the cells of the ADH), are released from the neurohypophysis. These hor-
corpus luteum. In males, LH maintains and stimulates the mones are synthesized by the neurosecretory cells in the
interstitial cells (of Leydig) in the testes to produce the hor- hypothalamus and then transported along unmyelinated
mone testosterone. As a result, LH is sometimes called inter- axons for storage in the axon terminals of the neurohypoph-
stitial cell-stimulating hormone (ICSH). ysis as Herring bodies. These hormones are synthesized by
Corticotrophs secrete adrenocorticotropic hormone various types of neurons but are found in the paraventricular
(ACTH). ACTH influences the function of cells in the adren- nucleus and the supraoptic nucleus of the hypothalamus.
al cortex. ACTH also stimulates the synthesis and release of Oxytocin performs important functions in the female dur-
glucocorticoids from the zona fasciculata and zona reticu- ing the final stages of pregnancy, parturition, and lactation of
laris of the adrenal cortex. mammary glands. During labor, the release of oxytocin
The release of these hormones from cells of the adenohy- induces strong contractions of smooth muscles in the uterus,
pophysis into the blood stream is directly influenced by the resulting in childbirth. During nursing, the suckling action of
releasing factors or hormones produced by the neurons in the the infant on the nipple triggers the milk-ejection reflex in a
hypothalamus. Cells in the hypothalamus also release lactating mammary gland. This reflex releases oxytocin.
inhibitory factors or hormones. These inhibitory factors are Oxytocin then stimulates the contraction of myoepithelial
growth hormone inhibitory factor and prolactin inhibitory cells around the secretory alveoli and ducts in the lactating
factor. mammary glands. Contraction of the myoepithelial cells
Pars Intermedia. The adenohypophysis also contains the ejects milk from the alveoli into the excretory ducts of the
pars intermedia. In lower vertebrates (amphibians and fish- mammary gland and the nipple.
es), this area is well developed and produces melanocyte- Vasopressin (ADH) controls blood pressure. Release of
stimulating hormone (MSH). In these animals, MSH increas- vasopressin into the blood stream contracts the smooth mus-
es pigmentation of the skin by causing dispersion of the cle layers in small arteries and arterioles. This action narrows
melanin granules. In humans and most other mammals, how- the lumina of these blood vessels and increases the blood
ever, this region of the hypophysis remains rudimentary. pressure. The main action of vasopressin, however, is to
increase permeability to water in the distal convoluted
Neurohypophysis tubules and collecting tubules of the kidney. This allows
The neurohypophysis is composed of supporting neu- more water to be resorbed by the kidney tubules and retained
roglial cells, pituicytes, and unmyelinated axon terminals in the body while increasing concentration of the urine.

260 Organs

Figure 17-1 Hypophysis (panoramic view, sagittal section)

Figure 17-2 Hypophysis (sectional view)

Endocrine System 261

Figure 17-1 Hypophysis (panoramic view, sagittal section)

The hypophysis (pituitary gland) consists of two major basophils (beta cells) (4). (These are illustrated at a higher
subdivisions, the adenohypophysis and neurohypophysis. magnification in Fig. 17-2 below.) It is currently believed
The adenohypophysis is further subdivided into pars distal- that the chromophobes represent acidophilic or basophilic
is (anterior lobe) (5), pars tuberalis (9), and pars interme- cells in an inactive state following degranulation.
dia (10). The neurohypophysis is divided into pars nervosa The pars nervosa (II) is the second largest of the four
or infundibular process (11), infundibular stalk (8), and divisions. Pars intermedia (10) and pars nervosa (II) form
tuber cinerum of the median eminence (not illustrated). The the posterior lobe of the hypophysis, which consists primar-
pars tuberalis (9) of the adenohypophysis surrounds the ily of unmyelinated nerve fibers and supporting cells (pitu-
infundibular stalk (8) and is, therefore, visible above and icytes). The connective tissue septa (12) that arise from the
below the stalk in a sagittal section; it extends higher on the surrounding capsule penetrate into the gland.
anterior surface than the posterior surface of the hypophysis. The pars intermedia (10) is situated between the pars dis-
The infundibular stalk (8) connects the hypophysis with the talis and the pars nervosa. This region contains colloid-filled
central nervous system (base of the brain). cysts lined by different cells, with basophils predominating.
The pars distalis (5) is the largest of the four divisions of The neurohypophysis develops as a ventral evagination or
the hypophysis and contains two main types of cells, chro- extension from the floor of the brain. The adenohypophysis
mophobe cells (1) and chromophil cells. The chromophils develops from the oral ectoderm diverticulum and Rathke's
are subdivided into acidophils (alpha cells) (3) and pouch.

Figure 1 7-2 Hypophysis (sectional view)

Under higher magnification, numerous sinusoidal capil- any granules in their cytoplasm. Follicles lined with
laries (6) and cell types are visible in the pars distalis. basophils (8) are often seen in pars intermedia, with some
Chromophobe cells (4) exhibit a light-staining, homoge- cells exhibiting secretory granules in their cytoplasm (8,
neous cytoplasm. They are normally smaller than the chro- lower leader).
mophils and are found in groups. The cytoplasm of chro- Also illustrated is a portion of pars nervosa (9). This
mophils stains red in acidophils (3) and blue in basophils (5). region is characterized by unmyelinated axons and cytoplas-
The pars intermedia contains colloid-filled cysts or vesi- mic processes of the pituicytes (9, 10), both of which stain
cles (7) lined by low columnar cells; some cells in these vesi- lightly. Oval nuclei of the pituicytes are seen (10), but not the
cles contain basophilic granules while others do not exhibit scanty cytoplasm.

262 Organs

8 Infundibular stalk

9 Pars tuberalis

10 Pars intermedia
with colloid

11 Pars nervosa

12 Connective
tissue septum

13 Blood vessels in
the capsule

Fig. 17-1 Hypophysis (panoramic view, sagittal section). Stain: hematoxylin-eosin. Low

1 Nuclei of 7 Vesicles (pars

endothelial cells intermedia)
2 Glandular cell groups
and columns

3 Acidophils (alpha cells) 8 Follicles (pars


4 Chromophobes
9 Nerve fibers and
pituicytes (pars

5 Basophils (beta cells)

10 Nuclei of
6 Sinusoidal capillaries

Fig. 17-2 Hypophysis (sectional view). Stain: hematoxylin-eosin. Medium magnification.

Endocrine System 263

Figure 17-3 Hypophysis: Pars Distalis (sectional viewl

Various cell types in the pars distalis can readily be iden- the cell outlines are poorly defined. The aggregation of chro-
tified following special fixation and/or staining. In the illus- mophobes in groups or clumps is apparent in this illustration.
tration, the hypophysis was fixed with a corrosive sublimate Two types of acidophils (1, 6) can be distinguished by
mixture, and the section stained with azocarmine and differ- their staining reaction (although not as clearly as after other
entiated with aniline oil. Phosphotungstic acid was then used specific stains); cells with coarse granules stain red with azo-
to destain the connective tissue, followed by cytoplasmic carmine (I) and those with smaller granules stain with
staining with aniline blue and orange G. The cytoplasmic orange G (6).
granules stain red, orange or blue, depending on their respec- The basophils (2, 5) are readily recognized by blue-
tive affinities; the nuclei of all cells stain orange. stained granules, but the different types of basophils are not
Chromophobes (3) usually stain lightly after any stain. distinguishable. The degree of granularity and the stain den-
Their nuclei stain pale, the cytoplasm stains pale orange, and sity vary in different cells.

Figure 1 7-4 Hypophysis: Various Cell Groups

Various cell types of the hypophysis are illustrated at idophils.

higher magnification after azan staining. Nuclei of all cells The basophiis (c) exhibit variable round, polyhedral, or
are stained orange-red. angular shapes. The blue granules vary in size and are not as
In the chromophobes (a), the light orange stain of the compact as in the acidophils.
cytoplasm indicates that they are nongranular and their cell The pituicytes (d) of pars nervosa exhibit variable shape
boundaries are indistinct. The cytoplasmic granules of acid- and size of the cells and nuclei (1). The small, orange-stained
ophiis (b) stain intense red and the cell outlines are distinct. cytoplasm has diffuse cytoplasmic processes (2).
A sinusoid capillary is visible in close proximity to the ac-

264 Organs

1 Acidophils (alpha
cells) with red
granules 4 Sinusoidal

5 Basophils

2 Basophils
(beta cells) 6 Acidophils (alpha
cells) with orange
3 Chromophobes

Fig. 17-3 Hypophysis: Pars Distalis (sectional view). Stain: azan (nuclei: orange; cytoplasmic
granules of alpha cells: red or orange; cytoplasmic granules of beta cells: deep blue; collagen and reticular fibers:
blue; erythrocytes: bright red; hemolyzed blood: deep yellow). High magnification.

1 Connective 1 Nuclei
2 Nucleus and

2 Cytoplasmic

a. Chromophobes b. Acidophils c. Basophils (beta cells) d. Pituicytes

(alpha cellsl

Fig. 17-4 Hypophysis: Various Cell Groups. Stain: azan (see detailed explanation of stain, above). Oil

Endocrine System 265

Section 2 Thyroid Gland, Parathyroid Gland, and
Adrenal Gland

Thyroid Gland Parathyroid Gland

The thyroid gland is unique in that it is characterized by Mammals generally have four parathyroid glands. These
spherical structures, called follicles, filled with its secretory small glands are situated on the posterior surface of the thy-
product. These are the structural and functional units of the roid gland, but are separated from the thyroid gland by a thin
thyroid gland. The follicular cells that surround the follicles connective tissue capsule.
secrete and store their product extracellularly in the lumen of The chief cells of the parathyroid glands produce the
the follicles as a gelatinous substance (colloid). The colloid parathyroid hormone (parahormone), which maintains prop-
is composed of thyroglobulin, a glycoprotein containing sev- er calcium level in the body fluids. This is accomplished by
eral iodinated amino acids. Thyroid hormones are stored in raising calcium levels in the blood, an action that is opposite
the form of colloid. or antagonistic to the action of the thyroid gland's calcitonin.
The secretory activity of the follicular cells in the thyroid The parathyroid hormone stimulates the activity and increas-
gland is controlled by the thyroid-stimulating hormone es the proliferation of the osteoclasts in the bones. As a result
(TSH) of the adenohypophysis. This highly complex activity of the increased osteolytic activities of the bone osteoclasts,
includes the synthesis of the thyroglobulin, iodination of the more calcium is ~eleased into the blood, thereby maintaining
thyroglobulin, temporary storage of the thyroglobulin in the normal calcium levels.
follicular lumen, and release of the thyroid hormones into In addition to bones, parathyroid hormone also targets the
general circulation when the need arises. In response to the kidneys and the intestines. The parathyroid hormone influ-
secretory stimulus, follicular cells in the thyroid gland engulf ences the distal convoluted tubules in the kidneys to increase
and hydrolyze the iodinated thyroglobulin, and then release their resorption of calcium from glomerular filtrate, increas-
thyroid hormones into the blood stream. ing the elimination of phosphate, sodium, and potassium ions
The thyroid hormones are thyroxine (T4) and triiodothy- in the urine. Parathyroid hormone also influences the kidneys
ronine (T3). Release of these hormones into the general cir- to form the hormone calcitriol, the active form of vitamin D.
culation accelerates the metabolic rate of the body and Calcitriol increases calcium absorption from the gastroin-
increases cell metabolism, growth, differentiation, and devel- testinal tract into the blood.
opment throughout the body. In addition, the thyroid hor- The secretion and release of parathyroid hormone
mones increase the rate of protein, carbohydrate, and fat depends primarily on the concentration of calcium levels in
metabolism. the blood and not on the pituitary hormones. Because the
In addition to the follicular cells, the thyroid gland also hormone of the parathyroid glands maintains optimal levels
contains the secretory parafollicular cells. These cells appear of calcium in the blood, these glands are essential to life.
on the periphery of the follicular epithelium as single cells or
as clusters of cells between the follicles. The parafollicular Adrenal (Suprarenal) Gland
cells synthesize and secrete the hormone calcitonin (thyro- The adrenal glands are paired and are situated near the
calcitonin). This hormone lowers blood calcium levels in the superior pole of the kidneys. Each gland is surrounded by a
body. This is accomplished primarily by reducing the number connective tissue capsule and consists of an outer cortex and
of osteoclasts in the bones and decreasing their activity, thus an inner medulla. Although these two regions of the adrenal
reducing bone resorption and calcium release. While the pro- gland are in one organ and linked by a common blood sup-
duction and release of thyroid hormone depends on the pitu- ply, they have distinct embryologic origin, structure, and
itary gland hormone, secretion and release of calcitonin by function.
the parafollicular cells is directly controlled by blood calci- Cortex. The adrenal cortex exhibits three concentric zones:
um levels. zona glomerulosa, zona fasciculata, and zona reticularis. The

266 Organs

cells of these zones in the adrenal cortex produce three class- bohydrate metabolism, especially in increasing blood sugar
es of steroid hormones: mineralocorticoids, glucocorticoids, levels of these substances. Glucocorticoids also suppress
and steroid sex hormones. inflammatory responses; they suppress the immune system
The cells of the zona glomeruIosa produce mineralocorti- by arresting mitotic activities in the lymphoid tissues and
coid hormones, of which aldosterone is the most potent. decreasing the production of antibodies.
Aldosterone increases sodium resorption from the glomeru- Although the cells of the zona reticularis are believed to
lar filtrate by distal tubules of the kidney and increases potas- produce sex steroids, the amount of the hormones produced
sium excretion in urine. Water follows sodium, therefore this are of little physiological significance.
action increases fluid volume in the circulation, restores nor- Glucocorticoid secretion, and the secretory functions of
mal electrolyte balance, and raises blood pressure. the zona fasciculata and the zona reticularis are regulated
Aldosterone secretion is initiated via the renin-angiotensin by the pituitary gland adenocorticotropic hormone
pathway in response to a decrease in arterial blood pressure (ACTH).
and plasma levels of sodium, as detected by the juxta- Medulla. The cells of adrenal medulla are modified post-
glomerular apparatus in the kidney. ganglionic sympathetic neurons that secrete catecholamines
The cells of the zona fasciculata-and probably those of (primarily epinephrine and norepinephrine). Their release
the zona reticularis-secrete glucocorticoids, of which corti- from the adrenal medulla is under the direct control of the
sol and cortisone are the most important. Glucocorticoid autonomic nervous system. The effects of these cate-
secretion is an important bodily response to stress. cholamines are similar to those produced by stimulation of
Glucocorticoids have a major effect on protein, fat, and car- the sympathetic division of the autonomic nervous system.

