Prolonged low serum ionized calcium can cause life-threatening cardiovascular events
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
AGD Biomedicals (Pvt) LTD.
Serum free (ionized) calcium deficiency can cause a prolongation of the QT interval on an electrocardiogram (ECG); which can predispose individuals to dangerous Torsades de Pointes (TdP), a form of polymorphic ventricular arrhythmia (Fig,1)(2,3,4). Symptoms of TdP include pain in the chest, dizziness, palpitations, slow heart rate, fainting and sudden cardiac death. Common causes of Torsades de pointes include hypoparathyroidism, untreated severe prolonged diarrhea, alkalosis, severe renal disease, and it could be drug-induced(1,8). Hypocalcemia-induced TdP can be observed mainly in the case of children, which manifest as central nervous system irritability, seizures, tetany, paresthesia, changes in cardiac function and psychiatric changes (10). In respiratory alkalosis, total serum calcium may be normal, however, ionized calcium can be significantly low, indicating true hypocalcemia(9). Electrolyte analyzer (e.g. AGD EL-120), with the facility to offer determination of serum free calcium in few minutes could be a lifesaving asset for any clinical laboratory.
Note : Chronic alcoholics, drug-abused and malnourished patients may suffer due to severe deficiency in serum calcium, potassium and magnesium(1,9)
Q1. How serum or plasma total calcium level may stay normal during respiratory alkalosis?
ANS: In respiratory alkalosis blood pH increases significantly. To maintain homeostasis, in the process of restoring blood pH, hydrogen ions bound to serum albumin are released in blood, while equal amount of free calcium ions bind tightly to serum albumin, leading to decrease in free serum (or plasma) calcium.
Q2. What is Torsades de pointes?
ANS: Torsades de pointes (TdP) is a specific type of polymorphic ventricular tachycardia (an irregular and rapid heartbeat originating in the ventricles) that is characterized by a distinctive twisting or oscillatory pattern of QRS complexes on an electrocardiogram (ECG)(Fig,1).
Note :
(A) “Torsades de pointes” is a French term. It is associated with a prolonged QT interval, either congenital or acquired. TdP may degenerate into ventricular fibrillation, which is a life-threatening condition that can lead to sudden cardiac death.
(B) The QRS complex on an electrocardiogram (ECG) represents the depolarization of the ventricles of the heart. This depolarization causes the ventricles to contract, leading to the initiation of systole. The QRS complex specifically appears as a sharp and prominent spike on the ECG. (Fig. 1).
Fig 1: Normal ECG and Torsades de pointes ECG
Q3. What is the role of calcium in regulating electrical activity of heart?
ANS: Calcium plays very important role in the regulation of the electrical activity of the heart.
Q4. How the function of the heart gets disturbed in hypocalcemia?
ANS : In hypocalcemia, the ability of the heart muscle to contract and relax properly is disrupted, which may lead to abnormal heart rhythms.
CASE STUDY – 1
A 14-year-old male child presented with generalized weakness, unable to get up from bed, with history of arrythmia, seizures and abnormal body movements in the form of spasms of hands; lasting for few minutes and subsiding subsequently. He did not respond to calcium supplementation. On admission to emergency room his physical examination findings were as follows: Body temperature 980 F, pulse rate of 65 beats/min, and blood pressure 110/60. Electrocardiogram (EKG) showed normal sinus rhythm with a prolonged QT interval. His laboratory reports related to serum electrolyte profile were as follows:
| TEST | RESULT | REFERENCE RANGE |
| Serum sodium | 135 mEq/l | 133–146 mEq/l |
| Serum potassium | 4.3 mEq/l | 3.8–5.6 me/l |
| Serum chlorides | 101 mEq/l | 95–106 mEq/l |
| Serum calcium corrected (Total) | 6.3 mg/dl | 9.5-10.5 mg/dl |
| Serum ionized calcium | 2.9 mg/dl | 4.6-5.3 mg/dl |
| Serum inorganic phosphorus | 10.4 mg/dl | 4.6-5.3 mg/dl |
| Serum parathyroid hormone | 145 ng/l | 4.0-7.0 mg/dl |
| Serum alkaline phosphatase (ALP) | 430 IU | 93-221 IU |
| Vitamin D | 10 ng/ml | 10-65 ng/ml |
Q5. What is the probable diagnosis?
ANS : Significantly low values of serum corrected total calcium, ionized calcium, increased inorganic phosphorus and serum ALP indicate a case of severe hypocalcemia due to hypoparathyroidism.
Note :
(A) Parathyroid glands are situated behind the thyroid gland. Parathyroid hormone plays important role in the control of metabolism of calcium and inorganic phosphorus by controlled absorption of calcium and controlled excretion of inorganic phosphorus. In hypoparathyroidism, very low values of serum calcium and high values of serum inorganic phosphorus are observed.
