LEC 7 - Bone Flashcards
What are the three cell types responsible in the maintaince and construction of bone?
Osteoblasts
Osteocytes
Osteoclasts
Where do osteoclasts orginate from?
Hematopoietic stem cells
What is the function of osteoclasts?
Responsible for bone resorption
Attach to mineralized bone surface
Where are osteocytes located?
Osteoblasts that have been surrounded bu mineralized osteoid
Occupying small clear spaces called lacunae
Where do osteoblasts arise from?
Mesenchymal cells
What is the function of osteoblasts?
Initiate mineralization
Produce matrix
Initiate resorption of the resorption by osteoclasts
What do osteocytes and osteoblasts control together?
Calcium homeostatisis
In what direction does bone grow?
In length by intersitial growth
Within metaphyseal growth plates
Describe: Endochondral ossification
Process in which bone desposited at mineralized longitudinal septa of the physes
How many zones are there in the physes?
3
What are the three physeal zones?
Resting
Proliferative
Hypertrophic
Describe: Resting Zone
Source cells for proliferative zone
Describe: Proliferative zone
Cell multiply
Accumulate glycogen
Produce matrix and become arranged in longitudinal columns
Describe: Hypertrophic zones
Chondrocytes secrete macromolecules to allow capillary invasion and initiate matrix calcification
What are the two sub-zones of hypertrophic zones?
Maturation
Degeneration
Calcification
How does growth of epihysis occur?
Endochondral ossification at articular-epiphyseal complexes
(AEC)
What is the AEC composed of?
Articular cartilage
Subajacent temporary growth cartilage
How does bone grow in width?
Intermembranous bone formation
What is the surfaces of bone covered by?
periosteom
What is periosteom made from?
Loosely attached membrane
Outer fibrous layer = structural support
Innter osteogenic layer = normal lamellar apossitional bone
What type of bone is laid down in response to injury?
Abnormal woven bone
What hormonal agents are released in response to insult on the bone?
Calcitrol
PTH
What are two examples of disruption of endochondral ossification?
Growth arrest lines
Growth retardation lattice
Describe: Growth arrest lines
Multiple nutrient deficiencies cause the growth plate to become narrow
Metaphyseal face of the plate can be sealed by layer of bone
= transverse trabeculation
Describe: Growth retardation lattice
Impairment of osteoclastic resporption of bone within primary trabeculae
= retention primary trabeculae
they then elongate because of continous EO
What does tension cause to the bone?
Resporption
What does compression cause to the bone?
Bone formation
Describe: Wolff’s Law
Ability of bone to change its shape and size to accomodate altered mechanical use
What happens with normal mechanical use?
Suppression of resorptive activity = maintaince of bone mass
What happens when there is a decrease in mechanical use of a bone?
Bone resorption = less mass
What happens with increased mechanical use of the bone?
Increased bone mass
Describe: Woven bone
Newly formed
Hypercellular bone deposited in reaction to injury
When is woven bone normal?
Young animals
When is woven bone pathologic?
Adult animals
What does woven bone look like in histiologically?
Collagen fibers randomly arranged
More numerous osteocytes
Osteocytes are larger
How does injured periosteum resond to injury?
Forms bone
What is reactive periosteal woven bone mostly made of?
Cartilage
What decides the production of cartilage from the injured periosteum?
Avalibility of oxygen
Low = cartilage predominates
What can happen to the cartilage once it is from in a low tension oxygen environment?
Endochondral ossification
What are the two paths that reactive woven bone can occur?
Remodeled lamellar bone
– or –
Removed by osteoclastic resorption
Describe: Osteophytes
New bone that occurs in response to joint injury/instability
What can occur with infectious inflammation of the periosteum?
Marked osteoclastic bone resorption at the periosteal surface
What is the problem with the articular cartilage responding to injury?
Minimal capacity of repair due to no blood supply
What happens with erosion of the cartilage?
Clusters of chondrocytes form
What happens if the erosion of the cartilage extends to the subchondral bone?
Mesenchymal cells access teh area and become quickly filled with vascular fibrous CT
What are the causes of sterile injury to the articular cartilage?
Trauma
Joint instability
Lubrication failure
What activates MMP’s?
Products of degenerating/reactive chondrocytes
– and –
Inflammatory cells
What is the function of MMP’s?
