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Overview of Acid-Base and Electrolyte Disorders: The Right Clinical Information, Right Where It's Needed
Overview of Acid-Base and Electrolyte Disorders: The Right Clinical Information, Right Where It's Needed
Overview of Acid-Base and Electrolyte Disorders: The Right Clinical Information, Right Where It's Needed
Conditions 4
References 10
Disclaimer 13
Overview of acid-base and electrolyte disorders Introduction
Introduction
INTRODUCTION
Disorders of blood chemistry may be caused by dietary factors, underlying medical conditions, and medical
treatments. Resulting imbalances include acidosis (pH <7.35), alkalosis (pH >7.45), and high or low levels
of key electrolyte ions, including sodium, potassium, calcium, magnesium, chloride, hydrogen phosphate,
and hydrogen carbonate (bicarbonate). They may be acute or chronic, may occur with varying degrees of
severity, and may not be sufficiently counteracted by the body's regulatory/compensatory mechanisms.
Electrolyte balance is normally regulated by the hypothalamus, kidneys, and various hormones, including
antidiuretic hormone (ADH), aldosterone (a mineralocorticoid hormone), and parathyroid hormone (PTH).
Acid-base balance is linked to fluid and electrolyte balance, and is normally controlled and maintained by
immediate buffer systems via the kidneys and the pulmonary system.[1] Respiratory acidosis and alkalosis
are accompanied by compensatory renal bicarbonate retention and loss, respectively; metabolic acidosis
and alkalosis are accompanied by compensatory hyperventilation and hypoventilation, respectively. Mixed
metabolic disorders can occur (e.g., diabetic ketoacidosis complicated by vomiting), and evaluation depends
on clinical history and examination, assessment of anion gap, serum electrolytes, and arterial blood gases.
These disorders can be effectively evaluated by a stepwise pathophysiological approach.[1] [2]
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Overview of acid-base and electrolyte disorders Conditions
Conditions
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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Overview of acid-base and electrolyte disorders Conditions
◊ Assessment of hyponatraemia
» see our comprehensive coverage of Assessment of hyponatraemia
Defined as a serum sodium <135 mmol/L (<135 mEq/L); severe hyponatraemia is defined as a serum
sodium <120 mmol/L (<120 mEq/L). Hyponatraemia is a common electrolyte disorder and is estimated
to occur in 15% of all hospital inpatients.[8] [9] With few exceptions, when the serum sodium level is
CONDITIONS
low, plasma osmolality is also low (hypotonic hyponatraemia). While defined by the level of sodium,
hypotonic hyponatraemia is, in fact, a disorder of water balance. Hyponatraemia is often iatrogenic and
avoidable. Common causes are administration of hypotonic fluids to patients and use of thiazide diuretics
(more likely to affect older people).[10] Hyponatraemia may also be a clue to the presence of serious
underlying medical disorders. Patients who develop hyponatraemia as a result of head injury, intracranial
surgery, subarachnoid haemorrhage, stroke, or brain tumours may have cerebral salt-wasting syndrome or
syndrome of inappropriate antidiuretic hormone (SIADH).
◊ Assessment of hypernatraemia
» see our comprehensive coverage of Assessment of hypernatraemia
Hypernatraemia is defined as a plasma sodium concentration of >145 mmol/L (>145 mEq/L).
Hypernatraemia is a state of hyperosmolality, and is primarily a result of water deficit or sodium gain.
