Regulation Of Calcium and Phosphate Flashcards
What is calcium?
Most abundant metal in the body
99% resides in skeleton and teeth
Unbound ionised calcium = biological active component
What increases calcium levels in the body?
Parathyroid hormone (PTH)- secreted by parathyroid gland Vitamin D
What decreases calcium levels in the body?
Calcitonin- secreted by thyroid parafollicular cells
There are no negative effects if parafollicular cells are removed
What are sources of vitamin D?
Diet- vitamin D2
Sunshine- vitamin D3 (cholecalciferol)
What is a good indicator of vitamin D status?
Serum 25-hydroxycholecalciferol (serum 25-OH vit D)
How do we get vitamin D from the sun?
UVB causes production of 7- dehydrocholesterol
This is then converted to pre- Vitamin D3 which is converted to Vitamin D3
How is vitamin D activated?
You need 2 hydroxylation steps:
- Hydroxylation of Vit D3 and D2 in liver to 25 Hydroxy-cholecalciferol
- In kidney: Hydroxylation of 25 (OH) cholecalciferol to 1, 25 dihydroxycholecalciferol by 1 alpha- hydroxylase
What is the active form of vitamin D?
Calcitriol (1,25 dihydroxycholecalciferol)
How does calcitriol regulate its synthesis?
Regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase
Negative feedback caused by high levels of calcitriol
What is the effect of calcitriol?
Effects bone, kidney and gut
Works to increase calcium by increasing calcium absorption by bone
Increases Ca2+ absorption from kidney and gut
Increases phosphate reabsorption from kidney and absorption from gut
What is parathyroid hormone secreted by?
chief cells in parathyroid gland
How is parathyroid hormone secreted?
Secreted as a large precursor (pre-pro-PTH) and is cleaved to parathyroid hormone
When is PTH secreted?
G- protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
PTH secretion is inversely proportional to serum calcium
What happens when theres high extracellular fluid calcium conc.?
Ca2+ binds to receptors on parathyroid cells
PTH secretion inhibited
What happens when theres low extracellular fluid calcium conc.?
Less Ca2+ binding to receptors on parathyroid cells
Increased PTH secretion
What are actions of PTH?
Increased Ca2+ reabsorption from bone,
Increased Ca2+ adsorption from kidney and gut
Increased phosphate absorption from gut
Increased phosphate excretion in kidney
Increased 1- alpha hydroxylase activity in kidney so increased calcitriol synthesis
What is the action of PTH in bone?
When PTH binds to PTH receptor, osteoblast activates osteoclast (osteoclast activating factors e.g. RANKL)
What is the effect of calcitriol on bone?
Calcitriol effects bone depending on serum calcium
Low serum Ca- calcitriol increases Ca2+ reabsorption from bone (releases calcium into blood) (osteoblast to osteoclast)
Normal serum Ca: calcitriol increases bone formation (osteoclast to osteoblast)
How is PTH regulated?
Increased plasma Ca2+ leads to less secretion of PTH in a negative feedback loop
What reduces serum phosphate?
Fibroblast growth factor 23 (FGF23)
Inhibits phosphate absorption through inhibition of Na+/PO4- co-transporter and removes phosphate via urine
It also inhibits calcitriol action
What is high serum calcium known as?
Hypercalcaemia
Ca2+ blocks Na+ influx so less membrane excitability
What is low serum calcium known as and what are symptoms?
Hypocalcaemia
More Na+ influx so more membrane excitability
Symptoms: parasthesia, convulsions, arythmias, tetany
How can we diagnose hypocalcaemia?
Chvostek’s sign: tap facial nerve just below zygomatic arch
Positive response= twitching of facial muscle
Trousseaus’s sign: inflation of BP cuff for several mins. Induces caropopedal spasm
What are causes of hypocalcaemia?
Low PTH levels Surgical Auto-immune Mg deficiency Congenital Vitamin D deficiency
What is low PTH levels known as?
Hypoparathyroidism
What are causes of vitamin D deficiency?
- Malabsorption or dietary insufficiency
- Inadequate sun exposure
- Liver disease
- Renal disease
- Vitamin D receptor defects
What are consequences of vitamin D deficiency?
Loss of bone mineralisation- soft bones
In children- rickets
In adults- osteomalacia
What are symptoms of hypercalcaemia?
‘stones, abdominal moans and psychic groans’
Reduced neural excitability
Stones: renal effects- Nephrocalcinosis: kidney stones
Abdominal Moans: GI effects- anorexia, nausea, dyspepsia, constipation
Psychic Groans: CNS effect- fatigue, depression, impaired concentration, coma
What are causes of hypercalcaemia?
Primary hyperparathyroidism
Too much PTH
Parathyroid gland adenoma
No negative feedback- high PTH and high Ca
Malignancy: bony metastasis produce local factors to activate osteoclasts increasing Ca reabsorption from bone
Vit. D excess
