Sodium ions (Na+) are necessary in small amounts for some types of plants, [1] but sodium as a nutrient is more generally needed in larger amounts [1] by animals, due to their use of it for generation of nerve impulses and for maintenance of electrolyte balance and fluid balance. In animals, sodium ions are necessary for the aforementioned functions and for heart activity and certain metabolic functions. [2] The health effects of salt reflect what happens when the body has too much or too little sodium. Characteristic concentrations of sodium in model organisms are: 10 mM in E. coli, 30 mM in budding yeast, 10 mM in mammalian cell and 100 mM in blood plasma. [3]
Additionally, sodium ions are essential to several cellular processes. They are responsible for the co-transport of glucose in the sodium glucose symport, are used to help maintain membrane polarity with the help of the sodium potassium pump, and are paired with water to thin the mucus of the airway lumen when the active Cystic Fibrosis Transport Receptor moves chloride ions into the airway. [4]
The minimum physiological requirement for sodium is between 115 and 500 mg per day depending on sweating due to physical activity, and whether the person is adapted to the climate. [5] Sodium chloride is the principal source of sodium in the diet, and is used as seasoning and preservative, such as for pickling and jerky; most of it comes from processed foods. [6] The Adequate Intake for sodium is 1.2 to 1.5 g per day, [7] but on average people in the United States consume 3.4 g per day, [8] [9] the minimum amount that promotes hypertension. [10] Note that salt contains about 39.3% sodium by mass [11] —the rest being chlorine and other trace chemicals; thus the Tolerable Upper Intake Level of 2.3 g sodium would be about 5.9 g of salt—about 1 teaspoon. [12] The average daily excretion of sodium is between 40 and 220 mEq. [13]
Normal serum sodium levels are between approximately 135 and 145 mEq/L (135 to 145 mmol/L). A serum sodium level of less than 135 mEq/L qualifies as hyponatremia, which is considered severe when the serum sodium level is below 125 mEq/L. [14] [15]
The renin–angiotensin system and the atrial natriuretic peptide indirectly regulate the amount of signal transduction in the human central nervous system, which depends on sodium ion motion across the nerve cell membrane, in all nerves. Sodium is thus important in neuron function and osmoregulation between cells and the extracellular fluid; the distribution of sodium ions are mediated in all animals by sodium–potassium pumps, which are active transporter solute pumps, pumping ions against the gradient, and sodium-potassium channels. [16] Sodium channels are known to be less selective in comparison to potassium channels. Sodium is the most prominent cation in extracellular fluid: in the 15 L of extracellular fluid in a 70 kg human there is around 50 grams of sodium, 90% of the body's total sodium content.
Some potent neurotoxins, such as batrachotoxin, increase the sodium ion permeability of the cell membranes in nerves and muscles, causing a massive and irreversible depolarization of the membranes with potentially fatal consequences. However, drugs with smaller effects on sodium ion motion in nerves may have diverse pharmacological effects that range from anti-depressant to anti-seizure actions.
Since only some plants need sodium and those in small quantities, a completely plant-based diet will generally be very low in sodium.[ citation needed ] This requires some herbivores to obtain their sodium from salt licks and other mineral sources. The animal need for sodium is probably the reason for the highly conserved ability to taste the sodium ion as "salty." Receptors for the pure salty taste respond best to sodium; otherwise, the receptors respond only to a few other small monovalent cations (Li+, NH+4 and somewhat to K+). The calcium ion (Ca2+) also tastes salty and sometimes bitter to some people but, like potassium, can trigger other tastes.
Sodium ions play a diverse and important role in many physiological processes, acting to regulate blood volume, blood pressure, osmotic equilibrium and pH. [8]
In C4 plants, sodium is a micronutrient that aids in metabolism, specifically in regeneration of phosphoenolpyruvate (involved in the biosynthesis of various aromatic compounds, and in carbon fixation) and synthesis of chlorophyll. [17] In others, it substitutes for potassium in several roles, such as maintaining turgor pressure and aiding in the opening and closing of stomata. [18] Excess sodium in the soil limits the uptake of water due to decreased water potential, which may result in wilting; similar concentrations in the cytoplasm can lead to enzyme inhibition, which in turn causes necrosis and chlorosis. [19] To avoid these problems, plants developed mechanisms that limit sodium uptake by roots, store them in cell vacuoles, and control them over long distances; [20] excess sodium may also be stored in old plant tissue, limiting the damage to new growth. Though much how excess sodium loading in the xylem is yet to be determined. However, anti porter CHX21 can be attributed to active loading of sodium into the xylem. [21]
Sodium is the primary cation (positively charged ion) in extracellular fluids in animals and humans. These fluids, such as blood plasma and extracellular fluids in other tissues, bathe cells and carry out transport functions for nutrients and wastes. Sodium is also the principal cation in seawater, although the concentration there is about 3.8 times what it is normally in extracellular body fluids.
