Pathology Exam Iii

Front 1

Bone

Back 1

-Tissue and an organ
-Site of active construction and demolition
-Tuned in to physiologic homeostatic regulatory processes
-Changes over time are documented

Front 2

Homeostatic regulatory processes of Bone

Back 2

-Mineral balance
--Ca and PO4
-Hematopoetic system
-Endocrine system
-Adaptation to stress and external environment

Front 3

Appendicular skeleton

Back 3

-Long bones
-Proximal and distal limbs
-Cuboidal bones are short versions of long bones

Front 4

Axial skeleton

Back 4

-Flat bones
-Calvaria (bones of skull)
-Hyoid apparatus
-Ossicles
-Scapulae
-Pelvis
-mandibles
-Ribs
-Sternum
-Vertebrae
-Some portion forms like flat bones, some portions can form like long bones

Front 5

Long bones

Back 5

-Predominantly mesenchymal tissue, formed from mesoderm
-Bone, cartilage, and connective tissue
-Has adipose elements, blood vessels, hematopoetic elements, and nerves

Front 6

Long bone Structure

Back 6

1. Epiphysis: articular cartilage and subchondral bone
-articulates with other bones
-Grows with development circumferentially
2. Physis: growth plate
3. Metaphysis: narrowing zone just below metaphyseal growth plate
-Trabeculae divert stress down into compact bone
4. Diaphysis: shaft
-cortical bone with large medullary cavity

Front 7

Cartilage

Back 7

-Specialized connective tissue
-3 types:
--Hyaline
--fibrocartilage
--elastic cartilage

Front 8

Hyaline cartilage

Back 8

-Lines articular surfaces of synovial joints
-Undergoes endochondral ossification during bone development
-Acts as center for growth during development

Front 9

Fibrocartilage

Back 9

-Forms strong connections between connective tissues
-Menisci, intervertebral discs, tendons, and ligament insertions

Front 10

Cartilage basic components

Back 10

-Chondroblasts: immature and developmental cells
-Chondrocytes: mature cells within lacunae
-Extracellular matrix: mostly collagen fibers type II
-Hydrophilic ground substance acts as a "sponge"
--proteoglycans attract water
--glycosaminoglycans
--hyaluronic acid
-Has to be able to move and squish, move material in and out of matrix to provide cushion
-Water is an important part of cartilage

Front 11

Bone

Back 11

-Specialized form of connective tissue
-ECM is mineralized to very hard cement-like tissue
-Provides structure and protection for vital organs
-Allows for ambulation and frame for muscles
-Homeostatic organ
--contains hematopoietic elements
--controls mineral electrolyte balance
--Tuned in and connected to many different organ systems

Front 12

Bone cellular components

Back 12

-Pleuripotent stem cells, can be induced to form blood cells and inflammatory cells
-Osteoblast progenitors
-Osteoblasts
-Osteocytes
-Osteoclasts

Front 13

Osteoblasts
Osteocytes
Osteoclasts

Back 13

-Osteoblats: immature cells that build bone
-Osteocytes: mature cells that maintain bone
-Osteoclasts: macrophage/monocyte lineage cells that breakdown/resorb bone

Front 14

Bone ECM components

Back 14

-Organic component of Osteoid
-Inorganic component of hydroxyapatite

Front 15

Osteoprogenitor cells

Back 15

-Bone stem cells
-Only bone cell capable of undergoing mitosis
-Pluripotent, are able to differeniate into osteoblasts, chondroblasts, fibroblasts, adipose tissue
-Line periosteal and endosteal surfaces of bone
-Connected via connective tissue structure
-Flattened, spindle-shaped cells with elongated nuclei

Front 16

Periosteum

Back 16

-Lines outer surface of bones
--except at ends and at tendon/ligament insertion sites
-Tough outer fibrous layer
-Inner cellular cambium layer
--contributes to bone progenitor cells for new bone formation

Front 17

Endosteum

Back 17

-Lines inner surfaces of bone
-Lines compact and trabecular bone
-Thin layer of osteogenic cells
-Interface between hematopoietic marrow and bone

Front 18

Periosteal reaction

Back 18

-Forms healing callus on injured bone
-Periosteal reaction tends to be more exuberant than endosteal reaction
-Used in radiology to give diagnosis of processes

Front 19

Osteoblasts

Back 19

-Big, plump cells with big golgi
-Pump out protein
-Secrete large amounts of bone matrix
-Line bone-forming surfaces
-Make new bone

Front 20

Osteocytes

Back 20

-Bone maintenance cells
-"Grown up" osteoblasts
-"old ladies in rent controlled apartments"
-Maintain bone matrix
-Embedded within matrix lacunae
-Are able to synthesize small amounts of bone matrix for bone maintenance
-Are also able to resorb small amounts of bone matrix
--osteolytic osteolysis to maintain blood calcium homeostasis
-Communicate with external environment and each other via canaliculi
--thin cytoplasmic processes extend to periosteal/endosteal surface through canaliculi
-Detect stress, strain, microfractures
-Sense pressure changes in fluids

Front 21

Osteoclasts

Back 21

-Bone resorption cells
-Multi-nucleate cells
-Monocyte/macrophage lineage
-Eat large amounts of bone, dissolve bone
-Give bone a scalloped margin appearance

Front 22

RANK-Ligand

Back 22

-Produced by osteoblasts
-Osteoclast differentiation factor
-Promotes resporption and inflammatory cytokines
--TNF-b, IL-1, IL-6

Front 23

Factors contributing to proliferation and activation of osteoclasts

Back 23

-RANK-Ligand
-Osteoprotegerin
-Calcitonin
-Parathyroid hormone

Front 24

Osteoprotegerin

Back 24

-Produced by osteoblasts
-Acts as a decoy receptor for RANK-ligand and inhibits osteoclast activation
-Latch onto RANKL

Front 25

Calcitonin

Back 25

-Produced in C-cells of the thyroid gland
-Directly inhibits osteoclast resorption
-Causes osteoclast apoptosis

Front 26

Parathyroid Hormone
PTH

Back 26

-Produced in parathyroid glands
-Indirectly stimulates bone resorption
-DEcreases osteoblast osteoid production
-Increases collagenase secretion
-Leads to decrease in unmineralized osteoid, allows osteoclasts to make contact with mineralized matrix
-Osteoclasts secrete HCl and cause bone resorption

Front 27

Hydroxyapatite

Back 27

-inorganic component of bone
-Mostly Ca and PO4 with some other stuff
-Osteoblast secretion is biphasic, allows for lag time between organic and inorganic matrix secretion
-Organic osteoid is produced first

Front 28

Bone matrix mineralization

Back 28

1. Degradation of inhibitors of type I collagen mineralization
2. Osteoblast production of molecules that promote mineralization
--osteocalcin, osteopontin, osteonectin
-Mineralization occurs 5-10 days after osteoid is deposited
3. Seams of unmineralized osteoid covers surfaces where bone is being deposited

Front 29

Types of Osteogenesis

Back 29

1. Intramembranous ossification
-forms membranous bone
2. Endochondral ossification
-forms endochondral bone

Front 30

Intramembranous ossification

Back 30

-Forms membranous bone
-Bone is formed directly from mesenchymal cells
-No cartilage precursor or template
-Mesenchymal stem cells migrate from neural crest
-Condensation of connective tissue cells → osteoblast differentiation → osteoid production → mineralization → anastomosing trabeculae of woven bone
-Centers of ossificaiton expand and condense to form bony plates separated by connective tissue sutures
-End of growth leads to bony union
-Matures to lamellar bone

Front 31

Endochondral ossification

Back 31

-Forms endochondral bone
-Bone is formed from cartilage plate
--Fetal hyaline cartilage differentiates from primitive mesenchyme
-Majority of bones in appendicular skeleton is formed via endochondral ossification
-fetal hyaline cartilage model → cartilage calcifies, bone collar forms around diaphysis → primary ossification center forms in diaphysis
-Primary ossification center in diaphysis
--lengthens bone from ends
-Secondary ossification center at epiphysis
-Blood supply encourages mineralization and calcification

Front 32

Endochondral ossification

Back 32

-Chondrocytes develop from the perichondrium
-Vascular in-growth at diaphysis
-Promotes differentiation to bone
-Gives rise to primary ossification center

Front 33

Zones of Endochondral ossification

Back 33

1. Resting zone
2. Zone of proliferation
3. Zone of hypertrophy
4. Zone of ossification

Front 34

Endochondral ossification: Resting Zone

Back 34

-Cartilage precursors
-Reserve cartilage

Front 35

Endochondral ossification: Zone of Proliferation

Back 35

-Chondrocytes proliferate into regular cords
-Extend towards metaphysis
-Divisions push older chondrocytes down the line towards zone of hypertrophy

Front 36

Endochondral ossification: Zone of hypertrophy

Back 36

-Cartilage cells degenerate and undergo apoptosis
-Secrete pro-minerlization molecules
-Leads to cartilage matrix mineralization and capillary ingrowth

Front 37

Endochondral ossification: zone of ossification

Back 37

-Mineralization
-Vessels bring in osteoclasts and osteoblasts
-Additional capillary ingrowth occurs with delivery of osteoprogenitor cells
-Leads to osteoid production and additional mineralization

Front 38

Bone classification by architecture

Back 38

1. Osteonal bone
-compact bone, cortical bone
-Occurs at ends, outside of bone
2. Trabecular bone
-Cancellous bone, apongy bone
-Occurs on the inside of bones

Front 39

Osteonal bone
Compact bone
Cortical bone

Back 39

-Lamellae form concentric layers of bone matrix
-Osteocytes hang out in lacunae
-Canaliculi contain communicating cytoplasmic processes of osteocytes
-Central canal contains central blood vessels, nerves, and mesenchyme
-Further out from central canal osteocytes die off
--results in remodeling
--no inflammation, inert process

Front 40

Osteonal canal

Back 40

-haversian canal, central canal
-Contains arteriole, vein, nerve fiber, and lymphatic
-Communicates directly with osteocyte canaliculi

Front 41

Trabecular bone
Cancellous bone
Spongy bone

Back 41

-intercnnecting plates of bone matrix with intervening marrow spaces
-Forms "honeycomb"
-Present in ends of bone at metaphysis and epiphysis
-forms anastomosing spicules of lamellar bone
-Gives large surface area
-Lined by osteoprogenitor cells
-Surrounded by hematopoietic marrow

Front 42

Bone classification by maturity

Back 42

1. Woven bone (immature)
2. Lamellar bone (mature)

Front 43

Woven bone

Back 43

-Primary bone, immature bone, reactive bone
-Highly cellular
-Haphazard organization of bone matrix
-Forms during rapid growth or in response to disease
-Laid down quickly during period of rapid growth or in response to disease
-Can heal fracture sites, inflammation/infection, invasive neoplasms
-not well mineralized

Front 44

Lamellar bone

Back 44

-Mature bone
-Can be osteonal or trabecular bone
-Organized parallel lamellae with regular linear cement lines
-Can be osteonal or trabecular bone
-MUCH stronger than woven bone
-Forms over time, takes time to organize
-Maximizes distance between lacunae and nutrient supply

Front 45

Osteonal lamellar bone

Back 45

-Collagen fibers are laid down in parallel arches around central osteonal canal
-Maximizes density and strength per unit of bone
-Maximum distance for nutrients/waste products to diffuse from central vessels through canaliculi

Front 46

Trabecular lamellar bone

Back 46

-Collagen fibers deposited parallel to flat surface (endosteal surface)
-Fibers are linear and aligned
-Width of one trabecula is one osteon radius

Front 47

Lamellar vs. Woven bone

Back 47

-Difference is rate of formation and TIME
-Slow formation: procollagen fibers have time to line up and mineralize into lamellae
-Fast formation, procollagen is haphazard in arrangement
--fracture healing
--Eventually collagen is remodeled into lamellar bone over time

Ex: duct tape and tarp fix vs. actual roof

Front 48

Bone as a plastic organ

Back 48

-Rigid, yet flexible
-Adapts to change while maintaining strength, rigidity, and flexibility
-Able to sense biomechanical, hormonal, and metabolic changes in body and respond
-Able to break down and reset along lines of force
-Can increase or decrease bone mass based on pressure
-Changes shape based on modeling and remodeling
--couples bone absorption and resorption

Front 49

Bone modeling

Back 49

-Mostly occurs in young bone
-Adaptive process
-Results in architectural change in bone
--size, structural orientation, contour
-Occurs during growth (increases in bone length and diameter
-Occurs during pathologic states
--architecture needs to change
--fracture healing, infection, neoplasia
-Strength is transferred from trabecular bone to osteonal bone
--trabeculae become fewer and thinner

Front 50

Bone Remodeling

Back 50

-Physiologic replacement of old bone tissue by new bone tissue
-3 month cycle
-mainly occurs in the adult skeleton
-Maintains bone mass
-Repairs microfractures from altered mechanical use, stress, or strain
-Responds to metabolic disease states
--altered Ca, PO4, PTH, calcitonin
-Occurs locally, coordinated efforts of osteoblasts and osteoclasts in 5 phases
-Systemic and local coordination

Front 51

Stages of Bone remodeling

Back 51

1. Activation: stimulation of preosteoclasts by cytokines and growth factors
--leads to mature osteoclasts
2. Resorption: Osteoclasts digest mineral matrix of old bone
3. Reversal: end of resorption, cement line
4. Formation: Osteoblasts synthesize new bone
5. Quiescence: Osteoblasts become resting bone lining cells on newly formed bone

Front 52

Cement line

Back 52

-End of resorption, marks "reversal" stage of bone remodeling
-Gravel that dissipates forces
-Prevent continuation of micro-cracks in bone

Front 53

Osteonal bone remodeling

Back 53

-Initiated from embedded vascular channels (osteons)
-Osteoclasts excavate a tunnel, form cutting (resorption) cone
-Basophilic cement lines delineate reversal zone at periphery of remodeling units
-Osteoblasts fill in the cone behind osteoclasts with concentric lamellae, centered on a haversian canal
-Interstitial lamellae are remnants of older Haversian systems that have been partially excavated or remodeled

Front 54

Trabecular Bone Remodeling

Back 54

-Remodeling occurs along the surfaces of trabeculae
-No cutting cone of osteoclasts

Front 55

Blood supply to Bone
Adults

Back 55

-Nutrient artery mid-diaphysis is the primary blood supply to medullary cavity cortex
--Centrifugal blood flow
-Periosteal arteries supply 25% of outer cortex
--proliferate with fractures
-Metaphyseal arteries anastomose with branches of nutrient arteries
-Epiphyseal arteries supply subchondral bone and chondrocytes
--enter bone at joint capsule insertion points

Front 56

Blood Supply to Bone
Growing Animals

Back 56

-Nutrient arteries supply diaphyseal marrow and most of central area of the metaphysis
-Metaphyseal arteries form tight hair-pin like loops
--low flow rate, can trap bacteria
--supply peripheral regions
-Epiphyseal arteries supply epiphysis and secondary centers of ossification
-Transphyseal blood vessels exist in newborn animals
--Allow infections to cross physis
--so not exist in small animals, mostly in horses and cattle

Front 57

Synovial joints

Back 57

-Diarthroses
-Allow movement of appendicular bones with minimal friction
-Stifle, hock, fetlock, elbow

Front 58

Synarthroses

Back 58

-Minimize movement
-Fibrous sutures of the skull

Front 59

Classifications of synovial joints
Range of Motion

Back 59

-Unaxial: range of motion in one plane
--hinge joint, elbow and hock
-Biaxial: motion in 2 planes
--condyloid joints, stifle
-Triaxial: motion in 3 planes
--ball and socket joints, shoulder, hip
--Planar joints, carpus

Front 60

Synovial joint structure

Back 60

-Articulation of 2 bones with ends covered by articular cartilage (hyaline) and subchondral bone plate
-Supported by fibrous joint capsule
-capsule is lined by synovial membrane that secretes synovial fluid

Front 61

Synovial joint capsule

Back 61

-Fibrous joint capsule
-Contains blood vessels and nerves
-Provides additional support to joint capsule via focal thickenings of the capsule with ligaments or menisci
-Lined by synovial membrane that secretes synovial fluid
--provides lubrication and nutrients for articular cartilage

Front 62

Articular cartilage

Back 62

-Provides articular surface
-Provides growth zone of epiphyseal ossification center in young animals
-Maintains structural integrity of the joint
-Defects in cartilage or junction with subchondral bone will lead to degenerative changes and joint instability
--fissures, ulcers, subchondral bone bruising, retained cartilage cores, etc.

