HYPERNATREMIA

1 Hypernatremia is defined as a
plasma Na+ concentration >145
mmol/L.
ETIOLOGY
Hypernatremia may be due to primary Na+ gain or water
deficit
GENERALLY THE CAUSE IS WATER DEFICIT IT IS
DUE TO
Access to water is limited
occurs in infants, the
physically handicapped, and patients with impaired
mental status; in the postoperative state; and in
intubated patients in the intensive care unit.
Impaired thirst
may be due to primary hypodipsia. This
usually occurs as a result of damage to the
hypothalamic osmoreceptors that control
thirst and tends to be associated with
abnormal osmotic regulation of AVP
secretion. Primary hypodipsia may be due to
a variety of pathologic changes,
including granulomatous disease, vascular
occlusion, and tumors. A subset of
hypodipsic hypernatremia, referred to as
essential hypernatremia, does not
respond to forced water intake. This appears
to be due to a specific osmoreceptor defect
resulting in nonosmotic regulation of AVP
release. Thus, the
hemodynamic effects of water loading lead
to AVP suppression and excretion of dilute
urine.
Free water loss is either renal or extrarenal
EXTRARENAL
evaporation from the skin and respiratory tract
(insensible losses) or loss from the gastrointestinal tract. Insensible
losses are increased with fever, exercise, heat exposure, and severe
burns and in
mechanically ventilated patients. Furthermore, the Na+ concentration of
sweat decreases with profuse perspiration, thereby increasing solute-
free water
loss. Diarrhea is the most common gastrointestinal cause of
hypernatremia. Specifically, osmotic diarrheas (induced by lactulose,
sorbitol, or
malabsorption of carbohydrate) and viral gastroenteritides result in
water loss exceeding that of Na+ and K+.
Renal water loss
Is the most common cause of hypernatremia
Drug-induced
Loop diuretics interfere with the countercurrent mechanism and produce
an isoosmotic solute diuresis. This results in a decreased medullary
interstitial tonicity and impaired renal concentrating ability.
The presence of non-reabsorbed organic solutes in the tubule lumen
impairs the osmotic reabsorption of water.
This leads to water loss in excess of Na+ and K+, known as an osmotic
diuresis. The most frequent cause of an osmotic diuresis is hyperglycemia
and
glucosuria in poorly controlled diabetes mellitus. Intravenous
administration of mannitol and increased endogenous production of urea
(high-protein diet)
can also result in an osmotic diuresis.

11/02/2021 5
DIABETES INSIPIDUS
Hypernatremia secondary to nonosmotic urinary water loss is usually due to: (1) Central diabetes
insipidus (CDI) characterized by impaired AVP secretion,
or (2) NDI resulting from end-organ (renal) resistance to the actions of AVP.
 The most common cause of CDI is destruction of the neurohypophysis. This
may occur as a result of trauma, neurosurgery, granulomatous disease, neoplasms, vascular accidents,
or infection. In many cases, CDI is idiopathic and
may occasionally be hereditary. The familial form of the disease is inherited in an autosomal
dominant fashion and has been attributed to mutations in the
propressophysin (AVP precursor) gene.
 Nephrogenic diabetes insipidus (NDI) may be either inherited or acquired. Congenital NDI is an X-
linked recessive trait due to mutations in the V2 receptor gene. Mutations in the autosomal
aquaporin-2 gene may also result in NDI. The aquaporin-2 gene encodes the
water channel protein whose membrane insertion is stimulated by AVP. The causes of sporadic NDI
are numerous and include drugs (especially lithium),
hypercalcemia, hypokalemia, and conditions that impair medullary hypertonicity (e.g., papillary
necrosis or osmotic diuresis). Pregnant women, in the
second or third trimester, may develop NDI as a result of excessive elaboration of vasopressinase by
the placenta
CLINICAL FEATURES
As a consequence of hypertonicity, water shifts out of cells, leading to a contracted
ICF volume. A decreased brain cell volume is associated with an
increased risk of subarachnoid or intracerebral hemorrhage. Hence, the major
symptoms of hypernatremia are neurologic and include altered mental
status, weakness, neuromuscular irritability, focal neurologic deficits, and
occasionally coma or seizures. Patients may also complain of polyuria or thirst.
For unknown reasons, patients with polydipsia from CDI tend to prefer ice-cold
water. The signs and symptoms of volume depletion are often present in
patients with a history of excessive sweating, diarrhea, or an osmotic diuresis. As
with hyponatremia, the severity of the clinical manifestations is related
to the acuity and magnitude of the rise in plasma Na+ concentration. Chronic
hypernatremia is generally less symptomatic as a result of adaptive
mechanisms designed to defend cell volume. Brain cells initially take up Na+ and K+
salts, later followed by accumulation of organic osmolytes such as
inositol. This serves to restore the brain ICF volume toward normal
DIAGNOSIS
TREATMENT
WATER DEFICIT
TO STOP ONGOING FLUID LOSS BY TREATING UNDERLYING CAUSE
TO CORRECT WATER DEFICIT
WATER DEFICIT =
PLASMA SODIUM-140 X0.6XBODY WEIGHT K
 14O
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 halfisotonic
saline can be given intravenously.
Treatment of CDI
administering desmopressin intranasally
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)
NDI
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