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When serum sodium is low (usually because total body Elderly people are more susceptible to sodium imbalances
water is high), antidiuretic hormone (ADH) is suppressed due to age-related decrease or decline in:1
and a dilute urine is excreted.1 In addition, the kidney ■ Total body water
produces renin, which stimulates aldosterone production, ■ Thirst mechanism
which decreases the excretion of sodium in the urine,
■ Maximal urinary concentrating ability
therefore increasing sodium levels in the body.
■ Ability to excrete water load
When serum sodium is high (usually because total body ■ Renal function
water is low), ADH is released, causing the kidneys to
conserve water and therefore a concentrated urine is
excreted.1 In addition, atrial natriuretic peptide (ANP) is Elderly people also commonly have multiple co-
secreted by the heart (in response to high blood pressure morbidities that can affect sodium levels and renal
caused by increased sodium levels) and promotes loss of function. In addition, use of medicines that affect
sodium by the kidney (by inhibiting renin and therefore electrolyte excretion or retention, e.g. diuretics, also
aldosterone secretion). commonly causes sodium imbalance.1
If no obvious cause for the hyponatraemia can be found, Other medicines associated with hyponatraemia
additional blood and urine tests may be useful. Discussion include: carbamazepine, tricyclic antidepressants,
with a renal physician is recommended. ACE inhibitors, angiotensin II receptor blockers (ARBs),
proton-pump inhibitors, sulphonylureas, dopamine
Normal results of lipids, glucose, protein and albumin can agonists, opiates, amiodarone, some chemotherapy
help exclude rare causes of low sodium levels, which can medicines, e.g. vincristine, vinblastine, and high dose
occur with marked hypertriglyceridaemia, hyperglycaemia cyclophosphamide.11
and hyperproteinaemia. A TSH may reveal hypothyroidism
which can also be a rare cause of hyponatraemia. Abnormal
LFTs may indicate cirrhosis.
Additional investigations
Additional investigations are indicated by the clinical
situation and may include: serum potassium, urea,
creatinine, calcium and glucose.3
Key concepts:
■ Serum potassium imbalance is more prevalent ■ The cause of the potassium imbalance is usually
in older people and people with co-morbidities, clinically apparent, e.g. vomiting and diarrhoea,
e.g. renal impairment, congestive heart failure secondary to medicines or renal impairment.
■ Both hypokalaemia and hyperkalaemia can ■ Further laboratory investigations may be
cause cardiac arrhythmias which may be life appropriate if the clinical assessment and
threatening patient history do not reveal the cause of the
■ Urgent referral to secondary care is potassium imbalance
recommended for patients with serum
potassium ≤ 2.5 mmol/L or ≥ 7 mmol/L, rapidly
The normal reference range for serum
decreasing or increasing levels, neuromuscular
potassium is 3.5 – 5.3 mmol/L
symptoms or ECG changes, or if the patient is
systemically unwell
Hypokalaemia alters the electrical activity of cardiac patients with serum potassium < 3.0 mmol/L.19 ECG
muscle cells increasing membrane excitability which changes characteristically seen in patients with
may cause bradycardia, tachycardia, fibrillation, hypokalaemia include: ST-segment depression,
premature beats or heart block. It is recommended T-wave flattening, prolonged QT interval, T-wave
that an electrocardiograph (ECG) be performed in inversion and the presence of U waves (Figure 1).18
T
P
Q
S
Assess clinical status Consider if the patient has hypokalaemia due to: 16, 21
Assess for signs and symptoms. If cardiac or significant
CNS symptoms are present, urgent transfer to hospital is Increased urinary excretion, e.g. with medicines such
indicated. as diuretics or corticosteroids, diabetic ketoacidosis,
Cushing’s syndrome or disease, hyperaldosteronism.
In moderate hypokalaemia (2.5 – 3.0 mmol/L), the need for
referral will depend upon individual patient circumstances. Increased losses from other sites, e.g. primarily from the
A suggested approach is to check for the presence of gastrointestinal tract (vomiting, diarrhoea or intestinal
symptoms, consider an ECG and arrange a repeat blood fistula discharge) and also from the skin with excessive
test (same day/next day).19 sweating.
