Kidney Handling of Calcium and Phosphate: Regulation and Transport Mechanisms

Calcium (Ca²⁺)

An essential mineral that the kidney helps to balance in the body.

Phosphate (PO₄³⁻)

An essential mineral that the kidney helps to balance in the body.

Ionized Calcium

50% of plasma calcium; active and diffusible, filtered by the kidney.

Calcium Bound to Anions

10% of plasma calcium; diffusible and filtered by the kidney.

Calcium Bound to Plasma Proteins

40% of plasma calcium; non-diffusible and not filtered by the kidney.

Filtered Calcium

Only ~60% of plasma calcium is filterable by the kidney.

Renal Calcium Reabsorption

Of the 60% filtered calcium, 99% is reabsorbed and 1% is excreted in urine.

Proximal Tubule (PCT)

Reabsorbs 65% of calcium, mostly paracellular with Na⁺ & H₂O, not regulated by PTH.

Thick Ascending Limb (Loop of Henle)

Reabsorbs 25-50% of calcium, regulated by PTH.

Distal Convoluted Tubule (DCT)

Reabsorbs 8-10% of calcium, only transcellular, regulated by PTH.

Paracellular Pathway

Calcium transport between tubular cells; moves with water and sodium.

Transcellular Pathway

Calcium transport through the cell via calcium channels, calcium ATPase pump, and Na⁺/Ca²⁺ exchanger.

Parathyroid Hormone (PTH)

Released when plasma calcium is low; increases calcium reabsorption in the Loop of Henle and DCT.

Vitamin D (Calcitriol)

Increases calcium reabsorption in the kidney and enhances intestinal absorption of calcium and phosphate.

Calcium-Sensing Receptors (CaSR)

Found in the Loop of Henle and PCT; reduces calcium reabsorption when plasma calcium is high.

Low ECF Volume / Low BP

Increases sodium and calcium reabsorption.

Acidic Blood

Increases filterable calcium as less calcium is bound to protein.

Alkaline Blood

Decreases free calcium, resulting in more calcium bound to protein.

High Plasma Phosphate

Increases PTH, leading to increased calcium reabsorption and decreased phosphate reabsorption.

Filtered Phosphate

~90% of plasma phosphate (diffusible forms) is filtered.

Phosphate Reabsorption

80% in PCT, 10% in DCT, and 10% excreted.

Sodium-Phosphate Co-Transporters

Transport mechanism in the apical membrane for phosphate reabsorption.

Transport Maximum (Tm)

Reabsorption of phosphate reaches Tm quickly, leading to excess phosphate spilling into urine.

Hormonal Control of Phosphate

PTH decreases phosphate reabsorption and increases excretion; Vitamin D increases phosphate reabsorption and decreases excretion.

Calcium

A mineral that plays a vital role in various physiological processes, existing in different forms in plasma.

Phosphate

An essential mineral that, along with calcium, is crucial for maintaining homeostasis in the body.

% Filtered Calcium

~60%

% Filtered Phosphate

~90%

PCT Calcium Reabsorption

65%

PCT Phosphate Reabsorption

80%

Major Site of Reabsorption for Calcium

Proximal Tubule

Hormonal Regulation of Calcium

PTH ↑ reabsorption, Vit D ↑ reabsorption

Hormonal Regulation of Phosphate

PTH ↓ reabsorption, Vit D ↑ reabsorption

Excretion of Calcium

~1%

Excretion of Phosphate

~10%

Coupled With Calcium

Sodium & water

Coupled With Phosphate

Sodium

Special Feature of Calcium Regulation

CaSR sensors, cAMP signaling

Special Feature of Phosphate Regulation

Transport maximum reached easily

P-L-D Mnemonic

Calcium path: PCT → Loop → DCT

PTH and Calcium Relationship

PTH loves Ca²⁺, hates PO₄³⁻

Vitamin D and Calcium Relationship

Vit D loves both Ca²⁺ and PO₄³⁻

ACE for Calcium

ATPase + Ca²⁺ channel + Exchanger

Phosphate Reabsorption Path

Phosphate Follows PCT

Filtered Calcium Forms

About 50% is free ionized calcium, 10% is bound to anions, and 40% is bound to plasma proteins.

Calcium Excretion Mechanism

99% of filtered calcium is reabsorbed, leaving only 1% excreted in urine.

Proximal Tubule Calcium Reabsorption

Coupled with sodium and water, mostly paracellular.

Thick Ascending Limb Calcium Reabsorption

About 25-50% of filtered calcium is reabsorbed here.

Distal Convoluted Tubule Calcium Reabsorption

About 8-10% of calcium is reabsorbed only via the transcellular route.

Epithelial Calcium Channels

ECaC/TRPV5

Low plasma calcium

Stimulates PTH secretion through calcium-sensing receptors (CaSR).

PTH

Increases calcium reabsorption in the thick ascending limb and distal tubule (but not in the proximal tubule).

cAMP

Acts via cyclic AMP and protein kinase A (PKA) to phosphorylate proteins that enhance calcium transport.

Calcium-Sensing Receptor (CaSR)

Detects high plasma calcium and reduces calcium reabsorption, especially in the thick ascending limb.

Na⁺-K⁺-2Cl⁻ symporter

Inhibited by binding of calcium to CaSR, altering membrane potential and decreasing driving force for calcium reabsorption.

Sodium and Volume Changes

Conditions that increase sodium reabsorption (e.g., low ECF volume, low blood pressure) also increase calcium reabsorption.

Blood pH

Hydrogen ions compete with calcium for binding to albumin.

Acidosis

High H⁺ leads to fewer calcium ions binding to albumin, resulting in increased free calcium and more filtered calcium.

Alkalosis

Low H⁺ leads to more calcium binding to albumin, resulting in decreased free calcium and kidney reabsorbing more calcium.

Plasma Phosphate

Calcium and phosphate levels are interconnected; high plasma phosphate stimulates PTH release.

PTH effect on phosphate

Increases phosphate excretion but enhances calcium reabsorption.

Renal Handling of Phosphate

About 90% of phosphate is filtered by the kidney; reabsorption occurs mainly in the proximal tubule (~80%) and distal tubule (~10%).

NaPi cotransporters

Reabsorb phosphate by moving it along with sodium; can become saturated, causing phosphate to spill into urine.

PTH phosphaturic effect

Increases phosphate excretion.

Vitamin D effect on phosphate

Increases phosphate reabsorption by upregulating NaPi transporters, thus reducing excretion.

In short, Vitamin D conserves phosphate by telling the kidneys to take it back instead of letting it go out in the urine.

PTH vs. Vitamin D in the Kidney

PTH increases calcium reabsorption and decreases phosphate reabsorption; Vitamin D increases both calcium and phosphate reabsorption.

Summary Trick

Vitamin D increases reabsorption of both calcium and phosphate; PTH increases calcium reabsorption but decreases phosphate reabsorption.

Kidney's role in mineral homeostasis

Regulates both calcium and phosphate balance through precise filtration and reabsorption mechanisms.

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