Endocrinology 11 - Endocrine Control of Calcium Metabolism Flashcards
List the roles of calcium in the body
- Neuromuscular excitability
- Muscle contraction
- Strength in bones
- Intracellular secondary messenger
- Coenzyme
- Involved in blood coagulation
- Neurotransmitter release
How is most calcium found in the body?
- In the form of salts
- Mainly present in the bone as a hydrated salt (hydroxyapatite)
- Some calcium is found as ionised calcium, bound to protein or bioactive
What percentage of calcium is bound and unbound in the blood?
50% unbound and ionised
45% bound to plasma proteins
5% diffusible salts
What hormones are involved in calcium ion regulation?
- Parathyroid hormone
- Calcitonin (decrease)
- Calcitriol (vitamin D3)
Where is parathyroid hormone (PTH) secreted from?
Parathyroid glands
Where is calcitonin secreted from?
The parafollicular cells.
What type of receptor are calcium sensing receptors?
G protein coupled receptors
How is parathormone initially synthesised?
As pre-proPTH
What receptors do parathormone and calcitonin bind to?
- Transmembrane G coupled receptors
- Activates adenyl cyclase and PLC
Describe the actions of parathyroid hormone.
- Increases breakdown of bone (resorption) via activation of osteoclasts and inhibition of osteoblasts
- Increases calcium in the blood by increasing absorption of the kidney and prodction of calcitrol (via 1-alpha hydroxylase)
- Also increases excretion of phosphate from the kidneys
- Increases calcium and phosphate absorption at the SI
Describe the process that occurs when PTH binds to receptors in bone
- PTH binds to receptors on osteoblasts
- Osteoblasts produce osteoclast activating factors
- An example of this is RANKL
- Osteoclasts then perform bone breakdown
Describe the regulation of PTH
- PTH release is stimulated by decreased plasma calcium, catecholamines (dopamine, noradrenaline - bind to beta receptors)
- PTH release is inhibited by negative feedback, when the plasma calcium increases and by calcitrol.
What are the actions of dihydroxycholecalciferol?
- Calcitrol
- Increases osteoblast activity in bone, and calcium absorption in the small intestine (for use in bones)
- Increases phosphate absorption in the SI
- Increases calcium and phosphate reabsorption in the kidney
What are the actions of fibroblast growth factor 23?
- Production is stimulated by phosphate and calcitrol
- It inhibits production of calcitrol (negative feedback)
- It reduces phosphate levels in the blood, reducing expression of the sodium phosphate transporter in the kidney
What is calcitonin synthesised as?
Pre-procalcitonin
Which factors regulate calcitonin production?
- Increases plasma calcium ion concentration increases calcitonin
- The hormone gastrin stimulates calcitonin production, as well as production of stomach acid
- Production decreases when the decreased plasma calcium ion conc occurs
Describe the actions of calcitonin
- Works to decrease plasma Ca2+, though it has a limited effect
- Increases excretion of Ca2+ at the kidneys
- Inhibits osteoclast activity
List the three endocrine causes of hypocalcaemia.
- Hypoparathyroidism
- Pseudohypoparathyroidism
- Vitamin D deficiency
What are the two signs of hypocalcaemia?
Tetany can be seen by these signs:
- Trousseaus sign (hand curling up)
- Chvosteks sign (face twitching too much at a small stimulus)
What is another name for pseudoypoparathyroidism?
Allbright hereditary osteodystrophy
What is the cause of pseudohypoparathyroidism?
- Target organ resistance to PTH
- Due to defective Gs protein, which increases cAMP in response to receptor activation
What are the features of pseudohypoparathyroidism?
- Short stature, round face
- Low IQ
- Subcutaneous calcification and bone abnormalities
- Endocrine disorders
What are the names for vitamin D deficiency in children and in adults?
- Rickets in children
- Osteomalacia in adults
What are the clinical features of vitamin D deficiency?
- Bone matrix has decreased calcification, resulting in the bone softening
- Bowing in children
- Fractures in adults
Describe levels of plasma Ca, PO4 and PTH in hypoparathyroidism.
- Low calcium
- Low PTH
- High plasma PO4
Describe levels of plasma Ca, PO4 and PTH in pseudohypoparathyroidism.
- High PTH
- High PO4
- Low clacium
Describe levels of plasma Ca, PO4 and PTH in vitamin D deficiency
- High PTH
- Low PO4
- Low calcium
What are the endocrine causes of hypercalcaemia?
- Primary hyperparathyroidism
- Tertiary hyperparathyroidism
- Vitamin D toxicosis
What happens in primary hyperparathyroidism?
- There is an ademona, casing excessive production of hormones
- Production is not stopped by negative feedback
What happens in secondary hyperparathyroidism?
- There is low plasma calcium, for example due to renal failure
- Therefore, the parathyroids overproduce PTH while levels of calcium are low or as they should be
What happens in tertiary hyperparathyroidism?
- There is initially chronic low plasma (secondary hyperparathyroidism), for example renal failure. The cause of low plasma is then treated.
- The parathyroid glands become autonomous and no longer respond to feedback
What does parathyroid hormone excess cause?
- High calcium
- Phosphate excretion
- Polyurea
- Kidney stones
- High calcitonin
- Gastric acid
- Bone lesions or rarefaction (shortening)
- Fractures
Where is calcitriol produced?
Kidney
