5. Regulation of Ca2+, Pi, Mg2+ Flashcards
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?
The ionized Ca and diffusible calcium complexes are filtered through the glomerlus.
60%
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?
Hyperalbuminemia (increased albumin) decreases the plasma [ca] because more is bound
Hypoalbuminemia (decreased protein) increases the plasma [ca] because more H+ is bound
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?
calcium and phophate plasma concentrations via bone resorption
In the bone calcitriol promotes resorption, in the intestine it increase Ca and P absorption, and in the kidney?
Increases calcium and phosphate reabsorption (2nd time so re)
Calcitonin ‘tones’ down calcium (opposes PTH) and is stimulated by hypercalemia. It lowers ca/p levels by inhibiting bone resorption and in the kidneys?
promotes phosphate and calcium excretion
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)
reabsorbs ca in the dct
decreases reabsorption of p in the pct
decreases na/h antiporter
decreases hco3 reabsorption
PTH can cause hypercalemia, hyperchloremic metabolic acidosis and what?
hypophosphatemia
Calcium sensing receptor (CaSR) on the basolateral side, monitors calcium levels and inhibits its reabsorption when calcium is high, how does it do this?
Inhibits NKCC2 in the TAL, so there is no gradient for Ca to pass paracellularly
What is the calculation for filtered load of Ca?
GFR * plasma concentration * (60% filterability)
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?
8% is reabsorbed but this is the major site of regulation!
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?
contraction increases Ca reabsorption becuase an increase In Na and h2o reabsoroption allows more ca reabsorption
this is opposite for volume expansion
In the TAL, dependent upon the lumen positive charge for paracellular, ADH stimulates reabsorption here, how?
ADH increases aqp2 in the CD AND INCREASE NACL reabsorption in the TAL
In the DT, there is a lumen negative voltage, ca reabsorption is active and crosses the apical membrane via which transporter?
TRPV5/6
then crosses basolateral membrane via Na/Cl exchanger (NCE)
What 2 things stimulate reabsorption via the TRPV5/6 transporter in the DT for calcium?
PTH, Vitamin D/calcitriol
Acidemia increases Ca2 excretion because acidosis inhibits trpv5/6. while alkalemia does what?
decreases ca2+ excretion because it stimulates the transporter to move more ca into the blood
How do you calculate the filtered load of phosphate?
Filtered load= GFR * plasma concentration * %filterability
80% of phosphate is reabsorbed by the PT. Phosphate reabsorption is driven by NaKATPase and associated with Na uptake using?
Na-P symporter
Once the Phosphate is symporteed across the apical membrane, how does the phosphate cross the basolateral membrane to be reabsorbed into the blood?
the transporter that does this is currently unknown
FGF23 is secreted by bones in response to?
PTH calcitriol and hyperphophetemia, inhibiting the Na/P symporter, preventing reabsorption of phosphate
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?
in the kidney 25-hydroxycholecalciferol is combined with 1A-hydroxylase (CYP1A) to make the active form of vitamin D (1,25(OH)2D3 / calcitriol
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?
upregulated by low calcium, low phosphate, hight PTH
downregulated by high calcium via CaSR
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?
lowers serum phosphate by increasing renal excretion
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?
PTH activates Ca channels to increase calcium plasma
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?
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
What are the molecular steps for PTH action in the proximal tubule (5)? might not need to know this?
- pth binds its receptor
- AC activates cAMP
- cAMP activates protein kinases
- which phosphorylate the Na/P transporter
- Inhibits which results in phosphaturia (inc P in urine)
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?
Na and K via NKCC2, which depends on the lumen positive voltage of TAL
What can inhibit the NKCC2 transporter in the TAL?
CaSR inhibtis the NKCC2 which ruins the lumen positive charge and results in decreased absorption of Mg
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?
apical via the TRPM6 and basolateral is currently unknown
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?
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)
