Electrolytes

In a typical adult male, total body water (TBW) is approximately 60% of body weight (somewhat more for infants and less for women).

Figure: Normal distribution of body water and electrolytes. Schematic representation of volume (L = litres) and composition (dominant ionic species only shown) of the ICF and ECF in a 70 kg male. The main difference in composition between the plasma and ISF is the presence of appreciable concentrations of protein in the plasma but not the ISF. ECF = extracellular fluid; ICF = intracellular fluid; ISF = interstitial fluid; IVF = intravascular fluid; TBW = total body water.

* Davidson’s Principles and Practice of Medicine, 22nd edition; Goldman’s Cecil Medicine 24th edition

Name	Average normal value* (mOsm/L H2O)	Reference Ranges**
Na+	142	135 – 145 mmol/L
K+	4.2	3.5 – 5 mmol/L
Ca++	1.3	8.4­ – 10.2 mg/dl
Mg++	0.8	1.5 – 2.4 mg/dL
Cl–	106	98 – 106 mmol/L
HCO3–	24	22 – 30 mmol/L
PO4– –	2	2.9 – 5.4 mg/dL
SO4– –	0.5	2.4 – 4.1 mg/dL

* Guyton and Hall Textbook of Medical Physiology 13th Edition; ** Step on to Paediatrics, Md Abid Hossain Mollah

Normal Na level: 135–145 mmol/L

Normal plasma concentration 3.5–5 mmol/L

When plasma sodium

Classifications—
According to severity—

1. Mild hyponatremia: When sodium level is 130–135 mmol/L (S/S:Malaise, nausea)
2. Moderate hyponatremia: When sodium level is 120– 130 mmol/L (S/S: Headache, vomiting, lethargy)
3. Severe hyponatremia: When sodium level is
4. Very severe hyponatremia: When Na level is

*Pre-exam preparation for medicine, HN Sarker

Neurological dysfunction showing:

• Anorexia
• Nausea and vomiting
• Apathy
• Dizziness
• Confusion
• Convulsion
• Coma.

*Pre-exam preparation for medicine, HN Sarker

Volume status	Examples
Hypovolaemic (sodium deficit with a relatively smaller water deficit)	Renal sodium losses Diuretic therapy (especially thiazides) Adrenocortical failure Gastrointestinal sodium losses Vomiting Diarrhoea Skin sodium losses Burns
Euvolaemic (water retention alone)	Primary polydipsia Excessive electrolyte-free water infusion SIADH Hypothyroidism
Hypervolaemic (sodium retention with relatively greater water retention)	Congestive cardiac failure Cirrhosis Nephrotic syndrome Chronic renal failure (during free water intake)
SIADH = syndrome of inappropriate antidiuretic hormone secretion

* Davidson’s Principles and Practice of Medicine, 22nd edition

Figure: The diagnostic approach to hyponatremia. U_Na = Urinary sodium (mmol/L).

* Harrison’s Principles of Internal Medicine, 19th Edition

The cause of hyponatraemia with apparently normal extracellular volume requires investigation:

1. Plasma and urine electrolytes and osmolalities.
   • The plasma plasma concentrations of sodium, chloride and urea are low, giving a low osmolality.
   • The urine sodium concentration is usually high and the urine osmolality is typically higher than the plasma osmolality. However, maximal dilution (
2. Further investigations. These are needed to exclude –
   • Addison’s disease,
   • hypothyroidism,
   • syndrome of inappropriate ADH secretion (SIADH) and
   • water retention induced by drugs, e.g. chlorpropamide.

