The Physiology Of Bone Flashcards
Excessive bone formation leads to?
Osteopetrosis
Excessive bone resorption leads to?
Osteoporosis
Osteopenia
Risk
Cortical bone?
Thick hard bone, isn’t organised in spicules
Spicules?
Web or mesh
Microscopic bone appearance?
Lamellar and woven
Bone is made of?
Osteoclasts
Osteoblasts
Osteocytes- maintain bone
Osteoblasts are found?
On surface bone
Produce protein component
Acellular matrix
Regulate bone growth and degradation
Osteocytes are?
Quiescent mature cells embedded in bone matrix, maintain bone
Osteoclasts responsible for?
Bone degradation and remodelling
Organic is?
Cells and proteins
Inorganic material?
Minerals , ca and PO, when they mix together they make hydroxyapatite
Hydroxyapatite is made up of?
Ca and PO
Haversian system runs?
Parallel to bone and along long axis of bone
The hydroxyapatite between osteocytes is called?
Ground substance
Osteocytes arise from?
Osteoblasts, from mesenchyme precursor cell in bone marrow stroma
Osteoblasts are?
Post mitotic, most go undergo apoptosis
Osteoclasts are?
Multinucleate, oval shaped nuclei, 40-100um
Precursor of osteoclasts?
Same as monocytes (haematopoietec stem)
Hence phagocytose and destroy bone matrix and crystals
Secrete acids
Secrete proteolytic enzymes from lysosomes
Where bone resorption occurs its called?
Ruffled border
Extracellular matrix is what percent minerals?
70
Tensile strength the strength to?
Manage being pulled apart
Compressive strength?
Able to withstand being bent
Bone is made of?
Collagen triple helix- bending
Hydroxyapatite- provide rigidity
( more than 50%)
Extracellular matrix contains?
Glycosaminoglyscans - long polysaccharide, highly negative.
Attract water but repel each other. Can resist compression. Fluffy stuff.
Abundant in cartilage
When do growth factors appear?
After osteoclasts action, leading to local proliferation and mineralisation
Where do osteoclasts resort bone?
Howships lacuna
How does bone remodelling happen?
Osteoclasts break down bone liberating matrix bound growth factors.
This causes osteoprogenitor cells to produce active osteoblasts
Difference between compact and cancellous?
Difference between intramembranous and endochondral bone formation?
Major factors governing remodelling?
Recurrent mechanical stress
Calcium homeostasis
Mechanical stress causes?
Promotes deposition
How does mechanical stress work?
Osteocytes and osteoblasts detect stresses, skeleton reflects forces acting on it
In an osteoporotic bones there are more spaces
Osteoporosis drug??
Bisphosphonates, alendronate looks like pyrophosphate.
Accumulate in bone and are taken up by osteoclasts Work by inhibit osteoclasts mediated bone resorption
Osteoporosis drug to encourage bone formation?
Teriparatide, portion of PTH, intermittent application activates osteoblasts
Drug to prevent osteoclasts maturation?
Denosumab, monoclonal antibody targets RANkL
Osteopetrosis is a condition that is?
Autosomal recessive
How does osteopetrosis work?
Prevents osteoclasts cannot remodel bone,
Can’t secrete acid due to defective chloride channel or vacuolar proton pump
Osteopetrosis happens at?
Foramina pressing on nerves.
Brittle bones
Blindness
Deafness
Severe anaemia (run out of bone marrow)
Phases of fracture healing?
- Haematoma and inflammation
- Soft callus formation- structural connection (woven bone or fibrocartilage)
- Hard callus formation ( lamellar bone replaces woven bone).
- Remodelling- trabecular bone replaces lamellar bone, compact bone formed
Duration of bone fracture phase?
Upper body- 2-3 weeks
Lower body more than 4 weeks
PTH and vitamin D causes?
Increase in Calcium plasma
Calcitonin works by?
Made by thyroid c cells
Lowers blood calcium
Used as treatment for osteoporosis
Calcitonin is used for treatment of?
Osteoporosis
What percent of peak bone mass is determined genetically?
60-70
How does PTH work on osteoblasts?
PTH bind on receptor consistently on osteoblasts, puts RANKL on its surface.
RANK receptor on osteoclasts precursor detects in, becoming activated.
How to protect from osteoclast activation
OPG- decoy receptor therefore prevents RANK binding so less osteoclast activation
Where does ca resorption happen at kidney?
DCT
Negative feedback for preserving calcium plasma level?
Bone mobilise ca to plasma
Kidney increase ca resorption in dct
Enterocytes increase calbindin so more absorption
Vitamin d3 is formed in?
Skin
Vitamin D production
D3 hydroxylated in liver 25 OH cholecalciferol
In kidney it becomes 1,25 di)H cholecalciferol, calcitriol active vitamin D
How does vitamin D cause release of calcium from bone?
Stimulates osteoclast indirectly via osteoblasts
Causes of low plasma calcium?
Pregnancy
Lactation
Kidney dysfunction
Insufficient ingestion of calcium
Rickets
Parathyroid dysfunction
Acute hypocalcaemia signs?
Bleeding Anaesthesia Dysphagia Convulsions Arrhythmia Tetany Spasms and stridor
Acute hypocalcaemia signs?
Chvosteks sign- hit them in face, squeezing of muscles
Trousseau’s sign- carpopedal spasm
Digeorge syndrome
Hypocalcaemia makes membrane?
More excitable less stable
Sodium is more able to leak through it, causing latent tenany
Hypercalcaemia makes membranes more?
Stable, less excitable
Hypercalcaemia signs symptoms?
Asymptomatic
Constipation
Depression and other psychiatric
Abnormal heart rhythms
Coma/ cardiac rest
Haversian canal contains?
Fluid for maintenance
Purpose of glycosaminoglycans?
Highly negative, attract water, but they repel each other, fluffy stuff, resist compression
Lots in cartilage
Chronic hypocalcaemia results in?
Skeletal deformities Impaired growth Short stature Dental deformities Increased tendency to bone fractured
