Test 4: 4: bones Flashcards
catilage is made of — and is a good shock absorber
type 2 hyaline articular cartilage
water
GAGs
long bones are formed by
EO
endochondral ossification
cartilage template
flat bones are formed by
IO
Intramembranous ossification
without cartilage template
how does Intramembranous ossification (IO) work
Bone formed directly from mesenchyme
WITHOUT a cartilage template
forms type 1 cartilage then as it matures forms Hydroxyapatite cyrstal and remodeled into lamellar bone
how does Endochondral Ossification (EO)
work
cartilage template
blood vessels bring trophic factors
form bone
EO requires what 3 things
normal template
blood supply
hormones and nutrition
zones of EO formation
reserve zone
zone of proliferation- chondrocytes stack and multiply
zone of hypertrophy- swell and mineralize and capillaries grow
zone of ossificaion- osteoCLASTs come in and eat chondrocytes leaving spicule template. osteroBLASTs come in and lay bone forming primary trabeculae
Defect in the cartilage template required for endochondral ossification
Chondrodysplasias
spontaneous or hertitable
what is the mutation that causes short legs in basset hounds
FGF4 mutations in K9 CDPA/CDDY
type of chondrodysplasia
error in EO
Disproportionate (chondrodysplastic) dwarfism
Disproportionate (chondrodysplastic) dwarfism in calves that is lethal is caused by —
Col2A1 & Aggrecan mutations (Dom. Neg effect)
K9 Chondrodysplastic phenotype (CDPA) is caused by — mutation and causes
CFA18-FGF4
short legs (breed standard for Dachshunds, Basset Hounds, Corgis)
different from Chondrodystrophic phenotype (CDDY) that is caused by CFA12-FGF4 mutation and lead to short legs and IVDD
K9 Chondrodystrophic phenotype (CDDY) that is caused by— mutation and lead to —
CFA12-FGF4
short legs and IVDD
different from Chondrodysplastic phenotype (CDPA) → short legs
what happens to nucleus pulposus during chondrodystrophy IVDD
mutate and then can rupture out of disc and cause neural issues by damaging the spinal cord
Osteogenesis Imperfecta is a — disease that causes — done density and increased bone —.
osteopenic
decreased
fragility
caused by mutation in type 1 collagen- affects both osteroblast and odontoblasts
type 1 collagen found in bone, dentin of teeth and eyes (blue)
how does OI cause fragile bones
mutates type 1 collagen, prevents helix and lining up and binding to form bone matrix
Developmental defects in EO at FOCAL, REPEATABLE sites → focal defects at articular cartilage/subchondral bone interface
Osteochondrosis
Osteochondrosis can lead to
Osteochondritis Dissecans (OCD)
Osteochondrosis forms — lesions in growth cartilage (— > —)
heterogeneous
epiphyseal (end of bone)
metaphyseal
— is caused by focal defect in EO and can effect multiple joints usually bilateral and leads to OA
Osteochondrosis & Osteochondritis Dissecans (OCD)
what causes Osteochondrosis & Osteochondritis Dissecans (OCD)
thought to be loss of vasculature to the growth cartilage
effects the stifle, shoulder, elbow and hock
explain how osterochondrosis causes OA
blood vessels in resting zone die
chondrocytes do NOT become mineralized and osteroclasts do not come and eat dead chondrocytes
leads to cartilage core that gets pushed, can cause crack in cortex of bone which leads to OA
Ost eochondrosis & Osteochondritis Dissecans (OCD) leads to dissecting cartilage — & flaps and retained —
fissures
cartilage cores
Chondrodysplastic dwarfism is a — defect that causes defect in — template leading to secondary bone defect
generalized (FGF4 mutation)
cartilage
Osteogenesis Imperfecta is caused by defect in — that leads to —
type 1 collagen formation
fragile thin collagen type 1, leading to thin/weak bones/dentin/ thin sclera and lax ligaments
osteopenia= a loss of bone mineral density (BMD) that weakens bones.
