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Fluid, electrolyte and acid–base balance


The realisation that the enzyme systems and metabolic processes responsible for the maintenance of cellular function are dependent on an environment with stable electrolyte and hydrogen ion concentrations led Claude Bernard to describe the milieu interieur more than 100 years ago. Complex homeostatic mechanisms have evolved to maintain the constancy of this internal environment and thus prevent cellular dysfunction.

Physiology of electrolytes and water balance

Mammalian intracellular and extracellular fluids (plasma) comprise about 70% water , containing a large variety of ions (electrolytes) and organic molecules (predominantly formed from carbon and hydrogen).

Water (H 2 O), the biological solvent, is a polar molecule – that is, it carries a non-uniform distribution of charge because of the greater positivity of the oxygen nucleus. This means as a solvent it only dissolves other polar molecules such as ions.

An ion is any charged molecule or atom. These may be small monoatomic structures such as sodium and potassium or much larger organic molecules such as proteins. The term electrolyte refers to any substance that produces an electrically conducting solution when dissolved in a polar solvent such as water. They can be divided into cations (+ve) and anions (–ve). pH is a determinant of the ionised state of some molecules (see later). Electrolytes have very diverse biological roles and in particular are a major source of osmotic pressure within body fluids.

Organic molecules are generally non-polar and therefore do not dissolve in water – that is, they are hydrophobic but lipophilic. These properties play an important biological role within the cell membrane and the subsequent control of movement of substances in and out of cells.

The concentration and distribution of these substances is fundamental to the maintenance of normal cellular function; systems to regulate water and sodium balance are particularly vital. The homeostasis of this environment occurs through both passive (non-energy consuming) and active transport processes.

Basic definitions

Osmosis refers to the movement of solvent molecules across a membrane into a region in which there is a higher concentration of solute. This movement may be prevented by applying a pressure to the more concentrated solution – the effective osmotic pressure. This is a colligative property: The magnitude of effective osmotic pressure exerted by a solution depends on the number rather than the type of particles present.

The amounts of osmotically active particles present in solution are expressed in osmoles. One osmole of a substance is equal to its molecular weight in grams (1 mol) divided by the number of freely moving particles which each molecule liberates in solution. Thus 180 g of glucose in 1 L of water represents a solution with a molar concentration of 1 mol L −1 and an osmolarity of 1 mOsm L −1 . Sodium chloride ionises in solution, and each ion represents an osmotically active particle. Assuming complete dissociation into Na + and Cl − , 58.5 g of NaCl dissolved in 1 L of water has a molar concentration of 1 mol L −1 and an osmolarity of 2 osm L −1 . In body fluids, solute concentrations are much lower (mmol L −1 ) and dissociation is incomplete. Consequently a solution of NaCl containing 1 mmol L −1 contributes slightly less than 2 mOsm L −1 .

The term osmolality refers to the number of osmoles per unit of total weight of solvent, whereas osmolarity refers to the number of osmoles per litre of solvent. Osmolality (unlike osmolarity), is not affected by the volume of various solutes in solution. Confusion regarding the apparently interchangeable use of the terms osmolarity (measured in osm L −1 ) and osmolality (measured in osm kg −1 ) is caused by their numerical equivalence in body fluids; plasma osmolarity is 280–310 mOsm L −1 and plasma osmolality is also 280–310 mOsm kg −1 . This equivalence is explained by the almost negligible solute volume contained in biological fluids and the fact that most osmotically active particles are dissolved in water, which has a density of 1 (i.e. osm L −1 = osm kg −1 ). As the number of osmoles in plasma is estimated by measurement of the magnitude of freezing point depression, the more accurate term in clinical practice is osmolality.

Cations (principally Na + ) and anions (Cl − and ) are the major osmotically active particles in plasma. Glucose and urea make a smaller contribution. Plasma osmolality (P OSM ) may be estimated from the formula:


P OSM = 2 [ Na + ] ( mmol L − 1 ) + blood glucose ( mmol L − 1 ) + blood urea ( mmol L − 1 ) = 290 mOsm kg − 1

