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I t:1":'!':r
I
I COLORATLAS
of
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urth edition
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LESLIEP. GARTNER,PH.D.
I Professor
of Anatomu

I JAMESL. HIATT,PH.D.
AssociateProfessorof Anatoma(Retired)
t
I Departmentof BiomedicalSciences
Baltimore llegeof DentalSurgerg
DentalSchool
I Universitgof Margland
Baltimore,Margland
I
r
I
I ^(D'
-7 LIppINCOTT
\XiILLIAMS
f' WIxnS
Kluwer
A Wolters Company
I . Baltimore
Philadelphia
Buenos
. NewYork. London
Aires. HongKong. Sydney. Tokyo

I
AcquisitionsEditor: Betty Sun
ManagingEditor: CrystalTaylor
Marketing Manager:JosephSchott
Production Editor: JenniferGlazer
Designer:RisaClow
Compositor:Maryland Composition
Printer: RR Donnelley-Willard

Copyright o 2006Lippincott Williams & Wilkins

351 West CamdenStreet

Baltimore,Maryland 21201-2436U SA,

530 Walnut Street

Philadelphia,Pennsylvania19106-3621US

All rights reserved.This book is protectedby copyright.No part ofthis book may be reproducedin any form or
by any means,including photocopying,or utilized by any information storageand retrievalsystemwithout writ-
ten permissionfrom the copyrightowner.

The publisheris not responsible(asa matter ofproduct liability, negligence,or otherwise)for any injury resulting
from any materialcontainedherein.This publicationcontainsinformation relatingto generalprinciplesofmed-
ical carethat should not be construedas specificinstructionsfor individual patients.Manufacturers'product in-
formation and packageinsertsshould be reviewedfor current information, including contraindications,dosages,
and precautions.

Printed in the United Statesof America.

First Edition, 1990

SecondEdition, 1994
Third Edition,2000

Translations:
Chinese(Taiwan),Ho-Chi Book PublishingCompany,2002
Chinese(Mainland China), Liaoning EducationPress/CITIC,2004
Greek,Parissianos, 2003
Italian, MassonItalia, 1999
f apanese,Igaku-Shoin,1997
Portuguese,Editora GuanabaraKoogan,2002
Spanish,Editorial Medica Panamericana,2002

Library of CongressCataloging-in-Publication Data

Gartner,LeslieP.. 1943-
Color atlasof histology/ LeslieP. Gartner,]amesL. Hiatt.- 4th ed.
P; cm'
Includesindex
ISBN 0-7817-s216-7- ISBN 0-7817-9828-0
1. Histology-Atlases. I. Hiatt, IamesL., 1934- II. Title. IDNLM: t. Histology-
Atlases.QS 517 G244c20061
Q M s s 7 . G 3 82 0 0 6
611'.018'0222-dc22
2005002800

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The favorable reception accorded the previous three
editions of our Color Atlasof Histology,as eiidencedby its
many reprints and its translations into eight foreign lan-
guages,hasbeen most gratifring and has sewed asan im-
petus to face the labor of preparing a new edition. We
have receivednumerous suggestionsfrom colleaguesand
students, many of which were implemented toward the
end of improving the atlas and making it more "user
friendly."
All ofthe photomicrographs havebeen retakenasdig-
itaLimagesfor the current edition to enhancethe quality
and clarity of the imagespresentedfor the student.Also,
we have made severalchangesin this edition by the addi-
tion of new photomicrographsdepicting regionsof the
oral cavity. Moreover, thumbnails of the pertinent four-
color illustrations that are present in eachchapter are in-
corporated as illustrative guideposts among the legends
to the photomicrographs and have been titled appropri-
ately. These illustrations are designedto trigger the stu-
dent's memory by providing a three-dimensionalrepre-
sentationof the two-dimensionalphotomicrographson
the facing page.These should prove to be helpful to the
student in providing a framework on which the student
may basedetailed knowledge of histology.
The didacticinformation appearsat the beginningof
eachchapter,and in this edition we added to the num-
ber of relevant clinical considerations to illustrate the
importanceand the pertinenceof Histologyto the Med-
ical Sciences.It was our intent to summarize in these
few pagesthat introduce each chapter the essentialcon-
cepts necessaryto the understandingof histology. We
also re-titled the section previouslyentitled "Histologi-
cal Organization" to its new title "Summary of Histo-
logical Organization," to reflect the true intent of that
section. We maintained the use of bold-faced type in the
text of eachchapter, highlighting important words to fa-
cilitate a quick recall of the material for the student, and
the expandedcross-referenced index to assistthe stu-
dent in locating items of interest.
As in the previous editions, most of the photomicro-
graphs of this atlas are of tissuesstained with hema-
toxylin and eosin. Each figure is supplied with a final
magnification,which takesinto considerationthe pho-
tographic enlargement, as well as that achieved by the
microscope.Many of the sectionswere prepared from
plastic-embeddedspecimens,as noted. Most of the
Iffi II
Preface
exquisite electron micrographs included in this atlas
were kindly provided by our colleaguesthroughout the
world as identified in the legends.
As with all of our textbooks, this Atlas has been writ-
ten with the student in mind, thus the material is com-
plete but not esoteric.We wish to help the student learn
and enjoy histology, not be overwhelmed by it. Further-
more, this Atlas is designednot only for use in the labo-
ratory, but alsoaspreparation for both didactic and prac-
tical examinations. Although we have attemPted to be
accurate and complete, we know that errors and omis-
sionsmay haveescapedour attention.Therefore,we wel-
come criticisms,suggestions,and comments that could
help improve this atlas.
INTERACTIVECOLORATLAS OF
HISTOLOGYCD.ROM
We are pleasedto announce that with this edition we
have expanded the companion CD-ROM, Intetactrve
Color Atlas of Histology. It contains every photomicro-
graph and electron micrograph and accompanyrnqleg-
inds present in the Atlas. The student has the capability
to study selectchapters or to look up a particular item
via a keyword search. Images may be viewed with or
without labels and/or legends, enlarged using the
"zoom" feature, and compared side-by-sideto other im-
ages.Also, the updated software now allows students to
self-teston all labelsusing the "hotspot" mode, facilitat-
ing learning and preparation for practical examinations.
For examination purPoses, the CD contains over 300
additional photomicrographswith more than 700 inter-
active fill-in and true/false questionsorganized in a fash-
ion to facilitatethe student'slearning and preparation
for practical exams.Additionally, we have included ap-
proximately 100 new USMLE Part I format multiple-
choice questions,based on photomicrographs created
specificallyfor the questions' that can be accessedin test
or study mode. The Student Version of the CD is rn-
cluded with this Atlas. In the Institutional Version, im-
agescan be exported for use in PowerPoint presenta-
tions. Visit LWW.com or contact your local LrvVWsales
representativefor information about purchasing the In-
stitutional Version of the CD.
Preface el vii
I
I II-IT
I
r Acknowl
I
We would like to thank Todd Smith for the ren- Editor; Crystal Taylor, Senior Managing Editor; Kathleen

I dering of the outstanding full-color platesand thumbnail

figures, ferry Gadd for his paintings of blood cells, and
Scogna, Senior Developmental Editor; Jennifer Glazer'
Production Editor; and Erica Lukenich' Editorial Assistant.
We would alsolike to thank the softwaredevelopersat Lip-
our many colleagueswho provided us with electron mi-

I crographs.We are especiallythankful to Dr. StephenW.

Carmichael of the Mayo Medical School for his sugges-
tions concerning the suprarenal medulla. Additionally,
we are grateful to our good friends at Lippincott Williams

I & Wilkins, including Betty Sun, Executive Acquisitions

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I Acknowledgments il ix
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I IIIII
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I Contents
I
Preface vii
t ..
Acknowledgments ix
.^.

r .-r.
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l I|€

GRAPHIC 1-1
--ll
LQrr

The Cell
l
6

I 1-2
1-3
The Organelles. .
Membranesand Membrane Trafficking . . .
7
8
1-4 Protein Synthesisand Exocytosis . . . 9

I PLATE 1-1
1-2
Typical Cell . .
Cell Organellesand Inclusions
10
12
1-3 Cell SurfaceModifications . . . L4

t 1-4
1-5
Mitosis, Light and Electron Microscopy
Typical Cell, ElectronMicroscopy . . . .
t6
18
1-6 Nucleusand Cytoplasm,ElectronMicroscopy 20

r 1-7
1-8
1-9
Nucleus and Cytoplasm,Electron Microscopy
Golgi Apparatus,ElectronMicroscopy . . . .
Mitochondria, ElectronMicroscopy
22
23
24

I 1@ Epitheliumand Glands 25
I GRAPHIC 2-1
2-2
functional Complex
SalivaryGland
30
3l
PL|TE 2-1 Simple Epithelia and PseudostratifiedEpithelium 32
I 2-2
2-3
Stratified Epithelia and Transitional Epithelium .
PseudostratifiedCiliated Columnar Epithelium,
34

ElectronMicroscopy 36
t 2-4
2-5
EpithelialJunctions,ElectronMicroscopy
Glands
38
40
2-6 Glands 42
I
Tissue
Connective 45
I IC 3-1 Collagen 52
3-2 ConnectiveTissueCells . 53

a PLATE 3-1
3-2
3-3
Embryonic and ConnectiveTissueProper I . . . .
ConnectiveTissueProper II . . . .
ConnectiveTissueProperIII . . .
54
56
58

I Contents t x i
 3-4 Fibroblastsand Collagen,ElectronMicroscopy
3-5 Mast Cell, ElectronMicroscopy
60
6I
r
3-6 Mast Cell Degranulation,ElectronMicroscopy
3-7 DevelopingFat Cell, ElectronMicroscopy
62
63 I
&"
w
Cartilageand Bone 65 I
GRAPHIC4-1 CompactBone . 72
4-2
PLATE4-1
EndochondralBone Formation
Embryonicand Hyaline Cartilages
73
74
t
4-2 Elasticand Fibrocartilages 76
4-3
4-4
CompactBone .
CompactBone and IntramembranousOssification
78
80
t
4-5 EndochondralOssification . . 82
4-6
4-7
EndochondralOssification. .
Hyaline Cartilage,ElectronMicroscopy
84
86
I
4-8 Osteoblasts,ElectronMicroscopy
4-9 Osteoclast,ElectronMicroscopy
87
88 r
Blood and Hemopoiesis
TE 5-1 CirculatingBlood
89
95
r
5-2 CirculatingBlood
5-j
5-4
Blood and Hemopoiesis
Bone Marrow and CirculatingBlood
96
97
98
r
5-5 Erythropoiesis
5-6 Granulocytopoiesis
100
101 I
Muscle l0S I
HIC 6-1 Molecular Structure of SkeletalMuscle 108
6-2
PLATE6-1
Tlpes of Muscle
SkeletalMuscle
109
110
I
6-2 SkeletalMuscle,ElectronMicroscopy ll2
6-3
6-4
Myoneural |unction, Light and ElectronMicroscopy
Myoneural function, ScanningElectronMicroscopy
II4
l 16
I
6-5 MuscleSpindle,Light and ElectronMicroscopy ll7
6-6
6-7
SmoothMuscle
Smooth Muscle,ElectronMicroscopy
l1g
I20
I
6-8 CardiacMuscle I22
6-9 CardiacMuscle,ElectronMicroscopy I24 I
NervousTissue
PHIC 7-1 Spinal Nerve Morphology
r25
r32
r
7-2 Neurons and Myoneural Junction r33
PLATE 7-1
7-2
SpinalCord
Cerebellum,Sy'napse,
134 I
Electron Microscopy 136
7-3 Cerebrum,NeuroglialCells .
7-4 SympatheticGanglia,SensoryGanglia
138
140 I
xii * Contents r
I 7-5 PeripheralNerye, Choroid Plexus I42
144
7-6 PeripheralNerve,ElectronMicroscopy
146
t 7-7 Neuron Cell Body,ElectronMicroscopy

g System
Circulatory 147
I GMPHIC 8-1 ArteryandVein 154
8-2 CapillaryTypes 155

I PLATE8-1
8-2
ElasticArtery
MuscularArtery,Vein .
156
158
8-3 Ly-ph Vessels
Arterioles,Venules,Capillaries, 160
I 8-4
8-5
Heart .
Capillary,ElectronMicroscopy
r62
t64
8-6 Freeze Capillary,ElectronMicroscopy
Etch,Fenestrated 165
I r67
e Tissue
Lymphoid
r GRAPHIC 9-1
9-2
Lymphoid Tissues
Ly,oph Node, Thymus, and Spleen
175
176
9-i B Memory and PlasmaCell Formation . . t77
I 9-4 Cytotoxic T Cell Activation and Killing of Virally
Transformed Cells t78

r 9-5
PLATE 9-1
9-2
MacrophageActivationbyTsl Cells.
LymphaticInfiltration, LymphaticNodule
Ly-ph Node .
t79
180
182
9-3 Ly-ph Node, Tonsils 184
I 9-4 Lyotph Node, Electron Microscopy 186
188
9-5 Thymus
9-6 Spleen 190
I
EndocrineSystem r93
) 201
rc rc-I Pituitary Gland and Its Hormones
10-2 EndocrineGlands 202
I 10-3 SympatheticInnervationof the Visceraand the
Medulla of the SuprarenalGland 203
PLATE 10-1 Pituitary Gland 204
I 10-2 Pituitary Gland
10-3 Thyroid Gland, ParathyroidGland
206
2OB
210
r 10-4 SuprarenalGland
10-5 SuprarenalGland,PinealBody.
10-6 Pituitary Gland, ElectronMicroscopy
212
214
215
r 10-7 Pituitary Gland,ElectronMicroscopy

Integument 217
I rc 11-1 Skin and Its Derivatives. . . . . 224
225
11-2 Hair, SweatGlands,Sebaceous Glands
PLATE 11-1 Thick Skin . . 226
I u-2 Thin Skin 228

I Contents f xiii
 11-3 Hair Folliclesand Associated
Structures,
SweatGlands
l1-4 Nail, Pacinianand Meissner'sCorpuscles. .
230 I
232
11-5 SweatGland,ElectronMicroscopy 234
I
RespiratorySystem 235
GRAPHIC 12-1 ConductingPortionof the Respiratory System 242
I
12-2 RespiratoryPortion of the RespiratorySystem 243
PLATE12-1
12_2
OlfactoryMucosa,Larynx
Trachea
244
246
t
12-3 Respiratory
Epitheliumand Cilia,ElectronMicroscopy 248
12-4
12-5
Bronchi,Bronchioles
Lung Tissue
250
252
t
12-6 Blood-AirBarrier,ElectronMicroscopy 254

DigestiveSysteml-Oral Region
I
255
GRAPHIC 13-1 Tooth and Tooth Development . . . .
I J-Z Tongueand TasteBud .
260 I
261
PLATE13-1 L i p . .
13-2 Tooth and Pulp
1 3 _ 3 PeriodontalLigamentand Gingiva
262
264
266
r
1 3 - 4 T o o t h D e v e l o p m e n.t. . .
13-5 Tongue
1 3 - 6 Tongueand Palate
268
270
272
r
1 3 - 7 Teethand NasalAspectof the Hard Palate 274
I
DigestiveSystemll-Alimentary Canal 277
GMPHIC 14-1 Stomachand SmallIntestine 285
I
14-2 LargeIntestine . . 286
PLATE14-1
14-2
Esophagus
Stomach
288
290
t
14-3 Stomach 292
14-4
14-5
Duodenum
fejunum, Ileum
294
296
I
14-6 Colon, Appendix 298
14-7
14-8
Colon, ElectronMicroscopy
Colon, ScanningElectronMicroscopy
300
301
I
DigestiveSystemlll-Digestive Glands 303 t
GRAPHIC 15-1 Pancreas 308
15-2
PLATE 15-1
Liver .
SalivaryGlands
309 I
310
15-2
15-3
15-4
Pancreas
Liver .
Liver, Gallbladder .
312
3r4
3t6
r
15-5 SalivaryGIand,ElectronMicroscopy
15-6
15-7
Liver,ElectronMicroscopy. . .
Isletof Langerhans,ElectronMicroscopy
318
320 t
32r
xiv ,r. Contents I
t urinarySystem 323
@
t GRAPHIC 16-1
16-2
Uriniferous Tubules
Renal Corpuscle . .
330
33r
PLATE 16-1 Kidney, Surveyand GeneralMorphology 332
I 16-2
16-3
RenalCortex.....
Glomerulus,ScanningElectronMicroscopy
334
336
16-4 RenalCorpuscle,ElectronMicroscopy . . . . 337
I 16-5
16-6
RenalMedulla . .. .
Ureter and Urinarv Bladder
338
340

I System
FemaleReproductive 343
IC 17-1 FemaleReproductive System 350
I 17-2 PlacentaandHormonalCycle 351
352
PLATE 17-1 Ovary
17-2 OvaryandCorpusluteum 354
I 17-3 OvaryandOviduct.... 356
358
17-4 Oviduct,Light andElectronMicroscopy

r 17-5
17-6
17-7
Uterus
Uterus
PlacentaandVagina
362
364
17-8 MammaryGland 366
I
Male ReproductiveSystem 369
I IC 18-1 Male ReproductiveSystem 376
18-2 Spermiogenesis. . 377
t PLATE 18-1
18-2
Testis .
Testisand Epididymis 380
18-3 Epididymis, Ductus Deferens,and SeminalVesicle 382
I 18-4
18-5
Prostate,Penis,and Urethra
Epididymis, Electron Microscopy
384
386

I @ SpecialSenses 387
GMPHIC 19-1 Eye .. 394
I 19-2 Ear .. 395
396
PLATE 19-1 Eye,Cornea,Sclera,Iris, and Ciliary Body .

r 19-2
19-3
19-4
Retina,Light and ScanningElectronMicroscopy
Fovea,Lens,Eyelid, and Lacrimal Glands
Inner Ear
398
400
402
19-5 Cochlea 404
I 19-6 SpiralOrgan of Corti 406

r Index 409

t
I Contents I xv
 II*II l
r The Cell
t
Cellsnot only constitutethe basicunits of the hu- Mitochondria
I man body but also function in executing all of the
activities that the body requires for its survival. Al-
Mitochondria are composedof two membranes,an
outer and an inner with an intervening compart-
though there are more than 200 differentcell types,

r most cellspossesscommon features,which permit

them to perform their varied responsibilities.The
living component of the cell is the protoplasm,
ment betweenthem known as the intermembrane
space (seeGraphic 1-2). The inner membrane is
folded to form cristae and enclosesa viscousfluid-
filled spaceknown as the matrix space.Mitochon-
t which is subdivided into the cytoplasm and the nu-
cleoplasm(seeGraphic 1-1).
dria function in the generation of ATP, utilizing a
chemiosmotic coupling mechanism that employs a
specificsequenceof en4tme complexesand proton

I CYTOPTASM translocator systems(electron transport chain and

Plasmalemma
I Cellspossessa membrane,the plasmalemma,that
provides a selective,structural barrier between the
cell and the outside world. The plasmalemma, a
I phospholipid bilayer with integral and peripheral
proteins and cholesterol embedded in it, func-
the ATP-synthasecontaining elementary particles)
embeddedin their cristae.Theseorganellesalsoas-
sist in the synthesis of certain lipids and proteins.
Mitochondria possessthe enzl.rnesof the TCA ry-
cle, circular DNA molecules, and matrix granules
in their matrix space.These organellesincreasein
number by undergoing binary fission.

r tions in cell-cellrecognition,exocltosisand endo-

cytosis, as a receptor site for signaling molecules,
and as an initiator and controller of the secondary
messengersystem.Materialsmay enter the cell via
Ribosomes
Ribososmes are small, bipartite organelles that
exist as individual unipartite particles that do not

I pinocytosis (nonspecificuptakeof moleculesin an

aqueous solution), receptor-mediated endocyto-
sis (specificuptake ofsubstances,such as low den-
sity lipoproteins), or phagocposis (uptake of
I particulatematter). Secretoryproducts may leave
the cell via constitutive or regulated secretion.
coalescewith eachother until protein synthesisbe-
gins.Thesestructuresarecomposedof proteinsand
r-RNA and function as an interactive "workbench"
that not only providesa surfaceupon which protein
synthesisoccursbut also as a catalystthat facilitates
the synthesisof proteins.

r Constitutive secretion, using non-clathrin-coated

vesicles,is the default pathway that does not re-
quire an extracellular signal for releaseand thus
Reticulum
Endoplasmic
the secretoryproduct (e.g.,collagen)leavesthe cell The endoplasmic reticulum is composed of

I in a continuous fashion. Regulated secretion re-

quiresthe presenceof clathrin-coatedstoragevesi-
tubules, sacs,and flat sheetsof membranesthat
delimit much of the intracellularspace(seeGraphic
cleswhose contents (e.g.,pancreaticenzymes)are 1-2). The rough endoplasmic reticulum (RER),

t releasedonly after the initiation ofan extracellular

signalingprocess.
Cells possessa number of distinct organelies,
manyofwhich areformed from membranesthat are
I similar to but not identical with the biochemical
compositionof the plasmalemma.
whose cytoplasmic surface possessesrecePtor
molecules for ribosomes and signal recognition
particles (known as ribophorins and docking
protein, respectively),is continuous with the outer
nuclear membrane. The RER functions in the
synthesis and modification of proteins that are to

I The Cell * I
be packaged,aswell asin the synthesisof membrane
lipids and proteins. Smooth endoplasmic reticu-
lum functions in the synthesisofcholesterols and
lipids as well as in the detoxification of certain
drugs and toxins. Additionally, in skeletal muscle
cellsthis organelleis specializedto sequesterand re-
leasecalcium ions and thus regulate muscle con-
traction and relaxation.
ERCIC,GolgiApparatus,and the
Trans-ColgiNetwork
The Golgi apparatus (complex) is composed of a
specificallyoriented cluster ofvesicles,tubules, and
fl attenedmembrane-boundedcisternaearrangedin
the following manner: ERGIC, cis-Golgi network,
cis-face, medial face, trans-face, and trans-GolgS
network (seeGraphic l-2). The Golgi complexnot
only packages but also modifies macromolecules
synthesizedon the surfaceof the rough endoplasmic
reticulum. Newly synthesizedproteins passfrom the
rough endoplasmicreticulum to the ERGIC (Endo-
plasmic Reticulum-Golgi Intermediate Compart-
ment) by COPII-coated transfer vesiclesand from
there to the cls-GolgiNetwork, probably via COPI-
coatedvesicles.The proteins continue to travel to the
cis-, medial-, and to the trans facesof the Golgi ap-
paratusby non-clathrin-coated vesicles(or, accord-
ing to someauthors,via cisternalmaturation). Lyso-
somal oligosaccharidesare phosphorylated in the
ERGIC and/or in the clsface;mannosegroupsarere-
moved and other sugarresiduesareaddedin the me-
dial face;whereas,the addition ofgalactoseand sialic
acid aswell asthe sulfation ofselectedresiduesoccur
in the trans face. Sorting and the final packaging of
the macromolecules are the responsibility of the
trans-Golgi network (TGN). It should be noted that
material can travel through the Golgi complex in an
anterogradefashion, asjust described,aswell asin a
retrograde fashion, which occursin situationssuch
as when escapedproteins that are residentsof the
RERor of a particular Golgi-facehaveto be returned
to their compartmentsof origin.
Endosomes
Endosomesare intermediate compartments within
the cell, utilized in the destructionofendocytosed,
phagocytosed, or autophagocytosed materials as
well as in the formation of lysosomes.Endosomes
possessproton pumps in their membranes,which
pump H- into the endosome,thus acidifring the
interior of this compartment. Also, theseorganelles
are intermediate stagesin the formation of lyso-
somes.Early endosomes are located at the periph-
ery of the cell, contain receptor-ligandcomplexes,
and their acidiccontents(pH =6) is responsiblefor
the uncoupling of receptorsfrom ligands.The re-
2 + Thecetl
ceptors are usually carried into a systemoftubular I
vesicles, the recycling endosomes, from which
the receptors are returned to the plasmalemma,
whereasthe ligands are translocated to late endo-
somes.Within late endosomesthe pH is evenmore
I
acidic(pH =s.s).
I
Lysosomes
Lysosomes are formed by the utilization of late
endosomesas an intermediary compartment. Both t
Iysosomal membranes and lysosomal enzymesare
packagedinthe trans-Golginetwork and are deliv-
ered in separate clathrin-coated vesicles to late
endosomes,forming endolysosomes, which then
I
mature to become lysosomes. These membrane-
boundedvesicleswhoseproton pumps are respon-
sible for their very acidic interior (pH =5.9)
I
contain various hydrolytic enzFmesthat function
in intracellular digestion. They degrade certain
macromoleculesaswell asphagocytosedparticulate
t
matter (phagolysosomes) and autophagocytosed
material (autophagolysosomes). Frequently, the
indigestible remnants of lysosomaldegradation re- I
main in the cell, enclosedin vesiclesreferred to as
residual bodies.
I
Peroxisomes
Peroxisomes are membrane-bounded organelles
housing oxidative enzymes such as urate oxidase,
I
D-amino acid oxidase, and catalase. These or-
ganellesfunction in the formation of free radicals
(e.g.,superoxides)and hydrogen peroxide,which I
destroyvarioussubstances, and in the protection of
the cell by degradinghydrogen peroxide by catalase.
They also function in detoxification of certain tox-
ins and in elongation of some fatty acids during
I
lipid synthesis. Most of the proteins intended for
inclusions into peroxisomesare synthesizedin the
cytosol rather than on the RER.All peroxisomesare
I
formed by fission from preexistingperoxisomes.
Proteasomes
t
Proteasomes are small, barrel-shaped organelles
that function in the degradation of cytosolic pro-
teins. The practice of cytosolic proteolysis is highly
I
regulatedand the candidateprotein must be tagged
by severalubiquitin moleculesbefore it is permitted
to be destroyedby the proteasomesystem.
I
Cytoskeleton I
The cytoskeleton is composedof a filamentous ar-
ray of proteins that act not only as the structural
framework of the cell but also to transport material
within it from one region of the cell to another and
r
I
provide it with the capability of motion and cell
division. Components of the cytoskeleton include
microtubules (consisting of a- and B-tubulins
arranged in 13 protofilaments), thin (actin)
filaments (also known as microfilaments), and
intermediate filaments. Microtubules are also
associatedwith proteins, known as microtubule-
associated proteins (MAPs), which permit or-
ganelles,vesicles,and other components of the
cytoskeletonto bind to microtubules.Most micro-
tubules originate fr om the microtubule-organizing
center (MTOC) of the cell, located in the vicinity
of the Golgi apparatus. These elements of the
cytoskeletonare pathwaysfor intracellular translo-
cation of organellesand vesiclesand, during cell di-
vision, chromosomesare moved into their proper
locations. Two important MAPs, kinesin and
dynein, are motor proteins that facilitate antero-
gradeand retrograde intracellular vesicularand or-
ganelle movement, respectively.The axoneme of
cilia and flagella,aswell asa framework of centrioles,
are formed mostly of microtubules.
lnclusions
Cytoplasmic inclusions, such as lipids, glycogen,
secretory granules, and pigments, are also consis-
tent constituents of the cytoplasm. Many of these
inclusions are transitory in nature, although some
pigments, e.g.,lipofuscin, are permanent residents
ofcertain cells.
NUCLEUS
The nucleus is enclosedby the nuclear envelope,
composedof an inner and an outer nuclear mem-
brane with an intervening perinuclear cistern (see
Graphic 1-2).The outer nuclearmembraneis stud-
ded with ribosomes and is continuous, in places'
with the rough endoplasmicreticulum' In areasthe
inner and outer membranes fuse with each other,
forming circular profiles, known as nuclear pores,
that permit communication betlveen the nucleo-
plasm and the cytoplasm.Theseperforations of the
nuclear envelopeare guardedby protein assemblies
which, together with the perforations, are known as
nuclear pore complexes, providing regulated pas-
sagewaysfor the transport of materialsin and out of
the nucleus.The nucleushouseschromosomes and
is the location of RNA synthesis. Both mRNA and
IRNA are transcribedin the nucleus,whereasrRNA
is transcribed in the nucleolus. The nucleolus is
also the site of assemblyof ribosomal proteins and
rRNA into the small and Iarge subunits of ribo-
somes. Theseribosomal subunits enter the cytosol
individually.
CYCTE
The cell rycle is subdivided into four phases,Gi, S,
G2, and M. During the presyntheticphase,Gr, the
cell increasesits sizeand organellecontent. During
the S phase,DNA (plus histone and other chromo-
some-associated protein) synthesisand centriole
replication occur. During G2,ATP is accumulated,
centriole replication is completed,and tubulin is ac-
cumulated for spindle formation. Gr, S, and Gz are
alsoreferredto asinterphase. M representsmitosis,
which is subdivided into prophase, prometaphase,
metaphase,anaphase,and telophase.The result is
the division of the cell and its genetic material into
two identical daughter cells.The sequenceofevents
in the cell cycleis controlled by a number of trigger
proteins, known ascyclins.
The Cell I 3

Histophgsiologg
I . M E M B R A N E SA N D M E M B R A N E
TRAFFICKING
The fluidity of the plasmalemmais an important
factor in the processesof membrane sl.nthesis,
endocytosis, exocytosis, as well as in membrane
trafficking (see Graphic l-3)-conserving the
membraneas it is transferredthrough the various
cellularcompartments.The degreeof fluidity is in-
fluenceddirectly by temperatureand the degreeof
unsaturationof the fatty acyltails of the membrane
phospholipids and indirectly by the amount of
cholesterolpresent.
Transport across the cell membrane may be
passive down an ionic or concentrationgradient
(simple diffrrsion or facilitated diffusion via ion
channelor carrier proteins;no energyrequired)or
active (energyrequired,usuallyagainsta gradient).
Ion channel proteins maybe ungated or gated.The
former arealwaysopen,whereasgatedion channels
require the presenceof a stimulus (alteration in
voltage,mechanicalstimulus,presenceof a ligand,
G protein, neurotransmittersubstance,etc.) that
opens the gate.Theseligands and neurotransmit-
ter substancesare t)?es of signalingmolecules.
Signaling molecules are either hydrophobic
(lipid soluble)or hydrophilic and are usedfor cell-
to-cell communication. Lipid-solublemolecules
diffuse through the cell membrane to activate
intracellular messengersystems by binding to re-
ceptor moleculeslocatedin either the cy.toplasmor
the nucleus.Hydrophilic signalingmoleculesiniti-
ate a specificsequenceof responsesby binding to
receptors (integral proteins) embeddedin the cell
memDrane.
Receptorspermit the endocltosis of a much
greater concentration of ligands than would be
possiblewithout receptors.This processis referred
to as receptor-mediated endocytosis and involves
the formation of a clathrin-coated endocytic vesi-
cle, which, once within the cell, shedsits clathrin
coat and fuses with an early endosome. The re-
ceptors and ligands are uncoupled in this com-
partment, permitting the receptors to be trans-
ported to a systemoftubular vesicles,the recycling
endosome,from which the receptorsare recvcled
to the cell membrane.The ligands,Ieft in the early
endosome (pH 6), are ferried to late endosomes
(pH 5.5), deeperin the qtoplasm. Two groups of
clathrin-coated vesiclesderived from the trans-
Golgi network ferry lysosomal enzymes and lyso-
4 m Thecetl
ttffirt
somal membranes (containing additional ATP-
energizedproton pumps) to the late endosome
forming an endolysosome (or lysosome). The
newly deliveredproton pumps further decreasethe
pH of the endolysosomalinterior (to a pH of 5.0).
Hydrolytic enzymes of the lysosome degrade the
ligand, releasingthe usable substancesfor use by
the cell. The indigestibleremnants of the ligand,
however, may remain in vesicles,residual bodies,
within the cytoplasm.
II. PROTEINSYNTHESISAND
EXOCYTOSIS
Protein synthesisrequiresthe code-bearingmRNA,
amino acid-carrying tRNAs, and ribosomes (see
Graphic l-4). Proteinsthat will not be packagedare
synthesizedon ribosomes in the qtosol, whereas
noncytosolic proteins (secretory, lysosomal, and
membraneproteins) are synthesizedon ribosomes
on the rough endoplasmic reticulum (RER). The
complex of mRNA and ribosomesis referred to as a
polysome.
The signal hyryothesis statesthat mRNAs that
code for noncytosolicproteins possessa constant
initial segment,the signal codon, which codesfor a
signal protein. As the mRNA entersthe cltoplasm,
it becomesassociated with the smallsubunit of a ri-
bosome.The small subunit has a binding site for
mRNA, as well as three binding sites(P, A, and E)
for tRNAs.
Once the initiation processis completed, the
start codon (AUG for the amino acid methionine)
is recognized,and the initiator tRNA (bearing
methionine) is attached to the P site (peptidyl-
tRNA-binding site), the large subunit of the ribo-
somebecomesattached,and protein synthesismay
begin. The next codon is recognizedby the proper
acylated IRNA, which then binds to the A site
(aminoacyl-tRNA-bindingsite).Methionine is un-
coupledfrom the initiator IRNA (at the P site) and
a peptide bond is formed between the two amino
acids (forming a dipeptide). The initiator IRNA
travels to the E site (Exit site) on the ribosome
eventually to drop off the ribosome, as the IRNA
with the attacheddipeptidemoves from the A site
to the recently vacatedP site.
The next codon is recognized by the proper
acylatedtRNA, which then binds to the A site. The
dipeptide is uncoupled from the tRNA at the P site,
and a peptide bond is formed between the dipep-
tide and the new amino acid, forming a tripeptide.
The empty IRNA againmovesto the E site to fall off
the ribosome, as the IRNA bearing the tripeptide
movesfrom the A siteto the P site.In this fashion.the
peptidechain is elongatedto form the signalprotein.
The cytosol contains proteins known as signal
recognition particles (SRP).SRPbinds to the signal
protein and inhibits the continuation of protein
synthesis,and the entire polysome proceedsto the
RER. A signal recognition particle receptor,known
as docking protein, located in the membrane of
the RER, recognizes and properly positions the
polysome. The docking of the polysome, probably
assistedby ribophorin I and ribophorin II, two inte-
gral membraneproteins of the RER,resultsin a pore
opening up in the RERmembrane,so that the form-
ing protein chain can enter the RER cisterna.The
signal recognition particle leavesthe polysome,and
protein synthesisresumesuntil the entire protein is
formed. During this process the enzyrne signal
peptidase,locatedin the RER cisterna,cleavessignal
protein from the growing pollpeptide chain. Once
protein synthesisis complete,the two ribosomalsub-
units fall offthe RER and return to the cytosol.
The newly synthesized protein is modified in the
RERby glycosylation,aswell asby the formation of
disulfide bonds, which transforms the linear pro-
tein into a globularform. The newly formed protein
is transportedin COPII-coatedtransfer vesiclesto
the ERGIC and from there in COPl-coatedvesicles
to the cis Golgi network and from there to the cls-
facefor further processing.
Within the clsface,the mannosegroupsof lyso-
somal enzyrnesare phosphorylated.Nonphospho-
rylatedmannosegroupsareremoved,and galactose
and sialic acid residuesare added (terminal glyco-
sylation) in the medial compartment of the Golgi
apparatus.Final modification occurs in the trans
compartment,where selectedamino acid residues
arephosphorylatedand sulfated.Modified proteins
are then transportedfrom the Golgi apparatusto
the trans-Golginetwork (TGN) for packagingand
sortlng.
All transfers between the various faces of the
Golgi apparatusincluding the TGN probablyoccur
via COPl-coatedvesicles.(A concurrenttheorysug-
geststhe possibility of cisternalmaturation, that is as
the ERGIC matures it is transformed into the
variousfacesof the Golgi and it is replacedby the co-
alescence of newly-derivedtransfervesicles.)Man-
nose 6-phosphatereceptorsin the TGN recognize
and packageenzymesdestinedfor lysosomes.These
lysosomal enzymes leave the TGN in clathrin-
coated vesicles.Regulated secretory proteins are
separatedand are alsopackagedin clathrin-coated
vesicles.Membrane proteins and proteinsdestined
for constitutive (unregulated)transport are pack-
agedin non-clathrin-coatedvesicles.
C l i n i c a lC o n s i d e r a t i o n s= I I
C e r t a i ni n d i v i d u a lssu f f e rf r o ml y s o s o m a l
storage diseases,whichinvolvea hereditary
d e f i c i e n ciyn t h e a b i l i t yo f t h e i rl y s o s o m etso
d e g r a d et h e c o n t e n t so f t h e i re n d o l y s o s o m e s
O n eo f t h e b e s t - c h a r a c t e r i zeexda m p l e o sf
thesediseasesis Tay-Sachsdiseasethat oc-
c u r sm o s t l yi n c h i l d r e nw h o s ep a r e n t sa r e d e -
s c e n d a n tosf N o r t h e a sEt u r o p e a Jne w s S i n c e
t h e l y s o s o m eosf t h e s ec h i l d r e na r e u n a b l et o
c a t a b o l i zC e M 2 g a n g l i o s i d edsu, e t o h e x o -
minidase d e f i c i e n c yt h, e i rn e u r o n sa c c u m u -
l a t em a s s i v a e m o u n t so f t h i sg a n g l i o s i di en
endolysosome o sf e v e ri n c r e a s i ndgi a m e t e r s
A s t h e e n d o l y s o s o m ei nsc r e a s ien s i z e ,l h e y
o b s t r u cn t e u r o n aflu n c t i o na n d t h e c h i l dd i e s
b y t h e t h i r dy e a ro f l i f e
Zellweger'sdiseaseis an inheritedauto-
s o m a lr e c e s s i vdei s o r d e trh a t i n t e r f e r ew s ith
n o r m a lp e r o x i s o m abli o g e n e s iwsh o s ec h a r -
a c t e r i s t i cisn c l u d er e n a lc y s t s ,h e p a t o m e g a l y ,
j a u n d i c eh, y p o t o n i ao f t h e m u s c u l asr y s t e m ,
a n d c e r e b r adl e m y e l i n a t i orne s u l t i n g in psy-
chomotoretardation
The Cell ffi 5
GRAPHIC
1-1 I TheCell t
g Lysosomes I
Roughendoplasmic
I
reticulum

Nuclearenvelope
I
Nucleus
I
Nucleolus

I
I
Smoothendoplasmic
reticulum
I
Mitochondrion

Centrioles I
I
I
r
Golgiapparatus
andtrans-Golgi
I
network

I
I
t
Secretorygranules t
I
t
CRAPHIC1-2 I TheOrganelles

Nucleus

Nuclearenvelope
is composedof
innerandouter
nuclearmembranes
Nucleolus
(rRNAsynthesis)

--!

*:

'
'{.(, l{

I "

Nuclearpore comPlex

Smoothendoplasmicreticulum
functions
in synthesisof
lioids
cholesterol-based

Roughendoplasmicreticulum
is thesiteof synthesisof
proteinsthatare to be packaged

M i t o c h o n d r i a f u n c t i o ni n
s y n t h e s i so l A T P a n d c e r t a i nl i p i d s

Golgi-apparatus andthe
trans-Golginetwork(TGN)
functionin oosttranslational
modificationand packaging
of oroteins

Centriolesactas microtubule
organizing
centers

T h eC e l l
CRAPHIC1-3 | Membranesand MembraneTraffiching

Signalingmoleculesbindto receptors(integral
proteins)embeddedin the cellmembraneand initiatea
specificsequenceof responses. Receptorspermitthe
endocytosis of a muchgreaterconcentration of ligands
than wouldbe otherwisepossible.This process,
receptor-mediatedendocytosis, involvesthe formation
of clathrin-coated endocytic vesicles. Once withinthe
cell,the vesicleshedsits clathrincoatand fuseswithan
earlyendosome(pH 6) wherethe receptoris uncoupled
from the ligand.The receptorsare carriedfrom the early
endosomeintoa systemof tubularvesicles,knownas the
recycling endosome, from whichthe receptorsare
returnedto the cellmembrane.

The ligandis transferred by the use of multivesicular

bodiesfromthe earlyendosometo anothersystem
of vesicleslateendosomeslocateddeeperin the
cytoplasm. Late endosomesare moreacidic(pH 5.5)
and it is herethatthe ligandbeginsto be degraded.Late
endosomesreceivelysosomalhydrolases and lysosomal
membranes and in thatfashionlateendosomesprobably
are translormedinto lysosomes(pH 5.0). Hydrolytic
enzymesof the lyosomesdegradethe ligand,releasing
the usablesubstances by the cell,whereas
for utilization
the indigestibleremnantsof the ligandmay remainin
vesicles,residualbodies,withinthe cytoplasm.

I r Theceil
CRAPHIC1-4 r ProteinSgnthesisand Exocgtosis

As the mRNA entersthe cytoplasm,it becomesassociated

Small
withthe small subunit of a ribosome.The smallsubunithas
ribosomal
a bindingsitefor mRNAas wellas threebindingsites(A, P,
subunit
and E) for tRNAs.Oncethe initiationprocessis completed
and the start codon (AUG,for the aminoacid methionine) is
recognized, and the initiator IRNA (bearingmethionine)is
A site attachedto the P site, the large subunitof the ribosome
P site becomesattached,and proteinsynthesismay begin.

t\
t>
\--/ Amino
Large acid
ribosomal
subunit The nextcodonis
recognizedby the proper
acylatedtRNA,whichthen
bindsto the A site.

Methionineis uncoupled
from the initiatorIRNA
(at the P site),and a
peptide bond is formed
betweenthe two amino
acids,resultingin a
dipeptide.
The initiatorIRNAmoves
to the E site and the IRNA
withthe dipeptidesmoves
to the P site,leavingthe A
site empty.As the A site
becomesoccupiedby a
new aminoacylIRNAthe
initiatorIRNAdropsotl the
E site and the mRNA
movethe distanceof one
codon(threenucleotides)
and the new aminoacyl
tRNA'saminoacidformsa
peptidebondwiththe
dipeptide.The two tRNAs
move to sites E and P, and
the cyclecontinues.
Afterthe signal
recognition particle is
boundto the comoleted
signalprotein,the entire
polysome dockson the
The newlysynthesizedproteinis modifiedin the RER membrane.A pore
RER by glycosylationas well as by the formationof opensup in the RER
disulfidebondsthattransformthe linearoroteininto membrane,so that the
globular form.The proteinsare transportedto the formingproteinchaincan
transitionalER (TER)elementsfrom wherethey are enterthe RERcisterna.
deliveredintothe ERGICvia COPIIcoatedvesicles.The
proteinsare sentto the cis Golginetworkin COPIcoated Onceproteinsynthesisis
vesiclesfor furtherprocessing.Phosphorylationof proteins completed,the two
occurswithinthe cis face.Nonphosphorylated mannosegroups
are removedin the medialcomoartment. Finalmodificationoccurs
in the transface.Modifiedproteinsare transportedfrom the Golgi
apparatusto the trans-Golginetwork (TGN)for packagingand
sorting.Lysosomalenzymesand regulatedsecretoryproteins
leavethe TGN in clathrin-coatedvesicles.Membraneand ribosomalsubunitstall off
unregulatedproteinsare packagedin non-clathrin-coated vesicles. the RERand returnto
the cytosol.

The Cell I 9
PLATE1-1 r TgpicalCell t
F I G U R EI Cells. Monkeg. Plastic section.
x 1323
The tlpical cell is a membrane-boundstructure that
F|GURE 2 Cells. Monkeg. Plqstic section. x 540
Cellsmay possess tall, thin morphologies,like thoseof
a collecting duct of the kidney. Their nuclei (N) are
I
consistsof a nucleus (N) and qtoplasm (C). Although locatedbasally,and their lateralcell membranes(arrow-
the cell membrane is too thin to be visualizedwith the
light microscope,the outline of the cell approximatesthe
heads) are outlined. Since these cells are epithelially
derived, they are separatedfrom connective tissue ele-
I
cell membrane(arrowheads).Observethat the outline of ments (CT) by a basalmembrane (BM).
theseparticularcellsmore or lessapproximatesa square
shape.Viewed in three dimensions,thesecellsare saidto
be cuboidalin shape,with a centrallyplacednucleus.The
I
nucleolus (n) is clearly evident, as are the chromatrn
granules(arrows) that are dispersedaround the periph-
ery, aswell asthroughout the nucleoplasm. I
F|GURE 3 Cells. Monkeg. Plastic section x 540
Cellscome in a variety of sizesand shapes.Note that
FfGURE 4 Cells. Monkeg. Plostic section. x 540
Some cells possessa rather unusual morphology, as
I
the epithelium (E) that lines the lumen of the bladderis exemplified by the Purkinje cell (PC) of the cerebellum.
composed of numerous layers.The surfacemostlayer
consistsof large, dome-shapedcells,some occasionally
Note that the nucleus (N) of the cell is housed in its
widestportion, known asthe soma (perikaryon).The cell
I
displayingtwo nuclei (N). The granulesevidentin the cy- possessesseveralcy'toplasmicextensions,dendrites (De),
toplasm (arrowhead)are glycogendeposits.Cellsdeeper and axon. This nerve cell integratesthe numerousdigits
in the epitheliumareelongatedand narrow, and their nu-
clei (arrow) are locatedin their widestregion.
of information that it receivesfrom other nervecellsthat
synapseon lt.
I
I
I
I
Cell I
I
t
I
I
I KEY
I
BM basalmembrane

r
De dendrite N nucleus
cytoplasm E epithelium n nucleolus
AT
connectivetissue tumen PC Purkinjecell

t0 T h eC e l l I
I
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PLATE1-2 I CellOrganellesand Inclusions
FIGURE | * Nucleus and Nissl bodies. Spinol cord.
Human. Paraffin section. x 540
The motor neuronsof the spinal cord are multipolar
neurons,since they possessnumerous processesarising
from an enlargedsoma (S), which housesthe nucleus
(N) and variousorganelles.Observethat the nucleusdis-
plays a large,denselystaining nucleolus (n). The c1'to-
plasm alsopresentsa seriesofdenselystainingstructures
known as Nissl bodies (NB), which have been demon-
stratedby electronmicroscopyto be rough endoplasmic
reticulum.The stainingintensityis due to the presenceof
ribonucleicacid of the ribosomesstuddingthe surfaceof
the rough endoplasmicreticulum.
FfGURE 2 a Secretorg products. Mast cell.
Monkeg. Plastic section. x 540
The connective tissue (CT) subjacentto the epithelial
lining of the small intestinesis richly endowed with mast
cells (MC). The granules (arrows) of mast cells are dis-
tributed throughout their cytoplasmand are releasedalong
the entire periphery of the cell. Thesesmall granulescon-
tain histamine and heparin, as well as additional sub-
stances.Note that the epithelial cells (EC) are tall and
columnar in morphology, and that leukocytes(Le) aremi-
grating, via intercellular spaces,into the lumen (L) of the
intestines.Arrowheads point to terminal bars, junctions
betweenepithelial cells.The brush border (BB) has been
demonstratedby electron microscopyto be microvilli.

FIGURE 3 | Zgmogen granules. Pancreas. FIGURE 4 a Mucous secretory products. Goblet

Monkeg. Plostic section. x 540
The exocrine portion of the pancreasproducesen-
zymes necessaryfor proper digestion of ingested food
materials.These enzymesare stored by the pancreatic
cells as zymogen granules (ZG) until their releaseis ef-
fectedby hormonal activity. Note that the parenchymal
cells are arranged in clusters known as acini (Ac) with a
central lumen into which the secretoryproduct is re-
leased.Observethat the zymogengranulesare stored in
the apicalregionofthe cell,awayfrom the basallylocated
nucleus (N). Arrows indicatethe lateralcell membranes
ofadiacent cellsofan acinus.
cells. Lorge intestines. Monkeg. Plqstic section.
x 540
The glands of the large intestine house goblet cells
(GC), which manufacturea largeamount of mucousma-
terial that acts as a lubricant for the movement of the
compactedresidueofdigestion.Eachgobletcellpossesses
an expandedapical portion, the theca (T), which con-
tains the secretoryproduct ofthe cell.The baseofthe cell
is compressedand housesthe nucleus (N), aswell as the
organelles necessaryfor the synthesis of the mucus-
namely,the rough endoplasmicreticulum and the Golgi
apparatus.Arrows indicatethe lateralcell membranesof
contiguousgobletcells.

Cell

T KEY

Ac acrnus lumen NB Nisslbody

BB brushborder t" leukocyte D soma
CT connectivetissue MC mast cell T theca
EC epilhelialcell N nucleus ZG zym09engranure
GC gobletcell n nucleolus

12 r T h eC e t l
 !3

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PLATE1-5 I CellSurfaceModifications
FTGURE I Brush border. Small intestines.
Monkeg. Plastic section. x 540
The cellslining the lumen (L) of the small intestine
are columnar cells,among which are numerous mucus-
producing goblet cells (GC). The columnar cells' func-
tion is absorbingdigestedfood material along their free,
apicalsurface.In order to increasetheir free surfacearea,
the cells possessa brush border (BB), which has been
demonstratedby electronmicroscopyto be microvilli-
short, narrow, finger-like extensionsof plasmalemma-
coveredcltoplasm. Each microvillus bears a glycocallx
cellcoat,which alsocontainsdigestiveenzymes.The core
of the microvillus containslongitudinally arrangedactin
filaments,aswell asadditional associated proteins.
FfGURE 3 Stereociliq. Epididgmis. Monkeg.
Plostic section. x 540
The lining of the epididymis is composed of tall,
columnar principal cells (Pi) and short basalcells (BC).
The principal cellsbearlong stereocilia(arrows)that pro-
trude into the lumen. It wasbelievedthat stereociliawere
long, nonmotile, cilia-like structures.However, studies
with the electronmicroscopehaveshown that stereocilia
are actuallylong microvilli that branch as well as clump
with eachother.The function, if any, of stereociliawithin
the epididymis is not known. The lumen is occupiedby
numerous spermatozoa,whose dark heads (asterisks)
and paleflagella(arrowhead)areclearlydiscernible.Flag-
ella are very long, cilia-like structures used by the cell for
propulsion.
I KEY
BB brushborder GC
BC basalcell L lumen
ciliatedcell
14 The Cell
FIGURE 2 Cilia. Oviduct. Monkeg. Plostic section.
x 540
The lining of the oviduct is composedof two t)?es of
epithelialcells:bleb-bearingpeg cells (pc), which proba-
bly produce nutritional factorsnecessary for the survival
of the gametes,and pale, ciliated cells (CC). Cilia (ar-
rows) arelong, motile, fingerJike extensionsof the apical
cell membrane and c1'toplasmthat transport material
alongthe cellsurface.The core of the cilium, asshown by
electronmicroscopy,containsthe axoneme,composedof
microtubules arranged in a specific configuration of
nine doublets surrounding a central pair of individual
microtubules.
FIGURE 4 Intercellulor bridges. Skin. Monkeg.
Plastic section. x 540
The epidermisof thick skin is composedof severalcell
layers,one of which is the stratum spinosum shown rn
this photomicrograph. The cells of this layer possess
short, stubby, finger-like extensionsthat interdigitate
with thoseofcontiguous cells.Beforethe adventofelec-
tron microscopy, these intercellular bridges (arrows)
were believedto representcltoplasmic continuities be-
tween neighboringcells;however,it is now known that
these processesmerely serveas regions of desmosome
formation so that the cellsmay adhereto eachother.
Cell
gobletcell pc peg cell
Pi principalcell
 .- tJ

cc
/

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FICURE
1

-c
=-:' !-t ?
-\
i {/|;-

W &
w
FICUR4
E
T h eC e l l 15
PLATE1-4 r Mitosis,Light and ElectronMicroscopg
FfGURE | €= Mitosis. Whitefish blastula. Paraffin
section. x 210
This photomicrograph of whitefish blastula shows
different stages of mitosis. The first mitotic stage,
prophase (P), displaysthe short, thread-like chromo-
somes(arrow) in the centerof the cell.The nuclearmem-
brane is no longer present.During metaphase(M), the
chromosomesline up at the equatorialplane of the cell.
The chromosomesbegin to migrate toward the opposite
polesofthe cellin eariyanaphase(A) and proceedfarther
and farther apart as anaphaseprogresses(arrowheads).
Note the denseregions,centrioles (c), toward which the
chromosomesmigrate.
FIGURE 3 € Mitosis. Mouse. Electron microscopg.
x 9423
Neonatal tissue is characterizedby mitotic activity'
where numerous cells are in the processof proliferation.
Observethat the interphasenucleus (N) possesses a typ-
ical nuclear envelope (NE), perinuclear chromatin
(asterisk),nucleolus,and nuclearpores.A cell that is un-
dergoing the mitotic phase of the cell cycle, however,
I KEY
A anaphase M metaphase
centriole N nucleus
ch cnromosome
l6 = T h eC e l l
FfGURE 2 n Mitosis. Whitefish blostula. Paraffin
section, x 540
During the early telophasestageof mitotic division'
the chromosomes (Ch) havereachedthe oppositepoles
of the cell. The cell membraneconstrictsto separatethe
cell into the two new daughter cells, forming a cleavage
furrow (arrowheads).The spindle apParatusis visible as
parallel,horizontallines (arrow) that eventuallyform the
mid-body. As telophaseprogresses' the two new daughter
cells will uncoil their chromosomesand the nuclear
membraneand nucleoliwill becomere-established.
losesits nuclear membrane and nucleolus,while its chro-
mosomes(Ch) are quite visible.Thesechromosomesare
no longerlined uP at the equatorialplate,but aremigrat-
ing to opposite poles, indicating that this cell is in the
.rily- to mid-anaphasestageof mitosis.Observethe pres-
ence of cytoplasmicorganelles,such as mitochondria,
rough endoplasmicreticulum, and Golgi apparatus.
NE nuclearenvelope
P propnase
I
'f i{
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I

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I 17
PLATE1-5 I TgpicalCell,ElectronMicroscopg
FfGURE | * Tgpical cell. Pituitarg. Rat. Electron
microscopg. x 8936
The gonadotrophs of the pituitary gland provide an
excellentexample of a typical cell, since they house many
of the cytoplasmicorganellespossessed by most cells.The
cltoplasm is limited by a cell membrane (arrowheads)
that is clearly evident, especiallywhere it approximates
the plasmalemmaof the adjacent electron-densecells.
Mitochondria (m) are not numerous,but are easilyrec-
ognizable,especiallyin longitudinal sections,sincetheir
cristae(arrows) are arrangedin a characteristicfashion.
Since this cell actively manufactures a secretoryproduct
that has to be packagedand deliveredoutsideofthe cell,
it possesses a well-developedGolgi apparatus (GA), po-
sitioned near the nucleus (N). Observethat the Golgi is
formed by severalstacksof flattenedmembranes.Addi-
tionally, this cell is well-endowed with rough endoplas-
mic reticulum (RER),indicatingactiveprotein synthesis.
The cytoplasm also displays secretory products (aster-
isks),which are transitoryinclusions.
The nucleus is bounded by the typical nuclear enve-
lope (NE), consistingof a ribosome-studdedouter nu-
clear membrane and an inner nuclear membrane.The
peripheralchromatin and chromatin islandsare clearly
evident, as is the nucleolus-associatedchromatin (NC).
The clearareawithin the nucleusis the nucleoplasmrep-
resentingthe fluid componentofthe nucleus.The nucle-
olus (n) presentsa sponge-likeappearancecomposedof
electron-lucentand electron-densematerials,suspended
free in the nucleoplasm.The electron-denseregion is
composed of the pars granulosaand the pars fibrosa,
while the electron-lucent region is probably the nucleo-
plasm in which the nucleolus is suspended. (From
Stokreef IC, Reifel CW, Shin SH: Cell Tissue Res 243:.
255-261,1986.)

Cell

T KEY
GA Golgi apparatus n nucleolus NE nuclearenvelope
m mitochondrion NC nucleolus-associated rER roughendoplasmic
N nucreus chromatin reticulum

l8 # T h eC e t l
t
I
I
I
I
I {
i\{

I :r';
I
I
t
r
t
I
I
I
I
I FICURE
1

I
I T h eC e l l 19
PLATE1-6 I Nucleusand Cgtoplesm,ElectronMicroscopg
FIGUREI a Nucleusand cgtoplasm.Liver. Mouse. pores (NP). The rough endoplasmic reticulum
Electronmicroscopg.x 48,116 (rER) is richly endowedby ribosomes (R). Note the
Thenucleus (N) displays its nucleoplasm andchro- presence of numerousmitochondria (m), whosedou-
matin (c) to advantage in thiselectronmicrograph.Note ble membraneand cristae (Cr) arequiteevident.Ob-
that the inner (arrowheads) and outer (doublearrows) microtubule (Mi) asit
servethe slightlyelectron-dense
membranes of the nuclearenvelope fuseto form nuclear coursesthroughthe cytoplasm.

Roughendoplasmicreticulum

Nuclearporecomplex

20 r Thecell
 t{P t

i 5r:-

Mi-,:

r\

T h eC e| 21
PLATE1 7 I Nucleusand Cgtoplosnt,ElectronMicroscopg

**
, *1i,

FIGURE 1 Nucleus and cAtoplasm. Liver. Mouse : c . r t t e r e tiln t h c n r l r t l i r o f t h c i n t e r c r i s t i rsl r r a c c sI I r e p c r

Electron microscopg. :. t t ':1.3
l - h i s c l c et r o n n r i er o u r i r p h o i . r l i v c r c c l l d i s p l a r s t h e
u u c l c u s ( N ) \ \ ' i t l )i t s c o n c l e n s c tcl h r o m a t i n ( c ) , a s n c ] l ; r s
n r i r n v c v t o p l . r s r n i co r g r r n c l l c sN o t c t h a t t h c m i t o c h o n -
d r i a ( n r ) p o s s c s cs l c c t n r n t l c n s cn t a t t ' i xg r a n r r l c s( i r rr o u , s )
i n r r c l c a ri l f e. l p r e s e u t st h e G o l g i a p p r r r a t u i t ( , , ' \) , \ \ ' h r ! h l s
. r et i r el v p i r c k a g i n gm a r t e l i a li n c o n d c n s i n g v e s i c l e s ( ( ) V )
I hc rough endoplasmic reticulum (rEl{) is obvious cluc
t o i t s r i b o s o m e s ( R ) , r v h e r c i r st h c s m o o t h e n d o p l a s m i c
r c t i c t t l u t n rs l R t i : l c s : o l r ri o t t s

Gnlnr ennaretr rc Mitochond

rron

22 T h eC e t l
PLATE1-8 r GolgiApparatus,ElectronMir

FIGURE I Golgi opporotus. Mouse. Electron rc

microscopg. x. 2B,5BB cr
The extensiveGolgr apparatusof this secrctoryccll w
presents severalflattcrrcd membrane-bound cisternae h(
(Ci), stackedone on top ofthe other.The convexfacc(f0 \\

,' .,--
': *,. * '
r
'"-r -\.)' -
,_ -j

l/itoc
Golgiapparatus
PLATE1-9 I Mitochondrio,ElectronMicroscopg
FTGUREI J Mitochondria.Kidneg.Mouse.
Electronmicroscopg.x 18,529
The basalaspectofthe proximaltubulecell presents
numerousinterdigitatingprocesses.Many of thesepro-
cesseshouselongitudinallyorientedmitochondria (m),
24r The Cell
whose outer membrane is smooth, while its inner mem-
brane is folded to form cristae (Cr). Note that the matrix
houses matrix granules (arrowheads). Observe also the
basallamina whoselamina densa(open arrowheads)and
lamina lucida (arrows) are clearly evident.
Mitochondrion

I Epithelium and Glands
Epithelium is one of the four basic tissuesof the
body and is derivedfrom all three germ layers.It is
composedof very closelypacked,contiguouscells,
with very little or no intercellular material in the
extracellularspaces.Epithelia either form mem-
branesthat are representedas sheetscoveringthe
body surfaceand lining its internal surfaceor occur
as secretoryelementsknown as glands.Almost al-
ways, epithelia and their derivatives are separated
from underlyingor surroundingconnectivetissues
by a thin, noncellular layer, the basal membrane
(basementmembrane). This is usually composed
of an epithelially derived basal lamina and the lam-
ina reticularis, derived from the connectivetissue.
EPITHELIUM
EpithelialMembranes
Epithelial membranes are avascular,deriving their
nutrientsby diffusion from blood vesselsin the un-
derlying connectivetissue.Thesemembranescan
cover a surface,line a cavity, or line a tube. Surfaces
covered may be dry, as the outer body surface,or
wet, as the coveringof the ovary.All lining epithe-
lia, on the other hand, havea wet surface(e.g.,those
lining the body cavities,blood vessels, and gastroin-
testinal tract). Membranes that line serousbody
cavitiesare referred to asmesothelia,whereasthose
lining the heart chambers and blood and ly-ph
vesselsareknown asendothelia.
Epithelial membranesare classifiedaccording
to the shape of the most superficial cell layer,
which may be squamous (flat), cuboidal, or
columnar, as observedwhen sectionedperpendic-
ular to the exposed surface of the membrane.
Moreover, the number of cell layers composing
the epithelium alsodeterminesits classification,in
that a singlelayer of cellsconstitutesa simple ep-
ithelium, whereastwo or more Iayersof cells are
referred to as a stratified epithelium (Table 2-1).
In a simple epithelium, all of the cells touch the
II*II
basallamina and reach the free surface.In pseu-
dostratified epithelia (which may or may not pos-
sesscilia or stereocilia),however, all of the cells
touch the basal lamina, although some cells are
much shorter than others and do not reach the
free surface.Therefore,this is a simple epithelium
that appearsto be stratified.
Stratified squamous epithelium may be kera-
tinized, nonkeratinized, or even parakeratinized.
The stratified epithelium found in the urinary tract
is known as transitional epithelium; its free sur-
face is characterizedby large, dome-shapedcells
( T a b l e2 - 1 ) .
Epithelial cell membranes are frequently spe-
cialized. The free surface may form microvilli
(brush border), cilia, or stereocilia.The lateralcell
membranes maintain intercellular junctions be-
tween contigtlous cells. These junctions are the
zonulae occludentes,zonulae adherentes,macula
adherentes, and\ap junctions. The basal cell
membrane forms hemidesmosomes,maintaining
the cell's attachment to the basal membrane (see
G r a p h i c2 - l ) .
Epithelial membranespossessnumerous func-
tions. Theseinclude protection; reduction of fric-
tion; absorption;secretion;excretion;synthesisof
variousproteins,enzymes,mucins, hormones,and
a myriad of other substances; and acting in a sen-
sory capacity.
GLANDS
Most glands are formed by epithelial downgrowths
into the surroundingconnectivetissue.Glandsthat
deliver their secretionsonto the epithelial surface
do so via ducts and are known as exocrine glands.
Glands that do not maintain a connection to the
outside (ductless)and whose secretionsenter the
vascularsystemfor delivery areknown asendocrine
glands. The secretorycellsofa gJandarereferred to
as its parenchyma and are separated from sur-
rounding connective tissue and vascular elements
Eoitheliumand Glands f 25
TABTE 2-l s Classification of Epithelia
Type Surface Cell Shape Examples(Some)
Simple
Simplesquamous Flattened Lining blood and lymphatic vessel
walls (endothelium),pleuraland
abdominalcavities(mesothelium)
Simplecuboidal Cuboidal Lining ducts of most glands
Simplecolumnar Columnar Lining much of digestivetract, gall
bladder
Pseudostratified All cellsreston basallamina with Lining ofnasal cavity,trachea,
only some reachingthe surface. bronchi, epididymis
Cells that reach the surfaceare
columnar
Stratified
Stratified squamous( nonkeratinized) Flattened(with nuclei) Lining mouth, esophagus,
vagina
Stratified squamous(keratinized) Flattened(without nuclei) Epidermisof the skin
Stratifiedcuboidal Cuboidal Lining ducts of sweatglands
Stratifiedcolumnar Columnar Conjunctivaof eye,lining some
large excretory ducts
Transitional Largedome-shapedcellswhen Lining renal calyces,renal pelvis,
bladderis empty; flattened ureter, urinary bladder, proximal
when bladderis distended Dortion ofurethra

by a basalmembrane.Exocrineglandsareclassified secretoryproducts.The classificationof endocrine

accordingto various parameters,e.g.,morphology glands is much more complex, but morphologi-
of their functional units, branching of their ducts, cally, their secretoryunits either are composedof
typesof secretoryproducts they manufacture,and follicles or are arrangedin cords and clumps of cells
the method wherebytheir component cellsrelease (seeGraphic2-2).

26 # Epithelium
andClands

Histophgsiologg
I. EPITHELIUM
Epithelium is avascularand is composedof closely
apposed cells with little intercellular space.These
cells frequently form epithelial sheetsthat receive
nutrients from the blood vesselsof the underlying
connective tissue via diffusion through the basal
lamina. Epithelium not only covers the body but
also lines body cavities,as well as lumina of vessels
and ducts and systems(e.g.,digestivetract, urinary
tract); consequently,material entering or leaving
the body must do so through these epithelial
sheets.
Epithelium functions in protection from me-
chanicalabrasion,chemicalpenetration,and bacte-
rial invasion;absorption ofnutrients as a result of
its polarized cells that are capable of performing
vectorial functions; excretion of waste products;
sensory reception from the external (or internal)
milieu; forming glands whose function is the se-
creting enzyrnes,hormones, lubricants, or other
products;and movementof material along the ep-
ithelial sheet (such as mucus along the respiratory
tract) by the assistanceof cilia.
Epithelial cellsmay presentspecializationsalong
their various surfaces.These surfacesare apical
(microvilli, stereocilia, cilia, and flagella), lateral
or basolateral(junctional complexes,zonula oc-
cludens, zonula adherens,macula adherens,gap
junctions), and basal (hemidesmosomes and basal
lamina).
A. ApicalSurfaceModifications
Microvilli are closelyspaced,finger-like extensions
of the cell membrane that increasethe surfacearea
of cellsthat function in absorptionand secretion.
Dense clusters of microvilli are evident in light
micrographs,asa striatedor brush border.
Stereociliaare located in the epididymis, as well
as in a few limited regions of the body. They were
named cilia becauseof their length; however, elec-
tron micrography proved them to be elongatedmi-
crovilli whose functions are, asyet, unknown.
Cilia are elongated, motile, plasmalemma-
coveredextensionsof the cytoplasm that move ma-
terial along the cell surface.Each cilium arisesfrom
a centriole (basalbody) and possesses an axoneme
core composedof nine pairs of peripheral (dou-
blets) and two single,centrally placedmicrotubules
IIIII
(singlets).Microtubules of the doublets Possess
dynein arms with ATPaseactivity, which functions
in energizingciliary motion.
B. BasolateralSurfaceModifications
functional complexes,which occupy only a minute
region of the basolateral cell surfaces,are visible
with light microscopy as terminal bars, a structure
that encircles the entire cell. Terminal bars are
composed of three components: zonula occludens
(tight or occluding junction), zonula adherens
(adheringjunction), and macula adheres(desmo-
somes, also adhering junction). The first two
encircle the cell, whereas desmosomesdo not.
Additionally, another type of junction, the gap
junction, permits cells to communicate with each
other.
C. BasalSurfaceModifications
The basal cell membrane of the cell is afiixed to
the basallamina by adheringjunctions known as
the hemidesmosomes.Morphologically, this struc-
ture resembleshalf of a desmosomebut its bio-
chemical composition and clinical significance
demonstrateenoughdissimilaritythat hemidesmo-
somesare no longer viewed asbeing merely a half of
a desmosome.
The basement membrane, interposed between
epithelium and connectivetissue,is composedof
an epitheliallyderived component' the basal lam-
ina, and a connective tissue-derivedregion, the
lamina reticularis. The basal lamina is further
subdivided into two regions,the lamina lucida and
the lamina densa.Basallaminae function as struc-
tural supports for the epithelium, as molecular
filters (e.g.,in the renal glomerulus),in regulating
the migration of certain cells across epithelial
sheaths(e.g., preventing entry to fibroblastsbut
permitting accessto lymphoid cells), in epithelial
regeneration(e.g., in wound healing where it
forms a surfacealong which regeneratingepithelial
cellsmigrate), and in cell-to-cellinteractions(e.g.,
formation of myoneuraljunctions).
CellRenewal
D. Epithelial
Epithelial cells usually undergo regular turnover
becauseof their function and location. For example:
andClands I
Epithelium 27
cells of the epidermis that are sloughed from the
surface,originated approximately 28 daysearlier by
mitosisfrom cellsof the basallayers.Other cells,such
asthoselining the small intestine,are replacedevery
few days. Still others continue to proliferate until
C l i n i c a lC o n s i d e r a t i o n s: r I
Bullous Pemphigoid
B u l l o u sp e m p h i g o i da,r a r ea u t o l m m u ndei s -
e a s e i, s c a u s e db y a u t o a n t i b o d i eb si n d i n gt o
s o m eo f t h e p r o t e i nc o m p o n e n t o sf
h e m i d e s m o s o m eI nsd i v i d u aal sf f l i c t e w d ith
t h i sd i s e a s e x h i b i ts k i nb l i s t e r i nogf t h e g r o i n ,
a n d a x i l l aa b o u tt h e f l e x u r ea r e a sa n d o f t e n
i n l h e o r a lc a v i t y F o r t u n a t e l iyt ,c a n b e c o n -
t r o l l e db y s l e r o i d sa n d i m m u n o s u p p r e s s i v e
drugs
Pemphigus Vulgaris
P e m p h i g uvsu l g a r i si s a n a u t o i m m u n d ei s e a s e ,
c a u s e db y a u t o a n t i b o d i ebsi n d i n gt o s o m eo f
t h e c o m p o n e n tos f d e s m o s o m e T s h i sd i s e a s e
c a u s e sb l i s t e r i nagn d i s u s u a l l yf o u n do c c u r r i n g
i n m i d d l e - a g eidn d i v i d u a l sl t i s a r e l a t i v e ldy a n -
g e r o u sd i s e a s es i n c et h e b l i s t e r i ncga ne a s i l y
l e a dt o i n f e c t i o n sF r e q u e n t ltyh i sd i s e a s ea l s o
r e s p o n d tso s l e r o i dt h e r a p y
Epithelium
andGlands
adulthood is reached,at which time the mechanism
is shut down. However,when largenumbers of cells
arelost, for examplebecauseof injury, certainmech-
anismstriggerthe proliferation of new cellsto restore
the cell population.
Tumor Formation
U n d e r c e r t a i n p a t h o l o g i cc o n d i t i o n s ,m e c h a -
c e l lp r o l i f e r a t i odno n o t f u n c -
n i s m st h a t r e g u l a t e
t i o n p r o p e r l yt;h u s ,e p i t h e l i apl r o l i f e r a t i ogni v e s
r i s et o t u m o r st h a t m a y b e b e n i g ni f t h e y a r e l o -
c a l i z e do, r m a l i g n a nitf t h e y w a n d e rf r o m t h e i r
o r i g i n a sl i t e a n d m e t a s t a s i z[es e e d )t o a n o t h e r
a r e ao f t h e b o d ya n dc o n t i n u et o p r o l i f e r a t eM a -
l i g n a nttu m o r st h a t a r i s ef r o ms u r f a c e p i t h e l i u m
a r e t e r m e dc a r c i n o m a sw,h e r e a st h o s ed e v e l o p -
i n g f r o m g l a n d u l aer p i t h e l i u ma r e c a l l e da d e n o -
carcrnomas
Metaplasia
E p i t h e l i acle l l sa r e d e r i v e df r o m c e r t a i ng e r m
c e l ll a y e r sp, o s s e sas d e f i n i t em o r p h o l o g ay n d
l o c a t i o na, n d p e r f o r ms p e c i f i fcu n c t i o n sh; o w -
e v e r ,u n d e rc e r t a i np a t h o l o g i c a col nditions,
t h e y m a y u n d e r g om e t a p l a s i at r, a n s f o r m i n g
i n l o a n o t h e re p i t h e l i acle l lt y p e A n e x a m p l eo f
s u c hm e t a p l a s ioac c u r si n t h e l i n i n ge p i t h e l i u m
o f t h e o r a lc a v i t yo f i n d i v i d u a lwsh o s m o k eo r
usechewinglobracco

Summargof HistologicalOrganization
I. EPITHELIUM
A. Types
l. Simple Squamous-single layer of uniform flat
cells.
2. Simple Cuboidal-single layer of uniform
cuboidalcells.
3. Simple Columnqr-single layerof uniform colum-
nar cells.
4. Pseudostratified Columncr-single layer of cells
ofvaried shapesand heights.
5. Stratified Squornous-severallayersof cellswhose
superficial layers are flattened. These may be
nonkeratinized,parakeratinized,or keratinized.
6. Stratified Cuboidal-two or more layers of cells
whosesuperficiallayersare cuboidalin shape.
7. Stratified Columnar-two or more layersof cells
whosesuperficiallayersare columnar in shape.
8. Transitionol-several layers of cells, charac-
terized by large, dome-shaped cells at the free
surface,that help maintain the integrity of the
epithelium during distention of the various
componentsof the urinarytract.
B. GeneralCharacteristics
l. Free Surtace Modifications
Cellsmay possess microvilli (brush border, striated
border), short finger-like projectionsthat increase
the surfaceareaofthe cell;stereocilia(long anasto-
mosingmicrovilli), which areonly found in the epi-
didymis; and cilia, which are long, motile projec-
tions of the cell with a 9 + 2 microtubular
substructure(axoneme).
2. Lateral Surfqce Modificqtions
For the purposesof adhesion,the cell membranes
form junctional complexesinvolving the lateral
plasmalemmaof contiguouscells.Thesejunctions
are known as desmosomes(maculaeadherentes),
zonulaeoccludentes.and zonulaeadherentes.For
the purpose of intercellular communication, the
lateralcell membranesform gap junctions (nexus,
septatejunctions).
3. Basal Surtqce Modifications
The basal cell membrane that lies on the basal
membrane forms hemidesmosomesto assistthe
cell adhereto the underlyingconnectivetissue.
lrilIl
4. Basal Membrane
The basal (basement) membrane of light mi-
croscopy is composed of an epithelially derived
basal lamina (which has two parts, lamina densa
and lamina lucida) and a lamina reticularis derived
from connectivetissue,which may be absent.
II. GLANDS
A. ExocrineGlands
Exocrine glands, which deliver secretions into a
system of ducts to be conveyed onto an epithelial
surface,may be unicellular (goblet cells) or multi-
cellular.
Multicellular glands may be classifiedaccording
to the branching of their duct system. If the ducts
are not branched, the gland is simple; if they are
branched,the gland is compound. Moreover, the
three-dimensionalshapeof the secretoryunits may
be tubular, acinar (alveolar),or a combination of
the two, namely tubuloacinar (alveolar). Addi-
tional criteriainclude 1) the type ofsecretoryprod-
uct produced:serous(parotid, pancreas),mucous
(palatal glands), and mixed (sublingual, sub-
mandibular), possessingserousand mucous acini
and serousdemilunes;and 2) the mode of secre-
tion: merocrine (only the secretory product is
releasedas in the parotid gland), apocrine (the
secretoryproduct is accompaniedby some of the
apicalcltoplasm, as perhapsin mammary glands),
and holocrine (the entirecell becomesthe secretory
product, as in the sebaceousgland, testes,and
ovary). Glands are subdivided by connective tissue
septa into lobes and lobules, and the ducts that
seivethem are interlobar, intralobar, interlobular,
and intralobular (striated,intercalated).
Myoepithelial (basket) cells are ectodermally
derived myoid cells that share the basement
lamina of the glandular parenchyma. These cells
possesslong processesthat surround secretory
acini and, by occasionalcontraction, assistin the
delivery of the secretory product into the system
of ducts.
Glands
B. Endocrine
Endocrine glands are ductless glands that release
their secretioninto the bloodstream.Theseglands
are describedin Chapter 10.
andClands m 29
Epithelium
 GRAPH|C2-l t JunctionalComplex

Zonulae occludentes are

occludingiunctionswhere the
outer leafletsof the apposing Strandsof
cell membranestuse with each transmembrane
other,preventingmat€rialfrom proteins
taking the parac€llularroute
betweenthe connectivetissue plasma
Adiacent
and the lumen.They extend membranes
along the entire circumference Extracellular
soac€
of the cell.

Zonulae adherentes are

locatediust basal to the zonulae
occludentesand are distinguished
by the presence of E-cadherins,
transmembraneglycoproteins.
Intracellurlaryactin filaments
form a meshworkthat is attached
to the E-cadherinsby the other

U molecules.

Desmogleins
E-cadherins

Plaque

0'
0 th

\\i lllaments

: \ -Q,/ , u""u,*"o#
Macufaeadne'1anles
\) arecnaracterized by desmoglelns
"'( :.- and E-cadherinstransmembrane
glycoproteins,whose cytoplasmicends
are associatedwith a plaque composed
of d€smoplaklns. Intermediate
filaments,forminghairpinloops,
enter and exit the plaque.

Adiacent
plasma
membranes

Conn€xons

lntegrins

Gaplunctlons
arecommunicating
junctionswher€ionsand small
Hemidesmosomes functionin moleculesare p€rmittedto pass
mediating theadherenceof €pithelial betweenadjoiningce[ls.They coupl€
cellsto theunderlying
basallamina. adiacentcells metabolicallyand el€ckically.

30 f Epithelium
andClands
t 2-2 t
GRAPHIC SolivargGland

I
r Myoepithelialcell

I Intercalatedduct
cell

I
I
lnterialated
I
I
t Striatedductcell

I STRATIFIED TRANSITIONAL

I '..

I Squamouskeratinized
Re axed

I
I Squamousdonkeratinized Distended

I Columnar

PSEUDOSTRATIFIED
I
I
Columnar

I
I andGlands I
Epithelium 3l
PLATE2-1 I SimpleEpitheliaond Pseudostratified
Epithelium
FfGURE | = Simple squamous epithelium. Kidneg.
Monkeg. Plastic section. x 540.
The lining of the lumen (L) of this small arteriole
is composed of a simple squamous epithelium (SE)
(known asthe endothelium).The cytoplasmof thesecells
is highly attenuatedand can only be approximatedin this
photomicrographasa thin line (betweenthe arrowheads).
The boundariesof two contiguousepithelialcellscannot
be determinedwith the light microscope.The nuclei (N)
of the squamousepithelial cells bulge into the lumen,
characteristicof this typeof epithelium.Note that someof
the nuclei appearmore flattenedthan others.This is due
to the degreeof agonaicontractionof the smooth muscle
(M) cellsof the vesselwall.
FfGURE 3 = Simple columnar epithelium. Monkeg.
Plastic section. x 540.
The simplecolumnar epithelium of the duodenum in
this photomicrograph displays a very extensive brush
border (MV) on the apicalaspectof the cells.The termi-
nal web (TW), where microvilli are anchored,appearsas
a dense line between the brush border and the apical
cltoplasm. Distinct dots (arrowheads) are evident,
which, although they appearto be part of the terminal
web, are actuallyterminal bars, resolvedby the electron
microscopeto be junctional complexesbetweencontigu-
ous cells.Note that the celisaretall and slender,and their
nuclei (N), more or lessoval in shape,arearrangedrather
uniformly at the samelevelin eachcell.The basalaspects
of thesecellslie on a basalmembrane(arrows),separat-
ing the epithelium from the connectivetissue(CTl. The
round nuclei (rN) noted within the epithelium actuailv
belongto leucocytesmigrating into the lumen (L) of the
duodenum.A few goblet cells(GC) are alsoevident.
SIMPLE
Sq"ano-s C u o oc t a
T KEY
BC basalcell GC
BV bloodvessel L lumen
C cilia LV
CE simplecuboidalepithelium M smoothmuscle
CT connectivetissue MV
32 : Epithelium
andGlands
FIGURE 2 :;] Simple squomous qnd simple cuboidal
epithelia. x.s. Kidneg. Paraffin section. x 210.
The medulla of the kidney providesideal representa-
tives of simple squamousand simple cuboidal epithelia.
Simplesquamousepithelium,asin the previousfigure,is
easily recognizable due to flattened, but somewhat
bulging,nuclei (N). Note that the cytoplasmof thesecells
appearsas thin, dark lines (betweenarrowheads);how-
ever,it must be stressedthat the dark lines are composed
ofnot only attenuatedcellsbut alsothe surroundingbasal
membranes.The simple cuboidal epithelium (CE) is very
obvious. The lateral cell membranes (arrow) are clearly
evidentin someareas;evenwhen they cannotbe seen,the
relationshipsof the round nuclei permit an imaginary
approximationof the extentof eachcell.Note that simple
cuboidal cells,in section,appearmore or lesslike small
squareswith centrallypositionednuclei.
FfGURE 4 'fr.Pseudostrqtified columnar epithelium
with cilia. Paraffin section. x 27A.
The first impression conveyed by this epitheliurn
from the nasal cavity is that it is stratified,being com-
posedofat leastfour layersofcells; however,carefulob-
servationof the inset(x 540) demonstratesthat theseare
closelypackedcellsofvarying heightsand girth, eachof
which is in contactwith the basalmembrane.Here, un-
like in the previousphotomicrograph,the nuclei (N) are
not uniformly arranged,and they occupy about three-
fourths of the epitheliallayer.The location and morphol-
ogy of the nuclei provide an indication of the cell t1pe.
The short basal cells (BC) display small, round-to-oval
nuclei near the basal membrane.The tall, ciliated cells
(arrows) possesslarge, oval nuclei. The terminal web
(TW) supportstall, slendercilia (C), which propel mucus
along the epithelial surface. The connective tissue is
highly vascularized and presentsgood examplesof simple
squamous epithelia (arrowheads) that compose the
endotheliallining of blood (BV) and lymph vessels(LV).
PSEUDOSTRATIFIED
Columnar Columnar
gobletcell N nucteus
rN roundnucleus
lymphvessel SE simplesquamous
epithelium
brushborder TW terminalweb
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PLATE2-2 t Stratified Epitheliaand TransitionolEpithelium
FfGURE I a Stratified cuboidal epithelium. Skin.
Monkeg. Plqstic section. x 540.
Stratified cuboidal epithelium is characterizedby two
or more layersof cuboid-shapedcells,asillustratedin this
photomicrographof a sweatglandduct. The lumen (L) of
the duct is surroundedby cellswhosecell boundariesare
not readily evident, but the layering of the nuclei (N)
demonstratesthat this epithelium is truly stratified.The
epithelium of the duct is surrounded by a basal mem-
brane (BM). The other thick tubular profilesare tangen-
tial sectionsof the secretory (s) portions of the sweat
gland,composedof simplecuboidalepithelium.Note the
presenceofa capillary (Cp) containinga singlered blood
cell,and the bulging nucleus(arrow) of the epithelialcell
constitutingthe endotheliallining. The largeempty space
in the lower right-hand corner of this photomicrograph
representsthe lumen of a lymph vessel(LV) whose en-
dotheliallining presentsa flattenednucleusbulging into
the lumen. Note that more cytoplasmis evidentnear the
pole ofthe nucleus(arrowhead)than elsewhere.
FfGURE 2 a Stotified squamous nonkerotinized
epithelium. Plastic section. x 210.
The lining ofthe esophagusprovides a good example
of stratified squamous nonkeratinized epithelium. The
lack of vascularity of the epithelium, which is approxi-
mately 30-35 cell layersthick, is clearly evident. Nourish-
ment must reach the more superficial cells via diffusion
from blood vesselsof the connective tissue (CT). Note
that the deepestcells, which lie on the basal membrane
and are known as the basal layer (BL), are actually
cuboidal in shape.Due to their mitotic activity, they give
rise to the cells of the epithelium, which, as they migrate
toward the surface,become increasinglyflattened. By the
time they reach the surface,to be sloughed off into the
esophageallumen (EL), they are squamous in morphol-
ogy. The endothelial lining of a vesselis shown as scat-
terednuclei (N) bulging into the lumen (L), providing an
obvious contrast betweenstratified and simple squamous
epithelia.

FIGURE 3 a Stratified squamous kerotinized FIGURE 4 | Transitionol epithelium. Blodder.

epithelium. Skin. Poraffin section. x 132.
The palm of the hand is covered by a thick stratified
squamouskeratinized epithelium. The definite difference
between this and the preceding photomicrograph is
the thick layerof nonliving keratin (K), which functions in
protecting the deeperliving cellsand tissuesfrom abrasion,
desiccation,and invasion by bacterial flora. Although the
variouslayersof this epithelium will be examinedin greater
detail in Chapter I l, certain featuresneed to be examined
here. Note that the interdigitation betweenthe connective
tissuedermal ridges (P) and the epithelial ridges (R) pro-
vides a larger surfaceareafor adhesionand providing nu-
trients than would be offeredby a merely flat interface.The
basal membrane (BM) is a very definite interval between
the epithelium and the connectivetissue.The basallayer of
this epithelium, composedof cuboidalcells,is known asthe
stratum germinatiwm, which possesses a high mitotic ac-
tivity. Cellsoriginating here presstoward the surface,and,
whi-leon their way, changetheir morphology, manufacture
proteins,and acquiredifferent names.Note the duct (D) of
a sweatgland piercing the baseof an epidermal ridge as it
continuestoward the outside (arrows).
Monkeg. Plastic section. x 132.
The urinary bladder, as most of the excretory portion
of the urinary tract, is lined by a specialized type of
stratified epithelium-the transitional epithelium. This
particular specimen was taken from an empty, relaxed
bladder, as indicated by the large, round, dome-shaped
(rC) cells, some of which are occasionally binucleated
(arrow), abutting the lumen (L). The epithelial cellslying
on the basal membrane (BM) are quite small, but in-
creasein sizeasthey migrate superficiallyand begin to ac-
quire a pear shape.When the bladder is distended, the
thickness of the epithelium decreases and the cells
become flattened, more squamouslike. The connective
tissue-epithelium interface is flat with very little interdig-
itation between them. The connective tissue (CT) is very
vascularimmediately deepto the epithelium, asis evident
from the sectionsof the arterioles (A) and venules (V) in
this field. Observethe simple squamous endothelial lin-
ings ofthese vessels,characterizedby their bulging nuclei
(arrowheads).

STRATIFIED STRATIFIED STRATIFIED TRANSITIONAL

Cuboidal Relaxed
Squamousnonkeratinized Souamouskeratinized
T KEY
A arteriole EL esophageallumen P dermalridge
BL basal layer K keratin R epithelialridge
BM basal membrane lumen rC round-shapedcell
Cp capillary LV lymphvessel s secretoryportion
CT connectivetissue N nucreus venute
D duct

34 r E p i t h e l i uamn dC l a n d s
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F I C U R3E F I C U R4F
mn d C l a n d s
E p i t h e l i ua 35
PLATE2-5 I PseudostratifiedCiliatedColumnarEpithelium,ElectronMicroscopg
FfGURE I n Pseudostratified ciliated columnar
epitheliu m. Homster trachea. Electron microscopg.
x 6480.
The pseudostratifiedciliatedcolumnar epithelium of
the tracheais composedof severaltypesof cells,someof
which are presentedhere.Sincethis is an oblique section
through the epithelium,it is not readilyevideni herethat
all of these cells touch the basal lamina (BL). Note
that the pale-stainingciliated cells (CC) display rough
endoplasmicreticulum (rER), mitochondria (M), Golgi
apparatus(G), aswell asnumerouscilia (C) interspersed
with microvilli (MV). Each cilium, some of which are
seenin cross-section, displaysits plasmamembraneand
its axoneme(A). The cilia are anchoredin the terminal
web via their basal bodies (BB). The mitochondria ap-
pearto be concentratedin this areaofthe cell.The second
cell types to be noted are the mucous cells (MC), also
known asgobletcells.Thesecellsproducea thick, viscous
secretion, which appears as secretory granules (SG)
within the apicalcytoplasm.The protein moiety of the se-
cretion is synthesizedon the rough endoplasmicreticu-
lum (rER), while most of the carbohydrategroups are
added to the protein in the Golgi apparatus (G). The
mucouscellsare nonciliatedbut do presentshort,stubby
microvilli (MV) on their apicalsurface.When thesecells
releasetheir secretoryproduct, they changetheir mor-
phology. They no longer contain secretory granules,
and their microvilli become elongatedand are known
as brush cells.They may be recognizedby the filamen-
tous structureswithin the supranuclearcytoplasm.The
lower right-handcorner ofthis electronmicrographpre-
sentsa portion ofa capillary (Ca) containinga red blood
cell (RBC). Observethat the highly attenuatedendothe-
lial cell (EC) is outside of but very close to the basal
lamina (BL) of the tracheal epithelium. (Courtesy of
Dr. E. McDowell.)

Pseudostratified
columnar
eoithelium

T KEY
A axoneme cc ciliatedcell MV microvillus
BB basalbody EC endothelialcell RBC red bloodcell
BL basallamina u Golgi apparatus rER roughendoplasmic
cilium M mitochondrion reticulum
Ca capillary MC mucouscell SG secretorygranule

55 r E p i t h e t i uamn dG l a n d s
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E p i t h e l r uamn d C l a n d s 37
PLATE2-4 a EpithelialJunctions,ElectronMicroscopg
F|GURE | * Epitheliol junction. Human. Electron
microscopg.x 27,B15.
This electron micrograph representsa thin section
of an intercellular canaliculusbetween clear cells of a
human eccrine sweat gland stained with ferrocyanide-
reducedosmium tetroxide.A tight junction (arrows)sep-
aratesthe lumen of the intercellular canaliculus (I-)
from the basolateralintercellularspace.Observethe nu-
cleus (N). (From BriggmanL Ban[ H, Bigelowf, Graves
L SpicerS:Am I Anat 162:357-368, 1981.)
38 W Epithelium
andClands
FIGURE 2 M Epithelidl junction. Zonula occludens.
Humon. Electron microscopg. x 83,700,
This is a freeze-fracturereplica of an elaboratetieht
junction along an intercellulai canaliculusbetweent-wo
clear cells.Note the smooth transition from a region of
wary, nonintersecting,densely packed junctional ele-
ments to an area of complex anastomoses. At the steo
fracture(arrows),it can bi seenthat the pattern ofridges
on the E facecorrespondsto that ofthe grooveson the P
faceof the plasmamembraneof the adjacentclearcell.In
certain areas(arrowheads),severalof the laterally dis-
posed,denselypackedjunctional elementsare separated
from the luminal band. The direction of platinum shad-
owing is indicatedby the circledarrow. (From Briggman
J, Bank H, Bigelowf, Graves/, SpicerS: Am / Anat 762:
357-368.1981.)
Zonulaeoccludentes
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I E p i t h e l i u amn d C l a n d s
PLATE2-5 I Glands
F|GURE I Goblet cells. Ileum. Monkey. Plastic
section. x 2-/0.
Goblet cells are unicellular exocrine glands that are
found interspersedamong simple columnar and pseu-
dostratified columnar epithelia.This photomicrograph
of an ileal vilius displaysnumerousgoblet cells (GC) lo-
cated among the simple columnar epithelial cells (EC).
The brush border (arrowhead)of the columnar cells is
only scantly presenton the goblet cells.The expanded
apicalregion ofthe goblet cell is known as the theca (T)
and is filled with mucin (m), which, when releasedinto
the lumen of the gut, coatsand protectsthe intestinallin-
ing. The lower right-hand corner of the simple columnar
epithelium was sectionedsomewhat obliquely through
the nuclei of the epithelialcells,producing the appear-
anceof a stratifiedepithelium (asterisk).Looking at the
epitheliumabovethe doublearrows,however,it is clearly
simple columnar. The occasionalround nuclei (rN) are
those of lymphocltes migrating through the epithelium
into the lumen (L). Figure 2 is a higher magnificationof
the boxed area.
FIGURE 3 Sebaceous gland. Scolp. Poraffin
section. x 132.
Sebaceousglands are usually associatedwith hair
follicles. They dischargetheir sebum into the follicle,
although in certain areasof the body they are present
independentof hair follicles.Theseglands,surrounded
by slender connective tissue capsules(Ca), are pear-
shapedsacculeswith short ducts. Each sacculeis filled
rvith large,amorphouscellswith nuclei in various states
of degeneration(arrows).The peripheryof the sacculeis
composedof small, cuboidalbasalcells (BC), which act
in a regenerativecapacity.As the cells move away from
the periphery of the saccule,they enlargeand increase
their cytoplasmicfat (f) content.Near the duct, the entire
cell degenerates and becomesthe secretion(se).There-
fore, sebaceous glandsare classifiedas simple,branched,
acinarglandswith a holocrinemode of secretion.Smooth
muscles(M), arrectorpili, are associated with sebaceous
glands.Observethe secretory(s) and duct (D) portions
ofa sweatgland abovethe sebaceous giand.
T KEY
AC adiposecell f fat
b base L, tJ gobletcell
BC basalcell GZ Golgizone
BM basal membrane L rumen
Ca capsure M smoothmuscle
D duct m mucrn
EC simplecolumnar
epithelial
cell
Eoithelium
andClands
FIGURE 2 ,;, Goblet cells. Ileum. Monkeg. Plastic
section. x 540.
This photomicrograph is a higher magnification of
the boxed areaof the previousfigure, demonstratingthe
light microscopic morphology of the goblet cell. The
mucin (m) in the expandedtheca (T) of the goblet cell
hasbeenpartly precipitatedand dissolvedduring the de-
hydration procedure.The nucleus(N) ofthe gobletcellis
relatively dense due to the condensedchromatin. Be-
tween the nucleus and the theca is the Golgi zone (GZ),
where the protein product of the cell is modified and
packagedinto secretory granules for delivery. The base
(b) of the goblet cell is slender, almost as if it were
"squeezedin" betweenneighboringcolumnar epithelial
cells,but it touchesthe basalmembrane (BM). The ter-
minal web and brush border of the goblet cell are greatly
reduced,but not completelyabsent (arrowheads).The
round nuclei (rN) belong to leucocltes migrating
through the epithelium into the lumen (L) of the ileum.
FIGURE 4 Eccrine sweat glands. Skin. Paraffin
section. x 210.
Eccrinesweatglandsarethe most numerousglandsin
the body, and they areextensivelydistributed.The glands
are simple,unbranched,coiled tubular, producing a wa-
tery solution. The secretoryportion (s) of the gland is
composed of a simple cuboidal tlpe of epithelium with
two celltypes,a lightly stainingcellthat makesup most of
the secretoryportion, and a darker stainingcell that usu-
ally cannot be distinguishedwith the light microscope.
Surroundingthe secretoryportion aremyoepithelialcells
(MC) that, with their numerousbranchingprocesses, en-
circle the secretorytubule and assistin expressingthe
fluid into the ducts. The ducts (D) of sweatglandsare
composed of a stratified cuboidal type of epithelium,
whosecellsaresmallerthan thoseof the secretoryunit. In
histologicsections,therefore,the ducts are alwaysdarker
than the secretoryunits. The large,empty-lookingspaces
are adipose (fat) cells (AC). Note the numerous small
blood vessels(arrows)in the vicinity of the sweatgland.
Gobletcell
MC cell
myoepithelial
N nucteus
rN rounonucteus
secretory
secretion
T theca
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E p i t h e l i u amn d C l a n d s 41
PLATE2-6 I Clands
FIGURE I Compound tubuloacinar (alveolar)
serous glond. Pancreas. Monkeg. Plastic section.
x 540.
This is a photomicrographof the exocrineportion of
the pancreas, a compoundtubuloacinar(alveolar)serous
gland. The duct systemof this gland will be studied in
Chapter l5 on the DigestiveSystem.Only its secretory
cellswill be consideredat this point. Each acinus,when
sectionedwell, presentsa round appearancewith a small
centrallumen (L), with the secretorycellsarrangedlike a
pie cut into pieces.The connectivetissue(CT) investing
eachacinusis flimsy in the pancreas.The secretorycells
are more or lesstrapezoid-shaped, with a round, basally
situatednucleus (N). The cltoplasm containsnumerous
zymogengranules(ZG), which arethe membrane-bound
digestiveenzyrnespackagedby the Golgi apparatus.
FIGURE 3 Compound tubuloacinar (alveolar)
mixed gland. Sublinguol glond. Monkeg. Plostic
section. x 540.
The sublingualgland is a mostly mucous,compound
tubuloacinar gland that containsmany mucous tubules
and acini. Theseprofiles of mucous acini are well repre-
sentedin this photomicrograph.Note the open lumen
(L) borderedby severaltrapezoid-shaped
cellswhoselat-
eral plasma membranesare clearly evident (double ar-
rows). The nuclei (N) of thesemucous cellsappearto be
flattenedagainstthe basalplasmamembraneand areeas-
ily distinguishablefrom the round nuclei of the cells of
serousacini.The cytoplasmappearsto possess
numerous
vacuole-likestructuresthat impart a frothy appearance to
the celi. The seroussecretionsof this sland are derived
from the few serouscellsthat appeart; cap the mucous
units, known as serousdemilunes (SD). The secretory
productsofthe serousdemilunesgain entranceto the lu-
men of the secretoryunit via smallintercellularspacesbe-
tweenneighboringmucous cells.
I KEY
CT connective
tissue N nucteus
D duct PC parenchymal cell
L lumen SA serousacrnl
42 = Eoithelium
andGlands
FIGURE 2 Compound tubuloocinar (alveolar)
mucous glands. Soft palote. Paraffin section. x 132.
The compound tubuloacinarglandsof the palateare
purely mucous and secretea thick, viscousfluid. The se-
cretory acini ofthis gland are circular in sectionand are
surroundedby fine connectivetissue(CT) elements.The
lumina (L) of the mucous acini are clearly distinguish-
able,asarethe trapezoid-shaped parenchymalcells(PC),
which manufacturethe viscousfluid. The nuclei (N) of
the trapezoid-shaped cellsare dark, densestructuresthat
appearto be flattenedagainstthe basalcell membrane.
The cltoplasm has an empty, frothy appearance,which
stainsa light grayish-bluewith hematorylin and eosin.
FIGURE 4 '. Compound tubuloocinor (olveolarJ
mixed glond. Submandibular gland. Monkeg. Plqstic
section. x 540.
The submandibulargland is a compound tubuloacr-
nar gland that producesa mixed secretion,as does the
sublingual gland of the previous figure. However, this
gland containsmany purely serousacini (SA) and very
few purely mucous ones, namely becausethe mucous
acini are capped by serous demilunes (SD). Also this
gland possesses an extensivesystemof ducts (D). Note
that the cltoplasm of the serouscellsappearsto be blue
when stainedwith hematorylin and eosin. Also notice
that the lumina of the acini are so small that they are not
apparent,while thoseof mucousunits (L) arequite obvi-
ous. Observethe differencein the cltoplasms of serous
and mucus-secreting cells,aswell asthe densityof the nu-
clei of individual cells. Finally, note that the lateral cell
membranes (arrows) of mucus-producing cells are
clearlydelineated,while thoseof the serouscellsarevery
difficult to observe.
Salivarygland
SD serousdemilunes
ZG zymogengranules
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I ConnectiveTissue
Connectivetissuesencompassthe major structural
constituentsof the body. Although seeminglydi-
verse, structurally and functionally they possess
many sharedqualities;therefore,they are consid-
eredin a singlecategory.Most connectivetissuesare
derivedfrom mesoderm,which form the multipo-
tential mesenchymefrom which bone, cartilage,
tendons,ligaments,capsules, blood and hematopoi-
etic cells,and lymphoid cellsdevelop.Functionally,
connectivetissuesservein support, defense,trans-
port, storage,and repair,among others.Connective
tissues,unlike epithelia,are composedmainly of
intercellular elements with a limited number of
cells.They are classifiedmostly on the basisof their
nonliving componentsrather than on their cellular
constituents.Although the preciseordering of the
various subtlpesdiffersfrom author to author, the
following categoriesaregenerallyaccepted:
A. Embryonicconnectivetissues
l. Mesenchymal
2. Mucous
B. Adult connectivetissues
l. Connectivetissueproper
a. Loose(areolar)
b. Reticular
c. Adipose
d. Denie irregular
e. Denseregular
(1) Collagenous
(2) Elastic
2. Specializedconnectivetissues
a. Supportingtissues
( I ) Cartilage
(2) Bone
b. Blood
EXTRACEIIUIAR MATRIX
The extracellularmatrix of connectivetissueproper
may be subdivided into fibers, amorphous ground
substance,and tissuefluid.
I rr
Three types of fibers are recognizedhistologi-
cally:collagen,reticular,and elastic.Collagenfibers
usuallyoccur as bundlesof nonelasticfibersof var-
ied thicknesswhosebasic subunits,tropocollagen
molecules,aggregateinto specificstaggeredassoci-
ations,producing a 67-nm banding once believed
to be characteristicof this protein (seeGraphic 3-
1). Some collagenqpes, however,such as qpe IV
collagenthat is present in basal laminae, do not
exhibit this banding characteristic.Reticularfibers
(once believedto have different composition) are
thin, branching, carbohydrate-coated fibers com-
posed of tlpe III collagen that form delicate
networks around smooth muscle cells,certain ep-
ithelial cells, adipocltes, nerve fibers, and blood
vessels.They also constitute the structural frame-
work of certain organs,such as the liver and the
spleen.Elastic fibers are, as their name implies,
highly elasticand may be stretchedto about 150o/o
of their resting length without breaking.They are
composedof an amorphous protein, elastin, sur-
rounded by a microfibrillar component. Elastic
fibersdo not displaya periodicity and are found in
regionsofthe body that require considerableflexi-
bility and elasticity.
The amorphous ground substance constitutes
the gel-like matrix in which the fibers and cells are
embeddedand through which tissue fluid diffuses.
Ground substanceis composedof glycosaminogly-
cans(GAGs),proteoglycans, and glycoproteins. The
major GAGsconstituentsarehyaluronic acid, chon-
droitin 4-sulfate, chondroitin 6-sulfate, dermatan
sulfate,and heparansulfate.Proteoglycansare com-
posedof a protein coreto which GAGsarecovalently
bound. Glycoproteins have also been localized in
connectivetissue proper. These substances,espe-
cially fibronectin, appearto be essentialin facilitating
the attachmentand migration of cellsalongconnec-
tive tissueelements,such ascollagenfibers.
An additional extracellular region, the basal
lamina (or basementlamina), is characteristicallyrn-
terposed between epithelia and connective tissues.
Tissue +l 45
Connective
Electron microscopy has elucidated this structure,
which is composedof a lamina lucida and a lamina
densa.The former is a thin electron-lucentlayer
directlybetweenthe laminadensaand the cellmem-
brane. The major constituents of the basal lamina,
laminin, entactin, and type IV collagen,are epithe-
lially derived, although other components, fi-
bronectin and perlacan,are probably of connective
tissueorigin. The basallamina is frequentlyassoci-
ated with a lamina reticularis, a reticular fiber net-
work from the underlying connectivetissueto which
the basallamina is anchoredmostly by fibronectin,
rlpe VII collagen, and microfibrils. Together, the
basallamina and lamina reticularisconstitutethe
basementmembraneof light microscopy.
CELTS
The following are cellsof connectivetissueproper-
or more accurately,Ioose(areolar)connectivetissue
(seeGraphic3-2).
Fibroblasts,the predominant cell t)?e, are re-
sponsiblefor the synthesisof collagen,elasticand
reticular fibers,and much, if not all, of the ground
substance. The morphologyof thesecellsappearsto
be a function oftheir syntheticactivities,and there-
fore,resting(or inactivefibroblasts)cellswereoften
referredto as fibrocytes,a term that is rapidly dis-
appearingfrom the literature.
Macrophages (histiocytes) are derived from
monocltes in bone marrow. They migrate to the
connectivetissueand function in ingesting(phago-
cy.tosing)foreignparticulatematter.Thesecellsalso
participatein enhancingthe immunologic activities
of lymphoqtes.
Plasmacellsarethe major cell type presentduring
chronic inflammation. Thesecellsarederivedfrom a
subpopulation of lymphocytes and are responsible
for the sgrthesisand releaseof humoral antibodies.
Mast cells are usually observed in the vicinity
of smallblood vessels, althoughthe relationshipbe-
tween them is not understood.Thesecells house
numerousmetachromaticgranulescontaininghis-
tamine, which is a smooth muscle contractant,
and heparin, which is an anticoagulant.Mast cells
also release eosinophilic chemotactic agent and
leukotriene. Because of the presence of im-
munoglobulins on the externalsurfaceof the mast
cell plasmalemma,thesecells,in sensitizedindivid-
uals, may become degranulated(i.e., releasetheir
granules), resulting in anaphylactic reactions or
evenin life-threateninganaphylacticshock.
Pericytesare also associatedwith minute blood
vessels, but much more closelythan are mast cells,
sincethey sharethe basallaminaeof the endothelial
cells. Pericytesare believed to be contractile cells
46 = Tissue
Connective
that assistin the regulationofblood flow through
the capillaries. Additionally, they may also be
pluripotential cells,which assumethe responsibili-
tiesof mesenchymalcellsin adult connectivetissue.
It is now believedthat mesenchymalcellsareprob-
ably not presentin the adult.
Fat cells (adipocytes)may form small clustersor
aggregatesin loose connectivetissue. They store
lipids and form adipose tissue, which protects,
insulates,and cushionsorgansof the body.
Leukocytes(white blood cells)leavethe blood-
streamand enterthe connectivetissuespaces.Here
they assumevariousfunctions,which are discussed
in Chapter5.
PE9._."_
coNNECTTVETTSSUE
Mesenchymaland mucous connectivetissuesare
limited to the embryo. The former consistsof mes-
enchymal cells and fine reticular fibers inter-
spersedin a semifluid matrix of ground substance.
Mucous connectivetissueis more viscousin con-
sistency,containscollagenbundlesand numerous
fibroblasts, and is found deep to the fetal skin
and in the umbilical cord (where it is known
as Wharton's jelly), surrounding the umbilical
vessels.
Loose (areolar) connective tissue is distributed
widely, sinceit constitutesmuch of the superficial
fascia and invests neurovascular bundles. The
cellsand intercellularelementsdescribedabovehelp
form this more or lessamorphous,waterytissue.
Reticular connective tissue forms a network of
thin reticular fibers that constitute the structural
framework of bone marrow and many lymphoid
structures, as well as a framework enveloping cer-
tain cells.
Adipose tissueis composedof fat cells,reticular
fibers,and a rich vascularsupply.It actsas a depot
for fat, a thermal insulator,and a shockabsorber.
Dense irregular connective tissue consists of
coarse,almost haphazardly arranged bundles of
collagen fibers interlaced with few elastic and
reticular fibers.The chiefcellular constituentsare
fibroblasts, macrophages,and occasional mast
cells.The dermis of the skin and capsulesof some
organsare composedof denseirregular connective
trssue.
Dense regular connectivetissue may be com-
posedeither ofthick, parallelarraysofcollagenous
fibers, as in tendons and ligaments,or of parallel
bundles of elastic fibers, as in the ligamentum
nuchae,the ligamentum flava, and the suspensory
ligament of the penis. The cellular constituentsof
both denseregularcollagenousand elasticconnec-
tive tissuesare almost strictly limited to fibroblasts.

I Histophgsiologg
I I. EXTRACELLULAR MATRIX
A. GroundSubstance
I Ground substanceis composedof GAGs, proteo-
glycans, and glycoproteins. Glycosaminoglycans
(GAGs) are linear polymers of repeating disaccha-
I rides, one of which is always a hexosamine, while
the other is a hexuronic acid. All of the GAGs, with
the exceptionofhyaluronic acid, are sulfatedand,
I thus, possessa predominantly negative charge.
Most GAGsare linked to protein cores,forming
huge proteoglycanmoleculei. Many of theseprol
I teoglycan molecules are also linked to hyaluronic
acid,forming massivemoleculesof enormouselec-
trochemical domains that attract osmotically active
cations (e.g., Na+), forming hydrated molecules
I that resistcompression.The sulfatedGAGsinclude
chondroitin sulfate,dermatan sulfate,heparan sul-
fate,heparin,and keratansulfate.
I Glycoproteins are large polypeptide molecules
with attendant carbohydrate side chains. The best
characterized are laminin, fibronectin, chon-
I dronectin, osteonectin,entactin, and tenascin.
Laminin and entactin are derived from epithelial
cells, and tenascin is made by glial cells of the em-
bryo, whereasthe remainder are manufactured by
I cellsof connectivetissue.Many cellspossessinte-
grins, transmembrane proteins, with receptor sites
for one or more of theseglycoproteins.Moreover,
I glycoproteins also bind to collagen, thus facilitat-
ing cell adherenceto the extracellular matrix.
I B. Fibers
l. Collagen
I Collagen,the most abundantof the fibers,is in-
elasticand is composedof a staggeredarray of the
protein tropocollagen,composedofthree a chains.
I There are at leasttwelve different tFpesof collagen,
basedon the amino acid sequenceof their crchains.
Interestingly, every third amino acid is glycine, and
a significant amount of proline, hydroxyproline,
t lysine, and hydrorylysine constitute much of the
tropocollagensubunit.
The most common collagensare tl?e I (dermis,
I bone, capsulesoforgans, fibrocartilage,dentin, ce-
mentum), type II (hyaline and elastic cartilages),
type III (reticular fibers), type IV (lamina densaof
I the basal lamina), type V (placenta), and type VII
(anchoring fibrils of the basal lamina). With the
I ConnectiveTissue ffi 47
II:II
exception of type IV, all collagenfibers display a 67-
nm periodicity as the result of the specificarrange-
ment of the tropocollagenmolecules.
o. CollagenSgnthesis
Synthesis of collagen occurs on the rough endo-
plasmic reticulum, where polysomes possessdif-
ferent mRNAs coding for the three a chains
(preprocollagens).Within the rough endoplasmic
reticulum (RER) cisternae,specific proline and Iy-
sine residuesare hydrorylated, and hydroxylysine
residues are glycosylated. Each o chain possesses
propeptides (telopeptides) located at both amino
and carboryl ends. These propeptides are respon-
sible for the precise alignment of the ct chains,
resulting in the formation of the triple helical pro-
collagen molecule.
Coatomer-coatedtransfer vesiclesconvey the
procollagenmoleculesto the Golgi apparatusfor
modification, mostly the addition of carbohydrate
side chains. Subsequentto transfer to the trans-
Golgi network, the procollagenmoleculeis exocy-
tosed (via non-clathrin-coated vesicles),and the
propeptidesare cleavedby the enzymeprocolla-
gen peptidase, resulting in the formation of
tropocollagen.
Tropocollagen molecules self-assemble, form-
ing fibrils with 67-nm characteristicbanding. Type
IV collagen is composed of procollagen rather
than tropocollagensubunits,hencethe absenceof
periodicity and fibril formation in this type of
collagen.
b. Reticulqr Fibers
Reticular fibers (type III collagen) are thinner than
type I collagenand possessa higher content ofcar-
bohydrate moieties than do the remaining collagen
types. As a result, when stained with silver stain,
the silver preferentially deposits on these fibers
giving them a brown to black appearancein the
light microscope.
2. Elastic Fibers
Elastic fibers may be stretched up to l50o/oof
their resting length before breaking. They are com-
posed of microfibrils (whose chief constituent is
fibrillin) and the protein elastin, where the latter
has desmosineand isodesmosine,that are respon-
sible for this fiber's elasticity. Individual elastin
moleculesare cross-linkedvia their lysine residues,
forming sizablenetworks of molecules.
C. Extracellular
Fluid
Extracellular fluid (tissuefluid) is the fluid compo-
nent of blood, similar to plasma, that percolates
throughout the ground substance,carrying nutri-
ents,oxygen,and otherblood-bornematerialsto and
carbon dioxide and wasteproducts from cells.Extra-
cellular fluid leavesthe vascularsupply at the arterial
end ofthe capillariesand returnsinto the circulatory
systemat the venousend ofcapillaries,the venules,
and the excessfluid enterslyrnphatic capillaries.
lipoprotein lipase, which is transported to the lu-
minal surfaceof the capillaryendothelialcell mem-
brane, where it hydrolyzes chylomicrons and very
low densitylipoproteins.The fatty acidsand mono-
glyceridesare transported to the adipocytes,diffuse
into their c1'toplasm,and are reesterified into
triglycerides.Hormone-sensitivelipase, activated
by cAMP, hydrolyzes the stored lipids into fatty
acids and glycerol,which are releasedfrom the cell
asthe needarises,to enter the capillariesfor distri-
bution to the remainderof the body.

