Regulation: Ca+ and phosphate Flashcards
(49 cards)
1
Q
dist and conc of Ca: features of Ca- found where and forms
A
- almost all Ca found in mineral component of bone (hydroxyapatite)
plasma: 3 forms
- free ionised Ca (Ca2)
- bound to plasma proteins (albumin and globulins) many -ve charges
- bound to anions (complexed) like phosphate and bicarbonate
2
Q
dist and conc of Ca: activity of Ca, ranges of conc
A
- activity depends on free ionised form
- tightly controlled in narrow range: 1.1-1.3 mM
- total Ca in plasma (2.2-2.5 mM)
3
Q
dist and conc of Ca: free Ca conc features
A
- extremely low (100 nM)
- sig non functional increases can kill cell
- low cytoplasmic [Ca2] essential for Ca function in cells
- large elctrochem grad across plasma mem driving movement of Ca into cell, opening Ca channels on plasma mem, can cause rapid increase free Ca in cytoplasm
- vital for numerous intracellular functions of Ca (NT release, mm contraction, 2nd messenger)
4
Q
dist and conc of Ca: conc in cell organelles
A
- allowed to be much higher (100-500µM) in mitochondria, SR/ endoplasmic reticulum
- within cytoplasm Ca binding proteins have various qualities of Ca attached
5
Q
dist and conc of Ca: permeability of Ca and how its maintained
A
- plasma mem impermeable to Ca
- low cytoplasmic Ca conc maintained by Na/Ca antiports, Ca pumps
- Ca pumps found on membranes of cell organelles
6
Q
major roles of Ca: list (6)
A
- cell signalling (2nd messenger)
- mm contraction
- secretion of NT and hormones
- maintenance of tight junctions btw cells
- cofactor required for blood clotting
- major mineral components (providing tensile strength of skeleton- hydroxyapatite crystals Ca10(PO4)6(OH)2))
7
Q
consequences of disturbed Ca homeostasis: <2.1mM in plasma
A
hypocalcaemia
8
Q
consequences of disturbed Ca homeostasis: >2.6mM in plasma
A
hypercalcaemia
9
Q
consequences of disturbed Ca homeostasis: problems
A
- membranes have fixed charges due to chemical structure
- outside: -ve charges (-ve head groups of phospholipids)
- fixed charges bind divalent cations like Ca
10
Q
consequences of disturbed Ca homeostasis: when ECF [Ca] increases
A
- more Ca bind to outside surface= increased polarisation across mem
- moves resting potential further from threshold potential = decreasing excitability of neuron
11
Q
consequences of disturbed Ca homeostasis: low ECF [Ca]
A
- increases excitability
- neuronal, mm excitability leading to mm spasms
- severe hypocalcaemia can cause tetany
- hypocalcaemic tetany of larynx = asphyxiation
12
Q
consequences of disturbed Ca homeostasis: cardiac mm contraction
A
- depends on opening Ca channels
- influx of Ca from ECF
13
Q
consequences of disturbed Ca homeostasis: high normal ECF [Ca]
A
- increases strength of contraction cardiac mm
- low Ca opp effect
- cardiac mm able to relax btw beats coz Ca conc returned to resting lvls, shifting Ca into SR (Ca pumps)
- exporting Ca from cell (Na/Ca antiports, Ca pumps)
14
Q
consequences of disturbed Ca homeostasis: hypercalcaemia
A
- inability of heart to export sufficient Ca to allow relaxation = tetanic contractions of heart
- death
15
Q
consequences of disturbed Ca homeostasis: hypocalcaemia
A
- reduced mineralisation of bone
- rickets (children)
- osteomalacia (adults)
- low accumulation of Ca in dev bone due to Ca deficiency in diet, low lvl of vitamin D3
16
Q
consequences of disturbed Ca homeostasis: mineral component of bone
A
- in bone, hydroxyapatite makes up 90% weight
- provides resistance to breaking when bearing weight (tensile strength) while collagen fibres provide rest of bone mass