OC/OCD are focal/bilateral defects in EO that leads to retained —
caritlage core
leads to dissecting cartilage fissures and OA
metabolic bone disease is also called
Osteodystrophies
Osteodystrophies are involved in — growth and remodeling. Either failure of — or abnormality occurring during remodeling of —
ex utero
Failure of normal growth or development
* nutritional/endocrine/metabolic imbalance
* Impact Trabecular AND Compact bone
Abnormality occurring during remodeling
process of mature or repair bone
* nutritional/endocrine/metabolic imbalance
* Impact Trabecular»_space; Compact Bone
how does kidney failure effect bone growth
increased PO4 leads to increased PTH trying to increase blood calcium
leads to weak bone
bone modeling is a — process in which there is a — change in bone.
adaptive
architectural (change in size, length and diameter, orientation, contour)
bone modeling occurs during
growth
pathologic state- fracture healing, infection, neoplasia
leads to bone repair/replacement
why does bone modeling lead to fewer trabeculae
replaces with organized stronger trabeculae
can do the job with less
bone remodeling is done to maintain —, replace — and in respnse to — changes
bone mass
old bones/repair microfractures
metabolic/nutritional change- pregnancy, lactation, eggs
bone remodeling occurs in what type of bone
trabecular bone
not compact- osteroclast and blast can’t fit in osteon as easily
RANKL activates — and is made by —
osteroclasts →promotes resorption of bone
osteroblasts
TNFa, IL1,6 also promote OCLs
PTH indirectly activates — to cause
OCL
increase serum Calcium by breaking down bone
Osteoprotegerin (OPG) is made by — and acts as —
Osteroblasts
decreases OCL function, used to inhibit OCL in cancer patients
2 causes of fibrous osterodystrophies
primary hyperparathyroidism
secondary hyperparathyroidism from renal failure or nutritional (too much phos)
OSTEOPENIA
decreased bone density/ mass
OSTEOPOROSIS
clinical syndrome from osteopenia (decreased bone density and mass)
bone pain and fracture
shape is normal but reduced trabecular» cortical bone
Bone quantity NOT quality is reduced
how does low copper effect bone
leads to decreased osteroblast activation and decreased collagen strength
osteroporosis will cause — osteroblast activity, will have — trabecular bone leading to —
decreased
decreased density and increased porosity
infractions= microfractures of trabecular bone → reduced bone length (shrinking)
rickets is a defect in — that affect —
mineralization
bone and growth cartilage of young, growing animals
what type of deformities are formed with rickets
problem with mineralization
(angular limb deformities “bow legs,”
scoliosis/lordosis, flared physes “rachitic rib rosary”)
rickets leads to
bone deformities
fractures + subchondral collapse
bone pain
soft, weak bones and growth plate cartilage
osteomalacia
softening of bones
occurs in adults, cartilage not afffected
different from rickets which effects children and bones and cartilage
what causes rickets
low Vit D
low phosphorous
Except in birds, calcium deficiency DOES NOT cause rickets or osteomalacia
need working kidneys for Vit D activation
what step of bone formation does rickets effect
2nd phase, when type 1 collagen (osteoid) becomes mineralized
step 1. osteoid formation
why does rickets lead to Flared metaphyses & retained
cartilage cores at growth plates
mineralization does not occur, so osteroclasts do not come in and eat dead chondrocytes
leads to build up of cartilage core and weak, soft bones
rickets
explain how rickets
bone is lined by unmineralized osteoid that can not be eaten by osteoclasts, lead to weakened trabecule→ infractions and bowing
what causes fibrous ostrodystrophy (FOD)
primary hyperparathyroidism leading to ↑↑↑ levels of PTH
secondary: renal failure, or high phosphorous diet
this causes
↑ ↑ OCL activity & bone resorption
↓↓ OB diff → ↓ Bone formation
↑ ↑ FB diff → Fibrsis
really high levels of PTH cause
— OCL activity & bone resorption
—OB diff → — Bone formation
— FB diff → Fibrosis
Fibrous Ostrodystrophy (FOD)
increased
decreased, decreased
increased
rubber jaw and big head syndrome
rubber jaw is caused by
Fibrous Ostrodystrophy (FOD)
really high levels of PTH
how does kidney failure cause Fibrous Ostrodystrophy (FOD)
causes increased phos, low Ca
parathyroid increases PTH to try to increase Ca by eating bones
also decreased Vit D activation
if this happen to much leads to rubber jaw and fibrosis of bone
to much decrease in Vit D activation can lead to rickets!
