Integration of Renal Mechanisms for Control of Extracellular Fluid
Extracellular fluid volume is determined mainly by the balance between intake and output of water and salt. In most cases, salt and fluid intakes are dictated by a person’s habits rather than by physiologic control mechanisms. Therefore, the burden of extracellular volume regulation is usually placed on the kidneys, which must adapt their excretion of salt and water to match intake of salt and water under steady-state conditions.
In discussing the regulation of extracellular fluid volume, we also consider the factors that regulate the amount of sodium chloride in the extracellular fluid, because changes in extracellular fluid sodium chloride content usually cause parallel changes in extracellular fluid volume, provided the antidiuretic hormone (ADH)-thirst mechanisms are also operative. When the ADH-thirst mechanisms are functioning normally, a change in the amount of sodium chloride in the extracellular fluid is matched by a similar change in the amount of extracellular water, so that osmolality and sodium concentration are maintained relatively constant.
An important consideration in overall control of sodium excretion—or excretion of any electrolyte, for that matter—is that under steady-state conditions, excretion by the kidneys is determined by intake. To maintain life, a person must, over the long term, excrete almost precisely the amount of sodium ingested. Therefore, even with disturbances that cause major changes in kidney function, balance between intake and output of sodium usually is restored within a few days.
If disturbances of kidney function are not too severe, sodium balance may be achieved mainly by intrarenal adjustments with minimal changes in extra-cellular fluid volume or other systemic adjustments. But when perturbations to the kidneys are severe and intrarenal compensations are exhausted, systemic adjustments must be invoked, such as changes in blood pressure, changes in circulating hormones, and alter-ations of sympathetic nervous system activity. These adjustments are costly in terms of overall homeostasis because they cause other changes throughout the body that may, in the long run, be damaging. These compensations, however, are necessary because a sustained imbalance between fluid and electrolyte intake and excretion would quickly lead to accumula-tion or loss of electrolytes and fluid, causing cardio-vascular collapse within a few days. Thus, one can view the systemic adjustments that occur in response to abnormalities of kidney function as a necessary trade-off that brings electrolyte and fluid excretion back in balance with intake.
The two variables that influence sodium and water excretion are the rates of filtration and the rates of reabsorption:
Excretion = Glomerular filtration - Tubular reabsorption
GFR normally is about 180 L/day, tubular reab-sorption is 178.5 L/day, and urine excretion is 1.5 L/day. Thus, small changes in GFR or tubular reab-sorption potentially can cause large changes in renal excretion. For example, a 5 per cent increase in GFR (to 189 L/day) would cause a 9 L/day increase in urine volume, if tubular compensations did not occur; this would quickly cause catastrophic changes in body fluid volumes. Similarly, small changes in tubular reabsorp-tion, in the absence of compensatory adjustments of GFR, would also lead to dramatic changes in urine volume and sodium excretion. Tubular reabsorption and GFR usually are regulated precisely, so that excre-tion by the kidneys can be exactly matched to intake of water and electrolytes.
Even with disturbances that alter GFR or tubular reabsorption, changes in urinary excretion are mini-mized by various buffering mechanisms. For example, if the kidneys become greatly vasodilated and GFR increases (as can occur with certain drugs or high fever), this raises sodium chloride delivery to the tubules, which in turn leads to at least two intrarenal compensations: (1) increased tubular reabsorption of much of the extra sodium chloride filtered, called glomerulotubular balance, and (2) macula densa feed-back, in which increased sodium chloride delivery tothe distal tubule causes afferent arteriolar constriction and return of GFR toward normal. Likewise, abnor-malities of tubular reabsorption in the proximal tubule or loop of Henle are partially compensated for by these same intrarenal feedbacks.
Because neither of these two mechanisms operates perfectly to restore distal sodium chloride delivery all the way back to normal, changes in either GFR or tubular reabsorption can lead to significant changes in urine sodium and water excretion. When this happens, other feedback mechanisms come into play, such as changes in blood pressure and changes in various hormones, that eventually return sodium excretion to equal sodium intake. In the next few sections, we review how these mechanisms operate together to control sodium and water balance and in so doing act also to control extracellular fluid volume. We should keep in mind, however, that all these feedback mech-anisms control renal excretion of sodium and water by altering either GFR or tubular reabsorption.