I I . A D I P O S ET I S S U E B. MultilocularAdiposeTissue
Therearetwo typesof adiposetissue,white (uniloc- Multilocular adiposecellsare rare in the adult hu-
ular) and brown (multilocular). man. They are presentin the neonate,as well as in
animalsthat hibernate.Thesecellspossessnumer-
ous dropletsof lipid in their cy-toplasmand a rich
A. Unilocular
AdiposeTissue supply of mitochondria. These mitochondria are
Cellsof unilocular adiposetissuestoretriglycerides capableof uncoupling oxidation from phosphory-
in a single,large fat droplet that occupiesmost of lation, and insteadof producing ATP, they release
the cell. Fat cellsof adiposetissuemake the enzyme heat,thus arousingthe animal from hibernation,

C l i n i c a lC o n s i d e r a t i o n sr r I Obesitg
Therearetwolypesof obesity-hypertrophlc
obesity, whichoccurswhenadipose cellsin-
Keloid Formation
crease in sizefromstoringfat (adultonset), and
Surgicalwoundsare repairedby the body first
hyperplastic whichischaracterized
obesity, by
w i t hw e a kt y p e l l l c o l l a g e tnh a t i s l a t e rr e p l a c e d
an increase in thenumber of adipose cellsre-
b y t y p e I c o l l a g e nw, h i c hi s m u c hs t r o n g e rS o m e
sultingfromoverfeeding a new-born for a few
i n d i v i d u a less, p e c i a l lbyl a c k sf,o r ma n o v e r a b u n -
weeksafterbirth Thistypeof obesityis usually
d a n c eo f c o l l a g e inn t h e h e a l i n g p r o c e s st ,h u sd e -
lifelong
veloping elevated s c a r sc a l l e dk e l o i d s .
Scurvg SgstemicLupus Ergthematosus
S c u r v ya, c o n d i t i o nc h a r a c t e r i z ebdy b l e e d i n g Systemic lupuserythemalosus is an autoim-
g u m sa n d l o o s et e e t ha m o n go t h e rs y m p t o m s , muneconneclive tissuedisease thatresults ln
r e s u l t sf r o ma v i t a m i nC d e f i c i e n c yV i t a m i nC i s the inflammation in theconnective tissueele-
n e c e s s a rfyo r h y d r o x y l a t i oonf p r o l i n ef o r mentsof certain organs aswellas of tendons
p r o p e rt r o p o c o l l a g efno r m a t i o ng i v i n gr i s et o andjointsThesymptoms dependon thetype
f i b r i l sn e c e s s a rfyo r m a i n t a i n i ntge e t hi n t h e i r andnumberof antibodies present andcanbe
bony sockets anywhere frommildto severeand,due to the
varietyof symptoms, lupusmayresemble
Marfan's Sgndrome otherconditions suchas growing pains,arthri-
Patientw s i t h M a r f a n ' s y n d r o m ea, g e n e t i cd e - tis,epilepsy, andevenpsychologic diseases
f e c ti n c h r o m o s o m e I 5 t h a t c o d e sf o r f i b r i l l i n , Thecharacteristic symptoms include facialand
p o s s e s us n d e v e l o p eedl a s t i cf i b e r si n t h e i rb o d y jointpains
skinrash,soresin theoralcavity,
a n d a r e p r e d i s p o s etdo r u p t u r eo f t h e a o r t a andinflammation, kidneymalfunction, neuro-
Edemo logicconditions,anemia, thrombocytopenia,
T h e r e l e a s eo f h i s t a m i n a e n d l e u k o t r i e n ef sr o m fluidon the lungs.Formildcasesthe usual
m a s tc e l l sd u r i n ga n i n f l a m m a t o rrye s p o n s e choiceof trealment is nonsteroidalanti-
e l i c i t sin c r e a s e cd a p i l l a r yp e r m e a bl i t y ,r e s u l t i n g inflammatory drugs,whereas in severe cases
i n a n e x c e s sa c c u m u l a t i oonf t i s s u ef l u i da n d , initially
steroidsandimmunosuppressants are
t h u s ,g r o s ss w e l l i n g[edema) administered

48 r Tissue
Connective

I Summargof HistotogicatOrganization
I . E M B R Y O N I CC O N N E C T I VT
EI S S U E
A. Mesenchymal
Connective Tissue
l. Cells
Stellateto spindle-shapedmesenchymalcellshave
processesthat touch one another. Pale scantycy-
toplasm with large clear nuclei. Indistinct cell
memDrane.
2. lntercellulor Materiqls
Delicate, empty-looking matrix, containing fine
reticular fibers. Small blood vesselsare evident.
B. MucousConnective
Tissue
l. Cells
Fibroblasts, with their numerous flattened pro-
cessesand oval nuclei,constitutethe major cellular
component. In section,these cells frequently ap-
pear spindle-shaped,and resembleor are identical
with mesenchymalcells when viewed with a light
microscope.
2. Intercellular Materials
When comparedwith mesenchymalconnectivetis-
sue,the intercellularspaceis filled with coarsecol-
lagen bundles, irregularly arranged, in a matrix of
precipitatedj elly-likematerial.
II. CONNECTIVE TISSUEPROPER
A. Loose(Areolar)
Connective
Tissue
l. Cells
The most common cell types are fibroblasts, whose
spindle-shapedmorphology closelyresemblesthe
next most numerous cells,the macrophages.The
oval nuclei of macrophagesaresmaller,darker,and
denserthan thoseof fibroblasts.Mast cells,located
in the vicinity of blood vessels,may be recognized
by their size,the numerous small granulesin their
cytoplasm,and their large,round, centrallylocated
nuclei. Occasional fat cells resembling round,
empty spacesborderedby a thin rim of cytoplasm
may also be present.When sectionedthrough its
peripherallysqueezed,flattenednucleus,a fat cell
has a ring-like appearance.
Additionally, in certain regions such as the
subepithelialconnectivetissue(lamina propria) of
the intestines,plasmacellsand leukocl'tesare com-
monly found. Plasma cells are small, round cells
TTffiTI
with round, acentricnuclei, whosechromatin net-
work presentsa clockface(cartwheel)appearance.
Thesecells also display a clear, paranuclearGolgi
zone. Lymphocytes, neutrophils, and occasional
eosinophils also contribute to the cellularity of
Iooseconnectivetissue.
2. lntercellular Materials
Slenderbundlesoflong, ribbon-like bandsofcolla-
gen fibers are intertwined by numerous thin,
straight, long, branching elasticfibers embeddedin
a watery matrix of ground substance,most of which
is extracted by dehydration procedures during
preparation. Reticular fibers, also present,are usu-
ally not visible in sectionsstainedwith hematorylin
and eosin.
B. ReticularConnective
Tissue
l. Cells
Reticular cells are found only in reticular connec-
tive tissue. They are stellate in shape and envelop
the reticular fibers, which they also manufacture.
They possesslarge,oval, pale nuclei, and their cy-
toplasm is not easilyvisible with the light micro-
scope.The other cellsin the interstitial spacesare
lymphocytes, macrophages, and other lymphoid
cells.
2. Intercellular Materiqls
Reticularfibers constitutethe major portion of the
intercellular matrix. With the use of a silver stain.
they are evident as dark, thin, branching fibers.
C. AdiposeTissue
l. Cells
Unlike other connectivetissues,adiposetissue is
composed of adipose cells so closely packed to-
gether that the normal spherical morphology of
these cells becomesdistorted. Groups of fat cells
are subdivided into lobules by thin sheathsof loose
connective tissue septa housing mast cells, en-
dothelial cells of blood vessels,and other compo-
nents of neurovascular elements.
2. Intercellulor Materials
Eachfat cell is investedby reticular fibers, which, in
turn, areanchoredto the collagenfibers ofthe con-
nectivetissuesepta.
Tissue r
Connective 49
D. DenselrregularConnective
Tissue 2. lntercellular Materials
l. Cells Parallelfibers ofdensely packedcollagenare regu-
Fibroblasts,macrophages,and cellsassociated larly arrangedin denseregularcollagenousconnec-
with
tive tissue.
neurovascular bundles constitute the chief cellular
elements.
2. Intercellular Materials F. DenseRegularElasticConnective
Haphazardlyorientedthick, wary bundlesof colla- Tissue
gen fibers, aswell as occasionalelasticand reticular
l. Cells
fibersarefound in denseirregularconnectivetissue.
Parallelrows of flattened fibroblasts are usually dif-
ficult to distinguish in preparations that use stains
E. DenseRegularCollagenous
Connective specificfor elasticfibers.
Tissue 2. Intercellular Materials
l. Cells Parallelbundlesofthick elasticfibers, surrounded
Parallel rows of flattened fibroblasts are essentially by slender elements of loose connective tissue,
the only cells found here. Even these are few in comprise the intercellular components of dense
number. regularelasticconnectivetissue.

50 = Connective
Tissue
I r NorEs

I
I
I
I
I
I

Tissue I
Connective 51
CraphicS-1 I Collagen

Muscle

.l/
F ''
L/

Each collagenfiber bundleis composedof smallerfibrils,which in lurn consistof

aggregatesof tropocollagen molecules.Tropocollagen moleculesself-assemblein the
extracellularenvironmentin such a fashionthat there is a gap betweenlhe tail of the one
and the head of the succeedingmoleculeof a singlerow.As fibrilsare formed,tails of
tropocollagenmoleculesoverlapthe headsof tropocollagenmoleculesin adjacentrows.
Additionally,the gaps and overlaps are arrangedso that they are in registerwith those of
neighboring(but not adjacent)rows of tropocollagenmolecules.When stainedwith a
heavymetal,such as osmium,the stainpreferentially precipitatesin the gap regions,
resultingin the repeatinglight and dark bandingof collagen.
I GRAPHIC
3-2 I Tissue
Connective cetts

Undifferentiated
mesenchymal cell

Osteocyte

:i:li:["'"..ffi

M a s tc e l l

Eosnophil

B a s o p hI

Chaoter3 = Connective
Tissue 53
PLATE3- 1 | Embrgonicand ConnectiveTissueProperI
FIGURE I Loose (areolar) connective tissue. FIGURE 2 := Mesenchgmal connective tissue. Fetal
Paraffin section. x 132. pig. Poraffin section. x 540.
This photomicrograph depicts a whole mount of Mesenchymalconnectivetissueof the fetusis very im-
mesentery,through its entire thickness.The two large mature and cellular.The mesenchymalcells (MeC) are
mast cells (MC) are easilyidentified, since they are the stellate-shapedto fusiform cells,whoseqtoplasm (c) can
largestcellsin the field and possessa granularcltoplasm. be distinguished from the surrounding matrix. The
Although their cytoplasmsare not visible,it is still possr- nuclei (N) are pale and centrally located. The ground
ble to recognizetwo other cell typesdue to their nuclear substanceis semifluidin consistencyand containsslender
morphology. Fibroblasts(F) possessoval nuclei that are reticularfibers.The vascularityofthis tissueis evidenced
palerand Iargerthan the nuclei of macrophages(M). The bv the presenceofblood vessels(BV).
semifluid ground substance(GS) through which tissue
fluid percolatesis invisible,sinceit was extractedduring
the preparation of the tissues.However, two tlpes of
fibers,the thicker,wary, ribbon-like, interlacingcollagen
fibers (CF) and the thin, straight,branchingelasticfibers
(EF) are well demonstrated.

FIGURE 3 Mucous connective tissue. Umbilical F|GURE 4 =-:Reticular connectivetissue. Silver

cord. Humon. Paraffin section. x 132.
This exampleof mucousconnectivetissue(Wharton's
jelly) was derived from the umbilical cord of a fetus. Ob-
servethe obvious differencesbetweenthe two embryontc
tissues.The matrix of mesenchymalconnectivetissue
(Fig. 2) containsno collagenousfibers,while this connec-
tive tissue displays a loose network of haphazardly ar-
rangedcollagenfibers (CF). The cellsare no longer mes-
enchymal cells;instead,they are fibroblasts (F), although
morphologically they resemble each other. The empty-
looking spaces(arrows) are areaswhere the ground sub-
stancewas extractedduring specimenpreparation.
Inset. Fibroblast. Umbilical cord. Human. Paraffin
section.X 270.
Note the centrally placed nucleus (N) and the
fusiform shapeof the qtoplasm (c) of this fibroblast.
stain. Paraffin section. x 210.
Silverstain,usedin the preparationof this specimen,
was depositedon the carbohydratecoatingof the reticu-
lar fibers (RF). Note that these fibers are thin, long,
branching structuresthat ramify throughout the field.
Note that in this photomicrographof a lymph node, the
reticular fibers in the lower right-hand corner are ori-
ented in a circular fashion. These form the structural
framework of a cortical lymphatic nodule (LN). The
small round cellsareprobablylymphoid cells(LC), while
the largercells,closelyassociated with the reticularfibers,
may be reticular cells (RC), although definite identifica-
tion is not possiblewith this stain. It should be noted that
reticular connectivetissueis characteristically associated
with lymphatic tissue.

Fibroblast

I KEY
BV bloodvessel GS groundsubstance MeC mesenchymalcell
C cytoplasm LC lymphoidcell N nucleus
CF collagenfiber LN lymphaticnodule RC reticularcell
EF elasticliber M macrophage RF reticularfiber
F fibroblast MC mastcell

54 Connective
Tissue
 t $
t
'7

\!

,/N * r;

s
=*
1

*BV
t

'i d ry'
:i
fp
,r $

t
',d
il
Q f
!
FICURE
2

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F I C U R4
E
C o n n e c t i vTei s s u e 55

PLATE3-2 r ConnectiveTissueProperll
FIGURE I Adipose tissue. Hapodermis. Monkeg.
Plastic section. x 132.
This photomicrographof adiposetissueis from mon-
key hlpodermis. The adipocltes (A), or fat cells,appear
empty due to tissueprocessingthat dissolvesfatty mate-
rial. The qtoplasm (c) ofthese cellsappearsasa periph-
eral rim, and the nucleus(N) is alsopressedto the sideby
the single,largefat droplet (FD) within the c1'toplasm.
Fat
is subdividedinto lobulesby septa(S) ofconnectivetissue
conducting vascular elements (BV) to the adipocltes.
Fibroblastnuclei (arrows)are clearlyevidentin the con-
nective tissuesepta.Note the presenceof the secretory
portions of a sweatgland (SG) in the upper aspectof this
photomicrograph.
Adipocyte
;
FIGURE 2 + Dense irregular collogenous
connective tissue. Palmar skin. Monkeg. Plastic
section. x 132.
I
The dermisof the skin providesa good representation
of dense irregular collagenousconnective tissue. The
thick, coarse,intertwinedbundlesofcollagen fibers (CF)
I
are arrangedin a haphazardfashion.Although this tissue
has numerousblood vessels(BV) and nerve fibers (NF)
branching through it, it is not a very vasculartissue.
Denseirregularconnectivetissueis only sparselysupplied
I
with cells, mostly fibroblastsand macrophages,whose
nuclei (N) appearas dark dots scatteredthroughout the
field. At this magnification,it is not possibleto identifi I
the cell tlpes with any degreeof accuracy.The large ep-
ithelial structure in the upper center of the field is the
duct (d) of a sweatgland.At higher magnification(Inset,
x 540), the coarsebundles of collagenfibers are com-
I
posedof a conglomerationof collagenfibrils (Cfl inter-
twined around eachother. The three cells,whosenuclei
(N) are clearlyevident,cannotbe identifiedwith any de-
gree of certainty,even though the qtoplasm (c) of the
I
two on the left-hand sideis visible.It is possiblethat they
are macrophages, but without employingspecialstaining
techniques,the possibilityof their being fibroblastscan-
l
not be ruled out.

I
FIGURE 3 - Dense regular collogenous connective FIGURE 4 = Dense regular collagenous connective
tissue. x.s. Tendon. Paraffin section. x 210.
fissue. /.s. Tendon. Monkeg. Plastic section. x 210.
Tendonsand ligamentspresentthe most vivid exam-
ples of denseregularcollagenousconnectivetissue.This
Transversesectionsof tendon presenta very tFPical
appearance.Tendon is organizedinto fasciclesthat are
I
connective tissue type is composed of regularly oriented separatedfrom eachother by the peritendineum (P) sur-
parallelbundlesofcollagen fibers (CF), whereindividual
bundles are demarcated by parallel rows of fibroblasts
rounding each fascicle.Blood vessels(BV) may be ob-
servedin the peritendineum.Collagenbundleswithin the I
(F). Nuclei ofthese cellsare clearlyevidentas thin, dark fasciclesare regularly arranged; however, shrinkage due
lines, while their cytoplasm (c) is only somewhat dis- to preparationcausesan artifactuallayering(arrows),al-
cernible.With hematorylin and eosin,the collagenbun-
dlesstain a more or lesslight shadeof pink with parallel
though in somepreparationsswellingof the tissueresults
in a homogenousappearance.The nuclei of fibroblasts
I
rows of dark blue nuclei of fibroblasts interspersed (F) appearto be strewn about in ahaphazatd manner.
among them.
I
a
I
I KEY
t
A
BV
adipocyte
bloodvessel
d
F
duct
fibroblast
P peritendineum
seprum
I
cytoplasm FD fat droplet i)I, sweatgland
a+
CF
collagenfibril
bundleof collagenfibers
N
NF
nucleus
nervefiber I
56 :":: Connective
Tissue I
t
I
t
I
I tt'

I FD,

I
I
t
FICURE
1 FIGURE
2
I *ruep

I
I
I
I
I tq

I
I
I
FICURE3 FICURE4
I ConnectiveTissue 'o 57
PLATE3-3 I ConnectiveTissueProperlll
FIGURE I Dense regular elastic connective
fissue. l.s. Poraffin section. x 132.
This longitudinalsectionofdenseregularelastictissue
demonstratesthat the elasticfibers (EF) are arrangedrn
parallel arrays. However, the fibers are short and are
curled at their ends(arrows).The white spacesamong the
fibersrepresentthe looseconnectivetissueelementsthat
remain unstained.The cellularelementsare composedof
parallelrows of flattenedfibroblasts.Thesecellsare also
unstainedand cannot be distinguishedin this prepara-
tlon.
FIGURE 3 ':'; Elastic laminae (membranes). Aorta.
Paraffin section. x 132.
The wall of the aorta is composedof thick, concentn-
cally arranged elastic membranes (EM). Since these
sheet-likemembraneswrap around within the wall of the
aorta, in transversesectionsthey presentdiscontinuous,
concentric circles,which in this photomicrograph are
representedby more or lessparallel,war.ydark lines (ar-
rows). The connective tissue material between mem-
branesis composedofground substance,collagenfibers
(CF) and reticularfibers.Also Dresentare fibroblastsand
smoothmusclecells,whosenucleimay be discerned.
Mastcell
KEY
BM basalmembrane EF elasticfiber
BV
CF
bloodvessel
collagenfiber
EM
MC
elasticmembrane
mastcell
58 , Connective
Tissue
I
FIGURE 2 =, Dense regular elostic connective
fissue. x.s. Paraffin section. x 132.
A transversesectionof denseregular elasticconnec-
I
a
tive tissue displaysa very characteristicappearance.In
someareasthe fiberspresentprecisecross-sectional pro-
filesasdark dots of variousdiameters(arrows).Other ar-
easpresentoblique sectionsof thesefibers, represented
by short linear profiles (arrowhead).As in the previous
figure, the white spacesrepresentthe unstained loose
connectivetissueelements.The largeclear area (middle
I
left) is also composed of loose connectivetissue sur-
rounding blood vessels(BV).
f
FIGURE 4 # Mast cells, plasma cells,
macrophages.
Mast cells(MC) are conspicuouscomponentsof con-
I
nectivetissueproper, Figure 4a (Tendon. Monkey. Plastic
section.x 540.), althoughthey are only infrequentlyen-
countered.Note the round to ovalnucleus,and numerous
I
small granulesin the cytoplasm.Observealso,among the
bundles of collagen fibers (CF), the nuclei of severalfi-
broblasts.Mast cells(MC) arevery common components
of the subepithelialconnectivetissue(lamina propria) of
I
the digestivetract, Figure 4b (Jejunum.Monkey. Plastic
section.X 540). Note the basalmembrane(BM) separat-
ing the connective tissue from the simple columnar ep-
ithelium (E), whosenuclei are oval in shape.The denser,
I
more amorphous nuclei (arrows) belong to lymphoid
cells,migratingfrom the connectivetissueinto the intesti-
nal lumen. The lamina propria also housesnumerous
I
plasma cells (PC), as evidencedin Figure 4c (Jejunum.
Monkey. Plasticsection.X 540). Plasmacellsarecharac-
terized by clockface("cart-wheel") nuclei, as well as by a
clear paranuclear Golgi zone (arrowhead). Figure 4d
I
(Macrophage.Liver, injected.Paraffinsection.x 270.) is
a photomicrograph of liver that was injected with India
ink. This material is preferentially phagocytosed by
I
macrophagesof the liver, known as Kupffer cells (KC).
Thesecellsappearasdense,black structuresin the liver si-
nusoids,vascularchannelsrepresented by clearareas(ar-
row). An individual Kupffer cell (Inset. Paraffin section.
I
X 540.) displaysthe nucleus(N), aswell as the granules
of India ink (arrowhead)in its cltoplasm.
I
Plasmacell
I
I
I
KC Kupffercell
N
PC
nucleus
plasmacell I
I
I
t
t tilt,
I
I
t
I
I
I
t FICURE
1 2
FICURE

I
I
b)
I
I c.-cl :
=w
t
t
t rri;:t€|.-
r':

I
t
 PLATE5-4 I Fibroblastsand Collagen,ElectronMicroscopg I
t
t
I
'.*\.]
C,-9.i
,,,,, I
ir.*'N\ll\\r,
;i1ii\NN
'qii;iilli\$:gii{
i,n..*l.' I
i,,,,.il\r'$,;."tn**..i\i
ii ; t
I
( .'fl.)
\
). 3
i,tlffi,fl,,;l' i:;r.i{r$*NNNrj
$[t I
t"i:\' -:,.'.' ffir:t-Si:.tN\t\t'
.:ii:.i.'.i', "tz:j,1
iii
l r{
I
I
iiiii';'i'i;:tiiffi :';u*:#iiiI
# I
; ri,iffirt1i';;,fll*iii
:'.:;.ij. :r;.1: :UffiI
;',';i,., ;,:.:
.r.:i..i1'....1'
I
" rtfiii
5tt:il,
I
I
I
FfGURE I Fibroblast. Baboon. Electron thesizethe intercellular
clementsofconnectivetissue,the
m i c r o s c o p gx. 1 1 , 0 7 0 .
This electronmicrographof fibroblasts(F) dcmon-
organellepopulationof fibroblastsis reducedin number,
anclthe plump, euchrornaticnucleus(N) becomesflat-
I
stratesthat they are long, fusifom cellswhoseprocesses tcnccland heterochrornatic. Note that the bundlesof
(p) extendinto the surrour-rding area,betweenbundlesof
collagenfibrils. Thesecellsrnanufacturecollagen,reticr-r-
lar, and elasticfibers,and the qround substance of con-
collagenfibrils (C0 are sectionedboth transversely
terisk)and longitudinally(doubleasterisks).
tibrilsdisplayalterr.rating
trans\rerse
(as-
Individual
dark and light band-
t
nectivetissue.Therefore, theyrrrerich in orgrrrelles,
such ing (arrows)alongtheir length.The specificbandingre-
as Golgi apparatus (G), rough endoplasmicreticulum
(rER),and mitochondria(m); however,in thc quiescent
stage,as in tendons,where they no lorrgcrrrctivelysyn-
sultsfror-nthc ordercd arrangementof the tropocollagen
r.noleculesconstitutingthe collagenfibrils.(From Simp-
I
son D, AveryB:J Periodontol 45:500-510,1974.)

Connective
Tissue t
PLATE3-5 I Mast Cell,ElectronMicroscopg
FIGURE I i:. Msst cell. Rqt. Electron microscopg.
x 14.400.
This electronmicrographof a rat peritonealmast cell
displavscharacteristicsof this cell. Note that the nucleus
(N) is not lobulated,and the cell containsorganelies,such
asmitochondria (m) and Golgi apparatus(G). Numerous
processes(p) extend from the cell. Observethat the most
characteristiccomponent of this cell is that it is filled with
numerous membrane-boundgranules(Gr) of more or less
uniform density. These granules contain heparin, his-
tamine, and serotonin (although human mast cellsdo not
containserotonin).Additionally,mastcellsreleasea num-
ber of unstored substancesthat act in allergic reactions'
(From Lagunoff D: J InvestDermatol 58:296-317,1972.)
ConnectiveTissue ffi' 6 |
 PLATE3-6 I Mast CellDegranulation,ElectronMicroscopg
' 7l-j
.

.f-ir

,4
t?
i'i

F"

FIGURE | * Most cell degronulation. Rat. Electron
miooscopg. x 20,250.
Mast cellspossessreceptormoleculeson their plasma
membrane,which are specificfor the constantregion of
IgE antibody molecules.These moleculesattach to the
mast cell surfaceand, as the cell comesin contact with
thosespecificantigensto which it wassensitized,
the anti-
gen binds with the active regions of the IgE antibody.
Such antibody-antigenbinding on the mast cell surface
causesdegranulation,i.e.,the releaseof granules,aswell
n
$,al'*
asthe releaseofthe unstoredsubstances that act in aller-
gic reactions.Degranulation occurs very quickly, but re-
quires both ATP and calcium. Granules at the periphery
of the cell are releasedby fusion with the cell membrane,
while granules deeper in the cytoplasm fuse with each
other, forming convoluted intracellular canaliculi that
connectto the extracellularspace.Sucha canaliculusmav
be noted in the bottom left-irandcorner of this electron
micrograph. (From Lagunoff D: J Invest Dermatol 58:
296-311,t972.)

62 W Connective
Tissue
PLATE3-7 r DevelopingFat Cell,ElectronMicroscopg
,^'R
.l!
FIGURE I M Developing fat cell. Rat. Electron
mitoscopg. x 3060.
This electron micrograph from the developing rat hy-
podermis displaysa region of the developing hair follicle
(h0. The peripheralaspectof the hair follicle presentsa
small adipoclte (sa)whosenucleus(n) and nucleolusare
clearly visible. Although white adipose cells are unilocu-
lar, in that the cltoplasm ofthe cell containsa single,large
droplet of lipid, during developmentlipid beginsto accu-
mulate as small droplets (l) in the cytoplasm of the small
adipoclte. As the fat cell matures to become a large
adipocl'te (la), its nucleus (n) is displaced peripherally,
and the lipid droplets (l) fuse to form severallarge
ltr
t.
f,t
f3
droplets, which will eventually coalesceto form a single,
centralfat deposit.The nucleusdisplayssomealterations
during the transformation from small to largeadipocytes'
in that the nucleolus becomessmaller and less promi-
nent. Immature adipocy'tes aredistinguishable, sincethey
possessaswell-developedGolgi apparatus(g) that is ac-
tively functioning in the biosynthesisof lipids. Moreover,
the rough endoplasmic reticulum (r) presentsdilated crs-
ternae, indicative of protein synthetic activity. Note the
capillary, whose lumen displays a red blood cell in the
lower left-hand corner of this Photomicrograph.(From
HausmanG, Campion D, RichardsonR, Martin R:'Am J
Anat 16l:85-100,1981.)
Tissue *
Connective 65
 IIffiII

I Cartilage and Bone

I
Cartilageand bone form the supporting tissuesof The fibrous layer, although poor in cells, is com-

I the body. In thesespecializedconnectivetissues,as

in other connectivetissues,the intercellular ele-
mentsdominatetheir microscopicappearance.
I CARTITAGE
t Cartilage forms the supporting framework of cer-
tain organs,the articulatingsurfacesofbones, and
the greaterpart of the fetalskeleton,althoughmost
t of that will be replacedby bone (seeGraphic4-2).
There are three tlpes of cartilagein the body,
namely, hyaline cartilage,elasticcartilage,and fi-
posedmostly of fibroblasts and collagenfibers' The
inner cellularor chondrogeniclayer is composedof
chondroblastsand chondrogeniccells. The latter
give rise to chondroblasts,cellsthat are responsible
for secretingthe cartilagematrix. It is from this layer
that the cartilagemay grow appositionally.
As the chondroblastssecretematrix and fibers
around themselves,they become incarceratedin
their own secretionsand arethen termed chondro-
qtes. The spacethat they occupy within the matrix
is known asa lacuna.Thesechondrocytes,at leastin
young cartilage,possess the capacityto undergocell
division,thus contributing to the growth of the car-

I brocartilage.Hyaline cartilage is found at the artic-

ulating surfacesof most bones;the C rings of the
trachea;and the laryngeal,costal,and nasal carti-
I lages,among others. Elastic cartilage,as its name
implies, possesses a greatdeal of elasticity,which is
due to the elasticfibers embeddedin its matrix. This
cartilage is found in areaslike the epiglottis, exter-
I nal ear and ear canal, and some of the smaller
la4.ngealcartilages.Fibrocartilage is found in only
a few places,namely, in some symphyses,the eu-
tilage from within (interstitial growth). When this
occurs,eachlacunamay houseseveralchondrocytes
and is referredto asa cell nest(isogenousgroup).
Hyaline cartilage is surrounded by a well-
defined perichondrium. The Qpe II collagenfibers
of this cartilageare mostly very fine and are, there-
fore, fairly well masked by the surrounding gly-
cosaminoglycans,giving the matrix a smooth,
$assyappearance.
Elastic cartilage possessesa perichondrium. The

I stachiantube, intervertebral(and some articular)

disks, and certain areaswhere tendons insert into
matrix, in addition to the type II collagen fibers,
containsa wealthof coarseelasticfibersthat impart
bone (Table4-l). to it a characteristicappearance.

I Cartilageis a nonvascular,strong,and somewhat

pliablestructurecomposedof a firm matrix of pro-
teoglycans whose main glycosaminoglycans are
chondroitin-4-sulfate and chondroitin-6-sulfate.
I The fibrous and cellular componentsof cartilage
are embedded in this matrix. The fibers are either
solely collagenousor a combination of elastic and
t collagenous,dependingon the cartilagetype. The
cellular componentsare the chondroqtes, which
arehousedin smallspacesknown aslacunae,inter-
spersedwithin the matrix, as well as chondroblasts
; and chondrogenic cells, both of which are in the
perichondrium.
Fibrocartilage differs from elastic and hyaline
cartilagein that it hasno perichondrium.Addition-
ally, the chondrocytes are smaller and are usually
oriented in parallel longitudinal rows. The matrix
of this cartilage contains a Iarge number of thick
type I collagen fiber bundles between the rows of
chondrocytes(Table4-1).
BONE
Bone has many functions,including support, Pro-
tection, mineral storage,and hemopoiesis.At the

I Most cartilageis surroundedby a connectivetis-

sue membrane,the perichondrium, which has an
outer fibrouslayerand an inner chondrogeniclayer.
specializedcartilage-coveredends,it permits artic-
ulation or movement.Bone, a vascularconnective
tissueconsistingof cellsand calcifiedintercellular

I Cartilageand Bone ffi 65

TABLE 4'l e Cartilage-Tgpes, Characteristics, Locations I
Type

Hyaline
Characteristics

Chondrocltesarrangedin
Perichondrium

Usuallypresentexceptat
Locations(Major Samples)

Articular endsoflong bones,

groups within a basophilic
matrix containingType II
collagen
Elastic Chondrocytescompactedin Present
matrix containingTlpe II
collagenand elasticfibers
Fibrocartilage Chondrocltesarrangedin rows Absent
in an acidophilicmatrix
containingType I collagen
bundlesin rows
materials,may be dense(compact) or sponge-like
(cancellous).Cancellousbone, like that found in-
side the epiphysisor head of long bones,is always
surroundedby compactbone.Cancellousbone has
large,open spacessurroundedby thin, anastomos-
ing plates of bone. The large spacesare marrow
spaces,and the platesof bonesare trabeculaecom-
posedof severallayersor lamellae.Compactbone is
much more densethan cancellousboni. Its spaces
are much reducedin size,and its lamellar orginiza-
tion is much more preciseand thicker.The calcified
matrix is composedof 500/ominerals (mostly cal-
cium hydroryapatite), 50Yoorganic matter (colla-
gen and protein-associated glycosaminoglycans),
and bound water.
Boneis alwayscoveredand lined by soft connec-
tive tissues. The marrow cavity is lined by an
endosteum composed of osteoprogenitor cells
(previouslyknown asosteogeniccells),osteoblasts,
and occasionalosteoclasts.The periosteumcover-
ing the bone surfaceis composedof an outer fi-
brous layerconsistingmainly of collagenfibersand
populatedby fibroblasts.The inner osteogeniclayer
consistsof some collagen fibers and mostly os-
teogenic cells and their progeny, the osteoblasts.
The periosteum is affixed to bone via Sharpey's
fibers, collagenousbundlestrapped in the caliified
bone matrix during ossification.
Bone matrix is produced by osteoblasts,cells
derived from their less differentiatedprecursors,
the osteoprogenitorcells.As osteoblastselaborate
bone matrix, they becometrapped,and as the ma-
trix calcifies, the trapped osteoblastsbecome
known as osteocytes.Osteocl'tes,occupying lentic-
ular-shapedspacesknown as lacunae,possesslong
processes that are housedin tiny canalsor tunnels
known as canaliculi. Sincebone, unlike cartilage,
is a vascularhard tissuewhoseblood vesselspene-
trate and perforate it, canaliculi eventually open
into channelsknown as haversiancanalshousrne
66 w Cartilage
andBone
I
articularsurfaces ventral rib cartilage,templates
for endochondralbone
formation
I
Pinna of ear,auditory canal,
laryngealcartilages
I
Intervertebraldiscs,pubic
syrnphysis
t
I
the blood vessels.Each haversian canal with its
surrounding lamellae of bone containing canali-
culi radiating to it from the osteocytestrapped in
the lacunae is known as an osteon or haversian
I
canal system.
The canaliculiofthe osteonextendto the haver-
sian canalin order to exchangecellularwastemate-
t
rial for nutrients and oxygen. Haversian canals,
which more or lessparallelthe longitudinal axis of
Iong bones,are connectedto each other by Volk-
t
mann's canals.
The bony lamellaeof compact bone are orga-
nized into four lamellar systems:external and inter- I
nal circumferential lamellae, interstitial lamellae,
and the osteons(seeGraphic4- 1).
t
Osteogenesis
Histogenesisof bone occurs via either intramem-
branous or endochondralossification.The former
I
arisesin a richly vascularizedmesenchlrnalmem-
brane where mesenchymal cells differentiate into
osteoblasts (possibly via osteprogenitor cells),
l
which begin to elaboratebone matrix, thus forming
trabeculaeof bone. As more and more trabeculae
form in the same vicinity, they will become inter- I
connected.As they fuse with each other, they form
cancellousbone, which will be remodeledio give
rise to compactbone. The surfacesof thesetrabec-
ulae are populated with osteoblasts.Frequently, an
t
additional cell type, the osteoclast,may be evident.
Theselarge,multinuclearcellsderivedfrom mono-
cytes are found in shallow depressions on the
t
trabecularsurface(Howship's lacunae) and func-
tion to resorb bone. It is through the integrated
interactionsofthese cellsand osteoblasts that bone
t
is remodeled. The region of the mesenchymal
membranethat doesnot participatein the ossifica-
tion processwill remain the soft tissuecomponent
of bone (i.e.,periosteum,endosteum).
I
I
 Newly formed bone is called primary or woven
bone, sincethe arrangementof collagenfiberslacks
the preciseorientation presentin older bone. The
integratedinteractionbetweenosteoblastsand os-
teoclastswill act to replace the woven bone with
secondaryor mature bone.
Endochondral ossification, responsible for the
formation of long and short bones, relies on the
presenceof a hyalinecartilagemodel that is usedas
a templateon and within which bone is made (see
Graphic 4-2). However,cartilagedoesnot become
bone.Instead,abonysubperiostealcollar is formed
(via intramembranousossification)around the
midriffof the cartilaginoustemplate.This collar in-
creasesin width and length. The chondrocytesin the
centerof the templatehlpertrophy and resorbsome
of their matrix, thus enlargingtheir lacunaesomuch
that somelacunaebecomeconfluent. The hypertro-
phied chondrocftes, subsequentto assistingin cal-
cification of the cartilage,degenerateand die. The
newly formed spacesare invaded by the periosteal
bud (composedof blood vessels, mesenchyrnal cells,
and osteoprogenitorcells). Osteoprogenitorcells
differentiateinto osteoblasts,and thesecellselabo-
rate a bony matrix lining on the calcified cartilage.
As the subperiostealbone collar increasesin thick-
nessand length,osteoclasts resorbthe calcifiedcar-
tilage-calcifiedbone complex,leaving an enlarged
space,the future marrow cavity (which will be pop-
ulatedby marrow cells).The entireprocessof ossifi-
cation will spread away from this primary ossifica-
tion center, and eventuallymost of the cartilage
templatewill be replacedby bone, forming the dia-
physis of a long bone. The formation of the bony
epiphysis(secondaryossification center)occursin a
modified fashion so that a cartilaginouscovering
may be maintained at the articular surface.The
growth in length of a long bone is due to the pres-
ence of epiphyseal plates of cartilage Iocated
betweenthe epiphysisand the diaphysis.
Cartilageand Bone t 67

Histophgsiologg
I. CARTILAGE
A. CartilageMatrix
Hyaline cartilageis an avascularconnectivetissue
whosepliable matrix providesa conduit for nutri-
ents and wasteproducts to and from its perichon-
drium and its chondrocytes.The matrix consistsof
type II collagen embedded in an amorphous
ground substancecomposedof the glycosamino-
glycan,hyaluronic acid,to which proteoglycansare
bound. The glycosaminoglycan componentsof the
proteoglycans are mainly chondroitin-4-sulfate
and chondroitin-6-sulfate.The acidic natureof the
proteoglycans, combinedwith the enormoussizeof
the proteoglycan-hyaluronic acidcomplex,results
in these moleculespossessinghuge domains and
tremendouscapacityfor binding cationsand water.
Additionally, the matrix contains glycoproteins
that help the cellsmaintain contactwith the inter-
cellularmatrix.
Elastic cartilage is similar to hyaline cartilage,
but it also possesses elastic fibers. Fibrocartilage
possesses no perichondrium,only a limited amount
of acidophilicmatrix, and an abundanceof type I
collagenarrangedin parallelrows.
B. Chondrocytes
The chondrocytesof hyaline and elasticcartilage
resembleeachother, in that they may be arranged
individually in their lacunae or in cell nests (in
young cartilage).Peripherallylocatedchondrocl'tes
are lenticular in shape, whereas those located
centrally are round. The cells completelyfill their
Iacunae.They possessan abundanceof glycogen,
frequent largelipid droplets,and a well-developed
protein synthetic machinery (rough endoplasmic
reticulum, Golgi apparatus,trans-Golgi network),
as well as mitochondria, sincethesecellscontinu-
ously turn over the cartilagematrix.
II. BONE
A. BoneMatrix
Bone is a calcified,vascularconnectivetissue.Its
cellsare locatedin the surroundingperiosteum,in
the endosteallining, or within lenticular cavities
calledlacunae.Tiny channelsknown as canaliculi,
68 := Cartilageand Bone
I rt
housing slender processesof osteocltes, convey
nutrients, hormones, and other necessarysub-
stances.
The organicmatrix of bone is composedmainly
of type I collagen,sulfatedglycoproteins, and some
proteoglycans.The matrix of collagenis calcified
with calcium hydroryapatite crystals,making bone
one of the hardest substancesin the body. The
presenceof these crystalsmakes bone the body's
storehouseof calcium,phosphate,and other inor-
ganicions. Thus, bone is in a dynamic stateof flux,
continuously gaining and losing inorganic ions
to maintain the body's calcium and phosphate
homeostasis.
B. Cells of Bone
Osteoprogenitor cells are flattened, undifferenti-
ated-appearingcellslocatedin the cellularlayer of
the periosteum,in the endosteum,and lining the
haversiancanals.They give rise to osteoblasts.
Osteoblastsare cuboidal to low-columnar cells
responsiblefor the synthesisof bone matrix. As they
elaboratebone matrix, they becomesurroundedby
the matrix and then becomeosteocltes.The bone
matrix is calcifieddue to the seedingof the matrix
via matrix vesiclesderived from osteoblasts.When
osteoblastsare quiescent,they lose much of their
protein synthetic machinery and resembleosteo-
progenitor cells.
Osteoqtes are flattened,discoid cellslocatedin
Iacunae;they areresponsiblefor the maintenanceof
bone.Their cytoplasmicprocesses contactand form
gap junctions with processesof other osteocl'tes
within canaliculi:thus thesecellssustaina commu-
nication network, so that a largepopulation of os-
teocltesare ableto respondto blood calciumlevels
aswell as to calcitonin and parathormone, released
by the thyroid and parathyroidglands,respectively.
Thus thesecellsare responsiblefor the short-term
calciumand phosphatehomeostasisof the body.
Osteoclasts are multinucleated cells derived
from monocytes;they are responsiblefor the re-
sorption of bone. Cooperationbetweenosteoclasts
and osteoblastsis responsiblenot only for the for-
mation, remodeling,andrepairof bone but alsofor
the long-term maintenanceof calcium and phos-
phatehomeostasisof the body.
t
C l i n i c aC
l o n s i d e r a t i o nns r I calcium bonesbecome
levelslf in excess,
brittleandaresusceptible to fracture
I Carti lage Degeneration Paget's Diseaseof Bone
H y a l i n ec a r t i l a g e
b e g i n st o d e g e n e r a tw e h e nt h e Paget'diseaseof boneisa generalized skeletal

I c h o n d r o c y t ehsy p e r t r o p h ay n d d i e ,a n a t u r a l
p r o c e s sb u t o n e t h a t a c c e l e r a t ewsi t ha g i n gT h i s
diseasethatusually
thedisease
affects
hasa famllial
olderpeople.
component
Oflen,
andits
g o b i l i t ya n dj o i n t p a i n
r e s u l t si n d e c r e a s i nm resultsarethickened,butsofterbonesof the
skullandextremities asymptomatic
lt is usually
I Vitamin Deficiencg
D e f i c i e n ciyn V i t a m i nA i n h i b i t sp r o p e rb o n ef o r -
andis frequently
examination
discovered
prescribed
afterradiographic
forolherreasons or as
m a t i o na n d g r o w t h w , h i l ea n e x c e s sa c c e l e r a t e s a result
of bloodchemistry showingelevated
t o s s i f i c a t i oonf t h e e p i p h y s e apll a t e sp r o d u c i n g
s m a l ls t a t u r eD e f i c l e n ciyn v i t a m i nD , w h i c hi s
alkalineohosohataselevels.
mentmaybe usedto slowtheprogression
treat-
Calcitonin
of
e s s e n t i af ol r a b s o r p t i o n
o f c a l c i u mf r o m t h e i n - thedisease
I ( s o f t )b o n e -
t e s t i n er, e s u l t si n p o o r l yc a l c i f i e d
r i c k e t sl n c h i l d r e na n d o s t e o m a l a c i a n adults
Osteoporosis
Osteoporosis isa decrease in bonemassarising
W h e nl n e x c e s sb, o n ei s r e s o r b e dD e f i c i e n ciyn
fromlackof boneformation or fromincreased
I V i t a m l nC , w h i c hi s n e c e s s a rfyo r c o l l a g e n
mationp , r o d u c e s c u r v y - r e s u l t i nign p o o r
bonegrowthand repair
for-
boneresorption.
because
lt occurs
of decreased
commonly
growthhormone
in oldage
andin
Dostmenooausal womenbecause of decreased
t Hormonal Influences on Bone
C a l c i t o n iinn h i b i t sb o n e - m a t r irxe s o r p t i o n by
estrogen secretion
ingto receptors
Inthelatter,estrogen
on osteoblasts stimulate
bind-
the
a l t e r i n go s t e o c l a sf tu n c t i o nt,h u s p r e v e n l i n g secretionof bonematrixWithout sufficient

I c a l c i u mr e l e a s eP a r a t h y r o ihdo r m o n ea c t i v a t e s
osteoblasts to secreteosteociast-stimulating
f a c t o r ,t h u sa c t i v a t i n og s t e o c l a s t so i n c r e a s e
estrogen,osteoclasticactivity
masswithouttheconcomitant
bone,therefore making
reduces bone
formation of
thebonesmoreliable
b o n er e s o r p t i o n resultlng i n i n c r e a s e bd l o o d to fracture
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Cartilage 69
 TTIII I
Summargof HistologicalOrganization I
I. CARTILAGE D. Fibrocartilage
I
A. EmbryonicCartilage l. Perichondrtum
l. Perichondrium
The perichondrium is very thin and cellular.
The perichondrium is usually absent.
2. Mqtrix
I
The ground substance of matrix is very scanty.
2. Matrix
The matrix is scantyand smooth in appearance. Many thick collagen bundles are located between
parallel rows of chondrocytes.
I
3. Cells
3. Cells
Numerous, small, round chondrocytesare housed
in small spacesin the matrix. These spacesare The chondrocytes in fibrocartilage are smaller than
those in hyaline or elasticcartilage,and they areab
I
known as lacunae.
ranged in parallel longitudinal rows between bun-

B. Hyaline Cartilage
dlesofthick collagenfibers. t
l. Perichondrium
The perichondrium hastwo layers,an outer fibrous
layer, which contains collagen and fibroblasts, and
II.BONE
A. Decalcified
Compact
Bone
I
an inner chondrogenic layer, which contains chon- l. Periosteum
drogenic cells and chondroblasts.
2. Mdtrix
The periosteum has two layers, an outer fibrous
layer, containing collagen fibers and fibroblasts,
I
The matrix is smooth and basophilic in appearance. and an inner osteogenic layer, containing osteo-
It has two regions,the territorial (capsular) matrix,
which is darker and surrounds lacunae,and the in-
progenitor cells and osteoblasts.It is anchored to
bone by Sharpey'sfibers.
I
terterritorial (intercapsular) matrix, which is
lighter in color. The collagen fibrils are masked by
the ground substance.
2. Lamellar Sgstems
Lamellar organization consists of outer and inner
circumferential lamellae, osteons (haversian canal
r
3. Cells systerns),and interstitial lamellae.
Either chondrocytes are found individuallyin lacu-
nae, or there may be two or more chondrocytes
3. Endosteum
The endosteum is a thin membrane that lines the
I
(isogenousgroup) in a lacuna.The latter casesigni- medullary cavity, which contains yellow or white
fies interstitial growth. Appositional growth occurs
just deepto the perichondrium and is attributedto
bone marrow.
4. Cells
I
chondroblasts.
Osteocytesare housed in small spacescalled lacu-

C. ElasticCartilage
l. Perichondrium
The perichondriumis the samein elasticcartilageas
in hyaline cartilage.
2. Matrix
The matrix contains numerous dark elastic fibers
in addition to the collagen fibrils.
3. Cells
The cells are chondrocytes, chondroblasts, and
chondrogenic cells, as in hyaline cartilage.
nae. Osteoblasts and osteoprogenitor cells are
found in the osteogenic layer of the periosteum, in
I
the endosteum,and lining haversiancanals.Osteo-
clasts are located in Howship's lacunae along re-
sorptive surfaces of bone. Osteoid, noncalcified I
bone matrix, is interposedbetweenthe cellsof bone
and the calcified tissue.
5. Vascular Supplg I
Blood vesselsare found in the periosteum,in the
marrow cavity, and in the haversian canals of os-
teons.Haversiancanalsareconnectedto eachother ;
by Volkmann's canals.

I
70 e Cartilage
andBone t
B. Undecalcified Compact Ground Bone
l. Lamellar Sgsfems
The lamellar organizationis clearlyevidentaswafer-
thin layersor lamellaeconstitutingbone. They are
then organized as outer and inner circumferential
lamellae,osteons,and interstitial lamellae.
Osteonsare cylindrical structurescomposedof
concentric lamellae of bone. Their lacunae are
empt/, but in living bone they contain osteocytes.
Canaliculi radiate from lacunae toward the central
haversiancanal,which in living bone housesblood
vessels,osteoblasts,and osteogeniccells.Cement-
ing lines demarcate the peripheral extent of each
osteon.Volkmann's canalsinterconnectneighbor-
ing haversiancanals.
C. Decalcified Cancellous Bone
1. Lamellar Sysfems
Lamellarorganizationconsistsof spiculesand tra-
beculaeofbone.
2. Cells
Cellsare asbefore,in that osteoqytesare housedin
lacunae.Osteoblastsline all trabeculaeand spicules.
Occasionally,multinuclear, large osteoclalts oc-
cupy Howship's lacunae. Osteoid, noncalcified
bone matrix, is interposedbetweenthe cellsof bone
and the calcifiedtissue.
Bone marrow occupiesthe spacesamong and
betweentrabeculae.
D. Intramembranous
Ossification
l. Ossification Centers
Centers of ossification are vascularized areas of
mesenchymal connective tissue where mesenchy-
mal cells probably differentiate into osteoprogeni-
tor cells,which differentiate into osteoblasts.
2. Lomellar Sgsferns
Lamellar organization begins when spicules and
trabeculae form into primitive osteons surround-
ing blood vessels.The first bone formed is primary
bone (woven bone) whose cells are larger and
whosefibrillar arrangementis haphazardcompared
with secondary(mature) bone.
3. Cells
The cellularelementsof intramembranousossifica-
tion are osteoprogenitorcells, osteoblasts,osteo-
cytes, and osteoclasts.Additionally, mesenchymal
and hemopoieticcellsare alsopresent.
E. Endochondral
Ossification
l. Primarg Ossification Center
The perichondrium of the diaphysis of the carti-
lage template becomes vascularized, followed by
hypertrophy of the centrally located chondrocytes,
confluence of contiguous lacunae, calcification of
the cartilage remnants, and subsequentchondro-
cytic death. Concomitant with these events, the
chondrogenic cells of the perichondrium become
osteoprogenitor cells, which, in turn, differentiate
into osteoblasts.The osteoblastsform the subpe-
riosteal bone collar, thus converting the overlying
perichondrium into a periosteum. A periosteal
bud invades the diaphysis, entering the confluent
lacunae left empty by the death of chondrocytes.
Osteogenic cells give rise to osteoblasts,which
elaborate bone on the trabeculae of calcified
cartilage. Hemopoiesis begins in the primitive
medullary cavitp osteoclasts (and, according to
some, chondroclasts)develop, which resorb the
bone-coveredtrabeculaeof calcified cartilage as
the subperiostealbone collar becomesthicker and
elongated.
2. Secondarg Ossification Center
The epiphyseal (secondary) center of ossification
is initiated somewhat after birth. It begins in the
center of the epiphysis and proceeds radially
from that point, leaving cartilageonly at the artic-
ular surface and at the interface between the
epiphysis and the diaphysis, the future epiphyseal
plate.
3. Epiphgseal Plqte
The epiphyseal plate is responsiblefor the future
lengthening of a long bone. It is divided into five
zones:1) zone ofreservecartilage,a region ofhap-
hazardly arrangedchondrocytes;2) zoneof cellpro-
liferation, where chondrocftes are arrangedin rows
whoselongitudinal axis parallelsthat of the growing
bone; 3) zone of cell maturation and hypertrophy,
wherecellsenlargeand the matrixbetween adjoining
cells becomes very thin; 4) zone of calcifying carti-
lage, where lacunaebecome confluent and the ma-
trix betweenadjacentrows of chondrocytesbecomes
calcified, causing subsequent chondrocytic death;
and 5) zone of provisional ossification, where os-
teoblastsdepositbone on the calcifiedcartilagerem-
nants between the adjacentrows. Osteoclasts(and,
according to some, chondroclasts)resorb the calci-
fied complex.
Cartilageand Bone ffi 7 |
CRAPHIC
4-1 I Compact
Bone

Concentriclamellae

Osteons

Innercircumferential
lamellae

Periosteum

Sharpey'sfibers

Bloodvessels

Volkmann's
canal

Haversiancanal

- Cancellous
bone

Marrowcavity

Compactbone

i /4t

CompactBone
Compactbone is surroundedby dense irregularcollagenousconnectivetissue,the
periosteum, which is attachedto the outer circumferential lamellae by Sharpey's
fibers. Bloodvesselsof the periosteumenterthe bone via largernutrientcanalsor small
Volksmann's canals, which not only conveybloodvesselsto the Haversiancanals of
osteons but also interconnectadjacentHaversiancanals.Each osteonis composedof
concentriclamellaeof bone whosecollagenfibersare arrangedso that they are
perpendicularto those of contiguouslamellae.The inner circumferential lamellaeare
lined by endosteallinedcancellousbone that protrudesinto the marrowcavity.

72 * Cartilageand Bone
I 4-2 r Endochondral
GRAPHIC BoneFormation

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I Endochondral Bone Formation

A. Endochondralbone formation reouiresthe
p r e s e n c eo f a h y a l i n ec a r t i l a g em o d e l .

t B . V a s c u l a r i z a t i oonf t h e d i a p h y s i sp e r i c h o n d r i u m
( 2 ) r e s u l t si n t h e t r a n s f o r m a t i o onf chondrogenic
c e l l st o o s t e o g e n i cc e l l s ,r e s u l t i n gi n t h e f o r m a t i o n
of a subperiostealbone collar (1) (via

I i n t r a m e m b r a n o ubs o n e l o r m a t i o n ) w
becomes perforatedby osteoclasticactivity
Chondrocytesin the center of the cartilage
, hichquickly

h y p e r t r o p h y( 3 ) , a n d t h e i r l a c u n a eb e c o m e

I confluent

C . T h e s u b p e r i o s t e abl o n e c o l l a r( 1 ) i n c r e a s e di n
l e n g t ha n d w i d t h ,t h e c o n f l u e n tl a c u n a ea r e

t invaded by the periosteal bud (4), and

osteoclasticactivityforms a primitivemarrow
cavity (5) whose walls are composed of calcified
cartilage-calcifiedbone complex. The epiphyses

t d i s p l a yt h e b e g i n n i n go f s e c o n d a r y o s s i f i c a t i o n
centers (7)

D a n d E . T h e s u b p e r i o s l e abl o n d c o l l a r( 1) h a s

t become sufficientlylarge to suppoft the

d e v e l o p i n gl o n g b o n e , s o t h a t m u c h o f t h e
cartilage has been resorbed,with the exception of
the epiphyseal plate (8) and the covering of the
e p i p h y s e s( 9 ) O s s i f i c a t i o ni n t h e e p i p h y s e s
I o c c u r sf r o m t h e c e n t e r( 10 ) , t h u s t h e v a s c u l a r
p e r i o s t e u m( 11) d o e s n o t c o v e r t h e c a r t i l a g i n o u s
s u r f a c e .B l o o dv e s s e l s( 1 2 ) e n t e rt h e e p i p h y s e s ,

r without vascularizingthe cartilage,to constitute

t h e v a s c u l a rn e t w o r k( 13 ) a r o u n dw h i c h s p o n g y
bone will be formed

rl Cartilageand Bone 73
PLATE4- 1 a EmbrAonicand HgalineCartilages
FIGURE I Embrgonic hgoline cartilage. Pig.
Poraffin section. x 132.
The developinghyalinecartilageis surroundedby em-
bryonic connective tissue (ECT). Mesenchymal cells
haveparticipatedin the formation of this cartilage.Note
that the developingperichondrium (P), investingthe car-
tilage,mergesboth with the embryonicconnectivetissue
and with the cartilage.The chondrocltesin their lacunae
are round, small cells packed closely together (arrow)
with little intervening homogeneouslystaining matrrx
(arrowheads).
FIGURE 3 Hgaline cartilage. Rabbit. Paraffin
section. x 2la.
The perichondrium is composedof fibrous (F) and
chondrogenic (CG) layers.The former is composedof
mostly collagenousfiberswith a few fibroblasts,while the
latter is more cellular, consistingof chondroblastsand
chondrogenic cells (arrows). As chondroblastssecrete
matrix they become surrounded by the intercellular sub-
stance,and areconsequentlyknown aschondrocytes(C).
Note that chondrocl'tesat the periphery of the cartilage
aresmalland elongated,while thoseat the centerarelarge
and ovoid to round (arrowhead). Frequently they are
found in isogenousgroups (IG).
I KEY
C chondrocyte Ep pseudostratif
Cg chondrogenic columnarepithelium
perichondrium F fibrousperichondrium
CT connectivetissue IG rsogenous group
ECT embryonicconnective
tissue
74 Cartilageand Bone
FIGURE 2 Hgoline cartilage. Trochea. Monkeg.
Parqffin section. x. 132.
The trachea is lined by a pseudostratifiedciliated
columnar epithelium (Ep). Deep to the epithelium ob-
servethe large,blood-filledvein (V). The lower half of the
photomicrographpresentshyalinecartilagewhosechon-
drocytes (C) are disposedin isogenousgroups (IG) in-
dicativeof interstitial growth. Chondrocytesare housed
in spacesknown aslacunae.Note that the territorial ma-
trix (arrow) in the vicinity of the lacunaestainsdarker
than the interterritorialmatrix (asterisk).The entire car-
tilageis surroundedby a perichondrium (P).
FIGURE 4 Hgaline cortilage. Trachea. Monkeg.
Plastic section. x 270.
The pseudostratifiedciliated columnar epithelium dis-
playsnumerousgobletcells(arrows).The cilia,appearing
at the free border of the epithelium, are clearly evident.
Note how the subepithelialconnectivetissue (CT) merges
with the fibrous perichondrium (F). The chondrogenic
layer ofthe perichondrium (Cg) houseschondrogeniccells
and chondroblasts.As chondroblastssurround themselves
with matrix, they become trapped in lacunae and are re-
ferredto aschondroqtes (C). At the peripheryofthe car-
tilage,the chondroqtes are flattened,while toward the in-
terior they are round to oval. Due to the various histologic
procedures,some of the chondrocltes fall out of their la-
cunae,which then appearas empty spaces.Although the
matrix (M) containsmany collagenfibrils, they aremasked
by the glycosaminoglycans; hence,the matrix appearsho-
mogeneousand smooth. The proteoglycan-richlining of
the lacunaeis responsiblefor the more intensestainingof
the territorial matrix, which is particularly evident in Fig-
ures2 and 3.
Chondrocytes
ied ciliated M matrix
P perichondrium
vern
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Cartilage
andBone 75
PLATE4-2 I Elasticond Fibrocortilages
F|GURE I Elastic cartilage. Epiglottis. Human.
Paraffin section. x l3).
Elasticcartilage,like hyalinecartilage,is envelopedby
a perichondrium (P). Chondrocytes (C), which are
housed in lacunae(arrow), have shrunk away from the
walls,giving the appearanceof empty spaces.Occasional
lacunaedisplaytwo chondrocltes(asterisk),indicativeof
interstitialgrowth. The matrix has a rich elasticfiber (E)
component that gives elasticcartilageits characteristic
appearance,as well as contributing to its elasticity.The
boxed areaappearsat a higher magnificationin Figure3.
FIGURE 3 Elastic cartilage. Epiglottis. Human.
Paraffin section. x 540.
This is a high magnification of the boxed area rn
Figure l. The chondroqtes (C) are large,oval to round
cellswith acentricnuclei (N). The cellsaccumulatelipids
in their cltoplasm, often in the form of lipid droplets,
thus imparting to the cell a "vacuolated" appearance.
Note that the elasticfibers (E) mask the matrix in some
areas, and that the fibers are of various thicknesses,
especiallyevidentin cross-sections (arrows).
Chondroblast
I KEY
C chondrocyte E elasticfiber
CF collagenfiber F fibrousperichondrium
Cg chondrogenic
perichondrium
76 = Cartilageand Bone
FIGURE 2 :: Elostic cortilage. Epiglottis. Human.
Paraffin section. x 270.
This higher magnificationof the perichondrialregion
of Figure I displaysthe outer fibrous (F) and inner chon-
drogenic (CG) regionsof the perichondrium. Note that
the chondrocytes(arrow) immediatelydeepto the chon-
drogeniclayerare more or lessflattenedand smallerthan
those deeperin the cartilage.Additionally, the amount
and coarseness of the elasticfibersincreaseadjacentto the
largecells.
FIGURE 4 , Fibrocortilage. lntervertebral disc.
Human. Paraffin section. x 132.
The chondrocytes(C) offibrocartilageare alignedin
parallel rows, lying singly in individual lacunae. The
nuclei of these chondrocFes are easilyobserved,while
their cltoplasm is not as evident (arrow). The matrix
containsthick bundlesofcollagen fibers (CF), which are
arrangedin a more or lessregular fashion betweenthe
rows of cartilagecells.Unlike elasticand hyaline carti-
lages,fibrocartilageis not envelopedby a perichondrium.
Chondrocytes
N nucteus
P perichondrium
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Cartilageand Bone 77
PLATE4-3 I CompactBone
FIGURE I Decalcified compact bone. Humqn.
Paraffin section. x 132.
Cross-sectionof decalcifiedbone, displayingskeletal
muscle (SM) fibersthat will insert a short distancefrom
this site.The outer fibrous periosteum(FP) and the inner
osteogenicperiosteum (OP) are distinguishabledue to
the fibrous component of the former and the cellularity
of the latter.Note the presenceof the inner circumferen-
tial (lC) lamellae,osteons(Os), and interstitial lamellae
(asterisk).Also observethe marrow (M) occupying the
marrow cavity,aswell asthe endosteallining (arrow).
FfGURE 2 Decqlcified compact bone. Humon.
Paroffin section. x 132.
This is a cross-sectionof decalcifiedcompact bone,
displayingosteonsor haversiancanal systems(Os), as
well as interstitial lamellae(IL). Each osteonpossesses
a
central haversian canal (HC), surrounded by several
lamellae(L) of bone.The boundaryof eachosteonis vrs-
ible and is referredto as a cementingline (arrowheads).
Neighboringhaversiancanalsareconnectedto eachother
by Volkmann's canals(VC), through which blood vessels
ofosteonsare interconnectedto eachother.

FIGURE 3 Decalcified compoct bone. Human.
Paraffin section. x 540.
A small osteon is delineatedby its surrounding ce-
menting line (arrowheads).The lenticular-shaped osteo-
cytes (Oc) occupy flattened spaces,known as lacunae.
The lacunaeareiined by uncalcifiedosteoidmatrix.
Inset. Decalcified compact bone. Human. Paraffin
section.X 540.
A haversiancanalof an osteonis shown to contain a
smallblood vessel(BV) supportedby slenderconnective
tissueelements.The canalis lined by flattenedosteoblasts
(Ob) and, perhaps,osteogeniccells (Op).
FIGURE 4 " Undecalcified ground compqct bone.
x.s. Human. Paraffin section. x 132.
This specimenwas treatedwith India ink in order to
accentuatesomeof the salientfeaturesof compactbone.
The haversiancanals(HC) aswell asthe lacunae(arrows)
appearblack in the figure. Note the connectionbetween
two osteonsat top center,known as Volkmann's canal
(VC). The canaliculiappearas fine, narrow lines Ieading
to the haversiancanalasthey anastomose with eachother
and with lacunaeofother osteocytes ofthe sameosteon.

Osteoblast Osteocyte

I KEY
BV bloodvessel IL lamella
interstitial Op osteogeniccell
FP fibrousperiosteum lamella OP osteogenicperiosteum
HC haversiancanal M marrow Os osleon
lC innercircumferential ob osteoblast SM skeletalmusclefiber
lamella Oc osteocyte VC Volkmann'scanal

78 Cartilageand Bone
 a

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Cartilageand Bone 79
PLATE4-4 I CompactBoneond lntramembranous
Ossificotion
FIGURE I Undecqlcified ground bone. x.s.
Human. Paraffin section. x 210.
This transversesection of an osteon clearly displays
the lamellae(L) ofbone surroundingthe haversiancanal
(HC). The cementingline actsto delineatethe periphery
of the osteon.Note that the canaliculi (C) arising from
the peripheral-mostlacunaeusually do not extend to-
ward other osteons.Instead,they lead toward the haver-
sian canal.Canaliculi,which appearto anastomosewith
eachother and with lacunae,houselong osteocyticpro-
cessesin the living bone.
FIGURE 2 tftllntromembranous ossificotion. Pig
skull. Paraffin section. x 132.
The anastomosingtrabeculae (T) of forming bone
appeardarkly stainedin a backgroundofembryonic con-
nectivetissue(ECT). Observethat this connectivetissue
is highly vascularand that the bony trabeculaeare form-
ing primitive osteons(Os) surrounding large,primitive
haversian canals (HC), whose center is occupied by
blood vessels(BV). Observethat the osteocytes(Oc) are
arranged somewhat haphazardly. Every trabecula is cov-
eredby osteoblasts(Ob).

F|GURE 3 Intramembranous ossification. Pig F|GURE 4 N lntramembranous ossificqtion. Pig

skull. Paraffin section. x 210.
This photomicrograph of intramenbranousossifica-
tion is taken from the periphery of the bone-forming
region.Note the developingperiosteum (P) in the upper
right-handcorner.Justdeepto this primitive periosteum,
osteoblasts(Ob) are differentiatingand are elaborating
osteoid (Ot), as yet uncalcified bone matrix. As the
osteoblastssurround themselveswith bone matrix, they
becometrappedin their lacunaeand areknown asosteo-
cltes (Oc). Theseosteocytesare more numerous,larger,
and more ovoid than those of mature bone, and the
organizationof the collagenfibers of the bony matrix is
lessprecisethan that of mature bone. Hence,this bone is
referredto as immature (primary) bone, and it will be
replacedby mature bone later in life.
skull. Paraffin section. x 540.
This photomicrographis takenfrom an areasimilarto
thoseofFigures2 and 3. This trabeculademonstratessev-
eralpoints, namelythat osteoblasts(Ob) coverthe entire
surface,and that osteoid (Ot) is interposedbetweencal-
cified bone and the cellsofbone and it appearslighter in
color. Additionally, note that the osteoblastmarked with
the asteriskis apparentlytrapping itselfin the matrix it is
elaborating.Finally, note the large, multinuclear cells,
osteoclasts(Ocl), which are in the processof resorbing
bone.The activityof theselargecellsresultsin the forma-
tion of Howship'slacunae(arrowheads),which are shal-
low depressionson the bone surface.The interactions
between osteoclastsand osteoblastsare very finely regu-
latedin the normal formation and remodelinsof bone.

Compactbone

T KEY
BV bloodvessel I lamella Os osleon
C canaliculus ob osteoblast ot osteoid
ECT embryonicconnective Oc osteocyte P periosteum
tissue Ocl osteoclast T trabecula
HC haversiancanal

80 i'ir Cartilageand Bone

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and Bone 81
PLATE4-5 I Endochondral
Ossification
FIGURE | | Epiphgseal ossification center.
Monheg. Paraffin section. x 14.
Most long bones are formed by the endochondral
method of ossification,which involvesthe replacementof
a cartilagemodel by bone. In this low power photomi-
crograph, the diaphysis (D) of the lower phalanx has
been replacedby bone, and the medullary cavity is filled
with marrow (M). The epiphysis (E) of the samephalanx
is undergoing ossification and is the secondary center of
ossification (2"), thereby establishing the epiphyseal
plate (ED). The trabeculae (T) are clearly evident on the
diaphysealside of the epiphysealplate.
FIGURE 2 f Endochondral ossification. l.s.
Monkeg. Paraffin section. x 14.
Much of the cartilagehasbeenreplacedin the diaphysis
of this forming bone. Note the numerous trabeculae (T)
and the developing bone marrow (M) of the medullary
cavity. Ossificationis advancingtoward the epiphysis (E),
in which the secondarycenter of ossification has not yet
appeared.Observethe periosteum (P), which appearsasa
definite line benveenthe subperiostealbone collar and the
surrounding connective tissue. The boxed area is repre-
sentedin Figure 3.

FIGURE 3 | Endochondral ossification. Monkeg.

Paraffin section. x 132.
This montage is a higher magnification of the boxed
area of Figure 2. The region where the periosteum and
perichondriummeetis evident(arrowheads).Deepto the
periosteumis the subperiostealbone collar (BC), which
was formed via intramembranous ossification.Endo-
chondral ossification is evident within the cartilage tem-
plate. Starting at the top of the montage,note how the
chondrocytesare lined up in long columns (arrows),
indicative of their intense mitotic activity at the future
epiphysealplate region. In the epiphysealplate this will be
the zone of cell proliferation (ZP). The chondrocytes
increasein sizein the zone ofcell maturation and hyper-
trophy (ZH) and resorb some of their lacunar walls,
enlargingthem to suchan extentthat someofthe lacunae
become confluent.The chondroqrtesdie in the zone of
calcifying cartilage (ZC). The presumptive medullary
cavity is being populated by bone marrow, osteoclastic
and osteogenic cells, and blood vessels.The osteogenic
cells are actively differentiating into osteoblasts,which
are elaborating bone on the calcified walls of the conflu-
ent lacunae. At the bottom of the photomicrograph
observethe bone-coveredtrabeculaeofcalcified cartilage
(asterisks).

Endochondralboneformation

I KEY
BC subperiostealbone collar P periosteum zc zone of calcityingcartilage
D diaphysis 2" secondarycenler of ZH zone of cell maturationand
E epiphysis ossitication hypertrophy
ED epiphysealplate trabecula ZP zone of oroliferation
M marrow

82 E Cartilageand Bone
FIGURE2 F I G U R5E
andBone ffi 83
Cartilage
PLATE4-6 lr Endochondral
Ossification
FfGURE I s Endochondral ossification. Monkeg.
Poraffin section. x 132.
This photomicrographis a higher magnificationof a
region of Plate4.5, Figure3. Observethe multinucleated
osteoclast(arrowheads)resorbingthe bone-coveredtra-
beculaeof calcifiedcartilage.The subperiostealbone col-
lar (BC) and the periosteum (P) are clearlyevident,as rs
the junction between the bone collar and the cartilage
(arrows).The medullarycavityis being establishedand is
populated by blood vessels(BV), osreogeniccells, os-
teoblasts,and hematopoieticcells.
F|GURE 2 * Endochondral ossificstion. Monkeg.
Poroffin section. x 210.
This photomicrograph is a higher magnification of
the boxedareain Figure1.Note that the trabeculaeofcal-
cified cartilage are covered by a thin layer of bone. The
darker staining bone (arrow) containsosteocytes,while
the lighter staining calcified cartilage (CC) is acellular,
since the chondroqtes of this region have died, leaving
behind empty lacunaethat areconfluentwith eachother.
Observethat osteoblasts(Ob) line the trabecularcom-
plexes,and that they are separatedfrom the calcifiedbone
by thin intervening osteoid (Ot). As the subperiosteal
bone collar increases in thickness,the trabeculaeofbone-
covered calcified cartilage will be resorbed so that the
cartilage template will be replacedby bone. The only car-
tilage that will remain will be the epiphysealplate and the
articular covering of the epiphysis.

FIGURE 3 ffi Endochondral ossification. x.s.

Monkeg. Pqraffin section. x 196.
A cross-sectionof the region of endochondralossifi-
cation presentsmany round spacesin calcifiedcartilage
that are lined with bone (asterisks).Thesespacesrepre-
sent confluent lacunaein the cartilagetemplate,where
the chondrocltes have hypertrophied and died. Subse-
quently, the cartilage calcified and the invading os-
teogeniccellshavedifferentiatedinto osteoblasts(arrow-
heads)and lined the calcifiedcartilasewith bone. Since
neighboring spaceswere separatedfiom each other by
calcified cartiiagewalls, bone was elaboratedon the sides
of the walls.Therefore,thesetrabeculae,which in longi-
tudinal sectionappearto be stalactite-likestructuresof
bone with a calcifiedcartilaginouscoreare,in fact,spaces
in the cartilage template that are lined with bone. The
walls betweenthe spacesare the remnants of cartilagebe-
tween lacunae that became calcified and form the sub-
structureupon which bone waselaborated.
Observethe forming medullary cavity (MC), housing
blood vessels (BV), hematopoietic tissue (HT), os-
teogenic cells, and osteoblasts(arrowheads).The subpe-
riosteal bone collar (BC) is evident and is covered by a
periosteum, whose two layers, fibrous (FP) and os-
teogenic(Og), are clearlydiscernible.

Endochondralbone lormation

I KEY
BC subperiostealbone collar HT hematopoietictissue Og osteogenicperiosteum
BV bloodvessel MC medullarycavity ot osteoid
CC calcifiedcartilage ob osteoblast P periosteum
FP fibrousoeriosteum

A4 # Cartilageand Bone
 I
,P l. 'f
I ,i ., i \Ji-' " il ;'+'

_r r r
- T.,

I'

'
i' B
. V
E l "ii o \, \i
-, \i < u
j1t\ '
L, l"r

' .::
FICURE
1 FICURE
2

' 'a'' ' 1; \'

T ' ' " "\
i . . : ; .ii: . '
-
,l) yi.:
,;t' ',-"t-'l
'
f"' ,, r.:'. ., -;i'' ,
.-:...:.,:ij*,;i '.
"I
i'''i,u
i l'tl, ,.1\,
'-:" ," '11.;tl; ,', JO..
ln'i.ldii- .:,',.-i i.' i-.,':'..i'.:;q,'tt:ii
'1,.,i-..- ,:u
. ,-'}tii,:,'!/i f ,{-,...,r',,-

;,' g.it :Xi*,''H

:,_t T'

9_

FICURE 3
Cartilage
and Bone
PLATE4-7 I HqalineCortilctge,ElectronMicroscopg

:" *"1

FIGURE I Hgaline cartitage. Mouse. Electron u l u m ( r E R ) r l n t l n u r n c r o u sm i t o c h o n d r i a ( N l ) . T h e n r l

microscopg. x rr ,)r-r.
The hvalincc.rrtilagcoizrneon.rtalntoLrsc plc
tr-irchea
scnts chonillocrtcs,rvhosccentritllvposrtioncclnuclei
(N) aresurrounrlcdrvitha rich rough endoplasmicretic-
trix dispi;rvsflnc collascn t'ibrils (irrrorls) (Fronr Seec
r n i i l e r R , F c rs L r s o r r C , S h e l d o n H : I L . ' l t r u s t r t r c tR e s
-lti:lllU 30l. l97l )

Cartilage
andBone
PLATE4-8 r Osteoblasts,ElectronMicroscopg
lfia
Iz
FfGURE | = Osteoblasts from long bone. Rat.
Electron microscopg. x I 350.
This low magnification electron micrograph displays
numerous fibroblastsand osteoblastsin the vicinity of a
bony trabecula(BT). The osteoblasts(asterisk)are pre-
sentedat a higher magnification in Figure 2. (From Ryder
M, JenkinsS,Horton J:J Dent Res60:1349-1355, 1981.)
FIGURE 2 '+| Osteoblssfs. Rof. Electron microscopg.
x 9450.
Osteoblasts,at higher magnification, present well-
developed Golgi apparatus (g), extensive rough endo-
plasmic reticulum (rer), and severalcoatedvacuoles (cv)
at the basalcell membrane.Observethe cross-sections of
collagen fibers (col) in the bone matrix. (From Ryder M'
JenkinsS,Horton J:J Dent Res60:1349-1355, 1981.)
Cartilageand Bone € 87
 PLATE4-9 I Osteoclast,ElectronMicroscopg

:#

8q
?
.ri., . 4 '

'.r
'cz
/,

lIt.',
FIGURE lA Osteoclost from long bone. Rat. FIGURE I B Osteoclast. Rat. Electron
Electron microscopg. r I 8t10. microscopg.x lOB00
Two nuclcioitu.rosteoclirst at-eevidentin this section l'his is rrhrehern-ragnification of a regionof FigurelA.
Observc that the cell is surroundir-rq a bony surtircc Notethepresence ofthe nucleus(N ) anclitsnucleolus( n ),
(astcrisk).Thc r ccion of the nucleus m.rlke.l br. ar.r asx,ellasthe ruffledborder (RB) and clearzone(CZ) of
. t r r o r r h c . t ,i lr 1 t 1 g r . ' ) , a.,t1t . r h i g . h e rn r . r g r r i l l e . r t i i, r, r r tlrcosteoclast Nurrerousvacuoles(v) of valioussizcntav
Fisr.rreI ll bc observecl throughoutthe c1'toplasnt. (Front llvclerNl,
J c n k i nS
s ,H o r t o nl : I D e n tR e s 6 0 : 1 - 1 4 9 - 1 315958,1 . )

4ft*q'"
q$ffi

FfGURE 2 Osteoclosts.Humon. Paraffjn sectjon. (HI_). Norc rhat the ruffled border (an'or,vhcad.s) is in
CO i r r t i n r . r tit(.) n t . t c tn'itli Holr.ship'slacunire.(Cor-rrtcsv
of
l'he nuclci(N) of thcsemultinuclearcellsare locatetl I)r f . Hollinr:e r..)
in tl-reirbasalregion(BR),lvav from Howship'slacunae

88 Cartilage
and Bone

I Blood and Hemopoiesis
The total volume of blood in an averageperson is
approximately 5 liters; it is a specialized qpe of
connectivetissue,composedof cells,cellfragments,
and plasma,a fluid extracellularelement.Blood cir-
culatesthroughout the body and is well adaptedfor
its manifold functions in transporting nutrients,
oxygen,wasteproducts,carbondioxide,hormones,
cells, and other substances.Moreover, blood also
functionsin the maintenanceof body temperature.
FORMED ETEMENTS
OF BLOOD
The formed elementsof blood are red blood cells
(erythrocytes),white blood cells (leukocytes),and
platelets.Redblood cells(RBC),the most populous,
are anucleatedand function entirelywithin the cir-
culatory systemby transporting oxygen and carbon
dioxide to and from the tissuesof the body. White
blood cells(WBC) perform their functionsoutside
the circulatorysystemand usethe bloodstreamasa
mode of transportationto reachtheir destinations.
Therearetwo major categoriesof white blood cells,
agranulocytesand granulocytes.Lymphocy'tesand
monocytescomposethe first group, whereasneu-
trophils, eosinophils,and basophilscomposethe
latter. Lymphocytesare the basic cells of the im-
mune systemand, although there are three cate-
gories (T lymphocytes, B lymphocytes, and null
cells),specialimmunocytochemicaltechniquesare
necessary for their identification.When monocytes
leavethe bloodstreamand enter the connectivetis-
sue spaces,they become known as macrophages,
cells that function in phagocytosisof particulate
matter, as well as in assistinglymphoqtes in their
immunologic activities.Granulocytesare recogniz-
ablebytheir distinctivespecificgranules,whosecol-
oration provides the classificationfor these cells.
Granulesof neutrophilspossess very limited affinity
to stains,whereasthoseof eosinophilsstain a red-
dish-orangecolor and those of basophils stain a
dark blue color with dyes used in studying blood
liltrIl
preparations.Neutrophilsfunction in phagocytosis
ofbacteria and becauseofthat they are frequently
referredto as microphages.Eosinophilsparticipate
in antiparasitic activities and phagocytoseantigen-
antibody complexes.Although the precisefunction
of basophilsis unknown, the contents of their gran-
ules are similar to those of mast cells and they also
releasethesepharmacologicagentsvia degranula-
tion. Additionally, basophils also produce and
releaseother pharmacologicagentsfrom the arachi-
donic acid in their membranes.
Circulating blood also contains cell fragments
known as platelets (thrombocytes). These small,
oval-to-round structures derived from megakary-
ocytes of the bone marrow function in hemostasis,
the clotting mechanismof blood.
PTASMA
Plasma,the fluid component ofblood, comprisesap-
proximately 550/oof the total blood volume. It con-
tains electrolytesand ions, such as calcium, sodium,
potassium, and bicarbonate; larger molecules,
namely, albumins, globulins, and fibrinogen; and
organic compounds asvaried as amino acids,lipids,
vitamins, hormones, and cofactors. Subsequentto
clotting, a straw-colored serum is expressedfrom
blood. This fluid is identical to plasmabut contains
no fibrinogen or other componentsnecessaryfor the
clottingreaction.
HEMOPOIESI$
Circulating blood cells have relatively short life
spansand must be replacedcontinuously by newly
formed cells.This processof blood cellreplacement
is known ashemopoiesis(hematopoiesis). Allblood
cellsdevelopfrom a singlepluripotential precursor
cell known as the pluripotential hemopoietic stem
cell (PHSC). These cells undergo mitotic activity,
wherebythey give riseto two typesof multipotential
Bloodand Hemopoiesis * 89
hemopoietic stem cells, CFU-S (colony-forming
unit-spleen) and CFU-Ly (colony-forming unit-
lymphocyte).Most PHSCsand other hemopoietic
stemcellsof adultsarelocatedin the red bone mar-
row of short and flat bones.The marrow of long
bonesis red in young individuals,but when it be-
comesinfiltratedby fat in the adult, it takeson a yel-
low appearanceand is known as yellow marrow.
Although it was once believedthat adiposecellsac-
cumulated the fat, it is now known that the cells
actuallyresponsiblefor storingfat in the marrow are
the adventitial reticular cells.Stemcells,in response
to varioushemopoieticgrowth factors,undergocell
division and maintain the population of circulating
erythrocytes,leukocytes,and platelets.
The nomenclaturedevelopedfor the cells de-
scribed below is based on their colorations with
dyesutilized in hematology.
ErythrocyticSeries
Erythrocyte development proceedsfrom CFU-S,
which, in responseto elevatedlevelsof erythropoi-
etin, givesriseto cellsknown asBFU-E,which, in re-
sponseto lower erythropoietinlevels,then give rise
to CFU-E.Although thereareseveralgenerationsof
CFU-E,the lateronesarerecognizable histologically
as proerythroblasts. These cells give rise to ba-
sophilic erythroblasts, which, in turn, undergo cell
division to form polychromatophilic erythroblasts
that will divide mitotically to form orthochro-
matophilic erythroblasts (normoblasts). Cells of
this stageno longerdivide,will extrudetheir nuclei,
and differentiate into reticulocytes (not to be con-
fused with reticular cells of connective tissue),
which, in turn, becomemature red blood cells.
Granulocytic
Series
The developmentof the granulocyticseriesis initi-
ated from the multipotential CFU-S.The first his-
tologically distinguishablemember of this seriesis
the myeloblast, which gives rise mitotically to
promyelocytes, which also undergo cell division to
yield myelocytes. Myelocytes are the first cells of
this seriesto possessspecificgranules;therefore,
neutrophilic, eosinophilic,and basophilic myelo-
cytesmay be recognized.The next cellsin the series
are metamyelocytes,which no longer divide, but
differentiate into band (stab) cells, the juvenile
form, which will become mature granulocltes that
enterthe bloodstream(Table5-l).

TABLE 5-l * FormedElementsof Blood

D i a m e t e r( m m )
o/oof
Element Smear Section No./mm3 Leukocytes Granules Function Nucleus
Erythroclte 7-8 5X106 None Transportof None
(males) Oz and COz
4.5 X 106
(females)
Lymphoclte 8 -1 0 7-8 1500-2500 20-25 Azurophilic Immunologic Largeround
only response acentnc
Monocyte t0-12 200-800 3-8 Azurophilic Phagocltosis Large,kidney-
only shaped
Neutrophil 9-12 8-9 3500-7000 60-70 Azurophilic and Phagocytosis Polymor-
small specific phous
(neutrophilic)
Eosinophil 9-1 1 150-400 24 Azurophilic and Phagocltosis Bilobed
largespecific ofantigen- (sausage-
(eosinophilic) antibody shaped)
complexes
and control
of parasitic
diseases
8- 10 7-8 50-100 0.5-l Azurophilic and Perhaps Large,
largespecific phagocy- S-shaped
(basophilic) tosrs
granules
(heparinand
histamine)
Platelets l-3 250,000- Granulomere Agglutination None
400,000 and clotting

90 I Bloodand Hemoooiesis

Histophgsiologg
I. COAGULATION
r fr::,*;5;iiiiffi'#T
:iHaH"':','#:::Ti:1
agulation factors.The regulatorymechanismsare in
r placeso that coagulationqpically occurs only if the
f endotheliallining of the vesselbecomesinjured. The
processofcoagulationensuesin one oftwo conver-
gent pathways,extrinsic and intrinsic, both of which
i:"dj: the final.stepof convertin-gfibrinogen to fib-
I trophils die and becomea major componentof pus.
rin. The extrinsic pathway has a fasteronset and de-
pends on the releaseof tissue thromboplastin. The
t ::Til:ti:##'":::i'#:Ht#:t
;lffiti:iJ(:lIII. POSTNATALHEMOPOIESIS
factor XII), and requiresthe presenceof von Wille-
r brand's factor and factor VIII. These two factors
I form a complex that not only binds to exposedcolla-
gen,but alsoattachesto receptorsiteson the platelet
rr- plasmalemma,affectingplateletaggregationand ad-
f herenceto the vesselwall.
I I . N E U T R O P H I LF U N C T I O N
Neutrophils possessthree tlpes of granules-
specificgranules,azurophilic granules,and tertiary
granules.Specific granules contain pharmacologic
agentsand enzymesthat permit the neutrophils to
perform their antimicrobial roles. Azurophilic
granulesarelysosomes, containingthe variouslyso-
somalhydrolases,aswell asmyeloperoxidase,bacte-
rial permeability increasingprotein, lysozl.rne,and
collagenase.Tertiary granules contain glycopro-
teins that are dedicated for insertion into the cell
membrane, as well as gelatinaseand cathepsins.
These cells use the contents of the three types of
granules to perform their antimicrobial function.
When neutrophils arrive at their site of action, they
exoc)'tosethe contentsof their granules.Gelatinase
increasesthe neutrophil's capability of migrating
through the basal lamina and the glycoproteins of
the tertiary granules aids in the recognition and
phagocltosis of bacteria into phagosomesof the
neutrophil.Azurophilic granulesand specificgran-
ules fuse with and releasetheir hydrolytic enzymes
into the phagosomes,thus initiating the enzymatic
degradation of the microorganisms. In addition to
the enzy'rnaticdegradation,microorganismsarealso
destroyed by the capability of neutrophils to un-
dergoa suddenincreasein 02 utilization,known as
a respiratoryburst.The 02 is usedby the cellto form
superoxides,hydrogenperoxide,and hypochlorous
TIilTI
acid, highly reactivecompounds that destroybacte-
ria within the phagosomes.Frequently,the avid re-
sponseof neutrophilsresultsin the releaseof some
of these highly potent compounds into the sur-
rounding connective tissue precipitating tissue
damage.The neutrophilsalsoproduceleukotrienes
from plasmalemmaarachidonic acids to aid in the
initiation of an inflammatory response.Subsequent
to the performance of these functions, the neu-
Hemopoiesis in the adult involves a single type of
stem cell, the pluripotential hemopoietic stem cell
(PHSC), which resemblesa lyrnphocyte and is a
member of the null cell population of linnphocytes.
PHSCsarelocatedin largenumbersin the bone mar-
row, but they are also present in circulating blood.
Thesecellshavea high mitotic index and form more
PHSCs,as well as two multipotential hemopoietic
stem cells, CFU-S and CFU-Ly. Morphologically,
CFU-S and CFU-Ly are identical with PHSCs,but
they have a more limited potential. CFU-Ly, known
asthe lymphoid stem cell, will give rise to CFU-LyB
and CFU-LyT, the progenitors of B and T lympho-
cytes,respectively.CFU-S is also referred to as the
myeloid stem cell, since it will give rise to BFU-E
(and/or CFU-E), the progenitor of erythrocytes;
CFU-Eo, the progenitor of eosinophils;CFU-Ba, the
progenitor of basophils;and CFU-NM, which will
give rise to CFU-N and CFU-M, the progenitors of
neutrophils and monocytes,respectively.Stem cells
and progenitor cellsresemblelymphocytes,whereas
precursor cells can be recognizedhistologically as
members of a cell population that will differentiate
into a particular blood cell. Furthermore, stem cells
are lesscommitted than are progenitor cells.
Severalhemopoietic growth factors activateand
promote hemopoiesis.These act by binding to
plasma membrane receptors of their target cell,
controlling their mitotic rate, aswell asthe number
of mitotic events.Additionally, they stimulate cell
differentiation and enhancethe survival ofthe pro-
genitor cell population. The best known factors are
erythropoietin (actson BFU-E and CFU-E), inter-
leukin-3 (actson PHSC,CFU-S,and myeloid pro-
genitor cells), interleukin-7 (acts on CFU-Ly),
granuloqte-macrophage colony-stimulating fac-
tor (actson granulocyteand monocyteprogenitor
r
BloodandHemopoiesis 91
cells),granulocytecolony-stimulatingfactor (acts
on,granulocyteprogenitor cells),and macrophage
colony-stimulatingfactor (actson monocyti pro-
genitor cells).
IV. LYMPHOCYTES
The three types of lymphocltes-B lymphocl'tes
(B cells),T lymphocltes (T cells),and null cells-
aremorphologicallyindistinguishable.It is custom-
ary to speakof T cells as being responsiblefor the
cellularly mediated immune responseand B cellsas
functioning in the humorally mediated immune
response.Null cellsare few in number, possessno
determinantson their cell membrane, ind are of
two types, pluripotential hemopoietic stem cells
and natural killer cells.
A. T Cells
T cellsnot only function in the cellularlymediated
immune response,but also are responsiblefor the
formation of cytokinesthat facilitaiethe initiation
of the humorally mediatedimmune response.They
are formed in the bone marrow and miqrateto the
thymic cortex to becomeimmunocomJetent cells.
They recognizeepitopes (antigenicdeierminants)
that are displayedby cellspossessing HLA (human
leukocy.teantigen;also known as major histocom-
patibility complex molecules).There are various
subtypesofT cells,eachpossessing a T-cell receptor
(TCR) surfacedeterminantand clusterof differen-
tiation determinants (CD molecules). The former
recognizesthe epitope, whereasthe latter recog-
nizesthe type of HLA on the displayingcell surface.
The varioussubtypesof T cellsare T helpercells
(Tsl and Ts2), cltotoxic T cells(Tc), T r.rppr.so.
cells(T5),and T memory cells.
B. B Cells
B cellsbear HLA qpe II (alsoknown asMHC II) sur-
facemarkersand surfaceimmunoglobulins (SIG) on
their plasmalemma.They are formed in and become
immunocompetent in the bone marrow. They are
responsiblefor the humoral responseand, under the
direction of Ts2 cellsand in responseto an antigenic
challenge,will differentiateinto antibody-manufac-
turing plasmacellsand B memory cells.
92 * Bloodand Hemopoiesis
C. Natural Killer {NK) Cells
NK cells belong to the null cell population. They
possessF6 receptorsbut no cell surfacedetermi-
nants and are responsiblefor nonspecific cytotoxi-
city againstvirus-infectedand tumor cells. They
also function in antibody-dependent cell-mediated
cytotoxicity (ADCC).
C l i n i c aC
l o n s i d e r a t i o nws * r
NADPH Oxidase Deficiencg
C e r t a i ni n d i v i d u a lssu f f e rf r o m D e r s i s t e n t
b a c t e r i ailn f e c t i o nd u et o a h e r e d i t a r y
N A D P Ho x i d a s ed e f i c i e n c yT h e n e u t r o p h i l s
o f t h e s ei n d i v i d u a lasr e u n a b l et o e f f e c ta r e s -
p i r a t o r yb u r s ta n d ,t h e r e f o r ea, r e i n c a p a b l e
o f f o r m i n gt h e h i g h l yr e a c t i v ec o m p o u n d s ,
s u c ha s h y p o c h l o r o uasc i d ,h y d r o g e np e r o x -
i d e ,a n d s u p e r o x i d teh a t a s s i s itn t h e k i l l i n g
o f b a c t e r i aw i t h i nt h e i rp h a g o s o m e s
Multiple Mgelomo
M u l t i p l em y e l o m ai s a r e l a t i v e luyn c o m m o n
mailgnantneoplasmwjth greaterincjdencein
m a l e st h a nf e m a l e sl t s o r r g i ni s t h e b o n em a r -
row and is characterized by the presenceof
l a r g en u m b e r so f m a l i g n a npt l a s m ac e l l st h a t
m a y a l s ob e a b n o r m ailn m o r p h o l o g yT h e s e
c e l l sa c c u m u l a tien t h e b o n em a r r o wo f v a r i -
ous regionsof the skeletalsystem Frequently
the cellproJiferation ls so greatjn the marrow
t h a t t h e h u g en u m b e ro f c e l l sp l a c ep r e s s u r e
on the wallsof the marrowcavitycausing
b o n ep a i n sa n d e v e nf r a c t u r eosf b o n e ss u c h
a s t h e r i b s T h e s ec e l l sa l s op r o d u c ea b n o r m a l
p r o L e i nssu c ha s B e n c e - J o n e p sr o l e i n st h a t
e n t e rt h e u r i n ew h e r et h e yc a nb e d e t e c t e dt o
provjdea diagnosis for multipJemyeloma.
T r e a t m e ni tn c l u d e lso c a lr a d i a t i o n therapy,
a i m e da t l h e b o n e si n w h i c ht h e p a t i e n its
e x p e r i e n c i npga i n ,P a t i e n tw s i t hB e n c e - J o n e s
p r o t e i n si n t h e i ru r i n ea r e i n s t r u c t etdo d r i n k
l o t so f f l u i d st o r e d u c et h e c h a n c eos f d e h y -
d r a t i o na n d o f k i d n e yf a i l u r eC h e m o t h e r a p y
hasbeenshownto be effectiveln reducingthe
p r o g r e s s i oonf t h e d i s e a s e

Summargof HistologicalOrganization
I. CIRCULATINCBLOOD"
A. Erythrocytes(RBC)
RBCsare pink, biconcavedisksthat are 7-8 pm in
diameter.They arefilled with hemoglobinand pos-
sessno nuclei.
B. Agranulocytes
l. Lgmphocgtes
Histologically,lymphocytes may be small, medium,
or large (this bearsno relationshipto T cells,B cells,
or null cells).Most lymphoc)'tesaresmall (8-10 p.m
in diameter)and possessa dense,blue, acentrically
positionednucleusthat occupiesmost of the cell,
Ieaving a thin rim of light blue, peripheral clto-
plasm. Azurophilic granules (lysosomes)may be
evidentin the cytoplasm.
2. Monocgtes
Monoqtes are the largestof all circulating blood
cells(12-15 p.m in diameter).Thereis a consider-
able amount of grayish-bluecytoplasmcontaining
numerous azurophilic granules. The nucleus is
acentricand kidney-shapedand possesses a coarse
chromatin network with clear spaces.Lobesof the
nucleusare superimposedon themselves, and their
outlinesappearto be distinctly demarcated.
C. Granulocytes
t. Neutrophits Neutrophils, the most populous of
the leukocytes,are 9-12 pm in diameter and
display a light pink cytoplasm housing many
azurophilic and smaller specificgranules.The
specificgranulesdo not stain well, hence the
name of these cells.The nucleus is dark blue,
coarse,and multilobed, with most being two-
to three-lobedwith thin connectingstrands.
2. EosinophitsEosinophilsare 10-14 pm in diam-
eter and possessnumerousrefractive,spherical,
large, reddish-orange specific granules.
Azurophilic granulesare also present.The nu-
cleus,which is brownish-black,is bilobed, re-
semblingsausage links united by a thin connect-
ing strand.
3. BasophilsBasophils,the least numerous of all
leukocytes, are 8-10 pm in diameter. Fre-
quently, their cytoplasmis so filled with dark,
large,basophilic specificgranulesthat they ap-
pearto pressagainstthe cell membrane,giving it
I ll
an angular appearance.The specific granules
usually mask the azurophilic granules,aswell as
the S-shaped,light blue nucleus.
D. Platelets
Platelets, occasionally called thrombocytes, are
small, round (2-4 p.m in diameter)cell fragments.
As such, they possessno nuclei, are frequently
clumped together, and presentwith a dark blue,
central granular region, the granulomere, and a
light blue, peripheral,clearregion,the hyalomere.
II. HEMOPOIESIS"
During the maturation process,hemopoietic cells
undergo clearly evident morphologic alterations.
As the cellsbecomemore mature, they decreasein
size.Their nuclei also become smaller,the chro-
matin network appearscoarser,and their nucleoli
(which resemblepale grayish spaces)disappear.
The granulocytesfirst acquireazurophilicand then
specific granules, and their nuclei become seg-
mented. Cells of the erythrocl'tic seriesnever dis-
play granulesand eventuallylosetheir nuclei.
A. ErythrocyticSeries
l. Proergthroblast
a Cgtoplosm
Light blue to deep blue clumps in a pale grayish-
blue background.
b. Nucleus
Round with a fine chromatin network; it is a rich
burgundy red with 3-5 pale gray nucleoli.
2. Basophilic Ergthroblast
a. CAtoplosm
Bluish clumps in a paleblue cytoplasmwith a hint
ofgrayish pink in the background.
b. Nucleus
Round, somewhatcoarserthan the previousstage;
burgundy red. A nucleolusmay be present.
" All of the colorsdesignatedin this summaryarebased
on the Wright or Giemsa'smodification of the
Romanovsky-t1pestainsasappliedto blood smears.
Bloodand Hemopoiesis € 93
3. Polgchromotophilic Ergthroblast
a. CAtoplasm
Yellowishpink with bluish tinge.
b. Nucleus
Small and round with a condensed,coarsechro-
matin network;dark, reddishblack.No nucleoliare
present.
4. Orthochromatophilic Ergthroblast
o. Cgtoplosm
Pinkishwith a slight tinge of blue.
b Nucleus
Dark, condensed,round structure that may be in
the processofbeing extrudedfrom the cell.
5. Reticulocgte
a. Cgtoplasm
Appears just like a normal, circulating RBC; if
stainedwith supravitaldyes(e.g.,methyleneblue),
however,a bluish reticulum-composed mostly of
rough endoplasmicreticulum-is evident.
b. Nucleus
Not present.
B. Granulocytic
Series
in their specificgranules,only the neutrophilic se-
ries is describedin this summary,with the under-
standingthat myelocltes,metamyelocytes, and stab
(band) cellsoccur in thesethreevarieties.
l. Mgeloblast
a. Cgtoplasm
Small blue clumps in a light blue background.No
granules.Cltoplasmic blebs extend along the pe-
riphery of the cell.
94 * Bloodand Hemopoiesis
b. Nucleus
Reddish-blue,round nucleuswith fine chromatin
network.Two or threepalegraynucleoliareevident.
2. Promgelocgte
a. Cgtoplosm
The cytoplasm is bluish and displays numerous,
small,dark, azurophilicgranules.
b. Nucleus
Reddish-blue, round nucleus whose chromatin
strands appear more coarse than in the previous
stage.A nucleolusis usuallypresent.
3. Neutrophilic Mgelocgte
a. Cgtoplasm
Pale blue cytoplasm containing dark azurophilic
and smallerneutrophilic(specific)granules.A clear,
paranuclearGolgi region is evident.
b Nucleus
Round, usually somewhat flattened, acentric nu-
cleus,with a somewhatcoarsechromatin network.
Nucleoli are not distinct.
4. Neutrophilic Metamgelocgte
a Cgtoplosm
Similar to the previous stageexceptthat the cyto-
plasm is paler in color and the Golgi areais nestled
in the indentationof the nucleus.
b Nucleus
Kidney-shaped,acentricnucleuswith a dense,dark
chromatin network. Nucleoli are not present.
5. Neutrophilic Stab (Band) Cell
a. Cgtoplasm
A little more blue than the cy'toplasmof a mature
neutrophil.Both azurophilicand neutrophilic (spe-
cific) granulesare present.
b. Nucleus
The nucleus is horseshoe-shaped and dark blue,
with a very coarsechromatin network. Nucleoli are
not present.
PLATE5- 1 I CirculatingBlood

L
Jt
\
FIGURE | 't Red Blood Cells.Human. x 1325.
Redblood cells(arrows)displaya centralclearregion
that representsthe thinnest areaof the biconcavedisc.
\
Note that the platelets(arrowheads)Possessa central
denseregion,the granulomere,and a peripherallight re-
gion, the hyalomere.

FIGURE2 "t Neutrophils.Human.x 1325.

Neutrophilsdisplaya somewhat granularcytoplasm
andlobulated(arrowheads)nuclei.

FIGURE 3 \ Eosinophils.Human. x 1325.

Eosinophilsare recognizedby their large pink gran-
ulesand their sausage-shapednucleus.Observethe slen-
der connectinglink (arrowhead)betweenthe two lobesof
the nucleus.

FIGURE 4 M Basophils. Human. x 1325'

by their dense,dark, large
Basophilsare characterized
granules.

lr

wsd,
.==
FIGURE 5 n Monocgtes. Human. x 1325.
Monocy'tes are characterizedby their large size,acen-
tric, kidney-shapednucleus,and lack ofspecificgranules-

FIGURE 6 iM LAmphocAtes.Human. x 1325.

Lymphocltes are small cells that possessa single,
large,acentricallylocatednucleus,and a narrow rim of
light blue cytoplasm.

Bloodand Hemoooiesis tu 95
 PLATE5-2 I CircutatingBlood r
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96 € Bloodand Hemopoiesis
t PLATE5-3 | Bloodond Hemopoiesis

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1. Basophilic 1. Myeloblast 1. Eosinophilic 1. Proerythroblast
I myelocyte
2. Basophilic
2. Promyelocyte
3. Neutrophilic
myelocyte
2. Eosinophilic
2. Basophilic
erythroblast
metamyelocyte myelocyte metamyelocyte 3. Polychromatophilic

I 3. Basophil
stab cell
4. Neutrophilic
metamyelocyte
3. Eosinophil
stabcell
erythroblast
4. Orthochromatophilic
4. Basophil 5 Neutrophilic 4. Eosinophil erythroblast

I stab cell
6. Neutrophil
5. Reticulocyte
6. Erythrocyte

I Bloodand Hemopoiesis ffi 97

 PLATE5-4 | BoneMarrow and CircutatingBlood
FIGURE I a Bone morrow. Humon. paraffin
section. x 132.
This transversesectionof a decalcifiedhuman rib dis-
plays the presenceof haversiancanals(H), Volkmann's
canals(V), osteocltes(O) in their lacunae,and the en-
dosteum (E). The marrow presentsnumerousadventitial
reticular cells (A), blood vessels,and sinusoids (S).
Moreover,the forming blood elementsarealsoevidentas
small nuclei (arrows). Note the large megakaryocytes
(M), cellsthat are the precursorsof platelets.The boxed
areais representedin Figure2.
FIGURE 2 * Bone merrow. Humon. Paraffin
section. x 210.
This photomicrograph is a higher magnification of
the boxed area of Figure l. Observethe presenceof os-
teocytes(O) in their lacunae,aswell as the flattened cells
ofthe endosteum(E). The endotheliallining ofthe sinu-
soids (arrows) are clearly evident, as are tlie numerous
cells that are in the processof hemopoiesis.Two large
megakaryocytes(M) are also discernible.

FIGURE 3 e Blood smeor. Human. Wright stain.
x 210.
This normal blood smearpresentserythrocytes(R),
neutrophils (N), and platelets(P). The apparentholesin
the centersof the e4,throcytesrepresentthe thinnest ar-
easof the biconcavediscs.Note that the erythrocltesfar
outnumber the plateletsand they,in turn, ar. -ucir m.r..
numerous than the white blood cells.Sinceneutrophils
constitute the highest percentageof white blood lek,
they are the ones most frequently encounteredof the
white blood cell population.
FIGURE 4 4 Bone mqrrow smear. Humon. Wright
stoin. x 210.
This normal bone marrow smear presentsforming
blood cells, as well as erythrocytes (R) and platelets (P).
ln comparison with a normal peripheral blood smear
(Figure3), marrow possesses many more nucleatedcells.
Some of these are of the erythrocytic series (arrows),
whereas others are of the granulocytic series (arrow-
heads).

I KEY
A Adventitialreticularcell M Megakaryocyte R Erythrocyte
BV Bloodvessel N Neutrophil Sinusoid
E Endosteum Osteocyte Volkmann'scanal
H Haversiancanal P Platelet

98 #$ Bloodand Hemopoiesis
t
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BloodandHemopoiesis 99
PLATE5-5 | Ergthropoiesis r
I
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FIGURE| | Humanmorrow smear. x 1325.
Proerythroblast.
I
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FIGURE2 | Humanmaffow smear. x 1325.
Basophilicerythroblast. I
I
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FIGURE3 | Humanmarrow smeqn x 1325.
Polychromatophilic
erythroblast.
I
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FIGURE4 | Humanmorrow smedr. x 1325. I
Orthochromatophilic
erythroblast.

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FIGURE5 | Humanmorrow smean x 1325.
Reticulocyte.
I
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FIGURE6 | Humanmdrrow smeor. x 1325.
Erythroclte.
t
100 I BloodandHemopoiesis t
PLATE5-6 I Cranulocgtopoiesis

FIGURE I Mgeloblast. Human

bone marrow smeor. x 1325.

FIGURE 2 Promgelocgte. Human

bone morrow smear. x 1325.

FIGURE 38 :''' NeutroPhilic

mgelocgte. Human bone
marrow smeor. x 1325.

FIGURE 3A Eosinophilic
mgelocgte. Humon bone
marrow smeor. x 1325.

FIGURE 48 i' Neutrophilic

metamAelocAte. Humon
bone marrow smeor. x
1325.

FIGURE 4A Eosinophilic
metamgelocgte. Humon
bone marrow smeor. x -e
1325.
iitr:
'i'r
FIGURE58 ,' Neutrophitic
stab cell. Humanbone
.#JrriirNu
I morrow smear. x 1325.

FIGURE 5A Eosinophilic FfGURE6 ,: Neutrophil.

stab cell. Human bone Humanbone marrow
marrow smeor. x 1325. smear.x 1325.

BloodandHemopoiesis | 0l
I
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r Muscle
The ability of animals to move is due to the pres-
enceof specificcellsthat havebecomehighly differ-
entiated, so that they function almost exclusivelyin
contraction.The contractileprocesshas been har-
nessedby the organismto permit variousmodesof
movement and other activitiesfor its survival. Some
ofthese activitiesdependon quick contractionsof
short duration; others depend on long-lasting
contractionswithout the necessityfor rapid actions,
whereasstill others depend on powerful, rhythmic
contractions that must be repeatedin rapid se-
quences.Thesevaried needsare accommodatedby
three typesof muscle,namely,skeletal,smooth, and
cardiac.There arebasicsimilarities among the three
muscle Qpes. They are all mesodermally derived
and are elongatedparallel to their axis of contrac-
tion; they possessnumerous mitochondria to ac-
commodate their high energy requirements,and
all contain contractile elementsknown asmyofila-
ments, in the form of actin and myosin, as well
as additional contractile-associated proteins. My-
ofilaments of skeletal and cardiac muscles are ar-
rangedin a specificorderedarraythat givesriseto a
repeated sequence of uniform banding along
their length-hence, their collectivename,striated
muscle.
Since muscle cells are much longer than they
are wide, they are commonly referred to as muscle
fibers. However, it must be appreciatedthat these
fibers are living entities, unlike the nonliving fibers
of connective tissue.Neither are they analogousto
nerve fibers, which are living extensionsof nerve
cells.Often, certain unique terms are used to de-
scribe muscle cells; thus, the muscle cell mem-
brane is sarcolemma (although earlier use of this
term included the attendant basal lamina and
reticular fibers), cytoplasm is sarcoplasm,mito-
chondria are sarcosomes,and endoplasmicreticu-
lum is sarcoplasmicreticulum.
IIreIT
SKELETATMUSCTE
Skeletalmuscle (seeGraphics6-1 and 6-2) is in-
vested by dense collagenous connective tissue
known as the epimysium, which penetrates the
substanceof the gross muscle, separating it into
fascicles.Each fascicle is surrounded by perimy-
sium, a looserconnectivetissue.Finally,eachindi-
vidual muscle fiber within a fascicle is enveloped
by fine reticular fibers, the endomysium. The vas-
cular and nerve supplies of the muscle travel in
theseinterrelatedconnectivetissuecompartments.
Each skeletalmuscle fiber is roughly cylindrical in
shape,possessingnumerous elongatednuclei Io-
cated at the periphery of the cell, just deep to the
sarcolemma. Longitudinally sectioned muscle
fibers display intracellular contractile elements,
which are the parallel arrays of longitudinally dis-
posed myofibrils. This arrangementproduces an
overall effect of cross-banding of alternating light
and dark bands traversing each skeletal muscle
cell. The dark bands are A bands, and the light
bandsare I bands.EachI band is bisectedby a thin
dark Z disc, and the region of the myofibril ex-
tending fromZ disc to Z disc,the sarcomere,is the
contractileunit of skeletalmuscle.The A band is
bisectedby a paler H zone, the center of which is
marked by the dark M disc. During muscle con-
traction, the various transversebands behavechar-
acteristically, in that the width of the A band re-
mains constant, the two Z discs move closer to
eachother approachingthe A band, and the I band
and H zone become extinguished.Electron mi-
croscopyhas revealedthat banding is the result of
interdigitation of thick and thin myofilaments.
These thin filaments are attached to Z discs by ct-
actinin. The I band consists solely of thin fila-
ments,while the A band, with the exceptionof its
H and M components,consistsof both thick and
Muscle E | 05
 thin filaments. During contraction the thick and
thin filaments slide past each other (sliding fila-
ment theory of contraction), and the Z discs are
brought near the ends of the thick filaments. It
should also be noted that the thin filaments are
held in registerby two moleculesof the inelastic
protein nebulin. Moreover,the thick filamentsare
affixed to each other at the M disc by C proteins
and myomesin and are connectedto the Z disc by
elasticproteins called titin. Since titin molecules
form an elasticlattice around the thick filaments
they facilitatethe maintenanceof the spatial rela-
tionship of thesethick filaments to eacirother, as
well as to the thin filaments.
Nerve impulses,transmitted at the myoneural
junction acrossthe synaptic cleft by acetylcholine,
causea wave of depolarizationof the sarcolemma,
with the eventual result of muscle contraction.
This waveof depolarizationis distributedthrough-
out the muscle fiber by transversetubules (T
tubules),tubular invaginationsof the sarcolemma.
The T tubules become closelyassociatedwith the
terminal cisternsof the sarcoplasmicreticulum
(SR), so that each T tubule is flanked by two of
theseelementsof the SR, forming a triad. Dunng
depolarizationthe T tubules carry the impulse
within the musclefiber, thus causinsthe releaseof
calcium ions from the SR. Calciuri ions interact
with the thin myofilamentsto permit contraction
to occur.
As a protectivemechanismagainstmusclefiber
tearsasa resultofoverstretchingand to provide in-
formation concerningthe position of the body in
three-dimensionalspace,tendons and musclesare
104 =:: Muscle
equippedwith specializedreceptors,Golgi tendon
organs and muscle spindles,respectively.
CARDIACMUSCLE
Cardiacmuscle(seeGraphic6-2) cellsare alsostri-
ated, but each cell usually contains only one cen-
trally placed nucleus.Thesecells form specialized
junctions known asintercalateddiscsasthey inter-
digitatewith eachother. Heart musclecontraction
is involuntary, and the cells possessan inherent
rhythm, which is coordinated by Purkinje fibers,
modified cardiacmusclecells.
SMOOTH MUSCTE
Smooth muscle (seeGraphic 6-2) is also involun-
tary. Each fusiform smooth muscle cell housesa
single, centrally placed nucleus, which becomes
corkscrew shapedduring contraction of the cell.
Smooth musclecellscontain an apparentlyhaphaz-
ard arrangementof thick and thin filaments,whose
interdigitation during contraction is harnessedby
an intermediatetype of filament. Theseintermedi-
ate filaments form densebodies where they cross
eachother and at points of attachmentto the cyto-
plasmicaspectof the sarcolemma.Smooth muscle
may be of the multiunit type, where eachcell pos-
sessesits own nerve supply, or of the visceral
smooth muscle type, where nerve impulses are
transmitted via nexus (gap junctions) from one
musclecell to its neighbor.
 IrffiIl

I Histophgsiotogg

I. MYOFILAMENTS thus, the sarcomerebecomesshorter,whereasthe

myofilamentsremain the samelength.As a conse-
Thin filaments(7 nm in diameterand 1 pm long)
quenceof the sliding of the filaments,the I and H
arecomposedof F actin,double-helicalpolymersof
bands disappear,the A band remains the same
G actin molecules,resembling a pearl necklace
width (asbeforecontraction),the Z discsarepulled
twistedupon itself.Eachgrooveof the helix houses
closer to each other, and the entire sarcomereis
linear tropomyosin moleculespositioned end to
shortenedin length.
end. Associatedwith eachtropomyosin moleculeis
Subsequentto the transmissionof the impulse
a troponin molecule composedof three polypep-
acrossthe myoneuraljunction, the T tubules con-
tides-troponin T (TnT), troponin I (TnI), and
vey the impulse throughout the muscle cell. Volt-
troponin C (TnC). TnI binds to actin, maskingits
age-sensitive integral proteins, dihydropyridine-
activesite (whereit is ableto interactwith myosin);
sensitivereceptors(DHSR), locatedin the T tubule
TnT binds to tropomyosin; and TnC (a molecule
membrane are in contact with calcium channels
similar to calmodulin) has a high affinity for cal-
(ryanodine receptors)in the terminal cisternaeof
cium ions. The plus end of each thin filament is
the sarcoplasmicreticulum (SR). This complex is
bound to a Z disc by cr-actinin. Additionally, two
visiblewith the electronmicroscopeand is referred
nebulins, inelastic proteins, entwine along the
to as junctional feet. During depolarizationof the
Iength of eachthin filament and anchor it to the Z
skeletal muscle sarcolemma, the DHSRs of the T
disc. The negativeend of eachthin filament extends
tubule undergo voltage-induced conformational
to the junction ofthe A and I bandsand is capped
change,causingthe calcium channelsof the termi-
by tropomodulin.
nal ciiternaeto open,permitting the influx of Ca2+
Thick filaments(15 nm in diameterand 1.5 pm
ions into the cytosol.Troponin C of the thin fila-
in length) are composed of 200-300 myosin
ment binds the calcium ions and changesits con-
molecules arrangedin an antiparallel fashion. Each
formation, pressingthe tropomyosin deeper into
myosin moleculeis composedof two pairs of light
the groovesof the F actin filament, thus exposing
chains and two identical heavychains.Eachmyosin
the active site (myosin-binding site) on the actin
heavy chain resemblesa golf club, with a linear tail
molecule.
and a globular head, where the tails are wrapped
ATP, bound to the globularhead (S1fragment)
around eachother in a helicalfashion.Digestingthe
of the myosin molecule, is hydrolyzed, but both
myosin healy chain with the enzyme trypsin
ADP and Pi remain attachedon the 51.The myosin
cleavesit into a linear (most of the tail) segment
(light meromyosin) and a globular segment with molecule swivelsso that the myosin head approxi-
mates the active site on the actin molecule. The Pi
the remainderof the tail (heavymeromyosin).An-
moiety is released,and in the presenceof calcium,a
other enzlme, papain, cleavesheary meromyosin
link is formed between the actin and myosin. The
into a short tail region (S2 fragment) and a pair of
bound ADP is freed,and the myosin head altersits
globular regions (Sl fragments). Each pair of
conformation, moving the thin filament toward the
myosin light chains are associatedwith one of the
centerof the sarcomere.A new ATP attachesto the
Sl fragments. Sl fragments have ATPase activity
globular head, and the myosin dissociatesfrom the
but requirethe associationwith actin for this activ-
activesiteofthe actin.This cycleis repeated200-300
ity to be manifest.Thick filamentsare anchoredto
times for completecontractionof the sarcomere.
Z discsby the linear, elasticprotein titin and are
Relaxation ensueswhen the calcium pump of
linked to adjacentthick filaments, at the M line, by
the SR transports calcium from the cytosol into
the proteinsmyomesin and C protein.
the SRcisterna,whereit is bound by calsequestrin.
The decreasedcytosolicCa2* inducesTnC to lose
its bound calcium ions, the TnC molecule re-
I I . S L I D I N GF I L A M E N TM O D E LO F
turns to its previous conformational state, the
SKELETALM USCLECONTRACTION tropomyosin moleculereturns to its original loca-
During contractionthe thin filamentsslidepastthe tion, and the activesiteof the actin moleculeis once
thick filaments,penetratingdeeperinto the A band; againmasked.

M u s c l em 1 0 5
I I I . S M O O T HM U S C L E rich in calmodulin and the enzyme myosin light-
chain kinase.

A. Contractile
Elements
Although the thick and thin filaments of smooth
muscle are not arranged into myofibrils, they are
organized so that they are aligned obliquely to
the longitudinal axis of the cell. Myosin molecules
of smooth muscle are unusual, since the light
meromyosin moiety is folded in such a fashion
that its free terminus binds to a "sticky region" of
the globular S1 portion. The thin filaments are
attachedto cytoplasmic densities,Z disc analogs
(containing ct-actinin),as are the intermediate
filaments (desmin in nonvascular and vimentin
in vascular smooth muscle cells). The cytosol is
B. Contraction
Calcium, releasedfrom caveolae,binds to calmod-
ulin. The Ca2+-calmodulin complex activates
myosin light-chain kinase, which phosphorylates
one of the myosin light chains, altering its confor-
mation. This causesthe free terminus of the light
meromyosin to be releasedfrom the S1moiety. ATP
binds to the Sl, and the resultantinteractionbetween
actin and myosin is similar to that of skeletal(and
cardiac)muscle.As long ascalciumandATP arepre-
sent,the smooth muscle cell will remain contracted.
Smooth musclecontraction IastsIongerbut develops
slowerthan cardiacor skeletalmusclecontraction.