* Kumar and Clark’s Clinical Medicine, 9th Edition

The treatment of hyponatraemia is critically dependent on its rate of development, severity and underlying cause. Treatments are:

1. If hyponatremia has developed rapidly (over hours to days), severe (
2. Treatment of underlying cause.
   • For hypovolaemic patients, controlling the source of sodium loss, and administering intravenous saline if clinically warranted.
   • Patients with dilutional hyponatraemia (euvolaemic) generally respond to fluid restriction in the range of 600–1000 mL/day, accompanied where possible by withdrawal of the precipitating stimulus (such as drugs causing SIADH).
   • Hypervolaemic patients with hyponatraemia need treatment of the underlying condition, accompanied by cautious use of diuretics in conjunction with strict fluid restriction.

*Pre-exam preparation for medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition

Note: Key points in the management of hyponatraemia

1. Always treat the underlying cause
2. What is the volume status of the patient?
   • If hypovolaemic: rehydrate with 0.9% saline
   • If euvolaemic (SIADH): restrict fluid to 500–700 mL/day
   • If hypervolaemic (chronic kidney disease/heart failure): restrict fluid and salt
3. Does the patient have symptomatic hyponatraemia (seizures/coma)?
   • Yes: involve critical care input early; 3% saline 1 mL/kg over 1 h
4. Is the hyponatraemia acute or chronic?
   • If acute: more likely to develop symptomatic hyponatraemia
   • If chronic: increased risk of osmotic demyelination due to rapid correction
   • If unsure: give 3% saline very slowly
5. Check sodium levels frequently: may need to check Na every 1–2 h
6. Correction must not exceed 10 mmol in first 24 h and 18 mmol in 48 h

* Kumar and Clark’s Clinical Medicine, 9th Edition

Rapid correction may lead to central pontine mylinolysis (osmotic demyelinating syndrome).

Note:

In hyponatraemia that has developed slowly (over weeks to months), brain cells adapt to slowly developing hypo-osmolality by reducing the intracellular osmolality, thus maintaining normal cell volume. Under these conditions, an abrupt increase in extracellular osmolality can lead to water shifting out of neurons, abruptly reducing their volume and causing them to detach from their myelin sheaths. The resulting ‘myelinolysis’ can produce permanent structural and functional damage to mid-brain structures, and is generally fatal. The rate of correction of the plasma Na concentration in chronic asymptomatic hyponatraemia should not exceed 10 mmol/L/day, and an even slower rate is generally safer.

Figure: Hyponatraemia and the brain. Numbers represent osmolality (osmo) in mmol/kg.

*Pre-exam preparation for medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition

Points to know:

1. Daily maximum Na⁺ sodium correction limit:
   • Acute case: 0.5 mmol/L/hours e.g. (weight in kg × 12) mmol/day
   • Chronic case: 10 mmol/L/day e.g. (weight in kg × 10) mmol/day
2. Total sodium deficit: 0.6 × weight in kg × (Desired Na⁺ – Observed Na⁺) mmol
3. In case of children, daily maintenance Na⁺ 2–3 mmol/kg/day for next 2 days needs to be added.
4. Total fluid requirement:
   • (Daily limit or requirement/154) L for normal saline (0.9% NaCl)
   • (Daily limit or requirement/514) L for 3% NaCl
5. Choice of fluid:
   • 0.9% NaCl in asymptomatic patient or Na⁺ >110 mmol/L
   • 3% NaCl in rapidly developed hyponatremia (over hours to days), severe hyponatremia (

Case 1: Patient asymptomatic or Na⁺ >110 mmol/L

Scenario: Patient weight 50 kg, serum Na+ 125mmol/L Calculation: 1.     In case of this patient, daily maximum sodium correction limit: 50 × 10 = 500 mmol 2.     His total sodium deficit: 0.6 × 50 × (135 – 125) = 300 mmol, that should be corrected within 1 day. 3.     Total fluid requirement: (300/154) = 1.9 ≈ 2 L normal saline

Case 2: Symptomatic rapidly developed hyponatremic patient or Na⁺

Scenario: Patient weight 50 kg, serum Na+ 105mmol/L Calculation: 1.     In case of this patient, daily maximum sodium correction limit: 50 × 12 = 600 mmol 2.     His total sodium deficit: 0.6 × 50 × (135 – 105) = 900 mmol, that should be corrected in 2 days. 3.     Total fluid requirement: a.     Day 1: (600/514) ≈ 1 L 3% NaCl b.     Day 2: correction of rest of the 300 mmol

