Calcium+Phosphate Flashcards
What is the most abundant metal in the body?
Calcium
What is the storage distribution of calcium like in the body?
Unbound’ ionised calcium = biologically active component
What molecules lead to an increase in serum calcium?
Parathyroid hormone (PTH) (secreted by parathyroid glands)
Vitamin D
Synthesised in skin or intake via diet
Main regulators of calcium & phosphate homeostasis via actions on kidney, bone and gut
What molecule lead to a decrease in serum calcium?
Calcitonin (secreted by thyroid parafollicular cells)
Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy
Where is vitamin D2 derived from?
Ergocalciferol-Derived from UV irradiation of plants
Where is vitamin D3 derived from?
Cholecalciferol-Derived from UV irradiation of skin and certain foods e.g egg yolk
What is a good indicator of vit-D levels that is biologically inactive?
Serum 25-OH cholecalciferol
How does 1,25(OH)2 cholecalciferol (calcitriol) regulate its own synthesis?
It decreases transcription of 1 alpha-hydroxylase
Give the pathways of 7-dehydrocholesterol and dietary vitamin D2 to 1,25(OH)2 cholecalciferol
-UV radiation causes 7-dehydrocholesterol to turn into pre vitamin D3, then into vitamin D3-This moves from skin cells into capillaries
-Vitamin D2 moves into capillaries, converting into vitamin D3
> D3 is converted into 25(OH)cholecalciferol in the liver by 25 hydroxylase
Then into 1,25(OH)2cholecalciferol by 1-a-hydroxylase
What is the active form of vitamin D
Calcitriol-Same as 1,25(OH)2-cholecalciferol
What is the major role of calcitriol?
Increase Ca2+ and PO4^3- reabsorption from the gut
What cells secrete PTH in parathyroid gland and do they secrete PTH directly?
Chief cells
No-Secreted as a large precursor (pre-pro-PTH) & cleaved to PTH
How are Ca2+ levels detected for PTH secretion to be released?
G-protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
PTH secretion inversely proportional to serum calcium
What is the function of PTH
PTH degrades bone to release Ca2+
How does PTH increase blood Ca2+ and PO4^3- levels
Increased bone reabsorption
Increased 1-a-hydroxylase activity
>Increased 1,25(OH)2 D3 synthesis
>Ca2+, PO4^3- gut absorption
What is the effect of PTH on bone?
> PTH binds to receptor on osteoblast
Produces OAFs(Osteoclast activating factors)
Conversion into osteoclast
Increased bone resorption
How does calcitriol work?
(Pretty similarly to PTH)
-Only difference is calcitriol binds to calcitriol receptors
How is Ca2+ alone regulated by PTH and calcitriol?
PTH-Ca2+ in a negative feedback loop
PTH increases calcitriol production
Calcitriol reduces PTH production
Calcitriol increases serum Ca2+
Where is calcitonin produced from?
Parafollicular cells
What is the impact of calcitonin?
Reduces serum Ca2+(with a limited effect)
-Increases Ca2+ excretion
-Decreases osteoclast activity
Does a thyroidectomy interfere with serum calcium levels?
Nope
What is the physiological role of calcitonin?
Remains unclear-Something to do with calcium
What is the impact/mechanism of FGF23?
-Reduces PO4^3- reabsorption
>Inhibits Na+/PO4^3- co-transport in renal tubule
>Reduces production of calcitriol, leading to less PO4^3- reabsorption from gut
What are the symptoms for hypocalcaemia?
Why does hyper/hypocalcaemia alter membrane excitability?
HIGH extracellular calcium (HYPERcalcaemia)
Ca2+ blocks Na+ influx, so LESS membrane excitability
LOW extracellular calcium (HYPOcalcaemia)
enables GREATER Na+ influx, so MORE membrane excitability
(Negative inside of membrane normally) -Ca2+ reduces the amount of Na+ influx needed to generate an AP
What is chvosteks’ sign?
What is trousseaus’ sign?
What are the causes of PTH deficiency?
Hyperparathyroidism
Vit D deficiency
How would this process be inhibited, causing vitD deficiency, Ergocalciferol->25-OH D3
How would this process be inhibited, causing vitD deficiency, 7-dehydrocholesterol->Vit D3
How would this process be inhibited, causing vitD deficiency, Vit D3->25-OH D3
How would this process be inhibited, causing vitD deficiency, 25-OH D3->Calcitriol
How would this process be inhibited, causing vitD deficiency, Calcitriol->(effects of calcitriol)
What diseases does lack of bone mineralisation(Vit D deficiency) cause in children and adults?
Lack of bone mineralisation = ‘soft’ bones
In children – rickets (bowing of bones)
In adults – osteomalacia (fractures, proximal myopathy)
What are the symptoms of hypercalcaemia?
Signs & symptoms
‘Stones, abdominal moans and psychic groans’
Reduced neuronal excitability – atonal muscles
Stones – renal effects
Nephrocalcinosis – kidney stones, renal colic
Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
What are the causes of hypercalcaemia?
Primary hyperparathyroidism
Too much PTH
Usually due to a parathyroid gland adenoma
No negative feedback - high PTH, but high calcium
Malignancy
Bony metastases produce local factors to activate osteoclasts, increasing calcium reabsorption from bone
Vitamin D excess (rare)