C l i n i c a lC o n s i d e r a t i o n sr I IDuchenne's M uscuIar Dgstrophg

Duchenne's muscular dystrophy isa muscle de-
generative disease thatisdueto anX-linked ge-
Mgasthenia Gravis neticdefectthatstrikes I in 30,000malesThe
lvlyastheniagravisis an auloimmune disease defectresults in theabsence of dystrophin
thatis characterized by incremental weakening molecules in themuscle cellmembrane Dys-
of skeletal
muscles Antibodies formedagainst trophin isa protein thatfunctions in lheintercon-
acetylcholinereceptors of skeletal muscle nectionof thecytoskeleton lo transmembrane
fibersbondto and,thus,blocktheserecep- proteins thatinteract withtheextracellular ma-
tors Thenumberof sitesavailable for the trixaswellasin providing structural supportfor
inltiation
of depolarizationof the muscle sar- themuscle plasmalemma. lndividualsafflicted
colemma is decreased Thegradual weakening withDuchenne's muscular dystrophy experience
affectsthe mostactivemuscles first[muscles muscle weakness by thetimetheyareseven
of theface,eyes,andtongue), but eventually yearsof ageandareusually wheelchair bound
the muscles of respirationbecome compro- by thetimetheyaretwelveyearsold lt isvery
misedandthe individual diesof resoiratorv unusual to havetheseDatients surviveintotheir
insuff
iciency. earlytwenties

106 * Muscle

Summargof HistologicalOrganization
I. SKELETAL
MUSCLE
A. Longitudinal Section
I. Connectivetissueelementsof perimysium con-
tain nerves, blood vessels,collagen, fibroblasts,
and occasionallyother cell types.Endomysium is
composedof fine reticular fibers and basallam-
ina, neither of which are normally evident with
the light microscope.
2. Skeletal muscle cells appear as long, parallel,
cylindrical fibers of almost uniform diameter.
Nuclei are numerous and peripherally located.
Satellitecell nuclei may be evident.Cross-stria-
tions, A, I, Z, should be clearlynoted at higher
magnifications, and with oil immersion (or even
high dry), the H zone and M disc may be distin-
guishedin good preparations.
B. TransverseSection
.L Connectivetissueelementsmay be noted, espe-
cially nuclei of fibroblasts, cross-sectionsof cap-
illaries, other small blood vessels,and nerves.
2. Muscle cells appear as irregular polygon-shaped
sectionsof fibers of more or lessuniform size.
Myofibrils present a stippled appearanceinside
the fiber, frequently clusteredinto distinct but ar-
tifactual groups known as Cohnheim's fields. Pe-
ripherally, a nucleus or two may be noted in
many fibers.Fasciculiare closelypacked,but the
delicateendomysium clearly outlines eachcell.
II. CARDIACMUSCLE
A. Longitudinal Section
l. Connectivetissue elementsare clearly identifi-
able becauseof the presenceof nuclei that are
considerablysmallerthan thoseof cardiacmuscle
cells. The connective tissue is rich in vascular
components, especiallycapillaries.The endomy-
sium is presentbut indistinct.
2. Cardiac muscle cells form long, branching, and
anastomosingmuscle fibers. Bluntly oval nuclei
areIarge,arecentrallylocatedwithin the cell,and
appear somewhatvesicular.A and I bands are
presentbut are not as clearly defined as in skele-
tal muscle. Intercalated discs, marking the
boundaries of contiguous cardiac muscle cells,
Itilll
may be indistinct unless special staining tech-
niques are used. Purkinje fibers are occasionally
evident.
B. TransverseSection
l. Connective tissue elements separatingmuscle
fibers from each other are obvious, since nuclei
of thesecells are much smaller than those of car-
diac musclecells.
2. Cross-sectionalprofiles of muscle fibers are
irregularly shaped and vary in size. Nuclei are
infrequent but are large and located in the cen-
ter of the cell. Myofibrils are clumped as Cohn-
heim's fields (an artifact of fixation) in a radial
arrangement. Occasionally, Purkinje fibers are
noted.
III.SM OOTHM USCLE
Section
A. Longitudinal
l. Connective tissue elements between individual
muscle fibers are scantyand consist of fine retic-
ular fibers. Larger bundles or sheetsof muscle
fibers are separated by loose connective tissue
housingblood vesselsand nerves.
2. Smooth muscle cells are tightly packed, stag-
gered, fusiform structures whose centrally lo-
cated nuclei are oblong in shape.When the mus-
cle fibers contract, their nuclei assume a
characteristiccorkscrewshape.
B. TransverseSection
I. A very limited amount of connective tissue,
mostly reticular fibers, may be noted in the in-
tercellularspaces.Sheetsand bundlesof smooth
muscle are separatedfrom each other by loose
connective tissue in which neurovascular ele-
ments are evident.
2. Since smooth muscle cells are tightly packed,
staggered, fusiform structures, transverse sec-
tions produce circular,homogeneous-appearing
profiles of various diameters.Only the widest
profiles contain nuclei; therefore, in transverse
sectiononly a limited number of nuclei will be
present.
M u s c l em 1 0 7
GRAPHIC
6- 1 t MoleculorStructureof SheletalMuscle

Striationsof skeletalmuscleare resolvedinto A bands

and I bands. I bands are dividedinto two equal halves
by a Z disk, and each A band has a lightzone,the
H band. The center of each H band is a dark M band.
Adjacentmyofibrilsare securedto each other by the
intermediatefilamentsdesmin and vimentin The basic
contractileunit ot the skeletalmusclecell is the
sarcomere, a precisely ordered collection of
myotilaments (thick and thin filaments). Tubular
invaginations, T tubules (transverse tubules), of the
musclecell membranepenetratedeep into the
sarcoplasmand surroundmyofibrilsin such a manner
that at the junctionof each A and I band these tubules
becomeassociatedwith the dilatedterminal cisternae
ot the sarcoplasmicreticulum(smoothER), forming
triads

One muscleliber

Bundleof
musclefibers (T)tubule
Transverse
Sarcolemma
Sarcoplasmic
reticulum
Mitochondrion
Myolibril
A band
z
disk I H band

One myofibril

aa

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ataa
aaaaa
aara
lal
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Each thick filamentis surroundedby a hexagonal

arravof thin filaments.

108 € Muscle
I 6-2 I
GRAPHIC Tgpesof Muscle

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I I Fiber

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PLATE6-1 t SheletalMuscle
FfGURE | | Skeletol muscle. I.s. Monkeg. Plastic
sector. x 800,
This photomicrograph displaysseveralof the charac-
teristics of skeletal muscle in longitudinal section. The
muscle fibers are extremely long and possessa uniform
diameter. Their numerous nuclei (N) are peripherally
located.The intercellularspaceis occupiedby endomy-
sium, with its occasionalflattened connective tissue cells
(CT) and reticular fibers. Two types of striations are
evident, longitudinal and transverse. The longitudinal
striations represent myofibrils (M) that are arranged in
almost precise register with each other. This ordered ar-
rangement is responsiblefor the dark and light transverse
banding that givesthis tlpe of muscle its name. Note that
the light band (I) is bisectedby a narrow dark line, the Z
disc (Z). The dark band (A) is alsobisectedby the clear H
zone (H). The centerofthe H zone is occupiedby the M
disc, appearing as a faintly discernible dark line in a few
regions.The basiccontractile unit of skeletalmuscleis the
sarcomere (S), extending from one Z disc to its neigh-
boring Z disc. During muscle contraction the myofila-
ments of eachsarcomereslide past one another, pulling Z
discs closer to each other, thus shortening the length of
each sarcomere.During this movement, the width of the
A band remains constant, while the I band and H zone
disappear.

FIGURE 2 J Skeletal muscle. x.s. Monkeg. Paraffin
section. x 132.
Portions of a few fasciclesare presentedin this pho-
tomicrograph. Each fascicleis composed of numerous
muscle fibers (F) that are surrounded by connective tis-
sueelements,known asthe perimysium (P), which house
nervesand blood vesselssupplying the fascicles.The nu-
clei of endothelial, Schwann, and connective tissue cells
are evident asblack dots in the perimysium. The periph-
erally placed nuclei (N) of the skeletal muscle fibers
appear as black dots; however, they are all within the
muscle cell. Nuclei of satellite cells are also present,just
external to the muscle fibers, but their identification at
Iow magnification is questionable.The boxed areais pre-
sentedat a higher magnificationin Figure3.
FIGURE 3 | Skeletal muscle. x.s. Monkeg. Poroffin
section. x 540.
This is a higher magnification of the boxed area of
Figure 2. Transverse sections of several muscle fibers
demonstratethat thesecells appearto be polyhedral, that
they possessperipherally placed nuclei (N), and that
their endomysia (E) house numerous capillaries (C).
Many of the capillariesare difticult to seebecausethey are
collapsedin a restingmuscle.The pale sarcoplasmocca-
sionally appears granular, due to the transversely sec-
tioned myofibrils. Occasionally,nuclei which appear to
belong to satellite cells (SC) may be observed,but defi-
nite identification cannot be expected. Moreover, the
well-defined outline of each fiber was believed to be due
to the sarcolemma,but now it is known to be due more to
the adherent basallamina and endomysium.

I KEY

A A band F musclefiber P perimysium

capillary H H zone b sarcomere
CT connectivetissue I I band sc satellitecell
E endomysium N nucleus z Z disc

l l0 I Muscle
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PLATE6-2 r SkeletalMuscle,ElectronMicroscopg
F|GURE I n Skeletol muscle. l.s. Rat. Electron
microscopg.x 17,100.
This moderatelylow power electron micrograph of
skeletalmusclewas sectionedlongitudinally.Perpendic-
ular to its longitudinal axis,note the dark and light cross-
bandings.The A band (A) in this view extendsfrom the
upper left-hand corner to the lower right-hand corner
and is borderedby an I band (l) on either side. Each I
band is traversedby a Z disc (Z). Observethat the Z disc
hasthe appearance of a dashedline, sinceindividual my-
ofibrils are separatedfrom each other by sarcoplasm.
Note that the extent of a sarcomere(S) is from Z disc to
Z disc,and that an almostprecisealignmentof individual
myofibrils assuresthe specificorientation ofthe various
bandswithin the sarcomere.The H zone (H) and the M
disc (MD) areclearlydefinedin this electronmicrograph.
Mitochondria are preferentiallylocated in mammalian
skeletalmuscle,occupyingthe region at the levelof the I
band asthey wrap around the peripheryofthe myofibril.
Severalsarcomeresare presentedat a higher magnifica-
tion in Figure2. (Courtesyof Dr. J. Strum.)
FIGURE 2 v& Skeletal muscle. l.s. Rat. Electron
microscopg. x 28,800.
This is a higherpower electronmicrographpresenting
severalsarcomeres.Note that the Z discs (Z) possesspro-
jections (arrows) to which the thin myofilaments (tM)
are attached.The I band (l) is composedonly of thin fil-
aments. Thick myofilaments (TM) interdigitate with the
thin filamentsfrom eitherend of the sarcomere,resulting
in the A band (A). However.the thin filamentsin a re-
laxed muscle do not extend all the way to the center of the
A band; therefore,the H zone (H) is composedonly of
thick filaments. The center of eachthick filament appears
to be attachedto its neighboring thick filament, resulting
in localized thickenings, collectively comprising the M
disc (MD). During musclecontraction,the thick and thin
filamentsslidepasteachother,thus pulling the Z discsto-
ward the center of the sarcomere.Due to the resultant
overlappingof thick and thin filaments,the I bandsand
H zonesdisappear,but the A bandsmaintain their width.
The sarcoplasmhousesmitochondria (m) preferentially
located, glycogengranules (arrowhead), as well as a spe-
cializedsystemof sarcoplasmicreticulum and T tubules,
forming triads (T). In mammalianskeletalmuscle,triads
are positioned at the junction of the I and A bands.
(Courtesyof Dr. J. Strum.)

Molecularstructureol
skeletalmuscle

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A band MD M disc TM thick myofilament

H zone 5 sarcomere z Z disc
I band T triad
mitochondrion tM thin myofilament
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PLATE6-3 r MgoneuralJunction,Lightand ElectronMicroscopg
FIGURE | * MAoneurol junction. Loteral view.
Paraffin section. x 540.
This view of the myoneural junction clearlydisplays
the myelinated nerve fiber (MN) approaching the skele-
tal muscle fiber (SM). The A bands (A) and I bands (I)
are well delineated,but the Z discsare not observablein
this preparation.As the axon nearsthe musclecell,it loses
its myelin sheath and continues on as a nonmyelinated
axon (nMN), but retains its Schwanncell envelope.As
the axon reachesthe musclecell,it terminat.r ur u itloto,
end plate (MEP), overlyingthe sarcolemmaof the mus-
cle fiber. Although the sarcolemmais not visible in light
micrographs,such as this one, its location is clearlyap-
proximated due to its associatedbasallamina and reticu-
lar fibers.
FIGURE 2 fr Mgoneural junction. Sufiace view.
Paraffin section. x 540.
This view of the myoneuraljunction demonstrates,as
in the previousfigure,that asthe axon reachesthe vicin-
ity of the skeletal muscle fiber (SM), it loses its myelin
sheath.The axon terminates, forming a motor end plate
(MEP), composedof a few clustersof numerous small
swellings(arrowhead)on the sarcolemmaof the skeletal
musclefiber. Although it is not apparentin this light mi-
crograph,the motor end plate is located in a slight de-
pression on the skeletalmuscle fiber, and the plasma
membranesof the two structuresdo not contact each
other. Figure 3 clearlydemonstratesthe morphology of
sucn a synapse.

FIGURE 3 * Mgoneural junction. Rat. Electron
microscopg. x 15,353.
This electron micrographis of a myoneuraljunction
taken from the diaphragm muscleof a rat. Observethat
the axon (ax) loses its myelin sheath, but the Schwann
cell (sc) continues,providing a protectivecover for the
nons)rnaptic surface of the end foot or nerve terminal
(nt). The myelinated sheath ends in typical paranodal
loops at the terminal heminode. The nerve terminal
possesses mitochondria (m) and numerous clearsynap-
tic vesicles.The margins of the 50-nm primary s1'naptic
cleft are indicated by arrowheads. Postsynaptically,the
junctional folds (j), many mitochondria (m), and por-
tions of a nucleus (n) and sarcomere(s) are apparent
in the skeletal muscle fiber. (Courtesv of Dr. C. S.
Hudson.)

Myoneuraljunction

I KEY
A A band MEP motorend plate s sarcomere
AX Axon MN myelinatednervefiber Schwann cell
I band n nucleus SM skeletalmusclefiber
junctionalfold nMN nonmyelinated axon
m mitochondria nt nerveterminal

114 € Muscle
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PLATE6-4 I MgoneuralJunction,ScanningElectronMicroscopg

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FIGURE I Mgoneural junction. Tongue. Cot.
Sconning electron microscopg. x 2610.
The striations(arrows)of an isolatedskeletalmtrscle
fiber are clearlyevidentin this scanningelectronmicro-
graph.Note the nerve "trvig" (N), which loops up and
at the myoneuraljunction
makescontactr.viththe mr.rscle
(MI). (Courtesyof Dr. L. Litke.)

l16
PLATE6-5 r MuscleSpindle,Lightand ElectronMicroscopg
FIGURE | '.' Muscle spindle. Mouse. Plostic
section. x 436.
Observethat the outer (oC) and inner (iC) capsulesof
the muscle spindle define the outer peraxial space(PS)
and the inner axial space(asterisk).The inner capsule
forms an envelope around the intrafusal fibers (lF).
(From OvalleW, Dow P: Am J Anat 166:343-357,1983.)
"\r4 ,r-:r.?
-r@
FIGURE 2 ::;.Muscle spindle. Mouse. Electron
microscopg. x 6300.
Partsofthe outer capsule(oC) may be observedat the
cornersofthis electronmicrograph.The periaxial space
(PS) surrounds the slender inner capsule (iC) whose
component cells form attenuatedbranches,subdividing
the axial space(AS) into severalcompartmentsfor the
nuclear chain (NC) and nuclear bag (NB) intrafusal
fibers and their correspondingsensoryterminals (ST).
Note that the atfenuatedprocessesof the inner capsule
ceils establishcontact with each other (arrows). (From
OvalleW, Dow P: Am I Anat 166:343-357,1983.)
M u s c l e= 117
PLATE6-6 | SmoothMuscle
FIGURE | * Smooth muscle. I.s. Monkeg. Plqstic
section, x 210.
The Iongitudinal section of smooth muscle in this
photomicrographdisplayslong fusiform smooth muscle
cells (sM) with centrallylocated,elongatednuctei (N).
Since the muscle fibers are arranged in staggeredarrays,
they can be packed very closely, with only a limited
amount of intervening connective tissue (CT). Using
hematorylin and eosin, the nuclei appear bluish, while
the cytoplasmstainsa light pink. Eachsmooth musclecell
is surroundedby a basallamina and reticularfibers,nei-
ther of which is evident in this figure. Capillariesare
housed in the connectivetissue separatingbundles of
smooth muscle fibers. The boxed area is presentedat a
highermagnificationin Figure2.
FfGURE 3 * Smooth muscle. lJterine mgometrium.
x.s. Monkeg. Plostic section. x 210.
The myometrium of the uterusconsistsof interlacing
bundlesof smooth musclefibers,surroundedby connec-
tive tissue(CT) elements.Note that someof thesebundles
are cut in longitudinal section (l), others are sectioned
transversely(2), and still others are cut obliquely (3). At
low magnifications,suchasin this photomicrograph,the
transversesectionspresenta haphazardarrangementof
dark nuclei (N) in a lightly stainingregion.With practice,
it will becomeapparentthat thesenuclei are intracellular
and that the palecircular regionsrepresentsmooth mus-
cle fibers sectioned transversely.Note the numerous
blood vessels(BV) traveling in the connective tissue
betweenthe smooth musclebundles.
.*rm,
-dt|r - containing nuclei of various diameters.Most of the field
"d#fie
Smoothmuscle
T KEY
BV bloodvessel CT connective
capillary u glandular
l 18 ffi Muscle
FIGURE 2 | Smooth muscle. I.s. Monkeg. Plastic
section. x 540.
This photomicrograph is a higher magnification of
the boxed areaofFigure l. Observethat the nuclei (N) of
the smooth musclefibersare long, taperedstructureslo-
cated in the center of the cell. The widest girth of the nu-
cleus is almost as wide as the muscle fiber. However, the
length of the fiber is much greater than that of the nu-
cleus.Note also that any line drawn perpendicular to the
direction of the fibers will intersect only a few of the nu-
clei. Observethe differencebetweenthe connectivetissue
(CT) and smooth muscle(sM). The smooth muscleclto-
plasm stainsdarker and appearssmooth relativeto the
palenessand rough-appearingtexture of the connective
tissue. Observe capi,llaries(C) located in the connectrve
tissueelementsbetweenbundlesof musclefibers.
Inset. Smooth muscle. Contracted. l.s. Monkey, Plas-
tic section.X 540.
This longitudinal section of smooth muscle during
contraction displaysthe characteristiccorkscrew-shaped
nuclei (N) of thesecells.
FIGURE 4A a Smooth muscle. x.s. Monkeg. Plastic
section. x 540.
In order to understand the three-dimensional mor-
phology of smooth muscleasit appearsin two dimensions,
refer to Figure 2 directly above this photomicrograph.
Once again note that the muscle fibers are much longer
than their nuclei and that both structures are spindle-
shaped,being tapered at both ends. Recallalso that at its
greatestgirth, the nucleus is almost as wide as the cell. In
transversesection this would appear as a round nucleus
surrounded by a rim ofcytoplasm (asterisk).Ifthe nucleus
is sectioned at its tapered end, merely a small dot of it
would be presentin the centerof a largemusclefiber (dou-
ble asterisks). Sectioned anywhere benveen these tlvo
points, the nucleuswould havevaried diametersin the cen-
ter of a large musclecell. Additionally, the cell may be sec-
tioned in a region away from its nucleus,where only the
sarcoplasmof the largemusclecell would be evident (triple
asterisks).Moreover, if the cell is sectionedat its tapered
end, only a small circular profile of sarcoplasmis distin-
guishable(arrowhead).Therefore,in transversesectionsof
smooth muscle one would expect to find only few cells
will be closelypackedprofi.lesof sarcoplasmcontaining no
nuclei.
FIGURE 48 fi Smooth muscle. Duodenum. Monheg.
Plastic section. x 132.
This photomicrograph of the duodenum demon-
stratesthe glandular portion (G) with its underlying con-
nective tissue (CT). Deep to the connectivetissue,note
the two smooth, muscle layers,one of which is sectioned
longitudinally ( I ) and the other transversely(2).
tissue N nucleus
portion SM smoothmusclecell
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PLATE6-7 | SmoothMuscle,ElectronMicroscopg
FIGURE | 3 Smooth muscle. l.s. Mouse. Electron
microscopg.x 15,120.
Smooth muscle does not display cross-bandings,
transversetubular systems,or the regularly arrangedarray
of myofilamentscharacteristicof striatedmuscle.How-
ever, smooth muscle does possessmyofilaments that,
alongwith a systemof intermediatefilaments,arerespon-
siblefor its contractilecapabilities.Moreover,the plasma
membrane appearsto possessthe functional, if not the
structural, aspectsof the T tubule. Observe that each
smooth muscleis surroundedby an externallamina (EL),
which is similar in appearanceio basallamina of epithe-
lial cells.The sarcolemma(SL) displaysthe presenceof
numerous pinocytotic-like invaginations,the caveolae
(Ca), that arebelievedto act asT tubulesof striatedmus-
cles in conducting impulses into the interior of the fiber.
Some suggestthat they may also act in concert with the
sarcoplasmicreticulum in modulating the availability of
calcium ions. The cytoplasmicaspectof the sarcolemma
alsodisplaysthe presenceofdense bodies (DB), which are
indicative of the attachment of intermediate microfila-
ments (IM) at that point. Dense bodies, composedof
B-actinin (Z disc protein found in striatedmuscle),are
alsopresentin the sarcoplasm(arrows).The nucleus(N)
is centrally located and, at its pole, mitochondria (m) are
evident. Actin and myosin are also present in smooth
muscle,but cannotbe identifiedwith certaintyin longitu-
dinal sections.Partsof a secondsmooth musclefiber may
be observedto the Ieft of the cell described.A small capil-
lary (C) is evident in the lower right-hand corner. Note
the adherens junctions (AJ) between the two epithelial
cells,one of which presentsa part of its nucleus(N).

Smoothmuscle

adherens iunction DB dense body m mitochondrion

capillary EL externallamina N nucteus
caveola IM intermediatefilament SL sarcolemma
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 PLATE6-8 I CardiacMuscle
FIGURE I a Cardiac muscle. I.s. Human. ptastic
section. x 210
This low magnification of longitudinally sectioned
cardiacmuscledisplaysmany of the characteristics of this
muscletype.The branching (arrow) of the fibersis read-
ily apparent,asarethe dark and light bands(arrowheads)
running transverselyalong the length ofthe fibers.Each
muscle cell possessesa large,centrallylocated,oval nu-
cleus (N), although occasionalmusclecells may possess
two nuclei.The intercalateddiscs (ID), indicating inter-
cellular junctions between two cardiac muscle cells,
FIGURE 3 J Cardiac muscle. x.s. Human. plastic
section. x 2-70.
Cross-sectionsof cardiac muscle demonstratepoly-
gon-shapedareasof cardiacmusclefibers (CM) with rel-
atively large intercellular spaceswhose rich vascular sup-
-of
ply (BV) is readilyevident.Note that the nucleus (N)
eachmusclecell is locatedin the center,but not all cells
display a nucleus.The clear areasin the center of some
cells (arrows) representthe perinuclear regions at the
polesof the nucleus.Theseregionsare rich in sarcoplas-
mic reticulum,glycogen,lipid droplets,and an occasional
Golgi apparatus.The numeroussmallernuclei in the in-
tercellularareasbelongto endothelialand connectivetis-
sue cells.In contrastto cardiacmuscle,cross-sections of
skeletalmusclefibersdisplaya homogeneousappearance
with peripherallypositioned nuclei. The connectivetis-
suespacesbetweenskeletalmusclefibersdisplaynumer-
ous (frequentlycollapsed)capillaries.
I KEY
BV bloodvessel EN endothelialnucleus
c capillary lD intercalateddisc
CM cardiacmuscleliber M mvofibril
122 ! Muscle
FIGURE 2 | Cardiac muscle. Ls. Human. Plostic
section. x 540.
This is a highermagnificationof the boxedareaof Fig-
ure l. The branchingofthe fibers(arrows)is evident,and
the cross-striations,I and A bands (arrowheads)are
clearly distinguishable. The presenceof myofibrils (M)
within each cell is well displayed in this photomicro-
graph,asis the "step-like"appearance ofthe intercalated
discs(ID). The oval, centrallylocatednucleus(N) is sur-
rounded by a clear area usuallyoccupiedby mitochon-
dria. The intercellular arcasarc richly supplied by capil-
laries (C) supported by slender connective tissue
elements.
FIGURE 4 | Cardiac muscle. x.s. Human. Plastic
section. x 540.
At high magnificationsof cardiacmusclein cross-sec-
tion, severalaspectsofthis tissuebecomequite apparent.
Numerous capillaries (C) and larger blood vessels(BV)
abound in the connectivetissue spaces.Note the en-
dothelial nuclei (EN) of thesevessels,aswell as the white
blood cells (WBC) within the venule in the upper right-
hand corner. Nuclei (N) of the musclecellsare centrally
located,and the perinuclearclearareas(arrow) housing
mitochondria are quite evident. The central clear zonesat
the nuclearpolesare denotedby asterisks.Cross-sections
of myofibrils (arrowheads)arerecognizableasnumerous
small dots of varyingdiameterswithin the sarcoplasm.
Cardiacmuscle
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124 \tLrse
c

I NervousTissue
Nervous tissue is one of the four basic tissuesof
the body and it specializesin receivinginforma-
tion from the externaland internal milieu. The in-
formation is processed,integrated,and compared
with storedexperiences and/or predetermined(re-
flex) responses,to selectand effect an appropriate
reaction.The receptionof information is the func-
tion of the sensorycomponent of the peripheral
nervous system (PNS). The processesof integra-
tion, analysis,and responseare performed by the
brain and spinal cord comprising the central ner-
vous system(CNS) with its gray and white matter.
The transmissionof the responseto the effector
organ is relegatedto the motor component of the
PNS. Therefore,it should be appreciatedthat the
PNS is merely a physical extension of the CNS,
and the separationof the two should not imply a
strict dichotomy.
The nervous systemmay also be divided func-
tionally into somatic and autonomic nervous
systems. The somatic neryous system exercises
consciouscontrol over voluntary functions, while
the autonomic nervous system controls involun-
tary functions.The autonomic nervoussystemis a
motor system,acting on smooth muscle, cardiac
muscle, and some glands. Its two components,
sympathetic and parasympathetic nervous sys-
tems, usuallyact in concertto maintain homeosta-
sis. The sympatheticnervous systempreParesthe
body for action as in a "fight or flight" mode,
whereasthe parasympatheticsystemfunctions to
calm the body and providessecretomotorinnerva-
tion to most exocrineglands.
The CNS is protectedby a bony housing, con-
sisting of the skull and vertebralcolumn, and the
meninges,a triple-layeredconnectivetissuesheath.
The outermost meninx is the thick fibrous dura
mater. Deep to the dura mater is the arachnoid,a
nonvascularconnectivetissuemembrane.The in-
nermost, vascularpia mater is the most intimate
TTffiII
investmentof the CNS. Locatedbetweenthe latter
two meningesis the cerebrospinalfluid (CSF).
NEURONSAND SUPPORTING
CETLS
The structural and functional unit of the nervous
pending on the number of dendritesa neuron Pos-
iesses,it may be unipolar (a singleprocessbut no
dendrites-rarein vertebrates, but seebelow),bipo-
lar (an axon and one dendrite), or the more com-
mon multipolar (an axon and severaldendrites).
An additional categoryexistswhere the single den-
drite and the axon fuseduring embryonicdevelop-
ment, givingthe falseappearance of a unipolar neu-
ron; therefore, it is known as a pseudounipolar
neuron, although recentlyneuroanatomistsbegan
to refer to this neuron q?e asa unipolar neuron.
Neuronsalsomay be classifiedaccordingto their
function. Sensoryneurons receivestimuli from ei-
ther the internal or external environment then
transmit theseimpulsestoward the CNS for pro-
cessing.Interneurons act as connectorsbetween
neuronsin a chain or tlpically betweensensoryand
motor neurons within the CNS. Motor neurons
conduct impulses from the CNS to the targets cells
(muscles,glands,and other neurons).
Information is transferredfrom one neuron to
another acrossan intercellular spaceor gaP, the
synapse.Dependingon the regionsofthe neurons
participating in the formation of the synapse'it
could be axodendritic,axosomatic,axoaxonic,or
N e r v o u s T i s s u#e 1 2 5
dendrodendritic. Most synapsesare axodendritic
and involve one of many neurotransmitter sub-
stances (such as acerylcholine) that is releasedby
the axon of the first neuron into the synaptic cleft.
The chemicalmomentarily destabilizesthe plasma
membraneof the dendrite,and a wave of depolar-
ization passesalong the secondneuron>which will
causethe releaseof a neurotransmittersubstanceat
the terminus of its axon. This type of a chemical
synapseis an excitatory synapse,which results in
the transmissionof an impulse. Another tlpe of
synapsemay stop the transmissionof an impulseby
stabilizing the plasma membrane of the second
neuron; it is calledan inhibitory synapse.
Neuroglialcellsfunction in the metabolismand
the support neurons. To prevent spontaneousor
accidental depolarization of the neuron's cell
membrane, specializedneuroglial cells provide a
physical covering over its entire surface.In the
CNS thesecells are known as astrocftes and oligo-
dendroglia, while in the PNS they are capsuleand
Schwanncells.Oligodendroglia and Schwanncells
have the capability of forming myelin sheaths
around axons (Graphic 7-2), which increasesthe
conductionvelocityof the impulse along the axon.
The region where the myelin sheath of one
Schwanncell (or oligodendroglion)ends and the
next one beginsis referredto as the node of Ran-
126 ffi Nervous
Tissue
vier. Additionally, the CNS possessesmicroglia,
macrophages derived from monocytes, and
ependymal cells, which line brain ventricles and
the central canal of the spinal cord.
Certain terms must be defined to facilitateun-
derstanding of the nervous system.A ganglion is a
collection of nerve cell bodies in the PNS, while a
similar collectionof somain the CNS is calleda nu-
cleus. A bundle of axons traveling together in the
CNS is known as a tract (fasciculus,column),
whereasthe samebundle in the PNS is known as a
peripheralnerve (nerve).
PERTPHERAT
NERVES
Peripheralneryesarecomposedof numerousnerve
fibers collected into several fascicles (bundles).
These bundles possessa thick connective tissue
sheath,the epineurium (seeGraphic 7-1). Eachfas-
ciclewithin the epineuriumis surroundedby a per-
ineurium consistingof an outer connectivetissue
layer and an inner layer of flattened epithelioid
cells.Eachnerve fiber and associatedSchwanncell
hasits own slenderconnectivetissuesheath,the en-
doneurium, whosecomponentsincludefibroblasts,
an occasionalmacrophage,and collagenousand
reticularfibers.

Histophgsiologg
POTENTIAL
I. MEMBRANERESTING
The normal concentrationof K* is about 20 times
greater inside the cell than outside, whereas the
concentrationof Na+ is l0 timesgreateroutsidethe
cell than inside, in part becauseof the action of a
Na*-K* pump. The resting potential acrossthe
neuron cell membrane is maintained by the pres-
ence of potassium leak channels in the plas-
malemma.It is through thesechannelsthat K+ ions
diffuse from inside the cell to the outside,thus es-
tablishing a positive chargeon the outer aspectand
a negative (lesspositive) charge on the internal as-
pect of the cell membrane, with a total differential
of about 40 to 100mV.
II. ACTIONPOTENTIAL
The action potential is an electrical activity where
chargesmove along the membranesurface.It is an
all-or-none responsewhose duration and ampli-
tude are constant.Someaxons are capableof sus-
taining up to 1000impulses/sec.
Generation of an action potential beginswhen a
region of the plasmamembraneis depolarized.As
the resting potential diminishes, a threshold level is
reached,voltage-gatedNa+ channelsopen, Na*
rushesinto the cell, and at that point the resting po-
tential is reversed,so that the inside becomesposi-
tive with respectto the outside.In responseto this
reversalof the resting potential, the Na* channel
closesand for the next l-2 mseccannot be opened
(the refractory period). Depolarizationalso causes
the opening ofvoltage-gatedK+ channelsthrough
which potassiumions exit the cell, thus repolarizing
the membrane and ending not only the refractory
period of the Na+ channelbut also the closureof
the voltage-gatedpotassium channel.
The movement of Na+ ions that enter the cell
causesdepolarization of the cell membrane toward
the axon terminal (orthodromic spread).Although
sodium ions also move away from the axon termi-
nal (antidromic spread), they are unable to affect
sodium channelsin the antidromic direction,since
those channelsare in their refractory period.
I I I . M Y O N E U R A LJ U N C T I O N
Mitochondria, synaptic vesicles,and elementsof
smooth endoplasmicreticulum are presentin the
IIIII
axon terminal. The axolemmainvolved in the for-
mation of the synapseis known as the presynaptic
membrane,whereasthe sarcolemmalcounterpart
is known as the postsynaptic membrane. The
presynapticmembranehassodium channels,volt-
age-gatedcalcium channels,and carrier proteins
for the cotransportof Na* and choline. The post-
synaptic membrane has acetylcholine receptors,
aswell as slight invaginationsknown asjunctional
folds. A basal lamina containing the enzyme
acetylcholinesteraseis also associatedwith the
postsynapticmembrane. As the impulse reaches
the end-foot, sodium channels open, and the
presynapticmembrane becomesdepolarized,re-
sulting in the opening ofthe voltage-gatedcalcium
channelsand the influx of Ca* into the end-foot.
The high intracellular calcium concentration
causesthe synaptic vesicles,containing acetyl-
choline, proteoglycans,and ATP, to fusewith the
presynapticmembrane and releasetheir contents
into the synapticcleft. This excessmembranewill
be recycled via the formation of clathrin-coated
vesicles,thus maintaining the morphology and
requisite surface area of the presynaptic mem-
brane. The releasedacetylcholinebinds to acetyl-
choline receptors of the sarcolemma'thus open-
ing sodium channels,resulting in sodium influx
into the muscle cell, depolarizationof the Postsy-
naptic membrane,and the subsequentgeneration
of an action potential and musclecell contraction.
Acetylcholinesteraseof the basal lamina cleaves
acetylcholineinto choline and acetate,ensuring
that a single releaseof the neurotransmitter sub-
stancewill not continue to generateexcessaction
potentials.The choline is returned to the end-foot
via carrier proteins that are powered by a sodium
gradient,where it is combined with activatedac-
etate(derivedfrom mitochondria), a reaction cat-
alyzed by acetylcholine transferase, to form
acetylcholine.The newly formed acetylcholineis
transported into forming synaptic vesiclesby a
proton pump-driven, antiport carrier protein.
IV. NEUROTRANSMIfiER
SUBSTANCES
Neurotransmitter substancesare signaling mole-
cules(chemicalmessengers) that are releasedat the
presynaptic membrane and effect a response by
binding to receptormolecules(integralproteins)of
NervousTissue : 127
the postsynaptic membrane. Neurotransmitter
substances arevaried in chemicalcompositionand
are categorizedaccording to their chemical con-
struction ascholinergic,monoaminergic,peptider-
gic, non-peptidergic, GABAergic, glutamatergic,
and glycinergic.
V. BLOOD.BRAIN
BARRIER
The selectivebarrier that exists betweenthe neural
tissuesof the CNSand manyblood-bornesubstances
is termed the blood-brain barrier. This barrier is
C l i n i c a lC o n s i d e r a t i o n s: I r
Huntington's Chorea
H u n t i n g t o n c' sh o r e ai s a h e r e d i t a r cy o n d i t i o n
t h a t b e c o m e se v i d e n ti n t h e t h i r da n d f o u r t h
d e c a d eo f l r f e I n i t i a l l yt ,h i sc o n d i t i o na f f e c t s
o n l y t h e j o i n t sb u t l a t e ri s r e s p o n s i b lfeo r m o t o r
d y s f u n c t i oann d d e m e n t i al t i s t h o u g h t o b e
c a u s e db y t h e l o s so f n e u r o n so f t h e C N St h a t
p r o d u c el h e n e u r o t r a n s m i t tG e rA B A T h ea d -
v e n to f d e m e n t i ai s t h o u g h t o b e r e l a t e dt o t h e
l o s so f a c e t y l c h o l i n e - s e c r ect ienlel s
Porkinson's Disease
P a r k r n s o nd' si s e a s ei s r e l a t e dt o t h e l o s so f t h e
n e u r o t r a n s m i t td eor p a m i n ei n t h e b r a i n T h i s
c r i p p l i nd g i s e a s ce a u s e sm u s c u l arri g i d i t y ,
t f e m o r ,s l o wm o v e m e n ta, n d p r o g r e s s i v edl yi f -
f i c u l tv o l u n t a r ym o v e m e n tL - d o p ac a n b e a d -
ministered b u t i t s b e n e f i c i ael f f e c t sa r e o n l y
t e m p o r a r yT r a n s p l a n t efde t a la d r e n a gl l a n d
t i s s u ep r o v i d e ss o m er e l i e fb u t i t i s a l s oo f
s h o r td u r a t i o n
Therapeutic Circumvention of the
Blood-Brain Barrier
T h e r a p e u t icci r c u m v e n t i oonf t h e b l o o d - b r a i n
b a r r i e rT: h es e l e c t i v ne a t u r eo f t h e b l o o d - b r a i n
b a r r i e rp r e v e n t sc e r t a i nt h e r a p e u t idc r u g s
a n d n e u r o t r a n s m i t t ecrosn v e v e db v t h e
128 € Nervous
Tissue
formed by the fasciaeoccludentesof contiquousen-
dothelial cellslining the continuous capiliariesthat
coursethrough the neural tissues.Certain substances
(i.e.,02, H2O, CO2,and selectedsmall lipid-soluble
substancesand some drugs) can penetratethe bar-
rier. However,others,including glucose,certainvita-
mins, amino acids,and drugs, among others, access
passageonly by receptor-mediatedtransport and/or
facilitated diffusion. Certain ions are also trans-
ported via active transport. It is also believed that
someof the perivascularneurogliamay play a minor
role in the maintenanceof the blood-brain barrier.
bloodstream f r o me n t e r i n gt h e C N S F o re x a m -
p l e ,l h e p e r f u s i o o n f m a n n i t o li n t o t h e b l o o d
s t r e a mc h a n g e tsh e c a p i l l a r yp e r m e a b i l i tbyy
a l t e r i n gt h e t i g h tj u n c t i o n st ,h u sp e r m i t t i n ga d -
m i n i s t r a l i oonf t h e r a p e u t idc r u g s ,O t h e rt h e r a
p e u t i cd r u g sc a n b e a t t a c h e dt o a n t i b o d i e s
developedagainsttransferrin receptors lo-
c a t e do n t h e I u mj n a la s p e c o t f the plasma
m e m b r a n eosf t h e s ee n d o t h e l i ca el l l st h a tw i l l
p e r m i tt r a n s p o ritn t o t h e C N S .
Cu i IIai n-Ba rre Sgnd rome
Cuillain-BarS r ey n d r o m ei s a f o r m o f i m m u n e -
m e d i a t e dc o n d i t i o nr e s u l t i n gi n r a p i d l yp r o -
gressing w e a k n e sw s i t h p o s s i b l ep a r a l y s i os f
t h e e x t r e m i t i eas n d o c c a s i o n a l l ey v, e no f t h e
r e s p i r a t o r ay n d f a c i a lm u s c l e sT h i sd e m y e l i -
n a t i n gd i s e a s ei s o f t e na s s o c i a t ew d itha recent
r e s p i r a t o r oy r g a s t r o i n t e s t i nianlf e c t i o nt;h e
m u s c l ew e a k n e s rse a c h e si t s g r e a t e s p l _o i n t
w i t hj n t h r e ew e e k so f t h e i n i t i a ls y m p t o m sa n d
5 0 / oo f t h e a f f l i c t e di n d i v i d u a ldsi e o f t h e d i s -
e a s e E a r l yr e c o g n i t i oonf t h e d i s e a s ei s i m p e r -
a t i v ef o r c o m p l e t e[ o r n e a r l yc o m p l e t er)e c o v -
e r y T r e a t m e nitn c l u d e si m m e d i a t e
h o s p i t a l i z a t i oann d m o n i t o r i n g f o r n e e df o r r e s -
p i r a t o rt h e r a p y M o n i t o r i n gf o r b e d s o r e sa n d
p h y s i c atlh e r a p ya r e a l s oi n d i c a t e dP l a s m a -
p h e r e s iasn d a d m i n i s t r a t i o n f autoimmune
g l o b u l i na r e t r e a t m e n t so f c h o i c e
 llnrl

I Summargof HistotogicatOrganization
I I . S P I N A LC O R D and intervening clear regions known as glomeruli
(or cerebellarislands).Thesemainly rePresentareas
A. GrayMatter
I The gray matter, centrallylocatedand more or less
ofsynapseson granulecell dendrites.

in the shapeof an H, hastwo dorsalhorns and two

ventral horns. Ventral horns display numerous
B. MedullarySubstance
I multipolar (motor) cell bodies. The perikaryon
possesses a large,clearnucleusand a densenucleo-
The medullary substance(internal white mass) is
the region of white matter deep to the granular
lus. Its cytoplasmis filled with clumpsof basophilic layerof the cerebellum,composedmostly of myeli-
I Nissl substance (rough endoplasmic reticulum)
that extends into dendrites but not into the axon.
natedfibersand associatedneuroglial cells'

The origin of the axon is indicated by the axon

III.CEREBRUM
I hillock of the soma.Numeroussmallnucleiabound
in the gray matter; they belong to the various neu- A. Cortex
roglia. The nerve fibers and neuroglial processesin
The cerebral cortex is composed of gray matter,
I the gray matter are referred to as the neuropil. The
right and left halves of the gray matter are con-
nectedto eachother by the gray commissure,which
mostly subdivided into six layers,with eachhousing
neuronswhosemorphologyis characteristicof that
particularlayer.The major neuronaltypesarepyra-
housesthe central canal lined bv simple cuboidal
I ependymal cells.
midal cells,stellate (granule) cells,horizontal cells,
and inverted (Martinotti) cells. The following de-
scription refersto the neocortex and is presented
B. White Matter from superficialto deeporder. The first Iayeris just
I The white matter of the spinal cord is peripherally deep to the pia mater, while the sixth level is the
deepestcortical layer, bordering the central white
located and consistsof ascendingand descending
matter of the cerebrum.
t fibers. These fibers are mostly myelinated (by
oligodendroglia),accountingfor the coloration in
live tissue.Nuclei noted in white matter belong to
l. Molecular Lager
Composedof horizontal cellsand cell processes.
the various neuroglia.
I 2. External Granular Lager
Consists mostly of granule (stellate) cells, tightly
C. Meninges packed.

I The meningesof the spinalcord form three layers.

The most intimate layer is the pia mater, sur-
rounded by the arachnoid, which, in turn, is in-
I vestedby the thick, collagenousdura mater.
I I . C E R E B E L LU M
I A. Cortex
The cortex of the cerebellumconsistsof an outer
I molecular layer and an inner granular layer with a
single layer of Purkinje cells interposedbetween
them. The perikaryons of the molecular layer are
3. External Pgramidal Lager
Largepyramidal cells and granule (stellate) cells'
4. Internal Cranular Lager
Closely packed granule (stellate) cells, most of
which are small,althoughsomeare larger.
5. Internql Pgramidal Loger
Medium and large pyramidal cells constitute this
layer.
6. Multiform Lager
Consistingof variouscellshapes,many of which are
fusiform. This layeralsohousesMartinotti cells.

I small and relatively few in number. Most of the

fibers are unmyelinated.Purkinje cellsareeasilydis-
tinguishedbytheirlocation,largesize,and extensive
dendritic arborization. The granular layer displays
I crowdedarraysofnuclei belongingto granulecells
B. White Matter
Deep to the cerebralcortex is the subcortical white
matter composedmostly of myelinatedfibers and
associatedneuroglial cells.

I Tissue *
Nervous 129
I V.CH O R O I D
P L EX U S
The choroid plexusconsistsof tufts of smallvascu-
lar elements(derivedfrom the pia-arachnoid)that
are covered by modified epeniymal cells (simple
cuboidal in shape).Thesestructures,locatedin ihe
ventriclesof the brain, are responsiblefor the for-
mation of the cerebrospinalfluid (CSF).
v. DoRSALROOTGANGL|ON(DRG)
A. Neurons
The somataof thesecellsare pseudounipolar,with
Iarge nuclei and nucleoli. Surrounding eachsoma
are capsulecells,recognizedbytheir small, round
nuclei. Fibroblasts(satellitecells)are also evident.
Synapses do not occur in the DRG.
B. Fibers
Fibersare mostly myelinatedand travel in bundles
throughthe DRG.
C. Connective
Tissue
The DRG is surroundedby collagenousconnective
tissue whose septapenetratethe substanceof the
ganglion.
| 30 ffi Nervous
Tissue
VI. PERIPHERAL
NERVE
A. Longitudinal Section
The parallel fibers stain a pale pink with hema-
toxylin and eosin,although Schwanncell and occa-
sional fibroblast nuclei are clearly evident. The
most characteristic feature is the apparent wavy,
zigzagcourseof the nervefibers.At low magnifica-
tion the perineurium is clearly distinguishable,
while at high magnification the nodes of Ranvier
may be recognizable.
B. TransverseSection
The most characteristic feature of transversesec-
tions of nervefibersis the numerous,small,irregu-
lar circleswith a centrallylocateddot. Thin spokes
appearto traversethe empty-looking spacebetween
the dot and the circumferenceof the circle.These
represent the neurolemma, the extracted myelin
(neurokeratin), and the central axon. Occasionally,
crescent-shaped nucleihug the myelin; thesebelong
to Schwanncells.The endoneurium may show evi-
denceof nuclei of fibroblasts also.At lower magni-
fication the perineuria of severalfasciclesof nlrve
fibers are clearlydistinguishable.When stainedwith
OsOr, the myelin sheath standsout as dark, round
structureswith lightly staining centers.
I
I
I
I
I
I
I
I
t
I
I
t
t
I
t
I
I
I
I
CRAPHIC
7- I t SpinalNerveMorphotogg

S p i n a lc o r d

Epineurium
Endoneurium
Bloodvessels
Perineurium
Basallamina

Nodeot
Ranvier
Bundleof nerves

Epineurium
Internode
Perineurium
Endoneurium

S c h w a n nc e l l

myelinatedfiber

Myelinsheath
Peripheralnervesarecomposedof Nervefibers
bundlesof axonand dendritesEach (silverstain)
nerveis enclosed by an epineurium.
Bundles(fascicles)of axonsand
dendritesare surrounded by several
layersof flatepithelioid cells,the
perineurium,thatformoccluding
junctionswitheachotherThe Fascicledetail
perlneurium is isolatedfromthe (H & E stain)
connective tissueelementsby basal Axon of
laminaeon bothits externaland internal myelinated
aspects.Eachaxonand dendriteis
investedby a protective Schwanncell
(forinsulation andmaintenance), which, Myelinsheath
in turn,is surrounded by itsbasallamina
anda networkof fine reticular fibers. Nervefibers
forming theendoneurium. (osmicstain)

132 Nervous
Tissue
 7-2 r Neuronsand Mgoneural
GRAPHIC Junction

UE| |u| |tv -------\

Nucleus
C e l lb o d y
N i s s lb o d y
Axonhillock

N e u r i l e m m as h e a t h
c e l ln u c l e u s
' M y e l i ns h e a t h \
A x i sc y l i n d e r - - . _ . \
\

\i\
\ \l
R,-*\

M o t o r n e u r o n s D o s s e s sn u m e r o u s
d e n d r i t e sa, l a r g ec e n t r a ln u c l e u s ,
a n d a l o n g m y e l i n a t e da x o n T h e
R E R ( N i s s l b o d i e s ) i s s e g m e n t e db y
n e u r o t u b u l e sa n d n e u r o fi l a m e n t s 1...I r
T h e a x o n b r a n c h e sa n d t e r m i n a t e s
lIilc.la+
as motor end plates

N e r v et e r m i n a l

Motor end plate

J u n c t i o n aflo l d s

Sarcoplasm

Mitochondrion

M u l t i p o l acr e l l U n i p o l a cr e l l
M u l t i p o l acr e l l
( c e r e b e l l acro r t e x ) ( c e r e b r o s p i n ag la n g l i a )
( a u t o n o m i cg a n g l i a )

N e r v o uTsi s s u e 133
PLATE7- 1 I SpinalCord
FIGURE | = Spinal cord. x.s. Cat. Silver stain.
Paraffin section. x 21.
The spinalcord is investedby a protectivecoating,the
three-layeredmeninges.Its outermost fibrous layer, the
dura mater (DM), is surrounded by epidural fat, not
presentin this photomicrograph.Deep to the dura is the
arachnoid (A) with its subarachnoidspace(SS),which
is closely applied to the most intimate layer of the
meninges,the vascularpia mater (PM). The spinal cord
itselfis organizedinto white matter (W) and gray matter
(G). The former, which is peripherallylocatedand does
not contain nervecell bodies,is composedof nervefibers,
most of which are myelinated,that travel up and down
the cord. It is cellular,however,since it housesvarious
rypes of glial cells. The centrally positioned gray matter
containsthe cell bodiesof the neurons,aswell asthe ini-
tial and terminal endsof their processes, many of which
arenot usuallymyelinated.Thesenervecellprocesses and
thoseof the numerousglial cellsform an intertwinednet-
work offibers that is referred to asthe neuropil. The gray
matter is subdividedinto regions,namelythe dorsalhorn
(DH), the ventral horn (VH), and the gray commissure
(Gc). The central canal (CC) of the spinal cord passes
through the gray commissure, dividing it into dorsal and
ventral components.Processes of neuronsleaveand en-
ter the spinalcord asventral (VR) and dorsal (DR) roots,
respectively.A region similar to the boxed area is repre-
sentedin Figure2.

FIGURE 2 4e Spinal cord. x.s. White and grog
matter. Human. Paroffin section. x 132.
This photomicrographrepresentsthe boxed region of
Figure l. Observethat the interfacebetweenwhite matter
(W) and gray matter (G) is readily evident (asterisks).
The numerousnuclei (arrowheads)presentin white mat-
ter belong to the various neuroglia,which support the
axons and dendrites traveling up and down the spinal
cord. The largenervecell bodies(CB) in the ventralhorn
of the graymatterpossess vesicular-appearingnucleiwith
dense,dark nucleoli.Blood vessels(BV), which penetrate
deepinto the gray matter,aresurroundedby processes of
neuroglialcells,forming the blood-brain barrier, not vis-
ible in this photomicrograph.Small nuclei (arrows) in
gray matter belong to the neuroglial cells,whose clto-
plasmand cellularprocesses arenot evident
FfGURE 3 ffi Sprnal cord. x.s. Ventrol horn. Human.
Poraffin section. x 210.
The multipolar neurons and their various processes
(arrows) are clearlyevident in this photomicrograph of
the ventral horn. Note the large nucleus (N) and dense
nucleolus (n), both ofwhich are characteristicofneu-
rons. Observethe clumps of basophilic material, Nissl
bodies (NB), that electron microscopy has demon-
strated to be rough endoplasmicreticulum. The small
nuclei belong to the various neuroglial cells (Ng),
which, along with their processesand processesof the
neurons, compose the neuropil (Np), the matted-
appearing background substanceof gray matter. The
white spaces (asterisks) surrounding the soma and
Lr^^r vesselsare due to shrinkageartifacts.

Multipolarcell
(spinalcord)

T KEY

A arachnoid u gray matter Np neuropil

BV bloodvessel Gc gray commrssure PM pia mater
CB nervecell body N nucleus SS subarachnoidspace
CC centralcanal n nucleolus VH ventralhorn
DH dorsalhorn NB Nisslbody VR ventralroot
DM dura mater Ng neuroglial
cell W white matter
DR dorsal root

134 w Nervous
Tissue
It
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FICURE

F I G U R2
E FICUR3
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N e r v o u sT i s s u e I 55
PLATE7-2 I Cerebellum,
Sgnapse,ElectronMicroscopg I
'::
FIGURE I
x 14.
Cerebellum. Human. Poraffin section.

The cerebellum,in contrastto the spinalcord,consists

FIGURE 2
x 132.
Cerebellum. Human. Paraffin section.

This photomicrographis taken from a region similar

of a core ofwhite matter (W) and the superficiallylocated
gray matter (G). Although it is difficult to tell from this
low-magnificationphotomicrograph,the gray matter is
subdivided into three layers,the outer molecularlayer
(ML), a middle Purkinje cell layer (PL), and the inner
granular layer (GL). The less dense appearanceof the
molecularlayeris due to the sparsearrangementof nerve
cell bodies,while the darker appearanceof the granular
layeris a function ofthe greatnumber ofdarkly staining
nuclei packed closelytogether.A region similar to the
boxed areais representedin Figure2.
I
to the areaboxed in Figure l. The granular layer (GL) is
composedof closelypackedgranulecells(GC), which, at
first glance, resemblelymphocytes due to their dark
round nuclei. Interspersedamong these cells are clear
t
spaces,calledglomeruli or cerebellarislands(CI), where
synapsesoccur between axons entering the cerebellum
from outsideand dendritesofgranule cells.The Purkinje
I
cells (PC) sendtheir axonsinto the granularlayer,while
their dendritesarborizein the molecularlayer (ML). This
layeralsocontainsunmyelinatedfibersfrom the granular
layer,as well as two tlpes of cells,basketcells (BC) and
I
the more superficiallylocatedstellatecells(SC).The sur-
faceof the cerebellumis investedby pia matter (PM), just
barely evident in this photomicrograph.The boxed area
t
is presentedat a higher magnificationin Figure3.

I
F|GURE 3 Purkinje cell. Humon cerebellum. FIGURE 4 .:. Sgnapse. Afferent terminals. Electron
Poraffin section. x 540.
This is a higher magnificationof the boxedareaof Fig-
ure 2. The granular layer (GL) of the cerebellumis com-
microscopg. x 16,200.
The lateral descendingnucleus of the fifth cranial
nerve displays a primary afferent terminal (AT) that is
I
posedof two cell t1pes,the smaller granule cells (GC) and forming multiple synapseswith dendrites (D) and axons
largerGolgi type II cells(G2). The flask-shaped Purkinje
cell (PC) displaysits largenucleus(N) and dendritic tree
(D). Nuclei of numerousbasketcells (BC) of the molec-
(Ax). Observethe presenceof synapticvesicles(SV) in
the postsynapticaxon terminals,aswell asthe thickening
of the membrane of the primary afferent terminal
I
ular layer (ML), as well as the unmyelinatedfibers (UF)
of the granulecells,are well definedin this photomicro-
graph. Thesefibers make synapticcontact (arrows)with
(arrows).This terminal alsohousesmitochondria (m), as
well as cisternae (Ci) for the s1'napticvesicles.(From
MeszlerRM: I CompNeurol220:299-309,1983.)
t
the dendritic processes ofthe Purkinje cells.
Iflset. Astrocyte. Human cerebellum. Golgi stain.
Paraffin section.x 132.
Note the numerousprocesses of this fibrous astrocyte
I
(A) in the white matter of the cerebellum.

t
t
Multipolar
cell
(cerebellarcortex) I
t
I KEY

A fibrous astrocyte gray matter PC Purkinjecell

I
AT primaryafferenttermtnal \22 Golgitype ll cell PL Purkinjecelllayer
Ax
BC
axons
basketcell
uv
GL
granulecell
granularlayer
PM
JU
pia mater
stellatecell
I
Cl cerebellar island m mitochondrion SV synapticvesicle
Ci
D
cistern
dendrite
ML
N
molecularlayer
nucreus
UF
W
unmyelinated
white matter
liber
I
| 36 :,' NervousTissue I
I
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PLATE7-3 I Cerebrum,NeuroglialCells
FIGURES I AND 2 & Cerebrum. Human. Paraffin
section. x 132.
Thesefigures representa montage of the entire hu-
man cerebralcortex, and some of the underlying white
matter (W) at a low magnification.Observethat the nu-
merousblood vessels(BV) that penetratethe entire cor-
tex are surroundedby a cleararea(arrow), which is due
to shrinkageartifact.The six layersof the cortex are not
clearly defined, but are approximatedby brackets.The
pia mater (PM), covering the surfaceof the cortex, is a
vasculartissuethat provideslargerblood vessels,as well
as capillaries(Ca) that penetratethe brain tissue.Layer
one of the cortex is known as the rnolecularlayer (1),
which containsnumerous fibers and only a few neuron
cell bodies.It is difficult to distinguishthesesoma from
the neuroglial cells at this magnification. The second,
external granular layer (2), is composedof small gran-
ule cells (GC), aswell as many neuroglialcells(Ng). The
third layer is known as the external pyramidal layer (3),
which is the thickest layer in this section of the cerebral
cortex. It consistsof pyramidal cells (Py), and some
F|GURE 3 * Astrocgtes. Silver stain. Poroffin
section. x 132.
This photomicrographof the white matter of the cere-
brum presentsa mattedappearance due to the interweav-
ing ofvarious nervecell and glial cell processes. Note also
the presenceof two blood vessels(BV) passinghorizon-
tally acrossthe field. The long processes ofthe fibrous as-
trocltes (FA) approachthe blood vessels(arrows)and as-
sistin the formation of the blood-brain barrier.
I
granule cells (GC) as well as numerous neuroglia (Ng)
interspersedamong the soma and fibers. The fourth
layer, the internal granular layer (4), is a relatively nar-
I
row band whosecell population consistsmostly of small
and a few large granule cells (GC) and the ever present
neuroglial cells (Ng). The internal pyramidal layer (5)
housesmedium and large pyramidal cells (Py) as well as
I
the ubiquitous neuroglia (Ng), whose nuclei appear as
small dots. Although not evident in this preparation,
nerve fibers of the internal band of Baillargerpasshori-
t
zontally through this layer, while those of the external
band of Baillarger traverse the internal granular layer.
The deepestlayer of the cerebral cortex is the multiform
layer (6), which contains cells of various shapes,many
I
of which are fusiform in morphology. Neuroglial cells
and Martinotti cells are also present in this layer, but
cannot be distinguishedfrom each other at this magni-
t
fication. The white matter (W) appears very cellular,
due to the nuclei of the numerous neuroglial cellssup-
porting the cell processesderived from and traveling to
the cortex.
I
FIGURE 4 4 Microglia. Silver stain. Paraffin
I
section. x 540.
This photomicrographis of a sectionof the cerebral
cortex,demonstratingnuclei (N) of nervecells,aswell as
the presenceof microglia (Mi). Note that microglia are
I
a densenucleus(N), aswell asnu-
very small and possess
merouscell processes(arrows).
I

I
t
I
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I
r KEY I
BV bloodvessel Ng neurologicalcell J externalpyramidallayer
Ca
FA
capillary
fibrousastrocyte
PM
Py
pia mater
pyramidalcell
4 internalgranularlayer
internalpyramidallayer I
GC granulecell W white matter b multiformlayer
Mi
N
microglia
nucleus
1
2
molecularlayer
externalgranularlayer t
138 # Nervous
Tissue t
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N e r v o uT
sissue 139
PLATE7-4 I SgmpatheticGanglia,SensorgCanglio I
F|GURE | ) Sgmpothetic ganglion. l.s. Paraffin FIGURE 2 . Sgmpothetic gonglion. l.s. Paroffin
section. x 132.
Sympatheticgangliaare structuresthat receiveaxons
section. x 540.
This photomicrographpresentsa higher magnifica-
I
of presynapticcells,whosesomaare within the CNS. Lo- tion of a region similar to the boxed areaof Figure l Al-
catedwithin the ganglionare soma of postsynapticneu-
rons upon which the presynapticcell axons synapse.
Thesegangliaare envelopedby a collagenousconnective
though neuronsof the sympatheticganglionaremultipo-
lar, their processesare not evident in this specimen
stained with hematorylin and eosin. The nucleus (N)
I
tissue capsule (C), which sends septa (S) containing with its prominent nucleolus(n) is clearlyvisible.The cy-
blood vessels(BV) within the substanceof the ganglion.
The arrangementof the cellbodiesof the multipolar neu-
toplasm contains lipofuscin (Li), a yellowish pigment
that is very prevalentin neuronsofolder individuals.The
I
rons (MN) within the ganglionappearsto be haphazard. clear spacebetweenthe soma and the supporting cells
This very vascularstructure contains numerous nuclei
which belong to endothelial cells (E), intravascular
(SS)is a shrinkage artifact.Note the numerous blood ves-
sels(BV) containing red blood cells(arrows) and a neu-
j
leukocytes(L), fibroblasts(F), Schwanncells (ScC),and trophil (Ne).
thoseof the supporting cells (SS)surrounding the nerve
cellbodies.A regionsimilar to the boxedareais presented
in Figure2. I
FIGURE 3 a Sensorg ganglion. l.s. Human. Paroffin
section. x 132.
FIGURE 4 ) Sensorg ganglion. l.s. Humon. Poraffin
section. x 210.
t
The dorsalroot ganglionprovidesa good representa- This photomicrographis a higher magnificationof a
tive exampleofa sensoryganglion.It possesses a vascular
(BV) connectivetissuecapsule(C), which alsoenvelops
region similar to the boxed areaof Figure 3. The spheri-
cal cell bodiesdisplay their centrallylocatednuclei (N)
I
its sensoryroot. The neuronsofthe dorsal root ganghon and nucleoli (n). Observethat both small (arrowheads)
are pseudounipolar in morphology; therefore, their
somata (So) appear sphericalin shape.The fibers (0,
many of which are myelinated,alternatewith rows of cell
and large (arrows) somata are present in the field, and
that the nuclei are not always in the plane of section.
Hematoxylin and eosin stainsthe somataa more or less
I
bodies.Note that some somataare large (arrow), while homogeneouspink, so that organellessuch as Nissl sub-
others are small (arrowhead).Each soma is surrounded
by neuroectodermallyderived capsulecells (Cc). A re-
stanceare not visible. However, the nuclei and cltoplasm
of capsulecells (Cc) are clearly evident. Moreover, the
I
gion similar to the boxedareais presentedat a high mag- small,elongated,denselystainingnucleiof fibroblasts(F)
nification in Figure4. are alsonoted to surround somata,just peripheralto the
capsule cells. Axons (Ax) of myelinated nerve fibers
belongto the largepseudounipolarneurons.
I
I
I
Multipolarcell (autonomicganglia)
Unipolarcell (pseudounipolar
from dorsalroot ganglion)
cell
I
I
T KEY I
Ax axon t nervefiber Ne neutrophil
BV
c
bloodvessel
capsure
L
Li
leukocyte
lipofuscin
S
ScC
septum
Schwanncell I
Cc capsulecell n nucleolus So soma
E
F
endothelialcell
fibroblast
MN
N
multipolar
nucleus
neuron SS supportingcell
I
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PLATE7-5 I PeripheralNerve,ChoroidPlexus I
FfGURE lA ,' Peripherol nerve. l.s. Monkeg. FIGURE 2 # Peripheral nerve. I.s. Paraffin section.
Plastic section. x 132.
The longitudinal sectionof the peripheralnerve fas-
x 210.
This is a higher magnificationof a region similar to
I
cicle presentedin this photomicrographis envelopedby the boxed areaofFigure 1a.A distinguishingcharacteris-
its perineurium (P), composedof an outer connective
tissuelayer (CT) and an inner layer of flattenedepithe-
lioid cells (E). The perineurium conducts small blood
tic of longitudinal sectionsof peripheral nervesis that
they appear to follow a ziz-zag course, particularly evi-
dent in this photomicrograph. The sinuous course of
t
vessels(BV), which are branchesof largervesselstravel- thesefibers is accentuatedby the presenceof nuclei of
ing in the surrounding epineurium, a structure com-
posedof looseconnectivetissuewith numerousfat cells.
Schwanncells(ScC),fibroblasts(F), and endothelialcells
of capillariesbelonging to the endoneurium. Many of
I
The peripheral nerve is composed of numerous non- thesenerve fibers are myelinated (M) as corroborated by
myelinatedand myelinatednerve fibers, an exampleof
which is presentedin Figure 1b. The densenuclei (ar-
rows) within the nerve fasciclebelong to Schwanncells
the presenceofthe nodesofRanvier (NR) and neuroker-
atin around the axons (Ax). I
and endoneurialcells.A region similar to the boxed area
is presentedin Figure2.
FIGURE 4 74 Choroid plexus. Parafftn section. x
210.
I
FfGURE lB r Teased, mgelinated nerve fiber.
Paroffin section. /.s. x 540. The choroid plexus,locatedwithin the ventriclesof
This longitudinal sectionof a singlemyelinatednerve
fiber displaysits axon (Ax) and the neurokeratin net-
the brain, is responsiblefor the formation of cere-
brospinal fluid. This structure is composedof tufts of I
work, the remnantsof the dissolvedmyelin (M). Note the capillaries(Ca) whosetortuous courseis followedby villi
(Vi) of the simple cuboidal choroid plexus epithelium
node of Ranvier (NR), a regionwheretwo Schwanncells
meet.It is here,where the axon is not coveredby myelin,
that saltatoryconductionofimpulsesoccur.Observethat
(cp). The connectivetissue core (CT) of the choroid
plexusis contributedby pia-arachnoid,while the simple
I
Schmidt-Lantermanincisures (SL) are clearly evident. cuboidalepithelium is modified ependymallining of the
Theseareregionswherethe cytoplasmofSchwanncellsis
trappedin the myelin sheath.
ventricle. The clear spacessurrounding the choroid
plexusbelongto the ventricleofthe brain. I
FIGURE3
x 132.
Peripheral nerve. x.s. Paroffin section.

This transversesection presentsportions of two fascr-

I
cles,eachsurroundedby perineurium (P). The intervening
loose connective tissue of the epineurium (Ep) with its
blood vessels(BV) is clearly evident. The perineurium
I
forms a septum (S), which su6dividesthis fascicleinto two
compartments.Note that the axon.s(Ax) are in the center
of the myelin sheath (MS) and occasionallya crescent-
shapednucleusof a Schwanncell (ScC) is evident.The
I
denser,smallernuclei(arrows)belongto endoneurialcells. Nervetrunk(crosssection)
Inser. Peripheral nerve. x.s. Silver stain. Paraffin sec-
tion. X 540. I
Silver-stainedsectionsofmyelinatednervefibershave
the large clearspaces(arrow) that indicate the dissolved
myelin. The axons (Ax) stain well as dark, dense struc-
tures,and the delicateendoneurium (En) is alsoevident.
I
I
T KEY I
Ax axon En enooneunum P perineurium
Fr\/
Ca
bloodvessel
capillary
Ep
F
eprneunum
fibroblast
S
ScC
septum
Schwanncell I
cp choroidplexusepithelium M myelin SL Schmidt-Lanterman
CT
E
connectivetissue
epithelioid
cell
MS
NR
myelinsheath
nodeof Ranvier Vi
incisure
villus t
| 42 dg NervousTissue I
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PLATE7-6 r PeripheralNerve,ElectronMicroscopg t
FIGURE I Peripheral nerve. x.s. Mouse. Electron mitochondria (m), as well as neurofilaments (Nf) and
microscopg. x 33,300.
This electronmicrographpresentsa cross-section of
neurotubules (Nt). Occasionally,the myelin wrapping
is surrounded by Schwann cell cltoplasm on its outer
I
three myelinatedand severalunmyelinatednerve fibers. and inner aspects,as in the nerve fiber in the upper
Note that the axons (Ax) (although they may be the af-
ferent fibers of pseudounipolarneurons) are sur-
rounded by a thick myelin sheath (MS), peripheral to
right-hand corner. The unmyelinated nerve fibers (f) in
the top of this electron micrograph display their rela-
tionship to the Schwanncell (ScC).The fibers are posi-
I
which is the bulk of the Schwanncell cltoplasm (ScC) tioned in such a fashion that eachlies in a complicated
housing mitochondria (m), rough endoplasmicreticu-
lum (rER), and pinocytotic vesicles(PV). The Schwann
membrane-linedgroove within the Schwanncell. Some
fibers are situated superficially,while others are posi-
I
cell is surroundedby a basallamina (BL) isolatingthis tioned more deeplywithin the grooves.However, a pe-
cell from the endoneurial connectivetissue (CT). The
myelin sheathis derived from the plasmamembrane of
the Schwann cell, which presumably wraps spirally
riaxonal (or peridendritic) space(arrows) is alwayspre-
sent. Mitochondria (m), neurofilaments (N0, and
neurotubules (Nt) are alsopresent.Note that the enttre
I
around the axon,resultingin the formation ofan exter- structure is surrounded by a basal lamina (BL), which
nal (EM) and internal (IM) mesaxon.The axolemma
(AI) is separatedfrom the Schwanncell membraneby a
narrow cleft,the periaxonalspace,The axoplasmhouses
covers but does not extend into the grooves (arrow-
heads) housing the nerve fibers. (Courtesy of Dr. J.
Strum.)
t
I
t
I
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I
I
of nervefiber
Myelination I
I
I
I KEY
I
AI
Ax
axolemma
axon
EM
I
externalmesaxon
nervefiber
Nf
Nt
neurofilament
neurotubule I
BL basallamina IM internalmesaxon PV pinocytoticvesicle
CT endoneurial
tissue
connective m
MS
mitochondrion
myelinsheath
rER
ScC
roughER
Schwanncell cytoplasm I
144 r, Nervous
Tissue I
I
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J N e r v o uTsi s s u e 145
PLATE7-7 I NeuronCellBodg,ElectronMicroscopg t
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numerousmitochondria (m), and elementsof rough en-
FIGURE I Neuron. Loteral descending nucleus.
Electron microscopg. x 3589.
The soma of this neuron presentsa tlpical appear-
doplasmic reticulum, which extend into the dendrites
(D). Myelinated (M) and nonmyelinated(nM) fibersare
I
ance.Note the largenucleus (N) and nucleolus (n) sur- alsopresent,as are synapses(arrows) aiong the cell sur-
rounded by a considerableamount of cyoplasm rich in
organelles.Observethe extensiveGolgi apparatus(GA),
face. (From Meszier R, Auker C, CarpenterD: I Comp
Neurol r96i57l-584, 1981.) I
I
t
146 Nervous
Tissue t

r CirculatorASgstem
The circulatorysystemis composedof two separate
but connectedcomponents:the blood vascularsys-
tem (cardiovasculaisystem)that transportsblood
and the lyrnphatic vascularsystemthat collectsand
returns excessextracellular fluid (lymph) to the
blood vascular system. Lymphoid tissue is pre-
sentedin Chapter9.
BLOOD VASCUTARSYSTEM
The blood vascularsystem,consistingof the heart
and blood vessels, functionsin propellingand trans-
porting blood and its variousconstituentsthrough-
out the body. The heart, acting as a pump, forces
blood at high pressureinto large,elasticarteriesthat
carry the blood away from the heart. Thesearteries
give way to increasinglysmallermuscular arteries.
Eventually,blood reachesextremelythin walled ves-
sels,capillariesand small venules,whereexchangeof
materialsoccurs.It is mostly herethat certaincells,
oxygen,nutrients,hormones,certainproteins,and
additionalmaterialsleavethe blood stream,whereas
carbon dioxide, waste products, certain cells,and
certain secretoryproducts enter the bloodstream.
Capillary beds are drained by the venous compo-
nentsof the circulatorysystem,which return blood
to the heart.The blood vascularsystemis subdivided
into the pulmonary and systemiccircuits, which
originate from the right and left sidesofthe heart,
respectively.The pulmonary circuit takes oxygen-
poor blood to the lungs to becomeorygenatedand
returns it to the left side of the heart. The oxygen-
rich blood is propelled via the systemiccircuit to the
remainder of the body to be returned to the right
sideof the heart,completingthe cycle.
HEART
The heart is a four-chamberedorgan composedof
two atria and two ventricles.The atria, subsequent
to receivingblood from the pulmonaryveins,venae
TSMII
cavae, and coronary sinus, discharge it into the
ventricles.Contractionsofthe ventriclesthen pro-
pel the blood either from the right ventricle into the
pulmonary trunk for distribution to the lungs or
from the left ventricle into the aorta for distribution
to the remainderof the body. Although the wallsof
the ventriclesare thicker than those of the atria,
thesechamberspossesscommon characteristics, in
that they are composedof three layers:epicardium,
myocardium, and endocardium.Epicardium, the
outermost layer, is coveredby a simple squamous
mesotheliumdeepto which is fibroelasticconnec-
tive tissue.The deepestaspectofthe epicardiumis
composedof adiposetissuethat housesnervesand
the coronary vessels.Most of the wall of the heart is
composedof myocardium, consistingof bundlesof
cardiac muscle that are attached to the thick col-
lagenousconnectivetissue skeleton of the heart.
The endocardium forms the lining of the atria and
ventriclesand is composedof a simple squamous
endothelium,aswell asa subendothelialfibroelastic
connectivetissue.The endocardiumparticipatesin
the formation of the heartvalves,which control the
direction of blood flow through the heart. Addi-
tionally, somecardiacmusclefibers are specialized
to regulatethe sequenceof atrial and ventricular
contractions.Thesearethe sinoatrialand atrioven-
tricular nodes, as well as the bundle of His and
Purkinje fibers.The sinoatrialnode (SA node), the
pacemakerof the heart,is locatedat the junction of
the superior vena cava and the right atrium. Im-
pulsesgeneratedat this point are conductedto the
atrioventricular node (AV node),which is located
on the medial wall of the right ventricle near the tri-
cuspid valve, as well as to the atrial myocardium.
Arising from the AV node is the bundle of His,
which bifurcatesin the septummembranaceumto
serve both ventricles. As these fibers reach the
subendocardium, they ramify and are known as
Purkinje fibers, which eventually merge with and
become indistinguishablefrom cells of the my-
ocardium. The inherent rhrthm of the SA node is
System s
Circulatory 147
modulatedby the autonomicnervoussystem,in
that parasympatheticfibersderivedfrom the vagus
nerve decreasethe rate of the heartbeat,whereas
fibersderivedfrom sympatheticgangliaincreaseit.
ARTERIES
Arteries, which conduct blood away from the
heart,may be classifiedinto three categories: elastic
(conductingor large), muscular (distributingor
medium), and arterioles(seeGraphic8-1). Elastic
arteries, such as the aorta, receiveblood directly
from the heart and, consequently,are the largestof
the arteries.Muscular arteriesdistribute blood to
various organs,whereasarterioles regulateblood
pressureand the distribution of blood to capillary
bedsvia vasoconstrictionand vasodilatationof ves-
selwalls.
Blood vessels,including all arteries,are com-
posed of three concentric layers: tunica intima,
tunica media,and tunica adventitia.The tunica in-
tima is composedof simple squamousendothelial
cells lining the lumen and of various amounts of
subendothelialconnectivetissue.The tunica me-
dia, usuallythe thickestof the three layers,is com-
posed of circularly arrangedsmooth muscle cells
and fibroelastic connective tissue, whose elastic
content increasesgreatlywith the sizeof the vessel.
The tunica adventitia is the outermost layer of the
vesselwall, consistingof fibroelasticconnectivetis-
sue.In larger vessels,the tunica adventitiahouses
vasavasorum, small blood vesselsthat supply the
tunica adventitiaand media of that vessel.
VEINS
Veins conduct blood away from body tissuesand
back to the heart (seeGraphic8-l). Generally,the
diameters of veins are larger than those of corre-
sponding arteries; however, veins are thinner
walled,sincethey do not bearhigh blood pressures.
Veins also possessthree concentric,more or less
definitelayers:tunica intima, tunica media,and tu-
nica adventitia.Furthermore,veinshavefewer lay-
ers of smooth muscle cells in their tunica media
than do arteries.Finally,many veins possess valves
that act to prevent regurgitation of blood. Three
categoriesof veins exist:small,medium, and large.
The smallestveins,frequentlyreferredto asvenules,
are also responsiblefor the exchangeof materials.
Moreover, vasodilator substances,such as sero-
tonin and histamine, appear to act on small
venules,causing them to become "leaky" by in-
creasing the intercellular distancesbetween the
membranesof contiguous endothelialcells. Most
suchintercellulargapsoccur in smallvenulesrather
than in capillaries.
| 48 Circulatorv
Svstem
CAPITTARIES I
Capillariesusuallyform thin-walled networksthat
are supplied by arterioles and metarteriolesand I
drained by venules(seeGraphic 8-2). Frequently,
capillarynetworksmay be circumventedby special-
ized vesselscalledarteriovenousanastomoses,in-
terposedbetweenthe arterial and venoussystems.
t
Capillariesare composedof highly attenuateden-
dothelial cellsthat form narrow vascularchannels
8-10 pm in diameter and are usually lessthan I
I
mm long. Associatedwith capillariesarebasallam-
inae and pericytes,but the capillary possesses
smooth muscle cells.Therefore,capillariesdo not
no t
exhibit vasomotoractivities.Control of blood flow
into a capillarybed is establishedat the siteswhere
individual capillariesarisefrom terminal arterioles
I
or metarteriolesand is accomplishedby smooth
musclecellsknown as precapillarysphincters.The
presenceof metarteriolesand thoroughfarechan-
nels permits the maintenanceof an adequateblood
t
supply during reduced flow through a capillary
bed. Basedon fine structuralcharacteristics, three
tlpes of capillaries are recognized: fenestrated,
I
continuous,and discontinuous.Fenestratedcapil-
laries possessnumerous pores,usually bridged by
diaphragms,through which material may enter or
I
leave the capillary lumen. Continuous capillaries
are devoid of pores,and materialmust traversethe
endothelial cell either via pinocytotic vesiclesor
I
betweenendothelialcell junctions. In certain areas
ofthe body (brain,thyrnus,testes),however,fasciae
occludentesformed by contiguousendothelialcells I
prevent the escapeor entry of material through
intercellularspaces.Discontinuous capillaries(si-
nusoids) are tortuous and possesslarge lumina. I
Their endothelialcells presentlarge fenestraeand
intercellular spaces.Moreover, their basal lamina
is not continuous. Frequently, macrophagesare
associated with discontinuouscapillaries.Someau-
I
thors recognizesinusoids,venous sinusoids,and
sinusoidal capillaries in place of discontinuous
capillaries.
I
LYMPH VASCULARSYSTEM
I
Excessextracellularfluid, which doesnot enter the
venousreturn systemat the levelofthe capillarybed
I
or venule, gains entry into lymphatic capillaries,
blindly ending thin vesselsof the lymph vascular
)
system.Subsequentto passingthrough chains of
lymph nodes and larger lymph vessels,the fluid,
known as lyrnph, entersthe blood vascularsystem
at the root ofthe neck. I
I

Histophgsiologg
I. HEART
The heart is a muscularpump that propelsblood at
high pressure,via elastiCarteiies,to th- lungs (pul-
monary circuit) for oxygenation,and via the aorta
(systemic circuit) for distribution of oxygenated
blood to the tissuesofthe bodv.
A. Generation and Conduction of lmpulse
The sinoatrial node (SA node) of the heart gener-
atesimpulses,which resultsin the contraction of
the atrial muscles,and blood from the atria enter
the ventricles. The impulse is then transmitted
to the atrioventricularnode (AV node).
The atrioventricularbundle (of His) arisesfrom
the AV node and travels in the interventricular
septum, where it subdividesto form the Purkinje
fibers. The Purkinje fibers deliver the impulse to
the cardiacmuscle cellsof the ventriclesthat con-
tract to pump the blood from the right ventricle
into the pulmonary trunk and from the left ventri-
cle into the aorta.
B. Valves
Atrioventricular valves between the atria and ven-
triclespreventregurgitationofblood into the atria.
Similarly, semilunar valves located in the pul-
monary trunk and the aortapreventregurgitationof
blood from thesevesselsback into their respective
ventricles.The closingofthesevalvesis responsible
for the soundsassociated with the heartbeat.
I I . A R T ER I E S
Arteriesare classifiedinto three Qpes:elastic,mus-
cular, and arterioles.Capillariesarisefrom the ter-
minal ends of arteriolesand their walls have no
smooth muscletunic.
A. ElasticArteries
Elasticarteriesare the largestof the arteries.Since
they arisedirectly from the heart, they are subject
to cyclic changesof blood pressure,high as the
ventriclespump blood into their lumina and low
betweenthe emptying of thesechambers.In order
to compensatefor these intermittent pressure
I ll
alterations,an abundanceofelasticfibersarelocated
in the walls of thesevessels.Theseelasticfibers not
only provide structuralstabilityand permit disten-
tion of the elasticarteries,but they alsoassistin the
maintenanceof blood Dressurein between heart
beats.
B. MuscularArteries
Muscular arteriescomprisemost of the named ar-
teriesof the body. Their tunica media is composed
mostly of many layersof smooth musclecells.Both
elasticand muscular arteriesare supplied by vasa
vasorum and nervefibers.
C.Arterioles
Arteriolesarethe smallestarteriesand areresponsi-
ble for regulatingblood pressure.Metarteriolesare
the terminal ends of the arterioles,and they are
characterized by the presenceof incompleteringsof
smooth muscle cells (precapillary sphincters) that
encirclethe origins of the capillaries.Metarterioles
form the arterial (proximal) end of a central chan-
nel, and they are responsiblefor deliveringblood
into the capillarybed.The venous(distal)end of the
central channel, known as a thoroughfare channel,
is responsiblefor draining blood from the capillary
bed and deliveringit into venules.Contraction of
precapillarysphinctersof the metarterioleshunts
the blood into the thoroughfare channel, and from
there into the venule;this way, the blood blpasses
the capillary bed. Arteriovenous anastomosesare
direct connections between arteries and venules
and they also function in having blood bypassthe
capillarybed. Theseshuntsfunction in thermoreg-
ulation and blood pressurecontrol.
and Vasodilation
D. Vasoconstriction
Vasoconstrictionis due to the action of sympa-
thetic nerve fibers that act on the smooth musclesof
the tunica media.This is especiallyimportant in the
arterioles,which are responsiblefor the regulation
ofblood pressure.
Vasodilation is accomplishedby parasympa-
thetic nerve fibers in an indirect fashion. Instead
of acting on smooth muscle cells, acetylcholine,
released by the nerveend-foot,is bound to receptors
System =
Circulatory 149
on the endothelialcells,inducing them to release
nitric oxide (NO), previouslyknown asendothelial-
derivedreleasingfactor (EDRF).Nitric oxideactson
the cGMP systemof the smooth muscle cells,caus-
ing their relaxation.
III. CAPILLARIES
Capillariesarevery small vesselsthat consistof a sin-
gle layer ofendothelial cellssurroundedby a basal
lamina and occasionalpericytes.Thesevesselsex-
hibit selective permeability and they, along with
venules,are responsiblefor the exchangeof gases,
metabolites, and other substancesbetween the
blood streamand the tissuesofthe body. There are
three types of capillaries,continuous, fenestrated,
and sinusoidal.
A. CapillaryTypes
Continuous capillaries lack fenestrae,display only
occasionalpinocltotic vesicles,and possessa con-
tinuous basallamina. They are presentin regions
such as peripheral nerve fibers, skeletalmuscle,
lungs,and thymus.
The endothelialcellsoffenestratedcapillariesare
penetratedby relatively large diaphragm-covered
pores.Thesecellsalsopossess pinocyticvesiclesand
are envelopedby a continuousbasallamina. Fenes-
trated capillariesare located in endocrine glands,
pancreas,and lamina propria of the intestines,and
they also constitute the glomeruli of the kidneys,
although their fenestrae are not covered by a
diaphragm.
Sinusoidal capillaries are much larger than
their fenestrated or continuous counterparts.
They are envelopedby a discontinuousbasallam-
ina, and their endothelial cells do not Dossess
pinocytic vesicles.The intercellular junctions of
their endothelial cells display gaps,thus permitting
leakage of material into and out of these vessels.
Sinusoidal capillaries are located in the liver,
spleen, lymph nodes, bone marrow, and the
suprarenalcortex.
B. CapillaryPermeability
Capillary permeability is dependent not only on
the endothelial cells comprising the capillary but
alsoon the Iphysico]-chemicalcharacteristics, such
as size, charge, and shape, of the traversing sub-
| 50 * Circulatory
System
stance. Some molecules, such as H2O diffuse I
through, whereasothers are actively transported by
carrier proteins acrossthe endothelialcell plasma
membrane.
Still others move through fenestraeor through
t
gapsin the intercellularjunctions.Certainpharma-
cologicalagents,such asbradykinin and histamine,
have the ability to alter capillary permeability.
I
Leukocytes leave the bloodstream by passing
through intercellular junctions of the endothelial
cells(diapedesis)to enterthe extracellularspacesof
I
tissuesand organs.
C. Metabolic Functions of Capillaries
r
Capillary endothelial cells possessthe capacity to
deactivatesubstances,such asprostaglandins,sero-
tonin, and bradykinin; catabolize lipoproteins into
l
triglycerides,fatty acids,and monoglycerides;con-
vert angiotensin I to angiotensin II; releaseprosta-
cyclins to inhibit the aggregation of platelets;
I
promote fibrinolysis by producing activators of
plasminogens;expressbinding sitesfor certain clot-
ting factors; and, if injured, releasetissue factors
I
that initiate the clotting response.
I
IV.VEINS
Veins, unlike arteries, are low pressurevesselsthat
conduct blood from the tissuesofthe body back to
I
the heart. Generally, they have larger lumina and
thinner walls with fewer layers of smooth muscle
cells than their companion arteries.Also, many I
veins contain valvesin the lumen that prevent ret-
rogradeblood flow.
I
V. LYMPHATIC
VASCULAR
SYSTEM
Lymphatic capillariesbegin asblind-ending vessels.
Excessextracellular fluid enters these capillaries,
t
becomes known as lymph; this fluid is delivered
into lymphatic vesselsof larger and larger diame-
ters.Interspersedamong thesevesselsarea seriesof
I
ll.rnph nodes that filter the lymph. The lymphatic
vesselseventually deliver their contents into the
thoracic and right lymphatic ducts that empty the
I
ly-ph into largeveins in the root of the neck. Large
lymphatic vesselsare similar in structure to small
veins,exceptthat they possessvalves,havelarger lu-
I
mina. and havethinner walls.
I
I
I
I Clinical Considerations I I I results in reduced bloodflowwithinthatvessel.
lf thiscondition involves thecoronary arteries,
t Valve Defects
thedecreased
causes coronary
bloodflowto themyocardium
heartdisease. Theconse-
Children whohavehadrheumatic fevermay quences of thisdisease maybe angina pectoris,
I developvalvedefectsThesevalvedefectsmay myocardial infarct,
be relatedto improperclosing(incompetency) thy,or evensudden
chronic
death
ischemic cardiopa-
or improperopening(stenosis)Fortunately,
mostof thesedefectscanbe reoalred Ragnaud'sDisease
I surgically Raynaud's disease
wherethearterioles
isan idiopathic
of thefingers
condition
andtoesgo
Aneurgsm
lntosudden spasms lasting minutes to hours,
I A damaged
weakened
bulging
vesselwallmay,overtime,become
andbeginto enlarge andforma
defectknownasan aneurysm. Thiscon-
cuttingoff bloodsupplyto thedigitswitha
resultant cyanosis andlossof sensation This
condition, affectingmostlyyounger women, is
t ditionoccursmostoftenin largevessels
theaorta.lf undetected
rupture withoutwarningandcause
suchas
or Ieftuntreated,it may
internal
believed

causes
to be dueto exposure
asto thepatlent's
include
emotional
to coldaswell
state.Other
atherosclerosis, scleroderma,
bleeding withfatalconsequences Surgical
t repairis possible
the individual
dependinguponthehealthof
injury, aswellasa reaction
tionsThetreatment
lo certain
of choice
sureto cold,prescribing
medica-
is limiting
mildsedatives,
expo-
and
Atherosclerosis discontinuing theuseof tobacco products.
I Atherosclerosis,
thedeposition
thewallsof large-
of plaque
andmedium-sized
within Occasionally,
arteries, therapy
thepracticing
mayalsocontrol
of relaxation
thecondition

I
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r
I Circulatory
System I 151
 rn#rl t
Summargof Histological Organization

(C ON D U C T T N C
r. E L A S T TACR T ER Y C. Tunica Adventitia
ARTERY) Usuallya very thick collagenousand elastictissue,
Among theseare the aorta, common carotid, and with some longitudinally oriented smooth muscle
subclavianarteries. fibers.Vasavasorum are alsopresent.

A. Tunica Intima III.ARTERIOLES

Lined by short, polygonal endothelial cells. The whosediameteris lessthan
Thesearearterialvessels
subendothelial connective tissue is fibroelastic and 100pm.
housessomelongitudinallydisposedsmoothmuscle
cells.Internal elasticlamina is not clearlvdefined.
A. Tunica lntima
B. Tunica Media Endothelium and a variable amount of suben-
dothelial connectivetissueare alwayspresent.The
Characterized by numerous fenestrated mem- internal elasticlamina is presentin largerarterioles,
branes (spiral to concentric sheetsof fenestrated
but absentin smallerarterioles.
elasticmembranes).Enmeshedamong the elastic
material are circularly disposed smooth muscle
cellsand associatedcollagenous,reticular,and elas- B. Tunica Media
tic fibers. The spirallyarrangedsmooth musclefibers may be
up to three layersthick. An external elastic lamina
C. Tunica Adventitia is presentin larger arterioles,but absentin smaller
arterioles.
Thin, collagenous connective tissue containing
some elastic fibers and a few longitudinally ori-
ented smooth muscle cells.Vasavasorum (vessels C. Tunica Adventitia
ofvessels)are alsopresent.
This is composedof collagenousand elasticcon-
nectivetissues,whosethicknessapproachesthat of
the tunica media.
I I . M U S C U L AR
ARTERY
(D T ST R T B U T A
TNRG
TERY)
Among these are the named arteries, with the IV. CAPILLARIES
exceptionofthe elasticarteries.
Most capillariesin crosssectionappearasthin, cir-
cular profiles8-10 p,m in diameter.Occasionally,a
A. TunicaIntima fortuitous section will display an endothelial cell
nucleus, a red blood cell, or, very infrequently, a
Theseare lined by polygonal-shapedflatteneden-
white blood cell. Frequently,capillarieswill be col-
dothelial cells that bulge into the lumen during
lapsedand not evident with the light microscope.
vasoconstriction.The subendothelial connective
Periqtes are usuallyassociated with capillaries.
tissue housesfine collagenousfibers and few longi-
tudinally disposedsmooth musclecells.The inter-
nal elasticlamina, clearly evident, is frequently split
into two membranes.
V. VENULES
Venules possessmuch larger lumina and thinner
wallsthan correspondingarterioles.
B. TunicaMedia
Characterizedby many layersof circularlydisposed
A. Tunica lntima
smooth muscle cells, with some elastic, reticular,
and collagenousfibers among the musclecells.The Endothelium lies on a very thin subendothelial
external elasticlamina is well defined. connectivetissue layer, which increaseswith the

152 m Circulatorv
Svstem
I sizeofthe vessel.Pericytesarefrequentlyassociated VII. LARGEVEINS
with smallervenules.
A. Tunicalntima
I B. TunicaMedia
Sameas that of medium-sizedveins, but displays
thicker subendothelial connective tissue. Some

r Absent in smaller venules,while in larger venules

one or two layers of smooth muscle cells may be
observed.
Iargeveins have well-defined valves.

B. Tunica Media

I C. Tunica Adventitia
Not very well defined, although it may presentsome
smooth muscle cells interspersedamong collage-
nous and elasticfibers.
Consists of collagenous connective tissue with
I fibroblasts and some elasticfibers.
C. TunicaAdventitia
Thickestof the threelayersand accountsfor most of

t V I . M E D I U M - S IZ EVDE IN S
A. TunicaIntima
The endothelium and a scant amount of suben-
t dothelial connective tissue are always present.
Occasionally,a thin internal elastic lamina is ob-
served.Valves may be evident.
I B. Tunica Media
the vesselwall. May contain longitudinally oriented
smooth muscle fiber bundles among the thick lay-
ersofcollagen and elasticfibers.Vasavasorumare
commonly present.
VIII. HEART
An extremely thick, muscular organ composed of
three layers: endocardium, myocardium, and epi-
cardium. The presenceof cardiacmuscleis charac-

I Much thinner than that of the corresponding

artery, but does possessa few Iayers of smooth
muscle cells. Occasionally,some of the muscle
teristic of this organ. Additional structural parame-
ters may include Purkinje fibers' thick valves,
atrioventricular and sinoatrial nodes, aswell asthe
fibers, instead of being circularly disposed, are chordae tendineae and the thick, connective tissue
I longitudinally disposed.Bundles of collagen fibers
interspersed with a few elastic fibers are also
cardiac skeleton.

present.
VESSELS
IX. LYMPHATIC
I Lymphatic vesselsare either collapsedand, there-
C. Tunica Adventitia fore, not discernible,or they are filled with lymph.

t Composed of collagen and some elastic fibers,

which constitutethe bulk of the vesselwall. Occa-
sionally, longitudinally oriented smooth muscle
cells may be present. Vasa vasorum are noted to
I penetrateeventhe tunica media.
In the latter case,they presentthe appearanceof a
clear, endothelial-linedspaceresemblinga blood
vessel.However,the lumina contain no red blood
cells,though lymphocytesmay be present.The en-
dothelium may display valves.

I
I
I
I
I
I C i r c u l a t o r y S y s t eum 1 5 3
 8-1 l
CRAPHIC Artergand Vein

Endothelium

Subendotheliallayer ) Tunica intima

Tunlcamedia
(smoothmusclecells;elastic,reticular,
collagenousfibers;external
elasticlamina)

Tunicaadventitla
andelastictissueand
(collagenous
vasavasorum)

Tunicaintima

Endothelium

Subendothelial
layer

Internalelastic
lamina

Tunicamedia
MuscularArtery (smoothmuscle
and fibroelastic
connective
tissue)

Valve

Tunicaadventitia
(collagenous
Veins,unlikearteries, tissue,
connective
maypossessvalves
fibroblasts,
that preventthe reflux
elasticfibers,
ot blood
smoothmuscle
cells,and
H & E stain Orceinstain vasavasorum)
LargeVein

Arterieshavea moremuscularwall,thusa
muchthickertunicamediathantheveins,and
theyhavea greateramountof elastictissue.
of veinsare
thetunicaadventitia
Conversely,
muchthickerthanthoseof thearteries.

Theoutermost layeris thetunicaadventitia,

comDosed of fibroelastic tissue,
connective
whosevessels, thevasavasorum,penetrate
the outerregionsol the tunicamedia,
supplying itscellswithnutrients.

| 54 il System
Circulatory
CRAPHIC
8-2 I CapillargTgpes

Arteriole

Precapillary
sphincter

Metarteriole

True capillaries

ContinuousCapillary

Some capillarybeds, such as those of the skin,

are designedso that they may be bypassed
under certaincircumstances.One method
wherebybloodflow may be controlledis the use
of central channels that conveybloodfrom and
arterioleto a venule.The proximalhalf of the
centralchannelis a metarteriole, a vesselwith
an incomolete smooth muscle coat. Flow oi
blood into each caprllarythat arisesfrom the
melarterioleis controlledby a smooth muscle
cell, the precapillary sphincter The distal halt
of the centralchannelis the thoroughtare
channel, which possessesno smooth muscle
cells and acceptsbloodfrom the capillarybed.
lf the capjllarybed is to be bypassed,the
precapillarysphincterscontract,preventingblood
tlow into the cap;llarybed, and the blood goes
directlvinto the venule

Capillariesconsistsof a simplesquamous
epitheliumrolledinto a narrowcylinder8-10 pm
in diameter.Continuous (somatic) capillaries
have no fenestrae;materialtransversesthe
endothelialcell in eitherdirectionvia pinocytotic
vesicles. Fenestrated (visceral) capillaries are
characterizedby the presenceof perforations,
fenestrae, 60-80 pm in diameter,which may or
may not be bridgedby a diaphragm.Sinusoidal
capillaries have a large lumen (3G-40pm in
diameter),possessnumerousfenestrae,have
discontinuousbasal lamina,and lack pinocytotic
vesicles Frequently,adjacentendothelialcells of
sinusoidalcapillariesoverlapone anotherin an
incomDletefashion. Sinusoidal(Discontinuous)
Capillary

System =
Circulatory 155
 PLATE8- I I ElasticArterg
FfGURE I Elastic qrterg. l.s. Aorta. Monkeg.
Plostic section. x 132.
This low magnificationphotomicrographdisplaysal-
most the entire thicknessof the wall of the aorta, the
largestarteryof the body. The tunica intima (TI) is lined
by a simple squamousepithelium whose nuclei (arrow-
heads)bulgeinto the lumen of the vessel.The lines,which
appear pale at this magnification,are elasticfibers and
laminae,while the nuclei belong to smooth musclecells
and connectivetissuecells.The internal elasticlamina rs
not readilyidentifiable,becausethe intima is rich in elas-
tic fibers.The tunica media (TM) is composedof smooth
musclecellswhosenuclei (N) are clearlyevident.These
smooth musclecellslie in the spacesbetweenthe concen-
trically layeredfenestratedmembranes(FM), composed
of elastictissue.The externalelasticlamina (xEL) is that
portion of the media that adjoinsthe adventitia.The out-
ermost coat of the aorta, the tunica adventitia (TA), is
composedof collagenousand elasticfibers interspersed
with connectivetissuecellsand blood vessels, ths vasava-
sorum (W). Regionssimilar to the boxed areasare pre-
sentedin Figures2 and 3.
FIGURE 3 Elostic arterg. x.s. Monkeg. Plostic
section. x 540.
This is a higher magnificationof the tunica adventitia
similar to the boxed region of Figure l. The outermost
region of the tunica media (TM) is demarcatedby the
externalelasticlamina (xEL). The tunica adventitia(TA)
is composed of thick bundles of collagen fibers (CF)
interspersedwith elastic fibers. Observe the nuclei of
fibroblasts(F) locatedin the interstitialspacesamong the
collagenfiber bundles.Sincethe vesselwall is very thick,
nutrients diffusing from the lumen cannot serve the
entirevessel;therefore,the adventitiais suppliedby small
vessels known asvasavasorum (\rV). Vasavasorumpro-
vide circulationnot only for rhe tunica adventitiabut also
for the outer portion of the tunica media.Moreover,lym-
phatic vessels(not observedhere) are alsopresentin the
adventitia.
I KEY
CF collagenfiber L lumen
EF elasticfiber N nucleus
F fibroblast SM smoothmusclecell
FM fenestratedmembrane TA tunicaadventitia
I 56 1+ CirculatorvSvstem
FIGURE 2 $iiitElastic arterg. x.s. Monkeg. Plastic
section. x 540.
This is a higher magnificationof a region of the tunica
intima, similar to the boxed area of Figure 1. The en-
dothelial lining of the blood vessel presents nuclei
(arrowhead),which bulge into the lumen (L). The nu-
merous elastic fibers (EF) form an incomplete elastic
lamina. Note that the intersticesof the tunica intima
housemany smooth musclecells(SM), whosenuclei are
corkscrew-shaped (arrows),indicativeof musclecontrac-
tion. Although most of the cellularelementsare smooth
muscle cells, it has been suggestedthat fibroblastsand
macrophagesmay alsobe present;however,it is believed
that the elasticfibers and the amorphous intercellular
substances are synthesizedby the smooth musclecells.
FfGURE 4 ffi Elastic arterg. x.s. Human. Elqstic
stain. Poraffin section. x 132.
The useofa specialstainto demonstratethe presence
of concentricelasticsheets,known as fenestratedmem-
branes (FM), displaysthe highly elastic quality of the
aorta.The number of fenestratedmembranes,as well as
the thicknessof each membrane, increasewith age, so
that the adult will possessalmost twice as many of these
structuresas an infant. Thesemembranesare calledfen-
estrated, since they possessspaces (arrows) through
which nutrients and wastematerialsdiffuse. The inter-
sticesbetweenthe fenestratedmembranesare occupied
by smooth musclecells,whosenuclei (N) are evident,as
well as amorphous intercellularmaterials,collagen,and
fine elastic fibers. The tunica adventitia (TA) is com-
posed mostly of collagenousfiber bundles (CF) and
some elasticfibers (EF). Numerous fibroblasts (F) and
other connectivetissuecellsoccupvthe adventitia.
Tl tunica intima
TM tunicamedia
W vasa vasorum
xEL externalelasticlamina
 I

N
FMat' q::-

EF 'w,
i't

ts *^{

xEL '::r sM- =

VV
F I T ] IR E f l C , [ ] R E. )

TM
-l

l*
o
00
--l

xEL
rar -

CF
TA
,:t._-
F

F
\ cq oo
S)

o dgvn {}
{ltr''
o EF/ Ft
FICL]RF F t ( ; l l R E4
( - r ' i L ,rr t r rr S i s t c r r 157
PLATE8-2 t MuscularArterg, Vein
FfGURE | -e Arterg and vein. x.s. Monkeg. Plastic
section. x 132.
This low magnificationphotomicrographpresentsa
muscular artery (MA) and correspondingvein (V). Ob-
servethat the wall of the artery is much thicker than that
of the vein and containsconsiderablymore musclefibers.
The three concentric tunicae of the artery are evident.
The tunica intima (TI) with its endotheliallayer (En) and
internal elastic lamina (iEL) is readily apparent. The
thick tunica media (TM) is identifiedby the circularlyor
spirallydisplayedsmooth musclecells(SM) that are em-
beddedin an elastictlpe of intercellularmaterial.These
elastic fibers, as well as the external elastic lamina-the
outermost layer of the tunica media-are not apparent
with hematoxylin and eosin stain. The tunica adventitia
(TA), almost as thick as the media, containsno smooth
musclecells.It is composedchiefly of collagen(CF) and
elastic (EF) fibers, as well as fibroblastsand other con-
nectivetissuecells.The wall of the companion vein pre-
sentsthe samethree tunicae:intima (TI), media (TM),
and adventitia(TA); however,all three (but especiallythe
media) are reducedin thickness.
FIGURE 3 - Arterg. x.s. Elqstic stdin. Paroffin
section. x 132.
This photomicrographis a higher magnificationof a
region similar to the boxed area of Figure 2. The en-
dothelium (En), subendothelialconnectivetissue (ar-
row), and the highly contracted internal elastic lamina
(iEL) are readily evident.Thesethree structuresconsti-
tute the tunica intima of the muscularartery.The tunica
media (TM) is very thick and consistsof many layersof
spirallyor circularlydisposedsmooth musclecells (SM),
whosenuclei (N) are readiiy identifiablewith this stain.
Numerouselasticfibers (EF) ramifi through the intercel-
lular spacesbetweensmooth muscle cells.The external
elastic lamina (xEL), which comprises the outermost
layer of the tunica media, is seen to advantagein this
preparation.Finally,note the collagenous(CF) and elas-
tic (EF) fibersof the tunica adventitia(TA), aswell asthe
nuclei (arrowhead)ofthe variousconnectivetissuecells.
I KEY
CF collagenfiber N nucleus
EF elasticfiber SM smoothmusclecell
En endotheliallayer TA tunicaadventitia
iEL internalelasticlamina TI tunicaintima
MA muscularartery
1 58 #: Circulatorv
Svstem
F|GURE 2 * Arterg dnd vein. x.s. Elastic stain.
Paroffin section. x 132.
The elastic stain used in this transversesection of a
muscular artery (MA) and corresponding vein (V)
clearly demonstratesthe differencesbetween arteriesand
veins. The tunica intima (TI) of the artery stains dark,
due to the thick internal elasticlamina, while that of the
vein doesnot stain nearly as intensely.The thick tunica
media (TM) of the artery is composedof numerouslay-
ers of circularly or spirally disposedsmooth muscle cells
(SM) with many elastic fibers ramifring through this tu-
nic. The tunica media (TM) of the vein has only a few
smooth muscle cell layers with little intervening elastic
fibers. The external elastic lamina (xEL) of the artery is
much better developedthan that of the vein. Finally, the
tunica adventitia (TA) constitutesthe bulk of the wall of
the vein and is composedof collagenous(CF) and elastic
(EF) fibers. The tunica adventitia (TA) of the artery is
also thick, but it comprises only about half the thickness
of its wall. It is alsocomposedof collagenousand elastic
fibers.Both vessels possess their own vasavasorum (W)
in their tunicaeadventitia.A region similar to the boxed
areais presentedat a higher magnificationin Figure3.
FIGURE 4 :z Large vein. x.s. Humon. Poraffin
section. x 210.
Largeveins, as the inferior vena cavain this photomi-
crograph, are very different from the medium-sized veins
of Figures I and2. The tunica intima (TI) is composedof
endothelium (EN) and some subendothelial connective
tissue,whereasthe tunica media (TM) is greatly reduced
in thicknessand containsonly occasionalsmooth muscle
cells.The bulk of the wall of the venacavais composedof
the greatly thickened tunica adventitia (TA), consisting
ofthree concentricregions.The innermost layer (1) dis-
plays thick collagenbundles (arrows) arrayed in a spiral
configuration,which permits it to becomeelongatedor
shortened, with respiratory excursion of the diaphragm.
The middle layer (2) presentssmooth muscle(or cardiac
muscle) cells, longitudinally disposed. The outer layer
(3) is characterizedby thick bundles of collagenfibers
(CF) interspersedwithelasticfibers.This region contains
vasa vasorum (W), which supply nourishment to the
wall of the vena cava.
TM tunicamedia
V vein
VV vasa vasorum
xEL externalelasticlamina
 CF
t\ /
M

TA TM

EFr.

F I C , L ] R1E I lLl RF -l

^\En

EF\
t-
-\
t
I

xEL CF
t l C l R E1 )
(.ritiJlltt\ 5\51('lll 159
PLATE8-5 t Arterioles,Venules,Capillaries,LgmphVessels
FIGURE I Arteriole and venule. t.s. Monkeg.
Plastic section. x 210.
This longitudinal sectionof a largearteriole (A) and
companion venule (Ve) from the connectivetissuesep-
tum of a monkey submandibulargland displaysa duit
(D) of the glandbetweenthe two vessels. Observethat the
thicknessof the arteriolewall approximatesthe diameter
of the lumen (L). The endothelialcellnuclei (N) areread-
iiy evidentin both vessels,asarethe smooth musclecells
(SM) of the tunica media. The arteriolealsopresentsan
internal elasticlamina (iEL) betweenthe tunica media
and the endothelialcells.The tunica adventitia (TA) of
the arterioledisplaysnuclei offibroblasts,while thoseof
the venuie merge imperceptibly with the surrounding
connectivetissue.Glandularacini are evidentin this field
asare serousunits (SU) and serousdemilunes(SD).
FfGURE 2 ., Arteriole and venule. x.s. Monkeg.
Plastic section. x 540.
This small arteriole (A) and its companion venule
(Ve) are from the submucosaof the fundic reeion of a
monkey stomach. Observe the obvious differince be-
tweenthe diametersof the lumina (L) of the two vessels,
as well as the thicknessof their walls. Due to the greater
muscularityof the tunica media (TM) of the arteriole,the
nuclei (N) of its endothelialcellsbulee into its round lu-
men. The tunica media (TM) of thivenule is much re-
duced,while the tunica adventitia (TA) is well developed
and is composedof collagenousconnectivetissue (CT)
interspersedwith elasticfibers (not evidentin this hema-
toxylin and eosinsection).

FIGURE 3 Copillorg. l.s. Monkeg. Plastic section.
x 540.
In this photomicrographof the monkey cerebellum,
the molecular Iayer displayslongitudinal sectionsof a
capillary.Note thar the endothelialcell nuclei (N) are oc-
casionallyin the field of view. The qroplasm (Cy) of the
highly attenuatedendothelialcellsis visible as thin, dark
lines,borderingthe lumina (L) of the capillary.Redblood
cells (arrows) are noted to be distorted as thev pass
throughthe narrowlumina of the vessel.
Inset. Capilary. x.s. Monkey. Plastic section. X 540.
The connectivetissuerepresented in this photomicro-
graph displaysbundlesof collagenfibers (CF), nuclei of
connectivetissuecelis(arrow), aswell asa crosssectionof
a capillary (C), whose endothelial cell nucleus (N) is
clearlv evident.
FIGURE 4 ,. Lgmphqtic vessel. Ls. Monkeg. Plastic
section. x 214.
This photomicrographpresentsa villus from monkey
duodenum.Note the simplecolumnarepithelium (E) in-
terspersed with occasionalgoblet cells(GC). The connec-
tive tissuelamina propria displaysnumerousplasmacells
(PC), mast cells (MC), lymphocl'tes (Ly), and smooth
muscle fibers (SM). The longitudinal sectionof the lu-
men (L) lined with endothelium (En) is a lacteal, a
blindly endinglymphaticchannel.Sincelymph vessels do
not transport red blood cells,the lacteaiappearsto be
empty,but in fact it containsllnnph. Subsequent to a fatty
meal, lactealscontain chylomicrons. Observe that the
wall of the lacteal is very flimsy in relation to the diame-
ter of the vessel.

