12 - calcium and phosphate regulation Flashcards
Where are the parathyroid glands and what do they produce?
4 of them , located behind the thyroid gland
produce parathyroid hormone (PTH)
What ion does PTH regulate?
calcium
PTH increases serum calcium
State the 3 functions of PTH
- interacts the kidney to absorb calcium (excrete less calcium)
- promotes calcium release from the bones
- regulates the conversion of inactive vitamin D (25-hydroxy-vitamin-D) -> active vitamin D (calcitriol)
What is the action of active vitamin D (calcitriol)?
it promotes calcium reabsorption from the gut and bones -> increases serum Ca
(and increases absorption of phosphate from the gut)
How is phosphate reabsorbed in the kidney?
in the proximal convoluted tubule, phosphate is reabsorbed using sodium-transport co-transporters - phosphate leaves the nephron tubules indenters the cells
Describe the mechanism by which PTH affects the mechanism of phosphate reabsorption in the kidney nephron
inhibits the sodium-transport co-transporters
Describe the excretion and serum levels of phosphate in a person with primary hyperparathyroidism
increased phosphate excretion.
low serum phosphate due to inhibition of phosphate reuptake at the proximal convoluted tubule.
What is FGF 23? Where does it come from?
Fibroblast growth factor 23 from osteocytes
In which 2 ways does FGF 23 inhibit the reabsorption of phosphate?
1- via the sodium-phosphate cotransporter
2- inhibits calcitriol (calcitriol assists phosphate reabsorption from gut).
Describe the mechanism of regulation of PTH secretion
Parathyroid cells have calcium-sensing receptors on their surface.
When you have high calcium in the ECF, calcium binds to these receptors.
THIS INHIBITS PTH SECRETION - when your Ca is high, PTH is inhibited.
When you have a low serum calcium in the ECF, less calcium binds to these receptiors -> less PTH inhibition -> more PTH release -> mechanisms to increase serum Ca.
What are 2 ways in which the body can get vitamin D?
- from the diet (ergocalciferol)
- via UVB light
Describe the mechanism by which we can get vitamin D via UVB light and the role of PTH in this process
- UVB light converts 7-dehydrocholesterol -> cholecalciferol
- In the liver, cholecalciferol is converted to 25-OH-D3 (BIOLOGICALLY INACTIVE)
- 1α-hydroxylase in the KIDNEY converts 25-OH-D3 -> 1,25-(OH)2-D3 (BIOLOGICALLY ACTIVE)
NOTE: ^this conversion is stimulated by PTH.
What is the role of vitamin D in calcium (and phosphate) homeostasis (4)
Active vitamin D:
- promotes Ca and phosphate reabsorption in the gut
- promotes Ca maintenance in the bones
- increases renal Ca reabsorption
- produces negative feedback on PTH (calcitriol receptors on PT cells).
(calcitriol and vitamin D work together to increase Ca2+)
State the causes of vitamin D deficiency (5)
- A poor diet and malabsorption
- not enough sunlight exposure/too much sun cream
- Liver and renal diseases of ANY CAUSE - because both organs are critical for vitamin D production
- vitamin D resistant rickets – vitamin D production is normal, but there are receptor defects (rare)
HOW DO CHANGES IN EXTRACELLULAR CALCIUM AFFECT NERVE AND SKELETAL MUSCLE EXCITABILITY?
(remember generation of 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
(i.e. Na+ and Ca2+ compete)
State the normal range for serum calcium
2.2–2.6 mmol/L
How can we assess for hypocalcaemia in a patient?
using Chvostek’s sign and Trousseau’s sign
assess for neuromuscular irritability
What are the general signs and symptoms for hypocalcaemia?
- involve sensitisation of excitable tissues (muscle cramps/tetany, tingling) - nerve hyperexcitability
- Paraesthesia (hands, mouth, feet lips), convulsions (EXTREME), arrhythmias and tetany may occur
(PCAT)
How do you test a patient for Chvostek’s sign?
What is a positive indicator response?
What does it indicate?
- Tap the facial nerve just below the zygomatic arch (cheek bone)
- A positive response will involve twitching of the facial muscles
- This indicates neuromuscular irritability due to hypocalcaemia
How do you test a patient for Trosseau’s sign?
