5. Regulation of Ca2+, Pi, Mg2+

Question 1

Calcium exists in ionized form, bound to plasma proteins or complexed in non-ionized form. 99% is stored in bone. Which of the three mentioned above are filtratible and what percent of total calcium?

Answer 1

The ionized Ca and diffusible calcium complexes are filtered through the glomerlus.

60%

Question 2

Hydrogen and calcium compete for binding sites on plasma albumin. In acidosis there is more free calcium in circulation and in alkalosis there is more calcium bound to albumin. What happens during hypo/hyperalbunemia?

Answer 2

Hyperalbuminemia (increased albumin) decreases the plasma [ca] because more is bound
Hypoalbuminemia (decreased protein) increases the plasma [ca] because more H+ is bound

Question 3

Vitamin D is also known as calcitriol and many other names. Calcitriol works with PTH to resorb bone (osteoclasts) which results in an increase in?

Answer 3

calcium and phophate plasma concentrations via bone resorption

Question 4

In the bone calcitriol promotes resorption, in the intestine it increase Ca and P absorption, and in the kidney?

Answer 4

Increases calcium and phosphate reabsorption (2nd time so re)

Question 5

Calcitonin ‘tones’ down calcium (opposes PTH) and is stimulated by hypercalemia. It lowers ca/p levels by inhibiting bone resorption and in the kidneys?

Answer 5

promotes phosphate and calcium excretion

Question 6

PTH (parathyroid hormone) increases osteoclastic resoprtion in the bone, increases Ca/P absorption in the intestines indirectly via Vitamin D production and in the kidneys? (4)

Answer 6

reabsorbs ca in the dct
decreases reabsorption of p in the pct
decreases na/h antiporter
decreases hco3 reabsorption

Question 7

PTH can cause hypercalemia, hyperchloremic metabolic acidosis and what?

Answer 7

hypophosphatemia

Question 8

Calcium sensing receptor (CaSR) on the basolateral side, monitors calcium levels and inhibits its reabsorption when calcium is high, how does it do this?

Answer 8

Inhibits NKCC2 in the TAL, so there is no gradient for Ca to pass paracellularly

Question 9

What is the calculation for filtered load of Ca?

Answer 9

GFR * plasma concentration * (60% filterability)

Question 10

65-70% of calcium is reabsorbed in the proximal tubule passivley following Na and water reabsorption. in the TAL a lumne positive voltage drives ca (and mg) reabsorption paracellularly. In the distal tubule?

Answer 10

8% is reabsorbed but this is the major site of regulation!

Question 11

in the proximal tubule, it is primarily paracellular with some transcellular via caatpase and Na/Ca antiporter. What does volume contraction do to Ca reabsorption? how about expansion?

Answer 11

contraction increases Ca reabsorption becuase an increase In Na and h2o reabsoroption allows more ca reabsorption
this is opposite for volume expansion

Question 12

In the TAL, dependent upon the lumen positive charge for paracellular, ADH stimulates reabsorption here, how?

Answer 12

ADH increases aqp2 in the CD AND INCREASE NACL reabsorption in the TAL

Question 13

In the DT, there is a lumen negative voltage, ca reabsorption is active and crosses the apical membrane via which transporter?

Answer 13

TRPV5/6

then crosses basolateral membrane via Na/Cl exchanger (NCE)

Question 14

What 2 things stimulate reabsorption via the TRPV5/6 transporter in the DT for calcium?

Answer 14

PTH, Vitamin D/calcitriol

Question 15

Acidemia increases Ca2 excretion because acidosis inhibits trpv5/6. while alkalemia does what?

Answer 15

decreases ca2+ excretion because it stimulates the transporter to move more ca into the blood

Question 16

How do you calculate the filtered load of phosphate?

Answer 16

Filtered load= GFR * plasma concentration * %filterability

Question 17

80% of phosphate is reabsorbed by the PT. Phosphate reabsorption is driven by NaKATPase and associated with Na uptake using?

Answer 17

Na-P symporter

Question 18

Once the Phosphate is symporteed across the apical membrane, how does the phosphate cross the basolateral membrane to be reabsorbed into the blood?

Answer 18

the transporter that does this is currently unknown

Question 19

FGF23 is secreted by bones in response to?

Answer 19

PTH calcitriol and hyperphophetemia, inhibiting the Na/P symporter, preventing reabsorption of phosphate

Question 20

UV light from the sun on the skin activates Vitamin D synthesis. In the liver, the vit d is made into its main circulatory form with low activity before being made into what in the PCT via what enzyme?

Answer 20

in the kidney 25-hydroxycholecalciferol is combined with 1A-hydroxylase (CYP1A) to make the active form of vitamin D (1,25(OH)2D3 / calcitriol

Question 21

Calcitriol is made by the pct epithelial cells via 1a-hydroxylase. what are the things that upregulate the enzyme (3) and what inhibits the enzyme?

Answer 21

upregulated by low calcium, low phosphate, hight PTH

downregulated by high calcium via CaSR

Question 22

FGF23 increases phosphate excretion, calcitriol increases serum P by increasing intestinal P absorption, insulin lowers serum levels by shifting phosphate into cells while PTH does what to phosphate?

Answer 22

lowers serum phosphate by increasing renal excretion

Question 23

PTH is the most important hormone that regulates P excretion because it inhibits the NaP transporters and NaH antiporter in the apical membrane of PT cells… What happens with PTH and calcium at the DCT?

Answer 23

PTH activates Ca channels to increase calcium plasma

Question 24

chronic acidosis increase Pi excretion becuase you have an increase in H+ which would increase the amount of Na inside the cell, so the Na/P symporter would be less active because less Na would be needed in the cell, resulting in an increased excretion of P. what about chronic alkalosis?

Answer 24

decreases Pi excretion, due to the low H+, Na concentration will be lower in the cell so the Na/P tranporter will need to ‘pick up the slack’ which would transport more Na and P into the cell to be reabsorbed

Question 25

What are the molecular steps for PTH action in the proximal tubule (5)? might not need to know this?

Answer 25

1. pth binds its receptor
2. AC activates cAMP
3. cAMP activates protein kinases
4. which phosphorylate the Na/P transporter
5. Inhibits which results in phosphaturia (inc P in urine)

Question 26

20% Mg is reabsorbed in the PT via paracellular following Na and h2o. In the TAL, 70% is reabsorbed, paracellularly and depends on the uptake of?

Answer 26

Na and K via NKCC2, which depends on the lumen positive voltage of TAL

Question 27

What can inhibit the NKCC2 transporter in the TAL?

Answer 27

CaSR inhibtis the NKCC2 which ruins the lumen positive charge and results in decreased absorption of Mg

Question 28

In the distal tubule, 10% mg is reabsorbed. the [mg] is the same in and outside the cell so electrical potential is the primary driver of Mg influx. How does Mg cross the apical and basolateral membrane to be reabsorbed?

Answer 28

apical via the TRPM6 and basolateral is currently unknown

Question 29

When there is a dietary depletion of Mg, mg reabsorption is increased via paracellular transport. PTH, metabolic alkalosis and ECF volume contraction all increase Mg reabsorption. What are the main things that decrease Mg reabsorption?

Answer 29

metabolic acidosis decreases paracellular permabililty of Mg

ECF volume expansion, d/t less Na/H2o reabsorbed in PT so not as much mg reabsorbed as well (follows na/h2o)