Musculoskeletal Flashcards
What area of the embryological animal does bone arise from?
Mesenchyme - mesoderm
Which type of ossification forms flat bones?
Intramembranous
Describe intramembranous ossification.
- Remember it must be an area of high oxygen tension.
- OBs cluster in the fibrous membrane forming a COO, start secreting osteoid
- OBs secrete collagen and ECM into which Ca is secreted leading to trabeculae formation
- Appositional growth occurs as woven bone is replaced by lamellar bone
- OBs become trapped in lacunae and become OCs
- Progenitor cells on the surface differentiate to OBs
- Bone marrow fills spaces between trabeculae
- The fibrous membrane from 2 becomes the periosteum
Describe the difference between appositional and interstitial growth.
Appositional = change in width
Interstitial = change in length
Describe Endochondral ossification.
- Originates from hypoxic mesechyme
- A cartilage model is laid down covered by perichondrium
- Blood vessels penetrate model mid-shaft, this stimulates differentiation to OBs
- OBs form a collar around the bone diaphysis
- Capillary beds penetrate diaphysis cause chondrocyte hypertrophy - cells burst increasing pH and intracellular calcification
- Intracellular substance degenerates and leaves cavities - forms marrow cavity when infiltrated by blood vessels
True or false
Bones grow in width by endochondral ossification
False, they grow in length by endochondral and in width by intramembranous
How do joint cavities develop?
By apoptosis.
Which structures of the joint are covered by synovium?
Surfaces of ligaments.
Not covered are articular surfaces and synovium
Osteoid seam
The layer of superficial non-mineralised osteoid.
Osteoid
Unmineralised bone matrix initially deposited by a layer of osteoblasts.
Primary mineralisation
Occurs around 8-10 days after osteoid secretion. The initial 70-75% of mineralisation.
Secondary mineralisation
Complete bone mineralisation to final bone density. Occurs over several months
Name and describe the four cell types found in bone.
- Osteoblasts - Osteoid formation, initial mineralisation and reg factors production
- Osteocytes - Produce and absorb immediately local bone. Communication
- Osteoclasts - Reabsorption of bone. Produce low pH acid which dissolves bone salts, and proteolytic enzymes which dissolve osteoid
- Bone marrow stromal cells - haematopoietic growth factors, OB progenitor cells, PTH, strain gauge (activate remodelling)
Describe the morphological features of active and inactive OBs.
Active = Pear shaped, cuboidal cells, abundant RER and golgi, basophilic, granular cytoplasm.
Inactive = flat, similar to squamous cells, line bone surface
Describe the morphology of osteocytes.
Minimal cytoplasm, projections which communicate with immediately adjacent cells through canaliculi of bone
Describe the morphology of an osteoclast.
Large, multinucleated cells, eosinophilic cytoplasms, found on bone surface.
Found within Howship’s lacunae when actively reabsorbing bones.
Describe the morphology of bone marrow stromal cells.
What four functions do they serve?
Spindle cells, margin of bone marrow, immediately above the osteoblast layer.
- Hematopoietic growth factors Eg: EPO and CSF
- Progenitor cells of the OB
- Provide vertical orientation of bone cell
- Establish the canalicular-lacunar system.
- React to parathyroid hormone stimulation
- Attract and stimulate OCl to remove bone
- Proliferate and form fibro-osseous matrix
- Strain gauges which activate bone remodelling.
What is the embryological origin of OCls?
Monomyelocytic stem cells
What are the organic components of the bone matrix?
- Osteoid - T1 collagen
- Other proteins - proteoglycans, osteonectin, osteopontin, etc
- Growth factors - FGF & TGFbeta - cause mitogenic responses in cells
Name the two main inorganic components of the bone matrix.
- Hydroxyapatite - Calcium and phosphorous
- Carbonate, Mg, Na, Zn, F also
Cancellous bone
aka Spongy
Tarbeculae surrounded by large spaces filled with marrow. Found along entire of flat bones and in the diaphysis of long bones.
Provides support and marrow storage.
Dense bone
aka compact bone.
Trabeculae are densely packed with few spaces. Deposited in layers over cancellous bone.
They layers of compact bone are thicker at the diaphysis.
Forms osteons in thick cortex
Cancellous and compact bones are both examples of which category of bone?
Lamellar - mature - layers of lamellae
Woven bone
Immature
Randomly oriented lamellae - becomes lamellar through remodelling.
Outline the process of OCl bone reabsorption.
An acid environment is created between the cell and the bone surface. Hydrogen and bicarbonate ions are generated from CO₂ and water by carbonic anhydrase on the brush border.
An ATP-mediated proton pump actively transfers hydrogen ions into the extracellular space. The acidity of the local environment induces demineralisation of bone and enhances the activity of acid hydrolases released from osteoclasts.
Fragments of degraded matrix are endocytosed by the osteoclast.
Outline the process of OB bone production.
A thin layer of un-mineralised osteoid, the osteoid seam covers the surface where bone is being formed.
Mineralisation of osteoid does not occur until 5-10 days after deposition.
Histologically, it is more eosinophilic than the mineralised bone, and in lamellar bone, it is separated from it by a basophilic line (The mineralisation front).
Which four processes are characteristic of bone remodelling?
- Activation of OB by external signals such as hormones, cytokines or growth factors.
- OCl activation, attachment to bone surface and resorption of the bone
- OCl inactivation: osteoclasts detach from the bone and undergo apoptosis
- OB recruitment to the resorption site, where they deposit new bone
Name the regulatory factors of bone growth.
