Regulation of Na+ Balance

Na+ and Extracellular Fluid Volume

Na+ (and its associated anions) are the predominant ions in the extracellular fluid (ECF). Because Na+ and its associated anions are non-penetrating solutes, they produce an osmotic pressure that holds water in the ECF. Because the osmolarity of the ECF is kept constant, the amount of Na+ in the body determines the volume of the ECF.

Na+ Reabsorption along the Nephron

To maintain the volume of the ECF, the amount of Na+ excreted needs to match Na+ intake via the diet. On a typical day, a large amount of Na+ is filtered, and nearly 99% of filtered Na+ is reabsorbed.


The figure provides an overview of Na+ reabsorption along the nephron. In different segments of the renal tubule, there are different proteins (cotransporters, countertransporters, or channels) on the apical surface of tubule cells that mediate Na+ reabsorption (see the figures on the lecture outline). The numbers in parentheses indicate the percent of Na+ reabsorption that typically occurs in that segment. Specific proteins involved in Na+ reabsorption are the targets of diuretics, drugs that increase urine flow by decreasing Na+ reabsorption (see web page on diuretics).

Although the apical transporters differ along the length of the renal tubule, one thing that is always true is that the energy for Na+ reabsorption depends upon the Na+ concentration gradient. Na+ moves readily across the apical membrane of cells of the renal tubule because the Na+ concentration is high in the renal filtrate and low inside of cells. The Na+ gradient is established by the Na+/K+-ATPase, which pumps Na+ across the basolateral membrane.

Regulation of Na+ Reabsorption

The principal regulator of Na+ reabsorption is the steroid hormone aldosterone, which is produced in the zona glomerulosa of the adrenal cortex. Aldosterone, like all steroid hormones, works as a transcription factor to alter gene expression in cells. Aldosterone works in the cells of the cortical collecting duct, depicted at left. Na+ reabsorption in this part of the renal tubule accounts for only 2% of total Na+ reabsorption, but this is the site where regulation of Na+ balance occurs.

What is the effect of aldosterone? Aldosterone saves salt. It works to increase Na+ reabsorption by promoting the expression of both of the channels and the Na+/K+-ATPase depicted in the figure.

Renin-Angiotensin-Aldosterone System

Aldosterone secretion is stimulated by angiotensin II. Recall that the limiting step for the formation of angiotensin II is the hormone renin, which is released by the juxtaglomerular cells located in the afferent arteriole. The juxtaglomerular cells are stimulated to secrete renin by three mechanisms, all of which are activated in response to decreased ECF volume.

Juxtaglomerular Apparatus

The juxtaglomerular cells are part of the juxtaglomerular apparatus, a structure that is present in every nephron. For each nephron, the first part of the distal tubule is nestled right near the afferent arteriole. A specialized portion of the distal tubule, known as the macula densa, is set up to sense the amount of Na+ flowing through the distal tubule. Decreased Na+ sensed by the macula densa cells elicits a signal that stimulates renin secretion by the juxtaglomerular cells.

Why would decreased Na+ at the distal tubule reflect a decrease in ECF volume? The sequence of events is as follows. A decrease in ECF volume will cause a decrease in mean arterial pressure. A drop in blood pressure will cause a drop in the glomerular filtration rate, with a resulting decrease in the flow rate through the renal tubule. Correspondingly more Na+ can be reabsorbed in the early part of the renal tubule, and so less Na+ is delivered to the distal tubule.

Atrial Natriuretic Peptide

An additional mechanism involved in the regulation of Na+ levels involves the hormone atrial natriuretic peptide (ANP). This hormone is synthesized by cells in the atrium of the heart, and is released in response to distension of the atria, in other words, when plasma volume increases. The effect of ANP is to increase natriuresis, that is the excretion of Na+ in the urine. ANP increases natriuresis by increasing GFR and decreasing Na+ reabsorption. ANP works to oppose the effects of the renin-angiotensin-aldosterone system, preventing volume overload by preventing excessive Na+ levels in the body.

Summary: Homeostasis of ECF Volume

The figure illustrates the homeostatic regulation of ECF volume. Although the effector mechanisms involve regulation of sodium levels, the sensors are primarily tuned to volume changes in the plasma. The sensors include the carotid baroreceptors, the juxtaglomerular cells (intrarenal baroreceptors) and the macula densa.  All of these increase renin secretion, which ultimately leads to increased aldosterone secretion.  This causes increased Na+ reabsorption, which keeps water with it to increase ECF volume.

Quick Quiz

Fill-in Answer Correct False Correct Answer
1. In what part of the nephron does regulated Na+ reabsorption occur?
2. Angiotensin II stimulates the secretion of this steroid hormone.
3. What structure detects changes in the delivery of Na+ to the distal tubule?
4. This factor is the rate-limiting step in the production of angiotensin II.
5. Which regulatory molecule stimulates an increase in GFR and a decrease in Na+ reabsorption?
6. The sympathetic nervous system stimulates renin secretion from the ____________ cells.
7. Where are these cells (from above answer) specifically located?
8. In what part of the nephron is the macula densa located?

(Spelling must be correct)

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