Jubb, Kennedy & Palmer's Pathology of Domestic Animals

2340 Pages·2007·316.52 MB·English

by  M. Grant Maxie (Eds.)

srotubirtnoC
VOLUME 1 John .F Van Vieet .MVD .DhP etomolpiD PVCA
School of Veterinary Medicine
Pamela .E Ginn .5B .MVD PVCAetomolpiD
Purdue University
Department of Infectious Diseases and Pathobiology
West Indiana Lafayette,
College of Veterinary Medicine
USA
University of Florida
,ellivseniaG Florida
Brian Witcock R ,MVD DhP
USA
Histovet Surgical Pathology
Guelph, Ontario
J0anne .E ..LK Manset[ .MVD .SM etomolpiD PVCA Canada
Department of Veterinary Pathobiology (Formerly: Department of Pathobiology, Ontario
College of Veterinary Medicine Veterinary College, University of Guelph, Canada)
saxeT A&M University
College Station, saxeT
Sameh Youssef BVSc MVSc .DhP DVSc etomolpiD PVCA
USA
Animal Health Laboratory
Laboratory Services Division
.M {3rant Maxie .MVD .DhP etomolpiD PVCA University of Guelph
Animal Health Laboratory Guelph, Ontario
Laboratory Services Division Canada
University of Guelph
Guelph, Ontario
VOLUME 2
Canada
Date .C Baker ,MVD .DhP etomolpiD RVCA etomolpiD ABT
Department of Toxicology and Pathology
Pauline .M hcikaR ,MVD ,?ihP PVCAetamolpiD
Portola Pharmaceuticals, Inc.
Veterinary Athens Diagnostic Laboratory
South naS California Francisco,
College of Veterinary Medicine
USA
University of Georgia
(Formerly: Department of Pathology, Colorado State
Athens, Georgia
USA) University,
USA
lan .K Barker ,MVD DhP
Thompson Keith BVSc .DhP PVCAetomolpiD
Department of Pathobiology
Pathobiology Section
Ontario Veterinary College
Institute of Animal Veterinary, and Biomedical Sciences
University of Guelph
Massey University
Guelph, Ontario
Palmerston North
Canada
New Zealand
Corrie .C Brown .MVD ,DhP PVCAetomotpiD
Beth .A Valentine ,MVO ,DhP etomolpiD PVCA Department of Pathology
Oregon State University College of Veterinary Medicine
College of Veterinary Medicine University of Georgia
Corvallis, Orlando Athens, Georgia
USA USA iiv
SROTUBIRTNOC
Jeff .L Caswei| ,MVD DVSc ,DhP etomolpiD PVCA Robert .A Foster BVSc ,DhP cSVCAM PVgAetomolpiD
Department of ygoloibohtaP Department of ygoloibohtaP
Ontario College Veterinary Ontario College Veterinary
University of Guelph University of Guelph
Guelph, Ontario Guelph, Ontario
adanaC adanaC
Jennifer .A Charles cSVB ,SVM PVCAetomolpiD Patricia .A Gentry DhP
Department of Veterinary ecneicS Department of Biomedical secneicS
ytlucaF of Veterinary ecneicS Ontario College Veterinary
University of Melbourne University of Guelph
airotciV,eebirreW Guelph, Ontario
ailartsuA adanaC
.M .A )ynoT( Hayes BgSc ,DhP etamolpiD PVCA W. Phitip Ladds cSVM cSVB ,DhP cSVCAF ,htePERF
Department of ygoloibohtaP etomolpiD PVCA
Ontario College Veterinary ,haballenooG New South selaW
University of Guelph ailartsuA
Guelph, Ontario
adanaC .M Maxi(e3 rant ,MVD ,DhP etomolpiD PVCA
Health Animal Laboratory
.M Maxi(e3 rant ,MVD ,?ihP etomolpiD PVCA Laboratory secivreS Division
Health Animal Laboratory University of Guelph
Laboratory secivreS Division Guelph, Ontario
University of Guelph adanaC
Guelph, Ontario
adanaC Richard .B Miiter ,MVD ,DhP etamolpiD PVEA
School of Medicine Veterinary
Sheitey .J Newman .MVD .cSVD etomolpiD PVCA Ross University
Department of ygolohtaP .tS tseW,sttiK seidnI
College of Medicine Veterinary
University of eessenneT Wayne E Robinson BVSc MVSc .DhP etomolpiD RVCA cSVCAM
,ellivxonK eessenneT Office Vice Chancellor's
USA University of tarallaB
airotciV,tarallaB
Margaret .J Stalker ,MVD ,DhP etomolpiD PVCA ailartsuA
Department of ygoloibohtaP
Ontario College Veterinary Donald .H Schtafer ,MVD ,DhP etomolpiD RVEA etomolpiD ,MVCA
University of Guelph TEAetemolpiD
Guelph, Ontario Department of Biomedical secneicS
adanaC College of Medicine Veterinary
Cornell University
J. Kurt Wittiams ,MVD ,DhP etamolpiD PVCA ,acahtI NewYork
Department of Pathobiology dna Diagnostic noitagitsevnI ASU
College of Medicine Veterinary
University Michigan State .V .E 0. )deT( Vale .MVD ,DhP etomolpiD PVCA
,gnisnaL tsaE Michigan Department of ygoloibohtaP
ASU College of Medicine Veterinary
University of sionillI ta Urbana-Champaign
3 VOLUME Urbana, sionillI
ASU
Char[es .C Capen ,MVD .DhP etomolpiD PVCA
Department of Veterinary secneicsoiB
Ohio University State
