Potassium

Potassium is the eighth or ninth most common element by mass (0.2%) in the human body, so that a 60 kg adult contains a total of about 120 g of potassium.^[55] The body has about as much potassium as sulfur and chlorine, and only calcium and phosphorus are more abundant (with the exception of the ubiquitous CHON elements).^[56] Potassium ions are present in a wide variety of proteins and enzymes.^[57]

Biochemical function

Potassium levels influence multiple physiological processes, including^[58][59][60]

• resting cellular-membrane potential and the propagation of action potentials in neuronal, muscular, and cardiac tissue. Due to the electrostatic and chemical properties, K+
  ions are larger than Na+
  ions, and ion channels and pumps in cell membranes can differentiate between the two ions, actively pumping or passively passing one of the two ions while blocking the other.^[61]
• hormone secretion and action
• vascular tone
• systemic blood pressure control
• gastrointestinal motility
• acid–base homeostasis
• glucose and insulin metabolism
• mineralocorticoid action
• renal concentrating ability
• fluid and electrolyte balance

Homeostasis

Potassium homeostasis denotes the maintenance of the total body potassium content, plasma potassium level, and the ratio of the intracellular to extracellular potassium concentrations within narrow limits, in the face of pulsatile intake (meals), obligatory renal excretion, and shifts between intracellular and extracellular compartments.

Plasma levels

Plasma potassium is normally kept at 3.5 to 5.0 millimoles (mmol) [or milliequivalents (mEq)] per liter by multiple mechanisms. Levels outside this range are associated with an increasing rate of death from multiple causes,^[62] and some cardiac, kidney,^[63] and lung diseases progress more rapidly if serum potassium levels are not maintained within the normal range.

An average meal of 40-50 mmol presents the body with more potassium than is present in all plasma (20-25 mmol). However, this surge causes the plasma potassium to rise only 10% at most as a result of prompt and efficient clearance by both renal and extra-renal mechanisms.^[64]

Hypokalemia, a deficiency of potassium in the plasma, can be fatal if severe. Common causes are increased gastrintestinal loss (vomiting, diarrhea), and increased renal loss (diuresis).^[65] Deficiency symptoms include muscle weakness, paralytic ileus, ECG abnormalities, decreased reflex response; and in severe cases, respiratory paralysis, alkalosis, and cardiac arrhythmia.^[66]

Control mechanisms

Potassium content in the plasma is tightly controlled by four basic mechanisms, which have various names and classifications. The four are 1) a reactive negative-feedback system, 2) a reactive feed-forward system, 3) a predictive or circadian system, and 4) an internal or cell membrane transport system. Collectively, the first three are sometimes termed the "external potassium homeostasis system";^{[citation needed]} and the first two, the "reactive potassium homeostasis system".

• The reactive negative-feedback system refers to the system that induces renal secretion of potassium in response to a rise in the plasma potassium (potassium ingestion, shift out of cells, or intravenous infusion.)
• The reactive feed-forward system refers to an incompletely understood system that induces renal potassium secretion in response to potassium ingestion prior to any rise in the plasma potassium. This is probably initiated by gut cell potassium receptors that detect ingested potassium and trigger vagal afferent signals to the pituitary gland.
• The predictive or circadian system increases renal secretion of potassium during mealtime hours (e.g. daytime for humans, nighttime for rodents) independent of the presence, amount, or absence of potassium ingestion. It is mediated by a circadian oscillator in the suprachiasmatic nucleus of the brain (central clock), which causes the kidney (peripheral clock) to secrete potassium in this rhythmic circadian fashion.

  The action of the sodium-potassium pump is an example of primary active transport. The two carrier proteins embedded in the cell membrane on the left are using ATP to move sodium out of the cell against the concentration gradient; The two proteins on the right are using secondary active transport to move potassium into the cell: this process results in reconstitution of ATP.

• The ion transport system moves potassium across the cell membrane using two mechanisms. One is active and pumps sodium out of, and potassium into, the cell. The other is passive and allows potassium to leak out of the cell. Potassium and sodium cations influence fluid distribution between intracellular and extracellular compartments by osmotic forces. The movement of potassium and sodium through the cell membrane is mediated by the Na+/K+-ATPase pump.^[67] This ion pump uses ATP to pump three sodium ions out of the cell and two potassium ions into the cell, creating an electrochemical gradient and electromotive force across the cell membrane. The highly selective potassium ion channels (which are tetramers) are crucial for hyperpolarization inside neurons after an action potential is triggered, to cite one example. The most recently discovered potassium ion channel is KirBac3.1, which makes a total of five potassium ion channels (KcsA, KirBac1.1, KirBac3.1, KvAP, and MthK) with a determined structure.^[68] All five are from prokaryotic species.

