Past Papers · SAQ
Calcium Regulation
2026A Q14
Exam questiona) Outline the distribution of calcium in the body and provide the normal range of plasma calcium concentration (20% of marks).
b) Outline the regulation of plasma calcium (50% of marks).
c) Outline other physiological factors that may influence plasma calcium concentration (30% of marks).
CICMWrecks answer
Master answer
a) Distribution of calcium and normal plasma concentration (20%)
- Total body calcium is approximately 1–1.2 kg in an adult.
- ~99% is stored in bone and teeth, predominantly as hydroxyapatite; this is the major reservoir.
- <1% is extraskeletal, within extracellular fluid and soft tissues.
Plasma calcium
| Fraction | Approximate proportion | Significance |
|---|---|---|
| Ionised Ca2+ | ~45–50% | Physiologically active fraction; tightly regulated. |
| Protein-bound | ~40% | Mainly bound to albumin; not freely diffusible. |
| Complexed | ~10% | Bound to anions such as phosphate, citrate and bicarbonate. |
- Normal total plasma calcium: approximately 2.2–2.6 mmol/L.
- Normal ionised calcium: approximately 1.1–1.3 mmol/L.
- Ionised calcium is the biologically active component and is the principal variable sensed by the calcium-regulating system.
b) Regulation of plasma calcium (50%)
Overall principle: plasma ionised calcium is maintained by coordinated control of bone, kidney and gastrointestinal tract, principally through parathyroid hormone (PTH) and calcitriol; calcitonin has a smaller physiological role in adults.
1. Parathyroid hormone (PTH)
- Source: chief cells of the parathyroid glands.
- Sensor: extracellular ionised calcium is detected by the calcium-sensing receptor (CaSR).
- Stimulus: ↓ ionised Ca2+ → ↓ CaSR activation → ↑ PTH secretion.
- Inhibition: ↑ ionised Ca2+ and calcitriol suppress PTH secretion.
| Target | PTH action | Effect on plasma calcium |
|---|---|---|
| Kidney | ↑ distal tubular Ca2+ reabsorption; ↓ proximal phosphate reabsorption; ↑ renal 1α-hydroxylase → ↑ calcitriol formation. | Retains Ca2+; lowers phosphate; indirectly ↑ gut calcium absorption. |
| Bone | Acts on osteoblast-lineage cells → ↑ RANKL signalling → ↑ osteoclast-mediated bone resorption. | Releases Ca2+ (and phosphate) into ECF. |
| Gut | No major direct effect; acts indirectly via ↑ calcitriol. | ↑ intestinal calcium absorption. |
Net effect of PTH: raises plasma calcium and lowers plasma phosphate.
2. Vitamin D / calcitriol
- Vitamin D is obtained from diet or formed in skin, converted in liver to 25-hydroxyvitamin D, then in the kidney to active 1,25-dihydroxyvitamin D (calcitriol).
- Renal 1α-hydroxylase is stimulated by PTH and low phosphate; calcitriol feeds back to suppress further PTH synthesis.
| Target | Calcitriol action |
|---|---|
| Gut | ↑ intestinal absorption of calcium and phosphate by increasing epithelial transport proteins. |
| Bone | Supports mineralisation when substrate is adequate; with PTH can facilitate mobilisation of calcium from bone. |
| Kidney | Modest increase in tubular Ca2+ reabsorption. |
| Parathyroid | Suppresses PTH gene transcription and secretion. |
Net effect of calcitriol: generally raises plasma calcium and phosphate.
3. Calcitonin
- Source: parafollicular C cells of the thyroid.
- Stimulus: increased plasma calcium.
- Action: inhibits osteoclast activity and can increase renal calcium excretion.
- Physiological importance: considerably less important than PTH and calcitriol in normal adult calcium homeostasis.
Integrated feedback
- ↓ ionised Ca2+ → ↑ PTH → renal Ca retention + phosphate loss + ↑ calcitriol → ↑ gut calcium uptake + mobilisation from bone.
- Rising Ca2+ and calcitriol then suppress PTH secretion, completing the negative-feedback loop.
c) Other physiological factors influencing plasma calcium (30%)
| Factor | Effect / mechanism |
|---|---|
| Albumin / plasma protein concentration | Changes total calcium by altering the protein-bound fraction; ionised calcium may remain unchanged. Hypoalbuminaemia therefore lowers measured total calcium without necessarily causing true hypocalcaemia. |
| pH | Alkalaemia increases albumin binding of Ca2+ → ↓ ionised calcium; acidaemia decreases binding → ↑ ionised calcium. Total calcium changes little acutely. |
| Phosphate / citrate / other anions | Complex Ca2+ and alter the ionised fraction. Hyperphosphataemia can reduce ionised calcium and stimulate PTH. |
| Magnesium | Mild deficiency may stimulate PTH, but severe hypomagnesaemia impairs PTH secretion and action → hypocalcaemia. |
| Renal function | Renal failure reduces calcitriol production and causes phosphate retention → tendency to hypocalcaemia and secondary hyperparathyroidism. |
| Glucocorticoids | Reduce intestinal calcium absorption and increase renal calcium loss; chronic excess promotes negative calcium balance. |
| Other hormones | Thyroid hormone, growth hormone, sex steroids and other endocrine states modify bone turnover and therefore calcium flux, but are less important acute regulators than PTH/calcitriol. |
Exam focus
- Part (a): give body distribution + plasma fractions + units.
- Part (b): organise around sensor → hormone → organ targets → feedback; PTH and calcitriol deserve most detail.
- Part (c): distinguish factors that change total calcium from those that change ionised calcium, especially albumin and pH.
Quick reference
Summary
| Feature | High-yield point |
|---|---|
| Body distribution | ~99% in bone/teeth; <1% extraskeletal |
| Plasma calcium | Total ~2.2–2.6 mmol/L; ionised ~1.1–1.3 mmol/L; ionised fraction is physiologically active |
| PTH | CaSR-driven; ↑ renal Ca reabsorption, ↓ phosphate reabsorption, ↑ 1α-hydroxylase/calcitriol, ↑ bone resorption |
| Calcitriol | ↑ intestinal Ca and phosphate absorption; supports mineral balance and suppresses PTH |
| Other factors | Albumin changes total Ca; alkalosis lowers ionised Ca; severe hypomagnesaemia impairs PTH; renal failure lowers calcitriol and retains phosphate |
Past papers
Exam appearances
| Exam | Exact exam wording | Candidate success |
|---|---|---|
| 2026A Q14 | a) Outline the distribution of calcium in the body and provide the normal range of plasma calcium concentration (20% of marks). b) Outline the regulation of plasma calcium (50% of marks). c) Outline other physiological factors that may influence plasma calcium concentration (30% of marks). | 74.7% |
| 2017A Q05 | Describe the regulation of plasma calcium concentration. | 51% |
| 2016B Q01 | Outline the distribution of calcium in normal plasma (20% of marks). Describe the hormonal control of the calcium concentration in the plasma (80% of marks) | 53% |
| 2008A Q07 | Outline the regulation of plasma calcium concentration. Outline the mechanism of action of biphosphonates for the management of hypercalcaemia. | 33% |