Columbus, Ohio
USA
! ecaferP
It was an honor to be asked by Drs. Jubb, Kennedy, and Palmer to organisms can be expected to be updated sa newer phylogenetic
assume the editorship of ygolohtaP of Domestic Animals. I studied analyses era reported.
from the first edition in Saskatoon sa a DVM student, used the sec- My thanks to the primary contributors to the 5th edition for their
ond edition sa a working pathologist, and encouraged production rigorous perusal of the literature in their areas of interest, for
of, and contributed to, the third and fourth editions. I'm delighted their addition of insightful information to their chapters, and for
to have been able to be part of this continuum. In this age of instan- their inclusion of many new figures. Additional contributors are
taneous global communication and virtually universal access to acknowledged in individual chapters, but I also offer my thanks to
databases through powerful search engines, does the need continue others who have labored in the background and provided helpful
for such print versions of textbooks? I firmly believe that printed suggestions and advice, including Dr. 1Lon Slocombe (University of
books continue to serve a useful function, partly through their Melbourne) and Dr. Murray Hazlett (University of Guelph). The
portability and ease of use, but primarily through provision of a chapter format of the 5th edition si similar to previous editions,
measured overview of important topics, with the relevance of com- with the exception of including Peritoneum within the Alimentary
peting topics put into perspective by authorities in the field. In system chapter. We have attempted to improve readability and
particular, this latest edition of these volumes si offered sa a com- usability by increased use of highlighting of text (boldfacing, itali-
prehensive, and we hope beneficial, overview of the diseases of the cization), use of bullet points, and updating of the graphic design,
major domestic mammals. including reorganization of tables of contents. The complete index
The literature and knowledge of veterinary pathology have to lla 3 volumes si printed in each volume, again sa an aid to read-
grown tremendously since publication of the fourth edition in ers. Of necessity, bibliographies have been pruned to save space,
1993. However, the foundations of these volumes remain sound, and with references being presented sa entry points to the literature
era firmly rooted in the detailed descriptions of gross and histologic through computerized search and retrieval systems embodied in
pathology recorded by Jubb and Kennedy in the first edition. major databases, such sa PubMed.
Etiologies and pathogeneses have been clarified over time, with the My thanks to Elsevier, and formerly Academic Press, for their
major revisions of the fifth edition involving the addition of knowl- help and support throughout this project, with particular thanks to
edge gained from molecular Diseases biology. dating from antiquity, Rita Demetriou-Swanwick (Associate Editor, Health Professions)
such sa tuberculosis, are still with ,su diseases thought to be under and Joyce Rodenhuis (Commissioning Editor,Veterinary Medicine).
control, such sa leptospirosis, have re-emerged sa significant con- Louisa Welch (Editorial Assistant, Health Sciences) has done a fine
cerns, and new diseases and agents have evolved, such sa porcine job of assembling permissions for use of previously published mate-
circovirus-associated caused disease enicbryo P surivocrd .2 I hope that rial. We have attempted to contact lla contributors of figures from
we have captured significant changes, and have synthesized this new previous editions, and apologize to any that we were unable to
knowledge to provide a balanced overview of lla topics covered. contact or overlooked. My sincere thanks to Sue Nicholls, Senior
Keeping pace with changing agents and their changing impacts si of Production Editor, Keyword Group Ltd, for her diligent checking
course a never-ending challenge. We have used current anatomical and cross-checking of text and figures, and for her coordination of
and microbial terminology, based on internationally accepted copyeditors, typesetters, and proofreaders.
