Calcium metabolism

Question 1

What are the physiological functions of calcium?

Answer 1

Muscle contraction
Bone strength
Intracellular messenger and co-enzyme
blood coagulation
hormone/neurotransmitter stimulus-secretion coupling

Question 2

How is calcium stored?

Answer 2

Mostly as salts
99% in blone as complex hydrated Ca2+ salt
Less in blood as ionised calcium and attached to proteins
Only free Ca2+ is bioactive - 50% unbound in blood, 45% to plasma proteins and 5% as diffusable salts

Question 3

How is calcium regulated?

Answer 3

Parathyroid hormone and calcitrol increases Ca2+
Calcitonin from parafollicular cells of thyroid decreases Ca2+
Homeostasis dependent on osteoclast:osteoblast ratio
-increased osteoclast activity = increased Ca2+ and (PO4)3- into blood
-Increased osteoblast activity = formation of calcium salts in bone

Question 4

How is calcium regulated in the parathyroid gland?

same receptors as in kidneys and GI

Answer 4

G-protein coupled receptors have transmembrane domains and an external binding site
Ligand binding changes G protein conformation to allow G subunit intracellular mechanism
When calcium high receptor suppresses PTH release as regulation not needed
When calcium low G protein receptors lead to parathyroid hormone release

Question 5

What causes increased osteoblast activity?

Answer 5

Low concentration of PTH, High calcitonin and low calcitrol

Question 6

What causes increased osteoclast activity and increased intestinal/renal Ca2+ absorption?

Answer 6

High PTH, Low calcitonin, high calcitrol

Question 7

How is hypocalcaemia identifiable?

Answer 7

Tetany due to Na+ entering cells more easily and increasing the likelihood of an action potential
Trousseau’s sign - BP cuff stops blood flow and hand starts to contract

Question 8

What are principle causes of hypocalcaemia?

Answer 8

Hypoparathyroidism - decreased PTH secretion
-idiopathic or due to hypomagnesaemia
-suppressed by raised blood Ca2+
Pseudohypoparathyroidism - target organ resistance to PTH
-Defective Gs protein
- Low IQ, short staturem subcutaneous calcification
Vitamin D deficiency
- rickets in children and osteomalacia in adults
-decreased calcification of bone matrix=bone softening (kids) fractures (adults)

Question 9

What are the main causes of hypercalcaemia?

Answer 9

endocrine 1°/2°/3° hyperparathyroidism

Vitamin D toxicosis - high intake

Question 10

What is the role of PTH?

Answer 10

preservation of plasma calcium concentration at the expense of bone

Question 11

What is the role of calcitrol?

Answer 11

Promotes laying of calcium/phosphate salts in bone

Question 12

What is the role of calcitonin?

Answer 12

Limited effect to protect bone

Question 13

How is PTH produced?

Answer 13

Pre-proPTH cleaved to 84aa PTH

Question 14

How is calcitrol produced?

Answer 14

VitD3 sourced from diet and conversion from cholesterol in skin under UV light
Hydroxylated twice in kidneys

Question 15

How is calcitonin produced?

Answer 15

Pre-procalcitonin cleaved to produce calcitonin

Question 16

What is the method of action of PTH?

Answer 16

Binds to transmembrane G protein linked receptors

activates adenyl cyclase and phospholipase C

Question 17

What is the method of action of calcitrol?

Answer 17

Increases bone osteoblast activity and calcium/phosphate absorption in the kidneys
increase levels for bile salts

Question 18

What is the method of action of calcitonin?

Answer 18

Inhibits osteoclast activity
Stops bone breakdown
Increases kidney’s secretion of calcium

Question 19

How is PTH regulated?

Answer 19

Decreased plasma conc of Ca2+ increases PTH secretion
Increase in plasma conc of Ca2+ produces -ve feedback via sensing receptor
Inhibited by VitD/Ca2+
Stimulated by catecholamines

Question 20

How is calcitrol regulated?

Answer 20

Inhibited by FGF23

Stimulated by high Ca2+

Question 21

How is calcitonin regulated?

Answer 21

Gastrin from stomach increases calcitonin

XS acid results from high circulating Ca2+

Question 22

What are the effects of PTH in the kidneys?

Answer 22

increase in phosphate excretion and Ca2+ reabsorption
Stimulates 1α hydroxylase to synthesise active form of VitD3 which acts on small intestine to increase Ca2+ and PO43- absorption

Question 23

What are the effects of PTH in bones?

Answer 23

Binds to the PTH receptors on osteoblasts to stimulate release of osteoclast activating factors
These bind to osteoclast receptors to cause bone resorption

Question 24

What are the effects of PTH in blood?

Answer 24

Increases circulating Ca2+ levels for contraction and signalling

Question 25

How does PTH regulate phosphate reabsorption?

Answer 25

Stimulates kidneys to increase phosphate excretion but also stimulates SI to increase phosphate absorption

Question 26

How does fibroblast growth factor 23 regulate phosphate reabsorption?

Answer 26

VitD3 stimulates phosphate absorption, but if to high then FGF23 stimulated so more Na+ and phosphate enters urine

Question 27

How does calcitrol regulate phosphate reabsorption?

Answer 27

Stimulates FGF23 in high phosphate concentration

negatively feeds back on calcitrol

Question 28

What hormones control phosphate reabsorption?

Answer 28

PTH
FGF23
Calcitrol

Question 29

What is 1° hyperparathyroidism caused by?

Answer 29

Parathyroid adenoma produces XS PTH

not regulated by increased Ca2+

Question 30

What is 2° hyperparathyroidism caused by?

Answer 30

Parathyroid glands secrete XS PTH in response to chronically low plasma Ca2+
Often seen in kidney failure

Question 31

What is 3° hyperparathyroidism caused by?

Answer 31

Began as 2°
PTH levels got so high that glands became hyperplastic
Underlying deficiency rectified, but autonomous parathyroid glands no longer -vely regulated by plasma Ca2+