Control of Mineral Metabolism (and other nonsense) Flashcards Preview

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Physiological roles for calcium (2)

  • Structural
    • Major constituent of mineral matrix of bone
    • Serves as reservoir for maintenance of plasma calcium
  • Biochemical
    • Essential regulator of:
      • Excitation-contraction coupling
      • Stimulus-secretion coupling
      • Blood clotting
      • Membrane excitability
      • Cellular permeability
      • Other metabolic function


Physiologic roles of phosphate (2)

  • Structural
    • Part of mineral matrix of bone
  • Biochemical
    • Required for:
      • Phosphorylation reactions (transfer of energy in form of high energy phosphate groups)
      • Intracellular buffer
  • 85% of serum phosphate free in ionized active form of HPO42- and H2PO42-


3 major compartments involved in calcium & phosphate homeostasis

  • Bone
    • 99% of calcium in form of hydroxyapatite
  • Intracellular compartment
    • 10 g = ~50-100 nM in resting cell
    • Cytosolic calcium level maintained by pumping calcium into ER for storage by ATP-linked pump and Na/Ca antiporter
  • Extracellular compartment (includes blood and interstitial space)
    • 2.5mM
    • 50% calcium in free form, filtered by kidney
    • 10% in salts (bicarbonate and phosphate)
    • Remainer bound to albumin
    • Kidney filters 10g/day - 98% reabsorbed


Regulation of PTH release

  • From 4 parathyroid glands
  • Regulated by typical negative feedback loop
    • Serum calcium = regulated variable
  • PTH made by chief cells in parathyroid gland
    • Released via Ca2+ dependent exocytosis
  • Increased serum Ca2+ --> decreased PTH release from parathyroid
  • Decreased serum Ca2+ --> increased PTH release from parathyroid


  • Decreased serum Ca2+ --> increased intracellular Ca2+ via calcium sensor protein
  • When serum Ca2+ decreases, sensor protein hooks up with Gq protein --> part of G protein subunit heads to ER and causes release of Ca2+ via IP3


Action of PTH

  • PTH = Phosphate Trashing Hormone
  • Bone: fast and slow response to PTH
    • Fast: efflux of labile bone calcium with no phosphate release from bone (encourages osteocytic osteolysis)
    • Slow: increased bone remodeling with release of both bone calcium and phosphate (usually pathologic)
  • Kidney:
    • Increased Ca2+ reabsorption in distal tubule
    • Decreased phosphate reabsorption (CaPO4 has very low solubility - body doesn't want it)
    • Increased synthesis of 1,25 (OH)2 Vitamin D
  • GI tract: indirect by way of vitamin D
    • Increased Ca2+ absorption (requires a day)
    • Increased phosphate absorption


Synthesis of vitamin D

  • Making active vitamin D
    • In skin: 7-dehydrocholesterol + sunlight = vitamin D3
    • D3 travels to liver --> converted to 25(OH) vitamin D3
    • 25(OH) D3 then activated in kidneys by 1a-hydroxylase --> turned into 1,25 (OH)2 D3
  • Alternatively: 
    • Kidney can produce inactive form 24,25(OH)2 vitamin D by 24-hydroxylase activity
      • In equilibrium with active form 
    • In absence of PTH, 24-hydroxylase is more active 
  • 1,25 (OH)2 vitamin D transported in serum by binding to transcalciferin


Regulation of vitamin D

  • Increased PTH -->
    • Increased 1a-hydroxylase activity and decreased 24-hydroxylase activity --> more active vitamin D to absorb Ca2+ from GI tract
  • Decreased phosphate -->
    • Increased 1a-hydroxylase activity and decreased 24-hydroxylase activity --> more active vitamin D to absorb phosphate from GI tract
  • Decreased [Ca2+] --> Increased PTH --> Increased 1,25(OH)2 vitamin D production
  • Decreased phosphate causes 1,25(OH)2 vitamin D production
  • Cortisol decreases vitamin D action
  • Estrogen + growth factors work opposite of PTH and drive Ca2+ into bone


Actions of vitamin D

  • Increased absorption of dietary calcium
  • Increased absorption of dietary phosphate
  • Increased bone resorption of Ca2+ and phosphate (mechanism unknown)


Regulation of serum calcium

  • Short-term: primarily PTH
  • Long-term: vitamin D-mediated GI absorption of calcium and phosphate
  • Decreased serum Ca2+ --> increased excitability --> muscle twitches, seizures
    • Cellular (-) surface charges are screened by Ca2+
  • Increased serum Ca2+ --> decreased excitability --> sluggishness


Calcium in the body

  • In blood: transported on albumin (50%), salts (10%), free (40%)
  • Rapid process under normal circumstances, Ca2+ in cannalicular fluid lower than serum Ca2+ 
    • Ca2+ flows into cannalicular fluid down concentration gradient, taken up by osteocytes
    • Osteocytes pump calcium out through long processes back to surface osteoblasts and back into blood
    • Rapid calcium exchange = osteocytic osteolysis
      • Causes 10g to be cycled daily
  • Slower process: exchange of 280mg of Ca2+ through bone resorption
  • Phosphate only undergoes slow exchange due to remodeling - no rapid process


3 important cell types in bones

  • Surface osteoblasts
  • Osteocytes
  • Osteoclasts