Calcium and phosphate regulation Flashcards
what does PTH do to the bone and kidney?
bone: releases calcium and phosphorus
kidney: increases calcitriol formation and decreases excretion of calcium (+too much decreases serum phosphate)
where is PTH released from?
parathyroid glands sense low serum calcium
explain how phosphate regulation works
Phosphate reabsorption occurs via the gut and the kidneys. Phosphate is reabsorbed via sodium phosphate transporter cells. In the kidney, shown here, reabsorption of phosphate via these transporters results in less sodium excretion in the urine. Increased phosphate loss in the urine would lower serum phosphate levels.
what affects phosphate regulation?
PTH inhibits renal phosphate reabsorption by inhibiting these transporters (NA/PO4) – so in primary hyperparathyroidism, serum phosphate is low due to increased urine phoshate excretion.
FGF23 – derived from osteocytes – also inhibits phosphate reabsorption in the kidneys by inhibiting these transporters and also inhibits synthesis of calcitriol, causing less phosphate absorption from the gut.
Parathyroid cells:
what events occur in
- high calcium conc
- low calcium conc
calcium binds to receptor and the receptor activation leads to inhibition of PTH secretion
calcium not bound to receptor so no inhibition and PTH is secreted.
how is calcitriol formed?
skin: 7-dehydrocholesterol goes to cholecalciferl with UVB Vit D (ergocalciferol can also be obtained from the diet)
In liver: cholecalciferol turns to 25 OH-D3 via 25 hydroxylase (measure his for vit D deficiency)
Kidney: 25 OH-D3 turns to 1,25 (OH)2 D3 (calcitriol) using renal 1-alpha-hydroxylase (stimulated by PTH)
what does calcitriol do?
Calcitriol is the active form of Vit D and needs to be synthesised in the kidney- KEY, using the enzyme 1-alpha-hydroxylase Ca absorption in gut Ca maintenance n bone Increases renal Ca reabsorption Neg feedback on PTH
causes of vit D deficiency
Diet
Lack of sunlight
GI malabsorption,eg coeliac disease, inflam bowel disease,
Renal failure, Liver failure
Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment)
HOW DO CHANGES IN EC CALCIUM AFFECT NERVE AND SKELETAL MUSCLE EXCITABILITY?
- high ec cal
- low ec cal
To generate an AP in nerves/skeletal muscle requires Na+ influx across cell membrane
HIGH ec calcium (HYPERcalcaemia) = Ca2+ blocks Na+ influx, so LESS membrane excitability
LOW ec calcium (HYPOcalcaemia) = enables GREATER Na+ influx, so MORE membrane excitability
what is normal Ca range?
normal range serum Ca2+ ~ 2.2–2.6mmol/L
signs and symptoms of hypocalcaemia:
muscle cramps/tetany,
tingling
Parasthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany
[CATs go numb]
2 clinical signs/tests that indicate hypocalcaemia
-Chvostek’s sign
Tap facial nerve just below zygomatic arch
Positive response = twitching of facial muscles
Indicates neuromuscular irritability due to hypocalcaemia
-Trousseau’s sign
Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia
causes of hypocalcaemia
Vitamin D deficiency
Low PTH levels = hypoparathyroidism
(Surgical –0 neck surgery, Auto-immune, Magnesium deficiency)
PTH resistance eg pseudohypoparathyroidism
Renal failure: Impaired 1a hydroxylation
leads to decreased production of 1,25(OH)2D3
signs and symptoms of hypercalcaemia
‘Stones, abdominal moans and
psychic groans’
Stones – renal effects
Polyuria & thirst
Nephrocalcinosis, renal colic, chronic renal failure
Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
causes of hypercalcaemia
Primary hyperparathyroidism
Malignancy – tumours/metastases often secrete a PTH-like peptide
Conditions with high bone turnover (hyperthyroidism, Paget’s disease of bone – immobilised patient)
Vitamin D excess (rare)
what are the Ca, phosphate and PTH levels like in primary hyperparathyroidism and why?
Raised calcium
Low phosphate
Raised (unsuppressed) PTH
NO negative feedback
Autonomous PTH secretion DESPITE hypercalcaemia. Abnormal functioning parathyroid gland keeps making PTH despite the raised Cal - does it’s own thing
what are the Ca, phosphate and PTH levels like in hypercalcaemia of malignancy?
Raised calcium
Suppressed PTH
-no issue with parathyroid hormone it’s to do with cancer deposits in the bones, so there is still negative feedback occurring
define vit D deficiency and what it can result in
- children
- adults
Definition: lack of mineralisation in bone
Results in “softening” of bone (leading to bowing of legs), bone deformities, bone pain; severe proximal myopathy.
In children - RICKETS
In adults - OSTEOMALACIA
treatment of primary hyperparathyroidism
parathyroidectomy
what happens in secondary hyperparathyroidism?
there is a vit D deficiency so Cal is low
PTH INCREASES TO TRY TO NORMALISE SERUM CALCIUM
= SECONDARY HYPERPARATHYROIDISM
So the PTH is high
what are the biochemical findings in vit D deficiency?
Plasma [25(OH)D3] usually low (NB we don’t measure 1,25 dihydroxy vitamin D (1,25 (OH)2 D) to assess body vitamin D stores)
Plasma [Ca2+] low (may be normal if 2o hyperparathyroidism has developed)
Plasma [PO43-] low (reduced gut absorption)
[PTH] high (2o hyperparathyroidism)
treatment of vit D deficiency in patients with normal renal functions
Give 25 hydroxy vitamin D (25 (OH) D)
Patient converts this to 1,25 dihydroxy vitamin D (1,25 (OH)2 D) via 1a hydroxylase
Ergocalciferol 25 hydroxy vitamin D2 (type found in food)
Cholecalciferol 25 hydroxy vitamin D3
treatment of vit D deficiency in patients with renal failure
inadequate 1a hydroxylation, so can’t activate 25 hydroxyl vitamin D preparations
Give Alfacalcidol - 1a hydroxycholecalciferol (active form)
what can vit D excess lead to?
Can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium
