MEH 21 - Calcium Metabolism Flashcards
How much calcium in the human body?
How is this distributed?
- 1kg (99% sequestered in bone as hydroxyapatite crystals)
- Only 2.2-2.6mM of serum Ca2+, about 50% of this is ionised (active form), other have is protein bound or complexed.
What are the 3 hormones involved in Ca2+ regulation + where are they released from?
1) PTH - released from chief cells of PT gland
2) Calcitrol /1,25(OH)2D - PT cells of nephron
3) Calcitonin - C cells of thyroid gland
Where are the parathyroid glands located?
- Typically 4 on posterior aspect of thyroid gland. Can be more/less and located elsewhere.
How is PTH synthesised?
How is its synthesis regulated?
What is its half life?
- Polypeptide hormone cleaved from pre-pro hormone
- Low serum calcium up-regulates gene transcription, high serum calcium down-regulates.
- T 1/2 = 4 mins, PTH continually synthesised + degraded by chief cells. Therefore reacts swiftly to small changes in serum Ca2+
What are the 3 target organs + effects of PTH?
Effect = to increase serum calcium
1) Bone - increases resorption of calcium from bones. Does this by increasing osteoclast activity (resorption) and decreasing osteoblast activity (deposition) to liberate calcium from bone.
2) Kidney - decreases loss of Ca2+ in urine by increasing calcium reabsorption
3) Intestine - activates Vit D and increases
transcellular uptake of dietary calcium from GIT (lesser effect)
How is calcitrol synthesised?
- Cholesterol is the main backbone, with the addition of sunlight 25(OH)D is converted into the active form of Vit D (calcitrol) produced by the kidney.
- Calcitrol increases free serum Ca2+ by increasing uptake from from intestines.
What is the effect of calcitonin secretion?
- Calcitonin decreases free serum calcium, released from parafollicular (C) cells of thyroid gland. Achieved this by …
1) Inhibiting osteoclast activity in bones (major effect)
2) inhibiting renal tubular reabsorption of phosphate and calcium (minor effect), more ca2+ excreted in urine
What are the symptoms of hypercalcaemia?
What are the symptoms of hypocalcaemia?
- Renal calculi (stones), depression (moans), abdominal pain (groans), muscle aches (bones), tiredness, constipation, kidney damage.
- Hyperexcitabiity of NMJ, lower Ca2+ causes increased Na+ entry into neurones, leading to DP and increased likelihood of firing AP’s, leading to pins/needles, tetany, paralysis + convulsions (way more dangerous)
What is one potential cause of hypercalcaemia?
- Malignant osteolytic bone metastasis - breakdown of bone, liberating calcium.
- Common cancers metastasising to bone = breast, lung, renal + thyroid.
- Common sites = vertebrae, pelvis, ribs, femur, skull, humerus (appears as dark hole punched like holes in bone X-ray)
What is the difference between primary + secondary hyperparathyroidism?
What is the result of hyperparathyroidism
- Primary = one of PT glands develops an adenoma secreting excessive PTH
- Secondary = All 4 PT glands become hyperplastic, seen in Vit D deficiency patients. Means Ca2+ absorption is low, so PTH level increase rapidly
- As a result, Ca2+ levels increase and phosphate levels decreases
What are the symptoms of hyperparathyroidism?
1) Stones - kidney stones + polyuria
2) Moans - tired, exhausted, depression
3) Groans - constipation, peptic ulcers
4) Bones - bone + muscle aches
Why is it that hypercalcaemia results in lethargy/confusion and hypocalcaemia leads to excitable nerves, tingling + tetany?
Calcium raises the threshold for nerve membrane depolarisation and therefore development of an AP
- Hypercalcaemia leads to suppression of neuronal activity (hence weakness/tiredness)
- Hypocalcaemia leads to over-excitability of neurones
