BL 18 Flashcards

1
Q

Bone functions

A

Mechanical
Protect important and delicate tissues and organs Provide a framework for the overall shape of the human body Form the basis of levers involved in movement

Synthetic
Haemopoiesis (holds and protects red bone marrow)

Metabolic
Mineral storage (calcium and phosphorus)
Fat storage (yellow bone marrow)
Acid-base homeostasis (absorbs or releases alkaline salts to help regulate blood pH)

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2
Q

Name and describe the two types of bone growth

A
  • *Endochondral ossification**
  • the formation of long bones from a cartilage template - continued lengthening is by ossification at epiphyseal plates - e.g. appositional growth (growth at edges)
  • *Intra-membranous ossification**
  • The process of bone development from fibrous membranes. It is involved in the formation of the flat bones of the skull, the mandible, and the clavicles.
  • The formation of bone from clusters of MSC in the centre of bone
  • Trabecular bone - e.g. interstitial growth (growth in the middle)
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3
Q

Are bones formed from intramembraneous and endochondral ossification remodelled in the same way?

A

Once a bony spicule has formed, osteoblasts, osteocytes and osteoclasts remodel it in much the same way, whether the initial ossification was endochondral or intra-membranous

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4
Q

What is the role of intramembraneous ossification in long bones?

A

The process also contributes to the thickening (not the lengthening) of long bones, at their periosteal surfaces (appositional growth).

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5
Q

What happens after intramembraneous ossification?

A

Intramembraneous ossification produces immature bone that undergoes remodelling into mature bone

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6
Q

Intramembraneous ossification (start to osteoblasts)

A
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7
Q

Intramembranous ossification (from osteoblasts to osteoid calcifying)

A
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8
Q

Intramembraneous ossification (ostoid to conversion of cancellous bone to cortical bone on the outside)

A
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9
Q

Intramembranous ossification (what happens to the internal spongy bone? where do the osteoblasts go?)

A
  • Osteoblasts remain on the surface of the bone so they can remodel it as required
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10
Q

In flat bones, how is the cancellous bone formed? how is the compact bone formed?

A
  • Spongy bone - through intramembranous ossification (talks about spicules forming…)
  • Compact bone - through bone remodelling (osteon’s form here)
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11
Q

Overview of intramembranous offication

A
  1. Mesenchymal stem cells (MSCs) form a tight cluster
  2. The MSCs transform into osteoprogenitor cells and then transform into osteoblasts
  3. Osteoblasts lay down a osteoid (extracellular matrix containing Type I collagen)
  4. The osteoid mineralises (crystals of calcium form in and around it) to form rudimentary bone tissue spicules [surrounded by osteoblasts and containing osteocytes]
  5. The spicules join to form trabeculae, which merge to form woven bone
  6. Trabeculae replaced by the lamellae of mature compact bone
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12
Q

Do long bones undergo remodelling?

A
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13
Q

Label this diagram of a growing fetal skull (flat bone)

A

Increased proliferation in the middel, pushes material out (appositional growth)

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14
Q

Label this diagram

A
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15
Q

Label the compact bone of skull (forming)

A

Labelled:

  • osteocytes, osteons, Haversian and Volkmann’s canals
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16
Q

Conversion of cancellous bone to cortical bone (after intramembranous ossification)… immature bone to mature bone

A
  1. MSC convert into osteoblast that line recently formed trabeculae
  2. Lay down osteoid that is mineralised
  3. Osteoblasts trapped – osteocyte
  4. Steps 1 to 3 repeat
  5. Central MSC convert into blood vessels, lymph vessels and nerves
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17
Q

Difference between mature bone and immature bone

A

• Immature bone has osteocytes in random arrangements
• Mature bone has osteocytes arranged in concentric lamellae of osteons
Resorption canals in mature bone run parallel with the osteons’ long axes

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18
Q

Look at the difference between immature bone (where osteon’s are forming) and mature bone (where osteon’s have formed)

A
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19
Q

Recap - what is cancellous bone?

