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204: The Musculoskeletal System > Physiology of bone repair > Flashcards

Physiology of bone repair Flashcards

1
Q

Imbalance towards bone resorption

A

Osteoporosis

Osteopenia

Rickets

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2
Q

Imbalance towards to bone formation

A

Osteopetrosis

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3
Q

Classifications of bone structure

A

Long bone

Flat bone

Macroscopic

  • cortical bone
  • cancellous

Microscopic

  • lamellar
  • woven
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4
Q

Lamellar bone

A

Secondary bone created by remodelling woven bone

Organised and stress oriented

Stronger and less flexible than woven bone

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5
Q

Woven bone

A

Collagen is randomly directed and the bone is not stress oriented

More osteocytes per unit volume, higher rate of turnover, weaker and more flexible than lamellar bone

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6
Q

Cancellous bone

A

Boney struts organised into a loose network with blood/ marrow between struts

Approximately 200 micrometers in diameter

30-90% of cancellous bone is porous and contains bone marrow

Increased porosity in osteoporosis

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7
Q

Cortical bone

A

Thick bone organised in osteons

Usually associated with or connected to the outer surface of the bone

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8
Q

Composition of bone

A

Osteoclasts

Osteocytes

Osteoblasts

Extracellular matrix

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9
Q

Osteoblasts

A

Formation of new bone and release of signalling substances

Produce protein component of acellular matrix to regulate bone growth and degradation

20-25 microns, round and regular in shape, mononucleate

Located on developing bone surfaces

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10
Q

Osteocytes

A

Quiescent mature cells embedded in bone matrix

For maintenance and detection of environmental and ageing stresses

Long and thin with extensive branches

The main cell body inside the lacuna

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11
Q

Osteoclasts

A

Giant multinucleate cells responsible for bone degradation and remodelling

Located in Howship’s lacunae at sites of bone resorption

Shape is regular, cube like, often with ruffled border

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12
Q

Ground substances

A

Substance surrounding the cells

Similar to extracellular matrix

This is the hard calcium phosphate

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13
Q

Haversian canal

A

Longitudinal canal within the bone tissue

Typically run parallel to the surface and along the long axis of the bone

The canals are surrounded by lamellae and all together thay are called a Haversian system or an osteon

A Haversian canal generally contains one or two capillaries and nerve fibres

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14
Q

Canaliculi

A

Microscopic canals between the lacuanae of ossified bone

The radiating processes of the osteocytes project into these canals

Osteocytes do not entirely fill up the canaliculi

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15
Q

Osteocytes arise from osteoblasts

A

From mesenchyme
- from precursor cells in bone marrow stroma

Osteoblasts are post-mitotic

  • most osteoblasts will undergo apoptosis
  • number of osteoblasts decreases with age

A low % of osteoblasts will become osteocytes locked in lacuna

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16
Q

Mesenchyme

A

A loosely organised, mainly mesodermal embryonic tissue which develops into connective and skeletal tissues, including blood and lymph

Composed mainly of ground substance with few cells or fibres

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17
Q

Osteoclast precursor

A

Same as monocytes

Phagocytose (bone matrix and crystals)

Secrete acids

Secrete proteolytic enzymes from lysosomes

18
Q

Ruffled border

A

Specialised part of osteoclast where bone resorption occurs

19
Q

Bone constituents

A

Extracellular matrix is 70% minerals

Plus abundant proteins and sparse cells

High compressive strength and tensile strength

A cellular elements of bone

  • collagen fibres: protein, flexible but strong
  • hydroxyapatite: mineral, provides rigidity
  • calcium/ phosphate crystals
20
Q

Glycosaminoglycans

A

Long polysaccharides

Highly negative

Attract water

Repel each other

Resists compression

Abundant in cartilage

21
Q

Growth factors

A

Suspended in matrix

Revealed by osteoclast action

Leads to proliferation and mineralisation

22
Q

Bone formation

A

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

23
Q

Endochondral ossification

A

Bone formation based on cartilage model

Chondrocytes proliferate and secrete extracellular matrix and proteoglycans

Osteoblasts arrive and tehn osteoid is laid down and mineralisation begins

Precise modelling of the final bone is done by osteoclasts

24
Q

Intramembranous ossification

A

Bone formation without a cartilage model

Osteoblasts lay down osteoid and begin mineralisation, forming tiny bony spicules