Osmolality is a chemical term and may be confused with the physiological term tonicity. Tonicity is used to describe the effective osmotic pressure of a solution relative to that of plasma; that is, it is the osmotic pressure gradient between two solutions. The critical difference between osmolality and tonicity is that all solutes contribute to osmolality, but only solutes that do not cross the cell membrane contribute to tonicity. Thus tonicity expresses the osmolal activity of solutes restricted to the extracellular compartment – that is, those which exert an osmotic force affecting the distribution of water between intracellular fluid (ICF) and extracellular fluid (ECF). As urea diffuses freely across cell membranes, it does not alter the distribution of water between these two body fluid compartments and does not contribute to tonicity. Other solutes that contribute to plasma osmolality but not tonicity include ethanol and methanol, both of which distribute rapidly throughout the total body water. In contrast, mannitol and sorbitol are restricted to the ECF and contribute to both osmolality and tonicity. The tonicity of plasma may be estimated from the formula:


plasma tonicity = 2 [ Na + ] ( mmol L − 1 ) + blood glucose ( mmol L − 1 ) = 285 mOsm kg − 1

Compartmental distribution of total body water

The volume of total body water (TBW) may be measured using radioactive dilution techniques involving either deuterium or tritium, both of which cross all membranes freely and equilibrate rapidly with hydrogen atoms in body water. Such measurements show that approximately 60% of lean body mass (LBM) is water in the average 70-kg male adult. As fat contains little water, females have proportionately less TBW (55%) relative to LBM. Total body water decreases with age, decreasing to 45%–50% in later life.

The distribution of TBW between the main body compartments is illustrated in Fig. 12.1 . One third of TBW is contained in the extracellular fluid volume (ECFV) and two thirds in the intracellular fluid volume (ICFV). The ECFV is subdivided further into the interstitial and intravascular compartments. In addition to the absolute volumes of each compartment, Fig. 12.1 shows the relative size of each compartment compared with body weight.

Fig. 12.1, Distribution of total body water in a 70-kg male and related to body weight (BW).

Solute composition of body fluid compartments

Extracellular fluid

The capillary endothelium behaves as a freely permeable membrane to water, cations, anions and many soluble substances such as glucose and urea (but not protein). As a result the solute compositions of interstitial fluid and plasma are similar. Each contains sodium as the principal cation and chloride as the principal anion. Protein behaves as a non-diffusible anion and is present in a higher concentration in plasma. The concentration of Cl − is slightly higher in interstitial fluid to maintain electrical neutrality (Gibbs–Donnan equilibrium).

Intracellular fluid

Intracellular fluid differs from ECF in that the principal cation is potassium and the principal anion is phosphate. In addition, there is a high protein content. In contrast to the capillary endothelium, the cell membrane is selectively permeable to different ions and freely permeable to water. Thus equalisation of osmotic forces occurs continuously and is achieved by the movement of water across the cell membrane. The osmolalities of ICF and ECF at equilibrium must be equal. Water moves rapidly between ICF and ECF to eliminate any induced osmolal gradient. This principle is fundamental to an understanding of fluid and electrolyte physiology.

Fig. 12.2 shows the solute composition of the main body fluid compartments. Although the total concentration of intracellular ions exceeds that of extracellular ions, the numbers of osmotically active particles (and thus the osmolalities) are the same on each side of the cell membrane (290 mOsm kg −1 of solution).

Fig. 12.2, Principal solute composition of body fluid compartments. All concentrations are expressed in mmol L −1 .

Water homeostasis

Normal day-to-day fluctuations in TBW are small (<0.2%) because of a fine balance between input and output. Fig. 12.3 depicts daily water balance in a healthy 70-kg adult under normal conditions, in whom input and output balance. Normal total water requirement in a 70-kg adult is 2.5 L from all sources. The principal sources of water are ingested fluid, water content of food and metabolic water. Intravenously administered fluid in the hospitalised patient may be a key source. Fluid losses are classified as insensible or sensible . Insensible losses emanate from the skin and lungs; sensible losses occur mainly from the kidneys and GI tract. It is important to be aware of increased potential losses secondary to pathological processes such as pyrexia.

Fig. 12.3, Daily water balance. Input and output in millilitres. Note the contributions of water from metabolism and solid food to water intake. Losses from skin and lungs may vary widely (e.g. fever, hyperventilation). Urinary water excretion also varies under the influence of antidiuretic hormone (ADH), aldosterone and other hormones.

