51.3 Regulation of Extracellular Calcium Flashcards
How much calcium is in the body?
1kg: teeth/ CT/ bones (99% Ca3(PO4)2)
What is the intake of Ca2+?
diet (daily 200 -1500 mg). Western - dairy/ flour (Ca salts added)
What are the three main primary sources of calcium?
Diet
Bone
Kidney
How is Ca2+ absorbed?
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.
How is Ca2+ excreted/ reabsorbed?
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
How much EC Ca2+ is there?
2.3-2.4 mmol l-1, 1.4 mmol l-1 free
How much IC Ca2+ is there?
1-2 mmol kg-1, 0.1μmol l-1 free
What are the IC functions of Ca2+?
*Exocytosis activation → stimulus-secretion coupling
*Muscle contraction → stimulus-contraction coupling
*AP propagation
*2nd messenger → enzyme regulation/ regulating cellular processes
What are the EC functions of Ca2+?
*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.
What are the effects of hypercalcaemia? (rhyme)
Bones, stones, moans, groans
Bones = fractures
Stones = kidney stones
Moans = lower mood
Groans = abdominal discomfort
along with decreased excitability of nerves
What are the effects of hypocalcaemia? (mnemonic)
CATs go numb: Convulsions, Arrhythmias, Tetany, Numbness
- Muscle hyperexcitability
- Confusion
- Arrhythmia
Why does hypocalcaemia cause muscle hyperexcitability?
There is less Ca2+ to block sodium channels –> lowered threshold for depolarisation
What is the difference between osteoporosis and osteomalacia?
Osteoporosis = decreased bone formation (less bone)
Osteomalacia = decreased calcification (bone softening)
What is the role of osteoblasts?
deposits new bony matrix
What are the functions of osteocytes?
secrete sclerostin which recruits osteoclasts.
Maintenance.
What is the function of osteoclasts?
resorbs bony matrix
How do osteoblasts activate osteoclasts?
By interaction of RANK-L on osteoblasts with RANK on osteoclasts
Osteoblasts [increase/decrease] Ca2+ levels while osteoclasts [increase/decrease] Ca2+ levels
Osteoblasts decrease plasma Ca2+ levels while osteoclasts increase plasma Ca2+ levels
Why are people at increased risk of osteoporosis as they age?
- Decreased vit D - less Ca2+ absorbed
- Women have less oestrogen which usually activates osteoblasts
What is the action of calcitriol?
↑absorption of ingested Ca2+ when ↓ plasma Ca2+.
How does calcitriol increase absorption?
Direct effect on intestinal mucosa.
Nuclear receptors → ↑ expression of Ca2+ channels + Na+/Ca2+X + Ca2+ATPase
How does calcitriol stimulate calcification of the bone matrix?
Stimulates calcification of bone matrix (observed from Vit.D deficiency) → bone remodelling
*Indirectly: ↑ Ca2+ in plasma
*Directly: stimulating osteoclast + osteoblast activity
What happens to calcitriol during pregnancy/ lactation/ ageing?
*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)
What is the action of PTH?
most broad activity: mobilises Ca2+ from bone + ↑ Ca2+ reabsorption in kidneys. ↑ when plasma Ca2+ ↓
What are the anabolic effects of PTH, when do they happen?
Continuous basal secretion rate (5 min ½ life) → maintains bony skeleton
*Promotes osteoblastogenesis + osteoblast survival + ↑ calcification of bone matrix
What are the catabolic effects of PTH?
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
What is the effect of PTH on the kidneys?
↑ Ca2+ + ↓ PO43- reabsorption
*Ca2+ → In Cortical ascending Thick LoH + DT
By stimulating Calcitriol synthesis
*↓ PO43- → ↑ ionised Ca2+/ ↓ [Ca3(PO4)2] - an insoluble salt.
What happens to PTH in hypocalcaemia?
hypocalcemia → PTH biosynthesis + PT cell proliferation
*most potent PTH stimulator. ↑ Ca2+ inhibits PTH release.
What happens to PTH during pregnancy?
↓ in 1st trimester (maintain ca2+ balance), ↑ throughout 2nd/ 3rd.
What happens to PTH during lactation?
PTHrp produced by lactating breast. ↑ bone resorption to ensure adequate Ca2+/ PO43- in breast milk.
What happens to PTH during development?
compensatory PTH ↑ drive Calcitriol production + enhance Ca2+absorption during ↑ demand.
What happens to PTH during ageing?
PTH ↑ w/ age. (due to ↓ renal function/ ↓ Ca2+ absorption frequency/ ↓ calcitriol)
What is the function of calcitonin?
↓ free plasma Ca2+
What are the actions of calcitonin?
*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+
What happens to calcitonin in pregnancy?
↑ (protect skeleton against PTH-induced resorption?)
What happens to calcitonin during lactation?
role in development of enteric neurons in breastfed infants?
What happens to calcitonin in development?
↑ opposes PTH action to limit skeletal loss during ↑ Ca2+ demand
What happens to calcitonin during ageing?
↓ (due to ↓ sunlight exposure etc)
What is osteomalacia?
*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
What is osteoporosis?
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
What is a common side effect of corticosteroid therapy?
Osteoporosis
