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Questions and Answers
Which of the following correctly describes the composition of total plasma calcium?
Which of the following correctly describes the composition of total plasma calcium?
What is the primary role of PTH in calcium regulation?
What is the primary role of PTH in calcium regulation?
What percentage of total body calcium is stored in bones?
What percentage of total body calcium is stored in bones?
Which factor most stimulates the secretion of PTH?
Which factor most stimulates the secretion of PTH?
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What is the primary physiological function of ionized calcium in the body?
What is the primary physiological function of ionized calcium in the body?
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Which of the following is a common cause of hypercalcemia?
Which of the following is a common cause of hypercalcemia?
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How does the body typically absorb calcium from dietary sources?
How does the body typically absorb calcium from dietary sources?
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What is the normal serum calcium range indicated in mmol/L?
What is the normal serum calcium range indicated in mmol/L?
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Which of the following relationships between ionized calcium and PTH is correct?
Which of the following relationships between ionized calcium and PTH is correct?
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What type of calcium is primarily measured to assess physiological calcium levels?
What type of calcium is primarily measured to assess physiological calcium levels?
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What is one common cause of hypercalcemia?
What is one common cause of hypercalcemia?
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Which condition is associated with depressive symptoms and mental status changes as a sign of hypocalcaemia?
Which condition is associated with depressive symptoms and mental status changes as a sign of hypocalcaemia?
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Which of the following signs is used to assess hypocalcaemia during a physical examination?
Which of the following signs is used to assess hypocalcaemia during a physical examination?
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What does Trousseau’s sign indicate when observed during a clinical exam?
What does Trousseau’s sign indicate when observed during a clinical exam?
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Which process is primarily disrupted in patients with malabsorption that can lead to hypocalcaemia?
Which process is primarily disrupted in patients with malabsorption that can lead to hypocalcaemia?
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What is a principal cause of Milk-alkali syndrome?
What is a principal cause of Milk-alkali syndrome?
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How does parathyroid hormone (PTH) affect renal calcium reabsorption?
How does parathyroid hormone (PTH) affect renal calcium reabsorption?
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Which of the following mechanisms does NOT contribute to hypercalcemia?
Which of the following mechanisms does NOT contribute to hypercalcemia?
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What is the primary function of calcitriol in the body?
What is the primary function of calcitriol in the body?
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Which function is associated with PTH in the proximal tubule of the kidney?
Which function is associated with PTH in the proximal tubule of the kidney?
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Which factor is a major stimulator of 1 alpha-hydroxylase activity?
Which factor is a major stimulator of 1 alpha-hydroxylase activity?
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How does calcitriol affect intestinal calcium absorption?
How does calcitriol affect intestinal calcium absorption?
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What condition might lead to hypercalcemia due to increased gastrointestinal absorption?
What condition might lead to hypercalcemia due to increased gastrointestinal absorption?
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What is the classic triad of symptoms for milk-alkali syndrome?
What is the classic triad of symptoms for milk-alkali syndrome?
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Which of the following conditions is most commonly associated with hypercalcemia due to excessive calcium intake?
Which of the following conditions is most commonly associated with hypercalcemia due to excessive calcium intake?
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What mechanism predominantly increases intestinal calcium absorption when vitamin D is elevated?
What mechanism predominantly increases intestinal calcium absorption when vitamin D is elevated?
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What role does alkalosis play in the pathophysiology of milk-alkali syndrome?
What role does alkalosis play in the pathophysiology of milk-alkali syndrome?
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In which condition is hypercalcemia due to activated macrophages producing calcitriol most commonly seen?
In which condition is hypercalcemia due to activated macrophages producing calcitriol most commonly seen?
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Which of the following drugs can lead to increased calcium resorption from bone?
Which of the following drugs can lead to increased calcium resorption from bone?
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What is the most likely health consequence of severe hypercalcemia?
What is the most likely health consequence of severe hypercalcemia?
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What primary factor leads to hypercalcemia in patients being treated with calcium and vitamin D supplements?
What primary factor leads to hypercalcemia in patients being treated with calcium and vitamin D supplements?
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How can hyperparathyroidism contribute to hypercalcemia?
How can hyperparathyroidism contribute to hypercalcemia?
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Which symptom is least likely to occur in mild hypercalcemia?
Which symptom is least likely to occur in mild hypercalcemia?
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Study Notes
Calcium Disorders
- 99% of total body calcium is stored in bone.
- Extracellular calcium is a small fraction; 50% is bound to albumin, with 40% available as physiologically active, free (ionized) calcium.
- Serum/plasma calcium concentration is measured as either total or ionized calcium.
- Total calcium includes ionized, complexed, and bound calcium, measured via colorimetric assay.
- Ionized calcium, measured by a calcium-specific electrode, represents physiologically regulated calcium.
- Total and ionized calcium can be expressed in mg/dL, mEq/L, or mmol/L (SI units). SI units (mmol/L) are converted to mg/dL by multiplying by 4.