Continuous
capillary

T KEY
A arteriole En endothelium PC plasmacell
capillary /:r\ gobletcell SD serousdemilune
CF collagenfiber iEL internalelasticlamina SM smoothmusclecell
CT collagenousconnective tumen SU serousunit
tissue Ly lymphocyte TA tunicaadventitia
Cy cytoplasm MC mastcell TM tunicamedia
D duct N nucleus Ve venule
E epithelium

| 60 ,- Circulatory
System
 TA; ...
ve<
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FICURE
3 FICUR4
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C i r c u l a t o rSy y s t e m
PLATE8-4 T Heart
FIGURE | * Endocardium. Human. paraffin
section. x 132.
The endocardium, the innermost layer of the heart. is
lined by a simplesquamousepitheliumihat is continuous
with the endothelialofthe variousblood vesselsentering
or exiting the heart. The endocardium is composedol
three layers,the innermost of which consistsoi the en-
dothelium (En) and the subendothelialconnective tissue
(CT), whosecollagenousfibersand connectivetissuecell
nuclei (N) are readily evident. The middle layer of the en-
docardium, although composed of dense collagenous
and elasticfibersand somesmooth musclecells,ii occu-
pied in this photomicrograph by branchesof the con-
ducting systemofthe heart,the Purkinje fibers (pF). The
third,layer of the endocardium borders the thick my-
ocardium (My) and is composedof looserconnectivetis-
sue elements housing blood vessels, occasional
adipocl'tes,and additionalconnectivetissuecells.
F|GURE 3 v Heart volve. I.s. paraffin section.
x 132.
This figure is a montage, displayinga valve leaflet (Le),
aswell asthe endocardium (EC) ofthe heart. The leaflet is
in the lumen (L) of the ventricle, as is evidencedby the
numeroustrappedredblood cells(RBC).The endothelial
(En) lining of the endocardium is continuous with the en-
dothelial lining ofthe leaflet.The three layersofthe endo-
cardium are clearly evident, asare the occasionalsmooth
T KEY
BV bloodvessel En endothelium
CM cardiacmusclecell L tumen
CT connectivetissue Le valve leaflet
EC endocardium m myofibril
162 f Circulatory
System
FfGURE 2 a Purkinje fibers. Iron hematoxglin.
Poroffin section. x 132.
The stain utilized in preparing this section ofthe ven-
tricular myocardium stains red blood cells (RBC) and
cardiac muscle cells (CM) very intensely. Therefore, the
thick bundle ofPurkinje fibers (PF) is shown to advan-
tage,due to its lessdensestaining quality. The connective
tissue (CT) surrounding these fibers is highly vascular-
ized, as evidencedby the red blood cell-filled capillaries.
Purkinje fibers are composed of individual cells, each
with a centrally placed single nucleus (N). These fibers
form numerous gap junctions with each other and with
cardiac muscle cells. The boxed area is presented at a
higher magnificationin the inset.
hsef. Purkinje fibers. Iron hematorylin. Paraffin sec-
tion. x 270.
Individual cells of Purkinje fibers are much larger
than cardiac muscle cells. However, the presenceof pe-
ripherally displacedmyofibrils (m) dispialng e anb t
bands (arrow) clearly demonstratesthat they are modi-
fied cardiac muscle cells. The nucleus (N) is surrounded
by a clear area,housing glycogenand mitochondria.
muscle cells (SM) and bloodvessels (BV). The core of the
leaflet is composed ofdense collagenousand elasticcon-
nective tissue, housing numerous cells whose nuclei are
readily observed.Sincethe core ofthese leafletsis devoid
of blood vessels,the connective tissue cells receive their
nutrients directly from the blood in the lumen of the heart
via simple diftrsion. The connective tissue core of the
leaflet is continuous with the skeleton of the heart that
forms a fibrous ring around the opening of the valves.
Cardiacmuscle
My myocardium
N nucleus
PF Purkinjefiber
RBC red bloodcell
I
I
.PF
{l$i i
I PF llr..0 t

T
j

I
I r*i

I
t'

I {
, r'iI
,1 r'j,,
t t,
I
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e/
til
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I
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FICURE

I
t
t System
Circulatory 163
 PLATEB-5 r Capillarg, Electron Microscopg t
I
t
t
I
r\ol , I
t
*
t
r$
n.
1lr I
,j
I
I
I
t
I
FIGURE I Continuouscapillarg. x.s. Cordioc
muscle. Mouse. Electron microscopg. x 29 33a.
t
This electronnticrographof atcontinuouscapillaryin
crosssectionrviistal<enfr'<lmmouseheart tissue.C)l>servc
that the sectionpasses
the enclothclial
thror-rghthe nucleus(N) of one of
cellsconstitutinsthewall ofthe vessel and
Continuous
capillary
r
that tl-relur.nencontair.rs
red btood cells(RBC) Note that
the endothelirlccllsare higl'rlyatter-ruated and that thcv
forn-rtigl-rtjunctions (".roi*sj rvith eachother. Arr-orv-
headspoint to grir.rocvtotic I'csiclesthat trat.ersethc cn-
t
dothelialcell Tlie lamina densa(LD) and laminalucida
(LL) of the basirllarlina arrcclearh,er.ident
I
| 64 C i r c u l a t o rSy y s t e m I
PLATE8 6 I FreezeEtch,FenestratedCapillarg,ElectronMicroscopg

FfGURE I Fenestrated capillarg. Homster. c c l l s , n ' h i c h i r r c p l c s e u t c c li u a s u r l a c c r . i c r v N o t e t h i r t t h e

Electron Microscopg. Freeze fracture. x 2OS )OO. nllnrcroLrsfenestrae (F), lvhosc cliametcrs ratlgc from
'fhis
electronr-nicrograph cxirml.lc
is rr reprcscntiitivc - 5 7 -l ( r 6 n m , a r c a r r i r t t g c d i n t r a c t s , n ' i t l - r t h e t ' c g i o n s
oftcnestratcclcapillariesfronr tl-rehan.rstcr
adrcnalcortex, Lrctl'ccn trit c ts n onfbtt cstr.1tecl.Occasiott aI caveolae ( Ca )
as revealeclby the frcczcfiacturereplicatechnicluc. Thc a r c a l s o p r e s en t . ( F r o n r l l y a n U , l { y a n J , S n r i t h D , W i n k l e r
parallellincs(arrorvs)rurnnir.rgcliagonallvacrossthe flelcl H : 7 - l - s . i r(u- it'rl 17 : l U 1 1 9 0 , 1 9 7 5 )
rcL)resent the line of runctionbenvccDt\\o cnclothelial

C i r c u l a t o rSy y s t e m

r LAmphoidTissue
Lymphoid tissueforms the basisof the immune sys-
tem of the body and is organizedinto diffuse and
nodular lymphatic tissues(seeGraphic 9-l). The
Iymphoclte, the principal cell of lymphoid tissue,is
responsiblefor the proper functioning of the rm-
mune system.Although morphologicallyidentical,
small lymphocytes may be further identified ac-
cording to function into three categories: null cells,
B lymphocytes, and T lymphocytes. Null cells are
composedof two categoriesof cells,namely stem
cellsand naturalkiller (NK) cells.Stemcellsare un-
differentiated cells that will sive rise to the various
cellularelementsof blood, *'i-re.eas NK cells are cy-
totoxic cellsthat are responsiblefor the destruction
of certaincategories of foreigncells.B lymphocytes,
which probably mature in bone marrowln mam-
mals (bursaof Fabriciusin birds), havethe capabil-
ity of transforming into plasma cells, and T lym-
phocytes, which are potentiated in the thymus.
Plasmacellspossess the abiliry to manufactuiehu-
moral antibodies specific againsta particular anti-
gen.Antibodies,oncereleased, bind to and thus in-
activatethe antigen.Additionally, the attachment
of antibodiesto antigensmay enhancephagocyto-
sis (opsonization)or precipitatecomplementacti-
rally-transformedcells.Severalsubgroupsof T and
B lymphocytesexist, such asmemory ce[s, T helper
cells(Tul and Tg2 cells),T suppressorcells,and T
cytotoxic cells (T killer cells);a discussionofthese
is found later in this chapter,Once a T lymphocyte
becomesactivatedby the presenceof an unlig.n, it
releases cytokines, substances that aitivate
macrophages,attract them to the site of antigenic
invasion,and enhancetheir phagocyticcapabifities.
Frequently, T lymphocytes also assist B lympho-
cytesin the performanceof their functions.
tilffitl
DIFFUSEIYMPHOID TISSUE
Diffuse lymphoid tissue occurs throughout the
body, especiallyunder wet epithelial membranes,
where the loose connectivetissueis infiltrated by
lymphoid cells,namely lymphocytes,plasma cells,
macrophages,and reticular cells. This is particu-
larly evidentin the lamina propria of the digestive
tract and in the subepithelialconnectivetissueof
the respiratory ftact. It may be noted that the lym-
phoid cellsare not arrangedin any particular pat-
tern but are scatteredin ahaphazard manner. Fre-
quently, lpnphoid nodules, transitory structures
that are a denser aggregationof lymphoid tissue
composed mainly of lyrnphocytes,may be ob-
served.Lymphoid nodulespresentthe characteris-
tic appearanceof a lighter germinal center and a
darker, peripherallylocatedcorona. The germinal
centers are sites of lymphoclte production,
whereasthe corona is composedmostly of newly
formed B lymphocytes.
LYMPH NODES
Lymph nodes are ovoid- to kidney-shaped organs
that filter lymph (seeGraphic 9-2). They possessa
convex surface,which receivesafferent lymph ves-
sels,and a hilum, whereblood vesselsenter and ef-
ferent lymph vesselsleave and drain lymph from
the organ. Each lymph node has a denseirregular
collagenousconnectivetissuecapsule.Connective
tissuesepta,derivedfrom the capsule,subdividethe
cortex into incompletecompartments.Attachedto
the septaand the internal aspectofthe capsuleis a
network of reticular tissue and associatedreticular
cells that act as a framework for housing the nu-
merous free cells,mostly lymphocytes,occupying
the organ. The cortex of the lymph node housesthe
capsular and cortical sinuses,as well as li'rnphoid
nodules,composedmainly of B lymphocytesand
Lymphoid
Tissue W 167
reticular cells. Betweenthe cortex and the medulla
is the paracortexpopulatedby T lymphocytes.The
medulla consists of medullary sinusoids and
medullary cords.The medullarysinusoidsare con-
tinuous with the capsular and cortical sinuses,
whereasthe medullary cords are composedmainly
of lymphoid cells.Additional cell componentsof
lymph nodesare macrophages,antigen-presenting
cells,and somegranulocytes.Aside from function-
ing in the maintenance and production of im-
munocompetent cells, lymph nodes also filter
lymph. The filtering processis facilitated by the
reticular cell processes
that span the sinusesof the
node and thui disturb and reiard Iymph flow, pro-
viding more time for the residentmacrophagesto
phagocytoseantigensand other debris.
TONSTTS
Tonsilsare aggregatesof more or lessencapsulated
Iymphoid tissue situated at the entrances to the
oral pharynx and to the nasalpharynx. Participat-
ing in the formation of the tonsillar ring are the
palatine, pharyngeal, and lingual tonsils. These
structuresproduce antibodiesagainstthe numer-
ous antigensand microorganismsthat abound in
their vicinity.
SPTEEN
The spleen is the largest lyrnphoid organ of the
body (seeGraphic 9-2). Its principal functions are
to filter blood, phagocltose senescentred blood
cells and invading microorganisms,supply im-
munocompetentT and B lymphocytes,and manu-
factureantibodies.Unlike lymph nodes,the spleen
is not divided into cortical and medullary regions,
nor is it supplied by afferent lymphatic vessels.
Blood vessels enterand leavethe sDleenat its hilum
and travelwithin the parenchymavia trabeculaede-
rived from its connectivetissuecapsule.The spleen
is subdivided into red and white pulps; the former
consistsof pulp cords (of Billroth) interposedbe-
tween sinusoids,whereasthe latter is composedof
lymphoid tissueassociated with arteries.This lym-
phoid tissueis arrangedin a specificfashion,either
asperiarterial lymphatic sheaths(PALS) composed
of T lymphocltes or as lymphoid nodules consist-
ing of B lyrnphocy.tes.The region between the red
and white pulps is known asthe marginal zone and
is rich in arterial vesselsand avidly phagocytic
macrophages.The red pulp is composed of a
spongynetwork of sinusoidslined by unusualelon-
gatedendothelialcellsdisplayinglargeintercellular
168 ,WtLymphoid
Tissue
spaces,supportedby a thick, discontinuous,hoop-
like basementmembrane.Reticularcellsand retic-
ular fibers associatedwith these sinusoidsextend
into the pulp cordsto contributeto the cell popula-
tion that consistsof macrophages, plasmacells,and
extravasated blood cells.
Understandingsplenicorganizationdependson
knowing the vascular supply of the spleen. The
splenicartery enteringat the hilum is distributedto
the interior ofthe organvia trabeculaeastrabecular
arteries.On leavinga trabecula,the vesselentersthe
parenchymato be surrounded by the periarterial
lymphatic sheathand occasionallymphoid nodules
and is termedthe centralartery.Centralarteriesen-
ter the red pulp by losing their periarterial lym-
phatic sheathand subdivideinto numerousstraight
vesselsknown as penicillar arteries. These small
vessels possess three regions: pulp arterioles,
sheathedarterioles, and terminal arterial capillar-
ies.Whether theseterminal arterialcapillariesdrain
directly into the sinusoids(closedcirculation) or
terminate as open-endedvesselsin the pulp cords
(opencirculation)hasnot beendeterminedconclu-
sively.Sinusoidsare drained by pulp veins,which
lead to trabecular veins and eventually ioin the
splenicvein.
THYMUS
The thymus is a bilobed lymphoid organ locatedin
the mediastinum, overlying the great vesselsof the
heart (seeGraphic 9-2). Its major functions are the
formation, potentiation,and destructionof T lym-
phoqtes. ImmunoincompetentT lymphocltes en-
ter the thyrnuswherethey becomeimmunocompe-
tent and are releasedinto the generalcirculation
with the caveatthat thoseT lymphocytesthat would
recognizeand attackthe selfarenot releasedbut are
destroyedin the cortex.The thin connectivetissue
capsuleof the thymus sendsseptainto the organ,
incompletelysubdividing it into lobules.The thy-
mus, unlike the previous lymphoid structures, is
derived from endodermal primordium that be-
comes invaded by lymphocytes. Additionally, the
thymus possesses no lgnphoid nodules;instead,it
is divided into an outer cortex, composedof ep-
ithelial reticular cells, macrophages,and small T
lymphocytes (thymocytes), and an inner, Iighter
staining medulla consisting of epithelial reticular
cells, large T lymphocytes, and thymic (Hassall's)
corpuscles. Blood vesselsgain entrance to the
medulla by travelingin the connectivetissuesepta,
which they exit at the corticomedullary junction,
where they provide capillary loops to the cortex.
Thesecapillariesare the continuous tfpe and are
surroundedby epithelialreticular cellsthat isolate
I them from the cortical lyrnphocytes,thus establish-
ing a blood-thymus barrier, providing for an anti-
form a specializedbarrier between the cortex and
medulla, preventing medullary material from gain-
gen-freeenvironment for the potentiation of the ing accessto the cortex. The thymus attains its
I immunocompetentT lymphoc)'tes.The blood ves-
selsof the medulla are not unusualand presentno
greatestdevelopment shortly after birth, but subse-
quent to puberty it involutes and becomes infil-
blood-thymus barrier. The thymus is drained by trated by adiposetissue;however, even in the adult
t venulesin the medulla, which also receivesblood
from the cortical capillaries.Epithelial reticular cells
the thymus retains its ability to form T lympho-
cltes.

I
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r Tissue I
Lymphoid 169

Histophgsiologg
I. THEIMMUNERESPONSE
The immune systemrelieson the interactions of its
primary cell components,lymphocytesand antigen-
presentingcells,to effectan immune response.These
responsesare meticulously controlled and directed
but a complete description of the mechanisms of
their actions is beyond the purposes of this Arlas.
Therefore, only the salient features of the mecha-
nisms of the immune processwill be described.
A. Cellsof the lmmuneSystem
The cellsof the immune systemmay be subdivided
into three major categories,clones of T lympho-
cltes and B lymphocytes, NK cells, as well as anti-
gen-presentingcells.A clone is a small population
ofidentical cellseachofwhich is capableofrecoe-
nizing and responding to one specific ior vefu
closely related) epitope (antigenic determinant).
RestingT and B cellsbecomeactivatedif they come
in contactwith the specificepitopeand certain cy-
tokines. Theseactivatedcellsproliferate and differ-
entiate into effector cells.Antigen-presenting cells,
such as macrophages,participate in the immune
process by phagocytosing foreign substances,
breaking them down to epitopes. They present
theseepitopeson their cell surfacein conjunction
with major histocompatibility complex molecules
(MHC molecules)and other membrane-associated
markers.It should be noted that in humans MHC
molecules are also referred to as human leukocyte
antigenmolecules(HLA molecules).
l. T Lgmphocgtes
T lymphocytes (T cells) are immunoincompetent
until they enterthe cortexof the thymus.Here, un-
der the influence of the cortical environment, they
expresstheir T cell receptors and cluster of differ-
entiation markers (CDz, CD3, CD4, CD8, and
CD28) and becomeimmunocompetent.Once im-
munocompetent, the T cellsare either killed if they
are committed againstthe selfor enter the medulla
of the thymus. In the medulla they will lose either
their CD4 or CD8 markers and thus developinto
CD8- or CD4- cells,respectively. Thesecellsenter
into blood vesselsof the medulla to becomemem-
bers of the circulating population of lymphocytes.
T cells encompassseveral categoriesof cells
that are responsiblenot only for the cell-mediated
l7O il Lymphoid
Tissue
II*II
immune response, but also for facilitating the
humorally-mediatedresponseof B cellsto thymic
dependent antigens. In order to be able to per-
form their functions, T cellspossesscharacteristic
integral membraneproteins on their cell surfaces.
One of theseis the T cell receptor (TCR), which
has the capability of recognizing that particular
epitope for which the cell is genetically pro-
grammed; however, T cells can recognize only
those epitopesthat are bound to MHC molecules
presenton the surfaceof antigen presentingcells.
Thus, T cellsare said to be MHC restricted.
a. T Helper Cells are subdivided into two cate-
gories,Tg1 and Ts2 cells and they are both
CD4* cells.The former coordinatethe cell-
mediated,whereasthe latter orchestratethe
humorally-mediatedimmune response.Tsl
cellsproduce and releasethe cytokines inter-
leukin 2, gamma interferon, and others that
modifr the immune response.Ts2 cellspro-
duce and releaseinterleukins 4, 5, and 6 that
induce B cells to proliferate and differentiate
into plasma cells that produce antibodies.
T Cgtotoxic Cetts (T, cells) are CD8+ cells.
I
Upon contacting the proper MHC-epitope
complex displayedby antigen-presentingcells
and having been activated by interleukin 2,
thesecellsundergo mitosis to form numerous
cytotoxic T lymphocytes (cTLs). Thesenewly
formed cells kill foreign and virally-trans-
formed self cells by secreting perforins and
fragmentins (seeGraphic 9-4).
T Suppressor Cel/s (T, cells) are CD8+ cells
that function in repressing the activities of
other cellsof the immune system.In this fash-
ion, they modulate and stop an immune re-
sponse.It is believedthat they may prevent
the initiation of an autoimmune response.It
should be understood that someinvestigators
questionthe existenceofT. cells.
T Memorg Cells are immunocompetent cells
that are the progeny of activatedT cellsthat
undergo mitotic activity during an antigenic
challenge.Thesecells are long lived, circulat-
ins cells that are added to and increasethe
nimber of cellsof the original clone.It is this
increasein the sizeofthe clonethat is respon-
sible for the anamnesticresponse(a more
rapid and more intensesecondaryresponse)
against another encounter with the same
antlgen.
2. B Lgmphocgtes
B lymphocyte (B cells)areformed and becomeim-
munocompetent in the bone marrow. They enter
the general circulation, establish clones whose
membersseedvariouslymphoid organs,and arere-
sponsiblefor the humoral immune response.In-
steadofT cellreceptors,B cellshaveantibodies(IgD
or the monomeric form of IgM) on their cell mem-
branes.Thesesurfaceimmunoglobulins (SIGs)of a
particular B cell target the sameepitope.Unlike T
cells,B cellshave the capability ofacting asantigen-
presentingcellsand presenttheir MHC Il-epitope
complexto Tsl cells.
Once activated,B cells manufacture and release
IL-12, a cytokine that promotes the formation of
Tsl cells.B cellsproliferateduring a humoral im-
mune responseto form plasmacellsand B memory
cells(seeGraphic9-3).
a. Plosma Cells arc differentiated cells that do
not possess surfaceimmunoglobulinsbut are
"antibody factories" that synthesizeand re-
leasean enormousnumber of identicalcopies
of the sameantibody that is specificasainsta
particular epitope (ilthough it may cioss re-
act with similar epitopes).
b. B Memorg Cellsaresimilar to T memory cells,
in that they are long-lived, circulating cells
that are addedto and-increase the num"berof
cellsof the original clone.Similarly,it is this
increasein the sizeofthe clonethat is respon-
sible for the anamnestic response against a
subsequentencounterwith the sameantigen.
3. Natural Killer Cells
Natural killer cells (NK cells) are members of the
null cell division of lymphocytes. NK cells do not
have the cell surfacedeterminants typical of T or B
cells and they are immunocompetent as soon as
they are formed in the bone marrow. Thesecells
kill virally altered cells and tumor cells in a non-
specificmanner and they are not MHC restricted.
NK cells also recognize and become activated by
the Fc portions of thoseantibodiesthat are bound
to cell surface epitopes. Once activated, NK cells
releaseperforins and fragmentinsto kill thesedec-
orated cellsby a procedure known as antibody-de-
pendent cell-mediated cytotoxicity (ADCC). per-
forins assembleas pores within the plasmalemma
of target cells,whereasfragmentins drive the target
cell into apoptosis.
4. Antigen-Presenting CelIs
Antigen-presenting cells (APCs), macrophages,
and B lymphocytespossess classII major histocom-
patibility complex molecules(MHC II molecules),
whereasall other nucleatedcells possessMHC I
molecules.
An APC phagocl"tosesand degradesthe antigen
into epitopes, small highly antigenic peptides 7 to
11 amino acidslong. Eachepitopeis attachedto an
MHC II molecule,and this complexis placedon the
externalaspectof its cell membrane.The MHC II-
epitope complex is recognizedby the T cell receptor
(TCR) in conjunctionwith the CD4 moleculeof the
Tsl or Ts2 cells,a processknown as MHC II re-
striction (seeGraphic 9-5).
Antigen-presentingcellsand, specifically,macro-
phagesproduce and releasea variety ofcytokines that
modulate the immune response.Theseinclude in-
terleukin l, which stimulatesT helper cellsand self-
activated macrophagesas well as prostaglandin E2
that attenuatessome immune responses.Cytokines,
such as interferon-"y, releasedby other lymphoid
cells,aswell asby macrophages,enhancethe phago-
cytic and cyto\tic avidity of macrophages.
II. LYMPHNODES
The convex aspectoflymph nodes receivesafferent
lymph vesselsthat deliver their contents into the
subcapsularsinuses.Paratrabecular(cortical) si-
nusesdrain subcapsularsinusesand convey their
Iymph to the sinusoids of the medulla, which are
drained by efferent lymph vesselsat the hilum. The
cortex is subdivided into severalincomplete com-
partments, with each housing a lymphatic nodule
rich in B cellsaswell asAPCs and macrophages.The
region of the lymph node between the cortex and
medulla, the paracortex, houses mostly T cells,
APCs, and macrophages.Cells that arisein the cor-
tex or paracortex migrate into the medulla, where
they form medullary cords composed of T cells, B
cells,and plasmacells.T cellsand B cellsenter the
sinusoids and leave the lymph node via efferent
lymph vessels.Lymphocytesalso enter lymph nodes
via arterioles that penetrate the lymph node at the
hilum, travel to the paracortex within connective
tissuetrabeculae,and form high endothelial vessels
(postcapillaryvenules).
I I I .S P L E E N
Branchesof the splenicartery,the trabeculararter-
ies, enter the white pulp by leaving their trabeculae
and, as they become surrounded by sheathsof T
cells,the periarterial lymphatic sheath (PALS), are
known ascentralarteries.Along the path ofthe cen-
tral arteriesare occasionallymphatic nodules com-
posedmostly of B cellsbut still surroundedby the
PALS. As central arteries lose their lymphatic
sheath, they branch repeatedly, forming straight
vessels,penicillar arteries,that possessthree re-
gions:pulp arterioles,macrophage-sheathed arteri-
LymphoT
i di s s u et 171
oles,and terminal arterialcapillaries.The terminal
arterialcapillarieseither terminatein the splenicsi-
nusoids (closed circulation) or freely in the red
pulp (open circulation). The red pulp is composed
of the sinusoids,the reticularfiber network, and the
cellsof the spleniccords.A region of smallersinu-
soidsforms the interfacebetweenthe white and red
pulps, and this interfaceis known as the marginal
zone. Capillariesarising from the central arteries
deliver their blood to sinusoids of the marginal
zone. APCs of the marginal zone monitor this
blood for the presenceofantigensand foreign sub-
stances.
I V.TH YM U S
The thymic cortex is completelyisolatedfrom all
vascularand connectivetissueelementsby reticu-
lar epithelial cells. Additionally, within the cortex,
thesecellsform a three-dimensionalmeshwork in
whose intersticesclustersof T cells become ma-
ture. Although there are six different types of ep-
C l i n i c a lC o n s i d e r a t i o n s= I I
Hodgkin's Disease
H o d g k i n 'ds i s e a s ei s a n e o p l a s t itcr a n s f o r m a t i o n
o f l y m p h o c y t etsh a t i s p r e v a l e nm t o s t l yi n
y o u n gm a l e s i t s c l i n i c asl i g n sa r e a s y m p t o m a t i c
i n i t i a l l yb e c a u s e
of theswellino gf the liver,
s p l e e na, n d l y m p hn o d e sa n d a r en o t a c c o m p a -
n i e db y p a i n O t h e rm a n i f e s t a t i o ni nsc l u d et h e
l o s so f w e i g h t e, l e v a t e dt e m p e r a t u r ed,i m i n -
i s h e da p p e t i t ea, n d g e n e r a l i z ewde a k n e s s
H i s t o p a t h o l o gcj ch a r a c t e r i s t jicnsc l u d et h e p r e s -
cnre nf Rped-Qtprnhpro rollc e:cilrr rprnoniz-
v v J I l J I v ! v b I ' ' L
a b l ec e l l sd i s t i n g u i s h b
e yd t h e i rl a r g es i z ea n d
172 ffi Lymphoid
Tissue
ithelial reticular cells(threein the cortex and three
in the medulla), they all presentthe same appear-
ance as large, pale cells with large, ovoid nuclei.
These cells are derived from the third pharyngeal
pouch and migrate into the developing thyrnus.
They manufacture the hormones thymosin, serum
thymic factor, and thymopoietin, all of which fa-
cilitatethe transformationof immature T cellsinto
immunocompetent T cells. During the transfor-
mation, which occurs in the thr.rnic cortex, the im-
mature T cells (thymocytes) undergo gene rear-
rangement, in that they express on their cell
membrane T cell receptors(TCRs) and cluster of
differentiation (CD) markers (especially CD2,
CD3, CD4, and CD8).
Most of the T cellsdie as they migrate from the
cortex to the medulla; their remnants are phagocy-
tosed by macrophages.It is believedthat the cells
that were killed were genetically programmed to
recognizeself-proteinsas antigens.In the thymic
medulla, T cells Iose either their CD4 or CD8
markers and developinto CD8+ and CD4+ cells,
respectively.
the presenco ef two largep
, a l e ,o v a ln u c l e i n
e a c hc e l l
Wishott- A Id ri ch Sg nd ro m e
W i s k o t t - A l d r i cshy n d r o m ei s a n i m m u n o d e f i -
c i e n c yd i s o r d e ro c c u r r i n go n l y i n b o y sa n d i s
c h a r a c t e r i z ebdy e x c e m a l. o w e r e dp l a t e l e t
c o u n t ,a n d l y m p h o c y t o p e n (i ao f b o t h B a n d
T c e l l p o p u l a t i o n sT) h e i m m u n o s u p p r e s s e d
s t a t eo f t h e s ec h i l d r e nl e a d st o r e c u r r i n g
b a c t e r i ailn f e c t i o ntsh a t r e s u l ti n s e v e r e
b a c t e r i ailn f e c t i o n sh,e m o r r h a g ea,n d d e a t ha t
a n e a r l ya g e l \ 4 o s ct h i l d r e nw h o s u r v i v et h e
f i r s td e c a d eo f l i f ea r e s t r i c k e nw i t h l e u k e m i a
or lymphoma
 ITffiIT

I Summargof HistologicatOrganization
I Lymphoid tissue consists of diffuse and dense II. TONSILS
lymphoid tissue. The principal cell of lymphoid
A. PalatineTonsils
I tissue is the lymphocyte, of which there are two
categories:B lymphocytes and T lymphocytes. l. Epithelium
Additionally, macrophages,reticular cells,plasma Covered by stratified squamous nonkeratinized

t cells,dendritic cells, and antigen-presentingcells

perform important functions in lymphatic tissue.
epithelium that extends into the tonsillar crfpts.
Lymphocytes may migrate through the epithelium.
2. Lgmphatic Nodules

I I. LYMPHNODE
A. Capsule
The capsule,usuallysurroundedby adiposetissue,
I is composedof denseirregular collagenousconnec-
tive tissue containing some elastic fibers and
smooth muscle. Afferent lymphatic vesselsenter
I the convex aspect;efferent lymphatics and blood
vesselspiercethe hilum.
Surround crypts and frequently display germinal
centers.
3. Capsule
Denseirregular collagenousconnectivetissuecap-
sule separatesthe tonsil from the underlying pha-
ryngeal wall musculature. Septa, derived from the
capsule,extendinto the tonsil.
4. Glands
Not present.

I B. Cortex
Lymphatic nodules, composed of a dark corona B. PharyngealTonsils
(mostly B lymphocltes) and lighter staining germi-
t nal centers, housing activated B lymphoblasts,
macrophages, and dendritic reticular cells are
l. Epithelium
For the most part, pseudostratified ciliated colum-
nar epithelium (infiltrated by lpnphocltes) covers
found in the cortex. Connective tissue trabeculae the free surface,as well as the folds that resemble
I subdivide the cortex into incomplete compart-
ments. Subcapsular and cortical sinuses display
cr'?ts.
2. Lgmphatic Nodules
lymphocytes, reticular cells,and macrophages.
Most lymphatic nodules display germinal centers.
I C. Paracortex 3. Capsule
The thin capsule,situateddeepto the tonsil, provides
The paracortex is the region betweenthe cortex and
septafor the tonsil.
I medulla, composed of T lymphocytes. Postcapil-
lary venules, with their characteristiccuboidal en- 4. Glands
dothelium, arepresent. Ducts of the seromucousglands,beneaththe cap-

t D. Medulla
sule, pierce the tonsil to open onto the epithelially
coveredsurface.
The medulla displaysconnective tissuetrabeculae,

I medullary cords (composed of macrophages,

plasmacells,and lymphocytes),and medullary si-
C. LingualTonsils
l. Epithelium
nusoids lined by discontinuous endothelial cells.
Stratified squamous nonkeratinized epithelium
Sinusoids contain lymphocytes, plasma cells, and
I macrophages.The region of the hilum is evident as
a result of the thickenedcapsuleand lack of lvrn-
covers the tonsil and extends into the shallow
crfpts.
phatic nodules. 2. Lgmphatic Nodules
I E. ReticularFibers
Most lymphatic nodules presentgerminal centers.
3. Capsule
With the use of specialstainsan extensivenetwork The capsuleis thin, not clearly defined.
I of reticular fibers may be demonstratedto consti-
tute the framework of lymph nodes.
4. Glands
Seromucousglands open into the baseofcrypts.

I Tissue t
Lymphoid 173
I I I .S P L E E N
A. Capsule
The capsule,composedof denseirregular collage-
nous connectivetissue thickestat the hilum, pos-
sesses some elasticfibers and smooth musclecells.
It is coveredby mesotheliumbut is not surrounded
by adiposetissue.Trabeculae,bearingblood vessels,
extend from the capsuleinto the substanceof the
spreen.
B. WhitePulp
White pulp is composed of periarterial lymphatic
sheathsand lymphatic noduleswith germinal cen-
ters.Both periarteriallymphatic sheaths(housingT
lymphocytes) and lymphatic nodules (housing B
lymphocytes) surround the acentrically located
central artery, a distinguishingcharacteristicof the
spleen.
C. Marginal Zone
A looser accumulation of lymphocytes, macro-
phages,and plasmacellsarelocatedbetweenwhite
and red pulps. It is suppliedby capillary loops de-
rived from the central artery.
D. RedPulp
Red pulp is composed of pulp cords and sinu-
soids.Pulp cords are composedof delicatereticu-
lar fibers, stellate-shapedreticular cells, plasma
cells, macrophages,and cells of the circulating
blood. Sinusoidsare lined by elongateddiscontin-
uous endothelial cells surrounded by thickened
hoop-like basement membrane in association
with reticular fibers. The various regionsof peni-
cilli are evidentin the red pulp. Theseare pulp ar-
terioles,sheathedarterioles,and terminal arterial
capillaries. Convincing evidence to determine
whether circulation in the red pulp is open or
closedis not available.
l7 4 frH Lymphoid
Tissue
E. Reticular Fibers
With the use of specialstains an extensivenetwork
of reticular fibers may be demonstratedto consti-
tute the framework of the spleen.
IV.THYMUS
A. Capsule
The thin capsuleis composedof denseirregular
collagenous connective tissue (with some elastic
fibers) that extendsinterlobular trabeculaethat in-
completelysubdividethe thymus into lobules.
B. Cortex
The cortex has no lyrnphatic nodules or plasma
cells. It is composed of lightly staining epithelial
reticular cells, macrophages,and densely packed,
darkly staining, small T lymphoqtes (thymoqtes)
responsiblefor the dark appearanceof the cortex.
Epithelial reticular cells also surround capillaries,
the only blood vesselspresentin the cortex.
C. Medulla
The medulla, which stains much lighter than the
cortex,is continuousfrom lobule to lobule. It con-
tains plasma cells,lymphocytes, macrophages,and
epithelial reticular cells. Moreover, thymic (Has-
sall's)corpuscles,concentricallyarrangedepithelial
reticular cells, are characteristic features of the
thymic medulla.
D. lnvolution
The thymus begins to involute subsequentto pu-
berty. The cortexbecomeslessdensebecauseits pop-
ulation of lymphocltes and epithelial reticular cells
is, to some extent, replacedby fat. In the medulla,
thymic corpusclesincreasein number and size.
E. ReticularFibersand Sinusoids
neither reticular fibers nor
The thymus possesses
sinusoids.
CRAPHIC
9-1 | LgmphoidTissues

Lymphoidtissueconsistsof several
encapsulatedorgans,lymphnodes,
tonsils,thymus, andspleen,as wellas
u$i 1r
diffuse lymphoidtissue,composedof
looseconglomerates of the lymphoid
cells:B lymphocytes, T lymphocytes,
/mus plasmacells,macrophages, and
antigen-preSenting cells.Frequently,
Cervicalnodes theselymphoidcellsare collectedas
lymphaticnodulesthatappearas they
Tracheobronchial sntaon are needed.althoughtheyare always
nooes presentin the gut (GALT,gut-associate
lymphoidtissue,and Peyer'spatches),
Axillarynodes in the bronchialtubes(BALT,
bronchiolar-associatedlymphoid
Thoracicduct tissue),and certainmucosae(MAIT,
mucosa-associated lymphoidtissue)
Aorticnodes

Peyer'spatches
(ileum)

l l i a c- T lymphocytes originate
in
nodes the bonemarrowand then
migrateto the thymusto
Inguinal becomeimmunologically /)t
nodes competentT cells

Thymus

B lymphocytes
are believedto
Bone remainin the bone
marrow marrowto become
immunologically
a6mnalanl

Theseimmunocompetent T
and B cellsthenseed
lymphoid tissues,especially
thespleen,lymphnodes,and
lymphatic nodules,andare
capableof becoming
activated(mature)and
responding to an antigenic
chalfenge
Matureand immuno-
competentcell$
circulateamongthe
variouslymphoid
tissues,usingblood
and lymphvessels.

LymphoT
i di s s u e I 75
CRAPHIC9-2 | LgmphNode, Thgmus,and Spleen I
Efferent
I
lymphaticvessel

I
Medullarycord I
I Medulla
I
Medullarysinus ,f

Trabecula t
Afferentlymphaticvessel
Capsule t
Adiposetissue
B cellformation,
well ias in the
as well
clearing of lymph.
t
I
I
I
Thethymusis responsible forthe
maturationof T cells.T helpercells
playa pivotalrolein the
t
developm€nt and maintenance of
the immuneresponse. They
interactwith antigen-presenting
cellsand releasecytokines,
I
resulting in the generation ol
plasmac€llstor the humoralandT
killer(cytotoxic)cellstor the
celFmediated resoonse.
I
Splenic
vern
I
I
Splenic
anery

The spleen cleansesthe

r
blood,eliminatesdefunct
red bloodcells,formsT
cellsandB cells,andin
I
someanimalsbutnot
humans,storesred blood
cells. I
176 I LymphoidTissue I
 CRAPHfC9'5 r B Memorgand PlasmaCellFormation

Antibodies
I
Antigen-dependent crosstinkingof the
surfaceantibodiesactivatesthe B cell Classll MHC-
whichplacesthe epitope-MHcll epitopecomplex
complexon the externalaspectof its
olasmalemma.

The TCR and CD4 moleculesof the TH2

cell recognizethe B cell'sMHC ll-epitope
complex.Additionally,bindingof the B
cell'sCD40moleculeto the Tr2 cell's cD 40
CD40receptorinducesthe B cellto recepror
prolilerateand the Tp2 cell to releaseof
lL4, lls, and lL6.

CytokineslL4,
lL4, lL5,and ILOinducethe activation
of B lL5,and lLo
cellsand theirditferentiation
intoB
memoryand plasmacells.

Plasmacell
B memorycell

Lymphoid
Tissue I 177
CRAPHIC9-4 I CgtotoxicT CellActivation and Killing of Virallg TronsformedCells

tL2

T cellreceptor
The T cell receptor(TCR)and CD4 CD4molecule
moleculeof the T"1 cell bindsto the 87 ----------
epitopeand the MHC ll of the antigen- molecule Classll MHO-epitope
complex
presentingcell (APC),respectively.
The bindinginducesthe APC to
exDress87 moleculeson its
plasmalemma,which then bindsto
the CD28 moleculeof the TH1cell,
inducingthat cell to releaselL2.
ClassIMHC-
epitopecomplex CytotoxicT
CD8 molecule
lymphocyte
The same APC exoressesthe MHC l-
epitopecomplex,which is recognized
by the CD8 moleculeand the TCR of
the cytotoxicT lymphocyte(CTL).
Additionally, the CD28 moleculeof the
CTL bindswith the 87 moleculeon the
APC plasmalemma. These interactions
inducethe expressionof lL2 receptors
on the CTL plasmamembrane.Binding
of lL2 (releasedby the Tg1 cell)to the
lL2 receptorsof the CTL inducesthat
cell to proliferate.

The plasmalemmaof virallytransformedcells

expressesMHC l-epitopecomplex,which is Fragmenting
recognizedby the CD8 moleculeand TCR of
the newly formed cytotoxicT lymphocytes.The
bindingof the CTL inducesthese cells to
secreteperforinsand fragmentins. The former
assembleto form oores in the plasma
membraneof the transformedcell,and
framentindrivesthe transformedcell into
apoptosis.
Virus-
transformed
cell
Perforins

178 I Lymphoid
Tissue
 9-5 .
GRAPHfC MacrophageActivationbg Tul Cells

,"",",,"
{

I Bacteria-infectedmacrophagesbear
\a
MHCll-epitopecomplexes on their Bacteria
plasmalemma that,if recognizedby proliferating

I theCD4molecule andTCRof Tp1

cells,activatestheseT cells,causing
Lysosomes
in phagosomes

themto releasell2 andto expressll2 comPlex

Classll MHG-epitope
receptors on theirplasmamembrane.
I Bindingof lL2to the lL2 receptors
inducesproliferation of theT111cells.
CD4molecule
cell receptor

t
t
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TheTCRandCD4molecules of the
t newlyformedTHI cellsrecognize
bindto the MHCll-epitopecomplexes
and

macrophages.
of bacteria-infected The

I bindingcausesactivationot theseTHl
cellsso thattheyrelease.pinterferon,
cytokinethatencourages the
a

macrophages to destroytheir
I endocytosedbacteria.

I
Macrophage
I
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t LymphoidTissue I 179
 PLATE9-1 r Lgmphaticlnfiltration,LgmphaticNodute
FIGURE I Lgmphatic infiltrotion. Monkeg. Ptastic
section. x 540.
The connectivetissue (CT) deep to wet epithelia is
usually infiltrated by loosely aggregaredlymphocytes
(Ly) and plasmacells(PC), asis exemplifiedby this pho-
tomicrograph of monkey duodenum. Observethat the
simple columnar epithelium (E) contains not only the
nuclei (N) of epithelialcells,but alsodark densenucleiof
lymphocltes (arrows),some of which are in the process
of migrating from the lamina propria (connectivetissue)
into the lumen of the duodenum. Note alsothe presence
of a lacteal(La), a blindly ending lymphaticchannelcon-
taining lymph. Thesevesselsmay be recognizedby the
absenceofred blood cells.
FIGURE 3 Lgmphatic nodule. Monkeg. Plastic
section. x 210.
This is a higher magnificationof a lymphatic nodule
from Peyer'spatchesin the monkey ileum. Note that the
lighter staining germinal center (Gc) is surrounded by
the corona (Co) ofdarker stainingcellspossessing only a
Iimited amount of cltoplasm around a dense nucleus.
Thesecellsare small lymphocy'tes(Ly). Germinal centers
form in responseto an antigenicchallengeand are com-
posed of lymphoblastsand plasmabiasts,whose nuclei
stain much lighter than thoseof small lymphocltes.The
boxed areais presentedat a higher magnificationin the
following figure.
I KEY
Co corona UU gobletcell
r\T connectivetissue lumen
E epithelium lacteal
FAE follicle-associated LB lymphoblast
epithelium Ly small lymphocyte
Gc germinalcenter
180 ;:,, Lymphoid
Tissue
FfGURE 2 .= Lgmphatic nodule. Monkeg. Plastic
section. x 132.
The gut-associated lymphaticnodule in this photomi-
crographis part of a clusterof nodulesknown asPeyer's
patches(PP) and is takenfrom the monkeyileum. The lu-
men (L) of the smali intestineis lined by a simplecolum-
nar epithelium (E) with numerous goblet cells (GC).
However, note that the epithelium is modified over the
lymphoid tissue into a follicle-associatedepithelium
(FAE) whosecellsare shofter,infiltratedby lymphocltes,
and display no goblet cells.Observethat this particular
lymphaticnodulepresentsno germinalcenterbut is com-
posedof severalcell t1pes,asrecognizedby nuclei ofvar-
ious sizesand densities.Thesewill be describedin Figures
3 and 4. Although this lymphatic nodule is unencapsu-
lated, the connectivetissue (CT) between the smooth
muscle(SM) and the lymphaticnoduleis freeof infiltrate.
FIGURE 4 = Lgmphotic nodule. Monkeg. Plastic
section. x 540,
This is a higher magnificationof the boxed areaof the
previous figure. Observe the small lymphoqtes (Ly) at
the peripheryof the germinal center (Gc). The activity of
this centeris evidencedby the presenceofmitotic figures
(arrows), as well as the lymphoblasts (LB) and plas-
mablasts(PB). The germinalcenteris the site of produc- I
tion of small lymphocytesthat then migrate to the pe-
riphery of the lyrnphaticnodule to form the corona.
N nucleus
PB plasmablast
PC plasmacell
PP Peyer'spatch
SM smoothmuscle
 SM
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FICURE
Lymphoid
Tissue
PLATE9-2 r LgmphNode
FIGURE I Lgmph node. Paraffin section. x 14.
Lymph nodesarekidney-shapedstructurespossessing
a convexand a concave(hilus) surface.They are invested
by a connectivetissuecapsule(Ca) that sendstrabeculae
(T) into the substanceof the node,subdividingit into in-
complete compartments.The compartmentalizationis
particularlyevident in the cortex (C), the peripheralas-
pectofthe lymph node.The lighter stainingcentralregron
is the medulla (M), while the zone betweenthe medulla
and cortexis the paracortex(PC). Observethat the cortex
displaysnumerous lymphatic nodules (LN), many with
germinal centers(Gc). This is the region of BJyrnpho-
cytes,while the paracortexis particularlyrich in T-lym-
phoc)'tes.Note that the medullais composedof sinusoids
(S),trabeculae(T) ofconnectivetissueconductingblood
vessels,and medullary cords (MC). The medullarycords
are composedof lymphocytes,macrophages, and plasma
cells.Lymph entersthe lymph node, and as it percolates
through sinusesand sinusoids,foreign substances are re-
moved from it by phagocltic activity of macrophages.
FIGURE 2 = Lgmph node. Monkeg. Plastic section.
x 210.
Afferent lymphatic vessels(AV) enter the lymph node
at its convex surface. These vesselsbear valves (V) that
regulate the direction of flow. Lymph enters the subcap-
sular sinus (SS),which containsnumerousmacrophages
(Ma), lymphocytes(Ly), and antigen-transportingcells.
These sinusesare lined by endothelial cells (EC), which
alsocover the fine collagenfibers that frequently span the
sinus to createa turbulence in lymph flow. Lymph from
the subcapsular sinus enters the cortical sinus, then
moves into the rnedullary sinusoids. It is here that lym-
phocltes also migrate into the sinusoids, leaving the
lymph node via the efferent lymph vesselseventually to
enter the eeneralcirculation.

FIGURE3 Lgmph node. Monkeg. Plastic section.
x 132.
The cortex of the lyrnph node is composedof numer-
ous lymphatic nodules,one of which is presentedin this
photomicrograph.Observethat the lymph nodeis usually
surroundedby adiposetissue(AT). The thin connective
tissue capsule (Ca) sendstrabeculae(T) into the sub-
stance of the lymph node. Observe that the lyrnphatic
nodule possesses a dark stainingcorona (Co), composed
mainly of small lymphocytes (Ly) whoseheterochromatic
nuciei are responsiblefor their staining characteristics.
The germinal center (Gc) displays numerous cells with
lightly staining nuclei, belonging to dendritic reticular
cells,plasmablasts, and lymphoblasts.
FIGURE 4 E; Lgmph node. Human. Silver stain.
Paraffin section. x 132.
The hilus of the human lymph node displaysthe col-
lagenousconnectivetissuecapsule(Ca),which sendsnu-
merous trabeculae (T) into the substanceof the lyrnph
node. Observe that the region of the hi-lus is devoid of
lymphatic nodules, but is particularly rich in medullary
cords (MC). Note that the basic framework of these
medullary cords, as well as of the lymph node, is com-
posed of thin reticular fibers (arrows), which are con-
nectedto the collagenfiber bundlesof the trabeculaeand
capsule.

Lymphnode

I KEY

AT adiposetissue Gc germinalcenter PC paraconex

AV atferentlymphaticvessel LN lymphaticnodule S sinusoid
C cortex Ly small lymphocyte SS subcapsularsinus
Ca capsule M medulla T trabeculae
Co corona Ma macrophage valve
EC endothelialcell MC medullarycord

182 ,fiil LymphoidTissue

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Tissuc, 183
PLATE9-5 | LgmphNode, Tonsils
FIGURE I Lgmph node. Paraffin section. x 132.
The medullaof the lymph node consistsof numerous
endotheliallylined sinusoids (S), which receivelymph
from the cortical sinuses.Surroundine the sinusoidsare
manymedullary cords (MC), composJdof macrophages,
small lymphocltes, and plasma cells,whose nuclei (ar-
rows) stain intensely.Both T- and B-lymphocltes are
found in medullarycords,sincethey are in the processof
migrating from the paracortexand cortex, respectively.
Someof theselymphocltes will leavethe lymph node us-
ing the sinusoidsand efferent lymphatic vesselsat the
hilus. The medulla alsodisplaysconnectivetissuetrabec-
ulae (T) housing blood vissels (BV), which enter the
lymph node at the hilus.
FIGURE 2 Lgmph node. Monkeg. Plastic section.
x 540.
This photomicrographis a high magnificationof a si-
nusoid (S) and surrounding rnedullary cords (MC) of a
lymph node medulla. Note that the medullary cords are
composedof macrophages, plasmacells (PC), and small
lymphocytes(Ly). The sinusoidsare lined by endothelial
cells (EC), which do not form a continuous lining. The
lumen contains lymph, small lymphocytes (Ly), and
macrophages(Ma). Thesecellsare activelyphagocytos-
ing particulatematter asis evidencedby their vacuolated
aPPearance.

FIGURE 3 Palatine tonsil. Human. Poroffin
section. x 14.
The palatinetonsil is an aggregateof lymphatic nod-
ules (LN), many of which possess germinal centers(Gc).
The palatine tonsil is coveredby a stratified squamous
nonkeratinizedepithelium (E) that lines the deep pri-
mary cr'?ts (PCr) that invaginatedeeply into the sub-
stanceof the tonsil. Frequentlysecondarycrypts (SCr)
areevident,alsolined by the sametl?e of epithelium.The
deep surfaceofthe palatinetonsil is coveredby a thick-
ened connective tissue capsule (Ca). The crypts fre-
quently contain debris (arrow) that consistsof decom-
posingfood particles,aswell aslyrnphocytesthat migrate
from the lymphatic nodules through the epithelium to
enter the cnDts.
FIGURE 4 ,, Phargngeal tonsil. Humqn. Paraffin
section. x 132.
The pharyngealtonsil, located in the nasopharynx, is
an aggregateof lymphatic nodules,often dispiayingger-
minal centers(Gc). The epitheliallining (E) is pseudos-
tratified ciliated columnar with occasionalpatches of
stratifiedsquamousnonkeratinizedepithelium (asterisk).
The lymphatic nodulesarelocatedin a loose,collagenous
connective tissue (CT) that is infiltrated by small lym-
phocytes (Ly). Note that lymphocltes migrate through
the epithelium(arrows)to gainaccess to the nasopharynx.

Lymphnode

T KEY

BV bloodvessel Gc germinalcenter PC plasmacell

Ca capsule LN lymphaticnodule PCr primarycrypt
CT connectivetissue Ly lymphocyte S sinusoid
E epithelium Ma macrophage T trabeculae
EC endothelial
cell MC medullarycord SCr secondarycrypt

184 ;r Lymphoid
Tissue
I
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I LymphoidTissue 185
PLATE9-4 | LgmphNode, ElectronMicroscopg
F|GURE I a Lgmph node. Mouse. Electron
microscopg. x 8608.
This electron micrograph of a mouse popliteal lymph
node presentsthe capsule(Ca) and the subcapsularsinus.
The sinus is occupiedby three lymphocytes, one ofwhich
is labeled (L), as well as the process (P) of an antigen-
transporting (antigen-presenting) cell, whose cell body
(arrowheads) and nucleus are in the cortex, deep to the
Lymphnode
Lymphoid
Tissue
sinus.The processentersthe lumen ofthe subcapsularsi-
nus via a pore (arrows) in its floor (FL). It is believedthat
antigen-transporting cells are nonphagocpic and that
they trap antigens at the site of antigenic invasion and
transport them to lymphatic nodules of lymph nodes
where they mature to become dendritic reticular cells.
(From SzakalA, Homes K, Tew l: I Immunol 131:1714-
r7r7,1983.)
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I LymphoT
i di s s u e 187
 PLATE9-5 I Thgmus
FIGURE I Thgmus. Human infont. paraffin F|GURE 2 -= Thgmus. Monkeg. Plastic section. x
section. x 14. 132.
The lobule of the thymus presentedin this photomi-
crograph appearsto be surrounded completelyby con-
nectivetissuesepta(Se);however,in a three-dimensional
reconstruction,it would be seenthat this lobule is con-
tinuous with surroundinglobules (Lo). Observethe nu-
merous blood vessels(BV) in the septa,as well as the
darker staining cortex (C) and the lighter staining
medulla (M). The light patchesof rhe cortex probably
that of other lobules.The connectivetissuecapsuleand present epithelial reticular cells and macrophages(ar-
septaconvey blood vesselsinto the medulla ol the thy- rows), while the darker staining structuresare nuclei of
mus. Shortlyafterpuberty the thyrnusbeginsto involute, the T-lymphocyteseries.The medulla containsthe char-
and the connectivetissueseptabecome infiltrated with acteristicthymic corpuscles(TC), aswell asblood vessels,
adipocl'tes. macrophages, and epitheliaireticularcells.

FIGURE 3 Thgmus.Monkeg. plastic section. x
2 10 .
The centerofthis photomicrographis occupiedby the
medulla (M) of the thymus, presentinga large thymic
(Hassall's)corpuscle(TC), composedof concentrically
arrangedepithelialreticular cells(ERC).The function, if
any, of this structureis not known. The thymic medulla
housesnumerousblood vessels(BV), macrophages, lym-
phocytes(Ly), and occasionalplasmacells.
FIGURE 4 ,i: Thgmus. Monkeg. Plastic section. x
540.
The cortex of the thl,rnus is bounded externallyby
collagenousconnectivetissuesepta (Se).The substance
ofthe cortexis separatedfrom the septaby a border ofep-
ithelial reticular cells (ERC), recognizableby their pale
nuclei.Additional epitheiialreticularcellsform a cellular
reticulum, in whose intersticeslymphocytes (Ly) develop
into mature T-lymphocytes. Numerous macrophages
(Ma) are also evidentin the cortex.Thesecellsphagocy-
toselymphocytesdestroyedin the thymus.

Thymus

I KEY

BV bloodvessel LO lobule Ma macrophage

C cortex Ly lymphocyte Se septum
Ca capsule M medulla T/\ thymiccorpuscle
ERC epithelialreticular
ce

188 Lymphoid
Tissue
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 PLATE9-6 I Spleen
FIGURE I Spleen. Human. poraffin section. F|GURE 2 Spleen. Monkeg. Plostic section.
x 132. x 132.
Lying within the periarterial lymphatic sheaths
(PALS)of the spleen,a secondarrangementofwhite pulp
may be noted, namelylymphatic nodules (LN) bearinga
germinal center (Gc). Lymphatic nodulesfrequentlyoc-
cur at branchingofthe central artery (CA). Nodules are
populatedmostly by B lymphocltes (arrows),which ac-
ofthe organ.The spleenis not subdividedinto cortexand count for the dark stainingofthe corona (CO). The ger-
minal centeris the site of activeproduction of B lympho-
cltes during an antigenicchallenge.The marginal zone
(MZ), alsopresentaround lymphatic nodules,is the re-
gion where lymphocl'tesleavethe small capillariesand
first enter the connectivetissuespacesofthe spleen.It is
from here that T lymphocytesmigrateto the periarterial
lymphatic sheaths,while B lymphocy'tesseekout lym-
phatic nodules. Both the marginal zone and the white
pulp house numerous macrophages,as well as antigen-
presentingcells(arrowheads)in addition to lyrnphocltes.

FIGURE3 Spleen. Monkeg. Plostic section.
x 540.
The red pulp of the spleen,presentedin this photomi-
crograph,is composedof splenicsinusoids(S) and pulp
cords (PC). The splenicsinusoidsare lined by a dision-
t i n u o u st y p eo f e p i t h e l i u ms,u r r o u n d ebdy a n u n u s u aal r -
rangementof basementmembrane(BM) that encircles
the sinusoidsin a discontinuousfashion.Sinusoidscon-
tain numerousblood cells (BC). Nuclei (N) of the sinu-
soidal lining cellsbulge into the lumen. The regionsbe-
FIGURE 4 Spleen. Human. Silver stoin. Poraffin
section. x 132.
The connective tissue framework of the spleen rs
demonstratedby the useof silversrain,which precipitates
around reticular fibers.The capsule(Ca) ofthe spleenis
piercedby blood vessels(BV) that enter the substanceof
the organvia trabeculae(T). Thewhite pulp (WP) and red
pulp (RP) are clearlyevident.In fact, the l1'rnphaticnod-
ule presentsa well-definedgerminalcenter(Gc) aswell as
a corona (CO). The centralartery (CA) is alsoevidentin
this preparation.Reticularfibers (RF),which form an ex-
tensivenetwork throughout the substanceof the spleen,
are attachedto the capsuleand to the trabeculae.

cle (SM) cellsare evidentin the centerof this field.

Spleen

I KEY

AR arteriole EC endothelial cell PC pulpcord

BC bloodcell Gc germinalcenter RF reticularfiber
BM basementmembrane LN lymphaticnodule RP red pulp
BV bloodvessel Ly lymphocyte S sinusoid
Ca capsule MZ marginalzone SE septum
CA centralartery N nucleus SM smoothmuscle
CO corona PALS periarteriallymphatic T lrabeculae
E epithelium sheath WP whitepulp

I 90 LymphoidTissue
 PALS

LN GA
<-
GC <--

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L v n r p h o rTdi s s r t e 19 1

r EndocrineSgstem
The endocrinesystemin cooperationwith the ner-
vous system,orchestrates homeostasisby influenc-
ing, coordinating, and integrating the physiological
functions ofthe body.
The endocrinesystemconsistsofseveralglands,
isolatedgroups of cellswithin certain organs,and
individual cellsscatteredamong parenchymalcells
ofthe body. This chapterconsidersonly that part of
the endocrine systemthat is composedof glands.
Isletsof Langerhans,interstitialcellsof Leydig,cells
responsiblefor ovarian hormone production, and
DNES (diffuseneurroendocrine) cellsare treatedin
more appropriatechapters.
The endocrine glands to be discussedhere
are the pituitary, thyroid, parathyroid, and supra-
renal glands, and the pineal body. All of these
glands produce hormones, low-molecular-weight
molecules that are transported via the blood-
stream to their target cells. Therefore, endocrine
glandspossessan extensivevascularsupply that is
particularly rich in fenestratedcapillaries.Since
some hormones are proteins, they do not cross
the target cell plasmalemma,but attachto specific
receptorson the plasma membrane of the target
cell, thus activatirrgits intracellular second mes-
sengersystem. Other hormones are lipid soluble
and, subsequentto enteringthe targetcell, bind to
their intracellular receptors,and thus exert their
influence. Still other hormones act to modify the
electrical potential difference across the pias-
malemma of certain cells,such as muscle cells or
neurons. Therefore, the activity of the hormone
will, to a largeextent, dependon the target cell re-
ceptors to which it becomesattached.The pres-
ence of most hormones also elicits a vascularly
mediatednegativefeedbackresponse,in that sub-
sequentto a desiredresponse,the further produc-
tion and/or releaseof that particular hormone is
inhibited.
IIruII t0
PITUITARY GTAND
The pituitary gland (hypophysis) is composed of
severalregions, namely, pars anterior (pars dis-
talis), pars tuberalis,infundibular stalk,pars inter-
media, and pars nervosa(the last fivo are known as
the pars posterior) (seeGraphic 10-1). Since the
pituitary gland developsfrom two separateembry-
onic origins,the epithelium of the pha4'ngealroof
and the floor of the diencephalon, it is frequently
discussedas being subdividedinto two parts: the
adenohypophysis(pars anterior, pars tuberalis,
and pars intermedia) and the neurohlpophysis
(pars nervosa and infundibular stalk). The pars
nervosais continuous with the median eminence
of the hypothalamusvia the thin neural stalk (in-
fundibular stalk).
The pituitary gland receives its blood supply
from the right and left superior hypophyseal arter-
ies, serving the median eminence,pars tuberalis,
and the infundibulum, and from the right and left
inferior hypophyseal arteries, that serve the pars
nervosa.
Hypophyseal Portal System: The two superior
hlpophyseal arteriesgive rise to the primary capil-
lary plexus located in the region of the median
eminence.Hypophysealportal veins drain the pri-
mary capillary plexus and deliver the blood into
the secondarycapillary plexus, located in the pars
distalis. Both capillary plexusesare composedof
fenestratedcapillaries.
ParsAnterior
The pars anterior is composed of numerous
parenchymal cells arranged in thick cords, with
large capillaries,known as sinusoids, richly vascu-
larizing the intervening regions. The parenchyrnal
E n d o c r i n e S v s t et m 1 9 3
 cells are classifiedinto two main categories:those
whose granulesreadily take up stain, chromophils,
and those cellsthat do not possessa strong af;finity
for stains,chromophobes.Chromophils aie of two
types, acidophils and basophils. Although consid-
erable controversysurrounds the classificationof
these cells vis-d-vis their function, it is probable
that at least six of the sevenhormones manufac-
tured by the pars anterior are made by separate
cells. Hormonesthat modulatethe secretoryfunc-
tions of the pituitary-dependentendocrineglands
are somatotropin, thyrotropin (TSH), follicle-
stimulating hormone (FSH), luteinizing hormone
(LH), prolactin, adrenocorticotropin(A-CTU),and
melanocyte-stimulating hormone (MSH). It is
believedthat two fypesof acidophils produce soma-
totropin and prolactin, whereasvarious popula-
tions of basophils produce the remaining five
hormones. Chromophobes, however, probably do
not producehormones.They arebelievedto be aci-
dophils and basophilsthat havereleasedtheir gran-
ules.
Control ofAnterior Pituitary Hormone Release:
Axons whosesoma are locatedin the hypothalamus
terminate at the primary capillary'ted. These
axons store releasinghormones (somatotropin-
releasinghormone, prolactin-releasinghormone,
primary capillary plexus and are conveyed to the
secondarycapillary plexus by the hypophysealpor-
tal veins.The hormones then activate(or inhibit)
chromophilsof the adenohypophysis, causingthem
to releaseor prevent them from releasingtheir hor-
mones.
An additionalcontrol is the mechanismof nega-
tive feedback,in that the presenceof specificplasma
levelsof the pituitary hormones prevents the chro-
mophils from releasing additional quantities of
thosehormones.
ParsIntermedia
The pars intermedia is not well developed.It is be-
lieved that the cell population of this region may
have migrated into the pars anterior to produce
melanocyte-stimulating hormone and adrenocor-
ticotropin. It is quite probablethat a singlebasophil
can produceboth of thesehormones.
ParsNervosaand InfundibularStalk
The pars nervosa doesnot present avery organized
appearance.It is composedof pituicytes, cellsbe-
194 ffi Endocrine
System
Iieved to be neuroglial in nature that may fulfill a
supporting function for the numerous unmyeli-
nated axons of the pars nervosa. These axons,
whose cell bodies are located in the supraoptic and
paraventricular nuclei of the hypothalamus, enter
the pars nervosavia the hypothalamo-hypophyseal
tract.,They porr.rr-.*pun-ded axon t.rrnirrulr, ..-
I
ferred to asHerringbodies, within the parsnervosa.
Herring bodies contain oxytocin and antidiuretic
;Hffff ;Tfi3r
il:ilffi$?,*""i,ll,il1"i1?;
manufactured in the cell bodies in the hypothala-
a::;:lff:H:j?jH::ilff
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r
ParsTuberalis
The pars tuberalis is composed of numerous
cuboidalcellswhosefunction is not known.
THYROID GLAND
The thyroid gland consistsof right and left lobes
that are interconnectedby a narrow isthmusacross
the thyroid cartilage and upper trachea (see
Graphic 10-2).It is envelopedby a connectivetissue
capsulewhoseseptapenetratethe substanceofthe
gland, forming not only its supporting framework
but also its conduit for a rich vascular supply. The
parenchyrnalcellsofthe gland are arrangedin nu-
merous follicles,composedof a simple cuboidal ep-
ithelium lining a central colloid-filled lumen. The
colloid, secretedand resorbedby the follicular cells,
is composedof the thyroid hormone that is bound
to a large protein and the complex is known asthy-
roglobulin. An additional secretory cell type,
parafollicular cells (clear cells), is present in the
thyroid. These cells have no contact with the col-
loidal material. They manufacture the hormone
calcitonin, which is releaseddirectly into the con-
nective tissuein the immediate vicinity of capillar-
ies. Thyroid hormone is essentialfor regulating
basal metabolism and for influencing growth rate
and mental processes,and generallystimulates en-
docrine gland functioning. Calcitonin helps control
calcium concentrations in the blood by inhibiting
boneresorptionby osteoclasts (i.e.,when blood cal-
cium levelsare high, calcitonin is released).
PI\RATHYROID GTANDS
The parathyroid glands, usually four in number,
are embeddedin the fascial sheathof the posterior
aspectofthe thyroid gland. The parathyroid glands
possessslender connective tissue capsulesfrom
which septaare derived to penetratethe glandsand
convey a vascular supply to the interior. In the
adult, two typesof cellsarepresent:numeroussmall
chief cellsand a smallernumber of large acidophilic
cells, the oxyphils. Fatty infiltration of the gland
is common in older individuals. Although there
is no know function of oxyphils, chief cells pro-
duce parathyroid hormone (PTH), the most im-
portant regulatorofcalcium in the body. PTH helps
control serum calcium levels by acting directly on
osteoblaststo increaseosteoclasticactivity, reduc-
ing calcium loss through the kidneys, and facilitat-
ing calcium absorption in the intestines.Lack of
parathyroid glandsis not compatible with life.
SUPRARENATGLANDS
The suprarenalglands(adrenalglandsin someani-
mals) areinvestedby a connectivetissuecapsule(see
Graphics l0-2 and 10-3). The glands are derived
from two different embryonic origins, namely,
mesodermalepithelium, which givesrise to the cor-
tex, and neuroectoderm, from which the medulla
originates.The rich vascularsupply of the gland is
conveyed to the interior in connective tissue ele-
mentsderivedfrom the capsule.
Cortex
The cortex is subdivided into three concentric
regions or zones.The outermost region, just be-
neath the capsule,is the zona glomerulosa, where
the cells are arranged in archesand spherical clus-
ters with numerous capillariessurrounding them.
The secondregion, the zona fasciculata,is the most
extensive.Its parenchynnalcells, usually known as
spongiocytes, are arranged in long cords, with
numerouscapillariesbetweenthe cords.The inner-
most region of the cortex, the zona reticularis, is
arranged in anastomosingcords of cells with a
rich intervening capillary network. Three types of
hormones are produced by the suprarenalcortex,
namely, mineralocorticoids (zona glomerulosa),
glucocorticoids (zona fasciculataand, to some ex-
tent, zona reticularis),and some androgens(zona
fasciculataand zonareticularis).
Medulla
The cells of the medulla, disposed in irregularly
arrangedshort cords surroundedby capillarynet-
works, contain numerous granules that stain in-
tensely when the freshly cut tissue is exposed to
chromium salts.This is referred to as the chromaf-
fin reaction, and the cells are called chromaffin
cells. There are two types of chromaffin cells: one
produces epinephrine, while the other manufac-
tures norepinephrine, the two hormones of the
suprarenalmedulla.Sincethesecellsareinnervated
by preganglionic sympathetic nerve fibers, chro-
maftin cellsare consideredto be related to postgan-
glionic spnpathetic neurons. Additionally, the
medulla of the suprarenalgland also houseslarge,
postganglionicsyrnpatheticnerye cell bodies whose
function is not known.
PINEATBODY
The pineal body (epiphysis)is a projection ofthe
roof of the diencephalon(seeGraphic l0-2). The
connectivetissuecovering of the pineal body is pia
mater, which sends trabeculae and septa into the
substanceof the pineal body, subdividing it into in-
complete lobules. Blood vesselssupplying and
draining the pineal body travel in theseconnective
tissueelements.The main cellular elementsof the
pineal body are pinealocytes and neuroglial cells.
The pinealocytesmanufacture melatonin and sero-
tonin, while neuroglial cells lend support to
pinealocytes.Interestingly,serotonin is only pro-
duced during daylight, while melatonin is manufac-
tured only at night. The intercellularspacesof the
pineal body contain calcified granular material
known as brain sand (corpora arenacea),whose
significance,if any, is not known.
E n d o c r i n e S y s t ecm 1 9 5

Histophgsiologg
I. MECHANISM
OFHORMONAL
ACTION
Hormones are substancessecretedby cells of the
endocrinesysteminto the connectivetissuespaces.
Some hormones act in the immediate viciniry of
their secretion,whereasother hormones enter the
vascularsystemand find their target cellsat a dis-
tancefrom their site of origin.
Somehormones (e.g.,thyroid hormone) havea
generalizedeffect,in that most cellsare affectedby
them; other hormones (e.g., aldosterone) affect
only certain cells.Receptorslocated either on the
cell membraneor within the cell are specificfor a
particular hormone. The bindine of i hormone
initiatesa sequenceofreactionstha'tresultsin a par-
ticular response.Becauseof the specificityof the
reaction,only a minute quantity of the hormone is
required.Somehormoneselicit and othersinhibit a
particularresponse.
Hormones are of two t)?es, nonsteroid and
steroid based. Nonsteroid-basedhormones may
be derivatives of tyrosine (catecholaminesand
thyroid hormone) and small peptides (ADH and
oxytocin) or small proteins (glucagon,insulin, an-
terior pituitary proteins, and parathormone).
Steroid-basedhormonesarecholesterolderivatives
(aldosterone,cortisol, estrogen,progesterone,and
testosterone).
A. Nonsteroid-Based Hormones
Nonsteroid-basedendocrinehormonesbind to re-
ceptors (some are G protein linked, and some are
catalytic)locatedon the targetcell membrane,acti-
vate them, and thus initiate a sequenceof intracel-
lular reactions.Thesemay actby alteringthe stateof
an ion channel(openingor closing)or by activating
(or inhibiting) an enzymeor group of enzymesas-
sociated with the cytoplasmic aspect of the cell
memDrane.
Opening or closing an ion channelwill permit
the particular ion to traverseor inhibit the particu-
Iar ion from traversingthe cell membrane,thus al-
tering the membranepotential.Neurotransmitters
and catecholaminesact on ion channels.
The binding of most hormonesto their receptor
will have only a single effect,which is the activaiion
of adenylate cyclase.This enzyme functions in the
transformationof ATP to cAMP (cyclic adenosine
monophosphate),the major secondmessengerof
195 e€ Endocrine
Svstem
Tffi;1 II
the cell. cAMP then activatesa specificsequenceof
enzymesthat are necessaryto accomplishthe de-
siredresult.There are a few hormonesthat activate
a similar compound, cyclic guanosinemonophos-
phate (cGMP), which functions in a comparable
fashion.
Some hormones facilitate the opening of cal-
cium channels;calciumentersthe cell,and threeor
four calcium ions bind to the protein calmodulin,
alteringits conformation.The alteredcalmodulinis
a secondmessengerthat activatesa sequenceof en-
z)'rnes,causinga specificresponse.
Thyroid hormones are unusual, in that they
directly enter the nucleus,where they bind with
receptor molecules.The hormone-receptor com-
plexes control the activities of operators and/or
promoters, resulting in mRNA transcription.
The newly formed mRNAs enter the cy'toplasm,
where they are translatedinto proteinsthat elevate
the cell'smetabolicactiviw.
B. Steroid-Based Hormones
Steroid-basedendocrine hormones diffirse into the
targetcell through the plasmamembraneand, once
inside the cell, bind to a receptor molecule. The
receptor molecule-hormone complex enters the
nucleus, seeksout a specific region of the DNA
molecule, and initiates the syntheiis of mRNA. The
newly formed mRNA codesfor the formation of spe-
cific enzymesthat will accomplishthe desiredresult.
I I . T H Y R O I DH O R M O N E
A. Synthesis
Iodide from the bloodstreamis activelytransported
into follicular cellsat their basalaspectvia iodide
pumps. Iodide is oxidizedby thyroid peroxidaseon
the apicalcell membraneand is bound to tyrosine
residues of thyroglobulin molecules.Within the
colloid the iodinated tyrosine residuesbecomere-
arrangedto form triiodothyronine (T:) and thy-
roxine (Ta).
B. Release
The binding of thyroid-stimulating hormone to
receptorson the basalaspectof their plasmalemma
induces follicular cells to become tall cuboidal
cells. They form pseudopodson their apical cell
 membranethat engulf and endoqtose colloid. The
colloid-filled vesiclesfuse with lysosomes,and T3
and Ta residuesare removed from thyroglobulin,
liberated into the cfiosol, and are releasedat the
basalaspectofthe cell into the perifollicularcapil-
lary network.
H OR MON EA N D
I I I . PA R A T H YR OID
CALCITONIN
Parathyroid hormone (PTH), produced by chief
cellsof the parathyroid, is responsiblefor maintain-
ing proper calcium ion balance.The concentration
of calcium ions is extremelyimportant in the nor-
mal function of muscleand nervecellsand as a re-
leasemechanismfor neurotransmittersubstance. A Zona reticularis cells secreteweak androgens
drop in blood calcium concentration activatesa
feedbackmechanismthat stimulateschief cell se-
cretion.PTH binds to receptorson osteoblasts that
release osteoclast-stimulating factor followed by
bone resorptionand a consequentincreasein blood
calciumion concentration.In the kidneysPTH pre-
I ventsurinary calciumloss;thus ions arereturnedto
the bloodstream.PTH alsocontrolscalciumuptake
in the intestinesindirectly by modulating kidney
I production of vitamin D, which is essentialfor cal-
cium absorption.
Increasei levels of PTH causesan elevation in
plasma calcium concentration;however, it takes
severalhours for this levelto peak.The concentra-
tion of PTH in the blood is also controlled by
plasmacalciumlevels.
Calcitonin actsas an antagonistto PTH. Unlike
PTH, calcitonin is fast acting and, since it binds
directly to receptors on osteoclasts,it elicits a
peak reduction in blood calcium levelswithin one
hour. Calcitonin inhibits bone resorption thus
reducingcalcium ion levelsin the blood. High lev-
elsof calciumions in the blood stimulatecalcitonin
release.
IV. SUPRARENALGLANDS
The suprarenal parenchyma is divided into an
externalcortexand an internal medulla.
A. Cortex
Parenchymal cells of the cortex, derived from
mesoderm,are regionalizedinto three zonesthat
secretespecific hormones. Control of these hor-
monal secretionsis mostly regulated by ACTH
from the pituitary gland.
Cells of the zona glomerulosa secrete aldos-
terone, a mineralocorticoidthat actson cellsof the
distalconvolutedtubulesof the kidney to modulate
water and electrolltebalance.
Zona fasciculatacells secretecortisol and corti-
costerone.Theseglucocorticoids regulatecarbohy-
drate metabolism,facilitatethe catabolismof fats
and proteins, exhibit anti-inflammatory activity,
and suppressthe immune resPonse.
that promote masculinecharacteristics.
B. Medulla
Parenchymal cells of the medulla are derived
from neural crest material. They consist of
two populations of chromaffin cells that se-
crete mainly epinephrine (adrenaline) or nore-
pinephrine (noradrenaline).Secretionof thesetwo
catecholaminesis directly regulated by pregan-
glionic fibers of the sympatheticnervous system
that impinge on the postganglionicsympathetic
neuron-like chromaffin cells. Catecholaminere-
leaseoccurs in physical and psychologicalstress.
Moreover, scatteredsympathetic ganglion cells in
the medulla act upon smooth muscle cells of the
medullary veins, thus controlling blood flow in
the cortex.
BODY( PINEAL
v. PTNEAL GLAND;
EPTPHYSIS)
Pinealocytes, parenchymalcellsof the pineal body,
synthesizeserotoninduring the day and melatonin
during the night. However, it is unclear how the
glandfunctionsin humans.Nonetheless, melatonin
is used to treat jet lag and in regulatingemotional
responses relatedto shorteneddaylightduring win-
ter, a condition called seasonalaffectivedisorder
(SAD).
EndocrineSystem [g 197
 C l i n i c a lC o n s i d e r a t i o n se I I
I
becomesenlargedandthereisevidenceof ex-
goiter(protrusion
ophthalmic of theeyeballs)
Pituitarg Gland Parathgroid GIand I
G a l a c t o r r h e ai s a c o n d i t i o nw h e r ea m a l eo r o - Hyperparathyroidism maybe dueto the pres-
d u c e sb r e a s tm i l ko r a w o m a nw h o i s n o t b r e a s t enceof a benigntumorcausing theexcess pro-
f e e d i n gp r o d u c e sb r e a s tm i l k I n m e n i t i s o f t e n ductionof parathyroidhormoneThehighlevels I
a c c o m p a n i ebdy i m p o t e n c eh, e a d a c h ea,n d l o s s of circulating
PTHcauseincreased boneresorp-
o f p e r l p h e r avli s i o na n d r n w o m e nb y h o t
f l a s h e sv,a g i n adl r y n e s sa, n d a n a b n o r m am l en-
s t r u a cl y c l e T h i sr a t h e ru n c o m m o nc o n d i t i o ni s
tionwitha resultant
ciumTheexcess
posited
greatly
calcium
in arterial
elevated
maybecome
bloodcal-
de-
wallsandin lhe kidneys,
r
u s u a l l ya r e s u l to f p r o l a c t i n o m a ,t u m o ro f p r o - creatingkidneystones
lactin-producin ce g l l so f t h e p i t u i t a r yg l a n d T h e
c o n d i t i o ni s u s u a l l yt r e a t e db y d r u gi n t e r v e n t i o n SuprarenalGland I
or surgery,or botn
Addison's diseaseisanautoimmunedisease,
although it mayalsobetheaftermathof tuber-
Thgroid Glond
Graves'diseaseis causedby bindingof autoim-
culosislt ischaracterlzed
tionof adrenocortical
by decreased
hormones
produc-
dueto thede-
I
r
munelgCantibodlesto TSHreceptorsthus stim- structionof thesuprarenal
cortexandwithout
u l a t i n gi n c r e a s etdh y r o i dh o r m o n ep r o d u c t i o n theadministrationof steroid
treatmentit may
[hyperthyroidism)Clinicalty, the thyroidgtand havefatalconsequences

I
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| 98 e Endocrine
Svstem t
 IIHTT

I Summargof HistologicalOrganization

Endocrineglandsarecharacterizedbythe absence of II. THYROIDGLAND

ducts and the presenceof a rich vascular network.
The parenchymal cells of endocrine glands are
usually arrangedin short cords,follicles, or clusters,
although other arrangementsare also common.
I. PITUITARY
GLAND
The pituitary gland is invested by a connective
tissue capsule. The gland is subdivided into four
componentparts.
A. ParsAnterior
l. Cell Tgpes
a. Chromophils
1. Acidophils
Stain pink with hematoxylin and eosin. They are
found mostly in the center of the pars anterior.
2. Basophils
Stain darker than acidophils with hematoxylin and
eosin. They are more frequently found at the pe-
riphery of the parsanterior.
b. Chromophobes
Chromophobes are smaller cells whose cytoplasm
is not granular and has very little affinity for stain.
They may be recognized as clusters of nuclei
throughout the parsantenor.
A. Capsule
The capsuleof the thyroid gland consistsof a thin
collagenous connective tissue from which septa
extend into the substanceof the gland, subdividing
it into lobules.
B. Parenchymal Cells
The parenchymal cells of the thyroid gland form
colloid-filled follicles composedof
l. Fotlicular Celts(simple cuboidal epithelium)
2. Parafotlicutar Cells (clear cells) located at the
periphery of the follicles
Tissue
C. Connective
Slender connective tissue elements support a rich
vascularsupply.
GLAND
III. PARATHYROID
A. Capsule
The gland is investedby a slendercollagenouscon-
nective tissue capsule from which septa arise to
penetratethe substanceofthe gland.

Cells
B. Parenchymal
B. Pars Intermedia
l. Chief Cells
The pars intermedia is rudimentary in man.
Chief cells are numerous, small cells with large
Small basophils are present,aswell ascolloid-filled nuclei that form cords.
follicles.
2. Oxgphils
Oxyphils are larger, acidophilic, and much fewer in
C. ParsNervosaand InfundibularStalk number than chief cells,
Thesehave the appearanceof nervous tissue.The
cells of the pars nervosa are pituicytes, resembling
neuroglial cells. They probably support the un- Tissue
C. Connective
myelinated nerve fibers, whose terminal portions Collagenousconnectivetissuesepta as well as slen-
are expanded, since they store neurosecretions der reticular fibers support a rich vascular supply.
within the pars nervosa.These expanded terminal Fatty infiltration is common in older individuals.
regions are known as Herring bodies.

D. ParsTuberalis CLAND
IV. SUPRARENAL
The pars tuberalis is composedof cuboidal cellsar- The suprarenal gland is invested by a collagenous
rangedin cords. They may form small colloid-filled connective tissue capsule.The gland is subdivided
follicles. into a cortex and a medulla.

il 199
EndocrineSvstem
A. Cortex ranged in short cords. Additionally, large auto-
The cortex is divided into three concentriczones: nomic ganglioncellsarealsopresent.A characteris-
zona glomerulosa,zona fasciculata,and zona retic- tic of the medulla is the presenceof largeveins.
ularis.
l. Zona Clomerulosa V. PINEALBODY
The zona glomerulosais immediately deep to the
capsule.It consistsof columnar cells arrangedin
A. Capsule
archesand sphericalclusters. The capsule,derived from pia mater, is thin col-
lagenousconnectivetissue.Septaderivedfrom the
2. Zona Fasciculata
capsule divide the pineal body into incomplete
The thickest zone of the cortex is the zona fascicu-
lobules.
lata. The more or lesscuboidalcells(spongiocl.tes)
are arrangedin long, parallel cords. Spongioqtes
appear highly vacuolatedexcept for those of the B. Parenchymal Cells
deepestregion, which are smaller and much less l. Pinealocgtes
vacuolated. Pinealocytesarerecognizedby the largesizeoftheir
3. Zona Reticulqris nuclel.
The innermost zone of the cortex is the zona retic- 2. Neuroglial Cells
ularis. It is composedof small, dark cellsarranged Neuroglial cellspossess
smaller,densernuclei than
in irregularlyanastomosingcords.The intervening the pinealocy'tes.
capillariesare enlarged.

B. Medulla
The medulla is small in humans and is composed
of large, granule-containingchromaffin celis ar-
C. Brain Sand
Characteristicof the pineal body are the calcified
accretionsin the intercellular spaces,known as
brain sandor corpora arenacea.

2OO = Endocrine
Svstem
CRAPHf
C 10- 1 | PituitargGlandond lts Hormones

Neurosecretorycells
locatedin hypothalamus Paraventricular Supraoptic
nuclei nuclei
secretereleasing
inhibitory
and
p\ Hypothalamus

Waterabsorption

Iedian
)minence I
I

Hypophyseal
Kidney stalk

Pars

Uterus Oxytocin

Mammarygland Growthhormone
viasomatomedins

-iy'genesls

Androg-en
-?secretion

nvrn,
vvqry

I
:o
of free
fatty acids / Mammary
V gland
Mitk
secretion

Endocrine
System f 201
CRAPHIC10-2 | EndocrineGlands
r
Thyrcld
Gland I
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2O2 I EndocrineSystem
I
I C 10-3 . SAmpathetic
GRAPH| Innervationof the Visceraand the Meduilaof the
SuprarenalGland
I
Preganglionic
sympatheticneuronand fiber *-

I neuronandfiber i-

Dorsalroot
ganglion
T
I
I
I Thoracic
spinalcord {ffi. f'
Ventralroot
ganglion _
Sympathetic
chain ganglion
I
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I System I
Endocrine 2O3
PLATE10-1 I PituitargGland
FIGURE I e Pituitarg gland. Paraffin section. x 19.
This surveyphotomicrograph of the pituitary gland
demonstratesthe relationship of the gland to the hy-
pothalamus (H) from which it is suspendedby the rn-
fundibulum. The infundibulum is composedof a neural
portion,the infundibularstem (lS) and-thesurrounding
pars tuberalis (PT). Note that the third ventricle (3V) of
the brain is continuouswith the infundibular recess(IR).
The largestportion of the pituitary is the pars anterior
(PA), which is glandular and secretesnumerous hor-
mones. The neural component of the pituitary gland is
the pars nervosa(PN) that doesnot manufactureits hor-
mones,but storesand releases them. Even at this magni-
fication, its resemblanceto the brain tissue and to the
substance of the infundibular stalk is readily evident.
Betweenthe pars anterior and pars nervosais the pars
intermedia (PI), which frequently presentsan intraglan-
dular cleft (IC), a remnant of Rathke'spouch.

F|GURE 2 z Pituitarg gland. Pors anterior.
Paroffin section. x 132.
The pars anterior is composedof large cords of cells
that branch and anastomosewith eachother.Thesecords
are surroundedby an extensivecapillarynetwork. How-
ever,thesecapillariesarewide, endotheliallylined vessels
known assinusoids(S). The parenchymalcellsof the an!
terior pituitary are divided into two groups: chromophils
(Ci) and chromophobes (Co). With hematoxylin and
eosinthe distinction betweenchromophils and chromo-
phobesis obvious.The former stain blue or pink, while
the latter stain poorly. The boxed area is presentedat a
higher magnificationin Figure3.
FTGURE 3 * Pituitarg gland. Pars anterior.
Poraffin section. x 210.
This is a higher magnification of the boxed area of
Figure 2. Note that the chromophobes(Co) do not take
up the stain well and only their nuclei (N) are demon-
strable.These cells are small; therefore,chromophobes
are easily recognizablesince their nuclei appear to be
clumped together. The chromophils may be classified
into two categoriesby their affinity to histologic dyes:
blue-stainingbasophils(B) and pink-colored acidophils
(A). The distinction between these two cell types in
sections stained with hematorylin and eosin is not as
apparentas with some other stains.Note also the pres-
enceofa largesinusoid(S).

gland
Pituitary

T KEY

A acidophils tc intraglandularcleft PI parsintermedia

B basophils IR infundibularrecess PN parsnervosa
ci chromophils IS infundibularstem PT parstuberalis
Co chromophobes N nucteus S sinusoids
H hypothalamus PA pars anterior 3V thirdventricle

204 w Endocrine
Svstem
I
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2 FICURE
3
EndocrineSystem
PLATE10-2 I PituitargGland
FIGURE | = Pituitarg gland. Paraffin section.
x 540.
It is somewhat difficult to discriminate between the
acidophils (A) and basophils (B) of the pituitary gland
stainedwith hematorylin and eosin.Evenat high magni-
fication, such asin this photomicrograph, only slight dif-
ferencesare noted. Acidophils stain pinkish and are
slightlysmallerin sizethan the basophils,which stainpale
blue. In a black and white photomicrograph,basophils
appeardarker than acidophils.Chromophobes(Co) are
readily recognizable,since their cytoplasm is small and
does not take up stain. Moreover, cords of chromo-
phobespresentclustersofnuclei (N) crowdedtogether.
-e
FIGURE 3 Pituitarg glond. Pors nervosa. Paraffin
section. x 132.
The parsnervosaofthe pituitary glandis composedof
elongatedcellswith long processes known as pituicpes
(P), which are thought to be neuroglialin nature. These
cells,which possessmore or lessoval nuclei, appearto
support numerous unmyelinated nerve fibers traveling
from the hypothalamus via the hypothalamo-hlpophy-
seal tract. These nerve fibers cannot be distinguished
from the cytoplasm of pituicltes in an hematoxylin and
eosin-stainedpreparation.Neurosecretorymaterialspass
along thesenerve fibers and are stored in expandedre-
gions at the termination of the fibers, which are then
referredto as Herring bodies (HB). Note that the pars
nervosaresemblesneural tissue.The boxed area is pre-
sentedat a higher magnificationin Figure4.
I KEY
A acidophils chromophobes
B basophils HB Herringbodies
BV bloodvessels N nucreus
CI colloid
206 w Endocrine
System
FIGURE 2 * Pituitarg glond. Pars intermedia.
Human. Poraffin section. x 210.
The pars intermedia of the pituitary gland is situated
between the pars anterior (PA) and the pars nervosa
(PN). It is characterizedby basophils (B), which are
smaller than those of the pars anterior. Additionally, the
pars intermedia contains colloid (Cl)-filled follicles,lined
by pale, small low cuboidal shapedcells (arrows).Note
that some ofthe basophilsextendinto the pars nervosa.
Numerous blood vessels(BV) and pituicytes (P) are evi-
dent in this areaof the pars nervosa.
FIGURE 4 * Pituitarg gland. Po,rsnerosq. Paraffin
section. x 540.
This photomicrograph is a higher magnification of
the boxed areaof Figure 3. Note the numerous more or
lessoval nuclei (N) of the pituicytes, some of whose pro-
cesses(arrows) are clearly evident at this magnification.
The unmyelinated nerve fibers and processesof pituicytes
make up the cellular network of the pars neryosa.The ex-
pandedterminal regionsofthe nervefibers,which house
neurosecretions,are known asHerring bodies (HB). Also
observe the presenceof blood vessels(BV) in the pars
nervosa.
gland
Pituitary
P pituicytes
PA parsanterior
PN parsnervosa
 "a

*"
r tl

t,
FICURE
2

\ r * .' .r'
t h.
PLATE10-3 I ThgroidCland,ParathgroidGlond
FIGURE | * Thgroid gland. Monkeg. Plostic
section. x 132.
The capsuleof the thyroid gland sendsseptaof con-
nectivetissueinto the substanceofthe gland,subdividing
it into incomplete lobules. This photomicrograph pre-
sents part of a lobule displaying many follicles (F) of
varied sizes.Each follicle is surroundedby slendercon-
nective tissue (CT), which supports the follicles and
brings blood vessels(BV) in close approximation. The
folliclesare composedof follicular cells (FC), whoselow
cuboidalmorphology indicatesthat the cellsare not pro-
ducing secretoryproduct. During the active secretory
cycle,thesecellsbecometaller in morphology. In addi-
tion to the follicular cells, another parenchymal cell qpe
is found in the thyroid gland. Thesecellsdo not border
the colloid, are locatedon the periphery of the follicles,
and areknown asparafollicularcells(PF) or C cells.They
are large and possesscentrallyplacedround nuclei, and
their cltoplasm appearspaler.
FIGURE 2 G Thyroid gland. Monkey. Plastic sec-
tion. X 540. The thyroid follicle (F) presented in this
photomicrograph is surrounded by severalother follicles
and intervening connectivetissue (CT). Nuclei (N) in the
connectivetissuemay belong either to endothelial cellsor
to connective tissue cells. Since most capillaries are col-
lapsed in excised thyroid tissue, it is often difficult to
identifr endothelial cellswith any degreeofcertainty. The
follicular cells (FC) are flattened, indicating that these
cells are not actively secreting thpoglobulin. Note that
the follicles are filled with a colloid (Cl) material. Observe
the presenceof a parafollicular cell (PF), which may be
distinguished from the surrounding cellsby its pale cyto-
plasm (arrow) and largernucleus.

FIGURE 3 x Thgroid and parathgroid glands.
Monkeg. Plastic section. x 132.
Although the parathyroid (PG) and thyroid glands
(TG) are separatedby their respectivecapsules(Ca), they
are extremely close to each other. The capsule of the
parathyroid gland sends trabeculae (T) of connective
tissuecarrying blood vessels(BV) into the substanceof the
gland. The parenchyrnaof the gland consistsof tlvo types
of cells, namely chief cells (CC), also known as principal
cells,and oryphil cells (OC). Chief cellsare more numer-
ous and possessdarker staining qtoplasm. Oryphil cells
stain lighter and areusuallylargerthan chiefcells,and their
cell membranesare evident.A region similar to the boxed
areais presentedat a higher magnification in Figure 4.
FTGURE4 w Parathgroid glond. Monkeg. Plastic
section. x 540.
This photomicrographis a region similar to the boxed
areaof Figure 3. The chief cells (CC) of the parathyroid
gland form small cords surrounded by slenderconnective
tissue (CT) elementsand blood vessels(BV). The nuclei
(N) of connectivetissue cells may be easilyrecognized
due to their elongated appearance.Oxyphil cells (OC)
possessa paler cytoplasm and frequently the cell mem-
branesare evident (arrows).The glandsofolder individ-
uals may become infiltrated by adipocltes.

Thyroidglandand parathyroidgland

T KEY
W
BV bloodvessels F follicle PF parafollicular
cells
Ca capsule FC follicular
cells PG parathyroidgland
chiefcells N nucteus T trabeculae
colloid oxyphilcells TG thyroidgland
CT connectivetissue

208 G Endocrine
System
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E n c l o cr nr eS y s t e r n 209
PLATE10-4 | SuprarenalCland
FIGURE | ffi Suprarenal gland. Paraffin section.
x 14.
The suprarenal gland, usually embedded in adipose
tissue(AT), is investedby a collagenousconnectivetissue
capsule (Ca) that provides thin connectivetissue ele-
ments that carry blood vesselsand nervesinto the sub-
stance of the gland. Since the cortex (Co) of the
suprarenal gland completely surrounds the flattened
medulla (M), it appearsduplicated in any section that
completelytransectsthe gland.The cortexis divided into
three concentric regions:the outermost zona glomeru-
losa (ZG), middle zona fasciculata(ZF), and the inner-
most zona reticularis (ZR). The medulla, which is always
bounded by the zona reticularis,possesses severallarge
veins (V), which are alwaysaccompaniedby a consider-
ableamount of connectivetissue.
FIGURE 3 fr Suprorenol gland. Monkeg. Plastic
section. x 132.
The columnar arrangementof the cords of the zona
fasciculata (ZF) is readily evident by viewing the archi-
tectureof the blood vesselsindicatedby the arrows.The
cells in the deeper region of the zona fasciculata are
smallerand appeardenserthan the more superficiallylo-
cated spongiocytes (Sp). Cells of rhe zona reticularis
(ZR) are arranged in irregular, anastomosingcords
whose intersticescontain wide capillaries.The cords of
the zona reticularis merge almoit imperceptibly with
those of the zona fasciculata.This is a relatively narrow
region of the cortex.The medulla (M) is clearlyevident
sinceits cellsare much larger than those ofthe zona retic-
ularis. Moreover, numerous large veins (V) are charac-
teristicof the medulla.
Suprarenal
I KEY
AT adiposetissue CT connectivetissue
BV bloodvessels M medulla
Ca capsule N nuclei
Cl collagenfibers Ne nerves
Co cortex Sp spongiocytes
21O ffi EndocrineSystem
FfGURE 2 t Suprarenal gland. Cortex. Monkeg.
Plastic section. x 132
The collagenousconnectivetissuecapsule (Ca) ofthe
suprarenalglandis surroundedby adiposetissuethrough
which blood vessels(BV) and nerves(Ne) reachthe gland.
The parenchymal cells of the cortex, immediately deepto
the capsule,arearrangedin an irregular array,forming the
more or lessovalto round clustersor arch-likecordsofthe
zona glomerulosa (ZG). The cells of the zona fasciculata
(ZF) form long straightcolumns ofcords oriented radi-
ally, eachbeing one to two cells in width. Thesecells are
largerthan thoseofthe zona glomerulosa.They presenta
vacuolatedappearance due to the numerouslipid droplets
that were extracted during processingand are often re-
ferred to as spongiocytes (Sp). The interstitium is richly
vascularizedby blood vessels(BV).
FfGURE 4 S Suprarenal gland. Monkeg. Plastic
section. x 540.
The capsule (Ca) of the suprarenal gland displays its
collagen fibers (C0 and the nuclei (N) of the fibroblasts.
The zona glomerulosa (ZG), which occupies the upper
part of the photomicrograph, displays relatively small
cells with few vacuoles (arrows). The Iower part of the
photomicrograph demonstrates the zona fasciculata
(ZF), whosecellsarelargerand displaya more vacuolated
(arrowheads)appearance.Note the presenceof connec-
tive tissue (CT) elements and blood vessels(BV) in the
interstitium between cords of parenchvmal cells.
gland
vetns
ZF zona fasciculata
ZG zona glomerulosa
ZR zona reticularis
I
AT Ca-
t
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ZR
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ZF
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I F I C U R IE

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I F l C i i R E5
PLATE10-5 | SuprarenalClond,PinealBodg
FIGURE I v Suprarenol gland. Cortex. Monkeg.
Plqstic section. x 540.
The upper part ofthis photomicrographpresentsthe
border between the zona fasciculata (ZF) and.the zona
reticularis (ZR). Note that the spongiocytes(Sp) of the
fasciculataare larger and more vacuolatedthan the cells
ofthe reticularis.The parenchymalcellsofthe zonaretrc-
ularis are arrangedin haphazardlyanastomosingcords.
The interstitium of both regionshouse large capillaries
containing red blood cells (RBC).
Inset. Zona fasciculata. Monkey. Plastic section.
x 540.
The spongiocytes(Sp) of the zona fasciculataare of
two differentsizes.Thosepositionedmore superficiallyin
the cortex,asin this inset,arelargerand more vacuolated
(arrows)than spongiocytescloseto the zona reticularis.
FTGURE2 I Suprarenol glond. Medulla. Monkeg.
Plastic section. x 270.
The cellsofthe adrenalmedulla, often referredto as
chromaffin cells (ChC), are arrangedin round to ovoid
clusters or in irregularly arranged short cords. The cells
are largeand more or lessround to polyhedralin shape
with a pale cytoplasm (Cy) and vesicular appearing nu-
cleus (N), displayinga single,large nucleolus (n). The
interstitium presents large veins (V) and an extensrve
capillary (Cp) network. Large ganglion cells are occa-
sionallynoted.

FIGURE 3 * Pinedl bodg. Humon. Poraffin section.
x 132.
The pineal body is coveredby a capsuleof connective
tissuederivedfrom the pia mater.From this capsulecon-
nective tissuetrabeculai (T) enter the substanceof the
pineal body, subdividing it into numerous incomplete
lobules (Lo). Nervesand blood vessels(BV) travel in the
trabeculaeto be distributed throughout the pineal,pro-
viding it with a rich vascularsupply. In addition to en-
dothelial and connectivetissuecells,two other types of
cellsare presentin the pineal,namely, the parenchymal
cells,known aspinealoqtes (Pi) and neuroglial support-
ing cells (Ng).A characteristicfeatureofthe pineal body
is the depositof calcifiedmaterial,known ascorporaare-
naceaor brain sand (BS).The boxed areais presentedat
a higher magnificationin Figure4.
FIGURE 4 e Pineal bodg. Human. Paraffin section.
x 540.
This photomicrograph is a higher magnification of the
boxed area of Figure 3. With the use of hematoxylin and
eosin stain, only the nuclei ofthe two cell types are clearly
evident.The larger,paler,more numerousnuclei belong
to the pinealocytes(Pi). The smaller,densernuclei are
those ofthe neuroglial cells (Ng). The pale background is
composedof the long, intertwining processes of thesetwo
cell types.The centerofthe photomicrographis occupied
by brain sand (BS). Observethat theseconcretionsin-
creasein sizeby appositionof layerson the surfaceof the
calcified material, as may be noted at the arrow.

gland
Suprarenal

I KEY

BS brainsand N nucteus Sp spongiocytes

BV bloodvessels n nucleolus T trabeculate
ChC chromaffin cells Ng neuroglial
cells verns
Cp capillaries Pi pinealocytes ZF zona fasciculata
Cy cytoplasm RBC red bloodcells ZR zona reticularis
Lo lobules

212 ffi EndocrineSvstem

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I E n d o c r i nS
eystem 213
PLATE10-6 t Pituitarg Gland,ElectronMicroscopg I
I
I
t
I
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t
I
I
I
I
t
I
I
F|GURE | | Pituitarg gland. Pars qnterior.
Eledron microscopg. x 4950.
Although considerable controversy surrounds the
light microscopy. The acidophils are: somatotropes (S)
and mammotropes (M), while only two types of ba-
sophils are included in this electron micrograph, namely,
I
precise fine structural identification of the cells of the type II gonadotropes (G2) and thyrotropes (T). The
pars anterior, it is reasonablycertain that the severalcell
types presented in this electron micrograph are aci-
chromophobes (C) may be recognizedby the absenceof
secretory granules in their cytoplasm. (From Poole M:
I
dophils, basophils, and chromophobes as observed by Anat Rec204:45-53,1982.)

I
I
214 a EndocrineSvstem I
I PLATE10-7 t PituitargGland,ElectronMicroscopg

t
I i
tDt.

t
t
I
I
I
I
I
I
I
I
I
I
I
I FfGURE | = Pituitarg glond. Rat. Electron
microscopg. x 8936.
The parsdistalisofthe rat pituitary housesvariouscell
demarcated by arrows. The functions of folliculostellate
cells are in question, although some believe them to be
supportive, phagocytic, regenerative,or secretoryin na-
types,two of which are representedhere. The granule-
t containinggonadotrophs(GN) are surroundedby non-
granular folliculostellate cells (FS) whose processesare
ture. (From StrokreefJC,ReifelCW, Shin SH: CeIITissue
Res243:255-261.I 986.)

I System *
Endocrine 215
I
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I

I Integument
t
The integument,the largestand heaviestorgan of
t the body, is composed of skin and its various
derivatives, including sebaceousglands, sweat
glands, hair, and nails. The skin covers the entire
I body and is continuous with the mucous mem-
branesat the lips, at the anus, in the nose, at the
leading edgesof the eyelids,and at the external ori-
I fices of the urogenital system.Some of the many
functions of skin include protection againstphysi-
cal,chemical,and biologic assaults; providing a wa-
terproof barrier; absorbingultravioletradiation for
I both vitamin D synthesisand protection;excretion
(i.e.,sweat)and thermoregulation;monitoring the
external milieu via its various nerve endings; and
I immunologic defenseof the body.
t SKIN
Skin is composed of a superficial stratified squa-
mous keratinized epithelium known as the epider-
I mis and of a deeper connectivetissue layer, the
dermis(seeGraphic1l-1). The epidermisand der-
mis interdigitatewith eachother by the formation
I of epidermal ridges and dermal ridges (dermal
papillae), where the two are separatedby a base-
ment membrane.Evidenceof this interdigitationis
t the ridgeson the finger tips that imprint as finger-
prints. Interposedbetweenskin and deeperstruc-
tures is a fascial sheath known as the hlpodermis,
I which is not a part of skin.
Epidermis
I Depending on the thicknessof the keratin layer,
skin is classifiedas thick or thin. The epidermis of
thick skin is describedfirst, since it is composed
I of all five layers, rather than just three or four
presentin thin skin. The deepestlayer, the stratum
basale(stratum germinativum),is a singlelayer of
I cuboidalto columnar cells.Thesecellsareresponsi-
ble for cell renewal,via mitosis (usually at night)
I fntegumentg
IIffiIT tl
and are pushed surfaceward, giving rise to the
thickest layer, the stratum spinosum. This layer is
composed of polyhedral prickle cells characterized
by numerous processes(intercellularbridges)that
form desmosomeswith processesof surrounding
prickle cells.Cellsof the stratum spinosum also dis-
play mitotic activity (usually at night). These two
Iayers are frequently referred to as the stratum
Malpighii and their continued mitotic activity is re-
sponsiblefor the continuous migration of these
cells into the next layer, known as the stratum
granulosum. Cells of this layer accumulatekerato-
hyalin granules, which eventually overfill the cells,
destroying their nuclei and organelles.The fourth
layer, the stratum lucidum, is relatively thin and
not alwaysevident.Presentonly in palmar and so-
lar skin, it usuallyappearsasa thin, translucentre-
gion, interposed between strata granulosum and
corneum. The cellsof the stratum lucidum have no
nuclei or organelles,but contain densely packed
keratin filaments and contain eleidin, a transforma-
tion product of keratohyalin. The surface-most
layer is the stratum corneum, composedof prefer-
entially arranged stacks of dead hulls known as
squames. The superficial layers of the stratum
corneum are desquamatedat the samerate as they
are being replaced by the mitotic activity of the
strata basaleand spinosum.
The epidermis is composedof four cell qpes:
keratinoc.ttes(described above), melanocytes,
Langerhanscells,and Merkel cells.Keratinocytes,
responsible for the production of keratin, are the
most populous of epidermalcells and are derived
from ectoderm. Melanocytes, derived from neural
crest cells, are responsible for the manufacture of
melanin, which is synthesizedon specializedor-
ganellescalled melanosomes. These melanocytes,
the secondmost populouscellt1pe,areinterspersed
among the keratinocytesof the stratum basaleand
are alsopresentin hair folliclesand the dermis.They
possess long thin qtoplasmic processes that extend
into the intercellular spacesbetween cells of the
217
stratum spinosum. Langerhanscells (dendritic
cells)derivedfrom bonemarrow and locatedmostly
in the stratum spinosum, function as antigen-
presentingcellsin immune responses. Merkel cells,
whose origin is uncertain,are interspersedamong
the cellsof the stratum basale,and are most abun-
dant in the fingertips.Afferent nerveterminalsap-
proximate thesecells,forming complexesthat are
believedto function as mechanoreceptors(touch
receptors).Thereis someevidencethat Merkel cells
may alsohavea neurosecretoryfunction.
Thin skin differs from thick skin in that it nas
only threeor four strata.Stratumlucidum is always
absentin thin skin,whereasstratacorneum,granu-
losum, and spinosumare greatlyreducedin size.In
fact,frequentlyonly an incompletelayerof stratum
granulosumis present.
De rm i s
The dermis of the skin, lying directly deep to the
epidermis is derived from mesoderm. It is com-
posed of dense irregular collagenousconnective
tissue containing mostly type I collagenand nu-
merouselasticfibersthat assistin securingthe skin
to the underlyinghypodermis.The dermisis subdi-
vided into a looselywoven papillary layer, a super-
ficial region that interdigitateswith the epidermal
ridges,and a deeper,coarser,and denserreticular
layer.The interfacebetweenthe papillaryand retic-
ular layers is indistinct. Dermal ridges display
encapsulatednerve endings, such as Meissner's
218 sr Integument
corpuscles,as well as capillary loops that bring
nourishmentto the avascularepidermis.
DERIVATIVESOF SKIN
Derivativesof skin include hair, sebaceous glands,
sweatglands,and nails (seeGraphic 11-2). These
structures originate from epidermal downgrowths
into the dermis and hypodermis, while maintaining
their connection to the outside. Each hair, com-
posedof a shaft of cornified cellsand a root con-
tainedwithin a hair follicle, is associated
with a se-
baceousgland that secretesan oily sebum into the
neck of the hair follicle.A small bundle of smooth
musclecells,the arrector pili muscle,attachesto the
hair follicle and, cradling the sebaceousgland, in-
sertsinto the superficialaspectsofthe skin.
Sweatglands do not develop in associationwith
hair follicles.Thesearesimplecoiledtubular glands
whosesecretoryunits produce sweat,which is de-
liveredto the surfaceof the skin by long ducts.My-
oepithelial cells surround the secretoryportion of
theseglands.
Nails are cornified structureson the distal pha-
lanx ofeach finger or toe. Thesehorny plateslie on
a nail bed and are bounded laterallyby a nail wall.
The cuticle (eponychium) lies over the lunula, an
opaque,crescent-shaped areaofthe nail plate,while
the hyponychium is locatedbeneaththe free edgeof
the nail plate.
I IIIII

I Histophgsiologg

I I. KERATINOCYTES
AND
KERATINFORMATION
t In the superficial layers of the stratum spinosum
and in the stratum granulosum,the cellsaccumu-
late a histidine-rich protein, keratohyalin granules
t in which the ends of intermediate filaments are
embedded.In the stratum lucidum. the cellular
organellesare no longer evident, the keratohyalin
II. MELANINFORMATION
Melanin is synthesizedby melanocytes, cells de-
rived from neural crest cells. Although these cells
are located in the stratum basale,they possesslong
processesthat extend into the stratum spinosum.
There are two tfpes of melanin, eumelanin, a dark
brown-to-blackpigment composedof polymersof
hydroryindole, and pheomelanin, a red-to-rust-

I granules have lost their identity, and they are

now referred to as eleidin, a combination of
colored compound composed of cysteinyl dopa
polymers. The former is presentin individuals with
filamentous material embedded in a densematrix. dark hair, and the latter is found in individuals with

I Cells of the stratum corneum are filled with

keratin, a scleroproteincomposedof lO-nm-thick
filaments rich in lysine residues. Additionally,
the cytoplasmic aspectsof the cell membranes
I of the keratinocytes of strata granulosum, lu-
cidum, and corneum are reinforced by involucrin,
a fibrous protein that forms a cross-linked mat
I whose individual componentsare 12 nm in diam-
eter. Cells of the strata spinosum and granulosum
house membrane-coatinggranuleswhose con-
red and blond hair.
Both typesof melanin arederivedfrom the amino
acid tyrosine, which is transported into specialized
tyrosinase-containing vesicles derived from the
trans-Golgi network, known as melanosomes.
Within theseoval (1.0by 0.5 pm) melanosomes, ty-
rosinaseconvertstyrosineinto 3,4-dihydroxypheny-
lalanine, which is transformed into dopaquinone
and, eventually,into melanin.
Melanosomespassto the tips of the melanocyte

I tents, a lipid-rich substance,are releasedinto the

extracellular spaces, forming a barrier that is
processes,which are engulfed and endocytosedby
keratinocytes of the stratum spinosum. The freed
impermeableto aqueousfluids. Moreover, Iysoso- melanosomesmigrate to the nucleus of the ker-

t mal enzymes released into the cytosol of cells

of the strata granulosum and lucidum digest the
cell's organellesand by the time the keratinocytes
reach the stratum corneum, they are non-living,
I keratin-filled husks. Keratin of skin is "soft" ker-
atin. whereas keratin of nails is "hard" keratin
becausethat of the nails has many more disulfide
I bonds.
Recent investigations indicate that ker-
atinocytesproduce immunogenic molecules and
atinocyte and form a protective umbrella, shielding
the nucleus(and its chromosomes)from the ultra-
violet raysof the sun. Soon thereafter,lysosomesat-
tack and destroythe melanosomes.
Ultraviolet rays not only increase the rates of
darkeningof melanin and endocltosisof the tips of
melanoqtic processes but also enhancetyrosinase
activity and, thus, melanin production.
Fewer melanocytesare located on the insides of
the thighs and undersides of the arms and face.

I are probably active in the immune process. Evi-

dence also shows that these cells are capableof
However, skin pigmentation is related to the loca-
tion of melanin rather than to the numbers of
melanocl'tes.Melanosomesare fewer and congre-
producing severalinterleukins, colony-stimulating
factors, interferons, tumor necrosis factors, as gatearound the keratinocytenucleusin Caucasians,
I well as platelet- and fibroblast-stimulating growth
factors.
whereasin blacks they are larger and are more dis-
persedthroughout the keratinocl'te cytoplasm.

I
t
;

I IntegumentI 219
 C l i n i c a lC o n s i d e r a t i o n sI I r basalefromdamage causedby ullraviolet radi-
I
ationThemostfrequent siteof basalcellcarci-
Psoriasis
Psoriasis isa condition characterized by patchy
nomarson thenose,occurnng
nodules,whicheventually
aspapules
cratersSurgery
or
is
t
lesions on theskln,especially around jointsand usually900/oeffective withno recurrence
thescalpThiscondition
creased proliferation
is produced
of keratinocytes
by in-
andan
Squamous
frequent
cellcarcinoma,
skinmalignancy,
thesecondmost
is invasive and
I
acceleration of thecellcycle,resulting in an ac- metastalic ltsprobable etiology isenvironmen-
cumulation
condition
of cellsin thestratum
iscyclicandisof unknown
corneumThe
etiology
talfactors,
suchasultraviolet
x-irradiation,
radiation
aswellasa varietyof chemical
and
I
carcinogens, inciudingarsenic. Thecarcinoma
Warts
Wartsarebenign
caused by papilloma
epidermal growths
viralinfection
on theskin
of theker-
originates
appears
plaque
in cellsof thestratum
clinically
withdeepinvasion
spinosum
asa hyperkeratotic
of underlying
scaly
and

tissues,
I
atinocytes Wartsarecommon in youngchil- oftenaccompanied by bleeding Surgery isthe
d r e ni,n y o u n ga d u l t sa,n di n i m m u n o s u p -
nrpcced n2tiantc
treatmentof choice.
Malignantmelanomamaybe a life-
I
Malignancies of Shin threateningmalignancy lt develops in the
T h et h r e em o s tc o m m o nm a l i g n a n c i eosf s k i n
a r eb a s acl e l lc a r c i n o m a
sq, u a m o ucse l lc a r c i -
melanocytes
invade
thatbecome
thedermis,
mitotically
eventually entering
actlveand
thelym-
I
nomaa , n d m a l i g n a nmt e l a n o m a phaticandcirculalory system to metastasize to
Basal cell carcinoma,the most common
h u m a nm a l i g n a n c yd,e v e l o p si n t h e s t r a t u m
otherorgansystems
combination
Treatment
of surgery
of choice
andchemotherapy
isa
I
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t
22O il Integument I
I Itulr
t Summargof HistologicalOrganization

I I. SKIN hlpodermis. Frequently, it houses hair follicles,

A. Epidermis sebaceousglands, and sweat glands. Krause's end

I The epidermis constitutes the superficial, epithe-

lially derived region of skin. It is composedof four
bulbs and pacinian corpuscles may also be
present.

cell types: keratinocytes, melanocytes,Langerhans

t cells, and Merkel cells. The keratinocytes are ar-
ranged in five layers, and the remaining three cell
II. APPENDAGES
q?es are interspersedamong them. The five layers A. Hair
t of the epidermisare
l. Stratum Basale
Hair is an epidermal downgrowth embedded into
dermis or hypodermis. It has a free shaft sur-
A single layer of cuboidal-to-columnarcells that rounded by severallayers of cylindrical sheathsof

I stand on the basementmembrane.This is a region

of cell division. It also contains melanocytes and
Merkel cells.
I 2. Stratum Spinosum
Composed of many layers of polyhedral prickle
cells bearing intercellular bridges. Mitotic activity
cells. The terminal end of the hair follicle is ex-
panded as the hair bulb, composedof connective
tissuepapilla and the hair root. The concentric lay-
ersofthe follicle are
l. ConnectiveTissueSheath
2. GlassgMembrane

t is alsopresent.It alsocontainsLangerhanscellsand
processes of melanocytes.
3. Stratum Granulosum
I Cells that are somewhatflattened and contain kera-
tohyalin granules. It is absent as a distinct layer in
thin skin.
I 4. Stratum Lucidum
A thin translucentlayerwhosecellscontaineleidin.
It is also absentin thin skin.
A modified basementmembrane.
3. External Root Shedth
Composed of a few layersof polyhedral cells and a
singlelayerof columnar cells.
4. Internal Root Sheath
Composedof three layers:Henle's layer, Huxley's
layer, and the cuticle. The internal root sheathstops
at the neck of the follicle where sebaceousgland
ducts open into the hair follicle, forming a lumen

I 5. Strqtum Corneum
Composedof squamespackedwith keratin. Super-
ficial squamesare desquamated.
into which the sebumis delivered.
5. Cuticle of the Hair
Composedof highly keratinizedcellsthat overlap

I B. Dermis
eachother.
6. Cortex
The bulk of the hair, composed of highly kera-
The dermis is a dense irregular collagenous con-
I nective tissue subdivided into two layers:papillary
and reticular.
tinized cells.
7. Medulla
A thin core of the hair whose cells contain soft
I L Papillarg Lager
The dermal ridges(dermalpapillae)and secondary
dermal ridges interdigitate with the epidermal
keratin.

ridges (and interpapillary pegs) of the epidermis. B. Sebaceous

I Collagen fibers are slender in comparison with
thoseof deeperlayersof the dermis.Dermal ridges
house capillary loops and Meissner'scorpuscles.
I 2. Reticular Lager
The reticular layer of skin is composedof coarse
bundles of collagenfibers. It supports a vascular
I plexus and interdigitates with the underlying
Glands
Sebaceousglands are in the forms of saccules
associatedwith hair follicles. They are branched
alveolar holocrine glands that produce an oily se-
bum. Secretionsare deliveredinto the neck of the
hair folliclevia short, wide ducts.Basalcellsare re-
generativecellsof sebaceous glands,locatedat the
peripheryof the saccule.

t lntegumentE 221
C.ArrectorPili Muscle 2. Ducts
Composedof a stratifiedcuboidal (two-cell-thick)
I
Arrector pili musclesarebundlesof smoothmuscle
cellsextendingfrom the hair follicle to the papillary epithelium.Cellsof the duct are darkerand smaller
layerof the dermis.Theycradlethe sebaceous gland.
Contractionsof thesemusclefiberselevatethe hair.
than those of the secretoryportions. Ducts pierce
the baseof the epidermalridgesto deliver sweatto
I
forming "goosebumps," releaseheat, and assistin the outside.
the deliveryof sebumfrom the gland into its duct.
E. Nail
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D. Sweat Glands
l. Sweqt Glands
The horny nail plate sits on the nail bed. It is
bordered laterally by the nail wall, the baseof which
forms the lateral nail groove. The eponychium
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Simple,coiled,tubular glandswhosesecretorypor- (cuticle) is abovethe nail plate,while the hypony-
tion is composedof a simple cuboidal epithelium.
Dark cells and light cells are present with intercel-
chium is locatedbelow the freeend ofthe nail plate.
The posterioraspectof the nail plateis the nail root,
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lular canaliculi betweencells.Myoepithelial cells which lies abovethe matrix, the arearesponsiblefor
surround the secretoryportion. the growth of the nail.
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I r NOTES

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GRAPHIC
I 1-l r Shinand ltsDerivatives

Hairshaft

Sebaceous
(oil)gland

Arrectorpili
muscle

\
Eccrinesweat
gland

Apocrinesweat
Eccrinesweatgland gland

Hairfollicle
Apocrinesweatgland
Hairroot

Roothairplexus
Pacinian
corpuscle
\- Artery
Vein
-\- Adipose
/ tissueof
hypodermis

Skinand itsappendages, hair,sweatglands(botheccrineandapocrine),sebaceousglands,and nails,are known

as the integumentSkinmaybe thick or thin, depending on thethicknessof itsepidermisThickskinepidermis is
composedof five distinctlayersof keratinocytes(stratabasale,spinosum,granulosum, lucidum,and corneum)
interspersedwiththreeadditional celltypes,melanocytes, Merkel'scells,and Langerhans'cellsThinskin
epidermis lacksstratagranulosum and lucidum,althoughindividual the absentlayersare presenr
cellsthatconstitute

Stratumcorneum\ --------
-- 1''-i;l';i{
Stratumlucidum---..-.--
Stratumgranulosum
Stratumspinosum
Langerhans'cell
Merkelcell
Melanocyt

Basement
membrane

Bloodvessel

Stratumbasale

224 Integument
I CRAPHfCI 1-2 | Hair, SweotGlands,SebaceousGlands

I Freeedge
Nailbody
Lunula

t Nail root

I Ductof
seoaceous
gland

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Gland
I Secretorycomponentsot
eccrlne sw6at glands
consistof simplecuboidal

I epitheliumcomposedof
dark cells, clear cells, and
myoeplthellalcells.The
ducts of theseglandsare

I composedof a stratified
cuboidal(two layersof
cuboidalcells)ePithelium.

t
Sebaceousglande are
I branchedacinarholocrine
glandswhoseshortducts
emptyinto a hairfollicleinto
the space created by the
I disappearance of the
internalrootsheath.

I lntegument I 225
 PLATE1 I Thick Skin

FfGURE | fl Thick skin. Paraffin section. x 132.
Skin is composedof the superficialepidermis(E) and
the deeperdermis (D). The interfaceof the two tissuesis
demarcatedby epidermal ridges (ER) and dermal ridges
(DR) (dermal papillae). Between successiveepidermal
ridgesare the interpapillarypegs,which divide eachder-
mal ridge into secondarydermalridges.Note that in thick
skin the keratinized layer, stratum corneum (SC), rs
highly developed.Observealso that the duct (d) of the
sweatgland piercesthe baseof an epidermalridge. The
dermis of skin is subdivided into two regions, a papillary
layer (PL), composedofthe looser,collagenousconnec-
tive tissueof the dermal ridges,and the deeper,denser,
collagenousconnectivetissueofthe reticular layer (RL).
Blood vessels(BV) from the reticularlayerenter the der-
mal ridges.
FIGURE 2 8 Thick skin. Monkeg. Plastic section.
x 132.
This photomicrograph of thick skin presents a view
similar to that in Figure l. However, the layersof the epi-
dermis (E) aremuch easierto delineatein this plasticsec-
tion. Observe that the squamesof the stratum corneum
(SC) appear to lie directly upon the stratum granulosum
(SG), whose cells contain keratohyalin granules. The
thickest layer oflining cellsin the epidermis is the stratum
spinosum (SS),while the stratum germinativum (SGe) is
only a single cell layer thick. The stratum lucidum is not
evident, although a few transitional cells (arrows) may be
identified. Note that the secondarydermal ridges (SDR),
on either side ofthe interpapillary peg (IP), present cap-
illary loops (CL). Regionssimilar to the boxed areasare
presentedin Figures3 and 4 at higher magnification.

F|GURE 3 M, Thick skin. Monkeg. Plastic section.
x 540.
This is a higher magnificationof a region similar to
the boxed areain the previous figure. The papillary layer
(PL) of the dermisdisplaysnuclei (N) of the variouscon-
nective tissue cells, as well as the interface between the
dermis and the stratum germinativum (SGe).Observe
that thesecellsare cuboidalto columnar in shapeand in-
terspersedamong them are occasionalclearceils,proba-
bly inactive melanocltes although it should be
stressed that Merkel cellsalsoappearasclearcells.Cellsof
the stratum spinosum (SS)are polyhedral in shape,pos-
sessingnumerous intercellularbridges,which interdigi-
tate with those of other cells,accountingfor their spiny
appearance.
FIGURE 4 ffi Thick skin. Monkeg. Plqstic section.
x 540.
This is a higher magnification of a region similar to
the boxed areaofFigure 2. Observethat asthe cellsofthe
stratum spinosum (SS) are being pushed surfaceward,
they become somewhat flattened. As the cells reach the
stratum granulosum (SG) they accumulate keratohyalin
granules(arrows),which increasein number as the cells
progressthrough this layer. Occasionaltransitional cells
(arrowheads)of the poorly defined stratum lucidum may
be observed, as well as the squames (S) of the stratum
corneum (SC).
/nser.Thick skin. Paraffin section. X 132.
This photomicrograph displaysthe stratum lucidum
(SL) to advantage.Note that this layer is betweenthe stra-
tum granulosum (SG) and stratum corneum (SC). Ob-
servethe duct (d) of a sweatqland.

