Bone Dynamics & Calcium Homeostasis Flashcards
What percentage of the body’s calcium is stored in bone (and teeth)? Where is the remainder found?
- 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)
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?
- 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
How does the body rapidly adjust calcium levels? How about for more long-term adjustments?
- short term/rapid: calcium transfer between ECF and bone fluid, excretion via kidneys
- long term/slower: bone remodeling, calcium gut absorption
95% of bone is made up of _________. What else is also present?
- 95% is type I collagen
- proteoglycans and non-collagenous proteins are also present
What is the sub-unit of bone called? What does each contain?
- the osteon (mineralized osteoid)
- each contains a Haversian canal (arteries, veins, and nerves pass through)
Which cells give rise to osteoblasts? To osteoclasts?
- osteoblasts come from mesenchymal stem cells
- osteoclasts come from hematopoietic stem cells
What are the two mature forms of an osteoblast?
- osteocyte: active; trapped inside the bone matrix
- bone-lining cells: inactive; lining the osteons
Bone is constantly being turned over and remodeled; how often is a completely new skeleton generated?
- every 10 years
OPG, RANK, RANKL, CSF
- 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
Which 5 organs measure plasma calcium levels?
- parathyroid, thyroid, kidneys, GIT, and brain
What are the three calcium controlling hormones?
- parathyroid hormone (PTH), active vitamin D, and calcitonin
Parathyroid Hormone (PTH); general affects, rapid actions, chronic actions.
- 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)
Vitamin D
- 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)
Calcitonin
- 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
Name three major bone turnover markers for resportion and three for formation.
- resorption: collagen I breakdown products, osteoclast markers, protease (cathepsin K)
- formation: collagen I pre-cursors, osteoblast activity, alkaline phosphatase (ALP, the bone specific isoform)
Explain the process of vitamin D activation.
- 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)
What are the five major actions the skeleton provides?
- support, movement, protection, hemopoiesis, storage (of calcium and phosphate as hydroxyapatite)
Describe the parts of a long bone.
- a shaft (diaphysis) with ends (epiphyses) that contain growth plates and are composed of articular cartilage
- a hollow medullary cavity where hemopoiesis occurs
What are the three types of bone tissue?
- 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
Explain the difference between the two types of mature lamellar bone.
- 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)
What type of bone tissue makes up fetal bone? Fractures?
- both contain immature woven bone
What is mesenchyme?
- mesenchyme is embryonic connective tissue that forms from the mesoderm
- it gives rise to cartilage, bone, and hematopoietic stem cells
What are the two types of bone development (osteogenesis)?
- 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
Which bones develop via intramembranous ossification? Via endochondral ossification?
- 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)
Where are primary and secondary ossification centers found?
- primary: in the shaft of the bone
- secondary: in the epiphyses
When does bone growth stop?
- when the secondary ossification centers fuse with the primary centers
What is the metaphysis?
- 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)
What is Wolff’s Law?
- the law of bone transformation: bone is laid down where it is needed and resorbed where it is not
What percentage of bone turnover occurs each year in infants? In adults?
- 100% in infants and only 18% in adults!
Which bone’s ossification centers are the last to fuse (ie which bone is the last to stop growing)?
- the epiphysis at the medial end of each clavicle
Which two bones of the hand can be used to help determine the age of a skeleton?
- 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)
What percentage of bone cells are osteoblasts? Osteocytes? Osteoclasts?
- 5% are osteoblasts
- 90-95% are osteocytes
- 1-2% are osteoclasts
How do osteoclasts generate the acidic environment needed for bone resorption? What is used to degrade the organic component of bone matrix?
- they generate H+ via carbonic anhydrase II (CA II)
- to dissolve the organic component, cathepsin is used
- sealing zone; ruffled border
What are the four zones of an epiphyseal growth plate?
- 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
