Small variations in glomerular filtration rate (GFR) occur despite the autoregulatory control. If these variations are not compensated for by adjusting sodium (Na+) reabsorption by the nephron, there would be significant changes in Na+ excretion. Fortunately, Na+ reabsorption, particularly by the proximal tubule, changes in parallel with changes in GFR in the euvolemic state. This is known as glomerulotubular balance. Therefore, an increase in GFR leads to an increase in Na+ reabsorption by the proximal tubule, while a decrease in GFR leads to a decrease in Na+ reabsorption.

The loop of Henle is capable of increasing its reabsorptive rate in response to an increased delivery of Na+, which helps maintain a constant delivery of Na+ to the distal tubule and collecting duct.

In regulating NaCl reabsorption by the distal tubule and collecting duct, small adjustments in Na+ reabsorption by the aldosterone-sensitive distal nephron (ASDN) are sufficient when the delivery of Na+ is constant. Aldosterone is the primary regulator of Na+ reabsorption in the ASDN, thus affecting NaCl excretion. Elevated aldosterone levels increase Na+ reabsorption (decrease NaCl excretion), while decreased aldosterone levels decrease Na+ reabsorption (increase NaCl excretion). Other factors, such as angiotensin II and natriuretic peptides, may also influence Na+ reabsorption by the ASDN, but their role during euvolemia is uncertain.

Under normal circumstances, the mechanisms described above can appropriately regulate renal Na+ excretion and maintain euvolemia as long as minor variations in dietary NaCl intake occur. However, these mechanisms are not effective in handling significant changes in NaCl intake. In cases of significant NaCl intake changes, extracellular fluid volume (ECFV) expansion or contraction occurs. Additional factors act on the kidneys to adjust Na+ excretion and restore euvolemia in such cases.

During ECFV expansion, signals from high-pressure and low-pressure vascular volume sensors prompt the kidneys to increase the excretion of NaCl and water. These signals include AVP, ANP, BNP, aldosterone, renin, urodilatin, and sympathetic activity. The integrated response of the nephron to these signals leads to decreased renal sympathetic nerve activity, release of ANP, BNP, and urodilatin, inhibition of AVP secretion, decreased AVP action on the collecting duct, decreased renin secretion, decreased production of angiotensin II, and decreased aldosterone secretion.
Despite the autoregulatory control of GFR, small variations occur. If these changes are not compensated for by an appropriate adjustment in Na+ reabsorption by the nephron, Na+ excretion would change markedly. Fortunately, Na+ reabsorption in the euvolemic state, especially by the proximal tubule, changes in parallel with changes in GFR. This phenomenon is termed glomerulotubular balance. Thus if GFR increases, the amount of Na+ reabsorbed by the proximal tubule also increases. The opposite occurs if GFR decreases (see for a more detailed description of glomerulotubular balance).
The final mechanism that helps maintain constant delivery of Na+ to the distal tubule and collecting duct involves the ability of the loop of Henle to increase its reabsorptive rate in response to increased delivery of Na+ .
Regulation of Distal Tubule and Collecting Duct NaCl Reabsorption
When delivery of Na+ is constant, small adjustments in Na+ reabsorption, primarily by the ASDN, are sufficient to balance excretion with intake. Aldosterone is the primary regulator of Na+ reabsorption by the ASDN and thus of NaCl excretion. When aldosterone levels are elevated, Na+ reabsorption by these segments is increased (Na+ excretion is decreased). When aldosterone levels are decreased, Na+ reabsorption is decreased (NaCl excretion is increased). Other factors have been shown to alter Na+ reabsorption by the ASDN (e.g., angiotensin II and natriuretic peptides), but their role during euvolemia is unclear.
As long as variations in dietary intake of NaCl are minor, the mechanisms previously described can regulate renal Na+ excretion appropriately and thereby maintain euvolemia. However, these mechanisms cannot effectively handle significant changes in NaCl intake. When NaCl intake changes significantly, ECFV expansion or contraction occurs. In such cases, additional factors act on the kidneys to adjust Na+ excretion and thereby reestablish the euvolemic state.
Control of NaCl Excretion With Volume Expansion
During ECFV expansion, the high-pressure and low-pressure vascular volume sensors send signals to the kidneys that result in increased excretion of NaCl and water. The signals acting on the kidneys include: ˜ AVP ° ANP and BNP Heart Brain ˜ Aldosterone Lung Adrenal gland ° Na+, H2O excretion ˜ Renin ° Urodilatin ˜ Sympathetic activity 2 1 3 ˜ Angiotensin I ˜ Angiotensin II Volume expansion UNa+V = °GFR ˜PNa+ – ˜R • Fig. 35.12 Integrated response to ECFV expansion. Numbers refer to the description of the response in the text. ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; GFR, glomerular filtration rate; PNa+, plasma [Na+]; R, tubular reabsorption of Na+; UNa+V, Na+ excretion rate.
1.
decreased activity of renal sympathetic nerves 2.
release of ANP and BNP from the heart and urodilatin in the kidneys 3.
inhibition of AVP secretion from the posterior pituitary and decreased AVP action on the collecting duct 4.
decreased renin secretion and thus decreased production of angiotensin II 5.
decreased aldosterone secretion, which is caused by reduced angiotensin II levels, and elevated natriuretic peptide levels The integrated response of the nephron to these signals is
Fig. 35.12 . Three general responses to ECFV expansion occur (the numbers match those encircled in