Regulatory Mechanisms in Salt and Water Reabsorption

Osmotic Equilibrium

The ability of the kidney to concentrate urine is dependent on the interaction of at least three processes: (1) the generation of a hypertonic medullary interstitium by the countercurrent mechanism and urea recycling, (2) concentration and then dilution of tubular fluid in the loop of Henle, and (3) the action of antidiuretic hormone (now known as AVP) in increasing water permeability in the last part of the distal tubule and collecting ducts.

The medullary interstitium is rendered hypertonic by the countercurrent multiplier effect of the loop of Henle. The primary mechanism is separation of solute from water (the single effect) by the combination of NaCl reabsorption and water impermeability in the ascending limb. This results in an increased NaCl concentration and osmolality in the medullary interstitium. The descending limb is freely permeable to water, which diffuses into the interstitium along the osmotic gradient, and the tubular fluid becomes progressively hyperosmotic at the bend of the loop.

The vasa recta, which are closely applied to the long loops of Henle of juxtamedullary nephrons, maintain this condition by removing water and adding solute as they pass through the medullary interstitium. A standing osmotic gradient is thereby set up between the cortex (300 mOsm/kg), juxtamedullary zone (600 mOsm/kg), and deep medulla (1200 mOsm/kg). This process is enhanced by the passive recycling of urea, which diffuses out of the inner medullary collecting duct into the interstitium and thence into the distal loop of Henle. These processes are summarized in Figure 20-8 .

Tubular Concentration and Dilution

Hypovolemia

Contraction of the extracellular volume (hypovolemia) activates a series of vasoconstrictor, salt-retaining neurohormonal systems: the sympathoadrenal system, the renin-angiotensin-aldosterone axis, and AVP. Initially, the GFR and the filtered load of sodium decrease. Sodium reabsorption in the proximal tubule is increased from about 66% to 80% by sympathetic activity and angiotensin II, as well as by the decline in peritubular capillary pressure induced by renal vasoconstriction. Sodium delivery to the thick ascending loop of Henle, distal tubule, and collecting duct is decreased, but aldosterone promotes reabsorption of sodium at these sites. Under the influence of AVP, water is also avidly reabsorbed in the collecting duct so that the urine becomes highly concentrated (osmolality, 600 mOsm/kg), but with virtually no sodium (10 mEq/L).

Diuretic agents abolish the kidney's ability to concentrate urine by washing out the hypertonic medulla. They do this either by an osmotic effect that prevents water reabsorption (e.g., mannitol) or by inhibition of active NaCl transport in the thick ascending loop (e.g., furosemide) or the first part of the distal tubule (e.g., hydrochlorothiazide). An early and important manifestation of acute tubular necrosis is the loss of urinary concentrating ability caused by breakdown of the energy-requiring Na-K-ATPase pump in the thick ascending loop of Henle.

Hypervolemia

Expansion of the extracellular volume, or hypervolemia, is controlled by a series of vasodilator, salt-excreting neuropeptides, of which atrial natriuretic peptide (ANP) is predominant. The GFR and filtered sodium load increase because of a combination of reflex decreases in sympathetic and angiotensin II activity and the release of ANP. Together with the increase in peritubular capillary hydrostatic pressure, these responses cause sodium reabsorption in the proximal tubule to decrease from 67% to 50%. The decline in plasma aldosterone decreases sodium absorption from the thick ascending loop of Henle to the collecting duct. The presence of ANP and absence of AVP impairs water absorption at the collecting duct so that dilute urine (osmolality, 300 mOsm/kg) with abundant sodium (80 mEq/L) is produced.

It is noteworthy that loop diuretics, which depress tubular resorptive capacity, and acute tubular necrosis, which abolishes it completely, may generate an identical urinary profile (low osmolality, high urinary sodium), even in the presence of hypovolemia.