reference sources, such sa the Universal Virus Database of the
International Committee on Taxonomy of Viruses http://www. Grant Maxie,
ncbi.nlm.nih.gov/ICTVdb/index.htm. Microbial taxonomy ,si of Guelph, Ontario, 2006
course, continually evolving, and classifications and names of
noitacideD
These volumes are dedicated to
Drs. Kenneth .V E Jubb, Peter C. Kennedy,
and Nigel C. Palmer, and to my family -
Laura, Kevin, and Andrea.
Drs. ,remtaP Jubb, dna ,ydenneK white working no the 3rd edition, Metbourne, .3891
ysetruoC( of University of ).enruobteM
Bones dna joints
htieK nospmohT
)iseases of ~enob
dezilacoL skeletal saisatpsyd 24
SNOITAREDISNOC LARENEG Limb saisalpsyd 42
Skull 43
ERUTCURTS AND FUNCTION FO TISSUE BONE 2
munretS 34
Cellular elements 2
sbiR 34
enoB matrix 4
sivleP 34
Matrix noitazilarenim 5
earbetreV 44
Structural noitazinagro fo enob eussit 6
lacivreC larbetrev citonets yhtapoteym relbbow( )emordnys 44
noitamroF fo [ainarc senob 7
CITENEG DISEASES INDIRECTLY GNITCEFFA
noitalugeR fo formation bone dna noitproser 7
THE NOTELEKS 74
gniledomeR fo bone eussit 9
Markers fo bone gniledomer 9 [amososyL storage sesaesid 74
cipotcE mineralization dna noitacifisso 01 latinegnoC erythropoietic airyhprop 48
DERIUOCA ABNORMALITIES NI SKELETAL ,HTWORG
SENOB AS SNAGRO 31
,TNEMPOLEVED AND GNILEDOMER 48
Development dna anatomy 31
Nutritional secnalabmi dna snixot gnitceffa skeletal growth 49
noitalugeR fo htworg [aesyhp 51
lareniM secnalabmi 05
gniledoM 61
nimatiV secnalabmi 55
doolB ylppus 71
tnalP seiticixot 06
METROMTSOP EXAMINATION FO THE NOTELEKS 81 rehtO seiticixot 26
ssorG noitanimaxe 81 anomalies Skeletal fo nwonknu ygoloite 26
seuqinhcet lacigolotsiH dna sniats 81 deformity [imb Angutar 36
noitaraperP artifacts ni lacigolotsih snoitces 81 tceffE fo suoitcefni agents no deve[opment sketeta[ dna
laboratory Other seuqinhcet 91 gnitedomer 66
CILOBATEM BONE DISEASES 76
ESNOPSER OT MECHANICAL SECROF AND INJURY 91
muic[aC dna sisatsoemoh surohpsohp 68
lacinahceM secrof 91
sisoropoetsO 69
htworG plate damage 02
stekciR dna aicatamoetso 57
[aetsoireP damage 12
suorbiF yhportsydoetso 82
erutcarF repair 12
SISORCENOETSO 88
sepyT of serutcarf 12
ssecorP of erutcarf repair 22 ygolohproM dna fate fo citorcen enob 89
snoitacilpmoC of erutcarf repair 22 Legg-Catv~-Perthes esaesid 19
detaler-ssertS snoisel ni sesroh 32 DISEASES INFLAMMATORY FO SENOB 29
LATELEKS DYSPLASIAS 42 [airetcaB snoitcefni fo senob 29
citocyM snoitcefni fo senob 99
dezilareneG skeletal saisatpsyd 52
Vira[ snoitcefni fo senob 001
saisalpsydardnohC 52
Metaphysea[ yhtapoetso 101
sisenegoetsO atcefrepmi 33
eninaC sitietsonap 401
sisortepoetsO 83
latinegnoC sisotsorepyh 04 CITOTSOREPYH DISEASES 601
sisotamordnohcoetsO 14 ratubidnamoinarC yhtapoetso 601
cihtapoidI lacofitlum yhtapoetso 14 cihportrepyH yhtapoetso 701
; AND JOINTS Structure and function of bone tissue
Canine diffuse idiopathic skeletal sisotsorepyh 108 dysplasia Hip 641
Canine sisonoozotapeh 901 snoitaxuL dna snoitaxu[bus 741
TUMORS AND TUMOR-LIKE LESIONS FO BONES 110 DEGENERATIVE DISEASES FO JOINTS 148
Bone-forming tumors 111 joints Synovia[ 148
,amoetsO gniyfisso dna ,amorbif suorbif aisalpsyd 111 evitorenegeD joint sesoesi8 of sesroh 151
