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Hypokalemia and Mineralocorticoid hypertention Nephrology R3 이 홍 주 Hypokalemia Mineralocorticoid hypertension Licorice & hypokalemia defined as a plasma K+ concentration <3.5 mmol/L • decreased net intake • shift into cells • increased net loss. Harrison • Triad hypertension metabolic alkalosis Hypokalemia Caused by • • increased retention of sodium by the nephron expansion of the extracellular fluid compartment suppression of plasma renin Diagnosis based on responsible mineralocorticoid… Aldosterone adrenal adenoma bilateral adrenal hyperplasia adrenal carcinoma GRA(glucocorticoid-remediable hyperaldosteronism) Cortisol via 11 β-hydroxysteroid dehydrogenase deficiency/inhibition AME(apparent mineralocorticoid excess) Licorice and carbenoxolone ingestion Ectopic ACTH syndrome ?? Essential hypertension variant ?? Pre-eclampsia Deoxycorticosterone Congenital adrenal hyperplasia Glucocorticoid receptor mutations Metyrapone, mifrestone ingestion Seminars in nephrology 2006 : 26(6) 434-440 Figure 2 Relation of the Plasma Aldosterone Concentration to the Ratio of Plasma Aldosterone to Plasma Renin Activity in Various Conditions of Mineralocorticoid Deficiency or Excess. N Engl J Med 1994; 331:250-258 root of the Glycyrrhiza glabra used throughout the millennia for its taste and for medical purposes name "liquorice" or "licorice" is derived from the old French licoresse and the ancient Greek work glukurrhiza, meaning "sweet root.“ Glycyrrhizin (GL), a component of licorice roots Metabolized to glycyrrhetinic acid (GA) In the Middle Ages) used for treatment of hypotension. In 1946) good results in the treatment of stomach ulcers … developed hypokalaemia and an increase in blood pressure. Ned Tijdschr Geneeskd. 1946;90:135-137 F.E. Revers aldosterone secretion was suppressed in liquorice-induced hypertension : ‘pseudohyperaldosteronism’ Conn reported use Adrenal insufficiency (Davis, 1991) Aphthous ulcers/cancer sores (Worner, 1974) Atopic dermatitis (Saeedi, 2003) Body fat mass reduction (Armanini, 2003) Crohn's disease (pharmacologic activity) Expectorant and antitussive (Bradley, 1992) Gastrointestinal ulceration (Dehpour, 1994) Herpes simplex (Sekizawa, 2001) Hyperkalemia (Murakami, 1993)(Nicola, 2008) J Clin Hypertens 2008;10:153–157 glycyrrhetinic acid Fatigue and muscle cramping Dark urine (myoglobinuria) Weakness (hypokalemia, myopathies) Polyuria/nocturia (increased extracellular volume) Edema (increased extracellular volume) Dyspnea (pulmonary edema) Headache (hypertension) Paresthesias/dysesthesias Impotence and diminished libido Amenorrhea High blood pressure Hypertensive encephalopathy with stroke-like effects Spasms/tetany Hyporeflexia, muscle wasting, weakness, flaccid paralysis Myoglobinuria/rhabdomyolysis Trousseau and Chvostek signs (from hypokalemia with alkalosis) Cardiac arrest, dysrhythmias (rare) from hypokalemia Hypokalemia, increased urinary excretion of potassium Mildly elevated creatine, metabolic alkalosis Elevated creatine kinase Decreased plasma renin activity, aldosterone levels Increased urinary cortisol , decreased cortisone Relatively small amounts of licorice, as little as 50 g daily for two weeks, produce a rise in blood pressure in normal people Regular daily intake of glycyrrhizic acid 100mg (licorice 2.5g) produces adverse effects in sensitive individuals Glycyrrhizic acid 400mg (licorice 10g) produces adverse effects in most subjects edema HTN World Health Organization Severe hypokalemia & rhabdomyolysis 1개월간 500g 가량의 감초를 복용 7 년간 280 mg/d의 글리시리진을 복용 5 g of licorice per day for the last 7 years 200 g of licorice a day for 4 weeks Cessation of licorice ingestion The time required for correction : varies from days to weeks Large volume of distribution and long biological half-life of glycyrrhetic acid Spironolactone KCl supplementation Dexamethasone causes suppression of endogenous cortisol production reduces the cortisol-mediated stimulation of the mineralocortcoid receptor