Chapter 046. Sodium and Water (Part 2) potx

Sodium and Water Part 2 Water Excretion In contrast to the ingestion of water, its excretion is tightly regulated by physiologic factors.. The binding of AVP to V2 receptors on the bas

Chapter 046 Sodium and Water

(Part 2)

Water Excretion

In 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 V2 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 encoded by the aquaporin-2 gene (Chap 334)

The net effect is passive water reabsorption along an osmotic gradient from the lumen of the collecting duct to the hypertonic medullary interstitium The major stimulus 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 hypothalamic osmoreceptors as a decrease or increase in cell volume, respectively, leading to enhancement or suppression of AVP secretion The osmotic threshold for AVP release is 280–290 mosmol/kg, and the system is sufficiently sensitive that plasma osmolality varies by no more than 1–2%

Nonosmotic factors that regulate AVP secretion include effective

circulating (arterial) volume, nausea, pain, stress, hypoglycemia, pregnancy, and

numerous drugs The hemodynamic response is mediated by baroreceptors in the carotid sinus The sensitivity of these receptors is significantly lower than that of the osmoreceptors In fact, depletion of blood volume sufficient to result in a decreased mean arterial pressure is necessary to stimulate AVP release, whereas small changes in effective circulating volume have little effect

To maintain homeostasis and a normal plasma Na+ concentration, the ingestion of solute-free water must eventually lead to the loss of the same volume

of electrolyte-free water Three steps are required for the kidney to excrete a water load: (1) filtration and delivery of water (and electrolytes) to the diluting sites of the nephron; (2) active reabsorption of Na+ and Cl– without water in the thick ascending limb of the loop of Henle (TALH) and, to a lesser extent, in the distal nephron; and (3) maintenance of a dilute urine due to impermeability of the

collecting duct to water in the absence of AVP Abnormalities of any of these steps 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 a result, 85–90% of all Na+ is extracellular, and the ECF volume is a reflection of total body Na+ content Normal volume regulatory mechanisms ensure that Na+ loss balances Na+ gain If this does not occur, conditions of Na+ excess or deficit ensue and are manifest as edematous or hypovolemic states, respectively It is important to distinguish between disorders of osmoregulation and disorders of volume 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 or expansion and imply abnormal Na+ balance

Sodium Intake

Individuals eating a typical western diet consume approximately 150 mmol

of NaCl daily This normally exceeds basal requirements As noted above, sodium

is the principal extracellular cation Therefore, dietary intake of Na+ results in ECF volume expansion, which in turn promotes enhanced renal Na+ excretion to maintain steady state Na+ balance

Sodium Excretion

(See also Chap 272) The regulation of Na+ excretion is multifactorial and

is the major determinant of Na+ balance A Na+ deficit or excess is manifest as a decreased or increased effective circulating volume, respectively Changes in effective circulating volume tend to lead to parallel changes in glomerular filtration rate (GFR) However, tubule Na+ reabsorption, and not GFR, is the major regulatory mechanism controlling Na+ excretion Almost two-thirds of filtered Na+

is reabsorbed in the proximal convoluted tubule; this process is electroneutral and isoosmotic Further reabsorption (25–30%) occurs in the TALH via the apical

Na+-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 and

medullary collecting ducts, the amount excreted being reasonably equivalent to the amount ingested per day