Case 3: 7 days old baby

Scenario: Patient weight 1.5 kg, serum Na+ 122mmol/L Calculation: 1.     In case of this patient, daily maximum sodium correction limit: 1.5 × 10 = 15 mmol 2.     Sodium requirement a.     His sodium deficit: 0.6 × 1.5 × (135 – 122) = 11.7 mmol, b.     Maintenance Na+: 3 × 1.5 × 2 = 9 mmol c.     Total: 11.7 + 9 = 20.7 ≈ 21 mmol, that should be corrected in 2 days.

Excess DA administration or sample collected from hand used for IV line.

*Pre-exam preparation for medicine, HN Sarker

Pseudohyponatremia is the spurious low value seen if a high proportion of the serum volume is free of water. For example severe hyperlipidemia.

*Pre-exam preparation for medicine, HN Sarker

When K⁺ level > 5 mmol/L, then its called hyperkalemia.

Types are:

1. Mild hyperkalemia: 5–6 mmol/L
2. Moderate hyperkalemia: 6–7 mmol/L
3. Severe hyperkalemia: >7 mmol/L

*Pre-exam preparation for medicine, HN Sarker

Common causes are:

1. Renal impairment
   • Acute renal failure
   • Chronic renal failure
2. Adrenocortical insufficiency (Addison’s disease)
3. Excess intake or load—
   • Exogenous—Dietary and IV therapy.
   • Endogenous—Hemolysis and rhabdomyolysis.
4. Transcellular shift—Acidosis (diabetic ketoacidosis), insulin deficiency, hyperkalemic periodic paralysis.
5. Drugs—ACE inhibitor and potassium sparing diuretics.

Figure: Diagnostic decision tree for hyperkalaemia. Creatinine of 500 μmol/L = 5.67 mg/dL.

*Pre-exam preparation for medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition

Clinical features –

1. Hyperkalaemia typically presents with progressive muscular weakness (unless (as is commonly the case) the hyperkalaemia is associated with metabolic acidosis, causing Kussmaul respiration).
2. Sometimes there are no symptoms until cardiac arrest (in diastole) occurs. Hyperkalaemia causes depolarization of cell membranes, leading to decreased cardiac excitability, hypotension, bradycardia and eventual asystole.

*Davidson’s Essentials of Medicine, 2nd Edition Page 147; Kumar and Clark’s Clinical Medicine, 9th Edition

ECG changes are:

1. Tall peaked T-waves
2. Wide QRS complexes
3. Loss of P-wave
4. Sine wave.

*Pre-exam preparation for medicine, HN Sarker; Figure: Davidson’s Principles and Practice of Medicine, 22nd edition

Management—

Treatment of hyperkalaemia depends on its severity and the rate of development.

1. In the absence of neuromuscular symptoms or ECG changes –
   • Reduction of potassium intake and correction of underlying abnormalities may be sufficient.
2. However, in acute and/or severe hyperkalaemia (plasma K > 6.5–7.0 mmol/L) more urgent measures must be taken.
   • Intravenous calcium gluconate (10 mL of 10% solution)— To stabilize conductive tissue membranes.
   • Inhaled β2 agonist, e.g. salbutamol. or, Intravenous glucose (50 mL of 50% solution) and insulin (5 U Actrapid).
   • Intravenous sodium bicarbonate (100 mL of 8.4% solution), if acidosis present.
   • Remove K⁺ from body, intravenous furosemide, and normal saline.
   • Ion-exchange resin (e.g. resonium) orally or rectally.
   • Dialysis.