Assess if there is any acute illness, e.g. acute renal disease, Increased movement of potassium into the intracellular
gastroenteritis, diabetic ketoacidosis. fluid, e.g. alkalosis, burns or other trauma, medicines, e.g.
high dose insulin.
Consider known conditions that may have caused the
hypokalaemia, e.g. acute or chronic renal failure, Cushing’s Decreased intake of potassium, reduced dietary intake of
syndrome. potassium is a rare cause of hypokalaemia, but may be an
important factor in patients taking diuretics, e.g. an elderly
Assess the medication history patient on a “tea and toast” diet, or in a person aiming to
Look for medicines usually implicated in hypokalaemia, achieve rapid weight loss on a diet of low calorie liquid
e.g. diuretics, corticosteroids (see below). protein drinks.
Insulin – high dose insulin (e.g. for the treatment of Excessive use of laxatives – promotes increased
non-ketotic hyperglycaemia) increases intracellular gastrointestinal loss of potassium
potassium and therefore decreases serum potassium
A medicine that is implicated in causing hypokalaemia
Atypical antipsychotics such as risperidone, can be stopped if appropriate, and the potassium
quetapine potentiate an increase in intracellular rechecked again in one to two weeks. If the medicine
potassium has been stopped but the potassium level remains
low, look for another underlying cause.
Severe hyperkalaemia is defined as a serum Check for previously high serum potassium measurements
potassium level ≥ 7.0 mmol/L or ≥ 5.4 mmol/L or repeat the test if time permits. A rapid increase in
with any ECG changes or symptoms potassium warrants referral to secondary care even if
the actual degree of hyperkalaemia is only moderate.
Conditions that are associated with a rapid rise in
A raised serum potassium level is most commonly caused potassium (e.g. acute renal failure, rhabdomyolysis) and
as an adverse effect of a medicine or secondary to a hypoxia of any cause are more strongly associated with the
disease process. Hyperkalaemia is most commonly seen development of cardiac conduction disturbances. Patients
in hospitalised patients,24 therefore it is less likely that with potassium levels rising over six to 12 hours by > 0.5
patients will present with hyperkalaemia in primary care. mmol/L are considered high risk.26
The cause will often be multifactorial, however, most Transcellular shift (intracellular to extracellular
cases of hyperkalaemia are associated with medicines compartment)
that inhibit the renin-angiotensin system or interfere with ■ Acidosis (including diabetic ketoacidosis)
renal function, especially in the setting of pre-existing ■ Medicines (digoxin poisoning, suxamethonium,
renal impairment. beta-blockade)
An ECG is recommended for patients with serum with potassium levels > 6.8 mmol/L had changes
potassium levels > 6.0 mmol/L. ECG changes are not consistent with hyperkalaemia.27
usually seen below this level in hyperkalaemia.19
ECG changes that can be seen with hyperkalaemia
ECG changes are not always seen, even if include: progressive abnormalities including peaked
hyperkalaemia is severe. One study showed that T waves, flattening or absence of P waves, widening
only 46% of patients with potassium levels > 6.0 of QRS complexes and sine waves (which can indicate
mmol/L had ECG changes, and only 55% of patients that arrest is imminent) (Figure 2).
T
P
Q
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5. Goh KP. Management of hyponatremia. Am Fam Physician 21. Rose B. Causes of hypokalemia. UpToDate 2010. Available
2004;69(10):2387-94. from: www.uptodate.com (Accessed Sep, 2011).
6. Jacob S, Spinler S. Hyponatraemia associated with 22. Clausen T. Hormonal and pharmacological modification
selective serotonin-reuptake inhibitors in older adults. Ann of plasma potassium homeostasis. Fund Clin Pharmacol
Pharmcother 2006;40(9):1618-22. 2010;24:595-605.
7. Clayton J, Rodgers S, Blakey J, et al. Thiazide diuretic 23. Rose B. Evaluation of the patient with hypokalemia.
prescription and electrolyte abnormalities in primary care. UpToDate 2010. Available from: www.uptodate.com
Br J Clin Pharmacol 2006;61(1):87-95. (Accessed Sep, 2011).
8. Chow K, Szeto C, Wong T, et al. (2003) Risk factors for 24. Nyirenda M, Tang J, Padfield P, Seckl J. Hyperkalaemia. BMJ
thiazide-induced hyponatraemia. QJM 2003;96(12), 911-7. 2009;339b4114.
