A. Normal Regulation of Potassium (K+) Balance

1. Very high levels of intracellular K+ (>100mM) relative to external levels (3.5-5mM)
2. This distribution is maintained primarily by two systems:
   1. Insulin - glucose: stimulates cellular K+ uptake
   2. ß-adrenergic catecholamines: stimulate K+ uptake
   3. Thyroid hormone may stimulate Na+/K+ ATPase as well
   4. Alkalosis stimulates hypokalemia (acidosis precipitates hyperkalemia)
3. Extracellular and total body stores of K+ are regulated by other hormone systems
   1. Aldosterone is the major hormone responsible for stimulating renal excretion
   2. Hyperkalemia stimulates angiotensin II and aldosterone secretion
   3. Hypokalemia inhibits aldosterone secretion

B. Causes

1. Diuretic Use - loss with natriuresis most common
2. Metabolic / Respiratory Alkalosis
3. Elevated Mineralocorticoid Levels [2]
   1. Hyperaldosteronism - Conn Syndrome, adrenal tumor, congenital adrenal hyperplasia
   2. Cushing Syndrome
   3. Synthetic mineralocorticoids (fludrocortisone)
   4. High dose glucocorticoids
   5. Liddle's Syndrome
   6. 11ß-hydroxysteroid dehydrogenase (11ß-HSDH) deficiency
   7. Licorice (glycyrrhizic acid) overingestion - inhibits 11ß-HSDH
4. Diabetic Ketoacidosis with Osmotic Diuresis
5. Renal Tubular Acidoses
   1. Bartter's Syndrome
   2. Gitelman's Syndrome
6. Loss through gastrointestinal tract
   1. Diarrhea and/or severe vomiting - including noninfectious causes
   2. Phenolphthalein (often due to laxative abuse)
   3. Sodium polystyrene sulfonate
7. Transcellular Shifts due to Drugs
   1. ß2-adrenergic agonists: epinephrine, decongestants, bronchodilators
   2. Tocolytic agents
   3. Theophylline - adenosine effects, probably through diuresis (mild)
   4. Caffeine
   5. Verapamil intoxication
   6. Insulin overdose
8. Inadequate oral intake

C. Symptoms and Signs

1. No symptoms in general with mild hypokalemia, 3.0-3.5mM
2. Nonspecific symptoms including weakness, lassitude, constipation at 2.5-3.0mM
3. Muscle cramps develop in the 2.0-2.5mM range, likely due to myonecrosis
4. Severe problems occur with [K+] <2.0mM
   1. Arrhythmias - including precipitation of digitalis toxicity
   2. Bradycardia
   3. Appearance of U Waves on electrocardiogram (ECG)
5. Bradypnea may occur to help correct for metabolic alkalosis
6. Development of symptoms occurs more with acute than with chronic changes in K+

D. Treatment

1. Replenish Potassium intravenously for [K+] <2.5mM ~10mEq K+ / 0.2mM [K+]
2. Do not give K+ in D5W as increased glucose may increase insulin and decrease [K+]
3. Replenish Potassium Orally with KCl: ~10mEq oral K+ for every 0.1mM desired rise
4. Must obtain immediate ("stat") [K+] levels when using IV potassium
5. Before repletion, urine electrolytes should be obtained (K+/Creatinine)
   1. This allows site of K+ loss to be determined
   2. Most diuretics have high K+ urine loss (renal effect) relative to Creatinine (Cr)
   3. Renal tubular acidosis types I and II (proximal) have high urine K+ relative to Cr
   4. Gastrointestinal tract losses cause urine K+ levels to be low relative to Cr
6. Chronic treatment with KCl supplements and high K+ content foods
   1. Dried fruits: figs, dates, prunes
   2. Nuts
   3. Wheat germ and bran cereals
   4. Fruits: bananas, kiwis, cantaloupe, oranges, mangos
   5. Vegetables: spinach, tomato, broccoli, winter squash, carrots, potatoes
   6. Meats: ground beef, steak, pork, veal, lamb

References

1. Gennari FJ. 1998. NEJM. 339(7):451
2. Lin SH and Chau T. 2002. Lancet. 360(9328):224