Chapter 046. Sodium and Water (Part 10) Figure 46-2 Many causes of hypernatremia are associated with polyuria and a submaximal urine osmolality. The product of the urine volume and osmolality, i.e., the solute excretion rate, is helpful in determining the basis of the polyuria (see above). To maintain a steady state, total solute excretion must equal solute production. As stated above, individuals eating a normal diet generate ~600 mosmol/d. Therefore, daily solute excretion in excess of 750 mosmol defines an osmotic diuresis. This can be confirmed by measuring the urine glucose and urea. In general, both CDI and NDI present with polyuria and hypotonic urine (urine osmolality <250 mosmol/kg). The degree of hypernatremia is usually mild unless there is an associated thirst abnormality. The clinical history, physical examination, and pertinent laboratory data can often rule out causes of acquired NDI. CDI and NDI can generally be distinguished by administering the AVP analogue desmopressin (10 µg intranasally) after careful water restriction. The urine osmolality should increase by at least 50% in CDI and will not change in NDI. Unfortunately, the diagnosis may sometimes be difficult due to partial defects in AVP secretion and action.[newpage] Hypernatremia: Treatment The therapeutic goals are to stop ongoing water loss by treating the underlying cause and to correct the water deficit. The ECF volume should be restored in hypovolemic patients. The quantity of water required to correct the deficit can be calculated from the following equation: In hypernatremia due to water loss, total body water is approximately 50 and 40% of lean body weight in men and women, respectively. For example, a 50- kg woman with a plasma Na + concentration of 160 mmol/L has an estimated free- water deficit of 2.9 L {[(160 – 140) ÷ 140] x (0.4 x 50)}. As in hyponatremia, rapid correction of hypernatremia is potentially dangerous. In this case, a sudden decrease in osmolality could potentially cause a rapid shift of water into cells that have undergone osmotic adaptation. This would result in swollen brain cells and increase the risk of seizures or permanent neurologic damage. Therefore, the water deficit should be corrected slowly over at least 48–72 h. When calculating the rate of water replacement, ongoing losses should be taken into account, and the plasma Na + concentration should be lowered by 0.5 mmol/L per h and by no more than 12 mmol/L over the first 24 h. The safest route of administration of water is by mouth or via a nasogastric tube (or other feeding tube). Alternatively, 5% dextrose in water or half-isotonic saline can be given intravenously. The appropriate treatment of CDI consists of administering desmopressin intranasally (Chap. 334). Other options for decreasing urine output include a low-salt diet in combination with low-dose thiazide diuretic therapy. In some patients with partial CDI, drugs that either stimulate AVP secretion or enhance its action on the kidney have been useful. These include chlorpropamide, clofibrate, carbamazepine, and nonsteroidal anti-inflammatory drugs (NSAIDs). The concentrating defect in NDI may be reversible by treating the underlying disorder or eliminating the offending drug. Symptomatic polyuria due to NDI can be treated with a low-Na + diet and thiazide diuretics, as described above. This induces mild volume depletion, which leads to enhanced proximal reabsorption of salt and water and decreased delivery to the site of action of AVP, the collecting duct. By impairing renal prostaglandin synthesis, NSAIDs potentiate AVP action and thereby increase urine osmolality and decrease urine volume. Amiloride may be useful in patients with NDI who need to be on lithium. The nephrotoxicity of lithium requires the drug to be taken up into collecting duct cells via the amiloride- sensitive Na + channel. . Chapter 046. Sodium and Water (Part 10) Figure 46-2 Many causes of hypernatremia are associated with polyuria and a submaximal urine osmolality. The product of the urine volume and. in AVP secretion and action.[newpage] Hypernatremia: Treatment The therapeutic goals are to stop ongoing water loss by treating the underlying cause and to correct the water deficit. The. The quantity of water required to correct the deficit can be calculated from the following equation: In hypernatremia due to water loss, total body water is approximately 50 and 40% of lean