Endocrine System 267

Figure 1 7-5 Thyroid Gland: Canine 'general view)

The thyroid gland is characterized by numerous spherical (1, 8). They occur as single cells or in clumps on the periph-
follicles (2, 12), with variable diameters, that are filled with ery of the follicles. They stain lightly and are clearly visible
an acidophilic colloid (2, 12) material. The follicles are usu- in this illustration of canine thyroid. Parafollicular cells (I, 8)
ally lined by a simple cuboidal epithelium consisting of fol- synthesize and secrete the hormone calcitonin.
licular or principal cells (3, 7). Follicles sectioned tangen- The connective tissue septa (5, 9) from the thyroid gland
tially (4) do not exhibit a lumen. The follicular cells (3, 7) capsule extend into the gland's interior, dividing it into lob-
synthesize and secrete thyroid hormones. In routine histolog- ules (9). Extensive distribution of blood vessels, arterioles
ic preparations, colloid often retracts from the follicular wall (6), venules (10), and capillaries (13) is seen within the con-
(12). nective tissue septa (5, 9) and around the individual follicles
In addition to the follicular cells (3, 7), the thyroid gland (2, 12). Relatively little interfollicular connective tissue
contains another secretory cell type, the parafollicular cells (11) is found between individual follicles.

Figure 1 7-6 Thyroid Gland Follicles: Canine 'sectional view)

A higher magnification of the thyroid gland shows the the follicles (2, 9) but within their basement membrane. The
detailed structure of individual follicles (2, 9). The height of parafollicular cells (I, 10), however, do not border directly
follicul~r cells (5, 11) varies among follicles, depending on on the follicular lumen. Instead, they are separated from the
their state of activity. In highly active follicles, the epitheli- lumen by the processes of neighboring follicular cells (5, I I).
um is mainly cuboidal (9) whereas in less active follicles, the The parafollicular cells (I, 10) are larger, oval or varied in
epithelium appears flattened (5). All follicles (2, 9) are filled shape, and exhibit cytoplasm that is lighter staining than that
with colloid (2), some of which show retraction (12) from of the follicular cells (5, I I).
the follicular wall or distortion (12) due to histologic prepa- Surrounding the follicles (2, 9) is a thin interfollicular
ration. connective tissue (3, 8), in which are found numerous blood
The parafollicular cells (1, 10) are situated within the vessels (6) and capillaries (4), closely associated with the
follicular epithelium (I) or in small clumps (10) adjacent to follicular (5, II) and parafollicular cells (I, 10).

268 Organs
Thyroid Gland

1 Parafollicular 7 Follicular cells


8 Parafollicular cells
2 Follicle with

3 Follicular cells 9 Interlobular


10 Venule
4 Follicle
(tangential 11 Interfollicular
section) connective

5 Connective 12 Follicle with

tissue septa retracted colloid

6 Arteriole
13 Capillaries

Fig. 17-5 Thyroid Gland: Canine 'general view). Stain: hematoxylin-eosin. Low magnification.

1 Parafollicular 6 Blood vessel

7 Follicle (tangential

2 Follicles with 8 Interfollicular

colloid connective tissue

9 Follicle with
3 Interfollicular colloid
connective tissue
10 Parafollicular
4 Capillary 11 Follicular cells
5 Follicular cells

12 Retracted or
distorted colloid

Fig. 17-6 Thyroid Gland Follicles: Canine ,sectional view). Stain: hematoxylin-eosin. High

Endocrine System 269

Figure 17-7 Thyroid and Parathyroid Glands: Canine (sectional view)

The thyroid gland (1) is closely associated with the (7) and oxyphil cells (10). The chief cells (7) are the most
parathyroid gland (3). A thin connective tissue capsule (2) numerous cells; they are round and exhibit a pale, slightly
with a rich capillary plexus (9) and blood vessels (8) sepa- acidophilic cytoplasm. The oxyphil cells (10) are larger and
rates the thyroid gland (1) from the parathyroid gland (3). less numerous than the chief cells (7), and exhibit a denser
Connective tissue trabeculae (6) from the capsule (2) extend acidophilic cytoplasm with smaller, darker staining nuclei
into the parathyroid gland (3) and bring larger blood vessels (10). The oxyphil cells (10) are distributed as single cells or
(8) into the interior of the gland. These blood vessels then in small clumps. In humans, the oxyphil cells (10) are not
branch into an extensive capillary (9) network around the normally present in the parathyroid glands of children under
parathyroid cells. four years of age.
The cells in the parathyroid gland (3) are arranged into The follicles with colloid (4) seen in the thyroid gland (1)
anastomosing cords and clumps, instead of the follicles with are not a characteristic feature of the parathyroid glands (3).
colloid (4), as seen in the thyroid gland (1). The parathyroid However, occasionally an isolated small follicle with colloid
gland (3) contains two types of cells, chief (principal) cells material may be observed in the gland.

270 Organs
Thyroid and Parathyroid Glands

4 Follicles with colloid

1 Thyroid

2 Connective

5 Follicular cells

6 Connective tissue
3 Parathyroid
7 Chief (principal)
B Blood vessel

9 Capillaries

10 Oxyphil cells

Fig. 17-7 Thyroid and Parathyroid Glands: Canine (sectional view). Stain: hematoxylin-eosin. Low

Endocrine System 271

Figure 1 7-8 Adrenal (Suprarenal) Gland

The-:raren:]}(suprarenal) gland consists of an outer cortex The nuclei of these cells are vesicular. Sinusoidal capillar-
(2) and an inner medulla (3). The gland is surrounded by a ies (9) between the cell columns follow a similar radial
thick connective tissue capsule (I) in which are found course.
branches of the main adrenal arteries, veins, nerves (5) The third cell layer, the zona reticularis (2c, 15), borders
(largely unmyelinated), and lymphatics. Connective tissue the adrenal medulla. The cells (10) of this layer form anasto-
trabeculae (4) from the capsule pass into the cortex of the mosing cords and are frequently filled with dark-staining,
gland and the larger trabeculae carry arteries (4) to the lipofuscin pigment (11). The capillaries in this layer exhibit
meduIJa (3). Sinusoidal capillaries (7, 9) are found through- an irregular arrangement.
out the cortex (2) and medulla (3). The medulla (3) is not sharply demarcated from the cor-
The adrenal cortex (2) is subdivided into three concentric tex. The cells that constitute the majority of the medulla (3,
zones that are not sharply demarcated from each other. 14) are arranged in groups. With normal histologic prepara-
Directly under the connective tissue capsule (I) is the first or tion of the adrenal gland, the cytoplasma in these cells
the outermost cell layer of the adrenal gland cortex; this is appears clear (14). After tissue fixation in potassium bichro-
the zona glomerulosa (2a). The cells (6) in this zone are mate, however, fine brown granules become visible in the
arranged into ovoid groups. The cytoplasm of these cells (6) cells of the medulla. This cellular alteration is termed the
contains sparse lipid droplets. In hematoxylin-eosin prepara- chromaffin reaction and indicates the presence of the cate-
tions, the lipid droplets appear as vacuoles while their nuclei cholamines epinephrine and norepinephrine in the granules.
stain dark. The medulla also contains sympathetic ganglion cells (13),
The middle cell layer is the zona fasciculata (2b), whose seen singly or in small groups. They exhibit the characteris-
cells (8) are arranged into columns or plates with radial tic vesicular nucleus, prominent nucleolus, and a smalJ
arrangement. An increased amount of lipid droplets in the amount of peripheral chromatin. Sinusoidal capillaries are
cytoplasm gives the cells of zona fasciculata (8) a vacuolat- also present in the medulla and drain its contents into the
ed appearance following a normal histologic preparation. medullary veins (12).

272 Organs
Adrenal (Suprarenal) Gland

4 Connective tissue
septum with artery

Fig. 17-8 Adrenal (Suprarenal) Gland. Stain: hematoxylin-eosin. Medium magnification (insets: high
magnification) .

Endocrine System 273


Male Reproductive System

The male reproductive system consists of gonads or sperm; and (5) production of androgen-binding protein and
testes, excretory ducts, accessory reproductive glands, and inhibin.
the copulatory organ penis. The testes perform two important The follicle-stimulating hormone (FSH), released from
reproductive functions: to produce the spermatozoa and the the adenohypophysis of the pituitary gland, controls the
male hormone, testosterone. secretion of androgen-binding protein by the Sertoli cells.
The androgen-binding protein increases the concentration of
Testes testosterone in the seminiferous tubules for proper spermato-
Each testis is subdivided by connective tissue septa into genesis. Sertoli cells also secrete inhibin, a hormone that sup-
lobules, each containing numerous highly coiled seminifer- presses or inhibits the production of FSH by the pituitary
ous tubules. Each seminiferous tubule is lined by the strati- gland.
fied germinal epithelium, consisting of two major cell types: Surrounding the seminiferous tubules are fibroblasts,
proliferating spermatogenic cells and nonproliferating sup- muscle-like cells, nerves, blood vessels, and lymphatic ves-
porting (sustentacular) or Sertoli cells. The spermatogenic sels. In addition, between seminiferous tubules are clusters
cells divide, differentiate, and produce the spermatozoa by a of epithelioid cells, the interstitial cells (of Leydig). These
complex process called spermatogenesis, which involves the cells produce testosterone, a male hormone necessary for
following three phases: (I) mitotic divisions of spermatogo- spermatogenesis, development and maintenance of the
nia to produce successive generations of cells that eventual- accessory glands of the male reproductive system, and the
ly form spermatocytes; (2) two meiotic divisions, in which secondary male sex characteristics. Production of testos-
the number of chromosomes in the spermatocytes is reduced terone depends primarily on the luteinizing hormone (LH)
by half, resulting in the production of spermatids; and (3) secreted by the pituitary gland.
spermiogenesis, during which the spermatids undergo mor- Normal spermatogenesis in the testes depends on several
phological transformation into spermatozoa. factors. Proper levels of both the luteinizing hormone (LH)
The supporting or Sertoli cells in the germinal epithelium and the follicle stimulating hormone (FSH) are needed; these
of the seminiferous tubules are joined laterally by tight junc- hormones are produced by the gonadotrophs in the adenohy-
tions. These junctions form the blood-testis barrier and pophysis of the pituitary gland. LH stimulates the production
divide the seminiferous tubules into basal and adluminal of testosterone by the interstitial cells. FSH stimulates the
compartments. The blood-testis barrier prevents the entrance Sertoli cells to produce the androgen-binding protein, which
of harmful substances from blood into the germinal epitheli- enters the lumina of the seminiferous tubules. High levels of
um of the seminiferous tubules and restricts the passage of testosterone are needed in the seminiferous tubules to sustain
membrane antigens from developing sperm into the blood the normal process of spermatogenesis.
and the immune system. Restricting the passage of antigens In addition to the circulating levels of these hormones,
into blood prevents an autoimmune response to the individ- proper temperature in the testes is crucial for normal sper-
ual's own sperm and induction of sterility. matogenesis. Testicular temperature is normally about 2 to
The Sertoli cells also perform numerous important func- 3°e cooler than the core body temperature. The location of
tions related to the process of spermatogenesis, among which the testes outside of the body in the scrotum accounts for
are: (I) support, protection, and nutrition of the developing some of this cooling. In addition, a venous (pampiniform)
sperm cells (spermatids); (2) phagocytosis of the excess plexus closely surrounds the testicular arteries and provides
cytoplasm of the developing spermatids (the residual bodies) an important mechanism for a countercurrent heat-exchange.
during spermiogenesis; (3) release of spermatozoa (spermia- By this method, blood in the testicular arteries that flows into
tion) into the seminiferous tubules after their development; the testes is cooled and blood in the veins that returns to the
(4) secretion of testicular fluid as transport medium for body is warmed.

