Calcium (Ca2+) is a divalent cation that plays a key role in many naturally occurring, physiological processes. Its critical role is exerted at the cellular level which mandates tight regulation of its extracellular fluid concentration to maintain normal function. Of particular concern is when extracellular calcium levels fall (hypocalcemia), which may result in serious pathophysiological derangements at the level of virtually every organ system in the human body.
Approximately 99% of calcium is primarily stored in bone as hydroxyapatite. In plasma, the concentration of its physiologically active form, ionized calcium, is kept in a narrow range through the actions of three major organs (bone, kidney, and intestine) along with three major hormones (PTH, Vitamin D, and Calcitonin). An understanding of the interactions between these key organs and hormones serves to provide a useful framework that can be utilized to accurately identify the etiology of hypocalcemia.
Calcium-sensing receptors in the parathyroid gland alter the secretion of PTH in response to changes in plasma levels of calcium. When plasma levels are decreased, PTH is secreted with the following effects on target organs:
- Promotes bone resorption, thereby liberating calcium and phosphate from bone and delivering it to plasma.
- Increases excretion of phosphate that would otherwise form complexes with calcium in the plasma, ultimately decreasing its concentration.
- Stimulates renal calcium reabsorption at the level of the distal convoluted tubule
- Stimulates renal 1α-hydroxylase which converts 25-hydroxycholecalciferol (Vitamin D) to the active form, 1,25-dihydroxycholecalciferol, which increases intestinal absorption of calcium.
- Responds to activated vitamin D (1,25-dihydroxycholecalciferol) formed by the kidney to increase intestinal calcium absorption.
When plasma levels of calcium are increased, calcitonin is released by the thyroid gland to mitigate the actions of PTH.
Causes of Hypocalcemia
Systemic illness and severe derangements in organ function contribute to hypocalcemia among critically ill patients; however, a useful method of classification incorporates the detected levels of PTH.
Clinical Features of Hypocalcemia
- Hypotension (↓Cardiac Output)
- QT Prolongation
- Cardiac Arrhythmias (Torsades de Pointes)
- Tetany (Trousseau Sign, Chvostek Sign)
- Cognitive Impairment
Important investigations and labs include:
- Serum Phosphate
- Ionized Calcium (normal 1.12 – 1.32 mmol/L)
- Serum Magnesium
- Creatinine Kinase
- Serum 25-hydroxycholecalciferol
- Mild/Asymptomatic (Ionized Ca: 1.0-1.12 mmol/L)
- Treatment not usually indicated, and patients can be safely monitored.
- Consider oral replacement (Calcium carbonate)
- Moderate-Severe/Symptomatic (Ionized Ca: <0.99 mmol/L)
- Intravenous Calcium: (1 g Calcium Chloride = 3 g Calcium Gluconate)
Hypomagnesemia: Will delay resolution of Hypocalcemia
Hyperphosphatemia: Risk of calciphylaxis with calcium replacement.
- The incidence of hypocalcemia in critically ill patients is variable depending on underlying disease process and comorbid conditions; however, it is a commonly observed occurrence.
- Clinical features of hypocalcemia may include tetany, seizures and cardiovascular abnormalities such as reduced cardiac output and life-threatening arrhythmias
- The approach to treatment should place emphasis on overall calcium homeostasis and how it may be impaired in the affected patient