9. Kirby D, Harrigan S, Ames D. Hyponatraemia in elderly 25. Lehnhardt A, Kemper MJ. Pathogenesis, diagnosis
psychiatric patients treated with selective serotonin and management of hyperkalemia. Pediatr Nephrol
reuptake inhibitors and venlafaxine: a retrospective 2011;26:377-84.
controlled study in an inpatient unit. Int J Geriatr Psychiatry
2002;17:231-7. 26. Guidelines and Audit Implementation Network (GAIN).
Guidelines for the treatment of hyperkalaemia in adults.
10. Meulendijks D, Mannesse C, Jansen P, et al. Antipsychotic- Ireland: 2008. Available from: www.gain-ni.org (Accessed
induced hyponatraemia: a systematic review of the Sep, 2011).
published evidence. Drug Saf 2010;33(2):101-14.
27. Acker C, Johnson JP, Palevsky P, Greenberg A. Hyperkalemia
11. Clinical Knowledge Summaries. Hyponatraemia. Available in hospitalized patients: causes, adequacy of treatment,
from: www.cks.nhs.uk/hyponatraemia (Accessed Sep, 2011). and results of an attempt to improve physician compliance
with published therapy guidelines. Arch Intern Med
12. Adrogue H, Madias N. Hypernatraemia. N Engl J Med
1998;158:917-24.
2000;342(20):1493-9.
28. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF.
13. Liamis G, Milionis H, Elisaf M. A review of drug-induced
Aldosterone antagonists for preventing the progression
hypernatraemia. NDT Plus 2009;2:339-46.
of chronic kidney disease. Cochrane Database Syst Rev
14. Kyle C (Ed). A handbook for the interpretation of laboratory 2009;(3):CD007004.
tests (4th edition). Diagnostic Medlab; Wellington, 2008.
29. Perazella M, Tray K. Selective cyclooxygenase-2 inhibitors: a
15. Mount D. Chapter 45. Fluid and electrolyte disturbances. pattern of nephrotoxicity similar to traditional nonsteroidal
In: Fauci A, Braunwald E, Kasper D, et al, Eds. Harrison’s anti-inflammatory drugs. Am J Med 2001;111:64-7.
This quiz feedback provides an opportunity to revisit Best Tests, July 2011 which focused on; making sense of serum
protein bands and routine laboratory testing during pregnancy. All general practitioners who responded to this quiz will
receive personalised online feedback and CME points.
1. Which of the following are alternative names for 2. Which of the following are appropriate
a monoclonal gammopathy? indications for requesting protein
electrophoresis?
Your peers Preferred
Your peers Preferred
M-band 88% Unexplained bone pain or
fracture
99%
Paraprotein 94%
Plasma cell dysmorphia 8%
Lytic bone lesions 98%
Bence-Jones proteinuria 6%
Recurrent infections 93%
Incidental finding of increased
serum total protein
96%
Comment:
The majority of respondents correctly identified the Comment:
alternative terms used to describe a monoclonal All four features are among the many indications for
gammopathy. ordering serum protein electrophoresis, which in turn can
detect a monoclonal gammopathy.
In addition to the term monoclonal gammopathy the
following names are frequently used: Serum protein electrophoresis separates proteins into
■ Monoclonal protein albumin, alpha, beta and gamma globulins. An increase in
gamma globulin is referred to as a gammopathy, which can
■ Paraprotein
either be polyclonal (displayed as a broad, diffuse band) or
■ M-protein/band/spike monoclonal (displayed as a sharp, well-defined band).
A monoclonal gammopathy is caused by the There are many reasons why serum protein electrophoresis
overproduction of a population of plasma cells, which in may be requested. Clinical findings which would indicate
turn produces a single immunoglobulin – known as the testing include; suspected multiple myeloma, unexplained
plasma cell dyscrasias. bone pain and recurrent infections. Laboratory findings
that would prompt testing include; an incidental finding
The presence of monoclonal urine light chains, often of increased serum total protein or unexplained anaemia,
referred to as Bence-Jones proteinuria, is found nearly hypercalcaemia or renal impairment. Radiological findings
exclusively in patients with lymphoproliferative processes such as lytic lesions in the bone can also indicate the need
such as multiple myeloma. for serum protein electrophoresis.