Bones / Joints Flashcards
Developmental skeletal dysplasias
K9 chondrodysplastic dwarfism
Osteogenesis imperfecta
Osteochondrosis/osteochondritis dissecans
Types of Cartilage
Hyaline cartilage - shock absorber, template for endochondral ossification
Fibrocartilage - connections between connective tissue, tendon/ligament insertions
Elastic cartilage - flexible structures
Generalized chondrodysplasias
Congenital defects involving cartilage template and generalized (polyostotic) defect in ECO
Origin of chondrodyplasias
Defect in cartilage template required for EO
Spontaneous or heritable mutation
Defect in any part of skeleton from cartilage template
Disproportionate (chondrodysplastic) dwarfism
Breed standard in Bassett hound/corgis (autosomal dominant FGF4 mutation)
Lethal mutation in bulldog calves (Dexter, Holstein) (Col2A1 and aggrecan mutations) —> shortened malformed limbs
Secondary defects in cells or ECM (lysosomal storage) —> limb, spine, skull malformations (+other organs)
+/- early DJD (from malformation in shape of epiphysis —> joint instability / incongruency
K9 Chondrodysplasia
Chondrodysplastic phenotype (CDPA)
CFA18-FGF4 mutation (autosomal dominant)
Dysproportionate dwarfism - shortened, malformed limbs (standard in certain breeds)
K9 Chondrodystrophy
Chondrodystrophic phenotype (CDDY)
CFA12-FGF4 mutation (incomplete autosomal dominant)
Shortened, malformed limbs (additive effect), IVDD (premature degeneration —> IVD herniation —> neurologic signs)
Generalized osteodysplasias
Skeletal defects in which cartilage cells/matrix are ok
Bone cell/matrix affected (generalized deformities, monostotic or polyostotic malformations
Osteogenesis imperfecta
Osteopenic disease (puppies, calves, lambs, humans)
Decreased bone density, excessive bone fragility
Mutation in both Type I collagen synthesis (BOTH osteoblasts and odontoblasts affected = bone + teeth affected)
Thin, weak bone matrix —> increased fragility, thin dentin, joint laxity + “blue” sclera (thinning)
Focal chondrodysplasia
Developmental defects in ECO at focal, repeatable sites
Osteochondrosis + Osteochondritis dissecans
Osteochondrosis + osteochonritis dissecans
Heterogenous lesion(s) in GROWTH cartilage (dogs, horses, pigs, cattle, poultry); epiphyseal > metaphyseal
Focal defect in endochondral ossification
~50% of lesions bilaterally symmetrical
Secondary OA common
Common joints: stifle, shoulder, elbow (pig), hock
Etiopathogenesis of OC/OCD
Damage to vasculature within growth cartilage (cartilage canals)
Pathogenesis of OCD
Focal interruption of endochondral vascular invasion or ischemic necrosis —> ECO failure —> retained cartilage core —> pressure induced fissure —> OCD
Retention of growth cartilage at AEC or metaphyseal growth plate —> defect if large retainined and heals or fissure —> dissecting cartilage flap (OCD) —> secondary DJD
Factors affecting bone response to injury
Etiology/inciting cause
Point at which injury occurs (pre/post natal development, mature skeleton)
Osteodystrophy due to failure of normal growth/development
Nutritional, endocrine, metabolic imbalance
Both trabecular and compact bone
Osteodystrophy due to abnormality during remodeling of mature bone or in repair
Nutritional, endocrine, metabolic imbalance
trabecular»_space; compact bone
Causes of osteodystrophy
Temporal imbalances:
Nutritional (protein, vitamins, minerals)
Endocrine/hormonal
Toxic origins (drugs)
GI/renal/hepatobiliary dysfunction
Affect all bone!
