Calcium homeostasis Flashcards
What physiological roles does calcium have in the body?
Muscle contraction
Bones and teeth
Blood coagulation
Hormone release
What cellular roles does calcium have in the body?
Exocytosis
Second messenger
Metabolism
What is the normal range of calcium?
2.2 - 2.7 mmol/L
Where is the majority of calcium found in the body?
99% in bones
1% in cells
0.1% in extracellular fluid
What is corrected calcium levels?
Levels corrected to the amount of protein in the patients body - as calcium attached to protein in blood, and amount of protein varies from person to person.
What percentage of dietary calcium is absorbed in the body?
10%
What factors can increase intestinal absorption of calcium?
Vitamin D
Low calcium uptake
Phosphate deficiency
Growth hormone
Oestrogens
Pregnancy and lactation
Furosemide
What factors can decrease intestinal absorption of calcium?
Age
High calcium uptake
glucocorticoids
Phosphate loading
Thyroid hormones
Thiazide diuretics
Vitamin D works in conjunction with which hormone?
PTH
Which hormone does the opposite of Vitamin D and PTH?
Calcitonin
Which gland secretes PTH?
The parathyroid
How are the levels of PTH and Calcium linked?
They are inversely proportional.
Higher PTH = lower Ca2+
Lower PTH = higher Ca2+
Which cells in the parathyroid gland synthesise and produce PTH?
Chief cells.
Which cells can be seen in secondary parathyroid hyperplasia, that synthesise and secrete PTH?
Oxyphil cells.
What is the main role of the parathyroid gland?
To monitor calcium concentration.
How long is the amino acid chain of PTH?
84 amino acids
The active part of PTH is in what part of the amino acid chain?
1-34
What part of the PTH amino acid chain is inactive?
35-84
The active part of the PTH (1-34) binds to which receptors?
PTH (Type 1) receptor - GPCR
Which receptor does calcium bind to, and that calcium is the agonist for?
Calcium sensing receptor (CaSR)
What type of receptor is the Calcium sensing receptor?
GPCR
Mutations to which receptor are correlated with hyper and hypocalcaemia?
Calcium sensing receptor (CaSR)
Which cells monitor plasma calcium concentration?
Chief cells in the parathyroid gland via a g-protein calcium sensing system - this controls PTH release.
Which ion is important for PTH to work?
Magnesium
What is the half-life of PTH?
4 minutes
Low levels of which ion inhibits the release of PTH?
Magnesium
What factors stimulate PTH to be released?
Fall in plasma ionised calcium (acute)
Rise in plasma phosphate (chronic)
What is parathyroid hormone released protein (PTHrP)?
Hormone secreted by tumours and contributes to the hypercalcaemia seen in malignancy.
What role does parathyroid hormone related protein have in the foetus?
It acts as a calciotropic hormone and stimulates the transport of calcium across the placenta.
Does a normal lab assay pick up PTHrP?
No, only PTH
How does PTH affect bones?
PTH binds to osteoblasts –> cells express RANKL and M-CSF –> Interact with preosteoclast cells –> Form mature osteoclasts –> Release enzymes and acids to dissolve bone
How does PTH affect the kidneys?
It binds to reduce Ca2+ excretion.
Causes increased absorption of calcium in the loop of henle, distal tubule and collecting ducts.
Reduces phosphate reabsorption in the proximal tubule.
Where are PTH receptors found?
Bone
Kidneys
Intestine
How does PTH affect the small intestine?
It binds and increases Ca2+ levels.
What is the active form of Vitamin D called?
1,25-Dihydroxycholecalciferol
Which hormone helps vitamin D be converted into it’s active form?
PTH
Where does the hydroxylation of vitamin d occur in the body?
Liver
Kidneys - active conversion here
Who do those with kidney problems need the active form of vitamin D?
Kidneys aren’t able to do the conversion to active vit D
How does Vitamin D, Calcium and PTH have a negative feedback loop?
PTH helps the conversion of vit D into active Vit D.
Active vit D increases the intestinal absorption of calcium.
Higher calcium concentration inhibits PTH, thus reducing the amount of vit D converted into active vit D.
How many amino acids are in calcitonin?
32
Where is calcitonin produced?
In the thyroid gland by parafollicular C cells.
What is calcitonin modulated by?
CaSR - Calcium Sensing Receptor
Also GI hormones e.g. Gastrin
What stimulates the parafollicular C cells to secrete calcitonin? What inhibits it?
A rise in extracellular calcium
Inhibited by a fall in calcium.
How does calcitonin affect bones?
It inhibits osteoclastic activity - therefore reducing bone resorption.
How does calcitonin affect the kidneys?
It reduces tubular reabsorption of calcium and phosphate, therefore increasing their excretion and lowering their serum levels.
Calcitonin is the major tumour marker of which cancer?
Medullary carcinoma of the thyroid gland.
Which bone-derived hormone suppresses phosphate reabsorption and vitamin D synthesis in the kidneys?
FGF23 - Fibroblast growth factor-23
What can an excess of FGF23 (Fibroblast growth factor-23) cause?
Hypophosphatemic rickets
