Potassium and its clinical application

Potassium and its clinical application

Potassium has atomic number 19 and the chemical symbol K, which is derived from its Latin name ‘kalium’. Potassium was first isolated from potash, which is potassium carbonate (K₂CO₃). Potassium occurs in nature only in the form of its ion (K⁺) either dissolved in the ocean or coordinated in minerals because elemental potassium reacts violently with water. Potassium ions are essential for the human body and are also present in plants. The major use of K⁺ can be found in fertilisers, which contains a variety of potassium salts such as potassium chloride (KCl), potassium sulfate (K₂SO₄) and potassium nitrate (KNO₃). KCl is also found in table salt, whereas potassium bromate (KBrO₃) is an oxidising agent and is used as flour improver. Potassium bisulfite (KHSO₃) can be used as a food preservative in wine and beer.

1. Biological importance of potassium ions in the human body – action potential

The so-called action potential occurs in a variety of excitable cells such as neurons, muscle cells and endocrine cells. It is a short-lasting change of the membrane potential and plays a vital role in the cell-to-cell communi-cation. In animal cells, there are two types of action potential. One type is produced by the opening of calcium ion (Ca²⁺) channels and this is longer lasting than the second type, namely the Na⁺-based action potential.

The Na⁺/K⁺-based action potential is short-lived (only 1 ms) and therefore mostly found in the brain and nerve cells. Potassium ions are crucial for the functioning of neurons, by influencing the osmotic balance between the cells and the interstitial fluid. The concentration of K⁺ within and outside the cells is regulated by the so-called Na⁺/K⁺-ATPase pump. Under the use of ATP, three Na⁺ ions are pumped outside the cell and two K⁺ ions are actively transported into the cell. As a result, an electrochemical gradient over the cell membrane is created; the so-called resting potential is established.

In the case of any cell-to-cell communication, changes of the membrane reach a specific part of the neu-ron first. As a result, sodium channels, which are located in the cell membrane, will open. As a result of the osmotic gradient, which has been established by the Na⁺/K ⁺-pump, Na⁺ ions enter the cytosol and the electrochemical gradient becomes less negative. Once a certain level, called the threshold, is reached, more sodium channels are opened, and more Na⁺ ions flow inside the cell – this creates the so-called action poten-tial. The electrochemical gradient over the cell membrane is thus reversed. Once this happens, the sodium ion channels close and the potassium channels open. The concentration of K⁺ in the cytosol is higher than in the extracellular fluid, and therefore potassium ions leave the cell. This allows the cell to shift back to its resting membrane potential. As the membrane potential approaches the resting potential, all voltage-gated K⁺ channels open. In actual fact, the membrane repolarises beyond the resting potential; this is known as hyperpolarisation. The last step is now to reintroduce the initial balance of sodium and potassium ions. This means that the Na⁺/K⁺-pump transports Na⁺ actively out of the cytosol and K⁺ into it. As a result, the initial steady state is reinstated (Figure 2.18).

Figure 2.18 Action potential. (1) Threshold of excitation. Na+ channels open and allow Na+ to enter the cell. (2) K+ channels open and K+ leaves the cell. (3) No more Na+ enters cell. (4) K+ continues to leave the cell. This causes the membrane to return to resting potential. (5) K+ channels close and Na+ channels resent. (6) Hyperpolarisation

2. Excursus: the Nernst equation

As previously outlined, the electric potential across a cell membrane is created by the difference in ion concen-tration inside and the outside the cell. The Nernst equation is an important equation that allows the calculation of the electric potential for an individual ion.

Looking at the Nernst equation, R is the gas constant, T is the temperature in kelvin, F is the Faraday constant and z is the net charge of the ion. [ion]_in and [ion]_out are the concentration of the particular ion inside and outside the cell. The equation can also be expressed as log₁₀. Furthermore, at room temperature (25 ^∘C), the term −RT/F can be seen as a constant, and the Nernst equation can be simplified:

The Nernst equation can also be used to calculate the overall potential in a redox equation by using the ion concentrations of both half-equations. This also allows the calculation of the reduction potential E of two different ions of varying concentration. The Nernst equation can be expanded to the following equation, where [Red] and [Ox] represent the concentrations of the reductant and oxidant (Ox + e⁻ → Red):

In order to calculate the reduction potential ΔE of two different ions of varying concentration, the Nernst equation can be expanded to the following equation:

It is also possible to calculate the overall electric potential across the cell membrane by taking several different ions into account. The so-called Goldman equation, which will not be further illustrated in this book, can be used to calculate this value.

