Hypokalemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

Potassium is one of the intracellular cation. Any derangement of potassium serum levels can disturb the transmembrane potential and renders excitable cells (nerve and muscle) hyperpolarized and less excitable. However, cardiac cells don't obey this rule and become hyperexcitable. Potassium regulation is essential to maintain a normal activity in cells. Any imparment in potassium serum levels will have severe consequences on several organs especially the heart and the nervous system.

Differentiating Causes of Hypokalemia

Differentiating the diseases that can cause hypokalemia is as following table:

Diseases Clinical manifestations Para−clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging
Fatigue Fever Urinary symptoms Blood Pressure Skin lesions Edema ABG Urinalysis Transtubular potassium gradient Urine Potassium:Creatinine Other Ultrasonography CT scan
Polyuria Oliguria Nocturia
Renal and adrenal disorders Loop diuretic use[1] +/− − + − +/− ↓ − + Metabolic alkalosis ↑K+ > 7 >20mEq/g ↑Na+ − − History of medication use −
Primary hyperaldosteronism[2] + − + − + ↑ Facial flushing − Metabolic alkalosis ↑K+, ↓Na+ ↓PRA, ↑PAC, ↓Na+ Unilateral adrenal hyperplasia Hypodense unilateral adrenal macroadenoma (>1 cm)  PAC:PRA ratio Mood disturbance, paresthesia, muscle cramps
Cushing syndrome[3] + +/− +/− − − ↑ Facial plethora, purple striae + Metabolic alkalosis Glucosuria ↑BS Unilateral adrenal hyperplasia − Urinary free cortisol (24−hour) Dorsicocervical fat pad, obesity, hirsutism
Hemodialysis[4] +/− +/− +/− − − Normal Pustular lesions − Metabolic alkalosis Normal ↓Na+ − − History Carpal tunnel syndrome
Bartter syndrome[5] + − + − +/− Normal or ↓ − − Metabolic alkalosis ↑K+, ↑Ca+2, ↑Cl- − − − Laboratory findings Mental retardation, sensorineural hearing loss
Gitelman syndrome[6] + − + − + Normal − − Metabolic alkalosis ↑K+, ↓Ca+2, ↑Cl- − − − Laboratory findings Growth retardation, tetany, muscle cramp
Liddle syndrome[7] − − +/− − − ↑ − +/− Metabolic alkalosis ↑K+, ↓Na+ ↓PRA, ↓PAC − − Laboratory findings Pseudohyperaldosteronism
Gastrointestinal disorders GI bleeding[8] + − − + − ↓ − − Normal Normal < 3 < 20 mEq/g Anemia − − Laboratory findings Orthostatic hypotension, bradycardia
Vomiting[9] + − − + − ↓ − − Metabolic alkalosis Cl- <20 mEq/L − − − Laboratory findings Dry mucous membranes, lethargy
Severe diarrhea[10] + − − + − ↓ − − Metabolic alkalosis K+<20 mEq/L − − − Laboratory findings Dry mucous membranes, lethargy
Villous adenoma[11] + − − + − ↓ − − Normal K+ and Cl- <20 mEq/L Anemia − − Colonoscopy Hematochezia
VIPoma[12] + +/− − + − ↓ Facial flushing, skin rash + Normal K+<20 mEq/L Stool osmolar gap <50 mOsm/kg Endoscopic ultrasound for VIPomas of 2−3 mm Pancreatic VIPomas >3 cm Laboratory findings Weight loss
Neuropsychiatric disorders Primary polydipsia[13] − − + − + Normal − +/− Normal ↓Urine osmolarity ↓Na+ − − Water restriction test Psychosis
Central diabetes insipidus[14] + − + − + Normal or ↓ − − Normal ↓Urine osmolarity ↑Na+ − − Water restriction test Ischemic encephalopathy
Bulimia nervosa[15] − − − +/− − Normal or ↓ Asteatotic skin Carotenodermia − Normal ↑K+, ↓Cl- − − − Psychological interview  Parotid gland enlargement, lanugo−like hair
Anorexia nervosa[16] + − − +/− − ↓ Xerosis, hair effluvium − Normal ↑K+, ↓Cl- − − − Psychological interview Orthostatic hypotension, bradycardia
Hypokalemic periodic paralysis[17] + − − − +/− Normal or ↓ − +/− Metabolic alkalosis K+<20 mEq/L Thyrotoxicosis, ↓Mg+, ↓PO4-3 − − Laboratory findings Paralytic episodes, arrhythmias
Systemic diseases Hypothermia[18] − − − +/− − Normal Frostbite − Normal Normal − − − Clinical findings Impaired mental state
Alcoholism[19] + +/− + − + Normal or ↓ Icterus, caput medusae + Metabolic alkalosis Ketonuria Anemia − − Clinical findings Digital clubbing, gynecomastia
Diabetic ketoacidosis[20] + +/− + − + ↓ Xerosis − Metabolic acidosis Ketonuria ↑Serum ketone, ↑ blood glucose − − Laboratory findings Dry mucous membranes, shock
Hypomagnesemia[21] + − − +/− − Normal − +/− Metabolic alkalosis − ↓Ca+2 − − Laboratory findings Trousseau and Chvostek signs
Burns[22] +/− − − + − ↓ Vesicle and bullae, erythema + Normal − Acute phase reactant − − Clinical findings Dehydration
Cystic fibrosis[23] +/− +/− − +/− − ↓ Early aquagenic skin wrinkling +/− Normal − − - Pulmonary infiltration Sweat chloride test Pancreatic insufficiency

