Endocrine Control of Calcium Metabolism Flashcards
State some roles of calcium in the body.
Control of neuromuscular excitability (hypocalcaemia leads to hyperexcitability because Ca2+ normally blocks the Na+ channels) Muscle Contraction Strength in bone Blood clotting Intracellular second messenger
Where is calcium mainly stored?
Bone - 99% is stored as hydroxyapatite crystals in bone
How is calcium present in the blood? What is the main component?
Unbound ionised calcium - 50%
Bound to plasma proteins - 45%
Tiny bit as soluble salts
What is the usual daily intake of calcium?
1000 mg/day
What is the concentration of unbound ionised calcium in the blood?
1.25 Mm
What two hormones raise plasma calcium concentration?
Parathyroid Hormone
Calcitriol (1,25-dihydroxycholecalciferol)
What hormone decreases plasma calcium concentration?
Calcitonin
Where is parathyroid hormone produced?
Parathyroid Glands (four of them) - produced in the follicular cells
Where is calcitonin produced?
Parafollicular cells in the thyroid gland
Describe the effects of parathyroid hormone on the kidneys.
Increases calcium reabsorption
Increases phosphate excretion
Describe the effects of PTH on bone.
Stimulates osteoclasts
Inhibits osteoblasts
Describe the effects of PTH on the small intestines.
PTH increases the activity of 1 alpha hydroxylase (in the kidneys), which is involved in the production of calcitriol, which increases calcium and phosphate absorption in the small intestine.
How does PTH increase calcium release from bone?
PTH has a direct effect in inhibiting osteoblasts. PTH makes the osteoblasts produce osteoclast activating factors (such as RANKL) that bind to receptors on osteoclasts and stimulates the break down of bone matrix to release calcium.
What can stimulate PTH release?
Low plasma calcium concentration
Catecholamines (by binding to beta receptors)
Describe the negative feedback loops on PTH.
Increased plasma calcium concentration has a negative feedback effect on PTH
Calcitriol also has a negative feedback effect
What is the precursor of calcitriol?
Cholecalciferol
Where does this precursor come from?
Diet
Sun Light (UV B converts 7-dehydrocholesterol to cholecalciferol)
NOTE: cholecalciferol is VITAMIN D3
Describe the reactions that have to take place to convert the precursor to calcitriol.
Cholecalciferol travels to the liver where 25-hydroxylase converts it to 25-hydroxycalciferol, which is then stored in the liver.
It then moves to the kidneys where 1 alpha hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (calcitriol)
Describe the effects of calcitriol.
MAIN ACTION: stimulates calcium and phosphate absorption in the SMALL INTESTINE
Minor effect on bone
Kidneys - increases calcium reabsorption and increases phosphate excretion
How does calcitriol and PTH decrease phosphate reabsorption in the kidney?
They block the sodium/phosphate cotransporter
Calcitriol does this via the action of FGF23 (fibroblast growth factor 23)
Describe the effects of calcitonin.
Calcitonin inhibits osteoclast activity
Calcitonin also affects the KIDNEYS - increase sodium excretion and hence increase urinary excretion of phosphate and calcium.
State a physiological benefit of calcitonin.
During pregnancy women need a higher plasma calcium concentration (e.g. for milk), calcitonin protects the bone from break down.
State three causes of hypocalcaemia.
Hypoparathyroidism
Pseudohypoparathyroidism
Vitamin D Deficiency
What two signs are used to demonstrate hypocalcaemia?
Trousseau’s Sign
Chvostek’s Sign
These are both signs of tetany
What is pseudohypoparathyroidism and what are some clinical features?
Target organ resistance to PTH (also called Allbright Heriditary Osteodystrophy)
Round face, short, low IQ, short 4th metacarpal, hypothyroidism, hypogonadism
What does vitamin D deficiency cause in children and adults?
Children - rickets
Adults - osteomalacia
State three causes of hypercalcaemia.
Primary hyperparathyroidism
Tertiary hyperparathyroidism
Vitamin D Toxicosis
Describe the differences between primary, secondary and tertiary hyperparathyroidism.
Primary - caused by parathyroid adenoma producing huge amounts of PTH
Secondary - caused by other reasons e.g. renal excretion of Ca2+ ions leading to compensatory increase in release of PTH (this causes low Ca2+ because it is being lost from the kidneys)
Tertiary - initial chronic low plasma calcium concentration - parathyroid gland is massively stimulated for a long time and so PTH production becomes autonomous and stops responding to negative feedback (leads to hypercalcaemia)
State some consequences of parathyroid hormone excess.
Kidney stones (calcium deposits) Increased risk of fracture
What is a distinctive clinical feature of primary hyperparathyroidism?
Clubbing of the fingers
