Hypocalcaemia: Correcting the Excitable State
If hypercalcaemia sedates — "stones, bones, groans and psychiatric moans" — hypocalcaemia does the opposite: it winds nerve and muscle up until they fire on their own. The same ion, read from the other end of its axis. Tingling fingers, a cramping hand, a twitching face, and — at the sharp end — a spasming larynx, a seizure, or a heart with a dangerously long QT. The management is a story in two speeds: rescue the excitable patient now with intravenous calcium, then think slowly about why the calcium fell — and the answer, more often than students expect, is a missing hormone, an unactivated vitamin, or a low magnesium that quietly blocks every attempt to fix it.
It is the morning after a total thyroidectomy. The nurse calls you: the patient's fingers and lips have gone numb and tingly, and now her hands are cramping into a claw. You inflate the blood-pressure cuff on her arm and within a minute her wrist and fingers draw up into a tight spasm — a positive Trousseau's sign. A tap over the facial nerve makes the corner of her mouth twitch — Chvostek's. The ECG shows a lengthening QT interval. Her total calcium has fallen overnight because the surgeon, working around a cancer, has bruised or removed her parathyroid glands. This is one of the classic post-operative emergencies: acute hypoparathyroidism. She does not need a tablet and a review in clinic — she needs intravenous calcium now, on a cardiac monitor, before the larynx or the heart joins in.
Why low calcium makes tissue excitable
Calcium sits on the outside of the nerve membrane like a hand on the trigger guard. Extracellular Ca2+ stabilises voltage-gated sodium channels — it raises the threshold a nerve must reach before it fires. When ionised calcium falls, that stabilising influence is withdrawn: sodium channels open more easily, the firing threshold drops, and nerves and muscles discharge spontaneously and repetitively. This is the mechanism behind every symptom of hypocalcaemia. It is the mirror image of hypercalcaemia, where abundant calcium raises the threshold and everything slows down and quietens. So the two disorders are not just "too much" and "too little" of a number — they are opposite states of membrane excitability, and remembering that single idea lets you predict the entire clinical picture from first principles.
Think of calcium as a heavy blanket lying over a bed of tightly-wound mousetraps (the nerve membranes). The weight keeps them from snapping. Pile on more blankets — hypercalcaemia — and nothing goes off; the patient is sluggish and constipated. Take the blanket away — hypocalcaemia — and the traps start snapping at the lightest touch, then snapping on their own: tingling, cramps, a hand clenched in spasm, a face that twitches when you tap it. Same traps, opposite blanket.
The clinical picture: from tingling to tetany
The symptoms climb a ladder of severity. The earliest and most sensitive is paraesthesia — tingling around the mouth (perioral) and in the fingertips and toes. Next come muscle cramps and carpopedal spasm, the involuntary clawing of the hands and feet. At the top of the ladder is frank tetany, elicited even in milder cases by two bedside signs every student must know: Chvostek's sign (tapping over the facial nerve just in front of the ear makes the facial muscles twitch) and Trousseau's sign (inflating a blood-pressure cuff above systolic for three minutes provokes carpal spasm — the more specific of the two). Beyond tetany lie the true emergencies: laryngospasm (a spasming airway), generalised seizures, and the cardiac danger — a prolonged QT interval that can degenerate into ventricular arrhythmia. That QT link is why hypocalcaemia belongs in the same conversation as the Cardiovascular section's teaching on QT prolongation and torsades.
Never react to a total calcium without correcting it first. Nearly half of plasma calcium is bound to albumin, and only the free, ionised fraction is biologically active. A patient with low albumin — the sick, the malnourished, the nephrotic — will show a low total calcium while their ionised calcium is perfectly normal, and treating that "low" number is a mistake. Use the albumin-corrected calcium (or measure ionised calcium directly). The reverse trap is even sneakier: alkalosis. Raising blood pH — most commonly acute hyperventilation from a panic attack — makes albumin bind more calcium, dropping the ionised fraction while the total stays normal. That is why an anxious, over-breathing patient can develop genuine perioral tingling and carpopedal spasm with a totally normal calcium level on the report.
