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Musculoskeletal > Bone Dynamics & Calcium Homeostasis > Flashcards

Bone Dynamics & Calcium Homeostasis Flashcards

1
Q

What percentage of the body’s calcium is stored in bone (and teeth)? Where is the remainder found?

A
  • 99%!
  • of the remaining 1%, 0.9% is in the cells and 0.1% is in the ECF (50% of the calcium in the ECF is bound to plasma proteins or phosphate and is therefore not biologically active)
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2
Q

What is the normal level of serum calcium? What level of hypocalcemia is lethal? What classifies as hypercalcemia? At what serum level does disseminated calcium-phosphate precipitation occur?

A
  • normal level: 9.4 mg/100 mL (2.4 mmol/L)
  • lethal hypocalcemia: 4mg/100 mL or less
  • hypercalcemia: anything greater than 10.5 mg/100 mL
  • precipitation occurs at a level of 17 mg/100 mL or higher
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3
Q

How does the body rapidly adjust calcium levels? How about for more long-term adjustments?

A
  • short term/rapid: calcium transfer between ECF and bone fluid, excretion via kidneys
  • long term/slower: bone remodeling, calcium gut absorption
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4
Q

95% of bone is made up of _________. What else is also present?

A
  • 95% is type I collagen

- proteoglycans and non-collagenous proteins are also present

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5
Q

What is the sub-unit of bone called? What does each contain?

A
  • the osteon (mineralized osteoid)

- each contains a Haversian canal (arteries, veins, and nerves pass through)

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6
Q

Which cells give rise to osteoblasts? To osteoclasts?

A
  • osteoblasts come from mesenchymal stem cells

- osteoclasts come from hematopoietic stem cells

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7
Q

What are the two mature forms of an osteoblast?

A
  • osteocyte: active; trapped inside the bone matrix

- bone-lining cells: inactive; lining the osteons

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8
Q

Bone is constantly being turned over and remodeled; how often is a completely new skeleton generated?

A
  • every 10 years
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9
Q

OPG, RANK, RANKL, CSF

A
  • osteoclast activation requires RANKL binding to RANK (a receptor for the NF-kB family) as well as CSF (colony stimulating factor; important for differentiation into osteoclast from hematopoietic stem cell)
  • OPG (osteoprotegerin) is a decoy receptor to RANKL, binding to it and preventing it from activating RANK (and therefore preventing osteoclast activation)
  • OPG, RANKL, and CSF are secreted by osteoblasts
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10
Q

Which 5 organs measure plasma calcium levels?

A
  • parathyroid, thyroid, kidneys, GIT, and brain
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11
Q

What are the three calcium controlling hormones?

A
  • parathyroid hormone (PTH), active vitamin D, and calcitonin
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12
Q

Parathyroid Hormone (PTH); general affects, rapid actions, chronic actions.

A
  • released when serum calcium levels are low
  • increases calcium levels, decreases phosphate levels, and increases vitamin D activation in the kidneys
  • rapid: activates ATP-driven Ca2+ pumps to pump calcium from the bone fluid into the osteocyte and into the plasma; increases calcium reabsorption and decreases phosphate reabsorption in the kidneys
  • chronic: stimulates osteoblasts to increase RANKL secretion to increase osteocyte activation
  • (at low levels, PTH is anabolic; at high levels, PTH is catabolic)
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13
Q

Vitamin D

A
  • increases absorption of both calcium and phosphate in the GIT, increases reabsorption of both in the kidneys
  • vit D is needed for transcription of calbindin (a calcium binding protein)
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14
Q

Calcitonin

A
  • released when calcium levels are too high (by C cells of the thyroid gland)
  • opposes to effects of PTH: decreases osteoclast activity and increases calcium and phosphate excretion in the kidneys
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15
Q

Name three major bone turnover markers for resportion and three for formation.

A
  • resorption: collagen I breakdown products, osteoclast markers, protease (cathepsin K)
  • formation: collagen I pre-cursors, osteoblast activity, alkaline phosphatase (ALP, the bone specific isoform)
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16
Q

Explain the process of vitamin D activation.