Digest the matrix
What is the mechanism by which the loss of proteoglycans lead to mechanical injury of the cartilage?
Alters hydraulic permeability
Abnormal joint lubrication
Increases susceptibility to mechanical injury
What does the surface of the articular cartilage look like when there is damage?
Surface is yellow-brown
Dull, slightly roughended appearance
Term: Fibrillation
Condensed + fray collagen ibers due to loss of proteoglycans
Term: Eburnation
Smooth + Shiny surface of subchondral bone after cartilage ulceration
How does the synovium respond to injury?
Villous hypertrophy + hyperplasia
Synoviocyte hypertrophy + hyperplasia
Pannus formation
Describe: Pannus
Fibrovascular + Histocytic tissue
Arises from synovial membranes
Spreads over articular cartilage
What is the mechanism by which pannus causes the fusion of joints?
Histocytes + Callagenases from fibroblasts
lead to lysis and destruction of underlying cartilage
Fibrous Tissues unite the surfaces = Fibrous ankyloses
Describe: Rickets
Affects bone and epiphyseal cartilage
Describe: Osteomalacia
Effects bones only
What is the cause of rickets and osteomalacia?
Vitamin D + Phosphorus deficency
What is rickets and osteomalacia?
Failure of mineralization with subsequent bone deformaties + fractures
Growing skeleton = Rickets
Adult Skeleton = Osteomalacia
What is the pathogenesis of Rickets and osteomalacia?
Vitamin D deficiency
Hypercalcemia
Stimulates secreation of parathyroid hormone
renal phosphorus loss is enhanced
Reduce the deposition of calcium further
What lesions are seen with rickets?
Diffuse, irregular thickened growth plates
Most common at the costo-chondral junctions
aka Rachitic rosary
What lesions are seen with osteomalacia?
Accumulation of microfractures or fractures
What lesions are seen in both rickets and osteomalacia?
Cortical bone can be softened
Increased depostion of osteoid in trabecular zone
Describe: Fibrous osteodystrophy
Increased, widespread osteoclastic resorption of bone
Replacement by primitive fibro-osseus tissue
= weak bones
What can cause primary fibrous osteodystrophy?
Pituitary adenoma
Carcinoma
Hyperplasa
What can cause secondary fibrous osteodystrophy?
Hyperparathyroidism
(nurtritional or renal)
– and –
Pseudohyperparathyroidism
What is the pathogenesis of fibrous osteodystrophy caused by increased PTH?
promotes excretion of phosphorous + retention of calcium
What is the pathogenesis of fibrous osteodystrophy when caused by renal disease?
Loss of glomerular function
Inability to excrete P + Inadequate calcitriol production
Hyperphsohatemia
What is the pathogenesis of fibrous osteodystrophy when caused by excess P or inadequate calcium?
Stimulation of osteocytic/osteoclastic bone resorption
Decrease bone mineralization
Replacement by fibrous CT
Weak bone structure
What are the disorders of encochondral ossification?
Chondrodysplasias
Osteochondroses
What are the different types of chondrodysplasias?
Primordial dwarfism
Spider lamb
Describe: Chondrodysplasias
Disorders of bone growth
Result in primary lesions in growth cartilage
What do chondrodysplasias result in?
Disporportionate dwarfism
What breeds are presdisposed to disportionate dwarfism?
Dachshunds
Pekingese
Basset hounds
What is the cause of chondrodysplasia resulting in disproportionate dwarfism?
Mutaiton in FGF4
Inapproriate activation of FGF3 receptor
Negative regulator of bone growth
Describe: Primordial dwarfism
Limb length proportional to body length
What causes primordial dwarfism?
Endocrine disease or malnutrion
What are examples of dog breeds that have primordial dwarfism?
Miniature schnauzer
Miniature pinchers
What lambs are at risk for spider lamb chondrodysplasia?
Suffolk
Hampshire
What causes spider lamb chondrodysplasia?
Mutation in FGF3 receptor
Impairs inhibition of chondrocyte proliferation
Results in elongation of limbs and multiple centers of ossification in the epiphyses
What are the three types of osteochondroses?
