Aims Potassium phosphate calcium and magnesium excretion Readings

Aims • Potassium, phosphate, calcium, and magnesium excretion • Readings: Sherwood, Chapter 14 & Guyton, Chapter 29.

Potassium • 98% in cells only 2% in extracellular fluid. • Most excretion of K+ is done by the kidneys ~90%. • Extracellular K+ levels are precisely controlled. • Too much (hyperkalemia) • Too little (hypokalemia). • Cells serve as an “overflow” for K+. Guyton’s Textbook of Medical Physiology 29 -1

Regulation of Potassium distribution (Extracellular vs. Intracellular) • Increase Intracellular K+ • Insulin & Aldosterone • Catecholamines (Epinephrine) • Metabolic alkalosis Guyton’s Textbook of Medical Physiology table 29 -1

Regulation of Potassium distribution (Extracellular vs. Intracellular) • Increase Extracellular K+ • Metabolic acidosis • Cell lysis • Strenuous exercise Guyton’s Textbook of Medical Physiology table 29 -1

Regulation of Potassium distribution (Extracellular vs. Intracellular) • Increased extracellular fluid osmolarity. – Causes water to leave the cell resulting in an increase in the cellular concentration of K+. – This results in an increase in K+ diffusion out of the cell.

Renal Potassium Excretion Amount of K+ excreted is determined by: Rate of K+ filtration. Usually fairly constant at ~750 m. Eq/day. Guyton’s Textbook of Medical Physiology 29 -2

Renal Potassium Excretion Amount of K+ excreted is determined by: Rate of K+ reabsorption. 65% of the filtered K+ is reabsorbed in the proximal tubule. 25 -30% of the filtered K+ is reabsorbed in the thick ascending limb of the loop of Henle. Remember this is due to 1 -Na+-2 Cl-1 K+ cotransporter in the lumenal membrane. Guyton’s Textbook of Medical Physiology 29 -2

Renal Potassium Excretion Amount of K+ excreted is determined by: Rate of K+ secretion. The cause of most daily variation in K+ excretion! In the late distal and cortical collecting tubules K+ can be reabsorbed or secreted. Guyton’s Textbook of Medical Physiology 29 -2

Renal Potassium Excretion During K+ depletion the ______________ cells of the distal and cortical collecting tubules can reabsorb K+. Actively transported with H+ via a H+/K+ ATPase Guyton’s Textbook of Medical Physiology 29 -2 and 27 -11

Renal Potassium Excretion Normally about 1/3 of the K+ intake is secreted into the distal and cortical collecting tubules. Guyton’s Textbook of Medical Physiology 29 -2

Renal potassium excretion High K+ diets can cause more K+ to be excreted than was in the glomerular filtrate. Due to elevated secretion. Guyton’s Textbook of Medical Physiology 29 -2

Renal Potassium Excretion Low K+ diets can cause net K+ reabsorption. The K+ excretion can fall to 1% of K+ in the glomerular filtrate. Guyton’s Textbook of Medical Physiology 29 -2

Mechanism of Potassium Secretion • Principal cells (90% of distal and cortical collecting tubule epithelial cells) – Na+-K+ ATPase (basolateral membrane) – K+ specific channels (luminal membrane) Guyton’s Textbook of Medical Physiology 27 -11 Sherwood’s Human Physiology 14 -24 5 th Ed. & 14 -21 6 th Ed.

Regulation of Potassium Secretion by Principal Cells Urinary K+ excretion • Increased extracellular fluid K+ concentration stimulates K+ secretion. Extracellular K + concentration Guyton’s Textbook of Medical Physiology 29 -4 • Stimulates Na+-K+ ATPase resulting in K+ diffusing out of the cell and into the tubule lumen. • Stimulates aldosterone secretion by adrenal cortex.

