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Module 204 Theme 2 > Physiology of bone repair > Flashcards

Physiology of bone repair Flashcards

1
Q

Describe the balance in healthy bone physiology

A

Balance between one resorption and bone formation

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2
Q

What does an imbalance in bone resorption lead to?

A

Osteoporosis
Osteopenia
Rickets

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3
Q

What does imbalance in bone formation lead to?

A

Osteopetrosis

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4
Q

Describe the classifications of bone structure

A

Long bone
Flat bone
Macroscopic - cortical bone, cancellous sponge
Microscopic - Lamellar (osteons) and woven (immature and disorganised)

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5
Q

Name the 3 types of cells in bone

A

Osteoclasts
Osteoblasts
Osteocytes

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6
Q

What is between the cells in bone?

A

Extracellular matrix

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7
Q

Where are osteoblasts found?

A

On surface bone

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8
Q

What do osteoblasts do?

A

produce protein component acellular matrix – regulate bone growth and degradation

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9
Q

Where are osteocytes found?

A

Embedded in bone matrix

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10
Q

What do osteocytes do?

A

Maintain bone.

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11
Q

What are osteoclasts responsible for?

A

Responsible for bone degradation and remodelling

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12
Q

What is meant by organic?

A

Cells and proteins

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13
Q

What is meant by inorganic?

A

Minerals, eg Ca2+ & PO4- (hydroxyapatite)

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14
Q

What is bone dominated by?

A

Extracellular matrix

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15
Q

What is the Harversian system in lamellar bone?

A

Osteons - structural unit which allows for cells of the bone to receive nutrients from central canal
Communication system between cells immobilised in bone matrix
HS runs Parallel to bone and along long axis of bone
Canaliculi allows communication
Haversian canal - allows main flow of nutrients

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16
Q

Where do osteocytes arise?

A

From osteoblasts from mesenchyme

From precursor cells in bone marrow stroma

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17
Q

Describe osteoblasts

A

Osteoblasts are post-mitotic
Most osteoblasts will undergo apoptosis
Number of osteoblasts decrease with age

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18
Q

What will happen to a small percentage of osteoblasts

A

A low % of osteoblasts will become osteocytes locked in lacuna

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19
Q

What is the function of osteoclasts?

A

Resorption

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20
Q

Describe the structure of osteoclasts

A

Multinucleate
40 micrometer in diameter.
15-20 closely packed oval-shaped nuclei.
Can proliferate

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21
Q

Give the function of osteoclasts

A

Phagocytose (bone matrix & crystals)
Secrete Acids - easier to manipulate the bone as acid causes re-solubilization of calcium
Secrete proteolytic enzymes from lysosomes

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22
Q

Where does bone resorption occur?

A

Ruffled border

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23
Q

What percentage of extracellular matrix is minerals

A

70%

24
Q

Describe compressive and tensile strength of bone

A

High

25
Q

List the acellular components of bone

A

collagen fibres – protein, flexible but strong
hydroxyapatite – mineral, provides rigidity
calcium/phosphate crystals > 50 %

26
Q

What are Glycosaminoglycans?

A 
long polysaccharides
Highly negative
Attract Water
Repel each other
Resists compression

Abundant in Cartilage

27
Q

Where are growth factors found in bone?

A

In the ECM

28
Q

What is the function of growth factors in bone?

A

They are revealed by osteoclast action

Which leads to proliferation & mineralisation

bone remodelling = bone turnover = the activation-resorption-formation sequence

29
Q

How does bone form?

A

bone forms either as compact or cancellous and by either intramembranous or endochondral bone formation

30
Q

What 2 factors remodel bone?

A

Recurrent mechanical stress

calcium homeostasis
Plasma calcium is essential in maintaining structural integrity of skeleton

31
Q

Describe the effect of mechanical stress on bone

A

inhibits bone resorption promotes deposition

Surface osteoblasts & osteocyte network detect stresses

skeleton reflects forces acting on it

32
Q

What happens to bone when there is not any mechanical stress?

A

Bone weakens

33
Q

Give two examples of where there is no mechanical stress to bone

A

Bed rest

Lack of gravity

34
Q

What are bisphosphonates used for?

