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BSMS204 Theme 2 Musculoskeletal > 12. Physiology of bone repair > Flashcards

12. Physiology of bone repair Flashcards

1
Q

Bone physiology basics

A

Healthy Bone Physiology is a balance
between:
Bone resorption
Bone formation

imbalance on bone resorption side leads to osteopetrosis (osteopenia, rickets)

imbalance on bone formation side -> osteoperosis

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2
Q

Classifications of bone structure

A 
• Long bone
	• Flat bone
Macroscopic:
	• Cortical bone
	• Cancellous (spongy)
		○ Spicules, trabeculae (bits and pieces)
Microscopic
	• Lamellar
		○ Osteons
	• Woven
		○ Immature
		○ Disorganised
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3
Q

Composition of bone

A 
living cells and acellular matrix
3 principle cell types:
osteoclasts
osteoblasts
osteocytes
Mostly extracellular matrix
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4
Q

Osteoblasts

A

on surface bone, produce protein component acellular matrix – regulate bone growth and degradation

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5
Q

Osteocytes

A

quiescent mature cells embedded in bone matrix.

Maintain bone.

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6
Q

Osteoclasts

A

responsible for bone degradation and remodelling

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7
Q

Organic vs inorganic components of bone

A

Organic – cells and proteins
Inorganic – minerals, eg Ca2+ & PO4- (hydroxyapatite)

bone dominated by extracellular matrix - few cells

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8
Q

Haversian system in lamellar bone

A

As opposed to woven bone

Communication system between cells immobilised in bone matrix

Osteons with Lamellae surrounding Haversian canals in centre to allow fluid movement

Osteocytes embedded in canaliculi in osteon

Ground substance between cells

Haversian system runs parallel to bone and along long axis of bone

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9
Q

Where do osteocytes come from?

A

From mesenchyme
From precursor cells in bone marrow stroma
Osteoblasts are post-mitotic
Most osteoblasts will undergo apoptosis
Number of osteoblasts decrease with age
A low % of osteoblasts will become osteocytes locked in lacuna

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10
Q

Osteoclasts

A 
Function: Resorption
Multinucleate
40-100 micrometer in diameter. 
15-20 closely packed oval-shaped nuclei.
Can proliferate

Same precursor as monocytes (haematopoietic stem)
- Phagocytose (bone matrix & crystals)
- Secrete Acids
- Secrete proteolytic enzymes from lysosomes
Ruffled border = where bone resorption occurs

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11
Q

Bone constituents

A

Extracellular matrix is 70% minerals
Plus abundant proteins and sparse cells
High compressive strength and tensile strength

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12
Q

Acellular elements of bone

A

collagen fibres – protein, flexible but strong

hydroxyapatite – mineral, provides rigidity

calcium/phosphate crystals > 50 %

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13
Q

What are glycosaminoglycans

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

Abundant in Cartilage

These are another set of organic molecules in bone ground matrix

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14
Q

Growth factors in bone ECM

A

Growth factors are suspended in matrix

They are revealed by osteoclast action

Which leads to proliferation & mineralisation

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

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15
Q

Bone cells remodel bone

A
  1. Osteoclasts resorb bone to make Howship’s lacuna, then migrates away
  2. Osteoblasts deposit bone onto pre-existing bone

osteoblasts lay down bone but also encourage osteoclasts

bone remodelling is very active

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16
Q

Bone formation

A

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

17
Q

Endochondral ossification

A

bone formation based on a cartilage model.
• Chondrocytes proliferate and secrete extracellular matrix and proteoglycans.
• Osteoblasts (derived from osteoprogenitor cells) arrive and then osteoid is laid down and mineralisation begins.
• Precise modelling of the final bone is done by osteoclasts.

18
Q

Intramembraneous ossification

A

bone formation without a cartilage model.
• Osteoblasts (derived from osteoprogenitor cells) lay down osteoid and begin mineralisation, forming tiny bony spicules.
• Nearby spicules join together into trabeculae (woven bone).

