51.3 Regulation of Extracellular Calcium

Question 1

How much calcium is in the body?

Answer 1

1kg: teeth/ CT/ bones (99% Ca3(PO4)2)

Question 2

What is the intake of Ca2+?

Answer 2

diet (daily 200 -1500 mg). Western - dairy/ flour (Ca salts added)

Question 3

What are the three main primary sources of calcium?

Answer 3

Diet
Bone
Kidney

Question 4

How is Ca2+ absorbed?

Answer 4

Gastrointestinal absorption
*Transcellular in duodenum + upper jejunum. Calcitriol ↑.
*Paracellular across entire length of intestines.
- Calcitriol ↑ (FGF-23 potent antagonist)
*↑ Ca2+ demands promote (e.g. growth/ pregnancy/ lactation/ physical activity)
*Ageing ↓ Ca2+ transport.

Question 5

How is Ca2+ excreted/ reabsorbed?

Answer 5

renal reabsorption/excretion
*~ 98% ultrafiltrate Ca2+ reabsorbed
- Paracellularly in PT + TAL of LoH (bulk)
- Transcellularly in DCT
*100–200 mg of Ca2+ excreted /day in urine

Question 6

How much EC Ca2+ is there?

Answer 6

2.3-2.4 mmol l-1, 1.4 mmol l-1 free

Question 7

How much IC Ca2+ is there?

Answer 7

1-2 mmol kg-1, 0.1μmol l-1 free

Question 8

What are the IC functions of Ca2+?

Answer 8

*Exocytosis activation → stimulus-secretion coupling
*Muscle contraction → stimulus-contraction coupling
*AP propagation
*2nd messenger → enzyme regulation/ regulating cellular processes

Question 9

What are the EC functions of Ca2+?

Answer 9

*Plasma membrane integrity + functioning → Ca2+ imp. Co-factor in proteins (e.g. adhesion molecules, clotting factors + secreted enzymes)
*Mineral phase of Skeleton → critical (also PO43-). Collagenous matrix + insoluble mineral phase = Tensile + compressive strength of bone. Protection/ ambulation.

Question 10

What are the effects of hypercalcaemia? (rhyme)

Answer 10

Bones, stones, moans, groans

Bones = fractures
Stones = kidney stones
Moans = lower mood
Groans = abdominal discomfort

along with decreased excitability of nerves

Question 11

What are the effects of hypocalcaemia? (mnemonic)

Answer 11

CATs go numb: Convulsions, Arrhythmias, Tetany, Numbness

• Muscle hyperexcitability
• Confusion
• Arrhythmia

Question 12

Why does hypocalcaemia cause muscle hyperexcitability?

Answer 12

There is less Ca2+ to block sodium channels –> lowered threshold for depolarisation

Question 13

What is the difference between osteoporosis and osteomalacia?

Answer 13

Osteoporosis = decreased bone formation (less bone)
Osteomalacia = decreased calcification (bone softening)

Question 14

What is the role of osteoblasts?

Answer 14

deposits new bony matrix

Question 15

What are the functions of osteocytes?

Answer 15

secrete sclerostin which recruits osteoclasts.
Maintenance.

Question 16

What is the function of osteoclasts?

Answer 16

resorbs bony matrix

Question 17

How do osteoblasts activate osteoclasts?

Answer 17

By interaction of RANK-L on osteoblasts with RANK on osteoclasts

Question 18

Osteoblasts [increase/decrease] Ca2+ levels while osteoclasts [increase/decrease] Ca2+ levels

Answer 18

Osteoblasts decrease plasma Ca2+ levels while osteoclasts increase plasma Ca2+ levels

Question 19

Why are people at increased risk of osteoporosis as they age?

Answer 19

• Decreased vit D - less Ca2+ absorbed
• Women have less oestrogen which usually activates osteoblasts

Question 20

What is the action of calcitriol?

Answer 20

↑absorption of ingested Ca2+ when ↓ plasma Ca2+.

Question 21

How does calcitriol increase absorption?

Answer 21

Direct effect on intestinal mucosa.
Nuclear receptors → ↑ expression of Ca2+ channels + Na+/Ca2+X + Ca2+ATPase

Question 22

How does calcitriol stimulate calcification of the bone matrix?