Important factors / hormones in bone control
Endocrine: PTH (parathyroid), Calcitonin (thyroid)
Kidneys: Ca/phosphate
Kidney/liver/skin/intestine: Vitamin D3
Local factors: RANKL
Bone modeling
Primary trabeculae removed/replaced with STRONGER/FEWER trabeculae WITHOUT cartilage template core —> less radioopaque
Function of bone remodeling
Maintain bone mass
Replace old bone / repair microfracture
Respond to metabolic/nutritional changes
Regulators of OCLs
RANKL (from osteoblasts —> OCL activation / diff)
PTH (indirect inc in OCL activation)
Calcitonin (dec bone resorption systemic)
Common metabolic osteodystrophies
Osteoporosis
Rickets/Osteomalacia
Fibrous osteodystrophies (Renal failure —> secondary hyperparathyroidism)
Osteopenia
Decreased bone density / mass
Osteoporosis
Clinical syndrome
Bone pain / pathologic fractures (due to osteopenia)
Bone shape is normal, but reduced trabecular»_space; cortical bone (i.e. QUALITY is reduced)
Causes of osteoporosis
Protein calorie malnutrition
Calcium deficiency
Copper deficiency
Severe GI parasitism or IBD
Physical inactivity (disuse/immobilization)
Lesions of osteoporosis
Dec osteoblast activity
Dec trabecular bone —> dec compact bone —> dec bone density + inc porosity
Pathologic fractures and infractions (micro fractures) —> reduced bone length
Rickets and osteomalacia
Defective mineralization —> affect bone and growth cartilage
—> bone deformities (angular limb deformities, scoliosis, flared physes)
—> pathological fractures + subchondral collapse
—> bone pain
Rickets
soft/weak bones + growth plate cartilage
(Young, growing animals)
Osteomalacia
Softening of bones
In ADULT animals, cartilage not affected
Causes of rickets/osteomalacia
Nutritional deficiencies:
Vitamin D deficiency (typically with unconventional diet)
Phosphorous deficiency (herbivores with P deficiency diet)
Calcium deficiency NOT a cause (except in birds)
Phases of bone formation
- Osteoid formation
- Mineral deposition (lacking in rickets/osteomalacia)
Rickets / osteomalacia pathogenesis
Reduced mineralization in bone (or bone + growth plate - young) —> deposition of large soma of osteoid along endosteal bone surfaces + osteomalacia canals —> dec OCL resorption —> inability to bind / resort old bone; growth plate deformities (in young) (unmineralized growth cartilage —> dec primary trabeculae)
Lesions of rickets
Flared metaphyses and retained cartilage core at growth plate
Compact bone: bowed legs, catastrophic fractures
Trabecular bone: infractions
Bone surfaces lined by large seams of unmineralized osteoid (any site of remodeling, trabecular»_space; cortical bone)
Lesions of osteomalacia
Bone surfaces lined by large seams of unmineralized osteoid (any site of remodeling, trabecular»_space; cortical bone)
Weaked trabeculae: microfractures
Weakened compact bone: catastrophic fracture
Fibrous ostrodystrophy pathogenesis
Persistent + extreme inc PTH
Primary hyperparathyroidism —> inc OCL activity/bone resorption —> dec OB diff —> dec bone formation —> inc fibroblast diff —> fibrosis
Renal insufficiency or High P diet —> inc phosphate —> inc Ca precipitation —> secondary hyperparathyroidism —> inc PTH —> inc OCL —> bone resorption / replace with fibrous
Clinical fibrous osteodystrophy
K9: Rubber jaw
EQ: big head syndrome
Renal osteodystrophy can cause components of rickets/osteomalacia AND FOD due to …
Decreased Vitamin D3
Dynamic response of bone
Respond to:
Physiologic homeostatic process
Mechanical stress
Metabolic stress
Inflammatory stress
Osteoblasts
immature cells that “build bone”
Osteocytes
Mature cells that maintain bone
Osteoclasts
Macrophage like cells that resorb bone
Woven bone
Immature bone
Temporary, high cellularity, poorly organized, rapid formation, poorly mineralized
Acts as a bandaid (weak)
Lamellar bone
Mature bone
Low cellularity, organized, slow formation, STRONG, well-mineralized
Sites of bone repair
Periosteum - outer surface of bones
Endosteum - lines inner surface of bone (interface between hematopoietic marrow and bone)
Mechanisms of bone formation
Cutting cones - compact bone, “miners in tunnels”; slow and limited
Intramembranous ossification - FAST
Endochondral ossification - slow conversion