*Pre-exam preparation for medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition Page 443

During venepuncture for blood sample collection, due to incorrect/repeated handling there may be—

• Tissue damage
• RBC damage
• Endothelial cell damage
• Delayed processing.
  This results in release of potassium and show hyperkalemia in blood sample, although patient’s K⁺ is normal.

*Pre-exam preparation for medicine, HN Sarker

Figure:  Causes and diagnostic decision tree for hypokalaemia. (ACTH = adrenocorticotrophic hormone)

* Davidson’s Principles and Practice of Medicine, 22nd edition

Causes of hypokalaemia:

1. Increased renal excretion (Urinary K⁺ >20 mmol/day)
   • Diuretics: – Thiazides, loop diuretics
2. Increased aldosterone secretion
   • Liver failure
   • Heart failure
   • Nephrotic syndrome
   • Cushing syndrome
   • Conn syndrome
   • ACTH-producing tumours
3. Exogenous mineralocorticoid
   • Corticosteroids
   • Liquorice (potentiates renal actions of cortisol)
4. Renal disease
   • Renal tubular acidosis types 1 and 2
   • Renal tubular damage (diuretic phase)
   • Acute leukaemia
   • Nephrotoxicity: Amphotericin, Aminoglycosides, Cytotoxic drugs
   • Release of urinary tract obstruction
   • Bartter syndrome
   • Liddle syndrome
   • Gitelman syndrome
5. Reduced intake of K⁺
   • Intravenous fluids without K⁺
   • Dietary deficiency
6. Redistribution into cells
   • β-Adrenergic stimulation
   • Acute myocardial infarction
   • Beta-agonists, e.g. fenoterol, salbutamol
   • Insulin treatment, e.g. treatment of diabetic ketoacidosis
   • Correction of megaloblastic anaemia, e.g. B12 deficiency
   • Alkalosis
   • Hypokalaemic periodic paralysis
7. Gastrointestinal losses (Urinary K⁺ 
   • Vomiting
   • Severe diarrhoea
   • Purgative abuse
   • Villous adenoma
   • Ileostomy or uterosigmoidostomy
   • Fistulae
   • Ileus/intestinal obstruction

* Kumar and Clark’s Clinical Medicine, 9th Edition Box 9.15

ECG changes are:

1. Small or inverted T waves,
2. Prominent U waves (after T wave), a
3. A long PR interval, and
4. Depressed ST segments.

** Oxford Handbook of Clinical Medicine, 9th Edition Page: 688; Figure: Davidson’s Principles and Practice of Medicine, 22nd edition

Treatments are:

1. The underlying cause should be identified and treated if possible.
2. Acute hypokalemia may correct spontaneously.
3. In most cases, the oral administration of potassium supplements in the form of slow-release potassium or effervescent potassium, is sufficient.
4. Intravenous potassium replacement is required only in conditions such as cardiac arrhythmias, muscle weakness or severe diabetic ketoacidosis.

*Pre-exam preparation for medicine, HN Sarker

Treatment

1. If mild: (>2.5mmol/L, no symptoms) give oral K+supplement. Review K+ after 3 days. If taking a thiazide diuretic, and K+ >3.0 consider repeating and/or K+ sparing diuretic.
2. If severe: (<2.5mmol/L, and/or dangerous symptoms) give IV potassium cautiously, not more than 20mmol/h, and not more concentrated than 40mmol/L. Do not give K+ if oliguric.

Note:

• Never give K+ as a fast stat bolus dose. *
• The rate of administration depends on the severity of hypokalaemia and the presence of cardiac or neuromuscular complications, but should generally not exceed 10 mmol of potassium per hour. **

* Oxford Handbook of Clinical Medicine, 9th Edition, Page: 688; ** Davidson’s Principles and Practice of Medicine, 22nd edition, Page: 442

Clinical assessment –

Mild hypocalcaemia is often asymptomatic but, with more profound reductions in serum calcium, tetany can occur.

