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Hypokalemia Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Aida Javanbakht, M.D. Aditya Govindavarjhulla, M.B.B.S. [3] ; Assistant Editor(s)-In-Chief: Jack Khouri
Synonyms and keywords: Hypokalaemia; potassium levels low (plasma or serum); potassium - low; low blood potassium; potassium depletion
Overview
Pathophysiology
Potassium is the principal intracellular cation, with a concentration of about 145 mEq/L, as compared with a normal value of 3.5 - 5.0 mEq/L in extracellular fluid, including blood. Any disorder of potassium serum levels can disturb the transmembrane potential and renders excitable cells (nerve and muscle) hyperpolarized and less sensitive. However, cardiac cells don't obey this rule and become hyperexcitable. Potassium regulation is essential to maintain a normal activity in cells. Any impairment in potassium serum levels will have severe consequences on several organs especially the heart and the nervous system. Typically, total potassium excretion in the stool is low and most ingested potassium is absorbed. The kidney is the primary regulator of potassium balance through excretion (the kidney excretes 90-95% of dietary potassium); the gut excretes a minimal amount of dietary potassium (approximately 10%).
Historical Perspective
Pathophysiology
Pathophysiology
Hypokalemia can result from several conditions:
- Trans-cellular shifts of potassium inside the cells (most common)
- Renal loss of potassium
- Increased distal Na delivery
- Increased urine flow
- Metabolic alkalosis
- Increased aldosterone level
- Gastrointestinal (GI) loss of potassium
- Increased hematopoiesis (increased cellular use of potassium)
- Decreased intake of potassium (least common)
Shown below is a table summarizing the different pathophysiological processes that can lead to hypokalemia. [1] [2] [3] [4]
Trans-cellular shifts | Renal loss | GI loss | Increased hematopoiesis | Decreased intake of potassium | |
|
Subject is normo or hypotensive Associated with alkalosis
Variable acid/base status |
Subject is hypertensive
Secondary hyperaldosteronism
Non aldosterone increase in mineralcorticoid
|
Associated with metabolic acidosis Associated with metabolic alkalosis
|
|
|
The Role of the Kidney
- The Kidneys play an important role in keeping the balance of potassium.
- At the glomerulus, potassium is freely filtered and reabsorbed mainly in the proximal tubule and thick ascending loop of Henle (>60 % of filtered potassium).
- The cortical collecting duct receives 10–15% of filtered potassium and constitutes the kidney’s primary site of potassium excretion.
- Potassium excretion at the cortical collecting duct depends on the amount of sodium delivered there and the activity of aldosterone.
- The absorption of sodium by the principal cells of the cortical collecting ducts is mediated by the apical epithelial sodium channels (ENaC); when the amount of sodium delivered to the cortical collecting duct is very high, the absorption of sodium increases without concomitant absorption of the accompanying anions (e.g., bicarbonates and chloride ions) which are not easy to absorb. This physiologic process causes the formation of a negative charge within the cortical collecting duct lumen, causing potassium and proton secretion.
- Aldosterone increases sodium absorption at the cortical collecting duct by means of enhancing the activity of Na-K-ATPase pumps and augmenting the number of the ENaC channels.
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Factors Increasing Kidney Potassium Excretion
- Increased aldosterone
- High urine flow rate
- High distal sodium delivery
- Metabolic alkalosis
- High extracellular fluid K+ concentration
Some Factors Affecting Potassium Distribution Between the Cells and the Extracellular Fluid
- Na/K ATPase
- Insulin
- Catecholamines
- Plasma potassium concentration
- Extracellular pH
- Hyperosmolarity [5]
The Physiologic Role of Potassium
- Potassium is essential for many body functions, especially excitable cells such as muscle and nerve cells.
- Diet, mostly meats and fruits, is the major source of potassium for the body.
- Potassium is the principal intracellular cation, with a concentration of about 145 mEq/L, as compared with a normal value of 3.5 - 5.0 mEq/L in extracellular fluid, including blood.
