Malattie del rene e delle vie urinarie - Hyponatriemia

The New Eng land Jour nal of Medicine

Extracellular Fluid Intracellular Fluid Normal conditions

A Hypotonic hyponatremia due to water

retention in the presence of essentially

normal sodium stores (e.g., from the

B syndrome of inappropriate secretion of

antidiuretic hormone)

Hypotonic hyponatremia without anticipated

C hypo-osmolality (e.g., from renal failure)

Hypertonic hyponatremia due to gain of impermeable

D solutes other than sodium (e.g., from hyperglycemia)

Hypotonic hyponatremia due to water

retention in association with sodium

E depletion (e.g., from diarrhea)

Hypotonic hyponatremia due to water

retention in association with sodium gain

F (e.g., from the nephrotic syndrome)

Hypotonic hyponatremia due to water retention in

association with sodium gain and potassium loss

G (e.g., from congestive heart failure treated with

diuretics)

Figure 1. Extracellular-Fluid and Intracellular-Fluid Compartments under Normal Conditions and during States of Hyponatremia.

Normally, the extracellular-fluid and intracellular-fluid compartments make up 40 percent and 60 percent of total body water, re-

spectively (Panel A). With the syndrome of inappropriate secretion of antidiuretic hormone, the volumes of extracellular fluid and

intracellular fluid expand (although a small element of sodium and potassium loss, not shown, occurs during inception of the syn-

drome) (Panel B). Water retention can lead to hypotonic hyponatremia without the anticipated hypo-osmolality in patients who have

accumulated ineffective osmoles, such as urea (Panel C). A shift of water from the intracellular-fluid compartment to the extracel-

lular-fluid compartment, driven by solutes confined in the extracellular fluid, results in hypertonic (translocational) hyponatremia

(Panel D). Sodium depletion (and secondary water retention) usually contracts the volume of extracellular fluid but expands the

intracellular-fluid compartment. At times, water retention can be sufficient to restore the volume of extracellular fluid to normal or

even above-normal levels (Panel E). Hypotonic hyponatremia in sodium-retentive states involves expansion of both compartments,

but predominantly the extracellular-fluid compartment (Panel F). Gain of sodium and loss of potassium in association with a defect

of water excretion, as they occur in congestive heart failure treated with diuretics, lead to expansion of the extracellular-fluid com-

partment but contraction of the intracellular-fluid compartment (Panel G). In each panel, open circles denote sodium, solid circles

potassium, large squares impermeable solutes other than sodium, and small squares permeable solutes; the broken line between

the two compartments represents the cell membrane, and the shading indicates the intravascular volume.

1582 May 2 5 , 2 0 0 0

· PR IMA RY CA R E

C H H .

T 1. AUSES OF YPOTONIC YPONATREMIA

ABLE

I C R W E

MPAIRED APACITY OF ENAL ATER XCRETION

Decreased volume of extracellular fluid Essentially normal volume of extracellular fluid

Renal sodium loss Thiazide diuretics*

Diuretic agents Hypothyroidism

Osmotic diuresis (glucose, urea, Adrenal insufficiency

mannitol) Syndrome of inappropriate secretion of antidiuretic

Adrenal insufficiency hormone

Salt-wasting nephropathy Cancer

Bicarbonaturia (renal tubular acido- Pulmonary tumors

sis, disequilibrium stage of Mediastinal tumors

vomiting) Extrathoracic tumors

Ketonuria Central nervous system disorders

Extrarenal sodium loss Acute psychosis

Diarrhea Mass lesions

Vomiting Inflammatory and demyelinating diseases

Blood loss Stroke

Excessive sweating (e.g., in mara- Hemorrhage

thon runners) Trauma

Fluid sequestration in “third space” Drugs

Bowel obstruction Desmopressin

Peritonitis Oxytocin

Pancreatitis Prostaglandin-synthesis inhibitors

Muscle trauma Nicotine

Burns Phenothiazines

Tricyclics

Increased volume of extracellular fluid Serotonin-reuptake inhibitors

Congestive heart failure Opiate derivatives

Cirrhosis Chlorpropamide

Nephrotic syndrome Clofibrate

Renal failure (acute or chronic) Carbamazepine

Pregnancy Cyclophosphamide

Vincristine

Pulmonary conditions

Infections

Acute respiratory failure

Positive-pressure ventilation

Miscellaneous

Postoperative state

Pain

Severe nausea

Infection with the human immunodeficiency virus

Decreased intake of solutes

Beer potomania

Tea-and-toast diet

E W I

XCESSIVE ATER NTAKE

Primary polydipsia†

Dilute infant formula

Sodium-free irrigant solutions (used in hysteroscopy, laparoscopy, or transurethral resection of the

prostate)‡

Accidental intake of large amounts of water (e.g., during swimming lessons)