A

Cancellous bone forms a network of fine bony columns or plates to combine strength with lightness. The spaces are filled by bone marrow.

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20
Q

Recap - what is compact bone?

A

Compact bone - forms the external surfaces of bones and comprises ca. 80% of the body’s skeletal mass.

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21
Q

Recap - structure of mature compact bone

A
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22
Q

Recap - structure of mature cancellous bone

A
  • tear shaped
23
Q

What is the direction of each layer in an osteon?

A

As each layer is laid down, they are laid down in 45 degree angles. In opposite directions for each layer = gives the structure immense strength

24
Q

Bone fracture (what are they, what type of pressure etc)

A

Many different types of fracture:
The amount of force required to break bone is considerable (estimates)
- 20,000 lbs/in2 when compressed
- 12,000 lbs/in2 when pulled (tension) (need less force to pull bones comapared to compressing bones)
- 150-160 lbs/in2 when in collision (side) e.g. putting your finger on a surface and hitting it with a hammer - would need a lot less force

25
Q

What are the different types of fracture?

A

There is 7!

26
Q

Bone strength - how can bones resist fracture?

A

Bone resists fracture because:
• it has great tensile and compressive strength, a small degree of flexibility
• Main force lines are through the cortical bone (small cancellous bone component)
Why can large forces not break bone?
• Osteon rings go in different directions. Lamella in one layer goes 45 degrees in one direction, in the next layer it is 45 degrees in the other direction, then swap again etc
• This althoughs the lamellae to slip past each other, resiting fracture - excessive load causes fracture

With lots of use e.g. weight lifting, the cortical bone will remodel and thicken, does this using osteons…

27
Q

How osteons rearrange themselves when thickening bone? (part of bone remodelling)

A
  • Bone is dynamic and constantly remodelling itself
  • Exercise is a key determinant of bone strength increased osteon.
  • Osteon will reposition itself along the stress line
  • Osteon’s also get bigger - the bigger the concentric circles = the stronger the bone is (increased osteoblast activity)
  • also lays down a new periosteum on the outside and new endosteum on the inside, also increases the number of trabeculae in the middle to try and strengthen the bone
  • Inactivity increases bone resorption (1/3 of mass lost when immobile)
28
Q

What happens with inactivity (to bone)

A

Don’t use it = lose it!

  • Increase resorption
  • Increased osteoclast activity = bone gets thinner = more boen resorption = lose mass
29
Q

Briefly describe calcium homeostasis

A
30
Q

What factors affect bone stability?

A

Activity of osteocytes (osteoid recycling)
Can act like osteoblasts and lay down ‘scavenged’ osteoid into their lacunae (increased by oestrogen/thyroid hormone)
Can act like osteoclasts and degrade bone (a little) – known as osteocyctic osteolysis (increased by PTH)

Activity of osteoblasts (bone deposition - thickening bones)
Stimulated by calcitonin, GH (via IGF-1), oestrogen and testosterone (also by PTH), thyroid hormones, vitamin A

Activity of osteoclasts (bone resorption - thinning bones)
Increased by PTH if the calcium ion conc in the blood is too low – releases calcium ions from the bone into the blood, increases the activity of osteoclasts
Calcitonin blocks the action of PTH at the PTH receptor

Nutrition (DIET)
Vitamin D3 controls the level of calcium and phosphate in the body (either absorbed from gut or synthesised in the skin) – produces calcitriol (calcium absorption, must have D3 to absorb calcium)
Vitamin C – synthesis of collagen
Vitamins K and B12 – synthesis of bone proteins (calcaneurin, oestopontin, osteonectin)

31
Q

What happens if there is low vitamin D in the diet?