Front 63

Hyaline Articular Cartilage

Back 63

-Covers articular surfaces of joints
-Withstands compressive forces of weight bearing
-Withstands shear forces during motion
-Utilizes lubricating synovial fluid and cartilage organization
-No nerves, blood vessels, lymphatics
--Capsule has nerves, not cartilage itself
-Synovial fluid and subchondral vessels allow for nutrient acquisition and waste removal
--requires motion, joints need to move and "squish" to get stuff to flow

Front 64

Chondrocytes

Back 64

-Cellular component of cartilage
-Create and maintain proteoglycan component of extra-cellular matrix
-Undergoes minimal mitotic activity
--damage is not repaired easily, no cell division
-Number decreases with age, undergoes atrophy

Front 65

Cartilage extracellular matrix

Back 65

-Very important
-Very hydrophilic, attracts water
-Acts as a shock absorber
-Composed of proteoglycans and type II collagen
-Proteoglycans: hyaluronic acid, glycoproteins, glycosaminoglycans

Front 66

Structure of Hyaline Articular Cartilage

Back 66

1. Superficial/gliding zone:
--small, flattened chondrocytes
--more type I collagen fibers resist shear forces
2. Intermediate/transitional zone
--Round chondrocytes
3. Radial zone:
--Large, round chondrocytes lined up vertically in short columns
4. Articular Epiphyseal Complex
--Mineralized zone
--separated from radial zone by tidemark
--Anchors cartilage to subcondral bone

Front 67

Articular Epiphyseal Complex

Back 67

-Mineralized zone of Hyaline articular cartilage
-Separated from radial zone of large chondrocytes by basophilic line
--tidemark
-Acts to anchor hyaline cartilage to subchondral bone

Front 68

Synovial membrane

Back 68

-Produced by Synoviocytes
-Line the inner surface of the joint capsule
-1-4 cell layers thick
-Multi-layered array of synoviocytes
-Inner fibrovascular stroma subtends the synoviocytes
--contains loose collagenous stroma, nerves, blood vessels, and inflammatory cells
-Outer fibrous capsule is made of dense collagen
--thickens with chronic injury and limits motion

Front 69

Synovial fluid

Back 69

-Dialysate of plasma
-Contains proteoglycans (hyaluronic acid and glycoproteins)
-Clear to straw-colored
-Very Viscous
-Increased amounts of protein will give yellow color
-Hemorrhage leads to pink-brown color due to clotted blood in joints
-Supprative inflammation leads to increased turbidity

Front 70

Subchondral bone

Back 70

-Provides support for overlying articular cartilage
-Dissipates concussive forces to peripheral cortical bone
-Thickness varies with degree of weight bearing and/or compressive forces
-In larger animals, can be composed of osteonal bone

Front 71

Factors determining reaction of bone to Injury

Back 71

-Depends on etiology, inciting cause
-Depends on when injury occurs
--during development
--in mature adult

Front 72

Disruption of Endochondral ossification

Back 72

-Modeling response to structural damage or abnormal use
-Involves osteoblast and osteoclast activation
-Remodeling in response to abnormal use or systemic disease
-Woven bone formation

Front 73

Abnormal Endochondral Ossificaion

Back 73

-Young, growing animals
-in Cartilage plate:
--chondrodystrophy
--osteochondrosis
--trauma or infectious physitis
-In trabecular bone:
--growth arrest lines
--growth retardation lattice

Front 74

Chondrodystrophy

Back 74

-Type of abnormal endochondral ossification
-Occurs in cartilage plate
-Generalized defect in endochondral template

Front 75

Growth Arrest Lines

Back 75

-Due to disruption of endochondral ossification in trabecular bone
-Transverse trabeculation
-Formation of mineralized trabeculae oriented perpindicular to the long axis of the bone
--parallel to the physis
-Caused by nutrient deficiencies, general malnutrition, or debilitating disease
-Slowed or temporary disruption of endochondral ossification during development

Front 76

Growth Retardation Lattice

Back 76

-Osteoclastic activity is imparied and results in abnormal osteoclastic modeling of primary trabeculae
-No osteoclasts, no proper remodeling
-Form of skeletal dysplasia, metaphyseal dysplasia
-Cartilagenous growth plate is normal
-Proximal metaphysis of newly formed bone is not normal
-Results in retention of primary trabeculae, trabeculae contain mineralized cartilage template
-Caused by osteoporosis
-Can also be caused by BVD, Canine Distemper Virus
-Toxic-induced osteoclast damage can also be cause
--lead poisoning

Front 77

Physeal Lead Line

Back 77

-Type of growth retardation lattice
-Osteoclasts are defective, do not remodel bone appropriately
-Will have a highly mineralized area that extends further into the growth plate
-Can be due to BVD, Parvo, Lead toxicity

Front 78

Normal primary Trabeculae

Back 78

-Will have inner mineralized cartilage spicules
-Newly deposited outer layers of woven bone
-Is rapidly remodeled into secondary trabeculae
--mineralized cartilage is removed, replaced with bone
-Trabeculae should become thinner and fewer in number

Front 79

Primary trabeculae in Growth Retardation lattice

Back 79

-Defect in osteoclasts and resorption
-No normal modeling of primary spongiosa
-Retained mineralized cartilage cores with thick bands of vertically oriented trabecular bone

Front 80

Premature physeal closure

Back 80

-Weakening or destruction of physeal chondrocytes or ECM
-Leads to primary closure of the growth plates (Physes)
--"Squashage"
-Local inflammation or trauma leads to focal closure of the growth plate and secondary angular limb deformities
-Nutrient deficiencies can lead to complete closure of the growth plate with shortening of the limb

Front 81

Traumatic Physis

Back 81

-Disruption in endochondral ossification
-Will not get ossification, cartilage core will remain and will continue to divide
-Vessels under cartilage core are destroyed

Front 82

Infectious physitis and epiphysitis

Back 82

-Infection that crosses the physes
-Abscess obliterates the growth plate, damages metaphyseal growth plate
-Will get necrosis in the bone
-May result in angular limb deformity

Front 83

Bone Modeling

Back 83

-Alterations to size and shape of bone in response to altered mechanical stress or structural damage
-Compressive forces favor bone formation, forms more bone
-Tensile forces favor bone resorption, bone disappears
-Bone trabeculae align along lines of stress
--osteoblasts sense currents, stretch receptors, stress forces

Front 84

Altered forced detected by Osteoblasts

Back 84

-Piezoelectric currents from crystal matrix deformation
-Streaming potentials generated from differentials in canalicular fluid flow rates
-Stretch receptors on osteoblasts

Front 85

Bone Remodeling

Back 85

-Occurs in response to abnormal use or systemic disease
-Leads to alterations in bone mass
-Activation-resorption/Formation-release cycle is activated
-Obvious changes occur in spongy/trabecular bone

Front 86

Bone Remodeling details

Back 86

-Increased mechanical use favors bone formation
-Decreased mechanical use decreases suppression of bone resorption
-Inflammation or infection of bone leads to increased oosteoblast bone resorption
--pro-osteoclast factors are induced, cytokines turn on osteoclasts
--M-CSF and RANK-L

Front 87

Bone Repair

Back 87

-Rapidly deposited bone, woven bone
-Formation of bone vs. cartilage callus vs. fibrous matrix production depends on O2 tension (vascularization) and instability factors

Front 88

Woven Bone and Rapid Bone Deposition

Back 88

-Rapidly deposited when repair is needed
-Formed by reactive periosteum, leads to woven bone "callus" formation that bridges fracture
-Low oxygen tension leads to chondroid differentiation within callus
-High motion leads to fibrous differentiation and non-union
-Woven bone is later modeled by osteoclastic resorption into lamellar bone

Front 89

Fracture callus on radiograph

Back 89

-Radiolucent due to low oxygen tension and chondrocyte differentiation
-Increased motion leads to fibroblast deposition and radiolucency

Front 90

Periosteal Reactions

Back 90

-Stimulated by instability, direct trauma, inflammation, infection
-Results in nodular woven bone proliferation
--Osteophytes
--Enthesiophytes

Front 91

Osteophytes

Back 91

-Discrete nodules of periosteal new bone
-Often forms near joints in response to Degenerative Joint Disease
-Periosteal reaction

Front 92

Enthesiophytes

Back 92

-Periosteal new bone
-Forms at insertion of a tendon or ligament
-Periosteal reaction

Front 93

Joint Injury

Back 93

-Response from all anatomic structures
-Cartilage, synovial membrane, joint capsule, subchondral bone
-ALL respond to injury

Front 94

Cartilage response to Injury

Back 94

-Cartilage has poor repair response
-No blood vessels or nerves, no pain and no nutrient supply
-Erosions, ulcers, and atrophy all occur

Front 95

Cartilage erosion due to injury

Back 95

-Partial thickness loss of articular cartilage
-Can persist for long periods of time
-Usually no progression until subchondral bone sclerosis, new bone built
-Matrix will fill in defect, fill in space
-Adjacent chondrocytes proliferate, form reactive clones
--clusters of chondrocytes stuck in matrix, cannot get out to heal erosion

Front 96

Cartilage ulceration due to injury

Back 96

-Loss of articular cartilage that extends to subchondral bone
-Extends to a vascularized surface
-Will fill with granulation tissue
-Metaplasia of cartilage to fibrocartilage
--fibrocartilage does not have shock-absorbing capacity
--will be a weak, friction point in the joint
-Signals to other structures in the joint

Front 97

Cartilage atrophy due to Injury

Back 97

-Thinning of articular cartilage
-Cartilage is "sick"
-Matrix degrades and thins, chondrocytes die off
-Can result from constant or excessive compression
-Can also result from a lack of weight-bearing
--need compressive forces to have nutrient delivery and waste product removal

Front 98

Intraarticular inflammation

Back 98

-Can occur in synovium, subchondral bone, or are aof immature vascularized growth
-Cell mediators or degenerating chondrocytes activate gelatinases, collagenases, stromolysins
--degrade molecules of hyaline cartilage
--Cartilage matrix is digested
-Net loss of chondrocytes and cartilage on the whole
-Inflammatory mediators prostaglandin and NO inhibit proteoglycan synthesis, lead to additional matrix degradation
-Hyaluronic acid and joint lubrication decreases
-Surface injury to superficial collagen layer occurs
--lose frictionless gliding surface

Front 99

Results of intraarticular inflammation

Back 99

-Yellow discoloration of cartilage due to ECM degeneration
-Cartilage will become fibrillar, will have fissures
-Can have focal or multi-focal erosions and ulcerations
-Cartilage and chondrocyte necrosis with reactive clone formation

Front 100

Supprative arthritis

Back 100

-Neutrophic inflammatory mediators are BAD for cartilage

Front 101

Reactions of Synovial Membrane to injury

Back 101

-Villous hypertrohy and hyperplasia of synovial membrane
--surface will not be smooth anymore
-Inflammatory cell infiltrates
--neutrophils and fibrin lead to lymphocytes, plasma cells, and macrophages
-Joint capsule thickening/fibrosis
-Pannus formation with additional distruction of articular cartilage

Front 102

Bone response to chronic joint inflammation

Back 102

-Subchondral bone sclerosis due to direct transfer of compressive forces from joint to subchondral bone
-Bone modeling
--"lipping" of the joint margin and periarticular osteophytosis
-Once articular cartilage is lost, will get joint instability
-Nodular proliferation of bone at joints

Front 103

Normal endochondral ossification

Back 103

-Chondrocytes proliferate to form columns
-Chondrocytes hypertrophy, alter ECM and promote ECM mineralization
-Hypertrophied chondrocytes are "bricked in" and cannot access nutrients, start to die
--release factors that promote capillary in-growth at Zone of Calcification
-Capillaries penetrate the zone of ossification, bring in osteoclasts
-Osteoclasts eat away at dying chondrocytes
-Osteoprogenitors become osteoblasts and deposit osteoid seams on mineralized cartilage spicules
-Eventually mineralixed cartilage cores are removed and modeled out to form more mature, stronger bone

Front 104

Types of Disorders of Bone Formation

Back 104

-Congenital/heritable
-Idiopathic
-Nutritional/metabolic/toxic (acquired)
-Infectious (acquired)
-Sometimes toxic/nutritional/metabolic diseases can resemble congenital disease and vice versa

Front 105

Types of disorders of osteoclast resorption

Back 105

-Congenital/heritable
-Infectious (acquired)
-Nutritional/metabolic/toxic (acquired)
-Sometimes toxic/nutritional/metabolic diseases can resemble congenital disease and vice versa

Front 106

Disorders of bone formation and endochondral ossification

Back 106

-Osteogenesis imperfecta
-Osteo chondrodystrophies
-Osteochondrosis
-Osteochondritis dissecans
-Epipihyseolysis

Front 107

Osteogenesis Imperfecta

Back 107

-Abnormality of bone formation
-Poor collagen synthesis
-Osteopenic disease, decreased bone production and decreased bone density
-Affects calves, lambs, puppies, humans
-Mutation in type I collagen synthesis
-Affects osteoblasts and odontoblasts, bone and dentine forming cells
-Will get blue sclera

Front 108

Osteogenesis Imperfecta clinical signs

Back 108

-Weak or decreased collagen fiber network
-Weak bone formation and increased bone fragility
-Pathological fractures with normal forces
-Joint laxity, joint capsule is thin
-Scleral thinning, results in blue sclera
-Defective dentin and abnormal tooth formation
-Decreased and thinned secondary spongiosa bone with pathological trabecular fractures
-Abrupt failure of secondary spongiosa formation
-No evidence of increased osteoclast activity or fibrous connective tissue
-Thinned cortical bone without compaction
-Thinned, abnormal tooth dentin and sclera

Front 109

Osteochondrodysplasia

Back 109

-Disorder of Endochondral ossification
-Primary defects in growth plate cartilage
-Results in disorders of bone growth
-Cartilage template is "wonky"
-Disease can be generalized or regional
--some bones or sites might be more predisposed than others
-Occurs in cattle, sheep, pigs, dogs, cats

Front 110

Disproportionate/chondrodystrophic dwarfs

Back 110

-Shortened malformed limbs and normal skull
-Standard for basset hounds
-Lethal bulldog calves
-Spider lamb syndrome
-Metaphyseal chondrodysplasia of norweigan elkhounds

Front 111

Primary osteo chondrodystrophy

Back 111

-Defective osteochondrogenesis in basset hounds

Front 112

Secondary osteo chondrodystrophy

Back 112

-Lysosomal storage disease (MPS VI)

Front 113

Osteochondrosis and Osteochondritis dissecans (OCD)

Back 113

-Heterogenous lesions in growth cartilage
-Occurs in young animals
-Species-specific sites of OCD development
-Focal defect of endochondral ossification
--delay or failure
-Necrosis of cartilage vessels within canals
-Inadequate capillary vascular ingrowth
-Damage to vasculature within growth cartilage
-Focal or multifocal sites affected
-Many lesions are bilaterally symmetric
--50%

Front 114

Epiphysiolysis

Back 114

-Separation of the epiphyseal plate from the metaphysis
-Due to formation of a horizontal fissure through the growth pate

