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Questions and Answers
What is the primary function of 1,25-dihydroxyvitamin D in the body?
How does parathyroid hormone (PTH) affect calcium reabsorption in the kidneys?
Which hormone is primarily involved in the regulation of second hydroxylation of vitamin D?
What could be a potential symptom of hypocalcemia?
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What is one possible effect of hypercalcemia on the body?
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What is the primary role of calcitonin in the body?
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Which hormone is primarily responsible for increasing calcium reabsorption in the kidneys?
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What condition is indicated by total serum calcium levels exceeding 2.62 mmol l-1?
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Which of the following symptoms is commonly associated with hypocalcaemia?
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Which hormone mimics the action of PTH and is involved in calcium homeostasis?
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What triggers the secretion of fibroblast growth factor 23 (FGF23)?
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What is a common mnemonic symptom associated with hypercalcaemia?
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Which hormones primarily influence bone turnover aside from PTH?
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What is primarily responsible for regulating calcium concentrations in the body?
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What condition can result from a lack of production of parathyroid hormone (PTH)?
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Which of the following is NOT a symptom of hypoparathyroidism?
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What is one potential effect of hyperparathyroidism on the body?
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Which vitamin D metabolite plays a critical role in calcium homeostasis?
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How does chronic kidney disease primarily affect calcium regulation?
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What can excessively high levels of calcium in the blood lead to?
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Which symptom is commonly associated with hypocalcaemia?
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What role do sex hormones play in calcium regulation?
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What is a primary physiological role of vitamin D in calcium metabolism?
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Which hormone is primarily responsible for increasing blood calcium levels?
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What is a common symptom of hypocalcaemia?
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How does calcitonin affect calcium levels in the body?
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What is an effect of hypercalcaemia on the neuromuscular system?
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Which factor plays a role in the regulation of calcium reabsorption in the kidneys?
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What is typically associated with hyperparathyroidism?
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Which mechanism does vitamin D primarily use to exert its effects on its target cells?
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Which symptom is commonly associated with chronic hypercalcaemia?
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Which of the following hormones directly inhibits the release of calcium from bones?
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Which hormones are primarily involved in calcium homeostasis in the body?
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What is the physiological role of inorganic phosphate (Pi)?
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What would likely occur in the body with a deficiency of parathyroid hormone (PTH)?
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What is a major symptom of hypocalcaemia?
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Which process is primarily responsible for calcium reabsorption in the kidneys?
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What effect does hypercalcaemia have on calcium-sensing receptors (CaSR)?
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What is the role of 1,25-dihydroxyvitamin D in calcium homeostasis?
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How do calcium-sensing receptors (CaSR) contribute to cellular functions?
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Which statement accurately describes calcium resorption from bones?
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PTH receptors are expressed on which of the following cellular locations?
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Study Notes
Calcium Homeostasis
- Calcium (and phosphate) are vital for skeletal and tooth formation, biochemical pathways, and signalling cascades.
- Calcium plays a role in skeletal rigidity, connective tissue, teeth, blood clotting (intrinsic/extrinsic cascades), muscle (excitation-contraction coupling), neurotransmission (stimulus-secretion coupling), and cell adhesion (cadherins).
- Calcium also acts as a second messenger for enzymatic activity (e.g., calmodulin).
Whole Body Calcium Handling
- Ionised calcium is the biologically active form.
- Total calcium concentration ranges from 2.1-2.8 mmol/L.
- Ionised calcium accounts for roughly 50% of the total.
- Most calcium is protein-bound (approximately 45%), which is inactive and not excreted.
- The remaining calcium is complexed with phosphate, bicarbonate, or citrate (approximately 5%).
- Dietary calcium intake plus calcium resorbed from bone equals calcium lost in faeces, sweat, and saliva, plus calcium deposited in the bone.
Inorganic Phosphate (Pi)
- Inorganic phosphate plays a role in bone formation (hydroxyapatite and hydroxyapatite crystals) and ATP formation.
- It is also a component of nucleotides, nucleosides, and phospholipids.
- Inorganic phosphate is involved in cellular signalling.
- Normal plasma inorganic phosphate concentration is 2.3 mmol/L.