Although the system for maintaining optimal salt and water balance in the body is a complex one, [22] one of the primary ways in which the human body keeps track of loss of body water is that osmoreceptors in the hypothalamus sense a balance of sodium and water concentration in extracellular fluids. Relative loss of body water will cause sodium concentration to rise higher than normal, a condition known as hypernatremia. This ordinarily results in thirst. Conversely, an excess of body water caused by drinking will result in too little sodium in the blood (hyponatremia), a condition which is again sensed by the hypothalamus, causing a decrease in vasopressin hormone secretion from the posterior pituitary, and a consequent loss of water in the urine, which acts to restore blood sodium concentrations to normal.
Severely dehydrated persons, such as people rescued from ocean or desert survival situations, usually have very high blood sodium concentrations. These must be very carefully and slowly returned to normal, since too-rapid correction of hypernatremia may result in brain damage from cellular swelling, as water moves suddenly into cells with high osmolar content.
In humans, a high-salt intake was demonstrated to attenuate nitric oxide production. Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. [23]
Because the hypothalamus/osmoreceptor system ordinarily works well to cause drinking or urination to restore the body's sodium concentrations to normal, this system can be used in medical treatment to regulate the body's total fluid content, by first controlling the body's sodium content. Thus, when a powerful diuretic drug is given which causes the kidneys to excrete sodium, the effect is accompanied by an excretion of body water (water loss accompanies sodium loss). This happens because the kidney is unable to efficiently retain water while excreting large amounts of sodium. In addition, after sodium excretion, the osmoreceptor system may sense lowered sodium concentration in the blood and then direct compensatory urinary water loss in order to correct the hyponatremic (low blood sodium) state.
The sodium-potassium pump works with the sodium and potassium leak channels to maintain the membrane potential between the cell and the extracellular space. Sodium moves down the concentration gradient from the cytosol into the extracellular matrix. Potassium moves down its concentration gradient from the extracellular matrix into the cytosol. In order to maintain the membrane potential, the sodium-potassium pump acts as a form of direct active transport where the hydrolysis of ATP to ADP and an inorganic phosphate at the P-type ATPase moves 3 potassium ions back out of the cell and 2 sodium ions into the cell. [4]
The sodium-potassium pump plays a large role in neural signaling due to the maintenance of cell membrane potential. This creates an action potential that causes the neurons to polarize and depolarize their membranes by opening and closing the voltage gated channels: this alters voltage potential and leads to neurotransmitter secretion and ultimately signal transmission. [24]
When the pump fails to function, patients are susceptible to illnesses like heart failure and chronic obstructive lung disease (COLD). Those who experienced an event of heart failure had on average, a 40% lower concentration of the sodium-potassium ATPase. This lack of polarization of the membrane leads to an inability of action potentials to propagate at their usual rate, leading to a lowered hear rate and potentially heart failure. [25] In COLD diagnoses, a majority of patients found to have a lowered amount of magnesium and potassium also had a decreased concentration of the sodium-potassium pump in skeletal and smooth muscle during respiratory failure. COLD is treatable in the short term by glucocorticoid which up-regulates the sodium-potassium pump, helping to support muscle endurance and increase muscle activity during these episodes of respiratory failure. [26]
In the sodium-glucose symporter, sodium moves down its concentration gradient to move glucose up its concentration gradient. Sodium has a greater concentration outside of the cell, and binds to the symporter, which is in its outward facing conformation. Once sodium is bound, glucose can bind from the extracellular space, causing the symporter to switch into the occluded formation (closed) before opening to the inside of the cell and releasing the two sodium ions and the one glucose molecule. Once both are released, the symporter re-orients itself to the outward facing conformation and the process starts all over again. [4] A major example of up-regulation of the sodium-glucose symporter is seen in patients with type 2 diabetes, where there is roughly a 3-4 fold up-regulation of the sodium-glucose symporter (SGLT1). This leads to an influx of glucose into the cell and results in hyperglycemia. [27]
The Cystic Fibrosis Transport Regulator (CFTR) works by binding two ATP to the A1 and A2, ATP-binding domain. This opens the CFTR channel and allows chloride ions to flow into the lungs and airway lumen. This influx of negatively charged chloride ions into the airway lumen causes sodium to move into the airway lumen to balance the negative charge. Water then moves in with the sodium to balance the osmotic pressure and ultimately leads to the thinning of mucus. In cases of Cystic Fibrosis, the CFTR is defective and only binds a single ATP, leading to the channel failing to open and preventing chloride ions from diffusing into the airway lumen. Since chloride ions cannot diffuse in, there is no movement of sodium into the airway lumen, and no need for water to move into the lumen, leading to thick mucus that clogs and infects the airway lumen. [4]
In cellular biology, active is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses adenosine triphosphate (ATP), and secondary active transport that uses an electrochemical gradient. This process is in contrast to passive transport, which allows molecules or ions to move down their concentration gradient, from an area of high concentration to an area of low concentration, without energy.
