hypocalcemia.10.10.pptx,hypomagnesemia.children

Hypocalcemia and management

1. Roles of Calcium and magnesium in pediatric health and disease Dr Sarfaraz Ahmad Assistant professor pediatrics

2. Calcium and magnesium are critical minerals for pediatric health, supporting bone development, neurodevelopment,neuromuscular function, cardiovascular function & metabolic processes. RDAs, established by the Institute of Medicine (IOM) and the European Food Safety Authority (EFSA), reflect needs for 97-98% of healthy children, factoring in bioavailability (calcium: 20-40% from food; magnesium: 30-50%).

3. Recommended Dietary Allowances (RDAs)

4. Dietary Sources of calcium and magnesium Calcium: Dairy: Milk (300 mg/cup), yogurt (200-400 mg/cup), cheese (200-300 mg/oz). Bioavailability ~30-35%. Non-dairy: Fortified plant milks/juices (100-300 mg/cup), kale (100 mg/cup), broccoli (50 mg/cup), tofu (200-400 mg/½ cup), almonds (75 mg/oz). Bioavailability lower (5-20%) due to oxalates/phytates. For Neonates/Infants: Human milk (200-250 mg/L), fortified formula (400-600 mg/L). Absorption enhanced by lactose/vitamin D. Magnesium: Nuts/seeds: Almonds (80 mg/oz), pumpkin seeds (150 mg/oz). Whole grains: Oats (50 mg/cup), brown rice (80 mg/cup). Legumes: Black beans (120 mg/cup). Leafy greens: Spinach (80 mg/cup). Dark chocolate (50 mg/oz). Bioavailability ~30-50%; reduced by refining (up to 80% loss). Neonates/Infants: Human milk (30-35 mg/L), formula (40-60 mg/L).

5. Importance of Calcium and Magnesium in Pediatrics Calcium is essential for: Bone mineralization: Approximately 99% of the body’s calcium is stored in bones and teeth as hydroxyapatite, critical during rapid growth phases (infancy, childhood, adolescence). Muscle function, nerve signaling, and blood clotting: Calcium plays a role in intracellular signaling and physiological processes. Pediatric-specific needs: Children require adequate calcium to achieve peak bone mass, reducing the risk of osteoporosis later in life. Inadequate intake during growth spurts can lead to rickets (in young children) or reduced bone density.

6. Magnesium is vital for: Enzyme function: Magnesium is a cofactor in over 300 enzymatic reactions, including energy metabolism and DNA synthesis. Bone health: About 60% of magnesium is stored in bones, contributing to their structure and strength. Neuromuscular and cardiovascular function: Magnesium stabilizes membranes and regulates muscle contractions and prevents arrhythmias. Pediatric-specific needs: Magnesium supports growth, neurological development, and immune function. Deficiency can lead to muscle cramps, fatigue, or, in severe cases, arrhythmias or seizures.

7. Roles of calcium in pediatric health Structural functions: More than 99% of the body’s calcium is stored in the bones and teeth as hydroxyapatite crystals. It provides strength and rigidity to the skeleton and teeth. During puberty, about 40% of adult bone mass(PBM) is formed — hence, adequate calcium intake during this phase is crucial for skeletal growth. Peak bone mass is typically reached by late adolescence, and achieving a higher peak bone mass helps reduce the risk of fractures & osteoporosis later in life.

8. Physiological Functions of calcium The remaining 1% of calcium circulates in the extracellular fluid, playing vital roles in: Muscle contraction (including the heart muscle). Nerve impulse transmission. Blood coagulation – calcium acts as Factor IV in the clotting cascade. Hormone secretion, e.g., parathyroid hormone (PTH) and calcitonin. Inside cells (intracellular Ca²⁺), calcium acts as a signaling molecule, essential for processes such as insulin release and enzyme activation.

9. Studies show that a dietary intake of 1,000–1,300 mg/day of calcium children is associated with: 5–10% higher bone mineral density (BMD) 20–30% lower risk of fractures in children and adolescents.

10. Disease association of calcium Deficiency: Rickets ( vitamin D-dependent or due to hypocalcemia) Growth retardation and delayed skeletal development Seizures due to neuronal membrane stability. Osteopenia and increased bone fragility In neonates, calcium deficiency may worsen outcomes in (HIE) because of impaired neuronal stability. Excess Intake (>2,500 mg/day): Can lead to hypercalciuria (high urinary calcium), nephrocalcinosis (calcium deposits in kidneys), and vascular calcification. Low calcium intake, on the other hand, has been linked to hypertension (due to altered vascular tone) and obesity (through effects on fat metabolism and lipogenesis).

