How does low calcium causes tetany

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How Low Calcium Causes Tetany

The Core Mechanism: Loss of Membrane Stabilization

Calcium ions (Ca²⁺) play a critical role in stabilizing voltage-gated sodium channels on the outer surface of neuronal and muscle cell membranes. Specifically, extracellular Ca²⁺ binds to negatively charged sites on the external surface of these channels, raising the activation threshold - meaning more depolarization is required before sodium can rush in and fire an action potential.

When ionized calcium falls (hypocalcemia), this stabilizing effect is lost:

Reduced Ca²⁺ = reduced threshold - The voltage-gated Na⁺ channels become much easier to open, requiring less membrane depolarization to trigger an action potential.
Spontaneous, repetitive firing - Peripheral motor neurons begin firing action potentials spontaneously or after minimal stimuli, without any voluntary signal from the nervous system.
Involuntary muscle contraction - These repetitive nerve discharges propagate to skeletal muscles, causing the sustained, involuntary contractions we call tetany.

As described in Plum and Posner's Diagnosis and Treatment of Stupor and Coma: "Tetany caused by spontaneous, irregular, repetitive nerve action potentials is a common complication of hypocalcemia." And from Mulholland and Greenfield's Surgery: "Tetany is defined as repetitive discharges after a single stimulus."

Threshold for Tetany

Tetany typically does not occur until ionized calcium < 4.3 mg/dL or total serum calcium < 7.0 mg/dL - Mulholland and Greenfield's Surgery
A free calcium level < 4.0 mg/dL is considered diagnostic of hypocalcemia - Plum and Posner's

Why Alkalosis Worsens Tetany (The pH Connection)

Alkalosis (e.g., from hyperventilation) dramatically worsens the tendency to tetany, even without a further drop in total calcium. Here is why:

At higher pH, more calcium is bound to albumin (protein-bound fraction increases)
This reduces the free ionized calcium fraction available to stabilize membranes
A patient can develop tetany with a "normal" total calcium simply due to alkalosis shifting calcium toward the protein-bound form

This explains a key clinical observation from Mulholland and Greenfield's Surgery: "Alkalosis also plays a strong role in the development of tetany, even beyond its association with hypocalcemia, as tetany is rarely seen in renal failure patients despite low calcium levels. This is likely due to the protective effect of concurrent metabolic acidosis."

Clinical Progression (Low → Very Low Calcium)

Severity	Ionized Ca²⁺	Manifestations
Mild	Slightly low	Perioral and acral (fingertip) paresthesias
Moderate	Decreasing	Carpopedal spasms, muscle cramps - latent tetany
Severe	< 4.3 mg/dL	Frank tetany, laryngospasm, seizures
Critical	Very low	Ventricular arrhythmias, cardiac arrest

Chvostek's sign: Tapping the facial nerve anterior to the ear causes ipsilateral facial muscle twitching - indicates neuromuscular hyperexcitability
Trousseau's sign: Inflating a BP cuff above systolic for 3 minutes triggers carpal spasm (carpopedal spasm) - considered more specific than Chvostek's
Both signs represent latent tetany (hypocalcemia present but not yet causing spontaneous tetany)

The Role of Alkalosis in Hyperventilation Tetany

This is why hyperventilation alone can cause tetany in normal patients:

Rapid breathing blows off CO₂ → respiratory alkalosis → blood pH rises
Albumin binding of calcium increases → ionized Ca²⁺ falls acutely
Neuromuscular threshold drops → carpopedal spasm, perioral tingling, tetany

This was demonstrated in the case vignette from Plum and Posner's: a patient's carpal spasms were reproducible with just 2 minutes of voluntary hyperventilation, later found to have ionized Ca²⁺ of 3.8 mEq/L (normal 4.8-5.3).

Summary

Low calcium → loss of Na⁺ channel membrane stabilization → lower action potential threshold → spontaneous, repetitive nerve firing → involuntary sustained muscle contraction = tetany

Sources:

Mulholland and Greenfield's Surgery, 7e
Plum and Posner's Diagnosis and Treatment of Stupor and Coma
The Washington Manual of Medical Therapeutics
Brenner and Rector's The Kidney, 2-Volume Set

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