- allow for deformity
- rickets, osteomalacia = softer bone w increased fragility -> breaks, deformities
17
Q
summary: hypercalcaemia
A
- assoc decreased neruomm excitability
- cardiac arrhythmias
- calcification of soft tissue (incl atheromas, heat, kidneys)
- lethargy
- disorientation
- hypercalcaemic heart failure
- death
18
Q
summary: hypocalcaemia
A
- increased incidence of bone fractures
- increased neuromm excitability
- mm spasms
- tetany
- asphyxiation
19
Q
control Ca conc in plasma:
A
- plasma Ca conc regulated by varying rates of uptake from sml intestine, rate of Ca excretion by kidney, rates of resorption/mineralisation of bone
- 2 hormones parathyroid hormones, calcitriol (activated vit D3) control this sys
- calcitonin: normally plays minor role in Ca reg vital in limiting bone loss in lactating mothers
20
Q
parathyroid hormone (PTH): function
A
- prevent plasma Ca lvls from falling too low
- without PTH death by asphyxiation would occur within few days
21
Q
parathyroid hormone (PTH): features
A
- peptide hormone released from parathyroid glands attached to thyroid gland, located behind trachea
- hormone released at high basal rate, increasing when free Ca lvls in plasma fall
- Ca plasma decrease, more PTA released
22
Q
parathyroid hormone (PTH): released controlled by
A
- binding of Ca to cell surface receptor (CaSR) on parathyroid cells
23
Q
parathyroid hormone (PTH): inhibited by
A
- when lrg no. Ca bind, G coupled sys inhibits release of PTA
24
Q
parathyroid hormone (PTH): response time
A
- CaSR/ G protein sys
- short half life of PTA in plasma (5 min)
- PTA controls plasma Ca conc on min-min basis
25
parathyroid hormone (PTH): effect on bone
- increases Ca conc in plasma by breakdown of hydroxyapatite in bone to release Ca and phosphate into plasma (resorption)
- Ca released rapidly from labile pool of Ca in bone, slower from mineralised bone
26
parathyroid hormone (PTH): bone remodelling by
- by osteoblasts, osteoclasts
27
parathyroid hormone (PTH): osteoblasts
- release organic matrix (collagen) on which hydroxyapatite crystals form
- bone marrow precursor (stromal cells)
28
parathyroid hormone (PTH): osteoclasts
- secrete HCl acid and enzymes to dissolve bone
- bone marrow precursor (macrophages)
- PTA promotes dev and survival of osteoclasts
29
parathyroid hormone (PTH): act on preosteoclasts, osteoblasts
- causes them to prod ligand RANKL
| - binding RANKL to RANK (receptor) on surface of preosteoclasts causes them to mature, resorb bone to release Ca and PO4
30
parathyroid hormone (PTH): when increased Ca conc causes fall in plasma PTA conc:
- osteoblasts reduce secretion of RANKL
- increase release of osteoprotegerin (OPG) binding RANKL preventing stimulatory effect on osteoclasts
- ratio of RANKL to osteoprotegerin determines whether bone resorbed or not
31
parathyroid hormone (PTH): effect on excretion through kidney features
- free Ca, Ca bound to inorganic phosphate/bicarb
- filtered into nephron but bound Ca is not
- nephron filtered Ca reab by paracellular routes, active transport
32
parathyroid hormone (PTH): reab of Ca by active transport
- in late thick ascending LOH, distal tubule (DT) increased by PTH
- PTA binds to receptors of BASOlateral mem of DT cells
- G protein responses increase no. Ca channels (LUMINAL mem)
- Ca pumps, Na/Ca antiports (BASOlateral mem)
33
parathyroid hormone (PTH): filtered Ca in kidney moves
- down elec grad into cells
| - Ca pumps, Na/Ca antiporters actively transport Ca from cells into int fluid, plasma
34
parathyroid hormone (PTH): increases what excretion?
