Potassium: Definition, Synthesis, Absorption, Transport, and Distribution

Potassium is a monovalent cation (positively charged ion, K+) and the seventh most abundant element in the Earth’s crust. It is in the 1st main group in the periodic table and thus belongs to the group of alkali metals.

Resorption

The absorption (uptake) of potassium, most of which occurs in the upper portions of the small intestine, occurs rapidly and with high efficiency (≥ 90%) paracellularly (transport of substances through the interstitial spaces of intestinal epithelial cells) by passive diffusion. Intestinal (gut-related) uptake of potassium is largely independent of oral intake and averages between 70 and 130 mmol/day. Magnesium deficiency decreases potassium absorption.

Distribution in the body

The total potassium content of the human body is approximately 40-50 mmol/kg body weight (1 mmol K+ is equivalent to 39.1 mg) and depends on body build, age, as well as gender. For example, men have an average total body potassium of about 140 g (3,600 mmol) and women have an average total body potassium of about 105 g (2,700 mmol). Unlike sodium, potassium is predominantly localized intracellularly (inside the cell). Potassium is quantitatively the most significant cation in the intracellular space (IZR). Approximately 98% of the total potassium in the human body is located inside the cell – about 150 mmol/l. There, the electrolyte is more than 30 times more concentrated than in the extracellular (outside the cell) fluid. Thus, the serum potassium concentration, which varies between 3.5 and 5.5 mmol/l, accounts for less than 2% of the total. Since extracellular potassium is very sensitive to fluctuations, even minor variations can lead to severe neuromuscular and muscular dysfunction. The potassium content of cells varies depending on the particular tissue and is an expression of their metabolic activity (metabolic activity). For example, muscle cells contain the highest percentage of the mineral (60%), followed by erythrocytes (red blood cells) (8%), liver cells (6%), and other tissue cells (4%). Approximately 75% of total body potassium is rapidly exchangeable and in dynamic equilibrium with the various body compartments. The regulation of potassium homeostasis or potassium distribution between the intracellular and extracellular space (EZR) is carried out by insulin (hormone lowering the blood sugar level), aldosterone (steroid hormone belonging to the mineralocorticoids) and catecholamines (hormones or neurotransmitters with a stimulating effect on the cardiovascular system). In addition, the ratio of intracellular to extracellular potassium is determined by magnesium and by the pH value in the blood. The extent to which these factors influence potassium metabolism is discussed in more detail below.

Excretion

Excess amounts of potassium in the body are largely excreted by the kidneys. When potassium is in balance, 85-90% is eliminated in the urine, 7-12% in the feces (stool), and approximately 3% in sweat. The secretion of potassium into the lumen of the renal tubules or renal potassium excretion is highly adaptive. In the presence of potassium deficiency, urinary potassium concentration may decrease to ≤ 10 mmol/l, whereas in the presence of hyperkalemia (potassium excess), it may increase to ≥ 200 mmol/l. A renal potassium excretion (excretion via the kidney) of about 50 mmol/24 hours indicates normal potassium balance. Because potassium can be actively secreted (excreted) throughout the gastrointestinal (GI) tract in exchange for sodium, emesis (vomiting), diarrhea (diarrhea), and laxative abuse (misuse of laxatives) result in increased potassium losses. In chronic potassium overload and impaired renal function, potassium is increasingly secreted into the colon (large intestine) lumen, resulting in fecal elimination of 30-40% of the daily ingested amount.

Regulation of potassium homeostasis

The distribution of potassium between EZR and IZR is influenced by the following factors:

