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
Where are the PTH receptors (i.e. where is the biological effect)?
Bone
kidney
What is the action of PTH in bone?
-PTH has a rapid action in bone -
rapid Ca2+ release through the osteocytic membrane pump
-calcium release from bone stimulates osteoclasts
How are osteoclasts stimulates?
- PTH acts on osteoblasts
- osteblasts then release rank ligand
- rank ligand binds osteoclasts and activates them
- Osteoclasts then break down bone, releasing Ca2+ into the bloodstream
What are the actions of PTH in the kidney
- Rapid calcium reabsorption
- Renal synthesis of active vitamin D
Describe calcium reabsorption in the kidney as a result of PTH
Rapid calcium reabsorption in kidney caused by PTH Calcium reabsorbed in: -loop of Henle -Distal tubule -Collecting ducts PO4 reabsorption at the proximal tubule
Vitamin D
Vitamin D (cholecalciferol) from diet (cod liver oil, wild oily fish, mushrooms and fortified foods) and skin following exposure to UV light from the sun, go to the liver and are metabolised into 25 OH vitamin D
Renal actions of PTH
- 25 OH Vitamin D is made into 1,25 OH by PTH
- 1,25 OH Vitamin D is used by calcium transporters and binding protein (calbindin) in gut cells
- this increases calcium absorption
Regulation of 1,25(OH) vitamin D in kidney
- PTH stimulates its production
- FGF23 inhibits its production
-1,25(OH)vitamin D inhibits PTH production and secretion from the parathyroid glands and stimulates FGF23 production from bone
The kidney and phosphate excretion
Osteocytes release FGF23
FGF23 causes renal phosphate excretion
Primary hyperparathyroidism diagnostic signs
- Serum calcium increased
- Serum phosphate reduced
- PTH increased
Complications of hyperparathyroidism
osteoperosis bone cysts (if severe)
Complications of hypercalcaemia
Renal stones
How do you locate a parathyroid adenoma
sesta mibi parathyroid scan
neck ultrasound
Hypoparathyroidism diagnostic signs
Low serum calcium
Low/normal PTH
Hypoparathyroidism causes
iatrogenic - thyroidectomy, radical neck surgery
Autoimmune
hypomagnesaemia
genetic mutations
Secondary hyperparathyroidism causes
Low/low normal serum Calcium + high PTH
Low serum 25 OH vitamin D - lack of sun exposure, GI problems (malabsorption or extensive surgery of small bowel)
Renal failure
What condition does reduced vitamin D concentration result in?
Ricketts
Osteomalacia in adults
Looser’s zone
What is linked with vitamin D deficiency in the elderly?
Increased risk of falls and fracture
What does low concentration of calcium in blood result in?
Release of parathyroid hormone
What are the effects of parathyroid hormone?
In bone: efflux of calcium from bone
In kidney: decreased loss of calcium in urine
Kidney makes vitamin D which enhances absorption of calcium from intestine
What does PTH do?
Maintains blood Ca2+ concentration and maintains bone mineral density
