Chapter outlines
| Basic Physiology |
| Distribution |
| Serum calcium |
| Ionized calcium |
| Corrected total calcium |
| Regulation |
| Role of parathyroid hormone |
| Role of vitamin D |
| Role of calcitonin |
| Calcium sensing receptor system |
| Effect of pH |
| Effect of phosphate and magnesium level |
| HYPOCALCEMIA |
| Etiology |
| Postsurgical |
| Vitamin D deficiency |
| Acute pancreatitis |
| Clinical Features |
| Diagnosis |
| History and physical examination |
| Confirm the diagnosis |
| Measure serum PTH |
| Measure serum phosphate, magnesium, and vitamin D status |
| Order other tests |
| Management |
| Acute management |
| - Emergency therapy |
| - Calcium gluconate infusion |
| - Monitoring |
| - Calcium chloride |
| - Massive transfusion |
| - Precautions |
| Long term management |
| - Calcium supplementation |
| - Vitamin D supplementation |
| Treatment of underlying etiology |
BASIC PHYSIOLOGY
Calcium (Ca) is essential for bone formation, neuromuscular function, and blood coagulation. If calcium intake is inadequate, it may impair bone mineralization in children and accelerate bone loss in adults.
Distribution
An average adult’s body contains 20 to 25 gm/kg or 1.2 to 1.4 kg of calcium, so it is the most abundant cation in the body. Out of this, about 99% is present in the bone, 1% in the soft tissue cells, and 0.15% in the extracellular fluid (ECF). As serum calcium concentration constitutes less than 1% of the total body calcium, it is a poor marker of overall total body calcium content.
Serum calcium
The normal value is about 8.5 to 10.5 mg/dL (4.3 to 5.2 mEq/L, 2.2 to 2.6 mmol/L). The total ECF calcium exists in three forms:
- Bound to proteins: About 40% of calcium is bound to protein (mainly albumin) which will not be diffusible and biologically active.
- Free-ionized: 50% of calcium is in an ionized form which is diffusible and biologically active.
- Bound to anions: 10% calcium is complexed with the anions of organic acids such as phosphate, bicarbonate, citrate, lactate, or sulfate phosphate. This form of calcium is diffusible but biologically inactive.
REFERENCES
- Steen O, Clase C, Don-Wauchope A. Corrected calcium formula in routine clinical use does not accurately reflect ionized calcium in hospital patients. Can J Gen Int Med. 2016;11(3):14–21.
- Lian IA, Asberg A. Should total calcium be adjusted for albumin? A retrospective observational study of laboratory data from central Norway. BMJ Open. 2018;8(4):e017703.
- Kenny CM, Murphy CE, Boyce DS, et al. Things We Do for No Reason™: Calculating a “Corrected Calcium” Level. J Hosp Med. 2021;16(8):499–501.
- Conigrave AD. The Calcium-Sensing Receptor and the Parathyroid: Past, Present, Future. Front Physiol. 2016;7:563.
- Witteveen JE, van Thiel S, Romijn JA, et al. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol. 2013;168(3):R45–53.
- Kaya C, Tam AA, Dirikoç A, et al. Hypocalcemia development in patients operated for primary hyperparathyroidism: Can it be predicted preoperatively? Arch Endocrinol Metab. 2016;60(5):465–471.
- Jain N, Reilly RF. Hungry bone syndrome. Curr Opin Nephrol Hypertens. 2017;26(4):250–255.
- Kelly A, Levine MA. Hypocalcemia in the critically ill patient. J Intensive Care Med. 2013;28(3):166–77.
- Ahmed A, Azim A, Gurjar M, et al. Hypocalcemia in acute pancreatitis revisited. Indian J Crit Care Med. 2016;20(3):173–177.
- Cooper MS, Gittoes NJL. Diagnosis and management of hypocalcaemia. BMJ 2008;336:1298–1302.
- Pepe J, Colangelo L, Biamonte F, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020;69(3):485–495.
- Kakava K, Tournis S, Papadakis G, et al. Postsurgical Hypoparathyroidism: A Systematic Review. In Vivo. 2016;30(3):171–9.
- Augustine M, Horwitz MJ. Are You Sure the Patient Has Hypocalcemia? Hypocalcemia Endocrinology Metabolism, Endocrinology Adviser February 4, 2019. Accessed on 27 Nov 2021: https://www.endocrinologyadvisor.com/author/mara-j-horwitz-dsm/.
- Walsh J, Gittoes N, Selby P. Society for Endocrinology Endocrine Emergency Guidance: Emergency management of acute hypocalcemia in adult patients. Endocr Connect. 2016;5(5):G9‒G11.
- Bove-Fenderson E, Mannstadt M. Hypocalcemic disorders. Best Pract Res Clin Endocrinol Metab. 2018;32(5):639–656.
- Byerly S, Inaba K, Biswas S, et al. Transfusion-Related Hypocalcemia After Trauma. World J Surg. 2020;44(11):3743–3750.
- Hall C, Nagengast AK, Knapp C, et al. Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines. Transfusion. 2021;61:S188–S194.
- Kyle T, Greaves I, Beynon A, et al. Ionised calcium levels in major trauma patients who received blood en route to a military medical treatment facility. Emerg Med J. 2018;35(3):176–179.
- Fong J, Khan A. Hypocalcemia: updates in diagnosis and management for primary care. Can Fam Physician. 2012;58(2):158–62.
- Mannstadt M, Clarke BL, Vokes T, et al. Efficacy and safety of recombinant human parathyroid hormone (1–84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol 2013;1(4):275–83.
- Vokes TJ, Mannstadt M, Levine MA, et al. Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults with Chronic Hypoparathyroidism. J Clin Endocrinol Metab. 2018;103(2):722–731.
- Mannstadt M, Clarke BL, Bilezikian JP, et al. Safety and efficacy of 5 years of treatment with recombinant human parathyroid hormone in adults with hypoparathyroidism. J Clin Endocrinol Metab. 2019;104(11):5136–5147.
- Laurer E, Grünberger J, Naidoo U, et al. Recombinant human parathyroid hormone (1–84) replacement therapy in a child with hypoparathyroidism. Bone. 2021;144:115834.