amocrasoetsO 211 evitorenegeD joint sesoesid of sgod 153
Cartilage-forming tumors 118 evitarenegeD joint sesoesid of el~oc 351
omordnohC 811 joints Cartilaginous 451
omordnohcoetsO 911 noitoimeH of lorbetrevretni sksid 51 5
rolubolitluM tumor of enob 911 sisolydnopS 51 7
omocrosordnohC 121
INFLAMMATORY DISEASES FO JOINTS 158
suorbiF bones tumors of 421
suoitcefnI arthritis 161
bones tumors of Vascular 421
airetcaB 162
Other primary bones tumors of 521
rehtO suoitcefni stnega 170
bones tumors of Secondary 721
Miscellaneous inflammatory joint structures of lesions 172
Tumor-like bones of lesions 921
sitisruB 271
)iseases of oint~ sititydnopsoksiD 371
muicloC detoicossa-totsyrc yhtoporhtno )tuogoduesp( 173
GENERAL CONSIDERATIONS 130
suoitcefninoN (immune-mediated) arthritis 174
suorbiF joints 131 evisorE sitirhtro 571
..... joints Cartilaginous 131 evisorenoN sitirhtro 177
joints Synovia[ 231
TUMORS AND TUMOR-LIKE LESIONS FO JOINTS 179
esnopseR of articular cartilage to injury 531
tumors Benign dna tumor-tike joints of [esions 179
DEVELOPMENTAL DISEASES FO JOINTS 631
joints Matignant tumors of 180
~ Osteochondrosis 631
ACKNOWLEDGMENTS
This update of Chapter 1 si based no the foundation developed ni previous contributions have also come from the transparency cot[ections of pathology
editions by Dr neK Jubb and, more recently, Dr Nige[ Palmer. si tI na honor to departments at Ontario Veterinary ,ege[toC Texas A&M University, Massey
fot[ow ni their footsteps. I am grateful to the many pathologists who have con- University, North Carolina State University, Ohio State University, University of
tributed ittustrations to this chapteE ni particular Dr boR Significant Fair[ey. Ca[ifornia-Davis, and Western College of Veterinary Medicine.
CONSIDERATIONS GENERAL
seldom examined in detail during routine necropsy and it si highly
likely that many disorders go undiagnosed. Even in cases where a
Bone si a highly specialized connective tissue, its properties depend- bone disease si suspected, many veterinary pathologists do not feel
ing largely on the unique nature of its extracellular matrix. In addi- confident in their approach to making a diagnosis. Familiarity with the
tion to providing mechanical support and protecting key organ ssorg and cipocsorcim anatomy ,senob:jo factors bone regulating formation and
systems from traumatic injury, bone si intimately involved in the ,noitproser and an understanding of the sesnopser of bone ot injury era key ot
homeostasis of calcium, an essential cation in a wide range of bodily an noitaicerppa f.o pathogenesis the and pathology of bone .sesaesid The ini-
functions. In spite of their apparent inertia, bones era dynamic ,snagro tial sections of this chapter will therefore focus on these aspects and
undergoing constant remodeling thwughout life. Even in mature individu- outline an approach to examining the skeleton at necropsy.
als, bone tissue si continually undergoing localized resorption and
replacement in response to the demands of mineral homeostasis and
ERUTCURTS AND FUNCTION FO BONE TISSUE
alterations in mechanical forces.The dynamic nature of bones si well
illustrated by their impressive powers of repair following injury.