Male Reproductive System 275

Excretory Ducts Accessory Reproductive Glands
The seminiferous tubules in the lobules of the testes ter- The accessory reproductive glands of the male reproduc-
minate as straight tubules, the tubuli recti. Spermatozoa tive tract consist of paired seminal vesicles, paired bul-
that were released into the seminiferous tubules pass from bourethral glands, and a single prostate gland. The structure
here into the rete testis, which then drain into the head of and function of these glands are dependent on proper testos-
the epididymis by way of the ductuli efferentes (efferent terone levels.
ducts ). The seminal vesicles produce a yellowish, viscous fluid
The ductuli efferentes are lined with tall ciliated and that contains a high concentration of fructose, the main car-
resorptive nonciliated cells. The cilia in these ducts assist in bohydrate of the semen, and which is metabolized by the
transporting the sperm through to the ductus epididymis, sperm as a source of energy for the sperm's motility.
and the nonciliated cells absorb some of the fluid that was The prostate gland produces a thin, watery, slightly acidic
produced in the seminiferous tubules. In conjunction with fluid rich in citric acid, acid phosphatase, and amylase. The
ductuli efferentes, the cells in the ducts of the epididymis enzyme fibrinolysin in the fluid liquefies the congealed
also absorb testicular fluid during the passage of sperm. As semen after ejaculation.
the sperm slowly pass through the highly coiled ducts of the The bulbourethral glands produce a clear, viscid, mucus-
epididymis, this organ functions as an important site for like secretion that, during erotic stimulation, is liberated and
accumulation, storage, and sperm maturation. functions as a lubricant for the urethra.
The ,ducts of the epididymis are surrounded by smooth The secretions of seminal vesicles, the prostate gland, and
muscle cells. During sexual stimulation and ejaculation, bulbourethral glands, mixed with sperm, constitute semen.
strong smooth muscle contractions around the ducts of the Semen provides the sperm with transport medium and nutri-
epididymis expel the sperm into the ductus (vas) deferens, ents, while neutralizing the acidity of the male urethra and
which conducts it to the urethra of the penis. vaginal canal, and activating sperm after ejaculation.

276 Organs

Figure 18-1 Testis (sectional view)

Figure 18-2 Seminiferous Tubules, Straight Tubules, Rete Testis, and Ductuli
Efferentes (Efferent Ductules)

Male Reproductive System 277

Figure f 8- f Testis (sectional viewl

Each testis is enclosed in a thick, connective tissue cap- loose connective tissue ceJIs, and clusters of epithelial inter-
sule, the tunica albuginea (1). Internal to this capsule is a stitial cells (of Leydig) (5, 11). The interstitial ceJIs (5, II)
vascular layer of loose connective tissue, the tunica vascu- are the endocrine ceJIs of the testis and secrete the male sex
losa (2, 8). A loose connective tissue extends inward from the hormone testosterone into the blood stream.
tunica vasculosa (2, 8) and forms the interstitial connective The seminiferous tubules (4, 6, 9) are long, highly con-
tissue (3, 12) of the testis. This connective tissue (3, ] 2) sur- voluted tubules in the testis that are normaJIy observed cut in
rounds, binds, and supports the seminiferous tubules (4, 6, transverse (4), longitudinal (6), or in tangential (9) planes of
9). Also, extending from the mediastinum testis (Fig. ] 8-2 section. The seminiferous tubules (4, 6, 9) are lined with a
below) toward the tunica albuginea (]) are thin fibrous septa specialized stratified epithelium caJIed the germinal epithe-
(7, 10). These septa (7, 10) divide the testis into numerous lium (14), which consists of two types of ceJIs, the sper-
compartments caJIed lobules. Each lobule contains one to matogenic cells that give rise to the spermatozoa and the sup-
four seminiferous tubules (4, 6, 9). Because the septa are not pOl.tive Sertoli ceJIs that nourish the developing spermatozoa.
complete, the lobules intercommunicate. Located in the These ceJIs rest on the basement membrane of the seminifer-
interstitial connective tissue (3, 12) around the seminiferous ous tubules (4, 6, 9) and are iJIustrated in greater detail in
tubules (4, 6, 9) are numerous blood vessels (13), various Figures 18-3 and 18-4.

Figure 1 8-2 Seminiferous Tubules, Straight Tubules, Rete Testis, and Ductuli
Efferentes (Efferent Ductules)

In the posterior region of the testis, the connective tissue 12) located in the connective tissue of the mediastinum testis
of tunica albuginea (see the figure above) extends into the (10, 16). The rete testis (7, 8, ] 2) are irregular, anastomosing
testis as the mediastinum testis. In this low magnification network of tubules with wide lumina lined by a single layer
illustration, the plane of section passes through a smaJI por- of squamous to low cuboidal or low columnar epithelium;
tion of the seminiferous tubules (3, 5) of the testis, the con- these tubules become wider near the ductuli efferentes
nective tissue and blood vessels of the mediastinum testis (efferent ductules) (9, 13) into which they empty. The duc-
(10, 16), and the excretory ducts of the testis, the ductuli tuli efferentes (9, 13) are straight; however, as they continue
efTerentes (efferent ductules) (9, 13). These structures are into the head of the epididymis, they become highly convo-
illustrated below in greater detail as three separate inserts. luted (see Fig. 18-5). The ductuli efferentes (9, ] 3) serve as
A few seminiferous tubules (3, 5) are visible on the left connecting channels from rete testis (7, 8, 12) to the epi-
side of the iJIustration; these are lined with spermatogenic didymis (see Fig. 18-5). In some of the rete testis (12) and
epithelium and the sustentacular (Sertoli) ceJIs. The intersti- ductuli efferentes (9, 13) are seen aggregations of sperm
tial connective tissue (4) of the testis contains the steroid (11, 14).
(testosterone) producing interstitial cells (of Leydig) (I) The epithelium of ductuli efferentes (9, 13) is distinctive
and is continuous with the connective tissue of the medi- because it consists of groups of taJI columnar cells that alter-
astinum testis (10, 16). In the mediastinum testis (10, 16), the nate with groups of shorter cuboidal ceJIs. Because of the
seminiferous tubules (3, 5) of each testicular lobule terminate alterations in the ceJI heights, the lumina of the ductuli effer-
and form straight tubules (2, 6). The straight tubules (2, 6) entes exhibit an uneven contours. The tall ceJIs in these
are short, narrow ducts lined with cuboidal or low columnar tubules generally exhibit apical cilia (15) while the cuboidal
epithelium that are devoid of spermatogenic ceJIs. ceJIs exhibit a brush-like border of microviJIi.
The straight tubules (2, 6) continue into rete testis (7, 8,

278 Organs
1 Tunica albuginea

2 Tunica vasculosa

8 Tunica vasculosa

9 Seminiterous
4 Seminiferous
10 Septa
5 Interstitial cells
11 Interstitial cells

12 Interstitial
6 Seminiferous

7 Septa - 13 Blood vessels

Stain: hematoxylin-eosin. Low magnification. 14 Germinal


Fig.18-1 Testis (sectional viewJ.

Fig. 18-2 Seminiferous Tubules, Straight Tubules, Rete Testis, and Ductuli Efferentes
(Efferent DuctulesJ. Stain: hematoxylin-eosin. Low magnification (inset: high magnification).

Male Reproductive System 279

Figure 1 8-3 Primate Testis: Spermatogenesis in Seminiferous Tubules
(transverse section)

Different stages of spermatogenesis are illustrated in var- nucleus are variable and the nucleo]us is centrally located.
ious seminiferous tubules (3). Each tubule (3) is surround- Type A spermatogonia (I 2a) serve as stem cells of the ger-
ed by an outer 1ayer of connective tissue with fibroblasts (1) minal epithelium and give rise to other type A and type B
and an inner basement membrane (2). Between the tubules spermatogonia. The final mitosis of type B spermatogonia
is the interstitia] tissue, consisting of fibroblasts (18), blood produces primary spermatocytes (5, 16). The nuclei of
vessels (10), nerves, and lymphatics. Also prominent these cells have variable appearances because of different
between the seminiferous tubules (3) are the interstitial cells states of activity of the chromatin. These cells promptly enter
(of Leydig) (11, 15). the first meiotic division and the representative meiotic fig-
The stratified germinal epithelium of the seminiferous ures are prevalent in the seminiferous tubu1es (3).
tubules consists of the supporting or Sertoli cells (6, 7, 14) Primary spermatocytes (5, 16) are the most obvious and
and the spermatogenic cells (5, 9, 12). The Serto]i cells (6, largest germ cells in the seminiferous tubules (3) and occupy
7, 14) are slender, elongated cells with irregular outlines the middle region of the germinal epithelium. Their cyto-
extending from the basement membrane to the lumen of the plasm contains large nuclei with coarse clumps or thin
seminiferous tubule (3). The nucleus of the Serto]i cells (6, 7, threads of chromatin. The first meiotic division of the prima-
]4) is generally ovoid or elongated and contains fine, sparse ry spermatocytes (Fig. 18--4 I, 5) produces smaller secondary
chromatin. A distinct nucle01us in the Sertoli cells (6, 7, 14) spermatocytes with less dense nuclear chromatin (Fig. 18--4
distinguishes them from the spermatogenic cells (5, 9, 12), I, 3). The secondary spermatocytes (Fig. 18--4 I, 3) undergo
which are arranged in rows between and around the Sertoli second meiotic division shortly after their formation and are
cells. In different sections, the spermatogenic cells often therefore not frequently seen in sections of the seminiferous
appear'superimposed on Sertoli cells (6, 7, ]4), obscuring tubules (3).
their cytoplasm. Completion of the second meiotic division produces sper-
The immature spermatogenic cells, the spermatogonia matids (4, 8, 9,13,17), which are smaller cells than the pri-
(12), .are situated adjacent to the basement membrane (2) of mary or secondary spermatocytes (Fig. 18--4 I, 2, 3, 5). These
the seminiferous tubules (3). The spermatogonia (] 2) divide cells lie in groups in the ad1umina] portion of the seminifer-
mitotically to produce severa] generations of cells. Three ous tubule in close association with the Sertoli cells (6, 13,
types of spermatogonia are usually recognized. The pale ]4). In this environment, the spermatids (4, 8, 9,13, 17) dif-
type A spermatogonia (12a) have a light-staining cytoplasm ferentiate into spermatozoa by a process called spermiogen-
and a round or ovoid nucleus with pale, finely granular chro- esis. The small, dark-staining heads of the maturing sper-
matin. The dark type A spermatogonia (12b) appear simi- matids (4, 8) lie embedded in the cytoplasm of the Sertoli
lar, but the chromatin stains darker. In type B spermatogonia cells (6, 7, 14), and their tails extend into the lumen of the
(not illustrated), the chromatin granules in the spherical seminiferous tubule (3).

Figure 1 8-4 Primate Testis: Stages of Spermatogenesis

Three different stages of spermatogenesis are illustrated tubule prior to being released. Also visible are clumps of
in greater detail. In the left illustration (I), the primary round spermatids (8) and primary spermatocytes (9) in
spermatocytes (5) are undergoing meiotic division to form close association with the Sertoli cells (10). Near the base of
the secondary spermatocytes (3), which in turn undergo the tubule are found spermatogonia (11).
rapid division to form the spermatids (1, 2). In this stage, the In the right illustration (III), the mature sperm have been
spermatids (I) are embedded deep in the Sertoli cell (4) released (spermiation) into the seminiferous tubule and the
cytoplasm. Adjacent to the basement membrane are the type germinal epithelium contains only spermatids (8), primary
A spermatogonia (6). spermatocytes (9), spermatogonia (11), and the supporting
In the middle illustration (II), the spermatids (7) are Sertoli cells (10).
located peripherally near the lumen of the seminiferous

280 Organs
Primate Testis

..... ~ ~

Fig. 1 8-4
Primate Testis: Stages of Spermatogenesis. Stain: hematoxylin-eosin. High magnification.

