Regulation of calcium and phosphate (14) Flashcards
How does Vitamin D synthesis work?
- UVB light shines on skin–> triggers series of reactions
- precursor= 7-dehyrocholesterol–> converted to pre-vitamin D3–> vitamin D3 (cholecalciferol) IN SKIN
- vitamin D2 (from diet) and vitamin D3 transported to liver- FIRST STEP: hydroxylated by 25-hyroxylase–> 25(OH)cholecalciferol (inactive)
- SECOND STEP: 25(OH) vitamin D hydroxylated in kidney by 1-alpha-hydroxylase–> 1,25(OH)2 cholecalciferol (active form of vitamin D/ CALCITRIOL)
What do we use as an indicator of body vitamin D status?
the inactive form of hormone- serum 25-OH vitamin D
measuring calcitriol v. hard
How does calcitriol regulate its own synthesis?
1, 25 (OH)2 cholecalciferol negatively feeds back onto the enzyme that activates it- 1 alpha hydroxylase
What are the effects of calcitriol?
- works on kidney to increase Ca2+ and PO43- reabsorption (less lost in urine)
- works on gut to stimulate Ca2+ and PO43- absorption
- increases osteoblast activity
What is the parathyroid hormone (PTH)?
- comes from ‘chief cells’ in parathyroid glands (at back of thyroid)
- made from a large precursor- pre-pro-PTH –> cleaved to become PTH
- G-protein coupled calcium sensing receptor on chief cells detect change in serum Ca+ conc.
- PTH secretion inversely proportional to serum calcium
How does the calcium sensing receptor work in chief cells?
high calcium levels–> calcium binds to G-protein coupled receptors on chief cells–> PTH secretion inhibited
low calcium–> less calcium binds to calcium sensing receptor–> more PTH secreted (to inc. calcium)
What are the actions of PTH/how does it regulate serum calcium and phosphate?
- in KIDNEY, inc. serum calcium by inc. calcium reabsorption, inc. phosphate excretion, and inc. 1-a-hydroxylase activity (meaning more vit. D made–> inc. calcium+phosphate absorption in GUT indirectly)
- stimulating calcium reabsorption from BONES
How does PTH act on bone?
converts osteoblasts (build bone)--> to osteoclasts (consume bone) by binding to PTH receptor--> osteoclast activating factors--> osteoclasts resorb bone--> calcium released
How is PTH regulated?
as calcium falls–> more PTH produced by parathyroid glands–> inc. plasma calcium and vitamin D synthesis–> inc. calcium
NEGATIVE FEEDBACK
1. more plasma Ca2+–> inhibits PTH production
2. active vitamin D negatively feeds back onto parathyroid cells
What is calcitonin?
- secreted from parafollicular cells in thyroid gland
- REDUCES serum calcium
- physiological role in calcium homeostasis unclear
How does calcitonin regulate calcium levels?
- dec. osteoclast activity
- inc. calcium excretion in kidney
- -> less plasma calcium
How is serum phosphate regulated?
- PTH inhibits phosphate reabsorption by inhibiting Na+/PO43- co-transporter
- FGF23 inhibits ^ co-transporter AND inhibits calcitriol (active vit.D)–> less phosphate reabsorption from gut
How does hypercalcaemia affect action potential generation?
Ca2+ in the way outside cell- blocks Na+ influx–> less membrane excitability
How does hypocalcaemia affect action potential generation?
enables greater sodium influx–> more membrane excitability
What are the signs and symptoms of hypocalcaemia?
- paraesthesia (pins and needles)- Numb
- Convulsions
- Arrhythmia
- Tetany
N.B. mnemonic: CATs go numb
What is Chvostek’s sign?
sign of hypocalcaemia- indicates neuromuscular irritability
- tap facial nerve just below zygomatic arch–> leads to twitching of facial muscles
What is Trousseau’s sign?
sign of hypocalcaemia- indicates neuromuscular irritability
- inflate BP cuff for several minutes on arm–> induces carpopedal spasm (flexion)
What are the causes of hypocalcaemia?
low PTH levels- hypoparathyroidism due to - surgery - autoimmunity - magnesium deficiency - congenital (rare)
vit. D deficiency
What are the causes of vitamin D deficiency?
- malabsorption or dietary insufficiency
- inadequate sun exposure
- liver disease
- renal disease (bc 1-alpha-hydroxylase)
- vit. D receptor defects (rare)
What are the consequences of vitamin D deficiency?
lack of bone mineralisation- soft bones
in kids- rickets (bowing of bones)
in adults- osteomalacia (fractures, proximal myopathy)
What are the signs and symptoms of hypercalcaemia?
reduced neuronal excitability–> atonal muscles
- kidney stones, renal colic
- GI effects: dyspepsia (heart burn), nausea, pancreatitis
- CNS effects: fatigue, impaired concentration, coma
‘STONES, ABDOMINAL MOANS, AND PSYCHIC GROANS’
What are the causes of hypercalcaemia?
Primary hyperparathyroidism: tumour making too much PTH–> inc. calcium- no negative feedback
Malignancy- bony metastases produce local factors to activate osteoclasts
- PTH-related peptide secreted by certain cancers acts at PTH receptors
Vitamin D excess (rare)
Why is calcium important?
- muscle contraction
- bone strength
- 2^y messenger
- blood clotting
Why is phosphate important?
- component of DNA + ATP etc…
- 2^y messenger
N.B. extracellular phosphate= inversely proportional to extracellular calcium (so both regulated by same hormones)
What hormones are involved in control of serum calcium and phosphate?
- increase calcium: PTH (secreted by parathyroid glands) and Vitamin D (synthesised in skin or intake via diet)
- decrease calcium: calcitonin (secreted by thyroid parafollicular cells)
What are the sources of vitamin D?
take in via diet- vitamin D2- ergocalciferol
or make via sunshine- vitamin D3- cholecalciferol
