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Year 2 Medicine > Physiology of Bone Formation and Repair > Flashcards

Physiology of Bone Formation and Repair Flashcards

1
Q
  • Healthy bone physiology is a balance between bone formation and bone resorption
    • More formation than resorption - …
    • More resorption than formation - …, osteopenia, rickets
A
  • Healthy bone physiology is a balance between bone formation and bone resorption
    • More formation than resorption - osteopetrosis
    • More resorption than formation - osteoporosis, osteopenia, rickets
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2
Q

More bone resorption than bone formation can lead to … (3)

A

Osteoporosis, osteopenia and rickets

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3
Q

More bone formation than bone resorption can lead to … (1)

A

osteopetrosis

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4
Q

Classifications of bone structure

  • Broadly:
    • Long bone
    • Flat bone
  • … level:
    • Cortical bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • … level:
    • Lamellar - Osteons
    • Woven - Immature, Disorganised
A
  • Broadly:
    • Long bone
    • Flat bone
  • Macroscopic level:
    • Cortical bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • Lamellar - Osteons
    • Woven - Immature, Disorganised
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5
Q

Classifications of bone structure

  • Broadly:
    • Long bone
    • Flat bone
  • Macroscopic level:
    • … bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • … - Osteons
    • Woven - Immature, Disorganised
A
  • Broadly:
    • Long bone
    • Flat bone
  • Macroscopic level:
    • Cortical bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • Lamellar - Osteons
    • Woven - Immature, Disorganised
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6
Q

Classifications of bone structure

  • Broadly:
    • Long bone
    • Flat bone
  • Macroscopic level:
    • Cortical bone
    • … (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • Lamellar - Osteons
    • … - Immature, Disorganised
A
  • Broadly:
    • Long bone
    • Flat bone
  • Macroscopic level:
    • Cortical bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • Lamellar - Osteons
    • Woven - Immature, Disorganised
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7
Q

Classifications of bone structure

  • Broadly:
    • … bone
    • Flat bone
  • Macroscopic level:
    • Cortical bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • Lamellar - …
    • Woven - Immature, Disorganised
A
  • Broadly:
    • Long bone
    • Flat bone
  • Macroscopic level:
    • Cortical bone
    • Cancellous (spongy) - Spicules, Trabeculae
  • Microscopic level:
    • Lamellar - Osteons
    • Woven - Immature, Disorganised
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8
Q

Composition of Bone

  • Living cells and … matrix
  • 3 principle cell types:
    • Osteo…
    • Osteo…
    • Osteoblasts
A
  • Living cells and acellular matrix
  • 3 principle cell types:
    • Osteoclasts
    • Osteocytes
    • Osteoblasts
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9
Q

Composition of Bone

  • Living cells and acellular …
  • 3 principle cell types:
    • Osteoclasts
    • Osteocytes
    • Osteo…
A
  • Living cells and acellular matrix
  • 3 principle cell types:
    • Osteoclasts
    • Osteocytes
    • Osteoblasts
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10
Q

Most of the bone and most of it’s structure is made up of … matrix

A

Most of the bone and most of it’s structure is made up of extracellular matrix

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11
Q

Osteoblasts

  • On the … of bone
  • Produce … component - acellular matrix
  • Regulate bone growth and degradation
A
  • On the surface of bone
  • Produce protein component - acellular matrix
  • Regulate bone growth and degradation
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12
Q

Osteoblasts

  • On the surface of bone
  • Produce protein component - acellular matrix
  • Regulate bone … and …
A
  • On the surface of bone
  • Produce protein component - acellular matrix
  • Regulate bone growth and degradation
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13
Q

… regulate bone growth and degradation

A

Osteoblasts regulate bone growth and degradation

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14
Q

Osteocytes

  • … mature cells embedded in bone matrix
  • They maintain bone
A
  • Quiescent mature cells embedded in bone matrix
  • They maintain bone
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15
Q

Osteocytes

  • Quiescent mature cells embedded in bone …
  • They maintain bone
A
  • Quiescent mature cells embedded in bone matrix
  • They maintain bone
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16
Q

What cells maintain the bone?

A

Osteocytes

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17
Q

Osteoclasts

  • They are responsible for bone … and …
A
  • They are responsible for bone degradation and remodelling
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18
Q

… are responsible for bone degradation and remodelling

A

Osteoclasts are responsible for bone degradation and remodelling

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19
Q

Organic v Inorganic materials - Bone

  • … - cells and proteins
  • … - minerals, eg. Ca2+ & PO4- (hydroxyapatite)
A
  • Organic - cells and proteins
  • Inorganic - minerals, eg. Ca2+ & PO4- (hydroxyapatite)
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20
Q

Inorganic materials of bone are …

A

minerals e.g calcium ions and phosphate ions - often formed with other ions in a structure called hydroxyapatite

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21
Q

Hydroxyapatite is present in … and teeth

A

Hydroxyapatite is present in bone and teet

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22
Q

Bone is dominated by …

A

extracellular matrix - few cells

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23
Q

Define quiescent

A

inactivity or dormancy.