11. Roles of magnesium in pediatric health Magnesium (Mg²⁺) is the fourth most abundant cation in the body and the second most abundant intracellular cation after potassium. It plays crucial roles in energy metabolism, enzyme activity, and neuromuscular function. About 50–60% of total body magnesium is stored in bone, while the rest is in muscle and soft tissues; less than 1% is extracellular.

12. Enzymatic roles of magnesium Magnesium is a cofactor in >300 enzymatic reactions, particularly those involving ATP — as Mg-ATP complex, it stabilizes the phosphate groups for energy transfer. It’s required for DNA and RNA polymerases, stabilization of nucleic acids ,ribosomal stability, and protein synthesis. Regulates glycolysis and oxidative phosphorylation, hence low Mg leads to impaired ATP generation, cellular energy deficit, neuromuscular irritability, fatigue & poor growth.

13. Structural Roles 50–60% of magnesium is incorporated into the bone matrix, where it supports hydroxyapatite crystal formation and bone mineralization with calcium and phosphate, ensuring proper skeletal development in growing children. Deficiency disturbs calcium homeostasis and reduces bone density, predisposing to osteopenia and growth retardation. Magnesium influences osteoblast and osteoclast activity, promoting bone formation and remodeling.

14. Physiological & Cellular Functions Membrane stabilization: Mg²⁺ regulates calcium and potassium channels >maintaining cell membrane potential and electrical stability in cardiac,muscular and neuronal cells. Neuroprotection: Mg inhibits NMDA receptors, preventing excitotoxic calcium influx → protects neurons during hypoxia (HIE) or ischemia. Ion regulation: Mg controls K⁺ and Ca²⁺ channels, preventing arrhythmias and smooth muscle spasm. Anti-inflammatory effect: Suppresses NF-κB pathway, reducing production of pro-inflammatory cytokines (IL-6, TNF-α) in those at risk for chronic inflammation. In children, adequate Mg supports brain development, attention regulation & metabolic balance.

15. Dietary intake of 200–400 mg/day Mg improves metabolic and neurobehavioral outcomes. 10–15% reduction in ADHD symptoms observed with adequate magnesium levels (possibly via NMDA modulation and dopamine regulation). Enhances insulin sensitivity by acting on tyrosine kinase activity of insulin receptors. Reduces arrhythmia risk by stabilizing myocardial action potentials.

16. Disease association of Magnesium Attention-Deficit,Hyperactivity Disorder (ADHD): Up to 95% of children with ADHD show low red blood cell (RBC) magnesium levels. Mg2+ > NMDA and GABA receptors inhibition>increases neuronal excitability and dopaminergic dysregulation, worsening hyperactivity and impulsivity. Low Mg enhances catecholamine release (epinephrine, norepinephrine), which further heightens arousal and anxiety. Autism Spectrum Disorders (ASD): Mg deficiency amplifies neuronal hyperexcitability and oxidative stress in developing brain tissue. It impairs synaptic pruning and GABAergic inhibition, contributing to sensory overstimulation and stereotypic behaviors.

17. Insulin Resistance and Type 2 Diabetes: Magnesium is a cofactor for tyrosine kinase on the insulin receptor. Deficiency → ↓ insulin receptor phosphorylation → ↓ GLUT4 translocation to cell membrane → ↓ glucose uptake → insulin resistance> increased risk of type 2 diabetes in obese children Cardiac Arrhythmias (especially Torsades de Pointes): Mg stabilizes myocardial membranes by modulating Ca²⁺ and K⁺ channels.Deficiency → delayed repolarization → prolonged QT interval → Torsades de Pointes and ventricular tachycardia. Restoring Mg corrects repolarization abnormalities, especially in digitalis toxicity or hypokalemia.

18. In Chronic Kidney Disease (CKD) and Celiac Disease: Malabsorption or renal wasting causes hypomagnesemia, which suppresses parathyroid hormone (PTH) release. Pathophysiology: Mg is required for PTH secretion and receptor binding. Low Mg → functional hypoparathyroidism → ↓ Ca²⁺ reabsorption → hypocalcemia. Simultaneous impairment of Na⁺/K⁺-ATPase → hypokalemia (due to increased renal K⁺ loss). Neonatal Manifestations: Mg deficiency in neonates can cause tetany, apnea, jitteriness, and seizures. Mechanism: Immature calcium regulation and neuronal instability due to low Mg-mediated NMDA receptor control..