Male Reproductive System 281

Figure 18-5 Ductuli Efferentes and Transition to Ductus Epididymi~

The ductuli efferentes (1, 4, 5) or efferent ductules cells may be present, giving the epithelium a pseudostratified
emerge from the mediastinum on the posterior-superior sur- appearance. The basal surface of the tubules has a smooth
face of the testis and connect the rete testis with the ductus contour. Located under the basement membrane is a thin
epididymis. The ductuli efferentes are located in the connec- layer of connective tissue containing a thin layer of circular-
tive tissue (2) and form a portion of the head of the epi- ly arranged smooth muscle fibers (3).
didymis (7). Because of the tortuous, spiral course of the The distal ends of the tubules near the epididymis are
tubules, they are seen as isolated tubules cut in various lined with columnar cells only (6), and the lumina exhibit an
planes of section (1, 5). even contour. As the ductuli efferentes terminate in the duc-
The lumina of the ducts exhibit a characteristic irregular tus epididymis, there is an abrupt transition of the epitheli-
contour. The lining epithelium is simple, consisting of alter- um to the tall pseudostratified columnar type of the epididy-
nating groups of tall ciliated and shorter nonciliated cells mis (7).
(4), which are believed to be absorptive. Occasional basal

Figure 1 8-6 Ductus Epididymis

The ductus epididymis is a long, highly convoluted tubule (10). The function of the columnar principal cells (9) with
surrounded by the connective tissue (1). A transverse section stereocilia (8) is primarily absorption of the tubular fluid; the
through. the epididymis shows the convoluted tubules (2, 5, function of the basal cells is not known. The stereocilia (8)
6) in highly varied forms. The individual tubules are sur- are long, branched microvilli.
rounded by smooth muscle fibers (7) and connective tissue The basement membrane (3) that surrounds each tubule
(1). Both the internal and external surfaces of the tubules is distinct. The lamina propria with the circularly arranged
have smooth contours. smooth muscle fibers (7) is thin and more pronounced than
The tubular epitheljum of ductus epididymis is pseudo- in the ductuli efferentes. Mature spermatozoa are seen in the
stratified (4, 9), consisting of tall columnar principal cells lumina of some of the tubules
(9) with long, nonmotile stereocilia (8) and small basal cells

282 Organs
Efferent Ducts and Epididymis

1 Ductuli -=
efferentes 5 DuctuJj
typical tubules

2 Connective
tissue of the

3 Smooth muscle
fibers in the 5 Ductuli
lamina propria efferentes:
distal transition

7 Ductus
4 Epithelium of
ductuli efferentes

Fig. 18-5 Ductuli Efferentes and Transition to Ductus Epididymis. Stain: hematoxylin-eosin. Low
magnification (inset: medium magnification).

1 Connective tissue
- 5 Sectionthrough
a U-bend of the
ductus epididyrnidis

2 Cross section of the

ductus epididymidis

- 6 Epididymal wall
cut tangentially

3 Basement membrane -7 Smooth muscle


-ij Stereocilia

~ Columnar cell

4 Pseudostratified
columnar epithelium -10 Basal cell
with stereocilia

Fig. 18-6 Ductus Epididymis. Stain: hematoxylin-eosin. Low magnification (inset: high magnification).

Male Reproductive System 283

Figure 18-7 Ductus Deferens ,transverse section,

The ductus deferens exhibits a narrow, irregular lumen, a didymis. The epithelium rests on a thin basement membrane
thin mucosa, a thick muscularis, and adventitia. The irregu- and stereocilia is usually seen on the cell apices.
lar outline of the lumen is caused by longitudinal folds of the The muscularis consists of a thin inner longitudinal
lamina propria (5, 6), which in transverse section appear as layer (3), a thick middle circular layer (2), and a thin outer
crests or papillae (6). The thin lamina propria (5, 6) consists longitudinal smooth muscle layer (1). The muscularis is
of compact collagen fibers and fine elastic network. surrounded by adventitia (4), which contains abundant
The epithelium is pseudostratified columnar (7) but is blood vessels and nerves. The adventitia (4) merges with the
somewhat lower than the epithelium lining the ductus epi- connective tissue surrounding the spermatic cord.

Figure 1 8-8 Ampulla of the Ductus Deferens 'transverse section'

The terminal portion of ductus deferens enlarges into an The epithelium lining the lumen and the crypts is simple
ampulla. The ampulla differs from the ductus deferens main- columnar or cuboidal (7) and is secretory in nature.
ly in the structure of its mucosa. The muscularis is similar to the ductus deferens. It con-
The lumen of the ampulla is larger and the mucosa sists of a thin outer longitudinal layer (3), a thick middle
exhibits numerous thin, irregular, branching folds (6) with layer (2), and a thin inner longitudinal smooth muscle
diverticula or glandular crypts (5, 9) located between them. layer (1) adjacent to the lamina propria (8).

284 Organs
Ductus Deferens

1 Outer longitudinal
muscle layer (t.s.)

2 Middle circular 5 lamina propria

muscle layer (t.s.)

6 longitudinal crest
3 Inner longitudinal of lamina propria
muscle layer (t.s.) 7 Epithelium

8 Adipose tissue

4 Nerve and blood

vessels in the adventitia'

Fig. 18-7 Ductus Deferens (transverse section). Stain: hematoxylin-eosin. Low magnification.

5 Glandular crypts
1 Inner longitudinal
muscle layer (t.s.)

6 Mucosal folds
2 Middle circular muscle
layer (t.s.) 7 Columnar secretory

8 lamina propria
3 Outer longitudinal
muscle layer (t.s.)

4 Adventitia 9 Glandular crypts (t.s.)

Fig. 18-8 Ampulla of the Ductus Deferens (transverse section). Stain: hematoxylin-eosin. Low

Male Reproductive System 285

Figure 1 8-9 Prostate Gland with Prostatic Urethra

In the prostate gland, the secretory acini (4,5) are part of epithelium in the prostatic urethra (I) is usually transitional
the many small, irregularly branched tubuloacinar glands; and a fibromuscular stroma surrounds the urethra (3); how-
the acini (4, 5) vary in size. The larger-sized acini exhibit ever, a thin lamina propria may be present.
wide, irregular lumina (4) and variable epithelium (see Fig. A ridge of dense fibromuscular stroma without glands, the
18-10). The glands are embedded in a characteristic, fibro- colliculus seminalis (2), protrudes into the urethral lumen
muscular stroma (3) in which strands of smooth muscle (I), giving it a crescent shape. The prostatic utricle (7, 10)
(6), collagen, and elastic fibers are oriented in various direc- is situated in the mass of the colliculus seminalis (2) and is
tions. often dilated at its distal end before entering the urethra. Its
The prostatic urethra (1) is as a crescent-shaped struc- thin mucous membrane is typically folded, and the epitheli-
ture with small diverticula (8) in its lumen; the diverticula um is usually of the simple secretory or pseudostratified
are especially prominent in the urethral recesses (9). The columnar type.

Figure 18-10 Prostate Gland (sectional view, prostatic glands)

A small section of the prostate gland from Figure 18-9 is in the distal regions, there is considerable variation. In some
illustrated with more detail and at a higher magnification. regions, the epithelium may be squamous or cuboidal.
The size of glandular acini (1) is variable. Their lumina The ducts (7) of the glands may resemble the acini and it
are wide and typically irregular because of the protrusion of is often difficult to distinguish the difference between the
the epithelium-covered connective tissue folds (5). A char- two structures. In the terminal portions of the ducts (7), the
acteristic feature in the acini of the prostate gland are the epithelium is usually columnar and stains darker before
spherical prostatic concretions (8) that are formed by con- entering the urethra.
centric layers of condensed prostatic secretions. The number The fibromuscular stroma (6) is a characteristic feature
of prostatic concretions increases with the age of the individ- of the prostate gland. Smooth muscle fibers (3) and the con-
ual, and they may become calcified. nective tissue fibers (9) can, at times, be distinguished; how-
Although the glandular epithelium (4) is usually simple ever, they blend together in the stroma (6) and are distrib-
columnar or pseudostratified and the cells are light-staining uted throughout the gland.

286 Organs
Prostate Gland

5 Prostatic glands

6 Smooth muscle
of the stroma

7 Dilation of
the utricle

8 Diverticula of
urethral wall
9 Urethral recess
10 Utricle

11 Ejaculatory

Fig. 18-9 Prostate Gland with Prostatic Urethra. Stain: hematoxylin-eosin. Low magnification.

1 Glandular

2 Capillaries

Fig. 18-10 Prostate Gland 'sectional view, prostatic glands). Stain: hematoxylin-eosin. Medium

Male Reproductive System 287

Figure 18-11 Seminal Vesicle

The paired seminal vesicles are elongated bodies or sacs The glandular epithelium (4) of the seminal vesicles
with highly convoluted and irregular lumina. A cross section varies in appearance but is usually of the low pseudostrati-
through the gland illustrates the complexity of the primary tIed type with basal cells and low columnar or cuboidal
folds (5). These folds branch into numerous secondary folds secretory cells.
which frequently anastomose, forming crypts (1) and The muscularis (2) consists of inner circular and outer
cavities. The lamina propria (7) projects and forms the core longitudinal smooth muscle layers. This arrangement of the
of the larger primary folds (5) and thin stroma of smaller sec- muscles is often difficult to observe because of the complex
ondary folds (6). These folds extend far into the lumen of the folding of the mucosa. The adventitia (3) surrounds the
seminal vesicle. muscularis and blends with the connective tissue.

Figure 18-12 Bulbourethral Gland ,sectional view)

This is a compound tubuloacinar gland. One lobule and variable other shapes. The secretory product is primarily
portions of other lobules of the gland are illustrated in the mucus (4). The secretory cells are cuboidal, low columnar or
figure. The bulbourethral gland is surrounded by skeletal squamous, and light-staining. Interspersed among the secre-
muscle (2) and connective tissue (1). The skeletal muscle tory cells are darker-staining acidophilic cells.
and some smooth muscle fibers are also present in the inter- Smaller excretory ducts may be lined with secretory cells,
lobular septa (3). whereas the larger excretory ducts (6) exhibit pseudostrati-
The secretory units vary in structure and size. Most of the fied or stratified columnar epithelium.
units have acinar (4) shape and others exhibit tubular (5) or

288 Organs
Seminal Vesicle and Bulbourethral Gland

4 Glandular epithelium

1 Crypts in the mucos

5 Primary fold in
the mucosa
6 Secondary folds

7 Lamina propria
2 Muscular coat

3 Adventitia

Fig. 18-11 Seminal Vesicle. Stain: hematoxylin-eosin. Low magnification.

4 Mucous acini (I.s.)

1 Connective tissue

2 Skeletal muscle
surrounding the gland

5 Tubular secretory
units It.s. and I.s.)

6 Interlobular
excretory duct
3 Skeletal muscle in
interlobular septa

Fig. 18-12 Bulbourethral Gland 'sectional view). Stain: Massons stain. High magnification.

Male Reproductive System 289

Figure f 8- f 3 Penis (transverse sectionl

A cross section of the penis (human) illustrates the three round the cavernous cavities or sinuses (veins) (12) of the
cavernous bodies: the two adjacent corpora cavernosa (9) corpora cavernosa (9). Nerves and blood vessels are present
and a single corpus spongiosum (16), through which passes in the trabeculae (14). The cavernous cavities or sinuses ( 12)
the urethra (15). Surrounding the corpora cavernosa (9) of of the corpora cavernosa (9) are lined with endothelium and
the penis is a thick, fibrous connective tissue capsule, the receive blood from the dorsal (8) and deep arteries (11) of
tunica albuginea (5); it also extends between the two bod- the penis. Smaller branches from the deep arteries (II) open
ie!ias the median septum {JU}. This septum is better de vel- into the cavemous cavities (12) of the corpora cavemoS3 (9).
oped at the posterior end of the penis than at the anterior end. The corpus spongiosum (16) receives its blood supply large-
The tunica albuginea (6) surrounding the corpus spongio- ly from the bulbourethral artery, a branch of the internal
sum (corpus cavernosa urethrae) (16) is thinner than that pudendal artery. Blood that leaves the cavernous cavities
around the corpora cavernosa (9) and contains smooth muscle exits mainly through the superficial veins (13) in the dermis
and elastic fibers. (2) and the deep dorsal vein.
All three cavernous bodies are surrounded by loose con- The urethra (15) is designated as the spongiosa or cav-
nective tissue, the deep penile (Buck's) fascia (4) which, in ernous urethra. At the base of the penis, the urethra (15) is
turn, is surrounded by the connective tissue of the dermis (2) lined with pseudostratified or stratified columnar epithelium;
that is located immediately under the epidermis (1). Strands however, at the external orifice, the epithelium becomes
of smooth muscle, the dartos tunic (3), and an abundance of stratified squamous. The urethra also exhibits numerous
peripheral blood vessels are located in the dermis (2). small but deep invaginations in its mucous membrane. These
Sebaceous glands (7) are present in the dermis on the ven- are the urethral lacunae (of Morgagni) with mucous cells.
tral side of the penis. Branched tubular urethral glands (of Littre) open into these
The core of each corpus cavernosum (9) is occupied by recesses. The lacunae and the urethral glands are not visible
numerous trabeculae (14), which consist of collagenous, at this magnification (see Fig. ] 8-]4).
elastic, and smooth muscle fibers. The trabeculae (14) sur-

Figure 18-14 Cavernous Urethra (transverse section)

A section of the cavernous urethra (4) is illustrated with the lamina propria of the corpus spongiosum (7, lowest
pseudostratified or stratified columnar epithelium (5) lin- leader). The urethral glands (7) are lined with the same type
ing. A thin lamina propria (3) merges with the surrounding of epithelium that lines the lumen of the cavernous urethra
connective tissue of the corpus spongiosum. (4) (stratified columnar in this illustration).
Numerous various-sized mucosa] outpockets or the ure- The corpus spongiosum (1) surrounds the urethra (4); its
thrallacunae (of Morgagni) (9) give the urethral lumen (4) internal structure is similar to that of the corpora cavernosa
an irregular form. Some of these urethral lacunae (9) contain described in Figure 18-13. In the illustration are seen the
mucous cells. The deeper urethral lacunae (9) are connected characteristic trabeculae (1, 11) of connective tissue and
with the branched urethral glands (of Littre) (7) located in smooth muscle between the cavernous veins (2, 8, 10).