(B) Parathyroid gland damage may result from self-autoantibodies, tumours, or injury.
Q6. What is the biochemical basis for a prolonged QT interval in ECG?
ANS : A prolonged QT interval in ECG was observed due to prolonged very low ionized serum calcium level.
Q7. What is the probable first line treatment.
ANS : Immediate restoration of serum ionized calcium and total calcium using intravenous sodium gluconate, ionized calcium can be restored in due course of time to normal, with total calcium.
Note :
For the determination of accurate and precise total (corrected) and ionized serum calcium the following precautions are necessary(9):
(A) Torniquet should not be used for fixing the desired vein. Instead, hand grip should be used for very short duration and it is released as soon as blood enters the container.
(B) Blood collection should be performed using evacuated tubes or plastic tubes, which are filled completely.
(C) Serum or heparinized plasma should be separated within 30-45 minutes of blood collection and test should be performed as early as possible.
(D) Cap of the blood collection tube 0r container should be placed tightly.
(E) Hemolyzed, lipemic and icteric samples are not preferred.
(F) Separated serum or plasma is stable at 2-80 C for 1 hour and at 0-40 for 4 hours.
Q8. What is the reason for the determination of corrected serum (or plasma) total calcium and how it is determined?
ANS : Total serum (or plasma) total calcium may vary according to the concentration of serum albumin value, since about 40% of total calcium is bound to serum albumin. Corrected serum (or plasma) total calcium is calculated using the following equation:
Corrected serum (or plasma) total calcium = Total calcium, mg/dl + 0.8 (4-serum albumin, g/dl)
NOTE:
Calcium present in serum or plasma: 50% as ionized calcium, 40% as bound to serum albumin and 10% bound to small molecules such as bicarbonate, phosphate, lactate and citrate).
CASE STUDY – 2
A 60-year-old woman was admitted to hospital following severe muscular weakness and inability to get up from bed. Her blood examination reports related to electrolytes were as follows:
| TEST | RESULT | REFERENCE RANGE |
| Serum sodium | 130 mEq/l | 133–146 mEq/l |
| Serum potassium | 2.3 mEq/l | 3.8–5.6 mEq/l |
| Serum chlorides | 98 mEq/l | 95–106 mEq/l |
Q9. What is the probable diagnosis?
ANS : From the case history it was found out that she had a habit of taking large amounts of purgatives to get rid of constipation. Frequent loss of body fluids due to excessive intake of purgatives, lead to drug-induced hypokalemia (Low levels of serum potassium).
Q10. What is the biochemical basis for severe muscular weakness in this case?
ANS : Hypokalemia is associated with malaise, cramping, myalgias, and weakness.
Q11. What is the probable first line treatment?
ANS : Immediate stoppage of purgatives, suggested dose of electrolytes and support of dietary intake of foods rich in potassium: Potatoes, bananas, spinach, nuts, dried fruits, etc.
References
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(2) Bradley TJ, Metzger DL, Sanatani S: Long on QT and low on calcium . Cardiol Young. 2004, 14:667-70. 10.1017/S1047951104006134
(3) Fernando MP, Perera PJ, Muthukumarana OJ, Uyangoda K: Hypocalcaemia leading to supra ventricular tachycardia in a three-month old Sri Lankan infant with vitamin D deficient rickets: A case report. Ceylon. Med J. 2017, 62:242-43. 10.4038/cmj.v62i4.8576
(4) Nijjer S, Ghosh AK, Dubrey SW: Hypocalcaemia, long QT interval and atrial arrhythmias . BMJ Case Rep. 2010, 2010:bcr0820092216. 10.1136/bcr.08.2009.2216
(5) Singhi A: Simultaneous presence of atrial arrhythmia and hypocalcemia in dilated cardiomyopathy: a series of two cases. J Indian Coll Cardiol. 2021, 11:201-4.
(6) Locker FG: Hormonal regulation of calcium homeostasis . Nurs Clin North Am. 1996, 31:797-803.
(7) Sualeha Khalid , Isam Albaba , Kristofer Neu. Hypocalcemia: A little known cause of supraventricular tachyarrhythmia internal medicine, Stratton VA Medical Center, Albany, USA. Open access case report. DOI: 10.7759/cureus.38456
(8) O. Mukarram, Y. Hindi, G. Catalasan, and J.Ward. Loperamide Induced Torsades de Pointes: A Case Report and Review of the Literature. Hindawi Publishing Corporation. Case Reports in Medicine.Volume 2016, Article ID 4061980, 3 pages. http://dx.doi.org/10.1155/2016/4061980
(9) Godkar PB, Godkar DP. Text book of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.
(10) P. Purohit, D. Khera, K. Sing. Hypocalcemia in an 11 Year Old Child: A Difficult Case to Treat. Ind J Clin Biochem (Oct-Dec 2018) 33(4):489–490. https://doi.org/10.1007/s12291-018-0744-z