What is a positive indicator response?
What does it indicate?
- You inflate a BP cuff and leave it like that for several minutes
- This induces carpopedal spasm = neuromuscular irritability (hand contracts and can’t be relaxed)
State the causes of hypocalcaemia
• Vitamin D deficiency
• hypoparathyroidism
—–> surgical causes (neck surgery)
—–> auto-immune
—–> magnesium deficiency (needed for PTH)
• PTH resistance e.g. pseudohypoparathyroidism (receptor defects)
• Renal failure: Impaired 1a hydroxylation -> decreased production of 1,25(OH)2D3
Describe the effect of hypercalcaemia on neuronal excitability.
It reduces neuronal excitability and you get atonal muscles
What are the main signs and symptoms of hypercalcaemia?
Stones, abdominal moans and psychic groans
Stones – renal effects
• Polyuria + polydipsia
• Nephrocalcinosis = deposition of calcium in the kidneys (can cause renal colic)
Abdominal moans – GI effects
• Anorexia, nausea, constipation, pancreatitis, dyspepsia
Psychic groans – CNS effects
• Fatigue, depression, impaired concentration, altered mentation, coma
State the causes of hypercalcaemia (4)
- 1° 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)
Give the normal physiological response that would occur when serum Ca2+ falls
PTH increases
-> Increased calcium reabsorption from the kidney
-> Increased production of calcitriol
-> Increased calcium reabsorption from bones
PTH exerts negative feedback, to stop production of PTH and maintain normal serum calcium
Describe how you would differentiate between primary hyperparathyroidism and malignancy causing hypercalcaemia.
(look at PTH levels)
In 1° hyperparathyroidism there is no negative feedback because the parathyroid adenoma will be producing PTH autonomously
• PTH = HIGH
• Plasma Calcium = HIGH
In malignancy, the negative feedback will be intact as it is due to increased bone turnover due to bony metastases
• PTH = LOW
• Plasma Calcium = HIGH
What is the treatment if primary hyperparathyroidism?
parathyroidectomy
Define Vitamin D Deficiency
lack of mineralisation in bone
What does vitamin D deficiency cause? State some symptoms.
Lack of bone mineralisation Softening of bone (can lead to bowing of the legs) Bone deformities Bone pain Severe proximal myopathy
What are the different names for vitamin D deficiency in children and adults?
Children – Rickets
Adults – Osteomalacia
What are the serum levels in secondary hyperparathyroidism? What is the usual cause?
PTH is high, secondary to low Ca2+
usually due to vitamin D deficiency
Describe what happens in tertiary hyperparathyroidism
- Initial chronic low plasma calcium ion concentration
- The parathyroid gland is being massively stimulated for a long time
- Eventually, the PTH becomes autonomous and stops responding to negative feedback
(causes an increased plasma calcium ion level - similar to 1° hyperparathyroidism)
PRIMARY and TERTIARY hyperparathyroidism are associated with _________
HYPERCALCAEMIA
Describe the biochemical finding in vitamin D deficiency
(very difficult to measure calcitriol) Plasma 25-hydroxycholecalciferol = LOW Plasma Calcium = LOW Plasma Phosphate = LOW Plasma PTH = HIGH (2° hyperparathyroidism stimulated by the hypocalcaemia)
Describe the treatment of vitamin D deficiency in the case of normal renal function.
Give 25-hydroxy vitamin D
This can be in the form of:
• Ergocalciferol = 25-hydroxy vitamin D2)
• Cholecalciferol = 25-hydroxy vitamin D3
Describe the treatment of vitamin D deficiency in the case of renal failure.
Alfacalcidol = 1-hydroxycholecalciferol (active vitamin D)
What can vitamin D excess lead to?
Hypercalcaemia and hypercalciuria (due to increased intestinal absorption of calcium)
What can vitamin D excess result from?
- Excessive treatment with active metabolites of vitamin D, as in patients with chronic renal failure (wrong dose)
- Granulomatous disease – granulomatous tissue has 1-hydroxylase so it can be a source of ectopic calcitriol