Cellular elements
Because of the difficulties associated with processing mineralized
tissue, the study of bones, both by researchers and diagnosticians, Bone tissue consists of four cell types" osteoblasts, osteocytes, lining
has lagged behind that of most other organ systems. The skeleton si ,sllec and osteoclasts. The first three are derived from primitive
; AND JOINTS Structure and function of bone tissue
Canine diffuse idiopathic skeletal sisotsorepyh 108 dysplasia Hip 641
Canine sisonoozotapeh 901 snoitaxuL dna snoitaxu[bus 741
TUMORS AND TUMOR-LIKE LESIONS FO BONES 110 DEGENERATIVE DISEASES FO JOINTS 148
Bone-forming tumors 111 joints Synovia[ 148
,amoetsO gniyfisso dna ,amorbif suorbif aisalpsyd 111 evitorenegeD joint sesoesi8 of sesroh 151
amocrasoetsO 211 evitorenegeD joint sesoesid of sgod 153
Cartilage-forming tumors 118 evitarenegeD joint sesoesid of el~oc 351
omordnohC 811 joints Cartilaginous 451
omordnohcoetsO 911 noitoimeH of lorbetrevretni sksid 51 5
rolubolitluM tumor of enob 911 sisolydnopS 51 7
omocrosordnohC 121
INFLAMMATORY DISEASES FO JOINTS 158
suorbiF bones tumors of 421
suoitcefnI arthritis 161
bones tumors of Vascular 421
airetcaB 162
Other primary bones tumors of 521
rehtO suoitcefni stnega 170
bones tumors of Secondary 721
Miscellaneous inflammatory joint structures of lesions 172
Tumor-like bones of lesions 921
sitisruB 271
)iseases of oint~ sititydnopsoksiD 371
muicloC detoicossa-totsyrc yhtoporhtno )tuogoduesp( 173
GENERAL CONSIDERATIONS 130
suoitcefninoN (immune-mediated) arthritis 174
suorbiF joints 131 evisorE sitirhtro 571
..... joints Cartilaginous 131 evisorenoN sitirhtro 177
joints Synovia[ 231
TUMORS AND TUMOR-LIKE LESIONS FO JOINTS 179
esnopseR of articular cartilage to injury 531
tumors Benign dna tumor-tike joints of [esions 179
DEVELOPMENTAL DISEASES FO JOINTS 631
joints Matignant tumors of 180
~ Osteochondrosis 631
ACKNOWLEDGMENTS
This update of Chapter 1 si based no the foundation developed ni previous contributions have also come from the transparency cot[ections of pathology
editions by Dr neK Jubb and, more recently, Dr Nige[ Palmer. si tI na honor to departments at Ontario Veterinary ,ege[toC Texas A&M University, Massey
fot[ow ni their footsteps. I am grateful to the many pathologists who have con- University, North Carolina State University, Ohio State University, University of
tributed ittustrations to this chapteE ni particular Dr boR Significant Fair[ey. Ca[ifornia-Davis, and Western College of Veterinary Medicine.
CONSIDERATIONS GENERAL
seldom examined in detail during routine necropsy and it si highly
likely that many disorders go undiagnosed. Even in cases where a
Bone si a highly specialized connective tissue, its properties depend- bone disease si suspected, many veterinary pathologists do not feel
ing largely on the unique nature of its extracellular matrix. In addi- confident in their approach to making a diagnosis. Familiarity with the
tion to providing mechanical support and protecting key organ ssorg and cipocsorcim anatomy ,senob:jo factors bone regulating formation and
systems from traumatic injury, bone si intimately involved in the ,noitproser and an understanding of the sesnopser of bone ot injury era key ot
homeostasis of calcium, an essential cation in a wide range of bodily an noitaicerppa f.o pathogenesis the and pathology of bone .sesaesid The ini-
functions. In spite of their apparent inertia, bones era dynamic ,snagro tial sections of this chapter will therefore focus on these aspects and
undergoing constant remodeling thwughout life. Even in mature individu- outline an approach to examining the skeleton at necropsy.
als, bone tissue si continually undergoing localized resorption and
replacement in response to the demands of mineral homeostasis and
ERUTCURTS AND FUNCTION FO BONE TISSUE
alterations in mechanical forces.The dynamic nature of bones si well
illustrated by their impressive powers of repair following injury.