Hypocalcaemia tetany

• This is characterised by muscle spasms due to increased excitability of peripheral nerves.
• Children are more liable to develop tetany than adults.
• In childern:
  • A characteristic triad of –
    1. carpopedal spasm,
       • flexion of the metacarpophalangeal joints of the fingers and
       • adduction of the thumb (‘main d’accoucheur’)
    2. stridor (caused by spasm of the glottis) and
    3. convulsions, although one or more of these may be found independently of the others.
  • Pedal spasm can also occur but is less frequent.
• In adult:
  • Adults can also develop carpopedal spasm in association with tingling of the hands and feet and around the mouth,
  • Stridor and fits are rare.

Signs:

Latent tetany may be detected by eliciting –

1. Trousseau’s sign; inflation of a sphygmomanometer cuff on the upper arm to more than the systolic blood pressure is followed by carpal spasm (tetanic spasm of the singers and wrist) within 3 minutes.
2. Less specific is Chvostek’s sign, in which tapping over the branches of the facial nerve as they emerge from the parotid gland produces twitching of the ipsilateral facial muscles.

Other features:

• Hypocalcaemia can cause papilloedema and prolongation of the ECG QT interval, which may predispose to ventricular arrhythmias.
• Prolonged hypocalcaemia and hyperphosphataemia (as in hypoparathyroidism) may cause calcification of the basal ganglia, grand mal epilepsy, psychosis and cataracts.
• Hypocalcaemia associated with hypophosphataemia, as in vitamin D deficiency, causes rickets in children and osteomalacia in adults.

*Davidson’s Principles and Practice of Medicine, 22nd edition Page 768, 769; Kumar and Clark’s Clinical Medicine, 9th Edition; Figure: Oxford Handbook of Clinical Medicine, 9th Edition Page: 692

 

The approach to treatment depends on –

• the severity of the hypocalcemia,
• the rapidity with which it develops, and
• the accompanying complications (e.g., seizures, laryngospasm).

Mild symptoms:

• Oral calcium 5mmol/6 hourly, with daily plasma Ca²⁺ levels.**

Acute, symptomatic hypocalcemia

• It is initially managed with 10–20 mL 10% calcium gluconate (diluted in 50 mL of 5% dextrose or 0.9% sodium chloride) given intravenously over 10-20 minutes.
• Continuing hypocalcemia often requires a constant intravenous infusion (equivalent of 10 mL 10% calcium gluconate/hr, typically 10 ampules of calcium gluconate or 900 mg of calcium in 1 L of 5% dextrose or 0.9% sodium chloride administered over 24 h).
• Cardiac monitoring is recommended.
• Accompanying hypomagnesemia, if present, should be treated with appropriate magnesium supplementation.

Chronic hypocalcemia due to hypoparathyroidism

• It is treated with calcium supplements and either vitamin D2 or D3 (25,000–100,000 U daily) or calcitriol [1,25(OH)₂D, 0.25–2 μg/d].

 

*Harrison’s Principles of Internal Medicine, 19th Edition Page: 315; Davidson’s Principles and Practice of Medicine, 22nd edition Page 790; ** Oxford Handbook of Clinical Medicine, 9th Edition Page: 692

 

 

Symptoms and signs of hypercalcaemia include –

• polyuria and polydipsia,
• renal colic,
• lethargy,
• anorexia,
• nausea,
• dyspepsia and peptic ulceration,
• constipation,
• depression,
• drowsiness and impaired cognition.

Patients with malignant hypercalcaemia can have a rapid onset of symptoms and may have clinical features that help to localise the tumour. The classic symptoms of primary hyperparathyroidism are described by the adage ‘bones, stones and abdominal groans’, but few patients present in this way nowadays and the disorder is most often picked up as an incidental finding on biochemical testing. A family history of hypercalcaemia raises the possibility of FHH or MEN**.

**FHH = Familial hypocalciuric hypercalcemia, MEN = Multiple endocrine neoplasia.

 

*Davidson’s Principles and Practice of Medicine, 22nd edition Page 767