In health, two key interrelated processes govern water balance: osmoregulation and volume regulation . Osmoregulation (the control of plasma osmolality) is vital in maintaining cell volume and preventing the serious ramifications of alterations of this, such as cerebral oedema. Plasma osmolality is principally determined by sodium concentration, but it is actually water balance (in vs. out) that regulates this rather than alteration in sodium excretion/retention. Osmoreceptors (adapted neurons) situated within the supraoptic nuclei of the hypothalamus but outside the blood–brain barrier are sensitive to changes in plasma osmolality more or less than that of 290 mOsm L −1 . An increase of only 1% triggers the release of antidiuretic hormone (ADH), stimulating thirst and renal water retention. By comparison volume regulation is controlled by alterations in renal sodium excretion. This is mediated through numerous systems, including baroreceptors in the carotid sinuses, aortic arch, and cardiac atria and within the juxtaglomerular apparatus of the kidney (see Chapters 9 and 11 ). As the name suggests, baroreceptors do not detect volume, but rather they respond to changes in pressure via stretch. This brings about stimulation of the sympathetic nervous system and the renin–angiotensin–aldosterone system, causing alterations in release of ADH, renin, angiotensin and natriuretic peptides. This process is fundamental in the biological response to hypovolaemia.

Practical fluid balance

Calculation of the daily prescription of fluid is an arithmetic exercise to balance the input and output of water and electrolytes.

Table 12.1 shows the electrolyte contents of five solutions used commonly for intravenous therapy in the UK. These solutions are adequate for most clinical situations. Two self-evident but important generalisations may be made regarding solutions for intravenous infusion:

Table 12.1
Electrolyte contents of commonly used intravenous fluids
Solution Electrolyte content (mmol L −1 ) Osmolality (mOsm kg −1 )
Saline 0.9% (normal saline) Na + 154 Cl − 154 308
Saline 0.45% (half-normal saline) Na + 77 Cl − 77 154
Glucose 4%/saline 0.18% (glucose–saline) Na + 31 Cl − 31 284
Glucose 5% Nil 278
Compound sodium lactate (Hartmann's solution) Na +
K +
Ca 2+ 		131
5
4		 Cl −
(as lactate)		 112
29		 281

Rule 1

All infused Na + remains in the ECF; Na + cannot gain access to the ICF because of the sodium pump. Thus if saline 0.9% is infused, all Na + remains in the ECF. As this is an isotonic solution, there is no change in ECF osmolality and therefore no water exchange occurs across the cell membrane. Thus saline 0.9% expands ECFV only. However, if saline 0.45% is given, ECF osmolality decreases; this causes a shift of water from ECF to ICF. If saline 1.8% is administered all Na + remains in the ECF, its osmolality increases and water moves from ICF to ECF to maintain osmotic equality.

Rule 2

Water without sodium expands the TBW. After infusion of a solution of glucose 5%, the glucose enters cells and is metabolised. The infused water enters both ICF and ECF in proportion to their initial volumes.

Table 12.2 illustrates the results of infusion of 1 litre of saline 0.9%, saline 0.45% or glucose 5% in a 70-kg adult.

Table 12.2
Compartmental expansion resulting from infusion of 1 litre of saline 0.9%, saline 0.45% or glucose 5%
Intravenous infusion of 1000 ml Change in volume (ml) Remarks
ECF ICF
Saline 0.9% +1000 0 Na + remains in ECF
Glucose 5% +333 +666 66% of TBW is ICF
Saline 0.45% +666 +333 33% of TBW is ECF
ECF, Extracellular fluid; ICF, intracellular fluid; TBW, total body water.

Intravenous fluids are widely and regularly prescribed and administered. In recent years there has been a growing realisation that poor fluid prescription can lead to harm. There is still much uncertainty as to optimal fluid types and regimens. In 2013 the National Institute for Health and Care Excellence (NICE) published guidelines to address this (Intravenous fluid therapy in adults in hospital; nice.org.uk/guidance/cg174 ). This introduced the concept of the 5 Rs:

  • Resuscitation: crystalloids preferred with sodium content between 130–154 mmol and i.v. boluses of 250–500 ml over 15 min

  • Replacement: consider ongoing fluid and electrolyte abnormalities and losses ( Fig. 12.4 )

    Fig. 12.4, Fluid and electrolyte losses in the adult surgical patient, absolute losses being dependent on measured volumes.