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24
Q

Classification of bone structure - this is a macroscopic view of bone structure - What is seen?

A

Cancellous (spongy) bone that have spicules and trabeculae (usually internal part of bone)

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25
Q

Classification of bone structure - this is a microscopic view of bone structure - What is seen?

A
  • Woven bone - immature and disorganised
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26
Q

Composition of Bone - Principle cell types

  • Label the diagram
A
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27
Q

Composition of Bone - Principle cell types

  • Label the diagram
A
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28
Q

Haversian System in Lamellar Bone

  • One type of … organisation of bone tissue (osteon) - the other is woven bone
  • … system between cells immobilised in bone matrix
A
  • One type of microscopic organisation of bone tissue (osteon) - the other is woven bone
  • Communication system between cells immobilised in bone matrix
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29
Q

Haversian System in Lamellar Bone

  • One type of microscopic organisation of bone tissue (osteon) - the other is … bone
  • Communication system between cells immobilised in bone matrix
A
  • One type of microscopic organisation of bone tissue (osteon) - the other is woven bone
  • Communication system between cells immobilised in bone matrix
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30
Q

This is an image of the microscopic structure of organised … bone - as opposed to woven bone

A

This is an image of the microscopic structure of organised lamellar bone - as opposed to woven bone (haversian system in lamellar bone)

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31
Q

This is an image of the microscopic structure of organised lamellar bone - as opposed to … bone

A

This is an image of the microscopic structure of organised lamellar bone - as opposed to woven bone (this is a picture of haversian system in lamellar bone)

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32
Q

Osteocytes arise from …

A

osteoblasts

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33
Q

Osteocytes arise from Osteoblasts

  • From mesenchyme
    • From precursor cells in bone marrow stroma
  • Osteoblasts are post-…
    • Most osteoblasts will undergo apoptosis
    • Number of osteoblasts … with age
  • A low % of osteoblasts will become osteocytes locked in lacuna
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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34
Q

Osteocytes arise from Osteoblasts

  • From mesenchyme
    • From precursor cells in bone marrow stroma
  • Osteoblasts are post-mitotic
    • Most osteoblasts will undergo …
    • Number of osteoblasts decrease with age
  • A low % of osteoblasts will become osteocytes locked in …
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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35
Q

Osteoblasts come from …

A

mesenchyme (from precursor cells in bone marrow stroma)

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36
Q

Osteoblasts are post-…

A

mitotic

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37
Q

A low % of osteoblasts will become … locked in lacuna

A

A low % of osteoblasts will become osteocytes locked in lacuna

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38
Q

… = a loosely organized, mainly mesodermal embryonic tissue which develops into connective and skeletal tissues, including blood and lymph. It is composed mainly of ground substance with relatively few cells or fibers.

A

Mesenchyme = a loosely organized, mainly mesodermal embryonic tissue which develops into connective and skeletal tissues, including blood and lymph. It is composed mainly of ground substance with relatively few cells or fibers.

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39
Q

… substance = substance surrounding the cells. Similar to extracellular matrix. In bone this is the hard calcium phosphate.

A

Ground substance = substance surrounding the cells. Similar to extracellular matrix. In bone this is the hard calcium phosphate.

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40
Q

… bone is strong mature bone. The collagen and cells are organised in cylindrical layers – as opposed to … bone that has disorganised collagen. … bone is structurally stronger than … bone.

A

Lamellar bone is strong mature bone. The collagen and cells are organised in cylindrical layers – as opposed to woven bone that has disorganised collagen. Lamellar bone is structurally stronger than woven bone.

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41
Q

Osteoclasts

  • Function: Resorption
  • …nucleate
    • 40-100 micrometer in diameter.
    • 15-20 closely packed oval-shaped nuclei.
    • Can …
  • Same precursor as … (haematopoietic stem)
    • Phagocytose (bone matrix & crystals)
    • Secrete Acids
    • Secrete proteolytic enzymes from lysosomes
  • Ruffled border = where bone resorption occurs
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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42
Q

Osteoclasts

  • Function: …
  • Multinucleate
    • 40-100 micrometer in diameter.
    • 15-20 closely packed oval-shaped nuclei.
    • Can proliferate
  • Same precursor as monocytes (… stem)
    • Phagocytose (bone matrix & crystals)
    • Secrete Acids
    • Secrete proteolytic enzymes from lysosomes
  • Ruffled border = where bone … occurs
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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43
Q

Osteoclasts phagocytose (bone matrix and crystals) - how?