- Low ionised Ca2+ destabilises sodium channels → nerves and muscle become hyperexcitable and fire spontaneously.
- Symptom ladder: perioral/finger paraesthesia → cramps and carpopedal spasm → tetany → laryngospasm, seizures, long QT.
- Chvostek's sign (facial tap → twitch) and Trousseau's sign (cuff → carpal spasm) reveal latent tetany at the bedside.
- Always interpret the albumin-corrected calcium or the ionised calcium, never the raw total.
- Alkalosis (e.g. hyperventilation) lowers ionised calcium and can cause acute symptoms with a normal total calcium.
Causes: a hormone, a vitamin, a kidney, and a hidden ion
Calcium is held up by parathyroid hormone and active vitamin D; knock out either arm and it falls. The single most important cause to recognise is hypoparathyroidism, and its commonest form is iatrogenic: damage to or removal of the parathyroid glands during thyroid or neck surgery. Without parathyroid hormone (PTH) the body cannot mobilise calcium from bone, reclaim it from the kidney, or drive activation of vitamin D — so calcium falls (and phosphate rises). This is the post-operative emergency in the opening scene; the same picture appears in the rarer autoimmune destruction of the glands. The second great cause is vitamin D deficiency or resistance — without it, calcium is not absorbed from the gut, which cross-links directly to the Vitamin D chapter. The third is chronic kidney disease (CKD): the failing kidney cannot perform the final 1-alpha-hydroxylation that turns vitamin D into its active form, and it retains phosphate, which further binds and lowers calcium — the disorder taught in full as CKD–mineral and bone disorder (CKD-MBD) in the Phosphate/CKD chapter. All of this sits on the endocrine backbone covered in the Endocrine section: PTH, vitamin D activation, and the consequences of thyroid and parathyroid surgery.
There is a fourth cause with a rule attached, and it is the one that catches clinicians out: hypomagnesaemia. Magnesium is required both for the parathyroid gland to secrete PTH and for PTH to act on its target tissues. So when magnesium is low, calcium falls — and, crucially, it will not correct however much calcium you give, until the magnesium is replaced first. This is the same "correct the magnesium first" rule taught in the Magnesium chapter, and it is a favourite exam trap: refractory hypocalcaemia that only responds once Mg2+ is restored. Beyond these four, remember the acute chelation causes: acute pancreatitis (calcium is soaped up by released fatty acids), tumour lysis syndrome and rhabdomyolysis (a flood of phosphate binds calcium), and massive blood transfusion (the citrate anticoagulant chelates circulating calcium — a Toxicology cross-link). Finally, drugs: bisphosphonates and denosumab (which shut down bone resorption), foscarnet (which chelates calcium directly — another Toxicology link), and cinacalcet (which lowers PTH by design).
The three numbers together name the cause. Low calcium with HIGH phosphate and LOW/inappropriately-normal PTH → hypoparathyroidism (the post-thyroidectomy patient). Low calcium with high phosphate but HIGH PTH → chronic kidney disease, where the parathyroids are working overtime (secondary hyperparathyroidism) but the kidney still can't activate vitamin D. Low calcium with LOW phosphate and HIGH PTH → vitamin D deficiency, where a healthy parathyroid gland is shouting to compensate. And any refractory hypocalcaemia with a stubbornly "normal" or low PTH should prompt a magnesium level before anything else.
- Hypoparathyroidism — most often iatrogenic after thyroid/neck surgery — is the key post-operative emergency; also autoimmune.
- Vitamin D deficiency/resistance and CKD (impaired 1-alpha-hydroxylation + phosphate retention) are the other major causes.
- Hypomagnesaemia lowers calcium by impairing PTH secretion and action — it won't correct until magnesium is replaced.
- Chelation causes: pancreatitis, tumour lysis/rhabdomyolysis (phosphate), and massive transfusion (citrate).
- Drug causes: bisphosphonates, denosumab, foscarnet, and cinacalcet.
- Calcium + phosphate + PTH read together pinpoint whether the problem is the gland, the kidney, or vitamin D.
