Dominant cation in extracellular fluid and the primary determinant of serum osmolality.

98% of total body sodium is confined to the extracellular fluid compartment in young, healthy people.

About 80% of exchangeable sodium is found in the interstitial and connective tissues, and about 15% of exchangeable sodium is in the plasma.

Bone contains a large amount of sodium, but much of it is non-exchangeable.

Cellular well-being depends on the body’s ability to regulate the salinity of extracellular fluids.

Sodium is an osmotically active anion, and one of the most important electrolytes in the extracellular fluid.

Sodium balance  is maintained in the face of variations in salt intake, typically consumed as sodium chloride, through exquisite regulation of salt excretion.

Sodium is responsible for maintaining the extracellular fluid volume, and for regulation of the membrane potential of cells. 

Pressure sensors in the vascular space and kidney detect extracellular volume as part of a mechanism to determine the adequacy of capillary perfusion.

Small changes in the extracellular volume trigger altered sodium excretion to match intake.

When salt intake is restricted, angiotensin II, aldosterone, norepinephrine, and epinephrine all increase, contributing to sodium retention.

These neurohormones link the extracellular volume and vasoconstriction.

Conversely, salt loading increases the extracellular volume and stimulates the release of natriuretic factors including atrial natriuretic peptide and endothelin.

Sodium is exchanged along with potassium across cell membranes as part of active transport. 

By the matching of urinary sodium excretion to sodium intake, the kidney prevents significant changes in electrolyte balance, extracellular fluid volume, and blood pressure.

Thirst reflex, vasopressin and the kidney maintain a relatively constant sodium concentration in a free flowing extracellular fluid compartment, matching the concentrations in plasma.

Plasma sodium concentration is tightly controlled by thirst and arginine vasopressin, but the plasma or  cerebrospinal fluid sodium concentration has also been postulated to play a role in neurogenic hypertension.

Arginine vasopressin itself may affect blood pressure as it stimulates the epithelial sodium channels in the aldosterone sensitive distal nephron.

Extracellular fluid compartments with very high concentrations of glycosaminoglycan such as cartilage, have fixed anionic charges that attract sodium irons, favoring swelling which is counteracted by the rigid collagen matrix.

These countervailing forces maintain cartilage structure and flexibility.

The osmoregulatory system prevents plasma sodium concentration from going outside its normal range of 135 to 142 mmol per liter by controlling water intake and excretion.

Even minuscule changes in the effective circulating volume of arterial blood that perfuses tissue, correlates directly with sodium intake, and signals adjustments in the kidney to maintain sodium excretion equal to sodium intake.

Total body sodium stores are approximately 2,500 mmol, or 58 g for a 70-kg person.

Failure to regulate sodium levels to the normal range exposes cells to hypotonic or hypertonic stresses.

Sodium regulation occurs in the kidneys. 

The proximal tubule is where the majority of the sodium reabsorption takes place. 


In the distal convoluted tubule, sodium undergoes reabsorption.  

Sodium transport takes place via sodium-chloride symporters, which is by the action of the hormone aldosterone.

When dietary sodium intake increases, urinary sodium excretion increases, but it does not match intake immediately and generates a positive sodium balance until excretion again equals intake.

This ingested anion affects internal sodium distribution, since sodium chloride increases body weight and extra cellular volume more than equimolar sodium citrate in which case the partially exchanged for potassium inside cells.

increasing sodium chloride intake also increases body water, although this does not result predominately from more fluid consumption but rather from fluid retention.

When dietary salt increases from low to moderate levels body water increases,.

When salt intake rises further, sodium accumulation may occur without an increase in water.

Sodium absorption occurs in two stages in the GI tract: The first is via intestinal epithelial cells.

Sodium passes into enterocyte cells by co-transport with glucose, via the SGLT1 protein.

From the intestinal epithelial cells, sodium is pumped by active transport via the sodium-potassium pump through the basolateral cell membrane into the extracellular space.

Hypernatremia indicates hypertonicity is present and hyponatremia usually indicates hypotonicity is present.

High sodium intake is associated with adverse cardiorenal outcomes, including oxidative stress, arteriolar damage, interstitial fibrosis, glomerular hyalinization, glomerular fibrosis, increased glomerular hydrostatic pressure in the kidneys, and ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction in the heart.

Only about 5% of sodium intake comes from salt added at the table or during home cooking and nearly 80% comes from sources of which consumers have a little control, including processed and restaurant foods with the added sodium.

Over 70% of the sodium that Americans eat comes from packaged, processed, store-bought, and restaurant foods. 

About 15% of sodium comes from the foods that naturally contains sodium.

About 11% of sodium intake is from sodium added at the table or in cooking at home amd almost all of the rest is inherent in foods.

Diets low in sodium are often rich in potassium, which may contribute to clinical benefits in as much as increase dietary potassium reduces blood pressure and lowers the risk of stroke and renal calculus disease.

Sodium has adaptation in taste, and individuals can adjust to lower sodium in foods. but the change needs to be broad and gradual.

Conversely, underconsumption of potassium, particularly when combined with high sodium intake, is associated with chronic disorders including: hypertension, diabetes, obesity, and renal calculi.

Plasma sodium hypoionic state causes cells to swell and hypertonicity makes them shrink.

The sodium pump excludes sodium from cells, exchanging it for potassium by active transport.

Sodium is extensively bound to large polyanionic macromolecules, proteoglycans, which make up the ground substance of bone, connective tissue, and cartilage.

Proteoglycans can serve as a sodium reservoir, and may be the reason that chronic hyponatremia is associated with osteoporosis and fractures.

Sodium concentration of cartilage is approximately two times that of plasma, resulting in high water content allowing it to withstand high pressure of exercise.

Excessive intake increases blood pressure,  which increases the risk for stroke, coronary artery disease, heart failure and renal disease.

Can cross capillary memories through clefts between endothelial cells, so that the sodium concentration of plasma and interstitial fluid arenearly identical, with a small difference created by intra-vascular albumin.

The brain, however, has tight endothelial junctions lined by astrocytic foot processes and creates a blood brain barrier that sodium cannot bridge.

Abnormal plasma sodium concentration causes water to enter or leave brain tissue.

Plasma sodium concentration affects brain volume.

Cell volume receptors responsible for adjusting thirst and vasopressin secretion are located in the brain.

Vasopressin levels are usually detectable at a plasma sodium concentration above 135 mmol per liter, and levels increase linearly with increasing sodium levels.

Vasopressin hormone may be secreted in response to inadequate circulation, or inappropriately secreted, and sometimes ectopically secreted, with no osmotic or hemodynamic stimulus.

When secreted without an osmotic or hemodynamic abnormality it is termed inappropriate.

Vasopressin binds to V2 receptor on basolateral membranes of principal cell lining the renal collecting duct.

Aquaporins in the presence of vasopressin insert into the luminal membrane and allow water to flow out, attracted by the high solute concentration of the surrounding medullary interstitium.

When plasma sodium level increases to 145 mmol per liter vasopressin levels are normally high enough to maximally concentrate urine at about 1200 mOsm per kilogram.

When the plasma sodium concentration is above 145 mmol per liter the presence of dilute urine implies either deficient vasopressin secretion as in neurogenic diabetes insipidus or failure of the kidneys to respond to vasopressin as in nephrogenic diabetes insipidus.

Tonicity receptors (osmoreceptors) are hypothalamus neurons that express cell membrane receptor potential cation channels subfamily vanillin 1 member (TRPV1) and member 4 (TRPV4).

Thirst and vasopressin secretion are inhibited when the plasmas sodium concentration is below 135 millimoles per liter.

Without vasopressin, urine osmolarity can decrease as low as 50 mOsm kilogram.

