Regulation Of Calcium/phosphate/magnesium

Question 1

Distribution and balance of phosphate

Answer 1

1) Intake 1400 mmol /day via GI system
- 1100 mmol is actually absorbed

2) ECF possesses 500 mmol at any given time, shuttling potassium to the bone, soft tissues and to be excreted out to the gut and kidneys
- bones have the highest storage of phosphate

3) kidneys reabsorb 6100 mmol/day, filter 7000 mmol/day and secrete 200 mmol/day
4) urine excretes roughly 900 mmol per day

Question 2

How is total plasma phosphate found in the plasma

Answer 2

50% = ionized H2PO4 and HPO4(2-)
- used as buffer

40% = diffusible phosphate complexes

10% = nondiffusible protein bound phosphate

total in plasma = 4.2 mg/dL

Question 3

Where does phosphate get filtered the most along the nephron?

Answer 3

PCT = 70%

• Na+-phosphate cotransporter
• **PTH presence inhibits this

Thick descending limb (straight limb) = 15%

other 15% is excreted

Question 4

How is phosphate reabsorbed in the PCT?

Answer 4

Via Na+/PO4(-3) cotransporters

Question 5

How does parathyroid hormone effect phosphate reabsorption

Answer 5

PTH binds to PTH receptors on PCT cells

• this is a Gs protein coupled receptor which activates and stimulates adenylate Cyclase activations and production of cAMP
• leads to PK activation and phosphorylation of Na+/phosphate cotransporter (turns it off)

leads to increases in urinary cAMP and phosphate = hallmark of PTH activity

Question 6

Distribution and balance of calcium

Answer 6

1) Intake 1000 mmol /day via GI system
- 500 mmol is actually absorbed

2) ECF possesses 1000 mmol at any given time, shuttling potassium to and from liver/muscles/bone/RBCs
- Muscles use the most/have the most potassium at any time!

3) kidneys reabsorb 800 mmol/day, filter 810 mmol/day and secrete 50 mmol/day
4) urine excretes roughly 60 mmol per day

Question 7

How is total plasma calcium (extracellular) found in the body?

Answer 7

45% = ionized calcium

40% = unfilterable protein bound calcium

15% = diffusible calcium complexes

total calcium = 10 mg/dL

because 40% is unfilterable, when calculating total filtered load of calcium, you have to multiply total plasma calcium concentration by 0.6 before multiplying by GFR

Question 8

How is calcium primary reabsorbed in the nephron?

Answer 8

67% = PCT
- most is absorbed by “solvent drag” with sodium

25% = TAL

• *gets blocked by furosemide/ loop diuretics
• most is absorbed via Na/K/Cl cotransporter

8% = DCT
- *gets enhanced by PTH and thiazide diuretics

Question 9

How does the TAL regulate its ability to reabsorb calcium?

Answer 9

It possess a Ca2+ sensing receptor that faces the interstital space
- once calcium builds up in high levels, this receptor turns of the Na/K/Cl cotransporter

a sort of “self-regulation

Question 10

What is the most important regulator of renal calcium reabsorption ?

Answer 10

PTH
- stimulates calcium reabsorption in the DCT By binding to DCT specific-PTH Gs receptors which upregulated cAMP/AC action

Question 11

How is total plasma magnesium found in the body?

Answer 11

62% = ionized magnesium

31% = nondiffusible protein bound magnesium

7% = diffusible magnesium complexes

Total = 2.0 mg/dL

Question 12

Where is most magnesium reabsorbed in the nephron?

Answer 12

60% = TAL
- via K+ being reabsorbed by Na/K+/2Cl- channel and then being sent back into the lumen to create an electro gradient to push calcium and magnesium through intercellualrly

30% = PCT

5% = DCT

Question 13

Pseudohypoparathyrodism

Answer 13

Genetic defect in the PTH receptor on the PCT which prevents PCT from reacting to PTH
- results in decreased urinary cAMP and phosphate levels (which is also seen in actually hypoparathyroidism)