290 Organs

Penis and Cavernous Urethra

1 Epidermis
8 Dorsal artery

2 Dermis
9 Corpus cavernosum

10 Median septum
3 Dartos tunic

11 Deep artery
12 Cavities (cavernous
veins) of corpus
13 Superficial vein
4 Deep penile fascia

14 Trabeculae
5 Tunica albuginea of
corpus cavernosum
15 Cavernous urethra

6 Tunica albuginea of 16 Corpus spongiosum

corpus spongiosum

7 Sebaceous gland
in dermis

Fig. 18-13 Penis

1 Trabecula of the corpus

spongiosum: smooth
muscle and connective

8 Cavernous veins
2 Veins in the corpus
(venous spaces)

9 Urethral lacunae
3 Urethral mucosa:
lamina propria and
4 Cavernous urethra

5 Stratified columnar 10 Cavernous veins

epithelium (venous spaces)
6 Urethral lacuna (of
7 Urethral glands (of
11 Smooth muscle in

Fig. 18-14 Cavernous Urethra ,transverse section). Stain: hematoxylin-eosin. Low magnification.

Male Reproductive System 291


Female Reproductive System

Section 1 Ovaries, Uterine Tubes, and Uterus

Introduction at fertilization, when the sperm penetrates the ovum. The lib-
The female reproductive system consists of the ovaries, erated egg remains viable for about 24 hours.
uterine tubes, uterus, vagina, mammary glands, and the After ovulation of the mature follicle, the ovary enters the
external genitalia. The individual organs of this system per- luteal phase. During this phase, LH presence induces rapid
form numerous important functions, including secreting transformation of the granulosa and theca interna cells of the
female sex hormones (estrogen and progesterone), producing ruptured ovarian follicle into the granulosa lutein and theca
ova, providing a suitable environment for fertilization of the lutein cells of a temporary endocrine gland, the corpus
oocyte, transporting and implanting blastocysts, driving luteum. LH then stimulates the lutein cells to secrete estro-
, development of the fetus during pregnancy, and nutrition of gen and large amounts of progesterone. The presence of
the newborn. these hormones will stop additional ovulation and stimulate
During reproductive life when the female is not pregnant, further development of the uterus and mammary glands in
the reproductive organs exhibit cyclical changes in both anticipation of pregnancy.
structure and function. In humans, these changes are called The development and functional activity of the corpus
menstrual cycles and are controlled primarily by the adeno- luteum depends on the presence of LH. The rising level of
hypophyseal (pituitary gland) hormones, the follicle stimu- progesterone produced by the corpus luteum, however, has
lating hormone (FSH) and the luteinizing hormone (LH), and an inhibitory effect on further release of LH by the adenohy-
the ovarian hormones estrogen and progesterone. pophysis. If the ovulated oocyte is not fertilized, 12 to 14
days after ovulation the corpus luteum regresses into a non-
functional corpus albicans. Estrogen and progesterone levels
The ovaries undergo several phases during the course of a then decline and menstruation follows. With the regression
menstrual cycle: follicular growth and maturation, ovulation, of the corpus luteum, the inhibitory effects of its hormones
and formation and degeneration of corpus luteum. The first on the pituitary gland are removed. This action causes a
half of the ovarian cycle is the follicular phase. During this release ofFSH from the adenohypophysis and an initiation of
phase, FSH is the principal circulating gonadotrophic hor-
a new ovarian cycle of follicular development.
mone. FSH influences the growth and maturation of ovarian
follicles and stimulates the granulosa and thecal cells of the
Uterine Tubes
maturing follicles to produce estrogen. As the circulating
level of estrogen rises during the follicular phase, however, it The uterine tubes extend from the ovaries to the uterus.
produces an inhibitory effect on further release of FSH from One end of the uterine tube opens into the uterine cavity and
the pituitary gland. In addition, inhibin, a hormone produced the other is closely associated with the ovary. The uterine
by the granulosa cells in the ovarian follicles, also exerts tubes perform several important functions. After ovulation,
inhibitory effects on the release of FSH from the pituitary the uterine tubes capture and conduct the oocyte toward the
gland. uterus. This function is accomplished by the gentle peristaltic
At midcycle or shortly before ovulation, estrogen secre- action of the smooth muscles in the uterine wall and by the
tion reaches a peak. This rise in estrogen causes a brief surge ciliary action of the ciliated cells in the lining epithelium.
of LH release and a concomitant smaller release of FSH from The uterine tubes also provide sites of fertilization for the
the adenohypophysis of the pituitary gland. The increased egg. Fertilization normally occurs in the ampullary region of
levels of LH and FSH induce several events: final maturation the uterine tubes, a proper environment for initial develop-
of the ovarian follicle and its rupture (ovulation); completion ment of the embryo.
of the first meiotic division and liberation of a secondary The epithelium of the uterine tube wall consists of ciliat-
oocyte into the uterine tube; and the formation of the corpus ed and non-ciliated (peg) cells. Most cilia beat toward the
luteum. Final maturation of the secondary oocyte occurs only uterus and, together with muscular contractions, transport the

Female Reproductive System 293

egg through the tube to the uterus. The non-ciliated cells are ing into the next. The proliferative (follicular) phase, charac-
secretory and contribute nutritive material to the environ- terized by rapid growth and development of the endometri-
ment of the uterine tubes. The uterine tube epithelium um, starts at the end of the menstrual phase. Increased mitot-
exhibits cyclic changes that are associated with the ovarian ic activity of cells in the lamina propria and in the remnants
cycles. The height of the epithelium in the uterine tubes is of uterine glands in the basalis layer begin to cover the raw
greatest during the follicular phase, at which time the ovari- surface of the mucosa that was denuded during menstruation.
an follicles are maturing and circulating levels of estrogen As the endometrium thickens, the uterine glands proliferate,
are high. lengthen, and become closely packed. The spiral arteries
begin to grow toward the endometrial surface and show only
Uterus slight coiling. The growth of the endometrium during the
During pregnancy, the uterus provides the site for implan- proliferative phase closely coincides with the growth of the
tation of the blastocyst and formation of the placenta, and a ovarian follicles and their increased secretion of estrogen.
suitable environment for the development of a fetus. The The secretory (luteal) phase begins shortly after ovula-
wall of the uterus is composed of three layers: an outer tion, corpus luteum formation, and the secretion of proges-
perimetrium (serosa or adventitia), a thick middle myometri- terone (primarily by granulosa lutein cells) and estrogen (by
um (smooth muscle), and an inner endometrium (epithelium theca lutein cells) of the corpus luteum. During this phase,
and lamina propria). The endometrium exhibits cyclic the endometrium continues to thicken and to accumulate
changes in structure and function in response to the ovarian fluid, becoming edematous. In addition, the uterine glands
hormones estrogen and progesterone. These changes prepare hypertrophy and become tortuous, and their lumina become
the uterus for implantation and nourishment of the embryo filled with secretory products that are rich in nutrients, espe-
and fetus. If implantation does not occur, the blood vessels in cially glycogen. The spiral arteries in the endometrium
the endometrium deteriorate and rupture, and a portion of the lengthen, become more coiled, and extend almost to the sur-
endometrium is shed during menstruation. face of the endometrium.
The endometrium of the uterus is normally subdivided The menstrual phase begins when fertilization and
into two layers, the luminal stratum functionalis and the implantation fail to occur. This phase is triggered by the
basal stratum basalis. These layers exhibit several changes reduced levels of circulating progesterone (and estrogen) as
during menstrual cycles. The superficial functionalis layer is the functional corpus luteum begins to regress. Decreased
sloughed off during menstruation, leaving intact the deeper levels of estrogen and progesterone cause the spiral arteries
basalis layer-the source of cells for regeneration of a new in the functionalis layer of the endometrium to constrict
functionalis layer. intermittently. This action deprives the functionalis layer of
The arterial supply to the endometrium is important to the oxygenated blood and produces transitory ischemia, necro-
menstrual cycle. Uterine arteries give rise to the arcuate sis, and shrinkage of the functionalis layer. After extended
arteries, which assume a circumferential course in the periods of vascular constriction, the spiral arteries dilate and
myometrium. These vessels divide into straight and spiral their walls rupture, leading to hemorrhage into the stroma.
arteries that supply blood to the endometrium. The straight The necrotic functionalis layer of the endometrium is then
arteries are short and supply the basalis layer of the shed in the menstrual flow. Blood, uterine fluid, stromal
endometrium, whereas the spiral arteries are long and coiled, cells, and epithelial cells from the functionalis layer mix to
and pass to the surface (functionalis) layer of the endometri- form the vaginal discharge. The shedding of the endometri-
um. In contrast to the straight arteries, the spiral arteries are um continues until only the raw surface of the basalis layer
highly sensitive to changes in hormone levels (estrogen and is left. The rapid proliferation of cells from the basalis layer,
progesterone) during the menstrual cycle. under the influence of rising levels of estrogen, restores the
During each menstrual cycle, the endometrium goes lost endometrial surface as the next phase of the menstrual
through three continuous phases, each phase gradually pass- cycle begins.

294 Organs
Section 1

Figure 19-1 Ovary: Dog (panoramic view)

Female Reproductive System 295

Figure 19-1 Ovary: Dog Ipanoramic viewl

The ovarian surface is covered by a single layer of low theca extern a (16), the granulosa cells (17), a large antrum
cuboidal or squamous cells called the germinal epithelium (18) filled with liquor folliculi (follicular fluid), and the
(1, 12). This layer is continuous with the mesothelium (14) cumulus oophorus (19), which contains the primary oocyte
of the viscera] peritoneum. Beneath the germinal epithelium (20). The smaller follicles with stratified granulosa cells
is a dense, connective tissue layer, the tunica albuginea (2). around the oocyte are the growing follicles (4, lower
The ovary has a peripheral cortex (8) and a central leader). Larger follicles with antral cavities of various sizes
medulla (24). The cortex (8) occupies the greater part of the are called secondary or antral follicles (7, 9, 28). These
ovary; its connective tissue stroma contains large, spindle- larger follicles are situated deeper in the cortex and are sur-
shaped fibroblasts. Compact collagen and reticular fibers rounded by modified stroma] cells, the theca folliculi (6).
course in all directions in the cortex (8). These cells differentiate into an inner secretory theca inter-
The medullary stroma (24) is a typical dense irregular na (16, upper leader) and an outer connective tissue theca
connective tissue, which is continuous with that of the meso- extern a (16, lower leader). Most of the illustrated large fol-
varium (13). Numerous blood vessels (10) in the medulla licles contain a primary oocyte (6, 20, 28) and its nucleus.
distribute smaller vessels to all parts of the cortex. The meso- In the primordial follicles the oocyte is small, but it gradua]-
varium (] 3) is covered by ovarian germinal epithelium (12) Iy increases in size in the primary, growing, and vesicular
and by peritonea] mesothelium (14). follicles.
Numerous ovarian follicles (3, 4, 7, 9, 16-20,22,25,28, Most follicles never attain maturity and undergo degener-
29) in various stages of development are located in the stro- ation (atresia) at various stages of growth, thus becoming
ma of the cortex (8). The detailed structure of some of these atretic follicles (11, 21, 26, 30; see also Fig. 19-4); these fo]-
follicles is illustrated in Figures] 9-2 and 19-3. The most licles are gradually replaced by the stroma.
numerou~ follicles are the primordial (3, 29, lower leader), After ovulation the follic]e collapses, its wall exhibits
located in the periphery of the cortex (8) and under the tuni- numerous folds, and the corpus luteum is formed (see Fig.
ca albuginea (2); these follicles are the smallest and simplest ] 9-4). Successive stages in corpus ]uteum regression are
in structure. The largest of the ovarian follicles is the mature indicated (5, 15, 23, 27). Figures 19-4 and 19-5 illustrate
follicle (16-20). Its various parts are the theca interna and these changes at a higher magnification.

