1. Hypernatremia

2. serum Na concentration > 145 mEq/L
deficit of total body water relative to total body Na

3. Causes of hypernatremia
Description
Category
Examples
Hypovolemic hypernatremia
Decreased TBW and Na with a relatively greater decrease in TBW
GI losses
Diarrhea
Vomiting
Skin losses
Burns
Excessive sweating
Renal losses
Intrinsic renal disease
Loop diuretics
Osmotic diuresis (glucose, urea, mannitol

4. Hypovolemic hypernatremia
Na loss accompanied by a relatively greater loss of water from the body
Loop diuretics inhibit Na reabsorption
most common cause of hypernatremia due to osmotic diuresis is hyperglycemia in patients with diabetes
Loop diuretics inhibit Na reabsorption in the concentrating portion of the nephrons and can increase water clearance
Osmotic diuresis can also impair renal concentrating capacity because of a hypertonic substance present in the tubular lumen of the distal nephron
The most common cause of hypernatremia due to osmotic diuresis is hyperglycemia in patients with diabetes. Because glucose does not penetrate cells in the absence of insulin, hyperglycemia further dehydrates the ICF compartment. The degree of hyperosmolality in hyperglycemia may be obscured by the lowering of serum Na resulting from movement of water out of cells into the ECF

5. Causes of hypernatremia
Description
Category
Example
Euvolemic hypernatremia
Decreased TBW with near-normal total body Na
Extrarenal losses from respiratory tract
Tachypnea
Extrarenal losses from skin
Excessive sweating
Fever
Renal losses
Central diabetes insipidus
Nephrogenic diabetes insipidus
Other
Inability to access water
Primary hypodipsia
Reset osmostat

6. Euvolemic hypernatremia
decrease in TBW with near-normal total body Na (pure water deficit)
Extrarenal causes of water loss, such as excessive sweating, result in some Na loss, but because sweat is hypotonic, hypernatremia can result before significant hypovolemia. A deficit of almost purely water also occurs in central and nephrogenic diabetes insipidus
Essential hypernatremia (primary hypodipsia) occasionally occurs in children with brain damage and in chronically ill elderly adults. It is characterized by an impaired thirst mechanism (eg, caused by lesions of the brain's thirst center). Altered osmotic trigger for ADH release is another possible cause of euvolemic hypernatremia; some lesions cause both an impaired thirst mechanism and an altered osmotic trigger. The nonosmotic release of ADH appears intact, and these patients are generally euvolemic.

7. Causes of hypernatremia
Description
Category
Examples
Hypervolemic hypernatremia
Increased Na with normal or increased TBW
Hypertonic fluid administration
Hypertonic saline
NaHCO3
TPN
Mineralocorticoid excess
Adrenal tumors secreting deoxycorticosterone
Congenital adrenal hyperplasia (caused by 11-hydroxylase defect)

8. Hypervolemic hypernatremia
grossly elevated Na intake associated with limited access to water
Hypernatremia in the elderly= Hypernatremia is common in the elderly, particularly postoperative patients and those receiving tube feedings or parenteral nutrition. Other contributing factors may include the following:
Dependence on others to obtain water
Impaired thirst mechanism
Impaired renal concentrating capacity (due to diuretics, impaired ADH release, or nephron loss accompanying aging or other renal disease)
Impaired angiotensin II production (which may contribute directly to the impaired thirst mechanism)

9. Causes of hypernatremia
Net water loss
Pure water
Unreplaced insensible losses (dermal and respiratory)
Hypodipsia
Neurogenic diabetes insipidus
Post-traumatic
Caused by tumors, cysts, histiocytosis, tuberculosis,
sarcoidosis
Idiopathic
Caused by aneurysms, meningitis, encephalitis,
Guillain–Barré syndrome
Caused by ethanol ingestion (transient)
Congenital nephrogenic diabetes insipidus
Acquired nephrogenic diabetes insipidus
Caused by renal disease (e.g., medullary cystic disease)
Caused by hypercalcemia or hypokalemia
Caused by drugs (lithium, demeclocycline, foscarnet,
methoxyflurane, amphotericin B, vasopressin V
receptor antagonists)
Adrogue, H., and N. Madias. Hypernatremia.The New England Journal of Medicine. Volume 342 Number 20.

10. Causes of hypernatremia
Hypotonic fluid
Renal causes
Loop diuretics
Osmotic diuresis (glucose, urea, mannitol)
Postobstructive diuresis
Polyuric phase of acute tubular necrosis
Intrinsic renal disease
Gastrointestinal causes
Vomiting
Nasogastric drainage
Enterocutaneous fistula
Diarrhea
Use of osmotic cathartic agents (e.g., lactulose)
Cutaneous causes
Burns
Excessive sweating
Adrogue, H., and N. Madias. Hypernatremia.The New England Journal of Medicine. Volume 342 Number 20.

11. Causes of hypernatremia
Hypertonic sodium gain
Hypertonic sodium bicarbonate infusion
Hypertonic feeding preparation
Ingestion of sodium chloride
Ingestion of sea water
Sodium chloride–rich emetics
Hypertonic saline enemas
Intrauterine injection of hypertonic saline
Hypertonic sodium chloride infusion
Hypertonic dialysis
Primary hyperaldosteronism
Cushing’s syndrome
Adrogue, H., and N. Madias. Hypernatremia.The New England Journal of Medicine. Volume 342 Number 20.