Treatment: two speeds
Match the urgency to the danger — the excitable heart and airway will not wait. Acute, severe or symptomatic hypocalcaemia — tetany, laryngospasm, seizures, or a prolonged QT — is a medical emergency treated with intravenous calcium. The agent of choice peripherally is calcium gluconate, given slowly and with continuous cardiac monitoring. Gluconate is preferred over calcium chloride for peripheral lines because chloride is far more irritant and causes tissue necrosis if it extravasates; chloride delivers more elemental calcium and is reserved for central access or arrest situations. Give the calcium too fast and you risk arrhythmia, which is exactly why the monitor is non-negotiable. And whatever the apparent cause, check and replace magnesium alongside — if it is low, the calcium simply will not stay up until the magnesium is corrected.
Chronic or mild hypocalcaemia is corrected far more gently, and the choice of vitamin D preparation is the whole point. The treatment is oral calcium supplementation plus vitamin D — but which vitamin D depends on whether the patient can still activate it. In hypoparathyroidism and in CKD, the final 1-alpha-hydroxylation step is impaired (no PTH to drive it, or no functioning kidney to perform it), so plain colecalciferol will not work — the body cannot switch it on. These patients need an ACTIVE vitamin D analogue that bypasses the missing step: alfacalcidol (1-alpha-hydroxyvitamin D) or calcitriol (the fully active 1,25-dihydroxyvitamin D). Plain colecalciferol is fine for simple dietary deficiency in a patient with intact parathyroids and kidneys, but it is the wrong drug when the activation machinery itself is broken. This is the recurring theme that ties the whole calcium axis together — a principle expanded in the Vitamin D and Phosphate/CKD chapters.
Two words summarise the whole management: magnesium and active. First, fix the magnesium — hypocalcaemia that resists calcium is hypocalcaemia with an unmeasured low magnesium until proven otherwise. Second, when the kidney or the parathyroids cannot activate vitamin D, give it already activated — alfacalcidol or calcitriol, not plain colecalciferol. Get those two reflexes right and you will correctly manage the large majority of hypocalcaemia you meet, from the crashing post-thyroidectomy patient to the quietly deficient outpatient with CKD.
- Treating a low total calcium without correcting for albumin — the ionised calcium may be normal, and you are chasing a number, not a patient.
- Pouring in calcium for refractory hypocalcaemia while ignoring a low magnesium — it will never correct until the magnesium is replaced first.
- Prescribing plain colecalciferol in hypoparathyroidism or CKD — with 1-alpha-hydroxylation impaired, only an active analogue (alfacalcidol/calcitriol) works.
The morning after a total thyroidectomy, a patient develops perioral tingling and carpopedal spasm, with a positive Trousseau's sign and a prolonged QT on the ECG. What is the most appropriate immediate management?
- Low ionised calcium raises neuromuscular excitability: perioral/finger paraesthesia, cramps, carpopedal spasm, tetany (Chvostek/Trousseau), laryngospasm, seizures, and a prolonged QT.
- Always interpret the albumin-corrected or ionised calcium; alkalosis (hyperventilation) lowers ionised calcium with a normal total.
- Causes: hypoparathyroidism (commonly post-thyroidectomy), vitamin D deficiency, CKD, hypomagnesaemia, pancreatitis, tumour lysis/rhabdomyolysis, massive transfusion (citrate), and drugs.
- Treat the acute crisis with IV calcium gluconate on a monitor and replace magnesium; treat the chronic state with oral calcium plus an ACTIVE vitamin D (alfacalcidol/calcitriol) when activation is impaired.
- Rang & Dale's Pharmacology — calcium metabolism, parathyroid hormone and vitamin D.
- Katzung Basic & Clinical Pharmacology — agents affecting bone mineral homeostasis.
- British National Formulary (BNF) — calcium salts, alfacalcidol, calcitriol and colecalciferol.
- Society for Endocrinology / Endocrine Society — Emergency management of acute hypocalcaemia guideline.
- NICE — Chronic kidney disease (CKD-MBD) and vitamin D management.
- Ganong's Review of Medical Physiology — parathyroid hormone, calcium and neuromuscular excitability.