bone is made of what cells
mesenchymal stem cells
OsteoBlasts- immature cells that “Build Bone”
OsteoCytes- mature cells that “Maintain Bone” (OB turn into OC
OsteoCLasts (Macrophage-like cells that RESORB bone) - multinucleated from myeloid lineage use HCL to eat bone
what makes up the ECM of bone
organic component (osteoid) = 90% type 1 collagen
inorganic component= hydroxyapatite mineral
compact bone is also called
osteonal
trabecular bone is also called
cancellous
woven bone is formed —
during development or repair
temporary bone
highlly cellular but unorganized and poorly mineralized→radiolucent
Duct tape bone→weak
woven bone is — mineralized
poorly
radiolucent
immature/temporary bone
— is mature bone
lamellar bone
low cellularity
organized, strong, radiopaque
difference between structure of lamellar vs woven bone is —
rate of formation
if need bone fast will form woven
if body has time will form lamellar
all woven will turn into lamellar if enough time is allowed
— covers the outersuface of bones except at the ends or where things attach
periosteum
periosteum is made of — and —
outer fibrous layer: can be peeled away
inner cellular layer (cambium): very cellular with MSC that form into OB and form new bone
— Lines the inner
surfaces of bone
(compact and
trabecular)
endosteum
thin layer that seperates hematopoietic marrow and bone
does not grow as fast as periosteum
3 ways to form new bone
cutting cones- compact bone- slow and limited
IO- fast but weak
EO- slow conversion of cartilage to bone
— is when bone is formed without a cartilage template from mesenchyme
IO
fast but disorganized
what three things can MSC turn into based on conditions in the bone
repair stimulus → OB
repair but low O2→chondrocytes leading to cartilage island that will eventually go through EO
high PTH and motion → fibroblasts = weak and movable but can’t heal into bone
healthy cartilage should grossly look
smooth, grey-white and glistening
has thin layer of type 1 cartilage for protection, but then large area of type 2 hyaline cartilage that acts as shock absorber, then leads into mineralized cartilage into bone
what formed across joint
osteophytes
Ankylosis (self fusion)
what happens during early cartilage degeneration on histo
los of PG layer- dehydration
collapse or compression of type 1 collagen shell
death of chondrocytes and loss of lacunae
grossly what will you see with progressive cartilage degeneration
severe thinning & “score lines”
yellow discoloration
histo: will have chondrocyte death and chodrones where condrocytes try to multiply inside lacunae. Loss of type 2 collagen
grossly what will you see for advanced cartilage degeneration
Erosions → full-thickness ulcers → subchondral bone hemorrhage → hemarthrosis
* Subchondral bone lysis → collapse “divots” (EQ MC3 arrowheads)
histo of advanced cartilage degeneration will show
Matrix Fibrillation (fraying) → Vertical Fissures
Erosions (middle image) → Ulcers +/- Fibrocartilage Repair
what happens during subchondral bone sclerosis
adaptive remodeling due to stress
bone will increase bone in area, but it will go to far and squish out blood supply leading to OCL unable to get in and remodel old bone, this can lead to bone failure and catastrophic fractures
eburnation
bone on bone contact that polish each other
caused from loss of cartilage in an area
In End-Stage DJD
Subchondral “bone cysts”
from synovial herniation
osteophytes
what would histo of the synovium look like
would also have inflammatory infiltrates (macrophages, lymphocytes and plasma cells)
also have neovascularization
what will severe synovial hypertrophy look like grossly
will cause hemorrhage that leads to hemosiderin and yellow brown discoloration
No Neutrophils! not infection, just inflammation macrophage, lymphocytes, plasma cells and fibrosis
name some things that are happening
hip dysplasia
eburnation- polishing on bone
bone cytes
osteophytes
— are fractures that involve the growth plates
salter-harris fracture
most common type of salter harris fracture
type 2
fracture extends across physis→ breaks out metaphysis
salter-harris fracture
What are the consequences of this injury if bone heals/ regenerates but growth plate cartilage doesn’t?
Early growth plate closure → Limb shortening
or
Angular Limb Deformity (if growth plate closure is partial)
stages of indirect bone healing
- inflammation and hematoma
- repair: early callus: granulation tissue, woven bone and cartilage islands (radiolucent)
- remodeling: takes a very long time
pannus- forms during chronic septic joints- will eat cartilage
necrotic bone islands are called
sequestrum
will be surrounded by OCL that try and fail to eat it, will form granulation tissue
where are osteosarcomas in dogs common
80% of all primary bone tumors in dogs are osteosarcomas
away from the elbow, toward the knee
DOES NOT CROSS JOINT
two things that went wrong
fracture
osteosarcoma (away from the elbow, toward the knee)
what kind of cancer spreads to these places
histiocytic
label
what do the arrows point to ?
what is their function?