Front 115

Factors leading to Osteochondrosis and OCD

Back 115

-Damage to vasculature within growth cartilage
-Excessive compressive forces leading to conformational defect or focal trauma
-Genetics
-Hemodynamic disorders
-Nutrition

Front 116

Osteochondrosis Histology

Back 116

-Chondrocytes are clonal and stuck in matrix trying to proliferate
-May have dissecting cartilage flaps
--will irritate joint
-Cartilage necrosis
-Cartilage extends into the bone, forms a weak point
-Vascular channels extend into growth cartilage plate

Front 117

Osteochondrosis pathology

Back 117

-Focal interruption of endochondral vascular invasion or ischemic necrosis → failure of endochondral ossification → retention of cartilage core → pressure induced fissure → OCD
-Growth cartilage retention or growth plate defect → resolved
-Defect → retained and heal, may leave weak point in bone
-Defect → retained → dissecting cartilage flap → OCD → secondary degenerative joint disease

Front 118

Causes of Epiphysiolysis

Back 118

-Separation of epiphysis from metaphysis
-Developmental
-Traumatic: Salter-Harris fractures

Front 119

Salter-Harris fractures

Back 119

-Fractures through growth plates
-Can result in premature partial or complete physeal closure
--results in angular limb deformities

Front 120

Common Developmental epiphysiolysis

Back 120

-Dog: ununited anconeal process on proximal ulna
--creates joint instability, leads to pain and lameness
-Cats: capital femoral epiphyseal slipping
-Pigs: femoral head or ischeal tuberosity

Front 121

Wobbler's syndrome

Back 121

-Form of OCD
-Cervical vertebral dysplasia and compressive myelopathy
-Neurological condition in young growing horses and dogs
-Common in large breed dogs and horses, fast-growing
-Vertebral malformation leads to irregularly shaped bones with multiple centers of ossification
-Static or dynamic compression of the cervical spinal cord
-Portions ossify with endochondral formation, others with membranous ossification
-Malformation closes down on the spinal cord and compresses cord

Front 122

Cervical Vertebral Myelopathy Vertebral malformations

Back 122

-Articular facet OCD or body/lamina
-Malarticulation with joint instability
-Stenosis of the spinal cord
-Spinal cord compression and secondary facet degenerative joint disease
-Wallerian degeneration of the spinal cord
-Neurological disease can be intermittent

Front 123

Equine Wommbler's

Back 123

-Cervical vertebral stenosis with compressive myelopathy
-Joint is enlarged, DJD in cassette joint
-Does not heal well
-White matter tracts degenerate

Front 124

Metabolic Bone Disease

Back 124

-Represents skeletal disease
-Nutritional
-Endocrine/hormonal
-Toxic origin
-GI, renal, hepatobiliary system dysfunction can affect vitamin/mineral absorption, excretion, or hormone production
-Vitamens A,D,E,K are lipid soluble

Front 125

Metabolic bone Disease age

Back 125

-Can affect skeletally immature animals during growth or immature/adults during remodeling processes
-Many osteodystrophies imply specidic morphological changes but NOT specific causes
-Different types of osteodystrophy can be present in the same animal
--due to different hormones

Front 126

Metabolic Osteodystrophies

Back 126

1. Osteopenia, osteoporosis
--too few or too weak trabeculae
2. Rickets (immature individuals), Osteomalacia (mature individuals)
3. Fibrous osteodystrophies
-primary hyperparathyrpodism
-Secondary hyperparathyroidism
--renal or nutritional deficiencies

Front 127

Osteopenia

Back 127

-Decreased bone density or mass

Front 128

Osteoporosis

Back 128

-Clinical syndrome of reduced bone mass manifested by bone pain and pathological fractures
-Bone structure is normal, reduced amount of trabecular and cortical bone
--trabecular bone has most surface area exposed to osteoclasts
-Quantity not quality of bone is reduced
-Eventual compromise in bone strength leads to pathological fractures

Front 129

Nutritional cause of osteoporosis/osteopenia

Back 129

1. Starvation directly leads to decreased bone formation
--no proteins, no collagen
2. Calcium deficiency stimulates PTH release, leads to resorption via osteoclasts
--tips balance towards bone resorption
3. Copper deficiency decreases osteoblast activation and collagen strength
4. Severe GI parasitism or IBD leads to malabsorption of vitamin D and release of inflammatory mediators leads to osteoclast activation
--TNF, IL-1, IL-6

Front 130

Physical inactivity as cause of osteoporosis/osteopenia

Back 130

-Disuse atrophy of bone
-Decreased bone formation and increased bone resorption

Front 131

Chronic glucocorticoid excess as source of osteoporosis/osteopenia

Back 131

-Increased osteoclast activity and decreased osteoblasts and pre-collagen synthesis
-Decreased calcium absorption in intestine and increased calcium excretion in the kidneys

Front 132

Hormonal loss as cause of osteoporosis/osteopenia

Back 132

-Not an issue in most domestic animals
-Menopause
-Estrogen increases TGF-beta. decreases IL-1, IL-6, TNF-a
--osteoclast promoting cytokines
-Decreases bone formation and increases bone resorption

Front 133

Trabecular bone lesions associated with Osteoporosis and Oteopenia

Back 133

-Trabecular bone is more affected than lamellar bone
-Ends up with reduced amount of trabeculae
-Thinner/fewer trabeculae with perforating holes in bony plates leads to conversion of trabecular bone to rods/struts
--get perforating holes
--bone and trabeculae change
-Infarctions can lead to compression fractures with reduction in bone length
--especially in vertebrae of women

Front 134

Compact bone lesions associated with Osteoporosis and Osteopenia

Back 134

-Thinning from osteoclast resorption on endosteal surface, leads to medullary cavity widening
-increased Porosity from osteoclast resorption in vascular space and haversian canals
-Decreased osteoblast activity
-Brittle bones with fractures

Front 135

Growth plate lesions associated with Osteoporosis and osteopenia

Back 135

-Occurs in younger animals
-Protein malnutrition may cause thinning

Front 136

Rickets

Back 136

-Metabolic bone disease that results in defective bone and cartilage mineralization
-Softening of bones and growth cartilage
--especially at sites of endochondral ossification
-Issue with mineral deposition phase of bone reodeling
-In young growing animals
-"Softening of bones"
-Bone pain
-Bone deformities
--kyphosis, scoliosis, rachitic rosary of ribs
-Fractures

Front 137

Osteomalacia

Back 137

-Metabolic bone disease that results in defective bone mineralization
-Softening of bones only
-Syndrome of adult animals, cartilage is not affected
-Issue with mineral deposition phase of bone remodeling

Front 138

Causes of Rickets and Osteomalacia

Back 138

-Vitamin D Deficiency
-Phosphorous deficiency
-Fluoride toxicity (rare)
-Hereditary
-Paraneoplastic syndrome
-GI malabsorption

Calcium deficiency does not result in rickets or osteomalacia except in birds

Front 139

Vitamin D Deficiency and Rickets/Osteomalacia

Back 139

-Uncommon in animals fed commercial pet foods with balanced nutrients
-Regular sunlight prevents
-Defective kidneys, do not make 1,25 OH-vitamin D3
--active vitamin D3

Front 140

Phosphorous Deficiency and RIckets/Osteomalacia

Back 140

-Herbivores on a phosphorous deficient diet
-Usually become unthrifty and anorexic
-Decreased reproductive performance

Front 141

Hereditary Rickets/Osteomalacia

Back 141

-Inborn errors in vitamin D metabolism
-Type 1: vitamin D dependent
--deficient 1-alpha hydroxylase enzyme
--gene is deficient, animal cannot make vitamin D on own
--Can give vitamin D and animal will be fine
-Type 2: vitamin D resistant
--defect in vitamin D receptor
--cannot treat
--common in marmosets

Front 142

Paraneoplastic Syndrome

Back 142

-Hypophoshatemic vitamin D resistant rickets
-Humoral substance that reduces phosphorous absorption
-Only in humans so far

Front 143

GI malabsorption and Rickets/Osteomalacia

Back 143

-Hepatobiliary disease that reduces vitamin D absorption
-Excessive minerals inhibits PO4 absorption
--Fe, Ca, Al

Front 144

Rickets and Osteomalacia Error

Back 144

-Mineralization of osteoid does not occur
-Reduction in mineralization results in deposition of large seams of osteoid along endosteal bone surfaces and osteonal canals
--thick seams, strong to support weak squishy bone
-Decreased osteoclast resorption
--inability of osteoclasts to bind and resorb old bone
-Growth plate deformities in young animals due to un-mineralized growth cartilage
--leads to decreased formation of primary trabeculae

Front 145

Lesions of Rickets

Back 145

-Physes are thickened and nodular
-Flared metaphyses with retained cartilage cores
--Rachitic rosary of ribs
--Normal resorption allows for tapered neck, no resorption flaring occurs
-Lesions occur due to failure of mineralization
-Failure of normal metaphyseal modeling
-Decreased numbers of chondrocytes in proliferative zone with fewer vascular channels
-Grossly deformed or bowed endosteal surfaces lined by thick seams of osteoid

Front 146

Fibrous osteodystrophies

Back 146

-Bones resorbed and replaced with fibrous tissue
-Disease caused by increased osteoclast activity and bone resorption
-Fibrous proliferation
-Relative decrease in bone formation with production of poorly mineralized, immature bone
-Loss of bone leads to bone weakening with pathologic fractures and deformities
-Caused by persistent high levels of PTH (hyperparathyroidism)

Front 147

Hyperparathyroidism Primary cause

Back 147

-Functional parathyroid gland tumors
--produces more PTH than body needs
-Idiopathic parathyroid gland hyperplasia
--hereditary disease
-Pseudohyperparathyroidism and hypercalcemia of malignancy
--paraneoplastic syndrome due to PTHrp, LSA, and anal sac adenocarcinoma

Front 148

Hyperparathyroidism Secondary cause

Back 148

-More common
-Chronic renal insufficiency or failure
-Dietary imbalance in Ca, P, or Vitamin D3 (uncommon)
--Can be achieved with cereal grains to pigs or all meat dishes to carnivores, excessive bran to horses

Front 149

Mechaisms of PTH-induced bone resorption

Back 149

1. Renal Secondary hyperparathyroidism
2. Nutritional secondary hyperparathyroidism

Front 150

Renal Secondary Hyperparathyroidism

Back 150

-Decreased GFR and PO4 excretion results in disturbances in electrolyte balances
-Ionized Ca is pulled out og the blood
-Decreased vitamin D3 production with decreased Ca absorption from GI and kidneys
-Stimulates PTH release
-Decreased bone formation
-Increased osteoclast differentation and activation, LOTS of osteoclasts
--increased osteoclast bone resorption with replacement fibrosis
-Increased fibroblast differentiation from bone marrow stromal cells

Take home: Decreased bone formation, increased osteoclasts and osteoclast activity, increased conversion of osteoblasts into fibrosis

Front 151

Nutritional secondary hyperparathyroidism

Back 151

-Relative increase in PO4 results in PTH release
-Similar pathways activated as in chronic renal failure

Front 152

Cortical bone lesions of Fibrous Osteodystrophy

Back 152

-Excessive bone resorption with replacement fibrosis and pliability
-"Rubber jaw" in dogs
--teeth are loose in the jaw
-Osteoclast resorption begins on endosteal surface and progresses to include haversian canals
-Replacement fibrosis
-Results in increased dimension of bone
-"Big head" in horses

Front 153

Trabecular bone lesions of Fibrous Osteodystrophy

Back 153

-Osteopenia and thinning of the trabeculae
-May or may not ahve intramedullay fibrosis
-Growth plate does not have any primary lesions

Front 154

Osteopetrosis

Back 154

-Disorder of bone resorption
-Extreme form of growth retardation lattice
-Defect in osteoclasts
-Autosomal recessive mutation, lethal mutation with cranifascial development defects
--brachygnathia inferior, impacted molar teeth, deformed cranial vaults with secondary brain compression
-Mutation results in osteoclast defect
-Unable to resorb and remodel primary trabeculae formed during development
--Entire medullary cavity is filled with trabecular bone

Front 155

Growth Retardation Lattice

Back 155

-Osteosclerotic disease
-Increase in bone density due to retained primary trabeculae
-Acquired defect in osteoclast resorption
-Infectious cause
--BVD, CDV, Toxic cause (Pb)
-Width of lattice indicates time and duration of impaired osteoclastic activity
-As osteoclast activity resumes, zone advances towards diaphysis with normal endochondral ossification and osteoclast modeling

Front 156

Physeal "Lead Line"

Back 156

-Acquired from retained primary trabeculae
-Broad radiodense line at the physis

Front 157

Transgenic KO osteopetrosis mice

Back 157

-Defect in RANK-L
--osteoclast differentiation factor missing, defect in osteoclast activity

Front 158

Nutritional imbalances and toxins affecting Skeletal growth

Back 158

-Mn and Co deficiencies
-Zn, Mb, F, Pb toxicity
-Vitamin A deficiency and toxicity
-Vitamin D deficiency and toxicity
-Vitamin C deficiency (scurvy)
-Toxic plants
--lupine, hemlock, tobacco

Front 159

Congenital Cortical Hyperostosis

Back 159

-Disorder of bone Modeling
-Diaphyseal dysplasia
-Autosomal recessive trait in neonatal pigs
-Causes new bone formation on the diaphyses
-Histologically will see extreme radiating periosteal reaction

Front 160

Craniomandibular Osteopathy

Back 160

-"Lion jaw"
-Autosomal recessive diseases in WHWTs
-Idiopathic condition in other dog breeds
-Hyperpstoses of the jaw and skull bones
-Can be quite painful for the dog
-Periosteal and endosteal new bone formation with disorganized modeling and remodeling
-Growth plates are normal
-Bilaterally symmetrical abnormal proliferation of trabecular and cortical bone
--mandibles, occipital, and temporal bone proliferation
-May have Temporomandibular muscle atrophy and painful mastication

Front 161

Bacterial Infectious Inflammation of Bone
Septic Osteomyelitis

Back 161

-Most common
-"Septic osteomyelitis"
-Arcanobacterium pyrogenes, Staph aureus, Strep zooepidemicus, Strep intermedius, Salmonella, E. coli
-Coliform bacteria
-Will get supprative inflammation
-May or may not get pyogranulomatous inflammation

Front 162

Viral Infectious Inflammation of Bone

Back 162

-Canine distemper, BVD, Canine hepatitis, Feline Leukemia Virus
-has variable effects on bone
--growth retardation lattice
--Endothelial necrosis with medullary hemorrhage
-Myelosclerosis
-Oteoclasts are affected, retain primary trabeculae

Front 163

Fungal Infectious Inflammation of Bone

Back 163

-Pyogranulomatous or granulomatous inflammation
-Stimulates bone lysis
-Can look like an aggressive bone neoplasm

Front 164

Routes of Bone Infection

Back 164

1. Direct inoculation or Direct extension
-Cutaneous wound, open fracture, puncture, or speptic joint
-More common in older animals
2. Hematogenous (through blood)
-Most common in neonates, immunocompromised, or debilitated animals
-Can originate from umbilicus, respiratory tract, or GI tract
-Infections on exposed orifices can become septic, bacteria lodges in bone

Front 165

Septic Physitis
Septic Epiphysitis

Back 165

-Occurs in young, growing animals
-Bacteria lodge in tight-looped vessels of metaphyseal plates
-Leads to septic physitis/epiphysitis with or without abscessation
-Increased intramedullary vascular pressure can result in thrombus and infarcts of fat, marrow, or bone
--Sequestrum formation with involucrum, will be radiolucent around the sequestrum
--Cortical bone periosteal reaction
--Can extend through epiphyseal vessels into joint with secondary arthritis

Front 166

Osteomyelitis on Radiograph

Back 166

-Wedge-shaped sequestrum with involucrum
--will have periosteal reaction
-Can look like an osteosarcoma
-Osteomyelitis can cross the joint, osteosarcoma usually does not
-May see soft-tissue swelling opacity around the injury
-Lytic areas of bone are visible

