Shricker Study Guide Flashcards
What is the mineral composition of bone?
Hydroxyapatite
What is the primary protein component of bone?
collagen
What is the major calcium reserve in our body?
bone
How do remodeling cycle and serum calcium levels affect one another?
decrease bone mass causes increase in remodeling = increase serum calcium
Where is calcium found other than bone?
teeth and bound to albumin
How is calcium distribute in serum?
ionized calcium = 50% (biologically active)
protein bound calcium (bound to albumin) = 40% (biologically inactive)
citrate or phosphate bound calcium = 10%
Which type of bound calcium is biological inactive? active?
- protein bound
- ionized calcium
What factors regulate the bone remodeling cycle?
Serum calcium, hormones, cytokines
- high serum calcium = inhibits resorption
- hormones (PTH, prolactin, prostaglandin, cytokines = promote bone resorption
estrogens and calcitonin = inhibit bone resorption)
What cells are involved in bone resorption
mesenchymal cells -> preosteoblast -> osteoblasts -> osteocyte
hematopoietic stem cells -> monocyte/macrophage -> preosteoclast -> osteoclasts
How are osteoclasts regulated?
RANKL bind RANK on osteoclasts to trigger osteoclasts to resorb bone
- estrogen activates OPG which inhibits RANKL from binding RANK
How do osteoblasts regulate osteoclasts?
PTH indirectly stimulates osteoclasts
PTH binds osteoblasts signaling them to up regulate expression of RANKL
Osteoblast RANKL contacts osteoclast RANK and osteoclast precursors differentiate into mature osteoclasts
What are the major consequences of increased PTH?
increases osteoclast activity which increases serum calcium and decreases serum phosphate
- increases calcium reabsorption in kidneys and small intestine
What regulates PTH production?
stimulated by low plasma calcium levels
What are consequences of increased vitamin D production?
increases serum calcium levels, gut absorbs calcium and increases bone resorption because of calcium intake from diet
What regulates vitamin D production?
synthesized in skin from sunlight
- stored in liver, converted to active form in kidney
- 1-alpha hydrolase in the kidney is major point of vitamin D maturation and regulation
What is the major cause of hypercalcemia (high calcium blood serum levels)?
Primary hyperparathyroidism, malignant disease, iatrogenic vitamin D
What is the treatment for hypercalcemia?
primary hyperparathyroidism = surgery
malignant disease = Bisphosphonates which inhibit osteoclast activity
iatrogenic = vitamin D (3rd leading cause)
How is hypercalcemia detected with intact PTH?
over expression of PTH overwhelms its half-life causing intact form rather than cleaved form for longer than normal, antibody detects
how do antibodies detect intact PTH?
two antibodies are used to detect both “cleaved segments” to determine if they are intact
What is the major cause of hypopcalcemia?
Damaged parathyroid gland
How is hypocalcemia treated?
Hypoparathyroid = surgery
non parathyroid =
PTH resistance = administer magnesium
What causes abnormal metabolism of vitamin D?
vitamin D deficiency, tissue resistance to vitamin D and from liver disease or renal failure
Defects in HA formation due to vit D deficiency
osteomalacia (rickets cured by Cod liver oil)
loss of mineral density with age, increase risk of fracture, rates of bone synthesis and resorption change
osteoporosis (treat with estrogens, bisphosphonates, calcitonin, PTH)
Numerous osteoclasts and osteoblasts, increase in alkaline phosphatase, large misshapen dense and brittle bones
Pagets disease (treat with bisphosphonates and calcitonin)
How does calcitonin affect serum calcium?
decreases serum calcium and increases Ca2+ in bone
