The causes of hypernatremia may be divided into extrarenal water loss, renal water loss and iatrogenic.
The causes of hypernatremia may be divided into:
-Extrarenal water loss
-Renal water loss
The first two are due to water loss with inadequate replacement. Patients are generally dehydrated, and water replacement is indicated. On the other hand, iatrogenic hypernatremia is due to administration of hypertonic saline or NaHC03, usually in the course of an acute, critical illness. Iatrogenic hypernatremia results from the addition of hypertonic sodium, rather than water loss.
- Hypernatremia from Extrarenal Water Loss
The most common causes of hypernatremia due to extrarenal water loss include fever, profuse sweating, hyperventilation, including mechanical ventilation, and severe diarrhea. Patients with hypernatremia caused by extrarenal water loss often have decreased ECFVs as well, indicating deficits in total body sodium as well as water. The proportionally greater deficiency of water than of sodium leads to the increase in the serum sodium concentration.
- Hypernatremia from Renal Water Loss
The hallmark of marked renal water loss is polyuria, defined as a urine volume greater than 3Ll24 hours. The common defect in all cases of renal water loss is an inability of the kidney to conserve water appropriately. There are several important causes of renal water loss. The key to the evaluation of the patient with renal water loss is measurement of the urine osmolality.
- Osmotic diuresis (urine osmolality >300 mOsm/L)
The excretion of an osmotic solute load by the kidney will obligate a certain loss of water. Polyuria is an important clue to the presence of an osmotic diuresis. How do we know if an osmotic diuresis is to blame for the hypernatremia? The osmotic load excreted by the kidney will be increased to more than 1200 mOsd24 hours instead of the usual 600-900 mosdday. A helpful clue to the presence of an osmotic diuresis is the osmolality of a "spot" urine specimen: it will generally be in the range >300 mOsm/L and may have a sodium concentration in the range of 50-80 rnEq/L. Patients with hypernatrernia due to osmotic diuresis often manifest clinical signs of ECFV depletion. Typical clinical settings for the development of an osmotic diuresis are:
-Poorly controlled diabetes mellitus (glucose is the osmotic agent)
-Hyperalimentation (central or enteral) with an increased load of urea from protein catabolism
-Mannitol administration for cerebral edema
-Administration of sodium-containing solutions with resultant sodiuminduced diuresis.
Remember that acute administration of hypertonic mannitol or marked hyperglycemia may initially result in hyponatremia with hypertonicity. The patient is hypertonic, even though the serum sodium concentration is low because of transcellular shift of water. Osmotic diuresis resulting from the mannitol or hyperglycemia then results in progressive water loss and the sodium concentration increases. Ultimately, hypematremia develops.
- Diabetes insipidus (urine osmolality 4 5 0 mOsm/L)
Diabetes insipidus results from the inability of the kidney to concentrate the urine appropriately due to either absence or deficiency of ADH (central diabetes insipidus) or unresponsiveness of the kidney to the effects of ADH (nephrogenic diabetes insipidus). The urine is inappropriately dilute and typically has a low sodium concentration in the presence of polyuria and a rising serum sodium concentration.
-Central diabetes insipidus is due to deficiency of ADH (vasopressin). It is often associated with severe CNS structural lesions or infections, head trauma, or pituitary surgery. The onset of polyuria may be abrupt, with large urine volumes (5-10 L per 24 hours, for example). Patients sometimes describe a preference for ice water. Because the patients excrete large volume of dilute urine, a brief period of water restriction may result in a significant increase in the serum sodium concentration. The administration of vasopressin is used as a diagnostic test to establish the diagnosis of central diabetes insipidus. Vasopressin will result in a significant decrease in urine volume and an increase in urine osmolality.
-Nephrogenic diabetes insipidus implies unresponsiveness of the kidney to ADH. It occurs in a number of interstitial renal diseases, electrolyte disorders, and in response to certain medications. The urine volumes are often less than those seen with central diabetes insipidus. Because the kidney is unresponsive to ADH, vasopressin administration will not result in a significant decrease in urine volume or a significant increase in urine osmolality.
- Primary polydipsia (urine osmolality < 150 mOsm/L)
Primary polydipsia is sometimes referred to as "psychogenic water drinking." Primary polydipsia is not a cause of hypernatremia but is mentioned here because these patients have polyuria and must be differentiated from patients who have polyuria due to diabetes insipidus. Patients with primary polydipsia do not develop hypernatremia; indeed they may develop hyponatremia if they have impaired ability to excrete excess water. These patients drink large volumes of water each day and often produce tremendous amounts of dilute urine. They do not develop hypematremia when fluid restricted, however, and their urine osmolalities rise when water is restricted. It is important to remember that prolonged ingestion of vast amounts of water will sometimes produce a "washout" effect, removing osmoles from the medullary interstitium and thereby decreasing the medullary concentration gradient. The kidney's ability to produce a concentrated urine in response to water deprivation is therefore impaired. It may take several days for the medullary concentration gradient to be regenerated, and with it the ability to produce a maximally concentrated urine.
Iatrogenic hypernatremia differs from the other categories of hypematremia in that it is caused by gain of hypertonic sodium (usually NaHC03 or 3% saline) rather than loss of water. This usually occurs in the critical care unit or emergency room. Compromised renal function aggravates the problem. One 50 ml ampule of NaHC03 has 50 rnEq of NaHC03-1000 mEq sodium per liter! One liter of 3% saline has 5 13 rnEq/L sodium.