4. Calcium homeostasis, hyper and hypocalcaemia Flashcards
Why is calcium important?
Calcium needed for exocytosis:
-neurotransmitter secretion
-hormone secretion
physical properties of bone
What does hypocalcaemia do to neurons?
- Hypocalcaemia destabilises neurones
- if someone has a first fit - check the serum calcium
- hypercalcaemia can cause seizures
What is a physical sign of hypocalcaemia?
Carpopedal spasm aka Trousseau’s sign
- occluding the brachial artery (blood pressure cuff) elicits a carpal spasm.
Chvostek’s sign
Describe Chvostek’s sign
- abnormal reaction to stimulation of facial nerve, sign of tetany in hypocalcaemia
- low plasma calcium increases permeability of neuronal membranes to sodium causing neuronal excitation. Tapping on the facial nerve exaggerates its activity
- present in 10% of normals
Acute consequences of hypercalcaemia
Thirst and polyuria
abdominal pain
chronic consequences of hypercalcaemia
- constipation
- musculoskeletal aches/weakness
- neurobehavioural symptoms
- renal calculi
- osteoperosis
Measuring serum calcium
Protein bound - 40%
- with 90% bound to albumin and 10% to globulin
10% bound to cations - phosphate and citrate
ionised (free) Ca2+ - 50%
When should ionised Ca2+ be measured directly?
- if albumin concentration is below 20 g/l
- in severe acute illness
because total serum Ca2+ is corrected for albumin concentration
What is the normal calcium level in the blood?
Controlled within a tight normal range of 2.15-2.55 mmoles/l
by the parathyroid glands
What are parathyroid chief cells?
- parathyroid chief cells are cells in the parathyroid glands
- produce parathyroid hormone
- chief cell secretions results in increase in serum level of Calcium
- regulate intracellular calcium levels as a consequence of extracellular changes in calcium concentration
- parathyroid chief cells take up calcium in response to increased serum calcium, sensed by calcium-sensing receptors
What determines PTH release?
Serum calcium concentration determines release of PTH
How does the parathyroid cell know when to make PTH or when blood Ca2+ is abnormal?
- Calcium sensing receptor in the parathyroid chief cells
- GPCR which when activated leads to activation of phospholipase C which leads to generation of diacylglycerol and inositol trisphosphate; AND inhibition of adenylate cyclase which suppresses intracellular conc of cyclic AMP
Calcium & PTH secretion
Less calcium molecules
- > altered calcium sensing receptor formation
- > modified chief cell processes (which use Mg2+)
- > PTH secretion
How does Magnesium influence PTH?
Low Magnesium prevents PTH release
How does PTH work?
PTH binds PTH/PTHrP receptor and activates it by changing its shape, leading to a biological effect
PTH type 1 and PTH type 2 receptors