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09. Locomotion > 9.15 Bone Physiology > Flashcards

9.15 Bone Physiology Flashcards

1
Q

What are the two types of bone growth and how are they measured?

A
  • Soft tissue: measured by weight
  • Bone: measured by height
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2
Q

Tissue and bone growth requires multiple hormones & paracrines have direct or permissive effects on growth

What are some examples of the hormone interactions involved?

A
  • GH and IGFs required for protein and cell division
  • Thyroid hormone plays permissive role in growth: Directly contributes to nervous system development
  • Insulin supports growth, provides glucose energy
  • Sex steroids
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3
Q

What are the two absolute essential requirements for bone and tissue growth?

A
  1. Adequate dietary calcium and protein
  2. Regulated hormonal control of calcium homeostasis
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4
Q

What is the most substantial component of bone?

What does it contain?

A

Extracellular matrix

  • Calcium phosphate crystals precipitate & attach to collagen fiber lattice
  • Most common calcium phosphate: Hydroxyapatite (Ca10(PO4)6(OH)2)
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5
Q

Describe the structure of bone

A
  • Compact or cortical bone (Outer)
    • Provides strength
  • Trabecular bone (Inner spongy layer)
    • Open, cell‐filled spaces
    • between struts of calcified lattice
  • Central bone marrow (only in some bones)
    • Hematopoiesis = blood formation
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6
Q

Describe the relationship between bone resorption and deposition required for bone growth

A

Matrix is deposited (osteoblast activity) faster than it is bone resorption (osteoclast activity)

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7
Q

What is the role of the osteoblast?

  • Lineage
  • What does it produce
  • Specialised proteins it produces
A
  • Specialised bone‐forming cells
  • Modified fibroblasts
  • Produce enzymes & osteoid (collagen & protein mix) to
  • which hydroxyapatite binds
  • Osteocalcin & osteonectin, proteins aid in deposition
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8
Q

In what direction does bone lengthening occur and how?

A

Bone diameter increases as the matrix deposits on outer surface

  • Epiphyseal plate is the site of linear growth of long bone growth
  • At the end of the bone shaft (diaphysis)
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9
Q

Describe the role of chondrocytes in bone growth

A

Form the growth plate of elongating bones

  • Located near the epiphysis
  • Cartilage cells that are collagen‐producing
  • Continuously dividing in columns; to 􏰀lengthen
  • Collagen layer thickens & old chondrocytes disintegrate leaving spaces
  • These spaces are then filled in with bone matrix by osteoclasts
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10
Q

Describe the role in more detail of the osteoblasts in bone elongation (growth)

A
  • Lay down bone ontop of cartilage bases where the old chondrocytes degenerated
  • They enable the shaft to lengthens, when the epiphyseal plate is active
  • Osteoblasts revert to less active form of osteocytes when complete work
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11
Q

Describe the difference in the role of osteoblasts vs. Osteoclasts in terms of calcium regulation

A

Osteoblasts

  • Deposit calcium as they create bone matrix thereby reducing caclium levels in the plasma

Osteoclasts

  • Are large, mobile, multinucleate cells derived hematopoietic stem cells
  • Secretes acid & protease enzymes dissolves calcified matrix & collagen support
  • To release Ca2+ into the plasma increasing levels
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12
Q

What three organs regulate calcium homeostasis in the body?

A
  1. Bone
  2. Kidneys
  3. Intestine

Each of which has its own mechanism of regulation

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13
Q

What are the three hormones involved in calcium regulation?

A
  1. Parathyroid hormone (PTH)
  2. Vitamin D3 (calcitriol)
  3. Calcitonin
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14
Q

What are the key roles of calcium in the body? [4]

A
  • important intracellular signalling molecule
  • Structural functions
    • contribute physical strength to bone matrix
    • help hold cells together at tight junctions
  • cofactor in blood coagulation
  • required for normal excitability of neurons and muscle
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15
Q

Complete the equation:

Total body calcium = _________ - ___________

A

Total body calcium = Calcium dietary intake - Calcium output

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16
Q

What are the three pools of calcium in the body?

  • Which of these is the most substantial?
  • What are the roles of calcium in each of these pools?
A
  • Bone matrix (Most substantial 99%)
  • Extracellular (0.1%) = ionized Ca2+
  • Intracellular (0.9%) = Free Ca2+
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17
Q

What is important about ECF concentrations of calcium (plasma concentrations)

A

This is the component that is very carefully regulated

  • ECF Ca2+ ions move freely in and out of plasma
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18
Q

What is the general concentration of extracellular (plasma) Calcium?

A

2.5 mM

19
Q

What is the main mechanism by which cells are able to regulate calcium plasma concentration

(ie balance intracellular [Ca] with extracellular [Ca])

A
  • Maintenence of the electrochemical gradient through active transport mechanisms
20
Q

Describe how Ca2+ Ions in the plasma exchange with Calcium in Bones

A

Via the action of osteoblasts and osteoclasts

(which are themselves regulated by PTH, Calcitonin, Calitriol and Cortisol)

21
Q

What proportion of dietary intake of calcium is absorbed in the gut?

How is this regulated?

