Calcium and Magnesium Metabolism Quiz
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Questions and Answers

What is the definition of hypocalcemia in terms of serum calcium levels?

  • Serum calcium level below 5.0 mg/dL
  • Total serum calcium level above 10.0 mg/dL
  • Serum calcium level above 4.65 mg/dL
  • Total serum calcium level below 8.5 mg/dL (correct)

    • Which of the following is a critical function of serum calcium?

  • Regulation of blood sugar levels
  • Transport of oxygen in the blood
  • Synthesis of vitamin D
  • Activation of several cellular enzyme cascades (correct)

    • What percentage of total body calcium is stored in the bone?

  • 99% (correct)
  • 25%
  • 50%
  • 75%

    • Which form of calcium constitutes approximately 50% of serum calcium?

    <p>Free (ionized) form</p> Signup and view all the answers

    How much magnesium is found in bone?

    <p>50%</p> Signup and view all the answers

    What regulates phosphate levels in the blood during cell proliferation?

    <p>Insulin-like growth factor 1 (IGF1)</p> Signup and view all the answers

    What percentage of phosphate is located in the mineral phase of bone?

    <p>85%</p> Signup and view all the answers

    Which of the following is NOT a function of calcium in the body?

    <p>Regulation of blood pressure</p> Signup and view all the answers

    What is a primary cause of early onset neonatal hypocalcemia related to birth asphyxia?

    <p>Increased calcitonin production</p> Signup and view all the answers

    Which condition is associated with late-onset neonatal hypocalcemia?

    <p>Exogenous phosphate load</p> Signup and view all the answers

    What underlies the hypocalcemia seen in infants born to diabetic mothers?

    <p>Magnesium depletion causing functional hypoparathyroidism</p> Signup and view all the answers

    What is the most common cause of chronic hypocalcemia in infants?

    <p>Post surgical hypoparathyroidism</p> Signup and view all the answers

    Which genetic disorder is characterized by hypocalcemia and is linked to a loss of the Tbx1 transcription factor?

    <p>DiGeorge syndrome</p> Signup and view all the answers

    What condition can cause transient hypoparathyroidism in infants?

    <p>Surgical removal of parathyroid glands</p> Signup and view all the answers

    Which of these conditions is NOT a known cause of neonatal hypocalcemia?

    <p>Severe dehydration</p> Signup and view all the answers

    What is a characteristic feature of DiGeorge syndrome?

    <p>Cellular T-cell deficiency</p> Signup and view all the answers

    What is the primary characteristic of Pseudohypoparathyroidism (PHP)?

    <p>Resistance to parathyroid hormone (PTH)</p> Signup and view all the answers

    Which gene variant is primarily associated with PHP type 1?

    <p>GNAS1</p> Signup and view all the answers

    What observable physical characteristic is commonly associated with Albright hereditary osteodystrophy (AHO)?

    <p>Short fourth metacarpal bones</p> Signup and view all the answers

    What biochemical change typically results from the PTH resistance seen in patients with PHP?

    <p>Hyperphosphatemia</p> Signup and view all the answers

    How does the parent of origin affect the manifestations of PHP?

    <p>Maternally inherited variants cause different symptoms compared to paternally inherited variants</p> Signup and view all the answers

    What distinguishes PHP type 1b from type 1a?

    <p>Normal serum calcium concentrations</p> Signup and view all the answers

    What is the mechanism behind the signal transduction failure in PHP?

    <p>Impaired activation of adenyl cyclase</p> Signup and view all the answers

    What describes PHP type 1c specifically?

    <p>Different coupling of G protein to the PTH receptor</p> Signup and view all the answers

    What is the effect of variants in the PRKAR1A gene?

    <p>Multiple hormone resistance with acrodysostosis</p> Signup and view all the answers

    Which of the following can lead to hyperphosphatemia?

    <p>Use of phosphate-containing enemas</p> Signup and view all the answers

    Which of the following is NOT a potential cause of abnormal vitamin D production or action?

    <p>Respiratory failure</p> Signup and view all the answers

    In patients with PHP type 2, what is observed with respect to urinary cAMP concentrations?

    <p>Elevated urinary cAMP without increased phosphate excretion</p> Signup and view all the answers

    What characterizes respiratory alkalosis?

    <p>Respiratory hyperventilation</p> Signup and view all the answers

    What condition involves rapid skeletal mineral deposition in infants following vitamin D therapy?

    <p>Hypoparathyroidism</p> Signup and view all the answers

    What effect can phenytoin have on vitamin D levels?

    <p>Increase 25-hydroxylation of vitamin D</p> Signup and view all the answers

    What syndrome is characterized by serum calcium concentration decreases due to low plasma albumin levels?

    <p>Pseudohypocalcemia</p> Signup and view all the answers

    What is indicated by low PTH levels?

