Water and Electrolyte Disturbances

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Chapter 32 Water and Electrolyte Disturbances

Disturbances in water and electrolytes are common in the intensive care unit (ICU). In the first section of this chapter the physiology of water balance, including the distribution of intravenous fluids and the effects of cardiopulmonary bypass (CPB), are briefly reviewed. In the second section, clinical abnormalities of water and electrolytes are discussed. Common terms are explained in Table 32-1. Relevant physiology discussed in Chapter 1 is referred to throughout.

Table 32-1 Definitions of Terms

Osmosis The movement of water caused by a concentration difference in the water on each side of a semipermeable membrane
Osmotic pressure The hydrostatic pressure that must be applied to stop osmosis
Osmole The number of molecules present in 1 g of a substance, multiplied by its molecular weight (of undissociated solute)
  Performing this calculation allows the concentration of a solute to be expressed in terms of the number of molecules. For example, if 60 g urea ([NH2]2CO, molecular weight = 60 g) is dissolved in 1 kg of water, the osmolality of the solution is 1 osmole per kg. For a substance that fully dissociates (e.g., NaCl), if the molecular weight (in grams) is dissolved in 1 kg of solute, the concentration is 2 osmoles per kg.
Osmolality The number of osmoles per kilogram of water
Osmolarity The number of osmoles per (total) liter of solution
  When solute is dissolved in solvent, the volume is greater than the volume of the solvent alone.
  In dilute solutions with small solute molecules, osmolarity is (approximately) equal to osmolality.
  In concentrated solutions of large solvent molecules, osmolality is greater than osmolarity.
Tonicity The “effective” osmolality
  Solutes that are distributed evenly across semipermeable membranes do not exert osmotic pressure.
  Solutes that are restricted in their movement across compartments are “effective osmoles,” and tonicity describes their concentration.


Body Water: Distribution, Constituents, and Movement

Depending on age and gender, between 45% and 60% of body weight is water. The percentage of water is higher in men and older people because they have a lower percentage of body fat than women and younger people. Body water is divided between intracellular (60%) and extracellular (40%) compartments. The extracellular compartment is composed of the interstitial, plasma, and transcellular (e.g., synovial fluid, cerebrospinal fluid, etc.) spaces, which constitute about 70%, 20%, and 10% of the extracellular fluid, respectively. Thus, a 70-kg male has about 10 liters of interstitial fluid, 3 liters of plasma, and 1 liter of transcellular fluid. The interstitium occupies the space between cells. It is a gel-like substance that contains extracellular fluid and two solid substances: collagen fibers, which provide tensile strength, and proteoglycan filaments, which trap water forming a “tissue gel.”

The intracellular and interstitial (extracellular) compartments are separated by cellular membranes. Water distributes freely between these two compartments according to the osmotic pressure difference across cellular membranes. At equilibrium, the number of osmotically active particles inside and outside cells is equal (about 285 mOsm/l). However, the constituents of the intracellular and extracellular fluids are quite different (Table 32-2). Some substances diffuse freely across cell membranes (e.g., oxygen, carbon dioxide, urea) and are therefore at the same concentration inside and outside cells. The movement of other substances (notably ions and glucose) across cell membranes is tightly controlled by selective permeability and active transport, which results in different concentrations inside and outside cells (see Table 32-2). The major cation in the extracellular fluid is sodium, and under normal circumstances it is the primary determinant of plasma osmolarity. The major anions in the extracellular fluid are chloride and bicarbonate. Because ions carry positive and negative charges, the active transport and selective permeability of ions allows variable charge separation to occur across the cell membrane, leading to the formation of resting and active membrane potentials (see Chapter 1).

Table 32-2 Composition of Intracellular and Extracellular Fluid

Electrolyte Intracellular Fluid (mmol/l) Extracellular Fluid* (mmol/l)
Sodium 10 140
Potassium 155 3.8
Chloride 3 108
Bicarbonate 10 26
Calcium (ionized) <0.01 1.2
Magnesium 10 0.8
Phosphate 105 1.0

* Because the plasma contains highly negatively charged protein molecules, minor differences exist between the electrolyte content of the interstitial fluid and the plasma.