A usual Western diet has an output of urinary solute of about 900 mOsm daily, and therefore urinary solute concentration of 50 mOsm

per liter would yield as much as 18 L of urine, or 750 mls per hour, per day.

Aging men with TRPV4 polymorphism have a greater risk of mild hyponatremia than men without such a polymorphism (Tian W et al).

Predictive modeling suggests reducing salt intake to 1200 mg per day would reduce the annual number of new cases of coronary at heart disease by 60-120,000 cases and stroke by 32-65,000 cases (Bibbins-Domingo K).

Globally, the population consumes between 3-6 gm of sodium per day.

The average American consumes about 3500 mg of sodium daily, an amount that has not changed over the past decades despite reduction in heart disease.

It is recommended that patients with hypertension, all middle-aged and older adults at all black individuals should limit their intake of sodium to  1500 mg per day:  These groups include nearly 70% of the US adult population.

For all other adults, the  recommendation for sodium Intake is for less than 2300 mg a day.

The National Health and Nutrition Examination Survey (NHANES  2005-2006)  found that only one in 10 adults met their applicable recommendations for sodium intake.

A diet high in salt diet due to eating processed foods, with adults consuming more than 3,400 mg of sodium per day, exceeding the more than the 2,300 mg limit recommended by the American Heart Association (AHA).

Most of the sodium in a person�s diet comes from packaged, processed foods.

More than 75% of sodium Americans consume comes from packaged, prepared and restaurant foods.

The AHA recommends no more than 2,300 milligrams a day, but patients should move toward an ideal limit of no more than 1,500 mg per day for most adults.

Even cutting back by 1,000 milligrams a day can significantly improve BP and heart health.

Sea salt and table salt both contain 40% sodium.

Consuming less sodium will also reduce the risk of patients developing other conditions, such as kidney disease.

Less sodium intake will significantly blunt the rise in blood pressure that occurs with age.

In the United States 77% of dietary sodium comes from process and restaurant foods and approximately 10% comes from table salt and cooking (Mattes RD).

Majority of sodium intake comes from food categories from which the most calories are consumed.

Grains contribute the largest amount of sodium intake followed by meats.

Sodium intake in meats is higher than expected because the meat category includes a luncheon meats and sausages.

Fruits and vegetables have low-salt content,  but this category of food is the third-largest contributor to sodium because of the content of vegetables in soups and sauces and canned vegetables.

High intake predicts mortality and risk of coronary heart disease.

While most studies identify a positive association between sodium intake and cardiovascular disease, some studies have failed to identify a significant relationship on a few studies show an inverse association.

Dietary salt intake in the United States is on the rise.

The Departments of Agriculture and Health and Human Services recommended daily intake of less than 5.8 g of salt (2300 mg of sodium), with a target of 3.7 g of salt per day for most adults.

WHO recommends a sodium intake of less than 2 g per day.

Goals for sodium intake for US adults range from 1500 mg per day to no more than 2300 mg per day, with no more than 1500 mg per day in individuals, middle-aged and older persons, and patients with hypertension diabetes or chronic kidney disease.

During the years 2005 through 2006 the average male in the United States consumed an estimated 10.4 g of salt per day and the average woman 7.3 g per day.

Decreasing dietary salt reduces blood pressure and the risk of cardiovascular disease (He FJ).

75 to 80% of salt in the US diet comes from processed foods, and not from added salt during food preparation or consumption (Hooper L, Mattes RD).

Using the Coronary Heart Disease Policy Model: reducing salt by 3 g per day can reduce the annual number of new cases of coronary artery disease by 60,000 to 120,000, stroke by 32,002 66,000 and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000 (Bibbins-Domingo K).

Lower urinary sodium excretion associated with higher cardiovascular disease mortality (Stolarz-Skrzypek K et al).

