Calcium and Magnesium Disorders - Dr Gayathri

Introduction The disorders of mineral metabolism, collectively include abnormalities of calcium, phosphorus and magnesium homeostasis. Calcium and, to a lesser extent, magnesium balance is achieved through a complex interplay between the parathyroid gland, bone, the intestine and the kidney. Ref: Disorders of calcium and magnesium balance: a physiology-based approach Pediatric Nephrology, August 2013, Volume 28, Issue 8, pp 1195–1206

CASE 1 70 hours old, Preterm 36 wks male infant was brought with multifocal clonic convulsions no fever, taking breastfeed well, no h/o top feeding BW - 2.4 kg, BCIAB O/E baby is alert, slightly jittery, AF is at level Tachycardia+ perfusion is good, No focal neurological deficits Inv - GRBS - 92 mg/dl, SE, CBC, Ca sent DD’s?? iCa - 3 mg/dl

Calcium in Newborns Last trimester calcium is actively transferred mother to the fetus high level of total calcium concentration in cord blood compared to maternal serum. Serum calcium (SCa) in the fetus is 10-11 mg/dL at term (1-2 mg higher as compared to mother). Parathyroid hormone (PTH) and calcitonin (CT) do not cross the placental barrier. The PTH related peptide (PTHrP) is the main regulator of the positive calcium balance across the placenta. Early onset hypocalcemia (within 72 hrs) requires treatment for at least 72 h. Late onset hypocalcemia usually presents after 7 days and requires longer term therapy

Hypocalcemia in Newborns Hypocalcemia is a frequently observed clinical and laboratory abnormality in neonates. (Ionic calcium is crucial for many biochemical processes including blood coagulation, neuromuscular excitability, cell membrane integrity, and many of the cellular enzymatic activities). Healthy term infants undergo a physiological nadir in serum calcium levels by 24-48 h of age. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia.

Causes of early onset hypocalcemia Prematurity Preeclampsia Infant of Diabetic mother Perinatal stress/ asphyxia Maternal intake of anticonvulsants (phenobarbitone, phenytoin sodium) Maternal hyperparathyroidism Iatrogenic (alkalosis, use of blood products, diuretics, phototherapy, lipid infusions etc

Diagnosis Laboratory: Total or ionized serum calcium (total <7mg/dl or Ionized < 4mg/dl) ECG: Q0TC >0.22 s or QTc >0.45s (QT interval is measured from origin of q wave to end of T wave on ECG; QoT is measured from origin of q wave to origin of T wave). A diagnosis of hypocalcemia based only on ECG criteria is likely to yield a high false positive rate. Although these parameters have good correlation with hypocalcemia in low birth weight infants (sensitivity of 77% and specificity of 94.7%) [8], neonates suspected to have hypocalcemia by ECG criteria should have the diagnosis confirmed by measurement of serum calcium levels.

Management of early neonatal hypocalcemia (1 ml of calcium gluconate (10%) gives 9 mg of elemental calcium) Total Serum Calcium levels < 7mg/dL Symptomatic Bolus of 2 mL/kg calcium gluconate 1:1 diluted with 5 % dextrose over 10 minutes under cardiac monitoring Asymptomatic 80 mg/kg/day for 48 hrs (8 mL/kg/day of 10% calcium gluconate ) F/b continuous infusion of 80mg mg/kg/day for 48 hrs (8 mL/kg/day of 10% calcium gluconate ) Document normal calcium at 48 hrs Taper to 40 mg/kg/day for one day, then stop Then taper to 40 mg/kg/day for one day,then stop

Prophylactic In Preterm< 32 wk, sick IDM, severe asphyxia etc., 40 mg/kg/day for 3 days (4ml/kg/day of 10% calcium gluconate ) IV or oral if can tolerate per oral treatment is for 72 hrs. Continuous infusion is better than bolus. Symptomatic babies treatment is 48 hrs continuous infusion. In case the hypocalcemia does not correct with the above by 72 hrs then investigate for causes of late hypocalcemia.

Precautions and side effects Bradycardia and arrhythmia are known side effects of bolus IV calcium administration. Hence, bolus doses of calcium should be diluted 1:1 with 5% dextrose and given slowly (over 10 to 30 min) under cardiac monitoring. Umbilical artery catheter (UAC) should never be used for giving calcium injections. Accidental injection into the UAC may result in arterial spasms and intestinal necrosis. Skin and subcutaneous tissue necrosis may occur due to extravasation. Ref: Hypocalcemia in the Newborn, Indian J Pediatr (2010) 77:1123–1128

Late onset neonatal hypocalcemia (LNH) This condition is rare as compared to ENH. It usually presents at the end of the first week of life. It is usually symptomatic in the form of neonatal tetany or seizures. This is usually caused by high phosphate intake (iatrogenic) Such babies should have an examination with special emphasis on cataracts, hearing problems, and any evidence of basal ganglia involvement (movement disorder).

Treatment of LOH The treatment of LNH is specific to etiology and may in certain diseases be life-long: 1. Hypomagnesaemia: Symptomatic hypocalcemia unresponsive to adequate doses of IV calcium therapy is usually due to hypomagnesaemia. It may present either as ENH or later as LNH. The neonate should receive 2 doses of 0.2 mL/kg of 50% MgSO4 injection, 12 h apart, deep IM followed by a maintenance dose of 0.2 mL/kg/day of 50% MgSO4, PO for 3 days. 2. High phosphate load: These infants have Hyperphosphatemia with near normal calcium levels. Exclusive breast-feeding should be encouraged and top feeding with cow’s milk should be discontinued. Phosphate binding gels should be avoided.