Normally, persistently high sodium levels trigger antidiuretic hormone (ADH) release, stimulating thirst
mechanisms so that hypernatraemia rarely develops. Hospitalised patients often have impaired thirst
mechanisms, restricted access to water, and an increased risk of water loss (e.g., due to vomiting or
fever). They are also at risk for iatrogenic inadequate fluid replacement. Endocrine abnormalities such as
diabetes insipidus and mineralocorticoid excess may also lead to hypernatraemia.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Overview of acid-base and electrolyte disorders Conditions
◊ Assessment of hypokalaemia
» see our comprehensive coverage of Assessment of hypokalaemia
Hypokalaemia is a serum potassium level <3.5 mmol/L (<3.5 mEq/L). Clinical manifestations are typically
seen only if the serum potassium level is <3.0 mmol/L (<3.0 mEq/L), and include muscle weakness,
ECG changes, cardiac arrhythmias, rhabdomyolysis, and renal abnormalities. Hypokalaemia may
result from decreased potassium intake, increased potassium entry into cells, increased potassium
excretion (e.g., from the gastrointestinal tract, via urine or sweat), dialysis, or plasmapheresis. Possible
causes include chronic alcoholism, anorexia nervosa, hypocaloric protein diets for rapid weight loss,[11]
metabolic or respiratory alkalosis or renal tubular acidosis, hypothermia, vomiting, severe diarrhoea,[12]
primary aldosteronism, salt-wasting nephropathies, exercising in a hot climate,[13] cystic fibrosis,[14]
hypomagnesaemia, polyuria, hypokalaemic periodic paralysis, and burns and other dermatological
conditions. Some medicines can cause hypokalaemia, including diuretics, insulin treatment for diabetic
ketoacidosis or nonketotic hyperglycaemia, beta-adrenergic agonists such as salbutamol or terbutaline,
theophylline, chloroquine, laxative abuse or bowel-cleansing agent use, and administration of vitamin B12
or folic acid in megaloblastic anaemia.[12]
◊ Assessment of hyperkalaemia
CONDITIONS
◊ Assessment of hypocalcaemia
» see our comprehensive coverage of Assessment of hypocalcaemia
Hypocalcaemia is a state of electrolyte imbalance in which the circulating serum calcium level is low.
Hypocalcaemia arises mainly from either insufficient entry of calcium into the circulation or an increased
loss of calcium from the circulation. Aetiologies include hypoparathyroidism, pseudohypoparathyroidism,
vitamin D deficiency, magnesium imbalance, hyperphosphataemia, hungry bone syndrome, acute
pancreatitis, extensive osteoblastic skeletal metastases, chelating agents (e.g., citrate, EDTA, lactate,
foscarnet), drug-induced, and use of gadolinium-based magnetic resonance imaging (MRI) contrast
agents. It is also seen in critically ill patients.
6 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Overview of acid-base and electrolyte disorders Conditions
◊ Assessment of hypercalcaemia
» see our comprehensive coverage of Assessment of hypercalcaemia
Symptoms from calcium elevation are typically not found unless the calcium is above 3 mmol/L (12 mg/
dL). Severe hypercalcaemia symptoms and coma are likely when calcium is >3.2 mmol/L (>13 mg/dL).
The most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy (e.g.,
multiple myeloma, leukaemia, lung cancer, and breast cancer). Chronic symptoms are more consistent
with hyperparathyroidism, whereas recent onset of symptoms suggests malignancy (the tumour is typically
very advanced). Signs and symptoms include renal stones (typical of hyperparathyroidism), lethargy, easy
fatigue, depression, irritability, constipation, gastrointestinal symptoms (e.g., nausea, vomiting, abdominal
pain, peptic ulcer disease, pancreatitis), polyuria, polydipsia, increased risk of cardiac arrest (shortened
QT interval), confusion, and coma. Hypercalcaemia may be asymptomatic.[16]
CONDITIONS
can be caused by decreased magnesium intake from the diet, decreased magnesium absorption, or
increased renal magnesium excretion (renal magnesium wasting). Symptoms are non-specific and include:
neuromuscular irritability similar to that produced by hypocalcaemia, manifesting with extensor plantar
reflexes, positive Trousseau's and Chvostek's signs, and, in severe cases, tetany; cardiovascular features
such as rapid heartbeats and an elevated blood pressure, tachycardia, and/or ventricular arrhythmias;
central nervous system symptoms of vertigo, ataxia, depression, and seizure activity.
◊ Primary hyperparathyroidism
» see our comprehensive coverage of Primary hyperparathyroidism
An endocrine disorder in which autonomous overproduction of parathyroid hormone (PTH) results
in calcium metabolism derangement. Single parathyroid adenomas are the most common aetiology
(approximately 80% of cases) and familial forms are also well defined.[17] Multiple adenomas and
hypertrophy of all 4 glands are less common. Diagnosis occurs through testing for a concurrent elevated
serum calcium level and an inappropriately elevated intact serum PTH level. Inherited forms, affecting
10% to 20% of patients,[18] lead to hyperfunctioning parathyroid glands. Importantly, <1% of cases
of hyperparathyroidism are caused by parathyroid carcinoma. Complications due to primary PTH are
uncommon and include osteoporosis and bone fracture due to leaching of calcium from bones, and renal
calculi due to elevated serum and urine calcium. In 2017, normocalcaemic primary hyperparathyroidism
was recognised as a variant of primary hyperparathyroidism and has yet to be thoroughly characterised.
