PHYS Calcium Balance - Week 11

Question 1

Normal total plasma Ca2+ levels

Answer 1

2.2-2.6mM

Question 2

Main side effect of low calcium levels & high.

Answer 2

Increased muscle excitability. Increased risk of cardiac arrhythmias.

Question 3

3 x types of bone cells and their derivatives.

Answer 3

Osteoclasts - haematopoetic SCs
Osteoblasts - mesenchymal SCs
Osteocytes - osteoblasts that become trapped in the matrix they secrete.

Question 4

Osteoclasts function

Answer 4

Secrete H+ ions -> dissolve crystals on osteoid & secrete hydrolytic enzymes -> digest osteoid -> Ca2+ & PO42- release back into the bloodstream.

Question 5

Osteoblasts function

Answer 5

Acquire Ca2+ & PO42- from blood -> synthesise hydroxyapatite -> deposited into the matrix to form mineralised tissue.

Question 6

Hormones that favour bone resorption

Answer 6

PTH, cortisol, thyroid hormone.

Question 7

Hormones that favour bone formation.

Answer 7

Growth hormone, insulin, IGF-1, oestrogen, testosterone, (calcitonin).

Question 8

How do hormones that favour bone resorption do this?

Answer 8

Stimulate RANK ligand secretion by osteoblasts -> RANKL bind to cell surface of osteoclasts -> increased bone resorption -> increased osteoclast differentiation.

Question 9

How do hormones that favour bone formation do this?

Answer 9

Stimulate OPG secretion by osteoblasts -> bind to RANKL to inhibit function.

Question 10

Do sex steroids promote bone resorption or deposition?

Answer 10

Deposition via activation of osteoblasts (& osteocytes) w inhibition of osteoclast activity.

Question 11

PTH mediates:

Answer 11

• calcium absorption & secretion @ the nephron level.
• calcium absorption @ intestines.

Question 12

How does PTH maintain Ca2+ homeostasis?

Answer 12

Extracellular Ca2+ binds directly to chief cells of the parathyroid gland via a membrane Ca2+ receptor.
If this receptor detects that Ca2+ levels are low:
PTH secreted by chief cells of the parathyroid glands (84 amino acid protein) when Ca2+ levels & enzymatic cleavage can release an N-terminal 34 amino-acid fragment (PTH 1-34).
If this receptor detects that Ca2+ levels are high:
PTH gene transcription & thus secretion is inhibited.

Question 13

Reduced circulating plasma Ca2+ has what affect on the PTH glands?

Answer 13

Increased PTH secretion.

Question 14

Increased plasma PTH concentration has what affect on the kidneys & bones.

Answer 14

Increased Ca2+ reabsorption & vit D formation.
Increased bone resorption.

Question 15

Increased vit D concentration has what affect on the intestines?

Answer 15

Increased Ca2+ absorption into bloodstream.

Question 16

Restoration of plasma Ca2+ concentration to towards normal has what affect on PTH glands?

Answer 16

-ve feedback - inhibits further secretion of PTH.

Question 17

How does PTH affect 1,25-OH2 D synthesis?

Answer 17

Stimulates activity of 1-hydroxylase which facilitates conversion from 25-OH D -> 1, 25-(OH)2 D.

Question 18

Causes of rickets and common symptoms?

Answer 18

Rickets – involves deficient mineralisation of bone matrix due to vit D deficiency, symptoms incl:
* Bowlegged
* Easy fractures.

Question 19

Pathophys & symptoms of hypercalcaemia.

Answer 19

Hypercalcaemia – primary hyperparathyroidism main cause -> increased Ca2+ resorption/absorption from gut & decreased renal excretion, symptoms incl:

• Fatigue
• Depression
• Lethargy
• Irritability
• Muscle weakness & aches
• Bone & joint weakening and/or pain
• Nausea
• Vomiting
• Abdominal pain
• Polyuria
• Kidney stones.

Question 20

Pathophys & symptoms of hypocalcaemia.

Answer 20

Hypocalcaemia – loss of parathyroid gland function -> decreased PTH levels & decreased vit D levels -> decreased bone resorption/absorption & increased renal excretion, symptoms incl:

• Seizures
• Muscle spasms.

Question 21

Function of calcitonin in humans.

Answer 21

Limited function - has more of an affect in other species.
However, does inhibit some osteoclastic bone resorption and is thus used clinically to treat Paget’s disease, hypercalcaemia & osteoporosis.`