Calcium phosphate regulation

Question 1

What is PTH?

Answer 1

Parathyroid hormone
Targets Kidneys - increases calcium retention
Releases calcium from bones
Regulates the production of active vitamin D (it regulates the enzyme that converts calciferol to calcitriol in the kidney)

Overall effect is to increase serum Ca2+

Question 2

Where is vitamin D made?

Answer 2

Liver –> in its inactive form (25-hydroxy vitamin D) Calciferol. When it gets to the kidney it becomes activated (1,25-dihydroxy vitamin D) Calcitriol

Question 3

What is the action of active vitamin D?

Answer 3

Calcitriol:
Increased absoption of phosphate in the gut
Increased reabsorption of Calcium in the gut
Calcium maintenance in bone
Increased renal Ca2+ reabsorption

Question 4

Draw the diagram for phosphate regulation

Answer 4

See diagram

Question 5

Define FGF23

Answer 5

Fibroblast growth factor 23 from osteocytes

Question 6

How PTH regulated?

Answer 6

High Ca2+ binds to calcium sensing receptor on the surface of parathyroid cells. This inhibits PTH secretion.

Low extracellular Ca2+ the opposite occurs.

Question 7

How is vitamin D synthesised in the skin?

Answer 7

7-dehydrocholesterol –> Catalysed by UVB light –> vitamin D3 (cholecalciferol). Vitamin D2 from diet (Ergocalciferol).
Results in 25 OH-D3 (in the liver - so liver disease would make you vitamin D deficient) (inactivated - calciferol)

Question 8

How is calciferol converted to calcitriol?

Answer 8

Renal 1a-hydroxylase (stimulated by PTH)

1,25 dihydroxycalcitriol

Question 9

What does calcitriol have a negative feedback on?

Answer 9

PTH

Question 10

Draw vitamin D synthesis and use diagram

Answer 10

See diagram

Question 11

Causes of vitamin D deficiency?

Answer 11

Malasorption (coeliac disease) or dietary insufficiency
Not enough sunshine
Liver disease (calciferol cannot be produced)
Renal disease (a1 hydroxlation can not occur)
Receptor defects

Question 12

How do changes in extracellular calcium affect nerve and skeletal muscle excitability?

Answer 12

To generate an AP nerves/muscles require Na+ influx across the cell membrane. Ca2+ competes with Na+ to get into the cell

Hypercalcaemia = means Ca2+ blocks Na+ influx so there is less membrane excitability
Hypocalcaemia = means greater Na+ influx, so more membrane excitability

Question 13

What is the normal serum range of Ca2+

Answer 13

2.2-2.6 mmol/L

Question 14

What are the signs and symptoms of hypocalcaemia?

Answer 14

Parasthesia (hands, mouth, feet, lips) - tingling sensation
Convulsions
Arrthymias
Tetany

CATs go numb

Question 15

What are the 2 ways of assessing hypocalcaemia in a patient?

Answer 15

Chvostek’s sign - tap facial nerve below zygomatic arch, if there is twitching of facial muscles it indicates neuromuscular irritability due to hypocalcaemia.

Trousseau’s sign - inflation of BP for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia

Question 16

Causes of hypocalcaemia?

Answer 16

Vitamin D deficiency
Low PTH levels = hypoparathyroidism - Surgical – neck surgery, Auto-immune, Magnesium deficiency (you need magnesium for parathyroid hormone to work)
PTH resistance eg pseudohypoparathyroidism
Renal failure - Impaired 1a hydroxylation decreased production of 1,25(OH)2D3

Question 17

What are the signs and symptoms of hypercalcaemia?

Answer 17

‘Stones, abdominal moans and psychic groans’

Stones – renal effects (stones being stuck in kidneys)
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)

Question 18

What are the causes of hypercalcaemia?

Answer 18

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)

Question 19

What diagnostic features are present in primary hyperparathyroidism?

Answer 19

Can be caused by a tumour producing lots of PTH

Raised Calcium
Low phosphate (PTH is promoting the excretion of PO4^3-) 
Raised PTH (unsuppressed)

Question 20

What are the diagnostic features present in hypercalcaemia of malignancy

Answer 20

Caused my bony metastasis - producing Ca2+

Raised calcium
Suppressed PTH

Question 21

Define vitamin D deficiency?

Answer 21

Lack of bone mineralisation in bone

Results in soft bones, bone deformities, bone pain; severe proximal myopathy.

Question 22

Vitamin D deficiency in children is called…

Answer 22

Rickets

Question 23

Vitamin D deficiency in adults is called…

Answer 23

Osteomalacia

Question 24

How do you treat primary hyperparathyroidism?

Answer 24

Parathyroidectomy

Question 25

Describe secondary hyperparathyroidism?

Answer 25

Vitamin D deficiency | High PTH because PTH increases to try to normalise serum calcium which is low.

Question 26

Biochemical findings in vitamin D deficiency?

Answer 26

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)

Question 27

How do you treat patients with vitamin D deficiency?

Answer 27

``` In patients with normal renal function 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 Cholecalciferol 25 hydroxy vitamin D3 ``` In patients with renal failure - inadequate 1a hydroxylation, so can’t activate 25 hydroxyl vitamin D preparations Give Alfacalcidol - 1a hydroxycholecalciferol

Question 28

What can vitamin D excess lead to?

Answer 28

Can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium Can occur as a result of: 1) excessive treatment with active metabolites of vitamin D eg Alfacalcidol 2) granulomatous diseases such as sarcoidosis, leprosy and tuberculosis (macrophages in the granuloma produce 1a hydroxylase to convert 25(OH) D to the active metabolite 1,25 (OH)2 D