19. High dietary Ca:Mg ratio (>2:1) leads to competitive inhibition of magnesium absorption at intestinal TRPM6/7 transporters and in renal tubules. Consequences: Chronic imbalance decreases Mg bioavailability despite adequate intake. Resultant hypomagnesemia → reduced PTH secretion and end-organ resistance to PTH → functional hypoparathyroidism and hypocalcemia.

20. Pathophysiology, Causes, Clinical Features, Diagnosis, and Management of calcium Deficiency Pathophysiology: Calcium homeostasis involves PTH, vitamin D (1,25(OH)2D), and calcitonin. PTH increases bone resorption, renal Ca reabsorption, and 1,25(OH)2D synthesis (which enhances gut ca2+ absorption). Hypocalcemia results from: Inadequate Supply: Low intake, vitamin D deficiency (reduces absorption by 50-70%), or high phosphate (binds Ca in gut). Increased Loss: Renal (Fanconi syndrome, loop diuretics,CKD), gastrointestinal (celiac, IBD,CF). Endocrine Dysfunction: Hypoparathyroidism (DiGeorge, autoimmune), Mg deficiency (blocks PTH release/action), pseudohypoparathyroidism. Neonatal: Immature PTH/vitamin D axis in preterm, maternal vitamin D deficiency, hyperinsulinemia (IDM) reducing bone mobilization.

21. Causes of hypocalcemia in children Neonatal (Early: <72h): Early: Prematurity (low PTH responsiveness), IDM (insulin inhibits bone Ca release), asphyxia (HIE reduces hepatic 25-OH-D conversion), maternal hyperparathyroidism (fetal PTH suppression). Late: (Late: 4-28 days): Vitamin D deficiency (maternal, exclusive breastfeeding without 400 IU/d supplement), hypomagnesemia, high phosphate feeds, hypoparathyroidism (DiGeorge, 22q11 deletion), transient pseudohypoparathyroidism. Older Children: Low intake (<RDA), vitamin D deficiency (dark skin, low sun exposure), malabsorption (celiac, CF, short gut), renal loss (Fanconi, CKD), drugs (phenytoin, rifampin enhance vitamin D catabolism).

22. Clinical Presentation of hypocalcemia Asymptomatic Phase: Mild hypocalcemia:Usually in older Children Total Ca: 7.5–8 mg/dL,Ionized Ca: <4.4 mg/dL,Often detected incidentally on screening Symptomatic Phase: Neuromuscular:Tetany – carpopedal spasms, Chvostek’s & Trousseau’s signs. Seizures – focal/generalized. Jitteriness, poor feeding, lethargy,paresthesias. Respiratory: Apnea (especially in neonates) Cardiac Symptoms: arrhythmias or Dilated cardiomyopathy.

23. Clinical features of chronic hypocalcemia Rickets: Soft, deformable bones leading to bowed legs, frontal bossing, rachitic rosary (costochondral junction enlargement), delayed fontanelle closure, and fractures. Dental enamel defects: Hypoplasia or delayed tooth eruption due to impaired mineralization. Growth and developmental retardation. Osteopenia and fractures.

24. Clinical features of rickets Poor growth/short stature Frontal bossing of skull Craniotabes Delayed closure of anterior fontanelle Delayed dentition Enamel hypoplasia Rickety rosary Harrison sulcus Expansion of metaphyses (especially wrist) Bowing of weight-bearing bones Pathological fractures Hypotonia Delayed motor milestones Seizures Cardiomyopathy/heart failure

25. Diagnosis of hypocalcemia Labs: Total Ca <8 mg/dL (term) or <7 mg/dL (preterm); ionized Ca <4.4 mg/dL (term) or <4 mg/dL (preterm). Check: PTH: High in vitamin D deficiency; low in hypoparathyroidism. 25-OH-D: <20 ng/mL (deficient); <12 ng/mL (severe). Phosphate: High in hypoparathyroidism/vitamin D deficiency; low in Fanconi. Mg: Low Mg induces hypocalcemia. ALP: Elevated in rickets (>500 IU/L). Imaging: X-rays show widened metaphyses, frayed epiphyses in rickets. ECG: Prolonged QTc (>440 ms). Screening: Preterm/IDM/asphyxia at 24-48h; breastfed infants at 1-2 weeks; high-risk (celiac, CKD) annually.