- PO4 3- excretion
35
calcitriol from vit D3: features
- sunlight on skin: cholesterol based precursor to prod vit D3
- vit also from food: oily fish, cod-liver oil, eggs
- dairy prod also be fortified w vit D3
36
calcitriol from vit D3: active form
- 1,25 dihydroxyvitamin D (calcitriol)
| - prod in multistep process from cholesterol precursor by enzymes in skin, liver, kidney
37
calcitriol from vit D3: rate of prod determined
- by activity of PTH activated 1å hydroxylase in kidney
| - low ECF [PO4 3-] increase activation of calcitriol
38
calcitriol from vit D3: half life
- steroid based hormone
| - calcitriol circulated assoc w binding protein, prolongs half like in plasma -> several hrs
39
calcitriol from vit D3: calcitriol function
- reg gene expression in duodenum, jejunum of sml intestine = increase uptake of Ca in diet
- plasma Ca at normal lvls: only 50% of Ca from diet is absorbed from gut into blood
- calcitriol increase no Ca channels in LUMINAL mem of epithelial cells that line sml intestine (enterocytes)
- increase activity of Ca pumps, Na/Ca exchanges on BASOlateral mem
40
integrated control of Ca, HPO4 2-, Pi: calcium phosphate
- relatively insoluble when Ca and Pi conc high in plasma, calcium phosphate will precipitate in bone, other body tissues
41
integrated control of Ca, HPO4 2-, Pi: increase conc of free Ca in plasma?
- plasma Pi conc must decrease
- PTA secretion increased by low plasma Ca, response kidney to increase filtered Ca, decrease reab of Pi
reverse if high Ca lvls
42
integrated control of Ca, HPO4 2-, Pi: both low plasma Pi and Ca conc activate
- PTH activated 1å hydroxylase in kidney is rate limiting step in prod of activated calcitriol
- it stimulates absorption of both Ca and Pi from sml intestine
43
calcitonin: features
- 23 aa peptide hormone
- mineral and electrolyte balance and pH control in fish, amphibians, birds
- certain fish (salmon) and amphibians hav hormone: maintain composition and conc of ECF despite osmotic gradient imposed by seawater
44
calcitonin: role in humans
- prod by parafollicular cells of thyroid, thought to oppose effects of PTH
- no apparent effect of absence/excess of endogenous calcitonin
- pathological Ca loading increases plasma calcitonin lvls
- calcium lowers effects of hormone
- needs high (salmon) calcitonin to lower plasma Ca conc by suppressed bone resorption
45
calcitonin: release reg by
- through CaSR, (vs PTA calcitonin release increased by high plasma Ca,) acts to reduce plasma Ca
- signal pathways stimulated by Ca to CaSR diff in PTH, calcitonin prod cells
- stimulation of CaSR increases calcitonin prod, inhibits PTA prod
46
calcitonin: numerous receptors on
- osteoclasts in humans
47
calcitonin, bone loss during lactation: features
- bone mass in mother fall 5-10% as Ca resorbed from bone to plasma, transferred to breast, to milk
- born resorption occurs despite 50% increase in proportion of ingested Ca absorbed across sml intestine
- 2 hormonal processes cont to increased bone resorption
48
calcitonin, bone loss during lactation: oestrogen effect
- lvls falls dramatically at birth
- at lactation prolactin inhibits gonadotropin releasing hormone (GnRH) release into ant pituitary keeping oestrogen low
- RANKL prod increases, release OPG in inhibited
- osteoclasts mature, survival promoted, leading to bone resorption
49
calcitonin, bone loss during lactation: PTH related peptide (PTHrP) effect
- certain mammary cells have CaSR and release PTHrP during lactation
- stimulated by prolactin, PTHrP stimulates osteoclasts to resorb bone, similar to PTH
- calcitonin also increase during lactation due to secretion from epithelial mammary (breast) cells
- calcitonin protects mum from excessive bone loss during lactation (inhibits effects of PTHrP and compensate low oestrogen lvls)