A

secrete acids and secreting proteolytic enzymes from lysosomes

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44
Q

What do osteoclasts secrete?

A
  • Secrete Acids
  • Secrete proteolytic enzymes from lysosomes
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45
Q

Osteoclasts have a … border

A

Osteoclasts have a ruffled border

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46
Q

Osteoclasts have a ruffled border - this is where bone … occurs

A

Osteoclasts have a ruffled border - this is where bone resorption occurs

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47
Q

Bone constituents

  • Bone is unique
    • Extracellular matrix is …% minerals
    • Plus abundant proteins and sparse cells
    • High compressive strength and … strength
  • Acellular elements of bone - similar to reinforced concrete*
    • … fibres - protein, flexible but strong (*‘the steel bars/rods’)
    • Hydroxyapatite - mineral, provides rigidity
    • Calcium/phosphate crystals >50% (*‘the cement’)
A
  • Bone is unique
    • Extracellular matrix is 70% minerals
    • Plus abundant proteins and sparse cells
    • High compressive strength and tensile strength
  • Acellular elements of bone - similar to reinforced concrete*
    • Collagen fibres - protein, flexible but strong (*‘the steel bars/rods’)
    • Hydroxyapatite - mineral, provides rigidity
    • Calcium/phosphate crystals >50% (*‘the cement’)
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48
Q

Bone constituents

  • Bone is unique
    • Extracellular matrix is 70% minerals
    • Plus abundant proteins and sparse cells
    • High … strength and tensile strength
  • Acellular elements of bone - similar to reinforced concrete*
    • Collagen fibres - protein, … but strong (*‘the steel bars/rods’)
    • Hydroxyapatite - mineral, provides …
    • Calcium/phosphate … >50% (*‘the cement’)
A
  • Bone is unique
    • Extracellular matrix is 70% minerals
    • Plus abundant proteins and sparse cells
    • High compressive strength and tensile strength
  • Acellular elements of bone - similar to reinforced concrete*
    • Collagen fibres - protein, flexible but strong (*‘the steel bars/rods’)
    • Hydroxyapatite - mineral, provides rigidity
    • Calcium/phosphate crystals >50% (*‘the cement’)
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49
Q

Extracellular matrix (bone) is …% minerals

A

Extracellular matrix (bone) is 70% minerals

50
Q

Acellular elements of bone

  • … fibres – protein, flexible but strong
  • … – mineral, provides rigidity
  • calcium/phosphate … > 50 %
A
  • collagen fibres – protein, flexible but strong
  • hydroxyapatite – mineral, provides rigidity
  • calcium/phosphate crystals > 50 %
51
Q

extracellular matrix includes …

A

extracellular matrix includes glycosaminoglycans

52
Q

Glycosaminoglycans

  • Glycosaminoglycans (GAG) make up a much smaller fraction of the Extracellular matrix, compared to …
  • Long …
  • Highly …
  • Attract water
  • … each other
  • Resists compression
  • Abundant in cartilage
    • These are another set of organic molecules in bone ground matrix
A
  • Glycosaminoglycans (GAG) make up a much smaller fraction of the Extracellular matrix, compared to collagen.
  • 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
53
Q

Glycosaminoglycans

  • Glycosaminoglycans (GAG) make up a much smaller fraction of the Extracellular matrix, compared to collagen.
  • Long polysaccharides
  • Highly negative
  • Attract …
  • Repel each other
  • Resists …
  • Abundant in …
    • These are another set of organic molecules in bone ground matrix
A
  • Glycosaminoglycans (GAG) make up a much smaller fraction of the Extracellular matrix, compared to collagen.
  • 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
54
Q

… (GAG) make up a much smaller fraction of the Extracellular matrix, compared to collagen.

A

Glycosaminoglycans (GAG) make up a much smaller fraction of the Extracellular matrix, compared to collagen.