Front 167

Septic physitis

Back 167

-Growth plate is bridged by infection and fibrosis
-Trabeculae will become thinner and necrotic
-Will see lots of supprative inflammation within the epiphysis

Front 168

Non-infectious inflammation of Bone
-Metaphyseal osteopathy

Back 168

-Common in young, growing large-breed dogs
-Signs: lameness, fever, swollen/painful metaphyses in multiple long bones
-Metaphyseal necrosis and inflammation with pathological infractions and secondary periosteal new bone formation
-Idiopathic]
-Will see microfractures in trabeculae

Front 169

Non-infectious inflammation of Bone on Radiograph

Back 169

-Trabecular bone will have bilaterally symmetrical alternating zones of radiolucency and increased radiodensity in metaphyses
--adjacent and parallel to physis
-Radiopacities= necrosis with fibrinosuppurative inflammation
-Cortical bone will have metaphyseal periosteal new bone formation
-Growth plate will not have any lesions

Front 170

Eosinophilic Panosteitis

Back 170

-Non-infectious inflammation of bone
-Enostoses-like lesion
-Not eosinophilic OR inflammatory (misnomer)
-Self-limiting infection in young growing large breed dogs
-Proliferations of well-differentiated woven bone and fibrosis
-Inflammation is not present
-Pain can come and go
-Also seen in horses and 1 camel
-Areas of increased radiopacity in medullary cavity
--radiopacities correspond to osteosclerosis of trabecular bone
--Patchy white opacities on radiographs

Front 171

Enostoses

Back 171

-Osteosclerosis of trabecular bone

Front 172

Aseptic necrosis of Bone in Humans

Back 172

-Many causes
-Occlusive vascular disease (infarct)
-Hyperadrenocorticism
-Fat emboli
-Nitrogenous emboli (the bends)
-Sickle cell anemia
-Intramedullary neoplasms

Front 173

Aseptic Necrosis of Bones in Animals

Back 173

-Uncommon with few causes
-Intramedullary neoplasms, osteosarcoma
-Ischemic infarction
--thromboembolic disease
--Venous outflow reduction/vascular compression
-Increased medullary pressure
-Can be idiopathic, Legg Calve Perthes disease

Front 174

Possible Sequelae of Bone necrosis

Back 174

-Incomplete necrotic bone resorption can lead to a sequestrum
-Impingement on the Physis can lead to premature physeal closure and angular limb deformities
--An infarct in the femoral head can lead to premature physeal closure
-May have a periosteal new bone response

Front 175

Histology of Bone necrosis

Back 175

-Will have areas of empty lacunae and viable bone
-Necrotic bone will have increased palor of the matrix

Front 176

Legg-Calve-Perthes Disease

Back 176

-Possible Sequelae of bone necrosis
-Idiopathic condition
--may be due to epiphyseal vascular occlusion?
-Necrosis of epiphyseal bone marrow and subchondral bone
-Collapse of overlying articular cartilage
-Treat with femoral head ostectomy (Remove!)
-Occurs in young dogs, esp. small breeds (pug)
-Subchondral infarct with continued weight-bearing leads to fracture and collapse of necrotic trabecular bone, which leads to flattening of the femoral head

Front 177

Legg-Calve-Perthes Disease Pathology

Back 177

Subcondral infarct, continued weight-bearing → fracture and collapse of necrotic trabecular bone → flattening of the femoral head

Front 178

Bone fracture classifications

Back 178

1. Traumatic: bone broken by excessive force
2. Pathologic: abnormal bone broken by minimal trauma or during normal weight-bearing forces

Cause directly informs treatment and prognosis

Front 179

Predisposing conditions for pathologic Fractures of Bone

Back 179

-Metabolic bone disease
--Rickets, osteomalacia, osteoporosis
-Primary or metastatic neoplasia
-Osteomyelitis (bone infection)
-Congenital disease

Cause directly informs treatment and prognosis

Front 180

Salter-Harris Fracture

Back 180

-Fracture that involves the growth plates
-Type I and II: hypertrophied cartilage or primary trabeculae
--heals well
-Type III and IV: cross the physis
-Type V and VI: crush growth plate
-Types III-VI can heal with growth deformities

Front 181

Cortical Bone fractures

Back 181

-Simple or Comminuted
-Closed or Open
-Transverse, oblique, spiral
-Sagittal or parasagittal
-Avulsions occur where tendon/ligaments insert
--bone is pulled off with tendon or ligament
-Greenstick: one side of cortical bone is fractured and other is not, just bent
--occurs in young animals

Front 182

Bone Fracture Healing

Back 182

-Bone heals through series of specific phases or events
-Involves coordination and communication between cytokines, growth factors, and cells
-Stable fracture repair needs immobilization of fracture ends and clinical stability

Front 183

Fracture repair #1
Soft tissue injuries associated with Bone fractures

Back 183

-Tearing of periosteum, displacement of fracture ends gives adjacent soft-tissue trauma
-Will get hemorrhage with clot formation
-Local tissue trauma → hemorrhage → hematoma → clot with fibrin

Front 184

Fracture repair #2

Back 184

-Impaired blood flow leads to necrosis of the fractured bone ends
--results in bone lysis and matrix acidifcation
-Cytokines are released, growth factors from platelets and macrophages within the blood clot
-Proliferation of undifferentiated mesenchymal cells and granulation tissue
--new capillaries will be embedded within a loose structural network of fibrous tissue
--granulation tissue forms with mesenchymal precursors

Front 185

Fracture repair #3

Back 185

-Differentiation of mesenchymal stem cells into Osteoblasts
-Metaplasia of granulation tissue into cartilage and bone
-Formation of woven bone and primary fracture callus
--Primary callus formation can take 4-6 weeks
-Extensive periosteal and endosteal woven bone with periosteal vessels
-Low O2 tension results in hyaline cartilage formation
--eventually hyaline cartilage undergoes endochondral ossification

Front 186

Primary Fracture Callus

Back 186

-Provides some stability to allow some limb function during healing process
-Degree of motion between the fracture ends determines the size of the fracture callus
-Also determines type of tissue produced
--bone
--fibrous non-union
-Callus will shrink down with time as woven bone is converted into lamellar bone
--lamellar bone is stronger than woven bone, need less of it

Front 187

Fracture Repair #4

Back 187

-Modeling and remodeling of primary callus into secondary callus
-Replacement of weaker woven bone by stronger lamellar bone
-Bone is restored to its original shape

Front 188

Complications of Fracture Healing

Back 188

1. Inadequate blood supply
2. Infection (osteomyelitis)
3. Sequestrum at fracture ends
4. Non-union
--fibrous or cartilagenous

Front 189

Inadequate blood supply as a complication of Fracture Healing

Back 189

-Usually due to extensive soft-tissue trauma and disruption of vasculature to site
-Problem in distal limb fractures of horses
-Can result in bone necrosis and secondary osteomyelitis or sequestrum

Front 190

Infection as a complication of fracture healing

Back 190

-Osteomyelitis
-Can be introduced at the time of injury or by direct inoculation or extension
-Can be secondary to inadequate blood supply and tissue necrosis

Front 191

Instability with fibrous non-union in fractures

Back 191

-Leads to "fake joint" or pseudoarthritis
-Fracture instability favors production of fibrous connective tissue instead of chondro-osseous tissue

Front 192

Excessive wear as a complication of fracture healing

Back 192

-Debris is produced with macrophage response
-Cytokines produced by macrophages stimulate osteoclastic resorption
-Osteoclast resorption leads to delayed union of fracture ends
-Usually a result of excessive motion or fracture instability

Front 193

Sequestrum as a fracture complication

Back 193

-Fracture fragments may be too large for osteoclastic resorption
-Inadequate blood supply and necrosis of bone

Front 194

Rigid Fracture Repair

Back 194

-maintains fracture ends in close proximity
-Can use metallic surgical implants
-Complete rigid fixation results in accelerated healing
--direct osteonal bridging of the fracture site
--No formation of a callus
-Gap less than 1mm results in lamellar bone at right angles to fracture
--fastest healing
-Gap more than 1mm results in woven bone formation first, later remodeled to lamellar bone
--slower healing

Front 195

Joint classifications

Back 195

Classified by degree of mobility and type of connection between adjacent bones
1. Synarthroses: fibrous joints with very little movement
2. Amphiarthroses: cartilagenous joints with limited movement
3. Diarthroses: synovial joints that facilitate motion

Front 196

Arthrogryposis

Back 196

-Congenital joint contracture
-"Funky angled limbs"
-Can be sporadic or idopathic, genetic
-Viral infections that damage fetal CNS can lead to abnormal innervation and stimulation of fetal muscles
--leads to muscle atrophy and contracture of limbs
-Anything that affects skeletal muscle innervation will affect joints
-Toxic agents
-Malformations at joint surface

Front 197

Canine Hip Dysplasia

Back 197

-Common in large and giant breed dogs
-Can be genetically predisposed
-Can be due to obesity or excessive exercise in growing animals
-Shallow acetabular cup and increased joint laxity are primary/predisposing lesions
-Can have DJD as a secondary lesion

Front 198

Canine Hip Dysplasia pathogenesis

Back 198

-Excessive joint laxity due to shallow acetabular cup
-Leads to instability and chronic subluxation of coxofemoral joint
-Leads to DJD with modeling of the femoral head and acetabular cup

Front 199

Secondary lesions of Canine Hip Dysplasia

Back 199

-Erosion and ulceration of the articular cartilage on the femoral head and acetabulum
-Thickening and stretching of the joint capsule
--Will also have osseous/cartilage metaplasia, may lead to rupture of the round ligament of the femur
-Synovium will be thickened, non-supprative inflammation, and villous proliferation
-Subchondral bone of acetabulum will become flattened
--acetabulum becomes shallow and wide
--femoral head is flattened
--May heave eburnation and periarticular osteophyte formation

Front 200

Eburnation

Back 200

-Bone on Bone contact
-Results in grinding and erosion of bone
-Polishing of bone surface due to bone-on-bone frictional forces

Front 201

Lesions with Canine Hip Dysplasia

Back 201

-Cartilage loss
-Flattening of femoral head, misshapen
-Osteophyte formation
-Acetabular cup becomes shallower

Front 202

Arthritis
Arthrosynovitis

Back 202

-Inflammatory lesion of the joint
-Can be an inflammatory or infective cause
-Exudates are fibrinous, suppurative, serous, or lymphoplasmacytic
-Persistent inflammation eventually leads to DJD, even if inciting agent is removed

Front 203

Arthritis causes

Back 203

-Infection (bacterial, viral, fungal)
-Immune-mediated
-Urate precipitates (gout)

Front 204

Damage to Joint Structures

Back 204

-Direct damage from inciting agent or joint instability
-Liberated inflammatory mediators
--prostaglandins, cytokines, leukotrienes, lysosomal enzymes, free radicals, NO, neuropeptides, products of complement and fibrinolytic systems
-Activation of proteolytic enzymes
--collagenases, proteases, MMPs

All lead to degeneration of articular cartilage matrix and degeneration/necrosis of chondrocytes

Front 205

Infectious Arthritis

Back 205

-Very common in Domestic Animals
-Causes:
--neonatal septicemia, bacterial entry from orifices
--direct penetration due to trauma, iatrogenic joint injection, surgery
--Extension of Osteomyelitis through transphyseal vessels or cortex, shared blood supply

Front 206

Manifestations of Infectious Arthritis
Articular Cartilage

Back 206

-Lysis, erosion, thinning of surface cartilage
-Collapse from chondrocyte degeneration and necrosis
-Ulceration from chronic suppurative process
-Pannus formation, macrophage and fibroblast proliferation

Front 207

Manifestations of Infectious Arthritis
Joint Capsule/Synovium/Synovial Fluid Acute Changes

Back 207

-decreased viscosity of synovial fluid
--due to enzymatic digestion of GAGs and dilution by edema
--cartilage matrix breaks down
-Increased turbidity from neutrophils and fibrin exudates
-Red/brown discoloration from hemorrhage
-Hyperemic synovium, thickened from Edema

Front 208

Manifestations of Infectious Arthritis
Joint Capsule/Synovium/Synovial Fluid Chronic changes

Back 208

-Lymphoplasmacytic inflammation
-Granulation tissue proliferation leading to villous hyperplasia and hypertrophy of the synovium
-Joint capsule fibrosis with or without intraarticular adhesions
-Subchondral bone sclerosis or disuse osteopenia

Front 209

Agents in Infectious Arthritis

Back 209

1. Bacteria:
-Gram- leads to fibrinous inflammation
-Gram+ leads to suppurative inflammation
2. Mycoplasma:
3. Viruses
4. Reoviruses in Chickens

Front 210

Mycoplasma and infectious arthritis

Back 210

-Very important in large animals
-Mycoplasma myorhinus: fibrinous arthritis in weanling pigs
-Mycoplasma bovis: fibrinous to pyogranulomatous arthritis in feedlot cattle
--hematogenous dissemination from pneumonia or mastitis
-Mycoplasma capri: chronic arthritis in goats

Front 211

Viruses and infectious arthritis

Back 211

-Lentiviruses
--Caprine Arthritis Encephalitis (CAE)
--Ovine Progressive Pleuropneumonia (OPP)
-Very important in goats and sheep
-Chronic fibrinous and lymphoplasmacytic arthrosynovitis with syynovial villous hyperplasia
--pannus formation
--Joint distension and secondary carpal hygromas

Front 212

Immune-mediated Arthritis

Back 212

-Non-infectious inflammatory arthritis
-Rheumatoid arthritis
--common in small and toy breeds of dogs
--chronic proliferative inflammatory arthritis
-Polyarthritis of greyhounds
-Feline chronic progressive polyarthritis
--associated with viral infection?
-Lupus

Front 213

Degenerative Joint Disease

Back 213

-Osteoarthritis, osteoarthrosis
-Mono or polyarticular process
-Mature or immature animals
-Clinically silent or symptomatic
-Final endpoint of joint disease regardless of inciting agent
-Once started progresses
-Can try to prevent with surgery

Front 214

Degenerative Joint Disease pathogenesis

Back 214

-Release of inflammatory mediators by degenerating/dying chondrovytes and synovial macrophages
--have phagocytosed cartilage breakdown products
-Leads to edema and reduced synovial viscosity
-Proteoglycan content is reduced, less water binds, and chondromalacia results
-Will get:
--chondroerosion
--Fibrillation
--ulceration of cartilage
--Eburnation
--Subchondral osteosclerosis
--Joint capsule fibrosis and periarticular osteophytosis
--Subchondral bone cyst formation

Front 215

Non-supprative synovitis

Back 215

-Edema and reduced synovial viscosity
-Lymphocytes, macrophages, plasma cells
-Reduction in proteoglycan content, decreased water binding and chondromalacia
-Manifests as linear grooves or score lines

Front 216

Chondroerosion

Back 216

-Loss of articular cartilage layers
-Grossly apparent thinning and exposure of subchondral vascular channels
-Surface layers have "melted" appearance

Front 217

Fibrillation

Back 217

-Fraying of superficial cartilage layers
--can see grossly and histologically
-Matrix is split along the vertical axis
--perpendicular to the joint surface

Front 218

Ulceration of Cartilage

Back 218

-Loss of articular cartilage to the subchondral bone
-DEEP loss of cartilage, all the way down to bone!