Renal filtration, reabsorption, and excretion

Renal handling of potassium is closely connected to sodium handling. Potassium is the major cation (positive ion) inside animal cells [150 mmol/L, (4.8 g)], while sodium is the major cation of extracellular fluid [150 mmol/L, (3.345 g)]. In the kidneys, about 180 liters of plasma is filtered through the glomeruli and into the renal tubules per day.^[69] This filtering involves about 600 g of sodium and 33 g of potassium. Since only 1–10 g of sodium and 1–4 g of potassium are likely to be replaced by diet, renal filtering must efficiently reabsorb the remainder from the plasma.

Sodium is reabsorbed to maintain extracellular volume, osmotic pressure, and serum sodium concentration within narrow limits; potassium is reabsorbed to maintain serum potassium concentration within narrow limits.^[70] Sodium pumps in the renal tubules operate to reabsorb sodium. Potassium must be conserved also, but, because the amount of potassium in the blood plasma is very small and the pool of potassium in the cells is about thirty times as large, the situation is not so critical for potassium. Since potassium is moved passively^[71][72] in counter flow to sodium in response to an apparent (but not actual) Donnan equilibrium,^[73] the urine can never sink below the concentration of potassium in serum except sometimes by actively excreting water at the end of the processing. Potassium is excreted twice and reabsorbed three times before the urine reaches the collecting tubules.^[74] At that point, urine usually has about the same potassium concentration as plasma. At the end of the processing, potassium is secreted one more time if the serum levels are too high.

With no potassium intake, it is excreted at about 200 mg per day until, in about a week, potassium in the serum declines to a mildly deficient level of 3.0–3.5 mmol/L.^[75] If potassium is still withheld, the concentration continues to fall until a severe deficiency causes eventual death.^[76]

The potassium moves passively through pores in the cell membrane. When ions move through pumps there is a gate in the pumps on either side of the cell membrane and only one gate can be open at once. As a result, approximately 100 ions are forced through per second. Pores have only one gate, and there only one kind of ion can stream through, at 10 million to 100 million ions per second.^[77] The pores require calcium to open^[78] although it is thought that the calcium works in reverse by blocking at least one of the pores.^[79] Carbonyl groups inside the pore on the amino acids mimic the water hydration that takes place in water solution^[80] by the nature of the electrostatic charges on four carbonyl groups inside the pore.^[81]

In diet

Detection by taste buds

Potassium can be detected by taste because it triggers three of the five types of taste sensations, according to concentration. Dilute solutions of potassium ions taste sweet, allowing moderate concentrations in milk and juices, while higher concentrations become increasingly bitter/alkaline, and finally also salty to the taste. The combined bitterness and saltiness of high-potassium solutions makes high-dose potassium supplementation by liquid drinks a palatability challenge.^[82][83]

Adequate intake

Adequate potassium intake is achieved by eating a variety of foods. Potassium is present in all fruits, vegetables, meat and fish. Foods with high potassium concentrations include yam, parsley, dried apricots, milk, chocolate, all nuts (especially almonds and pistachios), potatoes, bamboo shoots, bananas, avocados, coconut water, soybeans, and bran.^[84] Dried apricots have the highest concentration of potassium by weight of any food. Many processed foods contain no potassium.

Optimal intake

Epidemiological studies indicate that diets high in potassium can reduce the risk of hypertension and possibly stroke (by a mechanism independent of blood pressure). The 2004 guidelines of the Institute of Medicine specify a Dietary Reference Intake (DRI]) of 4,700 mg of potassium (100 mEq); most Americans consume only half that amount per day.^[85][86] Likewise, in the European Union, in particular in Germany and Italy, insufficient potassium intake is somewhat common.^[87] However, the British NHS recommends a lower intake, saying that adults need 3,500 mg per day and that excess amounts may cause health problems such as stomach pain and diarrhoea.^[88] A meta-analysis concluded that a 1640 mg increase in the daily intake of potassium was associated with a 21% lower risk of stroke.^[89]

Deficient intake

Diets low in potassium can lead to hypertension^[90] and hypokalemia.

Supplementation

Supplements of potassium are most widely used in conjunction with diuretics that block reabsorption of sodium and water upstream from the distal tubule (thiazides and loop diuretics), because this promotes increased distal tubular potassium secretion, with resultant increased potassium excretion. A variety of prescription and over-the counter supplements are available. Potassium chloride may be dissolved in water, but the salty/bitter taste make liquid supplements unpalatable.^[82] Typical doses range from 10 mmol (400 mg), to 20 mmol (800 mg). Potassium is also available in tablets or capsules, which are formulated to allow potassium to leach slowly out of a matrix, since very high concentrations of potassium ion that occur adjacent to a solid tablet can injure the gastric or intestinal mucosa. For this reason, non-prescription potassium pills are limited by law in the US to a maximum of 99 mg of potassium.

Since the kidneys are the site of potassium excretion, individuals with impaired kidney function are at risk for hyperkalemia if dietary potassium and supplements are not restricted. The more severe the impairment, the more severe is the restriction necessary to avoid hyperkalemia.