◊ Diabetic ketoacidosis
» see our comprehensive coverage of Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes that is potentially fatal and
requires prompt medical attention for successful treatment. DKA may be the initial presentation in people
with newly diagnosed diabetes. It is usually characterised by plasma glucose >13.9 mmol/L (>250 mg/
dL), arterial pH 7.0 to <7.3, and the presence of ketonaemia and/or ketonuria. Serum sodium, chloride,
magnesium, and calcium are usually low, and serum anion gap (SAG; calculated by subtracting the sum
of major measured anions, chloride and bicarbonate, from the major measured cation, sodium), serum
potassium, urea, and creatinine are usually elevated. Arterial bicarbonate ranges from <10 mmol/L (<10
mEq/L) in severe DKA to >15 mmol/L (>15 mEq/L) in mild DKA. Venous pH, which is usually 0.03 units
lower than arterial pH, is recommended for monitoring treatment, but the difference should be noted.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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of the topics can be found on bestpractice.bmj.com . Use of this content is
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Overview of acid-base and electrolyte disorders Conditions
(SAG; calculated by subtracting the sum of major measured anions, chloride and bicarbonate, from
the major measured cation, sodium) is normal. Proximal and classic distal RTA are characterised by
hypokalaemia.[21] [22] Hyperkalaemia in distal RTA indicates that aldosterone deficiency or resistance is
the cause of the problem.[22] There is minimal or absent urine ammonium in hyperkalaemic distal RTA.
Serum sodium is usually normal. RTA is rarely symptomatic. Patients with severe acidaemia can show
hyperventilation or Kussmaul's breathing due to respiratory compensation. The urine pH exceeds 5.5 in
classic distal RTA, but is lower than 5.0 in patients with untreated proximal RTA.
◊ Primary aldosteronism
» see our comprehensive coverage of Primary aldosteronism
In primary aldosteronism (PA), aldosterone production exceeds the body's requirements and is relatively
autonomous with regard to its normal chronic regulator, the renin-angiotensin II (AII) system.[23] [24] This
results in excessive sodium reabsorption via amiloride-sensitive epithelial sodium channels within the distal
nephron, leading to hypertension and suppression of renin-AII. Urinary loss of potassium and hydrogen
ions, exchanged for sodium at the distal nephron, may result in hypokalaemia and metabolic alkalosis
if severe and prolonged.[23] [24] This is the most common specifically treatable and potentially curable
form of hypertension, accounting for at least 5% of hypertensive patients.[25] Most of these patients are
normokalaemic.
◊ Addison's disease
» see our comprehensive coverage of Addison's disease
Primary adrenal insufficiency, or Addison's disease, is a disorder that affects the adrenal glands, causing
decreased production of adrenocortical hormones (cortisol, aldosterone, and dehydroepiandrosterone).
This may be caused by a destructive process directly affecting the adrenal glands or a condition that
interferes with hormone synthesis. Approximately 90% of the adrenal cortex needs to be destroyed
to produce adrenal insufficiency. Addison's disease may be either acute (adrenal crisis) or insidious.
The finding of low sodium and high potassium serum levels is typical. If untreated, it is a potentially life-
threatening condition.
8 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Overview of acid-base and electrolyte disorders Conditions
CONDITIONS
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Overview of acid-base and electrolyte disorders References
Key articles
• Berend K, de Vries AP, Gans RO. Physiological approach to assessment of acid-base disturbances. N
REFERENCES
• Seifter JL. Integration of acid-base and electrolyte disorders. N Engl J Med. 2014 Nov
6;371(19):1821-31. Abstract
• Foster GT, Varizi ND, Sassoon CS. Respiratory alkalosis. Respir Care. 2001 Apr;46(4):384-91.
Abstract
• Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of
hyponatraemia. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47. Full text Abstract
• Wakil A, Ng JM, Atkin SL. Investigating hyponatraemia. BMJ. 2011 Mar 7;342:d1118. Abstract
• Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes.
Diabetes Care. 2009 Jul;32(7):1335-43. Full text Abstract
• Batlle D, Moorthi KM, Schluter W, et al. Distal renal tubular acidosis and the potassium enigma. Semin
Nephrol. 2006 Nov;26(6):471-8. Abstract
References
1. Berend K, de Vries AP, Gans RO. Physiological approach to assessment of acid-base disturbances. N
Engl J Med. 2014 Oct 9;371(15):1434-45. Abstract
2. Seifter JL. Integration of acid-base and electrolyte disorders. N Engl J Med. 2014 Nov
6;371(19):1821-31. Abstract
3. Foster GT, Varizi ND, Sassoon CS. Respiratory alkalosis. Respir Care. 2001 Apr;46(4):384-91.
Abstract
4. Batlle DC, Hizon M, Cohen E, et al. The use of urinary anion gap in the diagnosis of hyperchloremic
metabolic acidosis. N Engl J Med. 1988 Mar 10;318(10):594-9. Abstract
5. Fencl V, Miller TB, Pappenheimer JR. Studies on respiratory response to disturbances of acid-base
balance, with deductions concerning the ionic composition of cerebral interstitial fluid. Am J Physiol.