Front 219

Subchondral osteosclerosis and DJD pathogenesis

Back 219

-Subchondral osteosclerosis is due to increased compressive forces from loss of shock-absorbing cartilage surface
-Reduction in osteoclastic bone remodeling

Front 220

Joint capsule Fibrosis and Periarticular Osteophytosis in DJD

Back 220

-Marked thickening of the joint capsule
--decreases articular range of motion
--eventually causes fibrous ankylosis
-Extensive periarticular osteophytosis can eventually lead to bony ankylosis

Front 221

Subchondral bone cyst formation in DJD

Back 221

-Occurs from fissures in the cartilage and synovial herniation into subchondral bone

Front 222

Diskospondylitis

Back 222

-Inflammation of the vertebral bone and/or intervertebral discs
-Often associated with prostatitis in dogs
--Erysipelas infection in pigs
--Enterococcus infection in chickens
--Streptococcus infection in farmed mink
-Can result in compressive myelopathy or myelitis

Front 223

Exostosis
Osteophyte

Back 223

-Proliferative, non-neoplastic lesion of bone
-Nodular benign proliferation
-Projects outward from the surface
-Commonly periarticular with DJD

Front 224

Enostosis

Back 224

-Proliferative, non-neoplastic bone lesion
-Sclerotic bone growth
-Originates from the endosteal surface within medullary cavity

Front 225

Enthesiophyte

Back 225

-Proliferative, non-neoplastic bone lesion
-Similar to Osteophyte
-Arises at site of tendon/ligament insertion

Front 226

Hyperostosis

Back 226

-Proliferative, non-neoplastic bone lesion
-Indicates increased diameter of bone
-Implies a uniform thickening of the periosteal surface

Front 227

Hypertrophic Osteopathy

Back 227

-Periosteal bone formation (progressive and bilateral) at diaphysis of distal limbs
-Dog: Associated with mediastinal or thoracic disease
--dirofilariasis
--rhabdomyosarcoma of young, large breed dogs
-Horse: ovarian neoplasms and intrathoracic disease
-Unknown pathogenesis
--changes in blood flow results in woven bone formation?
--Reflex vasomotor changes via vagus nerve, induced by thoracic disease?
-May regress if primary lesion or vagotomy is performed

Front 228

Osteochondroma
Osteochondromatosis

Back 228

-Caused by defect in perichodral ring during skeletal development
-Results in displaced focus of growth cartilage
--eventually cartilage undergoes endochondral ossification
-Can have one or many masses projecting from bone surfaces of long bones
--masses communicate with medullary cavity at the base
-Cure by surgical excision

Front 229

Osteochondroma Clinical Signs

Back 229

-Depends on location
-Can interfere with tendon or other musculoskeletal structures
-Space occupying mass that can protrude into the vertebral canal
-May undergo malignant transformation to chondrosarcoma
-In cats can be viral in origin (FeLV-like virus)
--occurs in flatbones and adult animals

Front 230

Osteochondroma Lesion

Back 230

-Outer cap of hyaline cartilage undergoes orderly endochondral ossification

Front 231

Bone Cysts

Back 231

-Well-circumscribed radiolucent areas that are not aggressively growing
-Can be simple, subchondral, or aneurysmal

Front 232

Simple Bone Cyst

Back 232

-Clear, colorless fluid-filled central cavity
-Surrounded by fibrous connective tissue and woven or lamellar bone

Front 233

Subchondral bone Cyst

Back 233

-Secondary to OCD or DJD

Front 234

Aneurysmal Bone Cyst

Back 234

-Spaces filled with blood of serosanguineous fluid
-Fluid has hemosiderosis
-Surrounded by well-differentiated fibro-osseous tissue
--mixed with mesenchymal cells/osteoblasts/multinucleate cells
-Can be congenital lesions in foals
--often occur in mandible

Front 235

Bone neoplasms

Back 235

-Primary tumors of bones
-Common in dogs, not as much in cats, rarely in other animals
-May arise from any mesenchymal tissues present in bone
--Bone (Osteoma, Osteosarcoma)
--Cartilage (Chondroma, Chondrosarcoma)
--Fibrous tissue (Fibroma, Fibrosarcoma)
--Adipose tissue (Lipoma, Liposarcoma)
--Vascular tissue (Hemangioma, Hemangiosarcoma)
-Tumors of bone and cartilage-forming cells are most common
-In dogs malignant tumors are more common than benign neoplasms

Front 236

Bone Neoplasms by Species

Back 236

-IN dogs, most tumors are malignant
-In cats, benign and malignant are equally common
-Other domestic animals, benign tumors are much more common than malignant tumors
-Secondary tumors of bone are rarely diagnosed in animals
--surveillance issue

Front 237

Primary Neoplasms of Bone

Back 237

-Osteoma/Osteosarcoma
-Chondroma/Chondrosarcoma
-Fibrosarcoma
-Histiocytic sarcoma
-Poorly differentiated sarcomas
-Giant Call tumors
-Multilobular tumor of bone
-Liposarcoma
-Hemangiosarcoma
-Lymphosarcoma
-Multiple Myeloma
-Ossifying fibroma (benign)

Front 238

Secondary processes occuring with bone tumors

Back 238

-Periosteal response
-Osteolysis
-Necrosis
-Osteomyelitis
-Pathologic fractures

Bone remodels and responds to neoplastic injury

Front 239

Osteosarcoma

Back 239

-Most common neoplasm of bone
-Malignant neoplasm of osteoblasts
-Produces variable amounts of osteoid and bone
-Histological morphology is extremely variable
-Radiographic appearance can be an aggressive lesion, lytic, sclerotic, or mixed types

Front 240

Osteosarcoma locations

Back 240

-80% of all primary neoplasms in dogs
-75% occur on appendicular skeleton
--65% occur in forelimbs
--30% occur in hindlimbs

Front 241

Osteosarcoma metastasis

Back 241

-Aggressive neoplasm with extremely poor prognosis
-Arises in the medullary cavity of bones
--has easy access to metaphyseal blood vessels
-Rapidly metastasizes to lungs, other organs and other bones
-Can "skip metastasis" to adjacent bones
-Will not cross cartilage plates or joint surfaces
-Usually has already metastasized by the time is has been identified

Front 242

3 features of Osteosarcoma

Back 242

1. Destruction of bone architecture
--no organization
2. Production of reactive periosteal and endosteal new bone
3. Production of osteoid and tumor bone

Front 243

Chondroma

Back 243

-benign neoplasm of hyaline cartilage
-Rare
-Occurs in dogs, cats, and sheep
-Tends to arise from flat bones of the head
--NOT articular cartilage
-Multiple lobules of slow-growing, well-differentiated hyaline cartilage
-May or may not have endochondral ossification
-Can metastasize and be invasive, but not overwhelmingly

Front 244

Chondrosarcoma

Back 244

-Malignant Neoplasm of hyaline cartilage
-Predilection site in flat bones
--nasal cavity, ribs, pelvis, cartilagenous exostoses
-Slow-growing multilobular mass of hyaline cartilage
--well-differentiated, anaplastic
-Tends to invade
-Slow to metastasize
-Often has areas of endochondral ossification
-Will look like blue-white multilobular islands of hyaline cartilage separated by thin, fibrous trabeculae
--often have foci of hemorrhage or necrosis
-Ddx: osteosarcoma

Front 245

Chondrosarcoma Histology

Back 245

-Cell morphology varies
-Can have undifferentiated mesenchymal cells (Myxosarcomatous) to chondroid cells that produce abundant ECM
-Clinical history and radiographs give diagnosis, not histology

Front 246

Fibroma/Fibrosarcoma

Back 246

-Originate from intramedullary fibroblasts or periosteal connective tissue
-Produce abundant collagenous connective tissue
--no cartilage or bone is produced
-Tumor can invade between fascial planes
-Can be difficult to remove surgically
-Recurrence is frequent if removed
-In cats, can be associated with vaccination
--Rabies Vaccine

Front 247

Maxillary Fibrosarcoma in Dogs

Back 247

-Specific type of fibrosarcoma
-Occurs in maxillae of large-breed dogs
-Histologically low grade, looks benign
--low mitotic index
--can look like scar tissue
-Biologically high-grade, invasive behavior

Front 248

Osteoma

Back 248

-Benign neoplasm
-Uncommon
-Arise from the bones of the head
-Single, dense protruding mass that projects from bone surface
-Slowly progressive growth of trabecular bone
--trabeculae will be lined by well-differentiated osteoblasts
--covered by layer of periosteum
-Does not invade or destroy parent bone

Front 249

Multilobular tumor of Bone

Back 249

-Locally aggressive and invasive
-Skull predilection site
--Causes brain compression and herniation
-50% post-surgical recurrence
-Metastasis is rare
-Well-defined lobules of neoplastic mesenchymal tissue

Front 250

Multiple Myeloma

Back 250

-Plasma cell Myeloma
-Produces monoclonal IgM
--Bence Jones proteins
-Produces lytic bone lesions
-Neoplastic Plasma cells replace marrow cells

Front 251

Ossifying Fibroma

Back 251

-Benign, no metastasis
-Commonly found on mandible or maxilla of horses and cattle
-Slowly expansile mass
-begins as intramedullary neoplasm, progressive destruction of trabeculae and overlying cortical bone
-Histologically can see well-differentiated proliferation of cellular fibrous tissue
--will be mixed with woven and lamellar bone lined by osteoblasts with osteocytes in lacunae

Front 252

Metastatic tumors to Bone

Back 252

-Typically occur on rib shafts, vertebral bodies, or humeral/femoral metaphyses
-Can be associated with pain, pathologic fractures, hypercalcemia of malignancy, osteolysis, reactive new bone formation

Front 253

Common metastatic neplasms to bone

Back 253

-Cats: Pulmonary carconima to the digits
-Dogs: Subungual SCC, prostatic carcinoma, thyroid carcinoma
-Horses and dogs: hemangiosarcoma, malignant melanoma

Front 254

Synovial Neoplasms

Back 254

-Somewhat rare
-Typically malignant behavior
-Occur in large joints of extremities
-most often in horses and middle-aged, large breed dogs
-Arise from fibrocytes of synovial membrane, within joints or tendon sheaths?
-May have myxoid component
-Negative for histiocytic IHC markers
-Locally invasive
-Metastasis is uncommon
-32 month average survival time

Front 255

Synovial Myxoma

Back 255

-Occurs in dobermans and horses
-Affects stifle and small joints
-30.7 months average survival time

Front 256

Histiocytic Sercoma

Back 256

-Often associated with joints
-Also has other primary sites
--bone marrow, lymph nodes, spleen
-Rottweiler dogs predisposed
-Stifle and elbow are frequently affected sites
-Occasionally classified as synovial sarcomas
-Large, bizarre histiocytic morphology with single or multiple nucleoli and bizarre mitoses
-One type has erythrophagocytosis and can result in aneima
-Poor prognosis, 5.3 month survival time
-Metastasizes to liver, lung, regional lymph nodes

Front 257

Function of Skeletal Muscle

Back 257

-Most energy demanding tissue in the body
-Function is related to function of peripheral nervous system
-Myofibers are innervated by axons
-Changes in muscle fibers can be neuropathic or myopathic

Front 258

Neuropathic muscle disease

Back 258

-Determined by effect or absence of nerve supply
-Denervation

Front 259

Myopathic disease

Back 259

-Primary change takes place in skeletal muscle

Front 260

Motor unit

Back 260

-Myofibers all innervated by one motor neuron
-Territory innervated by 1 motor neuron
-Myofibers contract simultaneously
-Gives checkerboard pattern of innervation to skeletal muscle

Front 261

Skeletal Muscle Fiber Types

Back 261

-Type I: slow, oxidative, small fibers
--Fatigue resistant
--Small diameter
-Type IIa: Fast, oxidative, glycolytic
--Fatigue resistant
--Medium diameter
-Type IIb: Fast, glycolytic
--Large motor units
--Maximal force
--Fatigues rapidly

Type I and II fibers are arranged in mosaic pattern

Front 262

Clinical Signs of Muscle Disease

Back 262

-Weakness
-Exercise intolerance
-Fatigue
-Muscle atrophy or hypertrophy
-Pain
-Lymphadenopathy
-Stiff gait

Front 263

Clinical Pathology of Muscle Disease

Back 263

-Muscle necrosis may lead to elevations in:
--Creatine Kinase
--Lactate Dehydrogenase
--Aspartate aminotransferase
--Alanine aminotransferase
-Myoglobinuria: released after muscle injury and ends up in urine

Front 264

Skeletal muscle reactions to injury

Back 264

-Atrophy
-Hypertrophy
-Degeneration
-Necrosis
-regeneration
-Fibrosis
-Mineralization/ossification
-Inflammation

Front 265

Muscle Atrophy

Back 265

-Reaction to muscle injury
-Decreases in size
-Loss of myofilaments causes myofibers to decrease in size
-Decrease in the diameter of the entire muscle or decrease in diameters of individual myofibers or decrease in both
-Can be due to denervation, disuse, malnutrition

Front 266

Denervation as a cause of muscle atrophy

Back 266

-Loss of connection with peripheral nerves
-Leads to Atrophy, NOT necrosis (decrease in cell size only)
-Can be caused by wallerian degeneration, axonal degeneration, or demyelination
-Laryngeal hemiplegia in horses
--axonal degeneration of left recurrent laryngeal nerve
--Brachial paralysis in dogs due to trauma

Front 267

Wallerian degeneration

Back 267

-Muscle atrophy and denervation secondary to trauma in a peripheral nerve

Front 268

Muslce denervation

Back 268

-Atrophy with loss of myofibrils
-Reduced synthesis of contractile proteins
-Increased expression of muscle regulatory proteins
-No signs of muscle regeneration, muscle just gets smaller

Front 269

Laryngeal Hemiplegia

Back 269

-Denervation atrophy of the cricoaretynoideus dorsalis muscle
-Due to denervation from recurrent laryngeal nerve
-Common in horses
-Causes "roaring"

Front 270

Muscle Reinervation

Back 270

-Schwann cells proliferate at the motor end plate of denervated fiber
-Collateral sprouting of neighboring neurons or axonal regrowth
-Will get hypertrophy with increase in myofibrils
-May have fiber type grouping
--May lead to a single neuron innervating more adjacent myofibers
--changes phenotype of myofibers

Front 271

Fiber Type Grouping

Back 271

-Hallmark of reinnervation
-Damage to certain neurons can result in adjacent neurons innervating denervated myofibrils
-A single neuron may innervate more adjacent myofibers
-Changes phenotype of myofibers
-Produces histological appearance of type grouping
-Homogenous area of fiber types
-Loss of checkerboard pattern
-Usually only part of the muscle is affected

Front 272

Hypertrophy of skeletal muscle

Back 272

-Increase in diameter of entire muscle or increase in diameter of individual myofibers or both
-Cannot get hyperplastic, cannot increase in cell number
-Can be a reaction to injury
-Can be due to increased workload
--physiologic hypertrophy and exercise
--Compensatory hypertrophy from loss of other myofibers

Front 273

Muscle degeneration as a reaction to injury

Back 273

-Reversible injury
-May or may not lead to cell death
-Causes hydropic swelling and fatty change

Front 274

Muscle necrosis as a reaction to injury

Back 274

-Generally necrosis is segmental, only a portion of the myofiber is involved
-Loss of striations and hypereosinophilic cytoplasm
-Can look like autolysis
-Inflammatory cells enter myofibrils to clean up debris within 24-48 hours
-Will get swelling of myofibrils and fragmentation with neutrophils
-May even get mineralization

Front 275

Possible outcomes of skeletal muscle necrosis

Back 275

1. Regeneration
-Occurs if basal lamina is intact
2. Fibrosis
-Occurs if basal lamina is destroyed

Front 276

Muscle regeneration as a reaction to skeletal muscle injury

Back 276

-Only happens if basal lamina is intact
--basal lamina serves as a scaffold
-Depends on satellite cell proliferation, myofiber nuclei cannot synthesize DNA or replicate
-Removal of debris by macrophages
-Seal off injured areas
-Satellite cell proliferation in basal lamina tube
--look like flat cells
-Regenerating cells will have central nuclei
-Fusion of satellite cell processes
-If basal lamina is destroyed, fibrosis occurs
--cannot have regeneration with fibrosis