The plasma and interstitial compartments are separated by the capillary endothelium. Spaces, known as gap junctions, exist between the endothelial cells that allow the free diffusion of all small particles between the interstitial and plasma spaces. Thus, the electrolyte, hydrogen ion, and glucose concentrations of the interstitium and plasma are identical. (However, the plasma concentration—but not the serum concentration—differs from the interstitial concentration because of the mass effect of the plasma proteins.) Under normal circumstances the capillary endothelium is impermeable to proteins larger than about 30 kiloDaltons (kD).

In addition to diffusion and osmosis, there is mass movement (filtration) of fluid between the capillary and the interstitium based on the balance of Starling forces across the capillary wall. The Starling forces are composed of the hydrostatic and the oncotic pressure gradients between the capillary lumen and the interstitial space (see Equation 1-12). The balance of the Starling forces varies among capillary beds, but overall there is a net loss of fluid from plasma to the interstitium. Filtered fluid is returned to the plasma through the lymphatic system.

Blood contains both extracellular and intracellular fluid. Approximately 35% to 45% of the blood water is intracellular, located almost exclusively within red blood cells. The circulating volume (cellular and extracellular fluid) in adults is about 70 ml/kg.

Intravenous Fluids

Intravenous fluids may be crystalloids (Table 32-3) or colloids. They are used mainly for treating hypovolemia (resuscitation fluid) and for replacement of obligatory daily losses (maintenance fluid). They are administered intravenously (i.e., into the plasma space) and, depending on their constituents and tonicity, the water is distributed to a variable extent throughout the extracellular and intracellular compartments.


Crystalloid solutions generally contain sodium (plus an anion) or glucose as their major osmotically active molecules, and they may be hypotonic (e.g., 0.45% sodium chloride), isotonic (e.g., 0.9% sodium chloride, 5% dextrose), or hypertonic in comparison to plasma. Because sodium is retained primarily within the extracellular fluid, the water in isotonic sodium solutions (e.g., 0.9% sodium chloride, Hartmann, Plasma-Lyte) is distributed to the extracellular compartment. Theoretically, assuming an extracellular volume of 14 liters and a plasma volume of 3 liters in a 70-kg patient, 1 liter of 0.9% sodium chloride increases the plasma volume (3/14 × 1) by about 200 ml. Isotonic, sodium-containing crystalloids are used to treat hypovolemia.

The anion in sodium-based crystalloids is predominantly chloride. Chloride is the only anion in 0.9% sodium chloride and Ringer solution and is therefore present in supraphysiologic concentrations. Large volumes of these solutions can cause a hyperchloremic metabolic acidosis (see Chapter 31). More physiologic concentrations of chloride are present in buffered, balanced electrolyte solutions such as Hartmann (lactated Ringer) and Plasma-Lyte. Because bicarbonate is not stable in solution for long periods, these solutions contain lactate (Hartmann) or acetate and gluconate (Plasma-Lyte) as the nonchloride anion.

Dextrose is rapidly taken up by cells and metabolized, so solutions in which dextrose is the osmotically active substance are equivalent to administering water (“free water”). Thus, the water in 5% dextrose is distributed evenly throughout the intracellular and extracellular spaces. Theoretically, assuming a total body water of 45 liters and a plasma volume of 3 liters in a 70-kg patient, 1 liter of 5% dextrose will increase plasma volume by (3/45), about 65 ml. Solutions that are entirely (i.e., 5% dextrose) or predominantly (0.18% sodium chloride + 4% dextrose) dextrose are used as maintenance fluids. Dextrose solutions should never be used to treat hypovolemia because not only do they result in minimal expansion of the plasma volume, they also can cause hyperglycemia, increased carbon dioxide production, and lactic acidosis (due to increased glycolysis).

Hypotonic sodium solutions reduce the tonicity of the extracellular fluid and therefore, by osmosis, some water will be distributed to the intracellular space. For instance, with 0.45% sodium chloride, which has an osmolarity of 150 mOsm/l, about half of the water will be distributed to the intracellular compartment. In contrast, hypertonic sodium solutions increase the tonicity of the extracellular fluid, and “drag” water from the intracellular compartment by osmosis. Thus, the extracellular compartment will expand by a volume greater than the volume administered. Hypotonic and hypertonic solutions are used in special circumstances. For instance, 0.45% sodium chloride is used to replace hypotonic renal losses during the polyuric phase of acute renal failure, whereas hypertonic sodium chloride is used to reduce intracranial pressure in patients with cerebral edema. Rapid administration of large volumes of hypotonic solutions (e.g., pure water) into a peripheral vein (where flow may be sluggish) may cause osmotically mediated swelling—and potential lysis—of red blood cells. Ideally these solutions should be administered slowly via a central line.