I KEY
BV bloodvessel IP peg
interpapillary dermalridges
SDR secondary
CL capillaryloop M melanocytes Ql/:
stratumgranulosum
D dermis N nucreus SGe stratumgerminativum
o duct PL papillarylayer SS stratumspinosum
DR dermalridges RL reticularlayer b squames
E epidermis SC slratumcorneum 5L stratumlucidum
ER epidermalridges

226 uM Integument
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FIGURE1 FIGURE2
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PLATE1 1-2 I ThinSkin
FIGURE I fhin skin. Human. Poroffin section.
x 19.
Thin skin is composedof a very slenderlayer of epi-
dermis (E) and the underlying dermis (D). While thick
skin has no hair folliclesand sebaceouselandsassociated
with it, most thin skin is richly endowei with both. Ob-
servethe hair (H) and the hair follicles (HF), whoseex-
panded bulb (B) presentsthe connectivetissuepapilla
(P). Much of the follicle is embeddedbeneaththe skin in
the superficial fascia,the fatty connective tissue layer
known asthe hypodermis(hD), which is not a part of the
integument.Sebaceousglands (sG) secretetheir sebum
into short ducts (d), which empty into the lumen of the
hair follicle.Smooth musciebundles,arrectorpili muscle
(AP), cradletheseglands,in passingfrom the hair follicle
to the papillarylayer of the dermis. Sweatglands (swG)
are alsopresentin the reticularlayerofthe dermis.A re-
gion similar to the boxed area is presentedat a higher
magnificationin Figure2.

FIGURE 2 Thin skin. Human. Paroffin section.
x 132.
This is a higher magnificationof a region similar to
the boxed area of the previous figure. Observethat the
epidermis(E) is much thinner than that of thick skin and
that the stratum corneum (SC) is significantlyreduced.
The epidermal ridges and interpapillary pegs (IP) are
well representedin this photomicrograph.Note that the
papillary layer (PL) of the dermis is composedof much
finer bundles of collagenfibers (CF) than those of the
denseirregularcollagenousconnectivetissueofthe retic-
ular layer (RL). The dermis is quite vascular,asevidenced
by the largenumber of blood vessels(BV) whosecross-
sectionalprofilesarereadilyobserved.The numerousnu-
clei (N) ofthe variousconnectivetissuecellsattestto the
cellularityof the dermis.Note alsothe presenceof the ar-
rector pili muscle (AP), whose contraction elevatesthe
hair and is responsiblefor the appearanceof "goose
bumps." The boxed areais presentedat a higher magnifi-
cation in the following figure.
FIGURE 3 :, Thin skin. Humon. Poroffin section.
x 210.
This photomicrograph is a higher magnification of
the boxed area of Figure 2. Epidermisof thin skin pos-
sesses only three offour ofthe layersfound in thick skin.
The stratum germinatir.um (SGe) is present as a single
layerof cuboidalto columnar cells.Most of the epidermis
is composedof the prickle cellsof the stratum rpittoru-
(SS),while stratum granulosumand stratumlucidum are
not representedas completelayers.However,individual
cells of stratum granulosum (arrow) and stratum lu-
cidum are scattered at the interface of the stratum
spinosumand stratum corneum (SC).The papillarylayer
of the dermis (D) is richly vascularizedby capillaryloops
(CL), which penetrate the secondary dermal ridges
(sDR). Observethat the collagenfiber (CF) bundles of
the dermis becomecoarseras the distancefrom the epr-
dermis increases.

Skin

I KEY
AP arrectorpilimuscle H hair RL reticularlayer
B bulb hD hypodermis JU stratumcorneum
Fl\/ bloodvessels HF hairfollicles s D R secondarydermalridges
CF collagenfibers lP interpapillarypeg SG sebaceousglands
^l
capillaryloops N nuclei S G e stratumgerminativum
D dermis P papilla SS stratumspinosum
ducts PL papillarylayer swG sweat glands
E epidermis

228 =. Integument
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FICURE
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I lntegument 229
PLATE1 I Hair Folliclesand AssociatedStructures.SweatClands
FIGURE I Hair follicle. l.s. Human. Paraffin
section. x 132.
The terminal expansionof the hair follicle,known as
the bulb, is composedof a connectivetissue,papilla (P),
envelopedby epitheliallyderived cells of the hair root
(HR). The mitotic activity responsiblefor the growth of
hair occursin the matrix, from which severalconcentric
sheathsof epithelialcellsemergeto be surroundedby a
connectivetissuesheath (CTS). Color of hair is due to
the intracellular pigment that accounts for the dark
appearanceof somecells(arrow).
FIGURE 2 & Hair follicle. x.s. Human. Paraffin
section. x 132.
Many of the layerscomprising the growing hair follicle
may be observedin thesecross-sections. The entirestruc-
ture is surroundedby a connectivetissuesheath(CTS),
which is separatedfrom the epitheliallyderivedcompo-
nents by a specializedbasementmembrane, the inner
glassymembrane (BM). The clearpolyhedralcellscom-
posethe externalroot sheath(ERS),which surroundsthe
internal root sheath (IRS), whose cells become kera-
tinized.At the neckof the hair follicle,where the ductsof
the sebaceous glandsenter,the internalroot sheathdisin-
tegrates,providing a lumen into which sebumand apoc-
rine sweatare discharged.The cuticle (Cu) and cortex
(Co) constitute the highly keratinized components of the
hair, while the medullais not visibleat this magnification.
Note the presenceof arrectorpili muscle(AP).

FIGURE 3 Sebaceous glond. Human. Paraffin
section. x 132.
Sebaceous glands(sG) are branched,acinarholocrine
glands,which produce an oily sebum. The secretionof
theseglandsis deliveredinto the lumen of a hair follicle
(HF), with which sebaceous glandsare associated.Basal
cells(BC), locatedat the peripheryofthe gland,undergo
mitotic activity, to replenish the dead cells which, in
holocrine glands, become the secretoryproduct. Note
that as thesecellsaccumulatesebum in their cltoplasm,
they degenerate, as evidencedby the gradualpyknosisof
their nuclei (N). Observethe arrector pili muscle (AP),
which cradlesthe sebaceous glands.
F|GURE 4 ilt Sweat gland. Monkeg. Plastic section.
x 132.
The simplecoiledtubular eccrineglandis dividedinto
two compartments,a secretoryportion (s) and a duct
(d). The secretoryportion of the gland consistsof a sim-
ple cuboidal epithelium,composedof dark and clearse-
cretory cells (which cannot be distinguishedfrom each
other unlessspecialproceduresareutilized).Intercellular
canaliculiarenoted betweenclearcells,which aresmaller
than the lumen (L) of the gland.Ducts (d) may be recog-
nizedreadilysincethey aredarkerstainingand composed
of stratifiedcuboidalepithelium.
Insetsa and b. Duct and secretory unit. Monkey. Plas-
tic section.X 540.
The duct is readilyevident,sinceits lumen (L) is sur-
rounded by two layersof cuboidal cells.Secretorycells (s)
of the eccrine sweat gland are surrounded by darker
staining myoepithelial cells (My).

Hair root,eccrinesweatgland,
and sebaceousgland

i);::i'

T KEY
AP arrectorpilimuscle d ducts My myoepithelialcells
BC basalcells ERS externalroot sheath N nucleus
BM innerglassymembrane HF hair follicle P papilla
Co cortex HR hair root secretory
CTS connectivetissuesheath IRS internalrootsheath sG sebaceousglands
Cu cuticle L lumen

23o ::' Integument

 t
1,, .,
TS

l$

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ao ta
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\t l

FICURE
3 4
FIGURE
Integument 231
PLATE1 1-4 I Nail,Pacinianand Meissner'sCorpuscles
FIGURE 1 Fingernail. l.s. Paraffin section. x 14.
The nail is a highly keratinizedstructurethat is located
on the dorsal surfaceof the distal phalanx (Ph) of each
finger and toe. The horny nail plate (NP) extendsdeep
into the dermis,forming the nai.lroot (NR). The epider-
mis of the distalphalanxforms a continuousfold, result-
ing in the eponychium (Ep), or cuticle,the nail bed (NB)
underlying the nail plate, and the hyponychium (Hy).
The epithelium (arrow) surrounding the nail root is re-
sponsiblefor the continuous elongationof the nail. The
dermis (D) betweenthe nail bed arid the bone (Bo) of the
distalphalanxis tightly securedto the fibrous periosteum
(FP).Note that this is a developingfinger,asevidencedby
the presenceofhyaline cartilage(HC) and endochondral
osteogenesis (arrowheads).
FIGURE 2 ; Fingernoil. x.s. Paraffin section. x 14.
The nail plate (NP) in cross-section presentsa convex
appearance.On either side it is bordered by a nail wall
(NIM) and the grooveit occupiesis referredto asthe lat-
eral nail groove (NG). The nail bed (NB) is analogousto
four layersof the epidermis,while the nail plate repre-
sentsthe stratum corneum. The dermis (D), deepto the
nail bed, is firmly attachedto the fibrous periosteum (FP)
of the bone (Bo) of the terminal phalanx. Observethat
the fingertip is covered by thick skin whose stratum
corneum (SC) is extremely well developed. The small
darkly staining structures in the dermis are sweat glands
(swG).

FIGURE3 Meissner's corpuscle. Paraffin section.
x 540.
Meissner's corpuscles are ovai, encapsulated
mechanoreceptors lying in dermal ridgesjust deepto the
stratum germinatirum (SGe).They are especiallypromr-
nent in the genital areas,lips, fingertips, and solesof the
feet.A connectivetissuecapsule(Ca) envelopsthe corpus-
cle.The nuclei (N) within the corpusclebelongto flattened
(probably modified) Schwannceils,which are arranged
horizontally in this structure.The afferentnervefiber (NF)
piercesthe baseofMeissner'scorpuscle,branches,and fol-
Iowsa tortuouscoursewithin the corouscle.
FIGURE 4 .c' Pocinian corpuscle. Paraffin section.
x 132.
Paciniancorpuscles,locatedin the dermis and hlpo-
dermis, are mechanoreceptors. They are composedof a
core with an inner (IC) and an outer (OC) region,aswell
asa capsule(Ca) that surroundsthe core.The inner core
invests the afferent nerve fiber (NF), which loses its
myelin sheathsoon after entering the corpuscle.The core
cellsaremodified Schwanncells,while the componentsof
the capsuleare continuouswith the endoneuriumofthe
afferentnervefiber.Paciniancorpusciesarereadilyrecog-
nizablein sectionsincethey resemblethe cut surfaceofan
onion. Observethe presenceof an arrector pili muscle
(AP) and profilesof ducts (d) of a sweatglandin the vicin-
iry of, but not associated
with, the paciniancorpuscle.

Fingernail
'\

I KEY
AP arrectorpili Hy hyponychium NR nail root
capsule tc Innercore NW nailwall
Bo bone N nuclei OC outer core
D dermis NB nailbed Ph distalphalanx
o duct NF nervefiber SC stratumcorneum
eponychrum NG nail groove SGe stratumgerminativum
FP fibrousperiosteum NP nailplate swG sweatglands
HC hyalinecartilage

232 .:' Integument

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PLATE1 1-5 I Sweat Gland,ElectronMicroscopg
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FIGURE I Sweat gland. x.s. Human. Electron
microscopg. \ 5040.
Iumenand tl-relatcralinterccllularspace;ancl(3) between I
the rrain lumen (L)
a clearccllancla clarkcell,scparating
Tight jLrnctions(arrows)occur at three locationsin
the sccreton'coil of hunran srveatglancls:( l ) bctl'ccn
clearcells (C) scparatingthe lumcr.rof the intercellular
anrl intercellularspacc.Note the prcsenccof secretory
granules(SG)anclmyoepithelialcell (ME) (Fror.r.r
gnrrn JV, BankHL, BigelorvJB,(lravcsJS,SpicerSS:Arr
I3rig- t
canaliculus (arrorvhead)rnd thc basolatcralinterccllular I Attat 162:337-3(r8,19{t1.)
space:(2) bctrvccntrvodark cells(D) separating
234 Intesument
the m.tin
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I TIEIT
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t
The respiratory system functions in exchanging
I carbon dioxide for oxygen, which will then be
distributed to all of the tissuesof the body. To
accomplishthis function, air must be brought to
I that portion of the respiratory system where
exchangeof gasescan occur. The respiratory sys-
tem, therefore, has a conducting portion and a
I respiratoryportion. Someof the Iargerconduitsof
the conducting portion are extrapulmonary
whereas its smaller components are intrapul-
t monary. The respiratory portions, however, are
completely intrapulmonary. The luminal diameters
of the variousconduitscanbe modified by the pres-
enceof smooth musclecellsalong their length.
I tive in function. Axons of the olfactory cells are
I CONDUCTINGPORTION OF
THE RESPIRATORYSYSTEM
I The extrapulmonary region of the conducting por-
tion consistsof the nasal cavities,pharymx,larynx,
trachea,and bronchi. The intrapulmonary region
entails the intrapulmonary bronchi, bronchioles,
I and terminal bronchioles(seeGraphic 12-1).
I ExtrapulmonaryRegion
The extrapulmonary region of the conducting por-
I tion modifies the inspired air by humidifying,
cleansing,and adjusting its temperature. Cleansing
and humidifring actions are accomplished by the
t mucosa of the respiratory tract. This mucosa is
composed of pseudostratified ciliated columnar
epithelium with numerous goblet cells and an
underlying connective tissue sheath that is well
I endowed with seromucous glands. Modulation of
the temperatureof the inspiredair is accomplished
in the nasal cavity by the rich vascularity of the
t connectivetissuejust deepto its respiratoryepithe-
lium. In certain areasof this cavity the mucosa is
modified to function in olfaction and is referred to
t System I
r2
as the olfactory mucosa. The glands in the lamrna
propria of this mucosa produce a thin mucous
secretionthat dissolvesodoriferoussubstances. The
olfactory cells lying within the pseudostratified
columnar olfactory epithelium perceive these sen-
sory stimuli. In addition to the olfactory cells, two
other cell tFpescompose the olfactory epithelium,
namely, supporting cellsand basalcells.Supporting
cells do not possessany sensory function. They
manufacture a yellowish-brown pigment that is
responsiblefor the coloration of the olfactory mu-
cosa.Thesecellsinsulateand support the olfactory
cells.Basal cells are small, dark cells that Iie on the
basement membrane and, probably, are regenera-
collectedinto small nervebundles that passthrough
the cribriform plate of the ethmoid bone asthe first
cranial nerve,the olfactory nerve.
The conducting portion ofthe respiratorysystem
is supportedby a skeletoncomposedof bone and/or
cartilagethat assistsin the maintenanceof a patent
lumen. The luminal diametersof these airways are
controlled by smooth muscle cells located in their
walls.The larynx, a region of the conductingportion,
is designedto prevent foreign objectsfrom gaining
entranceinto it and for phonation. It is composedof
nine cartilages,three of which are paired, numerous
extrinsic and intrinsic muscles, and several liga-
ments.The actionsof thesemuscleson the cartilages
and ligamentsmodulate the tension and positioning
of the vocal folds, thus permitting variations in the
pitch of the soundbeing produced.The lumen of the
larynx is subdivided into three compartments:
vestibule,ventricle, and infraglottic cavity. The last
named region is continuous with the lumen of the
trachea,a structuresupportedby 15to 20 horseshoe-
shapedsegmentsof hyaline cartilage. The tracheal
Iumen is lined by a respiratoryepithelium composed
of various cell types,namely,goblet cells,basalcells,
ciliated cells,brush cells, and, probably, hormone-
producing DNES cells.The tracheasubdividesinto
the two primary bronchi that leadto the right and the
left lungs.
Respiratory 235
Intrapulmonary
Region
The intrapulmonary region is composedof intra-
pulmonary bronchi (secondarybronchi) whose
walls are supported by irregular plates of hyaline
cartilage.Intrapulmonarybronchi giveriseto bron-
chioles,tubes of decreasingdiametersthat do not
possess
a cartilaginoussupportingskeleton.The ep-
ithelial lining of the larger bronchioles is ciliated
with a fewgobletcells,but thoseof smallerbranches
become simple columnar, with goblet cells being
replacedby Clara cells.Moreover, the thicknessof
their wallsalsodecreases, asdoesthe luminal diam-
eter. The last region of the conduction portion is
composedof terminal bronchioles whose mucosa
is further decreasedin thicknessand complexiW.
The patencyof thoseairwayswhosewalls do not
possessa cartilaginoussupport is maintained by
elasticfibers that radiatefrom their periphery and
intermingle with elastic fibers emanating from
nearbystructures.
RESPIRATORYPORTION OF
THE RESPIRATORYSYSTEM
The respiratoryportion beginswith branchesof the
terminal bronchiole, known as respiratory bron-
chioles(seeGraphic l2-2). Thesearevery similar to
terminal bronchiolesexceptthat they possessout-
pocketingsknown as alveoli,structureswhosethin
walls permit gaseousexchange.Respiratorybron-
chioles lead to alveolar ducts that end in an ex-
panded region, known as alveolar sacs,with each
sacbeing composedof a number of alveoli.The ep-
ithelium of alveolarsacsand alveoliis composedof
two t)?es of cells:highly attenuatedtype I pneumo-
cytes,which form much of the lining of the alveolus
and alveolarsac;and tlpe II pneumocytes,cellsthat
manufacture surfactant, a phospholipid that re-
ducessurfacetension.Associatedwith the respira-
236 = Respiratory
System
tory portion of the lungs is an extremelyrich capil-
lary network, supplied by the pulmonary arteries
and drainedby the pulmonaryveins.The capillaries
invest each alveolus,and their highly attenuated
nonfenestrated, continuousendothelialcellsclosely
approximate the type I pneumocytes.In fact, in
many areasthe basallaminaeof the two fuseinto a
singlebasallamina,providing for a minimal blood-
air barrier, thus facilitating the exchangeof gases.
Therefore,the blood-air barrier is composedof the
attenuatedendothelialcell of the capillary,the two
combined basal laminae, the attenuated type I
pneumoc).te,and the surfactantand fluid coatingof
the alveolus.
Sincethe lung containsa largenumber of alve-
oli, these small spacesthat crowd against each
other are separatedfrom one another by walls of
various thicknessesknown as interalveolar septa.
The thinnest of theseportions often presentscom-
municating alveolar pores, whereby air may pass
betweenalveoli.A somewhatthicker septum may
possessintervening connective tissue elements
that may be as slenderas a capillarywith its atten-
dant basal lamina, or it may have collagen and
elasticfibers as well as smooth muscle fibers and
connective tissue cells. Macrophages,known as
dust cells, are often noted in interalveolar septa.
Thesedust cells are derived from monocytesand
enter the lungsvia the bloodstream.Here they ma-
ture and becomeextremelyefficient scavengers, It
is believedthat dust cellsarethe most numerous of
all cell types,eventhough they are eliminatedfrom
the lungs at a rate of 50 million per day. Although
it is not known whether they actively migrate to
the bronchioles or reach it via fluid flow, it is
known that they aretransportedfrom there within
the mucus layer, via ciliary action of the respira-
tory epithelium, into the pharynx. Once they
reach the pharynx they are either expectoratedor
swallowed.

I Histophgsiotogg
I . M E C H A N I S MO F O L F A C T I O N
The sensorycells of the olfactory epithelium are
bipolar neuronswhosereceptorendsare modified
cilia that extendinto the overlyingmucus.Odorant-
binding proteins (integralmembraneproteins) ly-
ing within the plasmamembraneof the cilia aresen-
sitiveto moleculesof specificodor groups,and when
such a moleculebinds to the receptor,one of two
possibilitiesoccurs. The receptor itself may be a
gatedion channel,and the ion channelopensor the
receptor activatesadenylatecyclase,causingthe for-
mation of cAMP, which facilitatesthe opening of
ion channels.In eithercase,openingofthe ion chan-
nel resultsin ion flow into the cell with subsequent
depolarizationof the plasmalemma,and the olfac-
tory cell becomesexcited.
The odorant must satisfyat leastthree require-
ments, it must be volatile, water soluble,and lipid
soluble so that it can enterthe nasalcavity (volatil-
ity), penetratethe mucus (water solubility), and be
able to have accessto the phospholipid membrane
(lipid solubility).
I I . M E C H A N I S MO F R E S P I R A T I O N
The processofinspiration requiresenergy,in that it
depends on the contraction of the diaphragm
and elevationofthe ribs, increasingthe sizeofthe
thoracic cavity. Since the visceral pleura adheres
to the parietal pleura, the lungs becomestretched.
As the lung volume is increased,gaspressureinside
the lungs becomeslower than atmosphericpres-
sure,and air entersthe lunqs.
C l i n i c a lC o n s i d e r a t i o n se c I
Hgaline Membrane Disease
H y a l i n em e m b r a n e disease i sf r e q u e n t l y
observedln prematureinfantswho lack
adequate a m o u n t so f p u l m o n a r sy u r f a c t a nTt h i s
diseaseis characterized by labored breathing,
s i n c ea h i g ha l v e o l asr u r f a c e t e n s i o nc. a u s e db y
i n a d e q u a tlee v e l so f s u r f a c t a nm t , a k e si t d i f f i c u l t
t o e x p a n dt h e a l v e o l iT h ea d m i n i s t r a t i oonf g l u -
c o c o r t i c o i dpsr i o rt o b i r t hc a ni n d u c es y n t h e s i s
TN#TT
The processof expiration does not require en-
ergy,sinceit is dependenton relaxationof the mus-
cles resoonsiblefor inspiration as well as on the
stretched elastic fiberi of the expanded lungs,
which return to their restinglength.As the muscles
relax,the volume of the thoracic cagedecreases, in-
creasingthe pressureinsidethe lung, which exceeds
atmosphericpressure.The additional force of the
elasticfibers returning to their resting length drives
air out ofthe lungs.
M E C H A N I S MO F G A S E O U S
EXCHANCE
The partial pressuresof 02 and CO2areresponsible
for the uptakeor releaseofthese gasesby red blood
cells. Since cells convert 02 to CO2 during their
metabolism,the partial pressureof CO2 is high in
tissues,and this gasis preferentiallytakenup by red
blood cells. Simultaneouslythey releaseoxygen.
The converseis true in the lungs,where02 is taken
up by red blood cellsand COz is released.
Oxygen uptake and releaseis accomplishedby
the heme moiety of the hemoglobin molecule
without the requirement of enzymatic catalysis.
Carbon dioxide, however, is ferried in three differ-
ent ways: as a gas dissolvedin its molecular form
(7o/o); as carbaminohemoglobin, which as molecu-
lar CO2 forms a weak bond with hemoglobin
(23o/o); and as the bicarbonateion, HCOt (70Vo).
Red blood cellscontain the enzymecarbonic anhy-
drase, which facilitates the rapid formation of
HzCOr, which then immediately dissociatesto
form bicarbonateand hydrogenions.
thuscircumventing
of surfactant theappearance
of thedisease
Emphgsema
Emphysema isa disease thatresults
fromde-
structionof alveolarwallswiththeconse-
quentformation of largecystlikesacs.reducing
(continues)
System m 237
Respiratory
 (Continued)
ClinicafConsiderations
I
thesurfaceavailable forgasexchange Emphy- obstructed by airwayspasm(bronchio-
I
semais markedby decreasedelasticityof constriction),mastcell-induced inflammatory
thelungs,whichareunable
duringexpiration
to recoiladequately
lt isassociated withexposure
response to allergensand/orotherslimulithat
wouldnot affecta normallung,andthe forma- I
to cigarettesmokeandothersubstances that tionof excess mucusAsthmaattacksvary
inhibit a protein
ct1-antitrypsin, thatnormally wlththeindividual,in someil is hardlynoticed,
protects
produced
thelungsfromtheactionof elastase
by alveolar macrophages
whereas withothersshortness
veryevident andwheezing
of breathis
accompanies breath-
I
ingout.Mostindividuals whosufferfrom
BronchialAsthma
Bronchial
asthmais a condition
wherethe
asthmatic condition
bronchodilators,
usenebulizers
suchas albuterol,
containing
to relieve
I
bronchi
become partially
andreversibly the attack
I
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t
I
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238 m Respiratory
System I
I IIIII

I Summargof HistologicalOrganization
t I . CON D U C T I NG
P OR T ION Bronchi
E. Intrapulmonary
These and subsequentpassageways
are completely
I A. Nasal Cavity
l. Respiratorg Region surroundedby lung tissue.
The respiratory region is lined by respiratory l. Mucoso

I (pseudostratified ciliated columnar) epithelium.

The subepithelial connective tissue is richly vascu-
larized and possesses
Intrapulmonary bronchi are lined by respiratory
epithelium with goblet cells.The subepithelialcon-
nective tissueis no longer bordered by an elastic
seromucousglands.
lamina.
I 2. Olfactory Region
The epithelium of the olfactory region is thick 2. Muscle
pseudostratified ciliated columnar epithelium Two ribbons of smooth muscle are wound helically
composedof three cell types:basalcell,sustentacu- around the mucosa.
I lar cells, and olfactory cells. The lamina propria is
richly vascularizedand possesses Bowman's glands,
3. Caftilage
The C rings are replacedby irregularly shapedhya-
which produce a watery mucus. line cartilageplatesthat encirclethe smooth muscle
I layer. Dense collagenous connective tissue con-
nectsthe perichondriaofthe cartilageplates.
B. Larynx
I Thelarynxis linedby a respiratory
epitheliumex-
cept for certain regions that are lined by stratified
4. Glands
Seromucous glands occupy the connective tissue
between the cartilageplates and smooth muscle.
squamous nonkeratinized epithelium. From supe-
Lymphatic nodules and branchesof the pulmonary
t rior to inferior, the lumen of the lanrnx presents
three regions: the vestibule, ventricle, u.ti ittf.u-
arteriesare alsopresent.
glottic cavity. The ventricular and vocal folds are
F. Bronchioles
I the superior and inferior boundaries of the ventri-
cle, respectively.Cartilages,extrinsic and intrinsic
muscles,aswell as mucous and seromucousglands
Bronchioles are lined by ciliated simple columnar
to simple cuboidal epithelium interspersedwith
are presentin the larynx.
t nonciliated Clara cells. Goblet cells are found only
in largerbronchioles.The lamina propria possesses
no glandsand is surrounded by smooth muscle.The
C. Trachea
t I. Mucosa
The mucosaof the tracheais composedof a respi-
walls of bronchiolesare not supportedby cartilage.
The largestbronchioles areabout I mm in diameter.

ratory epithelium with numerous goblet cells, a

I lamina propria, and a well-defined elasticlamina.

2. Submucosa
G. TerminalBronchioles
Terminal bronchioles are usually lessthan 0.5 mm
The submucosahousesmucous and seromucous in diameter. The lumen is lined by simple cuboidal

I glands.
3. Adventitid
epithelium (some ciliated) interspersedwith Clara
cells.The connectivetissueand smooth muscle of
the wall of the terminal bronchioles are greatly re-
The adventitia is the thickest portion ofthe tracheal
I wall. It housesthe C rings of hyaline cartilage (or
thick connectivetissuebetweenthe rings). Posteri-
duced.

orly, the trachealis muscle (smooth muscle) fills in II. RESPIRATORY PORTION
I the gap betweenthe free ends of the cartilage.
A. RespiratoryBronchiole
Respiratory bronchioles resemble terminal bron-
D. Extrapulmonary
Bronchi
I Extrapulmonary bronchi resemble the trachea in
histologic structure.
chioles,but they possessoutpocketingsofalveoli in
their walls.This is the first region where exchangeof
gasesoccurs.

I System *
Respiratory 239
B. AlveolarDucts
Alveolar ducts possessno walls of their own. They
are long, straight tubes lined by simple squamous
epithelium and displaynumerousoutpocketingsof
alveoli. Alveolar ducts end in alveolar sacs.
C. Alveolar Sacs
Alveolar sacs are composed of groups of alveoli
clusteredaround a common air space.
D. Alveolus
An alveolus is a small air space partially sur-
rounded by highly attenuated epithelium. Two
240 RespiratorySystem
types of cells are present in the lining, type I pneu-
mocytes (lining cells) and type II pneumocytes
(produce surfactant).The opening of the alveolus
is controlled by elastic fibers. Alveoli are separated
from each other by richly vascularized walls
known as interalveolar septa, some of which
present alveolar pores (communicating spaces
between alveoli). Dust cells (macrophages),
fibroblasts, and other connective tissue elements
may be noted in interalveolarsepta.The blood-air
barrier is a part of the interalveolar septum, the
thinnest of which is composedof surfactant,con-
tinuous endothelial cells, t1ryeI pneumocyte, and
their intervening fused basal laminae.
 TABLE | 2-l ** Summarg Table of Respiratorg Sgstem
Division Region Skeleton Glands Epithelium Cilia Goblet Cells SpecialFeatures

Nasal cavity Vestibule Hyaline Sebaceousand Stratifiedsquamous No No Vibrissae

cartilage sweatglands keratinized
Respiratory Bone and Seromucous Pseudostratified Yes Yes Largevenousplexus
hyaline ciliatedcolumnar
cartilage
Olfactory Nasal conchae Bowman's Pseudostratified Yes No Basalcells;sustentacular
(bone) glands ciliatedcolumnar cells; olfactorycells;
nerve fibers
Pharynx Nasal Muscle Seromucous Pseudostratified Yes Yes Pharyngealtonsil;
glands ciliatedcolumnar eustachiantube
Oral Muscle Seromucous Stratifiedsquamous No No Palatinetonsils
glands non- keratinized
Larynx Hyaline Mucous and Stratifiedsquamous Yes Yes Vocal cords;epiglottis;
and elastic seromucous non-keratinized sometastebuds
cartilage glands and pseudostratified
ciliatedcolumnar
Trachea and C-rings of Mucous and Pseudostratified Yes Yes Trachealismuscle;
extra-pulmonary hyaline seromucous ciliatedcolumnar elasticlamina
(primary bronchi) cartilage glands
Intra- pulmonary Secondary Platesofhyaline Seromucous Pseudostratified Yes Yes Two helically oriented
conducting bronchi cartilage glands ciliatedcolumnar ribbons of smooth muscle
Bronchioles Smooth None Simplecolumnar Yes Only in larger Clara cells
muscle to simple cuboidal bronchioles
Terminal Smooth None Simple cuboidal Some None Lessthan 0.5 mm in
bronchiole muscle diameter;Clara cells
Respiratory Respiratory Somesmooth None Simplecuboidal Some None Outpocketings of alveoli
bronchiole muscle and simple squamous
o
Alveolar duct None None Simplesquamous None None Outpocketings of alveoli;
U) type I pneumocl'tes;
(D type II pneumocltes;
3 dust cells
€ Alveolus None None Simplesquamous None None Tlpe I pneumocytes;
type II pneumocytes;
N
I\ dust cells
GRAPHIC12- 1 r ConductingPortion of RespiratorgSgstem t
t
Intrapulmonary
I
bronchus
plate
Cartilage I
Smoothmuscle
fibers
t
t
I
Pulmonaryartery
(canyingdeoxygenated
blood)
t
Terminalbronchiole

Respiratory
I
bronchiole
I
I
Alveolarelastin
network
t
I
l
t
t
I
Alveolar
capillary
network
t
242 I Respiratory
System r
I GRAPHfC12-2 1 RespiratorgPortionof RespiratorgSgstem

I
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I
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t Dustcell
(macrophage)

I Lamellar
bodies
I
I Typell pneumocyte

I Gasexchangeoccurring
at thealveolar-capillary
barrier

I RespiratorySystem J 243
PLATE12-1 r OlfactorgMucosa,Lorgnx
FIGURE I Olfactorg area. Human. Paroffin
section. x 210.
The olfactory mucosaof the nasalcavity is composed
of a thick olfactory epithelium (OE) and a lamina
propria (LP) richly endowed with blood vessels(BV),
lymph vessels(LV), and nervefibers (NF) frequentlycol-
lected into bundles. The lamina propria also contains
Bowman's glands (BG) which produce a watery mucus
that is deliveredonto the ciliated surfaceby short ducts.
The boxed areais presentedat a higher magnificationrn
Figure2.
FTGURE 2 rrirOlfactorg epithelium. Human. Paraffin
section. x 540.
This is a higher magnificationof the boxed areaof the
previousfigure. The epithelium (OE) is pseudostratified
ciliated columnar, whose cilia (C) are particularly
evident.Although hematoxylin and eosin stainedtissue
does not permit clear identification of the various cell
types,the positionsof the nuclei permit tentativeidenti-
fication. Basalcells (BC) are short, and their nuclei are
nearthe basementmembrane.Olfactory cell (OC) nuclei
are centrallylocated,while nuclei of sustentacularcells
(SC) are positionednear the apexofthe cell.

FIGURE 3 lntroepitheliol gland. Human. Paroffin
section. x 540.
The epitheiium of the nasalcavity occasionallydis-
plays small, intraepithelial glands (IG). Note that these
structuresare clearlydemarcatedfrom the surrounding
epithelium. The secretoryproduct is releasedinto the
space(asterisk)that is continuous with the nasal cavity
(NC). The subepithelialconnectivetissue (CT) is richly
suppliedwith blood vessels(BV) and lymph vessels(LV).
Observe the plasma cells (PC), characteristicof the
subepithelialconnectivetissueof the respiratorysystem,
which alsodisplaysthe presenceof glands(GI).
FIGURE 4 ,,'-Largnx. I.s. Humon. Paraffin section.
x 14.
The right half of the larynx, at the level of the ventri-
cle (V), is presentedin this surveyphotomicrograph.The
ventricle is bounded superiorly by the ventricular folds
(falsevocal cords) (VF) and inferiorly by the vocal folds
(VoF). The spaceabovethe ventricularfold is the begin-
ning ofthe vestibule (Ve) and that below the vocal fold is
the beginningofthe infraglottic cavity (IC). The vocalis
muscle (VM) regulatesthe vocal ligament presentin the
vocal fold. Acini of mucous and seromucousglands(GI)
are scatteredthroughout the subepithelialconnective
tissue. The laryngeal cartilages (LC) are also shown to
advantage.

T KEY
BC basalcells LC laryngealcartilages SC sustentacularcells
BG Bowman'sglands LP laminapropria ventricle
BV bloodvessels LV lymphvessels Ve vestibule
C cilia NC nasalcavity VF ventricularfolds
CT connectivetissue NF nervefibers VM vocalismuscle
Gl glands olfactorycells VoF vocal folds
lC infraglotticcavity OE olfactoryepithelium
lG intraepithelialglands PC plasmacells

244 :i RespiratorySystem
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PLATE12-2 I Trachea
FIGURE I i Trachea. l.s. Monkeg. Paraffin section.
x 20.
This surveyphotomicrographpresentsa longitudinal
sectionofthe trachea(Tr) and esophagus(Es). Observe
that the lumen (LT) of the tracheais patent, due to the
presenceofdiscontinuous cartilaginousC-rings (CR) in
its wall. The C-rings of the tracheaare thicker anteriorly
than posteriorly and are separatedfrom each other by
thick, fibrous connectivetissue(arrows)that is continu-
ous with the perichondrium of the C-rings.The adventi-
tia of the tracheais adheredto the esophagusvia a loose
tlpe of connectivetissue(CT), which frequentlycontains
adiposetissue.Note that the lumen (LE) of the esophagus
is normally collapsed.A region similar to the boxed area
is presentedat a higher magnificationin Figure3.
FIGURE 2 | Trqchea. Ls. Monkeg. Plostic section.
x 210.
The trachea is lined by a pseudostratified ciliated
columnar epithelium (E), which housesnumerous gob-
let cells (GC) that actively secretea mucous substance.
The lamina propria (LP) is relatively thin, while the sub-
mucosa (SM) is thick and contains mucous and seromu-
cous glands (GI) whose secretoryproduct is delivered to
the epithelial surfacevia ducts that pierce the lamina pro-
pria. The perichondrium (Pc) ofthe hyaline cartilage C-
rings (CR) mergeswith the submucosal connective tis-
sue.Note a longitudinal sectionof a blood vessel(BV),
indicativeof the presenceof a rich vascularsupply.

FIGURE 3 tt Tracheq. l.s. Monkeg. Paroffin section.

x 200.
This photomicrograph is a higher magnificationof a re-
gion simi-larto the boxed area of Figure 1. The pseudos-
tratified ciliated columnar epithelium (E) lies on a base-
ment membrane that separatesit from the underlying
lamina propria.The outer extentof the lamina propria is
demarcatedby an elasticlamina (arrows), deepto which is
the submucosa (SM) containing a rich vascular supply
(BV). The C-ring (CR), with its attendant perichondrium
(Pc), constitutesthe most substantivelayer ofthe tracheal
wall. The adventitiaof the trachea,which someconsiderto
include the C-ring, is composedof a looseqpe of connec-
tive tissue,housing some adipose cells (AC), nerves (N),
and blood vessels(BV). Collagenfiber bundles of the ad-
ventitia securethe tracheato the surrounding structures.

Trachea

T KEY

AC adiposecells Es esophagus LT lumen-trachea

BV bloodvessels GC gobletcells N nerves
CR C-rings GI mucous/seromucous Pc perichondrium
CT connectivetissue glands SM suDmucosa
E epithelium LE lumen-esophagus Tr trachea
LP laminapropria

246 € Respiratory
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PLATE12-3 I RespiratorgEpitheliumand Cilia,ElectronMicroscopg
FIGURE | | Trocheal epithelium. Hamster.
Electron microscopg. x 7182.
The trachealepithelium of the hamsterpresentsmu-
cus-producing goblet cells (GC) as well as ciliated
columnar cells (CC), whosecilia (arrows) project into the
lumen. Note that both cell types are well endowed with
Golgi apparatus (GA), while goblet cells are particularly
rich in rough endoplasmic reticulum (rER). (Courtesy of
Dr. E. McDowell.)
Inset Bronchus. Human. Electron microscopy.
x 7182.
The apical region of a ciliated epithelial cell presents
both cilia (C) and microvilli (arrow). (Courtesyof Dr. E.
McDowell.)

Trachea

T KEY
C cilia GA Golgiapparatus rER roughendoplasmic
CC ciliatedcolumnarcell GC gobletcell reticulum

248 * Respiratory
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R e s p i r a t o rSyy s t e m 249
 PLATE12-4 I Bronchi,Bronchioles
FIGURE | * Lung, Paraffin section. x 14.
This surveyphotomicrographpresentsa sectionof a
lung, which permits the observationof the various con-
duits that conduct air and blood to and from the luns.
The intrapulmonary bronchus (IB) is recognizableby iis
thick wall containing platesof hyaline cartiage (HC) and
smooth muscle(Sm). Longitudinalsectionsof a bronchi-
ole (B), terminal bronchiole (TB), and respiratorybron-
chiole (RB) are also evident.Smallerbronchioles(aster-
isks) may also be recognized,but their identification
cannotbe ascertained. Arrows point to structuresthat are
probablyalveolarductsleadinginto alveolarsacs.Several
blood vessels(BV), branchesof the pulmonary circula-
tory system,may be noted. Observethat lymphatic nod-
ules (LN) are alsopresentalongthe bronchiai tree.
F|GURE 2 * lntrdpulmonarg bronchus. x.s. pardmn
section. x 132.
Intrapulmonary bronchi are relatively large conduits
for air, whoselumina (L) are lined by a tlpical respiratory
epithelium (E). The smooth muscle (Sm) is found be-
neath the mucous membrane and it encircles the entire
lumen. Note that gaps (arrows) appear in the muscle
layer, indicating that two ribbons of smooth muscle wind
around the lumen in a helical arrangement.Platesof hya-
line cartilage (HC) act as the skeletalsupport, maintain-
ing the patency of the bronchus. The entire structure ls
surroundedby lung tissue(LT).

F|GURE I * Bronchiole. x.s. paraffin section. x
2 10 .
Bronchiolesmaintain their patent lumen (L) without
the requirement of a cartilaginoussupport, since they
are attachedto surrounding lung tissueby elasticfibers
radiating from their circumference. The lumina of
bronchioles are lined by simple columnar to simple
cuboidal epithelium (E), interspersedwith Clara cells
(CC), dependingupon the diameter of the bronchiole.
The lamina propria (LP) is thin and is surrounded by
smooth muscle (Sm), which encirclesthe lumen. Bron-
chioleshaveno glandsin their walls and are surrounded
by lung tissue(LT).
FIGURE 4 8 Terminal bronchioles. x.s. Paraffin
section. x 132.
The smallestconducting bronchioles are referred to as
terminal bronchioles(TB). Thesepossess very small di-
ametersand their lumina arelined with a simpiecuboidal
epithelium (E) interspersed with Clara ceilj (CC). the
connective tissueis much reduced and the smooth mus-
cle layersare incomplete and difficult to recognizeat this
magnification. Terminal bronchioles give rise to respira-
tory bronchioles (RB) whose walls resemblethose of the
terminal bronchioles,exceptthat the presenceofalveoli
permit the exchangeofgasesto occur.

Bronchialsystemand lung

I KEY
B bronchiole lB intrapulmonarybronchus R B respiratorybronchiole
BV bloodvessels L lumen Sm smoothmuscle
CC Claracells LN lymphaticnodule TB terminalbronchiole
E epithelium LP laminapropria
HC hyalinecartilage LT lung tissue

250 * Respiratory
System
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 PLATE12-5 I LungTissue
FIGURE I a Respirotorg bronchiole. poroffin FIGURE 2 a Alveolar duct. l.s. Human. Paroffin
section. x 2lO. section. x 132.
The respiratorybronchiolewhoselumen (L) occupies Alveolar ducts (AD), unlike respiratory bronchioles,
the lower half of this photomicrographpresentsan ap- do not possessa wall of their own. These structures are
parently thick wall with small outpocketings of alveoli lined by a simple squamousepitheliurn (E), composedof
(A). It is in thesealveoli that gaseousexchangesfirst oc- highly attenuated cells.Alveolar ducts present numerous
cur. The
r ne wall of
ofthe
tne resplratory
resoi bronchiole
bronchrolers
is composed
comoosedof ol outpocketingsofalveoli (A), and they end in alveolar sacs
a simple cuboidalepithelium,consistingof someciliated (AS), consistingof groups of alveoli clusteredaround a
cellsand Clara cells(CC). The remainderof the wall pre- common air space. Individual alveoli possess small
sents an incomplete layer of smooth muscle cells iur- smooth muscle cells that, acting like a purse string, con-
rounded by fibroelastic connectivetissue.Careful exami- trol the opening into the alveolus.Theseappear as small
nation of this photomicrographrevealsthat the wall of knobs (arrow). A region similar to the boxed areais pre-
the respiratory bronchiole is folded upon itself, thus giv- sentedat a higher magnification in Figure 3.
ing a misleadingappearanceof thick walls.

FIGURE 3 f Interalveolor septum. Monkeg. plostic
section. x 540.
This photomicrographis a higher magnificationof a
region similar to the boxed areaof Figure2. Two alveoli
(A) arepresented,recognizable asempty spacesseparated
from eachother by an interalveolarseptum (lS). The sep-
tum is composedof a capillary (Ca), the nucleus(aster-
isk) of whose endothelial lining bulges into the lumen
containing red blood cells (RBC). The interalveolarsep-
tum as well as the entire alveolusis lined by tfpe I pneu-
mocytes(Pl), which arehighly attenuatedsquamousep-
ithelial cells,interspersedwith type II pneumocytes (p2).
Thicker interalveolarseptahouseblood vessels(BV) and
connective tissue elements including macrophages
known as dust cells (DC). Note the presenceof smooth
musclecells(Sm) and connectivetissueelementsthat aD-
pear asknobs at the entranceinto the alveolus.
FIGURE 4 ) Lung. Dust cells. Paraffin section.
x 210.
The highly vascularnature ofthe lung is quite evident
in this photomicrograph, since the blood vessels(BV)
and the capillaries (Ca) ofthe interalveolar septaare filled
with red blood cells. The dark blotchesthat appear to be
scatteredthroughout the lung tissuerepresentdust cells
(DC), macrophagesthat have phagocytosedparticulate
matter.
Inset. Ltng. Dust cell, Monkey. Plastic section,
x 540.
The nucleus (N) of a dust cell (DC) is surroundedby
phagosomescontaining particulate matter that was prob-
ably phagocytosedfrom an alveolusofthe lung.

portionof respiratory
Respiratory system

I KEY
A alveolus Clara cell N nucleus
AD alveolarduct DC dustcell P1 typeI pneumocytes
AS alveolarsac E epithelium P2 typell pneumocytes
BV bloodvessel IS interalveolarseptum RBC redbloodcells
Ca capillary L tumen Sm smoothmuscle

252 x Respiratory
System
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PLATE12-6 I Blood-AirBarrier,ElectronMicroscopg

FIGURE I Blood-oir barrier. Dog. Electron
microscopg. x 85,500.
The blood-air barrier is composedof highly attenu-
atedendothelialcells(EC), tlpe I pneumocltes (pt ), and
an intervening basal lamina (BL). Note that the cyto-
plasm (arrows)ofboth cell tlpes is greatlyreduced,asev-
idencedby the closeproximity of the plasmalemmaon el-
ther side of the cytoplasm.The air spaceof the alveolus
(A) is empty,while the capillarylumen (L) presentsa part
of a red blood cell (RBC). (From DeFouw D: Anat Rec
209:77-84.1984.)

254 RespiratorySystem

r Digestive SgstemI
The digestivesystemfunctions in the ingestion, di-
gestion, and absorption of food as well as in the
elimination of unusableportions of thesematerials.
To accomplishthesefunctions, the digestivesystem
is organizedinto three major components:l) the
oral cavity,which is responsiblefor reducing food in
sizeand introducing it into the alimentary canal;2)
a muscular alimentary canal,alongwhoselumen the
ingested foods are converted, both physically and
chemically,into absorbablesubstances;and 3) a
glandular portion, which provides fluids, enzyrnes'
and emulsifying agentsnecessaryfor the proper
functioning of the alimentary canal.
ORAL REGION:ORAL CAVITY
The oral cavity maybe subdivided into two smaller
cavities:the externally positioned vestibule and the
internally placedoral cavity proper. The vestibule is
the spaceboundedby the lips and cheeksanteriorly
and laterally, whereas its internal boundary is
formed by the dental arches. The ducts of the
parotid glands deliver their secretoryproducts into
the vestibule(seeGraphics13-1and 13-2).
The oral cavity proper is bounded by the teeth
externally,the floor of the mouth inferiorly, and the
hard and soft palatessuperiorly. At its posterior ex-
tent, the oral cavity proper is continuous with the
oral pharynx, where the two are separatedfrom each
other by an imaginary plane. Both the oral cavity
proper and the vestibulearelined by stratified squa-
mous epithelium, which in regions that are subject
to abrasiveforces is modified into stratified squa-
mous keratinized (or parakeratinized) epithelium.
Oral Mucosa
The epithelium and underlining connective tissue
constitutethe oral mucosa.If the epitheliumis ker-
atinized (or parakeratinized)the mucosais said to
be masticatory mucosa, and if the epithelium is not
IIreII r3
keratinized, the mucosa is referred to as lining mu-
cosa.It should be noted that most of the oral cavity
possesses lining mucosa,with the exceptionof the
gingiva, hard palate, and the dorsal surface of the
tongue that are covered by masticatory mucosa.
Additionally, the oral cavity has areasof specialized
epithelia where intraepithelial structures,known as
taste buds, function in taste perception. Most taste
buds arelocatedon the dorsalsurfaceofthe tongue,
although the palate and pharynx also possessa few
of thesestructures.Mucosa,whoseepitheliumcon-
tains taste buds is known as specialized mucosa.
Each tastebud recognizesone or more of the four
tastesensations:sour, sweet,salt, or bitter.
The contents of the oral cavity are the teeth, uti-
Iized in biting and mastication, and the tongue' a
muscular structure that functions in the Prepara-
tion of the bolus,tastingof the food, and beginning
of deglutition (swallowing), among others.
SalivaryGlands,Palate,and Tonsils
The parotid, sublingual, and submandibular glands
deliver their secretionsinto the oral cavity proper.
The hard palate assiststhe tongue in the prepara-
tion of the bolus, and the soft palate, a moveable
structure, sealsthe communication between the
oral and nasal pharynges,thus preventing Passage
of food and water from the former into the latter.
The connectivetissueunderlying the epithelium
of the oral cavity is richly endowedwith minor sali-
vary glands that, secreting saliva in a continuous
fashion,contribute to the maintenanceof a moist
environment. Saliva functions also in assistingin
the processof deglutition by acting as a Iubricant
for dry foods.Moreover, enzymesPresentin saliva
initiate digestion of carbohydrates,while secretory
antibodies protect the body against antigenic sub-
stances.
The entrance to the pharynx is guarded against
bacterial invasion by the tonsillar ring, composed
of the lingual, pharyngeal,and palatine tonsils.
D i g e s t i v e s y s t e m. l 2 5 5
Histophgsiologg

I . T I S S U EI N T E R A C T I O N
IN
ODONTOGENESIS ClinicatConsiderations m I I
Odontogenesisis induced by the ectodermallyde-
rived cells of the dental lamina that expresslym- HerpeticStomotitis
phoid enhancerfactor-l (Lef-1), a transcripiion Herpetic a relatively
stomalltis, common dis-
factor.Lef-I inducesthe epithelialcellsto synthesize easecaused by theherpes simplex virus
and releasebone morphogenicprotein-4 (BMP-4), [HSV) typeI, isdistinguished by painful
fever
sonic hedgehog (Shh), and fibroblast growth blistersappearing on or in thevicinityof the
factor-8 (FGF-8).Thesesignalingmoleculesact on lips Thlsisa recurring disease sincethe
the underlyingectomesenchymal cellsto differenti- virus,in itsdormant phase, inhabitsthe
ate into odontogenic tissues.These neural crest- trigeminal ganglion lt travels alongtheaxon
derivedcellsbegin to expressBMP-4, the adhesive to cause theappearance of theblistersDur-
glycoproteintenascin,and the membrane-bounded ingtheactivestagethepatientis highlycon-
proteoglycan,syndecan.Moreover, they also ex- tagious, sincethevirusisshedviatheseep-
press severaltranscription factors, namely Egr-l ingclearexudate
(earlygrowth response-1),Msx-l (homeobox-con-
taining genes),and Msx-2. This activationof the ec- Necrotizing UIcerative Gingiviti s
tomesenchymeelicitstheir role in the induction of Necrotizing ulcerative gingivitis isanacuteul-
the tooth morphology, so that it is the ectomes- cerative condjtion of thegingiva withaccom-
enchymethat will determine,for instance,whether panying necrosis, halitosis, erythematous ap-
the developingtooth will becomea molar or an in- pearance, andmoderate to severe pain
cisor. Signaling molecules from the ectomes- Fever andregional lymphadenopathy may
enchymeinducethe formation of the enamelknot, alsobe evidentThisis usually a disease of
an epithelialstructurethat appearsin the vicinity of t h ey o u n ga d u l w
t h oi se x p e r i e n c si nt rge s s
the stratum intermedium of the enamelorgan.The andis notparticularly attentive to dentalhy-
pieneFreorrpntlv
' Trenonema vincentii and
enamelknot synthesizes and releasesits own signal- b''""

ing molecules,namely FGF-4, BMP-2, BMP-4, s r e p r e s e n itn l a r g en u m b e r s

f u s i f o r mb a c i l l u a
BMP-7, and sonic hedgehog. These signaling a n d t h e ya r e a l s ob e l i e v e dt o b e c a u s a t i v e
moleculespromote the differentiationof the inner a g e n t so f t h e c o n d i t i o nT r e a t m e nut s u a l l y
enamelepithelial cellsinto ameloblastsand thoseof c o n s i s to s f r i n s i n gw i t h d i l u t eh y d r o g e np e r -
the peripheralmostlayer of the dental papilla into o x i d es e v e r atll m e sd a i l ya n d m e t l c u l o u s
odontoblasts. Continued maintenance of the c l e a n i n gb y a d e n t a lp r o f e s s i o n aAl n t i b i o t i c
enamelknot is responsiblefor the buckling of the r e g i m e nm t a y a l s ob e r e c o m m e n d e d
inner enamelepitheliumresultingin the morphod-
ifferentiation of the enamelorgan into a template
that is the prototfpe of a molar tooth, whereasif the
enamelknot undergoesapoptosismorphodifferen-
tiation is constrainedand an incisor is formed.

255 * Digestive
SystemI

I Summargof HistotogicatOrganization
I. LIPS
The lips control accessto the oral cavity from the
outsideenvironment.
A. ExternalSurface
The external surfaceis coveredwith thin skin and,
therefore,possesses glands,
hair follicles,sebaceous
and sweatglands.
B. Transitional
Zone
The transitional zone (vermilion zone) is the pink
areaof the lip. Here the connectivetissuepapillae
extend deep into the epidermis.Hair folliclesand
sweatglandsare absent,whereassebaceous glands
are occasionallypresent.
C. MucousMembrane
The vestibularaspectof the lip is lined by a wet ep-
ithelium ( stratified squamousnonkeratinized) with
numerous minor mixed salivary glands in the
subepithelialconnectivetissue.
D. Core of the Lip
The core of the lip containsskeletalmuscle.
II.TEETH
Teeth are composedof three calcifiedtissuesand a
looseconnectivetissuecore,the pulp.
A. Enamel
Enamel is the hardestsubstancein the body. It is
made by ameloblasts,cellsno longer presentin the
eruptedtooth. Enamelis presentonly in the crown.
B. Dentin
Dentin is a calcified,collagen-basedmaterial that
constitutes the bulk of the crown and root; it sur-
rounds the pulp. Dentin is made by odontoblasts,
whoselong processes remain in channels,dentinal
tubules, traversing dentin. The odontoblast cell
body forms the peripheralextentof the pulp.
tl#rl
C. Cementum
Cementum is locatedon the root of the tooth, sur-
rounding dentin. Cementum is a collagen-based
calcifiedmaterial manufacturedby cementoblasts,
which maybecomeentrappedand then arereferred
to as cementocytes.Fibers of the periodontal liga-
ment are embeddedin cementum and bone, thus
suspending the tooth in its bony socket, the
alveolus.
D. Pulp
The pulp is a gelatinous tfpe of mesenchyrnal-
appearingconnectivetissuethat occupiesthe pulp
chamber.It is richly suppliedby nervesand blood
vessels.
III. GINGIVA
The gingiva (gum) is that regionof the oral mucosa
that is closelyappliedto the neck ofthe tooth and is
attached to the alveolar bone. It is covered by a
stratified squamouspartially keratinized (paraker-
atotic) epithelium. The underlying connective tis-
sue is denselypopulatedwith thick bundlesof col-
lagenfibers.
IV.TONGUE
The tongue is a muscular organ whose oral region
is freely moving, while its root is attachedto the
floor of the pharynx. Skeletalmuscle forms the core
of the tongue, among which groups of serousand
seromucousglandsare interspersed.
A. Oral Region(AnteriorTwo-Thirds)
The mucosa of the dorsal surfaceof the anterior
two-thirds of the tongue is modified to form four
typesof lingual papillae.
l. Filiform Papillae
Filiform papillae are long and slender and are the
most numerous. They form a roughened surface
(especiallyin animals such as cats) and are dis-
tributed in parallel rows along the entire surface.
They are covered by a parakeratinized stratified
squamousepithelium (but bearno tastebuds) over
a connectivetissuecore.
s
DigestiveSysteml 257
2. Fungiform Papillae
Fungiform papillae are mushroom shaped, are
scatteredamong the filiform papillae,and may be
recognizedby their appearanceas red dots. They
contain tastebuds alongtheir dorsalaspect.
3. Foliate Papillae
Foliate papillae appear as longitudinal furrows
along the side of the tongue near the posterior as-
pectof the anteriortwo-thirds.Their tastebuds de-
generateat an earlyagein humans.Serousglandsof
von Ebner are associated with thesepapillae.
4. Circumvallote Papillae
Circumvallatepapillaearevery largeand form a V-
shapedrow at the border ofthe oral and pharyngeal
portions of the tongue. Circumvallatepapillaeare
eachsurroundedby a moat or groove,the walls of
which contain taste buds in their stratified squa-
mous nonkeratinized epithelium. Serousglands of
von Ebner open into the baseof the furrow. The
connectivetissuecore of the circumvallatepapilla
possessesa rich nerveand vascularsupply.
B. Pharyngeal Region (Posterior
One-Third)
The mucosa of the posterior one-third of the
tongue presentsnumerouslymphatic nodulesthat
constitutethe lingual tonsils.
258 s# Digestive
SystemI
V. PALATE
The palate, composed of hard and soft regions,
separatesthe oral and nasal cavities from each
other. Therefore,the palatepossesses a nasal and
an oral aspect.The oral aspectis coveredby strat-
ified squamous epithelium (partially keratinized
on the hard palate),while the nasal aspectis cov-
ered by a respiratory epithelium. The subepithe-
lial connective tissue presentsdensecollagenfibers
interspersed with adipose tissue and mucous
glands.The core of the hard palatehousesa bony
shelf, while that of the soft palate is composedof
skeletal muscle.
VI. TOOTHDEVELOPMENT
Tooth development (odontogenesis)may be di-
vided into severalstages(seeGraphic 13-1).These
arenamedaccordingto the morphologyandlor the
functional state of the developing tooth. Dental
lamina, the first sign of odontogenesis,is followed
by bud, cap,and bell stages.Dentin formation ini-
tiates the appo-sition stage, followed by root for-
mation and erup-tion. Thesestagesoccur in both
primary (deci-duousteeth)and secondary(perma-
nent teeth) dentition.
t
I

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 13-1 I
GRAPHIC Toothand ToothDevelopment

Enamel

Gingival
sulcus Pulp
of gingiva
Epithelium
Dentin
Gingiva
Alveolarbone Cementum
Rootcanal

Periodontal
ligament

Apicalforamen

Tooth

The tooth,composedof a crownand root,is suspendedin its bonysocket,the alveolus,

by a dense,collagenous connective tissue,the periodentalligament.The crownof the
toothconsistsof two calcifiedtissues,dentin and enamel, whereasthe root is composed
of dentinand cementum.The pulpchamberoJthe crownand the rootcanalof the root
are continuouswithone another.They are occupiedby a gelatinousconnectivetissue,
the pulp, whichhousesbloodand lymphvessels,nervefibers,connective tissue
elements,as wellas odontoblasts,the cellsresponsible for the maintenanceand repair
of dentin.Vesselsand nervesservingthe pulpenterthe rootcanalvia the apical
foramen,a smallopeningat the apexof the root.

(A) Bud stage (B) Cap stage (C) Bell stage

Oral
epithelium

Dentallamina Dentallamina

Bonycrypt

(D) Apposition (E) Beginningof (F) Eruption into oral cavity

Enamel
Enamel
Dentin
Alveolar
bone Pulp

Cementum

Periodontal
ligament

260 * Digestive
SystemI
 C 13-2 r
GRAPHf Tongueand TosteBud

Filiformpapilla
tonsil
Palatinetonsil

Salivary
glands

Vallatepapillae
Taste bud
lntrinsicmuscle
sutcus
papilla
The core of the tongueis composedof skeletal
musclefibersthat interlacewith one another,
connectivetissue,and minor salivaryglands.

Tastecell

Taste buds are small,intraepithelial structures

composed of a total of 40-70 cells, basal cells,
neurepith€lial(taste)cells,and sustentacular
(supporting)cells.They functionin the perception
of the four primarytaste sensations,salt, sl teet,
bitler,and sour.

The dorsalsurfaceof the tongueis subdividedinto an anteriortwo-thirds,populatodby

the four typss of lingualpapillae,and a posteriorone-thirdhousingthe lingualtonsils.The
two rsgionsare separatedtrom one anotherby a "V-shaped'depression, the sulcus
terminalis.Fllliorm paplllae are short,conical,and highlykeratinized.Fungifrom
paplllae are mushroom-shaped, and thg dorsalaspectof their epitheliahousesthree to
fiw taste buds.Clrcumvallato paplllae, the largestot the lingualpapillae,are six to
twelvein number.Eachcircumvallatepapillais d€pressedinto the surhce of the tongue
and is surroundedby a moat-liketrough.The lateralaspectof the papillaas well as the
liningof the trough housesnumeroustaste buds.Follate paplllae are locatedon the
lateralaspectof the tongue.

DigestiveSystemlI 261
P L A T E1 3 - 1 I Lip
Ff GURE I Lip. Humon. Paraffin section. x 14.
The human lip presentsthree surfacesand a core (C).
The externalsurfaceis coveredby skin, composedofepi-
dermis (E) and dermis (D). Associatedhair follicles(ar-
row) and glandsare clearlyevident.The vermillion (red)
zone (YZ) is only found in humans. The high dermat
papillae(arrowheads)carryblood vessels closeto the sur-
face,accountingfor the pinkish coloration ofthis region.
The internal aspectis lined by a wet, stratified,squamous
nonkeratinizedepithelium (Ep) and the underlyingcon-
nectivetissuehousesminor salivaryglands.The core of
the lip is composedof skeletalmuscleinterspersedwith
fibroelasticconnectivetissue.
F|GURE 3 Lip. Human. Externol ospect. Paraffin
section. x 132.
The externalaspectof the lip is coveredby thin skrn.
Neither the epidermis(E) nor the dermis (D) presentany
unusualfeatures.Numerous hair follicles (HF) populate
this aspectof the iip, and sebaceousglands(Sg)aswell as
sweatglandsare noted in abundance.
I KEY
BV vascularsupply D dermis
core E epidermis
connectivetissue Ep epithelium
papillae HF hairfollicles
262 =i DigestiveSystemI
FIGURE 2 tr Lip. Human. Internal aspect. Paroffin
section. x 210.
The internal aspectof the lip is lined by a mucous
membranethat is continuouslykept moist by salivase-
cretedby the three major and numerous minor salivary
glands. The thick epithelium (Ep) is a stratified squa-
mous nonkeratinized t1pe, which presents deep rete
ridges (RR) that interdigitatewith the connectivetissue
papillae (CP). The connectivetissueis fibroelasticin na-
ture, displayinga rich vascularsupply (BV).
FfGURE 4 = Lip. Human. Vermilion zone. Paraffin
section. x 132.
The vermilion zoneof the lip is coveredby a modified
skin, composedof stratified squamouskeratinizedep-
ithelium (Ep) that forms extensiveinterdigitationswith
the underlying dermis (D). Neither hair follicles nor
sweatglandspopulatethis area(though occasionalseba-
ceousglands may be present).Note the cross-sectional
profiles of skeletalmusclefibers (SM) and the rich vas-
cular supply (BV) of the lip.
Lip
RR rete ridges
Sg sebaceousglands
SM skeletalmuscle
vz vermillion(red)zone
F I C U R E1

,' '". -'-, ';'-ffili;

:. - ,t -

FICURE
3 FICURE
4
System|
Digestive 263
PLATE13-2 I Toothand Pulp
FIGURE I Tooth. Humon. Ground section. x 14.
The tooth consistsof a crown, neck, and root, com-
posedof calcifiedtissuesurrounding a chamberhousing
a soft, gelatinouspulp. In ground sectiononly the hard
tissuesremain.The crown is composedof enamel(e) and
dentin (d), whose interface is known as the dentinoe-
namel junction (DEJ). At the neck of the tooth, enamel
meetscementum (c), forming the cementoenameljunc-
tion (CEJ).The pulp chamber (PC) is reducedin sizeas
the individual ages.The gap in the enamel(arrows)is due
to the presenceofa cariouslesion(cavity).A region sim-
ilar to the boxed areais presentedat a higher magnifica-
tion in Figure2.
FIGURE 2 * Tooth. Human. Ground section. x 132.
This photomicrographis a higher magnificationof a
region similar to the boxed area of the previous figure.
The enamel (e) is composed of enamel rods (arrows)
each surrounded by a rod sheath.Hypomineralizedre-
gions of enamelpresentthe appearanceof tufts of grass,
enamel tufts (ET), which extend from the dentinoenamel
junction (DEf ) partwayinto the enamel.Dentin (d), not
ashighly calcifiedasenamel,presentsIong narrow canals,
dentinal tubules (DT), which in the living tooth house
processes ofodontoblasts,cellsresponsiblefor the forma-
tion ofdentin.

FIGURE 3 ,: Pulp. Humon. Paraffin section. x 132. FIGURE 4 # Pulp. Human. Paraffin section. x 210.
The pulp is surroundedby dentin (d) from which it is This is a higher magnificationof the lower right cor-
separatedby a noncalcified dentin matrix (DM). The ner ofthe previousfigure.Note the presenceofblood ves-
pulp is said to possessfour regions:the odontoblastic sels (BV) and nerve fibers (NF), as well as the numerous
layer (OL), the cell-free zone (CZ), the cell-rich zone fibroblasts(F) ofthis gelatinousconnectivetissue.
(CR), and the core (C). The core of the pulp is composed
of fibroblasts (F), delicate collagen fibers, numerous
nervebundles (NB), and blood vessels(BV). Branchesof
theseneurovascularstructuresreachthe peripheryof the
pulp, where they supply the cell-richzone and the odon-
toblastswith capillariesand fine nervefibers.

Tooth

T KEY

BV bloodvessel o dentin F fibroblasts

C core DEJ dentinoenamel junction NB nervebundles
c cementum DM dentinmatrix OL odontoblasticlayer
CEJ cementoenameljunction DT dentinaltubule DI'\
pulpchamber
CR cell-richzone enamel
CZ cell-freezone ET enameltufts

264 tH Digestive
SystemI
 DT-
FIGURE
1

: "-'t
FICURE
4
DigestiveSystem| 265
PLATE13'5 t PeriodontalLigamentand Cingivo
FIGURE I Periodontal ligament. Human. Paraffin
section. x 132.
The root ofthe tooth, composedofdentin (d) and ce-
mentum (c), is suspendedin its alveolus(A) by a collage-
nous tissue,the periodontal ligament (PL). The strong
bandsofcollagen fibers (CF) are embeddedin the bone
via Sharpey'sfibers (SF). Blood vessels(BV) from the
bone enter and supply the periodontal ligament. The
dentinocementaljunction (arrows) is clearly evident.
Near the apexof the root, the cementumbecomesthicker
and housescementoc)'tes.
FIGURE 2 Periodontal ligament. Human. Poroffin
section. x 210.
The root ofthe tooth, composedofdentin (d) and ce-
mentum (c), is suspendedin its bony alveolus (A) by
fibers of the periodontal ligament (PL). Note that this
photomicrographis takenin the regionofthe crest(cr) of
the alveolusabovewhich the periodontalligamentis con-
tinuous with the connectivetissue of the gingiva (G).
Note that both the gingivaand the periodontalligament
are highly vascular,as evident from the abundanceof
blood vessels(BV).

FIGURE3 Gingiva. Human. Paroffin section.
x 14.
This is a decalcifiedlongitudinal sectionofan incisor
tooth, thus all ofthe calciumhydroxyapatitecrystalshave
beenextractedfrom the tooth and from its bony alveolus
(A). Sinceenamelis composedalmost completelyof cal-
cium hydroryapatite crystals, only the space where
enamelusedto be, the enamelspace(ES),is represented
in this photomicrograph.The crest (cr) of the alveolusis
evident,asarethe periodontal ligament (PL) and the gin-
giva (G). The gingival margin (GM), free gingiva (FG),
attachedgingiva (AG), sulcular epithelium (SE), junc-
tional epithelium (JE), and alveolar mucosa (AM) are
aisoidentified.
FIGURE 4 r Cingiva. Human. Paraffin section.
x 132.
This photomicrograph is a higher magnification of
the gingival margin region of the previous figure. Note
that the enamel space(ES) is located between the dentin
(d) of the incisor tooth's crown and the junctional ep-
ithelium (JE). The sulcular epithelium (SE) of the free
gingiva (FG) borders a spaceknown as the gingival sul-
cus (GS), which would be clearlyevident if the enamel
were still presentin this photomicrograph.Observethe
well-developedinterdigitations of the epithelium and
connectivetissue,known as the rete apparatus(arrows)
of the free gingiva (FG) and attached gingiva, indicative
of the presenceof abrasiveforcesthat act upon thesere-
gions of the oral cavity.

Tooth

g,t

I KEY

A alveolus collagenfibers grngrva

AM alveolarmucosa d dentin GM gingivalmargin
AT attachedgingiva DEJ dentinoenamel junction GS gingivalsulcus
BV bloodvessel DT dentinaltubule JE junctional
epithelium
cemenlUm ES enamelspace PC pulpchamber
cr crestof alveolus ET enameltufts PL periodontalligament
CEJ cementoenameljunction FG freegingiva SE sulcularepithelium

266 :- Digestive
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DigestiveSysteml 267
PLATE13-4 I ToothDevelopment
F|GURE lA I Tooth development. Dental lamina.
Frontol section. Pig. Poroffin section. x 132.
The dental lamina (DL) is a horseshoe-shaped band
of epithelial tissuethat arisesfrom the oral epithelium
(OE) and is surroundedby mesenchymalcells (MC). A
frontal sectionofthe dentallamina is characterized by the
club-shapedappearancein this photomicrograph.The
mesenchyrnalcells in discrete regions at the distal aspect
of the dental lamina become rounded and congregateto
form the precursorof the dental papilla responsiblefor
the formation of the pulp and dentin of the tooth.
FIGURE 2 J Tooth development. Cap stage.
Frontol section. Pig. Poraffin section. x 132.
Increased mitotic activity transforms the bud into a
cap-shapedstructure. Observethat three epithelial layers
of the enamel organ may be recognized:the outer enamel
epithelium (OEE), the inner enamel epithelium (IEE),
and the intervening stellate reticulum (SR). The inner
enamel epithelium has begun to enclose the dental
papilla (DP). Note that mesenchymalcells become elon-
gated, forming the dental sac (DS), which will envelop
the enamel organ and dental papilla. Moreover, a bony
crfpt (BC) will enclosethe dental sac.

FIGURE lB a Tooth development. Bud stoge.

Frontal section. Pig. Paroffin section. x 132.
At various discrete locations along the dental lamina
(DL), an epithelialthickening,the bud (B), makesits ap-
pearance.Each bud will provide the cells necessaryfor
enamelformation for a singletooth. The dental papilla
(DP) forms a crescent-shaped areaat the distal aspectof
the bud.

FIGURE 3 / Tooth development. Bell stage. Frontal
section. Pig. Poroffin section. x 132.
As the enamel organ expandsin size,it resemblesa
bell, hencethe bell stageof tooth development.This stage
is characterizedby four cellular layers:outer enamel ep-
ithelium (OEE), stellate reticulum (SR), inner enamel
epithelium (lEE), and stratum intermedium (SI). Ob-
servethat the enamel organ is still connected to the den-
tal lamina (DL). The dental papilla (DP) is composedof
rounded mesenchymalcells,whoseperipheral-most layer
(arrows) will differentiate to form odontoblasts.Note the
wide basementmembrane (arrowheads) betweenthe fu-
ture odontoblastsand inner enamelepithelium (the fu-
ture ameloblasts).Observealso the spindle-shapedcells
of the dental sac(DS).
FfGURE 4 a Tooth development. Apposition.
Frontal section. Pig. Paraffin section. x 132.
The elaborationof dentin (d) and enamel (e) is rn-
dicative of apposition. Dentin is manufactured by odon-
toblasts (O), the peripheralmost cell layer of the dental
papilla (DP). The odontoblasticprocesses(arrows) are
visible in this photomicrograph as they traverse the
dentin matrix (DM). Ameloblasts (A) are highly elon-
gated columnar cells that manufacture enamel. The long
epithelial structure located to the left is the succedaneous
Iamina (SL) that is responsiblefor the development of the
permanenttooth.

Bud stage,Cap stage,

Bell stage,Apposition

I KEY

A ameloblast DP dentalpapilla OE oral eoithelium

B bud DS dentalsac OEE outerenamelepithelium
BC bony crypt enamel SI stratumintermedium
d dentin IEE innerenamelepithelium SL succedaneouslamina
DL dentallamina MC mesenchymal cell SR stellatereticulum
DM dentinmatrix o odontoblast

268 1 SystemI
Digestive
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PLATE15-5 I Tongue
FIGURE I a Tongue. Human. l.s. Parsffin section.
x 20.
Part of the anterior two-thirds of the tongue is pre-
sented in this photomicrograph. This muscular organ
bearsnumerous filiform papillae (FP) on its dorsal sur-
face,whosestratifiedsquamousepithelium is keratinized
(arrow). The ventral surfaceof the tongue is lined by
stratified squamousnonkeratinized epithelium (Ep). The
intrinsic musclesof the tongue are arranged in four lay-
ers:superior longitudinal (SL), vertical (V), inferior lon-
gitudinal (IL), and horizontal (not shownhere).The mu-
cosaof the tongue is tightly adhering to the perimysium
of the intrinsic tongue musclesby the subepithelial con-
nective tissue (CT).

FfGURE 2 a Tongue. Human. l.s. Paraffin section.
x 14.
The posterioraspectof the anterior two-thirds of the
tongue presents circumvallate papillae (Cp). These
papillae are surrounded by a deep groove (arrow), the
base of which acceptsa seroussecretionvia the ducts
(Du) of the glands of von Ebner (GE). The epithelium
(Ep) ofthe papilla housestastebuds along its lateralas-
pects,but not on its superior surface.The core of the
tongue contains skeletalmuscle (SM) fibers of the extrrn-
sic and intrinsic Iingualmuscles,aswell asglandsand adi-
pose tissue (AT). A region similar to the boxed area is
presentedat a higher magnification in Figure 3.
FfGURE 3 | Circumvollate papillo. Monkeg.
x.s. Plqstic section. x 132.
This photomicrograph is a higher magnification of a
region similar to the boxed areaof the previous figure ro-
tated90o.Note the presenceofthe groove (G) separating
the circumvallate papilla (Cp) from the wall ofthe groove.
Glands ofvon Ebner (GE) deliver a seroussecretioninto
this groove, whose contents are monitored by numerous
intraepithelial tastebuds (TB). Observethat tastebuds are
not found on the superior surface of the circumvallate
papilla, only on its lateral aspect.The connective tissue
coreof the papillais richlyendowedbybloodvessels(BV)
and nerves(N).

I
Tongue

T KEY
AT adiposetissue FP filiformpapillae SL superiorlongitudinal
BV bloodvessels G groove muscle
Cp circumvallatepapillae GE glandsof von Ebner SM skeletalmuscle
CT connectivetissue lL inferiorlongitudinalmuscle TB taste buds
DU clucts N nerves verticalmuscle
Ep epithelium

27O 3 Digestive
SystemI
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I Digestive
SystemI H 27 |
PLATE13-6 I Tongueand Palate
FfGURE | | Circumvqilote papiila. Monkeg.
Paraffin section. x 132.
The base of the circumvallate papilla (Cp), the sur-
rounding groove (G), and the wall ofthe grooveare evi-
dent in this photomicrograph.The glandsofvon Ebner
(GE) delivertheir seroussecretionsvia short ducts (Du)
into the baseofthe groove.Observethe rich vascular (BV)
and nerve (N) supply to this region. Numerous tastebuds
(TB) populatethe epithelium ofthe lateralaspectofthe
circumvallate papilla. Eachtastebud possesses a tastepore
(arrows)through which tastehairs (microvilli) protrude
into the groove.A region similar to the boxed area is pre-
sentedat a higher magnificationin Figure2.
FIGURE 2 f Taste bud. Monkeg. x.s. Plostic
section. x 540.
This is a higher magnification of a region similar to
the boxed area ofFigure 1 Note that the stratified squa-
mous parakeratinized epithelium (Ep) displays squames
in the processof desquamation(arrowheads).The taste
buds (TB) are composed of at leastthree cell qpes. Basal
(lateral) cells (BC) are believed to be regenerativein na-
ture, whereaslight (LC) and dark (DC) cellsare probably
gustatory and sustentacular, respectively. Observe the
presenceofblood vessels(BV) in the subepithelialcon-
nective tissue (CT).

FIGURE 3 a Hard palate. Human. Paraffin section.
x 132.
The hard palate possessesa nasal and an oral surface.
The stratified squamousparakeratinizedepithelium (Ep)
of the oral surfaceforms deep invaginations, rete ridges
(RR), which interdigitatewith the subepithelialconnec-
tive tissue (CT). The thick collagen fiber bundles (CF)
firmly bind the palatal mucosa to the periosteum of the
underlying bone. The hard palate also houseslarge de-
positsof adiposetissueand mucous glands.
FTGURE4 t Soft palate. Human. Poraffin section.
x 132.
The oral surfaceof the soft palate is lined by a strati-
fied squamous nonkeratinized epithelium (Ep), which
interdigitates with the lamina propria (LP) by the forma-
tion of shallow rete ridges (RR). The soft palateis a move-
able structure asattestedby the presenceofskeletal mus-
cle fibers (SM). The core of the soft palate also houses
numerous mucous glands (MG) that deliver their secre-
tory products into the oral cavity via short, straight ducts.

Tongue

I KEY
BC basalcells Du ducts MG mucousglands
BV bloodvessels Ep epithelium N nerve
CF collagentiber bundles u groove RR rete ridges
Cp circumvallatepapilla GE glandsof von Ebner SM skeletalmuscle
CT connectivetissue LC lightcells TB taste buds
DC dark cells LP laminapropria

272 r Digestive
SystemI
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PLATE13-7 I Teethand NasolAspectof the Hard Palate
FIGURE | = Human centrol incisor roots. Paraffin
section. x 132.
The roots of two human central incisors and their
supportingtissuesare noted in this compositephotomi-
crograph.Note that the root ofone incisor, Root l, is at
the top of the figure and progressingdown the pagethe
hyaline layer of Hopewell-Smith (HL) separatesthe
dentin (d) ofthe root from the cementum (c). The peri-
odontal ligament (PLl), with its attendantblood vessels
(BV), of this tooth suspendstooth 1 in its alveolus.The
interdental septum (IS), positionedbetweenthe two in-
cisorsand composedof woven bone, is formed by the fu-
sion ofthe alveolarbonesproper (ABP I and 2) ofeach
root. Note the presenceof osteons (Os) in the woven
bone and the center of theseosteonsapproximatesthe
line of fusion betweenthe two alveolarbones proper. The
periodontalligamentof the other incisor (PL 2) is located
betweenthe alveolarbone proper (ABP 2) and the ce-
mentum of this tooth. Its dentin (d) and hyaline layer of
Hopewell-Smith (HL) of root 2 are clearly evident.

FIGURE 2 e+ Hord palate. Human. Paraffin section.
x 132.
The hard palatepossesses a nasaland an oral surface.
Note that the pseudostratifiedciliated columnar epithe-
lium (Ep) displays cilia and an intraepithelial gland
(IeGL). Observethe presenceglands(Gl) and blood ves-
sels(BV) in the subepithelialconnectivetissue(CT).The
epithelium and the subepithelialconnectivetissue are
collectively referred to as the mucoperiosteum (MP)
which is firmly attached to the bony shelf (B) of the
palate.A higher magnificationof the boxed area is pre-
sentedin Figure3.
FIGURE 3 w, Hard polate. Humon. Paraffin section.
x 132.
This is a higher magnificationof a region similar to
the boxed areaof Figure 2. Note the presenceof glands
(GL), blood vessels(BV), and lymph vessels(LV) within
the subepithelialconnectivetissue(CT). The thick colla-
gen fiber bundles (CF) firmly bind the palatal mucosa to
the periosteum of the underlying bone. Observe the
clearly visible cilia (c) of the pseudostratifiedciliated
columnar epithelium (Ep) coveiing the nasalsurfaceof
the hard palate.

I KEY

ABP alveolarbone proper d dentin leGL gland

intraepithelial
B bonyshelf Ep epithelium lS interdentalseotum
BV bloodvessel ul gland MP palatalmucosa
cemenlum HL hyalinelayerof Os osteon
CT connectivetissue Hopewell-Smith periodontalligament

27 4 W Digestive
System
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DigestiveSystem| 275

I Digestive SgstemII
The alimentary canal is a long, hollow, tubular
structure that extends from the oral cavity to the
anus and is modified along its length to perform the
various facetsofdigestion. The oral cavity receives
food and, via masticationand bolus formation. de-
livers it into the oral phanTnx,from where it enters
the esophagusand eventuallythe stomach.The gas-
tric contents are reducedto an acidic chyrne,which
is dispensedin small spurts to the small intestine,
where most digestion and absorption occur. The
liquefied food residuepassesinto the large intes-
tine, where the digestion is completed and water is
resorbed.The solidifiedfecesare then passedto the
anus for elimination.
A common architectural plan is evident for the
alimentary tract from the esophagusto the anus, in
that four distinct concentric layers may be recog-
nized to constitute the wall of this long tubular
structure.Theselayersare describedfrom the lu-
men outward.
TAYERSOF THE WALL OF THE
ATIMENTARY CANAL
Mucosa
The innermostlayerdirectlysurroundingthe lumen
is known asthe mucosa,which is composedof three
concentric layers:a wet epithelial lining with secre-
tory and absorptive functions; a connective tissue
lamina propria containingglandsand components
of the circulatory system;and a muscularis mu-
cosae,usuallyconsistingof two thin smoothmuscle
Iayers,responsiblefor the mobility of the mucosa.
Submucosa
The submucosais a coarserconnectivetissuecom-
ponent that physically supports the mucosa and
provides nerve, vascular, and lymphatic supply to
the mucosa.Moreover, in some regionsof the ali-
mentary canalthe submucosahousesglands.
rrilrt l4
MuscularisExterna
The muscularis externa usually consistsof an inner
circular and an outer longitudinal smooth muscle
layer, which is modified in certain regionsof the al-
imentary canal.Although theselayersare described
ascircularly or longitudinally arranged,they are ac-
tually wrapped around the alimentary canal in tight
and loosehelices,respectively. Vascularand neural
plexusesreside between the muscle layers. The
muscularis externa functions in churning and pro-
pelling the luminal contents along the digestive
tr act via peristaltic action.
Serosaor Adventitia
The outermost layer of the alimentary canalis either
a serosaor an adventitia.The intraperitonealregions
of the alimentarycanal,i.e.,thosethat aresuspended
by peritoneum,possess a serosa.This structurecon-
sistsof connectivetissuecoveredby a mesothelium
(simplesquamousepithelium),which reducesfric-
tional forcesduring digestivemovement.Other re-
gions of the alimentary tract are firmly attachedto
surrounding structures by connective tissue fibers.
Theseregionspossessan adventitia.
REGIONSOF THE ATIMENTARV
CANAL
Esophagus
The esophagus is a short muscular tube whose
mucosa is composed of a stratified squamous
nonkeratinized epithelium, a loose type of connec-
tive tissue housing mucus-producing esophageal
cardiac glands in the lamina propria, and longitu-
dinally oriented smooth musclefibers of the mus-
cularis mucosae.The submucosaof this organ is
composedof denseirregular collagenousconnec-
tive tissue interspersedwith elastic fibers. This is
one of the two regions of the alimentary canal (the
Systemll t
Digestive 277
other is the duodenum) that housesglands in its
submucosa.Theseglandsare the mucus-producing
esophagealglands proper. The muscularis externa
of the esophagusis composedof inner circular and
outer longitudinal layers. Those in the upper one-
third are skeletal,those in the middle one-third are
skeletal and smooth, whereas those in the lower
one-third are smooth. The esophagusfunctions in
conveyinga bolus offood from the pharynx into the
stomach.
Stomach
Basedon the glandsof its lamina propria, histologi-
cally, the stomach is subdivided into three regions:
cardia,fundus,and pylorus (seeGraphic 14-l). The
mucosaof the empty stomach is thrown into longi-
tudinal folds, the rugae. The luminal surface,lined
by a simple columnar epithelium (surface lining
cells), displaysfoveolae (gastric pits), whosebaseis
perforated by severalgastric glands of the lamina
propria. All gastric glands are composedof parietal
(oxyntic) cells, mucous neck cells, surface lining
cells, diffr,rseneuroendocrine system (DNES, also
APUD) cells,and regenerativecells.Fundic glands,
in addition, alsohousechief (zymogenic) cells.
Oxyntic cells produce HCI and gastric intrinsic
factor, a factor that assiststhe ileum in absorbing
vitamin B12.Thesecellspossess intracellularcanali-
culi and a complextubulovesicularsystem.Mucous
neck cells, along with surface lining cells, are
responsiblefor the formation of mucus that pre-
sumably protects the stomach lining from autodi-
gestion. The various types of DNES cells produce
hormones such as gastrin, somatostatin, secretin,
and cholecystokinin. Regenerative cells, located
mainly in the neck and isthmus, replacethe epithe-
lial lining of the stomach and the cellsof the glands.
Chief cells,located in the baseof the fundic glands,
produce precursors of enzymes (pepsin, rennin,
and lipase).
SmallIntestine
The small intestineis composedof the duodenum,
jejunum, and ileum. The mucosaof all three regions
displaysvilli, extensionsof the lamina propria, cov-
ered by a simple columnar type of epithelium. The
278 - Digestive
Systemll
epithelium is composedof goblet,surfaceabsorp-
tive, and DNES cells.Goblet cellsproduce a mucus.
DNES cellsreleasevarioushormones(e.g.,secretin,
cholecystokinin, gastric inhibitory peptide, and
gastrin). The tall, columnar surfaceabsorptive cells
possessnumerous microvilli coveredby a thick gly-
cocalyx composed of severalenzymes.These cells
function in absorptionof lipids, amino acids,and
carbohydrates.Long chained lipids, in the form of
chylomicrons, are delivered to the lacteals,blindly
ending lymphatic channelsof the villus.
Simple tubular glands of the mucosa,the crypts
of Lieberkiihn, open into the intervillar spaces.
Thesecrypts are composedof simple columnar cells
(similar to surface absorptive cells), goblet (and
oligomucous)cells,DNES,and regenerative cells,as
well as Paneth cells. The last are located in the base
ofthe cryptsand houselargesecretorygranulesbe-
lieved to contain the antibacterial enzyme
lysozyrne. The lamina propria of the ileum houses
large accumulations of lymphatic nodules, Peyer's
patches. The surface epithelium interposed be-
tween Peyer'spatchesand the lumen of the ileum
displaysthe presenceofM cells.
The submucosaof the duodenum containsnu-
merous glands, duodenal (Brunner's) glands, that
produce an alkaline, mucin-containing fluid that
protects the intestinal lining. They also manufac-
ture urogastrone, a polypeptide that inhibits HCI
production and enhancesepithelial cell division.
LargeIntestine
The large intestine is subdivided into the cecum,
the ascending,transverse,descending,and sigmoid
colons, the rectum, the anal canal, and the ap-
pendix (seeGraphic A-2).The largeintestinepos-
sessesno villi but does house crypts ofLieberkiihn
in its lamina propria. The epithelial lining of the lu-
men and of the crypts is composed of goblet (and
oligomucous) cells, surfaceabsorptive cells,regen-
erative cells, and occasionalDNES cells. There are
no Paneth cells in the large intestine, with the pos-
sible exception of the appendix. The large intestine
functions in the absorption of the remaining amino
acids, lipids, and carbohydrates,as well as fluids,
electrolytes,and certain vitamins and in the com-
paction offeces.

Histophgsiologg
I. STOMACH
The stomach functions in acidifring and converting
the semisolid bolus into the viscous fluid, chyme,
which undergoesinitial digestion and is delivered
into the duodenum in small quantities.
The gastricmucosais lined by a simple colum-
nar epithelium whose surfacelining cells (not gob-
let cells)producea mucoussubstancethat coatsand
protectsthe stomachlining from the low pH envi-
ronment and from autodigestion.
The lamina propria of the stomachhousesgas-
tric glands;dependingon the region of the stom-
ach, these are cardiac,fundic, or pyloric. Fundic
glands are composed of five cell types: parietal
(ox1.ntic),mucous neck,chief (zymogenic),DNES,
and regenerativecells. Neither cardiac nor pyloric
glandspossess chief cells.
Parietal cells secrete hydrochloric acid (HCl)
into intracellular canaliculi. These cells alter their
morphology during HCI secretion,in that they in-
creasetheir number of microvilli that project into
the intracellularcanaliculi.It is believedthat these
microvilli are stored as the tubulovesicular system,
flanking the intracellular canaliculi when the cell is
not secreting HCI. Additionally, parietal cells also
secretegastric intrinsic factor, a glycoprotein re-
quired for the absorption of vitamin B12 in the
ileum.
Mucous neck cellsarelocatedin the neck of the
gastricglands.They secretea mucus that is distinct
from that secretedby surfacelining cells.
Chief cells are located in the deep aspect of
fundic glands.They secreteprecursorsof enzymes
pepsin, rennin, and lipase,which initiate digestion
in the stomach.
Enteroendocrine cells (DNES cells) belong to
cells of the diffuse neuroendocrine system and are
known by severalsynonyms. Although as a group
these cells produce a number of different hor-
mones,it is believedthat eachcell is capableof pro-
ducing only a singlehormone. The hormones that
thesecellsproducemay entervascularor lymphatic
channels,but the targetcellsfor most of thesehor-
monesare in the vicinity of their release,therefore,
thesehormones are referred to as paracrine hor-
mones.(SeeTable 14-1for hormonesproducedby
the alimentarvcanal.)
ITNII
II. SMALLINTESTINE
The luminal aspectof the small intestineis modi-
fied to increaseits surfacearea.Thesemodifications
range from the macroscopic,plicae circulares (in-
crease3X), through the microscopic,villi (increase
l0X), to the submicroscopic, microvilli (increase
20x).
A. Villi
Villi are lined by a simple columnar epithelium
composed of surface absorptive cells, goblet cells,
and DNES cells.
Surfaceabsorptive cellspossessdenseaccumula-
tions of microvilli, forming the striated border.
Their tips havea thick coat ofglycocalyx, rich in dis-
accharidasesand dipeptidases.Thesecellsfunction
in absorption of sugars,amino acids, fatty acids,
monoglycerides,electrolytes,water, and many other
beneficialsubstances.Theseepithelial cellsalsopar-
ticipate in the immune defenseof the body by man-
ufacturing protein f (secretory protein), which
binds to and protects immunoglobulin A (IgA) asit
traversesthe epithelial cell and enters the intestinal
lumen.
Goblet cells produce mucinogen, which, when
releasedinto the intestinal lumen, becomeshy-
drated, forming mucin, a slippery substancethat,
when mixed with material in its vicinity, becomes
the substanceknown asmucus. It is the mucus that
protectsthe intestinallining.
B. Crypts of Lieberkiihn
The simple tubular glandsof the lamina propria are
known asthe crypts of Lieberkiihn. They open into
the intervillar spaces and are lined by a simple
columnar epithelium composed of columnar cells
(surface absorptive cells), goblet cells, DNES cells,
regenerativecells,and Paneth cells.
Regenerativecells are located in the basalhalfof
the crypts of Lieberktihn and function as a popula-
tion of stem cells that replace the entire intestinal
epithelium every4-6 days.
Paneth cells are located in the baseof the crypts
of Lieberkthn and are easily recognizedby their
large apical granules. These cells manufacture the
enzymelysozyme, an antibacterial agent.
Systemll *
Digestive 279
TABLE l4-l'; HormonesProducedbg Cellsof the AlimentargCanal
Hormone Location Action

Cholecystokinin (CCK) Small intestine Contraction of gallbladder;releaseof

Pancreatlcenzymes
Gastric inhibitory peptide Smallintestine Inhibits secretionof HCI
Gastrin Stomachand duodenum Stimulatessecretionof HCI and eastric
enzymes
Glicentin Stomach,small and largeintestines Stimulatesglycogenolysisby hepatocl'tes
Glucagon Stomachand duodenum Stimulatesglycogenolysisby hepatocytes
Motilin Smallintestine Increases
intestinalperistalsis
Neurotensin Smallintestine Decreasesperistalsisin intestines;
stimulatesblood supply to ileum
Secretin Smallintestine Stimulatesbicarbonatesecretionby
pancreas
Serotonin Stomach,small and largeintestines Increasesintestinalperistalsis
Somatostatin Stomachand duodenum Inhibits DNES cellsin its viciniw of
release
SubstanceP Stomach,smalland largeintestines Increasesintestinalperistalsis
Urogastrone Duodenalglands(Brunner's) Inhibits secretionof HCI; increases
epithelialcell mitosis
Vasoactiveintestinalpeptide Stomach,small and largeintestines Increasesintestinal peristalsis;stimulates
secretionof ions and water by the
alimentarycanal

C. Duodenal Clands (Brunner's Glands)
Brunner's glands are locatedin the submucosaof
the duodenum. Theseglandsproduce an alkaline-
rich mucin-containingfluid that buffers the acidic
chyrneenteringthe duodenum from the stomach.
Additionally, Brunner's glands manufacture and
releaseurogastrone.
I I I .G U T - A S S O C IA TLEYDMP H OID
T I SS U E
Sincethe lumen of the digestivetract is rich in anti-
genic substances,bacteria, and toxins and since
only a thin simple columnar epithelium separates
the richly vascularizedconnectivetissuefrom this
threateningmilieu, the lamina propria of the in-
testinesis well endowedwith lvmphoid elements.
Theseinclude scatteredcells(B ielli, f ceils,plasma
cells,mastcells,macrophages, etc.),individual l1.rn-
phatic nodules,and, in the ileum, Peyer'spatches,
clustersof lymphatic nodules.Regionswhere lym-
phatic nodulescome in contactwith the epithelial
Iining of the intestinesdisplay flattened cells that
form the interfacebetweenthe lumen and the lym-
phatic nodule. Thesecells are M cells (microfold
cells) that phagocytoseantigens and transport
them, via clathrin-coatedvesicles,to the basal as-
pect of the cell. The antigensare releasedinto the
lamina propria for uptake by antigen-presenting
cellsand dendritic cells.
IV. DIGESTIONAND ABSORPTION
A. Carbohydrates
Amylases,presentin the salivaand in the pancreatic
secretion,hydrolyzecarbohydrates to disaccharides.
Disaccharidases,presentin the glycocalyxofsurface
absorptive cells, break down disaccharidesinto
monosaccharides that enterthe lamina propria by a
transepithelialroute,requiring activetransport.
B. Proteins
Proteins, denatured by HCI in the lumen of the
stomach, are hydrolyzed (by the enzyme pepsin)
into polypeptides. These are further broken down
into dipeptidesby proteasesofthe pancreaticsecre-
tions. Dipeptidases of the glycocalyx hydrolyze
dipeptidesinto individual amino acids,which enter
the lamina propria by a transepithelialroute involv-
lng actlvetransPort.

28O .= Digestive
Systemll
C. Lipids
Pancreatic lipase breaks lipids down into fatty
acids, monoglycerides, and glycerol within the lu-
men of the duodenum and proximal jejunum. Bile
salts, delivered from the gallbladder, emulsifr the
fatty acids and monoglycerides,forming micelles,
which, along with glycerol, diffuse into the surface
absorptive cells. Within these cells they enter the
smooth endoplasmic reticulum, are reesterifiedto
triglycerides, and are covered by a coat of protein
within the Golgi apparatus, forming lipoprotein
droplets known as chylomicrons. Chylomicrons
exit these cells at their basolateralmembranes and
enter the lactealsof the villi, contributing to the for-
mation of chyle. Fatty acidsthat are shorter than 12
carbon chainsin length passthrough the surfaceab-
sorptive cells without being reesterified and gain
entranceto the blood capillariesof the villi.
D. Waterand lons
Water and ions are absorbed through the surface
absorptivecellsof the small and the large intestine.

Clinical Considerations re I I

Crohn'sDisease t y p e s ,s l i d i n ga n d p a r a e s o p h a g ehai la t a lh e r n i a
Crohn's disease isa subcategory of inflamma- I n t h e f o r m e rc o n d i t i o nt h e c a r d i o e s o p h a g e a l
tory boweldisease,a condition of unknown j u n c t i o na n d t h e c a r d i a cr e g i o no f t h e s t o m a c h
etiology. lt usually involves thesmalljntestjne s l i d e si n a n d o u t o f t h e t h o r a x ,w h e r e a si n t h e
or thecolon,butmayaffectanyregion of the l a t t e rc a s et h e c a r d t o e s o p h a g e j uanl c t i o nr e -
alimentary canal, fromtheesophagus lo the m a i n si n i t s n o r m a lp l a c e ,b e l o wt h e d i a p h r a g m ,
anus,aswellasextra-alimentary canalstruc- b u t a p a r t [ o r o c c a s i o n a lal yl l )o f t h e s t o m a c h
tures,suchastheskln,kidney, andtheIarynx p u s h e si n t ot h e t h o r a xa n d i s p o s i t i o n e n d e x tt o
It ischaracterized by patchyulcers anddeep the e s o p h a g u sU. s u a l l yh, i a t a h
l e r n i ai s a symp-
fistulas in theintestinal wall.Clinical manifesta- t o m a t i ca l t h o u g ha c l dr e f l u xd i s e a s ei s q u i t e
t i o n si n c l u daeb d o m i npaal i nd, i a r r h e a n, d c o m m o ni n p a t i e n t sa f f l i c t e dw i l h t h i sc o n d i t i o n
fever,andtheserecuraftervarious periods Patienta s r e a d v i s e dt o e a t s m a l l e m r e a l sm o r e
of
frequentla y n d t h e a c i dr e f l u xd i s e a s ei s
evershortening remission
t r e a t e d .I n f r e q u e n t l yp,a r a e s o p h a g ehai la t a l
Hiotal Hernia h e r n i a sm a y r e s u l ti n s t r a n g u l a t i oonf t h e p r o -
Hiatalherniaisa condition
wherea regionof t r u d e dr e g i o nw i t ha p o s s i b l el o s so f b l o o ds u p -
thestomach herniates
throughtheesophageal p l y l n t h e s ec a s e ss u r g i c ai ln t e r v e n t i om n aybe
hiatusof thediaphragm lt maybeof two indicated

Digestive ll € 281
System

Summorgof HistologicalOrganization
I. ESOPHAGUS
The esophagusis a long muscular tube that delivers
the bolus of food from the pharynx to the stomach.
The esophagus,as well as the remainder of the ali-
mentary tract, is composed of four concentric lay-
ers: mucosa, submucosa, muscularis externa, and
adventitia. The lumen of the esophagusis normally
collapsed.
A. Mucosa
The mucosa has three regions: epithelium, lamina
propria, and muscularis mucosae.It is thrown into
longitudinal folds.
l. Epithelium
The epithelium is stratified squamous nonkera-
tinized.
2. Lamina Propria
The lamina propria is a loose connectivetissuethat
contains mucus-producing esophageal cardiac
glands in some regions of the esophagus.
3. Muscularis Mucosae
The muscularis mucosae is composed of a single
layer of longitudinally oriented smooth muscle.
B. Submucosa
The submucosa,composedof fibroelasticconnec-
tive tissue, is thrown into longitudinal folds. The
esophagealglands proper of this layer produce a
mucous secretion. Meissner's submucosal plexus
housespostganglionicparasympatheticnerve cells.
C. Muscularis
Externa
The muscularis externa is composedof inner circu-
lar (tight helix) and outer longitudinal (loosehelix)
muscle layers.In the upper one-third of the esoph-
agustheseconsist of skeletalmuscle, in the middle
one-third they consist of skeletaland smooth mus-
cle, and in the lower one-third they consist of
smooth muscle.Auerbach's myenteric plexus is lo-
cated betweenthe two layersof muscle.
D. Adventitia
The adventitia of the esophagusis composedof fi-
brous connective tissue. Inferior to the diaphragm
the esophagusis coveredby a serosa.
282 ry Digestive
SystemIl
tEffitr t
II. STOMACH
The stomach is a sac-likestructure that receivesfood
from the esophagusand deliversits contents,known
as chy.rne,into the duodenum. The stomach has
three histologicallyrecognizableregions: cardiac,
fundic, and pyloric. The mucosa and submucosaof
the empty stomach are thrown into folds, known as
rugae,that disappearin the distendedstomach.
A. Mucosa
The mucosapresentsgastricpits, the basesof which
acceptthe openings of gastric glands.
l. Epithelium
The simple columnar epithelium hasno goblet cells.
The cells composing this epithelium are known as
surfacelining cells and extend into the gastricpits.
2. Lamina Propria
The lamina propria houses numerous gastric
glands,slenderblood vessels,and various connec-
tive tissueand lymphoid cells.
a. Cellsof GastricGlonds
Gastric glands are composed of the following cell
types: parietal (oxyntic) cells, chief (zymogenic)
cells, mucous neck cells, DNES (enteroendocrine)
cells, and stem cells. Glands of the cardiac region
haveno chief and onlya fewparietal cells.Glandsof
the pyloric region areshort and possessno chiefcells
and only a few parietalcells.Most of the cellsaremu-
cus-secretingcells resembling mucous neck cells.
Glandsof the fundic region possessall five cell types.
3. Muscularis Mucosae
The muscularis mucosae is composed of an inner
circular and an outer longitudinal smooth muscle
Iayer.A third layermay be presentin certain regions.
B. Submucosa
The submucosacontains no glands. It houses a
vascular plexus, as well as Meissner's submucosal
plexus.
C. MuscularisExterna
The muscularis externa is composed of three
smooth muscle layers: the inner oblique, middle
circular, and outer longitudinal. The middle circu-
lar forms the pyloric sphincter. Auerbach's myen-
teric plexusis locatedbetweenthe circular and lon-
gitudinal layers.
D. Serosa
The stomach is coveredby a connectivetissuecoat
envelopedin visceralperitoneum,the serosa.
III. SMALLINTESTINE
The small intestine is composed of three regions:
duodenum, jejunum, and ileum. The mucosa of
the small intestine presents folds, known as villi,
that change their morphology and decrease in
height from the duodenum to the ileum. The sub-
mucosa displays spiral folds, plicae circulares
(valvesofKerckring).
A. Mucosa
The mucosa presentsvilli, evaginationsof the ep-
ithelially coveredlamina propria.
l. Epithelium
The simple colurnnar epithelium consistsof goblet,
surfaceabsorptive, and DNES cells.The number of
goblet cells increasesfrom the duodenum to the
ileum.
2. Lamina Propria
The lamina propria, composedof loose connective
tissue, houses glands, known as the crypts of
Lieberkthn, that extend to the muscularis mu-
cosae.The cellscomposingtheseglandsare goblet
cells, columnar cells, and, especially at the base,
Paneth cells, DNES cells, and stem cells. An occa-
sional caveolatedcell may also be noted. A central
lacteal, a blindly ending lymphatic vessel,smooth
muscle cells,blood vessels,solitary lymphatic nod-
ules, and lymphoid cells are also present. Lym-
phatic nodules, with M cell epithelial caps, are
especiallyabundant asPeyer'spatchesin the ileum.
3. Muscularis Mucosae
The muscularis mucosaeconsistsof an inner circu-
lar and an outer longitudinal layer of smooth
muscle.
B. Submucosa
The submucosais not unusual exceptin the duode-
num, where it contains Brunner's glands.
C. MuscularisExterna
The muscularis externa is composed of the usual
inner circular and outer longitudinal layers of
smooth muscle, with Auerbach's myenteric plexus
intervening.
D. Serosa
The duodenum is coveredby serosaand adven-
titia, while the jejunum and ileum are coveredby a
serosa.
IV. LARGEINTESTINE
The large intestine is composed of the appendix,
cecum, ascending, transverse, and descending
colons, rectum, and anal canal. The appendix and
anal canal are describedseparately,although the re-
mainder of the largeintestine presentsidentical his-
tologic features.
A. Colon
l. Mucosa
The mucosa presentsno specializedfolds. It is
thicker than that of the small intestine.
a. Epithelium
The simple columnar epithelium has goblet cells
and columnar cells.
b. LaminaPropria
The crypts of Lieberkthn of the lamina propria are
longer than those of the small intestine. They are
composed of numerous goblet cells, a few DNES
cells, and stem cells. Lymphatic nodules are fre-
quently present.
c. MuscularisMucosae
The muscularis mucosaeconsistsof inner circular
and outer longitudinal smooth muscle layers.
2. Submucoso
The submucosa resemblesthat of the ieiunum or
ileum.
3. Muscularis Externa
The muscularis externa is composedof inner circu-
lar and outer longitudinal smooth muscle layers.
The outer longitudinal muscle is modified into
teniae coli, three flat ribbons of longitudinally ar-
ranged smooth muscles.Theseare responsiblefor
the formation of haustra coli (sacculations).Auer-
bach's plexus occupiesits position betweenthe two
layers.
4. Serosa
The colon possessesboth serosa and adventitia.
The serosapresentssmall, fat-filled pouches,the
appendicesepiploicae.
B. Appendix
The lumen of the appendix is usually stellate
shaped, and it may be obliterated. The simple
columnar epithelium coversa lamina propria rich
in lymphatic nodules and some crypts of
Lieberktihn. The muscularis mucosae,submucosa,
and muscularis externa conform to the general
plan of the digestivetract. It is coveredby a serosa.
C.Anal Canal
The anal canal presentslongitudinal folds, anal
columns, which become ioined at the orifice of the
Systemll E 283
Digestive
anus to form anal valves, and intervening anal si-
nuses. The epithelium changesfrom the simple
columnar of the rectum, to simple cuboidal at the
analvalves,to stratifiedsquamousdistalto the anal
valves, to epidermis at the orifice of the anus.
284 E DigestiveSystemll
Circumanal glands, hair follicles, and sebaceous
glands are present here. The submucosa is rich in
vascularsupply, while the muscularis externa forms
the internal anal sphincter muscle. An adventitia
connectsthe anusto the surroundingstructures.
I CRAPHfC 14- 1 | Stomachand Small Intestine

I
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@,i

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I Oxyntic(parietal)
cell

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Small

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cMPHfC l4-2 | LargeIntestine I
I
The crypts of Lieberkiihn are
glandscomposedof a simple
columnartype of epithelium.Four I
typesof c€llsconstitutethis
epithelium:mucus-producing goblet
cells; absorptlve cells that function
in absorbingnutrients,electrolytes, I
and fluid;r€generatlvecells that
proliferateand replacethe othercells

The largeintestin€has no villi,but it does

possesscryptr ot Lleberkiihn.The outer
of the epithelium;and
onteroendocdnecells that r€lease
paracrinehormones.
I
longiludinallayerof the muscularls
extema is gatheredintothe teniaecoli.
Lymphaticnodulesand lymphoidinfiltration
are frequentlynotedin the largeand small
I
intestines.

t
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Absorpti\recell
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crypt
of
Lieberk0hn
Regenerativecell I
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Enteroendocrine
cell
(DNEScell)
I
286 I Digestive
SystemIl I
I r NorEs

Digestivesystemll I 247
 PLATE14-1 t Esophagus
F|GURE I Esophagus. x.s. paraffin section. x j 4.
This photomicrographof a cross-section of the lower
one-third of the esophagusclearly displaysthe general
structureof the digestivetract. The lumen (L) is lined by
a stratifiedsquamousnonkeratinizedepithelium (Ep) ly-
ing upon a thin lamina propria (Lp) that is surrounded
by the muscularismucosae(MM). The submucosa(Sm)
containsglandsand is surroundedby the muscularisex-
terna (ME), composedof an inner circular (lC) and an
outer longitudinal (OL) layer.The outermosttunic of the
esophagus is the fibroelasticadventitia(Ad). A regron
similar to the boxed areais presentedat a higher malgnr-
fication in Figure2.
FfGURE 2 ,': Esophogus. Human. x.s. Paraffin
section. x 132.
This photomicrographis a higher magnificationof a
region similar to the boxed area of the previous figure.
The mucosa (M) of the esophagusconsistsof a stratified
squamousnonkeratinizedepithelium (Ep), a loose col-
lagenousconnectivetissuelayer,the lamina propria (LP),
and a longitudinally oriented smooth muscle layer, the
muscularis mucosae (MM). The submucosa (Sm) is
composed of a coarser collagenousconnective tissue
(CT), housingblood vessels(BV) and variousconnective
tissuecellswhosenuclei (N) are readilyevident.

FIGURE 3 Esophagus. Human. x.s. parqffin
section. x 132.
The lamina propria (LP) and submucosa(Sm) of the
esophagusare separatedfrom eachother by the longitu-
dinally oriented smooth musclebundles,the muscularis
mucosae(MM). Observethat the lamina propria is a very
vascularconnectivetissue,housint numerousblood ves-
sels(BV) and lymph vessels(LVi whosevalves(arrow)
indicatethe direction of lymph flow. The submucosaalso
displaysnumerousblood vessels(BV), aswell asthe pres-
enceofthe esophageal glandsproper ( EG) that prodlce a
mucoussecretion to lubricatethelining of the esophagus.
F|GURE 4 Esophagogastric iunction. l.s. Dog.
Paroffin section. x 14.
Thejunction ofthe esophagus(Es)and cardiacstom-
ach (CS)is veryabrupt asevidencedby the suddenchange
of the stratified squamousepithelium (SE)to the simple
columnar epithelium (CE) of the stomach.Note that the
esophagealglandsproper (EG) continue for a short dis-
tanceinto the submucosa(Sm) of the stomach.Observe
alsothe presenceofgastricpits (arrows)and the increased
thicknessof the muscularisexterna(ME) of the stomach
comparedto that of the esophagus. The outermosttunic
ofthe esophagus inferior to the diaphragmis a serosa(Se)
ratherthan an adventitia.The boxedareais presentedar a
highermagnificationin FigureI of the nextplate.

Esophagus

I KEY

Ad adventitia Es esophagus N nucleus

BV bloodvessels lC innercircularmuscle OL outerlongitudinal
muscle
UE simplecolumnar L lumen SE stratifiedsquamous
epithelium LP laminapropria epithelium
CS cardiacstomach LV lymphvessels Se serosa
.T
connective tissue M mucosa Sm submucosa
EG esophageal glandsproper ME muscularisexlerna
EP epithelium MM muscularismucosae

288
t LP--_
t _EP \tuttut
T
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FICUR1
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t e y s t e ml l
D i g e s t i vS 289
 PLATE14-2 | Stomach
FIGURE I Esophagogastric junction. l.s. Dog.
Poraffin section. x 132.
This photomicrograph is a higher magnification of
the boxed region of Figure 4, Plate 14-1. The stratified
squamousepithelium (SE) of the esophagusis replaced
by the simple columnar epithelium (CE) of the stomach
in a very abrupt fashion (arrow). The lamina propria
(LP) displaysgastricpits (GP), lined by the tlpical mu-
cus-secretingsurfacelining cells (SC), characteristicof
the stomach.The structurelabeledwith an asteriskis not
a lymphatic nodule,but a more or lesstanqentialsection
through the esophageal epithelium.Note tf,e presenceof
the muscularismucosae(MM).
FIGURE 2 w Fundic stomoch. I.s. Paraffin section.
x 14.
The fundic regionpresentsall ofthe characteristics
of
the stomach,as demonstratedby this low-power pho-
tomicrograph.The lumen (L) is lined by a simplecolum-
nar epithelium,deepto which is the lamina propria (LP)
housing numerous gastric glands (GG). Each gland
opensinto the baseof a gastricpit (GP). The muscularis
mucosae (MM) separatesthe lamina propria from the
submucosa(Sm), a richly vascularized(BV) connective
tissue,thrown into folds (rugae)in the empty stomach.
The muscularis externa (ME) is composed of three
poorly defined layers of smooth muscle: innermost
oblique (IO), middle circular (MC), and outer longitu-
dinal (OL). Serosa(arrow) forms the outermosttunic of
the stomach.A region similar to the boxed area is pre-
sentedat a higher magnificationin Figure3.

FIGURE 3 Fundic stomoch. x.s. Dog. Paraffin
section. x 132.
This photomicrograph presentsa higher magnifica-
tion of a region similar to the boxed areaof Figure2. The
mucosaof the fundic stomachdisplaysnumerousgastric
pits (GP) that arelined by a simplecolumnar epithelium,
consisting mostly of mucus-producing surface lining
(surfacemucous) cells (SC).The baseof eachpit acceprs
the isthmusof two to four fundic glands(FGt. Although
fundic glands are composed of several cell t1pes, only
two, parietal cells (PC) and chief cells (CC), are readily
distinguishablein this preparation.The lamina propria
(LP) is richly vascularized (BV). Note the muscularis
mucosae (MM) beneath the lamina propria. A region
similar to the boxed areais presentedat a higher magni-
fication (positionedat a 90oangle)in Figure4.
FIGURE 4 E Fundic glands. x.s. Pardffin section.
x 540.
This photomicrographpresentsa higher magnifica-
tion (positionedat a 90'angle) of a region similar to the
boxed areaofFigure 3. The lumina (L) ofseveralglands
can be recognized.Note that chiefcells(CC) aregranular
in appearanceand are much smaller than the round,
plate-likeparietal cells (PC). Parietalcells,as their name
implies, are located at the periphery of the gland. Slender
connectivetissueelements(CT), housing blood vessels,
occupy the narrow spacesbetween the closely packed
glands.

Stomachand cells

I KEY
BV bloodvessels GP gastricpits MM muscularismucosae
CC chief cells lO innermostobliquemuscle OL outerlongitudinalmuscle
CE columnarepithelium L lumen PC parietalcells
CT connectivetissue LP laminapropria SC surfaceliningcells
FG fundicglands ME muscularisexterna SE squamousepithelium
GG gastricglands MC middlecircularmuscle Sm suomucosa

290 DigestiveSystemll
I
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I GG
GP
t MM

t LP
1..

I
MM
I LP t0 Sm \l/
BV
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II
ME
II
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PLATEl4-3 t Stomach
F|GURE | '; Fundic stomach. x.s. Monkeg. Plastic
section. x 210.
The gastricpits (GP) of the fundic stomachare lined
mostly by mucus-producing surface lining cells (SC).
Eachgastricpit receivestwo to four fundic glands,simple
tubular structuresthat are subdividedinto three regions:
isthmus,neck,and base.The isthmusopensdirectlv inro
the gastricpit and is composedof immature celli (fc),
which are responsiblefor the renewalof the lining of the
gastric mucosa, surface lining cells (SC), and parietal
cells (PC). The neck and baseof theseglands are pre-
sentedin Figure2.
FIGURE 2 *+ Fundic glond. Stomoch. x.s. Monkeg.
Plastic section. x 210.
The neck (n) and base (b) of the fundic gland both
contain the large, plate-shapedparietal cells (PC). The
neck also possesses a few immature cells, as well as mu-
cous neck cells (Mn), which manufacturea mucous sub-
stance.The baseof the fundic glandscontainsnumerous
acid-manufacturing parietal cells (PC) and chief cells
(CC), which produce digestiveenzymes.Note that the
lamina propria is tightly packedwith glandsand that the
interveningconnectivetissue(CT) is flimsy in character.
The basesof theseglandsextendto the muscularismu-
cosae(MM).

