Lecture 3- Physiology of bone repair Flashcards
What conditions result as imbalance of bone resorption?
Osteoprosis
Osteopenia
Rickets
what conditions result as imbalance of bone formation?
OsteoPETrosis
Name the two classifications of bone?
- Long bone
- Flat bone
Name the macroscopic features of different bones?
- Cortical Bone
- Cancellous bone –>has spicules and trabeculae
Name the microscopic features of different bones?
- Lamellar- osteons
- Woven- immature and disorganised
Name the three principle cell types of bone?
- Osteoclasts- degradation and remodelling of bones
- Osteoblasts- formation of new bone
- Osteocytes- maintenance and detection of environmental changes
Name the functions of the three principle cell types?
- Osteoblasts – on surface bone, produce protein component acellular matrix – regulate bone growth and degradation
- Osteocytes – quiescent mature cells embedded in bone matrix. They maintain bone.
- Osteoclasts – responsible for bone degradation and remodelling
What is the purpose of haversian system(Aka osteon) in lamellar bone?
-Communication system between cells immobilised in bone matrix
What do the osteocyte arise from?
Osteoblasts
describe the process osteocyte formation?
-From mesenchyme- precursor cells in bone marrow stroma
where are the osteocytes found?
inside the lacuna (spicules)
Describe the function of osteoclasts?
Resorption of bone
Describe the structure of osteoclasts?
- Multi-nucleate
- 40-100 micrometer in diameter
- 15-20 closely packed oval shaped nuclei
- can proliferate
what are osteoclasts same precursors as?
monocytes- haematopoietic stem
How do osteoclasts act?
- Phagocytose (bone and matrix)
- Secrete acids
- Secrete proteolytic enzymes from lysosomes
What does ruffled border show?
-Where bone resorption occurs
Describe the bone constituents?
Extracellular matrix=70% minerals
proteins and sparse cells
what are the acellular elements of bone?
- collagen fibres- protein, flexible but strong
- Hydroxyapatite- mineral- provides rigidity
- Calcium/phosphate >50%
what is the extracellular matrix of bones includes?
Glycosaminoglycans-
Describe the structure of glycosaminoglycans?
- Long polysaccharides
- Highly negative
- attract water
- Repel each other
- resist compression
Where are the growth factors found?
suspended in matrix
How are the growth factors revealed?
osteoclast action-proliferation and mineralisation
What is meant by bone remodelling?
Bone turnover- the activation-resorption -formation sequence
how do bone cells remodel bone?
- Osteoclasts resorb bone in Howship lacuna
- Osteoblasts deposit bone-onto pre-existing bone
- active process
- bone is layed down in different direction
What two types of bones are formed and by which mechanism?
Compact or cancellous
by either intramembranous or endochondral bone formation
what are the two major factors that govern bone remodelling?
recurrent mechanical stress
Calcium homeostasis
what does mechanical stress do to the bone?
strengthens bone
How does the mechanical stress strengthen bone?
- Inhibits bone resorption and promotes deposition
What two factors cause bones to weaken?
Bed rest
lack of gravity
Name one treatment option for osteoprosis and mechanism?
- Bisphosphonates- alendronate
- works by inhibiting osteoclast mediated bone resorption
What other drugs can be used for osteoprosis?
Teriparatide- encourage osteoblast formation of bone
-recombinat form Human parathyroid hormone
What other drugs can be used for osteoprosis?
Denosumab- prevents osteoclast maturation
-monoclonal antibody that targets RANK-ligand
Explain OsteoPETrosis?
- Autosomal recessive-
- Rare
Define the molecular mechanism of OsteoPETrosis?
- osteoclasts can not remodel bone
- defective vacuolar proton pump or defective chloride channel
Explain the consequences of OsteoPETrosis?
Brittle bones
Blindness
deafness
severe anaemia
what are the 4 phases of fracture healing?
- Reactive phase: haematoma and inflammation
- soft callous formation
- hard callous formation
- Hard callous formation
How long does bone take to heal in the upper body and lower body?
Upper . 2-3 weeks
Lower >4 weeks
Name the hormones of calcium regulation?
- PTH
- Vitamin D
- Calcitonin
Briefly explain the function of PTH in calcium regulation?
PTH- Parathormone- secreted by parathyroid chief cell –> increases plasma Ca2+
Briefly explain the function of Vitamin D in calcium regulation?
-Made in stages- skin>Liver>Kidney
Increases plasma Ca2+
Briefly explain the function of Calcitonin in calcium regulation?
- Made by thyroid C cells
- Tones down blood calcium>calcium goes into bones- used as treatment for osteoprosis
Describe the pathway of Vitamin D production and activation
Skin- absorbs vit D3
Liver- converts it to 25-OH cholecalciferol
Kidneys- convert it to 1, 25-di-OH cholecalciferol (calcitriol)
Gut- Calbindin- increases intestinal absorption of Ca2+
AND Ca2+ reabsorption in kidneys
RESULT - Increased plasma Ca2+
Describe the function of Vitamin D in calcium homeostasis?
- Increases intestinal Ca2+ absorption-increases calbindin
- Stimulates kidneys to reabsorb calcium
- stimulates osteoclasts indirectly- via osteblasts
- Facilitates bone remodelling- thus increases serum Ca2+
what are the possible causes of low calcium?
1. Loss- pregnanacy and lactation Kidney dysfunction 2. Low intake - Insufficent ingestion of calcium Rickets 3. Parathyroid dysfucntion
What does chronic hypocalcaemia result in?
- skeletal deformaties
- Increased bone fractures
- impaired grwoth
- short stature
- dental deformaties
What are the signs of acute hypocalcaemia?
C-convulsions
A- arrhythmia
T-tetany
Name two clincal signs used to detect hypocalcaemia?
Chovestek’s sign-Tapping masseter leads to twitch on same side of face
Trousseau sign-Hand spasm after 3 minutes with blood pressure cuff in place (above systolic pressure)
What does low calcium do the membrane excitabilty?
More excitable: Na is more able to leak through- explains tetany
What is the effect of hypercalcaemia on membrane excitabilty?
Makes membrane more stable
What are the signs and symptoms of hypercalcaemia?
- Can be asymptomatic
- Reduced excitability- constipation and depression
- Abnormal heart rhythms
What are the consequences of severe hypercalcaemia?
Coma
Cardiac arrest