Cellular elements
Because of the difficulties associated with processing mineralized
tissue, the study of bones, both by researchers and diagnosticians, Bone tissue consists of four cell types" osteoblasts, osteocytes, lining
has lagged behind that of most other organ systems. The skeleton si ,sllec and osteoclasts. The first three are derived from primitive
; AND JOINTS Structure and function of bone tissue
Canine diffuse idiopathic skeletal sisotsorepyh 108 dysplasia Hip 641
Canine sisonoozotapeh 901 snoitaxuL dna snoitaxu[bus 741
TUMORS AND TUMOR-LIKE LESIONS FO BONES 110 DEGENERATIVE DISEASES FO JOINTS 148
Bone-forming tumors 111 joints Synovia[ 148
,amoetsO gniyfisso dna ,amorbif suorbif aisalpsyd 111 evitorenegeD joint sesoesi8 of sesroh 151
amocrasoetsO 211 evitorenegeD joint sesoesid of sgod 153
Cartilage-forming tumors 118 evitarenegeD joint sesoesid of el~oc 351
omordnohC 811 joints Cartilaginous 451
omordnohcoetsO 911 noitoimeH of lorbetrevretni sksid 51 5
rolubolitluM tumor of enob 911 sisolydnopS 51 7
omocrosordnohC 121
INFLAMMATORY DISEASES FO JOINTS 158
suorbiF bones tumors of 421
suoitcefnI arthritis 161
bones tumors of Vascular 421
airetcaB 162
Other primary bones tumors of 521
rehtO suoitcefni stnega 170
bones tumors of Secondary 721
Miscellaneous inflammatory joint structures of lesions 172
Tumor-like bones of lesions 921
sitisruB 271
)iseases of oint~ sititydnopsoksiD 371
muicloC detoicossa-totsyrc yhtoporhtno )tuogoduesp( 173
GENERAL CONSIDERATIONS 130
suoitcefninoN (immune-mediated) arthritis 174
suorbiF joints 131 evisorE sitirhtro 571
..... joints Cartilaginous 131 evisorenoN sitirhtro 177
joints Synovia[ 231
TUMORS AND TUMOR-LIKE LESIONS FO JOINTS 179
esnopseR of articular cartilage to injury 531
tumors Benign dna tumor-tike joints of [esions 179
DEVELOPMENTAL DISEASES FO JOINTS 631
joints Matignant tumors of 180
~ Osteochondrosis 631
ACKNOWLEDGMENTS
This update of Chapter 1 si based no the foundation developed ni previous contributions have also come from the transparency cot[ections of pathology
editions by Dr neK Jubb and, more recently, Dr Nige[ Palmer. si tI na honor to departments at Ontario Veterinary ,ege[toC Texas A&M University, Massey
fot[ow ni their footsteps. I am grateful to the many pathologists who have con- University, North Carolina State University, Ohio State University, University of
tributed ittustrations to this chapteE ni particular Dr boR Significant Fair[ey. Ca[ifornia-Davis, and Western College of Veterinary Medicine.
CONSIDERATIONS GENERAL
seldom examined in detail during routine necropsy and it si highly
likely that many disorders go undiagnosed. Even in cases where a
Bone si a highly specialized connective tissue, its properties depend- bone disease si suspected, many veterinary pathologists do not feel
ing largely on the unique nature of its extracellular matrix. In addi- confident in their approach to making a diagnosis. Familiarity with the
tion to providing mechanical support and protecting key organ ssorg and cipocsorcim anatomy ,senob:jo factors bone regulating formation and
systems from traumatic injury, bone si intimately involved in the ,noitproser and an understanding of the sesnopser of bone ot injury era key ot
homeostasis of calcium, an essential cation in a wide range of bodily an noitaicerppa f.o pathogenesis the and pathology of bone .sesaesid The ini-
functions. In spite of their apparent inertia, bones era dynamic ,snagro tial sections of this chapter will therefore focus on these aspects and
undergoing constant remodeling thwughout life. Even in mature individu- outline an approach to examining the skeleton at necropsy.
als, bone tissue si continually undergoing localized resorption and
replacement in response to the demands of mineral homeostasis and
ERUTCURTS AND FUNCTION FO BONE TISSUE
alterations in mechanical forces.The dynamic nature of bones si well
illustrated by their impressive powers of repair following injury.