F|GURE 3 =: Pgloric gland. Stomach. x.s. Monkeg.
Plastic section. x 132.
The mucosaof the pyloric region of the stomachpre-
sentsgastricpits (GP) that are deeperthan those of the
cardiacor fundic regions.The deep aspectsof thesepits
are coiled (arrows).As in the other regionsof the stom-
ach, the epithelium (Ep) is simple columnar, consisting
mainly of surfacelining cells (SC). Note that the lamina
propria (LP) is looselypackedwith pyloric glands (PG)
and that considerableconnectivetissue (CT) is present.
The pyloric glandsare composedmainly of mucous cells
(mc). Observethe two muscle layersof the muscularis
mucosae(MM). A regionsimilar to the boxedareais pre-
sentedin Figure4.
FIGURE 4 ft4Pgloric gland. Stomdch. x.s. Human.
Poroffin section. x 210.
This is a photomicrographof a region similar to the
boxed areaof Figure3. The simple columnar epithelium
(Ep) of the gastricpit is composedmostly of surfacelin-
ing cells.Thesepits are not only much deeperthan those
of the fundic or cardiacregions,but are also somewhat
coiled (arrow) as are the pyloric glands (PG), which
empty into the baseof the pits. Theseglandsare popu-
lated by mucus-secretingcells (mc) similar to mucous
neck cellswhosenuclei (N) areflattenedagainstthe basal
cell membrane. Note that the glands are not ciosely
packedand that the lamina propria (LP) is very cellular
and possesses a rich vascularsupply (BV).

Stomachand cells

I KEY

b base tc immaturecells n neck

BV bloodvessels LP laminapropria PC parietalcells
CC chiefcells mc mucouscells PG pyloricglands
CT connectivetissue MM musculansmucosae SC surlaceliningcells
EP epithelium Mn mucousneckcell
GP gastricpits N nucteus

292 '.'+ Digestive

Systemll
 t
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FICU
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DigestiveSystemll 293
PLATEl4-4 I Duodenum
F|GURE lA * Duodenum. l.s. Monkeg. Plastic
section. Montoge. x 132.
The lamina propria of the duodenum possesses fin-
ger-like evaginations,known as villi (V), which project
into the lumen (L). The villi are coveredby surfaceab-
sorptivecells(SA), a simplecolumnar tlpe of epithelium
with a brush border. Interspersedamong thesesurface
absorptivecellsaregobletcells(GC), aswell asoccasional
APUD cells. The connectivetissue (CT) core (lamina
propria) of the villus is composedof lyrnphoid and other
cellularelementswhosenuclei stainvery intenselv.Blood
vesselsalsoaboundin the lamina prop.iu, aswell aslarge,
blindly endinglymphatic channels,known aslacteals(l),
recognizable by their largesizeand lack ofred blood cells.
Frequently,theselactealsarecollapsed.The deeperaspect
of the lamina propria houses glands, the cr'?ts of
Lieberkiihn (CL). These simple tubular glands deliver
their secretionsinto the intervillar spaces.The basesof
thesecrypts reachthe muscularis-,r.oru" (MM), com-
posed of inner circular and outer longitudinal layersof
smooth muscle.Deep to this musclelayer is the submu-
cosa,which, in the duodenum,is occupiedby compound
tubular glands of Brunner (GB). These glands deliver
their mucous secretionvia ducts (D), which pierce the
muscularismucosae,into the cryptsof Lieberktihn.A re-
gion similar to the boxed area is presentedat a higher
magnificationin Figure lb.
FIGURE lB e Epithelium and core of villus.
Monkeg. Plostic section. x 540.
This higher magnification of a region similar to the
boxed areapresentsthe epithelium and part ofthe con-
nective tissue core of a villus. Note that the surface ab-
sorptivecells (SA) displaya brush border (BB), terminal
bars (arrow), and gobletcells(GC). Although APUD cells
arealsopresent,they constituteonly a smallpercentage of
the cell population. The lamina propria (LP) core of the
villus is highly cellular, housing lymphoid cells (LC),
smooth muscle cells (SM), mast cells, macrophages
(Ma), and fibroblasts,among others.
FIGURE 2 f Duodenum. I.s. Monkeg. Plastic
section.x 132.
This photomicrographis a continuation of the mon-
tagepresentedin Figurela (compareasterisks). Note that
the submucosa (Sm), occupied by glands of Brunner
(GB), is a vascularstructure(BV) and alsohousesMerss-
ner's submucosalplexus. The submucosaextendsto the
muscularis externa (ME), composedof an inner circular
(IC) and outer longitudinal (OL) smooth muscle layer.
Note the presenceof Auerbach's myenteric plexus (AP)
betweenthesetwo muscle layers.The duodenum, in part,
is coveredby a serosa(Se), whose mesothelium provides
this organwith a smooth, moist surface.
FfGURE 3A t Duodenum. x.s. Monkeg. Plastic
section. x 540.
The baseof the crypt of Lieberkiihn displaysthe sev-
eral qpes of cells that compose this gland. Paneth cells
(Pc) are readily recognizabledue to the large granules in
their apical cytoplasm. DNES cells (APD) are clear cells
with fine granules usually located basally. Goblet cells
(GC), columnar cells (Cc), and stem cells (Sc) constitute
the remainingcell population.
FIGURE 38 r Duodenum. x.s. Monkeg. Plastic
section, x 540.
The submucosa of the intestinal tract displays small
parasympatheticganglia, Meissner's submucosal plexus.
Note the large, postganglionic cell bodies (PB) sur-
rounded by elementsof connective tissue (CT).

T KEY

AP Auerbach'splexus GC gobletcell OL outer longitudinalmuscle

APD DNEScell ln
innercircularmuscle PB postganglioniccell body
BB brush border I lacteal Pc Panethcell
BV bloodvessels L tumen JA surfaceabsorptivecell
Cc columnarcell LC lymphoidcell Sc stem cell
CL cryptsof Lieberkrihn LP laminapropria Se serosa
connectivetissue Ma macropnage Sm submucosa
D duct ME muscularisexterna SM smoothmusclecell
GB glandsof Brunner MM muscularismucosae villi

294 s Digestive
Systemll
 a)
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PLATE I Jejunum,Ileum
FIGURE I Jejunum. x.s. Monkeg. Plastic section.
x 132.
The mucosa(M) and submucosa(Sm) of the jejunum
are presentedin this photomicrograph.The villi (V) of
this region possessmore goblet cells (GC) than thoseof
the duodenum. Observethat the crypts of Lieberkiihn
(CL) open into the intervillarspaces(arrow) and that the
lamina propria displaysnumerousdensenuclei,evidence
of lymphatic infiltration. The flimsy muscularismucosae
(MM) separates the lamina propria from the submucosa.
Largeblood vessels(BV) occupythe submucosa,which is
composedof a loosetlpe of collagenous connectivetissue.
The inner circular (lC) layerof the muscularisexternais
evidentat the bottom ofthe photomicrograph.The boxed
region is presentedat a higher magnificationin Figure2.
FIGURE 3 lleum. l.s. Humon. Paroffin section. ^
14.
The entire wall of the ileum is presented,displaying
spiral folds of the submucosathat partially encirclethe
lumen. Thesefolds, known as plicae circulares(Pci) in-
creasethe surfaceareaof the small intestines.Note that
the lamina propria is clearlydelineatedfrom the submu-
cosa (Sm) by the muscularismucosae.The lamina pro-
pria forms numerousvilli (V) that protrude into the lu-
men (L), and glands, known as crypts of Lieberki.ihn
(CL), deliver their secretionsinto the intervillar spaces.
The submucosaabuts the inner circular (IC) laver of
smooth musclethat, in turn, is surroundedby the outer
longitudinal (OL) smooth musclelayerof the muscularrs
externa.Observethe serosa(Se) investingthe ileum. A
region similar to the boxed areais presentedat a higher
magnificationin Figure4.
T KEY
APD DNEScell lumen
BV bloodvessels ; mucosa
CL cryptsof Lieberkrlhn MM muscularismucosae
GC gobletcell PC Panethcell
lC innercircularmuscle Pci plicaecirculares
I lacteal Prc plasmacell
DigestiveSystemll
FIGURE 2 :, Jejunum. x.s. Monkeg. Plastic section.
x 540.
This photomicrograph is a higher magnification of
the boxed areaof Figure 1 The crypts of Lieberkiihnare
composedof severalcellt1pes,someof which areevident
in this figure. Goblet cells (GC) that manufacturemucus
may be noted in various degreesof mucus production.
Narrow stem cells (Sc) undergomitotic activity (arrow-
head),and newly formed cellsreconstitutethe cell popu-
lation of the crlpt and villus. Paneth cells (PC) are
located at the baseof crypts and may be recognizedby
their large granules.DNES cells (APD) appearas clear
cells,with fine granulesusuallybasallylocated.The lam-
ina propria displaysnumerousplasmacells (PIC).
FIGURE 4 ., lleum. x.s. Monkeg. Plastic section.
x 132.
This is a higher magnificationof a region similar to
the boxed area of Figure 3. Note that the villi (V) are
coveredby a simple columnar epithelium, whose cellu-
lar constituents include numerous goblet cells (GC).
The core of the villus displaysblood vessels(BV), aswell
as a large lymphatic vessel,known as a lacteal (1). The
crypts of Lieberktihn (CL) open into the intervillar
spaces(arrow). The group of lymphatic nodules of the
ileum are known as Peyer'spatches(PP).
Inset a. Crypt of Lieberktihn. l.s. Monkey. Plastic
section.X 540.
The crypts of Lieberkiihn also possessDNES cells
(APD), recognizableby their clear appearanceand usu-
ally basallyorientedfine granules.
Inset b. Crypt of Lieberki.ihn. l.s. Monkey. Plastic
section.X 540.
The baseof the crypt of Lieberkuhn displayscellswith
large granules.These celis are Paneth cells (PC) that
producethe bacteriocidalagentlysozyme.
Smallintestine
PP Peyer'spatch
OL muscle
outerlongitudinal
Sc stem cell
Se serosa
Sm submucosa
villi
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1 FICURE
2

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FICUR5
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DigestiveSystemll 297
PLATEl4-6 I Colon,Appendix
FIGURE T Colon. Ls. Monkeg. Plastic section.
x 132.
This photomicrographdepictsthe mucosaand part of
the submucosaof the colon. Note the absenceof surface
modificationssuch as pits and villi, which indicate that
this sectionis not of the stomachor small intestines.The
epithelium (Ep) lining the lumen (L) is simplecolumnar
with numerous goblet cells (GC). The straight tubular
glands are crypts of Lieberkiihn (CL), which extend
down to the muscularismucosae(MM). The inner cir-
cular (lC) and outer longitudinal (OL) layersof smooth
musclecomprisingthis region of the mucosaare clearly
evident.The submucosa(Sm) is very vascular(BV) and
housesnumerous fat cells (FC). The boxed area is pre-
sentedat a higher magnificationin Figure2.
FIGURE 2 Colon. I.s. Monkeg. Plostic section.
x 540.
This photomicrographis a highermagnificationof the
boxedareaof Figurel The cellpopulation of the cryptsof
Lieberkiihn (CL) is composedof numerous goblet cells
(GC), which delivertheir mucusinto the lumen (L) of the
crypt.Surfaceepithelialcells(SEC),aswell asundifferen-
tiatedstemcellsarealsopresent.The latterundergomito-
sis (arrow) to repopuiatethe epitheliallining. DNES cells
(APD) constitutea small percentageof the cell popula-
tion. Note that Panethcellsare not presentin the colon.
The lamina propria (LP) is very cellular,housing many
lymphoid cells (LC). The inner circular (IC) and outer
longitudinal (OL) smoothmusclelayersof the muscularis
mucosae(MM) are clearlyevident.

FfGURE 3 Appendix. x.s. Paraffin section. x 132.
The cross-sectionof the appendix displaysa lumen
(L) that frequentlycontainsdebris (arrow). The lumen is
lined by a simplecolumnarepithelium (Ep), consistingof
many goblet cells (GC). Crypts of Lieberkiihn (CL) are
relativelyshallowin comparisonwith thoseof the colon.
The lamina propria (LP) is highly infiltrated with lym-
phoid cells (LC), derived from lymphatic nodules (LN)
of the submucosa(Sm) and laminapropria.The muscu-
laris mucosae(MM) delineatesthe border betweenthe
lamina propria and the submucosa.
FIGURE 4 Anorectal junction. l.s. Human.
Paraffin section. x 132.
The anorectaljunction presentsa superficialsimilar-
ity to the esophagogastricjunction becauseofthe abrupt
epithelial transition. The simple columnar epithelium
(CE) of the rectum is replacedby the stratifiedsquamous
epithelium of the anal canal (AC). The crypts of
Lieberkiihn (CL) ofthe anal canalare shorterthan those
of the colon and the lamina propria (LP) is infiltratedby
lymphoid cells(LC).

Laroeintestineand cells

-'+ t'.
{

I KEY

anal canal FC fat cell MM muscularis mucosae

A P D DNEScell GC gobletcell OL outerlongitudinal
muscle
BV bloodvessels lC innercircularmuscle SE stratiliedsquamous
C E simplecolumnar L lumen epithelium
epithelium LC lymphoidcell SEC surfaceepithelial
cell
CL cryptsof Lieberktihn LN lymphaticnodule Sm submucosa
E P epithelium LP laminapropria

DigestiveSystemll
I ..EP
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BV 'tr'@ & *- -r
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<r-_-
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F I C U R ]E F I C U R2E
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D i g e s t i vS
e y s t e nlrl 299
PLATE14-7 I Colon,ElectronMicroscopg I
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F|GURE I J Colon. Rot. Electron microscopg. x FIGURE 2 J Colon. Rat. Electron miooscopg.
3 18 0 .
The deep aspectof the crypt of Lieberkiihn presents
x 12,600.
At a higher magnification of the deep aspect of the I
columnar cells (c) and deep crypt cells that produce a crypt of Lieberktihn, the deep crypt cells Present some-
what electron-densevacuoles (m). Note that many of
mucous type of secretionthat is delivered into the lumen
(L) of the cr)?t. (From A,ltmann GG: Am I Anat
167:95-ll7 , 1983.)
these vacuoles coalesce,forming amorphous vacuolar
profiles. The slender columnar cell (C) displays no vac-
t
uoles,but doespossessnumerous mitochondria and oc-
casional profiles of rough endoplasmic reticulum. Ob-
servethe large,oval nucleusand clearlyevident nucleolus.
(From Altmann GG:Am I Anat 167:95-117,1983.)
I
500 Ir Digestive
Systemll t
I PLATE14-8 I Colon,ScanningElectronMicroscopg

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I FIGURE | # Colon. Monkeg. Scanning electron Inset. Colon. Rabbit. Scanning electron microscopy'
microscopA. x 61 4. x 118.

I This scanningelectronmicrographdisplaysthe open-

ings of the crypts of Lieberktihn (CL), aswell as the cells
lining the mucosal surface.(From SpecianRD, Neutra
MR: Am I Anat 160:461-472,1981.)
The openings of the crJpts of Lieberktihn are not as
regularly arrangedin the rabbit asin the monkey. Observe
the mucusarisingfrom the crypt opening(arrow). (From
SpecianRD, Neutra MR: Am I Anat 160:461472,1981.)

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Largeintestineand cells

** tr

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t Digestive SgstemIII
I
The major glands of the digestive system are lo- LIVER
t catedoutsidethe wall ofthe alimentarycanalbut are
connectedto its lumen ofvia ducts.Theseglandsin- The liver is the largest gland of the body. It per-
clude the major salivaryglands,pancreas,and liver. forms a myriad of functions, many of which are not
I MAJOR SATIVARYGTANDS
glandular in nature (see Graphic l5-2). The
parenchymal cells of the liver, known as hepato-
cytes,perform eachofthe tasksofthe liver. The ex-

I The three major salivary glands, parotid, sub-

mandibular, and sublingual, deliver their secretory
product, saliva,into the oral cavity. Saliva is com-
t posed of a thin watery suspensionof enzl.rnes,mu-
cus, inorganic ions, and antibodies. The parotid
gland producesserous secretions,whereasthe sub-
I mandibular and sublingual glands manufacture
mixed secretions.
ocrine by-product, bile, is deliveredinto a systemof
bile ducts, which then directs the bile into the gall-
bladder, a storageorgan associatedwith the liver.
The releaseofconcentrated bile into the duodenum
via the cystic and common bile ducts is regulatedby
hormones of the DNES cellsin the alimentary tract.
Since eachhepatocl'te is bordered by a vascular si-
nusoid, liver cells can absorb toxic materials and
by-products of digestion, which they detoxifr and
store for future use. Additionally, hepatocytescan

I PANCREAS
release various biosynthetic molecules into the
bloodstream to be utilized throughout the body.
Moreover, foreign particulate matter is phagocy-
The pancreas is a mixed gland, in that it has exocrine
I and endocrinefunctions(seeGraphicl5-1). The ex-
ocrine pancreasproducesan alkalinefluid rich in di-
tosedin the liver by Kupffer cells, macrophagesde-
rived from monocytes.

gestiveen4rnes, which is deliveredto the duodenum

I via the pancreaticduct. The releaseof the enzymes
and alkalinefluid is intermittent and is controlled by
GATTBLADDER
the hormones cholecystokinin and secretin,respec- The gallbladder is a small, pear-shapedorgan that
t tively and the two types of secretionsmay be deliv-
eredindependentofeach other. Thesehormones are
producedbythe DNES cellsofthe epitheliallining of
receivesbile from the liver. It not only stores but
also concentratesbile and, in responseto the chole-
cystokinin releasedby the DNES cells of the ali-

I the alimentary tract mucosa. The endocrine pan-

creasis composedofscatteredsphericalaggregates
richlyvascularizedcordsofendocrine cells,known as
of
islets of Iangerhans. Five cell types are present in
I thesestructures:a (A) cells, producing glucagon; B
(B) cells, manufacturing insulin; G cells, producing
gastrin; 6 (D) cells, manufacturing somatostatin;
I and PP cells, secretingpancreatic polypeptide.
mentary tract, forcesthe bile into the lumen of the
duodenum via the cystic and common bile ducts.
The bile emulsifiesfats, facilitatingthe action of the
enzyme pancreatic lipase. The lamina propria,
lined by a simple columnar epithelium, is thrown
into highly convoluted folds in the empty gallblad-
der. Thesefolds disappearon distention.Occasion-
ally, tubuloalveolar mucous glands are present.

I
I Systemlll I
Digestive 3O3

Histophgsiologg
I. MAJORSALIVARY
CLANDS
The major salivary glands are the parotid, sub-
mandibular, and sublingrral glands. These pro-
duceabout I L of salivaper day,approximately957o
ofthe daily salivarysecretion.Theseglandspossess
a secretorycomponent that is responsiblefor the
formation of primary saliva, which is modified by
the initial portion of the duct system (striated
ducts) to form the secondary saliva. Salivais a hy-
potonic solution whosefunctions include lubrica-
tion and cleansingofthe oral cavity (and reducing
bacterial flora by lysozyme, lactoferrin, and im-
munoglobulin A [IgA]), initial digestionof carbo-
hydrates by salivary amylase, and assistingin the
processoftaste (by dissolvingfood substances).
II. PANCREAS
Acinar cells of the exocrine pancreas secretediges-
tive enzymesin responseto the hormone cholecys-
tokinin. releasedby the enteroendocrinecells of the
small intestine.Someof theseenzyrnesarereleasedas
proenzyrnes (chymotrypsin, trypsin, elastase,and
carboxypeptidase),and others are releasedas active
enzyrnes(DNase,RNase,pancreaticlipase,and pan-
creaticamylase).In responseto secretin (releasedby
enteroendocrine cells of the small intestine), cen-
troacinar cells and cellsofintercalated ducts release
a copiousamount of an alkalinefluid that is believed
to helo neutralizeand buffer the acidic chvme enter-
ing the duodenumfrom thestomach.
Islets of Langerhans are composedof five differ-
ent types of cells,eachof which is responsiblefor
the secretionof a hormone.
III. LIVERAND GALLBLADDER
A. Hepatocytes
It is believed that each hepatocyte is capable of
performing each of the approximately 100 func-
tions of the liver.
3O4 i+ Digestive
Systemlll
IEMII I
I
Bile formation and secretionare the exocrine
I
functions of the liver. Bile is a green, somewhat
viscousfluid composedof water, ions, cholesterol,
phospholipids, bilirubin glucuronide, and bile
acids. One of these components, bilirubin glu-
I
curonide, is a water-solubleconjugateof nonsolu-
ble bilirubin, a toxic breakdown product of
hemoglobin. It is in the smooth endoplasmic
t
reticulum (sER)ofthe hepatocytesthat detoxifica-
tion of bilirubin occurs.
Detoxification of various drugs, toxins,
I
metabolic by-products, and chemicals occurs
either by the microsomal mixed-function oxidase
system of the sER or by peroxidasesof peroxi- I
somes.
Endocrine functions of the liver include the
synthesisand releaseof numerousplasmaproteins
and components,such as fibrinogen, urea, albu-
I
min, prothrombin, and lipoproteins; storage of
glycogen and lipids for releaseduring intervals
betweeneating;synthesisof glucose;gluconeogen-
t
esis from noncarbohydratesources(amino acids
and lipids); and transport of IgA into the bile
and, subsequently,into the lumen of the small
I
intestine.
I
B. Kupffer Cells and lto Cells
Kupffer cells of the liver participate in removing
defunct red blood cellsand other undesirablepar-
I
ticulate matter from the bloodstream.Fat-storing
(Ito) cellsarebelievedto function in the accumula-
tion and storageof vitamin A.
I
C. Gallbladder
I
The gallbladder stores and concentratesbile. It
releasesbile in responseto the enteroendocrinecell I
hormone cholecystokinin.
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I C l i n i c a lC o n s i d e r a t i o n sI a I

I Castrinoma levelsof plasma andisinsulinresistant,

insulin
Castrinoma isa disease wheretheG cellsof whichisa majorfactorin itspathogenesisThe
isdueto decreasedbinding
I the pancreas
(frequently
undergo
cancerous)
excessproliferation
resulting
in anoverpro-
ductionof the hormonegastrin Thishor-
resistance
of insulin
defects
to insulin
to itsplasmalemma
in postreceptor
receptorsandto
actionTypell
insulin
monels responsible to parietal
for binding cells diabetes is usually by diet
controlled
I of thestomach
hydrochloric
causing themto over-secrete
acidwitha resultanlformation
of Jaundice(lcterus)
Jaundice (icterus) ischaracterized by excess
oeoticulcersin thestomach andtheduode-
I num Antrulcer drugsmayalleviate
acidityandresolve theulcerations;
thehyper-
otherwise
in thebloodanddeposition
bilirubin
pigmentin Lheskinandsclera
of bile
of theeyes,
resultingin a yellowish appearance lt maybe
surgicalintervention
maybe indicated
I TgpeI Diabetes
Type| (insulin-dependent)
hereditary
asexcess
or dueto pathologic
destruction
jaundice),
conditions
of redbloodcells
liverdysfunction,and
such

diabetes ischarac- [hemolytic

terizedby polyphagia(insatiablehunger), poly- obstruction of the biliarypassages (obstructive
I dipsia(unquenchable
cessive urination)
andpolyuria(ex-
thirst),
hasa sudden
lt usually onset
jaundice)

before20 yearsof age,isdistinguished by dam-GaIIstones (Bili arg CalcuIi)

I ageto anddestruction of betacells,results
a low levelof plasmainsulin,andistreated
Callstones
from Ibiliary
allyof fusedcrystals
areconcretions,
calculi) usu-
of cholesterolthatformin
gallbladder or bileduct Theymayaccumulate
wltha combination of insulin
therapy anddiet
I Tgpe II Diabetes Mellitus
Typell (non-insulin-dependent)
to suchanextentthatthecysticductis
blocked, thuspreventing emptying of thegall-
removal
surgical
diabetes mel- bladder, andtheymayrequire

t lituscommonly occurs in overweight

individuals if lessinvasive
over40 yearsof age lt doesnot resultfromlow pulverize them
methods failto dissolveor

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I Systemlll I
Digestive 505

Summargof HistologicalOrganization
I. MAJORSALIVARYGLANDS
Three major salivary glands are associatedwith
the oral cavity. These are the parotid, sub-
mandibular, and sublingual glands.
A. Parotid Gland
The parotid gland is a purely serous compound
tubuloalveolar gland whose capsule sends septa
(frequently containing adipose cells) into the sub-
stanceof the gland, dividing it into lobes and lob-
ules. Serous acini, surrounded by myoepithelial
cells,delivertheir secretionsinto intercalated ducts.
B. Submandibular
Gland
This compound tubuloalveolar gland is mostly
serous,although it contains enough mucous units,
capped by serous demilunes, to manufacture a
mixed secretion.Acini are surrounded by myoep-
ithelial (basket) cells. The capsule sendssepta into
the substanceof the gland, subdividing it into lobes
and lobules. The duct systemis extensive.
INIII a
I
III. LIVER
I
A. Capsule
Glisson's capsule invests the liver and sendssepta
into the substanceof the liver at the porta hepatis
I
to subdivide the parenchymainto lobules.
I
B. Lobules
l. ClqssicalLobule
Classical lobules are hexagonal with portal areas I
(triads) at the periphery and a central vein in the
center. Trabeculae (plates) of liver cells anasto-
mose. Sinusoids are lined by sinusoidal lining ,
cells and Kupffer cells (macrophages).Within the
space of Disse, fat-accumulating cells may be
noted. Portal areas housing bile ducts, lymph ves-
sels, and branches of the hepatic artery and the
I
portal vein are surrounded by terminal plates
composed of hepatocytes. Bile passesperipherally
within bile canaliculi, intercellular spacesbetween
I
liver cells, to enter bile ductules, then canals of

C. Sublingual Gland
Hering (and cholangioles), to be delivered to bile
ducts at the portal areas. I
The sublingual gland is a compound tubuloalveo- 2. Portol Lobule
lar gland whose capsule is not very definite. The
gland produces a mixed secretion, possessing
The apices of triangular cross-sectionsof portal
lobules are central veins. Thus, portal areas form I
mostly mucous acini cappedby serous demilunes the centersof these lobules. The portal lobule is
and surrounded by myoepithelial (basket) cells.
The intralobular duct systemis not very extensive.
basedon bile flow.
3. Acinus of Rappaport (Liver Acinus)
I
The acinus of Rappaport in section is a diamond-
II. PANCREAS
The exocrine pancreas is a compound tubulodve-
shaped area of the liver whose long axis is the
straight line between neighboring central veins
and whose short axis is the intersecting line be-
I
olar serous gland whose connective tissue capsule
tween neighboring portal areas.The liver acinus is
sendssepta to divide the parenchyma into lobules.
Acini present centroacinar cells, the beginning of basedon blood flow. I
the ducts that empty into intercalated ducts, which
Iead to intralobular, then interlobular ducts. The
main duct receivessecretoryproducts from the in-
terlobular ducts. The endocrine pancreas with its
IV. GALLBLADDER
The gallbladder is connected to the Iiver via its
I
islets of Langerhans (composed of A, B, G, and D rystic duct, which joins the common hepatic
cells) are scatteredamong the serousacini. duct. I
I
I
306 n Digestive
Systemlll I
I A. Epithelium C. MuscularisExterna
The gallbladder is lined by a simple columnar ep- Themusculatis of anobliquely
externaiscomposed
r itheliurn.

B. LaminaPropria
oriented smooth muscle layer.

I The lamina propria is thrown into intricate folds

that disappear in the distended gallbladder. Roki-
D. Serosa
Adventitia attachesthe gallbladder to the capsule
tansky-Aschoff sinuses(epithelial diverticula) may of the liver, while serosa covers the remaining

I be present. surface.

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Digestive 3O7
 15-1 |
CRAPHIC Pancreas I
Exocrlnefunctionof the pancreasis servedby its acinar
cells, centroacinarcells, and intercalatedducts.The
t
E acinarcells secretedigestiveenzymes,and the duct cells
supplyan alkalinebuffersolution.
I
tr
*ri
The endocrineportionis composedo{ the islets of
Langerhans,richlyvascularized sphericalaggregates of
cells encasedby reticularfibers.The isletsare composedof
from each
five types of cells,whichcan be differentiated
otheronlywithspecialstains. I
Commonbile
duct
Mainpancreatic raG!) ote" I
duct
Accessory
pancreaticduct I
\:
I
.?4, , O I
1"-

lntercalated
duct I
Capillary

Centroacinar
cells
I
lsletof
Langerhans
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Pancreatlcacinus
I
Zymogen
granures I
Golgi

RoughER
I
acinarcell
Pancreatic
I
508 | Digestive
Systemlll t
l

t 15-2 |
CRAPHIC Liver

I Left lobe
Falciform ligament
PORTALLOBULE:
Biledrainsto
bileduct.Portal
CLASSICLOBULE:
Sinusoidsdrain
to the central
area is center.

t Hepaticartery
Venacava
Portalvein

I
I
I HEPATICLOBULE:
Portalvein

I Centralvein
PORTALACINUS:
Tissuesuppliedby terminal
branchesof the hepaticartery
PORTALTRIAD: and portalvein.Cellsnearest

I Hepaticartery
Portalvein
thesevesselsare first to
receiveoxygenand nutrients.

Bileduct
I Sinusoids
Centralvein

t PORTALTRIAD:
Hepaticartery

Portalvein
I Bilecanaliculus Bileduct
Golgi

t
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i \$ Hepatocytes,livercells,deliverendocrinesecretionsintothe

I \". vascularsupply,and exocrinesecretion,bile, intoexcretory

[t' ducts,the bile ducts. Eachlivercellbordersa vascularspace,
sinusoid,on at leastone sideand otherhepatocytes on its
^. remainingsides.Wheretwo hepatocytes adjoin,theydelimita

I /] smallintercellular
s \ delivered.
space,bile canaliculus,intowhichthe bileis

Sincesinusoidsare linedby endothelial cells(sinusoidallining

cells) and macrophages (Kupffercells),hepatocytes do not

I come into contactwith the bloodstream.

intervenes betweenhepatocytes
The space of Disse
and sinusoidalliningcells.This
spacehousesmicrovilliof hepatocytes, occasional fat-storing
cells (lto cells),and slenderreticularfibers that helpformthe
Sinusoidal
liningcell
I Soaceof Disse
supportingframeworkof the liver.

I Digestive
Systemlll I 309
PLATE15-1 I SalivargGlands f
FIGURE I
section. x 132.
Parotid gland. Monkeg. Plostic

The parotid gland is purely serouswith a connective

tissuecapsulesendingtrabeculae(T) into the substance
of the gland, subdividing it into lobules (Lo). Slender
connectivetissuesheetspenetratethe lobules,surround-
ing small blood vessels (BV) and intralobular ducts
(iD). Interlobular ducts (ID) are surrounded by in-
creasedamounts of connective tissue (CT) and large
blood vessels.Observe that the acini (Ac) are closely
packedwithin eachlobule.
Inset. Parotid gland. Monkey. Plastic section.
x 540.
Note that the round nuclei (N) of theseserousacini
are basallylocated.The lateral cell membranes(arrows)
are not clearly visible, nor are the lumina of the acini.
Observethe slendersheetsof connectivetissue(arrow-
heads)investingeachacinus.
FIGURE 2 rt, Sublingual glond. Monkeg. Plastic
section. x 2'70.
The sublingualgland is a mixed gland in that it pro-
t
ducesboth serousand mucous secretoryproducts.The
mucous acini (MA) possess dark nuclei (N) that are flat-
tened againstthe basal cell membrane. Moreover, the I
cltoplasm is filled with a "frothy" appearingmaterial,
representingthe viscoussecretoryproduct. Many of the
mucous acini are cappedby serouscells,forming a cres-
cent-shapedcap, the serous demilune (SD). The sub-
t
lingual gland is subdivided into lobes and lobules by
connective tissue septa (CT) that act as the supporting
network for the nerves,vessels,and ducts of the gland.
The boxed areais presentedat a higher magnificationin
I
Figure3.
I

FIGURE 3 Sublingual gland. Monkeg. Plostic
section. x 540.
This photomicrograph is a higher magnification of
the boxed areaof Figure2. The flattened,dark nuclei (N)
of the mucous acini are clearlyevident as they appearto
be pressedagainstthe basalcell membrane.Observethat
much of the cltoplasm is occupiedby small,mucin-con-
taining vesicles(arrows),that the lateral cell membrane
(arrowheads)are clearlyevident,and that the lumen (L)
is usually identifiable.Serousdemilunes (SD) are com-
posed of serous-producingcells whose nuclei (N) are
round to oval in morphology. Note also that the lateral
cell membranesare not distinsuishablein serouscells.
I KEY
I
FIGURE 4 * Submandibular gland. Monkeg. Plastic
section. x 132.
The submandibulargland alsoproducesa mixed qpe
of secretion;however, unlike in the sublingual gland,
I
serousacini predominate.Serous(SA) and mucous acini
(MA) areeasilydistinguishablefrom eachother,but most
mucous units display a cap of serousdemilunes.More- I
over, the submandibular gland is characterizedby an
extensivesystemofducts (D), recognizableby their pale
cy'toplasm,comparatively large lumina (L), and round
nuclei. This gland is also subdivided into lobes and lob-
I
ules by connective tissue septa (CT).
Inset Submandibular gland. Monkey, Plastic sec-
tion. x 540.
Note the granularappearanceof the cellscomprising
I
the serous demilune (SD) in contrast with the "frothy"
appearingcltoplasm of the mucous acinus (MA).
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PLATE15-2 | Pancreas
FIGURE I Mt^Pancreas. Human. Paraffin section. x
132.
The pancreasis a complex gland since it has both
exocrineand endocrinecomponents.The exocrinepor-
tion comprisesthe bulk of the organ as a compound
tubuloaveolargland,secretinga serousfluid. The glandis
subdividedinto lobulesby connectivetissuesepta (CT).
Eachacinus (Ac) is composedof severalpyramid-shaped
cells,possessing round nuclei. Cellslocatedin the center
of the acinus, centroacinar cells (CA), form the smallest
ductsofthe gland.The endocrineportion ofthe pancreas
is composedof small, sphericalclumps of cells,islets of
Iangerhans (lL), which arerichly endowedby capillaries.
These islets of Langerhansare haphazardly scattered
among the serousacini of the pancreas.The boxed areais
presentedat a higher magnificationin Figure2.
FIGURE 3 n Pancreas. Monkeg. Plastic section.
x 540.
With the useof plasticsections,the morphologyof the
pancreaticacinusis well defined.Observethat in fortu-
itous sectionsthe acinus resemblesa pie, with the indi-
vidual cellsclearlydelineated(arrows).The nucleus (N)
ofeach trapezoid-shaped cell is round and the basalclto-
plasm (arrowhead)is relativelyhomogeneous,while the
apical cytoplasm is packedwith zymogen granules (ZG).
Centroacinar cells (CA) may be recognizedboth by their
locations,aswell asby the paleappearance oftheir nuclei.
Inset.Pancreas.Monkey. Plastic section. x 540.
Observe the centroacinar cell (CA), whose pale nu-
cleusis readily differentiatedfrom the surrounding acr-
nar cell nuclei.
I KEY
Ac acinus CT connectivetissuesepta
BV bloodvessel IL isletsof Langerhans
CA centroacinarcell N nucteus
312 * Digestive
Systemlll
FIGURE 2 m Poncreqs. Human. Paraffin section.
x 210.
This photomicrograph is a higher magnification of
the boxed area of Figure l. Note that the connective tis-
sue septa (CT), while fairly extensivein certain regions,
are quite slender in the interlobular areas.The trape-
zoidal morphologies of individual cellsof the serousacini
are clearly evident in fortuitous sections(arrow). Observe
also the centroacinar cells (CA), located in the center of
acini, which representthe smallestunits of the pancreatic
duct system.
FfGURE 4 m Islets of Langerhons. Monkeg. Plostic
section. x 210.
The islets ofLangerhans (IL), the endocrineportion
ofthe pancreas,is a more or lesssphericalconfiguration
ofcells randomly scatteredthroughout the exocrine por-
tion of the gland. As such, each islet is surrounded by
serousacini (Ac). The isletsreceivetheir rich blood sup-
ply (BV) from the connective tissue elements (CT) of
the exocrinepancreas.
Inset Islets of Langerhans. Monkey. Plastic section.
x 540.
Observe the rich vascularity of the islets of Langer-
hans, asevidencedby the presenceoferythrocyte (RBC)-
engorgedblood vessels. Although eachislet is composed
of A, B, C, and D cells, they can only be distinguished
from eachother by the use ofspecial stains.However,it
should be noted that in the human, B cells are the most
populousand areusuallylocatedin the centerofthe islet,
while A cellsare generallyfound at the periphery. This sit-
uation is reversedin the monkey.
Pancreasand cells
RBC erythrocyte
ZG zymogen granule
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PLATEl5-5 | Liver I
FIGURE | * Liver. Pig. Paraffin section. x 14.
Note that the liver is investedby a connectivetissue
capsule,Glisson'scapsule(GC), from which, in the pig,
FIGURE 2 s Liver. Dog. Paraffin sedion. x 132.
The portal areaofthe liver housesterminal branches
of the hepatic artery (HA) and portal vein (PV). Note
I
septa (S) extendto subdividethe gland into more or iess that the vein is much larger than the artery and its wall is
hexagon-shapedclassicallobules (Lo). Blood vessels,
lymph vessels,and bile ducts travel within the connective
very thin in comparisonto the sizeof its lumen. Branches
of lymph vessels(LV) and bile ducts (BD) are also pre-
I
tissue septa to reach the apicesof the classiclobules, sent in the portal area.Bile ducts may be recognizedby
which are known as the portal areas (PA). Bile reaches
the portal areasfrom within the lobules,while blood en-
ters the substanceof the lobules from the portal areas.
their cuboidal-to-columnarepithelium.Observethat un-
like in the pig, connectivetissueseptado not demarcate
the boundariesofclassicliver lobules,althoughthe vari-
I
Within each lobule, the blood flows throueh tortuous ous structuresofthe portal areaare investedby connec-
channels,the liver sinusoids,to enter the i-entral vein
(CV) in the middle of the classicallobule.
tive tissue elements.Plates of liver cells (PL) and sinu-
soids (Si) extendfrom the portal areas.
I
FIGURE 3 * Liver. Monkeg. Plqstic section. x 132.
The central vein (CV) of the liver lobule (a terminal
FIGURE 4 J Liver. Monkeg. Plastic section. x 210.
t
This photomicrograph is a higher magnification of
radix of the hepatic vein) collects blood from the sinu-
soids (Si) and deliversit to sublobularveins.The plates
ofliver cells (PL) and hepaticsinusoidsappearto radiate,
the boxed areaof the previous figure. Note that the lumen
of the central vein (CV) is lined by a simple squamous
epithelium (Ep), which is continuouswith the endothe-
I
as spokes of a wheel, from the central vein. The boxed lial lining ofthe hepaticsinusoids (Si), tortuous vascular
areais presentedat a higher magnificationin Figure4. channels that freely communicate with each other. Ob-
servealso that the liver plates (LP) are composedofhep- I
atocytes (H), one to two cell layers thick, and that each
plate is borderedby sinusoids.
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 PLATE15-4 I Liver.Gallbladder
FIGURE | & Liver. Monkeg. Plostic section. x 540.
This photomicrographis a high magnificationof liver
plates (LP). Observethat individual hepatocytes(H) are
polygonalin shape.Eachhepatocytepossesses one or two
nuclei, although occasionallysome have three nuclei.
Platesofhepatocltes enclosehepaticsinusoids (Si) that
arelined by sinusoidallining cells (SC);therefore,hepa-
tocytesdo not come into direct contact with the blood-
stream.The spacebetweenthe sinusoidallining cellsand
the hepatocytes, the spaceofDisse, is at the lim-itofreso-
lution of the light microscope.
Inset.Liver. Human. Paraffin section. x 540.
The hepatocytecell membranes are clearly evident in
this photomicrograph.Note that in fortuitous sections
small intercellular spaces (arrows) are recognizable.
Theseare bile canaliculithroueh which bile flows to the
peripheryofthe lobule.
FIGURE 3 4 Gallbladder. Human. Paroffin section.
x 132.
The gallbladderis a pear-shaped,hollow organ that
functionsin storing and concentratingbile. Its histologic
structure is relativelysimple,but its appearancemay be
deceiving.The mucosaof an empty gallbladder,asin this
photomicrograph, is thrown into numerous folds (ar-
rows), providing it with a glandularmorphology. How-
ever, close observation of the epitheliurn (Ep) demon-
stratesthat all of the simplecolumnar cellsof the mucous
membraneare identical.A looseconnectivetissue(CT),
sometimesreferredto asa lamina propria, liesdeepto the
epithelium. Observethat a muscularismucosaeis lack-
ing, and the smooth muscle (SM) surrounding the con-
nectivetissueis the muscularisexterna.The outermost
coat of the gallbladder is a serosaor adventitia. A regron
similar to the boxed area is presentedin Figure 4.
I KEY
BM basal membrane KC Kupflercell
CT connectivetissue LP liverplate
Ep epithelium N nucteus
H hepatocyte SC sinusoidal liningcell
51 6 ffi Digestive
Systemill
FIGURE 2 J Liver. Poroffin section. x 540.
A system of macrophages,known as Kupffer cells
(KC), are found interspersedamong the endotheliallin-
ing cells of liver sinusoids (Si). Thesemacrophagesare
larger than the epithelial cells and may be recognizedby
the presenceof phagocltosed material within them.
Kupffer cellsmay be demonstratedby injecting an animal
intravenouslywithIndia ink, asin this specimen.Observe
that some cells appear as large black smudgessince they
are filled with phagocytosedink (asterisk) while other
cells possessonly small quantities of the phagocytosed
material (arrowheads).Note alsothat much of the sinu-
soidallining is devoidofink, indicatingthat the endothe-
lial cells are probably not phagocltic.
FfGURE 4 a Gallbladder. Human. Paroffin section.
x 540.
This photomicrographis a higher magnificationof a
regionsimilar to the boxed areaof Figure3. Note that the
epithelium (Ep) is composed of identical-appearing tall
columnar cells,whose nuclei (N) are basallyoriented.
The lateral cell membranes are evident in certain regions
(arrows),while the apicalbrush border is usuallynot vis-
ible in hematorylin and eosin stainedspecimens.Observe
t
that a relatively thick basal membrane (BM) separates
the epithelium from the underlying loose connective tis-
sue (CT).
I
Qi sinusoid
SM smoothmuscle
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 PLATE15-5 | SalivargGland,ElectronMicroscopg I
FIGURE I r Sublingual gland. Human. Electron
microscopg. x 4050.
The human sublingualgland is composedmostly of
The serous cells (dc) may be recognized by their paler
cytoplasm and the presence of secretory granules
(arrows)housingelectron-dense materials.Note alsothe
I
mucous acini cappedby serousdemilunes.The mucous presenceof myoepithelial cells (myo), whose processes
cells (mc) display numerous filamentous bodies (0 and
secretorygranules,which appear to be empty (asterisks).
(arrowheads)encircle the acinus. (Courtesv of Dr. A.
Riva.) I
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31 8 g Digestive
Systemlll I
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Digestive
 PLATE15-6 I Liver, ElectronMicroscopg

.,rp'hd. sc
FfGURE I Liver. Mouse. Electron microscopg. charactcrized
si'' a
by the presenceof bile canaliculi (BC),
r11255. intercellularspacesthat are isolatedby the formationof
The hepatocytes of this electronmicrographdisplay occludingjunctions (OC). The cltoplasm of hepatocytes
tivo of their surfaces,one borderinga sinusoid (Si) and housesthe norrnalcellularcomplelnents, snchasnurner-
the otherwheretlvo parrcnchyntal cellscontacteachother ous mitochondria (m), elernentsof rough endoplasmic
(arrows).The sinusoidalsurfacedisplaysmicrovilli (mr') reticulum (rER), Golgi apparatus,smooth er-rdoplasmrc
thatextendinto thespaceofDisse(sD) Theyah-r'rost con- leticulum, l,vsosomes, suchasglycogen(g)
and inclusior-rs
tact sinusoidal lining cells (SC) that presentnumerous and lipid droplets(l). The nucleus(N) of oneof rhehep-
fenestrae(arrot'heads).The parenchvrnalcontactsare .rtoc\.tes
is clcarlvevident.

320 D i g e s t i vS
e y s t e ml l l
PLATE15-7 I ElectronMicroscopg
Islet of Langerhans,

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FIGURE | tr lslef of Longerhans. Robbit. Electron
microscopg. x 3578.
The islets of Langerhans house four types of
parenchymalcells,namely A, B, C, and D cells.B cells
(B) are the most numerous and may be recognizedby
the presenceof secretorygranuleswhose electron-dense
core is surroundedby a clearzone (arrows).A cells (A),
the second most numerous secretorycell, also house
many secretorygranules;however, these lack an elec-
tron-lucent periphery.D cells (DC) are the leastnumer-
ous and are characterizedby secretorygranules that are
much less electron-densethan those of the other two
cell types. (From Sato T, Herman L: Am J Anat
l6l:71-84,1981.)

Systemlll Y 321
Digestive
I
I Ig@TI l6
I
I UrinarASgstem
I The urinary system, composed of the kidneys, sels, afferent glomerular arterioles, arise, become
ureters,urinary bladder,and urethra, functions in envelopedby Bowman's capsule,and form a capil-
the formation of urine, regulation of blood pressure lary plexus known as the glomerulus.
I and fluid volume of the body, acid-basebalance,
and formation and releaseof certain hormones.
Collectively, Bowman's capsule and the
glomerulus are referred to as the renal corpuscle
The functional unit of the kidney is the urinifer- (seeGraphic 16-2). Efferent glomerular arterioles
I ous tubule (see Graphic 16-1), consistingof the
nephron and the collecting tubule, eachof which is
drain the glomerulus, passinginto the cortex, where
they form the peritubular capillary network, or
derived from a different embryologic primordium. into the medulla as arteriolae rectae spuriae, a part

I of the vasarecta.
The interstitium of the cortical labyrinth and the
KIDNEY capsuleare drained by interlobular veins, most of

I The kidneys possessa convexand a concaveborder,

the latter of which is known as the hilum. It is here
which enter the arcuateveins, tributaries of the in-
terlobar veins. Blood from the interlobar veins en-
ters the renal vein, which deliversits contentsto the
that arteriesenter and the ureter and veins leavethe inferior vena cava.
I kidney. Each kidney is divided into a cortex and a
medulla. UriniferousTubule
The cortical region is subdivided into the corti-
The functional unit of the kidney is the uriniferous
I cal labyrinth and the medullary rays. The medulla
is composed of 10-18 renal pyramids, each of
tubule, consistingofthe nephron and the collecting
tubule, each of which is derived from a different
whose apex is perforated by 15-20 papillary ducts
embryologicprimordium.
I (of Bellini) at the areacribrosa. Each renal pyramid
is said to constitute a lobe of the kidney. The region
Nephron
of the medulla betweenneighboring renal pyramids
is occupiedby cortical-like material known asrenal There are two types of nephrons, classifiedby the
I columns (of Bertin). Each medullary ray is an ex-
tension of the renal medulla into the cortex. where
location of their renal corpusclesin the kidney cor-
ter juxtamedullary, possessinglong thin limbs of

r it forms the core of a kidney lobule.

To understand the histophysiologyof the kid-
ney, its vascularsupply must be appreciated.Each
kidney is supplied by the renal artery, a direct
t branch of the abdominal aorta. This vesselsubdi-
vides into severalmajor branchesas it entersthe
hilum of the kidney. Each branch subsequently
Henle's loop, and cortical. It is the long thin limbs
of Henle'sloop that assistin the establishmentof a
concentration gradient in the renal medulla, per-
mitting the formation of hypertonic urine.
The nephron begins as a distended,blindly end-
ing invaginated region of the tubule, known as
Bowman's capsule.The modified cellsof the inner,

I divides to give rise to two or more interlobar ar-
Interlobar arteries pass between neighboring
pyramids toward the cortex and, at the corti-
I comedullary junction, give rise to arcuate arteries
that follow the baseof the pyramid. Small,interlob-
ular arteries derived from arcuatearteriesenter the
I cortical labyrinth (equidistant from neighboring
medullary rays) to reach the renal capsule.Along
the extent of the interlobular arteries,smaller ves-
visceral layer are known as podocytes. Some of
their primary (major) processesbut mainly their
secondary processesand terminal pedicels wrap
around the glomerular capillaries.Thesecapillaries
are fenestratedwith largepores (60-90 nm in diam-
eter) lacking diaphragms.
A thick basallamina is derived from and is in-
terposedbetweenthe podocytesand the endothe-
lial cells of the capillary. The spaces between
adjoining pedicels, known as filtration slits, are

I UrinarySystem il 323
 bridged by thin slit diaphragms that extend from
one pedicel to the next. Interstitial tissue com-
posed of intraglomerular mesangialcells and the
extracellularmatrix they manufacture is also as-
sociatedwith the glomerulus.
The ultrafiltrate from the capillariesenters
Bowman's (urinary) space and is drained from
there by the neck of the proximal tubule. The
simple cuboidal epithelium of the proximal
tubule adjoins the simple squamous epithelium
of the parietallayer of Bowman'scapsule.
The cells of the next portion, the proximal
convoluted tubule, possessan extensivebrush
border (microvilli) on their luminal surface.
Their lateral and basal plasma membranesare
considerablyconvoluted, forming numerous in-
terdigitations with membranesof adjoining cells.
The exaggeratedfolding of the basal plas-
malemmapresentsa region rich in mitochondria
and provides a striated appearancewhen viewed
with the light microscope.
The straight portion, or pars recta, of the
proximal tubules is also referred to as the
descendingthick limb of Henle's loop. It is histo-
Iogically similar to the convoluted portion; how-
ever,its brush border becomesshorter at its distal
terminus, where it joins the descendingthin limb
of Henle'sloop.
The descendingthin limb of juxtaglomerular
nephrons extends to the apex of the medullary
pyramid, where it forms a hairpin loop and con-
tinues toward the cortex as the ascending thin
limb of Henle's loop. The thin limbs of Henle's
loop are composedof simple squamousepithelial
cells (types I-IV) whose structure varies accord-
ing to their permeability to water, organellecon-
tent, and complexity of tight junctions. Type I
cells are present only in cortical nephrons,
whereas type II, III, and IV cells are present in
juxtaglomerular nephrons.
The ascending thick limb of Henle's loop is
also known as the pars recta of the distal tubule.
It is composed of simple cuboidal cells that re-
semble the cells of the distal convoluted tubule.
Cells of the distal tubule that contact the afferent
(and efferent) glomerular arteriole are modified,
in that they are thin, tall cuboidal cellswhose nu-
clei are close to one another. This reeion is re-
ferred to as the macula densaof the diital tubule.
Cells of the macula densa communicate with
modified smooth muscle cells, juxtaglomerular
(JG) cells, of the afferent (and efferent) glomeru-
lar arterioles.The macula densa and the TG cells
together form the juxtaglomerular apparatus.
Frequently, the extraglomerular mesangialcells,
also known as lacis cells, are likewise considered
to belong to the juxtaglomerular apparatus.
324 = UrinarvSvstem
CollectingDuct
Severaldistal convolutedtubulesjoin eachcollect-
ing duct, which is composedof a simple cuboidal
epithelium whose lateral cell membranes are
clearlyevident with the light microscope.The col-
lecting ducts descendfrom the medullary rays of
the cortex through the renal pyramids.As they de-
scend,severalcollectingducts merge to form the
ducts of Bellini, which terminate at the area
cribrosa.
The ductsofBellini then deliverthe urine formed
by the uriniferous tubule to the intrarenalpassage,
namely,the minor calyx,to be drainedinto a major
calyx and then into the pelvis of the ureter. These
excretorypassages, lined by transitionalepithelium,
possess a fibroelasticsubepithelialconnectivetissue,
a smooth muscletunic composedof inner longitu-
dinal and outer circular layers,aswell asa fibroelas-
tic adventitia.
EXTRARENALEXCRETORY
PASSAGES
The extrarenal excretory passagesconsist of the
ureters,urinary bladder, and urethra. The ureters
and bladderare alsolined by transitionalepithelia.
The ureters possessa fibroelasticlamina propria
and two to three layers of smooth muscle, ar-
ranged as above.The third muscle layer, the out-
ermost longitudinal layer, appearsin the lower
one-third of the ureter.
The transitional epithelial lining of the bladder
and of the other urinary passages offers an imper-
meablebarrier to urine. To be able to perform its
function, the plasmamembraneof the surfacemost
cells is thicker than the averageplasma membrane
and is composedof a latticestructureconsistingof
hexagonallyarrayedelements.Furthermore, since
cellsof the transitionalepitheliummust line an ever
larger surface as the urinary bladder distends, the
plasmamembraneis foldedin a mosaic-likefashion.
Folding occursat the interplaqueregions,whereas
the thickenedplaqueregionspresentvesicularpro-
files,which probablybecomeunfolded asurine ac-
cumulatesin the bladder.
The subepithelialconnectivetissueof the blad-
der is composed,accordingto most, of a lamina
propria and a submucosa.The three smooth mus-
cle layers are extensivelyinterlaced, making them
indistinguishablein some areas.
The urethra of the male differs from that of the
femalenot only in its length but alsoin its function
and epithelial lining. The lamina propria of both
sexescontain mucous glands of Littr6 and intraep-
ithelial glands,which lubricatethe lining of the ure-
thra, facilitatingthe passageof urine to the outside.

Histophgsiologg
I . F O R M AT I ON
OF T H E
ULTRAFILTRATE
Sincethe renal artery is a direct branch of the ab-
domirral aorta, the two kidneys receive20o/oof the
total blood volume per minute. Most of this blood
entersthe glomeruli, where the high arterial pres-
sure expressesapproximately l0o/o of its fluid
volume, 125 ml/min, into Bowman'sspaces.Vas-
cular pressureis opposedby two forces,the colloid
osmotic pressureof the blood and the pressureex-
erted by the ultrafiltrate present in Bowman's
space.
The renal filtration barrier, composed of the
fenestratedendothelialcell,the fusedbasallaminae
of the podoclte and capillary,and the diaphragm-
bridged filtration slits between pedicels,permits
only the passage of water,ions,and smallmolecules
into Bowman'sspace.The presenceof the polyan-
ionic heparansulfatein the lamina rara of the basal
lamina impedesthe passage of largeand negatively
charged proteins through the barrier. Moreover,
type lV collagen of the lamina densa acts as a
molecular sieve and traps proteins larger than
69,000MW.
To maintain the efliciencyof the filtering sys-
tem, intraglomerular mesangial cells phagocytose
the lamina densa,which then is renewed by the
combinedactionsof the podocytesand endothelial
cells.The modified plasma that enters Bowman's
spaceis known as the ultrafiltrate.
I I . F U N C T I O NO F T H E P R O X I M A L
TUBULE
The proximal tubule resorbsapproximately80o/o of
the water,sodium, and chloride,aswell as 1000/o of
the proteins, amino acids, and glucosefrom the
ultrafiltrate.
The resorbedmaterialsare eventuallyreturned
into the peritubular capillary network of the corti-
callabyrinth for distributionto the remainderof the
body. The movement of sodium is via an active
transport mechanismutilizing a sodium pump in
the basalplasmalemma, with chlorideand waterfol-
lowing passively. Sincesaltand waterareresorbedin
equimolarconcentrations, the osmolarity of the ul-
trafiltrate is not altered in the proximal tubule, but
remainsthe sameasthat of blood. The endocytosed
proteins are degradedinto amino acidsthat are also
T;ffiTT
releasedinto the renal interstitium tbr distribution
by the vascularsystem.The proximal tubule alsose-
cretesorganicacids,bases,and other substances into
the ultrafiltrate.
III. FUNCTIONSOF THETHINLIM BS
LOOP
OF HENLE' S
The descendingthin limb of Henle's Ioop is corrr-
pletelypermeableto water and salts,hencethe ul-
trafiltrate in the lumen will attempt to equilibrate
its osmolarity with the renal interstitium in its
vicinity.
The ascendingthin limb is mostly impermeable
to waterbut is relativelypermeableto salts;thus the
movementof water is impeded,but that of sodium
and chloride is not. The ultrafiltrate will maintain
the sameosmolarityas the renal interstitium in its
immediatesurroundingsas the concentrationgra-
dient decreases approachingthe cortex.
OF THEDISTAL
IV. FUNCTIONS
TUBULE
The pars recta of the distal tubule (ascendingthick
limb of Henle'sloop) is impermeableto water but
possesses a chloride pump (and possibly sodium
pump) that activelypumpschlorideout into the re-
nal interstitium. To maintain electricalneutrality,
sodium follows passively.Horvevcr,water cannot
enter or leavethc ultrafiltrate,lvhich consequently
losesits osmotic pressure,becoming hypoosmotic
by the tirne it reachesthe maculadensaregion.
The distalconvolutedtubule,whosecellspossess
aldosteronereceptors,resorbssodium ions from
and secretes hydrogen,potassium,and ammonium
ions into the ultrafiltrate,which it then deliversto
the collectingduct.
V. FUNCTIONOF THE
ERULARAPPARATUS
J UXTAGLOM
It is believedthat the macula densacells monitor
the osmolarityand volume of the ultrafiltrate.If ei-
ther of theseis elevated,the maculadensacells,via
gapjunctions, instruct the juxtaglomerularcellsto
releasetheir storedproteolyticenzylne,renin, into
the bloodstream.Renin cleavestwo amir.roacids
from the circulatingdecapeptideangiotensinogen,
UrinarySystem ffi 325
changing it to angiotensin I, which, in turn, is
cleavedby convertingenzymelocatedon the lumi-
nal surfacesof capillaries(especiallyin the lungs),
forming angiotensin II. This powerful vasocon-
strictor also prompts the releaseof the mineralo-
corticoid aldosteronefrom the suprarenalcortex.
Aldosterone binds to receptorson cells of the
distal convoluted tubules,prompting them to re-
sorb sodium (and chloride) from the ultrafiltrate.
The addition of sodium to the extracellularcom-
partment causesthe retentionof fluid with the sub-
sequentelevationin blood pressure.
V I . C O N C E N T R A T I OO
NF URINE
A. Nephron(Countercurrent Multiplier
System)
The concentration of urine occurs only in iux-
tamedullarynephrons,whose long thin'limbs of
Henle's loop function in the establishmentof an
osmotic concentration gradient. This gradient
graduallyincreasesfrom about 300 mOsm/L in the
interstitium of the outer medulla to as much as
1200mOsm/L at the renal papilla.
The chloride pump of the ascendingthick limb
of Henle's loop transferschloride ions from the
lumen into the renal interstitium. Sodium follows
passively,and water is not permitted to leave;
hencethe salt concentrationof the interstitium in-
creases.Sincethe supply of chloride inside the as-
cending thick limb decreasesas the ultrafiltrate
proceedstoward the cortex (becauseit is con-
stantly being removed from the lumen), less and
less chloride is availablefor transport; conse-
quently, the interstitial salt concentration de-
creasescloserto the cortex.
The osmoticconcentrationgradientof the inner
medulla,deepto the junction of the thin and thick
ascendinglimbs of Henle's loop, is controlled by
urea rather than sodium and chloride.
As the ultrafiltrate passesdown the descending
thin limb of Henle'sloop, it reactsto the increasing
gradient of osmotic concentrationin the intersti-
326 UrinarySystem
tium. Water leaves and salts enter the lumen,
reducing the volume and increasingthe salt con-
centration of the ultrafiltrate (which becomes
hypertonic).
In the ascendingthin limb of Henle'sloop, wa-
ter is conservedbut saltsare permitted to leavethe
ultrafiltrate, decreasingits osmolarity and con-
tributing to the maintenanceof the osmotic con-
centrationgradient.
B. Collecting Duct
The ultrafiltratethat entersthe collectingduct is hy-
poosmotic.As it passesdown the collectingduct it
is subjectto the increasingosmotic gradientof the
renal interstitium.
If antidiuretic hormone (ADH) is released
from the pars nervosaof the pituitaV, the cellsof
the collecting ducts become permeableto water,
which leavesthe lumen of the collectingduct, in-
creasingthe concentrationofthe urine. In the ab-
senceof ADH the cells of the collecting duct are
impermeable to water, and the urine remains
hypotonic.
The collectingduct is also responsiblefor per-
mitting urea to diffuse into the interstitium of the
inner medulla. The high interstitial osmolarity of
this region is attributed to the urea concentration.
C. VasaRecta(Countercurrent
Exchange
System)
The vasarectaassistsin the maintenanceof the os-
motic concentrationgradientof the renal medulla,
since these capillary loops are completelyperme-
ableto saltsand water.Thus. asthe blood descends
in the arteriarecta,it becomeshyperosmotic,but as
it ascendsin the venarecta,its osmolarityreturnsto
normal.
It is also important to realize that the arteria
rectacarriesa smallervolume than the vena recta.
permitting the removal of the fluid and salts
transported into the renal interstitium by the
uriniferous tubules.
t
C l i n i c a lC o n s i d e r a t i o n ss I I

I Tubular Necrosrs of thekidneyto concentrate

tubules The
urine.
T u b u l a rn e c r o s i ms a y r e s u l ti n a c u t e r e n a l f a i l - fluidlossin theformation
excess of copious
I u r e C e l l so f t h e r e n a lt u b u l e sd i e e i t h e rb y b e -
i n g p o i s o n e d u e t o e x p o s u r et o t o x l cc h e m i -
of diluteurineresultsin polydipsia
quantities
thirst)anddehydration
[excessive
c a l s ,s u c ha s m e r c u r yo r c a r b o nt e t r a c h l o r i d e ,
Kidneg Stones
t o r d i e b e c a u s eo f s e v e r ec a r d i o v a s c u lsahr o c k
t h a t r e d u c e sb l o o df l o wt o t h e k i d n e y sT h e Kidney stones usually
tionknownashyperparathyroidism,
formdueto thecondi-
where
d e a dc e l l sb e c o m es l o u g h e d o f f a n d o c c l u d et h e
l u m i n ao f t h e i rt u b u l e sl f t h e b a s a l a m i n a er e - theformation of excess parathyroid hormone
I m a i ni n t a c t ,e p i t h e l i acle l ld i v i s i o nm a y b e a b l e
(PTH)
increased
by theparathyroid
levelof osteoclastic
glands results
activityThere-
in an
t o r e p a i rt h e d a m a g ei n l e s st h a nt h r e ew e e k s
sorption of bone,aswellastheincreased ab-
I Acute CIomeru lon eph ritis
A c u t eg l o m e r u l o n e p h r i itsi su s u a l l yt h e r e s u l l -
sorption of calcium
gastrointestinal
andphosphates
tract.eventuate
fromthe
higher than
of a localized b e t aS t r e p t o c o c c ai nl f e c t i o ni n a normalbloodcalcium levelsAsthekidneys ex-

I r e g i o no f t h e b o d y o t h e rt h a n t h e k i d n e y( e g ,
s t r e pt h r o a t ) P l a s m ac e l l ss e c r e t ea n t i b o d i e s
cretehigher thannormalconcentration
ciumandphosphates, theirpresence
of cal-
in lhe
t h a t c o m p l e xw i t h s t r e p t o c o c c a ln t i g e n s , u r i n ee, s p e c i a u y d ear l k a l i nceo n d i t i o n s ,
l ln

t f o r m i n ga n i n s o l u b l e a n t i g e n - a n t i b o dc yo m p l e x
t h a t i s f l l t e r e db y t h e b a s a l a m i n ab e t w e e n
t h e p o d o c y t e sa n d t h e e n d o t h e l i acle l l so f t h e
causes
Continued
crystal
theirprecipitation
accretion
surface causes
in thekidneytubules.
of theseionsontothe
an increase in thesizeof
g l o m e r u l uA s s t h e i m m u n ec o m p l e xb u i l d su p thecrystals andtheybecome knownaskidney
I i n t h e g l o m e r u l abra s a l a m i n at,h e e p i t h e l i a l
c e l l sa n d m e s a n g i acle l l sp r o l i f e r a t eA d d i t i o n -
stones

a l l y ,l e u k o c y t eas c c u m u l a t ien t h e g l o m e r u l u s , Concersof the Kidneg

t c o n g e s t i nagn d b l o c k i n gi t M o r e o v e rp, h a r m a -
c o l o g i ca g e n t sr e l e a s e d a t t h e s i t eo f d a m a g e
Cancers
whereas
of thekidneyareusually

symptom
solidtumors,
cystsof thekidneyareusually benign
of kidneycancer is
c a u s et h e g l o m e r u l utso b e c o m el e a k ya n d Themostcommon
bloodin the urine,although theamountof
I p r o t e i n sp, l a t e l e t sa, n d e v e ne r y t h r o c y t em s ay
e n t e rt h e g l o m e r u l afri l t r a t e U s u a l l ya f t e rt h e bloodmaybe undetectable
examination
scopic
withouta micro-
of theurjne.Usually, kidney
a c u t ei n f l a m m a t i oanb a t e st h e g l o m e r u lri e p a i r
cancersareaccompanied by painandfever,but
t t h e m s e l v easn d t h e n o r m a lk i d n e yf u n c t i o nr e -
t u r n s O c c a s i o n a l lh
extensive
y ,o w e v e rt,h e d a m a g ei s
a n d k i d n e yf u n c t i o nb e c o m e sp e r m a -
frequently
palpation
theyarediscovered
duringroutine
by abdominal
physicalswhenthe
physiciandetectsa lumpin theregion of
n e n t l yi m p a i r e d
I Diabetes Insipidus
thekidneylf thecancer
treatmentof choice
didnotmetastasize
is removalof theaffected
the

D i a b e l e si n s i p i d uos c c u r sb e c a u s eo f d a m a g et o kidneyandregional lymphnodes. Sincekidney

r t h e c e l l so f t h e h y p o t h a l a m ut sh a t m a n u f a c t u r e
A D H f a n t i d i u r e t jhco r m o n e )T h e l o w l e v e l so f
A D H i n t e r f e r ew i t ht h e a b i l i t yo f t h e c o l l e c t i n g
cancersspread
prognosis
earlyandusually to thelungthe
is poorbutinterleukine-2
beenshownto be promising
therapy has

I
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I UrinarySystem 327

Summargof HistologicalOrganization
I. KIDNEY
A. Capsule
The capsuleis composedof denseirregularcollage-
nous connectivetissue.Occasionalfibroblastsand
blood vesselsmay be seen.
B. Cortex
The cortex consistsof parts of nephrons and col-
lecting tubules arranged in cortical labyrinths and
medullary rays.Additionally, blood vesselsand as-
sociatedconnectivetissue(renal interstitium) are
l. Cortical Labgrinth
The cortical labyrinth is composedof renal corpus-
cles and cross-sectionsof proximal convoluted
tubules,distal convolutedtubules,and the macula
densa region of distal tubules. Renal corpuscles
consist of mesangialcells, parietal (simple squa-
mous) and visceral(modified to podoqtes) layers
of Bowman's capsule,and an associatedcapillary
bed, the glomerulus, aswell asthe intervening Bow-
man's space,which receivesthe ultrafiltrate. The af-
ferent and efferent glomerular arterioles supply
and drain the glomerulus,respectively, at its vascu-
lar pole. Bowman's spaceis drained at the urinary
pole into the proximal convoluted tubule com-
posed of eosinophilicsimple cuboidal epithelium
with a brush border. The distal convolutedtubule
profilesarefewerin number and may be recognized
by the pale cuboidal epithelial cells. The macula
densaregion of the distal tubule is associatedwith
the juxtaglomerular (modified smooth muscle)
cells of the afferent (and sometimes efferent)
glomerulararterioles.
2. Medullarg Rags
Medullary rays are continuations of medullary tis-
sue extendinginto the cortex. They are composed
mostly of collecting tubules, pars recta of proximal
tubules,ascendingthick limbs of Henle'sloop, and
blood vessels.
C. Medulla
The medullais composedof renalpyramidsthat are
bordered by cortical columns. The renal pyramids
consist of collecting tubules whose simple cuboidal
328 # UrinarySystem
IT€II
epithelium displays 1) clearly defined lateral cell
membranes;2) thick descendinglimbs of Henle's
loop, whose cells resemblethose of the proximal
tubule; 3) thin limbs of Henle's loop, resembling
capillariesbut containingno blood; and 4) ascend-
ing thick limbs of Henle'sloop, whosecellsaresim-
ilar to those of the distal tubule. Additionally,
numerousblood vessels, the vasarecta,arealsopre-
sent,aswell asslightconnectivetissueelements,the
renal interstitium. The apex of the renal pyramid is
the renal papilla, whose perforated tip is the area
cribrosa, where the large collecting ducts (of
Bellini) open to deliver the urine into the minor
calyx.
D. Pelvis
The renal pelvis, subdivided into the minor and
major calyces, constitutes the beginning of the
main excretory duct of the kidney. The transitional
epithelium of the minor calyx is reflected onto the
renal papilla. The calycesare lined by transitional
epithelium. The subepithelialconnectivetissueof
both is looselyarrangedand abuts the muscularis,
composedof inner longitudinal and outer circular
layers of smooth muscle. An adventitia of loose
connectivetissuesurroundsthe muscularis.
II. EXTRARENAL
PASSAGES
A. Ureter
The ureter possesses lumen that is
a stellate-shaped
lined by transitional epithelium. The subepithelial
connectivetissue(sometimessaidto be subdivided
into lamina propria and submucosa)is composed
of a fibroelasticconnectivetissue.The muscularisis
again composedof inner longitudinal and outer
circular layers of smooth muscle, although in its
lower portion near the bladder a third, outermost
Iongitudinal layer of smooth muscle is present.
The muscularis is surrounded bv a fibroelastic
adventitia.
B. Bladder
The urinary bladder resemblesthe ureter except
that it is a much largerstructureand doesnot pos-
sessa stellatelumen, although the mucosa of the
t empty bladder is thrown into folds. The lamina
propria is fibroelastic in character and may con-
nal. The circular muscle coat forms the internal
sphincter at the neck ofthe bladder. An adventitia
tain occasionalmucous glands at the internal ori- or serosasurrounds the bladder. The urethra is de-
I fice of the urethra.The muscularisis composedof
three indefinite layers of smooth muscle: inner
scribedin Chapter 17, "FemaleReproductiveSys-
tem," and Chapter 18, "Male Reproductive
longitudinal, middle circular, and outer longitudi- System."
I
a
I
I
t
I
t
t
t
t
I
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I
J
I
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I UrinarySystem I 329
CRAPHICl6-1 r UriniferousTubules
Kidney\ The renalarteryentersthe renalveinand ureterleaveat the
hilus.The medulla,composed of 10-18renalpyramidsis
surroundedby the cortex, housingthe renal corpuscles,
the distal and the proximal convolutedtubules, and
medullary rays.

Distalconvolutedtuble

(Cuboidalepithelial
cells
withshortmicrovilli)

The distal tubule,

Proximal
convoluted
tubule comoosedof low
cuboidalcellswith
short,sparsemicrovilli,
beginsdeeperin the
medullathanthe
oroximaltubuleends.

Efterent
glomerular
arteriole
(Cuboidal
epithelial
cellswith
longdensemicrovilli)

The proximal tubule is composedof

cuboidalcellswhosebasalplasma (Cuboidal
epithelial
cells)
membrane displaysdeepinfoldings
(striations)housingmitochondria,
indicativeof active transport. lts
Thecollecting
apicalplasmamembranedisplays
ducts, possessing
numerouslongmicrovilli, denoting
cuboidalcells,begin
absorption and secretion.
in the medullaryrays
of the cortexand end
at the area cribrosa.

Thicksegmentof loopof Henle

Thinsegmentof loopof Henle

(Squamous
epithelial
cells) (Cuboidal
epithelial
cells)

Thethin limbs Henle'sloop,composed of
squamous cells,are longin juxtamedullary
and extremelyshortin corticalnephrons.
The arteria rocta of the vasa recta originatesal
a branchof the efterent glomerular arteriole ol
juxtamedullary nephrons. lts counterpartfrom
corticalnephronsestablishesthe peritubular
capillary network ot the cortex.

530 I UrinarySystem
 CRAPHf
C 16-2 | RenalCorpuscle

I Distaltubule
Maculadensa
Afferentarteriole cells
Juxtaglomerular
I Juxtaglomerular
cells
(modified
Efferentarteriole
smoothmuscle)

Bowman'scaosule
l (parietallayer) pole
Vascular

Bowman's capsule
I (visceral
layer
podocytes)
Theparietallayerof Bowmen'scapsule
I is composed
epithelium,
of simplesquamous
whereasitsviscerallayeris
modifiedto brm podocytes. The
iltrateentersBowman'r(urinery)
ultraf
I spaceand leavesthe renalcorpuscleat
itsurinarypol€,viatheproximal
convoluted tubule.Thediarant
glomcrularartcriolcentersandthe
I ctferontglomorulararterioleleavesthe
renalcorpuscleat its vatculrr pole,the
Parietallayer formersupplying andth6latterdraining
I Urinaryspace
Urinarypole
theglomerulus.
comoonent
Themrculadcnra
of thc distral
tubulecomesin
closeproximityto thejuxtaglomerular
cellsof the afterent(andefferent)
I glomerular arterioles.

t -tt'
Brushborder(microvilli)

convolutedlubul

I / Podocyto
Basallamina

t
I
Endothelium
t The fenestratedcapillariesconstituting
Secondary
process

the glomerulusare investedby pedicels

I arisinglrom the primary processes of

podocytes.Filtrationslits between
adjoiningpediclesare bridgedby thin
diaphragmsthat, in associationwith the
I fused basal laminae of the capillary
endotheliumand podocyte,contributeto Podocyte
the formationof the filtration barrier. cell body
Secondary
I process
(pedicel)

I UrinarySystem I 331
PLATE16-1 I Kidneg,Survegand CenerolMorphologg
FIGURE I Kidneg cortex ond medullo. Humon. FIGURE 2 Kidneg capsule. Monkeg. Plastic
Paraffin section. x 14. section. x 540.
The kidney cortex and part of the medullaare pre- The kidney is investedby a capsule(Ca) composedof
sentedat a low magnificationto providean insightinto dense collagenousconnective tissue containing occa-
the corticalarchitecture. The capsule(Ca) appearsas a sional fibroblasts (Fb). Although this structure is not
thin, light line at the top of the photomicrograph. The highly vascular,it does possesssome capsular vessels
darker areabelow it, occupyingthe top half of the pho- (CV). Observethe numerous red blood cells in the lu-
tomicrograph,is the cortex(C), whereasthe lowerlighter mina of thesevessels.The deeperaspectof the capsule
regionis the medulla(M). Note that longitudinalraysof possesses a rich capillary network (CN) that is supplied
the medullaappearto invadethe cortexitheseareknown by the terminal branchesof the interlobular arteriesand
as medullaryrays (MR). The tissuebetweenmedullary is drainedby the stellateveins,tributariesofthe interlob-
raysappearsconvolutedand is referredto asthe cortical ular veins.Note the cross-sections of the proximal con-
labyrinth (CL). It is occupiedby dense,round structures, voluted tubules (PT).
the renalcorpuscles(RC). Theseare the first part ofthe
nephrons,and their locationin the cortexis indicativeof
their time of development,as well as of their function.
They are referredto assuperficial( I ), midcortical (2), or
juxta-medullarynephrons(3). Eachmedullaryray and
one-halfofthecorticallabyrinthon eithersideofit con-
stitutesa lobuleofthe kidney.The lobuleextendsinto the
medulla,but its bordersare undefinablehistologically Kidney
(approximated by verticallines).The largevessels at the
corticomedullary junction are arcuate vessels (AV),
whereasthose in the cortical labyrinth are interlobular
vessels(lV).

FIGURE 3 Kidneg coftex. Human. Paraffin FIGURE 4 Colored colloidin-injected kidneg.

section. x 132.
The variouscomponentpartsofthe corticallabyrinth
and portions of two meduilary raysare evident.The on-
entationof this photomicrographis perpendicuiarto that
of Figure l. Note that two renal corpuscles(RC) in the
centerof the photomicrographdisplaya slight shrinkage
artifact and thus clearly demonstrateBowman's space
(BS). The renal corpusclesare surroundedby cross-
sectionsof proximal convolutedtubules (PT), distal con-
volutedtubules(DT), and maculadensa(MD). Sincethe
proximalconvolutedtubuleis much longerthan the con-
voluted portion of the distaltubule, the number of prox-
imal convolutedtubule profilesaround a renal corpuscle
outnumberthe distalconvolutedtubule profilesby ap-
proximately7 to 1. The medullaryrayscontainthe pars
recta (PR) of the proximal tubule, the ascendingthick
limbs of Henle'sloop (AT), and collectingtubules(CT).
Paraffin section. x 132.
This specimenwas prepared by injecting the renal
artery with colored colloidin, and a thick section was
takento demonstratethe vascularsupplyofthe renalcor-
puscle.Each renal corpusclecontainstufts ofcapillaries,
the glomerulus (G), which is supplied by the afferent
glomerular arteriole (AA) and drained by the efferent
glomerular arteriole (EA). Note that the outer diameter
ofthe afferentglomerulararterioleis greaterthan that of
the efferentglomerulararteriole:however,the diameters
of the two lumina areabout equal.It is important to real-
ize that the glomerulus is an arterial capillary network;
therefore,the pressurewithin thesevesselsis greaterthan
that of normal capillarybeds.This resultsin more effec-
tive filtration pressure.The largevesselon the lower right
is an interlobular artery (IA), and it is the parentvesselof
the afferentglomerulararterioles.

T KEY
AA afferentarteriole CN capillarynetwork lV interlobular
vessel
AT ascendingthicklimb CT collectingtubule M medulla
of Henle'sloop CV capsularvessel MD maculadensa
AV arcuatevessel DT distalconvolutedtubule MR medullaryray
BS Bowman'sspace EA efferentarteriole PR pars recta
conex Fb fibrobtast PT proximalconvolutedtubule
capsure G glomerulus RC renalcorpuscle
.\| codicallabyrinth lA interlobularartery

UrinarySystem
I - *==ca
I
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c,
't cv
I t\

I \^
|.\
\t
\lrr

\i/-7

t \3
r lN

r [--r
F I C U R E1 FIGURE
2
t
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3
I
PLATE16-2 I RenalCortex
FIGURE | ;. Kidneg cortical labgrinth. Monkeg.
Plastic section. x 210.
The centerof this photomicrographis occupiedby a
renal corpuscle. The urinary pole is evident as the short
neckemptiesinto the convolutedportion of the proximal
tubule (PT). The renal corpuscle is composed of the
glomerulus (G), tufts of capillaries,the viscerallayer of
Bowman's capsule(podocytes)that is intimately associ-
ated with the glomerulus, Bowman's space (BS), into
which the ultrafiltrate is expressedfrom the capillaries,
and the parietallayer (PL) of Bowman'scapsule,consist-
ing of a simple squamous epithelium. Additionally,
mesangialcells are also present in the renal corpuscle.
Most of the tubular profiles surrounding the renal cor-
pusclearetransversesectionsofthe darkerstainingprox-
imal tubules (PT), which outnumber the cross-sections
of the lighter stainingdistal tubules (DT).
FfGURE 3 ,: Kidneg cortical labgrinth. Monkeg.
Plastic section. x 210.
The vascularpole ofthis renalcorpuscleis very clearly
represented.It is in this region that the afferent glomeru-
lar arteriole (AA) enters the renal corpuscle and the ef-
ferent glomerular arteriole (EA) leaves,draining the
glomerulus. Observethat thesetwo vesselsand their cap-
illaries are supported by mesangial cells (Mg). Note that
although the outer diameter of the afferent glomerular
arteriole is greaterthan that ofthe efferent glomerular ar-
teriole, their luminal diameters are approximately the
same. The renal corpuscle is surrounded by cross-
sectional profiles of distal (DT) and proximal (PT)
tubules. The boxed area is presentedat a higher magnifi-
cation in Figure4.
Inset. Glomerulus. Kidney. Monkey. Plastic section.
x 120.
The glomerulus is composed of capillarieswhose
endothelial cell (En) nuclei bulge into the lumen. The en-
dothelial cells are separatedfrom podocytes (P), modi-
fied visceral cell layer of Bowman's capsule,by a thick
basal lamina (arrows). Mesangial cells (Mg) from both
supporting and phagocltic elementsof the renal corpus-
cle.Note that major processes (asterisks)ofthe podocltes
are also distinguishablein this photomicrograph.
I KEY
AA afferentarteriole En endothelialcell
BS Bowman'sspace G glomerulus
BV bloodvessel JC juxtaglomerular cell
DT distaltubule MD maculadensa
EA efferentarteriole Mg mesangialcell
334 = UrinarvSvstem
FfGURE 2 * Kidneg corticol lobgrinth. Monheg.
Plastic section. x 210.
The renal corpuscle in the center of the photomicro-
graph displaysall ofthe characteristicsidentified in Fig-
ure I, exceptthat instead ofthe urinary pole, the vascular
pole (VP) is presented.That is the region where the affer-
ent and efferent glomerular arteriolesenter and leavethe
renal corpuscle,respectively.Some of the smooth muscle
cells of the afferent (and sometimesefferent) glomerular
arterioles are modified in that they contain renin gran-
ules.These modified cells are known asjuxtaglomerular
cells (JC). They are closely associatedwith the macula
densa(MD) region of the distal tubule. Again, note that
most ofthe cross-sectional profilesoftubules surround-
ing the renal corpusclebelong to the convoluted portion
of the proximal tubules (PT) while only one or two are
distal tubules. Observethe rich vascularity (BV) ofthe re-
nal cortex, as well as the scant amount of connective tis-
sue elements(arrows) associatedwith thesevessels.
FTGURE4 tu Juxtaglomerular apparqtus. Kidneg.
Monkeg. Plostic section. x 1325.
The boxed areaofFigure 3 is magnifiedto presentthe
juxtaglomerularapparatus.This is composedof the mac-
ula densa (MD) region of the distal tubule and apparent
juxtaglomerular cells ()C), modified smooth muscle cells
of the afferent glomerular arteriole (AA). Observe the
granules(arrowheads)in the juxtaglomerular cells,which
are believed to be the enzyrnerenin. Note the nuclei (as-
terisks) of the endothelial cells lining the afferent
glomerulararteriole.
Renalcorpuscle
P podocyte
PL parietallayer
PT proximaltubule
VP vascularpole
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U ri n a r yS y s t e m 335
PLATE16-3 I Clomerulus,ScanningElectronMicroscopg I
I
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FIGURE| .+ Scanningelectronmicrographof a bottom, x 4000; ond inset, x 6000. (From RossMH,
glomerulus, displaging the primarg and secondorg
processesand pedicelsof podocgtes.Top, x 100;
Reith EJ, Romrell U: Histologg: A Text and Atlas. 2nd
ed. Boltimore: Willioms&. Wilkins, 1989:536.)
I
336 ii UrinarySystem I
PLATEl6-4 f RenalCorpuscle,ElectronMicroscopg
FIGURE I I Kidneg cortex. Renal corpuscle.
Mouse. Eledron microscopg. x 5780.
Various components of the renal corpuscle are dis-
played in this eleitron micrograph. Note the basallamina
(arrowhead) separatingthe simple squamous cells of the
parietal layer (PL) of Bowman's capsule from the renal
interstitium (RI). Bowman's space (BS) and the
podocytes (P) are shown to advantage, as are the
glomeruli (G) and surrounding pedicels (Pe). Mesangial
cells (Mg) occupy the spacebetween capillary loops, and
severalred blood cells (RBC) and endothelial cells (En)
are also evident.
Inset. Podoc'yte and glomerulus. Mouse. Electron
microscopy.x 6300.
This is a higher magnification of the boxed area,pre-
senting a portion of a podoqte. Observeits nucleus (N),
major process (MP), and pedicels (Pe). Notg that the
pedicelslie on a basal lamina (BL) that is composed of a
Iamina rara externa, lamina densa, and lamina rara in-
terna. Observethe fenestrations(arrows) in the endothe-
lial lining (En) of the glomerulus. The spacesbetweenthe
pedicels, known as filtration slits (FS), lead into Bow-
man's space(BS).
UrinarySystem I 337
PLATE16-5 I RenalMedulla
FIGURE | * Renol medullo. Monkeg. Plqstic
section. x 2lO.
This photomicrographof the renal medulla demon-
stratesthe arrangementofthe varioustubular and vascu-
lar structures.The formed connective tissue elements
among the tubulesand vesselsarevery sparseand consti-
tute mainly fibroblasts,macrophages,and fibers (aster-
isks).The major tubular elementsin evidencearethe col-
lecting tubules (CT), recognizableby the conspicuous
lateral plasmamembranesof their tall cuboidal (or low
columnar) cells,thick limbs of Henle's loop (TH), and
occasionalthin limbs of Henle'sloop (TL). Many vascu-
lar elementsare noted; these are the vasa recta spurra
whosethicker walled descendinglimbs are the arteriolae
rectae spuriae (AR) and thinner walled ascendinglimbs
are the venulae rectae spuriae (VR).
FIGURE 3 * Renol pdpilla. x.s. Monkeg. Plastic
section. x 540.
In the deeperaspectof the medulla collectingtubules
merge with each other, forming larger and larger struc-
tures. The largest of these ducts are known as papillary
ducts (PD) or ducts of Bellini that may be recognizedby
their tall, pale columnar cellsand their easilydiscernible
lateralplasmamembranes(arrows).Theseducts open at
the apex of the renal papilla,in the region known as the
area cribrosa.The thin limbs of Henle's loop (TL) are
clearly evident. These structuresform the hairpin-like
loops of Henle in this region, where the ascendingthin
limbs recur to ascend in the medulla, eventually to be-
come thicker, forming the straight portion of the distal
tubule. Note that the arteriolae rectae spuriae (AR) and
the venulae rectae spuriae (VR) follow the thin limbs of
Henle'sloop deepinto the renalpapilla.Someof the con-
nective tissueelementsare marked by asterisks.
I KEY
AR arteriolaerectaesouriae PD papillary
CT collectingtubule TH
thicklimbof Henle's
FIGURE 2 J Renal popilla. x.s. Humon. Paraffin
section, x 210.
The most conspicuous tubular elements of the renal
papilla are the collecting tubules (CT) with their cuboidal
cells,whoselateral plasmamembranesare clearly evident.
The numerous thin-walled structures are the thin limbs
of Henle's loop (TL), as well as the arteriolae rectae
spuriae (AR) and venulae rectae spuriae (VR) that may
be identified by the presenceof blood in their lumina.
The formed connectivetissueelements(asterisks)may be
discernedin the interstitium among the various tubules
of the kidney. An occasionalthick limb of Henle'sIoop
(TH) may alsobe observed.
FIGURE 4 | Renal medulla. I.s. Monkeg. Plqstic
section. x 210.
This photomicrograph is similar to Figure 1, except
that it is a longitudinal rather than a transversesection of
the renal medulla. The center is occupied by a collecting
tubule (CT), as is distinguished by the tall cuboidal cells
whose lateral plasma membranes are clearly evident. The
collecting tubule is flanked by thick limbs of Henle's loop
(TH). The vasarecta are filled with blood, and the thick-
nessof their walls identifies whether they are arteriolae
rectae spuriae (AR) or venulae rectae spuriae (VR). A
thin limb of Henle's loop (TL) is also identifiable.
tubule
Uriniferous
duct TL thin limb of Henle'slooo
loop
VR venulaerectaesouriae
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FICURE
3 FICUR4
E
U r i n a r yS y s t e m 339
PLATE16-6 I Ureterand UrinargBladder
FTGURE | .= Ureter. x.s. Humon. Poroffin section.
x 14.
This low power photomicrograph of the ureter dis-
lumen (L) and thick lining ep-
plays its stellate-shaped
ithelium (E). The interface between the subepithelial
connective tissue (SCT) and the smooth muscle coat
(SM) is indicated by arrows. The muscle coat is sur-
rounded by a fibrous adventitia (Ad), which housesthe
numerousvascularchannelsand nerve fibers that travel
with the ureter.Thus,the wall of the ureterconsistsof the
mucosa (epithelium and underlying connectivetissue),
muscularis,and adventitia.
FIGURE 3 -'. Urinorg bladder. Monkeg. Plastic
section. x 14.
The urinary bladderstoresurine until it is readyto be
voided. Sincethe volume of the bladderchangeswith the
amount of urine it contains,its mucosamay or may not
displayfolds. This particular specimenis not distended,
hencethe numerousfolds (arrows).Moreover, the tran-
sitional epithelium (TE) of this preparationis alsothick,
while in the distendedphase,the epithelium would be
much thinner. Note also that the thick muscularis is
composedof three layersof smooth muscle:inner longi-
tudinal (IL), middle circular (MC), and outer longitudi-
nal (OL). The musclelayersare surroundedeither by an
adventitiacomposedof looseconnectivetissue-as is the
casein this photomicrograph-or by a serosa,depending
on the resion of the bladderbeins examined.
I KEY
A arteriole lumen
Ad adventitia tt laminapropria
D dome-shapedcell MC middlecircularmuscularis
E epithelium OL outerlongitudinal
IL innerlongitudinal muscularis
muscularis SCT subepithelialconnective
tissue
34O ;: UrinarySystem
FfGURE 2 * Ureter. x.s. MonkeA. Plastic section.
x 132.
The mucosa is highly convoluted and consistsof a
thick, transitional epithelium whose free surface pos-
sessescharacteristicdome-shapedcells(D). The basalcell
layersits on a basallamina (arrows),which separates the
epithelium from the underlying fibrous connectivetis-
sue. The muscularis consistsof three layersof smooth
muscle:inner longitudinal (IL), middle circular (MC),
and outer longitudinal (OL). Thesethree layersare not
always present, for the outer longitudinal layer is found
only in the inferior one-third of the ureter, that is, the
portion nearestthe urinary bladder.The adventitia (Ad)
is composedoffibrous connectivetissuethat anchorsthe
ureterto the posteriorbody wall and adjacentstructures.
FIGURE 4 M UrinarA bladder. Monkeg. Plastic
section. x 132.
The bladder is lined by transitional epithelium (TE),
whosetypicalsurfacedome-shapedcellsareshownto ad-
vantage.Someofthese cellsare binucleated.The epithe-
lium is separatedfrom the underlying connective tissue
by a basallamina (arrows).This subepithelialconnective
tissue is frequently said to be divided into a lamina pro-
pria (LP) and a submucosa(Sm). The vascularityof this
regionis demonstratedby the numerousvenules(V) and
arterioles (A). Thesevesselspossesssmaller tributaries
and branchesthat supplythe regionscloserto the epithe-
lium.
Inset Transitional epithelium. Monkey. Plastic
section.X 540.
The boxedregionofthe transitionalepitheliumis pre-
sentedat a higher magnificationto demonstratethe large
dome-shapedcells(arrow) at the freesurface.Thesecells
are characteristicof the empty bladder.When that struc-
ture is distendedwith urine, the dome-shapedcells as-
sume a flattenedmorphology and the entire epithelium
becomes thinner (being reduced from five to seven to
only three cell layers thick). Note that occasionalcells
may be binucieated.
SM smoothmusclecoat
Sm su0mucosa
TE transitionalepithelium
venute
I
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FICURE
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I FemaleReproductiveSgstem
The femalereproductivesystem(seeGraphic 17-1)
is composedof the ovaries,genital ducts, external
genitalia, and the mammary glands, although, in a
strict sense,the mammary glandsare not genital or-
gans. The reproductive system functions in the
propagationof the speciesand is under the control
of a complex interplay of hormonal, neural and, in
the human, psychologicfactors.
OVARY
Each ovary is a small, almond-shaped structure
whose thick connectivetissue capsule,the tunica
albuginea, is covered by a simple squamous to
cuboidal mesothelium known as the germinal
epithelium. The ovary is divisible into a cortex rich
in ovarian follicles and a highly vascularmedulla.
The cortex, Iocatedjust deep to the tunica al-
buginea, housesthe female germ cells, oogonia,
which have undergone cell divisions to form nu-
merous oocltes. Each oocyte is surrounded by a
layer of epithelial cells,and thesetwo structuresto-
gether constitute an ovarian follicle. Under the in-
fluence of follicle stimulating hormone, follicles
enlarge,are modified, become encapsulatedby the
ovarianstroma (connectivetissue),and mature.
OvarianFollicles
The follicle passesthrough various maturational
stages,from the primordial follicle, to the primary,
the secondary,and, finally, the Graafian (mature)
follicle. The primordial follicle is composed of a
primary oocfte surrounded by a single layer of
flattened follicular cells.As maturation progresses,
the follicular cells become cuboidal in shape, and
the follicle is referred to as a unilaminar primary
follicle. Multilaminar primary follicles display an
ooclte surrounded by several layers of follicular
cellsand an intervening zona pellucida, aswell asan
externally oositioned theca interna.
IIGII t7
With further growth of the follicle, accumula-
tions of follicular fluid in the intercellular spacesof
the follicular cells form. At this point the entire
structure is known as a secondary follicle, and it
presentsa well-developed zona pellucida, a clearly
distinguishable basal membrane, and a theca in-
terna and a theca externa.
As maturation progresses,the Graafian follicle
stageis reached.This largestructure is characterized
by a follicular fluid containing the central antrum
whose wall is composed of the membrana granu-
losa. |utting into the antrum is the cumulus oopho-
rus housing the primary oocyte and its attendant
zona pellucida and corona radiata. The membrana
g."n.r1or" is separatedfrom the theca interna by the
basalmembrane. The theca externa mergesimper-
ceptibly with the surrounding ovarian stroma. The
Graafian follicle, mostly becauseof the activity of
luteinizing hormone, ruptures, thus releasingthe
oocytewith its attendant follicular cells.
CorpusLuteum
Once the Graafianfollicle losesits ooclte, it becomes
transformed into the corpus hemorrhagicum.
Within a couple of daysthe corpus hemorrhagicum
is transformed into the corpus luteum, a yellow
structure that produces estrogens and proges-
terone. When the corpus luteum degeneratesit
becomesthe fibrotic corpus albicans.
GENITAL DUCTS
Oviduct
Each oviduct (fallopian tube) is a short muscular
tube leading from the vicinity of the ovary to the
uterine lumen. The oviduct is subdivided into four
regions: the infundibulum (whose fimbriae
approximate the ovary), the ampulla, the isthmus,
and the intramural portion, which piercesthe wall
System ro 343
FemaleReproductive
of the uterus.The mucosaof the oviduct is exten-
sivelyfolded in the infundibulum and ampulla,but
the folding is reducedin the isthmus and intramu-
ral portions.
Uterus
The uterus, a pear-shapedviscus,is divisibleinto a
fundus, a body, and a cervix. During pregnancy it
is this organ that housesand supports the devel-
oping embryo and fetus. The uterus is composed
of a thick, muscular myometrium (covered by
serosaand/or adventitia) and a spongy mucosal
layer, the endometrium. The endometrium, com-
posedof an epitheliallylined lamina propria, with
its superficialfunctional and deepbasallayers,un-
dergoes hormonally modulated cyclic changes
during the menstrualcycle.The three stagesof the
endometrium are:
a. Follicular (proliferative) phase, during which
the free surfaceof the endometrium is reepithe-
lialized, and the glands, connectivetissue ele-
ments, and vascularsupply of the endometrium
are reestablished.
b. Luteal (secretory) phase, occurring within a
few days after ovulation, during which the
glandsfurther enlargeand becometortuous and
their lumina becomefilled with secretoryprod-
ucts. Additionally, the helical arteries become
more coiled,and fibroblastsof the stroma accu-
mulate glycogenand fat.
c. Menstrual phase, during which the functional
Iayerof the endometriumis desquamated, result-
ing in menstrual flow, while the basal layer re-
mains more or lessundisturbed.
PLACENTA
During pregnancythe uterus participatesin the
formation of the placenta,a highly vascularstruc-
ture that permits the exchangeof variousmaterials
between the maternal and fetal circulatory systems
(seeGraphic 17-2).It must be stressedthat the ex-
changeoccurswithout the commingling of the ma-
u FemaleReproductive
System
ternal and fetal bloods and that the placentais de-
rived from both maternaland fetaltissues.
VAGINA
The vagina is a muscular sheath adapted for the
reception of the penis during copulation and for
the passageof the fetus from the uterus during
birth. The wall of the vagina is composedof three
layers: an outer fibrous layer, a middle muscular
layer, and an inner mucosal layer. The lamina
propria of the mucosapossesses no glands.A strat-
ified squamous nonkeratinized epithelium lines
the vagina.
EXTERNALGENITATIA
The external genitalia,composedof labia majora,
labia minora, clitoris, and vestibular glands, are
also referred to as the vulva. These structures are
richly innervated and function during sexual
arousaland copulation.
MAMMARY GTANDS
Mammary Gland
The mammary glands, highly modified sweat
glands, are identical in males and femalesuntil the
onsetofpuberty, when under hormonal influences
the femalebreastsdevelop.The mammary gland is
composed of numerous individual compound
glands,each of which is considereda lobe. Each
lobe is drained by a lactiferous duct that deliversthe
secretiononto the surfaceofthe nipple.
Areola
The pigmentedregion of the skin surroundingthe
nipple, known as the areola,is richly endowedby
and areolarglands.The mammary
sweat,sebaceous,
glandsundergo cyclic changesand, subsequentto
pregnancy,producemilk to nourish the newborn.

Histophgsiologg
I. RECULATION
OF FOLLICLE
MATURATIONAND OVULATION
Gonadotropin-releasing hormones from the hy-
pothalamusactivategonadotrophsof the adenohy-
pophysis to release follicle-stimulating hormone
(FSH) and luteinizinghormone (LH).
FSH not only induces secondaryfollicles to ma-
ture into Graafian follicles but also causescells of
the theca interna to secreteandrogens.Addition-
ally, FSH prompts granulosacellsto developLH re-
ceptors,to convert androgensto estrogens,and to
secreteinhibin, activin, and folliculostatin. These
hormones assistin the feedbackregulationof FSH
release.Moreover, as estrogenreachesa threshold
level,it causesa surgeofLH release.
The LH surgeresultsnot only in resumption of
meiosis I in the primary oocyte and initiation of
meiosisII in the (now) secondaryooc)'tebut alsoin
ovulation. Additionally, LH induces the develop-
ment of the corpus luteum from the theca interna
and membranagranulosa.
I I . F U N C T I O NA N D F A T EO F T H E
CORPUSLUTEUM
The corpus luteum secretesprogesterone,a hor-
mone that suppressesLH releaseby inhibiting
gonadotropin-releasing hormone (GnRH) and fa-
cilitatesthe thickeningof the uterineendometrium.
Additionally, estrogen(inhibitor of FSH) and re-
laxin (which causesthe fibrocartilage of the pubic
symphysisto become more pliable) are also re-
Ieasedby the corpusluteum.
In casepregnancydoesnot occur,the corpuslu-
teum atrophies, and the absenceof estrogen and
progesteronewill once again permit the releaseof
FSH and LH from the adenohypophysis.
In casepregnancydoes occur, the syncytiotro-
phoblasts of the forming placenta releasehuman
chorionic gonadotropin (hCG), a hormone that
maintains the placenta well into the second
trimester.Thesecellsalsosecretehuman chorionic
mammotropin (facilitates milk production and
growth), thyrotropin, corticotropin, relaxin, and
estrogen.
IIilII
III. UTERINE TO
RESPONSE
HORMONES
A. Endometrium
The endometrium is separatedinto a deeper basal
and a more superficialfunctional layer, eachwith its
own blood supply. The basal layer, which remains
intact during menstruation, is served by short
straight arteries and is occupied by the baseofthe
uterine glands. The functional layer, servedby the
helicine (coiled) arteries, undergoes hormonally
modulated cyclic changes.
FSH facilitates the proliferative phase, a thick-
ening of the endometrium and the renewal of the
connective tissue, glandular structures and blood
vessels(helicine arteries) subsequentto the men-
strual phase.
LH facilitatesthe secretoryphase,characterized
by the further thickening of the endometrium, coil-
ing of the endometrial glands, accumulation of
glandular secretions, and further coiling and
Iengtheningof the helicine arteries.
DecreasedlevelsofLH and progesteroneare re-
sponsiblefor the menstrual phase,which begins
with long-term, intermittent vasoconstriction of
the helicinearteries,with subsequentnecrosisofthe
vesselwallsand endometrialtissueof the functional
layer. It should be understood that the basallayer is
unaffected because it is being supplied by the
straight arteries.During relaxation (betweenevents
of vasoconstriction),the helicine arteriesrupture'
and the rapid blood flow dislodgesthe blood-filled
necrotic functional layer, so that only the basallayer
remalns.
B. Myometrium
During pregnancythe smooth muscle cells of the
myometrium undergo both hypertrophy and hy-
perplasia, increasing the thickness of the muscle
wall. Additionally, these smooth muscle cells also
acquire gap junctions that facilitate their coordi-
nated contractile actions. At parturition, oxytocin
and prostaglandins cause the uterine muscles to
undergo rhythmic contractions that assist in ex-
pelling the fetus.
System x
FemaleReproductive 345
I V. HO R M O N ALEF F E C TON
S THE
MAMMARYGLAND
During pregnancy,severalhormones interact to
promote the developmentof the secretoryunits of
the mammary gland. Cells of the terminal inter-
alveolar ducts proliferate to form secretoryalveoli.
The hormones involved in promoting this process
are progesterone, estrogen, and human chorionic
mammotropin from the placenta and lactogenic
hormone (prolactin) from the acidophils of the
adenohypophysis.
Alveoli and terminal interalveolar ducts are sur-
rounded by myoepithelial cells that contract as
C l i n i c a lC o n s i d e r a t i o n s* r I
Popanicolaou (Pap) Smear
P a p a n i c o l a o[ u P a p )s m e a ri s p e r f o r m e da s p a r t
o f r o u t i n eg y n e c o l o g i ceaxl a m i n a t i otno e x a m -
i n e s t a i n e de x f o l i a t i vcee l l so f t h e l i n i n go f t h e
c e r v i xa n d v a g i n aE v a l u a t i oonf t h e s m e a r e d
c e l l sp e r m i t st h e r e c o g n i t i oonf p r e c a n c e r o u s
c o n d i t i o n sa,s w e l la s c a n c e ro f t h e c e r v i xA n
a n n u a sl m e a rt e s t i s r e c o m m e n d esdi n c ec e r v i -
c a l c a n c e ri s r e l a t i v e lsyl o wg r o w i n ga n d t h e P a p
s m e a ri s a n e x t r e m e l yc o s t - e f f e c t i vper o c e d u r e
t h a t h a sb e e nr e s p o n s l b lfeo r t h e e a r l yd e t e c -
t i o n o f c e r v i c acl a n c e ra n d f o r s a v i n sl i v e so f a f -
f e c t e di n d i v i d u a l s
Conorrhea
Conorrhea i s a s e x u a l l yt r a n s m i t t e d
b a c t e r i ailn -
f e c t i o nc a u s e db y t h e g r a mn e g a t i v e diplococ-
cus,,A/eisserio gonorrhoeae. In the United
Statesovera millioncasesof gonorrheaoccur
a n n u a l l yF r e q u e n t l yt h, i ss e x u a l l yt r a n s mj t t e d
d i s e a s e( S T Di)s r e s p o n s i b lfeo r p e l v i ci n f l a m m a -
t o r y d i s e a s ea n d f o r a c u t es a l p i n g i t i s
Pelvic Inflammatorg Disease (PID)
P e l v i ci n f l a m m a t o rdyi s e a s e( P l D )i s i n f e c t i o n
of thecervixu , t e r u s f, a l l o p i a n
t u b e s ,a n d / o r
o v a r y ,u s u a l l ya s e q u etl o m i c r o b i ai ln f e c t i o n
I n d i v i d u a sl su f f e r i nfgr o m P I De x h i b i t e n d e r -
n e s sa n d p a i ni n t h e l o w e ra b d o m i n arle g i o n ,
f e v e r ,u n p l e a s a n t - s m e l lvi n a g i n adl i s c h a r g e ,
a n de p i s o d eo s f a b n o r m abl l e e d i n gI.n s e v e r e
c o n d i t i o ntsh e p a i nm a y b e d e b i l i t a t i n gr e , quir-
i n gb e d r e s ta n d t h e a d m i n i s t r a t i oonf p o w e r f u l
an al g e s l c s
346 * FemaleReproductiveSystem
result ofthe releaseofoxytocin from the neurohy-
pophysis(in responseto suckling),forcing milk out
of the breast (milk ejection reflex).
V. MILK
Milk is composedof water, proteins, lipids, and
lactose.However, milk secretedduring the first
few days (colostrum) is different. It is rich in
vitamins,minerals,lymphoid cells,and proteins,es-
pecially immunoglobulin A, providing antibod-
ies for the neonatefor the first few months of life.
Endometriosis
E n d o m e t r i o siissd i s t i n g u i s h ebdy t h e p r e s e n c e
o f e c t o p i ce n d o m e t r i at il s s u ed i s p e r s e tdo v a r i -
ous sitesalongthe peritonealcavity Occasion-
a l l yt h e t i s s u e sm a y m i g r a t et o e x t r a p e r i t o n e a l
a r e a s i,n c l u d i n tgh e e y e sa n d b r a i n T h ee t i o l -
o g y o f t h i sd i s e a s ei s n o t k n o w n ,b u t p o s s i b l y
d u r i n gt h e m e n s t r u acl y c l es o m eo f t h e
e n d o m e t r i acle l l sm a y m i g r a t ea l o n gt h e
o v i d u c t sa n d l h u se n t e rt h e p e r i t o n e acla v i t y I n
m o s tc a s e st h e l e s i o n so f e n d o m e t r i o si ns v o l v e
s m a l lc y s t sa t t a c h e ds e p a r a t e loyr i n s m a l l
c l u m p so n t h e v i s c e r aol r p a r i e t apl e r i t o n e u m
Endometrial Concer
Endometria cal n c e irs a m a l i g n a n coyf t h e u t e r -
l n ee n d o m e t r i u m u s u a l l yo c c u r r i n ign p o s t -
menopausa wlo m e n T h em o s tc o m m o nt y p e o f
e n d o m e l r i acla n c e irs a d e n o c a r c i n o mSai n c e
duringthe earlystagesthe cancercellsdo not in-
vadethe cervix,Papsmearsare not very effec-
t i v ei n d i a g n o s i nt g
h i sd i s e a s u
e n t i li t h a se n t e r e d
its laterstagesThe majorsymptomof the en-
d o m e t r i acl a n c e irs a b n o r m aul t e r i n eb l e e d i n g
Paget's Disease of the Nipple
P a g e t ' sd i s e a s e
o f t h e n i p p l eu s u a l l yo c c u r si n
e l d e r l yw o m e na n d i s a s s o c i a t ew di t hb r e a s t
c a n c e ro f d u c t a lo r i g i n l n i t i a l l yt h e d i s e a s e
m a n i f e s tas s s c a l yo r c r u s t yn i p p l ef r e q u e n t l y
a c c o m p a n i ebdy a f l u i dd i s c h a r gfer o m t h e n i p -
p l e U s u a l l yt h e p a t i e n th a sn o o t h e rs y m p t o m s
a n d f r e q u e n t l yn e g l e c t tsh e c o n d i t i o nT h e
t r e a t m e not f c h o i c ei s a m a s t e c t o mw y i t hr e -
m o v a lo f r e g i o n ally m p hn o d e s

I Summargof HistologicalOrganization
I. OVARY
A. Cortex
The cortex of the ovary is covered by a modified
mesothelium, the germinal epithelium. Deep to
this simple cuboidal to simple squamousepithe-
lium is the tunica albuginea,the fibrous connective
tissue capsule of the ovary. The remainder of the
ovarianconnectivetissueis more cellularand is re-
ferred to as the stroma. The cortex housesovarian
follicles in various stagesof development.
l. Primordiql Follicles
Primordial follicles consistof a primaryoocyte sur-
rounded by a single layer of flattened follicular
(granulosa) cells.
2. Primarg Follicles
a. UnilaminarPrimary Follicles
Consistof a primary oocytesurroundedby a single
layer of cuboidal follicular cells.
b. Multilaminar PrimaryFollicles
Consistof a primary ooclte surroundedby several
Iayersof follicular cells. The zona pellucida is visi-
ble. The thecainterna is beginningto be organized.
3. Secondarg Uesicular) Follicle
The secondary follicle is distinguished from the
primary multilaminar follicle by its larger size,by a
well-establishedtheca interna and theca externa.
and especiallyby the presenceof follicular fluid in
small cavities formed from intercellular spacesof
the follicular cells. These fluid-filled cavities are
known as Call-Exner bodies.
4. Graafian (Mature) Follicles
The Graafian follicle is very large, the Call-Exner
bodies have coalescedinto a single space, the
antrum, filled with follicular fluid. The wall of the
antrum is referred to as the membrana granulosa,
and the region of the oocyte and follicular cellsjut-
ting into the antrum is the cumulus oophorus. The
single layer of follicular cells immediately sur-
rounding the oocyte is the corona radiata. Long
apicalprocesses of thesecellsextendinto the zona
pellucida. The theca interna and theca externa are
well developed;the former displaysnumerous cells
and capillaries,whereasthe latter is lesscellularand
more fibrous.
TTruIT
5. Atretic Follicles
Atretic follicles arein the stateofdegeneration.They
are characterizedin later stagesby the presenceof
fibroblasts in the follicle and a degeneratedoocyte.
B. Medulla
The medulla of the ovaryis composedof a relatively
loose fibroelasticconnectivetissuehousing an ex-
tensivevascular supply including spiral arteriesand
convolutedveins.
C. CorpusLuteum
Subsequent to the extrusion of the secondary
oocFte with its attendant follicular cells, the rem-
nant of the Graafian follicle becomespartly filled
with blood and is known asthe corpus hemorrhag-
icum. Cellsof the membrana granulosaare trans-
formed into large granulosa lutein cells.Moreover,
the cellsof the theca interna also increasein sizeto
become theca lutein cells, although they remain
smaller than the granulosalutein cells.
D. CorpusAlbicans
The corpus albicansis a corpus luteum that is in the
processof involution and hyalinization. It becomes
fibrotic with few fibroblasts among the intercellular
materials. Eventually, the corpus albicans will be-
come scar tissue on the ovarian surface.
II. GENITALDUCTS
A. Oviduct
l. Mucosa
The mucosaof the oviduct is highly folded in the in-
fundibulum and ampulla. It is composedof a loose,
cellular connectivetissuelamina propria and a sim-
ple columnar epithelial lining. The epithelium is
composedof peg cells and ciliated cells.
2. Musculqris
The muscle coat is composed of an inner circular
and an outer longitudinal smooth muscle layer.
3. Serosa
The oviduct is investedby a serosa.
FemaleReproductiveSystem ffi 347
B. Uterus
l. Endometrium
The endometrium is subdivided into a basal and a
functional layer. It is lined by a simple columnar
epithelium. The lamina propria varies with the
phasesof the menstrualcycle.
a. FollicularPhose
The glands are straight and display mitotic figures,
and the helicalarteriesgrow into the functional layer.
b. LutealPhase
Glands become tortuous, and the helical arteries
becomecoiled.The lumina of the glandsaccumu-
late secretoryproducts.Fibroblastsenlargeand ac-
cumulateglycogen.
c. MenstruolPhose
The functional layer is desquamated,and the lam-
ina propria displaysextravasated
blood.
2. Mgometrium
The myometrium is thick and consistsof three
poorly delineatedsmooth musclelayers:inner lon-
gitudinal, middle circular, and outer longitudinal.
During pregnancythe myometrium increases in size
as a result of hypertrophy of existingmuscle cells
and the accumulationof new smooth musclecells.
3. Serosa
Most of the uterus is coveredby a serosa:the re-
mainder is attachedto surrounding tissuesby an
adventitia.
C. Placenta
l. Decidua Basalis
The decidua basalis, the maternally derived en-
dometrial layer, is characterized
by the presenceof
large, glycogen-rich decidual cells. Coiled arteries
and straightveins open into the labyrinth-like in-
tervillous spaces.
2. Chorionic Plate and Vilfi
The chorionic plate is a region of the chorionic sac
of the fetus from which chorionic villi extend into
the intervillous spacesofthe deciduabasalis.Each
villus has a core of fibromuscular connective tissue
surrounding capillaries (derived from the umbilical
vessels).The villus is coveredby trophoblast cells.
During the first half of pregnancy,there are two lay-
ers of trophoblastcells,an inner cuboidal layer of
cytotrophoblasts and an outer layer ofsyncytiotro-
phoblasts. During the second half of pregnancy,
only the syncytiotrophoblasts remain. However, at
points where chorionic villi are anchored into the
decidua basalis,cytotrophoblasts are present.
348 I FemaleReproductiveSystem
D. Vagina
l. Mucosa
The vagina is lined by a stratified squamous
nonkeratinized epithelium. The lamina propria,
composed of a fibroelastic connective tissue, pos-
sessesno glands.The mucosais thrown into longi-
tudinal folds known as rugae.
2. Submucosa
The submucosa is also composed of a fibroelastic
typ. connectivetissuehousing numerous blood
9f
vessels.
3. Musculqris
The muscularisis composedof interlacingbundles
of smooth muscle fibers. Near its external orifice,
the vagina is equipped with a skeletal muscle
sphincter.
4. Adventitia
The vaginais connectedto surrounding structures
via its adventitia.
E. MammaryGlands
L Inactive Gland
The inactive gland is composedmainly of denseir-
regular collagenousconnective tissue interspersed
with lobules of adiposetissue and numerous ducts.
Frequently,at the blind endsofducts, buds ofalve-
oli and attendant myoepithelial cells are present.
2. Lactating Gland
The mammary gland becomesactive during preg-
nancy and lactation. The expanded alveoli that
form numerous lobules are composedof simple
cuboidal cells, resemblingthe thyroid gland. How-
ever, the presenceof ducts and myoepithelial cells
provides distinguishing characteristics.Alveoli and
the lumen of the ducts may contain a fatty secretory
product.
3. Areola and Nipple
The areolais composedof thin, pigmentedepider-
mis displayinglarge apocrine areolar glands.Addi-
tionally, sweat and large sebaceousglands are also
present. The dermis presentsnumerous smooth
muscle fibers. The nipple possesses severalminute
pores representing the distal ends of lactiferous
ducts. These ducts arise from lactiferous sinuses.
enlarged reservoirs at the base of the nipple. The
epidermiscoveringthe nipple is thin, and the der-
mis is richly supplied by smooth muscle fibers and
nerve endings. Although the nipple possesses no
hair follicles or sweat glands, it is richly endowed
with sebaceousglands.
t r NorEs

FemaleReproductive
System r 349
GRAPHIC17-1 t FemaleReproductiveSgstem
t
Intramural portion
of uterinetube Ampulla I
(Fallopian)
Uterine tube lnfundibulum

I
lsthmusof uterinetube
t
Ovarianligament
I
Broad ligament
I
Endometrium
Cervicalcanal
MyometriumWallof uterus I
Adventitia

t
I
MULTILAMINAR Thecafolliculi
PRIMORDAL
FOLLICLE:
UNILAMINAR
PRIMARY
FOLLICLE:
PRIMABY
FOLLICLE:
Granulosa cells
Zonapellucida
Membrana
Cumulus
granulosa
oophorus
I
Thecafolliculi Oocyte
Follicular Basement Zonapellucida
cells -
Oocyte-
Zona
Oocyte I
Coronaradiata

I
I
Corpusalbicans
I
CorpusIThecalutein
luteum
lGranulosalu
Theca
interna
t
Theca
exlerna I
Eachfolliclehousesa primaryoocyte
arrestedin the prophaseof the first meioticdivision.The
most developedGraafianfolliclereleasesits oocyte during Coronaradiata
I
ovulation.As that primaryoocyte is being released,it finishes its Oocyte
first meioticdivision,becomesa secondary oocyte, and is arrestedin
the metaphase stage of the second meioticdivision.Subsequentto ovulation
the Graafianfollicleditferentiatesinto the corpus luteum, which will eventually
Oocytenucleus t
degenerateintothe corpus alblcans.

