Water moves freely between compartments and the distribution is deter-mined by the osmotic equilibrium between them. The plasma osmolality can be calculated from the plasma concentrations of sodium, urea and glucose, as follows:
Calculated plasma osmolality (mmol) = (2 X plasma Na+) + [urea] + [glucose]
The factor of 2 applied to sodium concentration allows for associated anions (chloride and bicarbonate). The other extracellular solutes, e.g. calcium, potassium and magnesium, and their associated anions exist in very low concentrations and contribute so little to osmolality that they can be ignored when calculating the osmolality. The normal plasma osmolality is 285300 mosmol/kg.
The calculated osmolality is the same as the osmolality measured by the laboratory, unless there is an unmeasured, osmotically active substance present. For instance, plasma alcohol or ethylene glycol concentration (substances sometimes taken in cases of poisoning) can be estimated by subtracting the calculated from the measured osmolality.
Regulation of body water content
Body water is controlled mainly by changes in the plasma osmolality. An increased plasma osmolality, sensed by osmoreceptors in the hypothalamus, causes thirst and the release of antidiuretic hormone (ADH, vasopressin) from the posterior pituitary, which increases water reabsorption from the renal collecting ducts. In addition, non-osmotic stimuli may cause the release of ADH even if serum osmolality is normal or low. These include hypovolaemia (irrespective of plasma osmolality), stress (surgery and trauma) and nausea. In contrast, at a plasma osmolality of less than 275 mOsm/kg there is com-plete suppression of ADH secretion.
As discussed previously, sodium content is regulated by volume receptors, with water content adjusted to maintain a normal osmolality and a normal plasma sodium concentration. Disturbances of sodium concentration are usually caused by disturbances of water balance, rather than an increase or decrease in total body sodium.
Hyponatraemia reflects too much water in relation to sodium; affected patients may or may not have a concurrent abnormality in sodium balance.
Hyponatraemia (serum sodium <135 mmol/L) may be the result of the following:
■ Relative water excess (dilutional hyponatraemia)
■ Salt loss in excess of water, e.g. diarrhoea and renal diseases as described above.
■ Rarely, pseudohyponatraemia, in which hyperlipidaemia or hyperprotein-aemia results in a spuriously low measured sodium concentration. The sodium is confined to the aqueous phase but its concentration is expressed in terms of the total volume of plasma (i.e. water plus lipid). In this situation plasma osmolality is normal and therefore treatment of ‘hyponatraemia' is unnecessary.
■ True hyponatraemia must be differentiated from artefactual ‘hypo-natraemia' caused by taking blood from the drip arm into which a fluid of low sodium is being infused.
Once preliminary evaluation reveals that the hyponatraemia reflects hypo-osmolality (i.e. it is not pseudohyponatraemia or artefactual), assessment of the extracellular volume (pp. 329, 333) allows patients to be classified as hypovolaemic, euvolaemic or hypervolaemic (Fig. 8.2).
Hyponatraemia resulting from salt loss (hypovolaemic hyponatraemia)
These patients have a deficit of both total body sodium and water, with the sodium deficit exceeding the water deficit. As fluid is lost and the patient
Fig. 8.2 Diagnosis of hyponatraemia. Osmotic antidiuretic hormone (ADH) release refers to unmeasured osmotically active substances stimulating osmotic release of ADH. These include glucose, mannitol, chronic alcohol abuse and sick-cell syndrome (leakage of intracellular ions). SIADH, syndrome of inappropriate ADH secretion; ATN, acute tubular necrosis; BP, blood pressure.
becomes hypovolaemic there is stimulation of volume receptors leading to thirst and non-osmotic release of ADH. Measurement of urinary sodium helps differentiate between renal and extrarenal sources of fluid loss (Fig. 8.2). For example, vomiting and diarrhoea are associated with avid sodium retention as the kidney responds to volume contraction by conserving sodium chloride. Diuretics are the most common cause of hypovolaemic hyponatraemia with a high urinary sodium concentration ([Na+]).
These are usually a result of the hypovolaemia and extracellular volume depletion (p. 330). Symptoms directly related to the hyponatraemia are rare, as the loss of both sodium and water limits osmotic shifts in the brain.
Restoration of extracellular volume with crystalloids or colloids interrupts non-osmotic release of ADH and normalizes serum sodium. Oral rehydration solutions (p. 38) are appropriate treatments in diarrhoeal diseases, resulting in mild hypovolaemia.
Hyponatraemia resulting from water excess (dilutional hyponatraemia)
An excess of body water relative to sodium is differentiated from hyponat-raemia caused by sodium loss because there are none of the clinical features of extracellular volume depletion. This is the most common mechanism of hyponatraemia seen in hospitalized patients. The most common iatrogenic cause is overgenerous infusion of 5% glucose in post-operative patients; in this situation the hyponatraemia is exacerbated by an increased ADH secre-tion in response to stress.
