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Overview of Disorders of Fluid Volume

by James L. Lewis, III, MD

Because Na is the major osmotically active ion in the ECF, total body Na content determines ECF volume. Deficiency or excess of total body Na content causes ECF volume depletion (see Volume Depletion) or volume overload (see Volume Overload). Serum Na concentration does not necessarily reflect total body Na.

Dietary intake and renal excretion regulate total body Na content. When total Na content and ECF volume are low, the kidneys increase Na conservation. When total Na content and ECF volume are high, Na excretion (natriuresis) increases so that volume decreases.

Renal Na excretion can be adjusted widely to match Na intake. Renal Na excretion requires delivery of Na to the kidneys and so depends on renal blood flow and GFR. Thus, inadequate Na excretion may be secondary to decreased renal blood flow, as in chronic kidney disease or heart failure.

Renin-angiotensin-aldosterone axis

The renin-angiotensin-aldosterone axis is the main regulatory mechanism of renal Na excretion. In volume-depleted states, GFR and Na delivery to the distal nephrons decreases, causing release of renin. Renin cleaves angiotensinogen (renin substrate) to form angiotensin I. ACE then cleaves angiotensin I to angiotensin II. Angiotensin II does the following:

  • Increases Na retention by decreasing the filtered load of Na and enhancing proximal tubular Na reabsorption

  • Increases BP (has pressor activity)

  • Increases thirst

  • Directly impairs water excretion

  • Stimulates the adrenal cortex to secrete aldosterone, which increases Na 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 Na excretion and increase GFR even when BP 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.

Na depletion and excess

Na depletion requires inadequate Na intake plus abnormal losses from the skin, GI tract, or kidneys (defective renal Na conservation). Defective renal Na conservation may be caused by primary renal disease, adrenal insufficiency, or diuretic therapy.

Na overload requires higher Na intake than excretion; however, because normal kidneys can excrete large amounts of Na, Na overload generally reflects defective regulation of renal blood flow and Na excretion (eg, as occurs in heart failure, cirrhosis, or chronic kidney disease).

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