Hypocalcaemia

OVERVIEW

• calcium is a highly regulated cation
• involved in: cell death, duration and strength of cardiac muscle contraction, muscle contraction in blood vessels, airways and uterus, coagulation, bone metabolism, neurotransmitter and hormone release…
• Ca2+ exists in the extracellular plasma two states:
  1. free ionized state and
  2. bound to other molecules (mostly albumin, rest – beta-globulins, phosphate, citrate)
• ionized Ca2+ concentration is inversely related to pH -> an increase in pH results in a decrease in ionized Ca2+

Calcium levels

• total Ca2+ range = 2.2-2.5mmol/L (55% bound, 45% ionized)
• ionized Ca2+ range (50%) = 1.1-1.3mmol/L
• protein bound Ca2+ range (40%) = 0.95-1.2mmol/L
• complex Ca2+ (10% – calcium phosphate, salts) = 0.05mmol/L

CALCIUM METABOLISM

Vitamin D

• group of related sterols
  cholecalciferol is formed in the skin
  -> in liver to 25-hyrdroxcholecalciferol
  -> in kidney proximal tubules to 1,25-dihydroxycholecalciferol
  -> this then helps calcium absorption in the intestine
• controlled by parathyroid hormone

-> increases intestinal absorption of Ca2+
-> increases renal Ca2+ reabsorption
-> mobilises bone Ca2+ & PO43-

Parathyroid hormone

• secretion increased by hypocalaemia and hypomagnesaemia
• secretion decreased by hypercalcaemia and hypermagnesaemia

-> mobilses Ca2+ from bone
-> increases renal Ca2+ reabsorption
-> increases renal PO43- excretion
-> increases formation of 1, 25-dihyroxycholecalciferol

Calcitonin

• antagonist of parathyroid hormone
• secreted by the parafollicular cells of the thyroid gland in response to:
  – hypercalcaemia
  – catecholamines
  – gastrin

-> inhibits the mobilisation of bone Ca2+
-> increases renal Ca2+ & PO43- excretion

SUMMARY OF CAUSES

Intake reduced:

• Ca2+
• vitamin D
• phenytoin (increased metabolism of vitamin D)

Redistribution:

• alkalosis
• citrate toxicity
• hyperphosphataemia
• pancreatitis
• tumour lysis syndrome
• rhabdomyolysis
• decreased bone turnover
• hypoparathyroidism
• drugs (bisphosphonates, PPI’s, SSRI’s, gentamicin)

Output increased:

• urinary – ethylene glycol, cis-platin, protamine, loop diuretics
• non-urinary – bleeding, plasmapheresis, citrate RRT

CAUSES OF HYPOCALCAEMIA AND ACID-BASE DISTURBANCE

• Metabolic alkalosis – citrate toxicity
• Metabolic acidosis – acute renal failure, tumour lysis, rhabdomyolysis, pancreatitis, ethylene glycol poisoning, hydrofluoric acid, sepsis, burns

HISTORY

• perioral numbness
• paresthesias
• muscle cramps
• mild mental status changes (irritability)
• seizures
• tetany
• collapse
• to find cause: diet, drugs, symptoms specific to cause
• laryngospasm

EXAMINATION

• Chvostek sign (tapping facial nerve anterior to ear -> spasm of facial muscles)
• Trousseau sign (inflate BP cuff -> trap median nerve -> carpal spasm)
• hypotension
• arrhythmias (long QT)
• heart failure
• signs specific to cause

INVESTIGATIONS

• Ca²⁺ (total and ionized)
• PO₄^3-
• Mg²⁺
• PTH
• ECG: prolongation of ST segment and QT interval -> VT
• albumin
• lipase (rule out pancreatitis)
• U+E – renal failure, hyperkalaemia
• CK and urate – rhabdomyolysis

MANAGEMENT

• treat cause
• proportional to severity
• oral Ca²⁺
• replace Mg²⁺
• vitamin D
• IV calcium (10mL gluconate = 2.3mmol = 93mg, 10mL chloride = 6.8mmol = 272mg)
• indications for IV calcium therapy:

-> symptomatic hypocalcaemia
-> ionized Ca²⁺ <0.8mmol/L
-> hyperkalaemia
-> Ca²⁺ channel blocker OD
-> hypermagnesaemia
-> hypocalcaemia with high inotrope requirement
-> massive transfusion
-> post cardiopulmonary bypass

References and Links

• CCC – Calcium metabolism
• CCC – Calcium basics
• CCC – Hypercalcaemia Overview
• CCC – Hypercalcaemia DDx
• CCC – Hypocalcaemia
• CCC – Hypocalcaemia DDx
• CCC – Calcium replacement (advantages/disadvantages)
• CCC – Calcium as an inopressor