References

  1. ↑ Bourke E, Delaney V (1994). "Prevention of hypokalemia caused by diuretics". Heart Dis Stroke. 3 (2): 63–7. PMID 8199766.
  2. ↑ Wu C, Xin J, Xin M, Zou H, Jing L, Zhu C; et al. (2016). "Hypokalemic myopathy in primary aldosteronism: A case report". Exp Ther Med. 12 (6): 4064–4066. doi:10.3892/etm.2016.3864. PMC 5228118. PMID 28101185.
  3. ↑ Torpy DJ, Mullen N, Ilias I, Nieman LK (September 2002). "Association of hypertension and hypokalemia with Cushing's syndrome caused by ectopic ACTH secretion: a series of 58 cases". Ann. N. Y. Acad. Sci. 970: 134–44. PMID 12381548.
  4. ↑ Choi HY, Ha SK (2013). "Potassium balances in maintenance hemodialysis". Electrolyte Blood Press. 11 (1): 9–16. doi:10.5049/EBP.2013.11.1.9. PMC 3741441. PMID 23946760.
  5. ↑ Hebert SC (September 2003). "Bartter syndrome". Curr. Opin. Nephrol. Hypertens. 12 (5): 527–32. doi:10.1097/01.mnh.0000088732.87142.43. PMID 12920401.
  6. ↑ Knoers NV, Levtchenko EN (2008). "Gitelman syndrome". Orphanet J Rare Dis. 3: 22. doi:10.1186/1750-1172-3-22. PMC 2518128. PMID 18667063.
  7. ↑ Tetti M, Monticone S, Burrello J, Matarazzo P, Veglio F, Pasini B, Jeunemaitre X, Mulatero P (March 2018). "Liddle Syndrome: Review of the Literature and Description of a New Case". Int J Mol Sci. 19 (3). doi:10.3390/ijms19030812. PMC 5877673. PMID 29534496.
  8. ↑ Asmar A, Mohandas R, Wingo CS (2012). "A physiologic-based approach to the treatment of a patient with hypokalemia". Am J Kidney Dis. 60 (3): 492–7. doi:10.1053/j.ajkd.2012.01.031. PMC 4776048. PMID 22901631.
  9. ↑ Cheungpasitporn W, Suksaranjit P, Chanprasert S (February 2012). "Pathophysiology of vomiting-induced hypokalemia and diagnostic approach". Am J Emerg Med. 30 (2): 384. doi:10.1016/j.ajem.2011.10.005. PMID 22169581.
  10. ↑ Bazerbachi F, Haffar S, Szarka LA, Wang Z, Prokop LJ, Murad MH, Camilleri M (November 2017). "Secretory diarrhea and hypokalemia associated with colonic pseudo-obstruction: A case study and systematic analysis of the literature". Neurogastroenterol. Motil. 29 (11). doi:10.1111/nmo.13120. PMID 28580600.
  11. ↑ Sanchez Garcia S, Villarejo Campos P, Manzanares Campillo Mdel C, Gil Rendo A, Muñoz Atienza V, García Santos EP; et al. (2013). "Hypersecretory villous adenoma as the primary cause of an intestinal intussusception and McKittrick-Wheelock syndrome". Can J Gastroenterol. 27 (11): 621–2. PMC 3816940. PMID 24199207.