  • Routine maintenance: consider patient's normal maintenance needs ( Table 12.3 )

    Table 12.3
    Normal daily maintenance needs per kg ideal body weight
    Water 30–35 ml kg −1
    Sodium 1–2 mmol kg −1
    Potassium 1 mmol kg −1
    Chloride 1.5 mmol kg −1
    Phosphate 0.2–0.5 mmol kg −1
    Calcium 0.1–0.2 mmol kg −1
    Magnesium 0.1–0.2 mmol kg −1

  • Redistribution: depends on fluid given and ongoing pathological conditions (e.g. sepsis)

  • Reassessment: ABCDE (airway, breathing, circulation, disability, exposure), indicators of perfusion such as urine output, lactate.

This guidance emphasises the need to ‘assess the patient's likely fluid and electrolyte needs from their history, clinical examination, current medications, clinical monitoring and laboratory investigations’. Tables 12.3 and 12.4 and Fig. 12.4 summarise some of the key elements of practical fluid management.

Table 12.4
Practical fluid balance
Fluid composition of body compartments Typical blood volume
Infant 90 ml kg −1
Child 80 ml kg −1
Adult male 70 ml kg −1
Adult female 60 ml kg −1
Total water content (TWC)
60% male (55% female) of body weight (18–40 years)
55% male (46% female) of body weight (>60 years)
Volume of ECF 35% TWC
Volume of ICF 65% TWC
Intraoperative fluid requirements – adult
Initial volume 1.5 ml kg −1 h −1 for duration of preoperative starvation
+ (2) Maintenance 1.5 ml kg −1 h −1
+ (3) Operative insensible losses Guided by intraoperative monitoring (e.g. cardiac output); aim for neutral fluid balance.
+ (4) Blood loss Consider replacement with blood and appropriate clotting products when blood loss exceeds 20% of estimated blood volume or [Hb] <80 g L −1
ECF, Extracellular fluid; ICF, intracellular fluid; Hb, haemoglobin.

Dehydration

Dehydration with accompanying salt loss is a common disorder in the acutely ill surgical patient.

Assessment of dehydration

Assessment of dehydration is a clinical assessment based upon the following:

  • History. How long has the patient had abnormal loss of fluid? How much has occurred (e.g. volume and frequency of vomiting)?

  • Examination. Specific features are thirst, dryness of mucous membranes, loss of skin turgor, orthostatic hypotension or tachycardia, reduced jugular venous pressure (JVP) or central venous pressure (CVP) and decreased urine output. In the presence of normal renal function, dehydration is associated usually with a urine output of <0.5 ml kg −1 h −1 . The severity of dehydration may be described clinically as mild, moderate or severe, and each category is associated with the following water loss relative to body weight:

    • Mild: loss of 4% body weight (approximately 3 L in a 70-kg patient) – reduced skin turgor, sunken eyes, dry mucous membranes

    • Moderate: loss of 5%–8% body weight (approximately 4–6 L in a 70-kg patient) – oliguria, orthostatic hypotension and tachycardia in addition to the above

    • Severe: loss of 8%–10% body weight (approximately 7 L in a 70-kg patient) – profound oliguria and compromised cardiovascular function.

Laboratory assessment

The degree of haemoconcentration and increase in albumin concentration may be helpful if the patient was not previously anaemic. Increased blood urea concentration and urine osmolality (>650 mOsm kg −1 ) confirm the clinical diagnosis.

Perioperative fluid therapy, optimisation and enhanced recovery

The perioperative period is associated with significant alteration in fluid balance. It is practical to think in terms of preoperative dehydration secondary to nil by mouth status, which should be minimised where possible; intraoperative losses, whole blood loss in particular; and postoperative losses, often referred to as ‘third-space’ losses. Failure to maintain adequate fluid therapy during these periods results in reduced ECFV and circulating volume, reduced cardiac output and tissue oxygen delivery. This in turn is associated with increased perioperative morbidity and mortality. There is some evidence for the role of intraoperative fluid optimisation (or ‘goal-directed’ fluid therapy) during major surgical procedures. These approaches rely on manipulation of monitored physiological variables such as left ventricular stroke volume using appropriate monitors of cardiac output such as the oesophageal Doppler probe or pulse contour analysis (see Chapter 17 ) to optimise stroke volume and tissue perfusion. This has been associated with reduced duration of hospital stay and postoperative complications (see Chapter 30 ).