12. Clinical Features of Hypernatremia
altered mental status
weakness
neuromuscular irritability
Focal neurologic deficits
Occasionally, coma and seizures
Polyuria
thirst
Increased risk of subarachnoid or intracerebral hemorrhage due to decreased brain cell volume
Signs and symptoms of volume depletion often present in patients with history of excessive sweating, diarrhea, or an osmotic diuresis
Major symptoms are neurologic
As a consequence of hypertonicity, water shifts out of cells, leading to contracted ICF volume

13. DIAGNOSIS

14. can be induced by the administration of sodium in excess of water
a high plasma sodium concentration most often results from free water loss
appropriate renal response is excretion of the minimum volume (500 mL/d) of maximally concentrated urine (urine osmolality 800 mosmil/kg)

15. can be induced by the lack of replacement
or by urinary losses due to central or nephrogenic diabetes insipidus or to an osmotic diuresis resulting from increased excretion of glucose in uncontrolled diabetes mellitus or of urea with high-protein feedings
can be induced by the lack of replacement of insensible losses from the skin and respiratory tract; by diarrheal losses (as with lactulose, malabsorption, or some infectious diarrheas);

16. CDI and NDI can generally be distinguished by administering desmopressin (10 ug intranasally) after careful water restriction

17. Urine osmolality should increase by at least 50% in CDI

18. Hypernatremia
Treatment

19. Treatment Goals To determine the rate of correction
To correct the water deficit and hypovolemia at the rate desired
To correct the underlying disorder, thereby reducing ongoing water loss

20. Rate of correction
Depends on the acuity of its development and the presence of neurologic dysfunction
1. Symptomatic hypernatremia
Aggressive correction -> potentially dangerous
Rapid shift of water into brain cells -> increase risk of seizures and permanent neurologic damage
Water deficit: reduced gradually: 10 to 12 mEq/L/d

21. Rate of correction 2. Chronic asymptomatic hypernatremia
Cerebral adaptation to the chronic hyperosmolar state -> increased risk of treatment-related complication
Plasma Na+ : lowered at a more moderate rate
Between 5 and 8 meq/L/d

22. Fluid administration Mainstay: administration of water
Preferably be mouth or NGT
Alternative: D5W or quarter normal saline IV
D5W: pure water loss as in insensible losses or diabetes insipidus
Quarter normal saline: concurrent electrolyte loss as in GI and diuretic-induced losses

23. Fluid administration Traditionally..
Free water deficit= {([Na] – 140)/140} x (TBW)
Does not provide sufficient guidance regarding the rate and the content of the infusate

24. Fluid administration
Estimated change in [Na+] from fluid administration:
∆ [Na+] = {[Na+i] + [K+i] - [Na+s]} ÷ {TBW + 1}
[Na+i] and [K+i]: concentration in infused fluid
[Na+s]: starting serum sodium
Estimated TBW:
Men: Lean Weight (kg) x 0.5
Women: Lean Weight (kg) x 0.4

25. Water deficit Water deficit: corrected slowly over at least 48–72 h
To calculate the rate of water replacement:
Check for ongoing losses
plasma Na+ concentration should be lowered by 0.5 mmol/L per h
not more than 12 mmol/L over the first 24 h
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.
50 kg female: [( )/140] x (0.4 x 50kg) = 1.14 L free-water deficit

26. For example …
A 70kg with diarrhea (2L/d) from laxative abuse presents with obtundation and [Na+] = 164meq/L, [K+] = 3.0. A replacement fluid of D5W with 20mEq KCl/L is chosen.
The ∆ [Na+] with 1 L of this fluid would be -4mEq/L.
{ } ÷ {(70x0.5) + 1} = - 4mEq/L
3L is necessary for a ∆ [Na+] - 12 mEq/L/24hr
(-12mEq/L/d) ÷ (- 4mEq/L/L of solution)
Hourly rate of infusion: 125cc/hr (3L/d ÷ 24hr/d)
Close follow-up as it does not account for ongoing GI or insensible losses, which may account for another 1.4L/d of water required to keep [Na+] stable.

27. Water deficit
The quantity of water required to correct the deficit can be calculated from the following equation:

28. Specific therapies for underlying cause
Hypovolemic hypernatremia
Mild volume depletion: 0.45% NS used to replenish EDF and water deficit
Severe volume depletion: isotonic fluid over correction of the hyperosmolar state
Once stable: give hypotonic fluid to replace the free water deficit

29. Specific therapies for underlying cause
Hypernatremia from primary Na+ gain
Cessation of iatrogenic Na
Diabetes insipidus:
Treatment directed toward symptomatic polyuria
Central DI: impaired secretion of vasopressin
Tx: administration of dDAVP (vasopressin analog)
Nephrogenic DI:
Tx: low Na+ diet combined with thiazide diuretics -> enhances proximal reabsorption of salt and water - > decrease excess water loss
Decrease protein intake -> minimize solute load excreted -> decrease urine output

30. Specific therapies for underlying cause
Partial Central Diabetes Insipidus
chlorpropamide, clofibrate, carbamazepine, NSAIDs
stimulate AVP secretion or enhance its action on the kidney

31. Specific therapies for underlying cause
Nephrogenic Diabetes Insipidus
Treat underlying cause, eliminate offending drug
Symptomatic polyuria: low-Na+ diet and thiazide diuretics
induces mild volume depletion, → enhanced proximal reabsorption of salt and water, decreased delivery to the collecting duct (site of action of AVP)
NSAIDs: potentiate AVP action → increase urine osmolality, decrease urine volume
Amiloride: on lithium
nephrotoxicity of lithium requires the drug to be taken up into collecting duct cells via the amiloride-sensitive Na+ channel

32. Safest route: oral or NGT D5W or half-isotonic saline
 urine output: low-salt diet in combination with low-dose thiazide diuretic therapy
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.