    <p>Hypoparathyroidism</p> Signup and view all the answers

    In cases of pseudohypoparathyroidism, what effect is observed when PTH is administered?

    <p>Calcium levels do not rise</p> Signup and view all the answers

    What urine calcium-to-creatinine ratio suggests inappropriate calcium excretion in the presence of hypocalcemia?

    <p>0.3 or more</p> Signup and view all the answers

    What is a common ECG finding in acute hypocalcemia?

    <p>Prolongation of QT interval</p> Signup and view all the answers

    What is the typical first step in treating severe hypocalcemia?

    <p>IV calcium gluconate infusion</p> Signup and view all the answers

    Which imaging study is indicated to evaluate for thymic shadow in suspected DiGeorge syndrome?

    <p>Chest radiography</p> Signup and view all the answers

    What calcium dosage is typically recommended for oral supplementation in symptomatic patients with mild hypocalcemia?

    <p>100 mg/kg/day</p> Signup and view all the answers

    What may elevated alkaline phosphatase levels indicate in a patient?

    <p>Rickets</p> Signup and view all the answers

    Study Notes

    Definition

    • Hypocalcemia: serum calcium level below 8.5 mg/dL (corrected for albumin) or 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])

    Calcium Metabolism and Function

    • 99% of total body calcium is stored in bone
    • Serum calcium exists in two forms: free (ionized) and bound to proteins or complexed with bicarbonate, citrate, and phosphate.
    • Calcium plays a critical role in many essential biological functions, including:
      • Calcium messenger system regulating cell function
      • Activation of cellular enzyme cascades
      • Smooth muscle and myocardial contraction
      • Nerve impulse conduction
      • Secretory activity of exocrine glands

    Magnesium

    • Approximately 50% of magnesium is found in bone and the other 50% in muscle and other soft tissues
    • Magnesium in bone is readily exchangeable with the extracellular fluid and serves as a buffer against extracellular magnesium concentration changes.

    Phosphate Metabolism

    • 85% of phosphate is located in the mineral phase of bone, the remainder in the extracellular and intracellular compartments
    • Phosphate is regulated by growth factors like IGF1 in addition to hormones of bone mineralization.
    • Phosphate is crucial as a substrate or recognition site in kinase and phosphatase regulatory cascades.

    Regulation of Serum Calcium

    • Parathyroid Hormone (PTH) is vital in Ca regulation: it stimulates bone resorption, renal calcium reabsorption, and activated Vitamin D production.
    • Vitamin D increases intestinal calcium absorption and enhances PTH action in the kidney.
    • Calcitonin lowers serum calcium by inhibiting bone resorption.

    Early Onset Neonatal Hypocalcemia

    • Occurs within 48-72 hours of birth
    • Causes:
      • Prematurity: inadequate nutrition, decreased parathyroid hormone responsiveness to Vitamin D, increased calcitonin levels.
      • Birth asphyxia: Delayed feeds, increased calcitonin, and endogenous phosphate load.
      • Infants of a diabetic mother: Magnesium depletion in mothers with diabetes leads to functional hypoparathyroidism and hypocalcemia in the infant.
      • Intrauterine growth restriction: Decreased transplacental passage of calcium.

    Late-Onset Neonatal Hypocalcemia

    • Occurs 3-7 days after birth, occasionally as late as 6 weeks.
    • Causes:
      • Exogenous phosphate load: seen in developing countries, associated with 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 T-cell deficiency, characteristic facies, congenital heart disease, and hypocalcemia.

    Hypocalcemia in Infants and Children

    • Hypoparathyroidism:
      • Post surgical hypoparathyroidism: most frequent cause of chronic hypocalcemia.
      • Transient hypoparathyroidism: parathyroid gland function recovers within 12 months after parathyroid surgery.
      • Permanent hypoparathyroidism: hypoparathyroidism persisting 12 months after onset.
      • Aplasia or hypoplasia of parathyroid gland: DiGeorge syndrome, Haploinsufficiency of transcription factor GATA3 causes HDR syndrome.
      • Autoimmune parathyroiditis: (Autoimmune polyendocrine syndrome type 1)
      • Infiltrative lesions: Hemosiderosis, Wilson disease, thalassemia.
      • Idiopathic causes.

    Genetic Parathyroid Disorders

    • Disorders of Parathyroid Gland Formation:
      • Tbx1 transcription factor loss in the 22q11 deletion syndrome (DS), also known as DiGeorge syndrome I or velocardiofacial syndrome, is likely the cause of hypoparathyroidism often seen in this syndrome.

