Calcium, Phosphate, Magnesium Flashcards
Role of Phosphate in the body
- Constituent of bone
2. Urinary buffer for H+
T or F all plasma phosphate is filtered across the gomerulus?
FALSE
-only phosphate that is not bound to protein (90%) gets filtered through
How and where in the nephron is phosphate reabsorbed?
In the Proximal tubule only via an Na+-Phosphate cotransporter
Is there a limit to how much phosphate can be reabsorbed?
YES
- reabsorption is saturable (similar to glucose)
- once it reaches its saturation limit, the rest will be excreted
Parathyroid hormone (PTH) effect on reabsorption of phosphate?
Inhibits reabsorption (promotes excretion) of Phosphate?
- inhibits the Na-Phosphate cotransporter
MOA of Parathyroid hormone (PTH) on reabsorption of phosphate
PTH binds basolateral receptor in proximal tubule cell, which is couple to Adenylyl cyclase via a Gs protein
- AD converts ATP to cAMP which utimately leads to phosphorylation and inhibition of the Na-Phosphate cotransporter.
What in the urine would indicate that PTH is functioning?
- Increased Phosphate levels
- Urinary cAMP
- cAMP is excreted through a luminal membrane transporter
Inherited disorder caused by a defect in the PTH receptor, it’s Gs protein, or adenylyl cyclase causes and inherited disorder called?
Pseudohypoparathyroidism
- renal cells are resistant it PTH action despite elevated levels
- Leads to phosphate and cAMP wasting
Where is calcium found in the body?
99% within the bone
- rest in the ICF and ECF
What regulates the amount of Calcium in the plasma?
PTH
Compare the reabsorption of calcium to that of sodium
Pattern of reabsorption is similar:
- about 99% reabsorbed
- Na and Ca reabsorption coupled in the PT and LOH
- NOT couple in the DT!
Describe the filtration of calcium
Only the calcium that is not bound to plasma proteins may get filtered
- 60% of plasma calcium not bound and can get filtered
- filtered load = GFRxP[Ca]x.60
What happens to calcium when Na+ reabsorption is inhibited in the proximal tubule?
Calcium is also inhibited
- they are coupled in the PT
How is calcium reabsorbed in the Thick AL of the LOH?
Paracellular reabsorption driven by the lumen-positive potential difference generated by the Na/K/2Cl - cotransporter
- important for loop-diuretic action
Effect of loop-diuretic on calcium reabsorption?
Inhibit Ca reabsorption to the same extent as sodium reabsorption
- via blocking the Na/K/2Cl - cotransporter
- loop diuretics also helpful in tx of hypercalcemia
3 special features of Ca reabsorption in the DISTAL tubule?
- DT is the only nephron segment where Na and Ca are NOT coupled
- Ca reabsorption is regulated by PTH
- Thiazide diuretics have opposite effect as the other classes of diuretics in regards to Ca reabsorption
Effect of PTH on calcium reabsorption? Where does this occur?
PTH increases reabsorption in DT
- via a basolateral receptor called TRPV5
The effect of PTH on the nephron?
- Decreases Phosphate reabsorption (PT)
2. Increases Calcium reabsorption (DT)
Thiazide diuretics effects on calcium reabsorption?
Increase Ca+ reabsorption
- decreases excretion through urine and thus the likelihood of Ca2+ stone formation
Once reabsorbed, how does calcium get across the basolateral membrane?
- Na+/Ca2+ exchanger (NCX1), 2. Plasma membrane ATPase (PMCA1b
Effect of Klotho protein on calcium in the nephron?
- Enhances TRPV5 receptor (Luminal)
2. Klotho enhances Na+/K+-ATPase surface expression that in turn activates NCX1-mediated Ca2+ efflux.
Kidneys role in Vitamin D metabolism?
Calcidiol is metabolized to calcitriol (1,25(OH)2D) by the 1α-hydroxylase (CYP27B1) enzyme in the kidney.
Effect of Calcitrol (1,25(OH)2D) on PTH?
Calcitrol inhibits transcription of PTH in parathyroid tissue
How is the 1α-hydroxylase (CYP27B1) enzyme in the kidney regulated?
- Inhibited by:
1. Calcitrol (via VDR)
2. FGF23 - activated by PTH!
What stimulates parathyroid hormone?
- Decreased Plasma Calcium (via CaSR)
- Increased plasma Phosphate
- FGF23
The total effects of PTH
- Increases Ca reabsorption
- Decreases phosphorus reabsorption
- Increases Calcitrol (1,25(OH)2D) production
- Increase bone calcium resorption
Function of FGF23?
- Decreases phosphate reabsorption (phosphaturic)
2. Suppressor of 1-alpha hydroxylase in the kidney