A

low vitamin D = low Ca2+ absorbtion from food in the small intestine = low levels of Ca2+ in the blood = increases PTH production = to release calcium ions from the bones to blood (i.e. increases bone resorption)

32
Q

Fracture repair (overview)

A
33
Q

Fracture repair - haemoatoma formation

A
  • Blood vessels in bone and periosteum break
  • A mass of clotted blood (haematoma) forms
  • Bone cells at the fracture edge die (as they have no blood supply)
  • Bleeding leads to swelling and inflammation occurs (granulocytes enter the site)
  • Granulocyte cells enter and phagocytic cells and osteoclasts begin to remove dead and damaged tissue
  • Macrophages will eventually remove the blood clot
34
Q

Fracture repair - Fibrocartilaginous callus formation (soft callus formation)

A
  • New blood vessels infiltrate the fracture haematoma
  • A procallus (soft callus) of granulation tissue (i.e. tissue rich in capillaries and fibroblasts) develops
  • Fibroblasts produce collagen fibres that span the break. Others differentiate into chondroblasts that give rise to a sleeve (ring) of hyaline cartilage
  • [An externally bulging, fibrocartilaginous matrix thus splints the broken bone]
  • Simultaneously: osteoblasts from the nearby periosteum (outer white bit in the pic below) and endosteum, (and multipotent cells from the bone marrow) invade the fracture site and begin bone reconstruction by forming spongy/ trabecular bone
  • Can see the trabecular of spongy bone forming in the medulla region
35
Q

Fracture repair - Bony callus formation

A
  • Within a week, new bone trabeculae begin to appear in the fibrocartilaginous (soft) callus.
  • The trabeculae develop as the former fibrocartilaginous callus is converted to a hard (bony) callus of cancellous bone
  • Endochondral ossification replaces all cartilage with cancellous bone
  • Intramembranous ossification produces new cancellous bone in any gaps in the cortical region and spongy bone region
36
Q

Fracture repair - Bone remodelling (several months - years)

A

Cancellous bone -> compact bone

  • Cancellous bone (that was in the edges of the compact bone) begins to be re-modelled into compact bone, especially in the prior cortical region (i.e. in the region of the former bone shaft walls). This process continues for several months (or even years)
  • The material bulging from the outside of the bone, and inwards, into the medullary cavity, is removed by osteoclasts (removing any damage that has occured)
  • The final shape of the re-modelled area is the same as that of the original unbroken bone because it responds to the same set of mechanical stressors
  • The bone will be almost the same prior to the fracture, sometimes it is actually stronger if there was a weakness in the bone prior to the fracture before
37
Q

Summary of bone repairs

A
38
Q

Bone remodelling (two major steps)

A

Two steps: to create a new osteon

  1. Osteoclasts make a wide tunnel in the bone (cutting cone) this happens first
  2. Osteoblasts make a smaller tunnel of cortical bone (closing cone) this happens second (closing up the cutting cone)
39
Q

More detail - explain the remodelling unit

A

(numbered in a stupid way on the diagram) -

d. (1) Osteoclasts break down the bone (bone resorbing)
c. (2) Behind the osteoclats, osteoblasts then come in and lay down osteoid
b. (3) Then osteoblasts lay down the next layer of osteoid
a. (4) Then osteoblasts lay down the next layer of the osteoid

this process continues, creating a new osteon

As the osteoblasts are doing this, they put all the mesenchymal cells at the centre of the osteon, so they can create a blood vessel. This blood vessel will become the Haversian system within the cortical bone

40
Q

Name some diseases associated with the bones, name some of the similarities with these diseases

A
  • Osteogenesis imperfecta
  • Rickets and osteomalacia
  • Osteoporosis
  • Achondroplasia

Depletion of bone mass always characterises the disease
Loss of mass within the trabecular bone (spongy bone) is particularly relevant to: increased susceptibility to fracture

41
Q

Osteogenesis imperfecta (cause and effect of this)