Intramembranous ossification
Bone formed directly from mesenchyme WITHOUT cartilage template (fast)
Condensation of mesenchyme —> OB differentiation —> osteoid + HA —> ossification centers —> woven bone island —> remodeled to lamellar bone
Reaction of joint to injury
Joint cartilage + soft tissue supports (tendon, ligament, menisci) have POOR REGENERATIVE RESPONSE + limited healing capacity
Final common pathway = degeneration
Common etiologies of joint injury
Congenital instability/incongruence
Traumatic instability
Repetitive stress injury
Infection / inflammation
Common end-stage pathway = DJF
Degenerative joint disease
Incorporates all anatomic components
Articular cartilage; subchondral bone; synovium; soft tissue structures (joint capsule, ligaments, menisci)
End-points of DJD
Ankylosis (self fusion)
Arthrodesis (surgical fusion)
Arthroplasty (surgical reconstruction / replacement)
Features of early cartilage degeneration
Gross: surface dullness/roughness, thinning (focal, regional, or diffuse)
Histo: PG loss with matrix contraction + clefts (less pink on histo); chondrocyte necrosis + loss
Progressive cartilage degeneration
Gross: severe thinning + score lines, yellow discoloration
Histo: chondrocyte loss/dropout, chondrocyte clones
Advanced cartilage degeneration
Gross: erosions—> full thickness ulcers —> subchondral bone hemorrhage —> hemarthrosis —> subchondral bone lysis —> collapse divots
Histo: matrix fraying/vertical fissures, erosions/ulcers, +/- fibrocartilage repair
End-stage cartilage degeneration
Gross: full-thickness cartilage ulcers, subchonral bone hemorrhage
Histo: full thickness cartilage ulcer with horizotonal fissure; deep excavation/collapse of subchondral bone with subchondral hemorrhage
Progressive lesions of DJD
“Adaptive” remodeling —> pathologic inc bone density from decrease in cartilage shock absorption —> excessive compressive forces —> sclerosis —> dec vascular access —> dec OCL remodeling —> bone failure —> catastrophic fractures
Subchondral bone failure
Repetitive stress injury (overuse / obesity) —> subchondral failure + collapse —> catastrophic fractures
Sequeale of subchondral bone failure
DJD characterized by
Subchondral “bone cysts” from synovial herniation
Eburnation (polishing of bone cartilage ulcers —> bone on bone contact)
Osteophytosis
Progressive articular bone proliferation of DJD
Growth of osteophytes on bone
Progressive lesions to synovium and joint capsule in DJD
Synovitis: (histo) increased layers and large cells in intima; increased vascularity, fibrosis, inflammation in subintima
Gross: hypertrophied (thickened), hyperemia (red) synovial membrane, effusions from intimal/subintimal changes
Severe chronic lesions of synovium/joint capsule in DJD
Thickened synovium with subintimal neovascularization / fibrosis; superficial erosion; Proteinaceous exudate
Gross: super-thick synovial hypertrophy + hemosiderin from chronic hemorrage —> yellow-brown discoloration
Canine hip dysplasia
Congenital joint laxity; large/giant breed dogs predisposed
Factors: genetics, obesity, excessive exercise
Pathogenesis of canine hip dysplasia
Excessive joint laxity with instability —> chronic subluxation of coxofemoral joint —> secondary DJD with modeling of femoral head/acetabular cup + arthritis
Fracture classifications
Traumatic vs pathologic
Traumatic fracture
Normal bone broken by excessive force
Pathologic fracture
Abnormal bone broken by Minaj trauma or during normal weight bearing forces
(Repetitive stress injury, congenital/metabolic bone disease), osteomyelitis, primary/metastatic neoplasia
Fracture configurations
Closed vs open
Simple vs comminuted
Transverse vs Sagittal/parasagital
Avulsion
Articular
Salter-Harris fractures
Involve growth plates (occur in young)
Type I, II, III, IV, V
Type II Salter-Harris Fracture
Fracture extends across physis —> breaks out metaphysis
Consequences if in growth plate fracture bone heals, but growth plate cartilage does not
Limb shortening or angular limb deformity
Types of fracture healing
Direct (primary) healing —> rigid fracture stabilization
Indirect (secondary) healing —> biomechanical environment dictates how healing occurs, limited intervention (?)
