Potassium Homeostasis

1. Potassium Homeostasis • • The normal range of sodium in the plasma is 135-145 milliequivalents per liter. • Compare this range to the normal range of potassium in the plasma which • is 3.5 to 5.1 milliequivalents per liter. • • Because potassium has a much smaller range, the loss of a small amount of potassium can make a significant difference in the body. • • Although most potassium ion is found • inside cells, • its concentration is measured in the plasma. It ends up in the extracellular fluids in two ways: • 1. Like water and sodium, potassium is constantly entering the body in food and leaving the body mostly through the urine. • 2. Because the cell membrane is more permeable to potassium than sodium, more potassium leaks out of cells.

2. Roles of Potassium: • Osmosis • • As the major intracellular positive ion, potassium is responsible for intracellular fluid volume, through osmosis. • • What would happen if there was a slight increase in potassium ions in the extracellular fluid? • -Cells would shrink • Cells would expand • Membrane Potential • • Because most cells in the body leak potassium but not other ions, potassium will leave the cells though ion channels, significant amount of positive charge is leaving the cell. • • What charge will be left inside of the cell? • - Positive charge • - Negative charge • • Potassium plays a key role in maintaining resting membrane potential, and therefore a major role in nerve impulse conduction, muscle contraction, and maintenance of normal cardiac rhythm.

3. K+o  K+ H+ K+o  Acid/Base Balance • As hydrogen ions move into and out of the cells in the body, there is a corresponding movement of potassium in the opposite direction by ion transport proteins that link hydrogen ion movement to potassium ion movement. This movement helps maintain electrical balance inside the cells. Alkalosis: Acidosis: H+ (hypokalemia) H+ (hyperkalemia)

4. Overview of Potassium Homeostasis 1) Internal potassium homeostasis. Cells exist in a steady state where potassium uptake via the Na/K-ATPaseis balanced by potassium leak through ion channels. Regulation of exchange between intra- and extracellular fluid is known as internal potassium homeostasis. Factors which affect internal potassium balance are important in the regulation of plasma [potassium]. Skeletal muscle cells are the major single pool of potassium in the body and are the most important cells in relation to internal potassium homeostasis. 2)External potassium homeostasis. The typical Western diet contains around 80mEq of potassium per day. Maintenance of potassium homeostasis requires that the rate of potassium excretion matches daily intake. This is known as external potassium homeostasis. Fine regulation of renal potassium output is the major control mechanism ensuring external balance. Losses from the GI tract in feces are generally about 10% of dietary intake, though this can become a large source of potassium loss in diarrhea.

5. Exercise K+ ingestion insulin liver, skeletal muscle epinephrine skeletal muscle (beta2 receptors) High plasma [K+] aldosterone (skeletal muscle) Factors Affecting Internal K+ Exchanges K+ cell Insulin/glucose infusions are used clinically to control hyperkalemia. The final common pathway for increased cellular potassium uptake with insulin, aldosterone and epinephrine is increased Na/K-ATPase activity.

6. A K+ Load Must Be Quickly Removed To Protect Plasma [K+] 100 K+ moved into cells % response 50 Renal K+ excretion 0 6 12 Hours K+ load

7. Renal K+ Handling Involves Filtration, Reabsorption And Secretion Secretion: DCT & CCD (FE = 10 to 150%) Reabsorption: PCT (FE=30%), TALH (FE=10%)  In states of low dietary potassium intake The rate of renal potassium excretion varies over a wide range according to changes in dietary intake.  dietary potassium excess FE K+= 10 – 150+%

8. K+ Excretion Is Determined By K+ Secretion In The Collecting Duct aldosterone 3Na+ + Lumen Blood K+ Principal cell

9. Overview of Calcium Homeostasis Plasma calcium is finely regulated, with a normal range of 4.2-5.6 mg/dL.

10. What Is Normal Plasma [Ca2+]? mM mg/100ml 2.5 10 Ca-protein Non-diffusible 40% 2.0 8 40% 1.5 6 Ca-complex 15% 45% 1.0 4 Diffusible 60% Free ionized Ca2+ 0.5 2 0 0

11. Parathyroid Hormone And Vitamin D3 Are Central To Calcium Homeostasis  Intestinal absorption GUT 1,25(OH)2D Low plasma Ca2+o KIDNEY Parathyroid Gland Bone resorption  Renal excretion PTH

12. Segmental Ca2+ Handling Is Similar To That Of Na+ % Ca2+ remaining G PT LOH DT CD U

13. Calcium and the Proximal Tubule Interstitial fluid Proximal Tubule Cell lumen H+ Ca2+ Ca2+ Calcium binding proteins Na+ Ca2+ Ca2+

14. Calcium and the TALH (1) Interstitial fluid Thick Ascending LofH Tubule Cell lumen PTH H+ Ca2+ Ca2+ Calcium binding proteins Na+ Ca2+ Ca2+

15. CaR Regulates TALH Ca2+ Absorption A lumen positive transepithelial potential difference drives paracellular calcium reabsorption. Lumen Blood 3Na+ Na+ NKCC2 2Cl- 2K+ K+ Cl- CLC-Kb ROMK ↑ cAMP Ca2+ + cations

16. Calcium and the DCT Interstitial fluid lumen Distal Convoluted Tubule Cell PTH H+ Ca2+ Ca2+ Calcium binding proteins Na+ Ca2+ Ca2+