Osmotic Diuresis

c T3

vides an additional driving force for water reabsorption. The more water filtered at the glomerulus, the higher this oncotic pressure. Thus, the reabsorption of water at the proximal tubule is, to a certain extent, adjusted in accordance with the GFR (glomerulotubular balance).

Because the descending limb of the loop of Henle has aquaporins (AQP1) that make it permeable to water, the urine in it is largely in osmotic balance with the hypertonic inter-stitium, the content of which becomes increasingly hypertonic as it approaches the papillae (^ A5). The urine therefore becomes increasingly concentrated as it flows in this direction. In the thin descending limb, which is only sparingly permeable to salt, this increases the conc. of Na+ and Cl-. Most water drawn into the interstitium is carried off by the vasa recta (^ B). Since the thin and thick ascending limbs of the loop of Henle are largely impermeable to water, Na+ and Cl- passively diffuses (thin limb) and is actively transported (thick limb) out into the interstitium (^ B). Since water cannot escape, the urine leaving the loop of Henle is hypotonic.

Active reabsorption of Na+ and Cl- from the thick ascending limb of the loop of Henle (TAL; ^ p. 162) creates a local gradient (ca. 200 mOsm/kg H2O; ^A5) at all points between the TAL on the one side and the descending limb and the medullary interstitium on the other. Since the high osmolality of fluid in the medullary interstice is the reason why water is extracted from the collecting duct (see below), active NaCl transport is the ATP-con-suming "motor" for the kidney's urine-concentrating mechanism and is up-regulated by sustained stimulation of ADH secretion.

Along the course of the distal convoluted tubule and, at the latest, at the connecting tubule, which contains aquaporins and ADH receptors of type V2 (explained below), the fluid in the tubule will again become isotonic (in osmotic balance with the isotonic interstice of the renal cortex) if ADH is present (^ p. 168), i.e., when antidiuresis occurs. Although Na+ and Cl- are still reabsorbed here (^ p. 162), the osmolality does not change significantly because H2O is reabsorbed (ca. 5% of the GFR) into the interstitial space due to osmotic forces and urea increasingly determines the osmolality of the tubular fluid.

Final adjustment of the excreted urine volume occurs in the collecting duct. In the presence of antidiuretic hormone, ADH (which binds to ba-solateral V2 receptors, named after vasopressin, the synonym for ADH), aquaporins (AQP2) in the (otherwise water-impermeable) lumi-nal membrane ofprincipal cells are used to extract enough water from the urine passing through the increasingly hypertonic renal medulla. Thereby, the Uosm rises about four times higher than the Posm (Uosm/Posm ~ 4), corresponding to maximum antidiuresis. The absence of ADH results in water diuresis, where Uosm/Posm can drop to < 0.3. The Uosm can even fall below the osmolality at the end of TAL, since reabsorption of Na+ and Cl- is continued in the distal convoluted tubule and collecting duct (^ p. 162) but water can hardly follow.

Urea also plays an important role in the formation of concentrated urine. A protein-rich diet leads to increased urea production, thus increased the urine-concentrating capacity of the kidney. About 50% of the filtered urea leaves the proximal tubule by diffusion (^ C). Since the ascending limb of the loop of Henle, the distal convoluted tubule, and the cortical and outer medullary sections of the collecting duct are only sparingly permeable to urea, its conc. increases downstream in these parts of the nephron (^ C). ADH can (via V2 receptors) introduce urea carriers (urea transporter type 1, UT1) in the luminal membrane, thereby making the inner medullary collecting duct permeable to urea. Urea now diffuses back into the interstitium (where urea is responsible for half of the high osmolality there) via UT1 and is then transported by UT2 carriers back into the descending limb of the loop of Henle, comprising the recirculation of urea (^ C). The non-reabsorbed fraction of urea is excreted: FEurea ~ 40%. Urea excretion increases in water diuresis and decreases in antidiuresis, presumably due to up-regulation of the UT2 carrier.

Urine concentration disorders primarily occur due to (a) excessive medullary blood flow (washing out Na+, Cl- and urea); (b) osmotic diuresis; (c) loop diuretics (^ p. 172); (d) deficient secretion or effectiveness of ADH, as seen in central or peripheral diabetes insipidus, respectively.

|— B. Water reabsorption and excretion

Water follows NaCl

|— B. Water reabsorption and excretion

Water follows NaCl

Osmotic Diuresis Adh
|— C. Urea in the kidney
Urea Tubular Transport

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