Calcium and Phosphate Regulation

Question 1

Where is the majority of calcium and phosphate foudn physiologically?

Answer 1

Bone

Question 2

What are the 3 physiological states of calcium?

Answer 2

1) Complexed (5%)
2) Protein-bound (45%)
3) Ionised (50%)

Question 3

At higher pH, (more/less) ionised calcium is bound.

Answer 3

More
- bound to protein and H+

Question 4

What cells are responsible for the formation of bone?

Answer 4

Osteoblasts
Osteocytes

Question 5

What cells are responsible for bone resorption?

Answer 5

Osteoclasts

Question 6

What cells are responsible for the growth of bones?

Answer 6

Chondrocytes (epiphyses)

Question 7

What are the 2 components/composition of bone?

Answer 7

1) Hydroxyapatite (mineral)
2) Osteoid (organic matrix)

Question 8

What are 2 ways parathyroid hormone release can be stimulated?

Answer 8

1) ↓[Ca2+] (eg. alkalosis)
- via Ca2+ sensing receptor (GPCR)
- loss of inhibition of parathyroid cell PTH release by Ca2+

2) ↑[PO4-] (eg. late CKD)

Question 9

What are 4 biological actions of PTH?

Answer 9

1) Stimulates bone resorption

2) ↑Ca2+ reabsorption @ DCT

3) ↓ PO4- reabsorption @ PCT

4) ↑ Vit. D reabsorption @ PCT i) promotes PTH effect on bone resorption
ii) ↑Ca and PO4- absorption in gut
iii) ↑Ca and PO4- reabsorption in kidney

Question 10

How does Vit. D facilitate Ca2+ reabsorption in the GIT?

Answer 10

1) Ca2+ enter via Ca2+ channels or diffusion @ BBM

2) Ca2+ binds to calbindin (Vit D dependent)

3) Ca2+ efflux via (i) Na/Ca exchanger (ii) Calcium ATPase

Question 11

How is calcitonin secretion stimulated?

Answer 11

↑[Ca2+] detected by parafollicular/C cells in thyroid

Question 12

What are 2 biological effects of calcitonin?

Answer 12

1) ↓Bone resorption
2) ↓Ca2+ Reabsorption @ kidney

Question 13

Describe the process of phosphate homeostasis.

Answer 13

↑[PO4-] → ↑FGF23
i) ↓[PO4-] reabsorption in PCT → ↑[PO4- excretion)
ii) ↓production of active vit. D → ↓PTH-like effects

Question 14

What is osteoporosis?

Answer 14

Condition where bone resorption > formation → brittle bones
- effect of hormones (eg. estrogen deficiency, hypercortisolism)

Question 15

What is osteomalacia?

Answer 15

Soft, weakened bones (eg. rickets)

Question 16

What is the clinical definition of hypercalcemia?

Answer 16

Total calcium >2.6mM

Question 17

What are 2 causes of hypercalcemia?

Answer 17

1) Primary hyperparathyroidism
2) Malignancies (eg. mulitple myeloma, HHM)
3) Vitamin D excess (eg. sarcoidosis)
4) Milk alkali syndrome
5) Immobilisation
6) Familial hypocalciuric hypercalcemia
7) Endocrine disorders (eg. thyrotoxicosis, Addison’s)
8) Drugs (eg. Thiazide diuretics)

Question 18

What is the clinical definition of hypocalcemia?

Answer 18

<2.1mM

Question 19

How does secondary hyperparathyroidism cause hypercalcemia?

Answer 19

It doesnt lol
- secondary hyperparathyroidism is a compensatory response to ALREADY LOW [Ca2+]
- compensatory ↑in PTH to ↑[Ca2+] back to normal

Question 20

What are 3 causes of hypocalcemia?

Answer 20

1) Vit D deficiency (eg. dietary insufficiency, liver/kidney failure, poor exposure to sunlight)
2) Thyroid insufficiency (eg. iatrogenic thyroidectomy)
3) Hyperphosphatemia
4) Renal disease
5) Pseudohypoparathyroidism
6) Acute pancreatitis

Question 21

What are 4 clinical features of hypercalcemia?

Answer 21

“Stones, bones, moans and abdominal groans”
1) Renal
- stones, polydipsia, polyuria
2) Bones
3) Neurological
- eg. fits, confusion, irritability
4) GI
- eg. anorexia, abdo pain
5) Cardiac
- eg. arrythmias

Question 22

How is hypercalcemia treated?

Answer 22

1) Rehydrate w IV saline
2) Bisphosphonates
3) Treat underlying cause (eg. excision of parathyroid nodule)

Question 23

What is the likely diagnosis of a px with:
↑ plasma Ca
↓ plasma phosphate

Answer 23

Primary Hyperparathyroidism Malignancy (HHM)

Question 24

What is the likely diagnosis of a px with:
↑ plasma Ca
↑ plasma phosphate

Answer 24

1) Malignancy
2) Hypervitaminosis D

Question 25

What is the likely diagnosis of a px with: ↓ plasma Ca ↑ plasma phosphate

Answer 25

1) Hypoparathyroidism 2) Renal failure

Question 26

What is the likely diagnosis of a px with: ↓ plasma Ca ↓ plasma phosphate

Answer 26

Vitamin D deficiency

Question 27

How is primary hyperparathyroidism differentiated from HHM/malignancy?

Answer 27

Hyperparathyroidism: 1) <3.5mmol/L 2) mths/yrs 3) Slow rate of Ca ↑ 4) Renal stones common 5) ↑plasma PTH Malignancy: 1) > 3.5mmol/L 2) wks/mths 3) Rapid rate of Ca ↑ 4) Renal stones uncommon 5) Low PTH

Question 28

What are 3 causes of primary hyperparathyroidism?

Answer 28

1) Parathyroid adenoma 2) Parathyroid hyperplasia 3) Parathyroid carcinoma

Question 29

What are 3 biochemical features of primary hyperparathyroidism?

Answer 29

1) ↑Ca 2) normal/↓ PO4- 3) Metabolic acidosis

Question 30

How do tumours without bony metastases cause hypercalcemia (HHM)?

Answer 30

Produce PTHrP that mimics PTH action

Question 31

What are 3 clinical features of hypocalcemia?

Answer 31

1) Neurological (eg. tetany, fits) 2) Cardiovascular 3) Cataracts

Question 32

How is hypocalcemia treated?

Answer 32

1) Oral calcium 2) Vitamin D supplements

Question 33

How can the cause of hypocalcemia be elucidated?

Answer 33

1) Exclude renal (urea creatinine) 2) Measure PTH a) Low → Post-surgery, idiopathic, Mg deficiency b) High → Vit. D deficiency, Pseudohypoparaythyroidism