- Inorganic phosphate exists primarily as HPO42- or H2PO4-.
Calcium Homeostasis Hormones
- Calcium homeostasis is maintained by three hormones that act on bone, kidney, and intestines.
- These hormones include:
- Metabolites of vitamin D (1,25-dihydroxyvitamin D
- Parathyroid hormone (PTH)
- Calcitonin
Parathyroid Hormone (PTH)
- Manufactured in parathyroid chief cells.
- Biologically active peptide of 84 amino acids.
- PTH is involved in calcium homeostasis.
- PTH is involved in stimulating the recruitment of osteoblasts, which promote osteoclast activity.
- PTH stimulates Vitamin D synthesis resulting in increased calcium absorption from the gut.
- In kidneys PTH increases calcium reabsorption.
- Hypocalcaemia stimulates PTH secretion.
- Heterozygous CaSR inactivating mutation causes FHH (familial hypercalcemic hypocalciuria).
- Heterozygous CaSR and Ga11 gain-of-function mutation causes high urinary excretion of calcium in normal plasma calcium.
Calcium-Sensing Receptors (CaSR)
- GPCR which responds to numerous ligands.
- CaSRs mediate multiple physiological effects, including calcium homeostasis, nutrient sensing (parietal and G cells), and enzyme secretion ( alpha and beta cells).
- CaSRs are involved in regulating PTH secretion.
Vitamin D Metabolites (1,25-Dihydroxyvitamin D)
- Vitamin D, particularly its active form 1,25-dihydroxyvitamin D (calcitriol), is critical for calcium homeostasis.
- Vitamin D metabolites promote calcium absorption in the small intestine.
- Vitamin D metabolites stimulate sodium and phosphate co-transporters in the kidneys resulting in increased calcium reabsorption.
- Vitamin D metabolites increase osteoclast numbers.
- Vitamin D production is influenced by growth hormone, prolactin, and oestrogen.
- FGF23 reduces 1,25-dihydroxyvitamin D levels.
Calcitonin
- Produced in the thyroid gland (clear cells).
- Biologically active peptide of 32 amino acids.
- Calcitonin antagonises PTH's action on bone.
- Calcitonin reduces osteoclast activity, resulting in less calcium released from bone. Calcitonin reduces the bone turnover rate.
Other Hormones
- Sex hormones (e.g., oestrogen, testosterone) impact bone turnover.
- Glucocorticoids also influence bone density.
- PTHrP mimics PTH's action on bone and kidney.
Inorganic Phosphate Homeostasis
- FGF23 plays a key role in regulating inorganic phosphate concentrations.
- Increased plasma phosphate levels stimulate FGF23 production.
- PTH and calcitriol influence phosphate release from bone and renal excretion.
Hypocalcemia
- Low plasma Ca2+
- Clinical presentation: Pins and needles, muscle spasms (tetany), paralysis, convulsions
- Total plasma serum calcium < 0.5 mmol/l
- Ionised plasma serum calcium < 0.3 mmol/l
Hypercalcemia
- High plasma Ca2+
- Clinical presentation: Lethargy, depression, constipation, Renal calculi, frequent urination, Nausea, arrhythmias
- Total plasma serum calcium > 2.62 mmol/l
- Ionised plasma serum calcium > 1.31 mmol/l
Hypoparathyroidism
- Characterised by lack of PTH production or defects in responsiveness to PTH.
- Symptoms: Muscle spasms (tetany), hypocalcaemia, hyperphosphatemia
Hyperparathyroidism
- Characterised by excess PTH.
- Can be primary (tumours) or secondary (chronic kidney disease, vitamin D deficiency).
- Symptoms: Hypertension, constipation, weakness, confusion, hypercalcaemia.
Vitamin D Deficiency
- Mild Deficiency: Increased PTH, high bone turnover.
- Moderate Deficiency: reduced bone density, increased bone turnover, increased risk of hip fracture.
- Severe Deficiency: osteomalacia, rickets in children.
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Description
This quiz explores the vital roles of calcium and phosphate in the body, including their importance for skeletal formation, biochemical pathways, and signalling. It also covers the mechanisms of calcium handling and its various forms in the body, providing a comprehensive overview of calcium's physiological functions.