A

About 1/3rd is absorbed and this is regulated through hormone levels

  • Calcitriol
  • Also slightly via the action of PTH and prolactin
22
Q

How is calcium excreted from the body (another important factor in regulating calcium levels)

A
  • Most calcium lost via urine; some feces
  • The kidneys passively filter calcium into the urine while the distal nephron contains transporters to reabsorb calcium (these are all regulated by PTH and calcitonin)
    • ECaC
    • Na+‐Ca2+ antiporter
    • Ca2+ ‐ATPase
23
Q

Where are the parathyroid glands located?

  • What do they secrete?
  • Are the essential for life?
A

There are 4 small parathyroid glands located on the back of the thyroid gland

  • They secrete PTH
  • They are absolutely essential for life (death without it)
24
Q

What (and how) triggers release of PTH from the parathyroid gland?

  • What are the two basic actions of it once it is secreted?
A

Secreted in response to 􏰂 low serum [calcium] which is sensed by calcium sensitive receptors

Acts to

  • Increase􏰀 plasma calcium
  • Decrease􏰂 plasma phosphate
25
Q

Describe the role of PTH in

  • Bone
  • Kidney
  • Intestine
A

Actions on bone

  • Calcium and phosphate release from bone into plasma
  • favour bone resorption by increasing osteoclast activity
  • Includes actions of paracrines osteoprotegerin (OPG) & RANKL
    • Note: there are no receptors on osteoclasts - actions mainly through paracrine activity)

Actionsonkidney

  • distal nephron to increase calcium reabsorption by acting on transporters
  • Decrease phosphate reabsorption (Mismatch - phosphate acts in the opposite way: the regulation of calcium and phosphate is NOT always in parallel)

Actions on intestine

  • indirectly increases calcium & phosphate reabsorption by vitamin D activation
26
Q

Fill out the following table

A
27
Q

What is calcitonin and where is it released from?

  • What is it released in response to?
A

C cells of thyroid

released when plasma Ca2+ is high

28
Q

What is the role of calcitonin?

A

􏰂It has no role normally and only works with extreme hypercalcemia

It acts to:

  • Decrease plasma calcium & phosphate levels (opposite actions to PTH)
    • Release of calcium from bone
    • Inhibit bone resorption
    • Increase renal calcium excretion

Note: it has no action in the gut

29
Q

Fill in the following table

A
30
Q

Draw a mechanism that summarises the role of PTH and calcitronin in response to different plasma calcium levels

A
31
Q

How is vitamin D metabolised in the body?

  • What are the 2 sources of vitamin D?
A
  1. Dietary intake
  2. UV activation of the precursor present in skin
32
Q

What regulates the action of vitamin D?

A

The action is regulated by whether the hormone is in its active form or not.

This activation of the hormone is regulated in the kidney by PTH (increased serum Ca) and by decreases in plasma phosphate levels

33
Q

Fil in the following table

A
34
Q

Describe the role of vitamin D in calcium balance

A
35
Q

Draw what happens in the body in response to decreased plasma levels (include actions in bone, kidney and intestines)

A
36
Q

Most of the phosphate present in the body is in bone

What are the roles of phosphate in the body?

A
  • Key component of hydroxyapatite in bone
  • Energy transfer and storage; ATP, cAMP
  • Control of enzymes, transporters, ion channels
  • Part of DNA and RNA backbone
37
Q

How are phosphate levels related to calcium levels?

A

Phosphate movements parallel calcium

Its absorption and excretion (most reabsorbed in proximal tubule) are hormonally regulated

(Except in the gut)

38
Q

Describe phosphate regulation in the intestine, kidney and bone

A

Intestine:

  • enhances phosphate absorption via VitD3

Kidney:

  • PTH promotes phosphate excretion and , reduces reabsorption.
  • Vit D weakly promotes reabsorption

Bone:

PTH promotes reabsorption of phosphate (release)

39
Q

Describe PTH hypersecretion

A

= hyperparathyroidism

  • usually a tumor
  • hypercalcemia &hypophosphatemia
  • has variable effects
  • Thus treated by tumour resection
40
Q

Describe PTH hyposecretion

A

= hypoparathyroidism

  • Rare
  • autoimmune attack of glands
  • hypocalcemia & hyperphosphatemia
  • impact on neuromuscular excitability
  • Can occur via Inadvertent parathyroidectomy during thyroid surgery (but is rare because we have 4 of them)
41
Q

Describe Vitamin D deficiency

A

Due to poor vitamin D in the diet or inadequate UV sun exposure. It leads to…

  • impaired intestinal calcium absorption
  • The PTH is able to maintain calcium levels but at expense of bones leading to
    • bone demineralisation = rickets in children and osteomalacia in adults
42
Q

Describe osteoporosis

A

A Long term imbalance of bone resorption >>> bone formation

These people have a high fracture risk

  • cause not known
43
Q

What are the non-modifiable and modifiable risks for osteoporosis?

A

Non-modifiable:

Post menopausal lack of oestrogen, old age, endocrine disorders (Cushing’s)

Modifiable:

Malnutrition, alcoholism, smoking, lack of exercise

44
Q

What is another indirect way that calcium levels can be impacted?

A

If there are intrinsic problems with the gut and/or kidney, this has a large impact on calcium balance and thus on bone particularly for growing children, pregnant women and elderly

09. Locomotion (5 decks)

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