calcium regulation Flashcards
what substances in the blood can increase serum calcium?
-vitamin D (skin or diet)
-PTH SECRETED by parathyroid gland
what subst in blood can decrease serum calcium?
calcitonin, significant effect however its removal (after parathyroid cells removed) doesnt make a difference interestingly
what organs are the main regulators of calcium and phospate
gut, kidney, bone
(look at ipad) what reactions happen in skin cells in vit d synthetic process?
7- dehydrocholesterol -> pre vitamin D3 -> vitamin D3
what is vitamin d3 converted to? where? by what enzyme?
25 (OH) CHOLECALCIFEROL BY 25 HYDROXYLASE IN TH ELIVER
what is 25 (OH) cholecalciferol converted to? where? by what enzyme?
1,25 (OH)2 cholecalciferol by 1 alpha hydroxylase in the kidney
what is calcitriol?
1,25 (OH)2 cholecalciferol / active vit D
what is the measured indicator for vit d?
25-OH cholicalciferol (or 25-OH vit d)
how does calcitriol regulate its synthesis?
by decreasing the transcription of 1 alpha hydroxylase
what are the effects of lacitriol on calcium and phosphate absorption/ reabsorbtion/ secretion in gut bone and kidn?
kidney and gut both incr serum calcium bc incr reabsorption/ absorption
bone: decreases serum calcium because incr OSTEOBLAST activity
what are the direct actions of pth on calcium adn phosphate levels
increases OSTEOCLAST activity in bone so increasing calcium in serum
in kidney:
-incr calcium reabsorption
-incr phosphate EXCRETION
what are the indirect effects of pth on calcium and phosphate levels? what substance is involved?
PTH increases 1 a hydroxylase activity :
-> increases 1,25 (OH)2D3 synthesis
-> increases ca and po reabsorption in GUT
(SO OVERALL: PTH: KIDNEY AND BONE: DIRECT, GUT: INDIRECT)
what is the effect of hyperparathyroidism on serum phosphate levels? what is the mechanism?
remember: P.T.H: please transporter halt
-phosphate is reabsorbed in the kidney by na/ phosphate co-transporters
-PTH inhibits this transporter
- leads in less phosphate reabsorption so low phosphate in serum and more excreted
what is FGF23 derived form? what are its mechanisms for influencing serum phosphate levels?
derived from bone,
1) inhibits same transporters as PTH
2) Inhibits calcitriol ( leads to less phosphate reabsorption form gut) (indirect)
signs and sympotms of hypocalcemia
CAT goes numb
convulsions
arrhythmias
tetany
paraesthesia (nmbness in mouth, hands, feet, lips)
what is tetany
involuntary contraction of muscles due to LOW calcium levels
what are convulsions
rapid uncontrolable muscle movements like spasm
what is chvosteks’ sign
a specific facial paresthesia: when you tap check below eye and they close their eye on that side
what is trousseaus sign?
a specific type of tetany: carpopedal spasm (basically tetany below wrist/ palm)
causes of hypocalcaemia
- Low PTH levels
-low vitamin D
DEFICIENCY in what chemical element/ mineral can cause low pth levels
magnesium
causes of low PTH:
SURGery in neck
autoimmune
congenital (agenesis: rare)
MAGNESIUM DEFICIENCY
causes of vit d def
poor diet/ malabsorption
low uv exposure
impaired productIon (RENAL FAILURE) !!!
what happens to calcium levels in hypoparathyroidism?
decrease (hypocalcaemia)
AS a rule of thumb are systems underacting or overacting in hypercalcaemia?
under- so they overeact in hypo
what are the specific symptoms in hypercalcaemia?
broken bones, stones, psychic groans and abdominal moans, low muscles tones
specific renal effects- what si the medical name of having stones
nephrocalcinosis: kidney stones, renal colic (pain cuased by kidney trying to pass urine when theres kidney stone)
specific abdominal symptoms - GI effects
Anorexia (loss of apetite), nausea, dyspepsia, constipation, pancreatitis (mechanism is unclear )
Psychic groans - CNS effects specific, in which cases do these usually arise?
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L : probably very intense symptoms)
causes of hypercalcaemia and most common cause
primary hyperparathyroidism (most common) , malignancy, vit d excess (rare)
what happens in primary hyperparathyroidism, what is the cause?
too much pth,
usually due to parathyroid gland adenoma (benign tumour)
no negative feedback, due to AUTONOMOUS PTH SECRETION from adenoma: (body has enough calcium and pth is still abnormally released: more calcium absorbed)
what cancers usually cause hypercalcaemia and how?
bony metastases produce local factors to activate osteoclasts
Certain cancers (eg squamous cell carcinomas) secrete PTH-related hormones (like a peptide that acts at PTH receptors
HOW TO REMEMBER SPECIFIC LITTLE differences in pth and calcitriol effcets on excretions and absorptions
they both generally increase both calcium and phosphate from everywhere except from:
1) calcitriol: in bone: osteoblasts: steal ca from blood
2) pth: in kidney: increases phosphate EXCRETION - remove from blood
effect of primary hyperparathyroidism on phosphate?
low phosphate: increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
what is the treatment of primary hyperparathyroidsim?
Parathyroidectomy is treatment of choice for primary hyperparathyroidism
what are the risks of untreated hyperparathyroidism?
Osteoporosis
Renal calculi (stones) (Hypercalcemia: bad on bones too much calcium deposition makes them brittle )
Psychological impact of hypercalcaemia – mental function, mood
what is secondary hyperparathyroidism? (what pth and ca levels and why)
- clacium low or normal
- PTH high as a responce/ secondary to the low calcium
difference bwteen prim and secondary hyperparathyroidsim?
both pth high, calcium high in primary, low in secondary (means problem is not in the actual gland-like in primary, its in the calcium level)
what is the most common cause of secondary hyperparathyroidism?
vit d deficiency
commonly: diet and sunlight
less common: renal failure: cant make calcitriol (Active vit d)
common type of vit d in food
vit d2- ergocalciferol Ithing of ergo- energy in food)
treatment of secondary hyperparathyroidism if renal function normal?
- vit d replacement: Give 25 hydroxy vitamin D: either
1) ergocalciferol: 25 hydroxy vitamin D2 or
2)cholecalciferol: 25 hydroxy vitamin D3
treatment of secondary hyperparathyroidism if renal function abnormal?
inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations (no point in giving vit d they cant do anything with it so they need special vit d cant use over counter )
-need alfacalcidol -1a hydroxycholecalciferol
what is the difference between secondary and tertiary hyperparathyroidism? describe mechanism of disease in tertiary- treatment?
-the have same biochemistry : high pth low calcium but tertiary is when there is CHRONICALLY low calcium,
-so the parathyroids have been overworking for a long time to produce PTH so they start growing (all 4 glands hyperplasia) and releasing “basally” more pth than normal (diseased glands)
- this means that in contrast to secondary, parathyroids are damaged and treatment is removal (parathyroidectomy)
why does renal failure cause vit d def?
bc a 25 hydrohylase is in kidney and calcitriol produced by it in kidney
most common cause of tertiary hyperparathyroidism and on eless common in uk maybe more in developing counr
1) chronic renal failure
2) chronic malnutrition
when is there low PTH and hypercalcaemia?
malignancyy (bc parathyroid is doing its job fine, issue is alciujm secretion atopically)
Management of hypercalcaemia of malignancy? (bone cancer)
1) hydration
2) if nauseus??:
BISPHOSPHONATES – INHIBIT OSTEOCLASTS AND STOP THEM FROM ABSORBING BONE
LOWERS CALCIUM, LESS BONY PAIN