296 Organs
Ovary: Dog

1 Germinal epithelium

2 Tunica albuginea

3 Primordial follicles

4 Follicular cells of a
primary and a small
growing follicle

5 Corpus albicans
(residue of a corpus

6 Secondary
follicle: theca folliculi

7 Antrum
(follicular cavity)
with fluid

8 Cortex

9 Vesicular (secondaryl
follicle: granulosa cells

10 Blood vessels in the


11 Atretic follicles

12 Ovarian germinal

13 Mesovarium

14 Peritonea I

Fig. 19-1 Ovary: Dog (panoramic view). Stain: hematoxylin-eosin. Low magnification.

Female Reproductive System 297

Figure 1 9-2 Ovary: Ovarian Cortex, Primary and Growing Follicles

The cuboidal germinal epithelium (1) lines the ovarian form the corona radiata (13); these cells are more columnar
surface. Beneath the surface epithelium is a layer of dense than the other granulosa cells. Between the corona radiata (13)
connective tissue, the tunica albuginea (2). Numerous pri- and surrounding oocyte is the noncellular glycoprotein layer,
mordial follicles (5, 6) are located immediately below the the zona pelludda (12). Stromal cells surrounding the tol-
tunica alhuginea (2j. Each primordial follicle (5, 6) consists lieular cells differentiale ioto the theca interna (9); at tllls
of a primary oocyte (5) surrounded by a single layer of stage of follicular development the theca extern a-the cell
squamous follicular cells (6). In larger follicles, the follicu- layer outside of the theca interna (9)-has not differentiated.
lar cells (7) change to cuboidal or low columnar. The developing oocyte (4) has a large eccentric nucleus (11)
In growing follicles (4), the follicular cells proliferate by with a conspicuous nucleolus.
mitotis (3), form layers of cuboidal cells called the granu- A degenerating atretic follicle (15) is illustrated in the
losa cells (10), and surround the primary oocyte (4, 11). The lower right corner of the illustration.
innermost layer of the granulosa cells surrounding the oocyte

Figure 1 9-3 Ovary: Wall of a Mature Follicle

This figure illustrates a portion of the mature follicle with A local thickening of the granulosa cells on one side of the
an oocyte (11). The area represented in this figure is compa- mature follicle encloses the mature oocyte (11) and projects
rable to the area in Figure 19-1 that illustrates the mature fol- into the antrum (8), forming a hillock called the cumulus
licle, cumulus oophorus with its oocyte and the different oophorus (12). The oocyte is surrounded by a prominent,
thecae layers (Fig. 19- I, 16, 19, 20). acidophilic-staining zona pellucida (10) and a single layer
Granulosa cells (6) enclose the central cavity or antrum of radially arranged corona radiata (9) cells that are
(8) of the follicle. The antrum (8) is filled with follicular fluid attached to the zona pellucida (] 0).
that has been secreted by the surrounding granulosa cells (6). The basal row of granulosa cells rests on a thin basement
Smaller isolated accumulations of the follicular fluid (14) membrane (5). Adjacent to the basement membrane is the
may also occur among the granulosa cells (6). Some of these theca interna (4), an inner layer of vascularized, secretory
fluid accumulations appear as clear or faintly acidophilic cells. Surrounding the theca interna cells (4) is the theca
vacuoles (3, 7); their origin and function are not known. externa (2), a layer of connective tissue cells.

298 Organs

8 Ovarian stroma

9 Theca interna

10 Granulosa cells

11 Nucleus of
primary oocyte

12 Zona pellucida

13 Corona radiata

14 Arteriole (tg. s.1

Fig. 19-2

7 Vacuole of
intercellular fluid

8 Antrum with
follicular fluid

9 Corona radiata

10 Zona pellucida

11 Oocyte

12 Cumulus

13 Mitosis

14 Intercellular
follicular fluid

Fig. 19-3 Ovary: Wall of a Mature Follicle. Stain: hematoxylin-eosin. High magnification.

Female Reproductive System 299

Figure 1 9-4 Human Ovary: Corpora Lutea and Atretic Follicles

This figure illustrates a newly formed corpus luteum, cor- leaves a fibrous, hyalinized scar, the corpus albicans (15).
pora lutea in various stages of regression, and several stages A large, normal follicle (17) exhibits the theca interna
of follicular atresia. (17a) and the thick granulosa cell layer (17b), separated by
The ovarian surface is covered by a single layer of ger- a thin basement membrane. The cumulus oophorus (17d)
minal epithelium (1). Lying directly underneath this layer is contains a normal oocyte (17e); the antrum (17c) is filled
a connective tissue layer, the tunica albuginia. The cortex (2, with follicular fluid.
18) constitutes the greater portion of the ovary and contains Numerous follicles undergo degenerative changes called
the follicles and corpora lutea. The medulla (7) occupies the atresia at any time before reaching maturity. Atresia in large
central region of the ovary. In the medulla (7) are found larg- follicles is gradual; however, serial changes of degeneration
er blood vessels that branch and supply the cortical region (2, can be recognized by noting follicles in different stages of
18) of the ovary. atresia. A follicle in an early stage of atresia (14) is illustrat-
The newly formed corpus luteum (3) is a large structure. ed. The theca interna (14a) and the granulosa cells (14b)
It is formed after the rupture of the mature follicle and the are intact; however, some of the cells are beginning to slough
collapse of its walls. The thin zone of theca lutein cells (4), off into the antrum (14e), which still contains follicular
formed from the theca interna cells of the follicle, is located fluid (14d). Also, cumulus oQphorus has been disrupted and
on the periphery of the corpus luteum (3) and in the contours degeneration of the oocyte is advanced. A remnant of the
of its folds. (see Figs. 19-5 and 19-6 for higher magnifica- oocyte, surrounded by thickened zona pellucida (14c), is
tion and more details.) The mass of the corpus luteum wall visible in the antrum.
(3) is formed from the granulosa lutein cells (5), which are A follicle in later atresia (13) is also illustrated. The
the hypertrophied granulosa cells of the follicle. The con- theca interna (13a) is still visible; however, the cells appear
nective tissue (6) from the theca externa proliferates, forms somewhat hypertrophied. The granulosa cells are no longer
the stroma for the blood vessels and capillaries in the wall of present; all of the cells have sloughed off and been resorbed.
corpus luteum, and fills the former follicular cavity (6). The basement membrane between these two layers has thick-
Also illustrated in the ovary is a portion of corpus luteum ened and folded and is now called the hypertrophied glassy
in moderate regression (10) with the plane of section pass- membrane (13b). Loose connective tissue is growing in
ing through its outer wall. The granulosa lutein cells are from the stroma (13e) and has partially filled the reduced
smaller, the nuclei pyknotic (10a), and larger blood vessels follicular cavity (13d), in which follicular fluid (13c) is still
(10b) are growing in from the stroma. The theca lutein cells present.
are not visible. With further atresia (9), connective tissue stroma
A later stage of corpus luteum regression (16) indicates replaces the theca interna cells (9a). The hypertrophied
further shrinkage of lutein cells, pyknosis of their nuclei glassy membrane (9b) becomes thicker and more folded
(16b), and a fibrous central core (16a). Connective tissue and the loose connective tissue with small blood vessels fills
invades the regressing luteal cells and replaces them as they the former antrum (9c). In the last stages of atresia (11),
degenerate. The stroma forms a capsule (16c) around the the entire follicle is replaced by connective tissue; the hyper-
regressing corpus luteum; however, this is not a constant fea- trophied and folded glassy membrane (II) remains for some
ture. Replacement by the connective tissue of all lutein cells time as the only indication of a follicle.

300 Organs

Human Ovary: Corpora Lutea and Atretic Follicles

1 Germinal

4 Theca lutein

5 Granulosa lutein

6 loose
connective tissue
in central cavity

7 Medulla
with blood vessels

Fig. 19-4 Human Ovary: Corpora Lutea and Atretic Follicles. Stain: hematoxylin-eosin. Low

Female Reproductive System 301

Figure 1 9-5 Corpus Luteum 'panoramic view)

At higher magnification, the corpus luteum appears as a former follicular cavity) contains remnants of follicular t1uid,
highly folded, thick mass of glandular epithelium (3), con- serum, occasional blood cells, and loose connective tissue
sisting primarily of granulosa lutein cells (3, upper leader) (8, 9) from the theca extern a, which has proliferated and pen-
and peripheral theca lutein cells (3, lower leader), which etrated the layers of the glandular tissue. The connective tis-
extend along the connective tissue septa (2, 7). The theca sue also covers the inner surface of the luteal cells (8) and
externa cells form a poorly defined capsule (1) around the then spreads throughout the core of the corpus luteum (9).
developing corpus luteum that also extends inward between The ovarian stroma (4) around the corpus luteum is
the folds (2, 7). The central core of the corpus luteum (the highly vascular (5).

Figure 1 9-6 Corpus Luteum: Peripheral Wall

The granulosa lutein cells (7) constitute the tnass of the smaller than granulosa lutein cells (7); their cytoplasm stains
corpus luteum. These cells are the hypertroph'ied former deeper and their nuclei are smaller and darker.
granulosa cells of the mature follicle. The granulosa cells are Numerous capillaries (4, 8) and fine connective tissue
large, and have large vesicular nuclei. These cells stain light- septa (6) from the theca externa are visible between the anas-
ly because of lipid inclusions. The theca lutein cells (2) (the tomosing columns of lutein cells.
former theca interna cells) remain external to the granulosa The connective tissue capsule (5) around the corpus
lutein celis on the periphery of the corpus luteum and in the luteum is poorly defined and the surrounding stroma (1, 3,
depressions between the folds. Theca lutein cells (2) are 4) remains highly vascular.

302 Organs
Corpus Luteum

5 Blood vessels
in the stroma

6 Theca lutein cells

along a septum
1 Capsule (former
theca external

2 Septum of 7 Septa of
connective tissue connective tissue

8 Connective tissue
covering of inner
luteal cells

3 Glandular epithelium. 9 Connective tissue

(granulosa lutein cells and coagulated
and theca lutein cells) fluid

4 Ovarian stroma

10 Blood clot

Fig. 19-5 Corpus Luteum (panoramic view). Stain: hematoxylin-eosin. Medium magnification.

1 Artery

6 Se.ptum of
2 Theca lutein cells connective tissue

7 Granulosa lutein
3 Vein

4 Capillary

8 Capillaries

5 Capsule (former
theca external

Fig. 19-6 Corpus Luteum: Peripheral Wall. Stain: hematoxylin-eosin. High magnification.

Female Reproductive System 303

Figure 19-7 Uterine Tube: Ampulla 'panoramic view, transverse section}

Extensive ramification of talJ mucosal folds (9) forms an smooth muscle layers, an inner circular layer (1) and an
irregular lumen in the uterine (falJopian) tube. The lumen outer longitudinal layer (6). The interstitial connective tis-
extends between the mucosal folds (9) and forms deep sue (2) is abundant and, as a result, the smooth muscle lay-
grooves in the tube. The lining epithelium (10) is simple ers-especially the outer layer-are not distinct. The serosa
columnar and the lamina propria (8) is a well vascularized, (7) forms the outermost layer on the uterine tube.
loose connective tissue. The muscularis consists of two

Figure 1 9-8 Uterine Tube: Mucosal Folds 'Early Proliferative Phase)

The lining epithelium is simple but may appear pseudo- ciliated celJs increases. The epithelium of the uterine tube
stratified. It consists of ciliated cells (1) and nonciliated peg shows cycle changes and the proportion of ciliated and non-
(secretory) celJs. During the early proliferative phase of the ciliated celJs varies with the stages of the menstrual cycle.
menstrual cycle, the ciliated celJs hypertrophy, exhibit cilia The lamina propria (2) is a highly cellular, loose con-
growth, and become predominant. Secretory activity in non- nective tissue with fine colJagen and reticular fibers.

Figure 1 9-9 Uterine Tube: Mucosal Folds 'Early Pregnancy)

During the luteal phase of the menstrual cycle and early protrude into tubular lumina. The secretory celJs (2) intermix
pregnancy, peg or secretory cells (2) predominate. These with ciliated cells (3) in the uterine tube.
cells appear slender, with elongated nuclei and apices that

304 Organs

Uterine Tube

Fig. 19-7 Uterine Tube: Ampulla (panoramic view, transverse section). Stain: hematoxylin-eosin.
Low magnification.