    Pseudohypoparathyroidism (PHP)

    • Characterized by resistance to PTH, leading to hypocalcemia and hyperphosphatemia, similar to hypoparathyroidism.
    • Types:
      • Type 1: Mutations in the GNAS1 gene, encoding the alpha subunit of a GTP-binding protein (Gs), which couples to the PTH receptor. G protein's inability to activate adenyl cyclase upon PTH binding to its receptor results in reduced end-organ response to PTH.
        • Type 1a: Albright hereditary osteodystrophy (AHO): includes round facies, obesity, short stature, short fourth metacarpal bones, subcutaneous calcifications, and developmental delay.
        • Type 1b: Hypocalcemia without AHO. Autosomal dominant disorder caused by methylation defects or variants in regulatory elements of GNAS1.
        • Type 1c: Aberrant coupling of the G protein to the PTH receptor. Adenyl cyclase stimulation remains intact but is not coupled to PTH binding leading to a phenotype similar to Type 1a.
      • Type 2: No AHO features. Normal or elevated urinary cAMP concentrations in response to exogenous PTH administration without a concurrent increase in phosphate excretion. Caused by PRKAR1A gene variants encoding the catalytic subunit of adenylate cyclase and incorporating a phenotype of multiple hormone resistance with acrodysostosis.

    Other Causes of Hypocalcemia

    • Abnormal Vitamin D production or action:
      • Vitamin D deficiency: dietary insufficiency, maternal use of anticonvulsants.
      • Acquired or inherited disorders of vitamin D metabolism.
      • Resistance to Vitamin D actions.
      • Liver disease: affects 25-hydroxylation of Vitamin D. Certain drugs (phenytoin, carbamazepine, phenobarbital, isoniazid, and rifampin) can increase P-450 enzymes, increasing 25-hydroxylation and Vitamin D catabolism.
    • Hyperphosphatemia:
      • Excessive phosphate intake from cow milk or infant formula with improper calcium to phosphate ratio.
      • Excessive phosphate intake from phosphate-containing enemas.
      • Excessive phosphate or inappropriate Ca:P ratio in total parenteral nutrition.
      • Increased endogenous phosphate load from anoxia, chemotherapy, or rhabdomyolysis.
      • Renal failure.

    Drug-Induced Hypocalcemia

    • Bone-active agents: Bisphosphonates, denosumab.
    • Cinacalcet.
    • Phenytoin.
    • Fluoride toxicity.
    • Chemotherapy agents: Cisplatin and others.

    Other Causes of Hypocalcemia

    • Malabsorption syndromes.
    • Alkalosis: Respiratory alkalosis (hyperventilation). Metabolic alkalosis (bicarbonate, diuretics, or chelating agents).
    • Pancreatitis.
    • Pseudohypocalcemia (hypoalbuminemia): serum calcium concentration decreases by 0.8 mg/dL for every 1 g/dL fall in plasma albumin.
    • "Hungry bones syndrome:" Rapid skeletal mineral deposition seen in infants with rickets or hypoparathyroidism after starting Vitamin D therapy.

    Investigations

    • PTH levels: Low levels suggest hypoparathyroidism, serum calcium increases in response to PTH challenge. Elevated levels indicate Vitamin D abnormalities or pseudohypoparathyroidism, calcium levels do not rise with PTH challenge.
    • Vitamin D metabolite levels (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D): assess for uncommon causes of hypocalcemia (malabsorption, disorders of Vitamin D metabolism).
    • Urine calcium, magnesium, phosphorus, and creatinine levels: evaluate for renal tubular defects and renal failure.
    • Serum alkaline phosphatase levels: Elevated in patients with rickets.
    • ECG: Indicated for severe hypocalcemia. Lengthens the ST segment and prolongs QT interval, potentially leading to ventricular arrhythmias.

    Imaging Studies

    • Chest radiography: Evaluate for thymic shadow absence in patients with DiGeorge syndrome.
    • Ankle and wrist radiography: Assess for evidence of rickets, changes appear early in the radius and ulna.

    Treatment

    • Correct hypocalcemia
      • Severe hypocalcemia: serum calcium less than 1.9 mmol/L (7.6 mg/dL) or any level of hypocalcemia associated with severe symptoms. Medical emergency. Monitor ECG. Initiate IV calcium gluconate infusion or calcium chloride via central line. Dose: 100 to 200 mg/kg/dose (Max: 2 g/dose) IV every 6 hours as needed. Alternatively, 8 to 13 mg/kg/hour continuous IV infusion may be administered if symptoms recur. Titrate dose according to serum calcium concentrations.
      • Mild hypocalcemia: symptomatic patients with serum calcium level greater than 1.9 mmol/L (7.6 mg/dL). Begin oral calcium supplementation: 100 mg/kg/day elemental calcium PO in 3 to 4 divided doses.

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    Description

    Test your knowledge on the metabolism and functions of calcium and magnesium in the body. This quiz covers essential concepts such as hypocalcemia, serum calcium levels, and the roles these minerals play in biological functions. Perfect for students of biology or health sciences.

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