26. Treatment of calcium deficiency in children Acute/Symptomatic: IV calcium gluconate 10% (100-200 mg/kg/d elemental Ca, 1-2 mL/kg slow bolus over 10-20 min, monitor ECG for bradycardia). Central line preferred to avoid tissue necrosis. If Mg low, correct first (inj MgSO4 25-50 mg/kg IV). Neonates: Continuous infusion (20-80 mg/kg/d elemental Ca) if seizures persist. Maintenance: Oral Ca (50-100 mg/kg/d elemental, e.g., carbonate/gluconate, divided doses). Vitamin D: 400 IU/d (prevention); 2,000-5,000 IU/d x 2-3 months for rickets, then 400-800 IU/d maintenance. Calcitriol (0.01-0.05 µg/kg/d) for hypoparathyroidism. Treat underlying cause: Mg for hypomagnesemia, gluten-free diet for celiac.

27. Magnesium Deficiency (Hypomagnesemia) Magnesium homeostasis involves intestinal absorption (30-50% via TRPM6/7 channels) and renal reabsorption (95% in thick ascending limb, DCT). Deficiency results from: Reduced Intake/Absorption: Low dietary Mg, malabsorption (celiac, IBD, short gut,CF), high Ca/phytate diets (compete for absorption),processed foods. Increased Loss: Renal (Bartter, Gitelman, diuretics,PPI), gastrointestinal (chronic diarrhea, pancreatitis),burns. Redistribution: Refeeding syndrome, hungry bone syndrome. Neonatal: Immature renal reabsorption, maternal diabetes (insulin-mediated loss), genetic (TRPM6 mutations in hypomagnesemia with secondary hypocalcemia, HSH).

28. Effects of hypomagnesemia Low Mg impairs PTH secretion/action (via G-protein-coupled signaling), causing hypocalcemia. Increases NMDA receptor activity (neuronal excitability), leading to seizures/tetany. Disrupts K+ channels, causing hypokalemia (resistant until Mg corrected). Chronic deficiency impairs growth, insulin signaling, and immune function.

29. Causes and clinical features of hypomagnesemia Hypomagnesemia, defined as serum magnesium levels below 1.5 mg/dl is a significant electrolyte disorder in children, particularly in neonates, critically ill patients, and those with malabsorption or renal disorders. Clinical Features: Asymptomatic: Mild (<1.5 mg/dL; 0.6 mmol/L). Symptomatic: Tremors, irritability, seizures (often refractory), tetany (via hypocalcemia), arrhythmias (torsades, VT). Neonates: Jitteriness, apnea, poor feeding. Chronic: Growth delay, ADHD-like behaviors, insulin resistance, fatigue. Associated: Hypokalemia (40-60% cases), hypocalcemia (50% cases due to PTH suppression).

30. Diagnosis of hypomagnesemia Labs: Serum Mg <1.6 mg/dL (0.7 mmol/L); ionized Mg <0.5 mmol/L (more accurate). RBC-Mg (1.5-2.5 mmol/L) reflects intracellular stores. Check: Ca, K: Low in secondary deficiencies. PTH: High if hypocalcemia secondary; low in HSH. Urine Mg: >2 mg/dL suggests renal wasting; <0.5 mg/dL in deficiency. Tests: Mg loading test (IV MgSO4 0.1-0.2 mmol/kg; >20% retention indicates deficiency). Screening: NICU (preterm, TPN) q24-48h; celiac/ADHD annually; ICU patients on diuretics.

31. Management approach to hypomagnesemia Acute/Symptomatic: IV MgSO4 (25-50 mg/kg elemental infusion); monitor Mg, Ca, RR for apnea risk). Neonates: 0.25-0.5 mEq/kg/d IV. Correct hypokalemia/hypocalcemia concurrently (KCl, Ca gluconate). Maintenance: Oral Mg (5-10 mg/kg/d elemental). HSH: High-dose (30-100 mg/kg/d lifelong). Dietary: Increase nuts, whole grains, greens. Avoid high Ca:Mg foods. Monitoring: Serum Mg, Ca, K q6-12h (IV), q24-48h (oral). ECG for arrhythmias. Reassess rickets/ADHD at 3-6 months. Prognosis: Seizures resolve within hours of correction; chronic deficiency may leave neurodevelopmental deficits if untreated.