1 lamina

1 Simple
ciliated cells

2 Peg cells

3 Simple

Fig. 19-8 Uterine Tube: Mucosal Folds Fig. 19-9 Uterine Tube: Mucosal Folds
(Early Proliferative Phase). Stain: hematoxylin- (Early Pregnancy). Stain: hematoxylin-eosin.
eosin. High magnification. High magnification.

Female Reproductive System 305

Figure 1 9-1 0 Uterus: Proliferative 'Follicular) Phase

During a normal menstrual cycle, the endometrium usually straight in the superficial portion of the endometri-
exhibits a sequence of changes that are closely correlated um, but may exhibit branching in the deeper regions near the
with ovarian function. Cyclic activities in a nonpregnant myometrium. As a result, numerous uterine glands (4) are
uterus are divided into three distinct phases: a proliferative seen in cross sections.
(follicular) phase, a secretory (luteal) phase, and a menstrual During the proliferative phase of the cycle, coiled (spiral)
phase. The characteristic features of the endometrium during arteries (3) in cross section are seen primarily in the deeper
each of these phases are illustrated in detail in Figures 19-10, regions of the endometrium. As this stage (proliferative
19-11, and 19-12, respectively. phase), the coiled arteries (3) do not normally extend into the
The uterine wall consists of three layers: the inner superficial third portion of the endometrium, which, at this
endometrium (1, 2, 3, 4); a middle muscular layer time, contains veins and capillaries. The lamina propria (2)
myometrium (5, 6); and the outer serous membrane, the of the endometrium is cellular and resembles mesenchymal
perimetrium (not illustrated). The endometrium is further tissue. The branching fibroblasts are found in the network of
subdivided into two zones or layers: a narrow, deep basalis reticular and fine collagen fibers of the ground substance.
layer (8) adjacent to the myometrium (5) and the function- The connective tissue is more compact in the basilis layer
alis layer (7), a wider, superficial layer above the basalis (8) and appears somewhat darker in this illustration.
layer (8) that extends to the lumen of the uterus. The endometrium is firmly attached to the underlying,
The surface of the endometrium is lined with a simple highly vascular (10) myometrium (5, 6). This layer consists
columnar epithelium (1) overlaying the thick lamina pro. of compact bundles of smooth muscle (5, 6) separated by
pria (2). The surface epithelium (I) extends down into the thin strands of interstitial connective tissue (9). The bun-
connective tissue of the lamina propria (2) to form numerous dles of muscle are seen in cross, oblique, and longitudinal
long, tupular uterine glands (4). The uterine glands (4) are sections.

306 Organs

Uterus: Proliferative (Follicular) Phase

2 Lamina propria

3 Coiled arteries

4 Uterine glands

5 Smooth muscle

::::::::==- 9 Interstl
6 Smooth muscle connective tissue
(cross section)


::::::=- 10 Blood vessels

Fig. 19-10 Uterus: Proliferative (Follicular) Phase. Stain: hematoxylin-eosin. Low magnification.

Female Reproductive System 307

Figure 1 9-11 Uterus: Secretory (Luteal) Phase

During the secretory (luteal) phase of the menstrual cycle, become prominent in the uterine sections because of their
the functionalis layer (1) and basalis layer (2) of the thicker walls.
endometrium become thicker because of increased glandu- The alterations in the surface columnar epithelium (4),
lar secretion (5) and edema in the lamina propria (6). The uterine glands (5), and lamina propria (6) characterize the
epithelium of the uterine glands (5, 8) hypertrophies functionalis layer (I) of the endometrium during the secreto-
because of the accumulation of large quantities of secretory ry or luteal phase of the menstrual cycle. The basalis layer (2)
product (5, 8). The uterine glands (5, 8) become highly tor- exhibits minimal changes. Below the basalis layer is the
tuous and their lumina become dilated and filled with nutri- prominent myometrium (3), composed of smooth muscle
tive secretory material (5) that is rich in carbohydrates. The bundles (10) sectioned in both longitudinal and transverse
coiled arteries (7) now extend into the upper portion of the planes, and numerous blood vessels (9).
endometrium (functionalis layer) (I). These blood vessels (7)

308 Organs
Uterus: Secretory (Luteal) Phase

4 Columnar

5 Uterine
(with secretion)

1 Functionalis
6 lamina
(with edema)

7 Coiled

B Uterine glands
and tortuous)

2 Basalis layer

9 Blood vessel
1D Smooth
3 Myometrium

Fig. 19-11 Uterus: Secretory (Luteal) Phase. Stain: hematoxylin-eosin. Low magnification.

Female Reproductive System 309

Figure 19-12 Uterus: Menstrual Phase

During every menstrual cycle, the endometrium (1) in contains aggregations of erythrocytes (8); these have been
the functionalis layer is sloughed off during the menstrual extruded from the torn and disintegrating blood vessels. In
phase. The endometrium that is shed contains fragments of addition, endometrial stroma (6) exhibits moderate infiltra-
disintegrated stroma (6), blood clots (7), and uterine tion of lymphocytes and neutrophils.
glands. Some of the intact uterine glands (2) are filled with The basalis layer (4) of the endometrium remains gener-
blood. In the deeper layers of the endometrium, the basalis ally unaffected during this phase. The distal (superficial) por-
layer (4), the bases of the uterine glands (9) remain intact tions of the coiled arteries (3) become necrotic and the
during the menstrual flow. deeper parts of these vessels remain intact.
The endometrial stroma of most of the functionalis layer

310 Organs
Uterus: Menstrual Phase

1 Superficial
without epithelium

6 Fragments of
disintegrated stroma

2 Glandular lumen
filled with blood

7 Blood clots

3 Coiled arteries

8 Erythrocytes in
lamina propria

9 Intact bases of
uterine glands
4 Interglandular
lamina propria
of basal region

5 Smooth muscle
fibers (myometriuml

Fig. 19-12 Uterus: Menstrual Phase. Stain: hematoxylin-eosin. Low magnification.

Female Reproductive System 311

Section 2 Cervix, Vagina, Placenta, and Mammary Glands

Cervixand Vagina and produces sufficient amounts of progesterone to maintain

Unlike the functionalis layer of the uterine endometrium, pregnancy until birth. The placenta also produces placental
the cervical mucosa is not shed during menstruation. The lactogen, a hormone that promotes growth and development
cervix does, however, contain numerous glands, and these of the materna] mammary glands in some species.
exhibit altered secretory activities during the menstrual
cycle. The secretion of the cervical glands is thin and watery Mammary Glands
during the proliferative phase of the menstrual cycle. This The adult mammary gland consists of individual branched
type of secretion allows easier passage of sperm into the tubuloalveolar glands. The inactive mammary gland consists
uterus. During the luteal phase, the cervical secretion primarily of duct elements. Inactive mammary glands exhib-
becomes,highly viscous and hinders the passage of sperm or it slight cyclic alterations during the course of the menstrual
microorganisms into the uterus. cycle. Under estrogenic stimulation, the secretory cells
Like the cervical mucosa, the vaginal mucosa is not shed increase in height. Lumina appear in the ducts as a small
during menstruation. The vaginal epithelium does, however, amount of secretory material is accumulated.
exhibit cyclic changes during the menstrual cycle. During the During pregnancy, extensive growth of the mammary
follicular phase and estrogenic stimulation, the vaginal glands is promoted by the continuous and prolonged produc-
epithelium thickens. The vagina] cells synthesize and accu- tion of estrogen and progesterone. These hormones are pro-
mu]ate increased amounts of glycogen as they migrate duced initially by the corpus luteum of the ovary, and later by
toward and are desquamated into the lumen. Bacteria in the the placenta. ]n addition, further growth of the mammary
vagina metabolize the glycogen and increase the acidity of glands depends on the pituitary hormone prolactin, placental
the vaginal canal. lactogenic hormone, and adrenal corticoids. These hormones
Placenta stimulate the intralobular ducts of the mammary glands to
proliferate rapidly, branch, and form numerous a]veoli. The
During pregnancy, the fertilized ovum implants in the
alveoli then hypertrophy and become active sites of milk
endometrium and forms a placenta. The placenta consists of
secretion during lactation. At the end of pregnancy, the a]ve-
a fetal portion, formed by the chorionic plate and its branch-
oli produce a fluid called colostrum; it is rich in proteins and
ing villi, and a maternal portion, formed by the decidua
antibodies. Unlike milk, however, colostrum contains little
basalis of the endometrium. Fetal and maternal blood come
into close proximity in the placenta, where exchange of nutri-
After parturition (birth), circulating levels of estrogen and
ents, electrolytes, hormones, gaseous products, and waste
progesterone decrease in the blood, and the mammary glands
metabolites takes place.
begin active secretion of milk, which is promoted by the hor-
The placenta also serves as a temporary-yet major-
endocrine organ that produces essential hormones for the mone prolactin. During feeding, the tactile stimulation pro-
maintenance of pregnancy. P]acental cells (syncytial tro- vided by suckling by the infant promotes further release of
phoblasts) secrete the hormone chorionic gonadotropin prolactin, and milk production is prolonged. ]n addition, tac-
shortly after implantation of the fertilized egg. Chorionic tile stimulation of the nipple also initiates the milk ejection
gonadotropin is similar to luteinizing hormone (LH) in struc- reflex. This reflex causes the release of the hormone oxytocin
ture and function, and it maintains the corpus luteum during from the neurohypophysis of the pituitary gland. Oxytocin
the early stages of pregnancy. Chorionic gonadotropin also induces the contraction of myoepithe]ial cells around the
stimulates the corpus luteum to produce estrogen and pro- secretory alveoli and excretory ducts in the mammary glands,
gesterone, the two hormones that are essential for producing causing ejection of the accumulated milk from the mammary
a favorable uterine environment and maintaining the preg- glands toward the nipple.
nancy. Decreased nursing and suckling by the infant soon results
As pregnancy proceeds, the placenta takes over produc- in the cessation of milk production and eventual regression
tion of estrogen and progesterone from the corpus luteum of the mammary glands to an inactive state.

312 Organs


Section 2

Figure 19-13 Cervix, Cervical Canal, and Vaginal Fornix (longitudinal section)

Female Reproductive System 313

Figure 19-13 Cervix, Cervical Canal, and Vaginal Fornix "ongitudina'

The cervix is the lower part of the uterus. This figure illus- The lower end of the cervix, the os cervix (6), bulges into
trates a longitudinal plane of section through the cervix, the the lumen of the vaginal canal (13). The columnar epitheli-
endocervix or cervical canal (5), a portion of the vaginal um (2) of the cervical canal (5) at the lower end abruptly
fornix (8), and the vaginal wall (10). The cervical canal (5) changes to nonkeratinized stratified squamous epithelium.
is lined with tall, mucus-secreting columnar epithelium (2). This epithelium lines the vaginal portion of the cervix, called
This epithelium differs from the uterine epithelium with the portio vaginalis (7), as well as the external surface of the
which it is continuous. Similar epithelium also lines the vaginal fornix (8). At the base of the fornix the epithelium (7)
numerous highly branched and tubular cervical glands (3) of the vagina cervix reflects back to become the vaginal
which extend at an oblique angle to the cervical canal (5) epithelium (9) of the vaginal wall (10). The details of the
deep into the wide lamina propria (12). Some of these cer- vaginal wall are illustrated in greater detail in Fig. 19-17.
vical glands may become occluded and develop into small The smooth muscle of the muscularis (1) layer in the
cysts (4). The connective tissue in the lamina propria (12) of cervix is not as compact as in the body of the uterus; howev-
the cervix is more fibrous than in the uterus. Blood vessels, er, both the muscularis (I) and the lamina propria (12) are
nerves, and occasional lymphatic nodules (11) may be seen. well vascularized.

314 Organs
Cervix, Cervical Canal, and Vaginal Fornix

Female Reproductive System 315

Figure 1 9-1 4 Vagina ,'ongitudina' section)

The vaginal mucosa is highly irregular and exhibits tissue (8), lymphatic nodules (4), and numerous small
numerous folds (1). The epithelium lining the surface of the blood vessels (arterioles and venules) (9) are usually
vaginal canal is noncornified stratified squamous (2). observed in the lamina propria (7).
Connective tissue papillae (3) below the epithelium are The muscularis consists predominantly of longitudinal
prominent and val)' in height. (Sa) and oblique bundles of smooth muscle fibers. The
The wide lamina propria (7) contains moderately dense, transverse muscle fibers (5b) are less numerous but more
irregular connective tissue that is rich in elastic fibers. Fibers frequently found in the inner layers. The interstitial connec-
from the lamina propria extend down and pass into the mus- tive tissue (10) is rich in elastic fibers and the adventitia (6,
cularis layer as interstitial fibers (10). Diffuse lymphatic 12) contains blood vessels (11) and nerve bundles.