Cellular elements
Because of the difficulties associated with processing mineralized
tissue, the study of bones, both by researchers and diagnosticians, Bone tissue consists of four cell types" osteoblasts, osteocytes, lining
has lagged behind that of most other organ systems. The skeleton si ,sllec and osteoclasts. The first three are derived from primitive
Diseases of bones Structure and function of bone t~ssue lll
.................................. ...... ............. ............................................................................................... .............. ...................................... .lllllllll
I!i ~
I ....
Figure 2.1 Active osteoblasts ni showing preparation cytotogica[ a the char-
nucleus, eccentric acteristic ciLihposab cytoplasm dna prominent .enoz ig[oG
bone resorption and formation are mediated. In addition to osteoid,
Figure 1.1 Active osteobtasts at site a of rapid bone formation ni a new- they produce an array of factors regulatory that are deposited in bone
born kitten. Note the eccentric nuclei, basophiLic cytoplasm and prominent
matrix and which play a critical role in bone remodeling.
Goigi zone ni many of the celts. Some have osteobLasts surrounded them-
Inactive osteoblasts, or bone-lining cells, are flattened cells
selves with osteoid to become osteocytes.
with few organelles that cover endosteal bone surfaces that are
undergoing neither formation nor resorption.Although barely vis-
osteoprogenitor cells of mesenchymal origin, which are present in ible in histological sections, these are the most abundant cells on
bone sa well sa other tissues, and which can be induced to differen- the endosteal surface of the adult skeleton and link with each other
tiate into osteoblasts under the influence of appropriate paracrine to form a functional barrier between the extracellular fluid compart-
and autocrine stimuli. Osteoclasts are derived from hematopoietic ment of bone tissue and that of surrounding tissues. Bone-lining
stem cells, probably of the monocyte series. cells are believed to be involved in calcium homeostasis by regulat-
Osteoblasts era responsible for manufacturing osteoid, the organic ing the exchange of calcium and other ions, such sa sodium and
component of bone matrix. Active osteoblasts, which line surfaces magnesium, between bone fluid and extracellular fluid, under the
where bone formation si occurring, have abundant rough endoplas- influence of parathyroid hormone. It si likely that bone-lining cells
rnic reticulum and a prominent Golgi apparatus, reflecting their role can produce osteoid and contribute to bone deposition should the
in protein synthesis. Histologically they appear sa plump, cuboidal demand arise at a site of previous inactivity. Endosteal osteoprogen-
cells with basophilic cytoplasm, their nuclei sometimes being polar- itor cells may be residents of this population of bone-lining cells.
ized away from the adjacent bone surface (Fig. 1.1).The typical mor- During active bone formation, about 10-20% of osteoblasts at
phologic features of osteoblasts are often more easily appreciated in regular intervals along a bone-forming surface surround themselves
cytologic preparations (Fig. 1.2). Not only do osteoblasts produce the with osteoid and become osteoeytes (see Fig. 1.1). These era the
osteoid, they play a role in initiating its mineralization, although the most abundant cells of bone tissue, residing in small spaces (lacunae) within
mechanism si not fully understood.The membranes of osteoblasts are the mineralized matrix. Newly formed osteocytes retain some mor-
rich in alkaline phosphatase, which appears to be involved in miner- phological and functional characteristics of osteoblasts, but sa they
alization of both osteoid and cartilage. The high level of alkaline mature and become embedded deeper in the mineralized matrix,
phosphatase activity measured normally in the serum of rapidly the amount of rough endoplasmic reticulum in their cytoplasm si
growing young animals presumably reflects the intense osteoblastic reduced considerably and they develop features more typical of
activity that si occurring in the developing skeleton.There si mount- phagocytic cells. Osteocytes maintain contact with adjacent osteo-
ing evidence that the osteoblast si the central cell through which cytes, and with bone-lining cells or osteoblasts on the surface, by a
network of branching cytoplasmic processes extending through
canaliculi. In routinely stained histological sections, the canaliculi are
not visible and only the nuclei of osteocytes are usually apparent.
Osteocytes era thought ot eb capable of producing and bone resorbing in
their immediate vicinity, thereby decreasing or increasing the size of
their lacunae. This process si known sa osteolysis. osteocytic The peri-
lacunar bone matrix lseiss heavily mineralized and more labile than
that in other areas. The action of osteocytes on this perilacunar
bone si believed to be important in regulating the concentration of
calcium and other minerals in the bone fluid compartment.