Epiphysis- 1
Metaphysis- 2
Diaphysis- 3
Metaphyseal growth plates
Provide length to the bone
1) Identify this cell, provide its general lineage and primary function.
OsteobBLASTS (OBs): Mesenchymal lineage. Build bone (secrete the majority of osteoid and hydroxyapatite crystals during bone new formation (ie growth, remodeling/modeling, repair).
2) Identify this cell, provide its general lineage and primary function.
OsteoCYTES (OCs): Mesenchymal lineage. Maintains bone (can resorb and secrete small amounts bone matrix in their immediately surrounding lacunae.
3) Identify this cell, provide its general lineage and primary function
OsteoCLASTS (OCLs): Monocyte lineage. Breakdown bone. Differentiation & activation is stimulated by OB production of RANKL
Designated by the asterisk, name the extracellular matrix components (organic and inorganic)
Osteoid (organic) Hydroxyapatite (inorganic)
Name the extracellular matrix designated by “1”and the cells that create and maintain this matrix:
Hyaline cartilage produced by chondrocytes
Name the anatomic region designated by “2”:
Subchondral bone plate
From a molecular and functional standpoint, briefly list the key differences between the extracellular matrix in 1 versus 2 and the inherent response of these tissues to injury
ECM of hyaline cartilage is hydrophilic and acts as a shock absorber, distributing compressive forces to the subchondral bone. It also provides a smooth, gliding surface for moving articulations. Remember hyaline cartilage of the growth plates serves as a template for ECO. Subchondral bone serves to anchor the overlying hyaline articular cartilage to bone via the Articular-Epiphyseal complex (junction of mineralized cartilage & subchondral bone plate). Interconnecting trabeculae serve to transfer forces sustained during movement to the really strong compact (ie osteonal) bone that forms the diaphyseal cortices.
Identify the type of bone response featured in this image.
woven
Name the type of bone response featured in this image.
Lamellar bone (it also happens to be trabecular)
Briefly list the architectural and functional differences between the two types woven vs lamellar
Woven bone is hypercellular, disorganized and weaker in comparison to lamellar bone. WB forms during rapid growth & repair.
6-month-old Saanen goat ”rescue” presented for obstructive urolithiasis
Given the history and clinical findings, the skeletal lesion is characteristic of what general etiology/ies?
Degeneration
Genetic
Infectious
Nutritional
Neoplastic
Toxic
genetic
infectious
toxic
This malformation (missing or severely shortened humerus) is termed phocomelia and is characterized by aplasia or severe dysplasia of one or more segments of the appendicular skeleton. It often results from a genetic defect (in humans this can be autosomal recessive syndrome that also includes other congenital defects involving urogenital, cardiac, and nervous system), but especially in large animals we need to think of Teratogenic viruses and potential exposure to teratogenic toxins. The take home point is that any time you identify one congenital malformation, you should keep your eyes out for additional ones! Although this is an important concept, contents from this case (ie this slide and the previous one) will not be exam material.
These are the distal femurs from a 2-year-old gelding Thoroughbred is presented for progressive bilateral 2-3/5 degrees hind limb lameness localized to the stifle joints. There was moderate effusion within both femoropatellar joints, but the swelling was not hot. Synoviocentesis yielded slightly watery, clear yellow synovial fluid that contains moderate increases in macrophages and lymphocytes.
How would you describe the lesions?
There are bilaterally symmetrical wedge-shaped depressions in the articular cartilage surface that partially extend to the subchondral bone and are partially filled with roughened white-tan cartilaginous tissue. There is mild generalized cartilage thinning over both trochlear ridges and intertrochlear groove.
These are the distal femurs from a 2-year-old gelding Thoroughbred is presented for progressive bilateral 2-3/5 degrees hind limb lameness localized to the stifle joints. There was moderate effusion within both femoropatellar joints, but the swelling was not hot. Synoviocentesis yielded slightly watery, clear yellow synovial fluid that contains moderate increases in macrophages and lymphocytes
Given the gross appearance and clinical history, what is your diagnosis?
