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hypokalemia

Etiology: 1) renal a) osmotic diuresis, i.e. diabetes mellitus b) pharmacologic agents: - diuretics (most common cause) - amphotericin B - gentamicin - mineralocorticoids - glucocorticoids (some) - osmotic diuretics - tetracycline - theophylline - vitamin B12 - carbenicillin - high dose penicillin c) excessive mineralocorticoids - primary hyperaldosteronism (Conn's syndrome) - secondary hyperaldosteronism - Bartter's syndrome - Gitelman syndrome - renal artery stenosis - glucocorticoid excess - Cushing's disease - ectopic ACTH production - exogenous steroids d) distal renal tubular acidosis (RTA-1) e) hypomagnesemia causes loss of potassium into the urine [3] through the collecting tubule - alcoholism frequently associated with hypomagnesemia [9] - proton pump inhibitors are associated with hypomagnesemia [3] 2) gastrointestinal a) gastrointestinal (GI) loss of K+ - vomiting [3] - diarrhea through upregulation of K+ channels in the colon - villous adenoma - fistula - laxative abuse b) decreased dietary intake - starvation - clay ingestion 3) intracellular shift of K+ a) metabolic alkalosis b) pharmacologic agents - insulin - beta-adrenergic receptor agonists - ritodrine - theophylline c) familial hypokalemic periodic paralysis 4) insensible losses - sweating Epidemiology: - 90% of hypertensive patients with hyperaldosteronism Pathology: - alterations in action potential generation - skeletal muscle dysfunction - cardiac muscle dysfunction - alterations in renal tubular function - causes of renal potassium loss - increased urine flow or sodium delivery to distal nephron - increased mineralocorticoid activity Clinical manifestations: 1) signs/symptoms depend upon acute vs chronic nature of hypokalemia 2) musculoskeletal dysfunction a) muscle weakness b) flaccid paralysis (including respiratory paralysis) c) hypotonia d) hyporeflexia e) rhabdomyolysis 3) smooth muscle dysfunction a) paralytic ileus with nausea b) muscle cramps 4) renal failure 5) renal tubular dysfunction a) polydipsia b) polyuria 6) glucose intolerance [3] 7) cardiac arrhythmias a) sinus bradycardia b) premature atrial beats c) atrial tachycardia d) AV block e) junctional tachycardia f) premature ventricular beat g) ventricular tachycardia (especially in patients on digoxin) h) ventricular fibrillation Laboratory: 1) serum K+ < 3.5 meq/L 2) increased serum glucose - hypokalemia impairs insulin secretion 3) urine K+ a) > 20 meq/L suggests renal origin - urine Cl- > 20 meq/L - high blood pressure: excess glucocorticoids, mineralocorticoids (urine Cl- generally > 40 meq/L) - normal blood pressure: Bartter's syndrome, Gitelman's syndrome, current use of diuretics - renal tubular acidosis - urine Cl- < 20 meq/L suggests metabolic alkalosis - urine Na+ is generally < 20 meq/L with volume depletion but with metabolic alkalosis, Na+ accompanies bicarbonate excreted in the urine to maintain electroneutrality, thus becomes > 20 meq/L [3] b) < 20 meq/L non-renal origin - diarrhea, vomiting*, laxative abuse, villous adenoma - low potassium intake c) urine potassium/creatinine < 13 meq/g identifies non-renal origin [3] 4) serum Mg+2: may be low [3] 5) blood gas: pH - metabolic alkalosis - vomiting, NG suction, diarrhea, previous diuretics * urine K+ may be high or low with vomiting; check urine Cl- Special laboratory: - electrocardiogram (EKG) [12] a) flattening of T waves or inverted T waves b) ST segment depression [3] c) QTc prolongation [12] d) tachycardia e) increased prominence of U wave f) ventricular arrhythmias - severe hypokalemia - in patients taking digoxin Complications: 1) exacerbation of digitalis toxicity 2) glucose intolerance from impaired insulin secretion 3) excess risk for - 7-day mortality in hospitalized patients - intensive care admission - ventricular arrhythmia/cardiac arrest [12] 4) excess risk only when heart rate > 100/min & serum K+ < 3 mmol/L [12] Management: 1) fatal arrhythmias may occur in patients taking digoxin even if hypokalemia is mild 2) oral KCl (first resort) 3) intravenous KCl*, potassium phosphate a) do not exceed 40 meq/L b) do not exceed 20 meq/hr [3] c) EKG monitoring during rapid K+ infusion d) total body K+ deficits ~ 200 meq for each 1 meq/L decrease in serum K+ [3] 4) normal saline for chloride-reponsive hypokalemic metabolic alkalosis with low urine chloride 5) potassium sparing diuretics* a) amiloride b) triamterene c) spironolactone 6) hypomagnesemia & magnesium deficiency MUST be corrected before K+ depletion can be corrected 7) when hypokalemia is due to intracellular shift of K+ (see etiology), total body K+ is normal & K+ replacement may result in hyperkalemia [3] * no advantage to potassium acetate; acetate may exacerbate metabolic alkalosis [10] * use of K+ sparing diuretics questioned [10]

Related

potassium (K+) in serum/plasma

General

electrolyte disorder sign/symptom

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 831
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 674-676
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Sandle GI, Hunter M. Apical potassium (BK) channels and enhanced potassium secretion in human colon. QJM. 2010 Feb;103(2):85-9. PMID: 19892809
  5. Unwin RJ, Luft FC, Shirley DG. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephrol. 2011 Feb;7(2):75-84. PMID: 21278718
  6. Shin HS. Value of the measurement of urinary chloride in hypokalaemic metabolic alkalosis. PMID: 20377781
  7. Berl T, Rastegar A. A patient with severe hyponatremia and hypokalemia: osmotic demyelination following potassium repletion. Am J Kidney Dis. 2010 Apr;55(4):742-8. PMID: 20338465
  8. Medford-Davis L, Rafique Z. Derangements of potassium. Emerg Med Clin North Am. 2014 May;32(2):329-47. Review. PMID: 24766936
  9. Elisaf M; Liberopoulos E; Bairaktari E; Siamopoulos K Hypokalaemia in alcoholic patients. Drug Alcohol Rev. 2002; 21(1):73-6 PMID: 12189007 https://reference.medscape.com/medline/abstract/12189007
  10. NEJM Knowledge+ Endocrinology
  11. Palmer BF, Clegg DJ. Physiology and pathophysiology of potassium homeostasis: core curriculum 2019. Am J Kidney Dis. 2019;74:682-695. PMID: 31227226
  12. Kildegaard H, Brabrand M, Forberg JL et al. Prevalence and prognostic value of electrocardiographic abnormalities in hypokalemia: A multicenter cohort study. J Intern Med 2024 Apr; 295:544 PMID: 38098171 https://onlinelibrary.wiley.com/doi/10.1111/joim.13757