Endocrine control of calcium metabolism Flashcards
What is the main form of calcium
Hydroxyapatite crystals in bone
In what forms are calcium present in the blood
50% unbound
45% bound to plasma proteins
5% diffusible salts (citrate, lactate)
What form of calcium is bioactive
free Ca2+
What are the roles of calcium
Neuromuscular excitability Muscle contraction Strength in bones Intracellular second messenger Intracellular co-enzyme Hormone/neurotransmitter stimulus-secretion coupling Blood coagulation (factor IV)
What is the main route of calcium after intake
Intake -> GI tract -> blood -> kidneys
From the blood where may calcium travel
bone and other cells
kidney
Loss in hair, skin and nails
What is released when calcium levels are too low
Parathyroid hormone and calcitrol
Describe the calcium sensing receptor
G-protein coupled receptor that is activated by ligand binding (suppresses PTH)
Describe the process of PTH synthesis
- synthesised as pre-proPTH
2. cleavage to form PTH
Where is PTH synthesised
parathyroid glands
Where is calcitonin synthesised
parafollicular cells of the thyroid
How does PTH affect the kidneys
Increases calcium reabsoprtion
Increases phosphate excretion
Stimulate 1𝛼 hydroxylase activity to increase calcitrol synthesis
How does PTH affect the small intestine
Calcitrol synthesis in the liver stimulates increased calcium absorption
Increased phosphate absoprtion
How does PTH affect the bone
Stimulation of osteoclasts and inhibition of osteoblasts so an increase in bone resorption (decrease in bone mass)
Describe the process of PTH induced decreased bone resorption
- PTH binds to the PTH receptor on an osteoblast
- Osteoblasts release osteoclast activating factors (RANKL)
- Increased bone resorption
How is PTH regulated
Increased plasma calcium creates a negative feedback effect to reduce PTH levels from the parathyroid gland
How is calcitriol synthesised
- UV light converts 7-dehydrocholesterol into cholecalciferol/ obtained from the diet
- Synthesis of 2,5-hydroxy-cholecalciferol in the liver (+2 OH groups)
- PTH stimulates 1𝛼 hydroxylase
- synthesis of 1,25-di-hydroxycholecalciferol in the kidney
How does calcitriol affect the bone
Increased osteoblast activity
How does calcitriol affect the kidneys
Increased calcium and phosphate reabsorption
How does calcitriol affect the small intestine
Increased calcium and phosphate absorption
How are circulating phosphate levels regulated
Fibroblast growth factor 23 once stimulated by high phosphate and vitamin D3 levels in the kidney
How does FGF23 work
Inhibits the reabsorption of phosphate and sodium through the phosphate sodium cotransporter in the kidney (PTH does the same)
What are the main effects of calcitonin
Increased urinary excretion of calcium, sodium and phosphate
Inhibition of osteoclast activity
Decrease calcium levels
What are the three main causes of hypocalcaemia
Hypoparathyroidism
Pseudohypoparathyroidism
Vitamin D deficiency
What are the signs of hypocalcaemia
Trousseau’s
Chvostek’s
What are the features of hypoparathyroidism
low calcium, high phosphate, low PTH
Hypomagnesaemia
Suppression by raised calcium concentration
What are the features of pseudohypoparathyroidsm
Target organ resistance to PTH (may be due to defective Gs protein)
low calcium, high phosphate, high PTH
What are the clinical features of pseudohypoparathyroidism
Short stature
Round face
Low IQ
Subcutaneous calcification and one abnormalities
Endocrine disorders (hypothyroidism, hypogonadism)
What can vitamin D deficiency cause
Ricketts in children
Osteomalacia in adults
What are the clinical features of vitamin D deficiency
Decreased calcification of the bone matrix
Softening of the bone
Bowing of the bones
Fractures
What are the features of vitamin D deficiency
Low calcium, low phosphate, high PTH
What are some clinical features of hypercalcaemia
Increased calcium reabsorption Increase phosphate excretion Polyuria Renal stones Nephrocalcinosis Gastric acid release Duodenal ulcers Bone lesions Bone rarefaction (reduction in density) Fractures
What is primary hyperparathyroidism
High levels of PTH are produced due to an adenoma growing in the glands, increasing the circulating calcium levels. -ve feedback system does not work
What is secondary hyperparathyroidism
PTH levels remain high but calcium levels remain low, commonly due to kidney disease as it cannot reabsorb the calcium needed
What is tertiary hyperparathyroidism
The parathyroid glands grow due to secondary parathyroidism and once this has been treated, the glands remain large and become autonomous, not responding effectively to feedback
What is another cause of hypercalcaemia
Vitamin D toxicosis
