Endocrine control of calcium homeostasis Flashcards
Where is calcium important?
Exocytosis
- neurotransmitter secretion
- hormone secretion
Physical properties of bone
Hypocalcaemia causes neurone excitation
Decreased extracellular Ca2+ increases the neuron membrane’s permeability to Na+
Na+ easily depolarises the membrane so causes an action potential
If someone has a first fit, check the serum calcium
Physical signs of hypocalcaemia
Carpopedal spasm
Chvostek’s sign
Acute consequences of hypercalcaemia
Thirst and polyuria
Abdominal pain
Chronic consequences of hypercalcaemia
Constipation
Musculoskeletal aches/ weakness
Neurobehavioral symptoms
Renal calculo
Osteoporosis
Measuring serum calcium
Protein bound 40%
- albumin bound 90%
- globulin bound 10%
Bound to cations 10%
- phosphate and citrate
Ionised (free) 50%
Normal range of calcium level in the blood
2.15-2.55 mmoles/l
Chief cells in the parathyroid gland function
Produce parathyroid hormone
Calcium sensing receptors
Sensitive to increase in serum calcium
Stimulates uptake of calcium by parathyroid glad
Activation of calcium sensory effects
Activation of phospholipase C which leads to DAG and IP3
Inhibition of adenylate cyclase, suppresses intracellular cAMP
Sequence of events after less calcium molecules in blood
Altered calcium sensing receptor formation
Modified chief cell process
(Mg2+)
PTH secretion
Type 1 parathyroid hormone receptor
Bind both parathyroid hormone and amino terminal peptides of PTHrP
Binding activates adenylyl cyclase and phospholipase C systems
Generates protein kinase A and protein kinase C
Most abundant in bone and kidney
Type 2 parathyroid hormone receptor
Binds parathyroid hormone, has very low affinity for PTHrP
Expressed in only a few tissues
Coupled to adenylyl cyclase so ligand binding increases intracellular cyclic AMP
Mutations in type 1 parathyroid hormone receptor
Associated with rare human diseases
Jansen’s metaphyseal chondroplasia (short limbed dwarfism) has constitutively active receptor
Blombstrand’s chondroplasia has inactive mutation in receptor gene (leads to early death with defective bine meturation)
Where are the PTH1 receptors?
Bone
Kidney
PTH promotes absorption of Ca2+ from bone
Rapid phase
- rise in serum calcium
- PTH binds to receptor on osteoblast/cyte
- osteocytic membrane pumps out Ca2+ from bone fluid to extracellular fluid
Slow phase
- oesteoclasts activated to digest formed bone
- proliferation of osteoclasts occurs
Bone resorption
Removing bone tissue by removing bone’s mineralised matrix
Done by osteoclasts
Osteoclasts characterised by
High expression of tartrate resistant acid phosphate and cathepsin K
Actions of PTH on kidneys
Rapid calcium reabsorption
- increased Ca2+ reabsortion in LOH, DT, CD
- decreased PO4 reabsorption in PT
Renal synthesis of active vitamin D
Renal actions of PTH
Converts 25OH Vit D to 1,25 OH vit D
That leads to calcium transports and binding proteins in gut cells
So increased calcium absorption
Primary hyperparathyroidism diagnosis
Serum calcium increased
Serum phosphate reduced
PTH increased
Complications of hyperparathyroidism
Osteoporosis
Bone cysts
Complications of hypercalcaemia
Renal stones
Locating the parathyroid adenoma
Sesta mibi parathyroid scan
Neck ultrasound