350 r FemaleReproductive
System
I
CRAPHIC17-2 I Placentaand HormonalCucle

Placental
Structure

The humanplacentais
composedof a maternally
derived and a fetally derived
regionlt is constructed in such
a fashionthat the mothels
Anchoring blooddoesnot come in contact
(primary)
villi withthe bloodof the fetus,yet it
permitsthe exchangeof
Chorionic nutrients,gases,and waste
(secondary)
villi productsbetweenthem The
Branch maternaloortionof the olacenta
(tertiary)
villi is composed of the decidua
basalis,whereasthe fetal
Placental Dortionconsistsof the
septum chorionicplateand its
extensions. Therearethree
Deciduabasalis typesof villiarisingfromthe
chorionicplate:thosethat
Stratum
contactthedeciduabasalis
compactum (anchoringor primaryvilli,
Stratum thosethat arisedirectlyfromthe
spongrosum chorionicplatebutdo not
contactthe deciduabasalis
Myometrium (chorionicor secondaryvilli),
and branches arisrngfromthe
Afterdelivery,
the
secondary villi(branchor
deciduadetaches
tertiaryvilli)
at thispoint

The effectsof hypothalamic

and adenohypohyseal
hormones
on the ovariancortexand uterineendometrium

FemaleReproductive
Svstem 351
PLATE17-1 I Ovarg
FIGURE | . Ovarg. Monkeg. Plastic section x 14.
The ovary is subdividedinto a medulla (Me) and a
cortex (Co). The medullahouseslargeblood vessels(BV)
from which the cortical vascular supply is derived. The
cortex of the ovary contains numerous ovarian follicles,
most of which are very small (arrows) while a few matur-
ing follicles have reachedthe Graafian follicle (GF) stage.
The thick fibrous connectivetissuecapsule,tunica albug-
inea (TA), is shown to advantage, while the germinal
epithelium (GE) is evident occasionally.Observethat the
mesovarium (Mo) not only suspendsthe ovary but also
conveys the vascular supply to the medulla. A region
similar to the boxed areais presentedat a higher magni
fication in Figure2.
FIGURE 2 | Ovarg. Monkeg. Plastic section. x 132.
This photomicrographis a higher magnificationof a
region similar to the boxed areaof Figure L Observethat
the germinal epithelium (GE) covers the collagenous
capsule, the tunica albuginea (TA). This region of the
cortex (Co) housesnumerous primordial follicles (PF).
Observe that the connective tissue ofthe ovary is highly
cellular and is referred to as the stroma (St).
lnset. Ovary. Cortex. Monkey. Plastic section.
x 540
The primordial follicle is composed of a primary
oocyte (PO) whose nucleus (N) and nucleolus (arrow)
are clearly evident. Observethe singlelayer of flat follicu-
lar cells (FC) surrounding the oocyte. The tunica albug-
inea (TA) and the germinal epithelium (GE) are also
shown to advantagein this photomicrograph.

F|GURE 3 | Primarg follicles. Monkeg. Plastic
section, x 270,
Primary follicles differ from primordial follicles not
only in sizebut alsoin morphologyand number of follic-
ular cells. The unilaminar primary follicle of the inset
(x 270) displaysa single layer ofcuboidal follicular cells
(FC) that surround the relatively small primary oocyte
(PO), whose nucleus (N) is clearlyevident.The multil-
aminar primary follicle displays a primary oocyte (PO)
that has increasedin size.The follicular cells (FC) now
form a stratified layer around the oocyte, being separated
from it by the intervening zona pellucida (ZP). The
stroma (St) is being reorganized around the follicle to
form the thecainterna (TI). Note the presenceofa basal
membrane (BM) between the follicular cells and the
thecainterna.
F|GURE 4 a Secondorg follicle. Robbit. Paraffin
section. x 132.
Secondaryfollicles are very similar to primary multi-
laminar follicles, the major difference being their larger
size. Moreover, the stratification of the follicular cells
(FC) has increased, displaying more layers and, more
important, a follicular fluid (FF) begins to appear in the
intercellular spaces,which coalescesinto several Call-
Exner bodies. Note also that the stroma immediately
surrounding the follicular cells is rearranged to form a
cellular theca interna (Tl) and a more fibrous theca
externa(TE).

Ovary

T KEY
BM basal membrane GF Graafianfollicle st stroma
BV bloodvessel Me medulla TA tunicaalbuginea
Co conex Mo mesovanum TE thecaexterna
FC follicularcell N nucleus TI thecainterna
FF follicular
tluid PF primordialfollicle ZP zona pellucida
GE germinalepithelium PO primary oocyte

352 I FemaleReoroductive
Svstem
 ..GE

,.TA
\ GE

\
Co- ME

GF
BV I
lr ,i)
/',.\r! i'i,
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F I C U R IE F I C U R 2E

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F e r r r a lR
e e p r o d u c t i vSey s t e n r 353
PLATE17-2 I Ovargand CorpusLuteum
F|GURE | | Graafian follicle. Paraffin section.
x 132.
The Graafian follicle is the most mature of all ovarian
follicles, and is ready to releaseits primary ooqte in the
processof owlation. The follicular fluid (FL) fills a single
chamber, the antrum, which is surrounded by a wall of
granulosa (follicular) cells, known as the membrana
granulosa(MG). Someof the granulosacells,which sur-
round the primary oocyte (PO), jut into the antrum as
the cumulus oophorus (CO). Observe the basal mem-
brane (BM), which separates the granulosacellsfrom the
theca interna (TI). The fibrous theca externa (TE)
merges almost imperceptibly with the surrounding
stroma. The boxed area is presentedat a higher magnifi-
cation in Figure2.
FfGURE 2 ) Graafian follicle. Cumulus oophorus.
Paraffin section. x 270.
This photomicrograph is a higher magnification of
the boxed area of Figure 1. Observe that the cumulus
oophorus houses the primary oocyte (PO) whose nu-
cleus (N) is just visible in this section.The zona pellucida
(ZP) surrounds the oocyte, and processes(arrows) ofthe
surrounding follicular cells extend into this acellular re-
gion. The single Iayer offollicular cells appearsto radiate
as a crown at the periphery of the primary oocyte and is
referred to as the corona radiata (CR). Note the basal
membrane (BM), aswell asthe theca interna (TI) and the
theca externa (TE).

FIGURE 3 ) Corpus luteum. Human. Paraffin
section. x 14.
Subsequentto ovulation the Graafian follicle becomes
modified to form a temporary structure, the corpus hem-
orrhagicum, which will become the corpus luteum. The
cells comprising the membrana granulosa enlarge, be-
come vesicularin appearance,and are referred to asgran-
ulosa lutein cells (GL), which become folded, and the
spacesbetween the folds are occupied by connective tis-
sue elements,blood vessels,and cells ofthe theca interna
(arrows).Thesetheca interna cellsalso enlarge,become
glandular, and are referred to asthe thecalutein cells.The
remnants of the antrum are filled with fibrin and serous
exudate that will be replaced by connective tissue ele-
ments. A region similar to the boxed area is presentedat
a higher magnification in Figure 4.
FfGURE 4 s Corpus luteum. Human. Paraffin
section. x 132.
This photomicrograph is a higher magnification of a
region similar to the boxed area of Figure 3. The granu-
losa lutein cells (GL) of the corpus luteum are easily
distinguished from the connective tissue (CT) elements,
since the former display round nuclei (N) mostly in
the centeroflarge round cells(arrowheads).The center
of the field is occupied by a fold, housing theca lutein
cells (TL) amid numerous connective tissue (CT) and
vascular (BV) elements. A region similar to the boxed
area is presentedat a higher magnification in Figure I of
the next plate.

Ovary

T KEY
BM basalmembrane FL follicular
fluid TE theca externa
BV vascular
elements GL granulosaluteincells TI theca interna
CO cumulusooohorus MG membranagranulosa TL theca luteincells
CR coronaradiata N nucleus ZP zona pellucida
CT connective
tissue PO primary oocyte

354 r FemaleReproductive
System
,',.,
_ MG

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FemaleReproductive
System 355
PLATEl7-3 I Ovargand Oviduct
F|GURE | | Corpus luteum. Humon. Paroffin
section. x 540.
This photomicrographis similar to the boxed areaof
Figure 4 of the previous plate. Observe the large granu-
losa lutein cells (GL) whose cltoplasm appearsvesicular,
representingthe spacesoccupiedby lipids in the living
tissue.Note that the nuclei (N) of thesecellsare farther
away from eachother than the nuclei of the smaller theca
lutein cells (TL), which also appear to be darker staining
(arrowheads).The flattened nuclei (arrows) belong to
variousconnectivetissuecells.
FfGURE 2 J Corpus albicans. Human. Paraffin
section. x 132.
As the corpus luteum involutes, its cellular elements
degenerate,and undergo autolysis.The corpus luteum be-
comesinvadedby macrophagesthat phagocytosethe dead
cells,leavingbehind relativelyacellularfibrous tissue(FT).
The previously rich vascular supply (BV) also regressed,
and the entire corpus albicansappearspale in comparison
to the relatively dark staining ofthe surrounding ovarian
stroma (St). The corpus albican will regressuntil it be-
comesa small scaron the surfaceof the ovary.

FIGURE 3 a Oviduct. x.s. Humon. Poraffin section.
x 14.
The oviduct, alsoreferred to asthe fallopian or uterine
tube, extendsfrom the ovary to the uterine cavity. It is sus-
pended from the body wall by the broad ligament (BL),
which conveysa rich vascular supply (BV) to the serosa
(S) of the oviduct.The thick muscularis(M) is composed
of ill-definedinner circularand outer longitudinalmuscle
layers.The mucosa (Mu) is thrown into longitudinal
folds, which are so highly exaggeratedin the infundibu-
lum and ampulla that they subdivide the lumen (L) into
labyrinthine spaces.A region similar to the boxed area is
presentedat a higher magnificationin Figure4.
FfGURE 4 J Oviduct. x.s. Monkeg. Plostic section.
x 132.
This photomicrograph is a higher magnification of a
region similar to the boxed areaof Figure 3. The entire
thickness of the wall of the oviduct displays its vascular
(BV) serosa(S) that envelopsthe thick muscularis,whose
outer longitudinal (OL) and inner circular (IC) layers
are not very well delineated.The mucosa (Mu) is highly
folded and is lined by a simple columnar epithelium (Ep).
The loose connectivetissueof the lamina propria (LP)
is richly vascularized (arrows). The boxed area is pre-
sented in a higher magnification in Figure I in the fol-
lowing plate.

T KEY
BL broadligament rc innercircularmuscle N nucteus
BV vascular supply L lumen OL outerlongitudinalmuscle
Ep epithelium LP laminapropria S serosa
FT fibroustissue M muscularis St stroma
GL granulosa luteincell Mu mucosa TL theca luteincell

556 : Female
Reproductive
System
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F I L U R E5 F I C U R4E
I | ! , n . r l uR e p r o d u c t r vSey s t e n r 357
PLATE17-4 r Oviduct,Lightond ElectronMicroscopg
FIGURE | | Oviduct. x.s. Monkeg. Plastic section.
x 210.
This photomicrograph is a higher magnification of
the boxed area of Figure 4 of the previous plate. Observe
the inner circular muscle (IC) Iayer of the muscularis.
The lamina propria (LP) is very narrow in this region (ar-
rows), but presentslongitudinal epithelially lined folds.
The core of these folds is composed of a vascular (BV),
loose, but highly cellular connective tissue (CT). The
simple columnar epitheliurn (Ep) lines the labyrinthine
lumen (L) of the oviduct. A region similar to the boxed
area is presentedat a higher magnification in Figure 2.
FIGURE 2 | Oviduct. x.s. Monkeg. Plastic section.
x 540.
This photomicrograph is a higher magnification of a
region similar to the boxed area of Figure l. The lamina
propria (LP) is a highly cellular,loose connectivetissue
that is richly vascularized. The basal membrane (BM)
separatingthe connectivetissuefrom the epithelial lining
is clearly evident. Note that the epithelium is composed
of tr,rrodifferent cell t1pes,a thinner peg cell (PC), which
bears no cilia, but whose apical extent bulges above the
ciliated cells.Thesebulges (arrowheads)contain nutritive
materials that nourishes gametes.The secondcell type of
the oviduct epithelium is a ciliated cell (CL), whose cilia
move in unison with those of neighboring cells, pro-
pelling the nutrient material toward the uterine lumen.

FIGURE 3 | Oviduct epithelium. Human. Electron
microscopg. x 4555.
The human oviduct at midcycle (day la) presentstwo
types of epithelial cells,the peg cell (PC) and the ciliated
cell (CC). The former are secretorycells as indicated by
their extensiveGolgi apparatus (GA) situated in the
region of the cell apical to the nucleus (N). Observe the
electron-densesecretoryproducts (arrows) in the ex-
panded,apicalfree endsof thesecells.Note alsothat some
ciliated cellsdisplay large accumulationsof glycogen (Gl)
at eitherpole ofthe nucleus.(From VerhageH, Bareither
M, JaffeR, Akbar M: Am J Anat 156:505-522,1979.)

Ovary

KEY
BV vascularelements Ep epithelium L lumen
BM basal membrane GA Golgiapparatus LP laminapropria
CC ciliatedcell GI grycogen N nucteus
CT connectivetissue rc innercircularmuscle PC peg cell

558 I FemaleReproductiveSystem
I
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r 59
PLATEl7-5 I Uterus
FfGURE | | Uterus. Follicular phase. Human.
Poraffin section. x 14.
The uterusis a thick-walledorgan,whosewall consists
ofthree layers.The externalserosa(or in certainregions,
adventitia) is unremarkable and is not presentedin this
photomicrograph.The thick myometrium (My) is com-
posed of smooth muscle, subdivided into three poorly
delineatedlayers:outer Iongitudinal (OL), middle circu-
lar (MC), and inner longitudinal (IL). The endometrium
(En) is subdividedinto a basallayer (B) and a functional
Iayer (F). The functional layer varies in thicknessand
constitution and passesthrough a sequenceof phases
during the menstrualcycle.Note that the functionallayer
is in the processof being built-up and that the forming
glands (GL) are straight.The deeperaspectsof some of
theseglandsdisplaybranching(arrow). The boxed areais
presentedat a higher magnificationin Figure2.
FIGURE I 3 Uterus. Luteal phase. Human. Paraffin
section. x 14.
The myometrium (My) ofthe uterus remainsconstant
during the variousendometrialphases.Observeits three
layers,noting especiallythat the middle circular layer of
smoothmuscleis richlyvascularized and is,therefore,fre-
quently referred to asthe stratum vasculare(SV). The en-
dometrium (En) is richly endowed with glands (GL) that
becomehighly tortuous in anticipationof the blastocyst
that will be nourishedby secretionsoftheseglandssubse-
quent to implantation.A region similar to the boxed area
is presentedat a higher magnificationin Figure4.
T KEY
B basal layer GL gland
BV vascularsupply IL innerlongitudinal
En endometrium lumen
Ep epithelium MC middlecircularmuscle
F functionallayer
360 * Female
Reproductive
System
FTGURE 2 : Uterus. Follicular phase. Human.
Paraffin section. x 132.
This photomicrograph is a higher magnification of
the boxed areaof Figure l. Note that the functional layer
(F) of the endometrium is lined by a simple columnar
epithelium (Ep) that is displayrng mitotic activity (ar-
rows). The forming glands (GL) alsoconsistof a simple
columnar epithelium (Ep) whosecellsare activelydivid-
ing. The stroma (St) is highly cellular, asevidencedby the
numerousconnectivetissuecellnucleivisiblein this field.
Note also the rich vascular supply (BV) of the endome-
trial stroma.
FfGURE 4 a Uhrus. Eorlg luteol phase. Humon.
Paraffin section. x 132.
This photomicrograph is a higher magnification of a
region similar to the boxed area of Figure 3. The func-
tional layer of the endometrium is covered by a simple
columnar epithelium (Ep), separatingthe endometrial
stroma (St) from the uterine lumen (L). Note that the
glands (GL), also composedof simple columnar epithe-
lium, are more abundant than those in the follicular
phase(Figure 2, above).Observealso that theseglands
appearmore tortuous and are dilated and their lumina
contain a slight amount of secretoryproduct (arrow).
Femalereproductivesystem
My myometrium
muscle OL outerlongitudinal
muscle
St stroma
SV stratumvasculare
 /\
En \GL
B

IL

f,'

MC

FICU
R EI

(\'/4tr
f--- GL

En

My

sv
F I C U R3E 4
FICURE
R e o r o d u c t r vSev s t e m
Fenrale 361
PLATE17-6 I Uterus
FfGURE I a Uhrus. Midluteal phdse. Humon.
Pqraffin section. x 210.
During the midluteal phasethe endometrial glands
(GL) becomequite tortuous and corkscrew-shaped, and
the simple columnar cells (CC) accumulate glycogen
(arrow). Observe that during this phase of the en-
dometrium, the glycogenis basallylocated,displacingthe
nucleus (N) toward the centerof the cell. Note alsothat
the stroma (St) is undergoinga decidualreactionin that
someof the connectivetissuecellsenlargeasthey become
engorgedwith lipid and glycogen.A helical artery (HA)
is evidentasseveralcross-sections.
FIGURE 3 * Uterus. Menstrual phase. Humon.
Paraffin section. x 132.
The menstrual phaseof the endometrium is character-
ized by periodic constriction and sequentialopening ofhe-
lical arteries (HA), resulting in ischemiawith subsequent
necrosisof the superficial aspectof the functional layer.
Due to these spasmodic contractions sudden spurts of
arterial blood detach necrotic fragments (NF) of the su-
perficial layers of the endometrium that are then dis-
charged as menstrual flow. The endometrial stroma
becomesengorgedwith blood, increasingthe degreeofis-
chemia, and eventually the entire functional layer rs
desquamated.Observethat the lumen (L) no longer pos-
sesses a completeepitheliallining (arrowheads).The boxed
areais presentedat a higher magnification in Figure4.
I KEY
cc columnarcell HA helicalartery
F functionallayer lumen
UL gland Le leukocyte
362 m FemaleReproductive
System
FfGURE 2 a Uterus. Late luteal phose. Human.
Pqroffin section. x 132.
During the late luteal phaseof the endometrium,the
glandsassumea characteristic ladder (or sawtooth)shape
(arrows). The simple columnar epithelial cells (CC) ap-
pear pale and, interestingly, the position of the glycogen
is now apical (arrowheads)rather than basal.The apical
location of the glycogenimparts a ragged,torn appear-
anceto the free surfaceof thesecells.Note that the lumina
(L) of the glands are filled with a glycogen-rich, viscous
fluid. Observe also that the stroma (St) is infiltrated by
numerous leukocrtes (Le).
FfGURE 4 f Uterus. Menstrual phqse. Humon.
Pqraffin section. x 210.
This photomicrograph is a higher magnification of
the boxed area of Figure 3. Observethat some of the en-
dometrial glands (GL) are torn and a necrotic fragment
(NF) has been detachedfrom the functional layer (F) of
the endometrium. The stroma (St) is infiltrated by Ieuko-
c1tes,whosedensenuclei (N) mask most of the endome-
trial cells.Note that some of the endometrial cellsare still
enlarged,indicative of the decidual reaction.
Femalereproductive
system
N nucreus
NF necrotic
fragment
St stroma
 !

'\\
I

(f,
a'i'
t.i
I
I

?'.
,'

F I C U R4E
F c r r a l eR e p r o d u c t i vSey s t e m 363
PLATE17-7 1 Placentaand Vagino
FIGURE | | Placenta. Human. Paraffin section.
x 132.
The human placentais intimately associated with the
uterine endometrium. At this junction, the decidua
basalis(DB) is rich in clumpsoflarge,round to polygonal
decidualcells (DC), rvhosedistendedcytoplasmis filled
with lipid and glycogen.Anchoring chorionic villi (A\r)
are attachedto the deciduabasalis,while other villi are
blindly endingin the intervillousspace(IS). Thesearethe
most numerousand arereferredto asterminal villi (TV),
most of which are cut in crossor oblioue sections.These
villi are freelybranchingand, in the miture placenta,are
smallerin diameterthan in the immature olacenta.
Inset.Placenta.Human. Paraffin section, < 270.
Note that the decidualcells (DC) are round to polyg-
onal in shape.Their nuclei (N) are more or lesscentrally
located,and their cltoplasm appearsvacuolateddue to
the extraction of glycogenand lipids during histologic
preParauon.
FIGURE 2 a Placenta. Human. Paraffin section.
x 210.
Cross-sectionsof terminal villi (TV) are very simple
in the mature placenta.They are surroundedby the in-
tervillous space(IS) that, in the functional placenta,is
filled with maternalblood. Hence.the cellsof the villus
act asa placentalbarrier.This barrier is greatlyreducedin
the mature placenta,as presentedin this photomicro-
graph. The externallayer of the terminal villus is com-
posed of syncltial trophoblasts (ST), whose numerous
nuclei (N) are frequently clustered together as syncytial
knots (SK). The core of the villus housesnumerous fetal
capillaries(Ca) that are locatedusuallyin regionsofthe
villus void of syncl-tialnuclei (arrowheads).Largerfetal
blood vessels(BV) arealsofound in the core,surrounded
by mesoderm(Me). The cltotrophoblastsand phagocltic
Hofbauer cells of the immature placentamostly disap-
pearby the end of the pregnancy.

F|GURE 3 & Vogina. l.s. Monkeg. Plastic section
x 14.
The vagina is a fibromuscular tube, rvhosevaginal
space(VS) is mostly obliteratedsince its rvallsarc nor-
mally in contactwith eachother.This wall is composedof
four layers:mucosa (Mu), submucosa(Slv{),muscularis
(M), and adventitia(A). The mucosaconsistsof an ep-
ithelium (Ep) and underlf ng laminapropria (LP).Deep
to the mucosais the submucosa, rvhosenumerouslarge
blood vcsselsimpart to it an erectiletissueappearance.
The smooth muscleof the muscularisis arrangedin nvo
layers,an inner circular (IC) and a thicker outer longitu-
dinal (OL). A region similar to the boxed area is pre-
sentedat a highermagnificationin Figure4.
FfGURE 4 ffi Vagina. I.s. Human. Poroffin section.
x 132.
This photomicrographis a higher magnificationof a
regionsimilar to the boxedareain Figure3. The stratified
squamousnonkeratinizedepithelium (Ep) of the vagina
is characterizedby the empty appearanceof the cells
comprising most of its thickness.This is due to the ex-
traction lipids and glycogenduring histologic prepara-
tion. Obsen'ethat the cells in the deeperaspectof the
epitheliumpossess fewerinclusions;therefore,their cyto-
plasm appearsnormal. Note alsothat the lamina propria
(LP) is richly vascularized(BV) and alwayspossesses nu-
merous leukocytes(Le) (arrows). Finally, note the ab-
senceof glandsand musculansmucosae.

Placenta

A adventitia lC innercircularmuscle N nucteus

AV anchoringchorionicvillus lS intervillousspace OL outerlongitudinal
muscle
BV bloodvessel Mu mucosa SK syncytialknot
Ca capillary Le leukocyte SM suomucosa
DB deciduabasalis LP laminapropria ST syncytialtrophoblast
DC decidualcell M muscularis TV terminalvillus
Ep epithelium Me mesoderm VS vaginalspace

364 fr Female
Reproductive
System
I
I DGr
DB

I
t
ir" N
I I
t\, BV'il..
i 't'
*!

I
+;?

t IS

I t,
I
F I C U R1
E
I
I
VS
T
I A MSM MU

I -/Ep

t OL
tc
t LP

I
I
FICUR3
E FICUR4
E
System
FemaleReproductive 365
PLATE17-8 r MammargCland
FIGURE I Mammarg gland. lnactive. Human.
Poraffin section. x 132.
The mammaryglandis a modified sweatglandthat, rn
the restingstage,presentsducts (D) with occasionalbuds
ofalveoli (BA) branchingfrom the blind endsofthe duct.
The remainder of the breastis composedof densecol-
lagenousconnectivetissue(dCT) inierspersedwith lob-
ules of fat. However, in the immediate vicinity of the
ducts and buds of alveoli the connectivetissue (CT) is
more looselyarranged.It is believedthat this loosercon-
nective tissueis derived from the papillary layer of the
dermis.Comparethis photomicrographwith Figure2.
FIGURE 3 Mammorg gland. Lactdting. Human.
Paraffin section. x 132.
The active mammary gland presentsnumerous lob-
ules (Lo) ofalveoli (Al) that aretightly packedso that the
connectivetissue(CT) elementsare greatlycompressed.
This photomicrographclearlyillustratesthe crowdedna-
ture ofthis tissue.Although this tissuebearsa superficial
resemblanceto the histology of the thyroid gland, the
presenceof ducts and branchingalveoli(arrows),aswell
as the lack of colloid material, should assistin distrn-
guishingthis tissueasthe activemammary gland.
lnset Mammary gland. Active. Human. Paraffin sec-
tion. x 270.
Observethe branching(arrows)of this alveolus,some
of whose simple cuboidal epithelial cells (Ep) appear
vacuolated(arrowheads).Note also thar the lumen (L)
containsfatty secretoryproduct.
I KEY
Al alveolus D duct
Ar areola dCT denseconnective
BA buds o1alveoli Ed epidermis
CT connectivetissue Ep epithelium
365 FemaleReproductiveSystem
FIGURE 2 ., Mommarg gland. Loctating. Human.
Paraffin section. x 132.
During pregnancythe ducts (D) of the mammary
gland undergo major development,in that the buds of
alveoliproliferateto form lobules(Lo) composedof nu-
merous alveoli (Al). The interlobular connectivetissue
(CT) becomesreduced to thin sheetsin regions,while
elsewhereit maintains its previouscharacterto support
the increasedweight ofthe breast.Observethat the con-
nectivetissuein the immediatevicinity of the ducts and
lobules (arrows) retains its loose consistency.Compare
this photomicrographwith Figure 1.
F|GURE 4 Mammarg gland. Nipple. Human.
Paraffin section. x 14.
The large,conicalnipple ofthe breastis coveredby a
thin epidermis (Ed), composedof stratified squamous
keratinized epithelium. Although the nipple possesses
neither hair nor sweat glands, it is richly endowed with
sebaceousglands (SG). The denseirregular collagenous
connectivetissue(CT) core displaysnumerous longitu-
dinally positionedlactiferousducts that piercethe tip of
the nipple to conveymilk to the outside.The lactiferous
ducts are surroundedby an extensivenetwork ofsmooth
musclefibers(SM) that areresponsiblefor the erectionof
the nipple, elevatingit to faciiitatethe sucklingprocess.
The region immediatelysurrounding the nipple is know
as the areola(Ar).
rumen
tissue lo lobule
SM smoothmuscle
SG sebaceousgland
 i

.;

iAr

-t

SG
R E4
FICU
R e p t ' o d u r tci \S y s t e n r
Fenrale 367

r Male ReproductiveSgstem
The male reproductivesystem(seeGraphic l8-1)
consistsof the two testes(the male gonads),a sys-
tem of genitalducts, accessoryglands,and the pe-
nis. The male reproductivesystemfunctions in the
formation of spermatozoa,the elaborationof male
sex hormones, and the delivery of male gametes
into the femalereproductivetract.
TESTES
Eachtestisis an oval structurehousedin its separate
compartment within the scrotum. Its fibromuscu-
lar connectivetissue capsule,the tunica albuginea,
is thickened at the mediastinum testis, from which
septa are derived to subdivide the testis into ap-
proximately 250 small,incompletecompartments,
the lobuli testis. Each lobule housesone to four
highly tortuous seminiferous tubules that function
in the production of spermatozoa.The lumen of
eachseminiferoustubule is lined by a seminiferous
epithelium severalcell layers thick. The basal cells
of this epithelium are composedof Sertoli cells and
spermatogonia. The latter cells divide by mitotic
activity to replicatethemselvesand to producepri-
mary spermatocftes.Thesediploid primary sper-
matocytesenter the first meiotic division, forming
secondary spermatocftes that, by completing the
second meiotic division, give rise to haploid sper-
matids. Subsequentto sheddingmuch of their cy-
toplasm, reorganizingtheir organellepopulation,
and acquiring certain specializedorganelles,sper-
matids becomespermatozoa,the male gamete.The
differentiating cells are supported by Sertoli cells
both physically and nutritionally. Moreover, oc-
cluding junctions between adjacent Sertoli cells
establish a blood-testis barrier that protects the
developinggerm cellsfrom autoimmune phenom-
ena. The seminiferousepithelium sits on a basal
membranethat is surroundedby a fibromuscular
tunica propria.
The connectivetissuesurrounding the seminif-
eroustubuleshouses,in addition to neuraland vas-
Itrelr t8
cular elements,small clumps of androgen-produc-
ing endocrine cells, the interstitial cells of Leydig'
Thesecellsproduce the male sex hormone testos-
terone. Prior to puberty, testosteroneis not pro-
duced, but at the onset of puberty the pituitary
gland releasesluteinizing hormone (LH) and folli-
cle-stimulatinghormone (FSH). The former acti-
vates the interstitial cells of Leydig that release
testosterone,whereasFSH inducesthe Sertoli cells
to produce adenylate ryclase, which, via a cAMP
intermediary, stimulates the production of andro-
gen-bindingprotein (ABP). Testosteronebinds to
ABP, and the complexis releasedinto the lumen of
the seminiferoustubule, where the elevatedtestos-
terone concentration enhancesspermatogenesis.
GENITALDUCTS
A systemof genital ducts conveysthe spermatozoa
and the fluid component of the semento the out-
side. The seminiferous tubules are connected by
short straight tubules, the tubuli recti, to the rete
testis, which is composedof laby'rinthine spaceslo-
cated in the mediastinum testis.From here, sper-
matozoa enter the first part of the epididymis, the
15-20 ductuli efferentesthat lead into the ductus
epididymis. During their sojourn in the epi-
didymis, spermatozoamature.The headof the epi-
didymis is composedof the ductuli efferentes, while
the body and tail consistof the ductus epididymis,
whosecontinuation is the ductus deferens(vas def-
erens) (Graphic l8-l). This thick, muscular struc-
ture passesthrough the inguinal canal,as a part of
the spermaticcord, to gain accessto the abdominal
cavity. |ust prior to reachingthe prostate gland, the
seminal vesicle empties its secretionsinto the duc-
tus deferens,which terminatesat this point' The
continuation of the duct, known as the ejaculatory
duct, entersthe prostate gland. This gland delivers
its secretoryproduct into this duct. The right and
left ejaculatory ducts empty into the urethra, which
conveysboth urine and semen to the outside. The
System I
MaleReproductive 369
urethra,which passesthrough the length ofthe pe-
nis, has three regions:prostatic,membranous,and
cavernous( spongy)portions.
ACCESSORY
G TANDS
The three accessoryglandsof the male reproductive
system,which supplythe fluid componentof semen,
are the two seminal vesiclesand the prostate gland.
Additionally, a pair of small bulbourethral glands
deliver their viscoussecretionsinto the cavernous
(spongy)urethra.Eachseminalvesicleis a long,nar-
row gland that is highly folded on itself.Eachsemi-
nal vesicleproducesa rich, nutritive substancewith
a characteristicyellow color. The prostategland is
composedof numerousindividual glandsthat sur-
round, and whoseducts pierce,the wall of the ure-
thra. Theseglandsaredistributedin threeregionsof
the prostate and are, therefore, categorizedas
37O # Male Reproductive
System
mucosal, submucosal, and external (main) pro-
staticglands.The secretionofthe prostateglandis a
whitish, thin fluid containing proteolytic enzymes
and acid phosphatase.Prostatic concretions are fre-
quently found in the lumina of the prostategland.
PENIS
The penis, the male organ of copulation, is nor-
mally in the flaccid state.During erotic stimulation,
however, its three cylindrical bodies of erectile tis-
sues, the two corpora cavernosa and the corpus
spongiosum, become distendedwith blood. The
fluid turgid pressurewithin the vascular spacesof
the erectile tissues greatly enlargesthe penis, caus-
ing it to becomeerectand hard. Subsequentto ejac-
ulation or the termination of erotic stimulation,
detumescencefollows and the penis returns to its
flaccid state.
 IIilII

t Histophgsiologg

I. SERTOLICELLFUNCTIONS
Sertoli cellssit on the basallamina of the seminifer-
ous tubule and form zonulae occludenteswith one
another,thus separatingthe lumen of the seminif-
erous tubule into an outer basal compartment and
an inner adluminal compartment. By doing so'
they isolatethe adluminal compartment from con-
nective tissue elementsand thus protect the devel-

the seminiferoustubules,where it is maintained at a

sufficientlyhigh threshold level to permit spermato-
genesisto occur.Thesecellsalsosecretethe hormone
iohibio, which blocks the release of FSH via a
biofeedbackmechanism.
Spermatocytes,spermatids, and sPermatozoa
are physically and metabolically supported by Ser-
toli-cells. Moreover, c1'toplasmdiscardedduring
spermiogenesisis phagocytosedby Sertoli-cells'
Sirtoli cells also secretea fructose-rich fluid that
supports spermatozoa and provides a fluid
-.din- foitheir transPortthrough the seminifer-
embryo.
II. SPERMATOGENESIS
Spermatogenesis, the processof producing haploid
male gametes, is dependent on severalhormones'
including luteinizing hormone (LH) and FSH from
the adenohypophysis(seeGraphic l8-2). LH in-
duces interstitial cells of Leydig to secretetestos-
terone. and FSH causesSertolicellsto releaseABP'
ABP maintains a high enough concentration of
testosteronein the seminiferous epithelium for
compartment.
Meiosis phase starts when primary sPermato-
cytes ( CDNA content) undergo the first meiotic
division, forming two short-lived secondary sper-
matocytes(2CDNA content).Secondaryspermato-
cytes do not rePlicatetheir DNA but immediately
siart the t..ottd meiotic division' and each forms
two haploid (N) sPermatids.
Speimiogenesii(Graphic 18-2) is the processof
cytodifferentiation of the spermatids into sperma-
tozoa and involves no cell division. Instead, the
spermatid loses much of its cytoplasm (phagocy-
tosedby Sertolicells),forming an acrosomalgran-
ule, a long cilium, and associatedouter densefibers
and a coarse fibrous sheath. The spermatozoon
that is formed and releasedinto the lumen of the
seminiferous tubule is nonmotile and is incapable
of fertilizing an ovum' The spermatozoaremain
immotile until they leavethe epididymis' They be-
come capableof fertilizing once they have been ca-
pacitated in the female reproductive system'

slightly below normal body temperature.
AND EJACULATION
III. ERECTION
The penis during copulation deliversspermatozoa-
condining semen to the female reproductive tract'
It is also tle excretory organ for urine' The penis is
covered by skin and is composed of three erectile

SYstem ffi 37 1
MaleReProductive
bodies,the two corporacavernosaand the ventrally
positionedcorpus spongiosum(urethrae).
Each erectilebody, housing large endothelially
lined cavernousspaces,is surrounded by a thick
connective tissue capsule,the tunica albuginea.
The erectilebodies are supplied by helicine arter-
ies that are usually bypassedvia arteriovenous
shunts, maintaining the penis in a flaccid state.
Parasympatheticimpulses to these shunts cause
vasoconstriction,directing blood into the helicine
arteriesand thus into the cavernousspaces.The
erectile bodies (especiallythe corpora iavernosa)
become engorgedwith blood, and the penis be-
comeserect.
Subsequentto ejaculationor in the absenceof
continued stimulation, parasympatheticstimula-
tion ceases;blood flow to the helicinearteriesis di-
minished;blood slowlyleavesthe cavernousspaces;
and the penisreturns to its flaccidcondition.
C l i n i c a lC o n s i d e r a t i o n ss a 1
Crgptorchidism
C r y p t o r c h i d i sim sa developmentd ael fect
w h e r eo n e o r b o l h t e s t e sf a i lt o d e s c e n di n t o
t h e s c r o t u mW h e nn e i t h e rd e s c e n d si t, r e s u l t s
i n s t e r i l i t yb e c a u s en o r m a lb o d y t e m p e r a t u r e
i n h i b i t ss p e r m a t o g e n e sU i ss u a l l yt,h e c o n d i t i o n
c a n b e s u r g i c a l lcyo r r e c t e dh; o w e v e rt,h e p a -
t i e n t ' ss p e r mm a y b e a b n o r m a l
Vasectomg
V a s e c t o miys a m e t h o do f s t e r i l i z a t j ot n
hatis
p e r f o r m e db y m a k i n ga s m a l ls l i t i n t h e w a l lo f
t h e s c r o t u ml h r o u g hw h i c ht h e d u c t u sd e f e r e n s
is severed
A normalejaculateaveragesabout 3 mL of se-
m e nt h a t c o n t a i n s6 0 t o I 0 0 m i l l i o ns p e r m a t o -
z o a p e r m L l t i s i n t e r e s t l ntgo n o t et h a t a b o u t
2 0 0 / o f t h e e j a c u l a t esdp e r m a t o z oaar e a b n o r -
m a la n d 2 5 0 / o i m m o t i l eA n i n d i v i d u apl r o d u c i n g
l e s st h a n2 O m i l l i o ns p e r m a t o z opae r m L o f
e1aculate is consideredsterile
Benign Prostatic Hgpertrophg
T h e p r o s t a t eg l a n du n d e r g o ehs y p e r t r o p h w y ith
a g er e s u l t i n g i n b e n i g np r o s t a t i ch y p e r t r o p h ya,
c o n d i t i o nt h a t m a y c o n s t r i ctth e u r e t h r allu m e n
r e s u l l i n gi n d i f f i c u l t yi n u r i n a t i o nA t a g e5 0
a b o u t4 0 0 / o f t h e m a l ep o p u l a t i o ni s a f f e c t e d
a n d a t a g e8 0 a b o u t9 5 0 / o f t h e m a l ep o p u l a -
t i o n i s a f f e c t e db y t h i sc o n d i t i o n
372 € MaleReproductive
System
Ejaculation is the forceful expulsion of semen
from the male reproductive tract. The force re-
quired for ejaculation is derived from rhythmic
contractionof the thick smoothmusclelayersof the
ductus (vas) deferensand the rapid contraction of
the bulbospongiosusmuscle.
Eachejaculatecontainsspermatozoasuspended
in seminal fluid. The accessoryglands of the male
reproductive system, the prostate and bul-
bourethral glands, as well as the seminal vesicles
(and even the glands of Littrd) contribute to the
formation of the fluid portion of semen.Secretions
of the bulbourethral glands lubricate the urethra,
whereassecretionsof the prostateassistthe sperma-
tozoa in achieving motility by neutralizing the
acidic secretionsof the ductus deferensand of the
femalereproductivetract. Energyfor the spermato-
zoa is provided by fructose-richsecretionsof the
seminalvesicles.
Adenocarcinoma of the Prostote
A d e n o c a r c i n o moaf t h e p r o s t a t ea f f e c t sa b o u t
3 0 0 / o f t h e m a l ep o p u l a t i o n o v e r7 5 y e a r so f
a g e .A l t h o u g ht h i sc a r c i n o m ias s l o wg r o w i n gi t
m a y m e t a s t a s i zt e o b o n e A n a l y s i os f e l e v a t e d
levelsof prostate specificantigen (PSA)in the
bloodstream i s u t i l i z e da s a n e a r l yd i a g n o s t i c
t e s tf o r p r o s t a t i c a n c e rS u r g i c arle m o v aol f t h e
g l a n dw i t ho r w i t h o u tc h e m o -o r r a d i a t i o nt h e r -
a p y i s t h e u s u a tl r e a t m e n th; o w e v e rc, o m p l i c a -
t i o n sm a y r e s u l ti n i m p o t e n c a endincontinence
Testiculor Cancer
T e s t l c u l acra n c e ra f f e c t sm o s l l ym e ny o u n g e r
t h a n4 0 y e a r so f a g e l t i s d i s c o v e r eudp o np a l -
p a t i o na s a l u m pi n t h e s c r o t u ml f t h e l u m pi s
n o t a s s o c i a t ew d i t h t h e t e s t i si t i s u s u a l l yb e -
n i g n ,w h e r e a si f i t i s a s s o c i a t ew d i t h t h e t e s t i si t
i s u s u a l l ym a l i g n a n t h ; e r e f o r ea, l u m pn o t i c e d
o n t h e t e s t i sw , h e t h e ro r n o t i t i s p a i n f u ls, h o u l d
b e e x a m i n e db y a p h y s i c i a nF r e q u e n t l yi n, d i -
v i d u a l sw i l h t e s t i c u l acra n c e rp r e s e n w t ith
elevatedblood alpha-fetoproteinand human
chorionicgonadotropin IevelsThe common
t r e a t m e nfto r t e s t i c u l acra n c e ri s s u r g i c arle -
m o v a lo f t h e a f f e c t e dt e s t i s l f m e t a s t a s ihsa s
o c c u r r e dt h a nt h e s u r g e r yi s s u p p l e m e n t ebdy
r a d i a t i o na n d c h e m o t h e r a o v
 IINIT

t Summargof HistotogicatOrganization

t I. TESTES B. Rete Testis

A. Capsule The rete testis is composed of cuboidal cell-lined
t The fibromuscular connectivetissue capsuleof the
testesis known asthe tunica albuginea,whoseinner
labyrinthine spaceswithin the mediastinum testis.

vascularlayer is the tunica vasculosa,The capsuleis C. Epididymis

I thickened at the mediastinum testis from which
septaemanate,subdividingthe testisinto approxi-
mately 250 incompletelobuli testis,with eachcon-
I taining one to four seminiferoustubules embedded
in a connectivetissuestroma.
L Ductuli Efferentes
The ductuli efferentescomPosethe head of the epi-
didymis, whose lumina are lined by simple colum-
nar (tall ciliated and low nonciliated) epithelium.
The wallsof the ductulesconsistof fibroelasticcon-

I Tubules
B. Seminiferous
Each highly convoluted seminiferous tubule is
nectivetissueand smooth musclecells.
2. Ductus EPididgmis
composedof a fibromusculartunica propria, which The ductus epididymis comprisesthe body and tail
I is separatedfrom the seminiferous epithelium by a
basalmembrane.
of the epididyrnis. Its lumen is lined by a pseudos-
tratified type of epithelium composed of short
basal and tall principal cells bearing stereocilia
| . Seminiferous Epithelium
t The seminiferousepithelium is composedof sus-
tentacular Sertoli cells and a stratified layer of de-
(long microvilli). The epithelium is separatedby a
basal membrane from the connective tissue wall
that housessmooth muscle cells.
veloping male gametes. Sertoli cells establish a
t blood-testisbarrier by forming occludingjunctions
with each other, thus subdividing the seminiferous D. Ductus(Vas)Deferens
tubule into adluminal and basal compartments.
The enlarged continuation of the ductus epi-
I The basal compartment housesspermatogoniaA
(both light and dark), spermatogoniaB, and the
didymis, the ductus deferens,is a highly muscular
structure.The mucosallining of its small lumen is
basalaspectsof Sertoli cells.The adluminal com-
composed of pseudostratified stereociliated ep-
partment contains the apical portions of Sertoli
I cells,primary spermatocytes,secondaryspermato-
cytes,spermatids,and spermatozoa.
ithelium lying on a thin fibroelasticlamina propria.
Its thick muscularcoat is composedof three layers
of smooth muscle, an inner and outer longitudinal
and a middle circular layer. A loose fibroelastic ad-
I 2. Tunics Propria
The tunica propria consistsof loose collagenous
connectivetissue,fibroblasts,and myoid cells.
ventitia surrounds the outer longitudinal muscle
layer.

I C. Stroma
GLANDS
III. ACCESSORY
The loose vascularconnectivetissue stroma sur-

I rounding seminiferoustubules housessmall clus-

ters of large,vacuolated-appearing endocrinecells,
A. SeminalVesicles
As the seminal vesicles, two highly convoluted
the interstitial cells(of Leydig). tubular structures,join the ductus deferens,they

I II. GENITALDUCTS
A. TubuliRecti
I Short straighttubes,the tubuli recti, lined by Ser-
toli-like cells initially and simple cuboidal epithe-
lium later. connectthe seminiferoustubulesto the
I rete testis.
form the paired ejaculatory ducts. The highly
folded mucbus membrane of the seminal vesicleis
composedof a pseudostratified epithelium, whose
columnar cells are interspersed with short basal
cells,sitting on a fibroelasticlamina propria. The
muscular coat is composed of inner circular and
outer longitudinal layers of smooth muscle and is
investedby a fibrous adventitia.

I System *
MaleReproductive 373
B. ProstateGland
The ejaculatoryductsjoin the urethra asthesethree
structures traversethe substanceof the prostate
gland, whose capsuleis composedof fibroelastic
connective tissue and smooth muscle cells. The
densestroma of the gland is continuous with the
capsule.The parenchymaof the prostateis com-
posed of numerous individual glands disposedin
three layers: mucosal, submucosal,and external
(main). The lumina of thesethreegroupsdrain into
three systemsof ducts that lead into the expanded
urethral sinus.The folded mucosaof the glandsis
composedof simple cuboidal to columnar (with
regions of pseudostratifiedcolumnar) epithelia
supportedby fibroelasticvascularstroma display-
ing smooth musclecells.Frequently,the lumina of
the glands of older men possessround-to-ovoid
prostatic concretionsthat are often lamellatedand
may becomecalcified.
C. Bulbourethral
Glands
Each small bulbourethral (Cowper's) gland pos-
sesses a thin connectivetissuecapsulewhosesepta
subdividethe gland into lobules.The cuboidal-to-
columnar cells lining the lumen of the gland pos-
sessflattened,basallylocatednuclei.The main duct
of eachgland deliversits mucoussecretoryproduct
into the cavernouslspongy) urethra.
IV. PENIS
The penis, ensheathedin skin, possessesa thick
collagenouscapsule, the tunica albuginea, that
37 4 d{ Male Reproductive
System
enclosesthe three cylindrical bodiesof erectiletis-
sue. The two dorsally positioned corpora caver-
nosa are incompletely separatedfrom each other
by septa derived from the tunica albuginea.The
corpus cavernosum urethrae (corpus spongio-
sum) contains the spongyportion of the urethra.
The vascularspacesofthe erectiletissuesare lined
by endothelium.
V. URETHRA
The male urethra is subdivided into three regions:
prostatic, membranous,and spongy (penile) ure-
thra.
A. Epithelium
The prostatic portion is lined by transitional ep-
ithelium, whereasthe membranous and spongy
portionsarelinedby pseudostratified-to-stratifi
".1
columnar epithelium. The spongy urethra fr-el
I
quentlydisplaysregionsof stratifiedsquamousep-
ithelium. Goblet cellsand intraepithelial glands are
alsopresent.
B. LaminaPropria
The lamina propria is composedof a type of loose
connective tissue housing elastic fibers and glands
of Littr6. Smooth muscle, oriented longitudinally
and circularlv.is alsoevident.
I r NorEs

MaleReproductive
System I 375
CRAPHIC18- I I Male ReproductiveSgstem

Ureter
Ductusdeferens

Urinarybladder - -------------
$t Colon

Seminalvesicle
Pubis
Ampullaof
Penis ductsdeferens
Ejaculatory
duct

C o r p u sc a v e r n o s u m
Prostategland
Corpusspongiosum Bectum
Anus
Urethra
Glanspenis
. .--..---
_ gland
Bulbourethral
Prepuce
Bulbof penis
Scrotum

Eachtestisis subdivided
into
approximately250 lobules,
lobuli
testis,housingoneto fourhighly
convoluledseminileroustubules

Crosssectionof
tubule
seminiferous

Thewallof theseminiferous tubulesis

composed of slenderconnective tissue
elements whosechiefcellular components
arelibroblasts The seminiferous
(germinal)epitheliumis composed of
spermatogenic cellsandSertolicells lt is
thespermatogenic cellsthatundergo
mitosis.meiosis,andspermiogenesis
The Sertolicells formzonulae
occludenteswitheachother,thus
separatingthe lumenof theseminiferous
tubuleintotwo concentricspaces

376 Male Reproductive

Svstem
I CRAPHfC18-2 | Spermiogenesis

I
I
I
I
I Acrosomal

I
I
I
I
t uoturPHA.E
-./
ACROSOMAL
I PHASE Acrosomal
cap
Outer
dense
fibers

I Plasmalemma

Acrosome
Segmented
columns

Nuclear
I envelope
Nucleus

I
I
I
Outer
I dense
fibers

I System I
Male Reproductive 377
PLATE18-1 I Iesfis I
FTGURE I lesfis. Monkeg. Plastic section. x 14.
This low magnificationphotomicrographof the testis
displaysits thick tunica albuginea (TA), as well as the
FIGURE 2 rii lesfis. Seminiferous tubules. Monkeg.
Plastic section. x 132.
This photomicrographis a higher magnificationof a
I
slendersepta(Se)that attachto it. Observethat sections region similar to the boxed areaof Figure 1. Observethat
of seminiferoustubules (ST) presentvarious geometric
profiles,attestingto their highly convolutedform. Note
that eachlobule (Lo) is denselypackedwith seminiferous
the tunica vasculosa(TV) of the tunica albuginea (TA) is
a highly vascularregion (arrows) and that blood vessels
(BV) penetratethe lobuli testisin connectivetissuesepta
I
tubules,and the connectivetissuestroma (arrows)occu- (Se). The walls of the seminiferous tubules (ST) are
pies the remaining space.A region similar to the boxed
areais presentedat a higher magnificationin Figure2.
closelyapposedto eachother (arrowheads)although rn
certain regions the cellular stroma (St) is evident.
I
Observethat the lumen (L) of the seminiferoustubule is
lined by a stratifiedseminiferousepithelium (SE).
t
FfGURE 3 fesfrs. Seminiferous tubule. Monkeg.
Plostic section. x 540.
The adjacentwallsof two seminiferoustubules (ST),
FIGURE 4 ,: Testis. Seminiferous tubule. Monkeg.
Plostic section. x 540.
Observethat the fibromuscular walls of the two tubu-
I
in closeproximity to eachother, are composedof myoid lar cross-sections are very closeto each other (arrows);
cells(MC), fibroblasts(F), and fibromuscularconnective
tissue(CT). The stratifiedseminiferousepithelium (SE)
however,in regions,arterioles(A) and venules (V) are
evident.The Sertolicells(SC) may be recognizedby their
I
is separatedfrom the tubular wall by a basalmembrane palenucleiand densenucleoli (n). In comparingthe sem-
(arrowheads).Spermatogonia(Sg) and Sertolicells (SC)
lie on the basalmembrane,and are in the basalcompart-
ment (BC), while primary spermatocytes(PS), sec-
iniferous epithelia (SE) ofthe tubules in the right and left
halvesof this photomicrograph,aswell asthoseof Figure
3, it should be noted that their cellularcomoositionsare
I
ondary spermatocytes, spermatids(Sp), and spermato- different, indicativeof the cyclic stagesof the seminifer-
zoa (Sz) are in the adluminal compartment (AC).
Observethat the lumen (L) of the seminiferoustubule
containsspermatozoa,aswell ascellulardebrisdiscarded
ous epithelium.Note alsothat threetypesof spermatogo-
nia are recognizableby their nuclearcharacteristics:
spermatogoniaA (Ad) possessing
dark I
dark, flattenednuclei;
during the transformationof spermatidsinto spermato- pale spermatogoniaA (Ap) with flattened pale nuclei;
zoa. Compare the cells of the seminiferousepithelium
with thoseof Fisure4.
and spermatogoniaB (B) with round nuclei. I
I
Testis,epididymis,
and seminiferous
I
$i tubule
}l
I
I
T KEY I
A
AC
Ad
arterioles
adluminalcompartment
dark spermatogoniaA
L
Lo
MC
rumen
lobule
myoidcell
Sg
Sp
DI
spermatogonia
spermatid
seminiferous
tubules
t
Ap pale spermatogoniaA n nucleoli St stroma
B
BC
spermatogoniaB
basalcompartment
PS
5U
primaryspermatocyte
Sertolicell
Sz
TA
spermatozoa
tunicaalbuginea
I
BV bloodvessel SE seminiferousepithelium TV tunicavasculosa
CT
F
connectivetissue
fibroblast
Se septum venute
f
378 Male ReproductiveSystem I
I ,I.

I
I
I
I
a
I
I
I
FICU
R E1

I di ,:.

t
I
a
\{
I
I
ie
I MC
'ss
I Fr ._

I _r*
'j'r-.

./, ' ;
I F I C U R3E
\' 1S

I M a l e R e p r o d u c t i vSey s t e m 379
PLATE18-2 I Testisand Epididgmis
FIGURE 7 lnterstitial cells. Testis. Monkeg.
Plastic section. x )14.
The stroma (St) surrounding seminiferoustubules
(ST) possesses a rich vascularsupply (BV), aswell as ex-
tensivelymphatic drainage (LV). Much of the vascular
elementsare associatedwith the endocrine cells of the
testis,the interstitial cellsofLeydig (IC), which produce
testosterone.
Insef.Interstitial cells.Testis.Monkey. Plasticsection.
x 540.
The interstitial cells(IC),locatedin small clumps,are
recognizableby their round-to-oval nuclei (N) and the
presence of lipid (arrow)within their cltoplasm.
FIGURE 2 Rete testis. Human. Paraffin section.
x 132.
The rete testis(RT), locatedin the mediastinumtestis
(MT), is composedof labyrinthine,anastomosingspaces,
Iined by a simple cuboidal epithelium (Ep). The dense
collagenousconnectivetissue (CT) of the mediastinum
testisis clearlyevident,asare the profilesofserniniferous
tubules (ST). Spermatozoagain accessto the rete testis
via the short, straighttubuli recti (TR).

FfGURE 3 Ductuli efferentes. Human. Paraffin
section. x 132.
The first part of the epididymis,the ductuli efferentes
(De),receives spermatozoa (Sz)from the retetestis.The
lumina of the ductuli are lined by a simple columnar
epithelium(Ep),cornposedof tall and shortcells,which
are responsiblefor the characteristicfluted (uneven)
appearanceof thesetubules.The thick fibroelasticcon-
nectivetissue (CT) wall of the ductuli housesnumerous
smoothmusclecells(SM).
F|GURE 4 Ductus epididgmis. Monkeg. Plostic
section. x 132.
The ductus epididymis (DE) may be distinguished
from the ductuli efferenteswith relativeease.Note that
the nuclei (N) of the pseudostratifiedepithelial lining
(Ep) are oftwo t1pes,oval and round, whereasthose of
the ductuli are round. Observethat the lumen contains
numerousspermatozoa(Sz)and that the epithelium sits
on a basallamina. The connectivetissuewall of the duc-
tus epididymismay be differentiatedeasilyfrom its circu-
larlyarrangedsmoothmusclecoat (SM).

and
Testis,epididymis,
seminiferoustubule

I KEY
BV bloodvessel lC cellsol Leydig
interstitial SM smoolhmuscle
CT connective tissue LV lymphatic vessels ST seminiferoustubules
DE ductusepididymis MT mediastinum testis st stroma
De ductuliefferentes N nuclei Sz spermatozoa
F
Ly
n anifhalirrm RT rete testis TR tubulirecti

380 Male Reproductive

System
 ' {
':'

{, rv n .s!
t

. l '2 a
l. rl * b
|,?,t

t.3',
'+ '*
i,.

,
, ri'
\\, r
," 1.

t
F I C U R IE F I C U R 2E

r, ]
I

SM
t
io'
Sz \

F I C U R4
E

M a l e R e p r o d u c t i vSey s t e m
PLATE18-5 I Epididgmis,DuctusDeferens,and SeminalVesicle
FIGURE I Ductus epididgmis. Monkeg. Plastic
section. x 210.
The pseudostratifiedstereociliatedcolumnar epithe-
lium (Ep) lining the lumen of the ductus epididymis is
composedof two tlpes of cells:shortbasalcells(BC), rec-
ognizableby their round nuclei, and tall columnar prin-
cipal cells (PC), whose oval nuclei display one or more
nucleoli (n). The smooth muscle (SM) cells,composing
the wall of the epididymis,arecircularlyorientedand are
surroundedby connectivetissue(CT) elements.
lnser. Ductus epididymis. Monkey. Plastic section.
x 540.
Observethe round nuclei ofthe basalcells (BC) and
oval nuclei of the principal cells (PC). Clumped stere-
ocilia (arrows) extend into the spermatozoa(Sz)-filled
lumen.
FIGURE 2 \:trDuctus deferens. Monkeg. Plastic
section. x 132.
The ductus deferensis a thick-walled muscular tube
that conveysspermatozoafrom the ductusepididymisto
the ejaculatoryduct. The thick muscular coat is com-
posedof threelayersof smooth muscle:outer longitudi
nal (OL), middle circular (MC), and inner longitudinal
(IL). The fibroelasticlamina propria (LP) receivesits vas-
cular supply (BV) from vessels(arrow) that penetratethe
three muscle layers.A pseudostratifiedcolumnar epithe-
lium (Ep) lines the spermatozoa-filledlumen (L).
Insef. Ductus deferens. Monkey. Plastic section.
x 210.
A higher magnificationof the pseudostratified colum-
nar epithelium (Ep) displaysthe presenceof stereocilia
(Sc).

FIGURE 3 , Seminol vesicle. Human. Paroffin
section. x 132.
The paired seminal vesiclesare elongated tubular
glandswhoseductsjoin the ductus deferensjust prior to
the beginningof the ejaculatoryducts.The highly folded
mucous membrane (MM) of the seminalvesicleis com-
posed of pseudostratifiedepithelium (Ep) with a thin
connectivetissuecore (CT). The folded membraneanas-
tomoseswith itself, partitioning off small spaces(aster-
isks) that, although continuous with the central lumen,
appear to be discrete regions.A region similar to the
boxed area is presentedat a higher magnification rn
Figure4.
FIGURE 4 t'riSeminol vesicle. Monkeg. Plastic
section. x 540.
This photomicrographis a higher magnificationof a
region similar to the boxed areaof the previous figure.
Note that the tall columnar cells(CC) possess basallylo-
catedround nuclei (N) and that their cytoplasmdisplays
secretorygranules(arrows).Shortbasalcells(BC) areoc-
casionally present, which may function as regenerative
cellsfor the epithelium.The secretoryproduct is released
into the lumen (L) as a thick fluid that coagulatesin hrs-
tological sections.Observe the presenceof numerous
capillaries(C) in the connectivetissuecore deep to the
epithelium. Although spermatozoa(Sz) are frequently
noted in the lumen of the seminalvesicles,thev are not
storedin this structure.

Testisand epididymis

I KEY

BC basalcell L tumen OL muscle

outerlongitudinal
BV bloodvessel LP laminapropria layer
capillaries MC middlecircularmuscle PC principalcell
columnarcell rayer Sc stereocilia
CT connectivetissue MM mucousmembrane SM smoothmuscle
Ep epithelium N nucleus Sz spermarozoa
IL innerlongitudinal
muscle n nucleoli
rayer

382 I Male ReproductiveSystem

t :iT
I SM
Ep
t \
BV LP
IL
I
t
MC
t
I
OL
I Ep
I
t
I
I r, f')
,:.:::''^

I o\
o

,..i1:.
r.J

*'(l'

I /i\
-".. rl1
I
I
I i

.r>
(-J
I FICURE
3

I Male Reproductive
System
PLATE18-4 I Prostate,Penis,and Urethra I
FIGURE I a Prostate gland. Monkeg. Plastic FIGURE 2 a Prostste gland. Monkeg. Plastic
section. x 132.
The prostategland, the largestof the male reproduc-
section. x 540.
This photomicrograph is a higher magnification of a
I
tive accessoryglands, possessesa thick fibroelastic con- region similar to the boxed area of the previous figure.
nective tissuecapsulewith which the connectivetissue
stroma (St) is continuous.Note that the stroma houses
smooth muscle (SM) and blood vessels.The secretory
Observe that the fibroelastic connective tissue stroma
(St) presentsnumerous blood vessels(BV) and smooth
musclecells (SM). The parenchymaof the gland is com-
t
portion of the prostategland is composedof individual posed of columnar cells (CC), as well as short basal cells
glands of varied shapes,but consisting of a simple
cuboidal-to-low columnar type of epithelium (Ep), al-
(BC). Note that the dome-shapedapices (arrows) of
some of the columnar cells appear to protrude into the
I
though regionsofpseudostratifiedcolumnarepitheliaare lumen, which contain a prostatic concretion (Pc). The
readily apparent.A region similar to the boxed area is
presentedat a higher magnificationin Figure2.
number of these concretions, which may calcifr, in-
creases with age. I
FIGURE 3 | Penis. Human. x.s. Poroffin section.
x 14.
FfGURE 4 | Urethro. Human. Paraffin section.
x 132.
I
The penisis composedof threeerectilebodies:the two This photomicrograph is a higher magnification of
corpora cavernosaand the corpus spongiosum. The
cross-section ofthe corpusspongiosum(CS) displaysthe
urethra (U) that is surrounded by erectile tissue (ET)
the boxed area of the previous figure. Note that the
spongy urethra (U) is lined by a pseudostratifiedcolum-
nar epithelium (Ep) surrounded by a Iooseconnective
I
whose irregular, endothelially lined cavernous spaces tissue sheath (CT) housing a rich vascular supply (BV).
(Cs) contain blood. The spongytissueis surroundedby
the thick, fibrous tunica albuginea (TA). The three cav-
The entire urethra is envelopedby the erectile tissue (ET)
of the corpus spongiosum. Additionally, the mucous
I
ernousbodiesare surroundedby a looserconnectivetis- glands of Littr€ (GL) deliver their secretoryproduct into
sue sheathto which the skin (removedhere) is attached.
The boxed areais presentedat a higher magnificationin
Figure4.
the lumen of the urethra,lubricatingits epitheliallining.
I
Inser.Penis. Human. x.s. Paraffin section. X i 4.
The cavernous spaces(Cs) of the corpus cavernosum
are larger than those of the corpus spongiosum.More-
I
over, the fibrous trabeculae (FT) are thinner, resulting in
the corpora cavernosa becoming more turgid during
erectionthan the corpusspongiosum. t
I
I
Malereproductive
system
I
t
I KEY
t
BC
BV
basalcell
bloodvessel
CT
Ep
connectivetissue
epithelium
Pc
SM
prostaticconcretion
smoothmuscle I
CC columnarcell ET erectiletissue St stroma
CS
Cs
corpusspongiosum
cavernousspace
FT
GL
fibroustrabeculae
glandsof Littre
TA
U
tunicaalbuginea
urethra t
384 t MaleReproductive
Svstem t
I ?
'P oB f,',p
'St*
0614'*Sq F s
I st/ .i
$
a1
ii"-
SM
F- -*r\ \.
BU
I f
l"
,: '
r;i';'':''Fn
\H
Ep
I *
'
'a,J
il
6 ..i"
nt,.r
".,-',
Da
'
\
€i I

\
,"t''
'.
t /,
SM
:,

,"
J
I ^
r.i_^
t-{}
;
cc
-ii
t .i" i,. ::

I ..:ij,
,o ill
'
v\ v
"j
ir',',rri"'
-*1'
4*
,!7"'"
I + '.:l r ,6u$u
o\1# ,i$'[ o j
I Jt e)
&,*ou6{r*+*,Ft
ah
.1 ryfl'
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€i"' ,*
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I
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GLffi
'}.*..*.

I
TA ET
I F I C U R 3F FICLRE
4

I N l a l eR e p r o d u c t i vSey s t e n r 385
PLATE18-5 r Epididgmis,ElectronMicroscopg I
I
*rr
'.\
it
J
I
i\
a\
{\
I
.\ .Jl
I
I
I
I
I
I
t
I
I
I
I
FIGURE I Epididgmis. Rabbit. Electron types possessnumerous organelles,such as Golgi (G),
microscopg. x 1200.
The epitheliallining ofthe rabbit ductuli efferentesis
composedof two tlpes of tall columnar cells:principal
mitochondria (m), and rough endoplasmicreticulum
(arrows). Additionally, principal cells contain dense
bodies (DB), probably a secretorymaterial.(Courtesyof
I
cells (PC) and ciliated cells (CC). Note that both cell Dr. R. Tones.)

I KEY
I
CC
DB
ciliatedcell
densebodies
u
m
Golgi apparatus
mitochondrion
PC principalcell
J
Male Reproductive
System I
 lfffill t9
I Special Senses
I
The organs of specialsensesinclude the gustatory, generation. The two photoreceptors are the
I olfactory, visual, auditory, and vestibular appara-
tus. The gustatory apparatus,consisting of taste
rhodopsin-synthesizing rods and iodopsin-form-
ing cones,with the former sensitiveto dim and the
buds, is discussedin Chapter 13, and the olfactory latter sensitiveto bright light. Axons of connecting

I epithelium is treated in Chapter 12. The present

chapterdetailsthe microscopicmorphology of the
eye and the ear.
neurons, located within the retina, leavethe eyevia
the optic nerve to synapsein the brain.
The additional components of the orb are the
aqueous humor, a fluid; the vitreous body, a gel;
I EYE
and the lens, all of which serve as parts of the re-
fractive media.

I The eye is a sensoryorgan whose lens focusesrays

of light reflectedfrom the external environment on
photosensitive cells of the retina (see Graphic
The ear functions in the reception of sound, aswell
I 19-1). The intensity,location, and wavelengthsof
the transmitted light are interpreted by the visual
cortex of the brain as three-dimensionalcolor im-
as in the perception of the orientation of the head
and, therefore,the body in relation to the direc-
tional forcesofgravity (seeGraphic l9-2). To per-
agesof the external milieu. Each orb, protected by
I the eyelids,is movableby meansof a group of ex-
trinsic skeletalmusclesthat insert into the fibrous
form both functions of hearing and equilibrium
(balance),the ear is subdividedinto the external,
middle, and inner ears.
tunic of the orb, thus assistingin suspendingit in its The external ear is composedof a cartilaginous,
t bony orbit. The anteriorsurfaceofthe eyeis bathed
in tears, a fluid medium secretedby the lacrimal
skin-coveredauricle (pinna) and the external audi-
tory meatus with its cartilaginous outer and bony
gland. Three coatsconstitute the wall of the orb: the inner aspects,whose internal end is separatedfrom
I outer fibrous tunic, the middle vascular tunic
(uvea),and the inner retinal tunic.
The fibrous tunic (corneosclerallayer) is com-
the middle ear by the thin tympanic membrane.
The tympanic cavity of the middle ear houses
the three auditory ossicles: outermost malleus
posed of the opaque,white sclerathat coversthe
I posterior aspect of the orb, and the transparent
corneathat coversthe anterior l/6th ofthe orb. The
(hammer), middle incus (stirrup), and innermost
stapes (anvil). This cavity is connected to the
nasopharynx via the cartilaginous auditory (eu-
junction betlveen the sclera and the cornea is stachian) tube, which permits equalization of at-
I known as the limbus.
The vascular tunic is composedof severalre-
mosphericpressureson either sideof the trTmpanic
membrane.Sound wavesare funneledby the auri-
gions: the anteriorly positioned iris and ciliary cle to the $rnpanic membrane,whose vibrations
I body and the posteriorly located, highly vascular
and pigmented choroid. Intrinsic muscleslocated
are amplified and transmitted to the oval window
ofthe inner ear'scochleaby actionsofthe ossicles.
in the iris function to adjustthe apertureofthe iris, The inner ear, concernedwith both hearing and

I whereasintrinsic muscleslocatedwithin the ciliary

body function to releasetension on the lens, thus
permitting nearfocus(accommodation)by altering
its diameter.
I The innermost retinal tunic is composedof l0
layersresponsiblefor photoreceptionand impulse
balance,is housedwithin a labyrinth in the petrous
portion of the temporal bone. The region closest
to the middle ear, the bony cochlea,housesthe
apparatusresponsiblefor hearing, while its deeper
aspect contains the structures responsible for
vestibularfunction (balance).

I SpecialSenses E 387
 The bony cochleacontainsthe endolymph-filled canals,membranous structuresresponsiblefor bal-
space.
I
cochlearduct, which is surroundedby perilymph, anceand orientationin three-dimensional
housedin the superiorlylocatedscalavestibuli and The principal functional components of the
the inferiorly positioned scala tympani. The two
scalaecommunicatewith each other via the heli-
utricle and saccule,oriented perpendicularly to
eachother, areknown asmaculae.Thesestructures
I
cotrema,a smallslit-likeopening. house neuroepithelial hair cells whose microvilli
Within the cochlearduct is the spiral organ of
Corti whoseinner and outer hair cellsare in close
and kinocilia (nonmotile cilia) project into the
otolith-containing proteinaceousotolithic mem-
I
associationwith the tectorial membrane. Vibra- brane. The utricle and sacculerespond to linear
tions of the basilar membrane.induced by distur-
bancesin the perilymph,resultin stimulationof the
acceleration.
A similar collectionof hair cellsis locatedon the I
cochlearnervesby the hair cells.Dendritesof the crista ampullaris of the ampulla of eachsemicircu-
cochlearnervesleadto the spiralganglionIocatedin
the modiolus.Oscillationssetin motion at the oval
window are dissipatedat the secondarytympanic
lar canal.The microvilli and kinocilia of theseneu-
roepithelialcells also project into a proteinaceous
material, the cupula, which contains no otoliths.
I
membrane covering the round window of the Sinceeachsemicircularcanalis orientedperpendic-
cochlea.
The bony labltinth alsocontainsthe endoll'rnph-
ularly to the other two, angularaccelerationalong
any ofthe threeaxesis registeredand interpretedas
I
filled utricle. saccule. and the three semicircular a vectorin threedimensions.
I
I
I
I
t
t
I
I
I
I
t
t
588 = SpecialSenses t

Histophgsiologg
I. EYE
A. Orb
The eye functions as the photosensitive organ re-
sponsiblefor vision. It receiveslight through the
cornea,which is subsequently focusedon the retina
via the lens.It is herethat specializedcells(rods and
cones)recognizevarious patternsof the image for
transmission to the brain via the optic nerve.
Extrinsic muscles attached to the orb direct the
pupil to the most advantageousposition for per-
ceiving the image viewed.Becausethe eyesare set
apart, their visual fields overlap, thus enhancing
three-dimensionalimaging. Intrinsic musclesrep-
resented by the sphincter pupillae and dilator
pupillae musclesadjust the aperture of the iris, and
ciliary muscles manipulate the focal length of the
lens for accommodationfor closevision.
Melanocyteslocated in the epithelium and
stroma of the iris block light from passingthrough
the iris, exceptat the pupil. Additionally,eyecolor is
relatedto the abundanceof thesemelanocytes: large
numbersof melanocytesimpart dark eyes,whereas
fewermelanocytesrenderthe eyeslight in color.
Aqueous humor, a plasma filtrate produced by
the cellscoveringthe ciliary processespassesfrom the
posterior chamberof the eyeinto the anterior cham-
ber via the opening betweenthe lens and the pupil.
The wall of the orb is composedof three tunics:
the tunica fibrosa, tunica vasculosa,and tunica
retina. The tunica retina is responsiblefor photore-
ception.Although the retina displaysl0 distinctive
layers,most of its cells support and/or relay im-
pulsesto the optic nervefor transmittalto the brain.
The two deepestlayers,the retinal pigment epithe-
lium and the layerof rodsand cones,bearthe major
responsibiliryfor photoreception.
Retinal pigment epithelium functions in esteri-
fring vitamin A and transporting it to the rods and
cones, phagocytosingthe shed tips of rods and
cones, and synthesizingmelanin, which absorbs
light after rods and coneshavebeenstimulated.
Rodsare sensitiveto low light intensityand pos-
sessmany flatteneddiscscontainingrhodopsin (an
integralmembraneprotein opsin bound to retinal,
the aldehyde form of vitamin A) in their outer
segment.When light is absorbedby rhodopsin, it
dissociatesinto retinal and opsin (bleaching),per-
mitting diffusion of bound Caz* into the outer
segment.Excessof Ca2* hlperpolarizesthe cell by
closingNa* channels,thus preventingthe entry of
IIffiTI
Na+ into the cell.The electricalpotential thus gen-
eratedis relayedto other rods via gap junctions and
then along the pathway to the optic nerve. Dissoci-
ated retinal and opsin reassemble,and the Ca2*
ions are recaptured,establishinga normal resting
potential.
Cones, sensitiveto light of high intensity, pro-
ducing greater visual acuity, dte much more
numerous than rods and produce iodopsin, the
photopigmentsensitiveto red, green,or blue light.
The mechanism of transducing photoenergy into
electricalenergyfor transmissionto the brain via the
optic nerveis similar to that describedin the rods.
The optic disc, the region where fibers of the
optic nerveexit the orb, containsneither conesnor
rods; consequently,it is calledthe blind spot. Just
lateralto the blind spot is the fovea centralis,a de-
pressionin the wall of the orb. The foveacontains
mostly conesthat are packedso tightly that not all
layersof the retina arepresent.This is the region of
the retina wherevisual acuityis the greatest.
B. AccessoryStructures
Accessory structures of the eye include the con-
junctiva, eyelids,and lacrimal gland. The conjunc-
tiva is a transparentmucous membranethat lines
the eyelids and reflects on the orb. The eyelids
contain modified sebaceousglands, meibomian
glands,responsiblefor alteringthe surfacetension
of the watery tears,thus slowing evaporation.The
lacrimal glands secretetearsthat keep the conjunc-
tiva and corneamoist. Tears also contain lysozyme,
an antibacterialenz)rme.
II. EAR
The ear is composedofthree parts:the externalear
(pinna and external acoustic meatus), which re-
ceivesthe sound waveslthe middle ear (containing
the bony ossicles),which transmits the sound
waves;and the inner ear (containingthe cochlea),
where sound wavesare transduced into nerve im-
pulsesand the sensationof equilibrium is achieved
by the vestibularapparatus.
The tympanic membrane, located at the deepest
aspectof the external acousticmeatus, transmits
sound vibrationsto the bony ossiclesof the middle
ear. The tympanic cavity of the middle ear con-
tains the malleus,incus,and stapes(bony ossicles)
connectedin seriesto eachother and betweenthe
SpecialSenses H 389
tr//mpanicmembrane and the oval window of the sound waves are detected farther away from the
I
bony wall. They greatlyamplify and translatemove- oval window. It should be noted that loud sounds,
ments of the tympanic membrane to the oval
window.
The bony labyrinth of the inner ear,subdivided
suchasthoseat rock concerts,createa greatdeal of
energywithin the hearing mechanism, such that it
may take two or three days for the energy to be
t
into the semicircularcanals,vestibule,and cochlea, completely dissipatedand the buzzing to stop.
is filled with perilymph.Looselycontainedwithin it
and all of its subdivisions is the membranous
I
labyrinth containing endolymph. Movements of
the fluid environment within this systemare per-
ceivedby certainsensorycellscontainedwithin the
C l i n i c aC
l o n s i d e r a t i o n*ssm r I
membranouslabyrinth and ultimately transduced
to electricalimpulsesfor transmissionto the brain.
The saccule and utricle. specializationsof the
Glaucoma
Claucoma i s a c o n d i t i o no f h i g hi n t r a o c u l a r
p r e s s u r ce a u s e db y a n o b s t r u c t i o tnh a t p r e -
I
membranouslabyrinth in the vistibule, contain type
v e n t sa q u e o u sh u m o rf r o m e x i t i n gt h e a n t e -
I and type II hair cells(neuroepithelialcellscontain-
ing many stereociliaand a singlekinocilium) whose
free ends are embeddedin the otolithic membrane
r i o rc h a m b e o
b l i n d n e sm
r f theeye lf lefluntreated,
s ayresult
I
containing otoliths (otoconia). Static equilibrium
and linear acceleration are determined by move-
ments in thesehair cells,which s).napsewith nerve
Cataract
C a t a r a c ta, c o m m o nc o n d i t i o no f a g i n g i,s
c a u s e db y e x c e s s i vU a n db y p i g -
e Vr a d i a t i o n
t
cellsofthe vestibularportion ofthe acousticnerve. m e n t sa n d o t h e rsubstances a c c u m u l a t i ni n
g
Semicircularducts, specializations of the mem-
branous labyrinth in the semicircularcanals,con-
t h e l e n s ,m a k i n gi t o p a q u ea n d t h u si m p a i r i n g
v i s i o nT h i sc o n d i t i o nm a y b e c o r r e c t e db y
I
tain neuroepithelialhair cellslocatedin the cristae e x c i s i n tgh e l e n sa n d r e p l a c i n igt w i t ha p l a s -
ampullares(sensoryregions)of the ampullae.Free
endsof thesehair cellsareembeddedin a glycopro-
lic lens
Detached Retina
I
tein, the cupula.Movementsof the endolymphand
D e t a c h e dr e t i n am a y r e s u l tf r o ma t r a u m a
the cupula are translatedto the hair cells,which
s).napse with nervecellsof the vestibularportion of
the acousticnerve.This processis sensitiveto rota-
w h e r et h e n e u r a a l n d p i g m e n t e dl a y e r so f t h e
r e t i n ab e c o m es e p a r a t e dT h i sc o n d i t i o nm a y
I
c a u s ep a r t i a lb l i n d n e s sb,u t i t m a y b e c o r -
tional accelerationin any ofthe three directionsof
orientation of the semicircularcanals.
The endolymphatic sac (terminal end of the en-
rectedby surgicalintervenlion
Conductive Hearing Loss
t
dolymphatic duct) containsphagocyticcellsin its lu- C o n d u c t i vhee a r i n gl o s sm a y a r i s ef r o ma
men and may function in resorption of endolymph.
The cochlear duct contains the spiral organ of
m i d d l ee a r i n f e c t i o n( o t i t i sm e d i a )a, n o b -
s t r u c t i o no, r o s t e o s c l e r o soi fst h e m i d d l ee a r
I
Corti, which is bordered by the scalavestibuli and
Nerve Deafness
the scala tympani (both scalaecontain perilymph
and communicate at the helicotrema). The vestibu-
lar membrane located between the scala vestibuli
N e r v ed e a f n e s rse s u l t sf r o ma l e s i o ni n t h e
c o c h l e apr o r t i o no f t h e v e s t i b u l o c o c h l e a r
I
. h i sc o n d i t i o nm a y
n e r v e[ c r a n i anl e r v eV l l l ) T
and the cochlearduct functions to maintain the high
ion gradientbetweenthe perilymph and endolyrnph.
The spiral organ of Corti, sitting on the basilar
b e t h e r e s u l to f d i s e a s ep, r o l o n g e d
t o l o u ds o u n d sa, n d / o rd r u g s
exposure
I
membrane, contains, among other supporting M€niEre's Disease
cells, neuroepithelial inner and outer hair cells
whosefree endsare embeddedin the gel-liketecto-
M € n i e r e 'ds i s e a s ei s a n i n n e re a rd i s o r d e r
c h a r a c l e r i z ebdy s y m p t o m s u c ha s h e a r i n g
I
rial membrane. Sound wavestranslated to the oval l o s sd u e t o e x c e s sf l u i da c c u m u l a t i oi n t h e
window set the perilymph of the scalaqrnpani in
motion, which displacesthe basilar membrane,
endolymphatd i cu c t ,v e r l i g ot,i n n i t u sn, a u s e a ,
a n d v o m i t i n gM a n yo f t h e s y m p t o m sm a y b e I
thus moving the hair cells but not the tectorial r e l i e v e db y d r u g st h a t a r e p r e s c r i b efdo r v e r -
membrane.Bendingof the hair cellscausesthem to
releaseneurotransmitter substance,exciting the
bipolar cells of the spiral ganglion, resulting in
t i g oa n d n a u s e ao r i n m o r es e v e r ec a s e s
v e s t i b u l anr e u r e c t o m[yc u t t i n gt h e v e s t i b u l a r
nerve)may be performedIn very severe
t
transmissionof the impulseto higher centersof the c a s e sl a b y r i n t h e c t o mi syt h e t r e a t m e not f
brain. Although the basilar membranevibratesat
many frequencies,certainregionsvibrateoptimally
c h o i c ew , h e r et h e s e m i c i r c u l a
c o c h l e aa r es u r g i c a l lrye m o v e d
r n a l sa n d t h e
ca I
at specificfrequencies.For example,Iow frequency

390 ffi Special

Senses t
I tr*tl
I Summargof HistologicalOrganization
I I. EYE lessmeridianally, radially, and circularly, function
in accommodation. The vascular layer and glassy
I A . F I B R O U ST U N I C
l. Cornea
membrane of the choroid continue into the ciliary
body. The inner aspectofthe ciliary body is covered
The corneais composedoffive layers.From super- by the inner nonpigmentedand outer pigmented

I ficial to deep,they are

a. StratifiedSquamousNonkeratinized
Epithelium
layersof the ciliary epithelium.
3. Iris
b. Bowman's Membrone The iris, separatingthe anterior from the posterior
I The outer, homogeneouslayerof the stroma.
c Stroma
chamber, is attached to the ciliary body along
its outer circumference.The centerof the iris is in-
complete, forming the pupil of the eye. The iris
A transparent,denseregular collagenousconnec-
I tive tissuehousing fibroblasts and occasionallym-
phoid cells,comprisingthe bulk of the cornea.
is composedof three layers:the outer (frequently
incomplete) simple squamous epithelial layer, a
continuation of the corneal epithelium; the middle
d. Descemet'sMembrane fibrous layer, composedofthe nonvascularanterior
I A thick basallamina.
e. CornealEndothelium
stromal and vascular general stromal layers that
house numerous melanocytesand fibroblasts; and
Not a true endothelium, a simple squamous-to- the posterior pigmented epithelium. The sphincter
I cuboidal epithelium.
2. Sclera
and dilator musclesof the pupil are composedof
myoepithelial cells derived from the pigmented
epithelium.
The sclera,the white of the eye, is composedof
I three layers: the outer episcleral tissue housing
blood vessels;the middle stroma, composed of
dense regular collagenousconnectivetissue; and C. RetinalTunic
I the suprachoroidlamina, a looseconnectivetissue
housingfibroblastsand melanocytes.
The retinal tunic, the deepestof the three layers,
consists of the pars iridica, pars ciliaris, and pars
optica. The last of theseis the only region of the
I B. VascularTunic
retina that is sensitiveto light, extending as far an-
teriorly as the ora serrata, where it is continuous
The vascular tunic (uvea) is a pigmented, vascular with the pars ciliaris.

t layerhousingsmoothmuscles.It is composedof the

choroid membrane,the ciliarybody, and the iris.
l. Pars Optica
The pars optica is composedof ten layers.
l. Choroid Membrqne o. PigmentEpithelium
I The choroid membraneis composedof four layers.
The suprachoroid layer is shared with the sclera
The pigment epithelium is attachedto the choroid
membrane.
and housesfibroblasts and melanocytes.The vas-

t cular and choriocapillary layershouselarger vessels

and capillaries,respectively.The glassymembrane
(of Bruch), interposedbetweenthe choroid and the
b. Laminaof Rodsond Cones
The outer and inner segmentsofthe photoreceptor
cells form the first layer, while the remainder of
thesecellsconstitutesthe next three layers.
t retina, is composedof basallamina, collagen,and
elasticfibers.
2. Ciliarg Bodg
c. ExternalLimitingMembrane
The external limiting membrane is not a true mem-
brane. It is merely a junctional specializationbe-
I The ciliary body is the region of the vasculartunic
locatedbetweenthe ora serrataand the iris. The cil-
iarybody is composedof the numerous,radiallyar-
tween the photoreceptor cells and processesof
Miiller's ( supportive) cells.
ranged, aqueous humor-form ing ciliary processes d. OuterNuclearLoger
I that together compose the ciliary crown from
which suspensory ligaments extend to the lens.
The outer nuclearlayer housesthe cell bodies(and
nuclei) of the photoreceptor cells.At the fovea cen-
Three layers of smooth muscle, oriented more or tralis, only conesare present,
I Senses*
Soecial 391
 e. Outer PlexiformLoger
The outer plexiform layer is the region of synapse
formation betweenthe axonsof photoreceptorcells
and the processes ofbipolar and horizontal cells.
f. InnerNuclearLager
The inner nuclear layer housesthe cell bodies of
Mi.iller, amacrine (associative),
bipolar, and hori-
zontal cells.
g. InnerPlexiformLager
The inner plexiform layer is the region ofsynapses
between dendrites of ganglia cells and axons of
bipolar cells. Moreover, processesof Miiller and
amacrinecellsare alsopresentin this layer.
h GanglionCellLoger
The ganglion cell layer housesthe cell bodies of
multipolar neurons,which are the final link in the
neuronal chain ofthe retina, and their axonsform
the optic nerve.Additionally,neurogliaare alsolo-
catedin this layer.
i Optic NerveFiberLoger
The optic nerve fiber layer is composedof the un-
myelinated axons of the ganglion cells,which will
be collectedas the optic nerve.
j. lnnerLimitingMembrane
The inner limiting membrane is composedof the
expandedterminal processesof Miiller cells.
2. Pars Ciliqris and Pars lridico Retinae
At the pars ciliaris and pars iridica retinaethe reti-
nal layerhas beenreducedto a thin epitheliallayer
consistingof a columnar and a pigmentedlayerlin-
ing the ciliarybody and iris.
D. Lens
The lens is a biconvex, flexible, transparentdisc
that focusesthe incident raysof light on the retina.
It is composedof three layers,an elasticcapsule
(basementmembrane),an anteriorlyplacedsimple
cuboidal epithelium, and lens fibers, modified ep-
ithelial cellsderivedfrom the equator ofthe lens.
E. Lacrimal Cland
The lacrimal gland is external to the eye, located
in the superolateralaspectof the orbit. It is a com-
pound tubuloalveolarglandproducing a lysozyme-
rich serousfluid with an alkalineoH.
F. Eyelid
The eyelid is coveredby thin skin on its externalas-
pect and by conjunctiva,a mucous membrane,on
its inner aspect.A thick densefibrous connective
tissuetarsalplate maintainsand reinforcesthe eye-
lid. Associatedwith the tarsal plate are the tarsal
392 ffi SpecialSenses
glands secretingan oily sebum that is delivered to
the margin of the eyelid. Musclescontrolling the
eyelid are locatedwithin its substance.Associated
with the eyelashesare sebaceousglands, while cil-
iary glandsarelocatedbetweeneyelashes.
II. EAR
Ear
A. External
l. Auricle
The auricle is coveredby thin skin and is supported
by an elastic cartilage plate.
2. External Auditorg Meqtus
The external auditory meatus is a cartilaginous
tube lined by skin, containing ceruminous glands
and somefine hair. In the medial aspectof the mea-
tus the cartilageis replacedby bone.
3. TgmpanicMembrane
The tympanic membraneis a thin, taut membrane
separating the external from the middle ear. It
is lined by stratified squamouskeratinized epithe-
Iium externally and low cuboidal epithelium inter-
nallyand possesses a coreofcollagenfibersdisposed
in two layers.
B. Middle Ear
The middle ear is composedof the simple cuboidal
epithelium-lined tympanic cavity containing the
three ossicles(malleus, incus, and stapes).The
tympanic cavity communicateswith the nasophar-
ynx via the cartilaginous and bony auditory tube.
The medial wall of the middle ear communicates
with the inner ear via the oval (vestibular) and
round (cochlear)windows.
C. lnnerEar
l. Cochleq
The bony cochlea houses the endolymph-filled
cochlear duct that subdivides the perilymph-filled
cochleainto the superiorlypositioned scalavestibuli
and the inferiorly locatedscalatympani.
o. CochlearDuct
The cochlear duct housesthe spiral organ of Corti
that lies on the basilar membrane. The spiral organ
of Corti is composed of cells of Claudius, cells of
Boettcher,and cellsof Hensen,all of which assistin
the formation of the outer tunnel along with the
outer hair cells and outer phalangealcells.The tec-
torial membranelies over the outer hair cells,aswell
asthe inner hair cells,thus forming the internal spi-
ral tunnel. The region betweenthe inner and outer
hair cellsis occupiedby pillar cells,which assistin the
formation of the inner tunnel (of Corti). The stria
I vascularisconstitutesthe outer wall of the cochlear
duct. Nerve fibers lead to the spiral ganglion (hous-
two cell t)?es, neuroepithelial hair cells and sup-
porting cells.The free surfaceof the macula displays
ing pseudounipolarcells)in the modiolus. the otolithic membrane housing small particles
I b. MembranousLabgrinth
The membranous labyrinth is composed of the
calledotoliths.

2. Semicircular Candls

t utricle, the saccule, and the three semicircular

canals.
l. Utricle dnd Saccule
The utricle and saccule are both filled with en-
I dolymph and house maculae.Each macula is com-
posed of simple columnar epithelium composedof
The three semicircular canalsare oriented Perpen-
dicular to each other. The ampulla of each canal
houses a crista, a structure similar to a macula,
composed of neuroepithelialhair cells and sup-
porting cells. A gelatinous cupula is located at the
free surfaceof the crista,but it contains no otoliths.

I
t
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I SpecialSenses | 393
G RA P H I 1
C9 - 1 | Ege I
Retina
Chorold
Sclera
I
L€ns
lrls
Cornea
Ciliarymuscles I
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Photo6€nsitiv€
r€gion

I
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Sec-tlon of F€tlna
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Ganglion cellaxon
to opticnen€

Amacrinecell
I
Pigmentlayel
c€ll
Horizontal I
I
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594 a SpecialSenses I
t 19-2 t
GRAPHIC Ear

I
I
I
I Auditorytub€

I
Scalavestibuli

I Tectorialm€mbrane
V€stibularmembrane
Spilalganglion

I Organof Corti
Basilarmembran€

Scala tympani

I
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I Tsctorialmembran€

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I SpecialSenses t 595.
PLATE19-I I Ege,Cornea,Sclera,lris,and CiliargBodg
FIGURE | * Cornea. Monkeg. Paraffin section. FIGURE 2 * Sclero. Monkeg. Poroffin section.
x 132. x 132.
The corneais a multilayered,transparentstructure.Its The sclera is similar to and continuous with the
anterior surface is covered by a siratified squamous cornea,but it is not transparent.Note that the epithelium
nonkeratinizedepithelium (Ep), deepto which is a thin, (Ep) of the conjunctiva covers the anterior surfaceof
acellularBowman'smembrane.The bulk of the cornea, the sclera.Deep to the epithelium is the looseepiscleral
the stroma (St) is composedof regularlyarrangedcolla- tissue(ET), whoseblood vessels(BV) areclearlyevident.
gen fibers (CF) and interveningfibroblasts,whosenuclei The stroma (St) is composedof thick collagenfiber (CF)
(N) are readily evident. The posterior surface of the bundles housing numerous fibroblasts (F). The deepest
corneais lined by a simplesquamous-to-cuboidal epithe- layerof the sclerais the suprachoroidlamina (SL) whose
lium (Ep). A thin acellularDescement'smembrane lies melanocytes(M) housemelanin pigment.
betweenthe simple epithelium and the stroma.
Inset. Cornea.Monkey. Paraffinsection.X 270.
A highermagnificationofthe anterior surfacedisplays
the stratified squamousepithelium (Ep), as well as the
acellularBowman'smembrane (BM). Note the regularly
arrangedbundlesofcollagen fibers (CF) and intervening
fibroblasts(F).

FIGURE 3 .a lris. Monkeg. Paroffin section. x 132.
The iris (l) separates
the anterior chamber(AC) from
the posterior chamber (PC). The medial border of this
structuredefinesthe pupil (P) of the eye."The iris is com-
posed of three layers:an outer discontinuouslayer of
melanocpes and fibroblasts;the middle fibrous layer
(FL), housingpigment cells (Pc); and the posteriordou-
ble layeredpigmentedepithelium (PEp)." The sphincter
(sM) and dilatator musclesare composedof myoepithe-
lial cells.The pupillary region ofthe iris contactsthe cap-
sule (Ca) of the lens (L) in livins individuals.
FIGURE 4 # Ciliorg bodg. Monkeg. Pqroffin
section. x 132.
The ciliary body is composed of ciliary processes
(CP), projecting into the posterior chamber (PC) from
which suspensoryligamentsextendto the lens.The bulk
of the ciliary body is composedof smooth muscle (SM)
disposedmore or lessin three layers,not evidentin this
photomicrograph.Numerouspigment cells(Pc) arepre-
sent in this region.Note that the epithelium of the ciliary
body is composed of two layers:an outer pigmented
(OP) and an inner nonpigmented (IN) epithelium. The
narrow vascularlayer (VL) is evidentbetweenthe epithe-
lium and ciliary muscles.

Eye,ciliarymuscles,
iris,
andlens

I KEY

AC anteriorchamber FL fibrouslayer Pc pigmentcells

BM Bowman'smembrane tns PEp pigmentedepithelium
BV bloodvessel IN innernonpigmented layer sEp squamousepithelium
Ca capsule L lens SL suprachoroid lamina
UT collagenfibers M melanocytes SM smoothmuscle
UT ciliaryprocess N nucleus SM sphinctermuscle
Ep epithelium OP outer pigmentedlayer St stroma
ET episcleraltissue P pupil VL vascularlayer
F fibroblasts PC posteriorchamber

396 ffi SpecialSenses

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PLATE19-2 t Retina,Lightand ScanningElectronMicroscopg
FIGURE | € Tunics of the ege. Monkeg. paraffin
section. x 14.
This survey photomicrograph is of an anterolateral
section of the orb, as evidencedby the presenceof the
lacrimal gland (LG). Note that the three layersof the orb
are extremelythin in relation to its diameter.The sclera
(S) is the outermostlayer.The pigment choroid (Ch) and
multilayered retina (Re) are easilydistinguishableeven at
this magnification. The posterior compartment (pCo)
housesthe vitreous body. A region similar to the boxed
areais presentedat a higher magnificationin Figure2.
FIGURE 2 * Retina. Pars optica. Monkeg. Paroffin
section. x 210.
The pars optica of the retina is composedof l0 dis-
tinct layers.The pigment epithelium (l), the outermost
layer, is closely apposed to the vascular and pigmented
choroid (Ch). Various regionsofthe rods (R) and cones
(C) form the next four layers. These are the lamina of
rods and cones (2), external limiting membrane (3),
outer nuclear layer (4), and outer plexiform layer (5).
The inner nuclearlayer (6) housesthe cell bodiesofvar-
ious associativeglial (Miiller) and functional cells. The
inner plexiform layer (7) is a region of synapseforma-
tion, while the ganglioncell layer (8) housesthe cell bod-
ies of multipolar neurons and neuroglia.Fibersof these
ganglion cells form the optic nerve fiber layer (9), while
the inner limiting membrane( 10) is composedof the ex-
pandedprocesses of Mtiller cells.A region similar to the
boxed area is presentedin Figure 3, a scanningelectron
micrographofthe rods and cones.

FICURE 3 E Rods and cones. Monkeg. Scanning
electron microscopg. x 6300.
This scanning electron micrograph of the monkey
retina displays regions of severalcones (C) and of a
few rods (R). The inner segmentsof the lamina of
rods and cones (2), external limiting membrane (3),
and outer nuclear layer (4) are clearly recognizable.
The microvilli (Mv) noted in the vicinity of the ex-
ternal limiting membrane belong to the Miiller cells,
which were removed during specimen preparation.
Observe the longitudinal ridges (arrows) along the
surfaceof the inner segments.(From Borwein B, Borwein
D, Medeiros J, McGowan l: Am I Anat 159:725-146,
1e80.)

Sectionof retina

T KEY

1 pigmentepithelium 7 innerplexiformlayer LG lacrimalgland

2 laminaof rods and cones 8 ganglioncell layer Mv microvilli
3 externallimitingmembrane 9 optic nervefiber layer PCo posteriorcompartment
4 outernuclearlayer 10 innerlimitingmembrane R rods
outer plexiformlayer C cones Re retina
o innernuclearlaver Ch choroid S sclera

398 ffi SpecialSenses

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 PLATE19-3 I Fovea,Lens,Egetid,and LacrimalGlands
FIGURE | * Fovea centralis. Monkeg. paraffin
section. x 132.
The retina is greatlyreducedin thicknessat the fovea
centralis (FC) of the macula lutea. This is the region of
greatestvisual acuity, and cones (C) are the onl-ypho-
toreceptorcells in this area.Note that the retinal layers
present are the pigrnented epithelium (l), lamina of
cones(2), externallimiting membrane(3), outer nuclear
layer (4), outer plexiform layer (5), ganglion cell layers
(8), and inner limiting membrane (10). Observe the
presenceof the vascularchoroid (Ch) whose pigment
cellsimpart a dark colorationto this layer.
FfGURE 2A € Lens. Monkeg. Poraffin section.
x 132.
The lens is a biconvex,flexible,transparentdisc cov-
eredby a homogenouscapsule(Ca) deepto which liesthe
simple cuboidal lens epithelium (Ep). The fibers (ar-
rows), constitutingthe bulk of the lens,are composedof
closelypacked,hexagon-shaped cellswhoselongitudinal
axesare orientedparallelto the surface.
Inset. Lens.Monkey.Paraffinsection,X 270.
Note the presenceof the homogeneouscapsule(Ca)
overlyingthe simple cuboidallensepithelium (Ep).
FIGURE 28 * Lers. Monkeg. Paraffin section.
x 132.
The equator of the lens displays the presenceof
younger cellsthat still possesstheir nuclei (N). Note the
suspensoryligaments (SL), capsule (Ca), and the lens
epithelium (Ep).

FIGURE 3 * Egelid. Paraffin section. x 14.
The external aspectof the eyelid is coveredby thin
skin (Sk) and linedby a stratifiedcolumnar epithelium,
the palpebralconjunctiva(pC). The substanceofthe eye-
lid is formed by the thick connectivetissuetarsal plate
(TP), whose tarsal glands (TG) are clearly evident. Two
skeletalmusclesare associated with the upper eyelid,the
circularlydisposedorbicularis oculi (OO) and the longi-
tudinally orientedlevatorpalpebraesuperioris.Although
the latter muscleis not presentin this photomicrograph,
its connectivetissueaponeurosisis evident (arrow). Eye-
lashesand the sebaceous ciliary glands (CG) are present
at the inferior tip ofthe lid.
F|GURE 4 & Lacrimal gland. Monkeg. Paraffin
section. x 132.
Lacrimalglandsarecompound tubuloalveolarglands,
separatedinto lobes and lobules (Lo) by connectivetis-
sue (CT) elements. Since these glands produce a
lysozyme-rich,watery secretion,they are composedof
numerous serousacini (SA), as evidencedby the round,
basallylocatednuclei (N) ofthe secretorycells.

Ciliarymuscles,iris,and lens

I KEY
1 pigmentedepithelium Ca capsure OO orbicularisoculi
z laminaof cones ch choroid pC palpebralconjunctiva
3 externallimitingmembrane CG ciliarygland SA serousacini
4 outer nuclearlayer CT connectivetissue Sk skin
5 outer plexiformlayer Ep epithelium SL suspensoryligaments
I ganglioncelllayer FC Joveacentralis TG tarsalglands
10 innerlimitingmembrane Lo lobule TP tarsalplate
cones N nucleus

400 = SpecialSenses
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PLATE19-4 I InnerEar
FTGURE I a Inner ear. Parqffin section. x 21 .
This photomicrograph is a surveysectionofthe petrous
portion of the temporal bone displayingthe various com-
ponents of the inner ear. At the extreme right, note the
spirally disposed bony cochlea (BC) housing the en-
dolymph-filled cochlear duct (CD) and the perilyrnph-
filled scalatympani (ST) and scalavestibuli(SV). The apex
of the cochlea displays the helicotrema (H), the space
through which perilymph may be exchangedbetweenthe
scalatympani and the scalavestibuli. Innervation to the
spiral organ of Corti (OC), located within the cochlear
duct, is derived from the spiral ganglion (SG), housed in
the modiolus (M). Two cranial nerves,vestibulocochlear
(VN) and facial (FN), areevidentin this photomicrograph.
The vestibule (V), aswell assectionsof the ampullae (A) of
the semicircular canals containing the crista ampullaris
(CA), are clearly recognizable.Finally, note one of the
auditory ossicles(AO) of the middle ear.
Inset. Crista ampullaris, Paraffin section. X 132.
The crista ampullaris (CA) is housed within the ex-
panded ampulla (A) of each semicircular canal. Nerve
fibers (NF) enter the connectivetissuecore ofthe crista
and reach the neuroepithelial hair cells (HC) that are
supported by sustentacularcells (SC). Kinocilia and mi-
crovilli ofthe hair cells extend into the gelatinous cupula
(Cu) associatedwith the crista.

Ear

I KEY
A ampulla FN facial nerve SC sustentacularcells
AO auditoryossicle H helicotrema SG spiralganglion
BC bony cochlea HC haircells ST scalatympani
CA cristaampullaris M modiolus SV scalavestibuli
CD cochlearduct NF nervefibers vestibule
Cu cupula oc spiralorganof Corti VN vestibulocochlearnerve

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PLATEl9-5 I Cochlea

FIGURE I Cochlea.Paroffin section. x 211.
This photomicrograph is a higher magnification of
one of the turns of the cochlea.Observethat the scala
vestibuli (SV) and scalatympani (ST), enclosedin the
bony cochlea (BC), are epithelially (Ep) lined spaces,
filled with perilymph. The cochlear duct (CD), filled
with endolymph, is separatedfrom the scalavestibuli
by the thin vestibular membrane (VM) and from the
scala tympani by the basilar membrane (BM). Within
the bony casingis the spiral ganglion (SG), whose cell
bodiesareclearlyevident(arrows).Cochlearnervefibers
(CNF) from the spiral ganglion traversebony tunnels
of the osseousspiral lamina (OL) to reach the harr
cells of the spiral organ of Corti (OC). This structure,
responsiblefor the senseof hearing, is an extremely
complex entity. It restson the basilarmembrane,a taut
collagenoussheet extending from the spiral ligament
(SL) to the limbus spiralis (LS).Attachedto the limbus
spiralisis the tectorial membrane(TM) (whoseelevation
in this photomicrograph is an artifact of fixation) that
overliesthe spiral organ of Corti. Observethe presence
of the stria vascularis (Sv), which extends from the
vestibular membrane to the spiral prominence (SP).
The stria vascularispossesses a pseudostratifiedepithe-
lium (Ep) composed of basal, dark, and light cells,
which are intimately associatedwith a rich capillary
network. It is believedthat endolymph is elaboratedby
some or all of thesecells.The morphology of the spiral
organ of Corti is presentedat a higher magnificationin
Platel9-6.

Cochleaand acousticnerve

T KEY

BC bony cochlea spiralorganof Corti scalatympani

BM basilarmembrane OL osseousspirallamina SV scalavestibuli
CD cochlearduct spiralganglion Sv striavascularis
CNF cochlearnervefibers 5L spiralligament TM tectorialmembrane
trn epithelium SP spiralprominence VM vestibularmembrane
LS limbusspiralis

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PLATEl9-6 . SpiralOrganof Corti I
FIGURE | * Spiral organ of Corti (Montage). Proceedinglaterally, the inner pillar cell (lPC) and outer
Paraffin section. x 540.
The spiral organ of Corti lies upon the basilar mem-
pillar cell (OPC) form the inner tunnel of Corti (ITC).
The spacesofNuel (SN) separatethe three rows ofouter
I
brane (BM), whosetwo regions,the zona pectinata(ZP) hair cells (OH) from eachother and from the outer pillar
and zona arcuata(ZA), aredelineatedby the baseofthe
outer pillar cells (OPC). The basilarmembraneextends
from the spiral ligament (SL) to the tympanic lip (TL)
cells. Fine nerve fibers (NF) and phalangeal processes
(PP) traverse these spaces.The outer hair cells are
supported by outer phalangeal cells (OPh). The space
I
of the limbus spiralis, to whose vestibular lip (VL) the betweenthe cells of Hensen (CH) and the outermost row
tectorial membrane (TM) is anchored. The tectorial
membraneactsasa roof of the internal spiral sulcus(IS).
ofouter phalangealcellsis the outer tunnel (OT). Lateral
to the cells of Hensen are the darker staining, deeper
t
Observe the cochlear nerve fibers (CNF) traversing the positionedcellsofBoettcher (CB) and the lighter starn-
tunnels of the osseousspiral lamina (OL). The lateral
wall of the internal spiral sulcusis formed by the single
row of inner hair cells (IH), flanked by the inner pha-
ing, larger cells of Claudius (CC), which enclosethe
outer spiral sulcus (OSS). Note that the space above
the spiral organ of Corti is the cochlear duct (CD),
I
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internal spiral sulcusis formed by inner sulcuscells(IC). tvmpani.
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CB
CC
cellsof Boettcher
cells of Claudius
rTc innertunnelof Corti
NF nervefibers
SL
SN
spiralligament
spacesof Nuel
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CH
CNF
cells of Hensen
cochlearnervefibers
OL osseousspirallamina
oPc outerpillarcells
TM
VL
tectorialmembrane
vestibularlip I
lC innersulcuscells oPh outer phalangealcells ZA zona arcuata
lH
IPC
innerhaircells
inneroillarcells
OSS outerspiralsulcus ZP zona pectinata
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406 ffi SpecialSenses I
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 IIITT

Index

In this index, page numbers in italic designate figures; page numbers followed by the letter "t" designate tables; (seealso) cross-
referencesdesignaterelated topics or more detailed subtopic lists.

