Calcium and Phosphate Regulation

Regulation of Calcium and Phosphate
Most Ca in our bodies is in bone-reserve if we need it.
PTH activates vitamin D.
Oxalates in diet may bind Ca so it is not free to be absorbed.
Gut absorbs 700 mg and secretes 600 mg.
Bone breakdown releases Ca and phosphate.
Remember the terminology.
Forms of Ca:
Normal plasma Ca in 3 units:
mg/dL is total Ca content. 3 forms:
1. bound to plasma protein
2. complexed with anions
3. free Ca2+, Ca++, or free Ca.
Bound to protein is not filtered- the other 2 forms are.
Phosphate- less is bound to protein. More is complexed to cations. Know the numbers for phosphate and how it is different. Plasma phosphate varies- doubles in adults in the afternoon- nobody knows why. Also double listed value in children. Why important to regulate:
Muscle tetany. The ionized Ca is what affects things.
Other units- 10 mg/dl=2.5 mM or 5 mEq/L.
Kidneys are where Ca concentration can be regulated.
Phosphates are used as preservatives, so intake can be quite high. People who drink colas with phosphate can have high intake.
4 parathyroid glands. PTH protects against hypocalcemia. It is a protein with about 84 AAs. Many fragments circulate in plasma. For valid measurement of this hormone, need 2-site immunoassay for C and N terminal ends so the assay does not react for just one end, picking up a fraction in fragmented inactive form.
Graph in our handout is deceptive. PTH and calcitonin- slopes should be steeper. People with chronic low Ca- system regultes PTH- it becomes more sensitibve. Gland senses ionized Ca.
PTH is regulated by decreased degradation of hormone in gland.Gland makes and breaks down PTH a lot.
People who do not convert vitamin D can be treated with very high doses vitamin D and it will work.
Calcitonin or thyrocalcitonoin comes from thyroid. Weak hormone- probably almost no effect under most circumstances. To study- infuse Ca. That can be dangerous, so inject pentagastrin to look at secretion.
Response of PTH calciferolaxis to hypocalcemia graph- induced hypocalcemia- lowers serum Ca levels. PTH goes up 2.5x. Ca back up, PTH falls. PTH stimulates the activation of vitamin D, with a delay of 12-24 hours. Urinary cAMP spikes as well.
Other influences:
excess glucocorticoids, estrogens keep bones strong.
Text image- osteoBLasts build bone. Some get trapped inside and are called osteocytes. They connect to osteoblasts on surface by tight junctions. Can ship out Ca. OsteoCLasts are multinucleated cells which cause bone breakdown.
Osteocalcin secreted by osteoblasts. Osteocytes have most rapid cycling Ca into and out of bone. between cells and bone is bone fluid, high in Ca and phosphate. Ca can be sent out from osteocytes via osteoblasts.
Osteoclasts- no PTH receptors. Signal probably comes from osteoblasts through cytokine signalling. This signaling is inhibited by estrogens, which is how they protect bone from breakdown. Calcitonin also inhibits osteoclasts.
Ca pump from osteoblast sends Ca out to extracellular fluid.
See fig 4 for summary.
Kidneys:
Regulation in distal tubule is stimulated by PTH and maybe vitamin D. Excretion Ca decreased by PTH and vitamin D, unless a huge amount of calcium suddenly is coming in.
PTH acts on proximal tubule for phosphate to DECREASE reabsorption and flush it out. Broad range, highly variable.
Vitamin D precursor is cholesterol. B ring opened in vitamin D. 3 step activation: skin/diet, liver (calcidiol), kidney (calcitriol1- or 24- hydroxylation)
Liver uses enzyme 25-hydroxylase which is negatively regulated by 25-OH vitamin D.
What does vitamin D do? increases Ca and Phosphate absorption in the intestine.
Ca binding protein 2 functions: binds Ca absorbed to maintain gradient so more is absorbed. Ca levels kept low to not foul up metabolism.
2. increases activity of Ca pump to ECF. Vitamin D also promoted phosphate absorption by mechanisms nobody has paid attention to.
Notes on Problem Set:
Functions of Bone:
1. Support vs. gravity
2. movement muscles attach and work on
3. protection (skull, rib cage, pelvis)
4. Calcium reservoir (and phosphate)
5. blood cell formation in marrow
Other questions:
2 and 3 gone over in class today.
4. Too much PTH- primary hyperparathyroidism
A. Ca increased, because high PTH stimulates osteoclasts, resulting in bone breakdown and osteoblast Ca secretion. Kidneys increase reabsorption. Intestine- indirectly increases Ca absorption by increase in vitamin D. Urinary Ca excretion increases, esp chronically. Kidneys overwhelmed by increase in filtered load. Hypercalciuria happens.
B Phosphate: more from bone and intestine, decreased reabsorption in kidneys. increased excretion from kidneys. Plasma phosphate stays relatively constant, or slight decrease.
Likely to get kidney stones. Avoid stones- drink a lot of water.
C. Changes in bone metabolism:
demineralized bones, more likely to break.
5:
damage to proximal tubules AND glomeruli(add that part).
BSAP is from osteoblasts, stimulated by PTH.
proteinuria caused by protein leakage. Liver is fine. 1st step vitamin D activation probably OK. Step 2 activation of vitamin D is in proximal tubule- impaired 1,25 vitamin D formation. Less absorption Ca. Stimulates PTH.
A. low bone density.
B. 1,25 low.