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Calcium regulates nerve excitability and muscle contraction. Low calcium results in muscle twitches. Calcium competes with sodium for voltage gated channels. Calcium also plays a part in neurotransmitter release, blood clotting, bone composition (hydroxyapatite).

40% of calcium in the blood is bound to albumin, a protein. 60% is ultrafiltrable, being either complexed to anions (10%) or free, ionized, and biologically active (50%). These numbers vary a lot. Free calcium can cross the blood brain barrier. The ionized calcium level is influenced by protein, phosphate and acid.

More protein --> less free calcium.
More acid --> more free calcium.
More phosphate --> less free calcium, bad situation: high levels of both calcium and phosphorus in blood can result in precipitation of Ca PO4 in soft tissues

Normal calcium level: 8.6-10.6 mg/dl
Normal phosphate level 2.5-4.5 mg/dl

Notice: 3-4x more calcium than phosphate in blood is normal. This balance is maintained by different absorbtion and secretion in the kidneys. Calcium is mostly reabsorbed in the proximal tubules but reabsorption continues through to the collecting ducts where the last 8% is reabsorbed.

VITAMIN D
--Vitamin D stimulates calcium and phosphate absorption in the intestine (via upregulating calbindin and calcium ATPase pumps)
--Vit D3 is synthesized in the skin with exposure to both UV and IR radation, and can be consumed in the diet (have you had your cod liver oil today?)
--Vit D3 is hydroxylated in the liver and kidney, to its 25(OH)D form.
--PTH causes the kidney to change vit D to its active form 1, 25(OH)2D

PARATHYROID HORMONE
--continuous aplication stimulates osteoclasts to eat bone and dump calcium and phorphorus into blood
--intermittent application causes osteoblasts to blast out more bone, taking ca and po4 out of blood
--Brons says that bone is the least important part of regulating blood calcium, that intestinal absorbtion and renal reabsorption are the most important.
--PTH increases renal reabsorption of calcium in proximal tubules (67%) and ascending loop (25%) and distal & collecting tubules (8% "fine control")
--PTH increases intestinal absorption of calcium by activating vitamin D in the kidney, which upregulates calbindin for transport
--PTH inhibits phophorus reabsorbtion from PROXIMAL tubules, increases excretion, and prevents simultaneous elevation of plasma calcium and phosphorus.

CALCITONIN
--opposite of PTH, equilibrium between the two determines blood calcium and phosphate levels
--present mostly in children "adults don't need it"
--released from thyroid in response to high calcium levels
--inhibits osteoclasts, favors bone deposition
--reduces levels of both calcium and phosphate

BONE
--vitamin D and parathyroid hormone regulate osteoblast & clast activity, thus bone resorption and deposition
--the mineral in bone is hydroxyapatite = Ca10(PO4)6(OH)2 plus Mg, Na, K and carbonate
--in most tissues Ca++ and phosphate are at near saturation levels but kept solubilized by pyrophosphate
--osteoblasts (from mesenchyme) make and extrude collagen making the bone matrix, then emit alkaline phosphatase which cleaves pyrophosphate permitting precip of calcium and phosphate along collagen fibers
--without osteoblast action mineralization is inhibited by pyrophosphate
--deficit of pyrophosphate or excess calcium or phosphate can cause mineralization of soft tissues such as arteries, veins (esp in pelvic region), degenerating tissues, blood clots, etc. crunchy tissue as vs fibrotic.
--osteoclasts from hematopoietic stem cells resorb bone by secreting acid and hydrolases.
--inflammation affects pyrophosphate levels, increasing mineralization --> bone spurs, athlerosclerosis, etc.
--stress generates piezoelectric effect that initiates osteoblast & clast action to remodel bones relative to stress

PROBLEMS PROBLEMS

--Hyperparathyroid, too much calcium in blood, bones get eaten up, causes kidney stones, nervous sys depression, abdominal pain, ulcers, low appetite, depressed lreaxation of heart during diastole
--women more likely to have tumor in parathyroid gland, caused by stim by prenancy and lactation

--HyPOparathyroid, not enough calcium in blood, osteoclasts are bored, can cause muscle tetany esp in larynx, obstucting breathing

--Osteomalacia = demineralization of bone from low calcium or vit D, can be caused by kidney damage

--Osteoporosis = loss of bone matrix, not just calcium, can be cause by hyperparathyroid, inactivity, low vit C, low estrogen (esp post menopause), low growth hormone (old age), hyperadrenalism (Cushing's: cortisol decreases protein deposition in bod incl bones)

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