Front 277

Fibrosis as a reaction to skeletal muscle injury

Back 277

-If muscle is damaged down to basal lamina, fibrosis occurs
--No regeneration is possible
-May follow any non-fatal injury
-Will see firm tan/white foci or streaks in the muscle, collagen deposition
-Often associated with atrophy

Front 278

Mineralization as a reaction to skeletal muscle injury

Back 278

-Appears as chalky white areas
-Histologically will see blue-purple granular material
-Causes:
--necrosis
--primary myopathies
--Vitamin D toxicity

Front 279

Ossification as a reaction to skeletal muscle injury

Back 279

-Rare form of metaplasia
-Inherited in pigs
--fibrodysplasia ossificans progressiva
-Also seen in other species

Front 280

Inflammation as a reaction to skeletal muscle injury

Back 280

-Myositis
-Follows necrosis
-Associated with trauma, infectious agents, and infarcts
-Commonly idiopathic, some are thought to be immune-mediated

Front 281

Disorders of Skeletal Muscle

Back 281

-Congenital/inherited
-Trauma
-Metabolic
-Nutritional
-Denervation
-Circulatory
-Inflammatory
-Infectious
-Toxic
-Neoplastic

Front 282

Congenital/Genetic disorders of skeletal muscle

Back 282

-Ion channel disorders: ion channels have to be working for skeletal muscle to be working
--Hyperkalemic periodic paralysis
--Malignant hyperthermia
--Myotonia
-Myasthenia gravis
-Muscular dystrophy
-Carbohydrate metabolism defects

Front 283

Skeletal Muscle Action

Back 283

1. Myofiber receives AP signal from pre-synaptic neuron
2. Na channels open, myofiber floods with Na and is depolarized
3. Ca is released from sarcoplasmic reticulum
4. Na channels are inactivated, K leaves the cell
5. Cl- comes into cell and repolarizes myofiber
--Ca is resequestered in SR
--Muscle relaxes

Front 284

Hyperkalemic Periodic Paralysis

Back 284

-In quarter horses
-Autosomal dominant point Mutation in Na channel,
-Causes muscle hypertrophy, stiffness, and weakness
-Most common hereditary muscle disease in the horse
-Due to "Impressive," horse that had huge muscles
--offspring were bred to have big muscles also, genetic mutation was also passed on
-May have hyperkalemia, but issue is in the Na channel

Front 285

Na channels in Hyperkalemic Periodic paralysis

Back 285

-Na channel closure is delayed
-with constant contraction (due to Na channel being open), muscle runs out of Ca for contraction
--Needs period of relaxation to appropriately contact
-Point mutation of Na channel
-May appear as if K is high, but issue is in the Na channel

Front 286

Malignant Hyperthermia
Porcine Stress Syndrome

Back 286

-"Excessive contractions"
-Brought on by stress, halothane, and depolarizing muscle relaxants
-High incidence in breeds with increased lean muscle mass
--Pietrain, Landrace, Yorkshire, Poland China, Duroc
-Defect in ryanodine receptor of Ca channel results in muscle rigidity and hyperthermia
--channel open time is prolonged
--Ca is released from SR into cytoplasm in greater amounts than normal, results in excessive contractions
-Acute muscle necrosis is end result
-Muscles appear pale, moist, and swollen

Front 287

Myotonia

Back 287

-Defect in Cl channel in goat breeds
-Causes stiffness, muscle rigidity, and muscle hypertrophy
--Cl channel does not open, Ca stays bound and causes continual contractions
-Similar conditions occur in other species

Front 288

Myasthenia Gravis

Back 288

-NMJ disorder
-Can be congenital or acquired
--Both involve ACh and ACh receptor

Front 289

Congenital Myasthenia Gravis

Back 289

-Severe disease
-Deficiency of ACh receptors, fewer ACh receptors present on post-synaptic neuron
-No circulating antibodies to ACh receptors
-Responds to anti-acetylcholinesterase therapy
--decrease in AChase activity leads to more available ACh at synapse and allows for more muscle contraction
-Symptoms generally begin 6-8 weeks of age
-Common in Jack Russel terriers, springer spaniels, smooth haired fox terriers
-Weakness, exercise intolerance

Front 290

Acquired Myasthenia Gravis

Back 290

-Body produces auto-antibodies to ACh receptors
-Have reduced number of functional ACh receptors
-Responds to anti-AChase therapy
-Causes megaesophagus, voice changes, generalized or local muscle weakness
-Associated with thymoma (neoplasm in thymus)
-Often self-limiting disease
-Functional deficiency, receptors have antibodies bound to them

Front 291

X-linked muscular dystrophy

Back 291

-Due to mutation of dystrophin gene
-Dystrophin links ACh to ECM in skeletal and cardiac muscle
--Deficiency decreases stability of the plasma membrane, becomes friable and prone to damage
-Causes weakness, diffuse muscle atrophy, splaying of limbs (wide base stance)
-Leads to muscle necrosis, macrophage infiltration, regeneration, atrophy, and fibrosis
-Homologous to Duchenne's dystrophy in human males
-Occurs in canine, feline, and mice

Front 292

X-linked Muscular Dystrophy pathology

Back 292

-Lack of Dystrophin makes plasma membrane unstable, becomes friable and prone to damage
-Animal is weak, has muscle atrophy
-Eventually leads to muscle necrosis, macrophage infiltration, regeneration, atrophy, and fibrosis
-Continuous cycles of muscle damage and attempts of regeneration results in fibrosis and decreased regeneration
-Type IIb fibers are most susceptible to plasma membrane damage
--large volume to surface area, greatest force per unit area of membrane

Front 293

Histology of Skeletal Muscle Regeneration

Back 293

-Will get variation in muscle size
-Central nuclei (instead of on periphery)
-May see fibrosis and myofiber loss

Front 294

Equine Polysaccharide Storage Mrauma to yopathy

Back 294

-Carbohydrate metabolism defect
-Inherited disease of horses
-Leads to recurrent rhabdomyolysis and pelvic limb weakness
-Abnormal aggregates of acid-schiff positive material
--stored polysaccharide

Front 295

Trauma to Skeletal Muscle

Back 295

-Regeneration can occur
-Extensive trauma is usually followed by fibrosis
-Often trauma ends with hemorrhage and damage to other systems

Front 296

Equine Exertional Rhabdomyolysis

Back 296

-Chronic intermittent rhabdomuolysis, exertional myopathy, Monday Morning Disease
-have mild and severe forms
-Triggered by exercise, leads to acute muscle necrosis
-May see myoglobinuria due to myoglobin released after muscle necrosis
-Sudden onset of stiff gait, reluctance to move, swelling of affected muscles, pain, discomfort
-Will have skeletal muscle necrosis, swollen muscles, and yellow streaking of muscles
-Unknown pathogenesis
--underlying myopathy?
--Affected horses may have polysaccharide storage myopathy

Front 297

Circulatory disorders of Skeletal Muscle

Back 297

-Not common
-Infarcts and ischemia are due to thrombi and emboli
-External pressure due to prolonged recumbency
--downer cows, animals during surgery

Front 298

Inflammatory and Infectious disorders of skeletal muscles

Back 298

-Infectious: bacterial, protozoal, metazoan, fungal, immune-mediated, viral
-Idiopathic: masticatory myositis, polymyositis, dermatomyositis
-Any infectious agent can cause myositis
--Most often bacterial agents

Front 299

Clostridial Myositis

Back 299

-"Malignant Edema"
-"Blackleg"

Front 300

Malignant Edema

Back 300

-Clostridial myositis
-Caused by a variety of Clostridium
-Wound promotes growth of anaerobic bacteria
--necrotic tissue is anaerobic
-Results in necrosis/hemorrhage
-Occurs in horses
-Secondary to a penetrating wound

Front 301

Blackleg

Back 301

-Clostridium Chauvoei
-Spores are present in the tissue, waiting for anaerobic conditions (tissue necrosis)
-Results in necrosis/hemorrhage
-Occurs in cattle, sheep, goats
-Ingested spores lay dormant in skeletal muscle until localized trauma to muscle results in anaerobic conditions
--allows bacterial to proliferate and produce toxins

Front 302

Botulism

Back 302

-NMJ disorder
-Botulism toxin blocks ACh released in skeletal muscle
-Causes generalized flaccid paralysis
-Horses are most sensitive to toxin

Front 303

Parasites encysting in skeletal muscle

Back 303

-Trichinella spiralis
-Tapeworm cysts

Front 304

Idiopathic myositis

Back 304

-Polymyositis
-Masticatory myositis
-Dermatomyositis
-Immune-mediated? unknown cause

Front 305

Polymyositis

Back 305

-Acute or chronic immune-mediated inflammation of multiple muscles
-Occurs in dogs
-Unknown cause
-Presents as white streaks in muscles, bands of fibrosis

Front 306

Canine Masticatory Myositis

Back 306

-Bilateral atrophy of temporalis muscle
-Really only in dogs
-Animal cannot open mouth to eat
-Will have swollen, necrotic skeletal muscle
-MASSIVE necrosis of skeletal muscle
-Muscle cannot regenerate

Front 307

Toxic disorders of skeletal muscle

Back 307

-Plants: cause acute muscle necrosis
--glossypol, cofee senna, coyotillo
-Feed additives (ionophore toxicity)
-Drugs
-Mycotoxins

Front 308

Metabolic Disorders of Skeletal Muscle

Back 308

-Endocrine
--Hypothyroidism
--Iatrogenic and spontaneous hyperadrenocorticism
-Electrolyte abnormalities
--Hypokalemia
--Hypernatremia
--Hypocalcemia
--Hypophosphatemia
-Causes dysfunction and weakness

Front 309

Nutritional disorders of Skeletal Muscle

Back 309

-Vitamin E and Selenium deficiency
-Vitamin E and Selenium act as antioxidants
--if missing, will get oxidative damage
-Grossly appears as white/tan streaks in the muscle
--"White muscle disease"
-Histologically consists of necrosis with or without mineralization and later regeneration

Front 310

Vitamin E/ Selenium deficiency Pathogenesis

Back 310

-Deficiency in Vitamin E/Selenium leads to peroxidation of membrane lipids
--Can be exacerbated by stress
-Ca enters cytoplasm and mitochondria, damages respiratory mechanisms
-Cell dies without respiration, may get symmetrical necrosis of the most active skeletal muscle
-Grossly muscles are white, have white streaks
--may also get mineralization
-Occurs in cardiac AND skeletal muscle

Front 311

Neoplastic disease in Skeletal Muscle

Back 311

-Rare
-Primary neoplasms:
--rhabdomyoma/rhabdomyosarcoma
-Metastatic neoplasms:
--lymphosarcoma
--Hemangiosarcoma
--Malignant melanoma
--Carnimomas
--sarcomas
-Infiltrative lipoma, can form between skeletal muscle layers

Front 312

Laryngeal rhabdomyoma

Back 312

-Benign neoplasm, not invasive or destructive
-Can cause severe respiratory distress
-Requires a wide surgical excision area
-Are difficult to remove
-Occurs in dogs

Front 313

Rhabdomyosarcoma

Back 313

-Malignant neoplasm within skeletal muscle, subcutaneous tissue, or urogenital tract
-Locally invasive

Front 314

Urinary bladder rhabdomyosarcoma

Back 314

-RARE
-Occurs in the trigone of the urinary bladder
-Occurs in young, large breed dogs
-Can look like transitional cell carcinoma

Front 315

Skeletal Muscle Disease Principles

Back 315

-Skeletal muscle is one of the largest organ systems in the body
-Active, also has big energy demands
-Disease is commonly associated with weakness and fatigue
-Function is related to function of the PNS

Front 316

Type I muscle fibers

Back 316

-Slow fibers
-Postural muscles
-Most continuously active muscles in body
-Depend on oxidative metabolism for ATP
--have lots of mitochondria
-Resist fatigue with use
-Do not generate a lot of force
-Express type I myosin
--long contractile cycle, force is maintained while myosin is bound to actin

Front 317

Type II muscle fibers

Back 317

-Tension is maintained by more rapidly repeating the contraction cycle
-More ATP is used
-Fatigue faster than type I fibers
-Have large cross dimensions
-Generate high force
-Glycolytic instead of oxidative metabolism
-Less efficient system than OxPhos
--generates lactic acid

Front 318

Type IIb fiibers

Back 318

-Fast contracting
-High Oxidative enzymme activity
-Have lots of mitochondria
-Fatigue resistant
-Small diameter
-Do not generate high force

Front 319

Diseases unique to the nervous system

Back 319

-Diseases of myelin
-Diseases of neurons
-Tumors of neuroglia (astrocytes, oligodendrocytes)

Front 320

Diseases that affect the Nervous system AND other systems

Back 320

-Infections
--CDV, CAEV, bacteria, fungi
-Trauma
-Neoplasms

Front 321

Anencephaly

Back 321

-Brain is absent
-Due to neural tube closure failure

Front 322

Chromatolysis

Back 322

-Loss of normal staining characteristics of cytoplasmic RER in neuronal cell bodies
-Caused by degranulation of rough ER
--cell has switched protein synthesis to structural proteins from NT
-Cell body swells
-Cytoplasm becomes homogenous and glassy
-Nucleus moves to an eccentric position
-Will see Nissl substance (degranulation of rough ER) as damaged axon tries to fix

Front 323

Cranium bifidum

Back 323

-Failure of the sutures of the calvaria to close

Front 324

Demyelination

Back 324

-Degeneration or loss of myelin without axonal degeneration

Front 325

Encephalitis

Back 325

-Inflammation of the brain

Front 326

Exencephaly

Back 326

-Location of a large portion of the brain outside the cranial cavity or exposed by failure of development of the calvaria
-Abnormal brain tissue exposed through an incomplete calvaria

Front 327

Gemistocyte

Back 327

-Hypertrophied astrocyte reacting to non-specific central nervous tissue injury by sweling of its cytoplasm that stains it with eosin

Front 328

Gitter cell

Back 328

Mononuclear phagocyte Cell in the nervous system laden with myelin debris

Front 329

Gliosis

Back 329

-Astrocytosis: increase in number and size of astrocytes
-recognized by nuclei
-Astrocytic sclerosis: increase in size and number of astrocyte fibers

Front 330

Hepatoencephalopathy

Back 330

-Metabolic disorder of the CNS caused by imparied liver function
-Portosystemic shunts or cirrhosis decrease liver function
-Animal presents with seizures or blindness
-Toxic metabolites (NH3) not filtered by the liver cause CNS damage
-Vacuolization, spongiosis is present in brainstem nuclei
-Edema of the white matter tracts
-Astrocyte hyperplasia and hypertrophy in the gray matter
--prominent in horses

Front 331

Hydranencephaly

Back 331

-Absence of a large portion of the cerebrum
-Leaves a fluid-filled membranous sac instead of cerebrum
-No identifiable cortex remains

Front 332

Hydrocephalus

Back 332

-Increased volume of CSF in the ventricular system
-Obstructive hydrocephalus produces dilated lateral ventricles and thin cerebral mantle
-Leads to dilation of the ventricles
-Lateral ventricles are most vulnerable
-Cortex and white matter are still recognizable, although atrophic
-Externally looks like doming of the skin above the braincase
-Primary hydrocephalus: usually in young animals
--usually idiopathic
-Secondary hydrocephalus: occurs in older animals
--usually secondary to other diseases

Front 333

Leukoencephalitis

Back 333

-Inflammation of brain white matter

Front 334

Lissencephaly

Back 334

-Smooth-surfaced cerebrum that lacks gyral development
-On transverse section cortex is usually thicker than normal (Pachygyria)

Front 335

Malacia

Back 335

-Softening
-Gross manifestation of necrosis in the CNS with softening is palpable

Front 336

Meningitis

Back 336

-Inflammation of the meninges

Front 337

Meningoencephalitis

Back 337

-Inflammation of the meninges, brain, and spinal cord

Front 338

Meningoencephalocele

Back 338

-Extension of the meninges and spinal cord outside of the vertebral canal
-Usually through spinal bifida
-Smetimes with development of a fluid-filled cavity