Nearby spicules join together into trabeculae

25
Q

Factors governing remodelling

A

Recurrent mechanical stress

Calcium homeostasis
- plasma calcium is essential in maintaining structural integrity of skeleton

26
Q

Mechanical stress- strengthens bone

A

Inhibits bone resorption and promotes deposition

Without weight bearing bone rapidly weakens

Surface osteoblasts and osteocyte network detect stresses

Skeleton reflects forces acting on it

27
Q

Bisphosphates

A

For osteoporosis
- e.g. alendronate

Inhibit osteoclast mediated bone resorption

Related to inorganic pyrophosphate

  • the endogenous regulator of bone turnover
  • accumulate on bone and ingested by osteoclasts
28
Q

Other drugs for osteoporosis

A

Encourage osteoblast formation of bone

  • teriparatide
  • portion of human parathyroid hormone
  • intermittent application activates osteoblasts more than osteoclasts

Prevent osteoclast maturation

  • denosumab
  • monoclonal antibody that targets RANKL
29
Q

Osteoporosis molecular mechanism

A

Osteoclasts cannot remodel bone

Defective vacuolar proton pump or

Defective chloride channel

30
Q

Excess bone growth from osteoporosis

A

Bone growths at foramina press on nerves

Brittle (dense) bones

Blindness

Deafness

Severe anaemia

31
Q

Fracture healing: reactive phase: haematoma and inflammation

A

Blood cells enter wound

Haematoma forms

Inflammatory cells invade

Granulation tissue formed

Aggregation of blood vessels

Fibroblasts

Bone precursor cells arrive from periosteum

32
Q

Phase of fracture healing: soft callus formation

A

Woven bone (or hyaline cartilage) join the pieces

Woven bone near BVs

Fibrocartilage further away

33
Q

Phase of fracture healing: hard callus formation

A

Lamellar bone replaces woven bone

34
Q

Phase of fracture healing: remodelling

A

Trabecular bone replaces lamellar bone

Original bone shape

Compact bone formed where appropriate

35
Q

Hormones of calcium regulation

A

PTH

  • parathyroid chief cells
  • increases plasma Ca2+

Vitamin D: 1,25-di-OH cholecalciferol

  • made in stages: skin -> liver -> kidney
  • increases plasma Ca2+

Calcitonin

  • made by thyroid C cells
  • tones down blood calcium
  • calcium goes into bone
36
Q

Vitamin D: production and activation

A 
Skin: cholecalciferol (Vit D3)
->
25-OH cholecalciferol
-> (kidney)
1,25-di-OH cholecalciferol 
->
Increase calbindin in gut enterocytes
->
Increase in intestinal absorption of Ca2+
-> 
Increase Ca2+ reabsorption in kidneys 
->
Plasma Ca2+
37
Q

Effects of vitamin D

A

Increases intestinal Ca2+ absorption
- increases calbindin

Stimulates kidneys to reabsorb calcium

Stimulates osteoclasts indirectly

  • via osteoblasts
  • comparatively weak effect

Vitamin D facilitates bone remodelling and thus increases serum Ca2+

38
Q

Causes of low plasma calcium

A

Loss

  • pregnancy
  • lactation
  • kidney dysfunction

Low intake

  • insufficient ingestion of calcium
  • rickets (low vit D)

Parathyroid dysfunction (surgery)

39
Q

Chronic hypocalcaemia results in

A

Skeletal deformities

Increased tendency toward bone fractures

Impaired growth

Short stature (adults less than 5 feet tall)

Dental deformities

40
Q

Acute hypocalcaemia leads to

A 
Bleeding
Anaesthesia
Dysphagia 
Convulsions
Arrhythmias
Tetany 
Spasms and stridor
41
Q

Low plasma calcium

A

Leads to excitability

Effects seem paradoxical

Makes membrane more excitable and less stable

42
Q

Hypercalcaemia signs and symptoms

A

Can be asymptomatic

Reduced excitability

  • constipation
  • depression and other psychiatric

Abnormal heart rhythms

  • short QT interval, ST segment gone
  • widened T wave

Severe hypercalcaemia

  • coma
  • cardiac arrest

204: The Musculoskeletal System (23 decks)

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