Calcium Phosphate Metabolism

Question 1

What are the three important hormones to consider with calcium homeostasis

NB tightly regulated

Answer 1

Extracellular calcium
Parathyroid hormone
1,25(OH)2 vitamin D (bioactive vitamin D)

Question 2

What organs are important with calcium homeostasis

Answer 2

Bone, kidney and gut

Question 3

What is PTH and when is it released?

What are its effects?

Answer 3

Parathyroid hormone released by the parathyroid glands (4). CHIEF CELLS Binds to PTHR1 receptor

Released when there is a decrease in serum calcium to:

• Stimulate osteoclastic bone resorption
• Renal tubular absorption of calcium
• Renal hydroxylation of 25(OH) D

so acts on bone and kidmey directly. gut indirectly

Question 4

Example, decreased serum calcium

Answer 4

Parathyroid senses and releases PTH into blood stream. Bone resorption occurs and renal tubular absorption occurs of calcium (phosphate expelled?). calcitriol is made causing increased intestinal absoprtion of calcium and phosphate

Question 5

What is PTH release regulated by and how?

Answer 5

• Serum ionized calcium. Negatively (and increase will shut off)
• Serum phosphate (positive)
• Calcitriol (negative)

Question 6

ECF calcium consituents

Answer 6

45-50% ionized, bioactive
5-10% with anions, HCO3-
45-50% with globulins like albumin

Question 7

CaR in PT and kidney

Answer 7

When low, relatively unliganded, will form PTH. Also with Magnesium

CaR in kidney different. When high stops Ca reabsoprtion

Question 8

Vitamin D metabolism

Answer 8

Precursor in skin is converted to calciferol when exposed to sunlight. Also consumed in the diet.
In the liver this is converted to calcidiol with in the kidneys is converted to calcitriol. This acts on the gut to increase calcium an phosphate absorption.

Calcitriol production is enhanced when there is PTH or low phosphate

Question 9

What is unique about PTHrP

Answer 9

Important regulator of breast, bone and growth development (fetal?). It does not play a physiological role in calcium homeostasis.

However simialr function as PTH and in some cancers, typically epithelial, can cause hypercalcaemia

Question 10

Causes of hypercalcaemia (dependent vs independent)

Answer 10

PTH dependent: primary hyperparathyroidism (adenoma of gland)

PTH independent: Cancer- PTHrP, myeloma; Vitamin D dependent- too much, sarcoidosis or intoxication

Question 11

Causes of Hypocalcaemia

Answer 11

Hypoparathyroidism: Post neck op
PTH resistance
Abnormality of Vitamin D metabolism: deficiency, renal failure

Question 12

Key organs and hormones in phosphate metabolism

Hormone effects

Answer 12

Bone, gut, kidney

Vitamin D: Intestinal absorption, bone resorption
PTH: bone resorption, Kidney excretion
Phosphatonins: Kidney excretion. E.g FGF23
High pH: Pushes more phosphate into cells

Question 13

Causes of hyperphosphataemia

Answer 13

Increased input, IV phosphate or cell death

Renal failure, can not excrete. PTH deficiency

Question 14

Causes of hypophosphataemia

Answer 14

Vitamin D deficiency (no sun seen, old people)
Intracellular shift
Resp alkalosis, prolonged intense exercise,
Renal loss
increased PTH or phosphatonins

Question 15

How do phosphatonins work (FGF23, from bone osteocytes)

Answer 15

Decrease phosphate reabsoprtion (excretipon thus) in the kidneys
Decreases vitamin D synthesis, meaning less is absorbed.

Essentially lower phosphate.

Question 16

Hypophosphataemia causes

Answer 16

Fanconi syndrome(defective transporter in kidney tubules)
Too much FGF23 (tumour)
Genetic resistance of FGF23 to enzyme that breaks it down
genetic PHEX abnormality, won't break down FGF23 well

Question 17

Exemplifying vitamin D deficiency leading to hypocalcaemia

Answer 17

No absorption in gut of calcium
causes secondary hyperparathyroidism
Lead to sunlight deficiency, so less vitamin D, so increased malabsorption
osteomalacia

Question 18

Osteomalacia

Answer 18

Hypocalcaemia or hypophosphataemia(renally)

Presents with bone pain, proximal myopathy, fracture.
In children leads to rickets

Question 19

Pseudohypoparathyroidism

Answer 19

PTH resistance normally due to mutation in GsAlpha oh receptor.
Seen clinically due to shorter 4th and 5th metacarpals?

Question 20

Autosomal dominant hypercalcuric Hypocalcaemia

note no treatment if asymptomatic, vitamin D if necessary

Answer 20

Activation of CaSR, meaning PT reads ionized calcium as higher than it actually is. Meaning less PTH is secreted for any given level of Calcium.
Also at a renal level will cause less calcium reabsorption

Question 21

Oncogenic osteomalacia

Answer 21

Increased phosphatonins, caused hypophosphataemia