Insulin, aldosterone, and catecholamines are involved in the regulation of extrarenal (outside the kidney) potassium metabolism.In the presence of hyperkalemia (potassium excess, > 5.5 mmol/l), these hormones stimulate intracellular expression and incorporation of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase; enzyme that catalyzes the transport of Na+ ions out of the cell and K+ ions into the cell under ATP cleavage) into the cell membrane and thus potassium transport into the cells, resulting in a rapid decrease in extracellular potassium concentration. In contrast, in hypokalemia (potassium deficiency, < 3.5 mmol/l), there is inhibition of Na+/K+-ATPase – mediated by a decrease in insulin, aldosterone, and catecholamine levels – and consequent increase in extracellular potassium concentration. Various diseases can cause distributional disturbances of potassium between the IZR and EZR. For example, acidosis (hyperacidity of the body, blood pH < 7.35) leads to an efflux of potassium from the cells into the extracellular space in exchange for hydrogen (H+) ions. In contrast, alkalosis (blood pH > 7.45) is accompanied by an influx of extracellular potassium into the cells. Acidosis and alkalosis, respectively, result in hyperkalemia (potassium excess, > 5.5 mmol/l) and hypokalemia (potassium deficiency, < 3.5 mmol/l) – a decrease in blood pH by 0.1 causes an increase in serum potassium concentration by about 1 mmol/l. Potassium homeostasis is closely related to magnesium metabolism. The interactions of potassium and magnesium involve gastrointestinal absorption (uptake by the gastrointestinal tract) and renal excretion, as well as endogenous distribution between EZR and IZR and, in particular, various cellular processes. A deficiency of magnesium increases the permeability of potassium at the cell membranes by influencing the potassium channels, which has an effect on the cardiac muscle action potential.Significance of the kidney in potassium balanceBody potassium is balanced primarily by the kidney. There, potassium is glomerularly filtered. About 90% of the filtered potassium ions are reabsorbed in the proximal tubule (main section of the renal tubules) and in Henle’s loop (straight sections of the renal tubules and transition section). Finally, in the distal tubule (middle section of renal tubules) and collecting tubule of the kidney, the crucial regulation of potassium excretion (potassium excretion) occurs.With potassium balance, about 90% of orally supplied potassium is eliminated by the kidneys within 8 hours and more than 98% is eliminated within 24 hours.The following factors influence renal potassium excretion:

  • Mineral corticoids (steroid hormones synthesized in the adrenal cortex), such as aldosterone – hyperaldosteronism (increased aldosterone synthesis) increases renal potassium excretion
  • Sodium (antagonist (opponent) of potassium) – excessive sodium intake can lead to potassium depletion; a Na:K ratio of ≤ 1 is considered optimal
  • Magnesium – hypomagnesemia (magnesium deficiency) leads to renal potassium losses.
  • Diuresis (urinary excretion by the kidneys) – loop diuretics (dehydrating drugs that act on Henle’s loop of the kidney), thiazide-type diuretics, and the presence of osmotic diuresis in diabetes mellitus increase renal potassium excretion
  • Drugs, such as potassium-sparing diuretics (dehydrating drugs that act antagonistically to aldosterone), ACE (angiotensin-converting enzyme) inhibitors (used in hypertension (high blood pressure) and chronic heart failure (heart failure)), Nonsteroidal anti-inflammatory drugs (anti-inflammatory drugs, such as acetylsalicylic acid (ASA) and peripheral analgesics (pain relievers) – decrease renal potassium excretion.
  • Level of potassium intake
  • Acid-base balance (pH in the blood)
  • Increased influx of non-absorbable anions (negatively charged ions) into the tubular lumen (the inner space of the renal tubules).

The kidney is capable of sensing changes in extracellular potassium concentration via specific sensors:

When the serum potassium concentration is increased, the synthesis and secretion (release) of aldosterone is stimulated in the adrenal cortex. The main action of this mineral corticosteroid is to stimulate sodium secretion in the distal tubule and collecting tube of the kidney by increasing the incorporation of sodium channels (ENaC, English : Epithelial Sodium (Na) Channel) and Potassium Channels (ROMK).Renal Outer Medullary Potassium (K) Channel) and sodium-potassium transporters (Na+/K+-ATPase) into the apical and basolateral cell membrane, respectively, to promote sodium reabsorption and potassium secretion into the tubule lumen and thus potassium excretion [4-6, 13, 18, 27]. The result is a decrease or normalization of serum potassium levels. Decreased extracellular potassium concentration leads to a reduction in sodium reabsorption in the renal tubule system (renal tubules) through downregulation of ENaC and ROMK in the apical (tubule-facing) cell membrane, which is accompanied by decreased potassium excretion. The result is an increase or normalization of serum potassium concentration, respectively.