Multiple tap-water enemas

*Sodium depletion, potassium depletion, stimulation of thirst, and impaired urinary dilution are

implicated.

†Often a mild reduction in the capacity for water excretion is also present.

‡Hyponatremia is not always hypotonic.

Hyperglycemia is the most common cause of trans- nal insufficiency, has the same effect. In both condi-

locational hyponatremia (Fig. 1D). An increase of tions, the resultant hypertonicity can be aggravated

100 mg per deciliter (5.6 mmol per liter) in the se- by osmotic diuresis; moderation of hyponatremia or

rum glucose concentration decreases serum sodium frank hypernatremia can develop, since the total of

by approximately 1.7 mmol per liter, with the end the sodium and potassium concentrations in the urine

result a rise in serum osmolality of approximately falls short of that in serum. 20

2.0 mOsm per kilogram of water. Retention of hy- Massive absorption of irrigant solutions that do not

1

pertonic mannitol, which occurs in patients with re- contain sodium (e.g., those used during transurethral

1583

Vol ume 342 Numb e r 21 ·

The New Eng land Jour nal of Medicine

in psychiatric patients, and transurethral prostatec-

prostatectomy) can cause severe and symptomatic hy- tomy.

ponatremia. Reflecting the composition of the irri- Gastrointestinal fluid loss, ingestion of

1,17,23-25

gant, the resultant hyponatremia can be either hypo- dilute formula, accidental ingestion of excessive wa-

tonic (with an irrigant containing 1.5 percent glycine ter, and receipt of multiple tap-water enemas are the

or 3.3 percent sorbitol) or isotonic (with an irrigant main causes of severe hyponatremia in infants and

containing 5 percent mannitol). Whether the symp- children.

17,26

toms derive from the presence of retained solutes, CLINICAL MANIFESTATIONS

the metabolic products of such solutes, hypotonici-

ty, or the low serum sodium concentration itself re- Just as in hypernatremia, the manifestations of hy-

mains unclear. potonic hyponatremia are largely related to dysfunc-

21,22

The most common causes of severe hyponatremia tion of the central nervous system, and they are more

in adults are therapy with thiazides, the postoperative conspicuous when the decrease in the serum sodium

state and other causes of the syndrome of inappro- concentration is large or rapid (i.e., occurring within a

priate secretion of antidiuretic hormone, polydipsia Headache, nausea, vomiting, mus-

period of hours). 27

Immediate effect

of hypotonic state Water gain

Normal brain (low osmolality)

(normal osmolality) Rapid

adaptation

Proper therapy

(slow correction of the

hypotonic state) Loss

of sodium,

Water potassium,

and chloride

(low osmolality)

Osmotic

demyelination Loss of organic

Improper osmolytes

therapy Slow

(low osmolality)

(rapid correction of adaptation

the hypotonic state)

Figure 2. Effects of Hyponatremia on the Brain and Adaptive Responses.

Within minutes after the development of hypotonicity, water gain causes swelling of the brain and a decrease in osmolality of the

brain. Partial restoration of brain volume occurs within a few hours as a result of cellular loss of electrolytes (rapid adaptation). The

normalization of brain volume is completed within several days through loss of organic osmolytes from brain cells (slow adapta-

tion). Low osmolality in the brain persists despite the normalization of brain volume. Proper correction of hypotonicity reestablishes

normal osmolality without risking damage to the brain. Overly aggressive correction of hyponatremia can lead to irreversible brain

damage.

