Disorders of Water Balance

Usman Younus

Steven Cheng

General Principles

Disorders of sodium (hypo- or hypernatremia) reflect abnormalities in water homeostasis.
Antidiuretic hormone (ADH) is the key regulator of renal free water excretion.
- ADH controls water permeability at the collecting duct of the nephron, allowing water to be conserved or excreted as needed.
- ADH is secreted in response to an increase in plasma osmolality, decreased effective circulatory volume, and other factors such as pain, nausea, and certain medications.
- Disruption in ADH release or signaling, along with alterations in water intake, all contribute to the development of hypo- or hypernatremia.
Both hypo- and hypernatremia are associated with increased morbidity and mortality.
Rapid correction of hypo- and hypernatremia can also contribute to adverse outcomes.

Hyponatremia

General Principles

Definition

Hyponatremia is defined as a serum or plasma sodium concentration <135 mmol/L.
Acute hyponatremia is defined as a fall in sodium over a period of <48 hours.

Classification

The causes of hyponatremia can be categorized based on plasma osmolality.
Hyponatremia with normal plasma osmolality is termed pseudohyponatremia (isotonic hyponatremia). This is most commonly attributable to a laboratory error caused by severe elevations of plasma lipids or proteins. A marked increase in plasma lipids or plasma proteins essentially “dilutes” the sodium concentration, as measured by flame photometry. Alternate methods, using ion-specific electrodes, specifically measure the concentration in the aqueous portion of plasma and are thus unaffected by lipid or protein aberrations.
Hypertonic hyponatremia occurs when the plasma osmolality is increased, drawing water from the intracellular to the extracellular space. The increase in the aqueous fraction of plasma thereby lowers the serum sodium concentration.
Hypotonic hyponatremia occurs when the plasma osmolality is decreased and is the most common form encountered in clinical practice. This is primarily due to increased water intake and/or impaired water excretion.

Epidemiology

Hyponatremia is the most common electrolyte abnormality among hospitalized patients.
The prevalence of hyponatremia is lower in the general ambulatory population but is still associated with poor outcomes.
Hyponatremia is an independent predictor of mortality, even at mildly reduced levels.

Etiology

Isotonic hyponatremia:
- As described previously, pseudohyponatremia is due to elevated lipids or proteins.
- The absorption of sodium-free isotonic surgical irrigants (glycine, sorbitol, mannitol) can also result in isotonic hyponatremia.
Hypertonic hyponatremia:
- Hypertonic hyponatremia results in a shift of water from intracellular to extracellular spaces, thus reducing the serum sodium concentration.
- Hypertonic hyponatremia is most commonly caused by hyperglycemia. Serum sodium levels decrease by ∼2.4 mmol/L for every 100 mg/dL increase in the plasma glucose.
- Other causes of hypertonic hyponatremia include mannitol and intravenous immunoglobulin (IVIG).
Hypotonic hyponatremia:
- Hypotonic hyponatremia can be further characterized by whether renal free water clearance is intact (excretion of dilute urine) or impaired (suboptimal urinary dilution). See Figure 3-1.
  
  FIGURE 3-1. Causes of Hyponatremia.
- An appropriately dilute urine has a low urine osmolality (<100 mOsm/L). This occurs when the intake of water simply exceeds the capacity for renal water excretion. Causes include primary polydipsia, severe malnutrition, and beer potomania.
- Impaired urinary dilution is reflected by a urine osmolality >100 mOsm/L. This finding suggests that ADH is present, due to either an appropriate physiologic stimulus (such as a reduction in circulating volume) or an inappropriate state of oversecretion
  (such as the syndrome of inappropriate antidiuretic hormone [SIADH]). Common causes of SIADH are listed in Table 3-1.

TABLE 3-1 COMMON CAUSES OF SIADH

CNS disorders	Hemorrhage, psychosis, infection, alcohol withdrawal
Malignancy (ectopic ADH)	Small-cell lung carcinoma (most commonly implicated), CNS disease, leukemia, Hodgkin disease, duodenal cancer, pancreatic cancer
Pulmonary	Infection, acute respiratory failure, mechanical ventilation
Miscellaneous	Pain, nausea (powerful stimulator of ADH), HIV (multifactorial), general postoperation state
Pharmacologic agents (either mimic or enhance ADH)	Cyclophosphamide, vincristine, vinblastine, NSAIDs, tricyclics and related agents, selective serotonin reuptake inhibitors, chlorpropamide, nicotine, bromocriptine, oxytocin, DDAVP
ADH, antidiuretic hormone; CNS, central nervous system; HIV, human immunodeficiency virus; NSAID, nonsteroidal anti-inflammatory drug.

Pathophysiology

As plasma sodium falls, cells in the brain readjust intracellular osmolality by lowering the osmotic content. If changes occur rapidly or in the face of severe hyponatremia, this adaptation fails, leading to cerebral edema, altered mental status, and seizures.
Hyponatremia can be fatal should brainstem herniation result.
Patients with underlying disorders such as cirrhosis or pre-existing neurologic disease may be at particular risk of severe complications in acute hyponatremia.
Central pontine myelinolysis (osmotic demyelination) is thought to be due to rapid correction of chronic hyponatremia. Alcoholic patients and those with severe malnutrition appear to be at increased risk of this potentially devastating condition. Cognitive, behavioral, and movement disorders due to the occurrence of osmotic demyelination may not be apparent for days after the correction of hyponatremia, and visible changes on magnetic resonance imaging scan may take weeks to appear.

Risk Factors