19
Q

Factors governing remodelling

A

two major factors
Recurrent mechanical stress

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

20
Q

Effect of mechanical stress on bone

A

strengthens bone

  • inhibits bone resorption
    promotes deposition
  • Surface osteoblasts & osteocyte network detect stresses
    -skeleton reflects forces acting on it

Without weight bearing
bone rapidly weakens
e.g. bed rest, or lack of gravity e.g. astronauts

21
Q

Bisphosphonates

A

For osteoporosis
E.g. Alendronate

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
22
Q

Teripatide

A

For osteoperosis
Encourages osteoblast formation of bone
portion of human parathyroid hormone (PTH)
Intermittent application activates osteoblasts more than osteoclasts

23
Q

Denosumab

A

For osteoperosis
Prevent osteoclast maturation
Monoclonal antibody targetting RANKL

24
Q

Molecular mechanism of osteopetrosis (autosomal recessive)

A 
Molecular Mechanism
Osteoclasts cannot remodel bone
due to:
- Defective Vacuolar proton pump or
- Defective Chloride channel
25
Q

Results of osteperosis

A

Excess bone growth
Bone growths at foramina press on nerves

Brittle (dense) bones
Blindness
Deafness
Severe anaemia

26
Q

Phases of fracture healing stages

A
  1. Reactive phase: haematoma and inflammation
  2. Soft callus formation
  3. Hard callus formation
  4. Remodelling

Duration: upper body 2-3 weeks, lower body > 4 weeks

27
Q

Hormones of calcium regulation

A

PTH – parathryoid hormone, parathormone

  • Parathyroid chief cells
  • Increases plasma Ca2+

Vitamin D: 1,25-di-OH cholecalciferol (calcitriol)

  • Made in stages: Skin -> Liver -> Kidney
  • Increases plasma Ca2+

Calcitonin

  • Made by thyroid C cells
  • “tones down” blood calcium
    • Calcium goes into bone
    • Used as a treatment for osteoporosis
28
Q

Vitmin D: production and activation

A

Cholecalciferol (Vitamin D3) -> 25-OH cholecalciferol -> 1, 25-di-OH cholecalciferol (calcitriol) -> increased Calbindin in gut enterocytes -> increased Intestinal absorption of Ca2+ and increased
Ca2+ reabsorption in kidneys
-> increased plasma Ca2+

29
Q

How does PTH stimulate resorption via osteoblasts?

A

PTH binds PTH-R on osteoblast, causing RANKL to bind RANK on osteoclast precursor

osteoclast precursos differentiates and fuses and forms activated osteoclast

activated osteoclast carries out bone resorption

30
Q

Vitamin D

A

Increases intestinal Ca2+ absorption
-> Increases calbindin

Stimulates kidneys to reabsorb calcium

stimulates osteoclasts indirectly

  • > via osteoblasts
  • > This is a comparatively weak effect

Vitamin D facilitates bone remodelling and thus increases serum Ca2+

31
Q

Causes of low plasma calcium

A

Loss
Pregnancy
Lactation
Kidney dysfunction

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

Parathyroid dysfunction

32
Q

Vitamin D

A

Increases intestinal Ca2+ absorption
- Increases calbindin

Stimulates kidneys to reabsorb calcium

stimulates osteoclasts indirectly

  • via osteoblasts
  • This is a comparatively weak effect

Vitamin D facilitates bone remodelling and thus increases serum Ca2+

33
Q

Results of chronic hypocalcaemia

A

Skeletal deformities

Increased tendency toward bone fractures

Impaired growth

Short stature (adults less than 5 feet tall)

Dental deformities
Rickets can be caused by chronic hypocalcaemia

34
Q

Acute hypocalcaemia

A

Leads to excitability

C – Convulsions
A – Arrhythmias
T – Tetany

Chvostek’s Sign
(Latent Tetany)
Trousseau’s Sign
Carpopedal spasm
(Latent Tetany)
DiGeorge Syndrome
35
Q

How does low plasma calcium cause 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

36
Q

Signs and symptoms of decreased excitability

A

Can be asymptomatic

Reduced excitability
Esp. Constipation
Depression + other psychiatric

Abnormal heart rhythms
Short QT interval, ST segment gone
Widened T wave

Severe hypercalcemia
Coma
Cardiac arrest

BSMS204 Theme 2 Musculoskeletal (22 decks)

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