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Questions and Answers
What is hypocalcemia?
What is hypocalcemia?
Decreased total serum calcium level below 8.5 mg/dL (corrected for albumin) or serum calcium level below 4.65 mg/dL.
The ______ is calculated using the formula: measured total calcium level + (0.8 × [4 − measured albumin level in g/dL]).
The ______ is calculated using the formula: measured total calcium level + (0.8 × [4 − measured albumin level in g/dL]).
corrected total calcium level
What are the two forms of serum calcium?
What are the two forms of serum calcium?
Calcium in the serum constitutes more than 1% of total body calcium.
Calcium in the serum constitutes more than 1% of total body calcium.
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What role does phosphate play in the body?
What role does phosphate play in the body?
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Which condition can lead to early onset neonatal hypocalcemia?
Which condition can lead to early onset neonatal hypocalcemia?
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Which syndrome is characterized by congenital heart disease and hypocalcemia?
Which syndrome is characterized by congenital heart disease and hypocalcemia?
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Permanent hypoparathyroidism is defined as hypoparathyroidism persisting for 12 months after onset.
Permanent hypoparathyroidism is defined as hypoparathyroidism persisting for 12 months after onset.
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What are some causes of hypocalcemia in infants?
What are some causes of hypocalcemia in infants?
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Approximately 50% of magnesium is found in ________.
Approximately 50% of magnesium is found in ________.
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Study Notes
Hypocalcemia Definition
- Hypocalcemia is defined as a total serum calcium level below 8.5 mg/dL (corrected for albumin) or a serum calcium level below 4.65 mg/dL (1.16 mmol/L)
- Corrected total calcium level = measured total calcium level + (0.8 × [4 − measured albumin level in g/dL])
- A total serum calcium level between 7.6 mg/dL to 8.5 mg/dL may be symptomatic
- Hypocalcemia below the reference range can be asymptomatic or severe
Calcium Metabolism and Function
- 99% of the body's calcium is stored in bones
- Serum calcium can be present in free (ionized, 50%) or bound form (either bound to proteins, 40% or complexed with bicarbonate, citrate, and phosphate, 10%)
- Calcium plays critical roles in:
- Cellular function regulation by acting as a messenger system
- Activating cellular enzyme cascades
- Smooth muscle and myocardial contraction
- Nerve impulse conduction
- Secretory activity of exocrine glands
Magnesium
- Magnesium is found in bone (50%) and soft tissues (50%)
- Half of the magnesium in bone is readily exchangeable with the extracellular fluid, acting as a buffer against changes in extracellular magnesium concentration
Phosphate Metabolism
- 85% of phosphate is located in the mineral phase of bone, while the rest is found in inorganic or organic form in extracellular and intracellular compartments
- Phosphate levels in the blood are regulated by growth factors, such as insulin-like growth factor 1 (IGF1) and hormones of bone mineralization
- Phosphate plays a crucial role in numerous kinase and phosphatase regulatory cascades
Etiology: Early Onset Neonatal Hypocalcemia
- Occurs within 48-72 hours of birth
- Causes:
- Prematurity: inadequate nutritional intake, decreased parathyroid hormone response to vitamin D, increased calcitonin levels
- Birth asphyxia: delayed feeding, increased calcitonin production, increased endogenous phosphate load
- Infants of diabetic mothers: maternal magnesium depletion causes hypomagnesemia in the fetus, leading to functional hypoparathyroidism and hypocalcemia in the infant
- Intrauterine growth restriction: decreased transplacental passage of calcium
Etiology: Late-Onset Neonatal Hypocalcemia
- Occurs 3-7 days after birth, occasionally as late as 6 weeks
- Causes:
- Exogenous phosphate load: common in developing countries, due to phosphate-rich formula or cow's milk feeding
- Vitamin D deficiency: vitamin D insufficiency or deficiency and hypomagnesemia
- DiGeorge syndrome: primary immunodeficiency disorder characterized by cellular (T-cell) deficiency, facial features, congenital heart disease, and hypocalcemia
Etiology: Hypocalcemia in Infants and Children
- Hypoparathyroidism
- Post surgical hypoparathyroidism: most common cause of chronic hypocalcemia
- Transient: parathyroid function recovers within 12 months after parathyroid surgery
- Permanent: hypoparathyroidism persists beyond 12 months after onset
- Aplasia or hypoplasia of parathyroid gland: DiGeorge syndrome, Haploinsufficiency of GATA3 transcription factor causes HDR syndrome
- Autoimmune parathyroiditis: autoimmune polyendocrine syndrome type 1
- Infiltrative lesions: Hemosiderosis, Wilson disease, thalassemia
- Idiopathic causes
- Post surgical hypoparathyroidism: most common cause of chronic hypocalcemia
Genetic Parathyroid Disorders
- Disorders of Parathyroid Gland Formation:
- Tbx1 transcription factor loss in 22q11 deletion syndrome (DiGeorge syndrome, velocardiofacial syndrome) likely causes hypoparathyroidism in this syndrome
- CHARGE syndrome: rare disorders with phenotypic overlap between 21q11DS and HDR, caused by SEMAE3 or CHD7 mutations
- Haploinsufficiency of the transcription factor GATA3: causes the HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome
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