A J-shaped association between estimated sodium excretion and cardiovascular events has been noted in to observational studies of 28,880 patients (O Donnell MJ et al).

In the above study estimated 24 hour urinary sodium and potassium excretion from the morning fasting urine sample indicated that a compared to a baseline sodium excretion of 4-5.99 g per day, greater than 7 g per day sodium excretion was associated with an increased risk of cardiovascular events, and the sodium excretion of less than 3 g per day was associated with an increased risk of cardiovascular mortality and hospitalization for congestive heart failure.

In a meta-analysis of 13 prospective studies 85 g increase in salt , which reflects 2 g of sodium, is associated with a 23% increase in stroke and a 14% increase in cardiovascular disease (Strazzullo P et al).

In a study in which sodium intake was estimated on the basis of measured urinary excretion, and estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake (PURE Investigators).

it is estimated that globally in 2010, 1.65 million annual deaths from cardiovascular causes were attributable to sodium consumption above the reference level of 2 gm per day, with almost 62% of deaths occurring in men and 38% occurring in women (NUTRICODE Group).

About one in 10 deaths cardiovascular causes is attributable to sodium consumption more than 2.0 g per day, and 2 of 5 of these baths occur prematurely, before the age of 70 years.

Soluble effervescent drugs that contains sodium such as acetaminophen and vitamin C are associated with increased cardiovascular events compared to matched drugs without sodium (George J et al).

Sodium and fluid restriction are widely used measures in the treatment of acute decompensated heart failure, yet there is a lack of evidence of their therapeutic effect.

Clinical trials comparing fluid restricted diet versus liberal fluids in patients with heart failure have found no differences in time to clinical stabilization (Travers B et al).

A randomized controlled trial of patients stabilized after congestive heart failure failed to find benefits in fluid restriction and such treatment manifest increased thirst, dry mouth, dysgeusia, dry skin, and pruritus (Holst M et al).

Presently sodium restrictive intake recommendations for patients with acute decompensated heart failure are not specific.

In a study comparing the effects of a fluid restriction, maximum fluid intake of 800 mL per day, and sodium restricted diet, with a maximum dietary intake of 800 mg per day versus a diet with no such restrictions on weight loss and clinical stability during a three-day period in patients hospitalized with acute decompensated heart failure: There was no effect on weight loss or clinical stability, but there was an increase in thirst indicating that sodium and water restriction in patients admitted with acute decompensated heart failure are unnecessary (Aliti GB et al).

People who habitually consume more sodium find that foods tasted less salty than those who consumed less sodium.


The salt taste testing utilized multiple pre-made and validated test strips that the participant held in their mouth for 3 seconds. 


 About 61% of men and 79% of women could detect a difference between the no-salt strip and the strip containing 0.1% sodium. 


Those who could identify that the difference they tasted was a salty flavor was much smaller: between 15% and 24% for men and 24% and 32% for women.


Between 30% and 34% of men could not identify a salt concentration of 1.6% sodium while between 16% and 21% of women could not, either.


Women were better able to detect salty flavors overall, and that for men between 30 and 59 years of age, blood pressures were positively linked with both detection, tasting a difference, perception, knowing the flavor was saltiness, and salt intake.


Individuals who consumed more salty foods were also those who failed to detect difference in flavor in general and salty flavors in particular. 


Those same people tended to have increasingly higher blood pressures as their minimum flavor detection and recognition levels increased.


Those who tended to consume more salt were less able to taste or identify salty flavors and had higher blood pressures than those who consumed less salt.


Among individuals with a history of stroke or greater than 60 years of age or older and had hypertension, the rate of stroke, major cardiovascular events and death from any were lower with salt substitute them with regular salt (Neal, B).

Mechanisms by which salt intake raises blood pressure include: salt handling by the kidney must be altered for hypertension to develop, there may be primary vascular dysfunction, primary sympathetic nervous system dysfunction, and immune activation perhaps related to skin hypertonicity.


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