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

Sodium is a monovalent cation (positively charged ion) with the chemical symbol Na+, which is the sixth 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. Elemental sodium was first obtained from sodium hydroxide (NaOH) by fused-salt electrolysis in 1808 by the English chemist Sir Humphry Davy. Around 1930, St. John recognized the essentiality (vitality) of sodium for normal growth, while Clark described the mineral’s importance in maintaining the osmotic pressure (pressure that drives the flow of dissolved particles through a semipermeable membrane as part of osmosis) of body fluids. In 1966, there was the discovery of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase; enzyme that catalyzes the transport of Na+ ions out of the cell and potassium (K+) ions into the cell under ATP cleavage) in cell membranes by Woodbury. Six years later, Coleman et al postulated increased serum sodium concentration as a cause of hypertension (high blood pressure). Sodium exists in nature primarily in bound form. Its most important companion is chloride (Cl-) – sodium chloride (NaCl) or table salt – with which it influences water balance and the volume of extracellular (outside the cell) fluid (ECM; extracellular body mass). Any change in the body’s sodium levels causes a corresponding change in extracellular volume. Thus, an excess of sodium is associated with an osmotically induced increase in extracellular volume (hypervolemia)-3 g of sodium (7.6 g NaCl) can bind 1 liter of water-which may be accompanied by edema (water retention in tissues) and an increase in body weight. Sodium deficiency, on the other hand, leads to a reduction in extracellular volume (hypovolemia) as a result of increased water loss, which can result in exsiccosis (dehydration due to a reduction in body water) and a decrease in body weight.The positively charged electrolyte potassium (K+) is the most important antagonist of sodium, including in the regulation of blood pressure. While sodium exerts a hypertensive (blood pressure-increasing) effect, potassium causes a decrease in blood pressure. Accordingly, the sodium/potassium ratio in the diet is considered to be of major importance. Japanese studies have shown that in people who eat a diet very rich in salt (table salt), the sodium-potassium ratio also increases blood pressure. The most important source of sodium for humans is table salt – 1 g of NaCl contains 0.4 g of sodium, or 1 g of sodium is found in 2.54 g of NaCl. About 95% of sodium intake comes from sodium chloride. Common salt is used both as a seasoning and as a preservative. For this reason, industrially processed and prepared foods, such as meat and sausage products, canned fish, hard cheese, bread and baked goods, canned vegetables and ready-made sauces, have a high sodium content (> 400 mg/100 g), with long-life sausage products, smoked ham, certain types of cheese and foods preserved in brine, such as herring and cucumbers, being particularly high in sodium (> 1,000 mg/100 g). In contrast, unprocessed or natural plant foods, such as cereals, potatoes, nuts, fruits, and vegetables, with the exception of some root and leafy vegetables, are low in sodium (< 20 mg/100 g), although considerable regional differences must be expected – proximity to the sea, fertilization [1-5, 10, 12, 14, 18, 19, 22, 26, 27]. According to numerous professional societies and the WHO (World Health Organization), daily salt intake should be limited to ≤ 6 g – recommendation: 3.8 to ≤ 6 g NaCl/day (1.5 to ≤ 2.4 g sodium/day). The LOAEL (Lowest Observed Adverse Effect Level) for dietary sodium is 2.3 g sodium/day (5.8 g NaCl/day) according to the FNB (Food and Nutrition Board). An increase in blood pressure has been observed as an adverse effect. Due to the high consumption of industrially produced foods, such as cured meats and cheeses, the daily intake of sodium chloride in Western industrialized nations significantly exceeds the recommended daily amount-especially in men-and averages between 12-15 g NaCl/day (4.7-5.9 g sodium/day) with a dietary sodium-potassium ratio of 3:1.A strictly low-sodium diet is characterized by a daily intake of no more than 0.4 g sodium (1 g NaCl).