Name the disease process that would eventually result from these lesions (hint- it’s the reason the horse was euthanized)?
Bilaterally severe osteochondritis dissecans.
DJD
These lesions represent a defect in which developmental process in bone formation
EO: Endochondral ossification
This is a pelvic radiograph from a 9-year-old miniature horse mare who was severely (grade 5/5) lame right hind and euthanized for a severely displaced femoral neck fracture with luxation of the coxofemoral joint.
fed high phos diet
Are the fractures traumatic or pathologic?
Which historical and histologic features support this diagnosis?
pathologic
Numerous activated OCLs bone lysis with fibrous replacement and paucity of osteoblasts. This is likely caused by the high phosphorous diet resulting in bilateral parathyroid gland hyperplasia and PTH-activation of OCLs and differentiation of FBs over OBs bone resorption with fibrous replacement and pathologic fractures
Based on location, what general classification of fracture is this?
traumatic Salter Harris (growth plate fracture)
The owner elects conservative management (external coaptation & cage rest). Based on fracture configuration, which 2 complications of fracture healing are most likely if internal fixation is not performed?
What other complication could this dog develop based on trauma to the growth plate cartilage?
Fibrous non-union/malunion & DJD
This dog could also develop limb shortening or angular limb deformity associated with the growth plate trauma.
Radiographs (next slide) reveal shallow acetabular cups with flattened femoral heads, and lesions compatible with severe (end-stage) degenerative joint disease. A gross image of one of the coxofemoral joints extracted at autopsy is provided (next slide).
For each anatomic structure, list THREE common lesions of DJD (gross or histologic) in:
Synovial membrane/joint capsule/synovial fluid:
1) Synovial effusion with reduced viscosity of synovial fluid +/- hemarthrosis
2) Synovial membrane hypertrophy/hyperplasia
3) Joint capsule fibrosis (there may or may not be bone metaplasia w/in jt capsule)
Cartilage
Roughening/ Fissuring
2) Dullness/yellowing (from loss of water and PG matrix)
3) Thinning/Erosion→ ulcers (seen as decreased joint space on a radiograph)
Subchondral bone:
1) (Osteo)sclerosis- seen as increased subchondral radiopacity on a radiograph
2) Osteophytosis- seen as nodular bony exostoses or enlarged subchondral bony margins on a radiograph
3) Subchondral bone cysts (end-stage lesions)- seen as focal subchondral radiolucency surrounded by thin sclerotic rim
You examine a 14-day-old foal with a history of patent urachus and umbilical infection (omphalitis). 2-days ago, the foal developed severe (4/5) LH lameness warm effusion in the left tarsocrural (hock) joint. Arthrocentesis reveals Opaque, yellow, turbid fluid with flecks/strands/mats of fibrin and reduced viscosity (see photo of synovial fluid to right).
You suspect the origin of this joint infection is
Hematogenous
Direct Inoculation/Extension
Hematogenous
These infections often result from (circle one): ADEQUATE or INADEQUATE colostrum intake, which is called —
inadequate
Failure of Passive Transfer
A 10-year-old Labrador Retriever presents with acute forelimb lameness and painful swelling localized to the distal radius
Radiographs identify a poorly demarcated radiolucent foci containing irregular radioopaque foci centered within the distal metaphysis, extending to the distal diaphysis and epiphysis with a mildly displaced articular fracture (arrowheads)
The radiolucent foci indicate:
The radiopaque foci indicate:
Osteolysis
Osteoproliferation (neoplastic and reactive)
A 10-year-old Labrador Retriever presents with acute forelimb lameness and painful swelling localized to the distal radius
Radiographs identify a poorly demarcated radiolucent foci containing irregular radioopaque foci centered within the distal metaphysis, extending to the distal diaphysis and epiphysis with a mildly displaced articular fracture (arrowheads)
What is the likely diagnosis?
Based on your diagnosis, what is the biological behavior?
How would you confirm the diagnosis?
Osteosarcoma
Malignant- locally aggressive and invasive with rapid distant metastasis (lungs, lymph nodes, other organs and other bones)
Bone Biopsy (target the lytic foci) identifying neoplastic osteoblasts producing tumor osteoid matrix.