3. Potassium salts and their clinical application: hypokalaemia

In the human body, 95% of the K⁺ can be found inside the cells, with the remaining 5% mainly circulating in the blood plasma . This balance is carefully maintained by the Na⁺/K⁺ pump, and imbalances, such as seen in hypo or hyperkalaemia, can have serious consequences.

Hypokalaemia is a potentially serious condition where the patient has low levels of K⁺ in his/her blood plasma. Symptoms can include weakness of the muscles or ECG (electrocardiogram) abnormalities. Mostly, hypokalaemia can be a result of reduced K⁺ intake caused by GI disturbance, such as diarrhoea and vomit-ing, or increased excretion of K⁺ caused by diuresis. Hypokalaemia is often found in patients treated with diuretics such as loop diuretics and thiazides. These classes of drugs increase the secretion of Na⁺ in the nephrons in order to increase water excretion. Unfortunately, they also increase the excretion of K⁺ and lead to hypokalaemia. In contrast, potassium-sparing diuretics actively preserve potassium ions, and patients treated with loop diuretics or thiazides often receive also potassium-sparing diuretics [3a].

Potassium ions are excreted via the kidneys. Within the kidneys, ∼150–180 l of plasma is filtered every day through the glomerulus, which is part of the nephron, in order to produce urine. As previously described, the filtration process is followed by a series of processes along the nephron, where a variety of ions are secreted and re-absorbed in order to regulate plasma imbalances and manage the urine volume (Section 2.3.1). K⁺ is passively secreted at the proximal tubule and also moves into the interstitial fluid via a counter-flow process to Na⁺ mainly at the distal tubule (Figure 2.19).

Oral supplementation in form of potassium salts is especially necessary in patients who take anti-arrhythmic drugs, suffer from renal artery stenosis and/or severe heart failure or show severe K⁺ losses due to chronic diarrhoea or abusive use of laxatives. 

Regulation of the plasma K⁺ level may also be required in the care of elderly patients when the K⁺ intake is reduced as a result of changing dietary habits, but special attention has to be given to patients with renal insufficiency because K⁺ excretion might be reduced. Potassium salts are preferably given as liquid preparations, and KCl is the preferred salt used. Other potassium-based salts can be used if the patient is at risk of developing hyperchloraemia – increased chloride plasma levels. Typically potassium salts are dissolved in water, but the salty and bitter taste makes them difficult to formulate. Oral bicarbonate solutions such as potassium bicarbonate are typically given orally for chronic acidosis states – low pH of the blood plasma. This can be again due to impaired kidney function. The use of potassium bicarbonate for the treatment of acidosis has to be carefully evaluated, as even small changes of the potassium plasma levels can have severe consequences (Figure 2.20) [3a].

Potassium citrate is used in the United Kingdom as an over-the-counter drug for the relief from discomfort experienced in mild urinary-tract infections by increasing the urinary pH. It should be not given to men if they experience pain in the kidney area (risk of kidney stones) or if blood or pus is present in the urine. Also, patients with raised blood pressure or diabetes should avoid taking potassium citrate without consultation with their general practitioner (GP). Caution is generally advised to patients with renal impairment, cardiac problems and the elderly [3a].

4. Adverse effects and toxicity: hyperkalaemia

The therapeutic window for K⁺ in the blood plasma is very small (3.5–5.0 mmol), and especially hyper-kalaemia, an increased level of K⁺ in the plasma, can lead to severe health problems . Potassium salts can cause nausea and vomiting and in extreme cases can lead to small bowel ulcerations. Acute severe hyper-kalaemia is defined when the plasma potassium concentration exceeds 6.5 mmol/l or if ECG changes are seen. This can lead to cardiac arrest, which needs immediate treatment. Treatment options include the use of calcium gluconate intravenous injections, which minimises the effects of hyperkalaemia on the heart. The intravenous injection of soluble insulin promotes the shift of potassium ions into the cells. Diuretics can also be used to increase the secretion of K⁺ in the kidneys, and dialysis can be a good option if urgent treat-ment is required. Ion-exchange resins, such as polystyrene sulfonate resins, may be used in mild to moderate hyperkalaemia to remove excess potassium if there are no ECG changes present. As previously mentioned, especially in patients suffering from kidney diseases or end-stage renal failure, the potassium levels have to be monitored very carefully and corrected if necessary. Potassium excretion is likely to be disturbed, and a build-up of potassium in the blood plasma may trigger a cardiac arrest [3a].

Potassium salts are also available in the form of tablets or capsules for oral application especially as nonpre-scription medicine. Usually, their formulation is designed to allow the potassium ions to be slowly secreted, because very high concentrations of K⁺ are known to be toxic to tissue cells and can cause injury to the gastric mucosa. Therefore, nonprescription potassium supplement pills are usually restricted to <100 mg of K⁺ .