55
Q

Growth factors - also in extracellular matrix (bone)

  • Growth factors are … in matrix
  • They are revealed by … action
  • Which leads to proliferation and mineralisation
  • Bone remodelling = bone turnover = the activation-resorption-formation sequence
    • These are another set of organic molecules in bone ground matrix
A
  • Growth factors are suspended in matrix
  • They are revealed by osteoclast action
  • Which leads to proliferation and mineralisation
  • Bone remodelling = bone turnover = the activation-resorption-formation sequence
    • These are another set of organic molecules in bone ground matrix
56
Q

Growth factors - also in extracellular matrix (bone)

  • Growth factors are suspended in matrix
  • They are revealed by osteoclast action
  • Which leads to … and mineralisation
  • Bone … = bone turnover = the activation-resorption-formation sequence
    • These are another set of organic molecules in bone ground matrix
A
  • Growth factors are suspended in matrix
  • They are revealed by osteoclast action
  • Which leads to proliferation and mineralisation
  • Bone remodelling = bone turnover = the activation-resorption-formation sequence
    • These are another set of organic molecules in bone ground matrix
57
Q

Bone Cells remodel bone

  • Osteoclasts … bone - In Howship’s Lacuna
  • Osteoblasts … bone - onto pre-existing bone
    • Lays down bone in different directions
  • Bone remodelling is very active
A
  • Osteoclasts resorb bone - In Howship’s Lacuna
  • Osteoblasts deposit bone - onto pre-existing bone
    • Lays down bone in different directions
  • Bone remodelling is very active
58
Q

Bone Cells remodel bone

  • Osteoclasts resorb bone - In … Lacuna
  • Osteoblasts deposit bone - onto pre-existing bone
    • Lays down bone in different …
  • Bone remodelling is very …
A
  • Osteoclasts resorb bone - In Howship’s Lacuna
  • Osteoblasts deposit bone - onto pre-existing bone
    • Lays down bone in different directions
  • Bone remodelling is very active
59
Q

Activation Resorption Remineralisation sequence

  • Surface … control activation-resorption-mineralisation, because they detect the mechanical factors (stresses on that bone) and hormonal factors (from elsewhere in the body) that initially trigger bone remodelling.
A
  • Surface osteoblasts control activation-resorption-mineralisation, because they detect the mechanical factors (stresses on that bone) and hormonal factors (from elsewhere in the body) that initially trigger bone remodelling.
60
Q

Bone forms either as … or cancellous and by either … or endochondral bone formation

A

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

61
Q

Bone forms either as compact or …s and by either intramembranous or … bone formation

A

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

62
Q

… ossification = 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.

A

Endochondral ossification = 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.

63
Q

… ossification = 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).

A

Intramembranous ossification = 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).

64
Q

Factors governing remodelling (Bone)

  • Two major factors
    • Recurrent mechanical …
    • Calcium …
      • Plasma calcium is essential in maintaining structural integrity of skeleton
A
  • Two major factors
    • Recurrent mechanical stress
    • Calcium homeostasis
      • Plasma calcium is essential in maintaining structural integrity of skeleton
65
Q

Factors governing remodelling (Bone)

  • Two major factors
    • Recurrent mechanical stress
    • … homeostasis
      • Plasma … is essential in maintaining …. integrity of skeleton
A
  • Two major factors
    • Recurrent mechanical stress
    • Calcium homeostasis
      • Plasma calcium is essential in maintaining structural integrity of skeleton
66
Q

Mechanical stress — strengthens bone

  • … bone resorption and … deposition
  • Without weight bearing bone rapidly … (e.g. bed rest, lack of gravity (Astronauts))
  • Surface osteoblasts and osteocyte network detect stressors
  • Skeleton reflects forces acting on it
A
  • Inhibits bone resorption and promotes deposition
  • Without weight bearing bone rapidly weakens (e.g. bed rest, lack of gravity (Astronauts))
  • Surface osteoblasts and osteocyte network detect stressors
  • Skeleton reflects forces acting on it
67
Q

Mechanical stress — strengthens bone

  • Inhibits bone resorption and promotes deposition
  • Without … bearing bone rapidly weakens (e.g. bed rest, lack of gravity (Astronauts))
  • Surface … and … network detect stressors
  • Skeleton reflects forces acting on it
A
  • Inhibits bone resorption and promotes deposition
  • Without weight bearing bone rapidly weakens (e.g. bed rest, lack of gravity (Astronauts))
  • Surface osteoblasts and osteocyte network detect stressors
  • Skeleton reflects forces acting on it
68
Q

Bisphosphonates

  • For … - E.g. Alendronate
  • Inhibit osteoclast-mediated bone-…
  • Related to inorganic pyrophosphate
    • The endogenous regulator of bone turnover
    • Accumulate on bone & ingested by osteoclasts
      • Interfere with osteoclasts …
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
69
Q

Bisphosphonates

  • For osteoporosis - E.g. …
  • Inhibit …-mediated bone-resorption
  • Related to inorganic pyrophosphate
    • The endogenous regulator of bone turnover
    • Accumulate on bone & ingested by …
      • Interfere with osteoclasts metabolism
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
70
Q

Bisphosphonates inhibit what?