Stages of indirect bone healing
1 - Inflammation 0-7 d
2 - Repair
A - Soft callus 1-3 w. (Early callus - granulation tissue + woven bone + cartilage islands)
B - Bony callus 3-6 w
3 - Remodel > 8 w to yrs
Response to a fracture
1 - tearing of periosteum + displacement of fracture ends —> trauma to adjacent soft tissue
2 - hemorrhage with hematoma + clot formation by fibrin polymerization
3 - Imparied blood flow —> necrosis of fracture ends + bone fragments
4 - release of cytokines + growth factors by platelets, macrophages in clot
5 - influx / proliferation of MSCs and granulation tissue formation
6 - OB differentiation, woven bone
7 - bridging callus —> soft callus —> hard callus
Soft callus
Woven bone +/- cartilage with periosteal vessels forming within 1-3 w of fracture healing
Low O2 tension —> hyaline cartilage formation (radiolucent!) —> EO —> eventually radioopaque (hard callus)
Primary fracture callus
Provides some stability to allow some degree of limb function until healing complete
Complications of fracture healing
Mal-union / fibrous non-union
Inadequate blood supply
Infection (osteomyelitis, septic arthritis)
Mal-union / fibrous non-union
Caused by poor or delayed healing
Permanent + painful
If articular —> early degenerative OA
Impact of inadequate blood supply on fracture healing
Necrotic bone (sequestrum)
Poor healing / necrotic tissue —> substrate for infection
Osteomyelitis / septic arthritis
Occurs at time of injury or delayed
Bacterial “squatters” in sequestrum / bone biofilms
Inhibits neovascularization / callus formation (delayed healing —> mal-union / fibrous non-union)
Synovitis
Inflammation of synovial membrane and synovial fluid compartment
Arthritis
Inflammation/degeneration of all components of joint (synovial membrane + joint capsule, cartilage, subchondral bone)
Osteomyelitis
Inflammation of bone, including endosteum + medullary spaces
Osteitis
Inflammation of cortex only
Acute arthritis
Inflammatory cells + pro-inflammatory cytokines
- synovial hyperemia + edema
- reduced PG of synovial fluid + cartilage
- reduced synovial viscosity
- chondrocyte necrosis + loss of ECM
Orange, red, brown synovial fluid (if hemorrhage)
Increased turbidity (fibrin, neutrophils - if septic)
Chronic arthritis
Cartilage lesions progressive thinning/erosions/ulcers
Stiffening of joint
Subchondral bone involvement
Reduced joint function + DJD
Routes of joint infection
Septicemia (neonates > adults) : umbilicus, respiratory tract, GI
Direct penetration (more common in adults) - trauma, injection, surgery
Extension from local wound/septic epiphysitis
Acute changes in synovium
Decreased viscosity (digestion of GAG + dilution by edema)
Turbid (fibrin / neutrophil)
Red/orange/brown discoloration
Hyperemic joint
Chronic changes to synovium / joint
Suppurative —> lymphoplasmacytic inflammation
Synovial villus hypertrophy
Joint capsule fibrosis + Osteophytosis
Acute changes to articular cartilage / subchondral bone
Yellowing + thinning cartilage surface
Fissures / collapse from ECM degeneration + chondrocyte necrosis
Chronic changes to articular cartilage + subchondral bone
Focal or diffuse thinning, erosions, ulcers
Pannus formation “red velvet” surface
Subchondral bone sclerosis / disuse osteopenia
Bacterial causes of infectious arthritis / osteomyelitis
G -: coliforms, Salmonella
G+: Strep, Staph, Actinomyces bovis, T pyogenes
Mycoplasma
Fungal causes of infectious arthritis / osteomyelitis
Opportunistic fungi (Aspergillus, Candida)
Coccidiomycoides, Blastomyces
Septic physitis/epiphysitis
In young growing animals - bacteria within vessels in ossification front of growth plates
Thrombosis / infarcts of intramedullary fat, marrow, bone —> sequestrum —> septic arthritis
Sequestrum / sequestration
Necrotic bone islands —> will hypermineralize —> radioopaque; also resorption of surrounding bone (radiolucent rim)
Occurrence of primary bone tumors in animals
Dogs > cats»_space;> farm animals
Most common primary bone tumors in SA
Osteosarcoma (appendicular > axial)
Chondrosarcoma (cartilage; flat bone predilection)
Behavior of bone tumors
In dogs - most malignant
In cats - benign ~ malignant
In horses/cattle/other domestic - benign»_space; malignant
Osteosarcoma
80% of primary bone tumors in dogs
Large, giant breed dogs
75% appendicular skeleton; 2/3 in forelimbs, 1/3 hind
K9 osteosarcoma
Malignant neoplasm of osteoblasts
Aggressive, invasive neoplasm
Frequent + RAPID metastasis (LN, lungs, bones)
Poor prognosis
Site of origin: central (most common), parosteal, periosteal, extraskeletal
Radiographic appearance: lyric to sclerotic, proliferative
Doesn’t directly cross joints! Pathologic fractures
Diagnostic features of osteosarcoma
1 - osteolysis (destruction of bone architecture)
2 - osteoproliferation
3 - histology - neoplastic osteoblasts producing tumor osteoid (biopsy)
Feline osteosarcoma
Malignant + locally in vases / aggressive
Slower metastasis + longer survival than in dogs
Histiocytic sarcoma
Round cell neoplasm (interstitial dendritic cell or macrophage)
Locally invasive (joints) - often CROSSES joint!
Rottweiler (and black + tan) dogs
Stifle + elbow (elbow uncommon for OSA)
Hemophagocytic subtype —> anemia
Poor prognosis ~5.3 mo survival
Metastasis to liver, lung, lymph nodes
