calcium and phosphate metabolism Flashcards
what is calcium important for? (7)
- bone growth and remodelling
- secretion
- muscle contraction
- blood clotting
- co - enzyme
- stabilisation of membrane potentials
- important secondary messenger - stimulus response coupling
what is the distribution of calcium?
- 99% in bones
- extracellularly: 45% ionised and free and 45% bound to plasma proteins
- very small amount intracellularly
what are extracellular calcium levels controlled by? (2)
- PTH
2. Vitamin D
what are the functions of phosphate? (4)
- constituent of DNA/RNA and phospholipid membranes
- intracellular ion
- activation of enzymes by phosphorylation
what is the distribution of phosphate?
- 90% in bones
- small amount extracellular
- 10% intracellularly.
what is extracellular phosphate controlled by? (2)
- PTH
2. FGF23
what is PTH important for? (3)
- delivering elements to bone with vitamin D
- controlling flux of calcium in kidney
- controlling flux of phosphate in kidney with FGF23
Where is vitamin D’s major site of action?
in the gut for calcium and phosphate absorption.
what builds bone?
osteoblasts
what breaks or remodels bone?
osteoclasts
what do osteoblasts turn into?
osteocytes (mononuclear)
what are the two types of bone
- cortical (outside)
2. trabecular (inside like bracing)
what are osteoclasts actually
modified macrophages.
where do osteoclasts come from?
hematopoietic stem cells
where do osteoblasts come from?
mesenchymal derived cell
what activates osteoclasts?
RANK ligand - through activation of nuclear kappa beta - stimulates differentiation into osteoclasts
what signals the bone resorption and where are its receptors found?
- PTH
2. osteoblasts
what is the growth of the precursor promoted by?
GM - CSF promoted by T cells produced locally
what does the PTH receptor on the osteoblast do?
allows co-ordinated resorption of bone.
how do osteoblasts know where the line of stress is since bone grows on lines of stress?
because electricity is produced when you stress bone and tells osteoblasts when to switch on.
what produces FGF23 and what is its action
produced by osteocytes.
acts on kidney to decrease synthesis of active vitamin D and to increase excretion of inorganic phosphate.
what do osteoblasts produce that acts on pancreatic beta cells?
uncarboxylated osteocalcin.
what does uncarboxylated osteocalcin do? (2)
- increase insulin production and secretion.
2. acts on adipocytes to increase adiponectin on muscles to increase insulin sensitivity and glucose uptake
what other hormones are involved in bone turnover and bone resorption? (4)
- sex steroids - stimulate osteoblast precursors
- growth hormones stimulatee bone via IGF - 1
- thyroxine for boney growth
- glucocorticoids inhibit osteoblast maturation
what cells in the parathyroid gland produce PTH and what is the other type of cells that doesn’t produce hormone?
- chief cells
2. oxyphil cells.
what is the blood supply for parathyroid gland
inferior thyroid artery.
what is the synthesis of PTH
preopro hormone (signalling sequence)
prohormone
hormone
what is the process of using two antibodies to detect PTH, called?
immunometric assay
what does an increase in plasma proteins and alkalosis mean?
a decrease in free ionised calcium
what does an decrease in plasma proteins and acidosis mean?
an increase in ionised free calcium (H+ displaces calcium)
what is free calcium sensed by
calcium receptors on PTH producing chief cells - ultra short feedback loop
what happens in calcium receptors in PTH happen?
increase in PLC and decrease in cAMP - results in decrease PTH production.
once ionised calcium goes outside normal range what happens?
PTH secretion immediately shuts off - calcium has to be tightly regulated.
what does PTH do? (4)
produce it in response to low calcium in order to increase calcium
- stimulates osteoblasts to produce M-CSF and RANK ligand which increase bone resorption
- increases calcium reabsorption in DCT
- increases phosphate excretion
- increases 1-alpha hydroxyls in the PCT.
what is calcium bound to and transported to the basolateral membrane by?
bound to calbindin
how does PTH increase the amount of calcium channels on the luminal surface?
stimulates AC to increase cAMP and activates PKA which increases amount of calcium channels on the luminal surface.
what does the foetus produce?
PTHrp
what are the two major causes of hypercalcaemia?
- primary hyperparathyroidism
2. malignancy
symptoms of hypercalcaemia?
- shortening of QT interval - bradycardia
- decreased concentration, confusion, fatigue, fitting
- GI - hypo motility - constipation
- excess gastrin - leading to peptic ulcer formation.
- renal function - polyuria, polydipsia
- muscular weakness and bone pain
how is vitamin D produced
D3 - cholesterol to cholecalciferol
D2 - ergosterol to ergocalciferol
what is the main regulating enzyme in the kidney for vitamin D
1-alpha hydroxylase - regulates calcitriol
what is renal dysfunction tend to be associated with?
low levels of vitamin D
what diseases can result in hypercalcemia?
sarcoidosis, tubercolosis, and other granulomatous
what type of receptor are vitamin D receptors?
type 2 nuclear receptors
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