Latens
Manifesta
Dissecans
Describe: Joint mouse
Cartilage or Osteochondral flap that has fractured/detached from articular surface
Describe: Osteochondrosis latens
Well demarcated areas of necrosis of epiphyseal cartilage
Centered on necrotic blood vessels
Describe: Osteochondrosis manifesta
retained necrotic epiphyseal cartilage
Seen grossly
Describe: osteochondrosis dissecans
Lesion at AEC
Forms cleft in necrotic cartilage with subsequent fracture of articular cartilage
leads to joing mouse
Term: Osteitis
Inflammation of bone
Term: Periostitis
Inflammation of bone with involvement of medullary cavity
Term: Osteomyelitis
Inflammation of bone with involvement of medullary cavity
What are the three causes of infectious inflammation of bone?
Hematogenous bacteria
Fungi
Virus
What is the bacterial form of infectious inflammation of bone most common in?
neonatal foals
food animals
What are possible bacterial causes of infectious inflammation of the bone?
T. pyogenes
Strep/Staph
Salmonella
E. Coli
What fungi can cause infectious inflammation of the bone?
Coccidioides immitis
Blastomyces dermatitidis
What can coccidioides + blastomyces do to the bone?
Granulomatous to pyogranulomatous osteomylitis
What viruses are known to cause infectious inflammation in the bone?
Swine fever
infectious canine hepatitis
What does the viral form of infectious inflammation of the bone cause?
Endothelial damage
– and–
Ischemic necrosis
What does distemper virus do to the bone?
Infect osteoclast
Disrupt bone modeling
Leads to growth retardation
What does FeLV do to the bone?
Associated with myelosclerosis
What can cause reactive bone formation?
Fracture repair
Chronic osteomyelitis
DJD
Term: Exostosis
Nodular benign bony growth projecting outward from surface of bone
Term: Enthesophyte
Calcification of tendon or ligament at the point of its insertions
Term: Hyperostosis
Increased diameter of bone and implies uniform thickening on periosteal surface rather than nodularity
Term: Enostosis
Bony growth within medullary cavity
Originates from cortical-endosteal surface
= Medullary cavity obliteration
What are the characteristics of hypertrophic osteopathy?
Progressive, bilateral, periosteal new bone formation in diaphyseal regions of distal limbs
Secondary reaction to primary lesion
What are the characteristics of osteochonromas?
Eccentric masses loacted adjacen to physes
What are osteochondromas?
Multiple cartilaginous exostoses
Reflect a defect in skeletal development
What does osteochondromas look like microscopically?
Outer cap of hyaline cartilage
Undergo endochondral ossification that give rise to trabecular bone
What are the three types of bone cysts?
Subchondral
Simple
Aneurysmal
Describe: Subchrondral cysts
Sequela to osteochondrosis (failure of EO)
– and –
DJD (herniation of synovial fluid)
Describe: Simple cysts
Contain clear, colorless, seroanguious fluid
Wall composed of dense fibrous tissue + Woven bone
Term: Aneurysmal cyst
Filled with blood
Not lined by endothelium
What are common bones that are sites of secondary bone neoplasms, in dogs?
Rib shafts
Vertebral bodies
Humeral/Femoral metaphyses
In cats where do secondary neoplasms of the bone tend to go?
Appendicular skeleton
Where do pulmonary carcinomas tend to go in a cat?
Digits
What predispose an animals to pathologic fractures?
osteoporosis
osteomyelitis
bone neoplasia
By what method are fractures of the growth plate classified?
Salter-Harris
What does a grade V to VI fracture mean?
Crush growth plate
What does a grade III to IV fracture mean?
Cross growth plate
What does grade I and II fracture mean?
Only involve hypertrophied layers of cartilage
and/or
Primary bone trabeculae
What predisposes an animal to fractures of the trabecular bone?
Inflammation
Necrosis
Term: Infractions
Fractures without external deformation of the cortex
Term: Closed fracture
Skin is unbroken
Term: Open fracture
skin is broken
bone is exposed to exterior
Term: Comminuted
Bone is shattered in several small pieves
Term: Avulsed
Caused by traction of a ligament
Term: Greenstick
One cortex of the bone is broken and the other is bent
Term: transverse or spiral fracture
Depending on orientation of the fracture line, whatever it looks like
Describe: Stable fracture repair
Immobilization of fractured ends to give relative stability
but NOT surgically fixed
What is the first step in stable fracture repair?