In slight contrast to the concept of fluid optimisation there is the concept of enhanced recovery after surgery (ERAS), particularly for major elective GI surgery (see also Chapter 30 ). The aims of ERAS protocols are to attenuate the surgical stress response and reduce end-organ dysfunction through an integrated pathway before, during and after surgery. Enhanced recovery after surgery relies upon the application of a series of evidence-based interventions. The perioperative fluid strategy aims to minimise preoperative dehydration (e.g. limiting bowel preparation before bowel surgery), optimise intraoperative fluid therapy with goal-directed techniques and reduce the need for postoperative i.v. fluids with early commencement of oral intake, thus allowing return of normal gut function and early mobilisation. Some evidence suggests reduced duration of hospital stay and healthcare costs.

Normally potassium is not administered in the first 24 h after surgery as endogenous release of potassium from tissue trauma and catabolism warrants restriction. The postoperative patient differs from the ‘normal’ patient in that the stress reaction modifies homeostatic mechanisms; stress-induced release of ADH, aldosterone and cortisol cause retention of Na + and water and increased renal K + excretion (see Chapter 13 ). However, restriction of fluid and sodium in the postoperative period must be balanced with increased losses by evaporation and ‘third-spacing’, on one hand, and the common tendency for excessive i.v. fluid administration on the other.

This syndrome of inappropriate ADH secretion (see later) may persist for several days in elderly patients, who are at risk of symptomatic hyponatraemia if given hypotonic fluids in the postoperative period. Elderly patients, those undergoing orthopaedic surgery or taking long-term thiazide diuretics are especially at risk if given 5% glucose postoperatively. Such patients may develop water intoxication and permanent brain damage as a result of relatively modest reductions in serum sodium concentration.

After major surgery, assessment of fluid and electrolyte requirements involves clinical assessment of the patient, accurate fluid balance, blood tests and sometimes urinary electrolytes. Measurement of cardiac output surrogates such as stroke volume variability may also be needed in critically ill patients. Fluid and electrolyte requirements in infants and small children differ from those in the adult (see Chapter 33 ).

Patients with renal failure require fluid replacement for abnormal losses, although the total volume of fluid infused should be reduced to a degree determined by the urine output.

Crystalloids or colloids

The debate over whether to administer a crystalloid solution (e.g. saline 0.9%, Hartmann's/Ringer's lactate) or a colloid solution (e.g. gelatines, starches, albumin) to patients has been ongoing for many years. However, few high-quality studies have demonstrated any advantage for the administration of colloids over crystalloids. Theoretical advantages of colloids include rapid and sustained plasma volume expansion for a given administered dose (ml kg −1 ) with a smaller concomitant expansion of the ECFV, thereby limiting tissue oedema. However, there are some associated adverse effects with some colloids such as platelet dysfunction, acute kidney injury (particularly in sepsis), allergy and cost. Consequently the use of synthetic colloids is decreasing, with crystalloids recommended as first-line by most authorities. Albumin may have a role in certain circumstances.

Sodium, potassium, chloride, phosphate and magnesium

Sodium balance

Daily ingestion amounts to 50–300 mmol. Losses in sweat and faeces are minimal (approximately 10 mmol day −1 ), and the kidney makes final adjustments. Urine sodium excretion may be as little as 2 mmol day −1 during salt restriction or may exceed 700 mmol day −1 after salt loading. Sodium balance is related intimately to ECFV and water balance.

Disorders of sodium and water balance

Hypernatraemia

Hypernatraemia is defined as a plasma sodium concentration of >150 mmol L −1 and may result from pure water loss, hypotonic fluid loss or salt gain. In the first two conditions, ECFV is reduced, whereas salt gain is associated with an expanded ECFV. For this reason the clinical assessment of volaemic status is important in the diagnosis and management of hypernatraemic states. The common causes of hypernatraemia are summarised in Table 12.5 . The abnormality common to all hypernatraemic states is intracellular dehydration secondary to ECF hyperosmolality. Primary water loss resulting in hypernatraemia may occur during prolonged fever, hyperventilation or severe exercise in hot, dry climates. However, a more common cause is the renal water loss that occurs when there is a defect in either the production or release of ADH (cranial diabetes insipidus) or an abnormality in response to ADH (nephrogenic diabetes insipidus).