- PTH - parathryoid hormone - > blood Ca2+
- 1,25-dihydroxy vit D3 - > blood Ca2+
- Calcitonin - < blood Ca2+
Describe the action of PTH
- OCl activation via RANK-L pathway
- Inhibits activation of OBs
- Increases Ca2+ reabsorption from the kidney
- Increased vit D3 synthesis
- Decreased P reabsorption from the kidneys
Describe the action of vit D3
- Increases Ca2+ and P+ absorption from the gut
- Increases P+ reabsorption from the kidney
- Increases OCl activity
Describe the action of Calcitonin
- Inhibits OCls
- Loss of ruffled border and detachment from bone suraace
- Inhibits OCl formation
- Inhibits PTH bone resorption
Name and describe the three layers of the growth plate.
What type of ossification is occuring here?
- Resting - zone of reserve chondrocytes
- Proliferating/ maturing - Chondrocytes are proliferating and producing molecules which modify matrix and allow cap invasion and initiate mineralisation
- Hypertrophy - Enlargement and lysis of chondrocytes. Minerals from caps and trabeculae are formed by osteoprogenitors differentiating into OBs
What is the difference between the primary and secondary spongiosum?
Primary - rapidly mineralised osteoid formed on top of calcified cartilage.
Secondary - Primary remodelled to lamellar bone
Growth arrest line
Characterises something going wrong at the level of bone matrix production. eg insufficient nutrition.
Seen histologically as a transverse calcified line parallel to the growth plate.
Growth retardation lattice
Persistence of non-formed areas of endochondral ossification at the growth plate.
Persistence of non-mineralised cartilage
Impaired OCls or OBs
Resting lines
Longitudinal straight basophilic line within mineralised bone matrix. Evidence of OB resting at some point.
Reversal lines
Scalloped matrix lines, evidence of past bone remodelling
Achondroplasia
Absence of cartilage development
Chondrodysplasia
Name and describe a form of this abnormality in calves.
Disorder of cartilage development
Eg Bulldog calf
Gross: Abort ~7m, micromelia, brachygnathia, domed head, abdominal hernia,
Histo: Lack of distinct growth plates, densely packed, disorganised chondrocytes
Less severe buldog calves who are born unable to stand.
Telemark lethal
Describe a snorter.
Brachycephalic
Short broad heads, bulging forehead, prognathia
Histo: Shorter, irregular columns of hypertrophied chondrocytes
Point mutation in FGR3 which causes long limbs/ neck, shallow bodied and spinal abnormalities in lambs
What histological changes are seen with this?
Spider lamb syndrome
Histo: Small ossification centres within hypertrophic cartilage, lack of subchondral bone, irregular chondrocyte columns in growth plates. Very thin diphysis
What musculoskeletal abnormalities are seen with dwarfism?
Reduced longitudinal growth despite normal apositional growth.
Epiphyseal growth plate abnormality
Palatoschisis
Cleft palate
What is the difference between kyphosis, lordosis and scoliosis?
Kyphosis - dorsal curvature of the spine
Lordosis - ventral curvature of the spine
Scoliosis - lateral deviation of the spine
Complete or partial fusion of the hindlimbs.
Sirenomelia
Congenital deformity and shortening of the limbs
Permelia
—–dactyly
pertaining to digits
Diprosopus
Incomplete duplication of the head
Spina Bifida
Defective closure of dorsal vertebral laminae in a segment of the vertebral column
Which genes are affected with Osteogenesis imperfecta?
COL1A1/ COL1A2 mutation
Gross: Brittle bones, bowed limbs
Histo: Calcified cartilage, lined with basophilic bone matrix
ACAN mutation is associated with which disorder?
What histological changes are observed?
Osteopetrosis
Histo: avascular metaphyses, cartilage matrix, thin woven bone fills medulla
Marie’s disease
Hypertrophic osteopathy - periosteal growth secondary to neoplastic/ inflammatory growth in the thorax
Porphyria
AKA pink tooth disease
An inherited haemaglobin disorder which results in brown discolouration of bone
Osteonecrosis
Pale tan discolouration of bone, dry periosteum
Caused by reduced bone blood supply/ foreign body (bone)
Legg-calve-perthes disease
Femoral head necrosis
Ischemia due to abnormal blood vessel formation leading to necrosis
Flattening of the femoral head and fracture
Osteoporosis
Decreased blood calcium - increased PTH activity (OCl, vitD3, kidney and gut absorption increased)
Reduced bone quality
Cause:
- Parasitic
- Starvation
- Steroids - collagen synthesis inhibited
- Disuse
Rickets/ osteomalacia
Hypovitaminosis D3 - reduced absorption of Ca2+ leading to increased PTH activity (reduced mineralisation of bone)
Fibrous osteodystrophy
Hyperparathyroidism
- Primary secreting tumour
- Renal failure
- Nutritional
- PTH-like secreting tumour AS carcinoma
Excessive bone resorption, fibroblastic replacement with collagen
What conditions can lead to poor bone healing after a fracture?
Inadequate blood supply = necrosis
Instability = Pseudoarthritis (poor union)
Describe this lesion
Focal pale tan discolouration 3x3cm, affected bone appears soft.
Focal severe acute suppurative osteomyelitis
Cause:
- Foal - E.coli, Klebs, Salmonella, Rhodococcus
- Calf - A. pyogenes, Salmonella
- Dog - penetrating injury (E.coli, staph, strep)
Describe this lesion
Vertebrae - Focal acute severe suppurative osteomyelitis
Due to failure of passive transfer and systemic bacterial infection
- F. necrophorum
- A. pyogenes
- R. equi
- M. haemolytica
Predisposes bone to fracture
Lumpy jaw
Mandibular osteomyelitis - Actinomyces bovis
Multifocal round abscesses which distorts the external anatomy of the face