Urinary K+ excretion Regulation of Potassium Secretion by Principal Cells • Aldosterone stimulates K+ secretion. • Stimulates Na+-K+ ATPase resulting in K+ diffusing out of the cell and into the tubule lumen. • Increases the luminal membrane’s K+ permeability. Extracellular K + concentration • (negative feedback control) Guyton’s Textbook of Medical Physiology 29 -4

Regulation of Potassium Secretion by Principal Cells Guyton’s Textbook of Medical Physiology 29 -7

Summary of Aldosterone Control of Tubular Reabsorption & Secretion • Aldosterone Regulation – Increased plasma K+ – Decreased Na+ conc. – Decreased ECF volume – Decreased arterial pressure Sherwood’s Human Physiology 14 -25 5 th Ed. & 14 -22 6 th Ed.

Regulation of Potassium Secretion by Principal Cells • Increased distal tubular flow rate __________________ K+ secretion. • High flow rate washes K+ away resulting in the K+ concentration gradient driving the transport of K+. • Under high Na+ intake conditions blood pressure ↑ (and thus filtration and flow rate ↑) and aldosterone secretion is inhibited so this maintains a constant K+ secretion. – Remember aldosterone causes Na+ reabsorption and K+ secretion.

Regulation of Potassium Secretion by Principal Cells • Acute acidosis decreases K+ permeability. – Decreases the activity of the Na+-K+ ATPase.

Control of renal Calcium Excretion • Ca++ ___________ secreted in the kidneys. – Renal Ca++ excretion = Ca++ filtered - Ca++ reabsorbed. – Normally 99% of the filtered Ca++ is reabsorbed. – PTH is the main regulator of Ca++ reabsorption. • Increased PTH increases Ca++ reabsorption in thick ascending loop and distal tubules.

Control of Renal Calcium Excretion Guyton’s Textbook of Medical Physiology table 29 -2

Control of Renal Calcium Excretion Guyton’s Textbook of Medical Physiology 29 -10

Calcium Handling in the Nephron Costanzo’s Physiology 6 -31

Regulation of Renal Phosphate Excretion • Overflow mechanism – Normally the renal tubules have a transport maximum for reabsorbing phosphate. – Normally our diet supplies us with much more phosphate than we can reabsorb. • Thus it is excreted.

Regulation of Renal Phosphate Excretion • Changes in the amount of ingested phosphate can change the transport maximum for reabsorbing phosphate. – Low phosphate diet can increase transport maximum for reabsorbing phosphate. – ___________ can decease the transport maximum for reabsorbing phosphate.

Phosphate Handling in the Nephron Costanzo’s Physiology 6 -30

Magnesium Excretion • Normally about 10% of the renal filtrate of magnesium is excreted. • Regulation of magnesium excretion is achieved by changing the tubular reabsorption. – 25 -30% of magnesium reabsorption occurs in the proximal tubule. – 60 -65% of magnesium reabsorption occurs in the loop of Henle. – ~5% of magnesium reabsorption occurs in the distal and collecting tubules.

Magnesium Handling in the Nephron Costanzo’s Physiology 6 -31

Renal Clearance • Volume of plasma that is completely cleared of a given substance by the kidneys per unit time. – Useful way to quantify the excretory function of the kidney • Cs = Us x V / Ps (Us x V is urinary excretion rate) – Cs is the clearance rate of a substance – Us is the urine concentration of that substance – V is the urine flow rate – Ps is the plasma concentration of the substance

Renal Clearance = inulin, (filtered, not reabsorbed, not secreted) < inulin, (filtered, reabsorbed, not secreted) > inulin, (filted, not reabsorbed, secreted)

Next Time • Renal Regulation of Acid/Base Balance & Micturition • Readings; Sherwood, Chapters 14 & 15

Objectives 1. Describe the regulators of K+ distribution. 1. Intracellular vs. Extracellular 2. Describe renal K+ excretion. 1. Rate determinants 2. Location of reabsorption & secretion and cells involved. 3. Mechanism and regulation of K+ secretion. 3. Describe renal Ca++ excretion. 1. Factors that increase or decrease. 2. Location of reabsorption. 4. Describe renal PO 4 - excretion. 1. Overflow mechanism. 2. Location of reabsorption. 5. Describe renal Mg++ excretion. 1. Location of reabsorption.