A

osteoclast-mediated bone-resorption

71
Q

Other Drugs for Osteoporosis: mechanisms

  • … osteoblast formation of bone
    • Teriparatide
    • Portion of human … hormone (PTH)
    • … application activates osteoblasts more than osteoclasts
  • … osteoclast maturation
    • Denosumab
    • Monoclonal Antibody that targets RANKL
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
72
Q

Other Drugs for Osteoporosis: mechanisms

  • Encourage osteoblast formation of bone
    • T…
    • Portion of human parathyroid hormone (PTH)
    • Intermittent application activates osteoblasts more than osteoclasts
  • Prevent osteoclast maturation
    • D…
    • … Antibody that targets RANKL
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
73
Q

What is teriparatide used for? and what does it do?

A

osteoporosis - encourages osteoblast formation of bone

74
Q

What is denosumab used for? and what does it do?

A

Osteoporosis - prevent osteoclast maturation

75
Q

… = a recombinant form of parathyroid hormone. It is an effective anabolic (i.e., bone growing) agent used in the treatment of some forms of osteoporosis

A

Teriparatide = a recombinant form of parathyroid hormone. It is an effective anabolic (i.e., bone growing) agent used in the treatment of some forms of osteoporosis

76
Q

… is a fully human monoclonal antibody for the treatment of osteoporosis. It may also be used for treatment induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma and giant cell tumor of bone. It targets RANKL, thus inhibiting it.

A

Denosumab is a fully human monoclonal antibody for the treatment of osteoporosis. It may also be used for treatment induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma and giant cell tumor of bone. It targets RANKL, thus inhibiting it.

77
Q

Osteopetrosis (Autosomal Recessive)

  • Molecular Mechanism
    • Osteoclasts cannot … bone
      • Defective Vacuolar proton pump or
      • Defective … channel
    • Results in excess bone growth - bone growths at foramina press on …
    • Clinical presentation: Brittle (Dense) bones, blindness, deafness, severe anaemia
A
  • Molecular Mechanism
    • Osteoclasts cannot remodel bone
      • Defective Vacuolar proton pump or
      • Defective Chloride channel
    • Excess bone growth - bone growths at foramina press on nerves
    • Clinical presentation: Brittle (Dense) bones, blindness, deafness, severe anaemia
78
Q

Osteopetrosis (Autosomal Recessive)

  • Molecular Mechanism
    • … cannot remodel bone
      • Defective Vacuolar proton pump or
      • Defective Chloride channel
    • Results in excess bone growth - bone growths at foramina press on nerves
    • Clinical presentation: … (Dense) bones, blindness, …, severe anaemia
A
  • Molecular Mechanism
    • Osteoclasts cannot remodel bone
      • Defective Vacuolar proton pump or
      • Defective Chloride channel
    • Excess bone growth - bone growths at foramina press on nerves
    • Clinical presentation: Brittle (Dense) bones, blindness, deafness, severe anaemia
79
Q

What are the symptoms/signs of osteopetrosis?

A

brittle (dense) bones, blindness, deafness and severe anaemia

80
Q

Brittle (dense) bones, blindness, deafness and severe anaemia are all signs of what bone disease?

A

Osteopetrosis

81
Q

Phases of Fracture Healing: Stages 1 & 2 (out of 4)

  • Reactive Phase: Haematoma & Inflammation
  • Soft … formation
A
  • Reactive Phase: Haematoma & Inflammation
  • Soft Callus formation
82
Q

Phases of Fracture Healing: Stages 1 & 2 (out of 4)

  • Reactive Phase: … & …
  • Soft callus formation
A
  • Reactive Phase: Haematoma & Inflammation
  • Soft Callus formation
83
Q

Phases of Fracture Healing: Stages 3 & 4 (out of 4)

  • … Callus Formation
  • Remodeling
A
  • Hard Callus Formation
  • Remodeling
84
Q

Phases of Fracture Healing: Stages 3 & 4 (out of 4)

  • Hard Callus Formation
  • …
A
  • Hard Callus Formation
  • Remodeling
85
Q

Phases of Fracture Healing: All 4 stages

  • State the 4 phases
A
  • Reactive Phase: Haematoma & Inflammation
  • Soft Callus formation
  • Hard Callus Formation
  • Remodeling
86
Q

Phases of Fracture Healing: All 4 stages

  • … Phase: Haematoma & Inflammation
  • … Callus formation
  • … Callus Formation
  • Remodeling
A
  • Reactive Phase: Haematoma & Inflammation
  • Soft Callus formation
  • Hard Callus Formation
  • Remodeling
87
Q