Front 339

Myelitis

Back 339

-Inflammation of the spinal cord

Front 340

Myelodysplasia

Back 340

-Abnormal spinal cord development

Front 341

Myeloschisis

Back 341

-Failure of closure of the neural folds

Front 342

Neuronophagia

Back 342

-Accumulation of mononuclear cells
-Occasionally neutrophils or glia accumulate
-Accumulate around or at the site of a neuronal cell body that is undergoing dissolution or has disappeared
-Process of neuronal phagocytosis
-Monocytes eat up neuron
-Leads to neuronal loss

Front 343

Polioencephalomalacia

Back 343

-Necrosis of brain gray matter
-Usually used in reference to the cerebral cortex

Front 344

Polioencephalomyelitis

Back 344

-Inflammation of gray matter of the brain and spinal cord

Front 345

Poliomyelitis

Back 345

-Inflammation of gray matter of the spinal cord

Front 346

Polymicrogyria

Back 346

-Development of small gyri in larger numbers than normal
-Cerebrum is covered in many small gyri

Front 347

Porencephaly

Back 347

-Cavities in the brain, usually cerebrum

Front 348

Satellitosis

Back 348

-Accumulation of glial cells around neuronal cell body
-Usually oligodendrocytes

Front 349

Spinal bifida

Back 349

-Failure of the vertebral arch to develop

Front 350

Spinal Dysraphism

Back 350

-Abnormal spinal cord development with improper union between two contiguous structures

Front 351

Syringomyelia

Back 351

-Cavity in the spinal cord parenchyma, usually in white matter

Front 352

Wallerian degeneration

Back 352

-Combination of degenerative changes that occur in an axon and its myelin distal to an injury of the axon or its cell body
-Faster in PNS
-Slower in CNS
-Results from transection of axons by trauma, inflammation, tumor, etc.
-Ends self-seal and swell
-Myelin and axons degenerate in segment distal to the transection
-Chromatolysis can occur in cell body

Front 353

Nervous system and Focal lesions

Back 353

-Nervous system is very vulnerable to focal lesions
-Specific nuclei control very specific functions
-Location is KEY for impact of a lesion
--focal lesion in an important area can be VERY detrimental
-Focal lesions are compounded by the exceptionally limited ability of the nervous system to regenerate after injury
--no regeneration, injury is very detrimental

Front 354

Location and distribution of function in the nervous system

Back 354

-Location, Location, Location
-Clinical signs are based on LOCATION, not type of lesion or disease
-Different diseases affecting the same area of the nervous system will show same clinical signs
-Same disease at a different location in the nervous system will show different clinical signs
-Clinical signs are based on LOCATION

Front 355

Groups of neurons are selectively vulnerable to different diseases

Back 355

-Toxins
-Hereditary abiotrophies
-Metabolic diseases
-Nutritional deficiencies

-Specific diseases Affect specific groups of neurons

Front 356

Response of the Nervous System to Injury

Back 356

-Limited and non-specific
-Diagnosis may depend on location or distribution of the lesion instead of microscopic appearance of the lesion
-Only so many ways the nervous system can respond to injury

Front 357

Nervous system lesion location

Back 357

-Focal
-Multifocal
-Diffuse
-Involve systems of neurons

Front 358

Unique anatomic and physiologic features of the nervous system

Back 358

-Blood-brain barrier
-CSF
-Meninges
-Skull and vertebral column
-Peripheral nervous system
-Unique cells of the nervous system

Front 359

Blood-Brain Barrier

Back 359

-Maintains homeostasis of the CNS
-Endothelial cells regulate transport, form tight junctions
-Epithelial cells of choroid plexus produce CSF
-Arachnoid barrier cells
-Astrocytes send processes out to areas of Blood Brain Barrier
--Recycle neurotransmitters
--maintain K concentrations
--Modify CNS endothelial cells
--Protect neurons from injury

Front 360

Cerebrospinal Fluid
CSF

Back 360

-Produced by Choroid plexus
-Circulates in ventricles and subarachnoid space
-Functions as a shock absorber
-Transports nutrients, wastes, hormones
-Does job of lymphatics in rest of the body (no lymphatics in the CNS)
-Produced in lateral ventricles and 3rd ventricles, flows into 4th ventricle and spinal cord

Front 361

Meninges

Back 361

1. Dura mater: outer tough layer
2. Arachnoid mater: middle lyaer
3. Pia mater: thin, right on top of the brain

Arachnoid and pia make leptomeninges

Front 362

Skull and vertebral column

Back 362

-Bony structures that protect CNS from trauma
-Impose a limited and fixed volume on the brain case and vertebral canal
-Swelling of the CNS due to injury can compress vital centers and blood vessels in CNS
--leads to coma and death

-Injury → swelling → compression of important centers → death

Front 363

Pathology of focal lesions in the CNS

Back 363

-Focal lesion (neoplasm, hemorrhage, inflammation) occupies space with ongoing edema/hemorrhage
-Increases volume of the brain, brain swells
--Brain cannot really swell all that much in the limited space of the calvaria
-Swelling results in increased intracranial pressure
-Only place brain material can go, only hole is the Foramen Magnum
--Caudal herniation of the brain through the foramen magnum
-Cardiovascular and respiratory centers in the medulla are compressed
--important centers for life!
-Results in coma and death

Front 364

Biochemical lesions on neurons

Back 364

-Will not leave a histological mark
-Specific membrane proteins may be affected
-Creates a functional disease without obvious histological structural changes

Front 365

Axonal Injury

Back 365

-After trauma, ends of axon self-seal
--lipid bi-layer allows sealing
--Ends transport along axon
-Anterograde and retrograde axonal flow is halted
-Severed ends swell due to accumulations of neurofilaments, mitochondria, and debris
-Distal segment undergoes Wallerian degeneration, is removed by macrophages and glial/schwann cells

Front 366

Steps in Axonal Injury

Back 366

1. Injury to axon
2. Segments self-seal, transport stops, swelling occurs
3. Distal segment degenerates and is removed

Front 367

Axonal Injury Sequelae

Back 367

-Presynaptic terminals move out of synaptic contact while affected neuron is attempting repair
-If site of injury is close to axonal cell body, neuron may die
--Regeneration is very limited in CNS
--re-growth and reinnervation rarely occur
-Anterograde and retrograde transneuronal atrophy may occur

Front 368

Ischemic Nerve cell Change

Back 368

-Will result in cell death/necrosis
-Shrunken neurons

Front 369

Axonal degeneration

Back 369

-Axonodystrophy, neuroaxonal dystrophy
-Metabolic derangement of the entire neuron
-Distal portion of the axon dies back, leads to axonal swellings (spheroids)
-Myelin sheath breaks down at same time
-Toxin, inherited, nutritional, or metabolic diseases
-Metabolism changes the entire neuron
-Can see pink spheroids in gray matter histologically

Front 370

Neuronal Loss

Back 370

-Irreversible end-stage of pathological process involving neurons
-Can be caused by a variety of insults
-Difficult to evaluate if mild, hard to know what was there before
-Number of astrocytic nuclei is usually increased

Front 371

Vacuolated neurons

Back 371

-Occurs with prion diseases
-BIG vacuoles

Front 372

Neuronal storage diseases

Back 372

-Inherited due to deficient activity of lysosomal enzyme
-Progressive disease
-Usually occurs in young animals
-Accumulation of enzyme substrate leads to loss of neuronal or glial function
-Small vacuoles

Front 373

Neuronal Inclusion Bodies

Back 373

-Seen in some viral infection
-Canine distemper virus

Front 374

Lipofuscin accumulation

Back 374

-Neuronal injury
-Common change in aging brains
-Rare in storage diseases
-Causes neurological clinical signs

Front 375

Astrocytic Lesions

Back 375

-Can undergo hypertrophy, hyperplasia, or degeneration
-Response to neuronal cell death, demyelination, ischemia, edema, inflammation, metabolic and toxic diseases

Front 376

Astrocytic hypertrophy

Astrocytic Hyperplasia

Back 376

Hypertrophy
-Manifests as swelling of the cytoplasm
-Increase in astrocytic fibers, astrocytic sclerosis
-Looks like fibrosis, but is really just astrocytes

Hyperplasia
-Increase in the number of astrocytes

Front 377

Myelin-producing cells

Back 377

-Oligodendroglia in CNS
-Schwann cells in PNS

Front 378

Oligodendroglial Injury

Back 378

-Die in response to most insults resulting in the loss of myelin
--demyelination
-Will increase around neurons in response to aging or neurophagia
--satellitosis

Front 379

Ependymal Lesions

Back 379

-Ependymal cells line ventricles in the brain
-Loss or desquamation of ependymal cells can occur with hydrocephalus or ventriculitis
-May become hyperplastic in response to inflamamtion

Front 380

Choroid Plexus Lesions

Back 380

-Fibrosis of connective tissue stroma
--Occurs with age
-Focal masses of cholesterol and inflammatory cells
--cholesterol granulomas
--occurs in older horses

Front 381

Microglia

Back 381

-Antigen-presenting cells in the CNS
-react to injury via hypertrophy and hyperplasia
-Macrophages from the blood also enter brain with injury and act as phagocytes
--will look like foamy, lipid-laiden macrophages

Front 382

Atropy in the CNS

Back 382

-Decrease in size
-Best seen as gross lesions in cerebrum or cerebellum
-Can be secondary to hydrocephalus or slowly growing tumors
-Histologically looks like loss of neurons and myelin
--may or may not have astrocytosis and astrocytic sclerosis also

Front 383

Ventricular dilation in the CNS

Back 383

-Hydrocephalus
-Increased volume of CSF in the ventricles
-Usually unknown cause
--over-production of CSF
--Obstruction of CSF flow (most common)
--Decreased reabsorption of CSF
-With focal or diffuse loss of parenchyma ventricles expand and CSF is formed to fill dilated spaces

Front 384

Asymmetry in the Brain

Back 384

-Indicates lesion of some sort!!

Front 385

Hemorrhage in the CNS

Back 385

-Can occur epidurally, within the dura, subdural, arachnoid, intraparenchymal, or intraventricular
-Trauma, issues with vascular system, inflammation, toxic causes, some sort of deficiency, metabolic disorders, neoplasm
-May lead to increased ICP, can lead to death

Front 386

Necrosis of the CNS

Back 386

-Malacia (softening)
-Can be liquefactive or coagulative
-Acute lesions are grossly discolored and soft
-Chronic lesions may be cystic if large
-Encephalomalacia is necrosis in the brain
-Polioencephalomalacia is necrosis of the grey matter of the brain
-Leukoencephalomalacia is necrosis of the white matter of the brain
-Myelomalacia is necrosis of the spinal cord
--leukomyelomalacia
--poliomyelomalacia

Front 387

Edema in the CNS

Back 387

-Common with brain issues
-Compresses tissues, causes increased ICP and herniation
-Compression looks like clear vacuoles
-Vasogenic: increased permeability of CNS capillaries
--trauma, hemorrhage, infarcts, inflammation, toxic and metabolic diseases, tumors of CNS
-Cytotoxic: cellular swelling
--failure of the Na/K pump
-Interstitial: obstructive hydrocephalus

Front 388

Tissue lesions in the CNS

Back 388

-Spongiosis
-Demyelination
-Inflammation
-Non-specific vascular lesions
-Meningeal lesions

Front 389

Spongiosis

Back 389

-Tissue lesion in the CNS
-Vacuoles in the grey matter are Spongiform encephalopathies
-Vacuoles in the white matter are between myelin lamellae
--toxic and metabolic diseases
-Can look similar to edema

Front 390

Demyelination

Back 390

-Tissue lesion in CNS
-Loss of myelin can be detected by lack of staining using luxol-blue myelin stain
-Caused by damage to oligodendrocytes in CNS or schwann cells in PNS
--myelin producing cells are damaged
-Remyelination is very poor in CNS, usually successful in PNS
--schwann cells can regenerate and remyelinate, each cell only interacts with one internode on a single axon
--Oligodendrocytes myelinate 1-50 internodes on 1 or many axons

Front 391

Inflammation in the CNS

Back 391

-Local or disseminated infiltrates of inflammatory cells with perivascular cuffs, vascular dilation, and edema
-Often due to infectious agents
-Can also occur after trauma, infarcts, or secondary to neoplasms
-Is often idiopathic
-Pachymeningitis, FIP, toxoplasma gondii

Front 392

Pachymeningitis

Back 392

-Inflammation involves the dura mater

Front 393

Feline Infectious Peritonitis in the CNS

Back 393

-Causes inflammation in the brain
-Damages blood vessels to cause inflammation
-Monocytes are brought into tissues
-Causes unique lesions in the brain, type of damage is indicative of the virus
-No inclusion bodies

Front 394

Non-specific vascular lesions in the CNS

Back 394

-Ischemia
-Hypoxia
-Metabolic disorders
-Inflammatory disorders
-Result in capillary proliferation with endothelial cell hypertrophy

Front 395

Cellular Lesions of the PNS

Back 395

-Wallerian degeneration (usually after traumatic injury)
--axon is transected
-Segmental demyelination
--axon remains intact
--schwann cells can regenerate
-Axonal degeneration
--Swelling of axon, loss of axon and myelin sheath
--axonodystrophy
--neuroaxonaldystrophy

Front 396

Wallerian degeneration in PNS

Back 396

-Schwann cell proliferation occurs distally inside tubes of schwann cell basement membrane
-Axonal sprouts appear proximally at site of transection
-Axonal sprouts follow Schwann cells to former synapse
-Muscle undergoes denervation atrophy if motor nerves are severeed
-If muscle is reinervated, enlargement of motor units may occur
--fiber type grouping

Front 397

Wallerian Degeneration Steps
PNS

Back 397

1. Injury and initial reaction (24 hours)
2. Macrophages are recruited, Wallerian degeneration starts (1 week)
3. Schwann cells are aligned and axons are regenerated (weeks to months)
--schwann cells proliferate and guide axon back to the muscle
4. Successful target reinnervation (weeks to years)

Front 398

Wallerian Degeneration Outcome
PNS

Back 398

-Successful regeneration in PNS depends on 3 factors
1. Site of injury: more distal lesions have better recovery
2. Distance between severed ends: closer is better recovery
3. Amount of damage and debris at the injury site: less injury and debris leads to better recovery

If regeneration is unsuccessful, neuroma may develop
--small painful nodule of axons and Schwann cells

Front 399

Segmental Demyelination

Back 399

-Destruction of Myelin sheaths, leaving intact bare neuron
-Internode or segment is lost
-Results in conduction block or slowing of nerve impulse
-Schwann cells can proliferate, remyelination is usually complete
-Usually associated with inflammatory or toxic diseases

Front 400

Axonal Degeneration
Axonodystrophy

Back 400

-Metabolic derangement of the entire neuron
-Leads to dying back of the distal portion of the axon
-Myelin sheath breaks down at the same time
-regeneration is poor
-Associated with toxic, inherited, and metabolic diseases
-Inherent issue with a neuron

Front 401

Congenital Malformations of the Nervous System

Back 401

-Genetic or environmental factors
-Can be individual factors or interacting factors
-Most spontaneous malformations are idiopathic
-Nervous system has numerous precisely-timed developmental steps
--Critical part of determining the type and severity of a malformation is time of gestation when destructive agent acts on nervous system

Front 402

Neurulation

Back 402

-Formation of the neural tube
-Neural plate is formed first
-Neural groove forms from the neural plate
-Neural tube closes in middle of tube and extends cranially and caudally
--Rostral neural tube develops into the brain
--Rest of neural tube becomes the spinal cord

Front 403

Meningocele

Back 403

-Limited failure of neural tube closure with meninges under the skin
-Section of neural tube fails to close, meninges also fail to close