Answer 22

Stimulates calcification of bone matrix (observed from Vit.D deficiency) → bone remodelling
*Indirectly: ↑ Ca2+ in plasma
*Directly: stimulating osteoclast + osteoblast activity

Question 23

What happens to calcitriol during pregnancy/ lactation/ ageing?

Answer 23

*Pregnancy → sig ↑ to ↑ maternal Ca2+ absorption so sufficient Ca2+ for foetal growth.
*Lactation → ↑ to help maintain Ca2+ homeostasis.
*Ageing → ↓ synthesis efficiency (↑ by ↓ sunlight exposure/ ↓ renal function)

Question 24

What is the action of PTH?

Answer 24

most broad activity: mobilises Ca2+ from bone + ↑ Ca2+ reabsorption in kidneys. ↑ when plasma Ca2+ ↓

Question 25

What are the anabolic effects of PTH, when do they happen?

Answer 25

Continuous basal secretion rate (5 min ½ life) → maintains bony skeleton *Promotes osteoblastogenesis + osteoblast survival + ↑ calcification of bone matrix

Question 26

What are the catabolic effects of PTH?

Answer 26

Effect on bone: ↑PTH → biphasic action *Initially - rapid Ca2+ loss from readily releasable Ca2+ pool on bone surface *Long-term - resorption of stable bones by osteoclasts → + minerals to ECF

Question 27

What is the effect of PTH on the kidneys?

Answer 27

↑ Ca2+ + ↓ PO43- reabsorption *Ca2+ → In Cortical ascending Thick LoH + DT By stimulating Calcitriol synthesis *↓ PO43- → ↑ ionised Ca2+/ ↓ [Ca3(PO4)2] - an insoluble salt.

Question 28

What happens to PTH in hypocalcaemia?

Answer 28

hypocalcemia → PTH biosynthesis + PT cell proliferation *most potent PTH stimulator. ↑ Ca2+ inhibits PTH release.

Question 29

What happens to PTH during pregnancy?

Answer 29

↓ in 1st trimester (maintain ca2+ balance), ↑ throughout 2nd/ 3rd.

Question 30

What happens to PTH during lactation?

Answer 30

PTHrp produced by lactating breast. ↑ bone resorption to ensure adequate Ca2+/ PO43- in breast milk.

Question 31

What happens to PTH during development?

Answer 31

compensatory PTH ↑ drive Calcitriol production + enhance Ca2+absorption during ↑ demand.

Question 32

What happens to PTH during ageing?

Answer 32

PTH ↑ w/ age. (due to ↓ renal function/ ↓ Ca2+ absorption frequency/ ↓ calcitriol)

Question 33

What is the function of calcitonin?

Answer 33

↓ free plasma Ca2+

Question 34

What are the actions of calcitonin?

Answer 34

*Inhibits osteoclast activity → ↓ bone resorption, Ca/P not released into plasma *↑ Ca2+ + PO43- excretion by kidneys. Also other ions such as K+, Mg2+ and Na+

Question 35

What happens to calcitonin in pregnancy?

Answer 35

↑ (protect skeleton against PTH-induced resorption?)

Question 36

What happens to calcitonin during lactation?

Answer 36

role in development of enteric neurons in breastfed infants?

Question 37

What happens to calcitonin in development?

Answer 37

↑ opposes PTH action to limit skeletal loss during ↑ Ca2+ demand

Question 38

What happens to calcitonin during ageing?

Answer 38

↓ (due to ↓ sunlight exposure etc)

Question 39

What is osteomalacia?

Answer 39

*caused by a Vitamin D deficiency --> X calcification of bone matrix + impaired bone remodelling → hypocalcaemia *In adults *↓ bone density, lots of non-mineralised osteoid. ↑ susceptibility to fracture, bone pain + proximal muscle weakness

Question 40

What is osteoporosis?

Answer 40

unbalanced resorption(↑) and deposition. Results in porous bones/ lost density/ deterioration of architecture. 3 types. (1/ 2) 10 and 20. Type I primary osteoporosis → postmenopausal women due to ↓oestrogen. Sever long term effects as presents earlier

Question 41

What is a common side effect of corticosteroid therapy?

Answer 41

Osteoporosis