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Flashcards in Physiology of bone repair Deck (57):
1

Describe the balance in healthy bone physiology

Balance between one resorption and bone formation

2

What does an imbalance in bone resorption lead to?

Osteoporosis
Osteopenia
Rickets

3

What does imbalance in bone formation lead to?

Osteopetrosis

4

Describe the classifications of bone structure

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

5

Name the 3 types of cells in bone

Osteoclasts
Osteoblasts
Osteocytes

6

What is between the cells in bone?

Extracellular matrix

7

Where are osteoblasts found?

On surface bone

8

What do osteoblasts do?

produce protein component acellular matrix – regulate bone growth and degradation

9

Where are osteocytes found?

Embedded in bone matrix

10

What do osteocytes do?

Maintain bone.

11

What are osteoclasts responsible for?

Responsible for bone degradation and remodelling

12

What is meant by organic?

Cells and proteins

13

What is meant by inorganic?

Minerals, eg Ca2+ & PO4- (hydroxyapatite)

14

What is bone dominated by?

Extracellular matrix

15

What is the Harversian system in lamellar bone?

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

16

Where do osteocytes arise?

From osteoblasts from mesenchyme
From precursor cells in bone marrow stroma

17

Describe osteoblasts

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

18

What will happen to a small percentage of osteoblasts

A low % of osteoblasts will become osteocytes locked in lacuna

19

What is the function of osteoclasts?

Resorption

20

Describe the structure of osteoclasts

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

21

Give the function of osteoclasts

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

22

Where does bone resorption occur?

Ruffled border

23

What percentage of extracellular matrix is minerals

70%

24

Describe compressive and tensile strength of bone

High

25

List the acellular components of bone

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

26

What are Glycosaminoglycans?

long polysaccharides
Highly negative
Attract Water
Repel each other
Resists compression

Abundant in Cartilage

27

Where are growth factors found in bone?

In the ECM

28

What is the function of growth factors in bone?

They are revealed by osteoclast action

Which leads to proliferation & mineralisation

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

29

How does bone form?

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

30

What 2 factors remodel bone?

Recurrent mechanical stress

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

31

Describe the effect of mechanical stress on bone

inhibits bone resorption promotes deposition

Surface osteoblasts & osteocyte network detect stresses

skeleton reflects forces acting on it


32

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

Bone weakens

33

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

Bed rest

Lack of gravity

34

What are bisphosphonates used for?

For osteoporosis

35

Name a drug used for osteoporosis

Alendronate

36

Describe the function of bisphosphonates

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

What other drugs are used for osteoporosis

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

What is bone composed of?

Living cells and acellular matrix

39

Describe the mechanism o osteopetrosis

Osteoclasts cannot remodel bone

Defective Vacuolar proton pump or

Defective Chloride channel

40

What does osteopetrosis lead to?

Excess bone growth
Bone growths at foramina press on nerves

Brittle (dense) bones
Blindness
Deafness
Severe anaemia

41

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

2-3 weeks

42

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

> 4 weeks

43

How does parathyroid hormone regulate calcium?

Parathyroid chief cells
Increases plasma Ca2+

44

How does vitamin D regulate calcium?

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

45

How does calcitonin regulate calcium?

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

46

How does PTH stimulate resorption via osteoblasts?

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

List some causes of low plasma concentration

Loss - Pregnancy, Lactation, Kidney dysfunction

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

Parathyroid dysfunction

48

How is vitamin D produced and activated?

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

What does chronic hypocalcemia result in?

Skeletal deformities

Increased tendency toward bone fractures

Impaired growth

Short stature (adults less than 5 feet tall)

Dental deformities

50

What does acute hypocalcemia cause?

C - Convulsions
A – Arrhythmias
T – Tetany

51

List some signs of acute hypocalcemia

Chvostek's sign
Trousseau's sign

52

Name a syndrome where there is hypocalcemia?

DiGeorge syndrome

53

Describe how low calcium leads to excitability

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

List some signs and symptoms of hypercalcemia

Can be asymptomatic

Reduced excitability
- Esp. Constipation
- Depression + other psychiatric

Abnormal heart rhythms

Severe hypercalcemia
- Coma
- Cardiac arrest

55

How does hypercalcemia do to excitability?

Less excitability

56

Describe intramembranous ossification

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

Describe endochondral ossification

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