Calcium Metabolism Flashcards
where does calcium come from?
diet
why is calcium needed?
- neuromuscular functions
- strength in bones
- intracellular secondary messenger
- co enzyme
- blood clotting (F IV)
- exocytosis
where is most of the calcium found in the body?
as salts and minerals in bone (hydroxyapatite)
how is calcium found in the blood?
mostly Ca2+ unbound which is free and bioactive,
some bound to proteins
very little as diffusible salts like calcium citrate/lactate
from where can calcium be increased in blood?
- absorbtion from gut
- from bone minerals
- absorbed from kidney
from where can calcium be decreased in the blood?
- lost cells eg nails
- bone formation
- excreted from kidneys
- less absorbed from gut
which hormones control calcium metabolism?
- [Ca2+] increases using PTH and vitamin D3
- [Ca2+] decreases using Calcitonin, this is less well defined
where are the parathyroid glands located?
located posterior of the thyroid, 4 glands embedded within the thyroid gland.
where is Parathyroid Hormone (PTH) synthesised?
Parathyroid glands
where is Calcitonin produced?
parafollicular cells of the thyroid
how does the calcium receptor on parathyroid cells work?
GPCR: high calcium concentration acts as an antagonist meaning it surpasses PTH release.
Low calcium levels mean more PTH is released
What type of hormone is PTH?
Polypeptide, 84 aas, synthesised from pre-pro PTH.
in calcium metabolism why is phosphate co regulated?
as phosphate is associated with calcium mainly in bones which is the biggest store of calcium
what is 1,25(OH)2D3?
Active Vitamin D3 or Calcitriol, leading to increased absorption of calcium and phosphate from the small intestines
How does PTH cause and increase in calcium concentration?
- stimulates 1 alpha hydroxylase activity in kidney which causes increased vitamin D synthesis
- increased calcium reabsorption in kidneys and therefore increased phosphate excretion
- Bone resorption by stimulation of osteoclasts and inhibition of osteoblasts
how does PTH stimulate osteoclast activation?
PTH binds to osteoblasts receptors and cause osteoclast activating factors like RANKL which activate osteoclasts.
describe the PTH axis
decreased blood calcium and action of catecholamines cause PTH secretion which leads to the synthesis of Calcitriol and increase in calcium concentration which then negatively feedback on the parathyroid glands
why does liver and kidney function effect calcium metabolism?
UV light is needed for the conversion of 7-dehydrocholesterol to cholecalciferol which is vitamin D3 which can also be obtained from diet
cholecalciferol is then hydroxylated to 25(OH)D3 and stored in liver
This is then converted to 1,25(OH)2D3 by 1a-hydroxylase which is stimulated by PTH in the kidney
Actions of Calcitriol
increases calcium and phosphate absorption from gut and reabsorption from kidneys to increase calcium levels and replace resorbed bone.
it also increases osteoblast activity
how are phosphate levels regulated?
using Fibroblast Growth Factor 23 from osteocytes, if there is too much phosphate, FGF23 inhibits hydroxylases and therefore reduced phosphate and calcium reabsorption. also stimulates excretion of phosphate.
how does FGF23 work?
in presence of high phosphate and calcitriol stimulates FGF23 to inhibit Na/PO4 cotransporter meaning phosphate is not reabsorbed and therefore excreted.
what type of hormone is calcitonin?
polypeptide, 32aa, synthesised as pre-procalcitonin
describe the calcitonin axis
increased calcium and gastrin causes parafollicular cells to release calcitonin. This inhibits osteoclast activity and stimulates calcium excretion from kidneys which decreases the calcium concentration.
Causes of HYPOcalcaemia
Vitamin D deficiency
Hypoparathyroidism
Pseudohypoparathyroidism
common effects oh hypocalcaemia
neuromuscular spasms: eg Tetany
this is because low calcium makes cells more depolarised hence easier to fire APs.
Causes of HypoParathyroidism
- IDIOPATHIC
- hypomagnesaemia
- suppression by raised calcium levels
what is pseudohypoparathyroidism?
Genetic disorder known as:
Allbright hereditary Osteodystrophy
fault in GPCR of PTH on target cells hence resistance to PTH.
features of all bright hereditary osteodystrophy
- low IQ
- short stature
- bone deformities
- associated endocrine disorders eg hypogonadism
clinical features of vitamin D deficiency
- Rickets in children
- Osteomalacia in adults
leading to bowing and fracturing as bones weaker
diagnosis of hypoparathyroidism
low calcium, high phosphate as not excreted, low PTH
diagnosis of pseudohypoparathyroidism
low calcium, high poshphate, high PTH due to feedback
diagnosis of vitamin D deficiency
low calcium, low phosphate as not absorbed by gut, high PTH
causes of HYPERcalcaemia
Hyperparathyroidism (primary and tertiary only)
Vitamin D toxicosis
what is primary hyperparathyroidism?
adenoma of Parathyroid gland causes excess secretion of PTH leading to high calcium in blood. negative feedback systems are present
what is secondary hyperparathyroidism?
renal failure means most calcium is excreted hence low concentrations mean continual PTH secretion.
what is tertiary hyperparathyroidism?
as a result of secondary, initial chronic low calcium causes overstimulation of parathyroid glands hence grows and becomes autonomous (no feedback) releasing lots of pTH meaning Calcium levels rise.
hypercalcaemia effects
polyuria
renal stones
Gastrin release
hyperparathyroidism effect
increased vitamin D synthesis
bone lesions
clubbing
duodenal ulcers
Are the Parathyroid Glands on the front or back of the thyroid?
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