This shows the … healing process

A

This shows the fracture healing process

88
Q

Hormones of calcium regulation

  • PTH – parathryoid hormone, parathormone
    • Parathyroid … cells
    • … plasma Ca2+
  • Vitamin D: 1,25-di-OH cholecalciferol (calcitriol)
    • Made in stages: Skin à Liver à Kidney
    • … plasma Ca2+
  • Calcitonin
    • Made by thyroid C cells
    • “tones …” blood calcium
      • Calcium goes into bone
      • Used as a treatment for …
A
  • PTH – parathryoid hormone, parathormone
    • Parathyroid chief cells
    • Increases plasma Ca2+
  • Vitamin D: 1,25-di-OH cholecalciferol (calcitriol)
    • Made in stages: Skin à Liver à Kidney
    • Increases plasma Ca2+
  • Calcitonin
    • Made by thyroid C cells
    • “tones down” blood calcium
      • Calcium goes into bone
      • Used as a treatment for osteoporosis
89
Q

Hormones of calcium regulation

  • PTH – … hormone, parathormone
    • Parathyroid chief cells
    • Increases plasma Ca2+
  • Vitamin …: 1,25-di-OH cholecalciferol (calcitriol)
    • Made in stages: Skin -> Liver -> Kidney
    • Increases plasma Ca2+
  • …
    • Made by thyroid C cells
    • “tones down” blood calcium
      • Calcium goes into bone
      • Used as a treatment for osteoporosis
A
  • PTH – parathryoid hormone, parathormone
    • Parathyroid chief cells
    • Increases plasma Ca2+
  • Vitamin D: 1,25-di-OH cholecalciferol (calcitriol)
    • Made in stages: Skin à Liver à Kidney
    • Increases plasma Ca2+
  • Calcitonin
    • Made by thyroid C cells
    • “tones down” blood calcium
      • Calcium goes into bone
      • Used as a treatment for osteoporosis
90
Q

Hormones of calcium regulation

  • What are the 3 hormones?
A
  • PTH – parathryoid hormone, parathormone
    • Parathyroid chief cells
    • Increases plasma Ca2+
  • Vitamin D: 1,25-di-OH cholecalciferol (calcitriol)
    • Made in stages: Skin à Liver à Kidney
    • Increases plasma Ca2+
  • Calcitonin
    • Made by thyroid C cells
    • “tones down” blood calcium
      • Calcium goes into bone
      • Used as a treatment for osteoporosis
91
Q

PTH – parathryoid hormone, parathormone, Vitamin D: 1,25-di-OH cholecalciferol (calcitriol) amd Calcitonin are all hormones of…

A

calcium regulation

92
Q
A
93
Q

Vitamin D: 1,…-di-OH … (calcitriol)

A

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

94
Q

Overview: Requirements for Healthy Bone Growth

  • Diet
    • Calcium
    • Calories
  • Vitamin …
    • Diet
    • … (makes precursor of Vitamin ..)
  • Hormones: Gonadal & bone
    • … in male, … in Females
  • Exercise & bone loading
  • Genetics
    • 60-70% of peak bone mass is determined genetically
A
  • Diet
    • Calcium
    • Calories
  • Vitamin D
    • Diet
    • Sun (makes precursor of Vitamin D)
  • Hormones: Gonadal & bone
    • Testosterone in male, Oestrogen in Females
  • Exercise & bone loading
  • Genetics
    • 60-70% of peak bone mass is determined genetically
95
Q

Overview: Requirements for Healthy Bone Growth

  • Diet
    • C…
    • C…
  • Vitamin D
    • Diet
    • Sun (makes precursor of Vitamin D)
  • Hormones: Gonadal & bone
    • Testosterone in male, Oestrogen in Females
  • … & bone loading
  • Genetics
    • 60-70% of peak bone mass is determined genetically
A
  • Diet
    • Calcium
    • Calories
  • Vitamin D
    • Diet
    • Sun (makes precursor of Vitamin D)
  • Hormones: Gonadal & bone
    • Testosterone in male, Oestrogen in Females
  • Exercise & bone loading
  • Genetics
    • 60-70% of peak bone mass is determined genetically
96
Q