Because of the large surface area of mineralized bone exposed to
either osteocytes or their canaliculi, significant quantities of cal-
cium can be mobilized from this source very rapidly in response to
the demands of calcium homeostasis. Mthough osteocytes can
enlarge their lacunae by resorbing perilacunar bone matrix, this
process of osteocytic osteolysis does not play a significant role in
structural modifications of bones, or in the development of bone
lesions associated with disease processes.
Osteocytes probably survive for several years in the mature skele-
ton but eventually die, leaving empty lacunae. The gradual loss of
osteocytes si presumably a normal phenomenon, compensated by
the construction of new bone sa part of the remodeling process that
occurs throughout life. In disease states in which bone necrosis si a
feature, there si no immediate loss in structural integrity of the dead
bone tissue, but efforts to remove the remaining mineralized matrix
Figure 1.3 Muttinucteated osteoctast ni a shallow pit (Howship's
and replace it with new bone suggest that its function si impaired.
lacuna) no surface bone a undergoing resorption. the Note ruffted border of
Osteoclasts era primarily elbisnopser for noitproser of bone tissue. They the osteodast to adjacent the bone.
are probably related to monocytes and macrophages, which are capa-
ble of resorbing bone in vitro, but are sufficiently different histochem-
ically to suggest that they may possess a distinct stem cell. Osteoclasts
are rich in acid phosphatase and a range of other acid hydrolases,
lysosomes fuse with the cell membrane of the brush border.
packaged in primary lysosomes. The acid phosphatase isoenzyme
Fragments of degraded matrix are endocytosed by osteoclasts and
present in osteoclasts si tartrate-resistant, unlike the tartrate-sensitive further digested within secondary lysosomes.
acid phosphatase found in monocytes and macrophages. Osteoclasts
The potential rate of removal of bone by osteoclasts si much
are easily recognizable histologically sa large, multinucleated cells with
greater than the rate of formation by osteoblasts.An individual osteo-
eosinophilic cytoplasm, typically situated on bone surfaces and often
clast can erode approximately 400 Ixm 3 of bone, and travel 100 m~p
within shallow pits called Howship's lacunae. The presence of
across a bone surface, per hour. As a result, localized or generalized
Howship's lacunae on a bone surface si convincing evidence of previ-
removal of bone during the normal physiological processes of mod-
ous resorption at that site, even if no osteoclasts are present at the time eling and remodeling, or in disease states, can occur very rapidly.
of observation.Although not always apparent histologically, osteoclasts
Once osteoclasts have completed their required phase of resorp-
involved in active bone resorption have a highly specialized "ruffled"
tion, they most likely undergo apoptosis and disappear from resorp-
or brush border contiguous with the bone surface (Fig. 1.3).A clear
tion sites.This si characterized by condensation of nuclear chromatin,
zone adjacent to the brush border si free of organelles but contains loss of the ruffled border and detachment from the bone surface.
actin-like filaments, which may tsissa in anchoring the cell to the bone
Drugs that inhibit bone resorption have been shown to induce
matrix. This attachment of active osteoclasts to the bone surface si an
osteoclast apoptosis both in vitro and in vivo. Importantly, parathy-
essential requirement for resorption to occur, sa si the activity of a spe-
roid hormone promotes the survival of osteoclasts and in cases of
cific intracellular, membrane-bound tyrosine kinase. Deletion of the
either nutritional or renal hyperparathyroidism, surviving osteo-
gene coding for this enzyme in mice has been shown to induce
clasts are found in medullary spaces mixed with fibroblastic ele-
osteopetrosis, a disease characterized by defective osteoclastic activity.
ments. The abnormal persistence of osteoclasts in these sites si an
During osteoclastic bone resorption, an acid environment si important aid to the diagnosis of these conditions.
created in the narrow space between the cell and the bone surface.
Hydrogen and bicarbonate ions are generated from carbon dioxide
and water by the action of carbonic anhydrase II on the brush bor-
Bone matrix
der membrane of osteoclasts. An ATP-mediated proton pump, also
located on the brush border membrane, actively transfers hydrogen Bone matrix consists of an component, organic called osteoid, and an
ions into the extracellular space.The acidity of the local environment inorganic component comprised predominantly of hydroxyapatite crystals.
not only induces demineralization of the bone, it enhances the activ- The main constituent of osteoid (approximately 90%) si type I col-
ity of the acid hydrolases released from osteoclasts when primary lagen, which si also the predominant form of collagen in tendons,