Colloid solutions contain large, oncotically active molecules in a base solution of either 0.9% sodium chloride or a buffered, balanced electrolyte solution. Colloid molecules are too big to traverse gap junctions, so more of the water in these solutions tends to be retained within the plasma space. Theoretically, assuming a plasma volume of 3 liters in a 70-kg patient, 1 liter of an isooncotic colloid solution increases plasma volume by 1 liter, which is 4 to 5 times the plasma volume expansion achieved by the same volume of an isotonic sodium-based crystalloid. However, with critical illness, the vascular endothelium “leaks,” allowing colloid molecules to pass into the interstitium, where they exert an osmotic pressure effect. This probably explains the observation that when resuscitating critically ill patients with 0.9% sodium chloride only 1.3 times the volume is required (not four times as predicted) compared with 4% albumin to achieve the same hemodynamic end points.1

Commonly used natural colloids include albumin and fresh-frozen plasma. Albumin is available as 4%, 5%, and 20% preparations. Both 4% and 5% solutions are approximately isooncotic with plasma; 20% albumin is hyperoncotic and therefore expands the plasma volume by about four times its volume. Commonly used artificial colloids include modified gelatins (e.g., Gelofusine) and hydroxyethyl starch compounds. Hydroxyethyl starch comprises a family of colloids that are categorized on the basis of their average size into high (>400 kD), medium (200 kD), and low (70 kD) molecular weight preparations.2 Two commonly used hydroxyethyl starches are hetastarch (average molecular weight 480 kD) and pentastarch (average molecular weight 200 kD). By comparison, Gelofusine has an average molecular weight of about 35 kD. Most artificial colloids are isooncotic or slightly hyperoncotic. The plasma half-time of artificial colloids varies among preparations but is typically on the order of 4 to 6 hours. Thus, the colloid effect has largely dissipated by 24 hours. Large volumes of hydroxyethyl starch can cause impaired hemostasis, mainly because of reduced effectiveness of the factor VIII/von Willebrand factor complex (i.e., acquired von Willebrand disease).2 High molecular weight compounds such as hetastarch appear to cause greater impairment of hemostasis than do medium-sized compounds such as pentastarch.3,4 Impaired hemostasis may also occur with gelatin-based colloids.5 To avoid hemostatic problems, the dosages of these artificial colloids should be kept below 20 ml/kg. All artificial colloids can cause allergic (including anaphylactic) reactions.

Crystalloids Versus Colloids for Fluid Resuscitation

There has been a great deal of debate over many decades on the pros and cons of crystalloids versus colloids for fluid resuscitation. Some ICUs use predominantly colloids, others predominantly crystalloids. Colloids are popular in Europe, whereas crystalloids are popular in North America. However, as long as fluids are administered to appropriate physiologic end points the choice between a colloid and a crystalloid is not important.1,6 In view of the additional cost and potential for adverse events with artificial colloids, a primarily crystalloid-based fluid regime seems preferable.

In 1998, a metaanalysis found an apparent excess mortality rate associated with the use of albumin in critically ill patients.7 This and a subsequent analysis by the same group8 created a storm of controversy and led to the publication of other metaanalyses that did not support the original finding.9,10 The issue of the safety of albumin was resolved in 2004 with the publication of a prospective, randomized trial involving nearly 7000 patients that found no difference in mortality rates between patients resuscitated with 4% albumin and those given 0.9% sodium chloride.1

Regulation of the Osmolarity and Volume of the Extracellular Compartment

The osmolarity (i.e., sodium concentration) and volume of the extracellular spaces are tightly controlled and intimately connected. Plasma osmolarity is regulated by controlling the intake and loss of water, whereas extracellular volume is regulated by controlling the excretion of sodium.