Chapter 046. Sodium and Water (Part 2)

Water ExcretionIn contrast to the ingestion of water, its excretion is tightly regulated by physiologic factors. The principal determinant of renal water excretion is arginine vasopressin (AVP; formerly antidiuretic hormone), a polypeptide synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and secreted by the posterior pituitary gland. The binding of AVP to V 2 receptors on the basolateral membrane of principal cells in the collecting duct activates adenylyl cyclase and initiates a sequence of events that leads to the insertion of water channels into the luminal membrane. These water channels that are specifically activated by AVP are...
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Chapter 046. Sodium and Water (Part 2) Chapter 046. Sodium and Water (Part 2) Water Excretion In contrast to the ingestion of water, its excretion is tightly regulated byphysiologic factors. The principal determinant of renal water excretion isarginine vasopressin (AVP; formerly antidiuretic hormone), a polypeptidesynthesized in the supraoptic and paraventricular nuclei of the hypothalamus andsecreted by the posterior pituitary gland. The binding of AVP to V 2 receptors onthe basolateral membrane of principal cells in the collecting duct activatesadenylyl cyclase and initiates a sequence of events that leads to the insertion ofwater channels into the luminal membrane. These water channels that arespecifically activated by AVP are encoded by the aquaporin-2 gene (Chap. 334).The net effect is passive water reabsorption along an osmotic gradient from thelumen of the collecting duct to the hypertonic medullary interstitium. The majorstimulus for AVP secretion is hypertonicity. Since the major ECF solutes are Na +salts, effective osmolality is primarily determined by the plasma Na +concentration. An increase or decrease in tonicity is sensed by hypothalamicosmoreceptors as a decrease or increase in cell volume, respectively, leading toenhancement or suppression of AVP secretion. The osmotic threshold for AVPrelease is 280–290 mosmol/kg, and the system is sufficiently sensitive that plasmaosmolality varies by no more than 1–2%. Nonosmotic factors that regulate AVP secretion include effectivecirculating (arterial) volume, nausea, pain, stress, hypoglycemia, pregnancy, andnumerous drugs. The hemodynamic response is mediated by baroreceptors in thecarotid sinus. The sensitivity of these receptors is significantly lower than that ofthe osmoreceptors. In fact, depletion of blood volume sufficient to result in adecreased mean arterial pressure is necessary to stimulate AVP release, whereassmall changes in effective circulating volume have little effect. To maintain homeostasis and a normal plasma Na+ concentration, theingestion of solute-free water must eventually lead to the loss of the same volumeof electrolyte-free water. Three steps are required for the kidney to excrete a waterload: (1) filtration and delivery of water (and electrolytes) to the diluting sites ofthe nephron; (2) active reabsorption of Na+ and Cl– without water in the thickascending limb of the loop of Henle (TALH) and, to a lesser extent, in the distalnephron; and (3) maintenance of a dilute urine due to impermeability of thecollecting duct to water in the absence of AVP. Abnormalities of any of thesesteps can result in impaired free water excretion, and eventual hyponatremia. Sodium Balance Sodium is actively pumped out of cells by the Na+, K+-ATPase pump. As aresult, 85–90% of all Na+ is extracellular, and the ECF volume is a reflection oftotal body Na+ content. Normal volume regulatory mechanisms ensure that Na+loss balances Na+ gain. If this does not occur, conditions of Na+ excess or deficitensue and are manifest as edematous or hypovolemic states, respectively. It isimportant to distinguish between disorders of osmoregulation and disorders ofvolume regulation since water and Na+ balance are regulated independently.Changes in Na+ concentration generally reflect disturbed water homeostasis,whereas alterations in Na+ content are manifest as ECF volume contraction orexpansion and imply abnormal Na+ balance. Sodium Intake Individuals eating a typical western diet consume approximately 150 mmolof NaCl daily. This normally exceeds basal requirements. As noted above, sodiumis the principal extracellular cation. Therefore, dietary intake of Na + results in ECFvolume expansion, which in turn promotes enhanced renal Na + excretion tomaintain steady state Na+ balance. Sodium Excretion (See also Chap. 272) The regulation of Na+ excretion is multifactorial andis the major determinant of Na+ balance. A Na+ deficit or excess is manifest as adecreased or increased effective circulating volume, respectively. Changes ineffective circulating volume tend to lead to parallel changes in glomerularfiltration rate (GFR). However, tubule Na+ reabsorption, and not GFR, is the majorregulatory mechanism controlling Na+ excretion. Almost two-thirds of filtered Na +is reabsorbed in the proximal convoluted tubule; this process is electroneutral andisoosmotic. Further reabsorption (25–30%) occurs in the TALH via the apicalNa+-K+-2Cl–co-transporter; this is an active process and is also electroneutral.Distal convoluted tubule reabsorption of Na+ (5%) is mediated by the thiazide-sensitive Na+-Cl– co-transporter. Final Na+ reabsorption occurs in the cortical andmedullary collecting ducts, the amou ...