Malattie del rene e delle vie urinarie - Hyponatriemia

P R IMA R Y CA R E

Review Article

tention in the extracellular space of large volumes of

Primary Care isotonic fluids that do not contain sodium (e.g., man-

nitol) generates iso-osmolar and isotonic hypona-

tremia but no transcellular shifts of water. Pseudo-

H hyponatremia is a spurious form of iso-osmolar and

YPONATREMIA isotonic hyponatremia identified when severe hyper-

triglyceridemia or paraproteinemia increases sub-

H J. A , M.D.,

ORACIO DROGUÉ stantially the solid phase of plasma and the sodium

N E. M , M.D.

AND ICOLAOS ADIAS concentration is measured by means of flame pho-

The increasing availability of direct meas-

tometry.

1,2

urement of serum sodium with the ion-specific elec-

H YPONATREMIA is defined as a decrease in trode has all but eliminated this laboratory artifact.

5

the serum sodium concentration to a level A common clinical problem, hyponatremia fre-

below 136 mmol per liter. Whereas hyper- quently develops in hospitalized patients. Although

6

natremia always denotes hypertonicity, hyponatremia morbidity varies widely in severity, serious compli-

can be associated with low, normal, or high tonici- cations can arise from the disorder itself as well as

Effective osmolality or tonicity refers to the

ty.

1,2 from errors in management. In this article, we focus

contribution to osmolality of solutes, such as sodi- on the treatment of hyponatremia, emphasizing a

um and glucose, that cannot move freely across cell quantitative approach to its correction.

membranes, thereby inducing transcellular shifts in CAUSES

Dilutional hyponatremia, by far the most com-

water.

3

mon form of the disorder, is caused by water reten- Hypotonic (dilutional) hyponatremia represents an

tion. If water intake exceeds the capacity of the kid- excess of water in relation to existing sodium stores,

neys to excrete water, dilution of body solutes results, which can be decreased, essentially normal, or in-

causing hypo-osmolality and hypotonicity (Fig. 1B, creased (Fig. 1). Retention of water most commonly

1E, 1F, and 1G). Hypotonicity, in turn, can lead to reflects the presence of conditions that impair renal

cerebral edema, a potentially life-threatening com- ; in a minority of cases, it is

excretion of water

1,7,8

Hypotonic hyponatremia can be associat-

plication.

4 caused by excessive water intake, with a normal or

ed, however, with normal or even high serum osmo- nearly normal excretory capacity (Table 1).

7

lality if sufficient amounts of solutes that can permeate Conditions of impaired renal excretion of water

cell membranes (e.g., urea and ethanol) have been are categorized according to the characteristics of

retained (Fig. 1C). Importantly, patients who have the extracellular-fluid volume, as determined by clin-

hypotonic hyponatremia but normal or high serum With the exception of re-

ical assessment (Table 1).

9

osmolality are as subject to the risks of hypotonicity nal failure, these conditions are characterized by

as are patients with hypo-osmolar hyponatremia. high plasma concentrations of arginine vasopressin

The nonhypotonic hyponatremias are hypertonic Depletion

despite the presence of hypotonicity.

10,11

(or translocational) hyponatremia, isotonic hypona- of potassium accompanies many of these disorders

Translocational

tremia, and pseudohyponatremia.

1,2 and contributes to hyponatremia, since the sodium

hyponatremia results from a shift of water from cells concentration is determined by the ratio of the

to the extracellular fluid that is driven by solutes “exchangeable” (i.e., osmotically active) portions of

confined in the extracellular compartment (as occurs the body’s sodium and potassium content to total

with hyperglycemia or retention of hypertonic man- Patients with hyponatre-

body water (Fig. 1G).

12-14

nitol); serum osmolality is increased, as is tonicity, mia induced by thiazides can present with variable

the latter causing dehydration of cells (Fig. 1D). Re- hypovolemia or apparent euvolemia, depending on

the magnitude of the sodium loss and water reten-

tion.

1,15-17

Excessive water intake can cause hyponatremia by

From the Department of Medicine, Baylor College of Medicine and overwhelming normal water excretory capacity (e.g.,

Methodist Hospital, and the Renal Section, Department of Veterans Affairs

Medical Center, Houston (H.J.A.); and the Department of Medicine, Tufts primary polydipsia) (Table 1). Frequently, however,

University School of Medicine, and the Division of Nephrology and Tup- psychiatric patients with excessive water intake have

per Research Institute, New England Medical Center, Boston (N.E.M.). plasma arginine vasopressin concentrations that are

Address reprint requests to Dr. Madias at the Division of Nephrology, New

England Medical Center, Box 172, 750 Washington St., Boston, MA not fully suppressed and urine that is not maximally

02111, or at nmadias@infonet.tufts.edu. dilute, thus contributing to water retention.

18,19

©2000, Massachusetts Medical Society. 1581

Vol ume 342 Numb e r 21 ·

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 ·

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in psychiatric patients, and transurethral prostatec-

prostatectomy) can cause severe and