A

For osteoporosis

35
Q

Name a drug used for osteoporosis

A

Alendronate

36
Q

Describe the function of bisphosphonates

A

inhibit osteoclast-mediated bone-resorption

related to inorganic pyrophosphate
the endogenous regulator of bone turnover
Accumulate on bone & ingested by osteoclasts
Interfere with osteoclasts metabolism

37
Q

What other drugs are used for osteoporosis

A

Encourage osteoblast formation of bone
Teriparatide
portion of human parathyroid hormone (PTH)
Intermittent application activates osteoblasts more than osteoclasts

Prevent osteoclast maturation
Denosumab
Monoclonal Antibody that targets RANKL

38
Q

What is bone composed of?

A

Living cells and acellular matrix

39
Q

Describe the mechanism o osteopetrosis

A

Osteoclasts cannot remodel bone

Defective Vacuolar proton pump or

Defective Chloride channel

40
Q

What does osteopetrosis lead to?

A

Excess bone growth
Bone growths at foramina press on nerves

Brittle (dense) bones
Blindness
Deafness
Severe anaemia

41
Q

How long do fractures to bones in the upper body take to heal?

A

2-3 weeks

42
Q

How long do fractures to bones in the lower body take to heal?

A

> 4 weeks

43
Q

How does parathyroid hormone regulate calcium?

A

Parathyroid chief cells

Increases plasma Ca2+

44
Q

How does vitamin D regulate calcium?

A

1,25-di-OH cholecalciferol (calcitriol)
Made in stages: Skin - Liver - Kidney
Increases plasma Ca2+

45
Q

How does calcitonin regulate calcium?

A

Made by thyroid C cells
“tones down” blood calcium
Calcium goes into bone
Used as a treatment for osteoporosis

46
Q

How does PTH stimulate resorption via osteoblasts?

A

When PTH is high, Binds on osteoblast cell which presents RANK ligand
Precursor on osteoclast binds and differentiates to fuse and form an activated osteoclast - leads to bone resorption

47
Q

List some causes of low plasma concentration

A

Loss - Pregnancy, Lactation, Kidney dysfunction

Low Intake - Insufficient ingestion of Calcium, Rickets (low vit D)

Parathyroid dysfunction

48
Q

How is vitamin D produced and activated?

A

Cholecalciferol (Vitamin D3) - 25OH cholecalciferol - 1,25 OH cholecalciferol (calcitriol) - calbindin in gut enterocytes - increase intestinal absorption of calcium and increase calcium resoption by kidney - increase plasma calcium

49
Q

What does chronic hypocalcemia result in?

A

Skeletal deformities

Increased tendency toward bone fractures

Impaired growth

Short stature (adults less than 5 feet tall)

Dental deformities

50
Q

What does acute hypocalcemia cause?

A

C - Convulsions
A – Arrhythmias
T – Tetany

51
Q

List some signs of acute hypocalcemia

A

Chvostek’s sign

Trousseau’s sign

52
Q

Name a syndrome where there is hypocalcemia?

A

DiGeorge syndrome

53
Q

Describe how low calcium leads to excitability

A

Effect seems paradoxical
i.e. counter-intuitive

Hypocalcaemia makes membranes “more excitable” and “less stable”
Sodium is more able to leak through it
Explains latent tetany and its signs

Hypercalcaemia paradoxically reduces excitability
By making membranes more stable

54
Q

List some signs and symptoms of hypercalcemia

A

Can be asymptomatic

Reduced excitability

  • Esp. Constipation
  • Depression + other psychiatric

Abnormal heart rhythms

Severe hypercalcemia

  • Coma
  • Cardiac arrest
55
Q

How does hypercalcemia do to excitability?

A

Less excitability

56
Q

Describe intramembranous ossification

A

Direct mineralisation of connective tissue (mesenchyme)
Cells divide and condense around capillary network
Starting point is called primary ossification center
Grows radially, finally fusing together replacing the connective tissue
Connective tissue that remains penetrated by blood cells and undifferentiated mesenchyme gives rise to bone marrow.
Examples include the skull, mandible and clavicle

57
Q

Describe endochondral ossification

A

Cartilaginous template made from the mesenchyme
Template is replace by bone- osteogenesis
Different ossification centres emerge, a primary one in the diaphysis and secondary ones in the epiphysis
Initially a bone collar is produced and from here the primary centre develops
The epiphyseal plate (Growth Plate) exists between the diaphysis and the epiphysis

Module 204 Theme 2 (31 decks)

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