Adipoqtes (fat cells), 46,53, 56-57,63

*A Adipose (fat) cells,404 1, 49, 63, 298-299
, 0 5 ,1 0 7 ,1 0 8 ,1 1 0 - 1 1 11, 1 2 - 1 1 3 ,1 1 4 - 1 1 6
A b a n d s ,1 0 3 - 1 0 4 1 tracheal, 246-247
ABP ( androgen-bindingprotein), 369 Adiposetissue,46, 48,49, 56-57, 182-183,210-211
Absorption, 27, 280-281 rongue,270-271
Acceleration sense Adrenaline(epinephrine),I 95
linear, 390 Adrenocorticotropin(ACTH), 194
rotational, 390 Adventitia
Accessoryglands, male reproductive, 373-374 alimentary canal,277
Accommodation,visual,389,391 bladder, 329,340-j41
A cells(ofpancreaticislets),32I esophagus,282, 288-289
Acetylcholine, 104, 126, 127 gallbladder,30T
Acetylcholine receptors, 127 seminal vesicles,373-374
Acetylcholineste r ase, 127 trachea, 239
Acetylcholine transferase,127 veter,340-341
Acid vagina,348, 364-365
1-aminobutyric (GABA), 128 Afferent glomerular arterioles,3J0, 33 l, 332-333, 334-335
hexuronic,47 Afferent lyrnph vessels,171, 182-183
hyaluronic, 45, 47, 68 Afferent terminals, I 36-137
Acidophilic cells,195 primary, 136-137
Acidophils, 194, 204-205, 206-207, 2 14 A$anulocltes, 89, 90t, 93
Acinus (acini), .12-13 Albumins,89
m u c o u s ,3 1 , 3 1 0 - 3 1 1 Aldosterone, 196, 197, 325
ofRappaport (liver acinus),306 Aldosteronereceptors,325
serous,31, 310-i1 1, 40H01 Alimentary canal (seealso individual structures)
sublingualgland, 310-31I appendix,283
Acrosomal granule, 370, 377 clinical considerations,28 I
Acrosomal phase,of spermiogenesis,377 digestionand absorption,280-281
ACTH (adrenocorticotropin), 194 gut-associatedlymphoid tissue (GALT), 280
Actin, 105 histolo gical orga nization, 282-28 4
Actin (thin) filaments, 3 histophysiology, 279-281
Action potential,127 intestines
Active transport, 128 lar ge,278, 284-285, 286
Activin, 345 small, 277, 279, 283, 285
Acuity, visual, 389 layersof wall,277
Acute glomerulonephritis, 327 regions,278
Acute renal failure, 327 All-or-none response,127
Addison's disease,198 Alpha-actinin,103,105
Adenosine triphosphate (seeATP) Alpha chains,47
Adenylate cyclase,196,237, 369 Alpha-fetoprotein test, 372
ADH (antidiuretichormone, vasopressin),194,326 Alveolar bone, 257,258, 260, 274-275
Adherens |unction, 120- 12 1 Alveolar capillary network, 242

Index I 409
flJveolar cr est, 266- 267
Alveolar ducrs, 240,243, 252-253
Alveolarelastinnetwork,242
Alveolar mucosa, d,ental,266-267
Alveolarpores,240,24i
Alveolar sac,236,240, 252-253
Alveolus (aIveoli), 252-2 53, 254
dental (seeAlveolarbone)
lung,240, 242,252-253
mammary gland,366-367
Amacrine cells,392
Ameloblasts,256,257, 268-269
Amorphous ground substance, 45
Ampulla (ampullae)
of ductus deferens,376
of ear,390
of oviduct, 343,347-348
of semicircularcanal,393,402403
uterine,350
Amylases,280
Anal canal, 284-285, 298-299
Anal valves,285
Anamnesticresponse,170,178
Anaphase,l6-17
Anaphylacticreaction,46
Anastomoses, arteriovenous,148, 149
Androgen-bindingprotein (ABP), 369,371
Androgen-producingcells,369
Androgens,195,197,345
A n e u r y s m ,1 5 2
Angiotensin-convertingenzyme(ACE), 326
AngiotensinI and Il, 326
Angiotensinogen, 325-326
Anorectal junction, 298-299
Anterior chamber, of eye,j96-397
Antibodies,168
Antibody-dependent cell-mediatedqtotoxicity (ADCC), 92, t70
Antidiuretic hormone (ADH, vasopressin),194,326
Antidromic spread,,127
Antigen-presentingcells(APCs), 168, 170,178,179
Antrgens
prostatespecific(PSA),372
thymic-dependent,170
Antimiillerian hormone, 37I
Anus,326
Aorta, elasticlaminae, 58-59
APCs (antigen-presenting cells),170,179
Apical foramen,260
Apocrine secretion,29
Apocrine sweatglands,224, 225, 230-2i1
areolar,348
Apparatus
Golgi (seeGolgi apparatus)
juxtaglomerular, 324, 325-326,334-335
Appendix, 283,298-299
Appositional growth, 70
APUD (enteroendocrine) cells,279, 294-295, 296-297,
298-299,304
Aqueous humor, 384, 387, 389
Aqueoushumor-forming ciliary processes,
Arachnoid, 125,129,134-135
Arborization,dendritic, I 29
Arcuateveins,323
4l 0 s Index
Arcuate vessel,332-333
Area cribosa,323,328
Areola, 344, 348, 366-367
Areolar apocrineglands,348
Areolar (loose) connective tissue, 46, 49, 54-55
Arrector pili mtscle,222, 228-229, 2iO-2i1, 232-233
Arterial lumen, 156
Arteriolae rectae spuriae,j 3 8-3j9
Arterioles, 148, 149, 160- 161
glomerular
afferent,323,330, 331,332-333,334-335
efferent, 330, 331, 334-335
pulp, 168
sheathed,168
splenic,190-191
terminal, 148
testicular, 378-i79
Arteriovenous anastomoses,148, 149
Artery (arteries),148,154
centrallymphatic, 168
elastic,148, 149,153,156-157
helical,362-363
helicine(coiled),345,372
hepatic,314-j15
histophysiology of, 149- I 50
interlobular,323,332-333
muscular,148,149,153,154, 1 58-159
penicillar,168
pulmonary,242
splenic, 190-191
Ascendingcolon,278, 286
A site,9
Asthma, bronchial,237-238
Astrocltes, 126, I 36-1 37
fibrous, 136-1 37, 138- 139
Atherosclerosis, 152
ATP, I, los
ATPase,105
Atretic follicles,347
Atrioventricular(AV) node, 1,47-148,149
Atrophy
of corpusluteum, 345
follicular, 347
Auditory meatus(canal),external,387,395
Auditory ossicles,388, 395, 402-403
Auditory (eustachian)tube, 388,395
Auerbach's myenteric plexus, 282, 294-295
Auricle, 387,395
Autonomic nervoussystem,125
Autophagolysosomes, 2
Avascularity,2T
AV (atrioventricular)node, 147-148, 149
Axial space,I .lZ
Axolemma, 144-145
A x o n e m e ,3 , 2 7
Axon hillock, of soma, 129
Axons, 114-116,125-126,129,131,136-137
myelinated, 132
391 nonmyelinated,1 14-116
peripheral newe, 142- 143, 144-1 45
sensoryganglionic,140-14'
Azurophilic granules,91, 93
SB
Bag, nuclear, 117
BALT (bronchiolar-associatedlymphoid tissue), 775
Band (stab)cells,90,94,97, 101
Bands
A , 1 0 5 ,1 0 7 ,1 0 8 ,1 1 0 - 1 1 11, 1 2 - 1 1 3 1, 1 4 - 11 6
H, 108
I , r 0 5 , 1 0 7 ,1 0 8 ,1 1 0 - 1 1 11, 1 2 - 1 1 3 ,1 1 4 - 1 1 6
M, 108
Barrier
blood-air, 240, 243, 254
blood-brain, 128
blood-testis,369
blood-thymus, 168-169
filtration, 325, 330, 331
Basalbodies,27
Basalcell carcinoma, skin, 220
Basalcells, 14-15, 230-231
ductus epididl'rnis, 382-3 83
olfactory, 235,244-245
palate,272-273
prostate gland, 384-385
Basal(basement)lamina, 25,27, 45, 131
capillary, 148
peripheralnerve,144-145
veter,340-j41
Basal layer, uterine, 360-36 1
Basalmembrane, I O-I 1, 25, 27, 4H 1, 46, 58-59, 221
gallbladder,j16-j17
ovary,352-353, 354-355
oviduct, 358-359
spleen,I90-l9i
Basalregion, 88
Base(fundus), of stornach,292-293
Basementmembrane,27, 46
epidermis,22l
splenic, .190-l9l
Basilar membrane, 388, 392, 395
cochlear,404405
organ of Corti, 406407
Basket(myoepithelial) cells, 29, 1 36-137
Basophilic erythroblasts, 90, 93, 97
Basophilicmetamyelocytes,
Basophilic myelo cytes,97
Basophils,53, 89, 90t, 93, 95-97, 97, 194,206-207
pittitary, 204-205
B cells
immune system (seeB lymphocytes and specilictypes)
pancreatic islets,321
Beds
capillary,147,155
nat\ zJz-zJJ
Bellini, ducts of, 324, 328
Benign prostatic hlpertrophy (BPH), 372
Bertin, renal columns of, 323
B i l e ,3 0 3 , 3 0 4 , 3 0 5
Bile canaliculi, 309 (seealso Microvilli)
Bile ducts, 306,309,314-315
Bile ductules, 306
Biliary calculi (gallstones),305
Bilirubin,304
Bilirubin gluconuronide, 304
Billroth, pulp cords of, 168
Binaryfission,I
Bipolar neurons,125
Bladder, urinary (seeUrinary bladder)
Blind spot,389
Blisters,fever, 256
Blood, 89-105
clinical considerations,92
formed elementsof, 89, 90t (seeako specifictypes)
histological organization, 93
histophysiology, 91-92
plasma,89
in urine (hematuria),327
Blood-air barrier,240,243,254
Blood-brain barrier, 128
therapeutic circumvention of, 128
Blood cells
splenic,190-191
types, 89, 90t (seealsospecifictypes)
Blood circulation, 147-165
heart, 147-148
histological organization, I43-I54
histopathology,149-150
vascular system, 137
Blood smear,98-99
Blood-testis barriers, 369
Blood-thymusbarrier, I 68-169
Blood vessels
bone,72
bronchi,250-251
cardiac muscle, 122-123
cerebral,l3A-139
connective tissue,56-57
cotnea,396-i97
ductus (vas) deferens,382-383
duodentm, 294-295
epithelial lymph node, l7l
esophagus,288-289
eye,396-j97
ganglia,140-141
gingiva,266-267
kidney,334-3j5
lar ge intestine, 298- 299
97 lips,262-263
lung,252-253
male reproductive system,384-385
olfactory mucosa,244-245
ovary,356-357
oviduct,358-359
palate,272-273
pancreas,312-313
peripheral nerve, 142-143
pituitary gland, 206- 207
salivary gland, j10-j11
skln, 226-227, 228-229
small intestine, 296-297
smooth muscle,118-119
spinalcord, 131,134-135
stomach, 290-29 1, 292-29 3
suprarenalgland,2 1U21 1, 2 12-213
testis, 378-379, 380-3 I I
thymus, I88-189
thyroid gland,208-209

Index t 41 1
Blood vessels(contittned) Branchedalveolarholocrineglands,221
tongne.270-271 B r i d g e si,n t e r c e l l d a r ,1 4 - 1 5 ,2 2 ' l , 3 7 ' l ,3 7 7
tonsils, /84-185 Broad ligament, 350, 356-357
trachea,246-247 Bronchialasthma,237-238
uterus,J60-361 Bronchioconstri ction, 237-238
vagina, j64-365 Bronchiolar-associated lymphoid tissue(BALT), J75
B lymphoc).tes,167-168,171,175 Bronchioles, 236, 239, 242, 250-2 5 I
m e m o r y ,1 7 l , 1 7 7 respiratory, 236,239, 242, 243, 250-251, 252-253
Body (bodies) terminal, 236,239,242,250-251
oasat,t/ Bronchus (bronchi), 248-249, 250-251
Call-Exner,347 extrapulmonary, 239
cell,294-295 intrapulmonary,236, 239,242,25O-25I
ciliary, 384, 387,391, 396-397 Brunner's (duodenal) glands, 278, 280,285, 294-295
dense,120-121 Brushborder, 12-13, 14-15,25,27 (seealsoMicrovilli)
denseepididymal,386 duodenum, 294-295
erectte,S/t-J/z n e p h r o n ,3 2 4
filamentous,3l8-319 Buds
Herring, 194,206-207 alveolar,366-367
lamellar,243 dental,268-269
Nissl, .12-.13, 132,134-135 periosteal,67, 73
pineal, 195,197,200,202,212-213 Bulb
residual,2, 4, 8 hair,221, 228-229
vitreous,384,387 penile, j76
Boettcher, cellsof , 406-407 Bulbourethral(Couper's) glands,372, 374,376
Bonds,peptide,4, 9 Bullous pemphigoid,28
Bone,65-67 B u n d l eo f H i s , 1 4 9
cancellous,66, 72 Bundles,collagenfiber, 49, 272-273,274-275
cellsoi 68
c l i n i c a lc o n s i d e r a t i o n6s 9,
@C
compact,66,72
decalcifiedcancellous,7l Ca2*-calmodulincomplex, 106
decalcified compact,70, 7 \, 78-79 Calcitonin, 68, 192, 196,202
formation of (osteogenesis) (secOsteogenesis) Calcium channels,105, 127
histophysiology,68 Calcium hydroryapatite,66, 68
mature, 67 Calcium pump, 105
Paget'sdiseaseof, 69 Calculi
undecalcifiedcompactground, 7l biliary (gallstones),305
undecalcified ground, 80-81 kidney (nephrolithiasis),327
w o v e n( p r i m a r y ) , 6 7 Call-Exnerbodies,347
Bone collar, subperiosteal,
71, 73, 84-85 C a l m o d u l i n ,1 0 5
Bone marrow, 66,82-83, 98-99 Calpr (calyces),renal,324, 328
red, 90 c A M P ,4 8 , 1 9 6
yellorv,90 Canaliculus(canaliculi),66, 71, 80-81
Bone marrorv smear,98-99,100,101 6ile,309
Bone matrix,66, 68 intercellular,222
Bone morphogenicprotein-4, 256 intracellular,279
Bony cochlea,388, 395, 402403, 404405 Canals
Bony crypt,268-269 anal,284-285,298-299
Bony epiphysis,67 centralof spinal cord, 134-135
Bony labyrinth, 390 cervical,.150
Rony shelf,271-275 haversian, 66, 72, 78--79,8O-8I
Bony subperiostealcollar,67 of Hering, 306
Border semicircular,388, 190,393,39.5
brush (seeBrush border; Microvilli) Volkmann's, 66, 7 1, 72, 78-79
ruffled, 88 Cancellousbone, 66, 72
Rorder cells, 406 407 Cancer
Borvman'scapsulc,323, 328,i3l, 337 cervical,346
Borvman's glands,214-245 endometrial,346
Borvman'smembrarre,391,i96-397 kidney, 327
Bou'man's ( urinrrv) space,324, 328,331, j 32 333, 3j4-3 35, 3 3 7 prostate,372
Bradvkinin,150 skin, 220
Brain sand (corporaarenacea),195,200,2 12 -'2I i testicular,372

412 t Index
 Capillaries,148, 150, 153,155,t6O-i6t hyaline,65, 661,68, 70, 74-75, 86,235,239,246-247
cerebral, 138-139 laryngeal, 244-245
contrnuous,148, 150,155 t'?es,65,66t
discontinuous,148 Cartilage degeneration,69
ductus (vas) deferens, 382-383 Cartilagematrix, 65, 68, 70
fenestrated,148, 150,.155 Catalase,2
wng, zJz-z5J Cataract,390
lgnphatic, 148 Catecholamines, 196
metabolicfunctions oi 150 uaveon, tztFtzt
peripheral nerve, 142-i43 Cavernous (spongy) or ethra, 374
slnusorqal,t5u, I55 Cavity
skeletalmuscle, I l0-l I I infraglottic, 235, 239, 244-245
smooth muscle,I t9-t 19,120-12j marrow,72
suprarenai gland, 2 12-2 13 medullary,84-85
terminal arterial,i68 nasal,239,244-245
vaginal,364-365 oral, 255-27 5, 260, 261
Capillarybeds,147,155 tnoractc, 2J /
Capillary loops, 221,226-227, 228-229 tympanic, 388,395
Capillary network CD (cluster of differentia tion ) molecules,92, 170
peritubular, 323,331 Cecnm,278,286
renal,332-333 Cell body
Capillary permeabiliry, 150 multipolar (motor), 129
Capsular vessel,332-333 neuron, 125-126
Capsule postganglionic, 294-295
Bowman's,323,328, 331,337 Cell cycle,3
connective tissue,40-41 Cell-mediated immune response, 167, 170
ganglionic,140-141 Cell nests,68
Glisson's,306,3I 4-3 I 5 Cells, 1-24
tnner, I I / acidophilic,195
lens,40U40I adipose (fat), 40-41, 49,246-247, 29A-299
lyrnph node, 167,I73, 175,182-t83, t86-187 amacrine,392
ocriar,396-397 androgen-producing,369
otter, I 17 antigen-presenting (APCs), 168,170, 178,179
pacinian corpuscle,232-2 33 B, 167-168(seealsoB lymphoctes)
pancreatic,306 basal(seeBasalcells)
parathlroid gland, t99 basket(myoepithelial),29, 136-137
prostate gland,374 blood (seeBlood cellsand specifictypes)
renal,323,332-333 B memory, 17I, 177
splenic,174 of Boettcher, 406407
suprarenalgland,210-2I j bone, 68, 70
resilcular,J/J border,406407
thymic, 174, 188-189 cardiacmuscle,107
thyroid,, 199, 208-209 cartilage,70
tonsillar, 173, 184-185 centroacinar,304,308,312-313
Carbaminohemo globin, 237 chief (seeChief cells)
Carbohydrates,digestion and absorption, 290 chondrogenic,65
Carbonic anhydrase,237 chromaffin, 195,212-21 3
Carcinoma ciliated' 14-15
basalcell, 220 columnar tracheal,248-249
squamous cell,220 epididymal,3S6
Cardia, 278, 285, 2 88-289 ovlouctal,J5d-J5y
Cardiacgland,277,279 Clara, 236, 239,250-2 5 1, 252-2 53
Cardiacmuscle,104,107,109,122-i24, 162-i65 of Claudius, 392, 406407
Cardiac muscle ftbers, 122-j23, 124 clear,225,234
Cartilage,65-88 clinical considerations,5
clinical considerations,69 columnar, 294-2 95, 300, 3I 4- 385
ofear,388,395 terine, i62-363
elastic,65, 66t, 68,70, 76-77 connective tissue,46, 49-50, 5j, 110-11I
ernbryonic,70 contractile,46
fibrocartilage, 65, 66t, 68, 70 cytoplasm, L-3, 6, 10-l 1, 20-21, 22
histological organization of, 70 dark,225, 234, 272-273
histophysiology ol 68 decidual, 364-365

Index & 413

Cells (continued) organ of Corti, 406407
diffuseneuroendocrinesystem(DES),278,285 osteoprogenitor,66, 68,7 |
dome-shaped,340-341 Paneth, 278, 279, 285, 294-295, 296-297
dust,240,243,252-253 p ar af ollicular, 208- 209
endothelial,182-183,184-185,190-191 parietal, 279, 290-29 1, 292-293
enteroendocrine (APUD), 278,279, 285, 294-295, 296-297, peg, 14-15,358-359
298-299,304 phalangeal,392
ependymal, 129, 130 inner,406407
epithelial,J2-13 ofier,406-407
fat,46,63 pigment, 396-397
fat-storing (Ito), 304, 309 pillar,392
fibroblast,46, 49,50, 53-55,60, 130,156-157 inner,406-407
of fibrocartilage,70 ofier,406407
follicular, 192,202, 205-209, 352-353 plasma,46, 53, 58-59,92, 16U161, 167, 168, 17l, 177,
folliculostellate,2i5 18o- I 81, 184-185, 244-245, 296-297
G,30s pluripotential, 46
ofgastric glands,282 polar, ofspiral ganglion,390
goblet, 12- 13, 14- 15, 32-3i, 404 1, 160- 161, I 80- I I 1, 235, precursor,9l
239, 246-247, 248-249, 278,279, 28s, 294-295, prickle,22I
296-297,298-299 progenitor,91
Golgi qpe 11,136-137 protein synthesisand exocltosis, 4-5
granule, 136- 1j7, 138- I 39 pseudounipolar,130
granulosa,345 Purkinje, 1O-11, I29, 136-137
granulosalutein, 347,354-3 55,356-357 pyramidal, 129, I 38-139
hair, 388, 390,392,395,402403, 40H07 red blood,53
of Hensen,392,40H07 regenerative, 278,279,286
histophysiology of, 4-5 reticular, 49, 54-55, 167-168, 168, 188-189
horizontal,129 satellite,107,1 10-111
immature,292-293 Schwann, 114- 116, 1,26,130, 1i 1, 140-I 41, 142- 14i, 144- 145
of immune system, 170-171 (seealsospecifictypes) sebaceous,225
inner nerve, 406407 serous,31, 318-319
intercalatedduct, 3l Sertoli, 369, 370, 378-379
intraglomerularmesangial,324, 325 sinusoidallining,306, 309,3 16-317,320
inverted (Martinotti), 129 smooth muscle, 107, 118- 119, 156, 1 58- 159, I 6O-161
juxtaglomerular, 324, 328, 331, 334-3 35 s t a b( b a n d ) , 9 4
Kupffer, 58-59,304,306,309,i16-317 stellate (granule), 129, 1i6-1 37
Langerhans,218,221,224 stem (seeStem cells)
Leydig,373, 380-381 striatedduct, 3.1
light,272-273 supporting,l40-141
lymphocytic, 92 (seealso Lymphocytes) surfaceabsorptive, 278,279, 286, 294-295
lymphoid, 54-5 5, 294-295, 298-299 surfaceepithelial, 298-299
M (microfold), 278, 280,285 surfacelining, 279, 290-29 1, 292-293
mast,12-13,46,49, 53,54-55, 58-59,61, 160-161 surfacemodifications, I 4-1 5
degranulation, 62 sustentacular,244-245, 261, 402403
membranes and membrane trafficking, 4 T (seealsoT lymphocltes)
memory, 167 null, 167
Merkel,22l,224 raste,261
mesangial,334-335, 337 testicular interstitial, 380-381
mesenchymal, 49, 66, 268-269 thecalutein, 354-J55,356-357
mesothelial,53 T helper, 167,170
mucous, 3 1, 292-293, 3 18-3 19 T killer (cltotoxic),167,170, 178
mucous neck, 279, 292-293 T memory, 170,178
Miiller's (supportive), 39I T suppressor,167,I70, 178
myoepithelial, 31, 225, 230-23 1, 3 18-3 l9 qpical,18-19
myo\d,,j78-379 vascularendothelial,148
natural killer (NK), 92, 170 zygogenic,278,285
neuroglial, 1,95,200, 2 12-2 13 Cellularly-mediatedimmune response,92
nucleus,3,20-21, 22 Cpmpntncrdpc 767

null, 89, 90t,91 (seealsoLymphocltes) Cementoenameljunction, 264-265, 266-267

olfactory,235 Cementum, 257, 260, 264-265, 266-267, 274-275
olfactorysupporting,235 Center, germinal, 18O-1I 1
oligomucous,278,286 Central artery, splenic, 190-191
organelles,10-i.l Central canal, of spinal cord, 134-135

414 @ Index
 Centrallymphatic arteries,168 Ciliary glands,40M01
Central nervous system, 125 Ciliary muscles,389
Centralvein, 314-315 Ciliary processes,
391,396-397
Centrioles,6,7, 16-17 Ciliated cells, .14-.15
Centroacinar cells, 304, 308,312-3 I 3 epididymal,386
Cerebellar island, 136- 137 Circuit, pulmonary, 148,149
Cerebeflum,129,136-137 Circular muscles,290-291, 294-295, 296-297, 298-299,
cortex,129
340-341, 356-357, 3s8-3s9, 360-361, 364-36s
medullary substance,129
Circulatory system
Cerebralcortex, 129
blood, 147-165 (seealsoBlood)
Cerebrospinalfluid (CSF), 125,130
tymph, 148, 153, 160-161
Cerebrum, 129,138-139
Circurnanal glands, 285
Cervical canal,350
Circumferential lamellae, 66
Cervical cancer,346
Circumvallate pap illae, 258,270-2 71, 272-2 73
Cervix,344, 350
Cisterna(cisternae),23
CFU-E,90
cereDellar,15o-tJ/
CFU-Ly,90,91
in synapticterminal, 136-137
CFU-S,90,9l
cGMP, 196 terminal, 108
Chamber Clara cells,236,239,250-251,252-253
antelor,396-397 Clathrin-coatedvesicles,2, 4, 8
posterior, 396-397 Claudius, cells of, 392, 406407
pulp, 264-265, 266-267 Clear cells,225
Channels sweatgland, 234
calcium, 105 Clearzone,osteoclast, 88
thoroughfare, 1,48, I49 Cleft
Chemotaxis,167 intr aglan dtlar, 204- 205
Chief cells, 14-15, 195, 199, 208-209, 382-383 synaptic, 104
epididymal,3S6 Clinical considerations
stomach, 290-29 1, 292-29 3 alimentarycanal,281
zygogenic,278, 279, 285 blood,92
Chloride pump,326 bone,69
Cholangioles,306 cartilage,69
Cholecystokinin(CCK), 278,280t, 303 connectivetissue,48
Cholesterol,1,2, 305 digestiveglands, 305
Chondroblasts,53,65 ear,390
Chondrocltes, 53,65, 68, 70 endocrinesystem,198
Chondrocltic death,7l epithelium,28
Chondrogeniccells,65 eye,390
Chondrogeniclayer,of cartilage,65 female reproductive tract, 346
Chondroitin 4-sulfate, 45, 68
heart, 152
Chondroitin-6-sulfate,68
hemopoiesis,92
Chorionic plate, 348, 351
integument,220
Chorionic villi, anchoring, 364-365
lymphoid tissue,172
Choroid, 384,387, 398-399,400-40i
muscle,106
Choroid membrane,391
nervetissue,128
Choroid plexus,130,142-143
oral region,256
connective tissue,142-143
respiratory tract, 237-238
epithelium, 142-143
urinary system,327
Chromaffin cells,195, 2 I 2-2 13
vascularsystem,152
Chromatin,22
nucleolus-associated, 18- 19 Clone,cell, i70
Chromophils, 194,204-205 Clusterof differentiation(CD) molecules,92,170
Chromophobes, 194,204-205, 206-207, 2i 4 Coagulation,9l
Chromosomes,3, 16-17 Cochlea, 392-393
Chylomicrons,278,28I bony, 388, 395,402403, 404405
Chyme,277,279,281 Cochlear duct, 388, 390, 392-393, 395,402403, 404405,
Cigarette smoke, 238 406407
Cllia, 14-15, 25,27 , 32-33 Locnlear nerves,JUd,Jy)
olfactory, 244-245 C o d o n ,s t a r t , 4 ,9
tracheal, 248-249 Collagen, 46, 47, 52, 66
Ciliary body, 384,387,39 t , 396-i97 ocriar,396-i97
Ciliary epithelium,391 Collagen fiber bundles, 49,272-273, 274-275

Indexg 4l5
Collagen fibers, 45, 49, 54- 55, 58-59, 86, 156- 157, 158- 159,
210-21I
gingival, 266-267
skin,22l, 228-229
Collagen fibrtls, 56-57, 60
Collagenousconnectivetissue,I 53, .16G-.1
Collagensynthesis,46, 47
Collar, bony subperiosteal, 67
Collectingducts,324,326
Collectingtubul es,323.330
Colloid
pituitary gland, 206-207
thyroid gland, 208-209
Colloid osmotic pressure,325
Colon, 278, 286, 298-299, 300, 301, 376
Colony-forming unit-lymphoqte (CFU-Ly), 90
Colony-forming unit-spleen (CFU-S),90
Colony-stimulatingfactors(CSFs),9l-92
Colostrum,346
Columnar cells,294-295, i00
prostate gland,,j 84-j8 5
Columnar epithelium, 25, 26t, 3 1
pseudostratified,32-33
pseudostratified crliated,36- 37
Columns, neural, 126
Commissure,gray,129,134- 135
Common hepaticduct, 306
Compact bone, 66, 72, 78-79
Compartment
posterior, 398-399
of seminiferoustubules,371, 373,378-379
Complexes
Golgi (seeGolgi apparatus)
junclional,2T , 30
nuclearpore, 3
Concentration,of urine, 326
Concentrationgradient,osmotic,326
Concretions,prostatic,374, 384-385
Condensing vesicles,22
Conductivehearingloss,390
Cones(seeRodsand cones)
Conjunctiva,389,392
palpebral, 400401
Connective tissue, 12-1 3, 45-64
cells,46,53
choroid plexus,142-143
clinical considerations,48
collagenous,153,160-161
denseirregular, 46, 50
denseregular, 46
collagenous,50,56-57
elastic,50,58-59
dermis,2l9,22l
duodenum, 294-295
embryonic,80-81
endoneural,144-145
esophageal,288-289
extracellular matrix, 45-46
gallbladder,316-317
heart,162-165
histologicalorganization,49-50
connectivetissueproper, 49-50
embryonic tissue,49
histopathology, 47-48
lacrimal gland,40H01
lips,262-26j
loose(areolar),46, 49,54-55
lymphatic, 180-i8l
6/ mammary gland, 366-367
mesenchymal, 46, 49, 54-55
mucous, 46,49,54-55
olfactory, 244-245
ovarian, 354-355
oviduct, 358-359
palate,272-27 3, 274-27 5
parathyroid gland,208-209
reticular, 46,54-55
salivaryglands,310-i1 1
seminal vesicle,382-383
skeletalmuscle,I i0-I1.1
smooth muscle, 118-119
stomach, 290-291, 292-293
subendothelial, 153
suprarenalgland,2 10-211
testicular, 378-379, 380-38I
thymic, 174
tongue,270-271
tonsillar, 184-185
types,46
urethra,384-385
Connective tissuecapsules,40--4i
Connectivetissueelements,I0-l i
Connectivetissuesepta,pancreatic,312-313
Connective tissue sheath,hair follicle, 230-231
Constituted secretion, I
Continuous capillaries,148, 150,155
Contractilecells,46
Contraction,muscle,106
Convoluted tubules, 330
distal,334-335
proxima[, 332-333, 334-335
Cords
medullarylyrnph node, 171, 182-183,184-185
pulp (of Billroth), 168, 190-191
Cornea, 384, 387,389, 39I, 396-397
Corneal blood vessels,396-397
Corneosclerallayer (fibrous tunic), ofeye, 384,387
Corona
lymphatic, .18&-l8l
lymph node, 182-183
lymphoid nodules,167
splenic,190-.191
Corona radiata, 343,350, 354-355
Corpora arenacea(brain sand), 195,200,2 12-2 13
Corpus albicans,347, 356-357
Corpus carvernosum urethrae, 374
Corpus cavernoslum, 372,374, 376, 384-385
Corpuscles
Meissner's,221,224, 2i2-23 3
pacinian, 221,,224, 232-2 33
rcnal,323,331,337
thymic (Hassall's),168, 174, 188-189
Corpus hemorrh agicum, 347
Corpus luteum, 343, 345,347, i54-355, 356-357
Corpus spongioslum,374, 376, i 84-385
Cortex Decidual cells,364- 365
cerebral,129 Degeneration,cartilage,69
hair,221, 230-231 Degranulation, mast cell, 62
lymph node, 173, 182-183 Demilune,serous,3i, 160-161,310-311
ovarian, 3 43, 347, 352-3 53 Dendrites,1O-11,125-126,\29, 136-137,146
renal, 323, 328, 3 30,332-3 33, 334-3 35 cereDellar,1J6-tJ/
suprarenalgland, I95, 197,200,210-211, 212-213 Dendritic arbori zation, 129
thymic, 172, 174, I 88- I 89 Dendritic tree, I 36-l 37
Corti Densebodies,120-121,i86
spiral organ of, 388, 390, 392,395,402403,404405,406407 Denseirregular connective tissue,46, 50
tunnel of, 392,406407 Dense regular connective tissue, 46,50, 56-57
Cortical labyrinth, 328 Dental lamina, 258,260, 268-269
Corticotropin, 345 D ental p apillae, 268- 269
Countercurrent exchangesystem,of urine concentration, 326 Dental sac,268-269
Countercurrentmultiplier system,of urine concentration,326 Dentin,257 , 260, 264-265, 266-267, 268-269, 274-275
Cowper's(bulbourethral)glands,370, 372, 374,376 Dentinal tubules,257 , 264-265, 266-267
C proteins, 104 Dentin matrix, 268-269
Crest, alveolar, 266-267 Dentinoenamel junction, 264-265, 266-267
C rings, hyaline c artilage,239,246-247 Depolarization,127,237
Crista (cristae),2O-21,24 Dermal papillae (dermal ridges), 217, 228-229
of semicircular canal, 393 Dermatansulfate,45
Cristaampullaris,388, 390, 395,40240i Dermis,2lT , 224, 226-227, 228-229
Crohn's disease, 281 lips,262-263
Cross-banding,103 Descemet'smembrane,391
Cryptorchidism, 372 Descendingcolon,278, 286
Crypts Desmin, 106
bony,268-269 Desmosine,4T
of Lieberkrihn, 278, 279, 283, 285, 286, 294-295, 296-297, Desmosomes,2T
298-299,300 Detachedretina, 390
tonsillar, 173, 184-185 Detoxification, 2, 304
C S F( c e r e b r o s p i n a
f llu i d ) , 1 2 5 Diabetesinsipidus,327
CSFs(colony-stimulatingfactors),9 l-92 Diabetesmelllitus
Cuboidal epithelium,25, 26t, 3 1 t y p eI , 3 0 5
Cumulus oophorus,343, 350,354-355 t)?e II, 305
Cupula, 388, 390,393,395,402403 Diapedesis,150
Cuticle Diaphragm,237
hair,221,225 Diaphysis, 67, 82-83
nail (eponychium), 218, 222, 225, 232-233 Diftusefymphoid tissue,167,175
Cyclic adenosinemonophosphate(cAMP), 196 Diffuse neuroendocrinesystem(DES) cells,278,285
Cyclic guanosinemonophosphate(cGMP), 196 Diffusion
Cyclins, 3 facilitated,4,128
Cytokines, 167 simple,4
Cytoplasm, l-3, 6, 20-21, 22 Digestion,280-28I
adipocytes,56-57 intracellular, 2
muscle,103 Digestive system (seedlso individual components)
Schwanncell,144-145 alimentary canal, 277-301
suprarenal gland, 2 12-2 13 clinical considerations,305
Cytoplasmic densities, 106 glands, 303-321 (seealso individual glands)
Cytoplasmic inclusions, 3 oral region,255-275,260,261
Cytoskeleton, 2-3 Dihydropl,ridine-sensitive receptors(DHSRs), I05
Cytotoxicity,antibody-dependentcell-mediated(ADCC), 170 Dipeptidases, 279,280
Cytotrophoblasts, 348 Dipeptides,4,9
Disaccharidases, 279
@D Disaccharides, 280
Discontinuouscapillaries,148
D-amino acid oxidase,2 Discs
Dark cells,225,234, 272-273 intercalated,107, 109,I 22-123, 124
D cells (ofpancreatic islets),321 intewertebral, 76-77
Deactivation,capillary,150 M,103,112-113
Deafness,nerve, 390 z , r o 4 , r 0 5 , 1 1 0 - 1 1 1 1, 1 2 - 1 1 31, 2 4
Decalcified compact bone, 70, 7 l, 78-79 Disse,spaceof,306, 309,320
Deciduabasalis,348,351,364-365 Distal convoluted tubules, 324,325, 328, 3i0, 332-333, 334-335

lndex & 417

Distal phalanx, 232-233 Earlyendosomes,2, 4
Distendedtransitionalepithelium,3i Eccrine sweat glands,4041, 224, 225, 230-231
Edema,48
DNES (diffuseneuroendocrinesystem)cells,278,285 Efferent glomerular arterioles, 330, 331, 334-335
Docking protein, l, 5 Efferent lymph vessels,l7l
Domains Ejaculation,37l-372, 372
of cartilage,68 Ejaculatoryduct, 369,374, 376
electrochemical, 47 Elasticarteries,I48,149, I53, 156-157
Dome-shaped ce\Is,340-34 1 Elasticcartilage,65, 66t, 68, 70,76-77
Dopamine, 128 Elasticfibers,45,47,50, 58-59,68, 156-157, 237
Dorsal root ganglion,130 Elasticlaminae,5S-59
Dorsalhorns, 129,134-135 Elastic rnembranes,58-59
Elastin,45, 47, 242
Dorsal roots, 134-135
Electrochemicaldomains,47
Droplets,lipid, 320
Electron transport chain, I
Duchenne'smusculardystrophy,106
Eleidin,219,221
Ducts
Elementaryparticles,I, Z
alveolar, 240, 243, 252-253
Embryonic cartilage,70
of Bellini, 324, 328
Embryonic connective tissue,80-81
b i l e , 3 0 6 ,i 0 9 , 3 1 4 - 3 1 5
Embryonic hyaline cartllage, 74-7 5
of circumvallate paplllae,272-273
Emphysema,237
cochlear, 388, 390, 392-393,395, 402403, 404405, 406-407 Enamel, tooth,257, 260, 264-265, 268-269
c o l l e c t i n g3, 2 4 , 3 2 6 Enamel knot, 256
commonhepatic,306 Enamel space,266-267
dtodenal, 294-295 Enamel tufts, 264-265, 266-267
ejaculatory,369,374,376 Encapsulatedlymphoid tissue, 168
endolymphatic,390 End bulbs,Krause's,221
genital Endocardium, | 47-1 48, 162-1 65
female, 343-344, 347-348 Endochondralossification,66,67,7 I,73, 82-83, 84-85
male,369-370,373 Endocrine glands,25-26, 29
intercalated,31, 304,306,308 Endocrine pancreas(seeunder Pancreas)
interlobular, 306, 3 1O-311 Endocrinesystem,193-215(seealsoGlandsand individal
lactating,366-367 structures)
lactiferous,348 clinical considerations,198
mammary gland,366-367 histological organization, 199-200
renal papillary, 338-i39 histophysiology,196-198
salivary,31O-311 parathpoid gland, 19rt-195, 199,202,208-209
sebaceors, 226-227, 228-229, 230-23 1 pineal body (epiphysis),195,202
secretory,40-41 pituitary gland (hlpophysis), 193-194, 199, 201, 204-207
semicircular, 390 pituitary hormones,20i
striated,31, 304 suprarenalglands,195,199-200,202,210-211,212-213
sweat,56-57,222, 225, 232-233 thyroid gland, 192, 199,202, 208-209
terminal interalveolar, 346 Endoqtosis,219
vascular,160-161 receptor-mediated,l, 4, 8
Endolymph, 388,390,393
Ductules,bile, 306
Endolymphatic ducts, 390
Ductuli efferente s, 369-370,373,380-381
Endolymphatic sac,390
Ductus (vas)deferens,369-370,372,373,376,i82-383
Endolysosomes,4
Ductus epididymis,369-370, 373, 380-38 1, 382-383
Endometrialcancer,346
Duodenal (Brunner's)glands,278, 280,285,294-295
Endometriosis.346
Duodenum, 118-1 19,278, 279, 285,294-295
Endometrium, 344, 345, 3 48, 360-36I
Dura mater, I25, 134-135
Endomysium, 103, 107, 109,1 10-1I I
Dust cells, 240, 243, 252-253
Endoneural connective tissue,144-145
Dynein,3
Endoneurium, 126,130, 131
Dystrophy, Duchenne's muscular, 106 peripheral nene, 142-143
Endoplasmic reticulum Golgi intermediate compartment
@E (ERGIC),2,7
Endoplasmicreticulum, l-2
E a r ,3 8 7 - 3 8 8 , 3 9 5 rough (rER), l-26, 4, 6, 7, 18-19,
2o-21,36-37,60,86
clinicalconsiderations,390 144-145,248-249
external,392 smooth (sER), 2, 6, 7, 22, 304
histological organization, 392-393 Endosomes,2
histophysiology,389 early,4
inner, 388, 392-393-392-393, 395, 402403 late,4, I
middle,392 recycling,8

41 8 ffi Index
Endosteum,66, 70, 98-99 jtnctional, 266-267
Endothelia, 25 lar ge intestine, 298- 299
Endothelial cells, 182- I 83, I 84- I 85 laryngeal,239
splenic,190-l9l lens,392,400401
vascular,148 lyrnphatic, 180-.18J
Endothelial-derived relaxing factor (seeNitric oxide) mammary gland,366-367
Endothelial nucleus, I 22- 123 mesodermal,195
Endothelium, 160-J6.1 oral,268-269
heart,162-165 oviduct, i5g-359
vascular,l>J, t56-15y oviductal, 358-359
Entactin,46 palatal,274-275
Enteroendocrine (APUD) cells,279, 294-295, 296-297, parakeratotic, 257
298-299,304 pigment,391
Enzymes pigmented corneal, 396-397
angiotensin-converting (ACE), 326 pigmented ocular, 398-399,40H0 1
hydrolytic,2 pseudostratifiedciliated columnar, 36-37
lysosomal, 5 pseudostratified columr'at, 32-3 3
oxidativ€,2 respiratory tract, 235
stomach,278
retinal pigment, 389
Eosinophilic chemotactic agent, 46
seminal vesicle,373-374, 382-383
Eosinophilic me tamy elocltes, 97, 10I
seminiferous, 369, 37l, 373, 377, 378-379
Eosinophilic myelocytes,97, 101
simple columnar, 32-33, 58-59, 285-289, 298-299
Eosinophilicstab (band) cells,101
simple cuboidal, 32-33
Eosinophils, 49, 53, 89,90t,93,95-97, 97
simplesquamous,32-33
Ependymal cells, 129, 130
splenic, 190-191
Epicardium, 147-148
sguamous, 290-291
Epidermal ridges,221, 226-227
squamouscorneal, 396-397
Epidermis, 217-218, 221, 224, 226-227
stomach, 282, 290-291, 292-293
lips,262-263
stratified cuboidal, 34-35
mammary gland,366-367
stratified squamovs, 288-289, 298-299
thick skin, 226-227
stratified squamous
thin sl<rn,228-229
keratinized, 34-35
Epididymis, 373, 3 82-383, 386
nonkeratinized, 34-35
Epiglottis,76-77,261
sulcular, 266-267
Epimysium, 103, 109
suprarenal glands, I95
Epinephrine(adrenaline),I 95
rasteb\ds, 272-273
Epineurium, 126,.l3l
peripheral newe, 142-143 testicular, 380-381
Epiphysealossification center, thytoid,192,202
Ipiphyseal plate,7 1, 73, 82-83 tongue,270-271
Epiphyses,73,82-83 tonsillar, 173, 184-185
DOny,b/ tr acheal,246-247, 248-249
Epiphysis(pinealbody), 195, transitional,25,26t, 31,34-35
Episcleraltisssue,39A-397 bladder,324,340-341
Epithelial cells, l2-13 wes,29,31
Epithelial junction, 38-39 urethral,374
Epithelial membranes, classification,25, 26t vaginal, j64-365
Epithelium,25, 360-361 vascular, 160-161
bladder, l0-.ll Epitopes,92,170
bronchiolar, 239, 250-25 I Eponychium (cuticle),218,222,225,232-233
choroid plexus, I 42-143 Equilibrium, static, 390
ciliary,391 Erectilebodies,37I-372
clinical considerations,28 Erectile tissue,384-385
cochlear,404405 Erection,37l-372
cohtmnar, 290-291 ERGIC (endoplasmic reticulum Golgi intermediate
corneal,39I, 396-397 comPartment),2, 7
epididymal,3T3 Erythroblasts
esophageal, 277,282, 288-289 basophilic,90,93, 97
follicle-associated,I 80- I 8 I orthochromatophilic (normoblasts), 90, 94, 97
gallbladder,307,316-317 polychromatoph ilic, 90, 94, 97
germinal, 343, 347, 352-353, 376 Erythroqtes (red blood cells,RBCs), 53, 89, 9Ot,95-97, 98-99,
histological organization, 29 162-165,212-21i
histophysiology, 27-28 fung,252-253
intestinal,283 pancreatic,312-313

lndex I 419
Erythrocytichemopoiesis,93-94 Fenestrated capillaries,148,1,50,155
Erythropoietin,90, 91-92 Fenestrated membranes,I53, 156-157
E site,4 Feverblisters,256
Esophagealgland,s,278, 288-2 89 Fibers
E s o p h a g e ah li a t u s , 2 8 l ascending/descending, 129
Esophagogastricjunction, 288-289, 2n-29 I cardiacmuscle,122-123,124
Esophagus,246- 247, 277-27 8, 282, 288-289 collagen, 45, 49, 54-5 5, 58-59, 86, 156- 157, 158- 159,
Estrogen,345,346 210-211, 22r, 228-229
Eumelanin,2l9 elastic,45, 47, 50, 58-59, 68, 156- 157, 158- 159, 237
Eustachian(auditory) tube, 388,395 of extracellular matrix, 47
Excitation,237 intrafusal,I .17
Excitatorysynapses, I 26 muscle,103
Excretion,27 nerve,13.1,232-233
Exocrineglands,25-26, 29 (seealsoGlandsand individual cochlear,404-405
glands) of inner ear, 402403
compound,29 olfacrory, 244-245
multicellular,29 organ of Corti, 406407
simple,29 Purkinje, 107,147-I48, 149,162-165
u n i c e l l u l a r2, 9 reticular, 45,47, 49,54-55, 107,173, 174, 190-191
Exocrine pancreas,4243 (seealso und.erPancreas) Sharpey's,70,72
Exocltosis, 4-5 skeletalmuscle,114- 116
Externalear,392 unmyelinated,136-137
Externalelasticlamina, 156, 158-159 Fibrils, collagen,56-57, 60
Externalgranularlayer,138-139 Fibrinogen,89
External laminae, 120- 12 1 Fibrinolysis,150
Externallimiting membrane, 39I, 398-399 Fibroblastgrowth factor-8,256
Externalperipheralnervemesaxon,144-145 Fibroblasts,46, 49, 50, 53-55,60, 1,30,156-157
Externalpyramidal layer, 138-139 dental,264-265
Extracellularfl uid, histophysiology,48 ganglionic,140-l4l
Extracellularmatrix, 45-46 ocular,396-397
histopathology,47-48 peripheral nerve, 142-143
Extrapulmonarybronchi, 239 renal,332-333
Eye,384,387 testicular, 378-379
accessory structures,389,40H01 Fibrocartilage,65,6&, 68,70
clinicalconsiderations,390 Fibronectin,45,46
histologicalorganization,39l-392 Fibrousastrocltes,136-137, 1 38-139
histophysiology,389
Fibrouslayer
tunics of, 398-399
of perichondrium,65
Eyelids,389, 392,400-401
of periosteum,T0
Fibrous trabeculae,of penis, 384-385
@F Fibroustissue,ovarian,356-357
Facial nerve, 402-403 Fibrous tunic of eye (corneoscler al lay er), 384, 387, 39 |
Facilitateddiffusion,4, 128 Filamentousbodies,i 18-i 19
F actin, 105 Filaments
Factor,serum thymic, 172 intermediate, 120-121
F a c t o rV I I I , 9 l muscle,105,106
F a c t o rX I I , 9 i thin (actin), 3
Fascicles, of axons,13i Filiform papillae,257,261,270-271
Fasciculi,126 Filtration barrier,3i0, 331
Fat (adipose) cel\s,4041, 46, 49, 6i Filtration slits,324
Fat-storing(Ito) cells,304,309 Fimbriae,343
Feet,junctional, 105 Fingernails,218,222,225,2i2
Femalereproductivesystem,343-367,360 Fission,2
clinical considerations,346 Fluid
externalgenitalia,344 cerebrospinal(CSF), 125,130
genital ducts, 343-344 follicular,352-353,354-J55
histological organization, 347-348 seminal,372
histophysiology, 345-346 Folds
mammary glands,344 junctional, 114-116, 127
ovary,343 ventricular, 244-245
placenta,344,351 vocal,239, 244-245
uterus,344 Foliatepapillae,258
vagina,344 Follicle-associated epithelium, I 80-181

42O w lndex
Follicle maturation, 345 Germinal centers, 167, 180- 181, 182- 183, 184- 185, 190-19 1
Follicles Germinal epithelium, 343,347, 352-353, 376
atretrc,347 Gingiva (gum), 257, 260, 266-267
Graafian, 343,347, 350, 352-353, 354-355 Gingival mar gin, 266-267
hair, 63,221, 225, 228-229, 230-231 Gingival sulclus,266-267
ovarian, 343, 347, 350, 352-353, 354-355 Gingivitis, necrotizing ulcerative,256
thyroid gland, 208-209 Glands, 25-26 (seealso Endocrine systemand individual glands)
Follicle-stimulatinghormone (FSH), 194, 343, 345, accessorymale reproductive, 373-37 4
3 6 9 ,3 71 apocrine,348
Follicular atrophy, 347 Bowman's, 244-245
Follicular cells, 192,202, 352-3 53 branched alveolar holocrine, 22 I
parathyroid, 208-209 bulbourethral(Cowper's),370,372, 374,376
thyroid,208-209 cardiac,277, 279
f oilrcular fl ulo, Jtz-J5 J
ci|iary,400401
Follicular (proliferative) phase,of endometrium, 344, 348
circumanal,285
Folliculostatin, 345
compound tubuloacinar
Folliculostellatecells,215
n:xed,4243
Foramen, apical,260
serous,4243
Fovea centralis, 389, 391, 400401
of digestivesystem, 303-321
Foveolae(gastricpits), 278,285,290-291,292-293
duodenal(Brunner's),278,280,285,294-295
Fragmentins,170,178
endocrine, 25-26,29 (seealsoEnd,ocrinesystemand
FSH (follicle-stimulatinghormone), 194, 3 43,3 45,37|
i ndividual components)
Fundic gland, 279, 290-291, 292-293
esophageal, 278, 288-289
Fundus
exocrine,25-26,29
gastric,278,285
compound,29
uterine,344
multicellular, 29
Fungiform papillae, 258, 261
pancreas,4243
simple,29
unicellular,29
@G fundic, 279, 290-29 1, 292-293
gastrrc, 279, 282, 290-29 I
GABA (gamma-aminobutl.ricacid), 128
histological or ganization, 29
G actin, 105
GAGs ( glycosaminoglycans),45, 47 inrr a epi thelial, 2 74- 2 75
Galactorrhea,i98 respiratory, 244-245
Gallbladder,303,304, 306-307,316-317 lacrimal, 384, 387,389,392, 398-399, 400401
Gallstones(biliary calculi),305 of Littr6, 324, 384-385
GALT (gut-associated lymphoid tissue),.175,280 liver,303,309
Gamete,male,369 male reproductive accessory,372
Ganglion (ganglia),126 mammary, 3 44, 3 46, 3 48, 366-367
dorsalroot, 130 meibomian,389
sensory,140-l4l mucous of palate,272-273
spiral,402403, 404405 pancreas,303, i08
sympathetic,140-141 parathyroid, 198
Ganglion cell layer, rctinal,392, 398-399 pineal body, 197
Gap junctions, 25,30,68,104, 109 pituitary (hlpophysis) (seePituitary gland)
myometrial,345 prostate,369,370, 372, 374, 376, 384-385
Gaseousexchange,243 pyloric,279, 292-293
mechanismof, 237 salivary,31, 255,257,303, 304,306, 310-i1 1, 318-319
Gastric glands, 279, 290-29 1 sebaceous,4O-41, 21,8,221, 222, 225, 228-229, 230-231,
cells of, 282 262-263, 348, 366-367, 392
Gastric inhibitory peptide, 278, 280t seromucous,173, 235,239,246-247
Gastricmucosa,282 serousofvon Ebner, 258, 270-271, 272-273
Gastric pits (foveolae), 278,285, 290-291, 292-293 sublingual, 42-43
Gastrin,278,2803 t ,0 5 submandibular,42-43
Gastrin intrinsic factor, 279 suprarenal, 1,97,198
Gastrinoma,305 sweat,56-57, 218,221,222, 224, 225, 228-229, 230-231,
Gated/ungatedion channels,4 232-233, 234, 348, 366-367
G cells,305 eccrine,4041
G-CSF(granulocytecolony-stimulatingfactor ), 9l-92 tarsal,392, 400401
Generearrangement,172 thyroid, 198
Genital ducts, 369-370 tubuloacinar (alveolar) mucols, 424j
female, 3 43-3 44, 347-3 48 urethral intraepi thelial, 324
male,369-370,373 $erine, 360-361, 362-363

fndex t 421
Glandularportion, of smooth muscle, 118-119 Granuloclte colony-stimulatingfactor (G-CSF),91-92
Glanspenis,376 Granulocyte-macrophagecolony-stimulating factor (GM-CSF),
Glassymembran es,221, 230-23 1 9t-92
Glaucoma,390 Granuloqtes, 39, 90t, 93, 168
Glicentin,2801 Granulocytic hemopoiesis,94
Glisson'scapsule,306,314-315 Granulosacells,345
Globulins,89 Granulosa lutein cells,354-3 55, 356-3 57
Glomerular arterioles Graves'disease,198
afferent, 323, 331, 332-333, 334-335 Gray commissure, 129, I 34- I 35
efferent, 334-335 Gray matter, lZ9, 136-137
Glomerulonephritis,acute,327 cerebellar,136-137
Glomerulus (glomeruli), 129, 328, 332-333, 33,t-335, 336 spinalcord, 134-135
Glucagon,280t Groove, nail, 222, 232-2i3
Glucocorticoids,195 Ground substance,47,49, 54-55,70
Gluconeogenesis, 304 amorphous,45
Glycerol,281 Growth
Glycine,4T appositional,70
Glycocalyx,2T9 interstitial, 65, 70
Glycogen,3,304, 320, 358-359 Growth factors, hemopoietic, 9l
in cardiac muscle, .124 Guillain-Barr6syndrome,128
Glycoproteins,45,47, 68 Gut-associatedlymphoid tissue (GALT), 175, 280
Glycosaminoglycans (GAGs), 45,47, 65
protein-associated, 66 SH
Glycosylation,9,47
terminal,5 Hair, 218, 221, 225, 228-229
GM-CSF (granulocyte-macrophage colony-stimulatingfactor), Hair bulb, 22I,228-229
91-92 Hair cells
Goblet cells,12-13, 14-15,32-33, 4M1, 160-161,235,239, of ear, 388, 390, 392, 395, 402403, 406407
240-247, 248-249, 278, 279, 28s, 294-295, 296-297, neuroepithelial, 388, 395
298-299 Hair cuticle,221
Golgi apparatus(complex),2,7, 22, 23, 47, 60 Hair follicles, 63,22I,225, 22A-229,230-231
adipoclte,63 Hair lumen, 230-231
epididymal,386 Hair root, 221,230-2i1
mast cell, 6-l Hair shaft,22l
Hair sheath,221
neuronal,i46
Haploid spermatids,369, 371,377
osteoblasts,87
Hard palate, 272-273, 274-275
typical,18-19
Hassall's(thyrnic) corpuscles,168,174, 188-189
Golgi phase,of spermiogenesis,377
Haversian canals,66, 72,78-79, 8O-81
Golgi tendon organs, 104
H bands,105,108
Golgi qpe Il cells,136-137
Hearing loss, conductive, 390
Golgizone,404l
Heaft, 147-148, I49, 162-165
Gonadotropes,214
clinicalconsiderations,152
Gonadotrophs,2.15
histological organization, I 53
Gonadotropin-releasing hormones, 345
Heart valves, 149, 162-165
Gonorrhea, 346
Healy chains, myosin, 105
Graafian follicles, 343,347, i50, 352-353, 354-355
Hedgehog,sonic,256
Granular layers, 136-137
Helical arteries,362-363
of cerebellum, 129, 136-1 37
Helicine (coiled) arteries, 345, 372
external, 1 38-139
Helicotrema, 390, 402-403
internal, 1 38-139
Hematopoietic stem cells,53
Granule cells,136-1 37, 1 38-139
Hematopoietic tissue,84-85
Granules
Hematuria (blood in urine),327
acrosomal,5/u, J//
Heme,237
azurophilic, 9 l, 93 Hemidesmosomes,25, 27, 30
keratin,2l9 Hemoglobin,237
keratohyalin,217,221 Hemolltic jaundice, 305
mast cell, 6l Hemopoiesis, 89-90
neutrophilic,9l clinical considerations,92
secretory,3,6 erythrocytic, 90, 90t
secretorypituitary, 2i4 granuloqtic,90, 90t
specific,93 histological organization, 93-9 4
tertiary,9l lyrnphocytes,92
zymogen, I 2-1 3, 312-i1 3 postnatal,9l-92

422 ffi Index

Hemopoieticgrowth factors,9l antimiillerian,371
Henle,loop of,323,324,325,328, 330,332-333, 3i8-339 of DNES cells,278
r r e n l es l a y e r ,z z t , 2 2 5 of elementary canal, 2801
Hensen,cellsof,392, 406-407 follicle-stimulating(FSH), 343, 345,369,37|
Heparansulfate,45, 325 gonadotropin-releasing, 345
Hepatic artery,314-315 luteinizing (LH), 194,369
Hepatoqtes, 303, 304, 309, 314-3 15, 316-3 17 mechanismof action, 196
Hering, canalsof, 306 nonsteroid-based, 196
H e r n i a ,h i a t a l , 2 8 l paracrine,279
Herpeticstomatitis,256 p a r a t h y r o i d( P T H ) , i 9 5 , 1 9 6
Herring bodies, I94, 206-207 p|ttritary, 194,201
Hexosamine,47 steroid-based,196
Hexuronic acid,47 thyroid, 196-197
Hiatal hernia,281 Hormone-sensitivelipase,48
Hilum, renal,323 Horns
His, bundle of, 149 dorsal,129,134-135
Histamine,148, 150 Yentral,129,134-135
Histioqtes (macrophages),46 Howship's lacun ae,66, 70, 88
Histological organization Human chorionic gonadotropin(hCG), 345, 346,372
alimentary canal, 282-284 Human chorionic mammotropin, 345
blood,93 Human leukoclte antigen (HLA) molecules,
blood circulation, Humorally-mediatedimmune response,92,
cartilage,70 Huntington's chorea,128
connectivetissue,49-50 Huxley's layer, 221, 225
ear,392-393 Hyaline cartilage, 65, 66t, 68, 70, 74-7 5, 86, 235, 239,246-247
endocrine system, 199-200 embryonic,74-75
epithelium,29 Hyaline cartilageplates,239
eye,391-392 Hyaline layer of Hopewell-Smith, 274-275
neart, l)J Hyaline membrane disease,237
hemopoiesis,93-94 Hyaluronic acid, 45, 47,68
ihfad',nanr )fl
Hydrolltic en4'rnes,2
lympnolo ussue,l,/J-1,/J Hydroryindole, 2 l9
oral reglon,25/-256 Hydroxylation, 47
resprratory tract, 239-240 Hydroxylysine, 47
urinary system,328-329 Hydroryproline, 47
Histophysiology Hlperparathyroidism,I 98, 327
alimentary canal, 279-28\ Hlperthyroidism, 198
blood,9l-92, 149-150 H)?ertonicity, 326
cartilage,68 Hlpertrophy, benign prostatic (BPH), 372
connective tissue,47-48 Hlpodermis, 219, 224, 228-229
digestiveglands, 304 Hyponychium, 218, 222, 225
ear,389 Hypophysealportal system,193
endocrinesystem,196-198 Hlpophysis (seePituitary gland)
epithelium, 27-28 Hlpothalamo-hypophyseal tract, 194
extracellular fluid, 48 H1p othalamu,s,204- 2 05
extracellular matrix, 47--48 Hypotonicity, 326
eye,389 H z o n e ,1 0 3 ,1 1 0 - 1 1 1 1, 1 2 - 1 1 3
female reproductive system, 345-346
integument, 219-220 .@I
lymphoid tissue,170-172(seealsoImmune response)
male reproductivesystem,371-372 I bands,103,105,I07, 108, 112-113,114-116
muscle,105-106 Icterus(jaundice),305
nerve tissue, 1,27-129 Ilerm, 278, 285, 296-297
orai region,256 Immature cells,292-293
respiratory system,237 Immune response,92
unnary system,325 cell-mediated,167,170 (seealsoLymphocltes)
HLA molecules,l7S humorally-mediated,770, 171
Hodgkin's disease,172 lmmune tissue
Hopewell-Smith, hyaline layer of, 274-275 cells,170-171, 178
Horizontal cells,129 lymph nodes,l7l, 178
Hormonal influences,on bone,69 spleen,17l-172
Hormones, 193 Immunoglobulin A (IgA), 279, 304, 346
antidiuretic (ADH, vasopressin), 326 Immunoglobulins,surface(SIGs),92, 171

fndex ffi 423

Incisure,Schmidt-Lanterman, 142- 143 Intervertebral disc, 76-77
Inclusions,cytoplasmic,3 Intervillous space,364-365
Incompetency,valvular,152 Intestines
Incus,388, 389,395 large, 278, 284-285, 286, 298-299
Inferior longitudinal nuscle, 270-27 1 small, 277, 279-280, 283, 285,296-297
Infiltration, lymphatic, 180-181 I ntracellular canaliculi, 279
Inflammation,46 Intracellular digestion, 2
Inflammatory bowel disease(lBD), 281 Intracellular messengersystems,4
lnfraglottic cavity, 235, 239, 244-245 Intraepithelial glands,274- 275
Infundibular r ecess,204-205 Intrafusalfibers,117
Infundibular stem,204-205 Intraglandular cleft, 204-205
lnfundibulum, 343 Intraglomerularmesangialcells,324
oviductal, 347-348 Intramembranousossification,66,7 l, 8O-81
uterine,350 Intrapulmonarybronchi, 236,239,242,250-251
lnnloln, J4)t J/ I Intrinsic factor, gastric,279
Inhibitory synapses,126 Intrinsic ocular muscles,389
I n i t i a t o rt R N A , 4 , 9 Inverted (Martinotti) cells,129
l n n e r c a p s u l el,l 7 Involution, thymic, 174
Inner ear, 402403 Iodide pumps, 196
Inner limiting membrane,392, 398-399,400401 Iodopsin,389
Inner nuclearretinal layer,391 Iodopsin-forming cones,384, 387
Inner phalangeal cells,406407 Ion absorption,28l
Inner pillar cells,406407
Ion channelproteins,4
Inner plexiform retinal layer, 392, 398-399,400401
Ion channels,196,237
Insulin, 305
Iris, 389, 391,396-397
Insulin resistance, 305
Islands,cerebellar,136- I 37
Integrins,4T
Isletsof Langerhans,303, 304,306,308,312-313,i21
Integument,217-234
Isodesmosine,4T
clinicalconsiderations,220
Isthmus,of oviduct, 343
histologicalorganization,221
Ito (fat-storing)cells,304,309
histophysiology, 21'9-220
skin,217-218,224
skin appendages, Z2l-222
sl
skin derivatives,218, 225 Jaundice(icterus),305
Interalveolar septa,240,242, 243, 252-253 Jejunum, 278, 285, 296-297
Intercalateddiscs,107, 109,122-123,124 Iunctional complexes,27, 30
Intercalatedduct cells,3l |unctional epithelilum, 266-2 67
Intercalatedducts,31, 304, 306,308 functional feet, 105
Intercellular brid ges,14- 15, 221 functional folds, 114-116, 127
Intercellular canalicuJi,222 Iunctions
Interdental septum, 27't-27 5 adherens,120-121
Interferon-1, 170 anorectal, 298-299
Interleukin-1,I70 cementoenamel,264-265, 266-267
Interleukin-3,91 dentinoenamel, 264-265, 266-267
Interleukin-7,91 epithelial, 38-39
Interlobular arrery, 323, i 32-3 33 esophagogastric,288-289, 290-29 1
Interlobular duct, 310-311 gap,25, 1.04,109,345
Interlobularveins,323 myoneural,104,105,114-116,I27
Interlobular vessels,332-3 33 occfuding, j20
Intermediate filaments, 120- 12 1
fuxtaglomerular apparatus,324, 325-326, 334-335
Intermembranespace,i, 7
Iuxtaglomerular cells,324, 328, i3 1, 3i4-335
Internal elasticlaminae, -158-i59
f uxtaglomerularnephrons,324
Internal granular layer, 1j8-139
f uxtamedullary nephrons, 323-324
Internal pyramidal layer, 1 38- 139
Internal root sheath,225
Internal spiral sulcus,40H07
*K
Interneurons,l25 Keloid formation,48
Internodes,l3l Keratin,2IT-218,219
Interpapillary peg, 226-227, 228-229 Keratin formation, 219
Interphase,3 Keratin granules,219
Interphasenucleus,i6-i7 Keratinoqtes, 21,7-218, 219, 221
Interstitialcells,testicular,380-i81 Keratohyaline granlules,2l,7, z2l
Interstitialgrowth, 65, 70 Kidney (renal) cancer,327

424 re tndex
Kidneys, 323-324, 328, 3i0, 332-3 33 seminal vesicles,373-374
generalmorphology, 3j2-j j3 stomach, 282, 290-29 1, 292-293
Kidney stones(nephrolithiasis),327 tracheal, 246-247
Killer cells urethral, 374
qtotoxic T, 167, 170,178 vaginal j64-365
n a t u r a l( N K ) , 9 2 , 1 7 0 Laminarara,325
Kinase,myosin lighrchain, i06 Lamina reticularis, 27
Kinesin, 3 Laminin,46
Kinocilium,390 Langerhanscells,2 I 8, 221,224
Knot Langerhans,isletsof, 303, 304,306, 308, 312-313, 321
enamel,256 Large intestine, 278,284-285, 286, 298-299
synqtial, 364-365 Large ribosomal subunit, 9
Krause'send bulbs, 221 Laryngeal cartllage, 244-24 5
Kupffer cells, 58-59, 304, 306, 309, 316-317 Laryngealventri cle, 235, 244-245
Laryngealvestibule, 235, 239, 244-245
*t Larynx, 235, 239, 244-245
Labyrinth Lateendosomes,2, 4, 8
auditory, 388,395 Layers(seealsoLaminae)
bony,390 basal uterine, 360-361
membranous,390,393 cartilage,65
renal cortical, 328, 332-33i, 334-335 corneal,396-397
Lacrimal glands, 384, 387,389,392, 398-399,400401 corneoscleral(fibrous tunic), 384, 387
Lactating mammary gland, 348, 366-367 fibrous ocular, 396-397
Lacteals,180-181,278,281,294-295,296-297 functional uterin e, i62-363
Lactiferous ducts, 348 granular
Lactiferous sinuses,348 external, 1i8-139
Lactoferrin,304 internal, 138-i 39
Lacunae Henle's,221,225
b o n e ,6 6 , 6 8 Huxley's, 221,225
cartilage,65, 68,70 hyaline of Hopewell-Smith, 274-27 5
H o w s h i p ' s6, 6 , 7 0 , 8 8 molecular, 136-1 37, 138- 139
Lamella(lamellae) o dontoblastic, 264- 265
ofbone,66 optic nerve fiber,392
circumferential, 66 paplllary, 226-2 27, 228-22 9
inner,72 parietal, kidney, i34-i35
ovter,72 Purkinje cell, 136-137
interstitial, 66 pyramidal, 138-139
Lamellarbodies,243 reticular, 2Zl, 226-227, 228-229
Lamellarsystems,of bone,71 retinal
Lamina (laminae) (seealsospecific tlpes) ganglion cell, 392, 398-399
basal,25, 27 (seealso Basallamina) nuclear,391
dental, 258, 260, 268-269 pigmented, 396-397
elastic,58-59 plexiform, 392, 398-399, 40H0 1
externalr1Jo,t5d-1Jy Leaflets,valve, 162-165
l n t e r n a l ,l 5 d - l 5 y Lens, 384, 387, 389, 392, 396-397, 40040 I
external, 120-121 Leukoqtes, 12-13, 46, 89,90t (seealso LymPhoc)'tes)
osseousspiral, 404405, 40H07 Leukotrienes,46
of retinal rods and cones,398-399, 400401 Leydig cells,373, 380-381
succedaneots, 268-269 LH (luteinizinghormone), 194,369
suprachoroid, 396-i97 Lieberkiihn, cr)?ts of, 278, 279,283, 285, 286, 294-295,
Lamina densa,27, 46,325 296-297, 298-299, 300, 301
Laminalucida, 27, 46 Ligaments
Lamina propria, 244-245 broad,,350, 356-357
bladder, 329,340-341 ovarian,350
ofoncmolat, zJU-Z5I periodontal, 257, 260, 266-267, 27'I-275
ductus (vas) deferens,382-383 spir al, 404-40 5, 406407
dtodenal, 294-295 suspensoryocular,391, 40040 1
esophageal,282, 288-289 Ligands,4
gallbladder,307 Light cells,272-273
intestinal,2S3 , y o s i n ,1 0 5 ,1 0 6
L i g h tc h a i n s m
oviduct, 358-359 Light meromyosin,105, 106
palatal,272-27j Limbus, ocular, 384, 387

lndex il 425
Limbus spiralis, 404405
Limiting membrane
external, 398-399
rnner,392,398-399,400401
outer,400401
Linear accelerationsense,390
Lingual tonsils, 168, 173,258,261
Lip(s)
oral,257 , 262-263
tfmpanic, 406407
vestibular, 406-407
Lipases,278
hormone-sensitive,
lipoprotein,48
pancreatic,281,303
Lipid droplets,320
Lipids
cellular,1, 2
digestionand absorption,28I
Lipid synthesis,2
Lipofuscin,31 , 40-141
Lipoprotein lipase,48
Littrd, glandsof,324, 384-385
Liver, 303, 304, 306,309, 3 14-3 15, 3 16-3 17, 320
Lobules
of bulbourethral(Cowper's)glands,374
K l o n e yJ, z J
lacrimal gland, 400-40 1
l i v e r , 3 0 6 ,3 1 4 - 3 1 5
mammary gland, 348,366-367
parotid gland, 310-311
suprarenal gland, 2 12-2 13
testicular, 369, 376, 378-379
thymic, j88-189
Longitudinal muscles,290-29 1, 294-29 5, 296-297, 34O-34 1,
356-357, 360-36 1, 364-365, 382-38i
inferior , 270-27 I
slJpenor, 270-27 l
Loop(s)
capillary, 221, 226-227, 228-229
of Henle, 323,324, 325,328,330,332-333, 338-3i9
Loose(areolar)connectivetissue,46, 49, 54-55
Lumen, 12-13
arterial, l56
bladder,l0-l.l
bronchiolar, 250-251
duodenal, 294-295
esophageal,246-247, 288-2 I 9
hair,230-231
nearl,102-to>
lar ge intestine, 298-2 99
laryngeal,239
lyrnphoid nodule, I 80-18I
mammary gland,366-367
oviduct, 358-359
seminal vesicle, 382-383
small intestine, 14-15, 296-297
stomach,290-291
testicular, 378-379
trachea,246-247
ldleter,340-341
uterus, 360-361, 362-363
vascrlJar,160-161
426 w tndex
Lwg, 250-251, 252-253
Lung volume, 237
Ltrria,2l8, 225
Lupus erythematosus,systemic (SLE), 48
Luteal (secretory) phase,of endometrium, 344, 345, 348,
360-36r,362-363
Luteinizinghormone (LH), 194,369
Lyrnphatic capillaries, 148
Lymphatic circulation (seeLymphoid tissue)
Lyrnphatic infiltration, 180-1I I
Lymphatic valves, 153, 182- 183
Lymphatic vessels,testicular, 380-381
48 Lymph nodes,167-168,I70, 17l,173, 175,176, 182-183,
184-185,186-187
Lymphoblasts,i80-l8I
Lymphocytes,49, 53,93,95-97, I53, 160-161,180-181,
184-185
B (B cells),92, 167,171,175, 18A-189
splenic,190-i9l
T (T cells),92,168,170,175, 190-191
tlpes of, 89, 90t
Lymphoid cells,54-55, 294-295
lar ge inte stine, 298- 299
Lymphoid enhancer factor- l, 256
Lymphoid nodules, 54-5 5, 168, 173, 180- 181, 182- 183,
184-185,239
Droncntol.af,zJU-zJ I
splenic, l90-191
Lymphoid tissue, 167-191
bronchiolar-associated (BALT), I 75
clinicalconsiderations,172
diffuse, 167, 175
encapsulated, 168,175
gut-associated (GALT), 175,280
histologicalorganization,173-173
histophysiology, 170-172 (seealsoknmune response)
lymph nodes,167-168,173,175,176, 184-185,186-187
spleen,168, 174,176,190-191
thymus, 168-169,I7Z,174, 176,178, 188-189
tonsils,168, 173, 184-185
Lymph vessels
esophagus,288-289
,|vr, Jt4-51J
respiratory tract, 244-245
Lysine,47
Lysomal storagediseases,5
Lysosomalenzymes,5
Lysosomes, 2, 4,6, 219
Lysozyme,278,304,389
#M
Macrophage activation, 179
Macrophages(histiocytes), 46, 49, 53, 54-5 5, 89, 901, I 68,
182-183,184-185
dtodenal, 294-295
thyrnic, i88-189
Macula, 393
Macula adherentes,25, 27, 30
Macula densa,324,325,328,332-333,334-335
Maculae,of ear,388,395
Major histocompatibilitycomplex (MHC), 170
Male gamete,369 Melanosomes,217-218
Male reproductive system, 369-386, 376 Melatonin, 195,197
accessory glands,370,376 Membrane potential
clinicalconsiderations,372 acting, l,27
histologicalorganization,373-374 resting,127
histophysiology, 371-37 2 Membrane proteins, 5
penis,370, 376 Membranes
testes,379 basal,25,4041
Malignant melanoma,220 basilar, 388, 392, 395, 406-407
Malleus,388,389, 395 cochlear,404-405
Mammary glands, 344,348, 366-367 Bowman's,391,396-397
hormonal effects,346 cell,8
lactating, 366-367 choroid,39l
Mammotropes,2l4 Descemet's,391
Mannitol, 128 elastic,58-59
Mannose groups, 9 epithelial,25,26t
MAPs (microtubule-associated proteins),3 fenestrated,153, 156-157
Marfan's syndrome,48 glassy,22l, 2j0-2j 1
Margin, gingival, 266-267 choroid,39l
Marginal zone, 168 limiting
splenic,174, 190-191 external, 391,398-399
Marrow cavity,72 inner, 392, 398-i99, 400401
Martinotti (inverted) cells, 129 mucous, 382-383
Mast cells,12-13,46,49,53, 54-55, 58-59,61,160-161 otolith-containing proteinaceous,388, 395
degranulation, 62 otolithic, 390,393
Masticatory mucosa, 255 presynaptic,127
Matrix (matrices) tectorial,388,390, 392,i95,404405,406-407
bone,66,68 tympanic, 388,389, 395
cartilage,65, 68,70 vestibular, 390, 404-405
interterritorial (intercapsular), 70 Membrane traffi clong, 4, 6, 7, 8
territorial (capsular), 70 Membranous labpinth, 390, 393
dentin,268-269 Memory cells,167
Matrix space,l, 7 B,17I
Matrix vesicles,68 T, 170
Mature bone,67 Meni6re's disease,390
M (microfold) cells,278, 280,285 Meninges, 125, 129
M d i s c ,1 0 3 ,1 0 8 , 1 1 2 - 1 1 3 Menstrual phase,of endometrium, 344, 345, 348, 362-363
Meatus (canal), auditory, external, 387, 395 Merkel cells,22I,224
Mechanoreceptors,2 I 8 Merocrine secretion,29
Mediastinum testis, 369, 380-381 Meromyosin
Medulla hear,y,105
hair,22I light, los, 106
lyrnph node, 168,173, 182-183 Mesangial cells,334-335, 337
ovarian, 343, 347, 352-3 53 Mesaxon, external peripheral nerve, 14't-145
renal, 323, 328,330, 332-3i3, 338-339 Mesenchymal cells,49, 66, 268-269
suprarenalgland, 195, 197,200, 203 Mesenchymal connective tissue, 46,49, 54-55
thymus, 168,172, 174, 188-l 89 Mesodermal epithelium, 195
Medullary cavity, 84-85 Mesothelialcells,53
Medullary cord, 184-185 Mesothelium,25
Medullary lyrnph node cords, 171 alimentary canal,277
Medullary rays,ki dney, 328, j 32-j3 j Mesovarium, 352-353
Medullary substance,cerebellum, 129 Messengersystems,4
Megakaryocltes, 89 Metamyelocytes,90
Meibomian glands, 389 basophilic,97
Meiosis,sperm,369,371 eosinophilic,92,l0l
Meissner'scorpuscles,22I, 224, 2i2-233 neutrophilic, 94, 97, 101
Melanin, 217-218,389 Metaphase,i6-17
Melanin formation,2l9 of oocyte, 350
Melanocltes, 219, 2Zl, 224, 226-227 Metaplasia,28
in eye,396-j97 Metarterioles, 148, 155
Melanocpe-stimulatinghormone (MSH), 194 MHC (major histocompatibility complex), 170, 177, 178
Melanoma, malignant, 220 MHC restrictedT cells,170

lndex U 427
Microfibrils,4T Mucous membranes, seminal vesicle,382-383
Microfilaments,3 Mucous neck cells,279,292-293
Microglia, 138-139 Mucularis mucosae
Microscopic villi,279 dtodenal, 294-295
Microsomal mixed-function oxidase,304 esophageal,288-289
Microtubule-associated proteins (MAPs), 3 intestinal,283
Microtubule-organizingcenter (MTOC), 3 Mtiller's (supportive)cells,391
Microtubules,3,20-21 Multilocular adiposetissue,48
M i c r o v i l l i ( b r u s hb o r d e r ) ,2 5 , 2 7 , 2 7 8 , 2 7 9 , 3 2 0( s e ea l s oB r u s h Multiple myeloma,92
border) Multipolar (motor) cell bodies,129
ear, 388, 395 Multipolar neurons,125
retina,398-399 Multipotential hemopoieticstem cells,89-90, 9l
Middle ear,392 Muscle(s), lO3-124 (seealsoMuscula ris and specifictypes)
Milk,346 arrector pili, 222, 228-229, 230-231, 232-233
Milk ejectionreflex,346 cardiac,104, 107,109,122-123,124,162-165
Mineralocorticoids,195 ciliary,389
Mitochondrion (mitochondria), 1,6, 7, 20-21, 22, 24
cir cular, 2 90-29 1, 294-29 5, 296-297, 29t-299, 340-3 41,
epididyrnal,386 356-3 57, 35 8-3 59,360-36 1, 364-365
hyaline cartilage,S6
clinical considerations,106
liver,320
columnar, 382-383
mast cell, 6l
dilator pupillae,389
myoneuraljunction, I 1'l-l l6
esophageal
neuronal,146
inner cir cular, 2I 8- 289
peripheral nerve, 144-1 45
outer longitudinal, 288-289
smooth muscle cell,120-121
histological organization, 107
in synapticterminal, 136-137
histophysiology,I05-106
tlpical, l8-19
longitudinal, 290-291, 294-295, 296-297, 340-341, 356-357,
M i t o s i s , 3 i,F l T
360-361, 364-365, 382-383
Modiolus, 402403
inferior , 270-27 1
Molecular layer,136-137, 138-139
superior,270-271
of cerebellum,129,136-137
oblique,290-291
Molecules
ocular,intrinsic, 389
CD (clusterof differentiation),92
orbicularis oculi, 400401
signaling,4
pupillary dilator, 391
tropocollagen,45
skeletal,103-104,I07, 108,109, 11O-1I 1, I 12-1 13
Monocytes, 53, 93, 95-97
s m o o t h ,1 0 4 ,1 0 6 ,1 0 7 ,1 0 9 ,1 1 8 - 1 2 1 , 1 5 3 , 1 8 0 - 1 8 1 9, 0 - 1 9 1
Monoglycerides,28t
striated,103
Motilin,280t
M o t o r e n d p l a t e , 1 1 4 - 1 1 61, 3 2 trachealis,239
Motor neurons,132 vocalis,244-245
mRNA,4-5 Musclecontraction,106
MTOC (microtubule-organizingcenter),3 sliding filament model, 104
N r u c l n ,l / y Musclespindles,104,117
Mucinogen,279 Muscular arteries,148,149, 1,53,154,158-159
Mucoperiosteum, 274-275 Muscular dystrophy, Duchenne's, 106
Mucosa Muscularis,vaginal,348,364-365
alirnentary canal,277 Muscularis externa,290-29 1
alveolar, 266-267 alimentary canal,277
bronchial,239 duodenal, 294-295
esophageal,282, 288-289 esophageal,282,288-289
gastric,282 esophagus, 278
masticatory,255 gallbladder, 307
olfactory, 235,244-245 intestinal,283
oralt z)) stomach,282
palatal,274-275 MuscuLarismucosae
small intestinal, 296-2 97 esophageal,282
tracheaI,239 small inte stinal, 296- 297
vaginal,348,364-365 stomach, 282, 290-29 1, 292-29i
Mucous acinus(acini), 3J, 310-31I Myasthenia gravis, 106
Mucous cells,3.1,318-319 Myelin, 142-143
stomach,292-293 Myelinatedaxons,132
Mucous connectivetissue,46, 49,54-55 Myelinated nerve frbers, 114- 116
Mucous glands,42-43 Myelination, 1,29,131,144-145,146
palatal,272-273 Myelin sheath,126,130,133,142-143,144-145

428 # Index
Myeloblasts,90, 94, 97, 101 Nervous tissue, 125-146
Myelocytes blood-brain barrier, 128
basophilic,97 clinical considerations,128
eosinophilic,9T,l0l histological organization, 129-I30
neutrophilic,94, 97, 101 histophysiology, 127-129
Myeloid stem cells,9l neurons and supporting cells, 125-126
Myeloma,multiple,92 neurotransmitter substances,127-128
Myocardium, 147-1 48, I 62- I 65 peripheral nerves,126, 132
Myoepithelial (basket) cells, 29, 3 1, 136- 137, 225, 230-2 3 1, Nests,cell,68
3r8-319 Networks
Myofibrils, 107,122-123,124,162-165 alveolar caprllary,242
Myofilaments,103,104, 108,112-113 alveolarelastin,242
Myoid cells,378-379 Neuroectoderm,195
Myomesin, 104 Neuroepithelialhair cells,388, 390,395
Myometrium, 344,345, 348,351,360-361 Neurofi laments, 132, 144-1 45
Myoneuraljunction, 104, 105,1 14-116,127 Neuroglia,lZ9, 134-135, 195,200,212-213
M y o s i n ,1 0 3 ,1 0 5 ,1 0 6 Neurokeratin,130
M y o s i n l i g h t - c h a i nk i n a s e ,I 0 6 Neurolemma, 130
Myosin light chains,106 Neurons, 125-126,146
motor, .132
@N sensory,140-141
Neuropils, 129,134-135
NADPH oxidasedeficiency, 92
Neurotensin,2801
Nailbed,232-233
Neurotransmittersubstances, 4,
Nail groove,2j2-2j3
Neurotubules,.132
Nail plate, 222, 232-233
peripheral nerve, 144-1 45
Nails, 218, 222,225,232
Neutrophil function, 9 I
Nail wall, 232-233
Neutrophilic granules,9l
Na+-K+ pump, 127
Neutrophilic metamyeloqtes,94, 97, 101
Nasal cavity, 239, 244-245
Neutrophilic myelocytes,94, 97, 101
Natural killer (NK) cells,92,170
Neutrophils,49, 53,89,90t,93, 95-97, 97, 98-99,
Nebulins, 105
Nexus, 104,.109
Necrosis, uterine, 362-36j
Nipple,348, 366-367
Necrotizing ulcerative gingivitis, 256
Paget'sdiseaseof, 346
Neocortex,cerebral,129
Nissl bodies,12-13, 129,132,134-135
Nephrons, 323-324,326
Nitric oxide, 150
Nerve cell bodies,spinalcord, 134-135
NK (natural killer) cells,92,170
Nerve deafness,390
Nodes
Nerve fibers, 1i1, 232-23i
atrioventricular (AV), 147-148, I49
cochlear,404405
ganglionic,140-141 lymph, 167-168,17r, t73, 175,176,182-183,t84-185,
186-187
of inner ear, 402403
myelinated,1 14-116 of Ranvier, 130, 13 1, 142- 143
olfactory, 244-245 sinoatrial(SA), 147-148,149
organ of Corti, 406407 Nodules,lymphoid, 54- 55, 168,173, 180-181, 182- 183,
Nerves (seealsoNervous systemand specificnenes; Nervous 184- 185, 190- 191, 239, 250-2 5 1
ussue.) Noncytosolic proteins, 4
cochlear,388,395 Nongranular folliculostellate cells,2 15
facial,402-403 Nonmyelinated axon, 1I 4- I 16
optic, 389, 392, 398-399 Nonsteroid-basedhorrnones, 196
peripheral,126,130,1 31, 142-143, Norepinephrine(noradrenaline),195
suprarenal gland, 210-21 1 Normoblasts,90
tongte,270-271 Nuclearbag, l.l7
tracheal,246-247 Nuclearchain, ll7
vestibulocochlear, 402403 Nuclearenvelope,6, 7, 16-17, 18-19
Nerve terminal, 1 14-116 Nuclearlayers,ofretina, 398-399
Nerve trunk, .l3l inner, 391
Nervous system outer,392
autonomic, 125 Nuclear pore complex, 3, 7
central,l25 Nuclearpores,3
parasl'rnpathetic,125 Nucleolus (ntcleoli), 3, 6, 7, 1) t2

peripheral,125 ganglionic,140-141
somatic,125 neuronal,146
sympathetic,125 spinalcord, 134-135

lndex k 429
Nucleolus(nucleoli) ( continued) Orbicularis oculi, 40040 I
suprarenal gland, 2 12-2 13 Organelles,Z
rypical, 18-19 Organ of Corti, 390, 392, 402403, 40/1--405,
406-407
Nucleolus-associated chromatin, 18-l 9 Orthochromatophilic erythroblasts(normoblasts),90,
Nucleoplasm,6 94,97
Nucleus(nuclei), 3, 6, 7, 10-11, 20-21, 22 Orthodromic sprcad,127
arterialcell, 156,158-159 Osmolarity,325
caroraccell, t62-tot Osmotic concentration gradient, 326
cardiacmuscle,i09 Osmotic pressure,colloid, 325
cardiacmusclecell, 122-123,124 Osseousspiral lamina, 404405, 40H07
cereDellar, lJ6-lJ/ Ossicles,auditory, 388, 395, 40240i
cerebral,1 38-139 Ossification
endothelial,122-123 endochondral,66,67, 7 1, 73, 73, 82-83,84-85
endothelialcell, 153 intramembranous, 66, 7 l, 80-B 1
gobletcell, 12-13, 4041 Ossification centers
hair cell,230-231 epiphyseal,82-83
interphase,.1tsJ7 primary,7l
lateraldescending,146 secondary,71,73, 82-83
lymphocyte,180-l8l Osteoblasts,53, 66, 68, 70, 7 l, 80-81, 87
mast cell, 6l osteoclasts,53, 66, 68, 7 r, 80-81, 88
monoc1.te,93 Osteocltes, 53, 66, 68, 70, 7 1, 98-99
musclecell, 107 Osteogenesis,66-67
neuronal, 126,146 Osteogeniclayer, of periosteum, 70
pituitary cell, 204^205 Osteoid,70,80-81
Purkinje cell,136-1i7 Osteons,66, 7 l, 72, 274-275
skeletalmuscle, 109,110-111 Osteoporosis,69
skin cell, 226-227 Osteoprogenitorcells,66,68, 7l
smooth muscle cell,1)8-119, 120-121 Otolith-containing proteinaceousmembranes, 388, 395
spinalcord, 134-135 Otolithic membrane,390, 393
spleen, 190-191 Otoliths (otoconia),390
suprarenal gland, 2 12-2 1j Outer capsule,lJ7
Nuel, spacesof,406407 Outer circumferential lamellae,72
Null cells,89,90r.,91,167 Outer limiting membrane, 40H01
Nutrient absorption,27 Outer phalangeal cells,406407
Outer pillar cells,406407
60 Outer spiral sulcus,406407
Oval window, 390
Obesity,48 Ovarian cycle, 351
Obstructivejaundice,305 Ovarian ligaments,350
Occluding junctions, 25, 27, 30, 38-39, 320, 371 Ovary, 343,347, 352-353, 354-i55
Ocular capsule,396-397 Oviduct, 14-15, 347-348, 356-357, 35e-359
Odontoblastic layer, 264-265 Ovulation,345
Odontoblasts, 256, 257, 260, 268-269 Oxidase, microsomal mixed-function, 304
Odontogenesis(tooth development), 258, 260, 268-269 Oxidative enzymes,2
Odorant-bindingproteins,237 Oryphils, 195, 199,208-209
Olfaction, mechanism of, 237 Oxytocin, I94,345
Olfactory cells, 235
Olfactory mucosa, 235, 244-245
@P
Olfactory supportingcells,235
Oligodendroglia,126,1,29 Pacinian corpuscles,221,224, 232-2i3
Oligomucous cells,278, 286 Paget'sdisease
Oocytes, 343, 347, 350, 352-353, 354-355 ofbone,69
Oogonia,343 ofnipple, 346
Opsin,389 Palate,255,258
Optic nerve, 389,392, 398-399 hard,272-273, 274-275
Oral epithelium, 268-269 soft,272-273
Oral mucosa,255 Palatinetonsils,168,173, 184-185,261
Oral region, 255-275,260, 261 Palpebral conjunctiva, 40040 I
clinical considerations,256 PALS (periarteriallymphatic sheath),168,17l-172, 190-191
histological organization, 257-258 Pancreas,303,306,308,312-313
histophysiology, 256 endocrine (isletsof Langerhans),303, 304, 308
salivary glands, palate, and tonsils, 255 exocrine,4243, 30J,304, 308

43O ffi Index

Pancreaticlipase, 281, 303 Perichondrium,65, 70, 7 |, 246-247
Paneth cells, 278,279, 285, 294-295, 296-297 Pericltes,46, 148
Papanicolaou(Pap) smear,346 Perikaryon, 125-126
P aplllae, 228-229, 230-2 31 Perilymph, 388,395
circumvallate, 258, 270-27 1, 272-273 Perimysium,103, 107, 109,110-111
dermal (dermal ridges),217, 221,268-269 Perineurium,126, 1,30,131
filiform, 257, 261, 270-271 peripheral nerve, 142-143
foliate,258 Periodontal ligam ent,257, 260, 266-267, 274-275
fungiform, 258,261 rerrostealo\o, o/, /J
renal,328,33U339 Periosteum, 70, 72, 82-83, 84-85
vallate,26l Peripheralnerves,126, 130, 131,142-143,14'L-145
Papillary layer, 22G227, 228-229 Peripheralnervoussystem,125
Paracortex,lymph node, 168,171, 173,182-183 Peritendineum, 56-57
Paracrinehormones,279 Peritubular capillary network, 323, i31
Parafollicular cells,208-209 Perlacan,46
Parakeratotic epithelium, 257 Permeability
Parasympatheticnervous system, I 25 capillary, 150
Parathormone,68 selective,l50
Parathl.roid gland, 19tt-195, 199,202, 208-209 Peyer'spatches,I 8O-1I 1, 278, 280, 285, 296-2 97
clinical considerations,I 98 Phagocl4osis,1, 46, 89, 167
Parathyroidhormone (PTH), 195, 196
ocular,389
Paraventricular hlpothalamic nuclei, 194
Senoll-ce[, J,/I
Parenchyrna,25-26
Phagolysosomes,2
prostate gland, 374
Phalangealcells,392
Parenchymal cells
inner,406407
pineal body, 200
outer,406407
thyroid, 199
Phalangealprocesses,406407
Parietal cells,279, 290-291, 292-293
Phalanx (phalanges),distal,232-233
Parietallayer,kidney, 3J4-J35
Pharyngealtonsils, 168,173, 184-185
Parietalpleura,237
Pharynx,255-256
Parkinson'sdisease,128
Pheomelanin,2l9
Parotid glands,304,306, 310-311
Phosphorylation,9
Parsciliaris,39l,392
Photoreception,389
Parsiridica, 391,392
Photoreceptors(rods and cones), 384,387
Pars optica, 39I, 398-399
Pia mater, 125, 129, 134-1 35, 136-1 37, 1 38-139
Parsrecta,324,325,332-333
Particles PID (pelvicinflammatory disease),346
elementary,1,7 Pigment cells,396-i97
signalrecognition,9 Pigmented corneal epithelium, 396-397, 400401
PassivetransPort,4 Pigmented corneal layers,39G397
Patches,Peyer's,180-l8l ,278,280, 285,296-297 Pigment epithelium,391
Pedicels,323,330,331,337 Pillar cells,392
Pegcells,14-15, 358-359 inner,406407
Pegs,interpapillary, 226-227, 228-229 olrter,406407
Pelvic inflammatory disease(PID), 346 Pinealbody (epiphysis),I95, 197,200, 202,212-213
Pelvis Pinealocytes,I95,200
renal,328 Pinocl'tic vesicles,144- 145
Pemphigoid, bullous, 28 Pinocltosis,1
Pemphigus vulgaris, 28 Pits, gastric (foveoiae), 278, 285, 290-29 1, 292-293
Penicillararteries,168 Pituic)'tes, I94, 206-207
Penile bulb, 376 Pituitary gland (hypophysis), 193-194, 198, r99, 201, 204-207,
Penis,370, 374,376,384-385 215
glans,376 clinical considerations, 198
Pepsin,278,280 pars anterior, 193-194,199, 20,+-205,214
Peptidase,signal, 5 pars intermedia, 194, 199,204-205, 206-207
Peptide pars nervosa,204-205, 206-207
gastricinhibitory, 278,280t pars nervosaand infundibular stalk, 194, 199
vasoactiveintestinal(VIP), 280t pars tuberalis, 194, 199,204-205
Peptidebonds,4, 9 Pituitary hormones, 20-l
Perforins,170,178 Placenta,344,348,351,364-365
Periarteriallyrnphaticsheath(PALS), 168,17l-172, 190-191 Plaqueregions,ofbladder, 324
Periaxialspace,l.l7 Plasmablasts, 180-18.1

lndex s 431
Plasmacells,46, 53, 58-59,92, 160-161,167, 168, 17l, 177, Prolactin,346
180-18 1, I 84- I 85,244-245, 296_297 Proline,4T
P l a s m a l e m m(ac e l lm e m b r a n e,)1 , , 6 ,1 7 7 Promyelocltes,90,94, 97, 101
Plate(s) Propeptides( telopeptides),47
c h o r i o n i c ,3 4 8 , 3 5 1 Prophase,l6-.17
epiphyseal,7 1,,73, 82-83 Prostaryclins,150
hyalinecartilage,239 ProstaglandinE2,170
Iiver,314-315 Prostaglandins, 345
motorend, 114-116,132 Prostategland,369, 370,372,374,376, 384-i85
nail,222,232-233 adenocarcinomaof, 372
tarsal,392,400401 benign hypertrophyof (BPH), 372
Platelets(thrombocytes),89, 93, 98-99 Prostatespecificantigen(PSA),372
Yteura,zJ / Prostaticconcretions,374, 384-385
vtsceral, 242 Prostatic hlpertrophy, benign (BPH), 372
Plexiform retinal layer
Proteasomes, 2
inner, 392, 398-399,400401
Protein-associated glycosaminoglycans,
66
outer, 392, 398-399, 400-401
Protein I, 279
Plexus
Proteins (seealsospecifictypes)
Auerbach's myenteric, 282, 294-295
androgen-binding(ABP), 369,37|
choroid,130
bone morphogeric-4, 256
rcothair,224, 225
c, 104
vascular,22I
cellular,I
Plicaecircularis,279, 296-297
digestion and absorption of, 280
Pluripotentialhemopoieticstem cells,46, 89-90, 9 l,
d o c k i n g ,1 , 5
Pneumocltes,t}?e I/t'?e Il, 236,240,243,252-253,254
hormonal, 193
Podocltes,323,328, 330,331,334-335,337
ion channel,4
Pole, vascular,kidney, 3j4- 335
membrane,5
PolychromatophilicerJthroblasts,90, 94, 97
microtubule-associated (MAPs), 3
Polydipsia,305,327
muscle,104
Polypeptides,280
noncytosolic,4
Polyphagia,305
odorant-binding,237
Polysomes,4,9
secretory(protein I), 279
Poly.uria,305
Protein synthesis,1-2, 4-5, 9
Pores,9
Proteoglycans, 45,47,65, 68
alveolar, 240,243
nuclear,3 Proton pumps, 2,4
Portal area,306,314-315 Protoplasm,1, 6
Portal system,hypophyseal, 193 Proximal convolutedtubules,324,325,328,330,332-333,
Portal triad,309 334-335
Portal vein, 306, 314-315 PSA (prostatespecificantigen),372
Posteriorchamber,396-397 Pseudopods,196
Posterior compa rtment, 398-399 Pseudostratified columnar epithelium, 32-3 3
Postganglionic cell body, 294-295 ciltateo, Jo-J/
Potassiumleak channels,127 Pseudostratifi ed epithelia,25, 26t
Potential Pseudounipolarcells,130
membraneacting,l27 P site,4,9
membraneresting,127 Psoriasis,220
Precapillarysphincters,148, 149, 155 PTH (parathy'roidhormone), 195,196
Precursorcells,9l P u b i s ,m a l e , 3 7 6
Preprocollagens, 47 Pulmonary artery,242
Prepuce, male,376 Pulmonarycircuit, 147,149
Presynapticmembrane,127 PtImonary vein, 242
Pricklecells,221 Pulp
Primary afferentterminal, I 36- I 37 splenic,168,171,1,74,190-191
Primordial follicles, 352-3 53 tooth, 257, 260, 264-265
Principal (chie| cells(seeChiefcells) Pulp arterioles,168
Process Pulp chamber, 264-265, 266-267
ciliary, 391, 396-397 Puip cords (of Billroth), 168, 190-191
phalangeal, 406407 Pupil,391, 396-397
Procollagen,4T Pupillary dilator muscles,391
Procollagenpeptidase,47 Pupillary sphincter,391,396-397
Proerythroblasts, 90, 93, 97 Purkinje cell layer,136-137
Progenitorcells,9l Purkinje cells,l0-l1, 129,I36-137
Progesterone, 345,346 Purkinje fibers, \07, 147-148,149,162-165

432 # Index
Pyloric gland, 279, 292-293 histological organization, 239-240
Pyloric sphincter,282 histophysiology,237
P y l o r u s2
, 78,285 respiratory portion, 236, 239-240, 243
Pyramidal cells, 129, 138-139 summary table,24lt
Pyramidal layer Restingpotential,127
external,lJ6-lJy Rete ridges, 262-2 63, 272-27 3
internal, 138-139 Retetestis, 369-370,373, i80-381
Pyramids, renal,323 Reticularcells,49,54-55, 167-168,168
thymic, 188-.189
Reticular connective tissue, 46, 54-55
*R Reticular fibers, 45,47, 49, 54-55, 107, 173, 174
Ranvier,node of, 130,131,142-143 splenic,.190-l9l
Rappaport,acinusof (liver acinus),306 Reticular layer, 228-229
Raynaud's disease,I 52 ReticulocFtes,94, 97
Rays,renal medullary, 328,332-333 Reticulum
RBCs (red blood cells) (seeErythroqtes) endosplasmic(seeRough endoplasmic reticulum; Smooth
Receptor-mediatedendocltosis, l, 4, 8 endoplasmic reticulum)
Receptor-mediatedtransport, 128 sarcoplasmic,103,105
Receptors,4,8 stellate, 268-269
acetylcholine, 127 Retina,384,387,389, 398-399
aldosterone,325 detached,390
dihydropyridine-sensitive (DHSRs),105 Retinal,389
hormone, 196 Retinal tunic, 384, 387,391-392
ryanodine (calcium channels), 105 Rhodopsin,389
T cell, 170 Rhodopsin-synthesizingrods, 384,387
transferrin,l2S Ribophorins,l,5
Rectaespuriae, 323, 33I Ribosomal subunit
Rerycling endosomes,2, 8 large,9
Red blood cells (RBCs) (seeEr)'throcltes) small,9
Red bone marrow,90 Ribosomes,1,3, 6, 20-21, 22
Red pulp, 168,172,174, 190-191 Ridges
Refractory period, 127 dermal (dermal papillae), 217, 221, 228-229
Regenerative cells,278, 279,286 epidermal, 221, 226-227
Regulatedsecretion, I rete, 262-263, 272-273
Relaxation, muscle, 105 Ring, tonsillar, 168,255
Relaxedtransitional epithelium, 3i RNA synthesis,3
Relaxin, 345 Rods and cones,384, 387,389,391, 398-399, 40H01
Renalcalculi (nephrolithiasis),327 Rokitansky-Aschoff sinuses,307
Renalcallx (calyces),324,328 Root hair plexus, 224, 225
Renalcapsule,323 Roots
Renal columns of Bertin, 323 dorsal, l34-135
Renalcorpuscle,323,331 hair , 221, 230-23 1
Renal cortex, 3i2-333, 334-335 ventral, .l J4-l JJ

Renal cortical lab;r'rinth,332-333, 334-335 Rotational accelerationsense,390

Renal failure, ac:ute,327 Rough endoplasmicreticulum (RER), 1-2, 2-3,4,6, 7, 18-19,
Renal filtration barrier, 325 20-21, 36-37,60
Renal medulla, 332-333, 338-i39 adipoclte,63
Renal papillae, 328, i38-339 hyaline cartilage,86
Renal papillary dtcts, 338-3 39 liver,320
Renal pelvis, 328 osteoblast,86
Renal pyramids, 323 peripheralnerve,144-145
Renin,278, 325-326 tracheal, 248-249
Reproductive system Round window, 388,395
female,343-367, 360 (seealsoFemalereproductive system Ruftled border, 88
and individual structures) Ryanodine receptors (calcium channels), 105
male, 369-386, 376 (seealso Male reproductive systemand
indiv idual structures) @S
RER (seeRough endoplasmic reticulum)
Residualbodies, 2, 4, 8 Saccule,388, 393,395
Respiration, mechanism of, 237 Sacs
Respiratory bronchioles, 236, 239,242, 24i, 250-251, 252-253 alveolar, 236, 240, 252-253
Respiratory system,235-254 dental,268-269
clinical considerations,237-238 endolymphatic, 390
conducting portion, 239,242, 245-246 S a l i v a , 2 5 53, 0 4

Index & 433

Salivaryglands,31, 255,257, 303, 304, 306,3 I 0-3 1t, 3 I B-3 I g gallbladder, 307
S A ( s i n o a t r i a ln) o d e ,1 4 7 - 1 4 8 1
, 49 ovarian, 356-357
Sarcolemma,103, 109,120-121,124 small intestinal, 296- 2 97
Sarcomere,108,110-l I 1, I 12-l 13, 114-116 stomach,283
Sarcoplasm,lO3,109 uterine,348
Sarcoplasmicreticulum, I03, 105 Serotonin,148, 195,280t
Sarcosomes, 103 Serousacinus(acini), 31, 310-311, 40H01
Satellitecells,107,I10-1II Serouscells,31, 318-319
Scalaqnnpani, 388,390, 395,402403,40H05 Serousdemilune, 31,16O-161,310-31I
Scalavestibuli,388,390,395,402403,404405 Serousglands, ofvon Ebner, 258,270-271, 272-273
Schmidt-Lantermanincisure,142- 143 Serousunits, 160-16-l
Schwann cells, I I 4- 1I 6, 126, l3O, 13 1, 140-t 41, I 42- I 43 Sertoli cells, 369,370, 378-379
cytoplasm,144-145 Serum,89
Sclera,384, 387, 391, 396-397, 398-399 Serum thymic factor, 172
Scrotum, 369,376 Sexuallytransmitted diseases(STDs), 346
Scurvy,48 Sharpey'sfibers, 70, 72
Seasonalaffectivedisorder(SAD), 197 Sheath
Sebaceouscells,225 connective tissue,230-23 1
Sebaceousducts,226-227, 228-229, 230-231 external root, 2j0-2j1
Sebaceousglands, 404 I, 218, 221, 222, 225, 228-229, 230-23 I, hair,221
262-263, 348, 366_367 internal root, 225, 230-231
of eye,392 myelin, 126,130,142-143,144-145
S e b u m ,2 1 8 ,2 2 1 , 2 2 5 periarteriallymphatic (PALS), 168,17l-172, 19O-19I
Secondmessengersystems,193 Sheathedarterioles,168
Secretin,278,280t, 303 Shelf,bony dental, 274-27 5
Secretions,40-41 Sigmoidcolon, 278,286
constituted,I Signalhypothesis,,t-5
regulated, I Signaling molecules,4
Secretoryducts,4H.l Signal peptidase,5
Secretorygranules,3, 6 Signalrecognitionparticles(SRPs),5,9
Secr etory v,nits, 230-2 j 1 SIGs(surfaceimmunoglobulins),92, 17|
Selectivepermeability, t50 Simple columnar epithelium, 32-33, 58-59
Semen,369, 371-372 Simple cuboidal epithelium, 32-33
Semicircularcanals,388, 390, 393,395 Simplediffusion,4
Semicircularducts,390 Simple epithelium, 25, 26t, 3 I
Semilunar valves,149 Simple squamous epithelium, 32-33
Seminalfluid, 372 Sinoatrial(SA) node, 147-148,149
Seminal vesicles,369, 370, 372, 373-374, 376, 382-383 Sinuses
Seminiferous tubules, 369, 373, 378-379, 380-381 lactiferous, 348
Senses(seeEar; Eye) Rokitansky-Aschoff, 307
Sensoryganglia,I40-141 subcapsularlymph node,
Sensoryneurons,125 urethral,374
Sensoryreception, 27 Sinusoidalcapillaries,150,J55
Sensoryterminals,117 Sinusoidallining cells,309,316-317,320
Septum(septa) Sinusoids,148
connective tissue,56-57 liver, 306, 309, 314-315, 320
ganglionic,140-141 lymph node, 182-183,184-185
interalveolar, 240, 242, 243, 252-253 pit]uitary, 204-205
interdental, 274-275 splenic, 190-191
liver,3ltt-315 S k e l e t am
l u s c l e ,1 0 3 - 1 0 4 1
, 0 7 , 1 0 81, 0 9 , 1 1 0 - 1 1 1 1, 1 2 - 1 1 3
pancreatic,306 Skeletalmuscfefibers,I 14-116
pancreatic connective tissue,3I 2-3 13 Sktn, 2I7-218, 224 (seealso Integument)
peripheral nerve, I 42-I 43 clinicalconsiderations,220
splenic, I90-i91 dermis,219,22\,224, 226-227
testicular, 378-379 epidermis, 221, 224, 226-227, 228-229
thymic, 188-189 eyelids,400401
SER (seeSmooth endoplasmic reticulum) histological organization, 221
Seromucousglands, 173, 235, 239,246-247 histophysiology, 2 I 9
Serosa malignanciesof, 220
atrmentarycanat,2// thick,226-227
bladder,329 thin,228-229
dtodenal, 29tL-295 Skin appendages, ZZI-222
esophageal,288-289 SLE (systemiclupus erythematosus),48

434 fl Index
Sliding filament model, of muscle contraction, 104 S p i n a lc o r d , 1 2 - 1 3 , 1 2 9 ,1 3 1 ,1 3 4 - 1 3 5
Small intestine, 277,279-280,283, 285, 296-297 Spindles,muscle,104,.l17
Small ribosomalsubunit, 9 Spiral ganglion, 402403, 404405
Smear polar cellsof, 390
blood,98-99 Spiral lamina, osseous,406407
bone marrow, 98-99, 100,101 Spiral ligament, 404405, 406407
Papanicolaou(Pap),3a6 Spiral organ of Corti, 392,402403, 40E-105,406407
Smooth endoplasmic reticulum (SER),2, 6, 7, 22 Spiralsulcus
alimentarycanal,281 internal, 406-407
liver,304 outer,40H07
S m o o t hm u s c l e ,1 0 4 ,1 0 6 ,1 0 7 , 1 0 9 ,1 1 8 - 1 2 1 , 1 5 31, 5 6 ,1 8 0 - 1 8 1 Spleen,168,174,176,190-191
alimentary canal,277 Splenicseptum,190-l9J
a r l e n a t ,J ) d - t 5 y Splenicsinusoids,190-191
bladder, 34U341 Spongiocltes,195,2 10-2I 1, 2 12-213
bronchiolar, 250-25 I Spongy(cavernous)urethra,374
ductus epididymis, 382-383 Squames,217,226-227
duodenal, 294-295 Squamouscell carcinoma, skin, 220
eye,39I, 396-397 Squamousepithelium, 25, 26t, 3 1
gallbladder,316-317 cofneat, Jvo-Jv/
histophysiology, 106 keratinized,3l
fung,252-25j nonkeratinized, 3 l
mammary gland,366-367 simple,32-33
prostatic, 384-385 stratifi ed keratinized, 34-35
splenic,190-191 stratifi ed nonker atinized, 34-3 5
testicular,380-381 SRP (signal recognition particle), 5
veter,340-341 Sl/52 fragments,105
Sodium channels,127 Stab (band) cells,90, 94, 97
Sodium pump, 325 eosinophilic,l0l
Soft palate, 272-273 Stapes,388,389,395
Soma, 12-13, 125-126 S t a r tc o d o n , 4 , 9
ganglionic,140-141 Staticequilibrium, 390
Somaticnervoussystem,125 Stellate(granule)cells,129,136-137
Somatostatin, 278, 280t Stellatereticulum, 268-269
Somatotropes,214 Stem cells
Somatotropin,194 d:uodenal,294-295
Sonichedgehog,256 hemopoietic,53
Space multipotential, 89-90, 9 I
axra\ r I / pluripotential,89-90, 9l
Bowman's(urinary), 324,328,331,332-333,334-335,3i7 intestinal, 296-297
ofDisse, 306,309,320 lyrnphoid (CFU-Ly),9i
enamel,200-26/ myeloid,9l
intermembrane,l, 7 Stenosis,valvular,152
intervillous, 364-365 Stereocilia,14- I 5, 25, 27, 390
matrix, 1,7 seminal vesicles,382-383
of NueL406407 Steroid-based hormones, I 96
periaxial, l17 Stomach, 278, 282-283, 285
Specificgranules,93 cardia,288-289
Spermatazoa, 369 fundic, 290-29 1, 292-29 3
Spermatids,378-379 histophysiology, 279
haploid, 369,371,377 Stomatitis,herpetic,256
Spermatocytes,369, 378-379 Stones,kidney (nephrolithiasis),327
Spermatocytogenesis, 371 Stratified epithelium, 25, 26t, 3l
Spermatogenesis, 369,37I, 376,377 columnar, 3l
Spermatogonia,369,37l, 373,377,378-379 cuboidal,31,34-35
Spermatozoa,378-379, 380-381,382-383 squamous
Spermiogenesis, 37l, 377 keratinized, 34-35
S phase,3 nonkeratinized, 34-35
Sphincter Stratum basale,217,221,224, 351
bladder,329 Stratum corneum, 2I7 ,221, 224, 226-227, 228-229, 232-233
precapillary, 148, 149, 155 Stratum functionale,351
pupillary, 39r,396-i97 Stratum germinarivtm, 226-227, 228-229, 232-23i
pyloric,282 Stratum granulosum,217,221,224,226-227
Sphincterpupillae,389 Stratum interme dirm, 268-269

Index X 435
Stratum lucidum,2\7 , 221,224,226-227 Synapticvesicles,136-137
S t r a t u mM a l p i g h i i , 2 1 7 Syncytial knot, 364-365
Stratum spinosum,217,221, 224,226-227,228-229 Syncytial trophoblast, i64-365
Stratum vasculare,uterus,360-36I Synqtiotrophoblast,345
Striatedducts,3.1,304 Syndecan,256
Striatedmuscle,103 Systemiclupus erlthematosus (SLE), 48
Stria vascularis,392-393, 404405
Stroma
corneal,396-397
@T
ovarian, 352-353, 356-357 Tarsal gfands, 392, 40H01
prostatic,374, 384-385 Tarsal plate, 392, 400401
seminiferoustubules,373 Tastebuds, 255,258,261,270-271,272-273
testicular,378-379, 380'381 Tastecells,26l
uterus,360-36.1 Tay-Sachsdisease,5
Subarachnoidspace,1j4-1 35 TCA cycle, 1
Subcapsularlymph node sinus, 182-183 T cell receptor(TCR), 170
Subendothelialconnectivetissue,153 T-cell receptor (TCR) surfacedeterminant, 92
Sublingual glands,424 3, 306, 3 10-3 11, 3 18-3 19 T cells (seeT lymphocytes)
Submandibular glands,4243, 306, 310-31 1 Tectorialmembrane,388,390, 392,395,40+405, 406-407
) u D m u c o s al,, / , / Teeth,257, 260, 264-265, 274-275
bladder,340-341 Telopeptides(propeptides),47
dtodenum, 294-295 Tenascin,256
esophagus,282, 288-289 Terminal arterialcapillaries,168
lar ge int estine, 298-2 99 Terminal arterioles,148
small intestine, 296-2 97 Terminal bars,27
stomach, 282,290-291 Terminal bronchioles, 236, 239,242, 250-251
trachea,239,246-247 Terminal cisternae,108
vagina, 348 Terminal glycosylation, 5
Subperiosteal bone collar, 7 l, 7i, 84-85 Terminal interalveolar ducts, 346
S u b s t a n cP
e,280t Terminals
Subunit newe,114-116
largeribosomal,g primary afferent,136-137
small ribosomal,g sensory,I l7
Succedaneouslamina, 2 68-269 T er minal villi, 364- 365
Sulcular epithelivm, 266-267 Tertiary granules,9l
Sulcus(sulci) Testicular cancer,372
grngrval,2o0-26/ Testis,373,378-379
spiral r ete,369-370, 373, 380-381
internal, 406407 undescended(cryporchidism),372
outer,406407 Testosterone,371
Superior longitudinal mtscle, 270-27 1 Thecaexterna,343, 350,352-353,354-355
Supportingcells,140-141 Theca goblet cells, 12-13, 4041
Suprachoroid lamina, 396- i97 Theca interna, 343, 345,347, 350, 352-353, 354-355
Supraoptic hlpothalamic nuclei, 194 Theca lutein cells,354- 355, 35A-357
Suprarenalglands,195, 197,199-200,202,210-211, 212-213 T-helper cells,167, 170
clinicalconsiderations,I 98 Thin (actin) filaments,3
innervation,203 \avLtt) LJ/

Surfaceabsorptive cells,278, 279,286, 294-295 Thoroughfarechannels,148, 149

Surfaceepithelial cells,298-299 Thrombocytes(platelets),89, 93, 98-99
Surfaceimmunoglobulins (SIGs),171 Thromboplastin,tissue,9 I
SurfaceIining cells,279, 290-291, 292-293 Thymic (Hassall's)corpuscles,168, 188-189
Suspensoryligaments, ocular, 391, 400401 Thymic-dependent antigens, I 70
Sustentacuiarcells,244-245, 26 1, 402403 Thymic involution, 174
Sweatducts,222,225 Thymoqtes, 172,174
Sweatglands, 56-57, 218, 221, 222, 224, 225, 228-229, 230-2 31, rnymosln, r /z
232-233, 234, 348, 366-367 Thymus, 168-169,178
apocrine, 224, 225, 230-231 Thyroglobulin, 192, 196,202
eccrine,4041, 224, 225, 230-2 3 I Thyroid gland, 192, 199,202, 208-209
Sympatheticganglia,140-l4l clinicalconsiderations,I 98
Sympathetic nervous system, 125 Thl"roid hormone, 196-197
Synapses,1,25-126,1 36-137 Thyrotropes,2l4
Synaptic cleft, 104 Thyrotropin (TSH), 194,196,345

436 m Index
Tissue convoluted,330
adipose,46,48, 49,56-57, 182-183,210-211 distal, 324, 328, 332-333, 334-3 35
connective (seeConnective tissue) proximal, 324, 325,i28, 332-333, 334-335
episcleral,396-397 dentinal,257 , 264-265, 26G267
erectlle, 384-385 seminiferous, 369, 373, 37e-379, 380-381
hematopoietic, 8rt-85 T,104,105
lymphoid (seeLymphoid tissue) uriniferous, 323, 330, i32-333, fA-f9
nervous, 125-146 Tubuli recti, 369-370, 373, 380-381
Tissuethromboplastin,91 Tubuloacinar (alveolar) glands
Titin, 104 mued,4243
T killer (cytotoxic)cells,167, 170,178
mtcous,4243
T lymphocytes,92,168, 170,175, 190-191
serous,4243
MHC restricted,170
Tubulovesicular system,279
T memory cells,170,178
Tufts, enamel, 264-265, 266-267
Tongue, 257-258, 270-272
Tumor formation,28
Tonsillar crypts, 184-185
Tunic
Tonsillar ring, 168, 255
of eye,398-399
Tonsils,173, 184-185,255, 258,261
fibrous ofeye (corneosclerallayer), 384, 387,391
Tooth development (odontogenesis),258, 260, 268-269
retinal, 384, 387,391-392
Trabeculae,66, 80-8 1, 82-8 3
vascularof eye (uvea), 384, 387, 391
oony,6/
fibrous, of penis, 384-385 Tunica adventitia,148,153,154,156,15A-159,160-161
lyrnph node, 182-183,184-185 Tunica albuginea
pinealbody, 212-2) 3 female, 343, 347, 352-353
salivary,310-31 1 male, 369, 372,378-379, 384-385
spleen,.190-i9i Tunica fibrosa, 389
thyoid gland,208-209 Tunica intima, 148,153,154, 156,158-159,160-161
Trachea,239,246-247 Tunica media, 148,153, 154,156,158-159,160-161
Tracheali5muscle, 239 Tunica propria, 373
Tracts Tunica retina,389
hypothalamo-hypophyseal, 194 Tunica vasculosa,378-379, 389
neural, 126 Tunnel of Corti, 392, 40H07
Transferrin receptors, 128 Tympanic cavity, 388, 395
Transfer vesicles,2, 23 Tympaniclip,406407
trans-Golginetworls 2,7,9, 2i,47 Tympanic membrane, 388, 389, 395
Transitionalepithelium, 25,26t, i1, 34-35 Tl.rosinase-containingvesicles,219
bladder,324,340-i41 Tl,rosine, 196,219
Transitionalzone,of lips, 257
Transport
active,128
{FU
passive,4 Ulcerative gingivitis, 256
receptor-mediated,I28 Ultrafiltrate formation, 325
Transversecolon, 278, 286 umDlllcat corq, J4-))
Triads,skeletalmwcle, 112-113 Undecalcified ground bone, 8G-8.1
IRNA,3 comPact,71
initiator,4,9
Unilocular adiposetissue,48
Trophoblasts, 348
Unipolar neurons,125,140-141
syncytial, 364-j65
Units
Tropocoliagen molecules, 45, 47, 52
secretory,230-2j1
Tropomodulin, 105
serous,160-l6l
Tropomyosin, 105
Unmyelinated fiber, 1i6-l i7
Troponins, 105
Urate oxidase,2
Trypsin, 105
Ureteral adventitia, 340-341
TSH (thl,rotropin), 194,196
Ureters,328,340-341,376
I s u p p r e s s ocre l l s , 1 6 7 , ' 1 7 01,7 8
Urethra
T t u b u l e s , 1 0 4 ,1 0 5
female, 324
Tubes
auditory (eustachian),388,395 male,369,374,i76, 384-385
fallopian (seeOviducts) cavernous(spongy),374
Tubular necrosis,327 Urethral sinus,374
Tubules Urinary bladder,324, 328-329, 340-341, 376
collecting,323,3i0 transitional epithelium, 34-3 5, 324, 340-341

lndex tr 437
Urinary system, 323-341 Portal,306,314-315
clinical considerations, 327 pulmonary,242
extrarenalexcretorypassages, 324 suprarenal gland,,210-21 1, 212-213
histological organization, 328-329 Ventral horns, lZ9, 134-135
histophysiology,325 Ventral roots, 134-135
kid,ney, 323-324, 330, 332-3 33 Ventricles
Urine laryngeal, 235, 244-245
blood in (hematuria),327 third,204-205
concentrationof, 326 Ventricular folds, 244-245
Uriniferous tubules,323,330,332-333, 338-339 Venulae rectaespuriae, fA-n9
Urogastrone,278,280t Venules, 153-154, 160- I 6I
Uterine myometrium, .ll8-ll9 bladder, 340-341
Uterus, -154 360-361, 362-363 tesucular,J/6-J/v
responseto hormones,345 Vermillion zone,262-263
Utricle, 388, 390, 393,395 Vesicles
Uvea,384, 387, 391 clathrin-coated,2, 4, 8
condensing,22, 2j
EV matrix,68
pinocytic, 144-145
Vacuoles seminal,369,370,372,373-374,376,382-383
intestinalcells,300 synaptic,136-137
osteoblast,86 tfansref, z, /, z)
osteoclast,88 tyrosinase-containing,2 I 9
Vagina,344,J48,-150,364-365 Vessels
Vallatepapillae,26l arcuate,332-333
Valve defects,152 capsular,332-333
Valve leaflet, 162-165 interlobular, 332-333
Valves Yestibtiar lip,406407
anal,285 Vestibular membrane, 390, 404405
heart, 149,162-165 Vestibule
lymphatic, 153, 182-183 of inner ear, 390 402403
semilunar,149 laryngeal, 235, 2i9, 244-245
Valvular incompetency, 152 oral,255
Vahular stenosis,152 Vestibulocochlearnerve, 402403
Vasarecta,326,328 villi
Vasavasorum, 149,153, 154,156,155-159 anchoring
Vascular elements, ovarian, j 54-j 55 chorionic, 364-365
Vascularplexus,22I placental,35l
Vascular pole, kidney, 334-j 35 chorionic, 348
Vascularsupply (seeBlood vessels) duodenal, 294-295
Vascular system, 147 (seealso Bloodvesselsand specific intestinal, 296-297
components) microscopic,279
arteries,148,149-150, 154 peripheral nerve, 142-i 43
arterioles, 160-l 6l small intestinal, 278, 285
capillaries,148, 155,i60-161 terminal, 364-365
clinicalconsiderations,152 Vimentin, 106
lymphatic, 150 (seealso Lyrnphoid tissue) Viscera,innervation, 203
veins, 148,I50, I53, 154 Visceral pleura, 237, 242
venules, 153-154, 160-1 61 Visual accommodation, 391
Vasculartunic, ofeye (uvea),384 387,391 Visual acuity, 389
Vas (ductus)deferens,369-370,372,373,376, 382-383 Vitamin A, 304,389
Vasectomy, 372 Vitamin deficiency,48
Vasoactiveintestinal peptide (VIP), 2801 bone and cartilageeffects,69
Vasodilation,149-150 Vitreous body, 384,387
Vasodilatorsubstances, 148 Vocal folds, 239,244-245
Vasopressin(antidiuretichormone,ADH), 194,326 Y o calis mtscl e, 244-2 45
V e i n s ,1 4 8 ,1 5 3 , 1 5 4 Volkmann's canal, 66, 7 1, 72, 78-79
arcuate,323 Voltage-gatedcalciurn channels, 127
central,314-315 Voltage-sensitiveintegral proteins, 105
interlobular,323 Von Ebner's glands, 258, 270-27 1, 272-273
muscular, 158-159 Von Willebrand'sfactor,9l

438 ft Index
$w Zona arctata,40H07
Zona fasciculata,195, 197, 200, 210-21 1, 212-213
Wall, nail, 2j2-23j Zona glomerulosa,195, 197,200,210-211
Warts (verrucae),220
Zona pxtinata, /nH07
Water, absorption of, 281
Zona pellucida, 343, 347, 350, 352-353, 354-355
White blood cells (WBCs) (seeLeukoqtes)
Zona reticularis, 195, 197, 200, 210-21 1, 212-213
White matter, 129,136-137,138-1i9
cereDellar, 1Jo-[ J / Zones
cerebral, 129 of calcifiing carilage, 82-83
spinalcord, lZ9, 134-135 of cell maturation and hypertrophy, 82-83
White pulp, 168,171, 174, 190-191 of cell proliferation, 82-8j
Window cell-rich of tooth, 264-265
oval,389 clear,88
round,388,395
ofepiphyseal plate, 7l
Wiskott-Aldrich syndrome, 172
H, r03, 1 10-111, 112-113
Woven (primary) bone,67
marginal, 168,174
*Y splenic,190-191
transitional, of lips, 257
Yellow bone marrow, 90 vermillion, 262-263
,{il z Zonulae adherentes,25, 27, 30
Zonulae occludentes,25,27, 30, 38-39, 37I
Z discs,104, 105, I 1O-l I 1, I 12-t 13,124 Zymogenic cells,278, 279, 285
Zellweger'sdisease,5 Zymogen granules, 12-1 3, 3 12-3 13

Index r 439