Review of Medical Physiology - William F. Ganong 2002

Formation and Excretion of Urine
Renal Function and Micturition
Regulation of Na+ and Cl- Excretion

Significant filtration of Na⁺ occurs in the glomeruli, but it is actively reabsorbed from all segments of the tubule except the thin limb of the Loop of Henle. Normally, 96–99% of filtered Na⁺ is reabsorbed. The majority of Na⁺ is reabsorbed along with Cl^- (Table 38-9), while a portion is reabsorbed via reactions where one Na⁺ ion enters the Blood in exchange for each H⁺ ion secreted into the tubules. Additionally, in the distal tubule, a small amount of Na⁺ is actively reabsorbed coupled with K⁺ secretion.

Regulation of Na⁺ Excretion

Since Na⁺ is the most abundant cation in the ECF, and Na⁺ salts account for 90% of the osmotically active solutes in plasma and interstitial fluid, total body Na⁺ content is the primary determinant of ECF volume. Therefore, it is not surprising that terrestrial animals possess numerous regulatory mechanisms governing The excretion of this ion. Through these mechanisms, Na⁺ excretion matches dietary intake, thereby maintaining sodium balance. Consequently, urinary Na⁺ loss ranges from as little as 1 mEq/day on a salt-restricted diet to 400 mEq/day on a high-sodium diet. Furthermore, a marked increase in urinary Na⁺ excretion occurs following the intravenous infusion of NaCl solutions. Fluctuations in The rate of Na⁺ excretion are also evidently driven by changes in filtration rate (Table 38-10) and tubular reabsorption. Factors influencing GFR—such as tubuloglomerular feedback, glomerulotubular balance, and peritubular capillary oncotic pressure—were discussed earlier. Other factors influencing Na⁺ reabsorption include plasma concentrations of aldosterone and other Adrenocortical Hormones, circulating levels of ANP and other natriuretic Peptides, intrarenal levels of angiotensin II and PGE₂, and the rates of tubular H⁺ and K⁺ secretion.

Class="center">Table 38-9. Quantitative Aspects of Na⁺ Reabsorption in Healthy Humans on a Normal Sodium Diet

Effects of Corticosteroids

Mineralocorticoids synthesized by the adrenal cortex, such as aldosterone, enhance tubular Na⁺ reabsorption coupled with the secretion of K⁺ and H⁺, as well as promoting NaCl reabsorption (see Chapter 20). When these hormones are administered to adrenalectomized animals, a latency period of 10–30 minutes is observed before any effect on Na⁺ reabsorption becomes apparent, as time is required for Steroids to alter Protein Synthesis via genomic mechanisms.

While mineralocorticoids can also elicit rapid nongenomic membrane effects, these do not significantly alter overall net Na⁺ excretion in the experimental animal. Mineralocorticoids act primarily on the cortical collecting ducts. As noted in Chapter 20, these hormones bind to principal Cells (P cells), increasing the number of active epithelial sodium channels (ENaCs) in the apical membranes of these cells (Fig. 38-24).

In Liddle's syndrome, Mutations in the genes encoding the β and, less commonly, the γ subunits of the ENaC result in constitutively upregulated channel activity. This leads to profound renal Na⁺ retention and arterial Hypertension.

Other Humoral Factors

Reduced dietary salt intake stimulates aldosterone secretion (see Fig. 20-27), leading to a marked, albeit relatively slow, reduction in Na⁺ excretion. A variety of other humoral factors also influence Na⁺ reabsorption. PGE₂ enhances urinary Na⁺ excretion, likely by inhibiting Na⁺-K⁺-ATPase and increasing intracellular Ca²⁺ levels, which in turn suppresses Na⁺ transport through ENaCs. Endothelin and IL-2 also promote natriuresis, possibly by stimulating PGE₂ synthesis. ANP and related peptides elevate intracellular cGMP levels, which inhibit ENaC-mediated transport. Inhibition of Na⁺-K⁺-ATPase by other natriuretic factors—hypothesized to include endogenous ouabain-like steroids (see Chapter 24)—likewise promotes Na⁺ excretion.

Table 38-10. Changes in Na⁺ Excretion Resulting from GFR Fluctuations in the Absence of Parallel Changes in Na⁺ Reabsorption

Fig. 38-24. Renal principal (P) Cell. Na⁺ enters The Cell via apical ENaCs and is extruded into the interstitial fluid by basolateral Na⁺-K⁺-ATPase. Aldosterone activates a genomic pathway producing SGK and other Proteins, which increases the number of active ENaCs.

Angiotensin II enhances the reabsorption of Na⁺ and HCO₃^- by acting on the proximal tubules. The Kidneys contain high concentrations of angiotensin-converting enzyme (ACE), where approximately 20% of circulating angiotensin I is converted into angiotensin II. In addition, angiotensin I is synthesized locally within the kidneys.

Coupling with Acid and K⁺ Secretion

Na⁺ excretion is augmented by pharmacological agents that reduce renal acid secretion through Carbonic anhydrase inhibition. Following the titration of CO₂ or H⁺ in the blood, filtered Na⁺ accompanying acid anions escapes reabsorption and appears in the urine whenever the filtered load exceeds the tubular capacity for Na⁺-H⁺ exchange. Changes in Na⁺ excretion secondary to alterations in K⁺ secretory rates are minimal (see Table 38-10).