1966 Mar;210(3):459-72. Abstract
6. Miller RB. Central nervous system manifestation of fluid and electrolyte disturbances. Surg Clin North
Am. 1968 Apr;48(2):381-93. Abstract
7. Morrison RS. Management of emergencies: metabolic acidosis and alkalosis. N Engl J Med. 1966 May
26;274(21):1195-7. Abstract
10 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Overview of acid-base and electrolyte disorders References
8. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of
hyponatraemia. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47. Full text Abstract
REFERENCES
9. Mohan S, Gu S, Parikh A, et al. Prevalence of hyponatremia and association with mortality: results
from NHANES. Am J Med. 2013 Dec;126(12):1127-37.e1. Full text Abstract
10. Wakil A, Ng JM, Atkin SL. Investigating hyponatraemia. BMJ. 2011 Mar 7;342:d1118. Abstract
11. Liu T, Nagami GT, Everett ML, et al. Very low calorie diets and hypokalaemia: the importance of
ammonium excretion. Nephrol Dial Transplant. 2005 Mar;20(3):642-6. Full text Abstract
12. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. 5th ed. New York, NY:
McGraw-Hill; 2001:836-56.
13. Godek SF, Godek JJ, Bartolozzi AR. Hydration status in college football players during consecutive
days of twice-a-day preseason practices. Am J Sports Med. 2005 Jun;33(6):843-51. Abstract
14. Dave S, Honney S, Raymond J, et al. An unusual presentation of cystic fibrosis in an adult. Am J
Kidney Dis. 2005 Mar;45(3):e41-4. Abstract
15. Hollander-Rodriguez JC, Calvert JF. Hyperkalemia. Am Fam Physician. 2006 Jan 15;73(2):283-90.
Full text Abstract
16. Bilezikian JP, Potts JT Jr, Fuleihan G el-H, et al. Summary statement from a workshop on
asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol
Metab. 2002 Dec;87(12):5353-61. Full text Abstract
17. Arnold A, Staunton CE, Kim HG, et al. Monoclonality and abnormal parathyroid hormone genes in
parathyroid adenomas. N Engl J Med. 1988 Mar 17;318(11):658-62. Abstract
18. Farford B, Presutti RJ, Moraghan TJ. Nonsurgical management of primary hyperparathyroidism. Mayo
Clin Proc. 2007 Mar;82(3):351-5. [Erratum in: Mayo Clin Proc. 2007 Jul;82(7):890.] Abstract
19. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes.
Diabetes Care. 2009 Jul;32(7):1335-43. Full text Abstract
20. Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North
Am. 2001 Dec;30(4):817-31. Abstract
21. Batlle D, Moorthi KM, Schluter W, et al. Distal renal tubular acidosis and the potassium enigma. Semin
Nephrol. 2006 Nov;26(6):471-8. Abstract
22. Rodriguez Soriano J. Renal tubular acidosis: the clinical entity. J Am Soc Nephrol. 2002
Aug;13(8):2160-70. Full text Abstract
23. Conn JW. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med. 1955;45:6-17.
24. Conn JW. Plasma renin activity in primary aldosteronism. Importance in differential diagnosis and in
research of essential hypertension. JAMA. 1964 Oct 19;190:222-5. Abstract
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
11
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Overview of acid-base and electrolyte disorders References
25. Morillas P, Castillo J, Quiles J, et al. Prevalence of primary aldosteronism in hypertensive patients and
its effect on the heart [in Spanish]. Rev Esp Cardiol. 2008 Apr;61(4):418-21. Abstract
REFERENCES
12 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
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Overview of acid-base and electrolyte disorders Disclaimer
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This information is not intended to cover all possible diagnosis methods, treatments, follow up, drugs and
any contraindications or side effects. In addition such standards and practices in medicine change as new
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This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 27, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
13
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Contributors:
// Authors:
Editorial Team,
BMJ Publishing Group
DISCLOSURES: This overview has been compiled using the information in existing sub-topics.