Macrophages + Platelets in:
Blood clot
Proliferating osteogenic tissue
Produce growth factors which stimulate proliferation of repir tissue
aka woven bone
What are the growth factors secreted by the macrophages + platelets in the first stage of stable fracture repair?
Bone Morphogenic proteins
TGF-B
PDGF
What forms granulation tissue in stable fracture repair?
Undifferenitiated mesenchymal cells penetrate area
Where do the undifferentiated mesenchymal cells come from in stable fracture repair?
Periosteum
Endosteum
Medullary cavity
What is the outcome of the granulation tissue in stable fracture repair?
Cartilage
– and –
Bone metaplasia
What are the final stages of stable fracture repair?
Primary callus formation (woven bone)
Secondary callus formation forms when woven bone is replaced by lamellar bone
Describe: Rigid fracture repair
Surgical intervention that involves the application of devices to keep the bone ends in contact with each other for fracture stability during the repair process
What is the process of healing in rigid fracture repair?
Direct osteonal bridging of teh fracture
What do osteoclasts do during rigid fracture repair?
Osteoclasts forming channels for new osteons will jump fracture line
New osteons with will knit the bone ends together without formation of callus
What are the five complications of fracture healing?
Inadequate blood supply
Instability
Infection
Malnutrition
Associated with implants
What happens with fracture healing when there is an inadequate blood supply?
Hyaline cartilage will form
– or –
Necrosis if anoxia is present
What can cause instability during fracture healing?
Mechanical tension + compression
Developments fibrous CT
if there is excessive movement
What are the problems associated implants in fracture repair?
Too large
Blood supply damage
Bacterial growth
What happens when a fracture implant is too big?
Deprive the bone of normal mechanical forces
Leads to atrophy of disuse
What animals are at risk for arthrogryposis?
Cattle
Sheep
What is arthrogryposis?
Congenital contracture of a joint
Normally bilateral
What are the etiologies that can cause arthrogryposis?
Damage to the CNS
– or –
Fetal paralysis caused by maternal intoxications
What viral infections can lead to arthrogryposis?
Akabane virus
Bluetongue virus
What can toxins can cause fetal paralysis?
Lupine plants - Anagyrine
Poison hemlock - Coiine
Who is hip dysplasia a major problem for?
Dogs
Describe: Hip dysplasia
Biomechanical disease
Joint laxity of the hip = instability
What does hip dysplasia result in?
Chronic subluxation
Severe secondary DJD
Describe: DJD
Disease of synovial joints
What can cause DJD to occur?
traumatic injury to the articular cartilage
inflammation of synovium
Abnormalities in conformation/jt. stability
What are most cases of DJD secondary to?
Osteochondrosis
What is the three cellular reasons for degeneration of intervertebral discs?
Loss of water + proteoglycans
Hypocellularity
Increase collagen content
Where are cellular changes that lead to degeneration of the intervertebral disks occur?
Nucelus pulposus + Weakened annulus fibrosus
What happens to the IVD once cellular abnormalites occur?
Concentric/radial fissures in annulus
Leads to buldging or herniation of nucleus pulposus material
What occurs because of instability in the IVD?
Development of osteophytes at margins of vertebral margins
– – or –
Adjacent disks
Infectious arthritis (animal + presentation): Erysipleothrix rhusiopathiae
Pigs
Septicemia leading to synovial joint + IVD lesions
Infectious arthritis (animal + presentation): trueperella pyogenes
Cattle + Pigs
Suppurative arthritis
Infectious arthritis (animal + presentation): Haemophilus parasuis
Piglets
8 to 16 weeks
Polyarthritis
Infectious arthritis (animal + presentation): Borrelia burdogferi
Dog + Cattle + Horses
Arthrtis
Lyme disease
Infectious arthritis (animal + presentation): Mycoplasma hyorhinis
Pigs
Weaning
Fibrinous polyarthritis
Infectious arthritis (animal + presentation): Mycoplasma bovis
Cattle
Fibrinous to pyogranulomatous arthritis
What are viral causes of arthritis?
Caprine arthritis
Encephalitis virus
What disease is responsible for noninfectious arthritis?
Crystal deposition disease
What are the characterizations of crystal deposition disease?
Deposition of minerals such as urates + calcium phosphates
within articular cartilage +/- soft tissue joints
What speices lack the urease enzyme?
Primates
Birds
Reptiles
What does uriase do?
Promotes oxidation of uric acid