endocrine control of calcium metabolism Flashcards
describe Ca
most abundant metal in human body
5th most abundant element
essential
diet should meet all the requirements - people eat more than they need, as long as no GI or kidney problems
role of Ca
neuromuscular excitability - signal in neurons to
muscle contraction, reduce excitability so muscles not hyperactive
strength in bones - made of Ca salts
intracellular secondary messenger - something change Ca signalling, keep low so can be increased with secondary messenger
intracellular co-enzyme
hormone/NT stimulus-secretion coupling - release of hormones reflux Ca to edge, Ca at bouton of neuron, couple vesicle to membrane eg B cell releasing insulin
blood coagulation (factor IV) - vital for binding to phospholipids
how is Ca in the body
most as Ca salts
99% in bone as hydrated Ca salt - hydroxyapatite crystals, salt of calcium and phosphorus, their metabolism is closely linked
some ionised as Ca2+
some bound to protein
tiny bit - soluble and unsoluble eg citrate and lactate salt
only unbound Ca2+ is active - the rest is sequestered away
proportions of different stores of Ca
50% ionised - 1.25mM - biologically active component
45% - bound to plasma proteins -1.13mM
5% - diffusible salts -0.13mM
total Ca vol
2.5mM
describe Ca handling by the body
intake 1000mg/24hr into GI tract
850mg/24hr lost faeces
rest go to the blood
balance between bone and blood - as long as rate of growth and destruction of blood is the same
some secretions from blood back to GI
minute amounts - invisible loss - in dead cells, hair nails
most regulation of Ca through kidney, as long as no major differences in bone turnover - excretion 150mg/reabsorption
only when homeostasis of Ca changes that you need to stop some being secreted or absorb/ingest more
what increases Ca conc
parathyroid hormone (PTH)/parathormone 1,25 (OH)2 Vitamin D3 - active form is dihydroxycholecalciferol or Calcitriol
what decreases Ca conc
calcitonin - regulation of this is less pronounced
biological effect less significant
what releases PTH
parathyroid glands
how many parathyroid glands are there
4
what produces calcitonin
parafollicular cells, part of thyroid gland - surround follicles and release calcitonin when Ca is too high
describe the Ca sensing receptor
system for detecting Ca conc - cell surface receptor
G coupled protein receptor, transmembrane region
ligand (Ca) bind to external binding site
cause conformational change in receptor - change how associates and activates G protein and how they go and act as cell signalling by activating cAMP
if high levels of Ca - inhibit PTH
if low Ca/antagonist for receptor is used - g protein change - PTH
what is parathyroid hormone
initially synthesised as pre-proPTH
cleaved in an intracellular process
PTH polypeptide = 84AA
binds to transmembrane G protein linked receptors
activation of adenyl cyclase and PLC as a second messenger
the G protein receptor depends on the type of tissue
PTH action on kidney
increases Ca reabsorption
increase phosphorus secretion
this homeostasis is co-regulated
stimulates 1alpha hydroxylase activity - increases 1,25 (OH)2 Vitamin D3 synthesis - acts on small intestine - increase Ca absorption, increase phosphorus absorption
PTH action in bone
osteoclast stimulated
osteoblast inhibited
increase bone resorption - free Ca trapped in bone is released
3Ca + 2PO4 – Ca3(po4)2 equilibrium
PTH effect on blood
preserves circulating Ca conc for muscle and neurone effect
sacrifice bone
in break down of bone phosphorus is released and not needed so it is got rid of
explain the mechanism of PTH action in bone
PTH bind to PTH receptor on osteoblast
releases osteoclast activating factors eg RANKL - regulate osteoclast
OAF bind to receptor on osteoclast - activate it - cause bone resorption
what does RANKL stand for
receptor activator of nuclear factor kappa-B ligand
describe PTH regulation
catecholamines (via B receptors) decrease Ca stimulate PTH - increases plasma Ca conc and causes synthesis of 1,25 (OH)2D3, which also increases plasma Ca conc
1,25(OH)2D3 -ve feedback on parathyroid gland - reduce PTH production
describe the synthesis of 1,25(OH)2D3
from diet and 7-dehydrocholesterol in skin (with UV light) – cholecalciferol (vit D3)
25 hydroxy- cholecalciferol 25 (OH) vitD3, this is synthesised in the liver and stored in this form
enzyme 1 alpha hydroxylase - (stimulated by PTH) catalyse production of
1,25(OH)2 D3 - synthesised in kidneys and is the main active form
[need kidney and liver functioning normally to get the active form]
what else does calcium receptor detect
kidney - ca excretion
GI - bind to AA
other cells - nutritional purposes
vitamin D3 deficiency
because of where people come from and dress code
don’t know what normal range is and if it is different in different ethnicities
no signs of nationwide problems but a lot of ‘deficiency’
action of 1,25(OH)2 D3
in kidney increase Ca and phosphorus reabsorption
Ca that is reabsorbed goes into bone
increases osteoblast activity of the bone ]in mall intestine increase Ca and phosphorus absorption
phosphorus reabsorbed from kidney inhibit absorption from SI
attempts to restore bone but has a longer, chronic effect - lays down salt
if you treat people just with this it isn’t necessarily good for the bone
describe phosphate levels
pretty static
excreted in kidney