A
  • Also called Brittle bone disease
  • Mutation in COL1A gene
  • Incorrect production of collagen 1 fibres
  • Weak bones and increased fracture risk
  • Shortened height and stature
  • Mainly affects neonates and children
42
Q

Rickets (age group, caused by, effects)

A

Mainly affects children
• Vitamin D deficiency
• This leads to poor calcium mobilisation (as vitamin D is involved in the movement of calcium from the gut to where it is needed)
• Ineffective mineralisation
• Weakened bone development
• Soft bones
• Shortened height and stature
• Painful to walk
• Characteristic bowed legs caused by the forces that have been exerted onto the legs when walking

43
Q

Osteomalacia (age, cause)

A
  • ‘Rickets’ in the adult
  • Caused by vitamin D deficiency, it lower’s mineralisation and increases osteoid (osteoid isn’t mineralised)
  • Leads to increased calcium resorption as calcium is difficult to get from food due to low vitamin D: all of the situations below can lead to vitamin D deficiency:
  • Kidney disease
  • Protection from sunlight - sunlight produces vit D (e.g. often see in Muslim women)
  • Surgery to Stomach and intestine (may affect absorption of calcium from food)
  • Drugs – phenytoin prevents vit D absorption
  • Pic below shows the osteoid on the surface of the bone not being mineralised.
44
Q

Difference between osteoporosis and osteomalacia

A
45
Q

What types of osteoporosis is there?

A

3 types:
Primary type 1 - due to increase in osteoclast number (post-menopausal women)
Primary type 2 - due to loss of osteoblast function (older people)
Secondary (other factors)

46
Q

What happens in primary type 1 osteoporosis?

A
  • occurs in postmenopausal women
  • due to an increase in osteoclast number
  • loss of oestrogen after the menopause (oestrogen keeps the osteoclast number correct)
47
Q

What happens in primary type 2 osteoporosis?

A
  • occurs in (older) men and women
  • due to loss of osteoblast function (senile osteoporosis)
  • loss of both oestrogen and androgen (these hormones are important in maintaining bone density)
48
Q

What happens in secondary osteoporosis?

A
  • result of drug therapy (i.e., corticosteroids, these drugs prevent the action of oestrogen and androgen)
  • processes affect bone remodelling malnutrition, prolonged immobilisation, weightlessness (i.e., with space travel)
  • metabolic bone diseases (i.e., hyperparathyroidism - this increases osteoblast activity, metastatic cancers as it could lead to the individual not producing enough oestrogen and androgen hormones)
49
Q

What does osteoporosis look like? (bone affected by this)

A
  • Trabecular have got thinner, fill it up with more fat
50
Q

Mechanism of osteoporosis

A
  • oestoclasts degrading the bone, lead to an osteocytic depression
  • osteoblasts lay down oestoid
  • the osteoblasts should produce ostoid to fill the hole space in the osteocytic depression, however, in osteoporosis, the osteon isn’t fully reformed properly as the osteons do not have enough ostoid in them = leaves a hole in the bone
51
Q

Osteoporosis in the vertebrae:

A
52
Q

Osteoporosis - what can it do to body shape?

A

It can alter body shape

53
Q

How can someone modify their risks to prevent osteoporosis?

A

Insufficient calcium intake: recommended value for postmenopausal women is 700 mg/day

Exercise: immobilisation of bone (prolonged bed rest or application of a cast) leads to accelerated bone loss. Physical activity is needed to maintain bone mass. The weightlessness experienced by astronauts can result in osteoporosis due to increase resorption

Cigarette smoking: in women (data on shows women to be affected by this) - smoking is correlated with increased incidence of osteoporosi

54
Q

Anchodroplasia (what is this, what does it result in?)

A
  • Inherited mutation in the FGF3 receptor gene
  • FGF promotes collagen formation from cartilage (endochondrial ossification affected; intramembranous ossification unaffected)
  • Results in short stature, but normal sized head and torso
  • Long bones cannot lengthen properly