Treatment of LOH 3. Hypoparathyroidism: These infants tend to be hyperphosphatemic and hypocalcemic with normal renal function. These neonates need supplementation with calcium (50 mg/kg/day in 3 divided doses) and 1,25(OH)2 Vitamin D3 (0.5-1 μg/day). Syrups with 125 mg and 250 mg per 5 ml of calcium are available.1,25(OH)2 vitamin D3 (calcitriol) is available as 0.25 μg capsules. 4. Vitamin D deficiency states: These babies have hypocalcemia associated with Hypophosphatemia due to an intact parathormone response on the kidneys. They benefit from Vitamin D3 supplementation in a dose of 30-60 ng/kg/day

atypical cells, diminished plt CASE 2 10 year old girl recently diagnosed with ALL and planned for hydration f/b chemotherapy had pain abdomen, lethargy & myalgia. She was dehydrated and found to have a urine output of 6 ml/kg/hr. Hydration was started, flow cytometry was awaited. She was febrile and started having nausea/vomiting Blood urea - 54 mg/dl Creat - 0.8 mg/dl Na - 134 meq/dl K - 4.8 meq/dl Cl- 108 meq/dl Ca - 14.5 mg/dl PO4 - 7 mg/dl UA - 5.6 mg/dl Hb - 9.1 g/dl TLC - 64,000/mm3 Plt- 85,000/mm3 PS - NCNC, atypical cells, diminished plt Ca - 14.5 mg/dl

Causes of Hypercalcemia Hypercalcemia occurs in association with : Hematologic cancers, including lymphoma and acute leukemia, Rhabdomyosarcoma, Hepatoblastoma, Some Brain Tumors and Neuroblastoma.

Hypercalcemia Symptoms of hypercalcemia are dependent on both the serum level of calcium and the rate of rise. With mild hypercalcemia (<12 mg per deciliter [3 mmol per liter]), patients are usually asymptomatic. With moderately elevated calcium levels (12.0 to 13.5 mg per deciliter [3.0 to 3.4 mmol per liter]), weakness, anorexia, constipation, polyuria and polydipsia due to intravascular volume contraction usually develop. Severe hypercalcemia (>13.5 mg per deciliter) can manifest as a life-threatening metabolic emergency with cardiac and central nervous system effects including encephalopathy, seizure, and coma.

Management of Hypercalcemia 1.  Vigorous hydration with normal saline: replenishes intravascular volume, dilutes the serum calcium, and enhances renal calcium excretion 2.  If calcium levels remain elevated after volume repletion, administering furosemide to enhance calciuresis is recommended. 3. ?? Role of Bisphonates (pamidronate or zolendronate)

CASE 3 4 year old boy with ℅ not gaining weight and height. Has not yet attained full bladder control but mother feels that he passes urine quite frequently. Gets easily fatigued and cannot catch up with friends of his age during play. Past h/o seizure when mother was told that baby’s calcium was low and had been treated with Calcium & vitamin D. On examination he is lethargic, has FTT and BP is around 50th centile. Has Urine Output - 6 ml/kg/hr

Investigations Hb - 8.2 g/dl TLC - 10400/mm3 Plt - 1.8 lac/mm3 Blood urea - 11 mg/dl Creatinine - 0.4 mg/dl Na -136 K - 3.2 mg/dl pH - 7.49 pO2 - 89 mm Hg pCO2 - 48 mm Hg HCO3 - 32 BE - 8 iCa - 3.2 mg/dl Mg - 1.2 mg/dl

Hypomagnesaemia with secondary Hypocalcemia(HSH) HSH, also called primary intestinal hypomagnesaemia, is an autosomal-recessive disorder that is characterized by very low serum magnesium levels and low calcium levels. Mutations in the gene encoding for TRPM6, the active magnesium transporter in the DCT, have been identified. Patients usually present within the first 3 months of life with the neurologic symptoms of hypomagnesaemia hypocalcemia, including seizures, tetany, and muscle spasms. Usually, the hypocalcemia is resistant to calcium or vitamin D therapy. Normocalcemia and relief of clinical symptoms can be attained by administration of high oral doses of magnesium. As large oral amounts of magnesium may induce severe diarrhea and noncompliance in some patients, parenteral magnesium administration must sometimes be considered.

Bartter syndrome: It is an Autosomal Recessive disorder which is caused by mutations of genes encoding proteins that transport ions across renal cells in the thick ascending loop of the nephron. It is characterized by  Hypokalemia, Hyporeninemia, Metabolic alkalosis, Hyperaldosteronism, normal to low blood pressures, and urinary wasting of K, Na &Cl. Treatment consists of Potassium supplements and NSAIDs, Magnesium supplementation Gitelman syndrome: It is an Autosomal Recessive disorder characterized by Hypokalemia and Hypomagnesaemia, decreased calcium excretion in the urine, and Metabolic alkalosis. Potassium and Magnesium supplementation to normalize low blood levels of potassium and magnesium is the mainstay of treatment

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