Disruption of renal function

Regulation of potassium homeostasis by the kidneys occurs within narrow limits, provided renal function is normal. In individuals with acute or chronic renal insufficiency (kidney failure) or adrenocortical (NNR) insufficiency (adrenal hypofunction, primary adrenal insufficiency: Addison’s disease), potassium homeostasis is impaired because of significantly decreased renal potassium excretion. The increased potassium retention results in an increase in the total body potassium inventory, which manifests as an elevated serum potassium level – hyperkalemia (potassium excess). Patients with chronic renal failure have hyperkalemia (potassium excess) in 55%. In patients with acute renal failure (ANV), hyperkalemia (potassium excess) is almost always found, especially when the affected individuals are subjected to marked catabolic (degradative) processes, such as surgery, stress, and steroid therapy, or tissue breakdown, as in hemolysis (shortened red blood cell life), infections, and burns. Such patients with disorders of potassium homeostasis should be subject to constant monitoring for serum potassium levels and nutritive potassium intake. In addition to renal dysfunction, the following diseases or factors may be associated with hyperkalemia (excess potassium):

  • Diabetes mellitus with disturbances of autonomic cardiovascular (affecting heart and vessels) function.
  • Insulin deficiency – downregulation (downregulation) of Na+/K+-ATPase.
  • Hypoaldosteronism (deficiency of aldosterone).
  • Respiratory and metabolic acidosis (hyperacidity of the body, blood pH < 7.35), trauma, burns, rhabdomyolysis (dissolution of striated muscle fibers), acute hemolysis (shortened red blood cell life) – cause potassium efflux from cells into the extracellular space
  • Heart failure (cardiac insufficiency) – when taking ACE (angiotensin-converting enzyme) inhibitors and potassium-sparing diuretics (diuretic drugs that act antagonistically to aldosterone), such as spironolactone, there is a reduction in renal potassium excretion
  • Digitalis (plant genus, in German: Fingerhut)-Intoxication – digitalis glycosides (cardiac glycosides) inhibit the Na+/K+-ATPase.
  • Concurrent administration of cardiac glycosides and potassium-containing drugs, saline substitutes, or supplements.
  • Medications, such as heparin (anticoagulant), nonsteroidal anti-inflammatory drugs (anti-inflammatory drugs, such as acetylsalicylic acid (ASA)), and ciclosporin (cyclosporin A) (immune suppression) – reduce renal potassium excretion
  • Sudden extremely high enteral and parenteral (the intestinal tract immediately) potassium load.
  • Alcohol abuse (alcohol abuse)

In patients with uremia (occurrence of urinary substances in the blood above normal values), paradoxically, decreased intracellular potassium concentrations could be found. These result from the impaired glucose tolerance (elevated blood glucose levels) often present in uremic patients as a consequence of increasing insulin resistance (decreased cell response to insulin), which impairs potassium uptake into body cells by downregulation (downregulation) of Na+/K+-ATPase. Increased extracellular potassium levels lead to a decrease in the membrane potential of nerve and muscle cells. Clinically, impaired excitation formation and conduction is manifested by neuromuscular symptoms, such as:

  • General muscle weakness – manifested, for example, by “heavy legs” and breathing disorders.
  • Paresthesias of the hands and feet (damage to sensitive nerve fibers) – manifested as a sensation of discomfort, such as tingling, numbness, and itching, or as a painful burning sensation
  • Paralysis – only in extreme cases
  • Bradycardic arrhythmias (slowed cardiac activity (heart rate < 60 beats/minute), decrease in contractility due to conduction abnormalities) to ventricular fibrillation (pulseless cardiac arrhythmia) and asystole (arrest of electrical and mechanical cardiac action)

Symptoms of hyperkalemia (excess potassium) can occur at serum concentrations > 5.5 mmol/l. In contrast to hypokalemia (potassium deficiency, < 3.5 mmol/l), ECG (electrocardiogram) changes are typical in hyperkalemia (potassium excess), and the extent of these changes depends on the serum potassium concentration. An additional presence of hypocalcemia (calcium deficiency), acidosis (hyperacidity of the body, blood pH < 7.35), or hyponatremia (sodium deficiency) exacerbates the symptomatic course of hyperkalemia (potassium excess).