- More than 98% of the body's potassium is intracellular; measuring it from a blood sample is relatively insensitive, with small fluctuations in the blood corresponding to substantial changes in the total bodily reservoir of potassium.[6] [5]
The Cellular Effect of Hypokalemia
- The electrochemical gradient of potassium between intracellular and extracellular space is essential for the function of neurones; in particular, potassium is needed to repolarize the cell membrane to a resting state after an action potential has passed.
- Decreased potassium levels in the extracellular space will cause hyperpolarization of the resting membrane potential, i.e, it becomes more negative. This hyperpolarization is caused by the effect of the altered potassium gradient on resting membrane potential, as defined by the Goldman equation. As a result, the cell becomes less sensitive to excitation, and a higher than standard stimulus is required for depolarization of the membrane in order to initiate an action potential. Clinically, this membrane hyperpolarization results in flaccid muscle paralysis, rhabdomyolysis (in severe hypokalemia) and paralytic ileus.
- At the renal level, hypokalemia can cause metabolic alkalosis due to potassium/proton exchange across the cells and nephrogenic diabetes insipidus.
Pathophysiology of Hypokalemic Heart Arrhythmias
- Potassium is essential to the normal muscular function, in both voluntary (i.e. skeletal muscle, e.g. the arms and hands) and involuntary muscle (i.e. smooth muscle in the intestines or cardiac muscle in the heart).
- Severe abnormalities in potassium levels can seriously disrupt cardiac function, even to the point of causing cardiac arrest and death.
- As explained above, hypokalemia makes the resting potential of potassium [E(K)] more negative. In certain conditions, this will make cells less excitable. However, in the heart, it causes myocytes to become hyperexcitable. This is due to two independent effects that may lead to aberrant cardiac conduction and subsequent arrhythmia:
- There are more inactivated sodium (Na) channels available to fire.
- The overall potassium permeability of the ventricle is reduced (perhaps by the loss of a direct effect of extracellular potassium on some of the potassium channels), which can delay ventricular repolarization.
Pathophysiology of Hypokalemic in GI system:
- Low levels of potassium cause slow movement of the GI system and ileus. [7]
Causes
Differentiating Hypokalemia from other Diseases
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Algorithm | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Other Diagnostic Studies
Treatment
Medical Therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case Studies
Related Chapters
- ↑ Daly K, Farrington E (2013). "Hypokalemia and hyperkalemia in infants and children: pathophysiology and treatment". J Pediatr Health Care. 27 (6): 486–96, quiz 497–8. doi:10.1016/j.pedhc.2013.08.003. PMID 24139581.
- ↑ Unwin RJ, Luft FC, Shirley DG (February 2011). "Pathophysiology and management of hypokalemia: a clinical perspective". Nat Rev Nephrol. 7 (2): 75–84. doi:10.1038/nrneph.2010.175. PMID 21278718.
- ↑ 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.
- ↑ Bisogni V, Rossi GP, Calò LA (June 2014). "Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology". Blood Press. 23 (3): 189–92. doi:10.3109/08037051.2013.832967. PMID 24053336.
- ↑ 5.0 5.1 Guyton, A.C. & Hall, J.E. (2016) Textbook of Medical Physiology (13th ed.) Philadelphia: Elsevier Saunder ISBN 978-1-4557-7005-2
- ↑ Pohl, Hana R.; Wheeler, John S.; Murray, H. Edward (2013). "Sodium and Potassium in Health and Disease". 13: 29–47. doi:10.1007/978-94-007-7500-8_2. ISSN 1559-0836.
- ↑ Brigode, WilliamMatthew; Jones, Christian; Vazquez, DanielE; Evans, DavidC (2015). "Scrutinizing the evidence linking hypokalemia and ileus: A commentary on fact and dogma". International Journal of Academic Medicine. 1 (1): 21. doi:10.4103/2455-5568.172705. ISSN 2455-5568.