…-…% of peak bone mass is determined genetically

A

60-70% of peak bone mass is determined genetically

97
Q

How PTH stimulates resorption via osteoblasts

  • PTH finds receptor on … - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on … precursor
  • … precursor then differentiates and fuses
  • Becomes activated …
  • Bone resorption can now happen
  • OBG is a decoy receptor which binds RANKL - therefore regulates the process
A
  • PTH finds receptor on osteoblast - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on osteoclast precursor
  • Osteoclast precursor then differentiates and fuses
  • Becomes activated osteoclast
  • Bone resorption can now happen
  • OBG is a decoy receptor which binds RANKL - therefore regulates the process
98
Q

How PTH stimulates resorption via osteoblasts

  • PTH finds receptor on osteoblast - recognises PTH - … signals stuck out
  • Recognised by … receptor on osteoclast precursor
  • Osteoclast precursor then differentiates and fuses
  • Becomes activated osteoclast
  • Bone resorption can now happen
  • OBG is a decoy receptor which binds … - therefore regulates the process
A
  • PTH finds receptor on osteoblast - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on osteoclast precursor
  • Osteoclast precursor then differentiates and fuses
  • Becomes activated osteoclast
  • Bone resorption can now happen
  • OBG is a decoy receptor which binds RANKL - therefore regulates the process
99
Q

How PTH stimulates resorption via osteoblasts

  • PTH finds receptor on osteoblast - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on osteoclast precursor
  • Osteoclast precursor then … and fuses
  • Becomes … osteoclast
  • Bone … can now happen
  • OBG is a decoy receptor which binds RANKL - therefore regulates the process
A
  • PTH finds receptor on osteoblast - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on osteoclast precursor
  • Osteoclast precursor then differentiates and fuses
  • Becomes activated osteoclast
  • Bone resorption can now happen
  • OBG is a decoy receptor which binds RANKL - therefore regulates the process
100
Q

How PTH stimulates resorption via osteoblasts

  • PTH finds receptor on osteoblast - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on osteoclast precursor
  • Osteoclast precursor then differentiates and fuses
  • Becomes activated osteoclast
  • Bone resorption can now happen
  • … is a decoy receptor which binds RANKL - therefore regulates the process
A
  • PTH finds receptor on osteoblast - recognises PTH - RANKL signals stuck out
  • Recognised by RANK receptor on osteoclast precursor
  • Osteoclast precursor then differentiates and fuses
  • Becomes activated osteoclast
  • Bone resorption can now happen
  • OBG is a decoy receptor which binds RANKL - therefore regulates the process
101
Q

OBG is a decoy receptor which binds … - therefore regulates the process of bone resorption

A

OBG is a decoy receptor which binds RANKL - therefore regulates the process of bone resorption

102
Q

Vitamin D: production & activation

  • Vitamin D initially made often in skin - cholecalciferon (V D3)
  • … changes it to 25-OH cholecalciferol
  • …. changes that to 1,25-di-OH cholecalciferon (Calcitriol)
  • Increased calbindin in gut enterocytes
  • Increased intestinal absorption of calcium ions
  • Calcium ion reabsorption in kidneys
  • Increased plasma calcium ions
A
  • Vitamin D initially made often in skin - cholecalciferon (V D3)
  • Liver changes it to 25-OH cholecalciferol
  • Kidney changes that to 1,25-di-OH cholecalciferon (Calcitriol)
  • Increased calbindin in gut enterocytes
  • Increased intestinal absorption of calcium ions
  • Calcium ion reabsorption in kidneys
  • Increased plasma calcium ions
103
Q

Draw a negative feedback loop showing how transiently low plasma calcium triggered by lactation can be corrected physiologically by the action of PTH

A
104
Q

Vitamin D: production & activation

  • Vitamin D initially made often in skin - cholecalciferon (V D3)
  • Liver changes it to 25-OH cholecalciferol
  • Kidney changes that to 1,25-di-OH cholecalciferon (…)
  • Increased calbindin in gut enterocytes
  • Increased intestinal absorption of calcium ions
  • Calcium ion reabsorption in kidneys
  • Increased … calcium ions
A
  • Vitamin D initially made often in skin - cholecalciferon (V D3)
  • Liver changes it to 25-OH cholecalciferol
  • Kidney changes that to 1,25-di-OH cholecalciferon (Calcitriol)
  • Increased calbindin in gut enterocytes
  • Increased intestinal absorption of calcium ions
  • Calcium ion reabsorption in kidneys
  • Increased plasma calcium ions
105
Q

Vitamin D

  • Increases intestinal Ca2+ …
    • Increases calbindin
  • Stimulates kidneys to … calcium
  • Stimulates osteoclasts indirectly
    • via osteoblasts
    • This is a comparatively … effect
  • Vitamin D facilitates bone remodelling and thus increases serum Ca2+
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+
106
Q