A
  • 5-dihydrotachysterol (cholesterol derivative in the skin) gets hit by UV light and becomes cholecalciferol (vitamin D3)
  • cholecalciferol gets hydroxylated by the liver at C25 to become 25-hydroxycholecalciferol (25-OH-vitaminD3) AKA calcidiol - the pre-hormone form of vit D
  • calcidiol then gets hydroxylated by the kidneys at C1 (mediated by PTH) to become 1,25-dihydroxycholecalciferol (1,25-(OH)2-vitaminD3) AKA calcitriol (hormone form; active vit D)
17
Q

What are the five major actions the skeleton provides?

A
  • support, movement, protection, hemopoiesis, storage (of calcium and phosphate as hydroxyapatite)
18
Q

Describe the parts of a long bone.

A
  • a shaft (diaphysis) with ends (epiphyses) that contain growth plates and are composed of articular cartilage
  • a hollow medullary cavity where hemopoiesis occurs
19
Q

What are the three types of bone tissue?

A
  • osteoid: unmineralized bone matrix (“primitive bone”)
  • immature woven bone: temporary bone tissue that contains primary osteons (these lack concentric lamellae)
  • mature lamellar bone: compact cortical bone + trabecular/cancellous bone
20
Q

Explain the difference between the two types of mature lamellar bone.

A
  • compact cortical bone: contains concentric lamellae (secondary osteons, contain Haversian systems), circumferential lamellae, and interstitial lamellae; makes up the shafts of long bones
  • trabecular/cancellous bone: the spongy bone found at epiphyses and the axial skeleton; contains red marrow and is where hemopoiesis occurs)
21
Q

What type of bone tissue makes up fetal bone? Fractures?

A
  • both contain immature woven bone
22
Q

What is mesenchyme?

A
  • mesenchyme is embryonic connective tissue that forms from the mesoderm
  • it gives rise to cartilage, bone, and hematopoietic stem cells
23
Q

What are the two types of bone development (osteogenesis)?

A
  • intramembranous ossification and endochondral ossification
  • in intramembranous ossification, bone forms directly from condensed layers of mesenchyme (involves primary centers)
  • in endochondral ossification, bone formation is preceded by a hyaline cartilage model and requires both primary and secondary ossification centers
24
Q

Which bones develop via intramembranous ossification? Via endochondral ossification?

A
  • intramembranous ossification gives rise to the membranous bones: the cranial vault, facial bone, and the clavicles
  • endochondral ossification gives rise to the endochondral bones: the cranial base and all post-cranial bones (except the clavicles)
25
Q

Where are primary and secondary ossification centers found?

A
  • primary: in the shaft of the bone

- secondary: in the epiphyses

26
Q

When does bone growth stop?

A
  • when the secondary ossification centers fuse with the primary centers
27
Q

What is the metaphysis?

A
  • the temporary region just adjacent to the epiphyseal growth plate where new bone has just been formed (will eventually become a part of the diaphysis)
28
Q

What is Wolff’s Law?

A
  • the law of bone transformation: bone is laid down where it is needed and resorbed where it is not
29
Q

What percentage of bone turnover occurs each year in infants? In adults?

A
  • 100% in infants and only 18% in adults!
30
Q

Which bone’s ossification centers are the last to fuse (ie which bone is the last to stop growing)?

A
  • the epiphysis at the medial end of each clavicle
31
Q

Which two bones of the hand can be used to help determine the age of a skeleton?

A
  • the pisiform of the wrist and the adductor sesamoid of the thumb
  • the pisiform begins to ossify at the start of puberty (about 13 years)
  • the adductor sesamoid appears just after puberty (about 18)
32
Q

What percentage of bone cells are osteoblasts? Osteocytes? Osteoclasts?

A
  • 5% are osteoblasts
  • 90-95% are osteocytes
  • 1-2% are osteoclasts
33
Q

How do osteoclasts generate the acidic environment needed for bone resorption? What is used to degrade the organic component of bone matrix?

A
  • they generate H+ via carbonic anhydrase II (CA II)
  • to dissolve the organic component, cathepsin is used
  • sealing zone; ruffled border
34
Q

What are the four zones of an epiphyseal growth plate?

A
  • 1) resting cartilage: hyaline cartilage; inactive condrocytes
  • 2) proliferating cartilage: mitotic chondrocytes push the resting zone out (this is where lengthening occurs)
  • 3) hypertrophic cartilage: chondrocytes enlarge and mature
  • 4) calcified cartilage: very thin; dying and dead chondrocytes cement the epihphyseal plate to the diaphsysis; new bony matrix replaces this zone

Musculoskeletal (12 decks)

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