Potassium Balance Lecture PDF

Potassium Balance Objectives: 1. Explain the role of extracellular K + in maintaining normal nerve and muscle function. 2. Describe K + handling in the nephron. Identify the tubular sites of K + reabsorption and secretion. Generated: 9/24/2020 Page 20 of 23 3. Describe the factors that regulate K +...

Potassium Balance Objectives: 1. Explain the role of extracellular K + in maintaining normal nerve and muscle function. 2. Describe K + handling in the nephron. Identify the tubular sites of K + reabsorption and secretion. Generated: 9/24/2020 Page 20 of 23 3. Describe the factors that regulate K + secretion in the renal tubule by cells of the distal nephron (i.e., aldosterone, plasma K + , luminal fluid flow rate, acid-base disturbances). 4. Explain the physiological effects of aldosterone antagonists and epithelial sodium channel (ENaC) inhibitors at the distal part of the nephron, give specific examples of each. 5. Describe K distribution within the body, extrarenal K + homeostasis and movement of K + between intracellular and extracellular pools by insulin, epinephrine, aldosterone and other factors. 6. Examine the mechanisms and consequences of K + shifts caused by acidosis and alkalosis. 7. Compare causes and effects of hyperkalemia and hypokalemia Potassium, the most abundant cation in ICF Normal plasma K+ level = 3.5 to 5 mEq/l Importance: resting membrane potential repolarization intracellular fluid volume acid-base balance (K+ moves in, H+ moves out and vice versa) Potassium balance. Hyperkalaemia Gaw, Allan, MD PhD FRCPath FFPM PGCertMedEd, Clinical Biochemistry: An Illustrated Colour Text, 11, 22-23 Copyright © 2013 2013, Elsevier Ltd. All rights reserved. What would be a good source of potassium? K+ HANDLING IN THE NEPHRON Reabsorption in the proximal tubule and in the loop of Henle independent of the state of K+ balance: 60-70% in the proximal tubule, 20% - in the thick ascending limb Low K+ diet only of Henle’s loop via Na+/K+/Cltransporter Proximal tubule 70% 20% Dependent on the state of K+ balance secretion by the principal cells in the cortical collecting duct and outer medulla, reabsorption by H+-K+ ATPase in the α-intercalated cells of the inner medullary collecting duct K+ secretion varies and is promoted by high: dietary K+, aldosterone, high filtrate flow rate Excretion 1% -100 % K+ transport along the nephron. Excretion of K+ depends on the rate and direction of K+ transport by the distal tubule and collecting duct. Percentages refer to the amount of filtered K+ reabsorbed, secreted or excreted. CCD, cortical collecting duct; DT, distal tubule; IMCD, inner medullary collecting duct; PT, proximal tubule; TAL, thick ascending limb. Potassium, Calcium, and Phosphate Homeostasis Koeppen, Bruce M., MD, PhD, Berne and Levy Physiology, 36, 647-669 Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved. Secretion of K+ in the late distal tubule Potassium ions are usually secreted in the distal tubule, e. a. are transported from blood across the principal cells into the lumen. Lumen Na+ Na+ ATP K+ K+ K+ Blood Interstitium Principal cell Again, Na-K ATPase plays a pivotal role in this process. High activity of the pump creates a negative charge in the lumen (due to Na+ removal). Two forces determine the rate of K+ secretion: 1) the difference in K+ concentration between the cytosol of epithelial cells and filtrate (transepithelial chemical gradient) 2) electrical charge of filtrate (transepithelial electrical gradient) Lumen Na+ Na+ ATP K+ Blood K+ K+ Filtrate Flow Principal cell Factors which increase electrochemical gradient for K+ anywhere between the blood and lumen elevate K+ secretion. Thiazide diuretics inhibit Na/Cl symporter in the early distal tubule, and like other diuretics (furosemide, acetazolamide) increase tubular flow. As a result, secreted K+ is swept downstream in the renal tubule, and its luminal concentration decreases. Na+ ClH2 O High filtrate flow = K+ loss Since the concentration gradient between blood and filtrate gets greater, secretion of K+ and its loss with urine increases. Excessive K+ loss results in hypokalemia (low plasma potassium concentration), a frequent side effect of loop and thiazide diuretics. To avoid hypokalemia, they can be administered in combination with K+-sparing diuretics (spironolactone, amiloride, etc). Potassium sparing diuretics inhibit Na+ and K+ transport in the collecting duct by two different Principal cell mechanisms Na+ Epithelial Na channel blockers: amiloride and triamterene close K+ sodium channels on the apical membrane Spironolactone Na+ MR receptor ATP K+ In essence, potassium sparing diuretics are aldosterone antagonists Blood K+ Mineralocorticoid receptor (MR) blockers: spironolactone competes with aldosterone for MR, reduces activity of Na+- K+ ATPase in the principal cells. Effects of Diuretics on Excretion of Ions (approximate % with maximal effective doses) Na Cl K Pi Ca Mg Osmotic diuretics ↑(10–25%) ↑(15–30%) ↑(6%) ↑(5–10%) ↑(10–20%) ↑(>20%) Carbonic anhydrase inhibitors ↑(6%) ↑(4%) ↑(60%) ↑(>20%) ↑ or ⇔ (<5%) ↑(<5%) Loop diuretics ↑(30%) ↑(40%) ↑(60–100%) ↑(>20%) ↑(>20%) ↑(>20%) Distal ↑(6–11%) convoluted tubule diuretics ↑(10%) ↑(200%) ↓ ↑(5–10%) Spironolactone ↑(6%) ↓ ↑(3%) Source: Physiology and Pathophysiology of Diuretic Action by D.H. Ellison in Seldin and Giebisch’s The Kidney, 2013 p. 1353-1404. ↑(>20%) Regulation of potassium secretion by principal cells Increase in K+ secretion Decrease in K+ secretion High K+ diet Low K+ diet Hyperaldosteronism Hypoaldosteronism Loop & thiazide diuretics K+ sparing diuretics Alkalosis Acidosis Balance of K+ is linked to acid base balance Alpha intercalated cells promote hydrogen secretion and potassium reabsorption Intracellualr Buffering of Potassium Acute increase in plasma K+ (hyperkalemia) after meal consumption is prevented by cellular buffering of potassium ions. Intestinal Absorption 90 mEq of K+ per day Insulin Adrenaline Cells Renal Physiology Bailey, Matthew A., Comprehensive Clinical Nephrology, Chapter 2, 14-27 Copyright © 2015 Copyright © 2015, 2010, 2007, 2003, 2000 by Saunders, an imprint of Elsevier Inc. Extracellular Fluid 65 mEq of K+ K+ Kidney Urine 90 mEq of K+ per day Potassium – Hydrogen Exchange and Acid-Base Balance Plasma K+ balance involves H+-K+ exchange across cell membranes. Cells have considerable buffering capacity for H+, while their electroneutrality is preserved as a result of K+ efflux. K+ disturbances are frequently associated with acid-base abnormalities. K+ ICF Hypoxia, cell lysis, exercise K+ ECF H+ K+ Insulin, betaagonists (adrenaline) Factors which shift K+ Out of cells Into cells Insulin deficiency Insulin Β2 - blockers Β2 - agonists Hypoxia Cell lysis Clinical implications: In patients with diabetes mellitus, excess of insulin (overdose) or missed meal after insulin injection leads to hypoglycemia. Insulin also can cause hypokalemia as a result of K+ shift from the blood into cells. Crush Syndrome Breakdown of cells on a massive scale results in elevation of some substances and ions in the blood. The injury is believed to be due to the release into the bloodstream of muscle breakdown products as the consequence of rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions). Myoglobinuria. The dipstick is strongly positive for blood, with no red blood cells seen on microscopy. (From Roberts JR, Hedges JR. Clinical procedures in emergency medicine. 5th ed. Copyright 2009 Saunders, an imprint of Elsevier.) What are these substances and ions? Rhabdomyolysis Adams, Bruce D., Emergency Medicine, 169, 1429-1438.e1 Copyright © 2013 Hyperkalemia, the most dangerous electrolyte abnormality! The Cell and Fluid Homeostasis Mulroney, Susan E., PhD, Netter's Essential Physiology, Chapter 1, 2-11 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. The cocktail for lethal injection (capital punishment in some states) includes potassium chloride. By CACorrections (California Department of Corrections and Rehabilitation) http://www.flickr.com/photos/37381942@N04/4905111750/in/set-72157624628981539/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=11627466 Electrocardiographs from individuals with varying plasma [K+ ] . Hyperkalemia increases the height of the T wave, and hypokalemia inverts the T wave. Potassium, Calcium, and Phosphate Homeostasis Koeppen, Bruce M., MD, PhD, Berne and Levy Physiology, 36, 647-669 Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved. Hyperkalemia, the most dangerous electrolyte abnormality Hyperkalemia = plasma potassium > 5 mEq/L, - can cause cardiac problems including arrest, - ECG is abnormal. Other symptoms - muscle weakness and paralysis, fatigue, nausea and paresthesia (abnormal tingling sensation) Causes: renal failure, deficit of aldosterone, potassium sparing diuretics, severe damage of tissue in trauma prolonged and severe acidosis Why hyperkalemia tends to be associated with acidosis (high plasam H+) Extracellular K+ level is high, while intracellular can be low. Hyperkalaemia is associated with acidosis. One way to treat hyperkalemia and associated acidosis is to administer sodium bicarbonate. As patient becomes less acidotic from the action of bicarbonate, H+ ions move out of cells and K+ ions move in. Hyperkalaemia Gaw, Allan, MD PhD FRCPath FFPM PGCertMedEd, Clinical Biochemistry: An Illustrated Colour Text, 11, 22-23 Copyright © 2013 2013, Elsevier Ltd. All rights reserved. Like hyperkalemia, hypokalemia can cause cardiac and muscle weakness and ECG changes. It also can be associated with hypomagnesemia and cause rhabdomyolysis (lysis of skeletal muscle cells with release of myoglobin and possible renal complications) Causes: severe diarrhea, aldosterone hypersecretion, insulin plasma elevation, hyperglycemia, diuretics Factors in pathogenesis of hypokalemia [K+] < 3.5 mEq/L Inadequate diet Reduced absorption Aldosterone hypersecretion Inadequate intake Excessive loss Chronic diarrhea Excessive perspiration Loop and thiazide diuretics Renal malfunction Hyperglycemia Alkalosis Beta-2 adrenergic stimulation Chronic insulin elevation Hypokalemia K+ shifts into cells Homework: How the use of ACE inhibitors and ARB blockers affects K+ balance? Should one expect loss or gain of potassium?