Bone physiology, pathology and drugs Flashcards
What is compact bone and its structure?
Outer compact bone provides strength.
Thicker at diaphysis but thinner near the head.
Outermost part is oriented in concentric layers.
The rest are laid own in ‘Harvesian’ system
What is the Harvesian system/osteons?
Fundemental functional unit of bone. organised aroudn a central vascualr supply
Describe the structure of osteons
What is trabecular bone?
a calcified lattice that are arranged along lines of stress that better structural integrity.
Has continuous spaces of lattice which contain marrow and blood vessels
What is the medullary cavity?
Spaces within the diaphysis of certain long bones containing bone marrow.
May be yellow (fat) or red (haemopoeitic)
Mostly red when young, becomes more fat later in life.
Describe the structure an function of Periosteum
Connective tissue overlying bone.
Outer layer is mostly fibrous (fibroblasts, BVs, collagen)
Inner layer is more cellular (osteoprogenitor cells –> Osteoblast)
Inner layer has nerves and blood supply
Inner layer regenerates outer layer
What is the Endosteum?
Connective tissue lining inner marrow cavity.
Thinner than periosteum.
Has osteoprogenitor cells
Where are the 2 places where you don’t have peri/endosteum?
Where a tendon/ligament anchors to the bone
Describe the bone and nerve supply to bone
Arteries supply diaphysis, epiphysis and periosteum seperately
Enters via a nutrient foramen before running north and south
Perfusion is inside out
What is the function of Osteoprogenitor cells? Where are they located?
Locted in peri/endosteum
Mesenchymal stem cells
Flattened appearance
Usually quiescent
Differentiate into new ostoblasts
What are Osteoblasts?
Modified fibroblast that deposit osteoid on bone surface
Secrete collagen and vesicles containing alkaline phosphatase and pyrophosphatase
Increase local [Ca and PO4] to promote precipitation
Flattened when inactive, big when active
What is contained in the organic ECM (osteoid)?
T1 Collagen
Osteocalcin/osteonectin
Adhesive protein - sialoproteins, osteopontin
PGs
GF and cytokines embeded into the matrix
What are osteocytes?
Mature bone cells which have entomed themselves in bone.
Lie in their lacunae and maintain bone in response to loading
Sustained in tiny canaliculli in which BVs can go through
What are osteoclasts?
Large, mobile multiucelate cells of granulocyte-macrophage lineage whic hsissolve the mineral and organic matrix of bone.
Secretes HCL (from H2CO3 breakdown) and proteases
Response to PTH to increse activity
Calcitonin to decrease activity
What is the marker of osteoclast activity?
Tartarate resistant acid protease
How does osteoblast regulate osteoclast activity?
Osteoblast when stimulated by IL-6, Calcitriol and PTH express RANK-L
Osteoblast can also release Osteoprotegrin (OPG) to inhibit osteoblast
Define Intramembraneous Ossification
Bone forms from mesenchyme without a cartilaginous anlage
Occurs in facial, cranial vault, clavicle and mandible bones.
Membrane bones form from msesnchymal condensation.
Eventually primary ossification centres form: small group of cells differentiate into osteoblast to lay down spicules (islands of bone matrix) which then grow into the entire surface of bone
Define Endochondral ossification
Occurs in weight bearing bones + bones of extremities.
Mesenchymal stem cells condense and form a cartialge template in the shape of mature bone –> tiny bony collar form around diaphysis –> impermeable bone matrix causes the cartialge deeper to it to degenerate –> bone starts to inhabit area left by cartialge –> BVs of the periosteum invade and with it, more bone cell progenitors –> diaphysis lengtens and the medullary cavity is formed -> second centre of ossification occurs at the epiphysis. Eventually these two areas ossify, the only cartilage left is the articular cartialge and the cartialge at the epiphyseal plate.
Describe the process of bone growth
Deposition > resorption
Bone diameter increases as osteoblasts within the periosteum deposit matrix on the outer surface
Bone length, inncreases at the epiphyseal plate
Physiology
- At proximal end of epiphyseal plate chondrocytes divide in columns, thickening the epiphyseal plate
- As collagen rich plate thickens the chondrocytes on the diaphyseal border plate enlarge and the ECM become calcified.
- This inhibit diffusion of nutrient and cause degeneration
- Dead chondrocytes are cleared by osteoclast
- Osteoblast lay bone down where chondrocytes degenerate to increase diaphyseal length.
- Bulk of growth occur at diaphyseal side
What are the layers of growth plate?
- Resting zone - at epiphyseal border, normal hyaline
- Proliferation zone - dividing chondrocytes
- Maturation zone - mature chondrocytes
- Hypertrophic zone - dying cells
- Ossification zone
What is woven bone?
Bone seen during development or repair
More cellular and contains more collagen
No structure
No harvesian systems
Remodelled by osteoclasts and osteoblasts
Describe the process of bone remodelling
Born turnover is 5-10% a year
Osteoclast detect differences in force along the bone and resorb along the aces of stress. Cavitation bring with it blood vessels and endosteum
This process sets up Harvesian system.
Process happens outside in
What are the functions of PTH
- Released by PT glands at low plasma Ca
Bone
- Inc Ca + PO4 release from bone into plasma by bone resorption (Paracrine actions of OPC and RANKL)
Kidney - Distal nephron
- Increase Ca reabsorption
- Decrease PO4 reabsorption (Free PO4 binds free Ca causing [Ca] to drop thats why its excreted)
Intestine
- PTH enables second hydroxylation of Vitamin D synthesis.
- Vit D causes increase Ca absorption, decreased renal excretion and increased Osteoclast activity
What are the functions of Calcitonin?
Released when high plasma Ca from the C cells of thyroid
Bone
- Decrease osteoclast activity
Kidney
- Ca excretion
- PO4 excretion
Only works with extreme hypercalcemia
