Calcium Flashcards
What changes occur when serum calcium is low?
- PTH is released by chief cells in the parathyroid gland
- reduces the reabsorption/increases excretion of phosphate in the kidney while decreasing calcium excretion
- increases calcium and phosphate excretion in the bone
- increases the absorption of calcium and phosphate in the intestines
- causes vitamin D activation int he kidneys
- inhibits sodium/water/bicarbonate reabsorption via effects on Na/H exchanger and Na/K ATPase
Where did the superior and inferior parathyroid glands originate from?
Develop from endodermal outpouchings
Inferior parathyroid: III out pouching
Superior parathyroid: IV out pouching
What type of receptor is the calcium sensing receptor?
GPCR
What is the effect of calcium binding to the calcium sensing receptor?
- Reduces PTH secretion
- Increases breakdown of stored PTH
- Suppresses transcription of PTH gene
What is the result of inactivating mutations to the calcium sensing receptor?
Familial hypocalciuric hypercalcaemia (autosomal dominant)
- CaSR can’t sense high calcium –> PTH not suppressed by high calcium –> Ca2+ reabsorption not stopped
What is the effect of activated vitamin/calcitriol on PTH?
Suppresses PTH gene transcription
What is the effect of activated phosphate on PTH?
Stimulates PTH gene transcription
Where is most Ca2+ reabsorbed in the renal system?
Proximal tubule
How is Ca2+ reabsorbed at the:
- Proximal tubule
- Loop of henle
- Distal tubule
- Proximal tubule: paracellularly
- Loop of henle: para/transcellularly
- Distal tubule: via TRPV Ca2+ channels
What is the effect of PTH and calcitriol on RANKL and OPG?
- stimulate RANKL
- downregulate OPG
What is the role of RANKL?
RANKL is released by osteoblasts
- RANKL is a receptor activator for nuclear factor kB ligand and colony stimulating factor 1
- promotes osteoclastogenesis and osteoclast function
What is the role of OPG?
OPG = osteoprotegerin
- inhibits osteoclastogenesis
What is the effect of PTH on IGF1 and IL1?
Increases both
What can primary hyperparathyroidism result in?
- terminal tuft erosion
- rugger jersey spine
- subperiosteal erosion
- brown tumour
What type of receptor is vitamin D receptor?
nuclear and membrane bound
What occurs when vitamin D receptor is activated?
- inhibits action 1-alpha hydroxylase
- this reduces the amount of 1,25-vitamin D able to bind to VDR
*function of the VDR is to increase calcium and phosphate absorption from the gut and kidneys
Apart from inside the kidney, where else is calcitriol produced and why? In what situations doe this occur?
Macrophages
- inside a macrophage calcitriol acts as a cytokines
- modulates body defences against microbial invaders stimulating the innate immune response
Occurs when macrophages are activated (such as in TB and sarcoid granulomata) –> can lead to hypercalcaemia
Explain how calcium is absorbed from the gut.
- calcium in the lumen can travel to interstitial space in the gut para/transcellularly
- calbindin is produced in the gut cells (enterocytes) –> it grabs Ca2+ inside the cell and releases it into the interstitium
- Ca2+ in the interstitium can enter the blood
What are the effects of vitamin D on parathyroid glands?
- modest reduction in PTH transcription
What are the effects of vitamin D on bones?
- reduces expression of type 1 collagen
- increases level of osteocalcin + RANKL
- facilitates osteoclast differentiation
What are the effects of vitamin D on phosphate?
- increases phosphate absorption from the gut
- increases levels of FGF23 to remove it via renal excretion
What are the effects of vitamin D on amino acids?
increases amino acid uptake
*deficiency in vitamin D results in myopathy
What can vitamin D deficiency lead to?
- rickets
- osteomalacia
- osteoporosis
What is FGF23?
phosphatonin - hormones that reduces serum phosphate
- it is secreted by osteocytes
- actives inhibition of vitamin D
What is the result of an activating mutation in FGF23?
Autosomal dominant hypophosphataemic rickets
What is the result of a benign neoplasm that inappropriately produces fibroblast growth factor 23?
tumour-induced osteomalacia
What effect does familial tumoral calcinosis have on FGF23 levels?
FGF23 levels are low
Where is calcitonin produced? What is its role?
Produced by thyroid C cells
Lowers calcium levels
What are potential causes of primary HPT?
- parathyroid adenoma
- carcinoma
- hyperplasia
What are potential causes of secondary HPT?
- physiological compensation for hypocalcaemia
- vitamin D deficiency
What are potential causes of tertiary HPT?
- autonomous PTH production following chronic secondary PHPT
What are the S+S/is the result of HPT?
- hypercalcaemia
- polyuria and polydipsia
- kidney stones
- osteoporosis
- mood disorder
How is primary HPT diagnosed?
- serum calcium and PTH
- 24h urine calcium
- urine calcium creatinine excretion index
- renal ultrasound
- DEXA scan
What are the S+S of hypocalcaemia?
- convulsions
- confusion
- tetany
- tachyarrhythmia
What are the causes of hypocalcaemia?
- hypoparathyroidism: iatrogenic, autoimmune, genetic
- vitamin D deficiency
- chronic kidney disease
- PTH resistance
How would you treat acute and chronic hypoparathyroidism?
- acute: IV/oral calcium replacement
- chronic: alfacalcidol orally - increases gut absorption of calcium
- however there will still be hypercalciuria = increased risk of kidney stones