Table 12.5
Causes of hypernatraemia
Pure water depletion
Extrarenal loss Failure of water intake (coma, elderly, postoperative)
Mucocutaneous loss
Fever, hyperventilation, thyrotoxicosis
Renal loss Diabetes insipidus (cranial, nephrogenic)
Chronic renal failure
Hypotonic fluid loss
Extrarenal loss Gastrointestinal (vomiting, diarrhoea)
Skin (excessive sweating)
Renal loss Osmotic diuresis (glucose, urea, mannitol)
Salt gain
Iatrogenic (NaHCO 3 , hypertonic saline)
Salt ingestion
Steroid excess

The administration of osmotic diuretics results temporarily in plasma hyperosmolality. An osmotic diuresis may occur also in hyperglycaemia. During an osmotic diuresis, the solute causing the diuresis (e.g. glucose, mannitol) constitutes a significant fraction of urine solute, and the sodium content of the urine becomes hypotonic relative to plasma sodium. Thus osmotic diuretics cause hypotonic urine losses, which may result in hypernatraemic dehydration.

Hypertonic dehydration may occur also in paediatric patients. Diarrhoea, vomiting and anorexia lead to loss of water in excess of solute (hypotonic loss). Concomitant fever, hyperventilation and the use of high-solute feeds may combine to exaggerate the problem. Extracellular fluid volume is maintained by movement of water from ICF to ECF to equalise osmolality, and clinical evidence of dehydration may not be apparent until 10%–15% of body weight has been lost. Rehydration must be undertaken gradually to prevent the development of cerebral oedema.

Measurement of urine and plasma osmolalities and assessment of urine output help in the diagnosis of hypernatraemic, volume-depleted states. If urine output is low and urine osmolality exceeds 800 mOsm kg −1 , then both ADH secretion and the renal response to ADH are present. The most likely causes are extrarenal water loss (e.g. diarrhoea, vomiting or evaporation) or insufficient intake. High urine output and high urine osmolality suggest an osmotic diuresis. If urine osmolality is less than plasma osmolality, reduced ADH secretion or impairment of the renal response to ADH should be suspected; in both cases, urine output is high.

Hypernatraemia caused by salt gain is usually iatrogenic in origin. It occurs when excessive amounts of hypertonic sodium bicarbonate are administered during resuscitation or when isotonic fluids are given to patients who have only insensible losses. Treatment comprises induction of a diuresis with a loop diuretic if renal function is normal; urine output is replaced in part with glucose 5%. Dialysis or haemofiltration may be necessary in patients with renal dysfunction.

Consequences of hypernatraemia

The major clinical manifestations of hypernatraemia involve the central nervous system. Severity depends on the rapidity with which hyperosmolality develops. Acute hypernatraemia is associated with a prompt osmotic shift of water from the intracellular compartment, causing a reduction in cell volume and water content of the brain. This results in increased permeability and even rupture of the capillaries in the brain and subarachnoid space. The patient may present with pyrexia (a manifestation of impaired thermoregulation), nausea, vomiting, convulsions, coma and virtually any type of focal neurological syndrome. The mortality and long-term morbidity of sustained hypernatraemia (Na + >160 mmol L −1 for over 48 h) is high irrespective of the underlying cause. In many cases the development of hypernatraemia can be anticipated and prevented (e.g. cranial diabetes insipidus associated with head injury), but in situations where preventative strategies have failed, treatment should be instituted without delay.

Treatment of hypernatraemia

The magnitude of the water deficit can be estimated from the measured plasma sodium concentration and calculated TBW:


water deficit = ( measured [ Na + ] / 140 × TBW ) − TBW

Thus in a 75-kg patient with a serum sodium of 170 mmol L −1 :


water deficit = ( 170 / 140 × 0.6 × 75 ) − ( 0.6 × 75 ) = 54.6 − 45 = 9.6 L

For hypernatraemic patients without volume depletion, 5% glucose is sufficient to correct the water deficit. However, the majority of hypernatraemic patients are frankly hypovolaemic, and intravenous fluids should be prescribed to repair both the sodium and the water deficits. Regardless of the severity of the condition, isotonic saline is the initial treatment of choice in the volume-depleted, hypernatraemic patient, as even this fluid is relatively hypotonic in patients with severe hypernatraemia. When volume depletion has been corrected, further repair of any water deficit may be accomplished with hypotonic fluids. Fluid therapy should be prescribed with the intention of correcting hypernatraemia over a period of 48–72 h to prevent the onset of cerebral oedema.

