Calcium and Phosphate Metabolism

Question 1

What are the 3 actions of PTH?

Answer 1

PTH is parathyroid hormone, it is released by chief cells in the parathyroid gland in response to low Ca²⁺ levels and increases serum Calcium.

1. By Osteoclastic bone resorption.
2. Renal Calcium absorption.
3. Renal hydroxylation of 25(OH)D –> 1,25(OH)₂D, which stimulates Calcium uptake in the intestine.

Question 2

What are the 3 up-regulators of PTH?

Answer 2

1. Mainly low serum Calcium
2. Also high Phosphate
3. And low 1,25-(OH)₂D

All of these increase the amount of PTH released by the parathyroid gland.

Question 3

Why may a patient in late stage epithelial cancer have hypercalcemia?

Answer 3

Because of Parathyroid hormone related peptide (PTHrP).

This is normally a paracrine hormone that acts very similarly to PTH, important for bone/breast development in the fetus.

But in some cancers (esp. epithelial) it can be secreted into the circulation and increase serum Calcium (like PTH would).

Question 4

What does a high pH do to the serum phosphate level?

Answer 4

Reduces it.

High pH drives Phosphate from ECF to ICF

Question 5

What mainly causes hyperphosphataemia?

Answer 5

kidney faliure. cannot excrete enough Phosphate.

Or PTH deficiency ir resistance

Question 6

Label this image please

(Phosphate metabolism)

Answer 6

Here is the labeled image in case you couldn’t do it:

Question 7

What mainly causes hypophosphataemia?

Answer 7

Not enough Vit-D (also imp. for low Calcium)

High pH

Increased PTH or Phosphatonins –> Renal excretion

Question 8

What is FGF23 and what does it do?

Answer 8

FGF23 is a Phosphatonin derived from bone which causes hypophosphataemia.

1. By reducing phosphate reabsorption in the kidney
2. By inhibiting formation of 1,25(OH)₂D and reducing the amount of phosphate absorbed in the gut.

Question 9

What is Fanconi syndrome?

Answer 9

Fanconi syndrome is the result of inadequate reabsorption in the kidneys.

In particular (for this topic) is phosphate reabsorption which results in hypophosphataemia which can lead to osteomalacia/rickets in children.

Question 10

What are the 3 genetic causes of hypophosphataemia and 1 acquired cause?

Answer 10

Genetic:

1. Inadequate reabsorption in kidneys (Fanconi syndrome)
2. Abnormal PHEX enzyme which breaks down FGF23
3. Abnormal FGF23 which is over-expressed

Acquired:

1. Excessive FGF23 prodction from tumour

Question 11

what are the 4 main causes of hypercalcaemia?

Answer 11

1. Benign hyperparathyroidism
2. Cancer associated
3. Vitamin D toxicity - exogenous (supplement overdose) or endogenous (sarcoidosis)
4. Familial Benign Hypercalcaemia