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. Assistant Editor(s)-In-Chief: Jack Khouri

Low level of potassium (usually below 3.5 mEq/L) in body is called hypokalemia. The condition is also known as potassium deficiency.

The prefix hypo- means low and kal refers to kalium, which is Neo-Latin for potassium. The end portion of the word, -emia, means “in the blood” (note, however, that hypokalemia is usually indicative of a systemic potassium deficit).

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. Normally, total potassium excretion in stool is low and most ingested potassium is absorbed. The kidney is the main 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%).

The etiology of hypokalemia can be quite difficult to diagnose. Diferent organ systems play role in the regulation of potassium level and any derangement to their normal function can cause hypokalemia. Drugs, diarrhea, kidney disease, endocrine diseases and many others are potential culprits. Hypokalemia can be the consequence of decreased ingestion, increased losses (renal, GI or excessive sweating) or transcellular shift from the extracellular to the intracellular compartment. The most common causes are diarrhea, vomiting and diuretic use (mostly loop and thiazide diuretics).

Diagnosis relies on a constellation of findings including:

Past medical history and medication history are so important in finding the reason of hypokalemia (eg hyperthyroidism, hyperaldosteronism, Cushing’s disease,etc).

• Muscle weakness, cramping, and paralysis.
• Palpitation.
• Polyuria.
• Depression, psychosis, delirium.

Many labs can be helpful. The transtubular potasium gradient (TTKG), urine potassium, sodium, osmolality and chloride levels can help define the etiology of hypokalemia.

The most notable EKG findings in hypokalemia are due to the delayed ventricular repolarization, manifesting as (QT-U) with prominent U waves. The ECG changes of hypokalemia are commonly seen at potassium levels < 3 meq/Li. 90% of the patients with potassium levels <2.7 meq/L have abnormal ECG findings.

The oral route is the safest. There are many oral potassium salts that can be prescribed including potassium chloride (the most popular) and the organic alkalinizing salts that are metabolized to potassium bicarbonate in the body. Severe hypokalemia ca be treated via IV potassium chloride infusion with doses that shouldn’t exceed 60 mEq/L unless ECG monitoring is provided. A central line can be used for administration of greater concentrations of potassium chloride.

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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.Assistant Editor(s)-In-Chief: Jack Khouri, Alieh Behjat, M.D.[3]

• Potassium is the most common intracellular cation. Approximately 98% of total potassium exists in the intracellular fluid (ICF), which has a normal range of 140–150 mEq/l. Merely 2% of this cation is placed in the extracellular fluids (ECF), where it ranges from 3.5 to 5 mEq/l. Potassium is essential during numerous body functions, particularly for excitable cells such as muscle and nerve cells. 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%).

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]}

• The Kidneys play a vital role in keeping the balance of potassium.
• At the glomerulus, potassium is freely filtered and reabsorbed mainly in the proximal tubule and thick ascending limb of 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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• Aldosterone
• High urine flow rate
• High distal sodium delivery
• Metabolic alkalosis
• High extracellular fluid K+ concentration ^[5]

• Na/K ATPase
• Insulin
• Catecholamines
• Plasma potassium concentration
• Extracellular pH
• Hyperosmolarity ^[6]

• Potassium is the most common intracellular cation. Approximately 98% of total potassium exists in the intracellular fluid (ICF), which has a normal range of 140–150 mEq/l. Merely 2% of this cation is placed in the extracellular fluids (ECF), where it ranges from 3.5 to 5 mEq/l.
• Potassium is essential during numerous body functions, particularly for excitable cells such as muscle and nerve cells.
• Diet, mostly fruits and vegetables, is the major source of potassium for the body.^{[7] [8]}

The normal ratio of intracellular to extracellular potassium in the body is vital for the generation of action potential and results in appropriate cardiac and neuromuscular cells performance. By decreasing the potassium concentration in extracellular space, the amount of the potassium gradient across the cell membrane is risen and results in hyperpolarization. This alteration moves the resting membrane potential from the threshold to a higher level; hence, a bigger than standard stimulus is necessary to generate an action potential. Consequently, reduced excitability in the neurons and muscle cells would appear and cause flaccid muscle paralysis, rhabdomyolysis (in severe hypokalemia), and paralytic ileus.^[9]

• Hypokalemia in neurons and muscle cells reduces the membrane responsiveness and causes hyperpolarization. But in cardiac cells, specifically in the conducting system, depolarization is observed. The main reason is the alteration of ion selectivity of TWIK-1 K+ channels, which in standard situation leak potassium. During pathological hypokalemia, these channels transport sodium inward the cells, leading to paradoxical depolarization and may result in cardiac arrhythmias.

• Decreased extracellular potassium also suppresses the activity of some potassium channels conductance, and in turn, it delays ventricular repolarization. Prolonged repolarization could also predispose re-entrant arrhythmias.

• Moreover, Hypokalemia can inhibit Na+-K+ ATPase activity, leading to intracellular Na+ And Ca2+ increase. The accumulation of intracellular ca2+ activates calmodulin kinase and, in turn, induces late Na+ and Ca2+ currents and causes a further reduction in repolarization reserve. This would result in early after-depolarization (EAD)–mediated arrhythmias.^{[10] [11]}

• A low level of potassium causes dysfunctional gastrointestinal smooth muscle performance, the slow movement of the GI system, constipation, and paralytic ileus. The primary rationale behind them is the impairment of normal action potential in the muscle cell membrane, which disturbs favorable contraction and cellular depolarization. ^{[12] [9]}

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