HYPERKALEMIA AND BRAIN FUNCTION

C. Annichiarico^*

Independent Researcher, University of Bari, Bari, Italy.

*Correspondence to:
Ciro Annichiarico,
Independent Researcher,
University of Bari,
70100 Bari, Italy.
e-mail: annichiarico.ciro63@gmail.com

Received: 29 November, 2024 Accepted: 31 December, 2024

2974-6345 (2024) Copyright © by BIOLIFE This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Hyperkalemia is an increase in blood potassium (K+) that can affect multiple organs, including the functioning of the brain. K+ remains stable between meals due to K+ release primarily from muscle and liver cells, while it decreases with renal excretion and sequestration from muscle cells. K+ resides almost entirely within cells and is absorbed in the small intestine. Increases in this electrolyte can occur with impaired renal excretion or cellular dysfunction. Hyperkalemia is regulated by the kidneys, which dispose of excess K+. Physiological central nervous system (CNS) K+ levels are involved in nerve signaling and hyperkalemia can dysregulate normal brain processes and it may also play a role in neuroinflammation. Increased K+ can cause muscle weakness, fatigue, and, in severe cases, even cognitive dysfunction with confusion, disorientation, and coma. An abnormality in K+ levels can be reflected in the membrane potential of neurons and affects their polarization and excitability. Mild hyperkalemia can cause increased neuronal excitability, muscle spasms, paresthesias, and neuronal and muscular paralysis with respiratory failure and/or cardiac arrhythmias.

KEYWORDS: Hyperkalemia, potassium, brain, neuron, membrane potential

INTRODUCTION

Hyperkalemia is a pathology that varies from mild to severe and very often also involves neuronal dysfunction.  Hyperkalemia is a common electrolyte abnormality with high levels of potassium (K+) in the blood (1). It can significantly impact brain function and may cause neuroinflammation (2). Hyperkalemia can result in life-threatening arrhythmias and is associated with an increased risk of mortality (3). The development of hyperkalemia is often exacerbated by concomitant comorbidities such as diabetes mellitus or cardiovascular diseases (4). Hyperkalemia is managed by eliminating risk factors and through interventions aimed at directly lowering serum K+.

Most intracellular K+ is contained in muscle cells where it acts on the membrane potential. The physiological effect of this electrolyte depends on a normal serum concentration. K+ concentration decreases after renal excretion and sequestration of muscle and liver cells (5). K+ remains stable between meals due to its release mainly from muscle and liver cells. The distribution of K+ between the intracellular and extracellular space is maintained by balancing the activity of the Na/K-ATPase with K+ leak (6) (Table I). Effectors of K+ uptake and leak include insulin, catecholamines, mineral corticoids, tonicity, exercise, and acid-base status (7). More than 95% of K+ resides intracellularly and most of it is absorbed in the small intestine.

Table I. Na⁺/K⁺ ATPase dysfunction can cause the following dysfunctions to occur.

Increased K+ intake causes hyperkalemia which may result in impaired renal excretion and/or cellular redistribution (8). The kidney has an important role in maintaining K+ homeostasis and healthy kidneys possess a great ability to dispose of excess K+, maintaining normal K+ serum levels even with intakes as high as 400 mmol per day (9). Most of the filtered K+ is reabsorbed in the proximal convoluted tubule and the loop of Henle. Renal K+ balance is largely determined by K+ secretion occurring in the distal nephron and collecting duct (10).

DISCUSSION

In the brain, K+ is crucial for nerve signaling and for central nervous system (CNS) functioning, but excessive levels can disrupt normal neurological processes (11). Hyperkalemia is defined as an elevated level of K+ in the blood. It can significantly impact brain function and may contribute to neuroinflammation (12). In the brain, K+ is crucial for nerve signaling and CNS function, but excessive levels can disrupt normal neurological processes (13). Hyperkalemia impairs nerve transmission, causing muscle weakness, fatigue, and in some cases, even paralysis (14). In addition, severe cases of hyperkalemia can cause cognitive dysfunction with confusion, disorientation, and coma (12). In rarer cases, seizures can occur due to disrupted neuronal excitability.

K+ is also an important element for the function of immune cells (15). In cases of hyperkalemia, there may alterations in the functioning of immune cells, such as T lymphocytes, causing an Ig deficiency, because, in the immune system, antibody-producing B lymphocytes and T cells (particularly IL-4-producing T helper cells) are interdependent (16). Excess K+ can affect other immune cells such as macrophages by altering their ability to phagocytose infectious agents and to present antigen correctly (17,18). Immune dysfunction due to hyperkalemia affects inflammation and activation of the NLRP3 inflammasome (19). High extracellular K+ inhibits the NLRP3 inflammasome, reducing excessive inflammatory responses. In hyperkalemia, the dysregulation of immune cells can lead to chronic inflammatory disorders, while initially it may suppress inflammation (20).

Hyperkalemia significantly affects neurons because of the crucial role of K+ in maintaining resting membrane potential and neuronal excitability (21). Hyperkalemia causes neurons to depolarize from their resting membrane potential. Neurons maintain a resting membrane potential of about -70 mV, largely due to the Na⁺/K⁺ pump and K+ leak channels. Extracellular hyperkalemia reduces the K+ gradient with less influx, causing depolarization and mild hyperkalemia can produce increased neuronal excitability (22). If there is mild extracellular hyperkalemia of 5.5-6.5 mEq/L, neurons are more excitable because they are closer to the threshold for action potentials. These effects can lead to spontaneous or excessive discharges, potentially causing muscle spasms, paresthesias, or seizures, while severe hyperkalemia can lead to reduced excitability and paralysis. In severe hyperkalemia (>7.0 mEq/L), persistent depolarization inactivates voltage-gated Na⁺ channels, preventing them from reopening for further action potentials. These effects cause neuronal and muscle paralysis, which may contribute to respiratory failure or cardiac arrhythmias (23).

Non-physiological neuromuscular transmission leads to muscle weakness and paralysis, clinical manifestations related to neuronal dysfunction (24). In addition, abnormal sensations such as tingling or numbness (paraesthesia), and in extreme cases, seizures, and altered mental states such as confusion, lethargy, or coma may occur (25).

CONCLUSIONS

Hyperkalemia disrupts neuronal function by altering the resting membrane potential and action potential generation. Mild cases increase excitability, while severe cases lead to neuronal paralysis. Proper management of K+ levels is essential to prevent life-threatening complications.

Conflict of interest

The author declares that they have no conflict of interest.

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