13+14+15

• Calcium

  • Intracellular messenger
  • Extracellular functions (e.g.; blood clotting)

  
• Control of body calcium concentration is vital

  
• System that maintains Ca2+ homeostasis

  1. PTH: Secreted from parathyroid gland, mobilizes Ca2+ from bone and increases urinary phosphate excretion

  2. 1,25-DHC (steroid hormone): Derived from vitamin D3, increases Ca2+ absorption from intestine

  3. Calcitonin: Secreted from thyroid gland, inhibits bone resorption (decreases body Ca2+ concentration)

  
• These 3 hormones operate to maintain constant Ca2+ level in body fluids
• Phosphate


  Inclusion in ATP

  Biological buffer

  Modifying proteins (e.g.; activation of enzymes)
• Systems that regulate Ca2+ homeostasis also regulate phosphate in a reciprocal manner

  
• Calcium metabolism

  Total body Calcium = 1,100g (99% in bone & 1% out of bone)

  Plasma conc. = 10mg/dL

  5.36mg/dL is ionized (diffusible)

  4.64mg/dL is bound to plasma proteins (nondiffusible)

  
• Free calcium (ionized)


  Second messenger

  Blood coagulation

  Muscle contraction

  Nerve function
• Hypocalcemia


  Decrease in extracellular Ca2+ level

  Net excitatory effects on nerve and muscle cells

  
• Hypocalcemic tetany


  Characterized by extensive skeletal muscle spasm (especially the extremities and larynx (severe occlusive laryngospasm & fatal asphyxia))

  Occurs before compromising the clotting reactions
• Free Ca2+ vs plasma proteins


  The relation is inverse

  As plasma proteins increase, free Ca2+ decreases

  As plasma protein ionized (at high pH), free Ca2+ decreases (more binding causes low ionized levels)

  
• Hyperventilation in patients (decrease blood CO2 level)


  Causes blood pH to increase (respiratory alkalosis), thus symptoms of hypocalcemic tetany appear even if the blood calcium is high
• Bone calcium


  Readily exchangeable – reservoir (small pool)

  Slowly exchangeable - stable (large pool)

  
• Systems that affect bone calcium

  That regulate plasma Ca2+: by altering absorption (1,25-DCH) & excretion (PTH) - ~ 500mmol/day absorbed and excreted

  That involve bone remodeling: by activation of bone resorption (osteoclast activation) or bone deposition (osteoblast activation)

  About 7.5mmol/dL Ca2+ is exchanged between plasma and bone

  The transport (exchange) process is regulated by 1,25-DHC

  As Ca2+ uptake (hence plasma Ca2+) is increased, 1,25-DHC levels fall

  
• Renal excretion of calcium


  Ca2+ is filtered from plasma

  98-99% of the filtrated Ca2+ is reabsorbed

  60% in PCT

  40% in ascending LH and DCT

  Distal tubular reabsorption is regulated by PTH

  
• Phosphorus


  Present in ATP, cAMP & DAG, DNA & RNA, Many proteins
• Phosphorylation and dephosphorylation are involved in the regulation of cell signaling and function
• Body phosphorous


  Total body content: 500-800g

  Bone amount: 85-90% in the bone & 10-15% out of the bone

  Plasma conc.: 12mg/dL (2/3 is organic & 1/3 is inorganic "PO4 3-, HPO4 2-, H2PO4 – "

  Exchange rate: Amount entering bone 3mg/kg/day with equal amount leaving via reabsorption from bone
• Renal excretion of phosphate

  Pi is filtered from plasma

  85-90% of the filtrated is reabsorbed largely in PCT via NaPi-IIa and NaPi-IIc

  NaPi-Iia is powerfully inhibited by PTH by internalization and degradation and thus reduce renal reabsorption of Pi