Hyponatraemia

Hyponatraemia is defined as a plasma sodium concentration <135 mmol L −1 . Hyponatraemia is a common finding in hospitalised patients. It may occur as a result of water retention, sodium loss or both; consequently it may be associated with an expanded, normal or contracted ECFV. As in hypernatraemia, the state of ECFV is important in determining the cause of the electrolyte imbalance.

As plasma osmolality decreases, an osmolality gradient is created across the cell membrane and results in movement of water into the ICF. The resulting expansion of brain cells is responsible for the symptoms of hyponatraemia, or water intoxication: nausea, vomiting, lethargy, weakness and obtundation. In severe cases (plasma Na + <115 mmol L −1 ), seizures and coma may result.

A scheme depicting the causes of hyponatraemia is shown in Fig. 12.5 . True hyponatraemia must be distinguished from pseudohyponatraemia. Sodium ions are present only in plasma water, which constitutes 93% of normal plasma. In the laboratory the concentration of sodium in plasma is measured in an aliquot of whole plasma, and the concentration is expressed in terms of plasma volume (mmol L −1 of whole plasma). If the percentage of water present in plasma is decreased, as in hyperlipidaemia or hyperproteinaemia, the amount of Na + in each aliquot of plasma is also decreased even if its concentration in plasma water is normal. A clue to this cause of hyponatraemia is the finding of a normal plasma osmolality. Pseudohyponatraemia is not encountered when plasma sodium concentration is measured by increasingly used ion-specific electrodes, because this method assesses directly the sodium concentration in the aqueous phase of plasma.

Fig. 12.5, Causes of hyponatraemia.

True hyponatraemic states may be classified conveniently into depletional and dilutional types. Depletional hyponatraemia occurs when a deficit in TBW is associated with an even greater deficit of total body sodium. Assessment of volaemic status reveals hypovolaemia. Losses may be renal or extrarenal. Excessive renal loss of sodium occurs in Addison's disease, diuretic administration, renal tubular acidosis and salt-losing nephropathies; usually urine sodium concentration exceeds 20 mmol L −1 . Extrarenal losses occur usually from the GI tract (e.g. diarrhoea, vomiting) or from sequestration into the ‘third-space’ (e.g. peritonitis, surgery). Normal kidneys respond by conserving sodium and water to produce a urine that is hyperosmolal and low in sodium. In both situations, treatment should be directed at expanding the ECFV with saline 0.9%.

Dilutional hyponatraemic states may be associated with hypervolaemia and oedema or with normovolaemia. Again, assessment of volaemic status is important. If oedema is present, there is an excess of total body sodium with a proportionately greater excess of TBW. This is seen in congestive heart failure, cirrhosis and the nephrotic syndrome and is caused by secondary hyperaldosteronism. Treatment comprises salt and water restriction and spironolactone.

In normovolaemic hyponatraemia there is a modest excess of TBW and a modest increase in ECFV associated with normal total body sodium. Pseudohyponatraemia is excluded by finding high protein or lipid concentrations and a normal plasma osmolality. True normovolaemic hyponatraemia is commonly iatrogenic in origin. The syndrome of inappropriate intravenous therapy (SIIVT) is caused usually by administration of intravenous fluids with a low sodium content to patients with isotonic losses.

A more chronic water overload may occur in patients with hypothyroidism and in conditions associated with an inappropriately elevated concentration of ADH. The syndrome of inappropriate ADH secretion (SIADH) is characterised by hyponatraemia, low plasma osmolality and an inappropriate antidiuresis – that is, a urine osmolality higher than anticipated for the degree of hyponatraemia. It occurs in the presence of malignant tumours (e.g. lung, prostate, pancreas), which produce ADH-like substances; in neurological disorders (e.g. head injury, tumours, infections); and in some severe pneumonias. A number of drugs are associated with increased ADH secretion or potentiate the effects of ADH ( Box 12.1 ). In patients with SIADH, the urine is concentrated in spite of hyponatraemia. Management comprises restriction of fluid intake to encourage a negative fluid balance. In severe or refractory cases, demeclocycline or lithium may result in improvement. Both drugs induce a state of functional diabetes insipidus and have been used effectively in SIADH if the primary disease cannot be treated.

Box 12.1
Drugs associated with antidiuresis and hyponatraemia

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