- Plasma-ionized calcium is regulated by a complex interplay of parathyroid hormone (PTH) and vitamin D3 (calcitriol) in the intestine, bone, and kidney.
- The parathyroid gland senses extracellular fluid (ECF)-ionized calcium concentration via a calcium-sensing receptor.
- The parathyroid gland responds rapidly (within minutes) to ECF-ionized calcium changes.
- High ECF calcium inhibits PTH release.
- Low ECF calcium stimulates PTH secretion, and increases parathyroid gland mass.
- An inverse sigmoid relationship exists between ECF calcium concentration and PTH secretion.
- In bone, PTH, in the presence of calcitriol, increases osteoclastic activity, promoting calcium reabsorption.
- In the intestine, PTH indirectly enhances calcium and phosphate absorption by promoting calcitriol formation.
- In the kidney, PTH increases distal tubular calcium reabsorption and inhibits proximal tubular phosphate and bicarbonate reabsorption, while stimulating calcitriol formation in the proximal tubule.
- Calcitriol is produced in the proximal tubule through 1-alpha-hydroxylation of 25(OH) vitamin D3 (calcidiol).
- PTH and hypophosphatemia are the key stimulators of 1-alpha-hydroxylase.
- The primary function of calcitriol is to increase calcium and phosphate availability for bone formation and to prevent symptomatic hypocalcemia/hypophosphatemia.
- Calcitriol increases calcium-binding protein (calbindin) production in the intestine and kidney, aiding transcellular calcium movement.
- Calcitriol potentiates PTH activity in bone, inducing osteoclast differentiation, and stimulating osteoclastic reabsorption.
- Gut calcium absorption is regulated by calcitriol (active vitamin D).
- Falling calcium activates parathyroid calcium-sensing receptors, triggering parathyroid hormone (PTH) release.
- PTH increases renal tubular calcium reabsorption and vitamin D3 hydroxylation to the active metabolite, which enhances intestinal calcium uptake.
- PTH also increases bone osteoclastic activity.
Hypercalcemia
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Three factors cause hypercalcemia: increased calcium absorption from the gastrointestinal tract, decreased renal calcium excretion, and increased bone calcium resorption.
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Increased Calcium Absorption from the Gastrointestinal Tract:
- Milk-alkali syndrome caused by excessive calcium and alkali intake.
- Hypercalcemia in chronic kidney disease (CKD).
- Vitamin D intoxication.
- Granulomatous disorders (e.g., sarcoidosis).
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Milk-alkali syndrome:
- Historically, treated with milk and sodium bicarbonate.
- Now less common with usage of histamine antagonists and proton pump inhibitors.
- Commonly occurs in elderly women taking excess calcium carbonate or calcium citrate for osteoporosis treatment.
- Alkalosis decreases renal calcium excretion, causing hypercalcemia, nephrocalcinosis, and renal dysfunction, which then prevents correction of alkalosis.
- Patients often also receive vitamin D supplements, increasing intestinal calcium absorption.
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Hypercalcemia in CKD: Typically occurs with calcium and vitamin D supplements. Hypercalcemia from dietary calcium ingestion alone rarely occurs without renal impairment.
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Vitamin D Intoxication: Excess vitamin D leads to hypercalcemia as calcium is primarily absorbed in the small intestine, stimulated by calcitriol.
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Granulomatous disorders: Activated macrophages produce calcitriol, increasing intestinal calcium absorption.
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Causes of Increased Bone Calcium Resorption:
- Hyperparathyroidism
- Malignancy
- Hyperthyroidism
- Immobilization
- Paget's disease
- Thiazide diuretics
Signs and Symptoms of Hypercalcemia
- Signs and symptoms are related to severity and rate of plasma-ionized calcium rise.
- Mild hypercalcemia is often asymptomatic, detected during routine blood chemistries.
- Severe hypercalcemia leads to polyuria, polydipsia, neurological and gastrointestinal symptoms.
- Neurological symptoms (e.g., mental status changes, depression, confusion, coma).
- Gastrointestinal symptoms (e.g., constipation, anorexia, nausea, vomiting, abdominal pain due to peptic ulcer or pancreatitis).
Hypocalcemia
- Causes of Hypocalcemia:
- Vitamin D deficiency
- Malnutrition
- Malabsorption
- Chronic renal failure (CRF)
- Vitamin D-dependent rickets
- Hypoparathyroidism
- Hyperphosphatemia
- Acute pancreatitis
- Hypomagnesemia
Symptoms and Signs of Hypocalcemia
- Depression, anxiety, irritability, circumoral/distal extremity paresthesia, carpopedal spasm, tetany, convulsions, arrhythmias.
- Chronic hypocalcemia may cause cataracts, dental changes, bone pain, and muscle weakness/skeletal deformities.
- Chvostek's and Trousseau's signs.
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Description
This quiz explores the various aspects of calcium disorders, including the storage of calcium in the body, measurement techniques for total and ionized calcium, and the regulatory roles of parathyroid hormone and vitamin D3. Test your understanding of how calcium functions within the body and its implications for health.