The sodium–potassium pump is an enzyme found in the membrane of all animal cells. It performs several functions in cell physiology.
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be absent, mild or severe. Mild symptoms include a decreased ability to think, headaches, nausea, and poor balance. Severe symptoms include confusion, seizures, and coma; death can ensue.
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% of total body weight; women and the obese typically have a lower percentage than lean men. Extracellular fluid makes up about one-third of body fluid, the remaining two-thirds is intracellular fluid within cells. The main component of the extracellular fluid is the interstitial fluid that surrounds cells.
Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.
A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion, active transport, osmosis, or reverse diffusion. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers. Examples of channel/carrier proteins include the GLUT 1 uniporter, sodium channels, and potassium channels. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer, the German anatomist Friedrich Gustav Jakob Henle, the loop of Henle's main function is to create a concentration gradient in the medulla of the kidney.
Membrane potential is the difference in electric potential between the interior and the exterior of a biological cell. It equals the interior potential minus the exterior potential. This is the energy per charge which is required to move a positive charge at constant velocity across the cell membrane from the exterior to the interior.
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.
The relatively static membrane potential of quiescent cells is called the resting membrane potential, as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential.
Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnormal heart rhythm, which is often too slow and can cause cardiac arrest.
Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as the syndrome of inappropriate antidiuresis (SIAD), is characterized by a physiologically inappropriate release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH causes a physiologically inappropriate increase in solute-free water being reabsorbed by the tubules of the kidney to the venous circulation leading to hypotonic hyponatremia.
Metabolic alkalosis is an acid-base disorder in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.
Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.
In biology, an ion transporter is a transmembrane protein that moves ions across a biological membrane to accomplish many different biological functions, including cellular communication, maintaining homeostasis, energy production, etc. There are different types of transporters including pumps, uniporters, antiporters, and symporters. Active transporters or ion pumps are transporters that convert energy from various sources—including adenosine triphosphate (ATP), sunlight, and other redox reactions—to potential energy by pumping an ion up its concentration gradient. This potential energy could then be used by secondary transporters, including ion carriers and ion channels, to drive vital cellular processes, such as ATP synthesis.
The epithelial sodium channel(ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na+). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.
The Na–K–Cl cotransporter (NKCC) is a transport protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes. Two isoforms of the NKCC1/Slc12a2 gene result from keeping or skipping exon 21 in the final gene product.
A symporter is an integral membrane protein that is involved in the transport of two different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time, and is, therefore, a type of cotransporter. The transporter is called a symporter, because the molecules will travel in the same direction in relation to each other. This is in contrast to the antiport transporter. Typically, the ion(s) will move down the electrochemical gradient, allowing the other molecule(s) to move against the concentration gradient. The movement of the ion(s) across the membrane is facilitated diffusion, and is coupled with the active transport of the molecule(s). In symport, two molecule move in a 'similar direction' at the 'same time'. For example, the movement of glucose along with sodium ions. It exploits the uphill movement of other molecules from low to high concentration, which is against the electrochemical gradient for the transport of solute molecules downhill from higher to lower concentration.
Thus, a minimum average requirement for adults can be estimated under conditions of maximal adaptation and without active sweating as no more than 5 mEq/day, which corresponds to 115 mg of sodium or approximately 300 mg of sodium chloride per day. In consideration of the wide variation of patterns of physical activity and climatic exposure, a safe minimum intake might be set at 500 mg/day. [Note: Table 11-1 seems to clarify that 500 mg refers to sodium, not sodium chloride]