Calcium Regulation Flashcards
what is calcium important for?
muscle contraction
neuronal activity
exocytosis
coagulation of blood
communication between cells
structural integrity of bone
and more
intracellular calcium?
bound to proteins or within mitochondria/ER
describe the calcium found in bone?
hydroxyapatite crystals = calcium, phosphate and water
blood calcium is found in three forms - what are these?
bound to proteins (albumin) - 40%
complexed to anions (carbonate, citrate etc) - 10%
free ionised Ca2+ - 50%
canalicuculi?
connect osteocytes and osteoblasts
extracellular fluid importance for calcium?
important for control of calcium levels in blood
blood calcium and bone calcium pool (in solution)
what are the calcium-regulating hormones?
parathyroid hormone (PTH)
Vitamin D
Parathyroid hormone related peptide (PTHrP)
Calcitonin
two type of calcium store in bone - what are these?
readily exchangeable (0.1-1%)
slowly exchangeable (99%) - stable pool
Phosphate is controlled by what?
by the same systems that control calcium
where is phosphate absorbed from?
Intestines
where is phosphate stored?
in bone pools
where is phosphate excreted from?
from kidneys
what provides ready source of phosphate?
inorganic phosphate
acts as a buffer in the blood (maintain correct pH)
What is phosphate important for?
structure of boned and teeth
cell membranes (phospholipids)
DNA synthesis (sugar phosphate backbone)
ATP!
what is phosphate mainly regulated by?
kidney
what reabsorb 80-90% of filtered phosphate?
the renal tubules
close to renal threshold
what happens if dietary phosphate increases - renal?
exceeds renal threshold and excreted in urine
what does PTH decrease?
decreases renal reabsorption of phosphate thus increasing excretion
PTH decreases Na/P transporters
parathyroid gland?
main organ controlling central calcium and phosphate metabolism
four small nodules associated with the thyroid gland
describe the parathyroid gland histology and what cells we see?
Chief or Principal cells
- darker staining active cells secrete PTH
- lighter staining inactive cells - increase in number as animal ages
Oxyphil cells - not present in vet species
in humans
large and much lighter staining cells - unknown function
what is PTH secreted by and where is it metabolised and what is the action of PTH?
secreted by exocytosis
rapidly metabolised by liver and kidneys
acts to increase the ECF concentration of calcium
long-term calcium deficits?
when dietary uptake is low, calcium and phosphate is released from bone pools
PTH and vitamin D important for correction
if loss of calcium in ECF exceeds amounts available from bone pools, what does it lead to?
clinical signs of:
inappetence
ataxia (loss of co-ordination)
paresis (partial paralysis/weakness)
tetany (locked muscles)
describe the rapid exchange of calcium in the soluble portion of bone:
consists of crystals and soluble calcium
located in canaliculi between osteoblasts and osteocytes
These cells can mobilise calcium to the blood quickly
describe the slow exchange of calcium to the bone:
small movements
bone remodelling
growing animals transfer more calcium into stable store than adults do
when the free calcium in the plasma is low describe the rapid exchange of calcium:
Ca2+ is transported from the bone fluid to plasma by PTH stimulated pumps in osteocytes
when the free calcium in the plasma is low describe the slow exchange of calcium:
PTH increases osteoclast activity, but Ca2+ is transported by PTH independent process
when the free calcium in the plasma is high describe the rapid exchange of calcium:
opposite occurs
so the Ca2+ is transported from the plasma to the bone fluid
when the free calcium in the plasma is high describe the slow exchange of calcium:
osteoclast activity decreases
Where is there continual movement of calcium?
continual movement between the extracellular fluid, the bone, GI tract and kidneys
where is calcium absorbed?
GI tract
Different requirements depending on life stage
Describe the excretion of calcium?
controlled by kidneys
most of the calcium passing through the kidneys is reabsorbed
Loss is matched by dietary absorption
Distal tubules are under hormonal control
where is free calcium filtered, describe what type of calcium is not filtered?
it is filtered at the glomerulus whereas protein bound calcium is not
normally, how much filtered calcium is reabsorbed?
normally 96-98% of filtered calcium is reabsorbed
where does the majority of calcium excretion and reabsorption occur?
mostly (70%) occurs in the proximal convoluted tubule paracellularly secondary to osmosis
where is the remaining calcium reabsorbed?
in the distal convoluted tubule and convoluted tubule transcellularly via calcium channels in apical membrane and pumps on the basolateral membrane
what mediates DCT and CD absorption?
mediated by parathyroid hormone (PTH) - controllable calcium excretion
what is calcium regulated according to?
according to need
why is it essential that calcium remains low?
so calcium is bound to a protein during transport across the cell from apical to basolateral side
what is directly affected by the parathyroid hormone?
bone and kidney
what is indirectly affected by the parathyroid hormone?