Absorption

Sodium can be absorbed (taken up) in the small and large intestine by both an active and passive mechanism. Active uptake of the mineral into the mucosal cells (mucosal cells) of the intestine occurs via various transmembrane transport proteins (carriers) together with macronutrients, such as glucose, galactose, and amino acids, or ions, such as hydrogen (H+) and chloride (Cl-) ions. An example of a nutrient-coupled transport system is the sodium/glucose cotransporter-1 (SGLT-1), which transports glucose and galactose, respectively, and Na+ ions into the cell by means of a symport (rectified transport) in the upper small intestine. The ion-coupled carriers include the Na+/H+ antiporter, which transports Na+ in exchange with H+ ions in the small and large intestine, and the Na+/Cl- symporter, which transfers Na+ together with Cl- ions into the enterocytes and colonocytes (cells of the small and large intestinal epithelium, respectively) in the small and large intestine. The driving force of these carrier systems is an electrochemical, cell-inward sodium gradient, which is activated by the Na+/K+-ATPase, which is located in the basolateral (facing the blood vessels) cell membrane and is activated by the consumption of ATP (adenosine triphosphate, universal energy-providing nucleotide) catalyzes the transport of Na+ ions from the intestinal cell into the bloodstream and K+ ions into the intestinal cell. Sodium is rapidly and almost completely absorbed (≥ 95%) due to its good solubility. The rate of absorption is largely independent of the orally supplied amount.

Distribution in the body

Total body sodium in healthy humans is about 100 g or 60 mmol (1.38 g)/kg body weight. Of this, about 70%, corresponding to about 40 mmol/kg body weight, is rapidly exchangeable, while circa 30% is stored in bound form as a reserve in bone. 95-97 % of the body sodium is located in the extracellular space (outside the cell) – sodium serum concentration 135-145 mmol/l. The remaining 3-5% is present intracellularly (inside the cell) – 10 mmol/l. Sodium is the most significant cation of the extracellular fluid both quantitatively and qualitatively [1, 3-5, 6, 9, 11-13, 18, 22].

Excretion

Excess amounts of sodium in the body are eliminated largely by the kidneys-100-150 mmol/24 hours-and only slightly by feces-5 mmol/24 hours. An average of 25 mmol sodium/l is lost with sweat. Heavy sweating can be accompanied by sodium loss of more than 0.5 g/l, although the amount of sodium increases with increasing sweat volume, but can also decrease with acclimatization (adaptation). In addition, sodium is excreted to a small extent via tear fluid, nasal mucosa, and saliva. In the kidney, sodium is completely glomerular filtered and 99% reabsorbed in the distal tubules (renal tubules). The amount of sodium excreted in the urine depends on the amount supplied alimentarily (with food). In this context, renal excretion (excretion via the kidneys) is subject to a 24-hour rhythm. At a daily sodium intake of 120 mmol (~2.8 g), about 0.5% of glomerular filtered sodium is excreted in the urine if renal function is intact. A doubling of alimentary sodium intake (through food) also results in a doubling of the amount of sodium eliminated through the urine. The adaptation of renal (kidney) sodium excretion to dietary sodium intake takes about 3-5 days. During this time, the mineral is temporarily retained (retained). The following factors increase renal sodium excretion and may be associated with sodium deficiency:

  • Endocrine disorders, such as Addison’s disease (primary adrenocortical insufficiency) → renal sodium reabsorption is impaired by deficiency of the steroid hormone aldosterone
  • Renal diseases associated with impaired sodium reabsorption.
  • Polyuria (abnormally increased urine output, for example, in diabetes mellitus).
  • Inadequate intake of diuretics (dehydrating drugs).

Due to an effective enterohepatic circulation (livergut circulation), sodium secreted (secreted) via the bile is largely reabsorbed in the intestine.When reabsorption is disturbed, for example, in diarrhea (diarrhea), significant sodium losses through the stool may occur, increasing the risk of sodium deficiency.

