12. Calcium and phosphate regulation

Question 1

Where is parathyroid hormone (PTH) made?

Answer 1

Parathyroid glands

Question 2

What is the function of PTH?

Answer 2

• Promotes calcium absorption in kidney (less excretion)
• Promotes calcium release from the bones
• Regulates the conversion of inactive vitamin D (25-hydroxy-vitamin-D) => active vitamin D (calcitriol)
- vitamin D promotes calcium reabsorption from the gut and bones, as well as renal Ca reabsorption

PTH generally increases serum calcium

Question 3

How does PTH affect phosphate reabsorption?

Answer 3

• Phosphate is reabsorbed using sodium-phosphate co-transporters in the PCT (of the nephron)
• PTH inhibits this
• So if you have hyperparathyroidism, you increase phosphate excretion

Question 4

What is FGF23 and how does it affect phosphate levels?

Answer 4

• Fibroblast growth factor 23 from osteocytes
• Inhibits the reabsorption of phosphate in 2 ways:
- via the sodium-phosphate co-transporter
- inhibits calcitriol

Question 5

Describe how parathyroid cells work?

Answer 5

• Have calcium-sensing receptors on their surface
• High calcium in ECF => calcium binds to receptors => inhibits PTH secretion
• Low calcium => more PTH release

Question 6

How can we get vitamin D into our bodies (outline mechanisms to form active vitamin D?

Answer 6

• Ergocalciferol from the diet (activated in the liver and kidneys)
• UVB light converts 7-dehydrocholesterol => cholecalciferol
• Liver converts cholecalciferol => 25-OH-D3 (inactive)
• This is converted by 1α-hydroxylase in the kidney to 1,25-(OH)2-D3 (calcitriol) - biologically active
• The last step is stimulated by PTH

Question 7

What effect does active vitamin D have on PTH?

Answer 7

Negative feedback on PTH (calcitriol receptors on parathyroid cells)

Question 8

What can cause vitamin D deficiency?

Answer 8

• Poor diet
• Malabsorption e.g. IBD
• Lack of sunlight
• Liver and renal disease of any cause
• Vitamin D resistant rickets - receptor defects rather than vitamin D production

Question 9

How does hyper/hypocalcaemia affect nerve and skeletal muscle excitability?

Answer 9

• Nerves/skeletal muscles require Na+ influx to generate an AP
• Hyper/hypocalcaemia describes extracellular Ca2+
• Ca2+ blocks Na+ influx
• Hyper - less membrane excitability
• Hypo - more membrane excitability

Question 10

What is the normal range for serum Ca2+?

Answer 10

2.2-2.6 mmol/L

Question 11

What are the signs and symptoms of hypocalcaemia?

Answer 11

• Sensitisation of excitable tissues - muscle cramps/tetany, extreme convulsions, tingling
• Paraesthesia (hands, mouth, lips, feet)
• Arrhythmias
• Chvostek’s and Trousseau’s sign

Question 12

What is Chvostek’s sign?

Answer 12

• Tap the facial nerve just below the zygomatic arch
• Positive response - twitching of the facial muscles
• Indicates neuromuscular irritability due to hypocalcaemia

Question 13

What is Trousseau’s sign?

Answer 13

• Inflate a BP cuff and leave for several minutes

* Induces carpopedal spasm - hand contracts and can’t be relaxed

Question 14

What are the causes of hypocalcaemia?

Answer 14

• Vitamin D deficiency
• Low PTH - hypoparathyroidism (can be surgical cause, autoimmune or magnesium deficiency)
• PTH resistance (pseudoparathyroidism) due to receptor defects
• Renal failure - impaired 1α-hydroxylation => decreased production of 1,25(OH)2D3

Question 15

What are the signs and symptoms of hypercalcaemia?

Answer 15

• Kidney stones
• Polyuria and polydipsia
• Nephrocalcinosis, renal colic, chronic renal failure
• Abdominal moans
- anorexia, nausea, dyspepsia, constipation, pancreatitis
• Psychic groans (CNS effects)
- fatigue, depression, impaired concentration, coma if >3mmol/L

Question 16

What are the causes of hypercalcaemia?

Answer 16

• Primary hyperparathyroidism
• Malignancy - tumours often secrete a PTH-like peptide
• Conditions with high bone turnover e.g. hyperthyroidism
• Vitamin D excess (rare)

Question 17

What is primary hyperparathyroidism and how is it treated?

Answer 17

• Tumour in the parathyroid causing increased PTH secretion
• Unlikely to be regulated by normal negative feedback
• Leads to increased plasma [Ca2+]
• No negative feedback
• Low phosphate
• Treatment: parathyroidectomy

Question 18

What is a lack of mineralisation in the bone caused by vitamin D deficiency called in children and adults?

Answer 18

• Children - rickets

* Adults - osetomalacia

Question 19

What is secondary hyperparathyroidism?

Answer 19

• Usually due to vitamin D deficiency => low calcium
• Can also be due to renal failure leading to a loss of calcium in the urine
• Low calcium stimulates PTH release
• This is a response to try and normalise serum calcium

Question 20

What is tertiary hyperparathyroidism?

Answer 20

• Initial chronic low plasma calcium ion concentration
• Parathyroid gland is stimulated for a long time because of this
• PTH (release) eventually becomes autonomous and stops responding to negative feedback
• Increases plasma calcium ion (so high PTH and high Ca2+)

Question 21

Are the following high or low in vitamin D deficiency:
• Plasma [25(OH)D3] (used to assess body vitamin D stores)
• Plasma [Ca2+]
• Plasma [phosphate]
• [PTH]

Answer 21

• [25[OH]D3] - usually low
• [Ca2+] - low (may be normal in 2°)
• [Phosphate] - low
• [PTH] - high

Question 22

How can you treat vitamin D deficiency?

Answer 22

• Give 25(OH)D - calcifediol
- patients convert this to 1,25(OH)2D via 1α-hydroxylase
• Can be given as ergocalciferol (25(OH)D2) or cholecalciferol (25(OH)D3)
• In patients with renal failure (inadequate 1α-hydroxylase), give alfacalcidol - 1α-hydroxycholecalciferol - an active vitamin D3 metabolite (supplement)

Question 23

What can vitamin D excess lead to?

Answer 23

• Hypercalcaemia

* Hypercalciuria

Question 24

What can cause vitamin D excess?

Answer 24

• Excessive treatment with active metabolites of vitamin D
• Granulomatous diseases e.g. sarcoidosis, leprosy and TB
- macrophages in the granuloma produce 1α-hydroxylase producing more calcitriol