GI tract
what are the several forms of vitamin D?
vitamin D2
and vitamin D3
what synthesises vitamin D2?
synthesised by plants
what synthesis vitamin D3?
by animals
what must vitamin D be activated by?
must be activated by additions of hydroxyl (OH) groups
what is step 1 of vitamin D synthesis and where does this occur?
occurs in liver
25-hydroxylase adds 1st OH group to Vit D
Calcidiol - inactive (storage)
Where does step 2 of vitamin D synthesis occur?
in the kidney
describe step 2 of vitamin D synthesis when calcium levels normal:
24-hydroxylase adds 2nd OH group
24,25(OH)2 - vitamin D
Inactive (excreted)
describe step 2 of vitamin D synthesis when calcium levels low:
PTH (parathyroid hormone) stimulates 1α-hydroxylase
Calcitriol (1,25(OH)2 - vitamin D)
Active - increases GI tract absorption of calcium
what does calcitriol do?
it increases calcium uptake from the small intestine
how does calcitriol increase uptake of calcium from the small intestine?
binds to nuclear vitamin D receptor
upregulates
Apical Ca2+ channels (e.g. TRPV5)
Basolateral Ca2+ pumps (e.g. PMCA1b)
Ca2+ transporter protein calbindin - D9K
Increase transcellular calcium absorption from small intestine
what is calcitonin produced by?
produced by parafollicular cells (also called C-cells) in the thyroid gland
what does calcitonin act to reduce?
acts to reduce calcium and phosphate
what does calcitonin decrease the movement of?
decreases movement of ions from bone pools to the extracellular fluid
what does calcitonin inhibit?
inhibits osteoclasts - decreased bone resorption
what does calcitonin increase?
increases renal excretion of calcium and phosphate
what mechanism is responsible for the control of calcitonin and PTH secretion?
negative feedback mechanism
what causes an increase in calcitonin secretion?
GI hormones gastrin, CCK (cholecystokinin)
and secretin all increase calcitonin secretion
what does parathyroid hormone-related peptide (PTHrP) have a similar structure to?
similar in structure to PTH
what is PTHrP?
parathyroid hormone-related peptide
where is PTHrP produced?
produced in most tissues of the body
what receptor does PTHrP bind to?
binds to the same receptor as PTH (g-protein coupled) so has same effects
what other receptors does PTHrP bind to?
PTHrP also binds to other receptors not activated by PTH - diverse effects
when PTHrP binds to its ‘other receptors’ - what happens?
plays role in proliferation, differentiation and apoptosis
Important for regulation of placental transport of calcium to foetus and transfer of calcium from blood to milk
what is hypercalcaemia?
certain types of cancers produce PTHrP leading to increases levels of calcium
No negative feedback mechanisms so leads to hypercalcaemia
Can measure serum PTHrP as a useful diagnostic tool in differential diagnosis
what are eggshells mainly made up of?
calcium carbonate
where are eggshells produced?
in the shell gland
what part of the egg contain high levels of phosphate?
yolk and egg white
what is required in the diet for hens to continue laying eggs?
continuous dietary supply of calcium
eggshells are 10% of skeletal calcium
what is a pullet?
a young hen
what accumulates in pullets to aid with egg laying when older?
extra medullary bone accumulates in pullets prior to start of egg-laying as mature adults to increase the available bone pool of calcium
when shell synthesis begins - concentration of what falls?
extracellular fluid concentration of Ca2+ ions falls
how does PTH affect [Ca2+] in ECF?
PTH works to increase blood calcium levels by stimulating calcium release from bone and enhancing calcium reabsorption in the kidneys and intestines
how does Clacitriol affect [Ca2+] in ECF?
calcitonin acts to lower blood calcium levels by promoting calcium deposition into bones
