Regulation of Calcium and Phosphate Flashcards
What are the hormones that increase serum calcium and phosphate
Parathyroid hormone
Vitamin D
What are the hormones that decrease serum calcium and phosphate
Calcitonin
What is the most abundant metal in the body
Calcium
Whast is a good source of Vitamin D
Oily fish
What is the calcium distribution in the body
99% resides in skeleton and teeth
Extracellular calcium is tightly regulated
‘Unbound’ ionised calcium is the most biologically active compound
Bound Ca is to plasma proteins (albumin) or anions
What are the two sources of Vitamin D
Diet - ergocalciferol D2
Skin synthesis - sunshine - cholecalciferol D3
Which light shines on the skin
UVB
Show the synthesis of Vitamin D3 in the skin
What happens to Vitamin D when it enters the bloodstream
Has to undergo two hydroxylation reactions
Why do you not measure calcitriol
It is unstable in the body
Instead measures 25(OH) cholecalciferol as body stores
1,25 (OH)2 cholecalciferol regulates own synthesis to 1 alpha- hydroxylase
What are the effects of calcitriol
Increase Ca reabsorption
Increase Ca reabsorption from kidney
Increases Ca and PO4 absorption from gut
Where are the parathyroid glands
How are parathyroid hormones secreted
From chief cells
Secreted as a large precursor (pre-pro-PTH) and cleaved to PTH
G-protein coupled calcium sening receptor change in circulating calcium
PTH secretion is invesly proportional to serum calcium
Actions of the parathyroid hormone
Increase Ca reabsorption
Increase Ca bone reabsorptuion
Increase PO4 excretion
Increase 1 - alpha - hydroxylase activity
This increases calcitriol synthesis
This increase Ca and PO4
PTH action in bone
PTH receptor activates osteoblast (builds bone)
Makes osteoclast activating factors (RANKL which is the receptor activator of nuclear factor kappa-B ligand)
Osteoclast is activated
Bone resorption
How does osteoclast release enzymes
Through the ruffled border
Calcitriol action in bone
LOW serum calcium - Calcitriol increases calcium reabsorption from bone osteclasts > osteoblasts
NORMAL serum calcium - calcitriol works to increas ebone fomration osteoblasts > osteoclasts
PTH regulation
Negative feedback on calcium receptors on the parathyroid hormones
Vitamin D receptors as well on the chief cells
What does calcitonin do
Thryoid glands secreted from parafollicular cells
Reduces serum calcium
Removal of thyroid gland does not affect serum calcium
How does calcitonin regulate calcium
Increase in plasma Ca
Kidney Ca excretion
Decrease in osteoclast activity
Regulation of serum phosphate by FIbroblast Growth Factor 23 (FGF23)
It reduces phosphate
This inhibitors sodium-phosphate cotransporter
Inhibits calcitriol production - less PO4 reabsoprtion from the gut
What does high extracellular calcium indicate (HYPERcalcaemia)
Less membrane excitability
Ca blocks Na influx
What does LOW extracellular calcium (HYPOcalcaemia) indicate
Greater Na influx so more membrane excitability
Symptoms of hypocalcaemia
Parasthesia - tingling
Convulsions
Arrhythmias - irregular heartbeat
Tetany - muscle contract but not relax
How to test for hypocalcaemia
Tap facial nerve just below zygomatic arch
Positive response - twitching of facial muscles
Inflation of BP cuff for several minutes which induces carpopedal spasm
indicates neuromuscular irritability
What are the causes of hypocalcaemia
Low PTH levels - hypoparathyrodisim
Surgery
Auto-immune
Magnesium deficiency - need it to make PTH
Congenital
Vitamin D deficiency
Causes of Vitamin D deficiency
Malabsoprtion or dietary insufficency
Inadequate sun exposure
Liver disease
Renal disease
Vitamin D receptor defects (rare)
What are the conseuqneces of Vitamin D deficiency
Lack of bone mineralisations
Children - rickets.- bowing of bones
Adults - osteomalacia (fractures, proximal myopathy) - adult bone more developed
What are the symptoms in the hypercalcaemia
Stones - nephrocalcinosis - kidney stones
Abdominal - anorexia, nausea, dyspepsia, constipation, pa
Psychic groans - tiredness, low mood, coma, fatigue, depression
Causes of hypercalcaemia
Priamry hyperparathyroidism
Usually due to parathyroid gland adenoma
No negative feedback
Malignancy - tumours produce factors to activate osteoclasts
Vitamin D excess- tablet overdose
