Lecture 3- Physiology of bone repair

Question 1

What conditions result as imbalance of bone resorption?

Answer 1

Osteoprosis
Osteopenia
Rickets

Question 2

what conditions result as imbalance of bone formation?

Answer 2

OsteoPETrosis

Question 3

Name the two classifications of bone?

Answer 3

• Long bone

- Flat bone

Question 4

Name the macroscopic features of different bones?

Answer 4

• Cortical Bone

- Cancellous bone –>has spicules and trabeculae

Question 5

Name the microscopic features of different bones?

Answer 5

• Lamellar- osteons

- Woven- immature and disorganised

Question 6

Name the three principle cell types of bone?

Answer 6

1. Osteoclasts- degradation and remodelling of bones
2. Osteoblasts- formation of new bone
3. Osteocytes- maintenance and detection of environmental changes

Question 7

Name the functions of the three principle cell types?

Answer 7

• 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

Question 8

What is the purpose of haversian system(Aka osteon) in lamellar bone?

Answer 8

-Communication system between cells immobilised in bone matrix

Question 9

What do the osteocyte arise from?

Answer 9

Osteoblasts

Question 10

describe the process osteocyte formation?

Answer 10

-From mesenchyme- precursor cells in bone marrow stroma

Question 11

where are the osteocytes found?

Answer 11

inside the lacuna (spicules)

Question 12

Describe the function of osteoclasts?

Answer 12

Resorption of bone

Question 13

Describe the structure of osteoclasts?

Answer 13

• Multi-nucleate
• 40-100 micrometer in diameter
• 15-20 closely packed oval shaped nuclei
• can proliferate

Question 14

what are osteoclasts same precursors as?

Answer 14

monocytes- haematopoietic stem

Question 15

How do osteoclasts act?

Answer 15

• Phagocytose (bone and matrix)
• Secrete acids
• Secrete proteolytic enzymes from lysosomes

Question 16

What does ruffled border show?

Answer 16

-Where bone resorption occurs

Question 17

Describe the bone constituents?

Answer 17

Extracellular matrix=70% minerals

proteins and sparse cells

Question 18

what are the acellular elements of bone?

Answer 18

• collagen fibres- protein, flexible but strong
• Hydroxyapatite- mineral- provides rigidity
• Calcium/phosphate >50%

Question 19

what is the extracellular matrix of bones includes?

Answer 19

Glycosaminoglycans-

Question 20

Describe the structure of glycosaminoglycans?

Answer 20

• Long polysaccharides
• Highly negative
• attract water
• Repel each other
• resist compression

Question 21

Where are the growth factors found?

Answer 21

suspended in matrix

Question 22

How are the growth factors revealed?

Answer 22

osteoclast action-proliferation and mineralisation

Question 23

What is meant by bone remodelling?

Answer 23

Bone turnover- the activation-resorption -formation sequence

Question 24

how do bone cells remodel bone?

Answer 24

1. Osteoclasts resorb bone in Howship lacuna
2. Osteoblasts deposit bone-onto pre-existing bone
3. active process
4. bone is layed down in different direction

Question 25

What two types of bones are formed and by which mechanism?

Answer 25

Compact or cancellous | by either intramembranous or endochondral bone formation

Question 26

what are the two major factors that govern bone remodelling?

Answer 26

recurrent mechanical stress | Calcium homeostasis

Question 27

what does mechanical stress do to the bone?

Answer 27

strengthens bone

Question 28

How does the mechanical stress strengthen bone?

Answer 28

1. Inhibits bone resorption and promotes deposition

Question 29

What two factors cause bones to weaken?

Answer 29

Bed rest | lack of gravity

Question 30

Name one treatment option for osteoprosis and mechanism?

Answer 30

- Bisphosphonates- alendronate | - works by inhibiting osteoclast mediated bone resorption

Question 31

What other drugs can be used for osteoprosis?

Answer 31

Teriparatide- encourage osteoblast formation of bone | -recombinat form Human parathyroid hormone

Question 32

What other drugs can be used for osteoprosis?

Answer 32

Denosumab- prevents osteoclast maturation | -monoclonal antibody that targets RANK-ligand

Question 33

Explain OsteoPETrosis?

Answer 33

- Autosomal recessive- | - Rare

Question 34

Define the molecular mechanism of OsteoPETrosis?

Answer 34

- osteoclasts can not remodel bone | - defective vacuolar proton pump or defective chloride channel

Question 35

Explain the consequences of OsteoPETrosis?

Answer 35

Brittle bones Blindness deafness severe anaemia

Question 36

what are the 4 phases of fracture healing?

Answer 36

1. Reactive phase: haematoma and inflammation 2. soft callous formation 3. hard callous formation 4. Hard callous formation

Question 37

How long does bone take to heal in the upper body and lower body?

Answer 37

Upper . 2-3 weeks | Lower >4 weeks

Question 38

Name the hormones of calcium regulation?

Answer 38

1. PTH 2. Vitamin D 3. Calcitonin

Question 39

Briefly explain the function of PTH in calcium regulation?

Answer 39

PTH- Parathormone- secreted by parathyroid chief cell --> increases plasma Ca2+

Question 40

Briefly explain the function of Vitamin D in calcium regulation?

Answer 40

-Made in stages- skin>Liver>Kidney | Increases plasma Ca2+

Question 41

Briefly explain the function of Calcitonin in calcium regulation?

Answer 41

- Made by thyroid C cells | - Tones down blood calcium>calcium goes into bones- used as treatment for osteoprosis

Question 42

Describe the pathway of Vitamin D production and activation

Answer 42

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+

Question 43

Describe the function of Vitamin D in calcium homeostasis?

Answer 43

1. Increases intestinal Ca2+ absorption-increases calbindin 2. Stimulates kidneys to reabsorb calcium 3. stimulates osteoclasts indirectly- via osteblasts 4. Facilitates bone remodelling- thus increases serum Ca2+

Question 44

what are the possible causes of low calcium?

Answer 44

``` 1. Loss- pregnanacy and lactation Kidney dysfunction 2. Low intake - Insufficent ingestion of calcium Rickets 3. Parathyroid dysfucntion ```

Question 45

What does chronic hypocalcaemia result in?

Answer 45

1. skeletal deformaties 2. Increased bone fractures 3. impaired grwoth 4. short stature 5. dental deformaties

Question 46

What are the signs of acute hypocalcaemia?

Answer 46

C-convulsions A- arrhythmia T-tetany

Question 47

Name two clincal signs used to detect hypocalcaemia?

Answer 47

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)

Question 48

What does low calcium do the membrane excitabilty?

Answer 48

More excitable: Na is more able to leak through- explains tetany

Question 49

What is the effect of hypercalcaemia on membrane excitabilty?

Answer 49

Makes membrane more stable

Question 50

What are the signs and symptoms of hypercalcaemia?

Answer 50

- Can be asymptomatic - Reduced excitability- constipation and depression - Abnormal heart rhythms

Question 51

What are the consequences of severe hypercalcaemia?

Answer 51

Coma | Cardiac arrest