Hyponatraemia is often seen in patients with severe cardiac failure, cirrhosis or the nephrotic syndrome, in which there is an inability of the kidney to excrete ‘free water’. This is compounded by the use of diuretics. There is evidence of volume overload and the patient is usually oedematous. Where there is no evidence of extracellular volume overload (i.e. euvolaemic patient), causes include the syndrome of inappropriate ADH secretion (SIADH) (p. 647), Addison’s disease and hypothyroidism.
Symptoms rarely occur until the serum sodium is less than 120 mmol/L and are more conspicuous when hyponatraemia has developed rapidly, i.e. over hours. The symptoms result from the movement of water into the brain cells (cerebral oedema) in response to the fall in extracellular osmolality, and include headache, confusion, convulsions and coma. If hyponatraemia has developed slowly the brain will have adapted by decreasing intracellular osmolality, and symptoms occur at a lower serum sodium concentration e.g. <110 mmol/L.
Hyponatraemia in association with cardiac failure, cirrhosis or nephrotic syndrome is usually clinically obvious and no further investigation is neces-sary. If there is no evidence of volume overload the most probable cause is SIADH or diuretic therapy. Serum magnesium and potassium must be checked, as low levels potentiate ADH release and cause diuretic-associated hyponatraemia.
|Emergency Box 8.1|
Management of hyponatraemia resulting from
The underlying cause must be corrected where possible. Most cases (those without severe symptoms) are simply managed by water restriction (to 1000 mL or even 500 mL/day) with a review of diuretic treatment. Management of SIADH is described on page 648. Patients with hyponatraemia developing acutely, in less than 48 hours (often a hospitalized patient on intravenous dextrose), are at the greatest risk of developing cerebral oedema and should be treated more urgently (see Emergency Box 8.1). Vasopressin V2 receptor antagonists, e.g. conivaptan and tolvaptan, which produce free water diuresis, are being evaluated in clinical trials for the treatment of hyponatraemia.
Central pontine myelinolysis
Over-rapid correction of the sodium concentration by whatever means must be avoided, as this can result in a severe, neurological syndrome due to local areas of demyelination, called central pontine myelinolysis or the osmotic demyelination syndrome. Features of this include quadriparesis, respiratory arrest, pseudobulbar palsy, mutism, and, rarely, fits. The distribution of the areas of demyelination include most often the pons, but also, in some cases, the basal ganglia, internal capsule, lateral geniculate body and even the cerebral cortex. Diagnosis is by characteristic appearances on brain MRI.
Hypernatraemia (serum sodium >145 mmol/L) is almost always the result of reduced water intake or water loss in excess of sodium. Less commonly, it is due to excessive administration of sodium e.g. as intravenous fluids (sodium bicarbonate or sodium chloride 0.9%) or administration of drugs with a high sodium content.
Insufficient fluid intake is most often found in elderly people, neonates or unconscious patients when access to water is denied or confusion or coma eliminates the normal response to thirst. The situation is exacerbated by increased losses of fluid, e.g. sweating, diarrhoea.
Water loss relative to sodium occurs in pituitary diabetes insipidus, neph-rogenic diabetes insipidus, osmotic diuresis and water loss from the lungs or skin. Usually in these situations serum sodium is maintained because an increase in plasma osmolality is a potent stimulus to thirst; serum sodium only increases if thirst sensation is abnormal or access to water is restricted.
Symptoms are non-specific and include nausea, vomiting, fever and confusion.
Simultaneous urine and plasma osmolality and sodium should be measured.
The passage of urine with an osmolality lower than that of plasma in this situation is clearly abnormal and indicates diabetes insipidus (p. 645). If urine osmolality is high, this suggests an osmotic diuresis or excessive extrarenal water loss (e.g. heat stroke).
Treatment is that of the underlying cause and replacement of water, either orally if possible or intravenously with 5% dextrose. The aim is to correct sodium concentration over 48 hours, as over-rapid correction may lead to cerebral oedema. In severe hypernatraemia (>170 mmol/L), sodium chloride
0.9% (154 mmol/L) should be used to avoid too rapid a drop in serum sodium. In addition, if there is clinical evidence of volume depletion, this implies that there is a sodium deficit as well as a water deficit, and intravenous sodium chloride 0.9% should be used.
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER DISEASE IN PREGNANCY
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS
5. Haematological disease
Assessment and treatment of suspected neutropenic sepsis
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
6. Malignant disease
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
8. Water, electrolytes and acid–base balance
WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
9. Renal disease
INVESTIGATION OF RENAL DISEASE
URINARY TRACT INFECTION
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
10. Cardiovascular disease
COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
ISCHAEMIC HEART DISEASE
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
ARTERIAL AND VENOUS DISEASE
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS
11. Respiratory disease
12. Intensive care medicine
13. Drug therapy, poisoning, and alcohol misuse
14. Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
15. Diabetes mellitus and other disorders of metabolism
16. The special senses
COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES