Endocrine control of calcium metabolism

Question 1

What is the main form of calcium

Answer 1

Hydroxyapatite crystals in bone

Question 2

In what forms are calcium present in the blood

Answer 2

50% unbound
45% bound to plasma proteins
5% diffusible salts (citrate, lactate)

Question 3

What form of calcium is bioactive

Answer 3

free Ca2+

Question 4

What are the roles of calcium

Answer 4

Neuromuscular excitability
Muscle contraction
Strength in bones
Intracellular second messenger
Intracellular co-enzyme
Hormone/neurotransmitter stimulus-secretion coupling
Blood coagulation (factor IV)

Question 5

What is the main route of calcium after intake

Answer 5

Intake -> GI tract -> blood -> kidneys

Question 6

From the blood where may calcium travel

Answer 6

bone and other cells
kidney
Loss in hair, skin and nails

Question 7

What is released when calcium levels are too low

Answer 7

Parathyroid hormone and calcitrol

Question 8

Describe the calcium sensing receptor

Answer 8

G-protein coupled receptor that is activated by ligand binding (suppresses PTH)

Question 9

Describe the process of PTH synthesis

Answer 9

1. synthesised as pre-proPTH

2. cleavage to form PTH

Question 10

Where is PTH synthesised

Answer 10

parathyroid glands

Question 11

Where is calcitonin synthesised

Answer 11

parafollicular cells of the thyroid

Question 12

How does PTH affect the kidneys

Answer 12

Increases calcium reabsoprtion
Increases phosphate excretion
Stimulate 1𝛼 hydroxylase activity to increase calcitrol synthesis

Question 13

How does PTH affect the small intestine

Answer 13

Calcitrol synthesis in the liver stimulates increased calcium absorption
Increased phosphate absoprtion

Question 14

How does PTH affect the bone

Answer 14

Stimulation of osteoclasts and inhibition of osteoblasts so an increase in bone resorption (decrease in bone mass)

Question 15

Describe the process of PTH induced decreased bone resorption

Answer 15

1. PTH binds to the PTH receptor on an osteoblast
2. Osteoblasts release osteoclast activating factors (RANKL)
3. Increased bone resorption

Question 16

How is PTH regulated

Answer 16

Increased plasma calcium creates a negative feedback effect to reduce PTH levels from the parathyroid gland

Question 17

How is calcitriol synthesised

Answer 17

1. UV light converts 7-dehydrocholesterol into cholecalciferol/ obtained from the diet
2. Synthesis of 2,5-hydroxy-cholecalciferol in the liver (+2 OH groups)
3. PTH stimulates 1𝛼 hydroxylase
4. synthesis of 1,25-di-hydroxycholecalciferol in the kidney

Question 18

How does calcitriol affect the bone

Answer 18

Increased osteoblast activity

Question 19

How does calcitriol affect the kidneys

Answer 19

Increased calcium and phosphate reabsorption

Question 20

How does calcitriol affect the small intestine

Answer 20

Increased calcium and phosphate absorption

Question 21

How are circulating phosphate levels regulated

Answer 21

Fibroblast growth factor 23 once stimulated by high phosphate and vitamin D3 levels in the kidney

Question 22

How does FGF23 work

Answer 22

Inhibits the reabsorption of phosphate and sodium through the phosphate sodium cotransporter in the kidney (PTH does the same)

Question 23

What are the main effects of calcitonin

Answer 23

Increased urinary excretion of calcium, sodium and phosphate
Inhibition of osteoclast activity
Decrease calcium levels

Question 24

What are the three main causes of hypocalcaemia

Answer 24

Hypoparathyroidism
Pseudohypoparathyroidism
Vitamin D deficiency

Question 25

What are the signs of hypocalcaemia

Answer 25

Trousseau's | Chvostek's

Question 26

What are the features of hypoparathyroidism

Answer 26

low calcium, high phosphate, low PTH Hypomagnesaemia Suppression by raised calcium concentration

Question 27

What are the features of pseudohypoparathyroidsm

Answer 27

Target organ resistance to PTH (may be due to defective Gs protein) low calcium, high phosphate, high PTH

Question 28

What are the clinical features of pseudohypoparathyroidism

Answer 28

Short stature Round face Low IQ Subcutaneous calcification and one abnormalities Endocrine disorders (hypothyroidism, hypogonadism)

Question 29

What can vitamin D deficiency cause

Answer 29

Ricketts in children | Osteomalacia in adults

Question 30

What are the clinical features of vitamin D deficiency

Answer 30

Decreased calcification of the bone matrix Softening of the bone Bowing of the bones Fractures

Question 31

What are the features of vitamin D deficiency

Answer 31

Low calcium, low phosphate, high PTH

Question 32

What are some clinical features of hypercalcaemia

Answer 32

``` Increased calcium reabsorption Increase phosphate excretion Polyuria Renal stones Nephrocalcinosis Gastric acid release Duodenal ulcers Bone lesions Bone rarefaction (reduction in density) Fractures ```

Question 33

What is primary hyperparathyroidism

Answer 33

High levels of PTH are produced due to an adenoma growing in the glands, increasing the circulating calcium levels. -ve feedback system does not work

Question 34

What is secondary hyperparathyroidism

Answer 34

PTH levels remain high but calcium levels remain low, commonly due to kidney disease as it cannot reabsorb the calcium needed

Question 35

What is tertiary hyperparathyroidism

Answer 35

The parathyroid glands grow due to secondary parathyroidism and once this has been treated, the glands remain large and become autonomous, not responding effectively to feedback

Question 36

What is another cause of hypercalcaemia

Answer 36

Vitamin D toxicosis