LM 1.0: Calcium and Phosphate Metabolism

Question 1

which 4 organ systems are associated with calcium and phosphate metabolism

Answer 1

1. GI
2. endocrine
3. renal
4. bones

Question 2

where is most calcium stored in the body?

Answer 2

in the bones as hydroxyapatite

Question 3

what form of calcium is in the plasma?

Answer 3

45% free ionized form

45% bound to proteins; mostly albumin

10% complexed with anions like citrate, sulfate and phosphate

only the free ionized form is physiologically active yet blood tests measure all the types of calcium in the blood

Question 4

what is the corrected calcium form?

Answer 4

measured calcium + (0.8(4-albumin)

this corrects the calcium level in cases of hypoalbuinemia

Question 5

where is phosphate stored in the body?

Answer 5

in the bones as hydroxyapatite

the remainder of the body’s phosphate is intracellular as a component of phospholipids in cell membranes, DNA, RNA, ATP and ADP

the small fraction of phosphate that is in the serum exists as circulating phospholipids and inorganic phosphate

inorganic phosphate consists of HPO4 and H2PO4 in a 4:1 ratio –> the sum of HPO4 and H2PO4 is what is physiologically active and what gets measured in blood tests

Question 6

what does parathyroid hormone do?

Answer 6

PTH increases serum calcium and decrease serum phosphate

Question 7

what is the function of calcitriol?

Answer 7

aka the active form of vitamin D

it’s derived from diet or a cholesterol-derived precursor with help from UV light and it requires enzymatic steps in the liver and kidney to become active

it increases both serum calcium and phosphate

Question 8

where is PTH synthesize?

Answer 8

secreted by the chief cells of the parathyroid gland

Question 9

how is PTH regulated?

Answer 9

it’s regulated by serum calcium levels

increased calcium inhibits PTH while decreased calcium increases PTH production

however, there is an absolute maximum and minimum for PTH levels no matter how high or low calcium levels get

Question 10

how does magnesium play a role in PTH regulation?

Answer 10

magnesium plays a parallel role to calcium

small decreases in Mg lead to increase of PTH and vice versa

however, with significant magnesium depletion there is decreased PTH secretion and PTH resistance which leads to hypocalcemia

Question 11

what are the precursors for calcidiol?

Answer 11

1. dietary sources like fish
2. vitamin D3
3. vitamin D2
4. 7-dehydrocholesterol which gets converted to vitamin D3 by the sun

D2 and D3 get converted to calcidiol happens in the liver via 25-hydroxylase aka CYTP4502R1

then calcidiol gets converted to active vitamin D (calcitriol) in the kidney via vitamin D 1-alpha hydroxylase aka CYTPP4527B1

lower serum phosphate

Question 12

what effects the activity of vitamin D 1-alpha-hydroxylase?

Answer 12

1. PTH

PTH increases activity of 1-alpha-hydroxylase which converts calcidiol to calcitriol

2. serum phosphate

high serum phosphate inhibits vitamin D 1-alpha-hydroxlyase while low serum phosphate stimulates it

3. fibroblast growth factor 23 inhibits vitamin D 1-alpha-hydroxlyase (FGF23)

it’s released by osteocytes and osteoblasts in response to PTH and hyperphosphatemia

Question 13

how is calcium and phosphate homeostasis maintained?

Answer 13

1. calcium and phosphate are absorbed from the GI tract into the blood which is stimulated by calcitriol

from the blood, Ca and Ph undergo continuous exchange with bone – PTH inhibits bone formation and stimulates bone respiration while calcitriol only directly stimulate resorption

2. Ca and Ph can also go from the blood to the kidney – after filtration, PTH stimulates reabsorption of Ca but blocks reabsorption of Ph – calcitriol stimulates reabsorption of both Ca and Ph

PTH needs to cause phosphate excretion because otherwise, it would complex with Ca and there would be no net increase in free ionized Ca

FGF23 inhibits phosphate reabsorption in the renal tubules too – it’s expression is stimulated by hyperphosphatemia

Question 14

what is the function of calcitonin?

Answer 14

calcitonin blocks bone resorption secreted by the C cells of the thyroid but its role is minimal

Question 15

how does pH effect calcium/phosphate metabolism

Answer 15

PTH is regulated by acid base status on top of regulation b ycalcium

academia leads to increased PTH which acts on the kidney to increase urinary excretion of phosphate which increases the buffering capacity of H+ ions excreted in the distal tubule – with more h+ ions buffered, more can be excreted which increases serum pH

Question 16

how do you measure vitamin D levels?

Answer 16

you can test for:

1. 25(OH) vitamin D aka calcidiol

or

2. 1,25(OH) vitamin D aka calcitriol

there are issues when it comes to measuring vitamin D levels because:
1. there is lack of standardization of different assays

2. lack of consensus on what constitutes normal vitamin D level
3. lack of consensus on treatment implications after a low level is detected
4. confusion among providers regarding the clinical relevance of the different forms of vitamin D