  12. ↑ Krejs GJ (May 1987). "VIPoma syndrome". Am. J. Med. 82 (5B): 37–48. PMID 3035922.
  13. ↑ Gill M, McCauley M (2015). "Psychogenic polydipsia: the result, or cause of, deteriorating psychotic symptoms? A case report of the consequences of water intoxication". Case Rep Psychiatry. 2015: 846459. doi:10.1155/2015/846459. PMC 4320790. PMID 25688318.
  14. ↑ Nguyen FN, Kar JK, Verduzco-Gutierrez M, Zakaria A (2014). "A case of hypokalemic paralysis in a patient with neurogenic diabetes insipidus". Neurohospitalist. 4 (2): 90–3. doi:10.1177/1941874413495702. PMC 3975788. PMID 24707338.
  15. ↑ Rushing JM, Jones LE, Carney CP (2003). "Bulimia Nervosa: A Primary Care Review". Prim Care Companion J Clin Psychiatry. 5 (5): 217–224. PMC 419300. PMID 15213788.
  16. ↑ Liang CC, Yeh HC (2011). "Hypokalemic nephropathy in anorexia nervosa". CMAJ. 183 (11): E761. doi:10.1503/cmaj.101790. PMC 3153553. PMID 21670105.
  17. ↑ "Hypokalemic periodic paralysis | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program".
  18. ↑ Zydlewski AW, Hasbargen JA (October 1998). "Hypothermia-induced hypokalemia". Mil Med. 163 (10): 719–21. PMID 9795553.
  19. ↑ Elisaf M, Liberopoulos E, Bairaktari E, Siamopoulos K (March 2002). "Hypokalaemia in alcoholic patients". Drug Alcohol Rev. 21 (1): 73–6. doi:10.1080/09595230220119282. PMID 12189007.
  20. ↑ Davis SM, Maddux AB, Alonso GT, Okada CR, Mourani PM, Maahs DM (2016). "Profound hypokalemia associated with severe diabetic ketoacidosis". Pediatr Diabetes. 17 (1): 61–5. doi:10.1111/pedi.12246. PMC 4896141. PMID 25430801.
  21. ↑ Huang CL, Kuo E (October 2007). "Mechanism of hypokalemia in magnesium deficiency". J. Am. Soc. Nephrol. 18 (10): 2649–52. doi:10.1681/ASN.2007070792. PMID 17804670.
  22. ↑ Nielson CB, Duethman NC, Howard JM, Moncure M, Wood JG (2017). "Burns: Pathophysiology of Systemic Complications and Current Management". J Burn Care Res. 38 (1): e469–e481. doi:10.1097/BCR.0000000000000355. PMC 5214064. PMID 27183443.
  23. ↑ Bates CM, Baum M, Quigley R (February 1997). "Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent". J. Am. Soc. Nephrol. 8 (2): 352–5. PMID 9048354.


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