Endocrinology- Regulation of Ca2+ and Phosphate Flashcards
Where is the majority of calcium in the body? And what compound is it stored as?
Skeleton and teeth
stored as hydroxyapatite crystals
What 2 types of plasma calcium are there
Ionised (unbound) - Ca2+, BIOLOGICALLY ACTIVE compoment
Bound- plasma protiens OR anions such as bicarbonate
Which 2 hormones increase serum levels of calcium and posphate?
how are they synthesized?
parathyroid hormone - secreted by para gland
Vit D- synthesized in skin or diet. actions via kidney and bone, gut
Which hormones decrease Ca2+ and phosphate levels?
Calcitonin- not essneital, only reduces acutely
Where is calcitonin synthesized?
By thyroid parafollicular cells, no negative effect if removed
(not essential for regulation)
What are the 2 inactive molecules of Vit D and where are each one from?
Vitamin D3 (Cholecaliferol)- Skin when exposed sunlight
Vitamine D2 (Ergocalciferol) - from diet
How does Skin make Cholecalciferol?
7-dehydrocholesterol (produced by skin cells) UV LIGHT
—->pre- vitamin D3
—–> Vit D3
(then goes off to produce activated Vit D3)
What happens to the Vitamin D2 and D3 after take in (First step)?
1st hydroxylation- to liver
convert to 25(OH)cholecalicferol
by 25-hydroxylase enzyme
What happens to the Vitamin D2 and D3 after take in (second step)?
2nd- hydroxylation
transported to kidney converted
by 1-alpha-hydroxylase
to 1,25 diol cholecalciferol WHICH IS ACTIVE VIT D
Which molecule should be measured to determine Vitamin D levels?
25(OH)cholecalciferol as active Vitamin D is difficult to measure
Does calcitriol -ve feedback itself? And how?
Yes,
regulates own synthesis by decrease transcripiton of
1-alpha hydroxylase enzyme of 2nd hydroxylation
What effects does calcitriol have to increase phosphate levels and calcium?
Increases Ca2+ and phosphate reabsoportion from kidnet
increased Ca2+ and phosphate absorption from small intestine
Increased Ca2+ absoprtion into bones
Where are parathyroid glands located?
4 small pieces on poterior of thryoid gland
What types of cells in parathryoid glands secrete PTH?
Chief cells
How is PTH secreted from the chief cells?
As a large precursor pre-pro-PTH
cleaved in cell to PTH
How is PTH secretion from chief cells regulated?
have G coupled Ca2+ sensing receptor
detect circulating Ca2+ levels + secrete inversely to it
Effects of PTH?
increases osteoclast activity, increasing bone and Ca2+ resaborption
increase calcium reabsorption and excretion of phosphate from kidney
increase Vit D synthesis so increase absorption of minerals from small intestine
How does PTH regulate serum levels of Ca2+?
increases Ca2+ plasma concentration
by increasing Ca2+ mobilisation from bones and it’s reabsoprtion from kidney
absorption of Ca2+ from small intestine via increasing vitamin D
How does PTH regulate serum levels of phosphate ?
It doesn’t
as phosphate levels increase by absorption in small intenstine
but increases excretion in kidney
so overall no increase
What affect does PTH have on bones to regulate serum levels of calcium?
Binds to osteoblasts to release oeseoclast activating factors like RANKL
stimulate OSTEOCLAST bone eating cells,
breakdown bone into calcium and phosphate, which then go to kidneys. (Ca2+ is reabsorbed phosphate excreted)
What effect does calcitrol when low calcium serum levels on bones?
What effect does calictrol when normal calcium serum levels on bones?
increease calcium reabsoprtion from bone
clasts > blasts
increase bone formation
blasts > clasts
BOTH PTH and CALICITROL have similar effects on bone
How is PTH (negatively) regulated?
2 ways
1).increase in plasma Ca2+
detected by parathyroid glands + secrete less PTH
2). Chief cells also have vitamin D receptors, too much Vit D less PTH
Which types of cells produce calcitonin?
What is it’s effect?
Parafollicular cells of Thyroid cells
Reduce serum calcium levels
How does calcitron decrease serum levels of Calcium?
Increase Ca2+ secretion by kidney
decrease osteoclast (bone consumtion cells) activity
What molecule regulates phosphate?
And where is it produced?
FGF-23
specific cells in Bones
How does it reduce phosphate levels?
2 ways
- Prevents re uptake of phosphate in kidney from urine( proximal tubule)
blocks/prevents Na+/phosphate co-transporter
- inhibits calcitriol, less phosphate absoprtion from gut
How does PTH excrete phosphate in kidney?
same way as FGF 23
Prevents re uptake of phosphate in kidney from urine( proximal tubule)
blocks/prevents Na+/phosphate co-transporter
Main affect of HYPOcalcaemia and HYPERcalcaemia
HYPO- less Ca2+ in blood serum, Ca more Na influx
greater excitation of neurones membranes
HYPER- more Ca2+ in blood serum, Ca blocks Na influx
less excitation of neurones membranes
What function does Ca2+ have on Na+ channels?
At resting state sodium channels are stablizied by Ca2+,
prevents spontanous depolarisation
If low
Symptoms of hypocalcaemia?
sensitises, excitable tissues, cramps, tingling
paresthesia (chilling, burning, numbness)- hands, mouth
convulsions - fits
arrhythmias - problem HR
tetany- can’t relax muscle
What is Chvostek’s sign?
Tap facial nerve below zygomatic arch,
twitching of facial muscles, more sensitized
common with hypocalcaemia
What is trousseau’s sign?
increase BP induced carpopedal spasm-muscles contract + can’t stop ,
neuromusclar irritability
Causes of hypocalcaemia?
hypoparathyroidism
surgical- neck surgery, affect parathyroid gland
autoimmune- attacks any organs
magnesium. defincity- need to make PTH
agensis- failure organ grow
vitamin D deficincy- sun & diet
Causes of vitamin D deficincy?
Consequence of Vitamin D deficiency?
has importance in mineralism of bone increase bone formation, increase osteoblast activity> osteoclasts when Ca2+ levels are high
soft bones
rickets- bendt bones
osteomalacia- fractures, proximal mypoathy hips weakness
Symptoms of hypercalcaemia?
stones- kidney lots of calcium excreted causes stones + neuphrocalcinosis
adbominal moans- gut is long muscle, anoxia, dypsia- heart burn, conspitation, pancritis-inflmation
pyshic groans- fatigue, depression, altered mentation
atonal muscles
Causes of hypercalcaemia?
primary hyperparathyroidism- PTH gland adeonma
no negative feedback so increase PTH and Ca2=
cancer spread to bone, metastases.
local factors activate osteoclastsm increase calcium reabsoprtion from bone
excess vit D
