T3 L1: Bone physiology and homeostasis Flashcards
What is osteopetrosis?
A rare disorder that causes bones to grow abnormally and become overly dense because there is increased bone formation
What is osteopenia?
The stage before osteoporosis where the bone density decreases
What do osteoclasts do?
They’re phagocytes that create bone by degradation and remodelling
-They phagocytose, secrete acids, and secrete proteolytic enzymes from lysosomes
They originate from haematopoietic stem cells like monocytes
What do osteocytes do?
They are quiescent mature cells embedded in bone that maintain bone
What do osteoblasts do?
Found on the surface of bone. they regulate bone growth and degradation
What does organic and inorganic mean in bone?
Organic: cells and proteins
Inorganic: minerals like Ca2+, PO4-
What is the function of a Haversian canal?
Found in the centre of an osteon and contains maintenance nutrients
What is woven bone?
Produced when osteoblasts produce osteoid rapidly, which occurs initially in all foetal bones, but is later replaced by more resilient lamellar bone
Which cell do osteocytes arise from?
From osteoblasts
Osteoblasts are post-mitotic and most undergo apoptosis. A small % become osteocytes locked in lacuna
What is the ruffled border of bone for?
It’s where bone resorption occurs
What are the components of bone?
Collagen fibres: strong, flexible protein
Hydroxyapatite: rigid mineral
Calcium/phosphate crystals (50%)
Just like reinforced cement: collagen is the rods and crystals are the cement
What are glycosaminoglycans?
Long polysaccharides abundant in the extracellular matrix of bone. They are highly negative so attract lots of water
It helps the bone resist compression
What is the function of growth factors in the extracellular matrix of bone?
They allow for proliferation and mineralisation
What is Howship’s lacuna?
Any of the tiny depressions, pits, or irregular grooves in bone that is being resorbed by osteoclasts
What is the difference between cancellous and compact bone?
Compact: harder outer shell of the bone
Eg. long bones
Cancellous: porous, less dense layers of the bone
Eg. Cancellous bone is the meshwork of spongy tissue (trabeculae) of mature adult bone typically found at the core of vertebral bones in the spine and the ends of the long bones
What is the difference between intramembranous and endochondral ossification?
In intramembranous ossification, bone develops directly from sheets of mesenchymal connective tissue. In endochondral ossification, bone develops by replacing hyaline cartilage
How does mechanical stress promote bone growth?
Surface osteoblasts and osteocytes detect stresses and inhibit bone resorption to promote deposition instead
Without weight bearing, bone rapidly weakens
The skeleton reflects the forces acting on it
How do the drugs Bisphosphonates work?
Eg. Alendronate
They inhibit osteoclast-mediated bone resorption
What is the function of inorganic pyrophosphate in bones?
It’s the endogenous regulator of bone turnover
It accumulates in bone and is ingested by osteoclasts and interferes with their metabolism
How does the drug Teriparatide work?
It’s a portion of human parathyroid hormone (PTH) and it encourages osteoclast formation of bone
Intermittent application activates osteoblasts more than osteoclasts so more bone is laid down
How does the drug Denosumab work?
It’s a monoclonal antibody that targets RANKL
It prevents osteoclast maturation so less bone is degraded and remodelled
What is the mechanism behind osteopetrosis?
- Osteoclasts cannot remodel bone because they can’t secrete the acid to break down the bone so it continues to grow
- Defective vacuole proton pump
- Defective chloride channel
What are the consequences of osteopetrosis?
Excessive bone growth causing:
- Brittle bones (not enough collagen)
- Blindness
- Deafness
- Severe anaemia
What are the 4 stages of fracture healing?
Reactive phase: haematoma and inflammation
-Blood and inflammatory cells enter wound and
granulation tissue forms
Soft callus formation: woven bone formation
Hard callous formation: Lamellar bone replaces woven bone
Remodelling: trabecular bone replaces lamellar bone. original shape forms and bone becomes more compact
Which hormones help regulate calcium?
Parathyroid hormone
Vitamin D (calcitriol)
Calcitonin
How does Vitamin D help calcium absorption?
- It increases interstitial Ca2+ absorption by increasing calbindin
- It stimulates kidneys to absorb calcium
- Indirectly stimulates osteoclasts via osteoblasts
- It facilitates bone remodelling thus increases serum Ca2+
What can cause low plasma calcium?
- Loss through pregnancy, lactation, or kidney dysfunction
- Low intake of calcium or vitamin D
- Parathyroid dysfunction
What does chronic hypocalcaemia result in?
- Skeletal deformities (rickets)
- Increased bone fractures
- Impaired growth (short stature)
- Dental deformities
What are the effects of acute hypocalcaemia?
It causes excitability because it makes membranes less stable:
Convulsions
Arrhythmias
Tetany
Chvostek’s sign and Trousseaus sign caused by latent tetany
What are the effects of acute hyperexcitability?
Reduced excitability because it makes membranes more stable as less Na+ will be going through
Causes:
- Constipation
- Depression
- Abnormal heart rhythms
Coma and cardiac arrest is severe hypercalcaemia
