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33 Cards in this Set
- Front
- Back
___________ contains a labile pool of Ca2+ and allows for ________ exchange.
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Canaliculi bone fluid = labile pool of Ca2+ and allows for FAST exchange (to central canal plasma)
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__________ contains a stable pool of Ca2+ and allows for ________ exhange.
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Mineralized bone = stable pool of calcium and allows for SLOW exchange (to central canal plasma)
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50% of calcium is _________.
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Free (Ionized): Ca2+
(40% is bound to protein--90% albumin which is made in liver) (9% interacts with other anions such as citrate, phosphate) |
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__________ calcium is only 0.1% of total calcium.
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Extracellular
Excell phosphate is about 1% total P |
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Major crystalline salt of bone is _______
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Hydroxyapatite
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How is the matrix of bone formed?
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Type I collagen fibers organized in triple helix with other proteins to polymerize to form osteroid
Calcium deposition in osteoid converted to hydroxyapatite (calcium phosphate crystals) |
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Osteoblasts vs Osteoclasts
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Osteoblasts: bone forming cells; receptors for E2, PTH, Vit D; following calcification become OSTEOCYTES
Osteoclasts = bone-remodeling cells that are multinucleated macs |
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Bone mass peaks in ______ and declines with ____.
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20's and declines with age
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Bone formation is done by _________.
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osteoblasts
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Bone resorption is done by _________.
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osteoclasts
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PTH Effects
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Active osteoclasts indirectly through secretion of soluble factors from osteoblasts
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Vitamin D effects on bone
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Activate osteoclasts indirectly through secretion of soluble factors from osteoblasts
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Estrogen Effects
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Activates osteoblasts to produce IGF-1 and OSTEOPROTEGRIN
Inhibits osteoclasts indirectly by suppressing IL-6 and increasing OPG Loss of E2 at menopause increases resorption |
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GH effects
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Directly and indirectly (via IGF-1) regulates bone turnover and remodeling
Stimulates proliferation of articular chondrocytes, production of matrix |
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Molecular events following PTH binding osteoblast
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PTH binds receptor on osteoblast
Express Rank Ligand Rank Ligand binds osteoclast precursor and activates it |
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Function of osteoprotegerin
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Osteoblasts secrete osteoprotegerin which acts as a decoy receptor for RankL, preventing osteoclast activation
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PTH is synthesized by _______.
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Chief Cells of Parathyroid Glands
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When is PTH released? Describe the effects of PTH.
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Low Ca2+
Stimulates parathyroid glands (Ca-sensing receptors), release PTH PTH promotes resorption of Ca2+ from bone and kidney via G-protein coupled receptor, cAMP Bone: Increased Ca, P resoption via osteocyte (rapid) and osteoclast (slow: indirect) Kidney: Inc'd Ca absorption, dec'd P absorption (rapid); activates 1alpha hydroxylase to convert 25OH-D to active 1,25 OH-D (vitamin D) Active form of Vit D (Calcitriol: 1, 25 hydroxy Vit D) stimulates Ca2+ and Phosphorus resorption from gut |
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PTH-rp:
What is it? Expressed by? |
homologous to PTH; have common receptor and specific receptors
Expression in placenta, cancer |
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Effects of Mg on PTH.
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High Mg inhibits PTH
Low Mg stimulates PTH |
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Describe the relation between ionized calcium and PTH secretion.
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Free Calcium = ionized calcium
Calcium sensing receptor coupled to Gq, when activated (by Ca2+), inhibits PTH release As Ca2+ falls, PTH is not inhibited and is released |
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Where are calcium receptors located?
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Brain, skin, bone, stomach
Thyroid C Cells, Renal Distal Tubule |
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____ is required for increased PTH secretion due to low ionized calcium.
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Mg
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INACTIVATING mutations in calcium receptors can result in _______.
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Calcium sensing defects (leads to "benign" hypercalcemia)
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How is phosphate regulated? Include specific receptors.
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NPT2a mediates PO4 reabsoprtion in renal tubule
Decreased PTH and FGF23 decrease NPT2a expression to increase PO4 excretion and decrease serum [PO4] |
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FGF23 is synthesized in _____ and acts on ______ to ________.
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Synthesized in bone
Acts on kidney To inhibit PO4 absorption AND 1,25-OH Vit D production (FGF is a phatonin--a protein that makes you excrete PO4) |
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What cofactor is required for FGF23 activation?
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KLOTHO
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Vitamin D is derived from ______.
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Cholesterol
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What is the precursor of Vitamin D? What is it converted to?
Where is it stored? |
Cholecalficerol (D3)
Converted to storage form (25OH-D) in liver Activated by PTH in kidney to active form 1,25(OH)2D |
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Target tissue/Action of Vitamin D?
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Vitamin D acts on:
Bone (remodeling, mineralization) Small Intestine: Ca, P, Mg absorption (Ca-binding protein) Skin: keratinocyte dx/dy |
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Circulating 1,25 OH D is a reflection of ___________.
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PTH activity
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What is a non-calcemic effect of vitamin D?
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Regulation of cell growth (cancer prevention)
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Calcitonin is made by _____ and is released when _________.
What are its effects? |
Calcitonin is made in C Cells (neural crest derivs) in thyroid gland
Regulated acutely by elevated Ca levels Decreases resorption of bone due to inhibition of osteoclasts (DECREASES CA2+ concentration) Decreases Ca reasborption in kidney at high levels No consequences on Ca metabolism if athyroidal |