Vitamin D

  • Increases intestinal Ca2+ absorption
    • Increases …
  • Stimulates kidneys to reabsorb calcium
  • Stimulates osteoclasts indirectly
    • via osteoblasts
    • This is a comparatively weak effect
  • Vitamin D facilitates bone … and thus increases … Ca2+
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+
107
Q

Causes of Low Plasma Calcium

  • …
    • Pregnancy
    • Lactation
    • Kidney dysfunction
  • Low …
    • Insufficient ingestion of Calcium
    • Rickets (low vit D)
  • … dysfunction (is most typically caused by surgical misadventure)
A
  • Loss
    • Pregnancy
    • Lactation
    • Kidney dysfunction
  • Low Intake
    • Insufficient ingestion of Calcium
    • Rickets (low vit D)
  • Parathyroid dysfunction (is most typically caused by surgical misadventure)
108
Q

Causes of Low Plasma Calcium

  • Loss
    • P…
    • L…
    • Kidney dysfunction
  • Low Intake
    • Insufficient … of Calcium
    • R… (low vit D)
  • Parathyroid dysfunction (is most typically caused by surgical misadventure)
A
  • Loss
    • Pregnancy
    • Lactation
    • Kidney dysfunction
  • Low Intake
    • Insufficient ingestion of Calcium
    • Rickets (low vit D)
  • Parathyroid dysfunction (is most typically caused by surgical misadventure)
109
Q

Chronic Hypocalcaemia Results in: (5)

A
  • Skeletal deformities
  • Increased tendency toward bone fractures
  • Impaired growth
  • Short stature (adults less than 5 feet tall)
  • Dental deformities
110
Q

Skeletal deformities, Increased tendency toward bone fractures, Impaired growth, Short stature (adults less than 5 feet tall), Dental deformities are all as a result of …

A

chronic hypocalcaemia - rickets

111
Q

Acute Hypocalcaemia -> Excitability

  • BADCATS mnemonic (CAT is associated with neuromuscular excitability)
A
  • Mnemonic
    • B – Bleeding
    • A – Anaesthesia
    • D – Dysphagia
    • C – Convulsions
    • A – Arrhythmias
    • T – Tetany
    • S – Spasms and stridor
112
Q
  • C – Convulsions
  • A – Arrhythmias
  • T – Tetany
    • All associated with neuromuscular …
A

excitability (Acute hypocalcaemia)

113
Q

… sign is the twitching of the facial muscles in response to tapping over the area of the facial nerve. (result of …)

A

Chvostek’s sign is the twitching of the facial muscles in response to tapping over the area of the facial nerve. (result of hypocalcaemia)

114
Q

Trousseau’s sign for latent tetany is most commonly positive in the setting of acute ..

A

Trousseau’s sign for latent tetany is most commonly positive in the setting of acute hypocalcemia

115
Q

… sign for latent tetany is most commonly positive in the setting of acute hypocalcemia

A

Trousseau’s sign for latent tetany is most commonly positive in the setting of acute hypocalcemia

116
Q

Low Plasma Calcium -> excitability - how?

  • Effect seems paradoxical
    • i.e. counter-intuitive
  • Hypocalcaemia makes membranes “more excitable” and “less …”
    • … is more able to leak through it
    • Explains latent … and its signs
  • Hypercalcaemia paradoxically … excitability
    • By making membranes more …
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
117
Q

Why does low plasma calcium lead 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)
118
Q

The reason acute hypocalcaemia leads to … excitability is because the less stable membranes allow increased Na+ entry into cells, and thus the threshold for action potentials is lowered.

A

The reason acute hypocalcaemia leads to more excitability is because the less stable membranes allow increased Na+ entry into cells, and thus the threshold for action potentials is lowered.

119
Q

Hypercalcaemia Signs & Symptoms: Decreased Excitability

  • Can be …
  • Reduced excitability
    • Esp. …
    • Depression + other psychiatric
  • Abnormal heart rhythms (Short QT interval, ST segment gone, Widened T wave)
  • Severe hypercalcemia
    • Coma
    • … arrest
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
120
Q

Hypercalcaemia Signs & Symptoms: Decreased Excitability

  • Can be asymptomatic
  • Reduced excitability
    • Esp. Constipation
    • … + other psychiatric
  • … heart …
  • Severe hypercalcemia
    • …
    • Cardiac arrest
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
121
Q

Severe … can lead to Coma or cardiac arrest

A

Severe hypercalcemia can lead to Coma or cardiac arrest

122
Q

Hypercalcaemia can be asymptomatic - but most common symptom is …

A

Hypercalcaemia can be asymptomatic - but most common symptom is constipation

Year 2 Medicine (162 decks)

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