Because sodium is the major osmotically active cation in the extracellular fluid (ECF), total body sodium content determines ECF volume. Deficiency or excess of total body sodium content causes ECF volume depletion or volume overload. Serum sodium concentration does not necessarily reflect total body sodium. (See also Water and Sodium Balance.)
Dietary intake and renal excretion regulate total body sodium content. When total sodium content and ECF volume are low, the kidneys increase sodium conservation. When total sodium content and ECF volume are high, sodium excretion (natriuresis) increases so that volume decreases.
Renal sodium excretion can be adjusted widely to match sodium intake. Renal sodium excretion requires delivery of sodium to the kidneys and so depends on renal blood flow and glomerular filtration rate (GFR). Thus, inadequate sodium excretion may be secondary to decreased renal blood flow, as in heart failure or in chronic kidney disease (CKD).
Renin-angiotensin-aldosterone axis
The renin-angiotensin-aldosterone axis is the main regulatory mechanism of renal sodium excretion. In volume-depleted states, GFR and sodium chloride delivery to the distal nephrons decreases, causing release of renin. Renin cleaves angiotensinogen (renin substrate) to form angiotensin I. Angiotensin-converting enzyme (ACE) then cleaves angiotensin I to angiotensin II. Angiotensin II does the following:
Increases sodium retention by decreasing the filtered load of sodium and enhancing proximal tubular sodium reabsorption
Increases blood pressure (by direct pressor activity)
Increases thirst
Directly impairs water excretion
Stimulates the adrenal cortex to secrete aldosterone, which increases sodium reabsorption via multiple renal mechanisms
Angiotensin I can also be transformed to angiotensin III, which stimulates aldosterone release as much as angiotensin II but has much less pressor activity. Aldosterone release is also stimulated by hyperkalemia.
Other natriuretic factors
Several other natriuretic factors have been identified, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and a C-type natriuretic peptide (CNP).
ANP is secreted by cardiac atrial tissue. Concentration increases in response to ECF volume overload (eg, heart failure, chronic kidney disease, cirrhosis with ascites) and primary aldosteronism and in some patients with primary hypertension. Decreases have occurred in the subset of patients with nephrotic syndrome who have presumed ECF volume contraction. High concentrations increase sodium excretion and increase GFR even when blood pressure is low.
BNP is synthesized mainly in the atria and left ventricle and has similar triggers and effects to ANP. BNP assays are readily available. High BNP concentration is used to diagnose volume overload.
CNP, in contrast to ANP and BNP, is primarily vasodilatory.
Sodium depletion and excess
Sodium depletion requires inadequate sodium intake plus abnormal losses from the skin, gastrointestinal tract, or kidneys (defective renal sodium conservation). Defective renal sodium conservation may be caused by primary renal disease, adrenal insufficiency, or diuretic therapy.
Sodium overload requires higher sodium intake than excretion; however, because normal kidneys can excrete large amounts of sodium, sodium overload generally reflects defective regulation of renal blood flow and sodium excretion (eg, as occurs in heart failure, cirrhosis, or chronic kidney disease).