1584 May 2 5 , 2 0 0 0

· PR IMA RY CA R E

triggers demyelination of pontine and extrapontine

cle cramps, lethargy, restlessness, disorientation, and neurons that can cause neurologic dysfunction, in-

depressed reflexes can be observed. Whereas most cluding quadriplegia, pseudobulbar palsy, seizures,

patients with a serum sodium concentration exceed- coma, and even death. Hepatic failure, potassium de-

ing 125 mmol per liter are asymptomatic, those with pletion, and malnutrition increase the risk of this com-

lower values may have symptoms, especially if the plication.

disorder has developed rapidly. Complications of se-

4 1,37

vere and rapidly evolving hyponatremia include sei- MANAGEMENT

zures, coma, permanent brain damage, respiratory

arrest, brain-stem herniation, and death. These com- The optimal treatment of hypotonic hyponatremia

plications often occur with excessive water retention requires balancing the risks of hypotonicity against

in patients who are essentially euvolemic (e.g., those those of therapy. The presence of symptoms and

28

recovering from surgery or those with primary poly- their severity largely determine the pace of correction.

dipsia); menstruating women appear to be at partic- Symptomatic Hypotonic Hyponatremia

ular risk. 23,28

Hypotonic hyponatremia causes entry of water into Patients who have symptomatic hyponatremia with

the brain, resulting in cerebral edema (Fig. 2). Be- concentrated urine (osmolality, »200 mOsm per kil-

cause the surrounding cranium limits expansion of ogram of water) and clinical euvolemia or hyper-

the brain, intracranial hypertension develops, with a volemia require infusion of hypertonic saline (Table

risk of brain injury. Fortunately, solutes leave brain 2). This treatment can provide rapid but controlled

tissues within hours, thereby inducing water loss and correction of hyponatremia. Hypertonic saline is usu-

This process of adap-

ameliorating brain swelling. ally combined with furosemide to limit treatment-

29,30

tation by the brain accounts for the relatively asymp- induced expansion of the extracellular-fluid volume.

tomatic nature of even severe hyponatremia if it de- Because furosemide-induced diuresis is equivalent to

velops slowly. Nevertheless, brain adaptation is also a one-half isotonic saline solution, it aids in the cor-

the source of the risk of osmotic demyelination. rection of hyponatremia, as do ongoing dermal and

31-33

Although rare, osmotic demyelination is serious and respiratory fluid losses; anticipation of these losses

can develop one to several days after aggressive treat- should temper the pace of infusion of hypertonic sa-

ment of hyponatremia by any method, including line. Obviously, electrolyte-free water intake must be

water restriction alone. Shrinkage of the brain withheld. In addition to hypertonic saline, hormone-

34-36 F U M H

T 2. ORMULAS FOR SE IN ANAGING YPONATREMIA

ABLE C I .

AND HARACTERISTICS OF NFUSATES

F * C U

ORMULA LINICAL SE

Estimate the effect of 1 liter of

infusate Na ¡serum Na

+ +

1. Change in serum Na =

+ any infusate on serum Na

+

total body water + 1

(infusate Na +infusate K )¡serum Na Estimate the effect of 1 liter of

+ + +

2. Change in serum Na =

+ any infusate containing Na

+

total body water + 1 and K on serum Na

+ +

E -F

XTRACELLULAR LUID

I I Na D

+

NFUSATE NFUSATE ISTRIBUTION

mmol per liter %

5% Sodium chloride in water 855 100†

3% Sodium chloride in water 513 100†

0.9% Sodium chloride in water 154 100

Ringer’s lactate solution 130 97

0.45% Sodium chloride in water 77 73

0.2% Sodium chloride in 5% dextrose in water 34 55

5% Dextrose in water 0 40

*The numerator in formula 1 is a simplification of the expression (infusate Na ¡serum Na )¬

+ +

The estimated total body water

1 liter, with the value yielded by the equation in millimoles per liter.

38

(in liters) is calculated as a fraction of body weight. The fraction is 0.6 in children; 0.6 and 0.5 in

nonelderly men and women, respectively; and 0.5 and 0.45 in elderly men and women, respectively.

39

Normally, extracellular and intracellular fluids account for 40 and 60 percent of total body water,

respectively.

39

†In addition to its complete distribution in the extracellular compartment, this infusate induces

osmotic removal of water from the intracellular compartment. 1585

Vol ume 342 Numb e r 21 ·