Figure 19-15 Glycogen in Human Vaginal Epithelium

Glycogen is a prominent component of the vaginal epithe- phase of the cycle is illustrated in (A). During the follicular
lium except in the deepest layers, where it is minimal or lack- phase. glycogen content increases in the cells of the interme-
ing. During the follicular phase of the menstrual cycle, diate and the more superficial layers (B).
glycogen accumulates in the vaginal epithelium, reaching its The tissue sample illustrated in (C) is from the same spec-
maximum level before ovulation. Glycogen can be demon- imen as in (B), but was fixed by the Altmann-Gersch method
strated by iodine vapor or iodine solution in mineral oil (freezing and drying in a vacuum). This method produces
(Mancini's method); glycogen stains a reddish purple. less tissue shrinkage and illustrates abundant glycogen dur-
The vaginal specimens in illus~rations (A) and (B) were ing the follicular phase, and its diffuse distribution through-
fixed in absolute alcohol and formaldehyde. The amount of out the vaginal epithelium.
glycogen in the vaginal epithelium during the interfollicular

316 Organs

1 Mucosal folds -

~ ? c.'t\tmIDrmiA

- 8 Lymphatic

. 9 Blood vessels

- 10 Interstitial

,11 Blood vessels

. 12 Adventitia

Fig.19-14 Vagina (longitudinal section). Stain: hematoxylin-eosin. Low magnification.

A. Interlollicular phase B. Follicular phase c. Follicular phase

Fig. 19-15 Glycogen in Human Vaginal Epithelium. Stain: Mancinis iodine technique. Medium

Female Reproductive System 317

Figure 19-16 Vaginal Smears During Various Reproductive Phases

This figure ilJustrates cells in vaginal smears obtained genic stimulation normally observed before ovulation and is
from normal woman during the menstrual cycle, early preg- called the "follicular smear." The superficial cells (8)
nancy, and menopause. The Shorr's trichrome stain "mature" with increased estrogen levels and become acid-
(Bierbrich scarlet, orange G, and fast green) plus Harris' ophilic. A similar type of smear can be obtained from a
hematoxylin facilitates recognition of different cell types. menopausal woman treated with high doses of estrogen.
Figure G illustrates individual celJ types observed in a Figure C represents a vaginal smear taken during the
normal vaginal smear. The superficial acidophilic cell (a) of luteal (progestational) phase (21 st day of the menstrual
the vaginal mucosa appears flat and somewhat irregular in cycle). This phase is indicative of increased levels of proges-
outline, measures from 35 to 65 ,um in diameter, exhibits a terone. Predominant are large cells from the intermediate
smalJ nucleus, and contains cytoplasm stained light orange. layers (3) (precornified superficial cells) with folded borders
Adjacent to the acidophilic cell (a) is a similar superficial that aggregate into clumps. Superficial acidophilic cells (4),
basophilic cell (b) with blue-green cytoplasm. Illustration superficial basophilic cells (5), and leukocytes are scarce.
(c) is a celJ from the intermediate stratum of the vaginal The cells in Figure D represent the vaginal smear during
epithelium. It is flattened like the superficial cells but is the premenstrual phase (28th day of the menstrual cycle).
smalJer, measuring 20 to 40 ,um in diameter, and has a This stage is characterized by a great predominance of
basophilic blue-green cytoplasm. The nucleus is somewhat grouped intermediate cells (13, 14) with folded borders, an
larger than that of the superficial cells, and is often vesicular. increase of neutrophilic cells (12), a scarcity of superficial
Illustration (d) depicts intermediate cells in profile, charac- cells (11), and an abundance of mucus, which blurs the
terized by their elongated form with folded borders and elon- preparations.
gated, eccentric nucleus. Illustration (e) depicts basal cells, Figure E illustrates a vaginal smear taken from a 3-month
the cells of the internal basal layers of the vaginal epithelium. pregnancy, illustrating predominantly cells from the interme-
The larger cells are from the external portion of the basal lay- diate layers, many with folded borders (6). These cells typ-
ers. The smaller parabasal cells are from the more superfi- ically form dense groups or conglomerations (7). Cells from
cial portion of the basal layers. All basal cells are oval, mea- superficial layers and neutrophilic cells are scarce.
sure from 12 to 15,um in diameter, and exhibit a large nucle- The vaginal smear during menopause (Figure F) is differ-
us with a prominent chromatin. Most of these cells exhibit ent from all other phases. In a typical "atrophic" smear, the
basophilic staining. predominant cells are the oval basal cells (17) of various
Figure A illustrates a vaginal smear taken during the fifth sizes. Cells from the intermediate layers (15) are scarce,
day of the menstrual cycle (postmenstrual phase). The inter- whereas the neutrophilic cells (16) are abundant.
mediate cells (1) from the outer layers of the intermediate Menopausal smears vary according to the stage of
layer (transitions to the deeper superficial cells) are predom- menopause and estrogen levels.
inant. A few superficial acidophilic and basophilic (2) cells Vaginal exfoliate cytology is closely correlated with the
and leukocytes are present. ovarian cycle. Understanding its characteristic features per-
Figure B represents a vaginal smear collected during the mits recognition of follicular activity during normal men-
ovulatory phase (14th day) of the menstrual cycle. This strual phases or after estrogenic and other therapy. Also,
phase is characterized by predominance of large superficial exfoliate cytology provides important information (together
acidophilic cells (8), the scarcity of superficial basophilic with cells from the endocervix) for detecting regional patho-
cells (10) and intermediate cells (9), and the absence of logic or malignant conditions.
leukocytes. This smear is characteristic of the high estro-

318 Organs
Vagina: Exfoliate Cytology

a. Superficial b. Superficial c.lntermediate d.lntermediate e. Basal and parabasal

acidophilic cell basophilic cell cell (navicular) cells: basophilic and
cell in profile acidophilic cells
G. Detail of Individual Cells (high magnification).
Fig. 19-16 Vaginal Smears During Various Reproductive Phases. Stain: Shorrs trichrome. Medium

Female Reproductive System 319

Figure f 9- f 7 Placenta at Five Months (panoramic view}

The upper region in the figure illustrates the fetal portion sections of the anchoring villi (4, lower leader). These
of the placenta (10, 11). This includes the chorionic plate increase in size and complexity during pregnancy.
(10) and the villi (4, 5, 7) arising from it. The maternal pla- Numerous floating villi (chorion frondosum) (5, 11) are
centa is the decidua basalis (8) and includes the functional is seen. sectioned in various planes because of their outgrowth
layer of the endometrium (12, 13, 14), which lies directly in all directions from the anchoring villi (7). These villi
beneath the fetal placenta (10, II). Below this region is the "float" in the intervillous spaces (6), which are bathed in
basalis layer of the endometrium, containing the basal parts maternal blood. The structures of these villi are illustrated in
of the uterine glands (15); this region is not shed during par- detail in Figure 19-14.
turition. A portion of the myometrium (17) is visible in the The maternal portion of the placenta, the decidua basalis
lower right field of the figure. (8), contains embedded anchoring villi (7), groups of large
The surface of the amnion (1) is lined by the squamous decidual cells (8), and typical stroma. Also seen in the decid-
epithelium. The underlying layer represents the merged con- ua basalis (8) are the distal portions of the uterine glands (14)
nective tissue (2) of the amnion and chorion. Below the con- in various stages of regression. and maternal blood vessels
nective tissue layer (2) is the trophoblast of the chorion (3, (9), recognizable by their size or by red blood cells in their
10), details of which are not distinguishable at this magnifi- lumina. A maternal blood vessel opening into an intervillous
cation. The trophoblast (3, 10) and the underlying connective space (13) is visible.
tissue (2) form the chorionic plate (10). Coiled arteries (16) and basal portions of the uterine
The anchoring villi (4, 7) arise from the chorionic plate glands (15) are present deep in the endometrium. Fibrin
(10), extend to the uterine wall, and embed in the decidua deposits (12) appear on the surface of the decidua basalis
basalis (8). This continuity is not seen in this illustration; (8) and increase in volume and extent as the pregnancy con-
however. larger units in the fetal placenta probably represent tinues.

Figure 19-18 Chorionic Villi: Placenta at Five Months

Several chorionic villi are illustrated at a higher magnifi- which are branches of umbilical arteries and veins; both
cation from a placenta at 5 months of pregnancy. The tro- nucleated and non-nucleated erythrocytes may be present.
phoblast epithelium consists of an outer layer of syncytial The intervillous spaces (4) are bathed by maternal blood and
cells, the syncytiotrophoblast (1), and an inner layer of the erythrocytes are non-nucleated. One of the illustrated
cells, the cytotrophoblast (2). The core of the villus contains villi is attached to the endometrium (6) and several decid-
embryonic connective tissue (3) and fetal blood vessels (5), ual cells (7) are seen in the stroma.

Figure 19-19 Chorionic Villi: Placenta at Term

Several chorionic villi are illustrated from a placenta at tiated. illustrating more fibers. fewer typical fibroblasts. and
term. In contrast to the villi in Figure 19-14. the chorionic numerous large. round macrophages (Hofbauer cells) (4).
epithelium in these villi is observed only as syncytiotro- Fetal blood vessels (3) are numerous, having increased in
phoblast (I); its syncytial character is more pronounced than complexity during pregnancy.
in Figure 19- 14. The connective tissue (2) is more differen-

320 Organs

Fig. 19-17

1 SVncytiotrophoblast

2 Connective tissue
4 Intervillous space
5 Fetal blood cells
3 Fetal blood vessels

6 Attached villus

7 Decidual cell

Fig. 19-18 Chorionic Villi: Placenta at Five Fig. 19-19 Chorionic Villi: Placenta at
Months. Stain: hematoxylin-eosin. High Term. Stain: hematoxylin-eosin. High magnification.

Female Reproductive System 321

Figure (10-20) mammary ciana martve

The mammary gland (breast) consists of 15 to 25 lobes. These tubules resemble ducts and remain in this state as long
each of which is an individual compound tubulo-alveolar as the mammary gland remains inactive. Some cyclic
type of gland (see Fig. I-I I and accompanying text). Each changes may be seen in the mammary gland; however, these
glandular lobe is separated by interlobar stroma and has its regress at the end of the menstrual cycle. Occasionally a
own lactiferous duct. which emerges independently onto the more defined tubule is seen, such as a small intralobular
surface of the nipple. The interlobar stroma consists of dense duct (6) or a large intralobular excretory duct (8) that
connective tissue and varying amounts of fat (11). Each lobe emerges from the lobule to join the interlobular duct.
contains interlobular connective tissue (2, 4) between indi- Potential tubules may be present as undifferentiated solid
vidual lobules. One complete mammary gland lobule and a cords of cells (5).
portion of another lobule (I) are illustrated here. The excretory tubules are surrounded by a loose. fine con-
The inactive mammary gland is characterized by an abun- nective tissue, the intralobular connective tissue (4), which
dance of connective tissue and a minimum of glandular ele- contains fibroblasts, lymphocytes, plasma cells, and
ments. The lobule contains groups of small tubules (3, 10) eosinophils. Surrounding this region is the dense interlobular
that are lined with cuboidal or low columnar epithelium. connective tissue (2) and adipose tissue (ll).

Figure 1 9-21 Mammary Gland During First Half of Pregnancy

The mammary gland exhibits extensive structural changes the loose intralobular connective tissue (7) appears
in preparation for lactation. During the first half of the preg- reduced. On the other hand, there is an increased infiltration
nancy. the intralobular ducts undergo rapid proliferation and of lymphocytes and other cells. The interlobular dense con-
form terminal buds, which differentiate into alveoli (2, 6). nective tissue (3) appears as septa between the developing
Most of the alveoli are empty: however. some may contain a lobules (I). The interlobular excretory ducts (4) that are
secretory product (5). At this stage of mammary gland lined with taller columnar cells course in the interlobular
development. it is difficult to distinguish between small septa (3) and empty into the large lactiferous ducts (8),
intralobular excretory ducts (9) and alveoli (2. 6). The which are usually lined with low pseudostratified columnar
ducts appear more regular in outline and have a more distinct epithelium. Each lactiferous duct (8) collects the secretory
epithelial lining (9). product of a lobe and transports it to the nipple.
The glandular lobules contain numerous alveoli (2, 6) and

322 Organs
Mammary Gland

1 Part of a lobule

8 Intralobular excretory

2 Interlobular dense
connective tissue

3 Tubules 9 Arterioles

4 Intralobular loose
connective tissue

10 Tubules

5 Solid cord of cells

7 Artery and vein 11 Adipose cells

Fig. 19-20

6 Glandular