Calcium

1. increase in nerve excitability
   1. cause tetany

      Nota:

      • spasms
      1. if severe can cause death by asphyxiation

1. reduces neuromuscular excitability
   1. lead to cardiac arrhythmias, lethargy and death
2. causes
   1. 54% primary hyperparathyroidism
   2. 34% malignancy associated
   3. 12% other

1. 99% bones and teeth
2. intercellular

   Nota:

   • soluble in cytosol and nucleus.  insoluble in PM, ER and mitochondria  
3. extracellular

   Nota:

   • extracellular fluid for  Blood clotting,  exocytosis and contraction   

Nota:

• parathyroid hormone 

1. produced by chief cells of the parathyroid gland
2. 88a
3. synthesised as prep-pro PTH (115aa)
   1. cleaved to proPTH
      1. cleaved again to PTH

         Nota:

         • cleaved in the liver 88aa half life 20mins  
4. secretion is inversely proportional to serum Ca
5. effects
   1. increases bone resorption
   2. increase renal Ca reabsorption
   3. increase Pi excretion
   4. increase production of Vit D
6. PTHrP

   Nota:

   • PTH related peptide
   1. 141,139,173aa

      Nota:

      • alternate splicing 
   2. secreted in certain cancers causing humoral hypercalcaemia of malignancy
   3. similar to PTH
   4. widely expressed under normal conditions
   5. essential for normal skeletal development

      Nota:

      • identified from KO studies 
7. evolution

1. biosynthesis
   1. PTH increases transcription of 1 alpha hydroxalase gene in the renal proximal tubule
   2. in the skin UVB forms preVitD3
2. carried in the plasma bound to specific globulin VitD binding protein (DBP)

   Nota:

   • VitD is lipid soluble 
3. source
   1. oily fish

      Nota:

      • salmon 
   2. milk
4. Deficiency
   1. Rickets
   2. secondary hyperparathyroidism
   3. osteomalacia
5. actions
   1. increase net intestinal Ca2+ uptake
   2. increases calbindin expression
   3. increase bone resorption
   4. increases renal Ca reabsorption

1. Parafollicular thyroidal “C cells''
2. 32 aa peptide (from pro-calcitonin)
3. reduces Ca plasma levels after a meal
4. reduces osteoclast activity- reduces bone resorption
5. Secretion inhibited by low Ca2+ levels in the blood

1. total ~ 2.5 mM (10mg/dl)
   1. 35-40% bound to macromolecular proteins

      Nota:

      • especially albumin
   2. 5% complexed as salts

      Nota:

      •    Ca2+ salts of bicarbonate, phosphate, sulphate & citrate.   
   3. free ionised Ca2+ concentration is ~ 1.2 mM
2. Calcium sensing mechanism only senses free ionised Ca

   Nota:

   • The Ca2+-sensing mechanisms that oversee Ca2+ homeostasis sense changes in free, ionised Ca2+ levels rather than total Ca2+ levels

1. Calciotropic hormones

   Nota:

   • affect calcium
   1. PTH
   2. Vit D3
   3. calcitonin
2. Non-calciotropic hormones

   Nota:

   • affect bone formation but not calcium 
   1. Glucocorticoids
   2. Growth hormone
   3. thyroid hormones
   4. estrogen
   5. insulin
   6. EGF, FGF, PDGF
   7. PGE2, osteoclast activating factor