Lecture 7: Endocrine Control of Calcium Balance

Question 1

what is the effect of hypocalcaemia on membrane excitability?

Answer 1

• hypocalcaemia increases neuronal Na+ permeability leading to hyperexcitation of neurons.
• in extreme cases, causes tetany, if spreads to the larynx and respiratory muscles > asphyxiation.

Question 1

list the roles of calcium in the body

Answer 1

1. signalling molecule: exocytosis of synaptic vesicles e.g. neurotransmitters/hormones etc, contraction of muscle fibres, alters enzyme function.
2. blood clotting: essential component of clotting cascade.
3. apoptosis
4. skeletal strength: 99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton.
5. membrane excitability: Ca2+ decreases Na+ permeability. Most critical inshort-term homeostasis.

Question 2

what is the effect of hypercalcaemia on membrane excitability?

Answer 2

• decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias.

Question 3

what is the % of intracellular calcium distribution?

Answer 3

0.9%
- mostly stored in mitochondria and SR.
- free intracellular [Ca2+] very low.

Question 4

what is the % distribution of calcium in the extracellular fluid?

Answer 4

0.1%
- nearly half ECF Ca2+ is bound to protein.
- so only 0.05% of the calcium in the body is free in solution and physiologically active.

Question 5

1kg (99%) of calcium is stored in the calcified extracellular matrix of bone, mostly in the form of?

Answer 5

hydroxyapatite (Ca10(PO4)6(OH)2) so phosphate homeostasis is also important in determining calcium balance.

Question 6

what is the normal range of calcium found in plasma (mM)?

Answer 6

2.2-2.6 mM
only about 1.2mM is physiologically active

Question 7

what proteins does calcium bind to in the blood?

Answer 7

40% of EC calcium:
- albumin 80%
- globulin 20%

Question 8

what does the remaining 10% of calcium in the plasma that is neither protein bound or free do?

Answer 8

binds to plasma anions

Question 9

as the pH rises, the binding capacity of Ca2+….

Answer 9

binding capacity of Ca2+ increases, causing free plasma concentration to fall and therefore may precipitate hypocalcaemic tetany.

Question 10

as the pH falls, the binding capacity of Ca2+….

Answer 10

• binding capacity reduces, causing free Ca2+ in plasma to increase, can cause arrhythmias.

Question 11

which two hormones act to increase plasma [Ca2+]?

Answer 11

1. parathyroid hormone (PTH): polypeptide hormone produced by the parathyroid glands.
2. calcitriol (active form of vit D): steroid hormone produced from vitamin D by the liver and kidneys.

Question 12

which hormone acts to decrease plasma [Ca2+]?

Answer 12

Calcitonin: peptide hormone released from the parafollicular (clear) cells of the thyroid gland.

Question 13

parathyroid hormone (PTH) is released in response to…

Answer 13

decrease in free plasma [Ca2+]

Question 14

how does PTH increase free plasma [Ca2+]?

list

Answer 14

1. stimulating osteoclasts to increase resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs).
2. inhibiting osteoblasts thus reducing Ca2+ deposition in bone.
3. increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.
4. increasing renal excretion of phosphate: this elevates free [Ca2+] by preventing it from being deposited back into bone, a process that requires phosphate.
5. stimulates the kidney to syntheise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.

Question 15

formation of calcitriol is enhanced by which hormone in lactating women?

Answer 15

prolactin
- in association with increased demand for Ca2+ for milk production in lactation

Question 16

Calcitriol binds to nuclear receptors in target tissues (intestine, bone and kidney) to:

list the actions of cacitriol

Answer 16

1. increase absoprtion of Ca2+ from the gut
2. facilitates renal absorption of Ca2+
3. mobilises calcium stores in bone by stimulating osteoclast activity.

collectively, these action complement those of PTH and increase plasma [Ca2+]

Question 17

what is considered vitamin D deficiency and what are its complications?

Answer 17

• circulating vitamin D levels fall to less than 20ng/ml
• rickets in children
• osteomalacia in adults

Question 18

list some other endocrine hormones altering Ca2+ balance

Answer 18

1. cortisol inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+: Increases bone resorption, this together with reduced bone formation > osteoporosis.
2. insulin: increases bone formation, and atagonises the action of cortisol. Diabetics may have significant bone loss.
3. oestrogen/testosterone: promotes bone formation via receptors on osteoblasts. Post-menopausal osteoporosis a major problem.
4. growth hormone: constant stimulus for bone formation.
5. prolactin: promotes caclium absoprtion from the gut by stimulating synthesis of calcitriol.