Bone physiology Flashcards
Bone classifications
Long bone or flat bone
- Long= longer than it is wide
- Flat= thin, often curved
Cortical or cancellous (macroscopic)
- Cortical= thick bone, organised in osteons. 80% of skeleton
- Cancellous= spongy bone
Lamellar vs woven bone (microscopic)
- Lamellar= secondary to woven bone. Stronger and more flexible
- Woven= Less organised and stress oriented
Cancellous bone
Spongy bone
- Open porous network (bony struts) with blood/ marrow in-between
Less dense than cortical bone
Weaker but more flexible than cortical bone
High turnover to remodel when bone is under stress
Cortical bone
Thick bone, organised in osteons
- 80% of skeleton
Slow turnover rate
Composition of bone
Cells
- Osteoclasts
- Osteocytes
- Osteoblasts
Extracellular matrix= osteoid.
Osteoclasts
Multinucelate bone cell
- In Howship’s lacunae
- Can proliferate
- Same precursor as monocytes
Function–> creates ruffled borders during bone reabsorption
- Phagocytose bone matrix and crystals (bone degradation)
- Secretes acids [for hydroxyapatite
- Secretion of proteolytic enzymes from lysosomes [to digest matrix proteins]
Osteocytes
Quiescent bone cells in bone matrix
- Derived from osteoblasts
Functions
- Maintain bone and detects environmental stress
Osteoblasts
Mononucleate bone cell located on developing bone surfaces
- Most mitotic, gives rise to osteocytes
Function
- Formation of new bone
- Release of signalling substances
- Produces protein components of acellular matrix
Extracellular matrix
Hardened material surrounded cells.
Contains few cells:
- Inorganic material: minerals, hydroxyapatite
- Connective tissue sometimes
- Osteoid (unmineralised bone )
- Ground substance (organic, acellular)
- Growth factors
Haversian system
Communication system between cells in bone matrix
Osteon
- Functional unit containing everything
Haversian canal
- Runs parallel to bone and on long axis
- Lined by lamellae
- Contains one or two capillaries and nerve fibres
Osteocyte
- Contains radiating processes into canaliculi
Canaliculi
- Canals between lacunae of ossified bone
Acellular components of bone
Collagen fibres
- Give flexibility and strength
Hydroxyapatitre
- Provides rigidity
- Mainly calcium/phosphate crystals
Ground substance in bone
Things in ECM that is not inorganic and not collagen
Includes
- Proteoglycans
- Glyosaminoglycans
- Matrix proteins
- Water
Glycosaminoglycans
Component of ECM (Ground substance)
- Abundant in cartilage
Structure
- Long polysaccharide
- Highly negative–> attracts water, repels each other
- Resists compression
Activation-resorption-remineralisation sequence
Controlled by osteoblasts
- Osteoblast detects mechanical stresses/ hormonal factors/ cytokines on the bone–> releases IL-6 and other cytokines
- IL-6 and other cytokines active osteoclast to begin bone reabsorption
- Forms ruffled border as it absorbs bone - Reabsorbed bone releases growth factors bound to matrix which activates osteoprogenitor cells into active osteoblasts.
Endochondral ossification
Bone is formed on a cartilaginous template.
Chondrocytes proliferate and secrete ECM and proteoglycans.
Osteoblasts then lays down osteoid and begin mineralisation
Intramembranous ossification
No cartilage template
Osteoblast lays down osteoid and being mineralisation without cartilage
- Forms tiny bony spicules
Forms woven bone when nearby spicules join into trabeculae.
Factors that govern remodelling of bone
Recurrent mechanical stress
Calcium homeostasis
Mechanical stress on bone
Strengthens bone
Surface osteoblasts and osteocytes detect stresses
- Stimulates more deposition of bone minerals, inhibits bone resorption
- Bone trabeculae become more dense
Without weight bearing (i.e bed rest and lack of gravity) = loss in bone density
Osteopenia
Low bone density
- Considered to be precursor to osteoporosis sometimes
Bisphosphonates
- Mechanism
- Example
- Indication
Inhibits osteoclast from bone -resorption
- Related to inorganic pyrophosphate= interfere with osteoclast metabolism
Alendronate
For osteoporosis
Teriparatide
- Mechanism
- Indication
Encourage osteoblast formation of bone (PTH portion)
Indication
- Osteoporosis
Denosumab
- Mechanism
- Indication
Prevents osteoclast maturation
- Monoclinary antibody that targets RANK-ligand
Osteopetrosis
- Genetics
- Mechanism
- Symptoms
Autosomal recessive condition
Mechanism
- Osteoclast cannot remodel bone= excess bone growth
- Defective vacuolar proton pump/ chloride channels [cannot secrete acid]
Symptoms–> Excess bone presses on skull foramina
- Brittle bones
- Blindness
- Deafness
- Severe anaemia
Fatal within 10 year
Phases of fracture healing 1
Reactive phase- takes a week
- Haematoma forms
- Inflammation occurs= granulation tissue
Bone precursor cells from periosteum arrive
Phase 2 of fracture healing
Soft callus formation [week 2-3]
Woven bone/ hyaline cartilage is formed to join pieces
Phase 3 of fracture healing
Hard callus formation [week 4-16]
- Woven bone/ hyaline cartilage is replaced by lamellar bone
- Lamellar bone turned into tribecular bone
Phase 4 of fracture healing
Remodelling
- Osteoclast remodel trabecular bone to original bone shape
- Trabecular bone is replaced with compact bone where appropriate.
PTH and Ca2+
Release from chief cells
- Increase plasma calcium
Mechanism
- Stimulates osteoblast to activate osteoclast precursor via RANKL
Vit.D and Ca2+
1,25-OH Vit D increases plasma Calcium
- Stimulates more absorption in gut and kidney
Calcitonin
Made by thyroid C cells
- Decreases calcium levels–> stimulates entry into bones
Can be used as treatment for osteoporosis
OPG
Secreted by osteoblast–> signals reduced bone formation
- Binds to block RANKL
Stimulated by oestrogen in vivo
Stimulated by strontium renovate
Calbindin
Increase stimulated by calcitriol
- Increases intestinal and kidney absorption of calcium
Causes of low plasma calcium
Due to loss
- Pregnancy
- Lactation
- Kidney dysfunction
Low intact
- Insufficient ingestion
- Rickets due to low vit.D
Parathyroid dysfunction
Consequences of chronic hypocalcaemia
Skeletal deformities [i.e rickets]
Increased tendency for fractures
Impaired growth
Short stature
Dental deformities
Acute hypocalcaemia
Causes excitability
- Neurone become much more permeable to Na+
Symptoms = CAT
- Convulsions
- Arrhythmias
- Tetany
Signs
- Chvostek’s sign
- Trousseaus’s sign
-
Effects of hypercalcaemia
Reduces excitability of neurones
- Makes neurones more stable
- High calcium inactivates channels= less ions conducted
hypercalcaemia symptoms
Constipation
Depression + other psychiatric problems
Abnormal heart rhythm
If severe
- Coma
- cardiac arrest