Front 404

Mechanisms of Hydrocephalus

Back 404

1. Oversecretion of CSF (rare)
2. Obstruction of CSF flow (common)
-can be congenital or acquired
-Congenital blockages can be due to malformations of the mesencephalic aqueduct
-Acquired blockages are due to neoplasms, inflammation, astrocytic sclerosis
3. Impaired absorption of CSF (rare)

Front 405

Traumatic diseases of the Nervous System

Back 405

-Fractures
-Hemorrhage
-Edema
-Contusion (bruising)
-Concussion
-Luxation and ssubluxation of vertebrae
-Infarction secondary to vascular compression, occlusion, or rupture

Front 406

Consequences of Trauma to the Nervous system

Back 406

-Increased ICP
--leads to cerebellar herniation and compression of the medullary respiratory and cardiovascular centers, leads to death
-Infection of open injuries
-Scar formation
--leads to post-traumatic seizures
--glial scars cause abnormal electrical function in brain
-Wallerian degeneration of severed axons
--can have regeneration depending on severity and location

Front 407

Intervertebral Disks

Back 407

-Discs are composed of Nucleus pulposus (gelatinous watery substance)
-Nucleus pulposus is surrounded by Annulus fibrosus (concentric fibrous lamellae)

Front 408

Types of Intervertebral disk disease

Back 408

1. Herniation: extrusion of the nucleus pulposus through a tear in the annulus fibrosus
-Hansen's Type I
2. Protrusion: annulus fibrosus bulges into the spinal canal
-Hansen's type II

Front 409

Intervertebral Disc Disease

Back 409

-Occur in Cervical or thoracolumbar area
--T13-L1 are especially vulnerable
-Clinical signs and lesions depend on:
--direction (dorsal, ventral, lateral, etc.)
--Size or volume, determines degree of compression
--Speed (slow vs. explosive)
--Spinal cord location
--duration until recovery from edema or hemorrhage (shorter duration is better)

Front 410

Pathogenesis of Intervertebral Disc Disease

Back 410

1. Nucleus pulposus degenerates with age
--earliest lesion in chondrodystrophic dogs
2. Degeneration leads to protrusion or herniation of nucleus pulposus through damaged annulus fibrosus
--earliest lesion in non-chondrodystrophic dogs
--annulus fibrosus is damaged 1st
3. Direct compression of the spinal cord and/or nerve roots and spinal vessels
--causes hemorrhage and necrosis

Front 411

Sequelae of intervertebral Disc disease

Back 411

-Demyelination is least severe
--damage to schwann cells, can regenerate
-Leukomyelomalacia is more severe
-Edema and hemorrhage is more severe
-Poliomyelomalacia is MOST severe
--necrosis of gray matter on inside of the spinal cord
-Occasionally a syndrome of ascending myelomalacia occurs following severe disc disease

Front 412

Ascending Myelomalacia

Back 412

-Huge area of necrosis that ascends

Front 413

Vertebral Malformations

Back 413

-Lead to compression of the spinal cord
-Due to narrowing of the spinal canal (stenosis)
-Hemivertebrae: wedge-shaped vertebrae
-Cervical vertebral malformation and malarticulation in large dogs
-Cervical stenotic myelopathy (wobbler horses)
-Lumbosacral stenosis (cauda equina syndrome)

Front 414

Neurovascular Disease

Back 414

-Hypoxia: deprivation of Oxygen, blood flow is maintained
--issue is with O2, not delivery
--Usually respiratory disease
-Ischemia: blood flow is severely reduced or completely obstructed
--directly related to blood flow
-Hemorrhage
-Infarct: focal brain necrosis that follows obstruction of blood flow
--associated with cuterebra larva migration in cats
--Septic neoplastic emboli in dogs (bacteria and tumors)
--Fibrocartilagenous emboli
-Early infarcts may just be hemorrhage, chronicity will lead to loss of tissue

Front 415

Diagnosing Neural Disease

Back 415

-Need a FULL history!
-Same gross appearance of clinical signs can be caused by different processes

Front 416

Fibrcartilagenous Emboli in the Neural System

Back 416

-Unknown pathogenesis
--Intervertebral disc material?
-Occurs in dogs and pigs
-Often a history of excessive exercise
-Acute onset of clinical signs
-Clinical signs depend on site of embolization
-Myelomalacia results
-Disc emboli can be identified with toluidine blue stains
--in veins and arteries

Front 417

Pathogenesis of Fibrocartilagenous Emboli in the Nervous system

Back 417

-Intervertebral disc emboli leads to occlusion of small blood vessels
-Infarct occurs, causes necrosis
-Macrophages from the blood are recruited to remove necrotic debris

Front 418

Infectious Organism entry into the Nervous System

Back 418

1. Blood: crosses blood brain barrier
--most common route
--can enter within macrophages or on own if small enough
2. Local extension: areas near the brain get infected and infection spreads
--frontal sinusitis, discospondylitis, otitis interna
--usually bacterial and suppurative
3. Direct penetration: usually due to trauma
--fractures, bite wounds, surgical procedures
4. Retrograde axonal flow: from peripheral infection into the CNS
--rabies virus, herpesvirus, listeria monocytogenes
--tetanus neurotoxin

Front 419

Viral disease in Nervous System

Back 419

-Destruction of nerve cell bodies with or without neuronophagia
--Kills neurons
-Locally disseminated perivascular cuffs
--usually lumphocytes and plasma cells
-Inclusion bodies, intranuclear or intracytoplasmic
-Microglial proliferation
-Inflammation in the ventricles is atypical with viral diseases

Front 420

Rabies virus in the Nervous system

Back 420

-Will see inclusion bodies in neurons

Front 421

Canine Distemper Virus in the Nervous System

Back 421

-Will see inflammation and necrosis
-May have encephalitis
-Nuclear and cytoplasmic inclusion bodies

Front 422

Bacterial infection in the Nervous System

Back 422

-Rarely primary infection, usually there is another focus of infection
-Usually suppurative exudate
--many neutrophils and macrophages
-Often will get extensive necrosis with or without abscesses
-Young animals are likely to have bacterial meningoencephalitis secondary to bacteremia/septicemia
-Space-occupying abscesses will increase ICP and lead to compression of the medulla
--Will have TONS of neutrophils

Front 423

Suppurative Ventriculitis

Back 423

-Pus in the ventricles

Front 424

Suppurative meningitis

Back 424

-Pus in the meninges
-May have pockets of pus in the leptomeninges

Front 425

Parasitic Infections of the Nervous System

Back 425

-Usually necrotizing with secondary inflammation
-Need to look for underlying agent

Front 426

Neospora caninum in CNS

Back 426

-Will get blood vessels with perivascular cuffs

Front 427

Fungal infections in the Nervous System

Back 427

-Usually granulomatous inflammation
-Usually in multiple sites in the brain and other tissues
--can occur throughout the body

Front 428

Cryptococcus neoformans in the brain

Back 428

-Soap bubble exudate in the parenchyma

Front 429

Prions

Back 429

-Cause spongiform encephalopathies in the brain
-Bovine, sheep, and mink encephalopathies
-Cause neuronal vacuolation

Front 430

Necrotizing Encephalitis

Back 430

-Big areas of edema
-No distinction between white and gray matter
-Loss of symmetry in the brain
-Looks similar to an inflammatory disease

Front 431

Granulomatous meningoencephalitis

Back 431

-Big areas with lots of macrophages

Front 432

Demyelination

Back 432

1. direct effect on oligodendrocytes or Schwann cells and myelin
-Damage to myelin-producing cells
-Can be viral or toxins
2. Following Wallerian degeneration or axonodystrophy
-Axon is injured, myelin is injured with the axon

Remyelination may be complete in the PNS
Limited remyelination can occur in the CNS

Front 433

Leukodystrophies

Back 433

-Abnormal myelin formation, maintenance, or destruction
-Loss of white matter
-Histologically white matter can be darker or lighter than it should be
-Most are inherited disorders due to enzyme deficiencies
-Macrophages eat/digest myelin

Front 434

Fusarium and the CNS

Back 434

-From moldy corn
-Can lead to huge cavities in the white matter of the brain
-Leukoencephalomalacia

Front 435

Penetren

Back 435

-Moldy yogurt
-Lead to polioencephalomalacia
-Targets basal ganglia

Front 436

Polioencephalomalacia in Ruminants

Back 436

-Can be caused by a thiamine deficiency
-Thiaminase producing bacteria in the rumen destroy thiamine
-Will have a think amount of grey matter over the corona radiata in the cerebrum
-Pseudolaminar necrosis of the cerebral cortex
-Distribution helps with the diagnosis
-Metabolites fluoresce with UV light

Front 437

Copper deficiency and Leukoencephalomalacia

Back 437

-Occurs in sheep, deer, goats, pigs, elk
-degeneration of white matter involving specific tracts
-Molybdenum excess often leads to a relative copper deficiency
-Cavities are left where the white matter should be, looks like an "empty brain"

Front 438

Acute Neuronal Necrosis

Back 438

-Caused by hypocalcemia or ischemia, toxins, infections
-May also be due to a metabolic disease
-Neurons appear angular, surrounded by white space
--nuclei are lost
--"Kite-shaped" angular neurons

Front 439

Neuronal Storage Diseases
Gangliosidosis

Back 439

-Accumulations of uncatabolized material within neurons or glia
-Material may be exogenous, due to plant poisoning
-Endogenous, due to lysosomal enzyme deficiency
-Named by the substance that accumulates
--gangliosides
--sphingomyelin
--glucocerebrosides
-Usually due to an enzyme deficiency and buildup within the neuron
-Histologically may see vacuoles accumulating within the neuron
--impair function

Front 440

Neuronal Degenerative Diseases
Cerebellum

Back 440

-Cerebellar degeneration/atrophy/abiotrophy
-May result in dysfunction of voluntary movement and posture
-Can have Purkinje cell loss
--astrocytes proliferate to fill in space
-May also have loss of granular layer cells and astrogliosis
-Have normal development, then degeneration and atrophy occurs
-Cerebellum will look small

Front 441

Neuronal Degenerative Diseases
Spinal Cord

Back 441

-Loss of myelin and then axons from specific zones or tracts
--White matter tracts
-Eventually lose axons, over time
-Ex: canine degenerative myelopathy, equine degenerative myelopathy
-Looks like dilated myelin sheaths
-Swollen axons

Front 442

Lower Motor Neuron Diseases

Back 442

Neuronal Degenerative Disease
-canines will have degeneration of ventral horn cells
-equine lower motor neuron disease
-Glassy material accumulates in the neuron
--change in protein production in the neuron

Front 443

Neoplasms in the Nervous System

Back 443

-Neoplasms originating in the nervous system are common
-Neoplasms of embryonal remnants are rare
-Neoplasms of the skull and vertebral column are common
--do not arise in the CNS but compress the CNS
-Metastatic/secondary neoplasms in the CNS are common
-Neoplasia displaces normal parenchyma
--leads to ischemia, necrosis, gliosis, secondary inflammation
-Causes increase in ICP
-Can also cause hydrocephalus by blocking flow of CSF
-Eventually space-occupying masses lead to herniation of the cerebellum and medulla and death
-Are non-specific lesions

Front 444

Clinical signs of Neural system Neoplasia

Back 444

-Depends on localization, size, rate of growth, and secondary vascular lesions
-Can cause many different clinical signs, depending on location
-Loss of function of specific tracts and nuclei
--blindness (optic nerves)
--Head tilt (vestibular areas)
--endocrine abnormalities (pituitary area up into thalamus)
--Ataxia (ascending proprioceptive tracts in spinal cord, cerebellum)
--Weakness (descending motor tracts)
-Seizures (hippocampus or cerebral cortex)
-Coma and death (medulla)

Front 445

Suprasellar germ cell tumor

Back 445

-Compresses the optic tract and leads to blindness

Front 446

Pituitary carcinoma

Back 446

-2 different tumors can occur in same location that will have same clinical signs

Front 447

Types of Primary Neoplasms in the CNS

Back 447

1. Glial tumors
--astrocytoma, oligodendroglioma, ependymomas, glioblasstoma multiforme, glioma, mixed gliomas, gliomatosis cerebri
--COMMON, most common type of neural neoplasm
2. Choroid plexus timors
--Adenoma, carcinoma
--common
3. Primitive neuroectodermal tumors
4. Meningiomas
--common but easy to get rid of because they are on the surface
5. Nerve sheath tumors
--in spinal cord, common
6. Pituitary tumors
--adenoma, carcinoma
--common

Front 448

Glial Tumors

Back 448

-Astrocytoma
-Oligodendrogliomas
-Glioblastoma multiforme

Front 449

Astrocytoma

Back 449

-Glial tumor
-Very destructive space-occupying mass
-Diffusely infiltrative
-Destroy the normal architecture of the site
-Can involve the cerebral hemisphere, brainstem, or spinal cord

Front 450

Oligodendrogliomas

Back 450

-Glial tumor
-Most frequently involve a cerebral hemisphere, especially in the periventricular site
-Can cause extensive compression
-Soft, mucinous consistency
-May be hemorrhagic
-IN the dog, prominent endothelial proliferations create glomerular-like formations

Front 451

Glioblastoma multiforme

Back 451

-Glial tumor
-Common in humans
-Anaplastic glial tumors
-Typically found as palisades of neoplastic cells surrounding necrotic foci
-Vascular proliferations are common

Front 452

Meningiomas

Back 452

-Originate from the cells of the arachnoid
-Can occur in spinal column
-In the Dog can cause variety of clinical signs depending on location
--frequently infiltrates the adjacent brain parenchyma, sends tendrils into parenchyma
--Infiltration makes complete surgical removal difficult
-In Cats can produce clinical signs and can also be silent
--3rd ventricle is a common site without any signs
--Usually do not infiltrate brain parenchyma

Front 453

Classification of Meningiomas

Back 453

-Classifications have little biological significance
-Meningotheliomatous (syncytial)
-Fibrous (fibroblastic)
-Transitional (mixed)
-Psammomatous
-Angiomatous (angioblastic)
-Papillary
-Granular cell
-Microcystic
-Myxoid (choroid)
-Atypical
-Anaplastic (malignant)

Front 454

Choroid Plexus Tumors

Back 454

-Papillary mass within the ventricles
-Commonly infiltrates into the subarachnoid space
--causes extensive meningeal metastasis, especially in the spinal cord
-Infiltrates adjacent parenchyma

Front 455

Other primary tumors and cysts of the nervous system

Back 455

-Vascular hamartoma
-Epidermoid cyst, lined by stratified squamous epithelium
-Pituitary cyst

Front 456

Vascular hamartoma in the Nervous System

Back 456

-Need to look histologically to know what it is

Front 457

Metastatic tumors to the Nervous System

Back 457

-Hemangiosarcoma (dog)
-Carcinomas (dogs and cats)
-Lymphosarcoma (dog and cat)
--sometimes only occurs in the nervous system
-Histiocytic sarcoma
--sometimes only occurs in the nervous system
-Many others are less common

Front 458

Neoplasms of the skull and vertebral column

Back 458

-Osteosarcoma, osteoma
-Chondrosarcoma, chondroma
-Multilobular tumor of bone
-Synovial myxoma
-Multiple myeloma
-Nasal carcinoma
-Olfactory neuroblastoma
-Metastatic prostatic carcinomas

All cause clinical signs of nervous system disease

Front 459

Tumors of the PNS

Back 459

-Nerve sheath tumor
--Schwannoma, neurofiibroma (benign)
--Malignant Schwannoma, neurofibrosarcoma (malignant)
-Ganglioneuroma
-Peripheral neuroblastoma
-Paraganglioma

Front 460

Malignant Nerve Sheath Tumors

Back 460

-Common in the dog
-Nodular masses or varicose thickenings of the cranial and spinal roots, peripheral nerve trunks, or nerves
-Poor prognosis
-Highly invasive, often extend up the nerves to the spinal roots and spinal cord
-recur often
-Often involve different nerve roots