Regulation of sodium homeostasis

Whereas intracellular sodium concentration is controlled by Na+/K+-ATPase, regulation of extracellular space sodium concentration occurs via the renin-angiotensin-aldosterone system (RAAS) and atrial natriuretic peptide (ANP). Sodium deficiency results in an osmotically induced reduction in extracellular volume (hypovolemia)-a drop in blood pressure-which, controlled by pressor (pressure) receptors of the high-pressure system and volume receptors of the low-pressure system, leads to the release of a specific protease called renin (an enzyme that cleaves peptide bonds by water accumulation) from the juxtaglomerular apparatus of the kidney. Renin cleaves the decapeptide (peptide composed of 10 amino acids) and prohormone (hormone precursor) angiotensin I from the protein angiotensinogen in the liver, which is then converted to angiotensin I by a second protease, angiotensin-converting enzyme. Angiotensin Converting Enzyme (ACE), resulting in the octapeptide (peptide composed of 8 amino acids) and hormone angiotensin II. Angiotensin II has different mechanisms of action:

  • General vasoconstriction (vasoconstriction) except in coronary vessels → increase in extracellular volume and elevation of blood pressure.
  • Decrease in glomerular filtration rate (GFR) via vasoconstriction → decrease in renal sodium and water excretion.
  • Release of the mineral corticoid aldosterone in the adrenal cortex → aldosterone induces increased sodium channel incorporation (ENaC, English : Epithelial Sodium (Na) Channel) and potassium channels (ROMK, engl. : Renal Outer Medularry Potassium (K) Channel) and sodium-potassium transporters (Na+/K+-ATPase) into the apical (facing the lumen) and basolateral (facing the blood vessels) cell membranes of the distal tubules (renal tubules) and collecting tubules of the kidney, respectively, which is associated with increased sodium reabsorption and osmotic retention (retention) of water as well as increased potassium excretion
  • Secretion of antidiuretic hormone (ADH) from the neurohypophysis (posterior lobe of the pituitary gland) → ADH stimulates water reabsorption in the distal tubules and collecting tubes of the kidney and reduces water excretion
  • Increase in thirst sensation and salt appetite → fluid and salt intake increased

All these hormonally induced effects in their totality in the presence of sodium deficiency lead to an increase in sodium and water content of the body with increase in extracellular volume and increase in blood pressure.Negative feedback mechanisms prevent excessive activation of the RAAS by inhibiting the release of renin through higher blood pressure, aldosterone and angiotensin II. In the event of increased saline intake and a resulting osmotically induced increase in blood volume (hypervolemia) – blood pressure increase – synthesis and secretion of atrial natriuretic peptide (ANP) from the atria of the heart, especially from the right atrium, occurs, controlled by pressure receptors of the atria. ANP reaches the kidney, where it inhibits the secretion of renin from the juxtaglomerular apparatus and thus the activation of the RAAS. This results in increased renal sodium and water excretion, normalizing extracellular volume and thus blood pressure. In the presence of endocrine disease, sodium homeostasis may be disturbed. For example, Cushing’s disease (increased stimulation of the adrenal cortex as a result of an ACTH (adrenocorticotropic hormone)-producing tumor in the pituitary gland, leading to increased release of aldosterone) or Addison’s disease (primary adrenocortical insufficiency leading to a deficiency of aldosterone) is associated with increased or decreased sodium retention and ultimately with an excess (→ increased blood pressure, etc.) or deficiency of sodium. ) or a deficiency of sodium (→ lowered blood pressure, “salt starvation,” etc.). Serum sodium concentration is not a suitable measure for determining the sodium status of the human body. It merely reflects the stock of free water.Hyponatremia (low serum sodium level) does not necessarily indicate a sodium deficiency, but only a disturbed osmoregulation (regulation of the osmotic pressure of body fluids) or an increased extracellular volume (hypervolemia). Sodium excretion in 24-hour urine is considered the best marker of sodium intake or stock in the human body.